Geospatial Analysis of the Global Supply Chain and Transportation Infrastructure Considering Extreme Weather, Climate, and Sustainable Energy Policies

The basis of this research is an investigation into the demand, costs, and emissions of a container freight shipping route from South America to the Port of Charleston, South Carolina. Ports and shipping routes play the most crucial role in the global supply chain, allowing people to maintain their standard of living. Once ashore, the delivery routes to five major metropolitan market cities were optimized for the lowest shipping costs for road and freight rail. The costs of transportation are a major factor in the ultimate price of consumer goods and thus must be minimized in the transportation process. Increasing the rail modeshare from 20% to 40% reduced the costs of transport by 25.4%. Emissions were also reduced, with a decrease of 10.29% in PM10, 9.09% in NOx, 20.28% in SOx, and 12.17% in CO2. The impact of coastal disasters on the global shipping and supply chain was then conveyed, stressing how resilient infrastructure must be implemented to harden the supply chain to natural disasters and extreme weather events such as tsunamis, hurricanes, and sea level rise. Earth’s rising temperature plays the most significant role in sea level rise. The next step in this research deals with modeling the Earth’s temperatures through autoregressive integrated moving average (ARIMA) model equations. ARIMA modeling allows for cyclical and seasonal time series data, such as climate indicators, to be modelled with accuracy where otherwise a linear trend model would not do so. The temperature on the surface of the Earth is shown to decrease by 1.02 °C (7.56%) in 2050 when compared to 2016. Based on these results, the ARIMA (12,0,24) model equation is recommended for future temperature predictions. Sea ice extents of the northern and southern hemispheres, both previously recorded time series data and projected values, were also modelled using ARIMA methodology. Analysis shows that southern hemisphere (Antarctic) sea ice extents will increase 14.0% in 2050 compared to 2016. Northern hemisphere sea ice extents (Arctic), however, will lose 13.5% in 2050 compared to 2016. The result is a net gain of 0.5% (0.25 million sq km) of sea ice in 2050 on the combined surface area of both poles. Finally, this research looks at the current electricity generation technologies used to power the world and how the sources of fuel that drive power generation have changed over the past decades. Renewable sources have had recent technological advances, allowing for their wider implementation in the energy generation portfolio. However, before their implementation, the entire life cycle assessment, both in the cost of construction and operation/maintenance as well as sources of emission, and their reliability must be considered when drastically changing the energy landscape. For generating the same amount of electricity, life cycle costs of wind-driven energy is found to be 40% less expensive than solar. Based on 120 years analysis period, the value engineering analysis ranks the electric power generation technologies in the following order of least cost: 1) Nuclear, 2) Coal, 3) Wind, and 4) Solar

Effects of Heparin and Enoxaparin on APP Processing and Aβ Production in Primary Cortical Neurons from Tg2576 Mice

BACKGROUND Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS We examined whether heparin and enoxaparin influence APP processing and inhibit Aβ production in primary cortical cell cultures. Heparin and enoxaparin were incubated with primary cortical cells derived from Tg2576 mice, and the level of APP and proteolytic products of APP (sAPPα, C99, C83 and Aβ) was measured by western blotting. Treatment of the cells with heparin or enoxaparin had no significant effect on the level of total APP. However, both GAGs decreased the level of C99 and C83, and inhibited sAPPα and Aβ secretion. Heparin also decreased the level of β-secretase (BACE1) and α-secretase (ADAM10). In contrast, heparin had no effect on the level of ADAM17. CONCLUSIONS/SIGNIFICANCE The data indicate that heparin and enoxaparin decrease APP processing via both α- and β-secretase pathways. The possibility that GAGs may be beneficial for the treatment of AD needs further study.This work was funded by a project grant (490031) from the National Health and Medical Research Council of Australia (http://www.nhmrc.gov.au). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Study of Multi-scale Transport Phenomena in Tight Gas and Shale Gas Reservoir Systems

The hydrocarbon resources found in shale reservoirs have become an important energy source in recent years. Unconventional geological and engineering features of shale systems pose challenges to the characterization of these systems. These challenges have impeded efficient economic development of shale resources. New fundamental insights and tools are needed to improve the state of shale gas development. Few attempts have been made to model the compositional behavior of fluids in shale gas reservoirs. The transport and storage of reservoir fluids in shale is controlled by multiple distinct micro-scale physical phenomena. These phenomena include preferential Knudsen diffusion, differential desorption, and capillary critical effects. Together, these phenomena cause significant changes in fluid composition in the subsurface and a measureable change in the composition of the produced gas over time. In order to quantify this compositional change we developed a numerical model describing the coupled processes of desorption, diffusion, and phase behavior in heterogeneous ultra-tight rocks as a function of pore size. The model captures the various configurations of fractures induced by shale gas fracture stimulation. Through modeling of the physics at the macro-scale (e.g. reservoir-scale hydraulic fractures) and micro-scale (e.g. Knudsen diffusion in kerogen nanopores), we illustrate how and why gas composition changes spatially and temporally during production. We compare the results of our numerical model against measured composition data obtained at regular intervals from shale gas wells. We utilize the characteristic behaviors explicated by the model results to identify features in the measured data. We present a basis for a new method of production data analysis incorporating gas composition measurements in order to develop a more complete diagnostic process. Distinct fluctuations in the flowing gas composition are shown to uniquely identify the onset of fracture interference in horizontal wells with multiple transverse hydraulic fractures. The timescale and durations of the transitional flow regimes in shales are quantified using these measured composition data. These assessments appear to be robust even for high levels of noise in the rate and pressure data. Integration of the compositional shift analysis of this work with modern production analysis is used to infer reservoir properties. This work extends the current understanding of flow behavior and well performance for shale gas systems to encompass the physical phenomena leading to compositional change. This new understanding may be used to aid well performance analysis, optimize fracture and completion design, and improve the accuracy of reserves estimates. In this work we contribute a numerical model which captures multicomponent desorption, diffusion, and phase behavior in ultra-tight rocks. We also describe a workflow for incorporating measured gas composition data into modern production analysis

Study of Flow Regimes in Multiply-Fractured Horizontal Wells in Tight Gas and Shale Gas Reservoir Systems

Various analytical, semi-analytical, and empirical models have been proposed to characterize rate and pressure behavior as a function of time in tight/shale gas systems featuring a horizontal well with multiple hydraulic fractures. Despite a small number of analytical models and published numerical studies there is currently little consensus regarding the large-scale flow behavior over time in such systems. The purpose of this work is to construct a fit-for-purpose numerical simulator which will account for a variety of production features pertinent to these systems, and to use this model to study the effects of various parameters on flow behavior. Specific features examined in this work include hydraulically fractured horizontal wells, multiple porosity and permeability fields, desorption, and micro-scale flow effects. The theoretical basis of the model is described in Chapter I, along with a validation of the model. We employ the numerical simulator to examine various tight gas and shale gas systems and to illustrate and define the various flow regimes which progressively occur over time. We visualize the flow regimes using both specialized plots of rate and pressure functions, as well as high-resolution maps of pressure distributions. The results of this study are described in Chapter II. We use pressure maps to illustrate the initial linear flow into the hydraulic fractures in a tight gas system, transitioning to compound formation linear flow, and then into elliptical flow. We show that flow behavior is dominated by the fracture configuration due to the extremely low permeability of shale. We also explore the possible effect of microscale flow effects on gas effective permeability and subsequent gas species fractionation. We examine the interaction of sorptive diffusion and Knudsen diffusion. We show that microscale porous media can result in a compositional shift in produced gas concentration without the presence of adsorbed gas. The development and implementation of the micro-flow model is documented in Chapter III. This work expands our understanding of flow behavior in tight gas and shale gas systems, where such an understanding may ultimately be used to estimate reservoir properties and reserves in these types of reservoirs

Mast cells and hypoxia drive tissue metaplasia and heterotopic ossification in idiopathic arthrofibrosis after total knee arthroplasty

ABSTRACT: BACKGROUND: Idiopathic arthrofibrosis occurs in 3-4% of patients who undergo total knee arthroplasty (TKA). However, little is known about the cellular or molecular changes involved in the onset or progression of this condition. To classify the histomorphologic changes and evaluate potential contributing factors, periarticular tissues from the knees of patients with arthrofibrosis were analyzed for fibroblast and mast cell proliferation, heterotopic ossification, cellular apoptosis, hypoxia and oxidative stress. RESULTS: The arthrofibrotic tissue was composed of dense fibroblastic regions, with limited vascularity along the outer edges. Within the fibrotic regions, elevated numbers of chymase/fibroblast growth factor (FGF)-expressing mast cells were observed. In addition, this region contained fibrocartilage and associated heterotopic ossification, which quantitatively correlated with decreased range of motion (stiffness). Fibrotic, fibrocartilage and ossified regions contained few terminal dUTP nick end labeling (TUNEL)-positive or apoptotic cells, despite positive immunostaining for lactate dehydrogenase (LDH)5, a marker of hypoxia, and nitrotyrosine, a marker for protein nitrosylation. LDH5 and nitrotyrosine were found in the same tissue areas, indicating that hypoxic areas within the tissue were associated with increased production of reactive oxygen and nitrogen species. CONCLUSIONS: Taken together, we suggest that hypoxia-associated oxidative stress initiates mast cell proliferation and FGF secretion, spurring fibroblast proliferation and tissue fibrosis. Fibroblasts within this hypoxic environment undergo metaplastic transformation to fibrocartilage, followed by heterotopic ossification, resulting in increased joint stiffness. Thus, hypoxia and associated oxidative stress are potential therapeutic targets for fibrosis and metaplastic progression of idiopathic arthrofibrosis after TKA

Reactive oxygen and nitrogen species induce protein and DNA modifications driving arthrofibrosis following total knee arthroplasty

BACKGROUND: Arthrofibrosis, occurring in 3%-4% of patients following total knee arthroplasty (TKA), is a challenging condition for which there is no defined cause. The hypothesis for this study was that disregulated production of reactive oxygen species (ROS) and nitrogen species (RNS) mediates matrix protein and DNA modifications, which result in excessive fibroblastic proliferation. RESULTS: We found increased numbers of macrophages and lymphocytes, along with elevated amounts of myeloperoxidase (MPO) in arthrofibrotic tissues when compared to control tissues. MPO expression, an enzyme that generates ROS/RNS, is usually limited to neutrophils and some macrophages, but was found by immunohistochemistry to be expressed in both macrophages and fibroblasts in arthrofibrotic tissue. As direct measurement of ROS/RNS is not feasible, products including DNA hydroxylation (8-OHdG), and protein nitrosylation (nitrotyrosine) were measured by immunohistochemistry. Quantification of the staining showed that 8-OHdg was significantly increased in arthrofibrotic tissue. There was also a direct correlation between the intensity of inflammation and ROS/RNS to the amount of heterotopic ossification (HO). In order to investigate the aberrant expression of MPO, a real-time oxidative stress polymerase chain reaction array was performed on fibroblasts isolated from arthrofibrotic and control tissues. The results of this array confirmed the upregulation of MPO expression in arthrofibrotic fibroblasts and highlighted the downregulated expression of the antioxidants, superoxide dismutase1 and microsomal glutathione S-transferase 3, as well as the significant increase in thioredoxin reductase, a known promoter of cell proliferation, and polynucleotide kinase 3\u27-phosphatase, a key enzyme in the base excision repair pathway for oxidative DNA damage. CONCLUSION: Based on our current findings, we suggest that ROS/RNS initiate and sustain the arthrofibrotic response driving aggressive fibroblast proliferation and subsequent HO