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The biological mechanism of Dupuytren's contracture needs to be further studied in order to minimize postoperative recurrence and provide a pathological basis for the development of new therapeutic targets.HE staining, immunohistochemistry, PCR and western blotting were performed in pathological palmar aponeurosis specimens and normal palmar aponeurosis tissues for comparative study.(1) TNF-α expression was up-regulated: TNF-α mRNA was more highly expressed in the pathological tissues of DD patients than in the CT group, P0.05, and the difference between the two groups was statistically significant; (2) Dkk-1 expression was down-regulated: Dkk-1 mRNA was lower expressed in the pathological tissues of DD patients than in the CT group, P0.05, and the difference between the two groups was statistically significant; (3) TGF-β1 expression was up-regulated: TGF-β1 mRNA was higher expressed in the pathological tissues of DD patients than in the CT group, P0.05, and the difference between the two groups was statistically significant; (4) Pearson correlation analysis suggested that TNF-α expression was positively correlated with TGF-β1 expression, TNF-α expression was negatively correlated with DKK-1 expression, and TGF-β1 expression was negatively correlated with DKK-1 expression.TNF-α, DKK-1 and TGF-β1 may play a role in the pathogenesis of palmar aponeurosis contracture, and there is a relationship between them. The study of the relationship between the three and their related signaling pathways provides a therapeutic target and a basis for the prevention and early treatment of palmar aponeurotic contracture.Der biologische Mechanismus der Dupuytren-Kontraktur muss weiter untersucht werden, um ein postoperatives Rezidiv zu minimieren und eine pathologische Grundlage für die Entwicklung neuer therapeutischer Ziele zu liefern.HE-Färbung, Immunhistochemie, PCR und Western-Blotting wurden in pathologischen Palmaraponeurose-Proben und normalem Palmaraponeurose-Gewebe für vergleichende Untersuchungen durchgeführt. ERGEBNISSE: (1) TNF-α-Expression war hochreguliert: TNF-α-mRNA wurde in pathologischen Geweben von DD-Patienten stärker exprimiert als in der CT-Gruppe, P0,05, und der Unterschied zwischen den beiden Gruppen war statistisch signifikant; (2) Dkk-1-Expression war herunterreguliert: Dkk-1-mRNA wurde in pathologischen Geweben von DD-Patienten niedriger exprimiert als in der CT-Gruppe, P0,05, und der Unterschied zwischen den beiden Gruppen war statistisch signifikant; (3) TGF-β1-Expression war hochreguliert: TGF-β1-mRNA wurde in pathologischen Geweben von DD-Patienten stärker exprimiert als in der CT-Gruppe, P0,05, und der Unterschied zwischen den beiden Gruppen war statistisch signifikant; (4) Die Pearson-Korrelationsanalyse legte nahe, dass die TNF-α Expression positiv mit der TGF-β1-Expression korreliert war, die TNF-α-Expression negativ mit der DKK-1-Expression korrelierte und die TGF-β1-Expression negativ mit der DKK-1-Expression korrelierte.TNF-α, DKK-1 und TGF-β1 könnten eine Rolle bei der Pathogenese der Palmaraponeurose-Kontraktur spielen, und es besteht eine Beziehung zwischen ihnen. Die Untersuchung der Beziehung zwischen den drei und ihren verwandten Signalwegen bietet ein therapeutisches Ziel und eine Grundlage für die Vorbeugung und frühzeitige Behandlung der palmaraponeurotischen Kontraktur.

PDF file, 128K, Depletion of myeloid-derived suppressive cells.

PDF file, 197K, Antitumor activity of intracranial CNT-CpG.

PDF file, 73K, In vitro CNT-CpG activity assay.

Purpose: Recently, we showed that intratumoral delivery of low-dose, immunostimulatory CpG oligodeoxynucleotides conjugated with carbon nanotubes (CNT-CpG) was more effective than free CpG and not only eradicated intracranial (i.c.) gliomas but also induced antitumor immunity that protected mice from subsequent i.c. or systemic tumor rechallenge. Here, we examined whether the same “intracerebral immunotherapy” strategy could be applied to the treatment of metastatic brain tumors.Experimental Design: Mice with both i.c. and s.c. melanomas were injected intratumorally with CNT-CpG into either location. Antitumor responses were assessed by flow cytometry, bioluminescent imaging, and animal survival.Results: When given s.c., CNT-CpG response was mostly local, and it only modestly inhibited the growth of i.c. melanomas. However, i.c. CNT-CpG abrogated the growth of not only brain but also s.c. tumors. Furthermore, compared with s.c. injections, i.c. CNT-CpG elicited a stronger inflammatory response that resulted in more potent antitumor cytotoxicity and improved in vivo trafficking of effector cells into both i.c. and s.c. tumors. To investigate factors that accounted for these observations, CNT-CpG biodistribution and cellular inflammatory responses were examined in both tumor locations. Intracranial melanomas retained the CNT-CpG particles longer and were infiltrated by Toll-like receptor (TLR-9)–positive microglia. In contrast, myeloid-derived suppressive cells were more abundant in s.c. tumors. Although depletion of these cells before s.c. CNT-CpG therapy enhanced its cytotoxic responses, antitumor responses to brain melanomas were unchanged.Conclusions: These findings suggest that intracerebral CNT-CpG immunotherapy is more effective than systemic therapy in generating antitumor responses that target both brain and systemic melanomas. Clin Cancer Res; 18(20); 5628–38. ©2012 AACR.

INTRODUCTION Malignant gliomas consist of heterogenous cellular components that have adopted multiple overlapping escape mechanisms that overcome both targeted and immune-based therapies. The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily that is activated by diverse proinflammatory ligands present in the tumor microenvironment (TME). Activation of RAGE by its ligands stimulates multiple signaling pathways that are important in tumor growth, invasion, and immune escape. OBJECTIVE We aimed to demonstrate that blockade of RAGE expression may tackle resistance pathways by inhibiting GBM progression, invasion, and immune evasion. METHODS We evaluated genetic ablation of RAGE on the tumorigenicity of two syngeneic murine glioma models. RAGE expression was inhibited in the GL261 and K-Luc gliomas by shRNA and CRSPR/Cas9 techniques prior to intracranial implantation. Tumor growth, invasion, and inflammatory responses were examined by immunohistochemistry, qPCR, ELISA, western blotting, NanoString, flow cytometry, and in vivo survival analysis. RESULTS Intracellular RAGE ablation abrogated glioma growth and invasion by suppressing AKT and ERK1/2 activities and by downregulating MMP9 expression. Interestingly, RAGE inhibition also enhanced tumor inflammatory responses by downregulating the expression of galectin-3, rendered the immunotherapy resistant K-Luc gliomas responsive to immune checkpoint blockade therapy, and significantly increased survival. CONCLUSION This study is the first to link RAGE expression with galactin-3 as an immune modulator in glioblastoma and revealed that the effect of glioma RAGE expression on TME was mediated through downregulation of Gal-3 and subsequent polarization of Tumor-associated macrophages. The therapeutic significance of RAGE downregulation was demonstrated by sensitizing a highly invasive and immune-resistant glioma model to immune checkpoint blockade and strongly supports the development of RAGE ablation as a complementary treatment strategy for malignant gliomas.

Multi-contrast magnetic resonance (MR) image registration is useful in the clinic to achieve fast and accurate imaging-based disease diagnosis and treatment planning. Nevertheless, the efficiency and performance of the existing registration algorithms can still be improved. In this paper, we propose a novel unsupervised learning-based framework to achieve accurate and efficient multi-contrast MR image registration. Specifically, an end-to-end coarse-to-fine network architecture consisting of affine and deformable transformations is designed to improve the robustness and achieve end-to-end registration. Furthermore, a dual consistency constraint and a new prior knowledge-based loss function are developed to enhance the registration performances. The proposed method has been evaluated on a clinical dataset containing 555 cases, and encouraging performances have been achieved. Compared to the commonly utilized registration methods, including VoxelMorph, SyN, and LT-Net, the proposed method achieves better registration performance with a Dice score of 0.8397± 0.0756 in identifying stroke lesions. With regards to the registration speed, our method is about 10 times faster than the most competitive method of SyN (Affine) when testing on a CPU. Moreover, we prove that our method can still perform well on more challenging tasks with lacking scanning information data, showing the high robustness for the clinical application.

High-performance optoelectronic devices, such as solar cells and light-emitting diodes, have been fabricated with lead halide perovskites owing to their superior carrier properties. However, charge transport in such optoelectronics is intrinsically directional due to the existence of p–n junctions, which thus lacks the potential to elucidate any perturbations in light or electricity during energy conversion. Here, with the presence of a LiCl additive in a formamidinium chloride (FACl) solution, the as-grown LiCl:FAPbCl3 nanorods demonstrate greatly enhanced crystallinity and UV photoresponse as compared to pristine FAPbCl3 nanostructures without the LiCl additive. Most importantly, the LiCl:FAPbCl3 nanorod film exhibits unprecedented distinguishability to UV photons with different energies and oscillating intensities, in the form of bipolar and periodically oscillatory photocurrents. This work could advance the fundamental understanding of photoinduced carrier processes in halide perovskites and facilitate the development of novel UV-based optical communications.

Challenging aspects to heavy oil field development are the large volume of data which is collected, in particular from cored evaluation wells, and the difficulty in evaluating of the quality of such data. This paper outlines an approach to summarize coring data and procedures from two heavy oil fields in North Kuwait, and then to compare those summaries with similar heavy oil operations in other countries, in order assess their quality and degree of representativeness.For two North Kuwait heavy oil fields, data was tabulated for the cumulative amounts of core cut and recovered relative to their field areas. This data was then further analyzed to summarize recovery by rock type, and assess the quality and quantity of plug samples collected. Benchmarks were established by summarizing core data from similar heavy oil operations in other countries, and the North Kuwait heavy oil data was then compared with those benchmarks. In a similar manner, documented core handling procedures for North Kuwait Heavy Oil operations were compared with procedures from similar heavy oil operations in other countries.The benchmarks which were used to compare North Kuwait Heavy Oil data summaries with other countries include the following: 1) Coring Well Area Coverage Densities; 2) Coring Well Vertical Coverage of Cap Rock and Reservoir Intervals; 3) Core Plug Sample Rate and Survival Rate; and 4) Core Handling Procedures and Volume of Coring.For many of the benchmarks used, North Kuwait heavy oil operations compare favorably with similar operations from other countries. However areas of improvement were identified from these benchmarks in terms of areal core coverage, vertical core coverage, core plug rates and core handling procedures. It is expected that these improvements, when implemented, will lead to a more representative sampling of the areas and rock types (reservoir rocks, baffles and cap rocks) in North Kuwait. This in turn should lead to a better understanding of fluid volumetrics, reservoir characterization and subsequent life of field development. As well by applying a focused approach to future coring operations, a significant cost savings is expected relative to original evaluation well plans.A significant product from this study is a large summary database of all coring information for two North Kuwait heavy oil fields, which can be queried by area, rock type and sample type. This data base has been compared with similar operations in other countries using a series of benchmarks. Planned future coring and sampling operations have been modified through the use of this benchmarking tool.

A shallow, unconsolidated, sour heavy oil reservoir in North Kuwait is under primary production. Due to rapid decline in reservoir pressure, a development scenario was selected consisting of 10 years of water injection secondary recovery followed by enhanced oil recovery (EOR) polymer flood for which a pilot is being implemented. This pilot will provide vital information to establish feasibility for full-field implementation and in this paper, we describe the application of Interference Pressure Transient Test (IPTT) and stress testing. IPTT is utilized for proper understanding of the vertical permeability and permeability anisotropy (Kv/Kh) which are key for evaluating heavy oil sweep efficiency under injection. Stress testing will provide essential information about the cap rock integrity to monitor that water and polymer flooding is contained across the required reservoir. A combination of IPTT and stress testing utilizing the Wireline Formation Testing (WFT) tool and laboratory core analysis were the basis of a selected method for vertical permeability and permeability anisotropy determination. Laboratory measurement for permeability anisotropy has its own challenge due to unconsolidated nature of the formation. IPTT under such conditions can provide reliable and fast measurements, which can also help to calibrate the laboratory measurements later. Four EOR pilot vertical injectors wells were drilled in a symmetric 5-spot pattern, with a central vertical producer. Distance between the injectors is 60 meters, whereas each injector is at 50 meters spacing from the central producer. IPTT was carried out in all four EOR pilot wells, whereas this study involves only three of the injectors. Three-probe configuration along with advanced three-dimensional probe provided comprehensive evaluation for the sand and shaly reservoir intervals. It was observed that main sand body under consideration showed Kv/Kh ranging between 0.05 to 0.15. Some of the main shaly intervals were observed to be either fully isolating the sub-layers or have some vertical communication. It should be noted that downhole fluid analysis and sampling was conducted in one of the wells utilizing WFT. The obtained fluid properties were included in the IPTT analysis for more accurate results. The acquired data from three pilot wells were used to update the reservoir simulation models to have a more representative sweep efficiency evaluation utilizing polymer flooding for the planned EOR. It provides an efficient way to derive the vertical permeability and permeability anisotropy in the challenging unconsolidated formation. This paper adds to the literature of case studies where vertical permeability and permeability anisotropy have been obtained in the challenging environment of unconsolidated formation. It demonstrates how accurate planning combined with advanced technology and innovative workflow yielded the required input data for the dynamic reservoir simulation model.

Within North Kuwait heavy oil fields, integrated reservoir modelling is challenged by inherent reservoir heterogeneities, regional non-stationarity (i.e. trends), asymmetrical well and seismic distributions, and the need to maintain alignment between various the model scales required and multiple purposes for which the models will be used. This paper presents a number of customized workflows adapted to characterize these reservoir architectures and heterogeneities within one field, appropriately at all model scales and in regions with variable well control.A reliable new rock type classification scheme was derived from cross plot analyses of Gamma Ray and Bulk Density (GR-DENS) logs. Within an initial production area containing over 900 regularly spaced wells, 3D variograms for these lithotypes were estimated, calibrated with 3D seismic and reservoir equivalent surface outcrops. The lithotypes were distributed into full field static models using these variograms and the Sequential Indicator Simulation (SIS) algorithm. An additional declustering step was implemented to express regional trends and account for asymmetrical data distribution. Petrophysical property modeling (shale volume, effective porosity, water saturation) was performed using the Kriging algorithm conditioned to lithofacies.From these full field models, sector models were created to capture geological heterogeneity at a smaller grid increment. Full-field facies were downscaled onto the sector model grids, and then the Sequential Gaussian Simulation (SGS) algorithm was used to interpolate petrophysical properties, constrained by histograms of the kriged background models. This allowed information from wells outside of sector models to be incorporated efficiently into them.The facies and heterogeneities represented within the full-field static models have improved upon earlier versions, by being distributed more consistently relative to known seismic and well control, and to outcrop reservoir analogues. Modelled petrophysical properties also show a more consistent linkage with known values derived from core analyses. This consistent set of models can now be used with greater confidence, to answer questions ranging from in-place volume uncertainties to dynamic production forecasting, to life of field development. This has also led to reduced dynamic model run times, and improved reservoir management and operations optimization.In summary a robust series of full-field and sector models was developed and customized to a North Kuwait heavy-oil field, with information from data-rich areas being elegantly applied to reduce uncertainties in data-poor areas. These nested models can now be matched to the detail required for the model purpose. For example heterogeneities that matter-for-flow in dynamic simulation models can be represented explicitly, whereas for full-field volume estimations property averages can be used.

North Kuwait heavy oil development continues to benefit from detailed study of outcrops at the Jal Az-Zor escarpment that are stratigraphic equivalents to some of their reservoirs. During the 2018-19 field season, focus was placed on recording the internal architectures of specific stratigraphic layers, developing a deeper understanding of the diagenetic processes in the basin and relating these observations to the North Kuwait reservoirs. These are all key controls on reservoir quality and connectivity. Inter-well scale heterogeneities were identified for inclusion into subsurface models to predict steam/polymer conformance and oil production better.Building on work of the 2017-18 field season when the Jal Az-Zor sequence was logged, measured, described and interpreted; units were tracked and correlated laterally for around 3km. Internal architectures of prominent layers were mapped through conventional and drone mounted photographic surveys, and satellite images. X-Ray Diffraction and thin section studies of hand samples were analyzed, to understand mineralogical controls on porosity & permeability.Integrated field trips were conducted with members from subsurface, reservoir and well-engineering disciplines, to engender common perspectives on subsurface uncertainties and development risks. They also served to close the communications gap between disciplines.Interpreted high-resolution photographic data, sediment flow direction measurements and other observations gave clues to environments of deposition and their implications for lateral connectivity for each layer. Observations on vertical connectivity between and within layers were recorded. Geological heterogeneities were considered in the context of the typical inter-well separation spacing for their implications on injected steam or polymer conformance, & water-cut.Depositional models were compiled and interpreted with regard to their implications for reservoir plumbing, H2S risk, top-seal integrity, sand production etc. Additionally, increased awareness of the stratigraphic relationships between zones was utilized to resolve correlation ambiguities for closed spaced wells in a water injection pilot and led to the development of a screening tool to predict water-coning risk in wells and informed a similar study for injected steam-conformance risk mapping.Field analogues at Jal Az-Zor are key to defining and characterizing the key genetic flow units of the heavy-oil reservoirs in North Kuwait and it is rare to have closely linked field-outcrop analogues so readily accessible. They represent an important cost-effective resource for field development and operations as they bridge the scale gap between well-derived and seismic data as they provide insight to the nature of flow unit connectivity (i.e. the reservoir plumbing – heterogeneities that matter-for-flow) in way that other data types do not. Field analogue observations therefore directly inform the grid scale permeability estimates that are used in the dynamic simulator for production forecasting and field development and operations optimization.

This paper presents a method for facies classification derived from cross plots of basic gamma ray and bulk density wireline log data. It has been specifically developed in-house for two North Kuwait heavy-oil fields, and has been calibrated against both field analogues and core sample measurements. This new facies classification scheme has proven to be quick and cost effective, with multiple practical applications for future field development and operation optimization.For two heavy oil fields in North Kuwait basic Gamma Ray and Bulk Density (GR-DENS) curve data from over 1300 wells were cross-plotted. The resulting relationship characteristics were used to delineate eight separate facies, which plot along a continuum from clean porous sands with little cement and clay, to less porous sands with increasing clay and cementation content, to carbonate and shale. The properties for these facies were calibrated against data from core analyses and with outcrop analogues in North Kuwait. These facies were populated into static reservoir models using the Sequential Indicator Simulation (SIS) method, and petrophysical modeling was then conditioned to these facies. These resulting modeled facies, with their associated petrophysical properties, have been used in a wide variety of subsequent analytical studies.The eight facies which have been newly delineated by the GR-DENS classification scheme capture the transitional nature of petrophysical properties for oil saturation, porosity and permeability. This has enabled several improvements for heavy-oil field development including: 1) better delineation of reservoir and baffle zones; 2) better calibration of oil saturation with core data; 3) calibration of facies with 3D seismic amplitude response; 4) better understanding of reservoir geomechanics and seal integrity assessment; 5) greater confidence in the results of static and dynamic reservoir modeling; 6) more effective decision making in the WRFM process; and 7) alignment of the petrophysical and facies characterization approach between two separate heavy oil asset teams, which allows for direct comparisons between their data sets. Although more complex software exists for specialized facies classification, the GR-DENS workflow newly developed for North Kuwait heavy oil has proven to be simple, rapid, accurate and cost effective.In summary a robust facies classification scheme was developed in-house which is appropriately customized for two North Kuwait heavy oil fields. This methodology has enabled the creation of more representative reservoir models, with resulting improvements in understanding for multiple aspects of both fields. These improvements in turn will lead to better production forecasting and optimization as well as enhance future life of field planning.

Boron nitride nanotubes (BNNT) were functionalized under mild conditions, using a difunctional amine, such as glycine, with one of three targeting ligands, folic acid, a nerve growth factor, or an antibody against nerve growth factor. In addition, non-fouling BNNTs were obtained by a facile and versatile, non-destructive method via controlled surface-initiated grafting of polyzwitterions. The BNNTs were loaded with a fluorescent probe for convenient imaging of glioblastoma multiforme cells treated with BNNTs. BNNTs bearing targeting factors on their outer surface demonstrated an increased efficiency of internalization in glioblastoma multiforme cells, compared to non-modified BNNTs. The degree of internalization was affected both by the nature of the ligand/agonist linked to the BNNTs surface and by the presence of serum proteins. The polyzwitterion grafts prevented the spontaneous adsorption of serum proteins on the BNNTs.

A heavy oil field (Field X) in Northern Kuwait is in the early stages of development but it is clear from production pilots that tight units (baffles) of variable lithology, thickness and continuity, within the reservoir will play a key role in influencing steam conformance and recovery efficiency. The high well/core density of the field’s production startup area allows re-evaluation of baffles in light of cross-discipline integration of pilot production data, petrophysical data and detailed core review.A process was followed to update and calibrate all core descriptions against logs, follow a consistently picked set of petrophysically defined markers, compare visually defined lithofacies with log defined ones, and then map out key surfaces. The key next step is to define appropriate reservoir properties by facies/rock types, apply these to understanding pilot behaviour and predict steam conformance for Well, Reservoir and Facilities Management (WRFM) and the next phases of the wider field development planning. The field’s baffles play a role far beyond just understanding steam conformance, they are a first barrier for cap rock integrity and their presence/absence will also influence the path and rate of the aquifer influx.The petrophysical redefinition (Baffle Quality Index) of a "semi-stratigraphic" interval - which will stop or slow steam migration depending on its quality and lateral extent - has enabled efficient communication about the baffle, and allowed the wider team of petroleum engineers from a number of subsurface disciplines to focus on dynamic properties impacting recovery – steam conformance, aquifer influx, windows between isolated reservoir units – and then evolve the development strategy, effectively respond to WRFM issues, optimize observation and infill well placement and increase UR in a cost effective way.

Kuwait Oil Company (KOC) is developing its shallow heavy oil field using thermal method. Top risk of this project is the cap rock failure. If failure occur, it may lead to the steam leakage, overlying aquifer contamination, ground heave or subsidence and surface collapse. For the monitoring ground deformation caused by cyclic steam stimulation (CSS) and steam flooding (SF) thermal operation in Kuwait, InSAR technology is being considered. Interferometric Synthetic Aperture Radar (InSAR) is a remote sensing technique to measure surface heave and subsidence. First stage of heavy oil thermal development in North Kuwait comprises production from shallow Miocene reservoirs covering an area of roughly 30 square kilometers, by two or three cyclic steam stimulation (CSS) process followed by steam flooding (SF) process. Main reservoirs are the shallow Tertiary un-consolidated sandstone within the measured depth of 650 to 750 feet, sealed off by Up Shale layer that is about 30 FT thick. High pressure and temperature steam will be injected to reservoirs zones, which could result in cap rock breach causing surface heave or subsidence. High-precision and frequent measurements of surface deformation is very important for the study of cap rock integrity. With the advancement of InSAR technology, millimetric precision of ground deformation measurement is possible. The important factors affecting measurement accuracy of ground deformation is Radar microwave length. The most common of microwave is the L band with 24 cm wavelength, the C band with 4-8 cm wavelength and the X band with 2.5-4 cm wavelength. The choice of wavelength influences the precision. However, there are some other factors which have impact on measurement quality such as spatial density of the measurement points, climatic condition, distance between the measurement points and reference points, number and temporal distribution of acquisitions. InSAR technology is expected to provide regular surface deformation maps during heavy oil production to monitor the cap rock integrity and to optimize wells and reservoir management. This technology has many benefits, such as reliability, simplicity, low cost, weather independent, minimal field intervention and ability to acquire at night. The absence of vegetation growth in our field area makes this technology very effective. To increase the frequency of data collection and to improve the accuracy of the deformation maps, satellite ascending and descending images are also used. Use of ascending and decending images helps in calculating the vertical and horizontal deformations from the Line of Sight (LOS) measurmemnts.

Cap rock integrity assessment is one of the corner stones for heavy oil field development where thermal, water flooding, or other Enhanced Oil Recovery (EOR) related fluid injection operation is involved. In this paper, we present our recent work related to cap rock in a heavy oil field in Northern Kuwait. The cap rock in our field is unique in many aspects compared to other heavy oil fields around the world, in that it is very shallow in burial depth, highly unconsolidated with high porosity and permeability and very ductile in terms of geomechanical properties. Furthermore, there are multiple pay reservoirs separated by different mudstone layers, so the term of cap rock becomes somewhat vague and complicated by itself. The unique properties of the cap rock in our field call for unique core analysis approaches and put up exciting challenges to petrophysical data acquisition and interpretation. A special core analysis approach has been adopted to provide mudstone porosity and permeability that is different from either the Gas Research Institute (GRI) shale analysis or the more conventional routine core analysis suitable for clastic rocks. Integrated study has been performed to understand these special attributes of the mudstones in this field, using core analysis, downhole wireline and surface mini frac measurements, which are all used as inputs into geomechanical model initiation. Based on integrated study, we have established the fracture gradient of different layers of mudstone intervals, gain initial understanding of the rock property of mudstones in this field, and identified data and information gaps that need to be closed by further data collection and study. In the end, we have made recommendations on future mini frac data collection and core analyses for shallow unconsolidated ductile mudstones.

Routine and Special Core analysis (RCAL and SCAL) are the cornerstone of Petrophysics Modeling and Formation Evaluation. In order to obtain the required information, it is important to have quality core, its processing and analysis. This paper summarizes current practices vis-à-vis improvements made in key technical areas. Coring and core analysis are cost-intensive processes. Only quality data from representative core plugs can offset the high cost and can help to achieve the objectives of coring and core analysis. To obtain consistent quality core plugs, coring practice, on-site handling and plugging procedure have to be the best in class. Coring and core analysis in the shallow-depth Heavy Oil Fields in Northern Kuwait have been in place for some time. The processes like i) coring operation ii) on-site core handling and preservation iii) core slabbing iv) core plugging and finally v) core analysis are continually improved. In order to be efficient and cost-effective, all the above processes were re-visited, quality gaps identified and improvements implemented by incorporating unconsolidated formation characterization from the available extensive petrographic studies. For example in the coring practice front, coring and core handling protocols were modified for sour heavy oil-bearing formations noticed in parts of the fields. On-site dry ice was used in addition to the prevalent practice of normal freezing. In the laboratory analysis front, obtaining representative plugs and getting useful results from them were the key challenges. Compared to the previous practice of liquid N2 injection from top only during core slabbing by band saw, liquid N2 injection from both top and bottom resulted in improved core integrity. The previous practice of plunge cutting of plugs with liquid N2 was continued. Before any analysis, Computer Tomography (CT) scan of the plugs was performed to discriminate plug-integrity related issues. This paper discusses lessons learnt from past coring and core analysis processes and their impact on heavy oil development. Improvements to these processes as cost-effective measures are presented through real examples. Recommendations for improvement include field procedure, laboratory process, and usability of the tests performed, which may be useful to the industry where heavy oil core analysis is used.

Free gas along with heavy oil production affects the progressive cavity pump (PCP) performance. This necessitates the strategy to perforate away from the free gas zone. To be able to do this, it requires an integrated approach to evaluate and map the spread of the free gas accumulation in the field. The paper shall present how this resulted in improved well performance with less free gas interference. The methodology included the understanding of the production data, sub-surface geology and petrophysics; reservoir heterogeneity and free gas presence from wireline logs, core data and isotope analysis of gas collected during mud-logging and creation of maps and cross-sections showing both vertical and aerial spread of free gas accumulation. This was then integrated with existing production and well management practices, along with numerical simulation results. Such in-depth analysis helps to bring significant changes in well completion strategy and is a vital contribution to the WRFM strategy. Unlike in conventional fields where depth is more and buoyancy pressures are large, gas can easily displace oil to accumulate in structural highs, in shallow heavy oil fields, free gas accumulation is a result of combination of structural and stratigraphic entrapment process. Vertical migration and lateral migration of gas is likely restricted by non-reservoir facies. As a result a consistent gas-oil contact (GOC) may not be present across large distances. Gas oil contact separates heavy oil by possible structural spill point and lithological boundary, dipping from south to north. Structurally higher areas are prone to localized gas accumulation. The completion stand-off from the gas base has a direct correlation with gas production. So the well management and production practice is to increase the stand-off from gas base to top perforations in future wells and to perform gas shut-off job in current wells to avoid free gas production. The novelty of the current approach is that it will proactively help in completion strategy to reduce future free gas production, subsequent loss in natural reservoir energy and maintain the oil production target.

A heavy oil field in Northern part of Kuwait has developed which requires appropriate disposal of produced formation water. Some important questions for water disposal well planning include: Where to inject?Where to inject?What is the maximum operation pressure (MOP)?How far away the disposal wells should be spaced?How much water can be inject in each well? Integrated subsurface evaluation performed to address above questions. Seismic data provide a good overview lof the structuration and imporatant insight where sweet spots for injection may be found. Wireline logs and core information are used to derive petrophysical properties, characterize fracture, and gather geomechanical information. Injectivity tests established the injection rate and confirmed the estimated minimum horizontal stress. Analogue water injection data from nearby fields are used to provide information on the dynamic behavior of the reservoir, to reduce uncertainties owing to the limited injection rate data available. The integrated analysis of the relevant, available subsurface data reveals that the Tayarat formation has significant variations in lithologies, mineralogies, and mechanical properties. Important information such as the receiving zone thickness, fracture orientation, injection rate, and storage capacity have been derived. Based on this information, we have made important recomemndations on disposal well spacing and maximum operational operating pressure (MOP).

Objectives/Scope The shallow depth unconventional reservoir in Northern Kuwait is essentially a monoclinal structure. Sediments have undergone significant shallow depth diagenesis, which resulted in selective oil/water accumulation, controlled mainly by lithological variations. Thus, the reservoir can be classified as stratigraphic-dominant trap. A correlation approach required addressing these variations, which can also be well understood by non-geologist, and the scheme should be appropriate for selection of perforation intervals. Methods, Procedures, Process Reservoir sands are in the form of multi-stacked distributary/fluvial channels. Subsequent to sediment deposition, moderate to intense diagenesis took place. The diagenesis resulted in formation of cemented baffles under low reservoir pressure (250psi) regime. For demarcation of bed boundaries, mapping and modelling purpose the reservoir sand, shale, baffles, gas, water, water above oil, this petrofacies classification method is proposed. The method is well capable of defining the various bed boundaries with fluid/gas content in it with confidence. The method developed after extensive core, core data and log calibration and study. More than one thousand wells correlated. Results, Observations, Conclusions The classification method is simple, yet robust to characterise reservoir vs. non-reservoir variations and oil/gas vs. water quite effectively. Cementation activities typically noticed on top/bottom of the units but many times in between the reservoir sand also. We are able to correlate cemented layers across the area. The cementation also gives rise to water perched above oil phenomenon due to relatively higher capillary pressure in the zone. Oil is migrated post-cementation and occupied reachable pore spaces. Oil also has undergone significant biodegradation because of favourable temperature and restricted nutrient supply. As a result, thin layers of thermal/biodegraded gas also formed locally. The method allows for surface related categorisation representing clean sand, cemented sand, shale, gas/oil/trapped water zones. Novel/Additive Information This unconventional reservoir is being developed with thermal application. Thickness of baffles, barrier, gas, water zones are critical in selection of perforation interval for steam application. This classification method is part of perforation selection for first phase of development and modelling purpose, and it was applied to hundreds of wells, many of them are undergoing production operations successfully.

As KOC prepares for production ramp up in a North Kuwait Heavy Oil field, one key for cost efficient development is in optimizing information from observation wells. Given multiple objectives for data collection and restrictions due to dense well spacing and surface infrastructure, it is critical to apply an efficient methodology for the selection of observation well locations. This paper describes the interplay between subsurface needs and urban planning in decisions for placement of observation wells to reduce operational costs, enforce effective field development planning and ensure robust production levels.The observation well location selection protocol in a heavy-oil steam development requires initial focus on identifying the key subsurface parameters and risks including cap-rock integrity, role of baffles in steam conformance, gas caps, aquifer influx as well as development decisions like adequate well spacing to apply micro-seismic, e.g. Key parameters were mapped and rated with a "traffic-light" approach to distill the diverse datasets into manageable form. Next, different observation well location strategies (evenly distributed, clustered and blended) were assessed and locations (driven by subsurface objectives) were chosen. Finally these locations were reconciled against the surface restrictions, HSSE and operational constraints to determine the final program.A successful observation well strategy will have:– Good subsurface models capturing heterogeneities in order to predict production performance – Sufficient well number and thorough reservoir architecture characterization underpinning well placement – Robust data collection plan (including production data) – Proper staff resources applied to monitor and QC the data – Up-to-date and accessible data-base, that can be interactively interrogated – Cross-discipline integration, regular data reviews and alignment with urban planningThe inherent value in observation wells is optimized by defining key objectives with broad across discipline engagement, aligning data collection objectives and engaging urban planning and field development with sufficient lead time. This collaborative approach reduces costs for KOC by avoiding rework, missed data collection opportunities or missed value adds if options such as conversion of observers to producers are not considered.

Patients with malignant glioma (MG) are often treated with corticosteroids to reduce cerebral edema, but chronic use of steroids may cause glucose intolerance and development of type 2 diabetes (Db). Individuals with Db not only have significantly higher likelihood of developing malignant tumors, but also, have a higher risk of cancer-related mortality than non-Db patients. The goal of this study was to evaluate the effect of hyperglycemia on glioma growth in mouse models. Because MG are heterogeneous tumors with both invasive and “nodular” phenotypes, two different syngeneic glioma models were examined in streptozotocin-induced Db mice. We found that in the GL261 gliomas that typically grow as “nodular” tumors, hyperglycemia activated receptor for advanced glycation endproducts (RAGE) by upregulating HMGB1 expression, and promoted tumor growth irrespective of tumor microenvironment (TME). Similarly, the K-Luc gliomas, which are invasive and elicit a robust macrophage infiltration, grew faster in subcutaneous (s.c.) location in Db mice. However, intracranial (i.c.) K-luc gliomas were smaller and less invasive in hyperglycemic mice. Our studies showed that a reduction in K-Luc growth in the brains of Db mice was mostly due to the abrogation of inflammatory responses and suppression of pro-inflammatory cytokines such as IL-1b and IL-6 in TME. We conclude that hyperglycemia may enhance glioma growth by activating the RAGE pathway and suppressing antitumor responses. But, suppression of tumor inflammation may also inhibit glioma growth by abrogating i.c. tumor invasion under hyperglycemic conditions.

When developing and operating oil and gas fields, a large number of engineering decisions need to be taken. These decisions range from the very high-level such as recovery mechanism, facility sizing or well count to more detailed decisions such as individual well placements, well design and completion strategies. Typically, subsurface models play a role in informing these decisions by testing their effect on forecasted production and it is generally held best practice to test them against a wide range of subsurface conditions, a range that expresses the envelope of subsurface uncertainty. Whilst these commonly held objectives are more or less universal, selecting an appropriate subsurface modelling strategy (i.e. what to model & how to model it) to achieve these objectives usually generates more divergent views. Whilst there are always various valid modelling approaches available which are both geologically and numerically valid, a good modelling strategy pays close attention to the type of the specific decisions being taken for the project and the accuracy required to take those decisions. To align these views, in decision-based modelling, business decisions and their timing were mapped to the models needed to make the estimates that inform them. Dialogue between the disciplines established the accuracy required for these estimates, and these discussions often revealed surprising opportunities to simplify processes and accelerate delivery. The outcome is a common view on a decision-driven modeling strategy that enables business decisions to be taken efficiently. This strategy, and the subsequent delivery plan that is developed from it is seen as a key to success. This paper describes the decision-based approach taken in the subsurface modelling required to support quality development decisions for the development of two of KOC's Heavy oil fields through the Enhanced Technical Service Agreement (ETSA) between Shell and KOC. In this particular application of the process, the suite of models to be built has been mutually agreed at the start by the integrated development team through a structured collaborative workshop, or Model Framing Event. A fullfield and a sector model for 2 different fields are discussed to exemplify the link between required decision and supporting modelling approach.

The aim of the present study was to measure the prevalence of multimorbidity in Bangladesh, India and China, and to assess the relationship between multimorbidity and patient's opinion regarding their involvement in healthcare decision-making and overall satisfaction of healthcare system. Cross-sectional data on 18 696 men and women aged 18 and above were collected from the World Health Survey of World Health Organization (WHO). Outcome variables were subjective rating of (1) healthcare system's ability to involve patients in decision-making, and (2) satisfaction with the way healthcare system runs in the country. Self-reported chronic conditions were used to measure the prevalence of multimorbidity. Out of 9 chronic conditions, back pain, arthritis, and chronic cough appeared to be the most prevalent ones among majority of the participants. About one-third of the participants in China (30.7%) and two-thirds in Bangladesh (66.1%) and India (66.6%) reported having at least one chronic illness. Prevalence of multimorbidity was highest in India (34.3%) followed by Bangladesh (28.8%) and China (14.3%). In Bangladesh, India and China, respectively 70.5%, 41.7%, 61.3% women and 54.5%, 42.8% and 58.8 % men expressed dissatisfaction regarding the way healthcare system runs in their country. In Bangladesh and India, men who were living with multimorbidity were more likely to rate the patient-centeredness as "bad" than those who had no disease illness. This study suggests that the prevalence of multimorbidity was remarkably high especially in Bangladesh and India. Higher likelihood of dissatisfaction about healthcare system among multimorbid patients might be indicative of inadequacy in the provision of care in qualitative and quantitative terms.

We use numerical simulations to investigate the possibility of enabling steel-cased wells as galvanic sources to detect and quantify spatial variations of electrical conductivity in the subsurface. The study assumes a vertical steel-cased well that penetrates electrically anisotropic horizontal layers. Simulations include a steel-cased vertical well with a finite-length thin wire of piecewise-constant electric conductivity and magnetic permeability. The steel-cased well is energized at the surface or within the borehole at an arbitrary depth with an electrode connected to a current source of variable frequency. Electromagnetic (EM) fields excited by the energized steel-cased well are simulated with an integral-equation approach. Results confirm the accuracy of the simulations when benchmarked against the whole-space solution of EM fields excited by a vertical electric dipole. Additional simulations consider a wide range of frequencies and subsurface conductivity values for several transmitter-receiver configurations, including borehole-to-surface and crosswell. The distribution of electric current along the steel-cased well is sensitive to vertical variations of electric conductivity in the host rock. In addition, numerical simulations indicate that crosswell and borehole-to-surface receiver configurations could reliably estimate vertical variations of electric conductivity within radial distances of up to [Formula: see text] for frequencies below [Formula: see text] and for average host rock electric conductivities below [Formula: see text].

Microglia (MG) and macrophages (MPs) represent a significant component of the inflammatory response to gliomas. When activated, MG/MP release a variety of pro-inflammatory cytokines, however, they also secrete anti-inflammatory factors that limit their cytotoxic function. The balance between pro and anti-inflammatory functions dictates their antitumor activity. To evaluate potential variations in MG and MP function in gliomas, we isolated these cells (and other Gr1+ cells) from intracranial GL261 murine gliomas by FACS and evaluated their gene expression profiles by microarray analysis. As expected, arginase 1 (Arg1, M2 marker) was highly expressed by tumor-associated Gr1+, MG and MP. However, in contrast to MP and Gr1+ cells that expressed Arg1 shortly after tumor trafficking, Arg1 expression in MG was delayed and occurred in larger tumors. Interestingly, depletion of MPs in tumors did not prevent MG polarization, suggesting direct influence of tumor-specific factors on MG Arg1 upregulation. Finally, Arg1 expression was confirmed in human GBM samples, but most Arg1+ cells were neutrophils and not MPs. These findings confirm variations in tumor MG and MP polarization states and its dependency on tumor microenvironmental factors.

Objective To explore the anti-fibrotic mechanism of Salviae miltiorrhizae from the view of proliferation and apoptosis of hepatic stellate cells (HSC).

2066 Background: WT2725 is a Wilms’ tumor (WT1)-derived-oligopeptide vaccine intended to induce WT1 specific cytotoxic T-lymphocytes against WT1 positive tumors in HLA-A*0201+ or HLA-A*0206+. This first in human study of WT2725 was conducted to evaluate the safety, tolerability, and efficacy. Methods: Subjects with progressive or recurrent glioblastoma (GBM), acute myeloid leukemia (AML) (patients in morphologic remission with minimal residual disease determined by WT1 RT-PCR were allowed), non-small cell lung cancer (NSCLC), or ovarian cancer despite standard therapy were treated with 0.3, 0.9, 3, and 9 mg of WT2725 subcutaneously (s.c.) every week for 4 weeks, then every other week for 6 weeks, and every 4 weeks thereafter until progression or other discontinuation event (part 1); and with 18 mg and 27 mg of WT2725 s.c. every week for 8 weeks, then every other week for 10 weeks, and every 4 weeks thereafter until progression or other discontinuation event (part 2). Responses were evaluated by Immune-related Response Criteria (irRC) for solid tumors and modified International Working Group (IWG) for AML. Results: 62 subjects were dosed, the most frequent adverse events were grade 1 injection site reactions (no grade 3 injection site reactions or dose limiting toxicities observed). Of the 21 GBM subjects who were dosed, seven survived for ≥ 1 year (33%). Of these seven subjects, three survived for ≥18 months (14%), and two for ≥2 years (both in complete radiologic remission, 9.5%). One of the seven subjects with ≥1 year survival had previous treatment with bevacizumab. Two subjects continue dosing (1 complete response with no measurable disease >3 years and 1 partial response > 13 months on study). Results in subjects with non-GBM tumors (12 subjects with AML, 21 with ovarian CA, 7 with NSCLC, and 1 other cancer) are not presented here. WT1-specific CTLs and tumor burden was monitored. WT1 specific CTLs were associated with decrease of tumor burden in two patients with low tumor burden. Some patients with high disease burden did not respond. Conclusions: Preliminary data suggests WT2725 is well tolerated with potential antitumor activity in GBM patients, supporting future development of WT2725 for treatment of GBM in selected subjects. Clinical trial information: NCT01621542.

Interaction of RAGE with its ligands can promote tumor progression, invasion and angiogenesis. Although blockage of RAGE signaling has been proposed as a potential anti-cancer therapy, the contribution of RAGE expression in tumor microenvironement (TME) to tumorigenesis has not been investigated in detail. Here, we evaluated the effect of genetic depletion of RAGE in TME on the growth of gliomas. In both invasive and non-invasive glioma models, animal survival was prolonged in Rage−/- mice. This improvement in animal survival, however, was not due to changes in tumor growth rate, but a reduction in tumor-associated inflammation in Rage−/- mice. Furthermore, RAGE ablation in TME abrogated angiogenesis by downregulating the expression of pro-angiogenic factors which prevented vessel pruning, and resulted in the generation of leaky vasculature. These alterations, however, were most prominent in non-invasive gliomas where the expression of VEGF and pro-inflammatory cytokines were also lower in Rage−/- tumor-associated macrophages. Interestingly, reconstituting Rage−/- tumor macrophages with either wild-type microglia or macrophages normalized tumor vascularity. This is the first report to demonstrate the pro-angiogenic function of RAGE signaling in tumor macrophages and underscores the complex role of RAGE and its ligands in gliomagenesis.

Factors released by glioma-associated microglia/macrophages (GAMs) play an important role in the growth and infiltration of tumors. We have previously demonstrated that the co-chaperone stress-inducible protein 1 (STI1) secreted by microglia promotes proliferation and migration of human glioblastoma (GBM) cell lines in vitro. In the present study, in order to investigate the role of STI1 in a physiological context, we used a glioma model to evaluate STI1 expression in vivo. Here, we demonstrate that STI1 expression in both the tumor and in the infiltrating GAMs and lymphocytes significantly increased with tumor progression. Interestingly, high expression of STI1 was observed in macrophages and lymphocytes that infiltrated brain tumors, whereas STI1 expression in the circulating blood monocytes and lymphocytes remained unchanged. Our results correlate, for the first time, the expression of STI1 and glioma progression, and suggest that STI1 expression in GAMs and infiltrating lymphocytes is modulated by the brain tumor microenvironment.

7-hydroxyquinoline (7-HQ) is a kind of organic molecule with excited state proton transfer (ESPT) effect, and can be used as the material for all optical switching. This optical switching takes place via the ESPT effect depending on its intermolecular hydrogen bond formed with the solvent, and can have the effect of all optical switching. 7-HQ can not form intermolecular hydrogen bond with dimethyl sulfoxide (DMSO), so 7-HQ in DMSO solution cannot display the ESPT effect. However, after the solution was radiated by an UV laser, we found that 7-HQ could have ESPT effect. This phenomenon is reported and the mechanism is investigated for the first time in this paper.

Mass spectrometry (MS) data are becoming common in recent years. Prior to other statistical inferential procedures, alignment of spectra may be needed to ensure that intensities of the same protein/peptide are accurately located/identified. However, the enormous number of peaks poses challenge in handling such data. Direct applications of available curve alignment methods often do not produce satisfactory results. In this work, we propose an Automated Pairwise Piecewise Landmark Registration (APPLR) method for aligning MS data. For a pair of spectra, the most prominent peaks are given the priority to be aligned first. A weighted Gaussian kernel based similarity score is used to test warp these top peaks and spectra are then aligned according to the best match. The algorithm is implemented in an iterative way until all spectra are aligned. We illustrated the new method and two other curve alignment methods to the unlabeled total ion count data.

Integrated service companies have recently developed multi-component induction wireline and LWD resistivity logging tools. The new wireline induction logging tools are 3DEX from Baker Hughes and Rt Scanner from Schlumberger. The directional LWD resistivity tools include azimuthal propagation resistivity (APR) from Baker Hughes, azimuthal deep resistivity (ADR) by Halliburton, and PeriScope15 and PeriScope100 from Schlumberger.