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This case study of the waste management at a pharmaceutical company investigates the current situation and possible improvements for future work in terms of amount of waste generated, treatment methods and economy. The scope of the project was to assess all current waste streams from the everyday activities and find potential areas for improvement. Chemical/solvent waste have not been investigated thoroughly because of the complexity to make changes within the manufacturing processes. Waste generated during demolition and construction by external contractors have been excluded since it is not a part of the business as usual. The company has set the goal to decrease greenhouse gas emissions by 20% and waste generated by 15% and to achieve these goals the waste diagnostic project have been initiated. Waste reports and guided tours at each department have been compiled to assess and map out all waste streams at the site. The waste management hierarchy has been used as a tool together with performance measurements to evaluate current situation and with examples from literature, other sites and industries recommendations have been made. The waste management hierarchy is a tool used to prioritize waste management to reach a circular economy, with landfill at the bottom and reduction/reuse at the top of the hierarchy the current status of a company can be assessed and also what areas that have to be improved in order to climb the hierarchy. The company shows a good environmental performance today and comply with internal standards, the waste metric scoring calculation results in a value of, , 464 which corresponds to energy recovery level of the waste management hierarchy. An ISO certificate ensures customers that a product or service meet the standards the customer have. There are ISO standards within many different areas and ISO 14001 applies to environmental management which the company is not certified with. The company comply with the internal standards but an ISO certificate would result in extra credibility. Some of the recommendations to the site includes a waste management communication program to engage employees, reuse of disposable pallets, drying of wastewater sludge and installation of paper shredder to reduce costs related to classified documents. / Denna fallstudie om avfallshanteringen på ett läkemedelsföretag undersöker den nuvarande situationen och potentiella förbättringsmöjligheter för framtida arbete beträffande mängd avfall som genereras, behandlingsmetoder och ekonomi. Projektets mål var att utvärdera alla avfallsströmmar från de dagliga aktiviteterna och identifiera potentiella områden för förbättring. Kemiskt/lösningsmedelavfall har inte undersökts på djupet på grund av komplexiteten att göra ändringar inom tillverkningsprocesserna. Projektavfall som genererats under rivning och byggande av externa entreprenörer har uteslutits eftersom det inte är en del av den dagliga verksamheten. Företaget har satt som mål att minska utsläppen av växthusgaser med 20% och avfall genererat med 15% och för att uppnå dessa mål har ”waste diagnostic” projektet inletts. Avfallsrapporter och guidade turer vid varje avdelning har sammanställts för att utvärdera och kartlägga alla avfallsströmmar på siten. Avfallshierarkin har använts som ett verktyg tillsammans med prestandamätningar för att utvärdera den aktuella situationen och med exempel från litteratur, andra siter och branscher har rekommendationer gjorts. Avfallshanteringshierarkin är ett verktyg som används för att prioritera avfallshantering för att uppnå en cirkulär ekonomi, med deponering i botten och minskning / återanvändning högst upp i hierarkin kan den aktuella statusen för ett företag bedömas och även vilka områden som måste förbättras för att nå högre upp i avfallshierarkin. Siten visar på en bra miljöprestanda idag och uppfyller de interna standarder som fastställts. Beräkningen av ”waste metric scoring” resulterar i ett värde, , på 464 vilket motsvarar nivån för energiåtervinning i avfallshanteringshierarkin. Ett ISO-certifikat garanterar kunder att en produkt eller tjänst uppfyller de standarder kunden har. Det finns ISO-standarder inom många olika områden och ISO 14001 är certifikatet för miljöledning som siten inte är certifierad med. Företaget följer de interna standarder som har satts men ett ISO-certifikat skulle resultera i ökad trovärdighet. Några av de identifierade rekommendationerna till företaget inkluderar ett kommunikationsprogram för avfallshantering för att engagera och utbilda anställda, återanvändning av engångspallar, torkning av slam och installation av dokumentförstörare för att minska kostnaderna kring sekretessbelagda dokument.

<p>Ion permeation through voltage gated sodium channels is modulated by many drugs and toxins. However, the atomistic mechanisms of action of most these ligands are poorly understood. This study focuses on three compounds: a steroidal alkaloid batrachotoxin (BTX), a pyrethroid insecticide deltamethrin, and an alkylamide insecticide BTG 502, which bind to distinct but allosterically coupled receptor sites. BTX belongs to the class of the sodium channel agonists (activators), which cause persistent channel activation by inhibiting channel inactivation. Traditionally, BTX is believed to bind at the channel-lipid interface and allosterically modulate ion permeation through the channel. However, in the last decade, amino acid residues that affect BTX action have been found in the pore-facing inner helices of all four domains, suggesting that BTX binds in the channel pore (Tikhonov and Zhorov, <em>FEBS Letters</em> 2005). An alkylamide insecticide BTG 502 reduces sodium currents and antagonizes the action of BTX on cockroach sodium channels, suggesting that it also binds inside the pore. Conversely, pyrethroids bind at the lipid-exposed cavity formed by a short intracellular linker-helix IIS4-S5 and transmembrane helices IIS5 and IIIS6.</p> <p>In this study we first developed a new method of electrostatic-energy calculations, a new protocol of ligand docking, and tested this methodology on 60 ligand-protein complexes of known structure (Garden and Zhorov 2010). We then applied this methodology to rationalize effects of various mutations in the domain III inner helix of the cockroach sodium channel BgNav1.1 on the action of BTX, BTG 502 and deltamethrin. Our collaborators, Dr. Ke Dong et al. from Michigan State University, mutated all residues in the pore-lining helix of domain III (IIIS6) and found several new BTX and BTG 502 sensing residues. Using these data along with other published data on BTX- and deltamethrin-sensing residues as distance constrains, we docked BTX, BTG 502 and deltamethrin in a Kv1.2-based homology model of the open BgNav1.1 channel. We arrived at models, which are consistent with all currently available data on the action of the ligands. In the BTX-binding model, the toxin adopts a “horseshoe” conformation and binds in the channel pore with the horseshoe plane normal to the pore axis. In this binding mode BTX allows would allow ion permeation through the hydrophilic inner face of the horseshoe, and resist the activation-gate closure. Various BTX moieties interact with known BTX sensing residues. In particular, the tertiary ammonium group of BTX is engaged in cation-p interactions with the newly discovered BTX-sensing residue Phe³ⁱ¹⁶. In the BTG 502-binding model, the ligand wraps around IIIS6 making direct contacts with all known BTG 502-sending residues, including buried residues on the IIIS6 helix side, which does not face the pore. Deltamethrin binds within the cavity formed by the linker-helix IIS4-S5, the outer helix IIS5, and the inner helix IIIS6 at the interface between domains II and III, similar to the pyrethroid-binding mode predicted by others (O'Reilly, Khambay et al. 2006). Our study revealed a unique mode of action of BTX in which the agonists enables the ion permeation by forming a “channel within a channel”. We also found that the BTG 502 receptor site overlaps with receptors for BTX and deltamethrin, which are located in different parts of the channel.</p> / Doctor of Philosophy (PhD)

This study proposes several decision-making tools utilizing optimization and machine learning frameworks to assess and improve the safety of the workplaces. The first chapter of this study presents a novel mathematical model to optimally locate a set of detectors to minimize the expected number of casualties in a given threat area. The problem is formulated as a nonlinear binary integer programming model and then solved as a linearized branch-and-bound algorithm. Several sensitivity analyses illustrate the model's robustness and draw key managerial insights. One of the prevailing threats in the last decades, Active Shooting (AS) violence, poses a serious threat to public safety. The second chapter proposes an innovative mathematical model which captures several essential features (e.g., the capacity of the facility and individual choices, heterogeneity of individual behavioral and choice sets, restriction on choice sets depending on the location of the shooter and facility orientation, and many others) which are essential for appropriately characterizing and analyzing the response strategy for civilians under an AS exposed environment. We demonstrate the applicability of the proposed model by implementing the effectiveness of the RUN.HIDE.FIGHT.® (RHF) program in an academic environment. Given most of the past incidents took place in built environments (e.g., educational and commercial buildings), there is an urgent need to methodologically assess the safety of the buildings under an active shooter situation. Finally, the third chapter aims to bridge this knowledge gap by developing a learning technique that can be used to model the behavior of the shooter and the trapped civilians in an active shooter incident. Understanding how the civilians responded to different simulated environments, a number of actions could have been undertaken to bolster the safety measures of a given facility. Finally, this study provides a customized decision-making tool that adopts a tailored maximum entropy inverse reinforcement learning algorithm and utilizes safety measurement metrics, such as the percentage of civilians who can hide/exit in/from the system, to assess a workplace's safety under an active shooter incident.

This thesis outlines the development of a control system for a series-parallel plugin hybrid electric vehicle. The vehicle, developed at McMaster University for the EcoCAR 3 Advanced Vehicle Technology Competition, was produced in an effort to provide a Chevrolet Camaro with a high-performance, fuel efficient, hybrid powertrain. A rational design methodology was adopted and guided the development of the control system and the implementation of its respective algorithms. A simulation tool was created using MATLAB and Simulink which, in turn, allowed for the effectiveness of the supervisory control logic to be evaluated by approximating the vehicle’s energy consumption, fuel consumption, and emissions. The impact of hybridizing the vehicle’s powertrain was similarly assessed by comparing it against its unelectrified counterpart, the 2016 Chevrolet Camaro LT. A solution to the vehicle’s energy management problem was proposed in the form of an Adaptive Equivalent Consumption Minimization Strategy (A-ECMS) which was then evaluated against more common heuristic approaches as well as non-adaptive instantaneous minimization methods. An artificial neural network was selected as the strategy’s adaptation mechanism and it was used to identify specific vehicular driving patterns in real-time. The neural network addresses many issues that arise due to the sensitivity of algorithms that attempt to solve the energy management problem without prior knowledge of the driving cycle. The methods used during the process of the control system’s verification and calibration are also discussed in this thesis and, in addition, encompass the use of software representations of the vehicle’s Electronic Control Units (ECUs), the development of test cases, and the supervisory control software’s evaluation in the Model-in-the-Loop (MIL), Software-in-the-Loop (SIL), and Hardware-in-the-Loop (HIL) environments. / Thesis / Master of Applied Science (MASc) / Compared to conventional combustion vehicles, an automobile with an electrified propulsion system has the potential to reduce fuel consumption and emissions due to the presence of an energy storage system and one or more electric machines. These benefits, however, come at the cost of increased control system complexity. The question of how and when to use alternative energy sources – whether it be electrical or fuel energy – in a hybrid vehicle is at the epicenter of research and development initiatives in the automotive industry. Traditional heuristic methods have proven to be unstable due to their sensitivity to driving conditions and that optimal control policies require prior knowledge of the vehicle’s route and destination, and therefore, are not suitable in most applications. Strategies which attempt to instantaneously minimize a vehicle’s fuel or energy consumption, however, can overcome these aforementioned obstacles. As such, this area of research and development has received much interest. The objective of this research was twofold: the first being to develop a control system for a series-parallel plug-in hybrid electric vehicle in a rational and systematic manner, and, secondarily, to evaluate the benefits of instantaneous minimization methods for energy management.

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