bluuebunny/crossref_metadata_2025_split huggingface dataset:
Live Imaging of Calcium Dynamics during Axon Degeneration Reveals Two Functionally Distinct Phases of Calcium Influx
Authors: Vargas Mauricio Enrique , Yamagishi Yuya , Tessier-Lavigne Marc , Sagasti Alvaro 
Published: November 2015

Calcium is a key regulator of axon degeneration caused by trauma and disease, but its specific spatial and temporal dynamics in injured axons remain unclear. To clarify the function of calcium in axon degeneration, we observed calcium dynamics in single injured neurons in live zebrafish larvae and tested the temporal requirement for calcium in zebrafish neurons and cultured mouse DRG neurons. Using laser axotomy to induce Wallerian degeneration (WD) in zebrafish peripheral sensory axons, we monitored calcium dynamics from injury to fragmentation, revealing two stereotyped phases of axonal calcium influx. First, axotomy triggered a transient local calcium wave originating at the injury site. This initial calcium wave only disrupted mitochondria near the injury site and was not altered by expression of the protective WD slow (WldS) protein. Inducing multiple waves with additional axotomies did not change the kinetics of degeneration. In contrast, a second phase of calcium influx occurring minutes before fragmentation spread as a wave throughout the axon, entered mitochondria, and was abolished by WldS expression. In live zebrafish, chelating calcium after the first wave, but before the second wave, delayed the progress of fragmentation. In cultured DRG neurons, chelating calcium early in the process of WD did not alter degeneration, but chelating calcium late in WD delayed fragmentation. We propose that a terminal calcium wave is a key instructive component of the axon degeneration program.SIGNIFICANCE STATEMENTAxon degeneration resulting from trauma or neurodegenerative disease can cause devastating deficits in neural function. Understanding the molecular and cellular events that execute axon degeneration is essential for developing treatments to address these conditions. Calcium is known to contribute to axon degeneration, but its temporal requirements in this process have been unclear. Live calcium imaging in severed zebrafish neurons and temporally controlled pharmacological treatments in both zebrafish and cultured mouse sensory neurons revealed that axonal calcium influx late in the degeneration process regulates axon fragmentation. These findings suggest that temporal considerations will be crucial for developing treatments for diseases associated with axon degeneration.
The Transient Receptor Potential Melastatin 2 (TRPM2) Channel Contributes to β-Amyloid Oligomer-Related Neurotoxicity and Memory Impairment
Authors: Ostapchenko Valeriy G. , Chen Megan , Guzman Monica S. , Xie Yu-Feng , Lavine Natalie , Fan Jue , Beraldo Flavio H. , Martyn Amanda C. , Belrose Jillian C. , Mori Yasuo , MacDonald John F. , Prado Vania F. , Prado Marco A.M. , Jackson Michael F. 
Published: November 2015

In Alzheimer's disease, accumulation of soluble oligomers of β-amyloid peptide is known to be highly toxic, causing disturbances in synaptic activity and neuronal death. Multiple studies relate these effects to increased oxidative stress and aberrant activity of calcium-permeable cation channels leading to calcium imbalance. The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+-permeable nonselective cation channel activated by oxidative stress, has been implicated in neurodegenerative diseases, and more recently in amyloid-induced toxicity. Here we show that the function of TRPM2 is augmented by treatment of cultured neurons with β-amyloid oligomers. Aged APP/PS1 Alzheimer's mouse model showed increased levels of endoplasmic reticulum stress markers, protein disulfide isomerase and phosphorylated eukaryotic initiation factor 2α, as well as decreased levels of the presynaptic marker synaptophysin. Elimination of TRPM2 in APP/PS1 mice corrected these abnormal responses without affecting plaque burden. These effects of TRPM2 seem to be selective for β-amyloid toxicity, as ER stress responses to thapsigargin or tunicamycin inTRPM2−/−neurons was identical to that of wild-type neurons. Moreover, reduced microglial activation was observed inTRPM2−/−/APP/PS1 hippocampus compared with APP/PS1 mice. In addition, age-dependent spatial memory deficits in APP/PS1 mice were reversed inTRPM2−/−/APP/PS1 mice. These results reveal the importance of TRPM2 for β-amyloid neuronal toxicity, suggesting that TRPM2 activity could be potentially targeted to improve outcomes in Alzheimer's disease.SIGNIFICANCE STATEMENTTransient receptor potential melastatin 2 (TRPM2) is an oxidative stress sensing calcium-permeable channel that is thought to contribute to calcium dysregulation associated with neurodegenerative diseases, including Alzheimer's disease. Here we show that oligomeric β-amyloid, the toxic peptide in Alzheimer's disease, facilitates TRPM2 channel activation. In mice designed to model Alzheimer's disease, genetic elimination of TRPM2 normalized deficits in synaptic markers in aged mice. Moreover, the absence of TRPM2 improved age-dependent spatial memory deficits observed in Alzheimer's mice. Our results reveal the importance of TRPM2 for neuronal toxicity and memory impairments in an Alzheimer's mouse model and suggest that TRPM2 could be targeted for the development of therapeutic agents effective in the treatment of dementia.
Weight Loss Pharmacotherapy: Brief Summary of the Clinical Literature
Authors: Egan Brent M. , White, PhD, MPH Kellee 
Published: November 2015

<p class="Default"> </p><p> The disparity in obesity rates between White, Black, and Hispanic individuals, especially women, is striking. Moreover, at any given body mass index or abdominal girth, incident diabetes is greater in Black, Hispanic and other racial-ethnic minorities than Whites. In addition to the growing health burden, the total costs of obesity in 2030 could exceed $500 billion (USD). Weight loss of 5%–15% from baseline can be attained with anti-obesity pharmacother­apy approved for long-term use in com­bination with lifestyle change. Weight loss of ≥5% is associated with medical benefits including reduction of incident diabetes and cardiovascular risk. While medical weight loss after one year or more in the US popu­lation is better than previously seen in many clinical trials, &gt;60% of adults fail to sustain a 5% weight loss. Drug therapies approved for long-term weight loss may permit even more subjects to sustain healthful weight reduction. <em>Ethn Dis. </em>2015;25(4):511-514; doi:10.18865/ed.25.4.511</p>
Sand Control Screen Cyclic Thermal Testing for Life of SAGD Wells
Authors: Guobin Ma , Gordon Shaelyn M , Arshad Adil , Carriere Marc R , Olson Jamie L , Hamilton Kirk , Droessler Mark , Dessein Thomas 
Published: November 2015

Abstract
Wire Wrapped Screens (WWS) have received more attention from Steam assisted Gravity Drainage (SAGD) operators. A WWS is commonly fabricated with a wedge-shaped wire that is spiral-wound around a perforated base pipe to form a Wire wound Mesh (WWM). This produces a single, continuous, keystone-shaped helical slot with a large open flow area to enable for fluid flow while maintaining the structural rigidity of the base pipe and providing sand control to the wellbore.
The structural integrity of a WWS with dual ring Wrap-On-Pipe (WOP) WWM and gap opening and closing within the WWM during thermally-induced loading were assessed through a full-scale thermal test program and Finite Element Analysis (FEA), during which the WWS was subjected to thermal cycle loading between 20°C (68°F) (room temperature) and 280°C (536°F), simulating the target temperature of a relatively high-temperature SAGD project in northern Alberta. The loading condition selected as the worst-case scenario from a service limit state perspective for the testing and FEA was to enable the WWS specimens to freely expand during the initial heating phase and then axially constrain them for the subsequent thermal cycle loading. This loading condition was selected because it was the scenario most likely to cause gap width opening between the wire wraps to an extent where the WWS could no longer provide suitable sand exclusion.
The FEA was used to determine the peak plastic strains within the base pipe and the effect that the residual stresses, introduced by the welding process, have on the structural integrity of the WWS. The frictional conditions between the spiral-wound wire and base pipe were found to have a significant impact on limiting axial movement between the WWM and base pipe, and the axial strains developed in the screen. In addition, an analytical model is presented that estimates the gap opening of the WWM because of thermal strains, which compared well to the results obtained through FEA.
The testing was conducted to assess the structural capacity of the WWS design and monitor change in gap widths during thermal cycling at key structural locations of the WWS design. The strain monitoring results from the full-scale test program were found to be consistent with the predicted strains from the FEA assessment.
This paper presents testing and FEA results for a WWS with WOP WWM, and investigates the potential of a WWS to provide long-term and reliable sand control for SAGD wells.
Using Prepack Sand-Retention Tests (SRT's) to Narrow Down Liner/Screen Sizing in SAGD Wells
Authors: Devere-Bennett N. 
Published: November 2015

Abstract
Due to the unconsolidated nature of the Athabasca Oil Sands in the Western Canadian Sedimentary Basin, it is common practice to complete Steam Assisted Gravity Drainage (SAGD) well pairs with the use of standalone screens (SaS's). The sizing of the liner/screen types are commonly determined by: first, getting a particle size distribution (PSD) by dry-sieve analysis and/or Laser Particle Sand Analysis (LPSA); and second, running a number of prepack Sand-Retention Tests (SRT's).
In this Nexen Long Lake study, five batches of unconsolidated McMurray Formation sand were collected from six different cored wells. Using these batches of sand, more than twenty SRT's were run with a variety of fine-tuned modifications to the traditional test protocols to best duplicate fluid production conditions as observed in the field. Some of these modifications included: altering the injected fluid/gas rate and reconfiguring the order in which the fluids / gas were injected.
The SRT results were then plotted to identify if they passed the general criteria for a successful sand control device design. Unexpectedly, many of the SRT results did not meet the pass criteria for solids production and therefore, altered the direction in which future tests were run. However, when reviewing the solids production with the cumulative fluids / gas injected, the outcome commonly reverted to being favourable.
Understanding the laboratory derived test results, and how they applied to the field, was instrumental in the lab testing process. By redefining the tests results and pass/fail criteria, based upon observed in-situ production conditions, it was possible to make both qualitative as well as quantitative analysis and therefore, more confidently decide on the optimal reservoir completion type.
The study discusses an alternative approach to interpretation of conventional SRT results relative to observed field production conditions and how ultimately, this analysis influenced the choice of liner/screen sizing selected for implementation in future Long Lake field development projects.
Downsizing Steam Injection Insulated Tubing through the Use of Superior Thermal Performance
Authors: Damour J. , Brown T. 
Published: November 2015

Abstract
In steam injection processes such as steam flooding, SAGD, or huff & puff, the selection of the injection tubing is an important factor that determines the steam quality downhole. For example, insulated tubing will decrease the heat loss in the well. The tubing dimensions also have an impact on the process. The objective of this study is to evaluate how the combination of superior thermal performance and down-sized injection tubing can improve the steam quality downhole.
A detailed analysis of steam flows was performed for a project in the Middle East to quantify the effect of thermal performance and tubing size on steam quality downhole. Using a steam flow analysis model, different tubing size and thermal insulation performance combinations were compared for the same well. The thermal performance (Overall Heat Transfer Coefficient) of different types of insulated tubing was confirmed with a field trial by the operator prior to use as input into the model. The output of the model is the quality, temperature, and pressure of the steam as a function of position in the well, including the downhole conditions.
Unsurprisingly, the results of the study show that to get the highest steam quality downhole, the best thermal performance is required. It was also found that, with the best thermal performance, downsizing the tubing can have a positive effect on the economics of the system. Conversely, it was found that, using tubing with relatively poorer thermal performance, downsizing the tubing was not practical. The results were used by the operator to select the type and size of tubing for its new injector wells.
With the analysis now complete, the steam wells in the studied field are being modified according to the study recommendations. Vacuum-Insulated tubing is being replaced with a design with improved thermal performance and the tubing size is being reduced. The result is a system with decreased, overall costs and increased downhole steam quality.
Casing Integrity: Strain-Based Fatigue Life Estimation Coupled with Numerical Thermal-Flow Simulation and Multistring Stress Analysis
Authors: Liu Zhengchun , Samuel Robello , Gonzales Adolfo , Kang Yongfeng 
Published: November 2015

Abstract
Casing and tubing strings are generally considered to be exposed to static or quasistatic loads. Usually, this assumption is correct; however, in some cases (e.g., huff-and-puff heavy oil production, geothermal wells, deepwater high-pressure/high-temperature wells), changes in temperature or internal pressure can lead to variable loads and thus fatigue failure. This paper presents an integrated solution for fatigue life estimation and fatigue failure analysis during the tubular design of thermal wells.
The varying casing temperatures and temperature-dependent casing loads were obtained through numerical simulations of cyclic operations such as steam injection, soaking, and production. All these simulations were accomplished using commercial software, including a thermal flow simulator and a stress analyzer. The previously simulated casing loads were then used to calculate localized stress amplitude, strain amplitude, and mean stress. Finally the localized strain and stress values were used as input parameters of a strain-based fatigue model to estimate the lifetime (cycles) of the peak-load casing section. This fatigue model was implemented in a computer program and integrated with the aforementioned software.
A field case of a steam injection well was studied with the integrated thermal fatigue simulation. The casing fatigue life was predicted using four different fatigue life models. The results were compared with each other and with actual field data. The statistical fatigue life model exhibits best performance. The casing failure locations were analyzed and explained in terms of multistring stress analysis including casing-cement-soil interactions. It seems that the fatigue failure at the previous casing shoe or perforation is related to the axial load peaks at these places during the thermal cycles.
Heat Transfer Modeling of Wellbore with Vacuum-Insulated-Tubing (VIT)
Authors: Kang Yongfeng , Samuel Robello , Gonzales Adolfo , Liu Zhengchun 
Published: November 2015

Abstract
Wellbore heat transfer induces wellbore temperature redistribution and can impact wellbore integrity and the ability of the well to perform its required functions effectively as the design intended. Vacuum-insulated-tubing (VIT) is purposed to reduce wellbore tubing fluid heat loss to protect the tubing fluid or the outside components. Accurate prediction of the wellbore operating temperature during the design phase is essential especially for a VIT well because of its natural difference from the regular pipe.
VIT pipe consists of a vacuum section and connector section. The vacuum section has a much better insulation effect than that of the connector, inducing "nonuniform" heat transfer. This generates significant annulus temperature spikes along the axial direction; up to 50°F in half VIT unit length, 20 ft in field observation (Gosch et al. 2004). Conventionally, axial temperature gradient is ignored with regular pipe because it is negligible compared with radial temperature gradient. This is no longer applicable for VIT because these temperature spikes enhance free convection significantly. This paper presents a novel wellbore heat transfer model to provide accurate temperature prediction for a VIT well.
Operators use a higher averaged overall thermal conductivity values over VIT because it yields acceptable conservative incremental pressure in annular pressure buildup (APB) calculation, which matches their field observations. There is still uncertainty about modeling with different thermal conductivity values for the VIT vacuum section and connector in conventional commercial simulators that produce high-temperature spikes and relative unreasonable low incremental pressure. Field case study results with this new model show that compared with conventional simulator results the wellbore average temperature increases and the spikes amplitude in the temperature distribution decreases. In addition, whether the connection is insulated or non-insulated plays a critical role in the overall VIT performance. Good connection insulation will increase the overall insulation effect significantly.
Literature surveys show few studies on modeling wellbore heat transfer with the enhanced free convection effect inherent to VIT. A conventional wellbore temperature simulator ignores this effect and underestimates the overall wellbore temperature. This paper provides a novel solution model for VIT wellbore temperature prediction, which will be integrated into a commercial advanced casing and tubing design software platform.
Assessing Subcool Control Issues in SAGD Producers and Methods for Mitigation
Authors: Taubner S. P. , Subramanian V. , Kaiser T. M. 
Published: November 2015

Abstract
Industry experience indicates the vast majority of well failures in SAGD wells occur in the liner, and most of these appear to be related to a loss of subcool control. This paper presents an example of how two factors, well trajectory and reservoir performance, can combine to produce problems with subcool control that are difficult to discern under normal operation and likely to lead to a steam breakthrough event. Simulation of steam trap conformance is an important tool for optimizing SAGD efficiency, but it can also be instrumental for diagnosing, avoiding, and resolving subcool control issues. To be effective, the simulator must account for the parameters that govern conformance, which include reservoir performance, well geometry, reservoir properties, completion details, and operational controls. This example employs a rigorous simulation basis that captures the contributions of both injection well hydraulics and production well hydraulics to steam trap conformance, or the lack thereof. The example demonstrates how enhanced monitoring systems and procedures can be used to diagnose subcool control problems before a failure results. Furthermore, various mitigation strategies are explored to alleviate the subcool control problem and facilitate more efficient SAGD operation. The mitigation strategies include changes to the initial well design, such as customized injector or producer liners. The simulation basis enables the mitigation strategies to be assessed based on the uniformity and stability of the liquid level above the production well. The simulation results reveal different levels of effectiveness between the various mitigation options. This paper provides new insight into how factors like well trajectory and reservoir performance can compromise subcool control and explores creative solutions for improving SAGD performance.
Thermosetting Polymer Based Flexible Synthetic Cement for Successful Zonal Isolation in Thermal Wells – A New Approach
Authors: Shanbhag R. , Melrose Z. , Nutt S. , Cleveland M. , Keese R. 
Published: November 2015

Abstract
Conventional Portland cements present significant challenges in thermal wells due to a high degree of brittleness, low strength, and inconsistent strength development following set. These challenges are further compounded by progressive degradation of the material with repeated thermo-mechanical loading. A new, highly flexible synthetic cement based on a thermosetting polymer, that overcomes many of these challenges, is presented. The material exhibits significantly higher strength and lower modulus (thus, a higher elastic strain to failure) than conventional cements and also shows a very high degree of resilience to thermal as well as mechanical fatigue. Further, the material exhibits right angle set and immediate strength development following set.
The material was tested for various mechanical properties in tension as well as in compression. Rheological testing was conducted and the effect of variability in BHCT as well as in initiator concentrations on cure kinetics was determined. A yard test was conducted using conventional oilfield equipment to assess suitability of large-scale deployment of the cement.
Typical compressive strength, tensile strength and compressive modulus values are greater than 8,000 psi, greater than 1,500 psi, and less than 500 ksi, respectively. The density of the material can be modified in the 10.0 to 17.0 pounds/gallon range. In this paper, the 12.0 and 14.5 pound/gallon variations were tested. Poisson's ratio of the material was determined to be 0.27 at 77°F and increases at higher temperatures, showing a very high degree of flexibility. The material exhibits a right angle set at a range of temperatures with little variation in set times due to variations in bottom hole circulating temperature and initiator concentration. Further, the strength development is immediate following set in each case. The system also exhibits zero shrinkage upon cure, an important attribute in preventing vent flow.
The high strength and flexibility, high temperature performance, as well as the "set on demand", zero shrink and "right angle set" properties of the material render it ideal for placement in thermal wells where wellbore integrity is of concern. Further, use of conventional oilfield equipment in placement allows for an easy deployment of this new solution that may solve a number of problems associated with thermal wells.