Leader-follower relationships in technologically advanced operations

Advanced technologies reshape operations at a staggering pace, with promises of lucrative improvements in a plethora of performance indicators, such as safety, speed, productivity, accuracy, and turnover. Companies that seek competitive advantage, however, often adopt new technologies without considering crucial human factors. Humans will remain an essential part of operations systems for the foreseeable future. As such we need to consider them when designing and implementing any advanced technology that affects their objective performance as well as their subjective experience. This dissertation includes three studies that deepen our understanding of human factors in terms of traditional and emerging leader-follower relationships, for the benefit of effectively designing and implementing advanced technologies within the field of operations management. Study 1 investigates a traditional hierarchical leader-follower relationship between a truck driver and his or her direct manager. It establishes the effect of safety-specific transformational leadership (SSTL) on the performance metrics of safe driving and driving productivity in long and short-haul truck cargo transport. Study 2 recognizes and investigates the novel leader-follower relationship that emerges during the interaction of humans with robots in collaborative order picking in warehouses. It empirically investigates this relationship and compares the objective performance outcomes of productivity and accuracy in two human-robot collaborative order picking setups (human leading the robot, human following the robot). Study 3 expands on the concept of human-robot collaborative order picking, and explores the effects that introducing this novel leader-follower relationship has on the subjective experience of human workers

Leader-follower relationships in technologically advanced operations

Advanced technologies reshape operations at a staggering pace, with promises of lucrative improvements in a plethora of performance indicators, such as safety, speed, productivity, accuracy, and turnover. Companies that seek competitive advantage, however, often adopt new technologies without considering crucial human factors. Humans will remain an essential part of operations systems for the foreseeable future. As such we need to consider them when designing and implementing any advanced technology that affects their objective performance as well as their subjective experience. This dissertation includes three studies that deepen our understanding of human factors in terms of traditional and emerging leader-follower relationships, for the benefit of effectively designing and implementing advanced technologies within the field of operations management. Study 1 investigates a traditional hierarchical leader-follower relationship between a truck driver and his or her direct manager. It establishes the effect of safety-specific transformational leadership (SSTL) on the performance metrics of safe driving and driving productivity in long and short-haul truck cargo transport. Study 2 recognizes and investigates the novel leader-follower relationship that emerges during the interaction of humans with robots in collaborative order picking in warehouses. It empirically investigates this relationship and compares the objective performance outcomes of productivity and accuracy in two human-robot collaborative order picking setups (human leading the robot, human following the robot). Study 3 expands on the concept of human-robot collaborative order picking, and explores the effects that introducing this novel leader-follower relationship has on the subjective experience of human workers

Sparse representations and harmonic wavelets for stochastic modeling and analysis of diverse structural systems and related excitations

In this thesis, novel analytical and computational approaches are proposed for addressing several topics in the field of random vibration. The first topic pertains to the stochastic response determination of systems with singular parameter matrices. Such systems appear, indicatively, when a redundant coordinate modeling scheme is adopted. This is often associated with computational cost-efficient solution frameworks and modeling flexibility for treating complex systems. Further, structures are subject to environmental excitations, such as ground motions, that typically exhibit non-stationary characteristics. In this regard, aiming at a joint time-frequency analysis of the system response a recently developed generalized harmonic wavelet (GHW)-based solution framework is employed in conjunction with tools originated form the generalized matrix inverse theory. This leads to a generalization of earlier excitation-response relationships of random vibration theory to account for systems with singular matrices. Harmonic wavelet-based statistical linearization techniques are also extended to nonlinear multi-degree-of-freedom (MDOF) systems with singular matrices. The accuracy of the herein proposed framework is further improved by circumventing previous “local stationarity” assumptions about the response. Furthermore, the applicability of the method is extended beyond redundant coordinate modeling applications. This is achieved by a formulation which accounts for generally constrained equations of motion pertaining to diverse engineering applications. These include, indicatively, energy harvesters with coupled electromechanical equations and oscillators subject to non-white excitations modeled via auxiliary filter equations. The second topic relates to the probabilistic modeling of excitation processes in the presence of missing data. In this regard, a compressive sampling methodology is developed for incomplete wind time-histories reconstruction and extrapolation in a single spatial dimension, as well as for related stochastic field statistics estimation. An alternative methodology based on low rank matrices and nuclear norm minimization is also developed for wind field extrapolation in two spatial dimensions. The proposed framework can be employed for monitoring of wind turbine systems utilizing information from a few measured locations as well as in the context of performance-based design optimization of structural systems. Lastly, the problem of with data-driven sparse identification methods of nonlinear dynamics is considered. In particular, utilizing measured responses a Bayesian compressive sampling technique is developed for determining the governing equations of stochastically excited structural systems exhibiting diverse nonlinear behaviors and also endowed with fractional derivative elements. Compared to alternative state-of-the-art schemes that yield deterministic estimates for the identified model, the herein developed methodology exhibits additional sparsity promoting features and is capable of quantifying the uncertainty associated with the model estimates. This provides a quantifiable degree of confidence when employing the proposed framework as a predictive tool

Hierarchically designed hybrid nanoparticles for combinational photochemotherapy against a pancreatic cancer cell line

© The Royal Society of Chemistry 2018. Here, we report the formulation of hybrid nanoparticles consisting of aggregated gold nanoparticles (GNPs) impregnated into a gemcitabine-polymer conjugate matrix that exhibit synergistic photo-chemo-therapeutic activity against pancreatic cancer. Well-defined, sub-100 nm hybrid NPs were successfully formulated and their photothermal conversion efficiency was evaluated, which was found to be as high as 63% in the red-visible spectrum. By varying the GNP and GEM-polymer feed, it was possible to control the red-shifting of the surface plasmon resonance at therapeutically relevant wavelengths. The hybrid NPs exhibited significant cytotoxicity against MiaPaCa-2 cells with a half-maximal inhibitory concentration (IC 50 ) of 0.0012 mg mL -1 ; however the IC 50 decreased by a factor of 2 after the cells were irradiated with a continuous wave red laser for 1 min (1.4 W cm -2 ). Although the irradiation of the aggregated GNPs loaded in the hybrid NPs produced a higher thermal effect for the same amount of non-loaded GNPs, the IC 50 of the hybrid NPs was significantly lower than that of the free GNPs, hence indicating a synergistic effect of the polymer bound GEM and the GNPs

Macromolecular cell surface engineering for accelerated and reversible cellular aggregation.

We report the synthesis of two simple copolymers that induce rapid cell aggregation within minutes in a fully reversible manner. The polymers can act as self-supporting "cellular glues" or as "drivers" of 3D cell spheroids/aggregates formation at minute concentrations

Polymer coated gold nanoshells for combinational photochemotherapy of pancreatic cancer with gemcitabine

Pancreatic cancer is one of the most lethal malignancies with limited therapeutic options and dismal prognosis. Gemcitabine is the front-line drug against pancreatic cancer however with limited improvement of therapeutic outcomes. In this study we envisaged the integration of GEM with gold nanoshells which constitute an interesting class of nanomaterials with excellent photothermal conversion properties. Nanoshells were coated with thiol-capped poly(ethylene glycol) methacrylate polymers of different molecular weight via Au–S attachment. It was found that the molecular weight of the polymers affects the in vitro performance of the formulations; more importantly we demonstrate that the EC50 of nanoshell loaded GEM can be suppressed but fully restored and even improved upon laser irradiation. Our proposed nanoformulations outperformed the cytotoxicity of the parent drug and showed confined synergism under the tested in vitro conditions

New insights into the regulation of apoptosis, necroptosis, and pyroptosis by receptor interacting protein kinase 1 and caspase-8

Necroptosis and pyroptosis are inflammatory forms of regulated necrotic cell death as opposed to apoptosis that is generally considered immunologically silent. Recent studies revealed unexpected links in the pathways regulating and executing cell death in response to activation of signaling cascades inducing apoptosis, necroptosis, and pyroptosis. Emerging evidence suggests that receptor interacting protein kinase 1 and caspase-8 control the cross-talk between apoptosis, necroptosis, and pyroptosis and determine the type of cell death induced in response to activation of cell death signaling

Complementation of Lymphotoxin α Knockout Mice with Tumor Necrosis Factor–expressing Transgenes Rectifies Defective Splenic Structure and Function

Lymphotoxin (LT)α knockout mice, as well as double LTα/tumor necrosis factor (TNF) knockout mice, show a severe splenic disorganization with nonsegregating T/B cell zones and complete absence of primary B cell follicles, follicular dendritic cell (FDC) networks, and germinal centers. In contrast, as shown previously and confirmed in this study, LTβ-deficient mice show much more conserved T/B cell areas and a reduced but preserved capacity to form germinal centers and FDC networks. We show here that similar to the splenic phenotype of LTβ-deficient mice, complementation of LTα knockout mice with TNF-expressing transgenes leads to a p55 TNF receptor–dependent restoration of B/T cell zone segregation and a partial preservation of primary B cell follicles, FDC networks, and germinal centers. Notably, upon lipopolysaccharide challenge, LTα knockout mice fail to produce physiological levels of TNF both in peritoneal macrophage supernatants and in their serum, indicating a coinciding deficiency in TNF expression. These findings suggest that defective TNF expression contributes to the complex phenotype of the LTα knockout mice, and uncover a predominant role for TNF and its p55 TNF receptor in supporting, even in the absence of LTα, the development and maintenance of splenic B cell follicles, FDC networks, and germinal centers

Realising the artificial chemical cell with vesicles

Responsive biomedical materials span a plethora of applications in the biomedical field, from stents, hydrogels, degradable implants to drug delivery systems, and are in constant further development to give properties that ultimately improve the quality of life and prevent disease. In an effort to develop cell-interacting constructs we sought to synthesize polymers with bioresponsive and even “life-like” properties. By exploiting living polymerization techniques we aim to build self-assembled capsule-mimicking structures (i.e. vesicles) that can serve as prototype copycats of natural cell membranes. Also, we aim to establish a primitive communication platform of the artificial structures with their natural counterparts (i.e. bacterial cells) by using the “glyco-code” as a means of biochemical language. First, model thermoresponsive polymers are utilized that bear carbohydrate moieties to study polymer-cell interactions via multivalency and ligand-receptor interactions. The glycopolymers were found to induce bacterial aggregation of a specific bacterial strain through specific molecular recognition effects. In chapter three, block-copolymer vesicles are synthesized that comprise sugar groups on their coronae and also interact with bacteria through multiple specific ligand-receptor interactions. Also, molecular transport of a model dye from the vesicles to the bacterial cells is facilitated by discrete vesicle-bacteria complex formation. Chapter four explores the communication networks employed by bacterial cells, that is quorum sensing, and simple polymers are tested as molecular quorum quenchers that modulate the quorum sensing response of bacteria through autoinducers scavenging. Ultimately, we seek for an integrated platform to set up an “imitation game” where artificial entities, such as the polymer vesicles, can act as prototype cell-mimics that can actively intervene to the bacterial communication networks. Aspects of the principles and practical requirements to prove the concept are discussed in the final chapter

Endothelial and Macrophage-Specific Deficiency of P38α MAPK Does Not Affect the Pathogenesis of Atherosclerosis in ApoE−/− Mice

BACKGROUND: The p38α Mitogen-Activated Protein Kinase (MAPK) regulates stress- and inflammation-induced cellular responses. Factors implicated in the development of atherosclerosis including modified low-density lipoprotein (LDL), cytokines and even shear stress induce p38 activation in endothelial cells and macrophages, which may be important for plaque formation. This study investigates the effects of endothelial- and macrophage-specific deficiency of p38α in atherosclerosis development, in Apolipoprotein E deficient (ApoE(-/-)) mice. METHODOLOGY/PRINCIPAL FINDINGS: ApoE(-/-) mice with macrophage or endothelial cell-specific p38α deficiency were fed a high cholesterol diet (HCD) for 10 weeks and atherosclerosis development was assessed by histological and molecular methods. Surprisingly, although p38α-deficiency strongly attenuated oxidized LDL-induced expression of molecules responsible for monocyte recruitment in endothelial cell cultures in vitro, endothelial-specific p38α ablation in vivo did not affect atherosclerosis development. Similarly, macrophage specific deletion of p38α did not affect atherosclerotic plaque development in ApoE(-/-) mice. CONCLUSIONS: Although previous studies implicated p38α signaling in atherosclerosis, our in vivo experiments suggest that p38α function in endothelial cells and macrophages does not play an important role in atherosclerotic plaque formation in ApoE deficient mice