Search results for: semi-public spaces
6 Amifostine Analogue, Drde-30, Attenuates Radiation-Induced Lung Injury in Mice
Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath
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Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.Keywords: amifostine, fibrosis, inflammation, lung injury radiation
Procedia PDF Downloads 5035 Morphological and Molecular Abnormalities of the Skeletal Muscle Tissue from Pediatric Patient Affected by a Rare Genetic Chaperonopathy Associated with Motor Neuropathy
Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia
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The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis
Procedia PDF Downloads 624 Developing a Place-Name Gazetteer for Singapore by Mining Historical Planning Archives and Selective Crowd-Sourcing
Authors: Kevin F. Hsu, Alvin Chua, Sarah X. Lin
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As a multilingual society, Singaporean names for different parts of the city have changed over time. Residents included Indigenous Malays, dialect-speakers from China, European settler-colonists, and Tamil-speakers from South India. Each group would name locations in their own languages. Today, as ancestral tongues are increasingly supplanted by English, contemporary Singaporeans’ understanding of once-common place names is disappearing. After demolition or redevelopment, some urban places will only exist in archival records or in human memory. United Nations conferences on the standardization of geographic names have called attention to how place names relate to identity, well-being, and a sense of belonging. The Singapore Place-Naming Project responds to these imperatives by capturing past and present place names through digitizing historical maps, mining archival records, and applying selective crowd-sourcing to trace the evolution of place names throughout the city. The project ensures that both formal and vernacular geographical names remain accessible to historians, city planners, and the public. The project is compiling a gazetteer, a geospatial archive of placenames, with streets, buildings, landmarks, and other points of interest (POI) appearing in the historic maps and planning documents of Singapore, currently held by the National Archives of Singapore, the National Library Board, university departments, and the Urban Redevelopment Authority. To create a spatial layer of information, the project links each place name to either a geo-referenced point, line segment, or polygon, along with the original source material in which the name appears. This record is supplemented by crowd-sourced contributions from civil service officers and heritage specialists, drawing from their collective memory to (1) define geospatial boundaries of historic places that appear in past documents, but maybe unfamiliar to users today, and (2) identify and record vernacular place names not captured in formal planning documents. An intuitive interface allows participants to demarcate feature classes, vernacular phrasings, time periods, and other knowledge related to historical or forgotten spaces. Participants are stratified into age bands and ethnicity to improve representativeness. Future iterations could allow additional public contributions. Names reveal meanings that communities assign to each place. While existing historical maps of Singapore allow users to toggle between present-day and historical raster files, this project goes a step further by adding layers of social understanding and planning documents. Tracking place names illuminates linguistic, cultural, commercial, and demographic shifts in Singapore, in the context of transformations of the urban environment. The project also demonstrates how a moderated, selectively crowd-sourced effort can solicit useful geospatial data at scale, sourced from different generations, and at higher granularity than traditional surveys, while mitigating negative impacts of unmoderated crowd-sourcing. Stakeholder agencies believe the project will achieve several objectives, including Supporting heritage conservation and public education; Safeguarding intangible cultural heritage; Providing historical context for street, place or development-renaming requests; Enhancing place-making with deeper historical knowledge; Facilitating emergency and social services by tagging legal addresses to vernacular place names; Encouraging public engagement with heritage by eliciting multi-stakeholder input.Keywords: collective memory, crowd-sourced, digital heritage, geospatial, geographical names, linguistic heritage, place-naming, Singapore, Southeast Asia
Procedia PDF Downloads 1183 Blue Economy and Marine Mining
Authors: Fani Sakellariadou
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The Blue Economy includes all marine-based and marine-related activities. They correspond to established, emerging as well as unborn ocean-based industries. Seabed mining is an emerging marine-based activity; its operations depend particularly on cutting-edge science and technology. The 21st century will face a crisis in resources as a consequence of the world’s population growth and the rising standard of living. The natural capital stored in the global ocean is decisive for it to provide a wide range of sustainable ecosystem services. Seabed mineral deposits were identified as having a high potential for critical elements and base metals. They have a crucial role in the fast evolution of green technologies. The major categories of marine mineral deposits are deep-sea deposits, including cobalt-rich ferromanganese crusts, polymetallic nodules, phosphorites, and deep-sea muds, as well as shallow-water deposits including marine placers. Seabed mining operations may take place within continental shelf areas of nation-states. In international waters, the International Seabed Authority (ISA) has entered into 15-year contracts for deep-seabed exploration with 21 contractors. These contracts are for polymetallic nodules (18 contracts), polymetallic sulfides (7 contracts), and cobalt-rich ferromanganese crusts (5 contracts). Exploration areas are located in the Clarion-Clipperton Zone, the Indian Ocean, the Mid Atlantic Ridge, the South Atlantic Ocean, and the Pacific Ocean. Potential environmental impacts of deep-sea mining include habitat alteration, sediment disturbance, plume discharge, toxic compounds release, light and noise generation, and air emissions. They could cause burial and smothering of benthic species, health problems for marine species, biodiversity loss, reduced photosynthetic mechanism, behavior change and masking acoustic communication for mammals and fish, heavy metals bioaccumulation up the food web, decrease of the content of dissolved oxygen, and climate change. An important concern related to deep-sea mining is our knowledge gap regarding deep-sea bio-communities. The ecological consequences that will be caused in the remote, unique, fragile, and little-understood deep-sea ecosystems and inhabitants are still largely unknown. The blue economy conceptualizes oceans as developing spaces supplying socio-economic benefits for current and future generations but also protecting, supporting, and restoring biodiversity and ecological productivity. In that sense, people should apply holistic management and make an assessment of marine mining impacts on ecosystem services, including the categories of provisioning, regulating, supporting, and cultural services. The variety in environmental parameters, the range in sea depth, the diversity in the characteristics of marine species, and the possible proximity to other existing maritime industries cause a span of marine mining impact the ability of ecosystems to support people and nature. In conclusion, the use of the untapped potential of the global ocean demands a liable and sustainable attitude. Moreover, there is a need to change our lifestyle and move beyond the philosophy of single-use. Living in a throw-away society based on a linear approach to resource consumption, humans are putting too much pressure on the natural environment. Applying modern, sustainable and eco-friendly approaches according to the principle of circular economy, a substantial amount of natural resource savings will be achieved. Acknowledgement: This work is part of the MAREE project, financially supported by the Division VI of IUPAC. This work has been partly supported by the University of Piraeus Research Center.Keywords: blue economy, deep-sea mining, ecosystem services, environmental impacts
Procedia PDF Downloads 722 Reassembling a Fragmented Border Landscape at Crossroads: Indigenous Rights, Rural Sustainability, Regional Integration and Post-Colonial Justice in Hong Kong
Authors: Chiu-Yin Leung
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This research investigates a complex assemblage among indigenous identities, socio-political organization and national apparatus in the border landscape of post-colonial Hong Kong. This former British colony had designated a transient mode of governance in its New Territories and particularly the northernmost borderland in 1951-2012. With a discriminated system of land provisions for the indigenous villagers, the place has been inherited with distinctive village-based culture, historic monuments and agrarian practices until its sovereignty return into the People’s Republic of China. In its latest development imperatives by the national strategic planning, the frontier area of Hong Kong has been identified as a strategy site for regional economic integration in South China, with cross-border projects of innovation and technology zones, mega-transport infrastructure and inter-jurisdictional arrangement. Contemporary literature theorizes borders as the material and discursive production of territoriality, which manifest in state apparatus and the daily lives of its citizens and condense in the contested articulations of power, security and citizenship. Drawing on the concept of assemblage, this paper attempts to tract how the border regime and infrastructure in Hong Kong as a city are deeply ingrained in the everyday lived spaces of the local communities but also the changing urban and regional strategies across different longitudinal moments. Through an intensive ethnographic fieldwork among the borderland villages since 2008 and the extensive analysis of colonial archives, new development plans and spatial planning frameworks, the author navigates the genealogy of the border landscape in Ta Kwu Ling frontier area and its implications as the milieu for new state space, covering heterogeneous fields particularly in indigenous rights, heritage preservation, rural sustainability and regional economy. Empirical evidence suggests an apparent bias towards indigenous power and colonial representation in classifying landscape values and conserving historical monuments. Squatter and farm tenants are often deprived of property rights, statutory participation and livelihood option in the planning process. The postcolonial bureaucracies have great difficulties in mobilizing resources to catch up with the swift, political-first approach of the mainland counterparts. Meanwhile, the cultural heritage, lineage network and memory landscape are not protected altogether with any holistic view or collaborative effort across the border. The enactment of land resumption and compensation scheme is furthermore disturbed by lineage-based customary law, technocratic bureaucracy, intra-community conflicts and multi-scalar political mobilization. As many traces of colonial misfortune and tyranny have been whitewashed without proper management, the author argues that postcolonial justice is yet reconciled in this fragmented border landscape. The assemblage of border in mainstream representation has tended to oversimplify local struggles as a collective mist and setup a wider production of schizophrenia experiences in the discussion of further economic integration among Hong Kong and other mainland cities in the Pearl River Delta Region. The research is expected to shed new light on the theorizing of border regions and postcolonialism beyond Eurocentric perspectives. In reassembling the borderland experiences with other arrays in state governance, village organization and indigenous identities, the author also suggests an alternative epistemology in reconciling socio-spatial differences and opening up imaginaries for positive interventions.Keywords: heritage conservation, indigenous communities, post-colonial borderland, regional development, rural sustainability
Procedia PDF Downloads 1991 From Core to Hydrocarbon: Reservoir Sedimentology, Facies Analysis and Depositional Model of Early Oligocene Mahuva Formation in Tapti Daman Block, Western Offshore Basin, India
Authors: Almas Rajguru
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The Oligocene succession of the Tapti- Daman area is one of the established petroleum plays in Tapti-Daman block of the Mumbai Offshore Basin. Despite good control and production history, the sand geometry and continuity of reservoir character of these sediments are less understood as most reservoirs are thin and fall below seismic resolution. The present work focuses on a detailed analysis of the Early Oligocene Mahuva Formation at the reservoir scale through laboratory studies (sedimentology and biostratigraphy) of core and sidewall cores in integration with electro logs for firming up facies’ distribution, micro-depositional environment and sequence stratigraphy, diagenesis and reservoir characterization from seventeen wells from North Tapti-C-37 area in Tapti Daman Block, WOB. The thick shale/claystone with thin interbeds of sandstone and siltstones of deeper marine in the lower part of Mahuva Fm represents deposition in a transgressive regime. The overlying interbedded sandstone, glauconitic-siltstone/fine-grained sandstone, and thin beds of packstone/grainstone within highly fissile shale were deposited in a prograding tide-dominated delta during late-rise normal regression. Nine litho facies (F1-F9) representing deposition in various microenvironments of the tide-dominated delta are identified based on their characteristic sediment texture, structure and microfacies. Massive, gritty sandstone (F1) with poorly sorted sands lithic fragments with calcareous and Fe-rich matrix represents channel fill sediments. High-angle cross-stratified sandstone (F2) deposited in rapidly shifting/migrating bars under strong tidal currents. F3 records the laterally accreted tidal-channel point bars. F3 (low-angle cross-stratified to parallel bedded sandstone) and F4 (Clean sandstone) are often associated with F2 in a tidal bar complex. F5 (interbedded thin sand and mud) and F6 (bioturbated sandstone) represent tidal flat deposits. High energy open marine carbonate shoals (F8) and fossiliferous sandstone in offshore bars (F7) represent deepening up facies. Shallow marine standstill conditions facilitated the deposition of thick shale (F9) beds. The reservoir facies (F1-F6) are commonly poorly to moderately sorted; bimodal, immature sandstone represented by quartz-wacke. The framework grains are sub-angular to sub-rounded, medium to coarse-grained (occasionally gritty) embedded within argillaceous (kaolinite/chlorite/chamosite) to highly Fe-rich matrix (sideritic). The facies F7 and F8, representing the sandy packstone and grainstone facies, respectively, exhibit poor reservoir characteristics due to sanitization, diagenetic compaction and matrix-filled intergranular spaces. The various diagenetic features such as the presence of authigenic clays (kaolinite/dickite/smectite); ferruginous minerals like siderite, pyrite, hematite and other iron oxides; bioturbations; glauconite; calcite and quartz cementation, precipitation of gypsum, pressure solution and other compaction effects are identified. These diagenetic features, wherever present, have reduced porosity and permeability thereby adversely affecting reservoir quality. Tidal bar sandstones possess good reservoir characteristics such as moderate to good sorting, fair to good porosity and geometry that facilitates efficient lateral extension and vertical thickness of reservoir. The sand bodies of F2, F3 and F4 facies of Well L, M and Q deposited in a tidal bar complex exhibit good reservoir quality represented by relatively cleaner, poorly burrowed, loose, friable sandstone with good porosity. Sandstone facies around these wells could prove a potential hydrocarbon reservoir and could be considered for further exploration.Keywords: reservoir sedimentology, facies analysis, HST, tide dominated delta, tidal bars
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