12,249 research outputs found
Skeletal and compact validated mechanisms for iso-dodecane using a decoupling methodology
Iso-dodecane is an important component in developing surrogate fuel mixtures for conventional and alternative jet fuels. Despite some progress in recent years, there is still a requirement for a compact mechanism that is well validated in both low and high temperatures when compared to the experimental data. This paper develops a new compact mechanism with the aid of a decoupling methodology for iso-dodecane validated against available experimental data over a wide range of pressures and equivalence ratios. The ignition delay results show excellent agreement over a wide range of temperatures from 600 to 1300 K that covers low and high limits compared to the empirical data at 15, 20, and 40 bar and at lean, stoichiometric, and rich conditions. The maximum discrepancy between the simulations and the experiments by a factor of 1.7 was observed for 750 K at the rich condition at 15 bar. Laminar burning velocity simulations at two different pressures were conducted for iso-dodecane, and the results were compared with the available experimental data for alcohol-to-jet (ATJ) fuel, which is mostly composed of iso-dodecane. It was found that there was very good agreement between the modeling results and the experimental data. The final version of the new mechanism includes 158 species and 986 reactions and has potential in further functional kinetic investigations and to use for complex geometries of combustion systems such as Equivalent Reactor Network analyses
Towards personalized immunotherapy : development of in vitro models for imaging natural killer cell behavior in the tumor microenvironment
Tremendous advances in the tumor immunology field have transformed immunotherapy
from a promising approach to a standard clinical practice. However, a subset of cancer
patients is non-responsive to immunotherapy. More research is therefore needed to
understand the mechanisms underlying tumor resistance to immunotherapeutic treatments.
The aim of this doctoral work was to develop new tools to study the mechanisms of cancer
immunosurveillance and to test immunotherapeutic treatments in vitro. In this thesis, I
describe the methods developed, and I discuss the main biological findings obtained by
using these methods.
The thesis is organized as follows. A short historical background of immunotherapy is
provided in Chapter 1. Chapter 2 describes the principles of NK cell-mediated cancer
immunosurveillance, and provides an overview on rare cancers, mainly focusing on
sarcoma. The research aims are listed in Chapter 3. In Chapter 4, I describe the cell culture
methods and cell analysis techniques relevant for my doctoral work. In Chapter 5, I
describe the methods we developed to culture tumor spheroids in vitro using ultrasonic
standing waves in microwell chips, focusing on the theory, design, and applications.
Chapter 6 and Chapter 7 focus on the biological findings obtained using our platform in
combination with traditional immunological methods, followed by future implementations
discussed in Chapter 8. The constituent papers are provided at the end of the thesis.
In Paper I, we combined the use of the microwell chip, ultrasonic standing waves and a
protein-repellent polymer coating to enable the production of spheroids from multiple cell
types. In absence of cell adhesion to the chip, spheroids could be collected and further
analyzed by off-the-chip techniques.
In Paper II, we designed a novel multichambered microwell chip to perform multiplexed
fluorescence screening of two- or three-dimensional cell cultures. The platform allows the
direct assessment of drug or immune cell cytotoxic efficacy, making it a promising tool for
individualized cytotoxicity tests for personalized medicine.
In Paper III, we investigate the function of PVR receptors in NK cells interacting with
renal carcinoma spheroids, and the impact of PVR in NK cell-based cellular
immunotherapy. We demonstrated that variations in PVR expression are primarily
recognized by the inhibitory receptor TIGIT, while DNAM-1 strongly contributes to NK
cell activation mainly through PVR-independent mechanisms. We performed NK
cell-based cytotoxicity assays against renal carcinoma spheroids in the microwell chip.
Anti-TIGIT treatment was effective only for TIGIThigh NK cells both when used as
monotherapy or in combination with other drugs, suggesting that only a fraction of patients
might respond to anti-TIGIT therapy.
In Paper IV, a similar approach was used with primary sarcomas. We cultured
patient-derived sarcoma spheroids and tested NK cell-based immunotherapy in the
microwell chip, either alone or in combination with antibody therapy, and we identified
promising treatment combinations.
In Paper V, we applied the use of expansion microscopy to visualize NK cells infiltrating
renal carcinoma spheroids. In conclusion, our multi-disciplinary work shows the
development of new imaging-based platform and its use to study the mechanisms of NK
cell-mediated tumor surveillance and for personalized therapy
Oxidative aging and fracture behavior of polymers and composites: theory, modeling and experiments
Polymers and their composites (PMC) have emerged as effective alternative materials in structural, aerospace, and automotive industries due to their lightweight and tunable properties compared to metals. However, these materials tend to degrade during their operations in extreme environments. In this work, two extreme conditions are considered: - i) high-temperature oxidative degradation of polymers and polymer-based composites ii) Fracture and damage of polymer-based composites under thermo-mechanical loading.
Polymer oxidation starts when oxygen from the ambient diffuses into the bulk material and initiates chemical reactions to develop a coarse, brittle oxide layer on the exposed surface. The oxidative degradation process is inherently complex in nature, as it involves a coupling between diffusion, reaction, and mechanics. As oxygen diffuses into the polymer, a series of chain reactions occur, resulting in residual shrinkage strain on the oxidized layer of the material due to escaping of the volatiles. Consequently, residual stress develops within the material, causing spontaneous cracking even without the application of external loading. Thus, the oxidative aging can cause premature cracking in the material and requires a better understanding of the interaction between the chemistry and mechanics at different length scales and timescales to comprehend the effect of thermo-oxidative aging of polymeric materials. In this work, a fully coupled thermodynamically consistent chemo-mechanical phase-field fracture model is developed that attempts to bridge the gap between the experimental observations and a constitutive theory for thermo-oxidative aging in polymeric materials. To accomplish this, a novel approach has been adopted considering the chemical reactions at the polymer macromolecular level, a reaction-driven transient network evolution theory at the microscale, and a constitutive model at the macroscale. Finally, a phase-field fracture theory is added to the chemo-mechanical model to predict the oxidation-induced fracture in the polymer under mechanical loading. The model has been further extended to a homogenized continuum theory to capture the anisotropic oxidation characteristic of the fiber-reinforced polymer matrix composites. Specialized forms of the constitutive equations and the governing partial differential equations have also been developed for the polymers and the composite systems and numerically implemented in finite elements by writing ABAQUS user-defined element (UEL) subroutine.
Lastly, a unified phase-field fracture model is developed to create an experimentally validated, physically motivated, and computationally tractable model to predict the fracture response of the unidirectional fiber reinforced polymer matrix composites. A homogenized, coupled thermo-mechanical model is developed considering a thermo-viscoelastic polymer matrix. The model is numerically implemented by writing a ABAQUS user-element subroutine (UEL). The model can predict the constitutive response and direction-dependent damage propagation and final fracture in commercially acquired unidirectional glass-fiber-reinforced epoxy composite both at different fiber orientations and at different temperatures in substantial agreement with the experiments
Micro-Electro Discharge Machining: Principles, Recent Advancements and Applications
Micro electrical discharge machining (micro-EDM) is a thermo-electric and contactless process most suited for micro-manufacturing and high-precision machining, especially when difficult-to-cut materials, such as super alloys, composites, and electro conductive ceramics, are processed. Many industrial domains exploit this technology to fabricate highly demanding components, such as high-aspect-ratio micro holes for fuel injectors, high-precision molds, and biomedical parts.Moreover, the continuous trend towards miniaturization and high precision functional components boosted the development of control strategies and optimization methodologies specifically suited to address the challenges in micro- and nano-scale fabrication.This Special Issue showcases 12 research papers and a review article focusing on novel methodological developments on several aspects of micro electrical discharge machining: machinability studies of hard materials (TiNi shape memory alloys, Si3N4–TiN ceramic composite, ZrB2-based ceramics reinforced with SiC fibers and whiskers, tungsten-cemented carbide, Ti-6Al-4V alloy, duplex stainless steel, and cubic boron nitride), process optimization adopting different dielectrics or electrodes, characterization of mechanical performance of processed surface, process analysis, and optimization via discharge pulse-type discrimination, hybrid processes, fabrication of molds for inflatable soft microactuators, and implementation of low-cost desktop micro-EDM system
Command and Persuade
Why, when we have been largely socialized into good behavior, are there more laws that govern our behavior than ever before? Levels of violent crime have been in a steady decline for centuries—for millennia, even. Over the past five hundred years, homicide rates have decreased a hundred-fold. We live in a time that is more orderly and peaceful than ever before in human history. Why, then, does fear of crime dominate modern politics? Why, when we have been largely socialized into good behavior, are there more laws that govern our behavior than ever before? In Command and Persuade, Peter Baldwin examines the evolution of the state's role in crime and punishment over three thousand years. Baldwin explains that the involvement of the state in law enforcement and crime prevention is relatively recent. In ancient Greece, those struck by lightning were assumed to have been punished by Zeus. In the Hebrew Bible, God was judge, jury, and prosecutor when Cain killed Abel. As the state's power as lawgiver grew, more laws governed behavior than ever before; the sum total of prohibited behavior has grown continuously. At the same time, as family, community, and church exerted their influences, we have become better behaved and more law-abiding. Even as the state stands as the socializer of last resort, it also defines through law the terrain on which we are schooled into acceptable behavior. This title is also available in an Open Access edition
Structure, Activity, and Function of Protein Methyltransferases
This collection of review articles describes the structure, function and mechanism of individual protein methyltransferase enzymes including protein lysine methyltransferases, protein arginine methyltransferases, and also the less abundant protein histidine methyltransferases and protein N-terminal end methyltransferases. The topics covered in the individual reviews include structural aspects (domain architecture, homologs and paralogs, and structure), biochemical properties (mechanism, sequence specificity, product specificity, regulation, and histone and non-histone substrates), cellular features (subcellular localization, expression patterns, cellular roles and function, biological effects of substrate protein methylation, connection to cell signaling pathways, and connection to chromatin regulation) and their role in diseases. This review book is a useful resource for scientists working on protein methylation and protein methyltransferases and those interested in joining this emerging research field
Sustainability Analysis and Environmental Decision-Making Using Simulation, Optimization, and Computational Analytics
Effective environmental decision-making is often challenging and complex, where final solutions frequently possess inherently subjective political and socio-economic components. Consequently, complex sustainability applications in the “real world” frequently employ computational decision-making approaches to construct solutions to problems containing numerous quantitative dimensions and considerable sources of uncertainty. This volume includes a number of such applied computational analytics papers that either create new decision-making methods or provide innovative implementations of existing methods for addressing a wide spectrum of sustainability applications, broadly defined. The disparate contributions all emphasize novel approaches of computational analytics as applied to environmental decision-making and sustainability analysis – be this on the side of optimization, simulation, modelling, computational solution procedures, visual analytics, and/or information technologies
Biofuels Production and Processing Technology
The negative impacts of global warming and global environmental pollution due to fossil fuels mean that the main challenge of modern society is finding alternatives to conventional fuels. In this scenario, biofuels derived from renewable biomass represent the most promising renewable energy sources. Depending on the biomass used by the fermentation technologies, it is possible to obtain first-generation biofuels produced from food crops, second-generation biofuels produced from non-food feedstock, mainly starting from renewable lignocellulosic biomasses, and third-generation biofuels, represented by algae or food waste biomass.Although biofuels appear to be the closest alternative to fossil fuels, it is necessary for them to be produced in competitive quantities and costs, requiring both improvements to production technologies and the diversification of feedstock. This Special Issue is focused on technological innovations, including the utilization of different feedstocks, with a particular focus on biethanol production from food waste; different biomass pretreatments; fermentation strategies, such as simultaneous saccharification and fermentation (SSF) or separate hydrolysis and fermentation (SHF); different applied microorganisms used as a monoculture or co-culture; and different setups for biofuel fermentation processes.The manuscripts collected represent a great opportunity for adding new knowledge to the scientific community as well as industry
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