Hand-held optical imagers are developed towards clinical breast cancer imaging. Herein, a Gen-2 hand-held optical imager has been developed with unique features: (i) image curved breast tissues with ~86% surface contact, and (ii) perform reflectance and transillumination imaging using the novel forked probe heads. Extensive phantom studies were performed using 1% Liposyn solution (background, ~ 300 ml and 1000 ml volumes) and 0.45 cc India Ink (absorption) targets, under different target:background contrast ratios and target depths. Two-dimensional surface images detected target(s) up to 2.5 cm deep via reflectance imaging, and up to 5 cm deep via transillumination imaging. Preliminary studies on gel-based breast phantoms (~700 ml) detected targets via reflectance and transillumination imaging. Preliminary in-vivo reflectance studies on normal and cancerous breast tissues also detected targets, although with artifacts. In future, the portable Gen-2 imager has potential for clinical breast imaging via reflectance and transillumination approach after extensive in-vivo studies.

A partir de 2002, grâce à l'introduction du concept de la Qualité par la Conception (en anglais Quality by Design : QbD) par l'agence américaine des produits alimentaires et médicamenteux, l'industrie pharmaceutique a intensifié les efforts et les investissements pour permettre une libération en temps réel des lots commerciaux. Le QbD propose que la qualité soit construite dès la conception initiale du médicament plutôt que d'être évaluée à la fin de sa fabrication. Ainsi, avec l'initiative QbD, les tests de contrôle de la qualité de médicaments, réalisés après la fabrication des comprimés, peuvent être éliminés si les paramètres qui les influencent sont contrôlés.En effet, ces tests de contrôle qualité dits traditionnels requièrent en général plusieurs heures pour leurs préparations et leurs réalisations. Tel est le cas du test de dissolution. Ce test est très consommateur de ressources matérielles et humaines. La réalisation de stratégies de contrôle pour les tests de dissolution basée sur une approche QbD pourrait être bénéfique pour l'industrie pharmaceutique.À travers ce travail, nous avons pu :• proposer différentes stratégies novatrices de contrôle du test de dissolution de comprimés pharmaceutiques sur la base des principes du QbD,• apporter un nouvel éclairage sur la compréhension des phénomènes impliqués dans la dissolution de comprimés pharmaceutiques.Les résultats de ce projet de recherche ont permis 1) la mise en évidence des paramètres critiques influençant le test de dissolution, 2) l'élaboration et l'évaluation de modèles statistiques pour les combinaisons de variation de paramètres selon un plan d'expérience préalablement conçu, 3) la corrélation du test de dissolution à des paramètres critiques de procédés de fabrication et d'attributs de matériaux grâce aux technologies d'analyse de procédés. / With the introduction in 2002 of the concept of Quality by Design (QbD) by the Food and Drug Administration, the pharmaceutical industry intensified efforts and investments to reach real time release of commercial batches, reducing time between manufacturing and availability to the patient. QbD proposes that quality should be built in the initial design of a product rather than being assessed at the end of the tablet manufacturing. Thus, with the QbD initiative, quality control tests of tablets like dissolution testing performed after tablets manufacturing could be removed if the parameters impacting them are controlled.Indeed, quality control tests such as traditional dissolution tests generally require several hours for their preparation and their realizations. Dissolution tests are very consuming of time, material, equipment and human resources. The elimination of these tests through a QbD approach could be beneficial for the pharmaceutical industry.Thanks to this work, it was possible to :• propose different innovative strategies to control the dissolution test of pharmaceutical tablets based on the principles of Quality by Design,• have a better understanding of this quality control test.The main results relies on 1) the identification of critical parameters influencing the dissolution test, 2) the development and evaluation of statistical models for the combination of variation of parameters according to an experimental design, 3) the correlation of dissolution test to critical manufacturing process parameters and attributes of materials through process analysis technology.

Toutes les cellules libèrent plusieurs types de vésicules extracellulaires (VEs) qui transportent protéines, lipides et acides nucléiques. Ces vésicules de petite taille se retrouvent dans tous les fluides biologiques tel que le sang et la lymphe et interagissent avec les cellules environnantes. Le système lymphatique constitue une voie de prédilection pour la mobilisation des accepteurs de cholestérol à partir de la paroi artérielle. Nous avons démontré dans un modèle murin qu’une dysfonction lymphatique précède la formation de la plaque d’athérome et que cette dysfonction touche a priori la capacité de contraction des vaisseaux collecteurs. À la base de toutes ces observations, nous avons émis l’hypothèse que les VEs contribuent à la dysfonction lymphatique liée à l’athérosclérose. Pour répondre à ceci, nous avons mis en place un projet translationnel composé de deux groupes de sujets sains, sans maladie cardiovasculaire, qui se distinguent par la présence d’antécédents familiaux d’accidents cardiovasculaires prématurés chez un parent du premier degré. Nous avons quantifié plusieurs sous-types d’intérêt de VEs en circulation à partir du plasma exempt de plaquettes, par cytométrie en flux ultraspécialisés dans la détection de petites particules (> 100 nm) combiné à d’autres techniques complémentaires standardisées. Ensuite, nous avons évalué la fonction lymphatique grâce à l’imagerie par proche infrarouge après injection du vert indocyanine (ICG). Nos résultats préliminaires sont prometteurs quant aux rôles des VEs et de la dysfonction lymphatique dans le développement de l’athérosclérose et corroborent avec nos observations faites chez la souris. Les sujets avec antécédents familiaux de maladie cardiovasculaire (MCV) présentent des signes de dysfonction lymphatique avant même l’apparition de plaques d’athérome subcliniques. La réponse mécano-sensible de leurs vaisseaux collecteurs paraît défectueuse et est observable de concert avec un profil de VEs qui présument une atteinte lymphatique. Ces résultats restent à être confirmer avec le recrutement de sujets additionnels et l'évaluation de la corrélation avec le score de risque polygénique de développer une MCV, dans l’objectif ultime de faire des VEs et de la fonction lymphatique de nouveaux biomarqueurs dans l’identification précoce des MCV. / All cell types release extracellular vesicles (EVs) that carry different types of cellular cargo, such as proteins, lipids and nucleic acids. These small vesicles are found in all biological fluids including blood and lymph and can interact with neighboring cells. The lymphatic system is a preferred route for the mobilization of cholesterol from the arterial wall. We have demonstrated in a mouse model that lymphatic dysfunction precedes the development of atherosclerosis and that that this dysfunction affects the contraction capacity of the collecting vessels. Based on these observations, we hypothesized that EVs contribute to atherosclerosis-associated lymphatic dysfunction. Therefore, we have initiated a translational study involving two groups of healthy subjects that differ in their risk of cardiovascular disease (CVD). We quantified several subtypes of circulating EVs on platelet-free plasma by ultraspecialized flow cytometry in the detection of small particles (> 100 nm) combined to other state-of-the art complementary techniques. Next, we assessed the lymphatic function using near-infrared imaging and injection of indocyanine green (ICG). Our preliminary results are promising for the role of EVs and lymphatic dysfunction in the development of atherosclerosis and corroborate with our observations made in mice. Individuals at high risk of CVD have signs of lymphatic dysfunction even before the onset of subclinical atherosclerosis. The mechano-sensitive response of their collecting vessels appears to be defective and is observable in concert with a profile of EVs that presume lymphatic damage. These results remain to be confirmed with the recruitment of additional subjects and the assessment of the correlation with the polygenic risk score of developing a CVD, in the hope of making these specific EV subsets and lymphatic function new biomarkers in the early detection of CVD.

No description available.

<p dir="ltr"><i>The high heat fluxes generated in electronic devices must be effectively diffused through </i><i>the semiconductor substrate and packaging layers to avoid local, high-temperature “hotspots” </i><i>that govern long-term device reliability. In particular, advanced semiconductor packaging </i><i>trends toward thin form factor products increase the need for understanding and improving </i><i>in-plane conduction heat spreading in anisotropic materials. Furthermore, predicting thermal </i><i>transport in vertical stacks of thinned and bonded die hinges on accurately characterizing </i><i>unknown buried interfacial thermal resistances. The design of semiconductor thermal packaging </i><i>solutions is hence limited by the functionality and accuracy of metrology available </i><i>for thermal properties characterization of engineered anisotropic heat spreading materials </i><i>and buried interfaces. This work focuses on the development of two separate innovative </i><i>metrology techniques for characterizing in-plane thermal properties of both isotropic and </i><i>anisotropic materials, and the measurement of low thermal interfacial resistances embedded </i><i>in stacks of semiconductor substrates.</i></p><p dir="ltr"><i>In the first portion of this thesis, a new measurement technique is developed for characterizing </i><i>the isotropic and anisotropic in-plane thermal properties of thin films and sheets, </i><i>as an extension of the traditional Ångstrom method and other lock-in thermography techniques. </i><i>The measurement leverages non-contact infrared temperature mapping to quantify </i><i>the thermal response to laser-based periodic heating at the center of a suspended thin film </i><i>sample. This novel data extraction method does not require precise knowledge of the boundary </i><i>conditions. To validate the accuracy of this technique, numerical models are developed </i><i>to generate transient temperature profiles for hypothetical anisotropic materials with known </i><i>properties. The resultant temperature profiles are processed through a fitting algorithm to </i><i>extract the in-plane thermal conductivities, without the knowledge of the input properties </i><i>to the forward model. Across a wide range of in-plane thermal conductivities, these results </i><i>agree well with the input values. The limits of accuracy of this technique are identified based </i><i>on the experimental and sample parameters. Further, numerical simulations demonstrate </i><i>the accuracy of this technique for materials with thermal conductivities from 0.1 to 1000 W </i><i>m</i><i>−1 </i><i>K</i><i>−1</i><i>, and material thicknesses ranging from 0.1 to 10 mm. This technique effectively</i> <i>measures anisotropy ratios up to 1000:1. Data from multiple heating frequencies can be </i><i>combined to fit for a single set of thermal properties (independent of frequency), which improves </i><i>measurement sensitivity as the thermal penetration depth varies across frequencies. </i><i>The post-processing algorithm filters out regions within the laser absorber and heat sink to </i><i>eliminate regions in the sample domain with boundary effects. Based on these guidelines, </i><i>experiments demonstrate the accuracy of this measurement technique for a wide range of </i><i>known isotropic and anisotropic heat spreading materials across a thermal conductivity range </i><i>of 0.3 to 700 W m</i><i>−1 </i><i>K</i><i>−1</i><i>, and in-plane anisotropy ratios of 30:1. These steps contribute </i><i>towards standardization of this measurement technique, enabling the development and characterization </i><i>of engineered heat spreading materials with desired anisotropic properties for </i><i>various applications.</i></p><p dir="ltr"><i>The second portion of this thesis focuses on characterization of thermal resistances across </i><i>“buried” interfaces that are challenging to characterize in situ due to their low relative magnitude </i><i>and embedded depth within a material stack. In particular, we target characterization </i><i>of interfaces that are buried deeper than the thermal penetration depth of available transient </i><i>measurement techniques, such as thermoreflectance, but have low thermal resistances </i><i>that prohibit the use of steady-state techniques, such as the reference bar method, due to </i><i>the very high temperature gradients that would be necessary resolve the resistances, among </i><i>other sample preparation challenges. This work develops a technique for the non-destructive </i><i>characterization of such deeply buried interfaces having thermal contact resistances of the </i><i>order of 0.001 cm</i><i>2</i><i>K/W. Two different embodiments of the measurement approach are first </i><i>assessed before down-selecting to a single experimental implementation. The working principle </i><i>for both embodiments includes a combination of non-contact periodic heating and </i><i>thermal sensing to measure the transient temperature response of a two-layer stack of materials </i><i>with a bonded interface of unknown thermal resistance. The approaches aim to </i><i>eliminate the preparation requirement of cutting samples to investigate their temperature in </i><i>cross-section. In the first embodiment, the sample stack is heated periodically at the center </i><i>of the sample, and cooled at the periphery, to create a radial temperature gradient. The </i><i>second embodiment involves generating a one-dimensional temperature gradient across the </i><i>stack by periodic heating of one face and steady cooling of the other face. The corresponding </i><i>ing amplitude and phase delay of the temperature responses are used to fit for the thermal </i><i>interfacial resistance, assuming a time-periodic solution for the heat diffusion equation for </i><i>a system with periodic heating. Numerical models developed for both approaches simulate </i><i>the transient temperature profiles across a two-layer bonded silicon stack of known thermal </i><i>properties, and enable an assessment of both approaches. The one-dimensional (1D) gradient </i><i>approach is found to have higher sensitivity and measurable signal compared to the </i><i>radial spreading approach, at the same mean temperature of the sample. </i></p><p dir="ltr"><i>Based on this 1D gradient concept, an experimental facility is developed, which includes </i><i>a IR-transparent heat sink, laser-based heating, and two IR temperature sensors for noncontact </i><i>temperature measurement of both sides of the sample. The unique IR transparent </i><i>heat sink design allows for simultaneous cooling and non-contact temperature measurement </i><i>of the bottom surface of the sample. An inverse fitting method is developed to extract </i><i>the thermal resistances using the steady periodic temperature amplitude and phase delay </i><i>across the thickness of the material. Thermal data generated using numerical simulations, </i><i>along with the data fitting method, is first leveraged to validate the extracted thermal resistance </i><i>values for two-layer material systems with an bonded interface, as well as for the </i><i>thermal conductivity measurement of bulk materials without an interface. The data extraction </i><i>process is shown to accurately extract thermal contact resistances on the order of </i><i>0.0001 cm</i><i>2</i><i>K/W in silicon-based packages for interfaces that are a few millimeters from the </i><i>exposed surface. For bulk materials, this technique demonstrates accuracy in extracting </i><i>the thermal conductivity of a wide range of materials ranging from thermal insulators to </i><i>highly conductive materials, spanning a range of 0.1 to 2000 W m</i><i>−1 </i><i>K</i><i>−1</i><i>. Physical measurements </i><i>of thermal conductivity of bulk silicon nitride and zinc oxide agree well with expected </i><i>reference values, and these measurements also align well with data from independently performed </i><i>experiments on the same materials using an established ASTM D5470 standard, </i><i>thereby validating this new measurement technique experimentally. Two-layer dry-contact </i><i>stacks of these two materials demonstrate the extraction of the thermal resistance across </i><i>interfaces buried up to 2 mm from the exposed surface. This work contributes toward standardization </i><i>of this technique for measurement of thermal resistances with low magnitudes </i><i>and buried depths, which are commonly found in modern electronic packages, ranging from </i><i>near-junction epitaxial semiconductor films to interconnect layers in emerging die-to-die and </i><i>wafer hybrid bonding technologies.</i></p><p dir="ltr"><i>Ultimately, these measurement techniques of in-plane thermal conductivity measurement </i><i>of anisotropic materials and the interfacial contact resistance measurements across buried </i><i>interfaces offer an important contribution to the area of thermal metrology, and advance the </i><i>field of next-generation semiconductor packaging.</i></p>

Suite à la découverte d’environ 2000 naines brunes au cours des deux dernières décennies, on commence à bien comprendre la physique de ces objets de masse intermédiaire entre les étoiles et les planètes. Malgré tout, les modèles d’atmosphère et d’évolution de ces objets peu massifs peinent toujours à reproduire fidèlement leurs caractéristiques pour les âges les plus jeunes. Ce travail propose la caractérisation de quatre compagnons de masse sous-stellaire (8-30 MJup) en orbite à grande séparation (300-900 UA) autour d'étoiles jeunes (5 Ma) de la région de formation Upper Scorpius. De nouveaux spectres (0,9-2,5 um) et de nouvelles mesures photométriques (YJHKsL') sont présentés et analysés, dans le but de déterminer la masse, température effective, luminosité et gravité de surface de ces compagnons, tout en évaluant la fidélité avec laquelle les spectres synthétiques tirés de deux modèles d’atmosphère récents reproduisent les spectres observés. / Following the discovery of about 2000 brown dwarfs over the past two decades, we begin to understand the physics of these objects of mass intermediate between stellar and planetary masses. Nevertheless, the atmosphere and evolution models for these low-mass objects are still struggling to reproduce their characteristics at young ages. This work presents the characterization of four sub-stellar mass (8-30 MJup) companions orbiting at large separation (300-900 AU) around young stars (5 Myr) in the Upper Scorpius formation region. New spectra (0,9-2,5 um) and new photometric measurements (YJHKsL') are presented and analyzed in order to determine the mass, effective temperature, luminosity and surface gravity of these companions, while assessing the fidelity with which the synthetic spectra from two recent atmosphere models reproduce the observed spectra.

Suite à la découverte d’environ 2000 naines brunes au cours des deux dernières décennies, on commence à bien comprendre la physique de ces objets de masse intermédiaire entre les étoiles et les planètes. Malgré tout, les modèles d’atmosphère et d’évolution de ces objets peu massifs peinent toujours à reproduire fidèlement leurs caractéristiques pour les âges les plus jeunes. Ce travail propose la caractérisation de quatre compagnons de masse sous-stellaire (8-30 MJup) en orbite à grande séparation (300-900 UA) autour d'étoiles jeunes (5 Ma) de la région de formation Upper Scorpius. De nouveaux spectres (0,9-2,5 um) et de nouvelles mesures photométriques (YJHKsL') sont présentés et analysés, dans le but de déterminer la masse, température effective, luminosité et gravité de surface de ces compagnons, tout en évaluant la fidélité avec laquelle les spectres synthétiques tirés de deux modèles d’atmosphère récents reproduisent les spectres observés. / Following the discovery of about 2000 brown dwarfs over the past two decades, we begin to understand the physics of these objects of mass intermediate between stellar and planetary masses. Nevertheless, the atmosphere and evolution models for these low-mass objects are still struggling to reproduce their characteristics at young ages. This work presents the characterization of four sub-stellar mass (8-30 MJup) companions orbiting at large separation (300-900 AU) around young stars (5 Myr) in the Upper Scorpius formation region. New spectra (0,9-2,5 um) and new photometric measurements (YJHKsL') are presented and analyzed in order to determine the mass, effective temperature, luminosity and surface gravity of these companions, while assessing the fidelity with which the synthetic spectra from two recent atmosphere models reproduce the observed spectra.

Il y a de plus en plus d'indications que les trous noirs super-massifs ont joué un rôle important dans l'évolution des galaxies, en particulier au moment de la formation des galaxies les plus massives à haut décalage spectral vers le rouge (z ~ 2 - 3). Nous nous sommes attachés à quantifier les effets sur le milieu interstellaire des galaxies hôtes que peuvent avoir les jets des radio-galaxies, d'une part, et les importantes luminosités bolometriques des quasars, d'autre part. Pour cela, nous avons étudié la cinématique du gaz ionisé dans 12 radio-galaxies modérément puissantes et dans 11 quasars (6 avec une détection en radio et 5 sans jet détectable) à grand décalage spectral vers le rouge avec le spectro-imageur proche infra-rouge SINFONI du VLT, qui nous donnait accès aux raies d'émission normalement sitées dans le domaine visible. Afin d'évaluer la capacité du NAG à stopper la formation d'étoiles, nous avons cherché des traces de leur rétroaction dans ces galaxies, comme de vents de gaz s'échappant de la galaxie hôte. Dans notre échantillon de radio-galaxies modérément puissantes, nous observons des dispersions de vitesse presque aussi importantes que dans les plus puissantes (avec une FWHM ~ 1000 km/s), mais les quantités de gaz ionisé observées y sont inférieures d'un ordre de grandeur (Mion gas ~ 10^8 - 10^9 Msun) et les gradients de vitesse sont plus faibles (Δv < 400 km/s), quand ils sont observés. Dans notre échantillon de quasars, nous devions d'abord soustraire la composante large des raies d'émission avant de pouvoir étudier leur composante étroite, celle susceptible d'être étendue spatialement. Nous détectons des régions d'émission véritablement étendue autour de quatre des six sources avec une détection en radio et autour d'une seule des cinq sans détection radio. Nous estimons qu'il y a moins de gaz ionisé dans ces sources que dans notre échantillon de radio-galaxies (avec Mion gas ~ 10^7 - 10^8 Msun) et la cinématique de ce gaz est aussi plus calme, similaire à ce qui est observé autour de certains quasars proches. Enfin, de nouvelles observations de deux radio-galaxies particulières nous ont révélé que l'une d'entre elles est entourée de quatorze galaxies-companions et qu'elle se trouve donc dans une partie sur-dense de l'Univers. Nous expliquons donc la morphologie inhabituelle du gaz ionisé présent autour de ces deux radio-galaxies par des cycles répétés d'activité du NAG, en analogie à ce qui est observé dans les amas de galaxies proches, qui sont d'excellents exemples de rétroaction du NAG dans l'Univers local. / There is growing evidence that supermassive black holes may play a crucial role for galaxy evolution, in particular during the formation of massive galaxies at high redshift (z ~ 2 - 3). Our work focuses on quantifying the effects of jets of radiogalaxies and of large bolometric luminosities of quasars on the interstellar gas in their host galaxies. To this end, we studied the kinematics of the ionized gas in 12 moderately powerful radio galaxies and 11 quasars (6 radio-loud and 5 radio-quiet) at high redshifts with rest-frame optical imaging spectroscopy obtained at the VLT with SINFONI. We searched for outflows and other signatures of feedback from the supermassive black holes in the centers of these galaxies to evaluate if the AGN may plausibly quench star formation. In our sample of moderately powerful radiogalaxies, we observe velocity dispersions nearly as large as those observed in the most powerful ones (with FWHM ~ 1000 km/s), but the quantity of ionized gas is decreased by one order of magnitude (Mion gas ~ 10^8 - 10^9 Msun) and velocity gradients tend to be less dramatic (Δv < 400 km/s), when they are observed. In our sample of quasars, we had to carefully subtract the broad spectral component of emission lines to have access to its narrow, and spatially extended, component. We detect truly extended emission line regions in 4/6 sources of our radio-loud subsample and in 1/5 source of our radio-quiet subsample. We estimate that masses of ionized gas in these sources are smaller than in our sample of high-redshift radiogalaxies (with Mion gas ~ 10^7 - 10^8 Msun) and kinematics tend to be more quiescent, akin to what is observed in local quasars. Finally, detailed observations of two outliers among our sample of high-redshift radiogalaxies revealed that one of them is closely surrounded by 14 companions galaxies, hence lying in an overdensity. We therefore interpret the presence and morphology of ionized gas around these galaxies as evidence for repeated cycles ouf AGN outbursts, akin to what can be observed in local clusters of galaxies, which are prime examples of AGN feedback in the nearby Universe.

<p> </p> <p>Learning about ‘behavior’ has always been at the heart of my research endeavors. While my undergraduate work in evolution and ecology exposed me to the science behind why a behavior exists, in my graduate work, I intended to explore how to use something’s behavior to widen its applicability. In this thesis, <em>I will present three works that utilize some of the fundamental</em></p> <p><em>behaviors (i.e., properties) of elastin-like polypeptides (ELP) to improve existing protein purification methods or explore their applicability in bladder cancer imaging and immunotherapy. </em></p> <p>Bladder cancer has high recurrence rates (60-70 % annually) that necessitate multiple follow-up therapies making it one of the costliest cancers per patient. In this work, we have attempted to address two leading causes of the recurrence. First is a low sensitivity (62-84 %) and variable specificity (43-95 %) of white light cystoscopy used to diagnose and remove tumors. We aimed to address the heart of this problem, i.e., the non-specific mode of detection using white light. Only the trained eyes can discern abnormal from normal-appearing tissues even then, leaving up to 45% of tumors unresected to colonize and spread. <em>We developed and characterized near infrared dye-peptide-ligand conjugates (NIR-ELP-ligand) that undergo receptor-mediated binding and internalization to human bladder cancer cells in vitro and tissues ex vivo.</em> By using a molecular target-based probe in combination with NIR imaging, we can aid in improving the detection limit via selective binding to the tumor and reduction in background autofluorescence.</p> <p>Bacillus-Calmette Guérin (BCG) instillation in the bladder is the gold-standard</p> <p>immunotherapy used after surgical removal of bladder tumors. This was approved as a response to the inefficiency of surgery alone in improving cancer status. It has succeeded by reducing the recurrence rate to 30-50 %. But it comes with the complications of putting a live mycobacterium</p> <p>in the human body and giving a patient a urinary tract infection right after surgical tumor resection. <em>Thus, we aimed to deliver nucleic acid as immunotherapeutic cargo in a selective manner to elicit robust anti-tumor immune responses while minimizing the side effects due to its carrier.</em> Towards</p> <p>this goal, we have developed a highly modular and adaptable ELP-ligand fusion protein-based nucleic acid delivery carrier targeted toward bladder cancer. Before developing targeted peptide-based cancer imaging and nucleic acid delivery modalities, we addressed the Achilles heel of peptide-based approaches. The peptide and protein industry suffers</p> <p>through complex, time-consuming, inconsistent, and low-yielding purification methods. <em>We have developed a scalable, facile, and reproducible protein purification method that delivers ELP and ELP fusion proteins free of host cell proteins and nucleic acids and has low lipopolysaccharide</em></p> <p><em>content in just 3 h starting from a bacterial pellet. </em>Thus, for a coherent narrative, the thesis is structured as follows:</p> <p>1. Introduction</p> <p>2. ELP as a protein purification tag: Development of a rapid purification method for ELPs and ELP fusion proteins.</p> <p>3. ELP as a cancer imaging agent: Development of NIR-ELP-Ligand imaging probe targeting bladder cancer.</p> <p>4. ELP as a drug delivery agent: Utilizing ELP-ligand fusion protein in the formulation of targeted nucleic acid delivery carrier to bladder cancer.</p>

Measures of workload have been developed on the basis of the various definitions, some are designed to capture the multi-dimensional aspects of a unitary resource pool (Kahneman, 1973) while others are developed on the basis of multiple resource theory (Wickens, 2002). Although many theory based workload measures exist, others have often been constructed to serve the purpose of specific experimental tasks. As a result, it is likely that not every workload measure is reliable and valid for all tasks, much less each domain. To date, no single measure, systematically tested across experimental tasks, domains, and other measures is considered a universal measure of workload. Most researchers would argue that multiple measures from various categories should be applied to a given task to comprehensively assess workload. The goal for Study 1 to establish task load manipulations for two theoretically different tasks that induce distinct levels of workload assessed by both subjective and performance measures was successful. The results of the subjective responses support standardization and validation of the tasks and demands of that task for investigating workload. After investigating the use of subjective and objective measures of workload to identify a universal and comprehensive measure or set of measures, based on Study 2, it can only be concluded that not one or a set of measures exists. Arguably, it is not to say that one will never be conceived and developed, but at this time, one does not reside in the psychometric catalog. Instead, it appears that a more suitable approach is to customize a set of workload measures based on the task. The novel approach of assessing the sensitivity and comprehensive ability of conjointly utilizing subjective, performance, and physiological workload measures for theoretically different tasks within the same domain contributes to the theory by laying the foundation for improving methodology for researching workload. The applicable contribution of this project is a stepping-stone towards developing complex profiles of workload for use in closed-loop systems, such as human-robot team iv interaction. Identifying the best combination of workload measures enables human factors practitioners, trainers, and task designers to improve methodology and evaluation of system designs, training requirements, and personnel selection