Topics in equilibrium and nonequilibrium thermodynamics: computing crystalline free energies and engineering Maxwell’s demon.

This dissertation covers two separate topics in statistical physics. The first part of the dissertation focuses on computational methods of obtaining the free energies (or partition functions) of crystalline solids. We describe a method to compute the Helmholtz free energy of a crystalline solid by direct evaluation of the partition function. In the many-dimensional conformation space of all possible arrangements of N particles inside a periodic box, the energy landscape consists of localized islands corresponding to different solid phases. Calculating the partition function for a specific phase involves integrating over the corresponding island. Introducing a natural order parameter that quantifies the net displacement of particles from lattices sites, we write the partition function in terms of a one-dimensional integral along the order parameter, and evaluate this integral using umbrella sampling. We validate the method by computing free energies of both face-centered cubic (FCC) and hexagonal close-packed (HCP) hard sphere crystals with a precision of $10^{-5}k_BT$ per particle. In developing the numerical method, we find several scaling properties of crystalline solids in the thermodynamic limit. Using these scaling properties, we derive an explicit asymptotic formula for the free energy per particle in the thermodynamic limit. In addition, we describe several changes of coordinates that can be used to separate internal degrees of freedom from external, translational degrees of freedom. The second part of the dissertation focuses on engineering idealized physical devices that work as Maxwell's demon. We describe two autonomous mechanical devices that extract energy from a single heat bath and convert it into work, while writing information onto memory registers. Additionally, both devices can operate as Landauer's eraser, namely they can erase information from a memory register, while energy is dissipated into the heat bath. The phase diagrams and the efficiencies of the two models are solved and analyzed. These two models provide concrete physical illustrations of the thermodynamic consequences of information processing.

Free-flight experiments in LISA Pathfinder

The LISA Path finder mission will demonstrate the technology of drag-free test masses for use as inertial references in future space-based gravitational wave detectors. To accomplish this, the Path finder spacecraft will perform drag-free flight about a test mass while measuring the acceleration of this primary test mass relative to a second reference test mass. Because the reference test mass is contained within the same spacecraft, it is necessary to apply forces on it to maintain its position and attitude relative to the spacecraft. These forces are a potential source of acceleration noise in the LISA Path finder system that are not present in the full LISA con figuration. While LISA Path finder has been designed to meet it's primary mission requirements in the presence of this noise, recent estimates suggest that the on-orbit performance may be limited by this 'suspension noise'. The drift-mode or free-flight experiments provide an opportunity to mitigate this noise source and further characterize the underlying disturbances that are of interest to the designers of LISA-like instruments. This article provides a high-level overview of these experiments and the methods under development to analyze the resulting data.

A principal component approach to space-based gravitational wave astronomy

The current approach to data analysis for the Laser Interferometry Space Antenna (LISA) depends on the time delay interferometry observables (TDI) which have to be generated before any weak signal detection can be performed. These are linear combinations of the raw data with appropriate time shifts that lead to the cancellation of the laser frequency noises. This is possible because of the multiple occurrences of the same noises in the different raw data. Originally, these observables were manually generated starting with LISA as a simple stationary array and then adjusted to incorporate the antenna's motions. However, none of the observables survived the flexing of the arms in that they did not lead to cancellation with the same structure. The principal component approach is another way of handling these noises that was presented by Romano and Woan which simplified the data analysis by removing the need to create them before the analysis. This method also depends on the multiple occurrences of the same noises but, instead of using them for cancellation, it takes advantage of the correlations that they produce between the different readings. These correlations can be expressed in a noise (data) covariance matrix which occurs in the Bayesian likelihood function when the noises are assumed be Gaussian. Romano and Woan showed that performing an eigendecomposition of this matrix produced two distinct sets of eigenvalues that can be distinguished by the absence of laser frequency noise from one set. The transformation of the raw data using the corresponding eigenvectors also produced data that was free from the laser frequency noises. This result led to the idea that the principal components may actually be time delay interferometry observables since they produced the same outcome, that is, data that are free from laser frequency noise. The aims here were (i) to investigate the connection between the principal components and these observables, (ii) to prove that the data analysis using them is equivalent to that using the traditional observables and (ii) to determine how this method adapts to real LISA especially the flexing of the antenna. For testing the connection between the principal components and the TDI observables a 10x 10 covariance matrix containing integer values was used in order to obtain an algebraic solution for the eigendecomposition. The matrix was generated using fixed unequal arm lengths and stationary noises with equal variances for each noise type. Results confirm that all four Sagnac observables can be generated from the eigenvectors of the principal components. The observables obtained from this method however, are tied to the length of the data and are not general expressions like the traditional observables, for example, the Sagnac observables for two different time stamps were generated from different sets of eigenvectors. It was also possible to generate the frequency domain optimal AET observables from the principal components obtained from the power spectral density matrix. These results indicate that this method is another way of producing the observables therefore analysis using principal components should give the same results as that using the traditional observables. This was proven by fact that the same relative likelihoods (within 0.3%) were obtained from the Bayesian estimates of the signal amplitude of a simple sinusoidal gravitational wave using the principal components and the optimal AET observables. This method fails if the eigenvalues that are free from laser frequency noises are not generated. These are obtained from the covariance matrix and the properties of LISA that are required for its computation are the phase-locking, arm lengths and noise variances. Preliminary results of the effects of these properties on the principal components indicate that only the absence of phase-locking prevented their production. The flexing of the antenna results in time varying arm lengths which will appear in the covariance matrix and, from our toy model investigations, this did not prevent the occurrence of the principal components. The difficulty with flexing, and also non-stationary noises, is that the Toeplitz structure of the matrix will be destroyed which will affect any computation methods that take advantage of this structure. In terms of separating the two sets of data for the analysis, this was not necessary because the laser frequency noises are very large compared to the photodetector noises which resulted in a significant reduction in the data containing them after the matrix inversion. In the frequency domain the power spectral density matrices were block diagonals which simplified the computation of the eigenvalues by allowing them to be done separately for each block. The results in general showed a lack of principal components in the absence of phase-locking except for the zero bin. The major difference with the power spectral density matrix is that the time varying arm lengths and non-stationarity do not show up because of the summation in the Fourier transform.

Confronto fra metodi di stima di frequenza tramite auto-regressione e metodi di analisi spettrale per la generazione di osservabili radiometriche in ambito Deep-Space

A partire dal problema di orbit determination per una sonda in deep-space, la tesi si concentra su sviluppo e confronto di algoritmi di stima della frequenza di segnali analitici per la verifica delle loro performance di accuratezza nella generazione di osservabili doppler. Le tecniche poste a confronto appartengono a due categorie: due tempo-discrete ed una spettrale; in particolare si vuole valutare come la modellazione ARMA dei segnali possa beneficiare le prime al punto da poterle considerare alternative all'altezza degli standard del settore aerospaziale.

Impossible Space circolare per favorire la locomozione naturale

In questa relazione di tesi verrà affrontato il problema della locomozione naturale in ambienti virtuali che possiedono una grandezza maggiore dello spazio reale nel quale l'utente si muove. Negli anni sono stati sviluppati numerosi metodi di navigazione, ma tra tutti la locomozione naturale è il sistema che porta un livello di immersione maggiore nello spazio virtuale, più di qualsiasi altra tecnica. In questo lavoro di tesi verrà proposto un algoritmo in grado di favorire la locomozione naturale all'interno di lunghi spazi chiusi, andando a modificare la geometria dello spazio virtuale (che andrà ad assumere una forma circolare) e mantendendo comunque un certo grado di realismo dal punto di vista dell'utente. L'obiettivo è quello di tradurre uno spazio virtuale chiuso e lungo (caso comune: un corridoio) in una forma circolare inscritta in una stanza di 2x2m, con un approccio simile a quello degli impossible spaces, con l'obiettivo di studiare in futuro entro quale percentuale di sovrapposizione l'utente si accorge di trovarsi in una geometria impossibile. Nel primo capitolo verranno introdotti i concetti chiave di VR e AR, nonché un'introduzione all'Engine Unity e al software Blender. Nel secondo capitolo si tratterà di computer graphics, quindi si introdurranno i concetti base della grafica 3D con un focus sulla matematica alla base di ogni processo grafico. Nel terzo capitolo verrà affrontano il concetto di embodiment, quindi la percezione del proprio corpo, l'importanza dell'immersitvità dei sistemi virtuali e verrà descritto un paper precedentemente realizzato riguardante tale concetto. Nel capitolo quattro si parlerà del movimento all'interno dei sistemi di realtà virtuale, della locomozione naturale e delle tecniche per rendere tale metodo più accessibile. Nel capitolo cinque infine verrà descritto l'algoritmo realizzato e verranno mostrati i risultati.

Implementazione e caratterizzazione di PLL digitali per doppler tracking di sonde deep space

I Phase-Locked Loops sono circuiti ancora oggi utilizzati per la generazione di segnali coerenti in frequenza e in fase con i segnali in ingresso, motivo per cui sono uno degli strumenti della radio scienza per la ricostruzione dei segnali scambiati con le sonde e nascosti dal rumore accumulato nel tragitto che separa le sonde stesse dalle stazioni di tracking a terra. Questa tesi illustra l'implementazione di un PLL digitale linearizzato in Matlab e Simulink in una nuova veste rispetto al modello implementato durante l'attività di tirocinio curricolare, al fine di migliorarne le prestazioni per bassi carrier-to-noise density ratios. Il capitolo 1 si compone di due parti: la prima introduce all'ambito nel quale si inserisce il lavoro proposto, ossia la determinazione d'orbita; la seconda illustra i fondamenti della teoria dei segnali. Il capitolo 2 è incentrato sull'analisi dei Phase-Locked Loops, partendo da un'introduzione teorica e approdando all'implementazione di un modello in Simulink. Il capitolo 3, infine, mostra i risultati dell'applicazione del modello implementato in Simulink nell'analisi dei segnali di una missione realmente svolta.

Generazione di osservabili radiometriche per navigazione deep space tramite reti neurali convoluzionali

Grazie all’evoluzione degli strumenti di calcolo e delle strutture digitali, le intelligenze artificiali si sono evolute considerevolmente negli ultimi anni, permettendone sempre nuove e complesse applicazioni. L’interesse del presente progetto di tesi è quello di creare un modello di studio preliminare di intelligenza artificiale definita come Rete Neurale Convoluzionale, o Convolutional Neural Network (CNN), al fine di essere impiegata nel campo della radioscienza e dell’esplorazione planetaria. In particolare, uno degli interessi principali di applicazione del modello è negli studi di geodesia compiuti tramite determinazione orbitale di satelliti artificiali nel loro moto attorno ai corpi celesti. Le accelerazioni causate dai campi gravitazionali planetari perturbano le orbite dei satelliti artificiali, queste variazioni vengono captate dai ricevitori radio a terra sottoforma di shift Doppler della frequenza del segnale, a partire dalla quale è quindi possibile determinare informazioni dettagliate sul campo di gravità e sulla struttura interna del corpo celeste in esame. Per poter fare ciò, occorre riuscire a determinare l’esatta frequenza del segnale in arrivo, il quale, per via di perdite e disturbi durante il suo tragitto, presenterà sempre una componente di rumore. Il metodo più comune per scindere la componente di informazione da quella di rumore e ricavarne la frequenza effettiva è l’applicazione di trasformate di Fourier a tempo breve, o Short-time Fourier Transform (STFT). Con l’attività sperimentale proposta, ci si è quindi posto l’obiettivo di istruire un CNN alla stima della frequenza di segnali reali sinusoidali rumorosi per avere un modello computazionalmente rapido e affidabile a supporto delle operazioni di pre-processing per missioni di radio-scienza.

Numerical integration errors in deep space orbit determination

Il progetto di tesi è stato sviluppato durante il periodo di tirocinio svolto all’interno del “Laboratorio di Radio Scienza ed Esplorazione Planetaria” da un'esperienza da cui prende il nome lo stesso elaborato: ”Numerical integration errors in deep space orbit determination”. Lo scopo del sopraccitato laboratorio è stato quello di studiare in modo approfondito il problema kepleriano dei due corpi, per poi passare ad un’analisi del problema dei tre corpi e successivamente a n corpi (con particolare attenzione alle orbite dei satelliti medicei di Giove). Lo studio è stato affiancato ad un costante utilizzo della piattaforma di programmazione Matlab per l’elaborazione e la stesura di codici per il calcolo di traiettorie orbitali ed errori numerici. Infatti, il fulcro del lavoro è stato proprio il confronto di vari integratori e degli errori numerici derivanti dall’integrazione. Nella tesi, dapprima, viene introdotto il sistema Gioviano, vengono presentati i satelliti medicei, delineate le caratteristiche fisiche fondamentali e i principali motivi che portano ad avere particolare interesse nel conoscere lo sviluppo orbitale di tale sistema. In seguito, l'elaborato, dopo una dettagliata descrizione teorica del problema dei due corpi, presenta un codice per la rappresentazione di orbite kepleriane e il calcolo dei relativi errori commessi dal metodo numerico rispetto a quello analitico. Nell'ultimo capitolo, invece, il problema è esteso a più corpi dotati di massa e a tal proposito viene proposto un codice per la rappresentazione delle orbite descritte nel tempo da n corpi, date le condizioni iniziali, e il calcolo dei rispettivi errori nel sistema di riferimento (r,t,n). In merito a ciò, vengono infine testati diversi integratori per cercare quello con le migliori performance e sono poi analizzati alcuni parametri in input al problema per verificare sotto quali condizioni l’integratore lavora meglio.

Unibo-BP: an innovative free software implementation of Bundle Protocol Version 7 (RFC 9171)

The BP (Bundle Protocol) version 7 has been recently standardized by IETF in RFC 9171, but it is the whole DTN (Delay-/Disruption-Tolerant Networking) architecture, of which BP is the core, that is gaining a renewed interest, thanks to its planned adoption in future space missions. This is obviously positive, but at the same time it seems to make space agencies more interested in deployment than in research, with new BP implementations that may challenge the central role played until now by the historical BP reference implementations, such as ION and DTNME. To make Unibo research on DTN independent of space agency decisions, the development of an internal BP implementation was in order. This is the goal of this thesis, which deals with the design and implementation of Unibo-BP: a novel, research-driven BP implementation, to be released as Free Software. Unibo-BP is fully compliant with RFC 9171, as demonstrated by a series of interoperability tests with ION and DTNME, and presents a few innovations, such as the ability to manage remote DTN nodes by means of the BP itself. Unibo-BP is compatible with pre-existing Unibo implementations of CGR (Contact Graph Routing) and LTP (Licklider Transmission Protocol) thanks to interfaces designed during the thesis. The thesis project also includes an implementation of TCPCLv3 (TCP Convergence Layer version 3, RFC 7242), which can be used as an alternative to LTPCL to connect with proximate nodes, especially in terrestrial networks. Summarizing, Unibo-BP is at the heart of a larger project, Unibo-DTN, which aims to implement the main components of a complete DTN stack (BP, TCPCL, LTP, CGR). Moreover, Unibo-BP is compatible with all DTNsuite applications, thanks to an extension of the Unified API library on which DTNsuite applications are based. The hope is that Unibo-BP and all the ancillary programs developed during this thesis will contribute to the growth of DTN popularity in academia and among space agencies.

An Efficient Protocol For The Generation Of Monocyte Derived Dendritic Cells Using Serum-free Media For Clinical Applications In Post Remission Aml Patients.

Protocols for the generation of dendritic cells (DCs) using serum as a supplementation of culture media leads to reactions due to animal proteins and disease transmissions. Several types of serum-free media (SFM), based on good manufacture practices (GMP), have recently been used and seem to be a viable option. The aim of this study was to evaluate the results of the differentiation, maturation, and function of DCs from Acute Myeloid Leukemia patients (AML), generated in SFM and medium supplemented with autologous serum (AS). DCs were analyzed by phenotype characteristics, viability, and functionality. The results showed the possibility of generating viable DCs in all the conditions tested. In patients, the X-VIVO 15 medium was more efficient than the other media tested in the generation of DCs producing IL-12p70 (p=0.05). Moreover, the presence of AS led to a significant increase of IL-10 by DCs as compared with CellGro (p=0.05) and X-Vivo15 (p=0.05) media, both in patients and donors. We concluded that SFM was efficient in the production of DCs for immunotherapy in AML patients. However, the use of AS appears to interfere with the functional capacity of the generated DCs.

Growth Factor Stimulation Improves The Structure And Properties Of Scaffold-free Engineered Auricular Cartilage Constructs.

The reconstruction of the external ear to correct congenital deformities or repair following trauma remains a significant challenge in reconstructive surgery. Previously, we have developed a novel approach to create scaffold-free, tissue engineering elastic cartilage constructs directly from a small population of donor cells. Although the developed constructs appeared to adopt the structural appearance of native auricular cartilage, the constructs displayed limited expression and poor localization of elastin. In the present study, the effect of growth factor supplementation (insulin, IGF-1, or TGF-β1) was investigated to stimulate elastogenesis as well as to improve overall tissue formation. Using rabbit auricular chondrocytes, bioreactor-cultivated constructs supplemented with either insulin or IGF-1 displayed increased deposition of cartilaginous ECM, improved mechanical properties, and thicknesses comparable to native auricular cartilage after 4 weeks of growth. Similarly, growth factor supplementation resulted in increased expression and improved localization of elastin, primarily restricted within the cartilaginous region of the tissue construct. Additional studies were conducted to determine whether scaffold-free engineered auricular cartilage constructs could be developed in the 3D shape of the external ear. Isolated auricular chondrocytes were grown in rapid-prototyped tissue culture molds with additional insulin or IGF-1 supplementation during bioreactor cultivation. Using this approach, the developed tissue constructs were flexible and had a 3D shape in very good agreement to the culture mold (average error <400 µm). While scaffold-free, engineered auricular cartilage constructs can be created with both the appropriate tissue structure and 3D shape of the external ear, future studies will be aimed assessing potential changes in construct shape and properties after subcutaneous implantation.

Chemical Composition And Free Radical-scavenging, Anticancer And Anti-inflammatory Activities Of The Essential Oil From Ocimum Kilimandscharicum.

The essential oil from the leaves of Ocimum kilimandscharicum (EOOK), collected in Dourados-MS, was investigated for anticancer, anti-inflammatory and antioxidant activity and chemical composition. The essential oil was extracted by hydrodistillation, and the chemical composition was performed by gas chromatography-mass spectrometry. The essential oil was evaluated for free radical-scavenging activity using the DPPH assay and was tested in an anticancer assay against ten human cancer cell lines. The response parameter (GI50) was calculated for the cell lines tested. The anti-inflammatory activity was evaluated using carrageenan-induced pleurisy in mice. The chemical composition showed 45 components with a predominance of monoterpenes, such as camphor (51.81%), 1,8 cineole (20.13%) and limonene (11.23%). The EOOK exhibited potent free radical-scavenging activity by the DPPH assay with a GI50 of 8.31 μg/ml. The major constituents, pure camphor (IC50=12.56 μg/ml) and mixture of the limonene: 1, 8 cineole (IC50=23.25 μg/ml) displayed a potent activity. The oral administration of EOOK (at 30 and 100 mg kg(-1)), as well as the pure camphor or a mixture of 1,8 cineole with limonene, significantly inhibited the carrageenan (Cg) induced pleurisy, reducing the migration of total leukocytes in mice by 82 ± 4% (30 mg kg(-1) of EOOK), 95 ± 4% (100 mg kg(-1) of EOOK), 83 ± 9% (camphor) and 80 ± 5% (mixture of 1,8 cineole:limonene 1:1). In vitro cytotoxicity screening against a human ovarian cancer cell line displayed high selectivity and potent anticancer activity with GI50=31.90 mg ml(-1). This work describes the anti-inflammatory, anticancer and antioxidant effects of EOOK for the first time. The essential oil exhibited marked anti-inflammatory, antioxidant and anticancer effects, an effect that can be attributed the presence of majorital compounds, and the response profiles from chemical composition differed from other oils collected in different locales.

Analysis Of The Contribution Of Immunologically-detectable Her2, Steroid Receptors And Of The Triple-negative" Tumor Status To Disease-free And Overall Survival Of Women With Epithelial Ovarian Cancer."

We assessed associations between steroid receptors including: estrogen-alpha, estrogen-beta, androgen receptor, progesterone receptor, the HER2 status and triple-negative epithelial ovarian cancer (ERα-/PR-/HER2-; TNEOC) status and survival in women with epithelial ovarian cancer. The study included 152 women with primary epithelial ovarian cancer. The status of steroid receptor and HER2 was determined by immunohistochemistry. Disease-free and overall survival were calculated and compared with steroid receptor and HER2 status as well as clinicopathological features using the Cox Proportional Hazards model. A mean follow-up period of 43.6 months (interquartile range=41.4 months) was achieved where 44% of patients had serous tumor, followed by mucinous (23%), endometrioid (9%), mixed (9%), undifferentiated (8.5%) and clear cell tumors (5.3%). ER-alpha staining was associated with grade II-III tumors. Progesterone receptor staining was positively associated with a Body Mass Index≥25. Androgen receptor positivity was higher in serous tumors. In stand-alone analysis of receptor contribution to survival, estrogen-alpha positivity was associated with greater disease-free survival. However, there was no significant association between steroid receptor expression, HER2 status, or TNEOC status, and overall survival. Although estrogen-alpha, androgen receptor, progesterone receptor and the HER2 status were associated with key clinical features of the women and pathological characteristics of the tumors, these associations were not implicated in survival. Interestingly, women with TNEOC seem to fare the same way as their counterparts with non-TNEOC.

Seven-membered Rings Through Metal-free Rearrangement Mediated By Hypervalent Iodine.

A versatile and metal-free approach for the synthesis of carbocycles and of heterocycles bearing seven- and eight-membered rings is described. The strategy is based on ring expansion of 1-vinylcycloalkanols (or the corresponding silyl or methyl ether) mediated by the hypervalent iodine reagent HTIB (PhI(OH)OTs). Reaction conditions can be easily adjusted to give ring expansion products bearing different functional groups. A route to medium-ring lactones was also developed.

Impact Of Drug Formulation And Free Platinum/cisplatin Ratio On Hypersensitivity Reactions To Cisplatin: Formulation Matters.

Use of cisplatin can induce type I hypersensitivity reactions that may also be linked to the quality of the drug utilized. We observed cases of hypersensitivity that appeared to be associated with the brand of cisplatin used. The aim of this study was to compare two different brands of cisplatin in relation to type I hypersensitivity reactions. Brand A was used in a tertiary care teaching hospital until 2012, and use of brand B started from January 2013, when the first hypersensitivity cases were observed. Patients were categorized based on symptom. Cisplatin of both brands was analysed by high-performance liquid chromatography (HPLC) and high-resolution electrospray ionization mass spectrometry (ESI-(+)-MS) and characterized according to US Pharmacopeia. There were no cases of hypersensitivity associated with the use of cisplatin brand A, whereas four of 127 outpatients that used cisplatin brand B were affected. The two brands were in accordance with the US Pharmacopeia parameters, and there was no significant difference in the total platinum levels between the two brands when analysed by HPLC. However, high-resolution ESI-(+)-MS analyses show that brand B contains approximately 2.7 times more hydrolysed cisplatin than brand A. The increase in the hydrolysed form of cisplatin found in brand B may be the cause of the hypersensitivity reaction observed in a subset of patients. We present the first study of the quality of drugs by high-resolution ESI-(+)-MS. Drug regulatory agencies and manufacturers should consider including measurement of hydrolysed cisplatin as a quality criterion for cisplatin formulations.