Rozprawy doktorskie na temat „Plasmoidi”

La reconnexion magnétique est une modification de la topologie du champ magnétique, responsable de la libération explosive d'énergie magnétique dans les plasmas astrophysiques, comme dans le cas des orages magnétosphériques et des éjections de masse coronale, ainsi que dans les plasmas de laboratoire, comme dans le cas des crashs en dents de scie dans les tokamaks. Dans les plasmas sans collisions comme, par exemple, la magnétosphère et le vent solaire, l'inertie des électrons devient particulièrement pertinente pour provoquer la reconnexion dans les régions de courant localisé intense, appelées feuilles de courant. Dans ces environnements non collisionnels, la température peut souvent être anisotrope et les effets à l'échelle électronique sur le processus de reconnexion peuvent devenir non négligeables.Dans cette thèse, la stabilité des feuilles de courant bidimensionnelles dans des plasmas sans collisions avec un fort champ guide est analysée sur la base de modèles gyrofluides assumant des ions froids. Ces modèles peuvent prendre en compte une anisotropie de température d'équilibre, et un βe fini. Ce dernier est un paramètre correspondant au rapport entre la pression cinétique électronique d'équilibre et la pression magnétique.Nous dérivons et analysons une relation de dispersion pour le taux de croissance des modes tearing sans collisions tenant compte de l'anisotropie de la température d'équilibre des électrons. Les prédictions analytiques sont testées par des simulations numériques, montrant un très bon accord quantitatif.Dans le cas isotrope, en tenant compte des effets βe finis, nous observons une stabilisation du taux de croissance du mode tearing lorsque les effets du rayon de Larmor fini des électrons deviennent pertinents. Dans la phase non linéaire, des phases de ralentissement et des phases d'accélération sont observées, de manière similaire à ce qui se produit en présence d'effets de rayon de Larmor fini ionique.Nous étudions également les conditions de stabilité marginale des feuilles de courant secondaires, pour le développement de plasmoïdes, dans des plasmas sans collisions. Dans le régime isotrope βe → 0, nous analysons la géométrie qui caractérise le feuillet de courant, et identifions les conditions pour lesquelles elle devient instable à l'instabilité plasmoïde. Notre étude montre que des plasmoïdes peuvent être obtenus, dans ce contexte, à partir de feuille de courants aillant un rapport d'aspect beaucoup plus petit que dans le régime collisionnel. De plus, nous étudions la formation de plasmoïdes en comparant les simulations gyrofluides et gyrocinétiques.Ceci a permis de montrer que l'effet de βe favorise l'instabilité plasmoïde. Enfin, nous étudions l'impact de la fermeture appliquée sur les moments, effectuée lors de la dérivation du modèle gyrofluide, sur la distribution et la conversion de l'énergie lors de la reconnexion
Magnetic reconnection is a change of topology of the magnetic field, responsible for explosive release of magnetic energy in astrophysical plasmas, as in the case of magnetospheric substorms and coronal mass ejections, as well as in laboratory plasmas, which is the case of sawtooth crashes in tokamaks. In collisionless plasmas as, for instance, the magnetosphere and the solar wind, electron inertia becomes particularly relevant to drive reconnection at regions of intense localized current, denoted as current sheets. In these non-collisional environments, the temperature can often be anisotropic and effects at the electron scale on the reconnection process can become non-negligible.In this thesis, the stability of two-dimensional current sheets, with respect to reconnecting perturbations, in collisionless plasmas with a strong guide field is analysed on the basis of gyrofluid models assuming cold ions. These models can take into account an equilibrium temperature anisotropy,and a finite βe, a parameter corresponding to the ratio between equilibrium electron kinetic pressure and magnetic pressure.We derive and analyze a dispersion relation for the growth rate of collisionless tearing modes accounting for equilibrium electron temperature anisotropy. The analytical predictions are tested against numerical simulations, showing a very good quantitative agreement.In the isotropic case, accounting for finite βe effects, we observe a stabilization of the tearing growth rate when electron finite Larmor radius effects become relevant. In the nonlinear phase, stall phases and faster than exponential phases are observed, similarly to what occurs in the presence of ion finite Larmor radius effects.We also investigate the marginal stability conditions of secondary current sheets, for the development of plasmoids, in collisionless plasmas. In the isotropic βe → 0 regime, we analyze the geometry that characterizes the reconnecting current sheet, and identify the conditions for which it is plasmoid unstable. Our study shows that plasmoids can be obtained, in this context, from current sheets with an aspect ratio much smaller than in the collisional regime. Furthermore, we investigate the plasmoid formation comparing gyrofluid and gyrokinetic simulations.This made it possible to show that the effect of finite βe, promotes the plasmoid instability. Finally, we study the impact of the closure applied on the moments, performed during the derivation of the gyrofluid model, on the distribution and conversion of energy during reconnection
La riconnessione magnetica è un cambiamento nella topologia delcampo magnetico, responsabile del rilascio esplosivo di energia magnetica nei plasmiastrofisici, come nelle tempeste magnetosferiche e nelle espulsioni di massa coronale,nonché nei plasmi di laboratorio, come nel caso delle oscillazioni a dente di sega neitokamak. Nei plasmi non-collisionali come, ad esempio, la magnetosfera e il vento solare,l’inerzia elettronica diventa particolarmente efficace nel causare la riconnessionein regioni di corrente intensa e localizzata, detti strati di corrente. In tali plasmi noncollisionali,la temperatura può essere spesso anisotropa e gli effetti su scala elettronicasul processo di riconnessione possono diventare non trascurabili.In questa tesi, viene analizzata la stabilità di strati di corrente bidimensionali inplasmi non-collisionali con un forte campo guida, sulla base di modelli girofluidi cheassumono ioni freddi. Questi modelli possono tenere conto di un’anisotropia di temperaturadi equilibrio e di un βe finito. Quest’ultimo è un parametro corrispondente alrapporto tra la pressione cinetica elettronica di equilibrio e la pressione magnetica.Deriviamo e analizziamo una relazione di dispersione per il tasso di crescita dei moditearing non-collisionali tenendo conto dell’anisotropia della temperatura di equilibriodegli elettroni. Le previsioni analitiche sono verificate mediante simulazioni numeriche,che mostrano un ottimo accordo quantitativo. Nel caso isotropico, tenendoconto degli effetti di βe finito, si osserva una stabilizzazione del tasso di crescita delmodo tearing quando diventano rilevanti gli effetti del raggio finito di Larmor deglielettroni. Nella fase non lineare si osservano fasi di decelerazione e fasi di accelerazione,simili a quanto avviene in presenza di effetti del raggio di Larmor finito ionico.Studiamo anche le condizioni di stabilità marginale degli strati di corrente secondaria,per lo sviluppo di plasmoidi, in plasmi senza collisioni. Nel regime isotropicocon βe → 0, analizziamo la geometria che caratterizza lo strato di corrente e identifichiamole condizioni in cui esso diventa instabile a causa di un’instabilità che generaplasmoidi. Il nostro studio mostra che i plasmoidi possono essere ottenuti, in questocontesto, da strati di corrente aventi un rapporto d’aspetto molto più piccolo rispettoal regime collisionale. Inoltre, studiamo la formazione di plasmoidi confrontando simulazionigirofluidi e girocinetiche. Ciò ha permesso di dimostrare che l’effetto di βe promuove l’instabilità che genera plasmoidi. Infine, si studia l’impatto della chiusuraapplicata ai momenti, eseguita durante la derivazione del modello girofluido, sulla distribuzionee conversione dell’energia durante la riconnessione

Within the framework of an Institutional Partnership of the Alexander von Humboldt Foundation, the Budker Institute of Nuclear Physics Novisibirsk (BINP) and Forschungszentrum Dresden-Rossendorf worked together in a joint project devoted to the research at the coupled GDT-SHIP facility of the BINP with the focus on the study of plasma phenomena within the SHIP mirror section. The project began at July 1st, 2005 and ended on August 30th, 2008. It included work packages of significant theoretical, computational and analyzing investigations. The focus of this final report is on the presentation of results achieved whereas the work that was done is described briefly only. Chapter 2 illustrates the GDT-SHIP facility and describes shortly the planned topics of the SHIP plasma research. Chapter 3 explains the main extensions and modifications of the Integrated Transport Code System (ITCS) which were necessary for the calculations of the fast ion and neutral gas particle fields in SHIP, describes briefly the scheme of computations and presents significant results of pre-calculations from which conclusions were drawn regarding the experimental program of SHIP. In chapter 4, the theoretical and computational investigations of self-organizing processes in two-component plasmas of the GDT-SHIP device are explained and the results hitherto achieved are presented. In chapter 5, significant results of several experiments with moderate and with enhanced plasma parameters are presented and compared with computational results obtained with the ITCS. Preparing neutron measurements which are planned for neutron producing experiments with deuterium injection, Monte Carlo neutron transport calculations with the MCNP code were also carried out. The results are presented. Finally, from the results obtained within the joint research project important conclusions are drawn in chapter 6.

Within the framework of an Institutional Partnership of the Alexander von Humboldt Foundation, the Budker Institute of Nuclear Physics Novisibirsk (BINP) and Forschungszentrum Dresden-Rossendorf worked together in a joint project devoted to the research at the coupled GDT-SHIP facility of the BINP with the focus on the study of plasma phenomena within the SHIP mirror section. The project began at July 1st, 2005 and ended on August 30th, 2008. It included work packages of significant theoretical, computational and analyzing investigations. The focus of this final report is on the presentation of results achieved whereas the work that was done is described briefly only. Chapter 2 illustrates the GDT-SHIP facility and describes shortly the planned topics of the SHIP plasma research. Chapter 3 explains the main extensions and modifications of the Integrated Transport Code System (ITCS) which were necessary for the calculations of the fast ion and neutral gas particle fields in SHIP, describes briefly the scheme of computations and presents significant results of pre-calculations from which conclusions were drawn regarding the experimental program of SHIP. In chapter 4, the theoretical and computational investigations of self-organizing processes in two-component plasmas of the GDT-SHIP device are explained and the results hitherto achieved are presented. In chapter 5, significant results of several experiments with moderate and with enhanced plasma parameters are presented and compared with computational results obtained with the ITCS. Preparing neutron measurements which are planned for neutron producing experiments with deuterium injection, Monte Carlo neutron transport calculations with the MCNP code were also carried out. The results are presented. Finally, from the results obtained within the joint research project important conclusions are drawn in chapter 6.

La couronne solaire est le lieu de phenomenes encore inexpliques. Des nuages de plasma se deplacent en son sein. Ces nuages sont aussi appeles plasmoides. Dans mon travail de these, j'ai analyse trois observations de plasmoides. Chacune presente des resultats originaux. Les plasmoides sont plus denses, plus froids et plus magnetises que la couronne ambiante. Leur vitesses varient de 20 km s#-#1 a 150 km s#-#1. Leur dynamique est tres particuliere. Pour l'expliquer, j'ai determine les forces agissant sur ces nuages. L'interaction des nuages avec la couronne est non collisionnelle et est dominee par le champ magnetique. La mhd ideale est applicable. Le champ magnetique interne au plasmoide est modelise par celui cree par un dipole situe en son centre de masse. J'ai calcule le mouvement de ce dipole dans le champ magnetique coronal. Ce modele permet d'expliquer en partie les resultats obtenus lors des observations. Ce travail montre que les plasmoides sont frequemment emis dans la couronne et qu'il peuvent participer a l'initiation du vent solaire.

Kyoto University (京都大学)
0048
新制・課程博士
博士(理学)
甲第12104号
理博第2998号
新制||理||1447(附属図書館)
23940
UT51-2006-J99
京都大学大学院理学研究科物理学・宇宙物理学専攻
(主査)教授 柴田 一成, 助教授 岩室 史英, 教授 長田 哲也
学位規則第4条第1項該当

Sinusoidally patterned metallic surfaces, known as plasmonic gratings, constitute one of the principal structures which allow to achieve the coupling between an incident light beam and a Surface Plasmon Polariton mode. A variety of phenomena are available when the grating is rotated of an azimuthal angle with respect to the incidence plane. Aim of this work is a comprehensive investigation of the propagation properties of the surface mode under this configuration, correlating the role of the anisotropy introduced by the grating to the position and shape of the plasmonic resonance dip in the reflectance spectra. Analytical models and physical interpretations are provided; both experimental and computational means are exploited in order to validate the models, including the observation of innovative effects. Thin-film coupled modes, the Long Range and Short Range Surface Plasmon Polaritons, are studied and experimentally observed in the azimuthally rotated configuration. Special attention is paid to the role of the plasmon radiative losses, due to the scattering by the grating. Their dependence on the grating amplitude and the plasmon propagation direction is unraveled, and correlated to the width of the observed plasmonic resonances. The outcomes of these analyses lead to the evaluation of the sensitivity and Figure of Merit achievable when the considered configurations are exploited in the framework of Surface Plasmon Resonance sensing. The developed concepts and methods are proved to be valuable tools to predict and understand the response of actual plasmonic structures applied as sensing devices against gaseous analytes. Experimental tests of the plasmonic platforms as TNT, hydrogen and aromatic compounds sensors are reported, giving promising results. A particularly remarkable experiment is the combined exploitation of Long Range modes and azimuthally rotated configuration to sensibly enhance the performance of a xylene sensor
Superfici metalliche con modulazione sinusoidale, note come grating plasmonici, costituiscono una delle principali strutture che permettono di ottenere l’accoppiamento tra un fascio di luce incidente e un Plasmone Polaritone di Superficie. Una varietà di fenomeni sono accessibili quando il grating viene ruotato di un angolo azimutale rispetto al piano di incidenza. Scopo di questo lavoro è uno studio approfondito delle proprietà di propagazione del modo di superficie in questa configurazione, correlando il ruolo dell’anisotropia introdotta dal grating con la posizione e forma del dip di risonanza plasmonica negli spettri in riflettanza. Vengono presentati modelli analitici e interpretazioni fisiche; metodi sia sperimentali che computazionali vengono impiegati per validare i modelli, includendo l’osservazione di nuovi effetti. I modi accoppiati di film sottile, ovvero i Plasmoni Long Range e Short Range, vengono studiati e osservati sperimentalmente nella configurazione ad azimuth ruotato. Una particolare attenzione è dedicata al ruolo delle perdite radiative del plasmone, dovute allo scattering da parte del grating. La loro dipendenza dall’ampiezza del grating e dalla direzione di propagazione del plasmone è spiegata, e correlata con la larghezza delle risonanze plasmoniche osservabili. I risultati di queste analisi conducono alla valutazione delle sensibilità e Figura di Merito che si possono ottenere quando le configurazioni considerate sono sfruttate nell’ambito della sensoristica a Risonanza Plasmonica di Superficie. I concetti e metodi sviluppati si dimostrano strumenti di valore per predire e interpretare la risposta di strutture plasmoniche reali, applicate come dispositivi di sensing verso analiti allo stato gassoso. Le piattaforme plasmoniche vengono testate come sensori per TNT, idrogeno e composti aromatici, con risultati promettenti. Un esperimento particolarmente interessante è l’uso combinato dei modi Long Range e della configurazione ad azimuth ruotato per incrementare notevolmente le performance di un sensore di xylene

The control of gene expression by rearrangement of DNA sequences, in prokaryotes and eukaryotes, is recorded in several instances. These accompany the differentiation of cells, yielding a new phenotype. The possibility of such a means of gene control operating in Physarum was considered; this organism undergoes marked changes in cell morphology and function during the amoebal-plasmodial transition. Genes activated or inactivated in this transition were examined for possible changes in structure. This was done by using amoebal- and plasmodial-specific cDNAs to probe Southern blots of amoebal and plasmodial DNA, digested with restriction endonucleases. This procedure should have revealed any restriction enzyme polymorphisms that might have existed between amoebae and plasmodia as a result of DNA rearrangements. However, no changes in DNA structure were observed between amoebae and plasmodia. The scope of this investigation is critically assessed. The methylation of cytosine residues has also been proposed as a means of controlling gene expression in eukaryotes. The available amoebal- and plasmodial-specific cDNAs were used therefore to probe Southern blots of amoebal and plasmodial DNA digested with methylation sensitive and insensitive restriction enzymes, in order to examine the methylation patterns of DNA from the two forms. For all phase-specific genes tested, the patterns in amoebae and plasmodia were identical, suggesting that no changes had occurred. Again, the scope of this investigation is assessed, and the possibility of a more extensive search for putative DNA rearrangements or changes in methylation pattern is mooted. To study closely the structure of three plasmodial-specific genes, attempts were made to clone regions of Physarum genomic DNA containing these sequences. It was not possible to isolate positive clones in any useful quantity. The probable reasons for the difficulties encountered are discussed.

Isolement d'une cysteine proteinase de p. Falciparum et elaboration, a l'aide de substrats specifiques, d'inhibiteurs irreversibles et reversibles de cette enzyme. Determination in vitro de l'activite antipaludique de ces inhibiteurs peptidiques ainsi que des prodrogues

Lo scopo della presente tesi, svolta presso il Laboratorio LAPLACE di Tolosa, è quello di indagare sulle proprietà ottiche di campioni composti da un substrato di materiale polimerico (bi-axially oriented polyprophilene, BOPP) ricoperto con diversi tipi di elettrodi principalmente tramite misure di elettroluminescenza e di comprendere come queste siano legate al suo deterioramento e invecchiamento Nella prima parte della tesi, verranno illustrate le misure effettuate su due diverse strutture MIM (metal-insulator-metal), la prima ottenuta utilizzando oro e la seconda utilizzando ITO come elettrodi. Nella seconda parte, invece, le misure sono state effettuate su campioni multistrato contenenti nano compositi a base di argento, ricoperte con uno strato di ITO che fungerà da elettrodo. Le misure sulla prima tipologia di campioni hanno evidenziato la presenza di due componenti principali nelle emissioni dovute a elettroluminescenza, una prodotta dal materiale bulk (BOPP) e una scaturita dall’interazione tra il substrato e l’elettrodo metallico, grazie al coinvolgimento dei plasmoni di superficie. Lo scopo della seconda parte della tesi è quello di comprendere l’effetto che le particelle di argento potrebbero avere sui plasmoni superficiali e sulle emissioni luminose dovute a elettroluminescenza. I risultati ottenuti su questi campioni hanno evidenziato un livello di luce prodotto da elettroluminescenza incredibilmente maggiore rispetto ai campioni aventi ITO e oro come elettrodi. In conclusione l’impatto delle nano particelle di argento sulle emissioni per elettroluminescenza da BOPP possono essere molteplici e saranno necessari ulteriori studi per comprendere in modo dettagliato tale meccanismo. L’effetto mostrato qui potrebbe risultare molto utile per capire meglio l’elettroluminescenza nei materiali polimerici isolanti da un lato e dall’altro le proprietà foto-fisiche delle nanoparticelle metalliche.

Les differentes signatures des sous-orages causes par des populations variees de plasma qui constituent la magnetosphere sont etudiees statistiquement. Les decroissances transitoires des flux de particules associes a ces sous-orages sont interpretees en terme d'amincissement de la couche de plasma. Des correlations avec le phenomene d'injection de particules energetiques dans la partie interne de la magnetosphere cote nuit sont mises en evidence. Ceci permet de developper un modele decrivant le processus physique responsable a la fois des amincissements et des injections

Malaria is a critical and global public health problem, affecting over 200 million people every year, resulting in over 500,000 deaths. A vaccine is not currently available and only one drug, primaquine, is effective against the dormant stages of Plasmodium vivax. Preclinical assessment of novel therapeutic drugs and vaccines is hampered by the lack of an in vitro liver model for P. falciparum and P. vivax. To provide a stable human hepatocyte-based culture platform for parasite development, we engineered a microfluidic bilayer device capable of both simple and complex culture methods, including perfusion and co-culture, to better understand the requirements of both hepatocytes as host cells and parasite liver stage development. As only the mechanical compaction of the device channels was found necessary for stable hepatocyte culture, and only a validated host cell lot was found necessary for improved parasite development rates, we present an efficient and simple Plasmodium liver model capable of supporting P. vivax dormant forms. Device liver platforms were used to generate kill curves of P. vivax and P. falciparum after three days under primaquine drug pressure. Furthermore, an anti-CSP antibody-based inhibition of development assay with P. falciparum successfully demonstrated antibody-specific liver stage inhibition. Ongoing studies aim to identify the minimal unit of the culture system necessary to be multiplexed in a fully functional and efficient drug and vaccine discovery platform.

Questo lavoro ha l’obbiettivo di analizzare i principi che stanno alla base della plasmonica, partendo dallo studio dei plasmoni di superficie fino ad arrivare alle loro applicazioni. La prima parte di questa tesi riguarda l’aspetto teorico. Essendo essenzialmente eccitazioni collettive degli elettroni nell'interfaccia fra un conduttore ed un isolante, descritti da onde elettromagnetiche evanescenti, questi plasmoni superficiali, o polaritoni plasmonici di superficie (SPP), vengono studiati partendo dalle equazioni di Maxwell. Viene spiegato come questi SPP nascano dall’accoppiamento dei campi elettromagnetici con le oscillazioni degli elettroni del materiale conduttore e, utilizzando l’equazione dell’onda, si descrivono le loro proprietà in singola interfaccia e in sistemi multistrato. Il quinto capitolo analizza le metodologie di eccitazione di SPP. Sono descritte varie tecniche per l’accoppiamento di fase, per accennare poi a eccitazioni di SPP in guide d’onda, tramite fibra ottica. L’ultimo capitolo della prima parte è dedicato alla seconda tipologia di plasmoni: i plasmoni di superficie localizzati (LSP). Questi sono eccitazioni a seguito dell’accoppiamento fra elettroni di conduzione di nanoparticelle metalliche e il campo elettromagnetico ma che, a differenza dei SPP, non si propagano. Viene esplorata la fisica dei LSP trattando prima le interazioni delle nanoparticelle con le onde elettromagnetiche, poi descrivendo i processi di risonanza in una varietà di particelle differenti in numero, forma, dimensione e ambiente di appartenenza. La seconda parte della tesi riguarda invece alcune applicazioni. Vengono proposti esempi di controllo della propagazione di SPP nel contesto delle guide d’onda, analizzando l’indirizzamento di SPP su superfici planari e spiegando come le guide d’onda di nanoparticelle metalliche possano essere utilizzate per trasferire energia. Infine, viene introdotta la teoria di Mie per la diffusione e l’assorbimento della luce da parte di nanoparticelle metalliche, per quanto riguarda la colorazione apparente, con esempi sulla colorazione vitrea, come la famosa coppa di Licurgo.

Master of Science
Statistics
Nora M. Bello
Big bluestem (Andropogon gerardii) is a wide-ranging dominant prairie grass of ecological and agricultural importance to the US Midwest while edaphic subspecies sand bluestem (A. gerardii ssp. Hallii) grows exclusively on sand dunes. Sand bluestem exhibits phenotypic divergence related to epicuticular properties and enhanced drought tolerance relative to big bluestem. Understanding the mechanisms underlying differential drought tolerance is relevant in the face of climate change. For bluestem subspecies, presence or absence of these phenotypes may be associated with RNA transcripts characterized by low number of read counts. So called low-count transcripts pose particular inferential challenges and are thus usually filtered out at early steps of data management protocols and ignored for analyses. In this study, we use a plasmode-based approach to assess the relative performance of alternative inferential strategies on RNA-seq transcripts, with special emphasis on low-count transcripts as motivated by differential bluestem phenotypes. Our dataset consists of RNA-seq read counts for 25,582 transcripts (60% of which are classified as low-count) collected from leaf tissue of 4 individual plants of big bluestem and 4 of sand bluestem. We also compare alternative ad-hoc data filtering techniques commonly used in RNA-seq pipelines and assess the performance of recently developed statistical methods for differential expression (DE) analysis, namely DESeq2 and edgeR robust. These methods attempt to overcome the inherently noisy behavior of low-count transcripts by either shrinkage or differential weighting of observations, respectively. Our results indicate that proper specification of DE methods can remove the need for ad- hoc data filtering at arbitrary expression threshold, thus allowing for inference on low-count transcripts. Practical recommendations for inference are provided when low-count RNA-seq transcripts are of interest, as is the case in the comparison of subspecies of bluestem grasses. Insights from this study may also be relevant to other applications also focused on transcripts of low expression levels.

Background: Knee osteoarthritis (OA) is the most common type of OA and is a major cause of pain and thus results in disability for daily activities among persons living in the community. OA currently has no cure. In addition to the conflicting recommendations from clinical guidelines, evidence about the extent to which long-term use of intra-articular injections improves patient outcomes is also lacking. Methods: Using data from the Osteoarthritis Initiative (OAI), marginal structural models (MSMs) applying inverse probability treatment weights (IPTW) were used to examine the effectiveness of intra-articular injections and changes in symptoms over time. The specific aims of this dissertation were to: 1) evaluate longitudinal use of intra-articular injections after treatment initiation among persons with radiographic knee OA; 2) quantify the extent to which intra-articular injection relieves symptoms among persons with radiographic knee OA; and 3) evaluate the performance of missing data techniques under the setting of MSMs. Results: Of those initiating injections, ~19% switched, ~21% continued injection type, and ~60% did not report any additional injections. For participants initiating corticosteroid (CO) injections, greater symptoms post-initial injection rather than changes in symptoms over time were associated with continued use compared to one-time use. Among participants with radiographic evidence of knee OA, initiating treatments with either CO or hyaluronic acid (HA) injections was not associated with reduced symptoms compared to non-users over two years. Compared to inverse probability weighting (IPW), missing data techniques such as multiple imputation (MI) produced less biased marginal causal effects (IPW: -2.33% to 15.74%; -1.88% to 4.24%). For most scenarios, estimates using MI had smaller mean square error (range: 0.013 to 0.024) than IPW (range: 0.027 to 0.22). Conclusions: Among participants with radiographic evidence of knee OA living in the community, the proportion of those switching injection use and one-time users was substantial after treatment initiation. In addition, initiating injection use was not associated with reduced symptoms over time. With respect to issues of missing data, using MI may confer an advantage over IPW in MSMs applications. The results of this work highlight the importance of using comparative effectiveness research with non-experimental data to study these commonly used injections and may help to understand the usefulness of these treatments for patients with knee OA.

Background: Knee osteoarthritis (OA) is the most common type of OA and is a major cause of pain and thus results in disability for daily activities among persons living in the community. OA currently has no cure. In addition to the conflicting recommendations from clinical guidelines, evidence about the extent to which long-term use of intra-articular injections improves patient outcomes is also lacking. Methods: Using data from the Osteoarthritis Initiative (OAI), marginal structural models (MSMs) applying inverse probability treatment weights (IPTW) were used to examine the effectiveness of intra-articular injections and changes in symptoms over time. The specific aims of this dissertation were to: 1) evaluate longitudinal use of intra-articular injections after treatment initiation among persons with radiographic knee OA; 2) quantify the extent to which intra-articular injection relieves symptoms among persons with radiographic knee OA; and 3) evaluate the performance of missing data techniques under the setting of MSMs. Results: Of those initiating injections, ~19% switched, ~21% continued injection type, and ~60% did not report any additional injections. For participants initiating corticosteroid (CO) injections, greater symptoms post-initial injection rather than changes in symptoms over time were associated with continued use compared to one-time use. Among participants with radiographic evidence of knee OA, initiating treatments with either CO or hyaluronic acid (HA) injections was not associated with reduced symptoms compared to non-users over two years. Compared to inverse probability weighting (IPW), missing data techniques such as multiple imputation (MI) produced less biased marginal causal effects (IPW: -2.33% to 15.74%; -1.88% to 4.24%). For most scenarios, estimates using MI had smaller mean square error (range: 0.013 to 0.024) than IPW (range: 0.027 to 0.22). Conclusions: Among participants with radiographic evidence of knee OA living in the community, the proportion of those switching injection use and one-time users was substantial after treatment initiation. In addition, initiating injection use was not associated with reduced symptoms over time. With respect to issues of missing data, using MI may confer an advantage over IPW in MSMs applications. The results of this work highlight the importance of using comparative effectiveness research with non-experimental data to study these commonly used injections and may help to understand the usefulness of these treatments for patients with knee OA.

Dalla scoperta del grafene, molte ricerche sono state condotte sui cosiddetti “materiali 2D”. Questo elaborato si focalizza sulle proprietà strutturali, elettroniche, ottiche ed eccitoniche di due materiali bidimensionali, ossia il grafene il disolfuro di molibdeno (MoS2-1H), quest’ultimo un importante semiconduttore. Le proprietà di questi materiali sono diverse rispetto alla loro controparte massiva (bulk) grafite e MoS2-2H, e un loro confronto è stato preso in considerazione. Come metodo di indagine sono state scelte simulazioni quanto- meccaniche ab initio dei sistemi in esame, un approccio che, negli ultimi decenni, sta avendo un impatto sempre più importante sulla fisica, sulla chimica dello stato solido e sulla scienza dei materiali, promuovendo non solo una comprensione più profonda, ma anche la possibilità di contribuire in modo significativo alla progettazione di materiali per nuove tecnologie. Questo importante passo avanti è stato possibile grazie a: (i) una descrizione migliorata ed efficiente degli effetti elettronici a molti corpi (many-body) nella teoria del funzionale della densità (DFT), nonché lo sviluppo di metodi post-DFT per lo studio di proprietà specifiche; (ii) un’accurata implementazione di questi metodi in software altamente efficienti, stabili e versatili, capaci di sfruttare il potenziale delle architetture informatiche moderne. Tra i possibili software ab initio basati su DFT, abbiamo scelto il pacchetto di simulazione di Vienna ab initio VASP, considerato un gold standard per questo tipo di indagini. I risultati ottenuti per le varie proprietà di bulk e di superficie (bidimensionale) dei materiali scelti sono in ottimo accordo con dati ottenuti in precedenza, sia a livello teorico, sia sperimentale. Questo elaborato getta quindi le basi per futuri studi nel campo dei materiali 2D per comprendere, analizzare, ingegnerizzare nuovi materiali con proprietà desiderabili e per sviluppare nuove applicazioni degli stessi.

The interest for plasmonic nanolasers has been growing in the last ten years, since they are one of the most promising ways to reach the miniaturization of lasers. In fact, these devices could break the limit of physical confinement of light thanks to the virtual cavity given by plasmonic nanostructures which substitutes the current macroscopic optical cavities. These plasmonic devices can also support high speed operation mode, low lasing threshold and a narrow directional emission. For this reason, during this project, we focused on the design, the synthesis and the characterization of plasmonic nanolasers based on Au nanodome arrays and Ag nanodisk arrays. In order to synthesize highly ordered nanostructure arrays, we used Nanosphere Lithography (NSL), which is a cost effective and high throughput technique based on the self-assembling of polystyrene nanospheres. Thanks to the versatility of NSL, we have developed different nanofabrication protocols, combining NSL with Reactive Ion Etching (RIE) and Physical Vapor Deposition (PVD). Therefore, we investigated the optical properties of our synthesized arrays, recreating the optical band structure along the high symmetry directions of the reciprocal space. Suitable dye emitters (Pyridine 2 and Styryl 9M) were selected in order to couple their emission with the optical modes of the nanoarrays, on the basis of optical band structure information. In addition, in order to optimize the plasmonic properties and the local field enhancement of the metallic nanostructures, numerical simulations by COMSOL Multiphysics were performed. The interaction between dye and plasmonic structure generated an amplified emission. In particular, for Au nanodome arrays coupled with Pyridine 2 dissolved in ethanol, an amplification on the emission arises at 720 nm with a threshold behavior at 0.9 mJ/cm^2 and the FWHM of 14 nm. Furthermore, a highly directional emission was obtained at 17° with an angular divergence of 3° which takes place along the Rayleigh anomaly mode. By comparing the results of Au nanodome arrays and silica nanodome arrays, we concluded that lattice modes give a contribution to the emission directionality, while plasmonic modes provide a reduced lasing threshold overcoming the energy loss. Ag hexagonal nanodisk array showed a similar behavior to the Au nanodome arrays: we found a lasing threshold at 1.6 mJ/cm^2 , with also a similar FWHM. In this case, the emission is directed at 65° and presents an angular divergence of about 14° . Moreover, we investigated a nanolaser with a solid-state gain medium for the interest in applications and for the device integration on a chip. The Styryl 9M laser dye is embedded in a PMMA film and coupled with an Au nanodome array. This solid-state system presents an amplified emission at 795 nm with a threshold of 1.2 mJ/cm^2 and a FWHM of about 26 nm. The sample shows also a directional emission at 24° and with an angular divergence of 6° . Further investigations have shown the possibility to eliminate the substrate, creating a self-standing device, which exhibits an amplified emission with similar properties of that with the substrate. Finally, in order to discern the spontaneous or stimulated nature of the emission, we performed coherence measurements of the emitted beam. By a modified Michelson interferometer, a coherence length of about 29 um was determined for Au nanodome arrays above threshold. This result demonstrated that a coherent, low-threshold and highly directional emission can be obtained by coupling a suitable fluorescent dye to a properly designed virtual cavity realized by an ordered array of plasmonic nanostructures.
Nell'ultima decina di anni, l'interesse per i nanolaser plasmonici è cresciuto siccome sono uno tra i modi più promettenti per la miniaturizzazione dei laser. Infatti, questi dispositivi possono superare il limite di confinamento fisico della luce, grazie alla cavità virtuale data dalle nanostrutture plasmoniche che sostituiscono la convenzionale cavità ottica macroscopica. Inoltre, questi dispositivi plasmonici possono supportare modalità di funzionamento ad alta velocità, bassa soglia di emissione laser e una direzionalità ben definita. Per questa ragione, durante questo progetto, ci siamo concentrati sulla progettazione, la sintesi e la caratterizzazione di nanolasers plasmonici basati su array di nanocupole di oro e array di nanodischi di argento. Al fine di sintetizzare reticoli di nanoparticelle con un ordine elevato, abbiamo utilizzato la Nanosphere Lithography (NSL), una tecnica economica e ad alta produttività basata sull'autoassemblaggio di nanosfere di polistirene. Grazie alla versatilità della NSL, abbiamo sviluppato diversi protocolli di nanofabbricazione, combinando la NSL con i processi di Reactive Ion Etching (RIE) e deposizione fisica da vapore (PVD). Successivamente, abbiamo studiato le proprietà ottiche dei campioni sintetizzati, ricostruendo la struttura a bande ottica lungo le direzioni di alta simmetria dello spazio reciproco. Abbiamo selezionato due adeguati emettitori coloranti, la Pyridine 2 e lo Styryl 9M, al fine di accoppiare la loro emissione con le modalità ottiche dei reticoli nanostrutturati, sulla base delle informazioni della struttura a bande ottica. Inoltre, per ottimizzare le proprietà plasmoniche e l'amplificazione del campo locale delle nanostrutture metalliche, delle simulazioni numeriche sono state effettuate tramite il software COMSOL Multiphysics. L'interazione tra il colorante e la struttura plasmonica ha generato un'emissione amplificata. In particolare, nel reticolo di nanocupole di oro accoppiato alla piridina 2 disciolta in etanolo, un'amplificazione dell'emissione si presenta a720nm con un comportamento a soglia a 0.9 mJ/cm^2 . Inoltre, è stata ottenuta un'emissione direzionale a 17° con una divergenza angolare di 3° che avviene lungo l'anomalia di Rayleigh. Confrontando i risultati dei reticoli di nanocupole di oro con quelli dei reticoli di nanocupole di silice, abbiamo concluso che i modi di reticolo danno un contributo alla direzionalità dell'emissione, mentre i modi plasmonici forniscono una riduzione della soglia laser superando così la perdita di energia. Il reticolo esagonale di nanodischi di argento mostra un comportamento simile a quello con le nanocupole di oro: abbiamo trovato una soglia laser a 1.6 mJ/cm^2 , con anche una simile FWHM. In questo caso, questo fascio è diretto a 65° e presenta una divergenza angolare di circa 14° . Inoltre, abbiamo studiato anche un nanolaser con un mezzo di guadagno a stato solido per l'interesse nelle applicazioni e nell'integrazione di dispositivi su chip. Il colorante laser Styryl 9M è incorporato in un film di PMMA e accoppiato con un reticolo di nanocupole di oro. Questo sistema a stato solido presenta un'emissione amplificata a 795 nm con una soglia di 1.2 mJ/cm^2 e una FWHM di circa 26 nm. Questo campione manifesta anche un'emissione direzionale a 24° con una divergenza angolare di 6° . Ulteriori ricerche hanno dimostrato la possibilità di eliminare il substrato, creando un dispositivo autoportante, che presenta un'emissione amplificata con proprietà simili a quella con il substrato. Infine, per discernere la natura spontanea o stimolata dell'emissione, abbiamo misurato la coerenza del raggio emesso. Tramite un interferometro di Michelson dedicato, la lunghezza di coerenza è stimata a circa 29 um per i reticoli di nanocupole d'oro sopra la soglia. Questo risultato ha dimostrato che è possibile ottenere un'emissione coerente, a bassa soglia e altamente direzionale, accoppiando un colorante fluorescente adeguato con una cavità virtuale opportunamente progettata e realizzata da una reticolo ordinato di nanostrutture plasmoniche.

In questa tesi ho discusso sulle caratteristiche delle antenne per le teleco- municazioni partendo dal punto di vista storico, fino a riportare i recenti sviluppi nell’ambito delle più innovative ricerche sulle nanoantenne pla- smoniche. Nel primo capitolo è riportata una breve trattazione storica dell’anten- na, dalla scoperta del loro funzionamento, descrivendone il primo uso in ambito delle telecomunicazioni presentato da Marconi per la prima co- municazione transatlantica. Nel secondo capitolo vengono confrontate le antenne, in termini di strut- tura, caratteristiche fisiche e differenti tipologie, in modo da capire il per- chè conviene usare un tipo di antenna rispetto ad un’altra, presentando un confronto con le nanoantenne. Nel terzo capitolo, è descritta la teoria delle risonanze plasmoniche di nanoparticelle metalliche e i cambi delle proprietà tra le antenne e le na- noantenne. Infine vengono spiegati gli usi delle nanoantenne per svaria- te applicazioni, dall’uso per la spettroscopia ad usarle per dispositivi di emissione di luce.

博士
國立中央大學
太空科學研究所
99
Prominence/filament eruptions and coronal mass ejections (CMEs) usually show an initial acceleration followed by a nearly constant propagation speed. Concerning about solar flares, it is a local feature in comparison with global feature of the initiation of CME. The magnetic reconnection rate deduced from the foot point motions of the solar flares and the magnetic field component normal to the solar surface and the acceleration of filament/CME show a good temporal correlation [Zhang et al., 2001; 2004; Qiu et al., 2004; Jing et al., 2005]. In this thesis, a two-dimensional resistive magnetohydrodynamic (MHD) simulation is carried out to study (1) the time evolution of the magnetic reconnection and its relation to the acceleration of plasma flow, (2) the forces that lead to the acceleration of the plasma and the plasmoid, and (3) the rate of magnetic flux variation effects on the reconnection rate. Our results show that the fast flows are not limited to the direction perpendicular to the local magnetic field. The fast parallel flows are accelerated by the parallel component of the pressure gradient force. The net force perpendicular to the magnetic field can accelerate the plasma and the plasmoid along the current sheet. The acceleration of the plasmoid is also controlled by the mass contained in the plasmoid. We found that the magnetic reconnection in MHD plasma is due to the non-uniform magnetic annihilation rate along the current sheet. The reconnection/reconfiguration site does not necessary stay at the neutral point. It can move with the Y-line next to the bifurcated current sheets. We also found that the fast ejection of the plasmoid can stretch the current sheet and consequently reduce the magnetic reconnection/reconfiguration rate temporally before a new plasmoid is formed. A mutual coupling theory of magnetic reconnection and acceleration of plasmoid is proposed: the magnetic tension force resulting from the magnetic reconnection will lead to the acceleration of plasmoid; however, the acceleration of plasmoid can stretch the current sheet and reduce the magnetic reconnection rate. But the stretched thin current sheet is favorable for the formations of small scale plasmoids. We also found that the speed of the plasmoid increases with decreasing the size of the plasmoid.

**English** Plasmonic particles such as gold nanorods (GNRs) are showing themselves as powerful contrast agents for important applications such as photoacoustic imaging and photothermal ablation of cancer. However, their unique photothermal conversion efficiency can turn into a practical disadvantage, and expose them to the risk of overheating and irreversible photodamage. The processes of prefusion and remodeling of GNRs under illumination with optical pulses of typical duration of the order of a few ns will be studied in depth. A retrospective classification of these approaches will be undertaken according to often implicit principles, such as: constraining the initial shape, speeding up their thermal coupling with the environment by lowering their thermal resistance at the interface, or redistributing the incoming energy among several particles. Advantages and disadvantages and contexts of practical interest in which one solution may be more appropriate than the other will be discussed. Stabilization of the optical properties of anisotropic plasmonic particles by thermal heating and laser irradiation is an important issue in many biomedical applications. The effect that small thiols have on the thermal photostability of gold nanorods will be addressed. The nanoparticles were treated with mixtures of poly-ethylene-glycol thiolate (PEG-SH) and methyl-benzene-thiol (MBT) with molar ratios ranging from 0 (for the case of pure PEG) to 20, and then incubated in an oven. under sub-boiling conditions. Small thiols have been found to greatly improve the thermal stability of GNRs. For example, after 1 hour at 90 °C the samples with pure PEG lost more than 70% of the optical absorbance in their initial peak position, while the particles covered with a dense layer of MBT remained almost unchanged. It is possible to attribute this effect to a modulation of the activation barrier for the superficial diffusion of the gold atoms. Furthermore, we addressed the translation of this effect on the photostability of irradiated gold nanorods under conditions of interest for photoacoustic imaging and it was found that small thiols delay the damage thresholds by up to a factor of 2. In this work of thesis also describes the effect of the thermal resistance at the gold-water interface (Kapitza resistance) on the photoacoustic conversion performance of gold nanorods. The results indicate possible strategies for optimizing plasmonic particles as contrast agents for imaging, or even as transducers for biosensors. An effective approach is also suggested to modulate the Kapitza resistance by including features not yet well studied such as roughness or the presence of adsorbates. Following this idea, a rough variant of gold nanorods was synthesized by galvanic deposition and replacement of a silver shell, where roughness provides photoacoustic signals approximately 70% higher and damage thresholds of 120%. Furthermore, the particles were coated with a protein crown, which brings about a decrease in photoacoustic signals as the thickness of the shell increases; this could inspire new solutions for biosensors based on a photoacoustic transduction mechanism. Both of these results are consistent with effective modulation of Kapitza resistance, which can decrease with roughening, due to an increase in specific surface area, and can increase with the introduction of a protein coating (which can act as insulation thermal). Hybrid materials consisting of core/shell Au/Ag nanorods have also been developed, included in porous biomimetic phantoms (scaffolds) of chitosan/polyvinyl alcohol (chitosan/PVA) for applications in tissue engineering and wound healing. The combination of Au and Ag in a single construct provides synergistic opportunities for optical activation of functions such as near-infrared laser tissue welding and remote interrogation for the acquisition of prognostically relevant parameters in monitoring wound healing. In particular, the bimetallic component ensures improved optical tunability, shelf life and photothermal stability, acts as a reservoir for germicidal silver cations. At the same time, the polymer blend is ideal for bonding to connective tissue following photothermal activation and for supporting manufacturing processes that provide high porosity, such as electro-spinning, thus setting all the conditions for cell repopulation and antimicrobial protection. In summary, in this work, the optimization of an important system such as GNRs for complementary applications in different biomedical fields has been addressed; their stability and photoacoustic conversion efficiency have been optimized for use as contrast agents optical, developing functional coatings with small organic molecules or with metal porous layers. Finally, the integration of Au/Ag bimetallic nanorods into hybrid scaffolds for tissue engineering was evaluated, exploiting both the photothermal conversion efficiency and the optical sensitivity to oxidative stress conditions, in order to activate processes and monitor parameters of interest in scope of wound healing. **Italiano** Le particelle plasmoniche come i nanorods d'oro (GNRs) si stanno mostrando potenti agenti di contrasto per applicazioni importanti come l'imaging fotoacustico e l'ablazione fototermica del cancro. Però, la loro efficienza unica di conversione fototermica può trasformarsi in uno svantaggio pratico, e esporli al rischio di surriscaldamento e fotodanneggiamento irreversibile. Verranno approfonditi i processi di prefusione e rimodellazione dei GNRs sotto illuminazione con impulsi ottici di durata tipica dell'ordine di pochi ns. Verrà intrapresa una classificazione retrospettiva di tali approcci secondo principi spesso impliciti, come: vincolare la forma iniziale, velocizzare il loro accoppiamento termico con l'ambiente abbassando la loro resistenza termica all'interfaccia, oppure ridistribuire l'energia in ingresso tra più particelle. Saranno discussi vantaggi e svantaggi e contesti di interesse pratico in cui una soluzione può essere più appropriata dell'altra. La stabilizzazione delle proprietà ottiche delle particelle plasmoniche anisotrope tramite riscaldamento termico e irradiazione laser è una questione importante in molte applicazioni biomediche. Verrà affrontato l'effetto che piccoli tioli hanno sulla fotostabilità termica dei nanorods d'oro. Le nanoparticelle sono state trattate con miscele di poli-etilen-glicole tiolato (PEG-SH) e metil-benzen-tiolo (MBT) con rapporti molari compresi tra 0 (per il caso del PEG puro) e 20, e poi incubati in stufa in condizioni di sub-ebollizione. È stato scoperto che i piccoli tioli migliorano notevolmente la stabilità termica dei GNRs. Ad esempio, dopo 1 ora a 90 °C i campioni con PEG puro hanno perso più del 70% dell'assorbanza ottica nella loro posizione di picco iniziale, mentre le particelle ricoperte di un denso strato di MBT sono rimaste pressoché invariate. È possibile attribuire questo effetto ad una modulazione della barriera di attivazione per la diffusione superficiale degli atomi d'oro. Inoltre, abbiamo affrontato la traduzione di questo effetto sulla fotostabilità dei nanorods d'oro irradiati in condizioni di interesse per l'imaging fotoacustico ed è stato scoperto che i piccoli tioli ritardano le soglie di danneggiamento fino a un fattore di 2. In questo lavoro di tesi viene descritto inoltre l'effetto della resistenza termica all'interfaccia oro-acqua (resistenza di Kapitza) sulle prestazioni di conversione fotoacustica dei nanorods d'oro. I risultati indicano possibili strategie per l'ottimizzazione delle particelle plasmoniche come agenti di contrasto per l'imaging, o anche come trasduttori per i biosensori. Viene inoltre suggerito un approccio efficace per modulare la resistenza di Kapitza includendo caratteristiche ancora non ben studiate come rugosità o presenza di adsorbati. Seguendo questa idea è stata sintetizzata una variante rugosa di nanorods d'oro per deposizione e sostituzione galvanica di un guscio d'argento, dove la rugosità fornisce segnali fotoacustici più elevati di circa il 70% e soglie di danneggiamento del 120%. Inoltre, le particelle sono state rivestite con una corona proteica, la quale apporta una diminuzione dei segnali fotoacustici con l'aumentare dello spessore del guscio; questo potrebbe ispirare nuove soluzioni per biosensori basate su un meccanismo di trasduzione fotoacustica. Entrambi questi risultati sono coerenti con un'efficace modulazione della resistenza di Kapitza, che può diminuire con l'irruvidimento, a causa di un aumento della superficie specifica, e può aumentare con l'introduzione di un rivestimento proteico (il quale può fungere da isolamento termico). Sono stati anche sviluppati materiali ibridi costituiti da nanorods core/shell Au/Ag, inclusi in fantocci biomimetici (scaffold) porosi di chitosano/polivinilil alcol (chitosano/PVA) per applicazioni nell'ingegneria tissutale e nella guarigione delle ferite (wound healing). La combinazione di Au e Ag in un unico costrutto fornisce opportunità sinergiche per l'attivazione ottica di funzioni come la saldatura dei tessuti con laser nel vicino infrarosso e l’interrogazione remota per l’acquisizione di parametri di rilevanza prognostica nel monitoraggio della guarigione delle ferite. In particolare, la componente bimetallica assicura sintonizzabilità ottica, durata di conservazione e stabilità fototermica migliori, funge da serbatoio di cationi d'argento germicidi. Allo stesso tempo, la miscela polimerica è ideale per essere legata al tessuto connettivo a seguito di attivazione fototermica e per supportare i processi di fabbricazione che forniscono un’elevata porosità, come l'elettrofilatura, ponendo così tutte le premesse per il ripopolamento cellulare e la protezione antimicrobica. In sintesi, in questo lavoro, è stata affrontata l'ottimizzazione di un sistema importante come i GNRs per applicazioni complementari in diversi ambiti biomedici; ne è stata ottimizzata la stabilità e l'efficienza di conversione fotoacustica per essere utilizzati come agenti di contrasto ottico, sviluppandone rivestimenti funzionali con piccole molecole organiche oppure con strati porosi metallici. Infine è stata valutata l'integrazione di nanorods bimetallici di Au/Ag in scaffold ibridi per ingegneria tissutale, sfruttandone sia l'efficienza di conversione fototermica sia la sensibilità ottica alle condizioni di stress ossidativo, allo scopo di attivare processi e monitorare parametri di interesse nell'ambito del wound healing.

Infections or diseases are not just stressful for the one who encounters it. The pathogens causing the same also have to deal with the hostile environment present in the host. The maintenance of physiological homeostatic balance is must for survival of all organisms. This becomes a challenging task for the protozoan parasites which often alternate between two different hosts during their life cycle and thereby encounter several environmental insults which they need to acclimatize against, in order to establish a productive infection. Since their discovery as proteins up-regulated upon heat shock, heat shock proteins have emerged as main mediators of cellular stress responses and are now also known to chaperone normal cellular functions. Parasites like Plasmodium falciparum have fully utilized the potential of these molecular chaperones. This is evident from the fact that parasite has dedicated about 2% of its genome for this purpose. During transmission from the insect vector to humans, the malaria parasite Plasmodium falciparum experiences a temperature rise of about 10oC, and the febrile episodes associated with asexual cycle further add to the heat shock which the parasite has to bear with. The exact mechanism by which the parasite responds to temperature stress remains unclear; however, the induction of chaperones such as PfHsp90 and PfHsp70 has been reported earlier. In other eukaryotes, there are three main factors which regulate heat shock response (HSR): heat shock factor (HSF), heat shock element (HSE) and HSF binding protein (HSBP). Bioinformatics analysis revealed presence of HSE and HSBP in P. falciparum genome; however, no obvious homolog of HSF could be identified. Either the HSF homologue in P. falciparum is highly divergent or the parasite has evolved alternate means to tackle temperature stress. Therefore, we decided to biochemically characterize HSBP and understand the heat shock response pathway in the parasite using transcriptomics and proteomics. The expression for PfHSBP was confirmed at both mRNA and protein level and it was found to translocate into the nucleus during heat shock. As previously reported for HSBP in other organisms, PfHSBP also exists predominantly in trimeric and hexameric form and it interacts with PfHsp70-1. Nearly 900 genes, which represent almost 17% of the parasite genome, were found to have HSE in their promoter region. HSE are represented by three repeating units of nGAAn pentamer and its inverted repeat nCTTn; however, the most abundant class of genes in P. falciparum possessed an atypical HSE which had only 2 continuous repeat units. Next, we were interested to find out if these HSE could actually bind to any parasite protein. Therefore, we performed EMSA analysis with the parasite nuclear extracts using HSE sequence as the oligonucleotide. We observed retarded mobility of the oligonucleotide suggesting that it was indeed able to recruit some protein from the nuclear extract. The importance of transcriptional regulation during heat shock was further confirmed when parasite culture subjected to heat shock in the presence of transcription inhibitor did not show induction in the levels of PfHsp70. These evidences suggest that parasite indeed possesses all the components of heat shock response pathway with either a divergent homologue of HSF or an alternate transcription factor which would have taken its role. Next, we performed global profiling of heat shock response using transcriptomic analysis and 2DDIGE based proteomic profiling. Overall, the parasite’s response to heat shock can be classified under 5 functional categories which aim at increasing the folding capacity of the cell, prevent protein aggregation, increase cytoadhesion, increase host cell remodelling and increase erythrocyte membrane rigidity. Out of the 201 genes found to be up-regulated upon heat shock, 36 were found to have HSE in their promoter region. This suggested that HSE-mediated protein up-regulation could be responsible for the induction of only 18% of total number of genes up-regulated upon heat shock. How would the parasite bring about up-regulation of rest of the heat shock responsive genes? It has been previously reported that genes for some of the heat shock proteins in P. falciparum possess G-box regulatory elements in their promoters and recently, it was shown that these elements served as the binding site for one of the transcription factors (PF13_0235) of AP2 family. Therefore, we looked for the status of this AP2 factor and its targets in our transcriptome data. Although, PF13_0235 was itself not up-regulated, we found up-regulation of its target genes which included another AP2 factor gene PF11_0404. The target genes of PF11_0404 were also up-regulated upon heat shock, thereby suggesting the functioning of an AP2 factor mediated response to heat shock. The next major challenge which the malaria parasite has to deal with is the remodelling of the erythrocyte as these cells do not have a cellular machinery which the parasite can take control of. The parasite remodels the erythrocyte with the help of its large repertoire of exported proteins and develops protrusions known as “knobs” on the erythrocyte surface. These protrusions are cytoadherent in nature and constitute the main virulence determinants of malaria. They also represent variable antigens that allow immune escape. Our lab has previously demonstrated an exported PfHsp40, termed as KAHsp40, to be involved in knob biogenesis. Apart from KAHsp40, there are 19 other PfHsp40s which possess the PEXEL motif required for protein export to erythrocytes. Although, Hsp40s work with an Hsp70 partner, none of the parasitic Hsp70s were known to be exported and was always a missing link in the field of malaria chaperone biology. A genomic re-annotation event could fill this gap by re-annotating the sequence for a pseudogene, PfHsp70-x and described it to contain a functional ORF. According to the re-annotated ORF sequence, PfHsp70-x possessed an ER signal peptide and thus could be targeted to the secretory pathway. Following validation of the re-annotation using a PCR-based approach, we confirmed the expression of this protein at the protein level by immunoblot analysis. Using various subcellular fractionation approaches and immunolocalization studies we established that PfHsp70-x indeed gets exported to the erythrocyte compartment; however, it did not contain the PEXEL motif required for protein export. It gets secreted into the vacuole around the parasite via the canonical ER-Golgi secretory pathway. Its trafficking from vacuole into the erythrocyte was mediated by a hexameric sequence which was present just after the signal peptide cleavage site and before the beginning of ATP-binding domain. In the erythrocyte compartment, it was found to interact with KAHsp40 and MAHRP1, proteins previously implicated in knob biogenesis. Most importantly, PfHsp70-x interacted with the major knob component PfEMP1; however, itself did not become part of knobs. Instead, it localized to the Maurer’s clefts in the erythrocyte compartment. Inside the parasite, PfHsp70-x was present in a complex with Plasmepsin V and PfHsp101. These proteins have been shown to be essential for host cell remodelling process. Plasmepsin V recognizes the PEXEL motif and brings about its cleavage and PfHsp101 specifically targets these PEXEL-cleaved exported proteins to the translocon in vacuolar membrane thereby facilitating their export into the erythrocyte. Thus, PfHsp70-x could also be involved in directing the export of knob constituents apart from just facilitating their assembly. Since, we found out that heat shock or the febrile episodes encountered during the asexual cycling of the parasite promote host cell remodelling; we wanted to find out if PfHsp70-x has any specific role under conditions of temperature stress. PfHsp70-x gene expression was not influenced upon heat shock, however, its export into the erythrocyte was inhibited and the protein got accumulated within the parasite compartment. Surprisingly, immunolocalization studies revealed that the accumulated pool of PfHsp70-x localized into the nucleus instead of ER thus suggesting an alternate role to be associated with PfHsp70-x under stress. Overall, our study addresses two major aspects of malaria pathogenesis. First, response to heat shock and second, remodelling of the host cell. We, for the first time describe global profiling of the parasite’s heat shock response and identify a novel P. falciparum specific heat shock protein member to be involved in malaria pathogenesis.