<p><a>Molecular imaging revolutionized the way researchers and clinicians visualize and investigate complex biochemical phenomena, and it is beneficial </a><a>for disease diagnosis, drug design and therapy assessment</a>. Among a variety of different imaging techniques, the non-ionizing and non-invasive photoacoustic (PA) imaging is attracting increased attentions, owing to its high spatial and temporal resolutions with reasonable penetration depth in tissue. Parallel efforts have been the preparation of PA imaging agents which has high PA efficacy and can specifically label the targets at cellular or molecular level. Particularly, there is exponentially growing interest in imaging in the second near-infrared (NIR-II) window (1000–1700 nm), where offers reduced tissue background and improved penetration depth. However, study of PA imaging in the NIR-II window is incomplete, partly due to the lack of suitable materials. Therefore, in my dissertation work I studied NIR-II PA imaging through semiconducting polymer. </p> <p>Firstly, the performance of PA imaging in the NIR-II window is explored by using a semiconducting polymer nanoparticle (SPN) which has strong absorption in the NIR-II window. Compared with lipid, blood and water, such SPN shows outstanding PA contrast in the NIR-II window <i>in situ</i> and <i>in vivo</i>, and an imaging depth of more than 5 cm at 1064 nm excitation is achieved in chicken-breast tissue. These results suggest that SPN as a PA contrast in the NIR-II window opens new opportunities for biomedical imaging with improved imaging contrast and centimeter-deep imaging depth.</p> <p>Next, targeted PA imaging of prostate cancer is achieved by functionalizing a NIR-II absorbing SPN with prostate-specific membrane antigen (PSMA)-targeted ligands. Insights into the interaction of the imaging probes with the biological targets are obtained from single-cell to whole-organ by transient absorption (TA) microscopy and PA imaging. TA microscopy reveals the targeting efficiency, kinetics, and specificity of the functionalized SPN to PSMA-positive prostate cancer at cellular level. Meanwhile, the functionalized SPN demonstrates selective accumulation and retention in the PSMA-positive tumor after intravenous administration <i>in vivo</i>. Taken together, it is demonstrated that BTII-DUPA SPN is a promising targeted probe for prostate cancer diagnosis by PA imaging. </p> <p>Lastly, PA imaging in the NIR-II window is also achieved water-soluble semiconducting polymer, which is prepared by oxygen-doping. After doping, it shows broadband absorption in the entire NIR-II window, with great chemical stability, photostability and biocompatibility. Owing to its merit of broadband absorption, the imaging depth comparison among different NIR-II wavelengths is also achieved. Moreover, this doped semiconducting polymer is readily soluble in normal physiological pH by virtue of carboxyl groups on side chains and tends to aggregate at an acidic environment which results in a 7.6-fold PA enhancement at pH 5.0. Importantly, a 3.4±1.0-fold greater signal in tumor tissue than that in muscle is revealed <i>in vivo</i>. This study provides a more attainable yet effective platform to the field for achieving water-soluble NIR-II absorbing contrast agents for activatable PA imaging. </p>

Orientador: João Francisco Escobedo / Resumo: O trabalho apresenta uma análise estatística e climática das irradiações global (HG) e global infravermelha (HGNIR) e das frações global total (Kt = HG/H0) e global infravermelha (KtNIR = HGNIR/H0NIR), transmitidas na atmosfera no período de 2001 a 2006 em Botucatu/SP/Brasil. Os valores das frações médias Kt e KtNIR (horária e diária) calculadas estatisticamente foram: Kth = 50,0%, KtNIRh = 42,0%, e Ktd = 56,0%, KtNIRd = 48,0%, respectivamente. O estudo mostra ainda a obtenção e a validação da equação de estimativa para KtNIR em função de Kt obtidas por regressão linear (y = ax), onde KtNIRh = 0,850Kth e KtNIRd = 0,855Ktd apresentaram elevados coeficientes de determinação: R2 = 0,981 e R2 = 0,987, respectivamente. Os valores horários obtidos na validação (ano típico e atípico) foram (rMBE)h = 1,0% e 0,2%, (rRMSE)h = 6,3% e 5,3%; dh = 0,994 e 0,996 respectivamente, enquanto que os valores diários foram (rMBE)d = 0,9% e 0,05%; (rRMSE)d = 3,4% e 2,6%; dd = 0,995 e 0,998. Os resultados mostram que as equações podem ser utilizadas com precisão e exatidão nas estimativas de KtNIR. A análise sazonal mostrou que a equação KtNIRh = 0,850Kth anual superestima KtNIRh no verão e primavera em 2,8% e 1,0%, e subestima-o no outono e inverno em 1,0% e 2,6%, respectivamente. Similarmente, KtNIRd = 0,855Ktd anual superestima KtNIRd no verão e primavera em 2,8% e 1,3% e subestima-o no outono e inverno em 1,0% e 2,1%, respectivamente. A análise por cobertura de céu mostrou que: o valor KtNIRh an... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This paper describes the statistical and climatic analysis of global (HG) and infrared global (HGNIR) irradiations, and total global (Kt = HG/H0) and infrared global (KtNIR = HGNIR/H0NIR) fractions, transmitted in the atmosphere from 2001 to 2006 in Botucatu/SP/Brazil: Values of mean fractions Kt and KtNIR (hourly and daily) calculated statistically were as follows: Kth = 50,0%, Kth NIR = 42,0%, and Ktd = 56,0%, KtNIR d = 48,0%, respectively. The study also presents obtaining and validation of the estimate equation for KtNIR as a function of Kt. The equations obtained by linear regression (y = ax) KtNIR h = 0,850Kth and KtNIR d = 0,855Ktd had high determination coefficient: R2 = 0,981 and 0,987 respectively. Hourly values based on validation (typical and atypical years) were as follows: (rMBE) h = 1,0% and 0,2%, (rMSE) h = 6,3% and 5,3%; d h = 0,994 and 0,996, respectively. Daily values were as follows: (rMBE) d = 0,9% and 0,05%; (rMSE) d = 3,4% and 2,6%; d d = 0,995 and 0,998. The results show that the equations can be used precisely and accurately for KtNIR estimates. Seasonal analysis showed that the annual KtNIR h = 0,850Kth equation overestimates KtNIR h in the summer and spring by 2,8% and 1,0% and underestimates it in the autumn and winter by 1,0% and 2,6%, respectively. Similarly, KtNIR d = 0,855Ktd equation anual overestimates KtNIR d in the summer and spring by 2,8% e 1,3% and underestimates it in the autumn and winter by 1,0% e 2,1%, respectively. Considering sky c... (Complete abstract click electronic access below) / Mestre

The fluid bed granulation is a well-established method how to improve such properties of powders as flowability and increase content uniformity of the tablets. In this thesis, there was evaluated a granulation process on a lab scale fluid Glatt bed granulator and optimized for highest possible yield. Product yield in the size range of 80-90 % of granules and process reproducibility were stated as most effective. The product was analysed for its particle size distribution, the API distribution within the different particle size fractions and the flowability of the final granules. For process optimization, the most critical parameters such as spraying rate, particle size of raw materials and fluid bed pressure were identified and evaluated. As the highest-yielding dosage for the powder binder was found the spraying rate of 9 g/min. Changes in bed fluid pressure and nozzle pressure showed no significant improvement. Different grades of caffeine were compared for their impact on the granulation properties. Sieved caffeine enhanced yield of the product and reproducibility compared to bulk or disagglomerated caffeine.

The selection of a representative sample is a delicate problem when drug seizures comprised of large number of units arrive at the Swedish National Forensic Centre (NFC). If deviating objects in the selected sample size are found, additional analyzes are required to investigate how representative the results are for the entire population. This generates further pressure on operational analysis flow. With the goal to provide a tool which forensic scientists at NFC can base their assessment of the representative nature of the selected sampling of large drug seizures on, this project investigated the possibilities of evaluating the level of homogeneity in drug seizures using near-infrared (NIR) hyperspectral imaging along with principal component analysis (PCA). A total of 27 sample groups (homogeneous, heterogeneous and seized sample groups) were analyzed and different predictive models were developed. The models were either based on quantifying the variation in NIR spectra or in PCA scores plots. It was shown that in the spectral range of 1300-2000 nm, using a pre-processing combination of area normalization, quadratic (second polynomial) detrending and mean centering, promising predictive abilities of the models in their evaluation of the level of homogeneity in drug seizures were achieved. A model where the approximated signal-dependent variation was related to the quotient of significant and noise explained variance given by PCA indicated most promising predictive abilities when quantifying the variation in NIR spectra. Similarly, a model where a rectangular area, defined by the maximum distances along PC1 and PC2, was related to the cumulative explained variance of the two PCs showed most promising predictive abilities when quantifying the variation in PCA scores plots. Different zones for which within sample groups are expected to appear based upon their degree of homogeneity could be established for both models. The two models differed in sensitivity. However, more comprehensive studies are required to evaluate the models applicability from an operational point-of-view.

En este trabajo se han desarrollado cinco sistemas de fotoliberación de doxorrubicina basados en tres tipos de nanopartículas: nanoestrellas de oro recubiertas de una capa mesoporosa de sílice (AuNSt@mSiO2), nanoestrellas de oro (AuNSt) y nanopartículas Janus formadas por nanoestrellas de oro y nanopartículas mesoporosas de sílice (AuNSt-MSNP). Los sistemas sintetizados se basan en dos mecanismos de activación de la liberación, asociados con las propiedades ópticas de las AuNSts. El primer mecanismo está relacionado con la conversión de la energía luminosa en calor, debido a la absorción de la radiación electromagnética por las partículas de oro. El calor generado durante la irradiación de las nanopartículas con un láser del infrarrojo cercano (NIR) se usa, en este caso como estímulo para activar la liberación del fármaco asociado a las nanopartículas. El otro mecanismo está relacionado con la amplificación del campo electromagnético de la radiación en la superficie de las nanopartículas. La amplificación del campo electromagnético favorece la absorción multifotónica de las radiaciones NIR en moléculas que absorben un fotón de mayor energía. Utilizando este mecanismo, se puede activar la fotoliberación del fármaco mediante el empleo de ligandos fotolábiles, que pueden enlazar directamente el fármaco a la partícula permitiendo su liberación después de la fotodescomposición. El primer sistema desarrollado está constituido por AuNSt@mSiO2 funcionalizadas con moléculas de parafina que actúan como puertas moleculares termosensibles. Estas moléculas de parafina en la superficie externa de los poros evitan la liberación de la doxorrubicina. La irradiación del sistema produce la fusión de la parafina debido al calor generado, provocando la liberación al medio del fármaco. Los otros sistemas desarrollados están basados en dos profármacos de la doxorrubicina que se activan al irradiarlas en presencia de las AuNSts generando el fármaco correspondiente. La doxorrubicina se modifica a través de un enlace carbamato con dos ligandos fotolábiles que poseen un espaciador 2-nitrobencílico. Uno de estos ligandos tiene un grupo disulfuro que permite unir el profármaco a la superficie de las AuNSts. La activación se produce debido a la absorción multifotónica de la radiación NIR por los profármacos que se favorece en presencia de las AuNSts, provocando la ruptura del ligando fotolábil y la generación de la doxorrubicina. También se obtuvo un sistema formado por nanopartículas Janus AuNSt-MSNP. El fármaco se encapsula en la MSNP que se funcionaliza con un complejo supramolecular entre el benzimidazol, unido covalentemente a la superficie externa de los poros, y la &#946;-ciclodextrina. Este complejo actúa como puerta molecular sensible al pH evitando la difusión de la doxorrubicina. La superficie de la AuNSt se funcionaliza con un ligando fotolabil tiolado que posee un espaciador 2-nitrobencílico y que tiene enlazado el ácido succínico. La irradiación del sistema híbrido produce la descomposición del ligando en la superficie de la AuNSt y la generación de ácido succínico que provoca la disociación del complejo supramolecular en la superficie de la MSNP, conduciendo finalmente a la liberación del fármaco. Por último, se obtuvo un sistema basado en AuNSt@mSiO2 funcionalizadas con moléculas de polietilenglicol a través de un ligando fotolábil que tiene un espaciador 2-nitrobencílico. El polietilenglicol modificado con el ligando fotolábil actúa como puerta molecular fotosensible impidiendo la difusión del fármaco encapsulado. Al irradiar las partículas se produce la descomposición del ligando, la liberación del PEG y la difusión del fármaco. / En aquest treball s'han desenvolupat cinc sistemes de foto-alliberació de doxorrubicina basats en tres tipus de nano-partícules: nano-estreles d'or recobertes d'una capa mesoporosa de sílice (AuNSt@mSiO2), nano-estreles d'or (AuNSt) i nano-partícules Janus formades per nano-estreles d'or i nano-partícules mesoporoses de sílice (AuNSt-MSNP). Els sistemes sintetitzats es basen en dos mecanismes d'activació de l'alliberament associats amb les propietats òptiques de les AuNSts. El primer mecanisme està relacionat amb la conversió de l'energia lluminosa en calor degut a l'absorció de la radiació electromagnètica per les partícules d'or. La calor generat durant la irradiació de les nano-partícules amb un làser de l'infraroig pròxim (NIR) pot utilitzar-se com a estímul per a activar l'alliberament del fàrmac associat a les nano-partícules. L'altre mecanisme està relacionat amb l'amplificació del camp electromagnètic de la radiació en la superfície de les nano-partícules. L'amplificació del camp electromagnètic afavoreix l'absorció multifotònica de les radiacions NIR en molècules que absorbeixen un fotó de major energia. Utilitzant aquest mecanisme es pot activar la foto-alliberació del fàrmac per mitjà de l'ús de lligants foto-làbils que poden enllaçar directament el fàrmac a la partícula permetent el seu alliberament després de la foto-descomposició. El primer sistema desenvolupat està constituït per AuNSt@mSiO2 funcionalitzada amb molècules de parafines que actuen com a portes moleculars termosensibles. Aquestes molècules unides a la superfície externa dels porus eviten la difusió de la doxorrubicina. La irradiació del sistema produeix la fusió de la parafina a causa de la calor generada, provocant l'alliberament al medi del fàrmac. Els altres sistemes desenvolupats estan basats en dos prodrogues de doxorrubicina que s'activen a l'irradiar-les en presència de les AuNSts generant la droga corresponent. La doxorrubicina es modifica a través d'un enllaç carbamat amb dos lligants foto-làbils que posseeixen un espaiador 2-nitrobencílic. Un dels lligants té un grup disulfur que permet unir la prodroga a la superfície de les AuNSts. L'activació es produeix a causa de l'absorció multifotònica de la radiació NIR per les prodrogues que s'afavorix en presència de les AuNSts, provocant la ruptura del lligant foto-làbil i la generació de la doxorrubicina. També es va obtindre un sistema format per nano-partícules Janus AuNSt-MSNP. El fàrmac s'encapsula en la nanopartícula mesoporosa de sílice que es funcionalitza amb un complex supramolecular entre el benzimidazol, unit covalentment a la superfície externa dels porus, i la &#946;-ciclodextrina. Este complex actua com a porta molecular sensible al pH evitant la difusió de la doxorrubicina. La superfície de la AuNSt es funcionaliza amb un lligant foto-làbil tiolat que posseeix un espaiador 2-nitrobencílic i que té enllaçat l'àcid succínic. La irradiació del sistema híbrid produeix la descomposició del lligant en la superfície de l'AuNSt i la generació d'àcid succínic que provoca la dissociació del complex supramolecular en la superfície de la MSNP conduint finalment a l'alliberament de la droga encapsulada. Finalment, es va obtindre un sistema basat en AuNSt@mSiO2 funcionalitzada amb molècules de polietilenglicol a través d'un lligant foto-làbil que té un espaiador 2-nitrobencílic. El polietilenglicol modificat amb el lligant fotolábil actua com a porta molecular fotosensible impedint la difusió de la droga encapsulada. A l'irradiar les partícules es produeix la descomposició del lligant, l'alliberament del PEG i la difusió del fàrmac des de l'interior dels porus. / Herein, five doxorubicin photo-release systems based on three types of nanoparticles: gold nanostars coated with a mesoporous silica shell (AuNSt@mSiO2), gold nanostars (AuNSts) and Janus gold nanostars-mesoporous silica nanoparticles (AuNSt-MSNP) have been developed. Photo-release mechanisms are directly related to optical properties of AuNSts. One of them is concerned to the light-heat energy conversion efficiency of AuNSts due to localized surface plasmon resonance associated with the strong absorption of electromagnetic radiation at near infrared wavelengths by anisotropic nanoparticles. Heat evolved during the irradiation of nanoparticles with NIR laser is used as stimulus for triggering drug delivery from the nanoparticles. Another mechanism is related to the strong electromagnetic field enhancement taking place onto nanoparticle¿s surface, which could favour multiphoton absorption of NIR radiations by photolabile molecules. Drug photo-release can be triggered by using photolabile linker which attaches drug to nanoparticle surface due to multiphoton molecular dissociation of linker induced by NIR irradiation. The first developed system is formed by AuNSts coated with mesoporous silica shell capped with paraffins, which act as thermo-sensitive molecular gates. These paraffin molecules onto the external silica surface form a hydrophobic layer that blocks the pores and avoids drug release. NIR irradiation of the hybrid nanoparticles produces plasmonic heating of nanoparticle¿s surrounding and subsequent paraffin melting and drug delivery. Other developed systems are based on two doxorubicin prodrugs, which can be activated by NIR laser irradiation in presence of AuNSts. Doxorubicin was coupled with two photolabile molecules bearing a 2-nitrobenzyl linker via carbamate linkage. One of them has a disulphide group, allowing directly attachment of the prodrug to the nanoparticle¿s surface. Multiphoton absorption of NIR radiation by the doxorubicin prodrug is favoured in presence of AuNSts provoking molecular photodissociation of the 2-nitrobenzyl linker and drug release. A system based on Janus AuNSt-MSNP was also synthesized. Doxorubicin was loaded into MSNPs functionalized onto external surface with a supramolecular complex between benzimidazole (Bzi) and &#946;-cyclodextrin (CD), which acts as pH sensitive molecular gate. AuNSts were modified with thiolated photolabile molecules bearing a 2-nitrobenzyl linker, which anchor succinic acid to nanoparticle¿s surface. NIR irradiation of the hybrid nanoparticles produce photocleavage of 2-nitrobenzyl linker and succinic acid release resulting in dissociation of the Bzi-CD complex and doxorubicin delivery from MSNPs. Finally, a system based on AuNSts coated with mesoporous silica shell capped with polyethyleneglycol (PEG) molecules bearing a 2-nitrobenzyl linker, was developed. These modified PEG molecules act as photosensitive molecular gates, preventing drug release from the mesoporous silica shell. NIR irradiation of these nanoparticles produces the photodissociation of 2-nitrobenzyl linker, leading to PEG release and doxorubicin delivery from the mesoporous silica. / Hernández Montoto, A. (2018). Desarrollo de nanodispositivos basados en nanoestrellas de oro y nanopartículas mesoporosas de sílice para la fotoliberación de fármacos empleando radiaciones del infrarrojo cercano con potenciales aplicaciones en la terapia del cáncer [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/115488 / TESIS

As a result of the standardizability of SNe Ia light curves over a wide range of photometric bands, they are used as standard candles to accurately measure distances in the cosmos up to z ≈ 1 [22]. As dust extinction is smaller in the NIR than in the optical [21] there is less dispersion seen in the peak brightnesses of SNe Ia, making them truly standard candles. We use SNPY to fit light curves for 192 SNe Ia. The mean of all Hubble residuals of our sample is ≈ 0.101 mag with a standard deviation of ≈ 0.234 mag. After applying an original set of cuts, the mean of 173 Hubble residuals reduces to ≈ 0.080 mag with a standard deviation of 0.203 mag. We next estimate host galaxy stellar masses of 175 SNe. From our sample we detect a 0.039 ± 0.026 mag (1−2σ) mass-step. For reasons outlined in section 4.1.1 and 4.1.2 respectively, we increase our sBV cut to sBV &gt; 0.8 and decrease our extinction cut to E(B −V ) ≤ 0.2 mag to see the mass step disappear entirely (0.004 ± 0.034 mag). Fast-declining SNe occur with preference in high-mass galaxies, possibly pointing to an intrinsic contribution to this mass step [22]. As NIR data is seen to significantly reduce the 3−4σ [14] mass-step detected with optical data, it is concluded that extinction likely plays a large role in the mass-step, as proposed in Brout &amp; Scolnic 2020 [2]. / <p>Presentation given over zoom due to the COVID-19 crisis.</p>

Carbon nanotubes (CNTs) have special characteristics that made them good agents especially for biomedical applications. In this study, Fe3O4 nanoparticles were incorporated onto the surface of CNTs followed by polyethylene glycol (PEG) grafting forming CNTs-Fe3O4-PEG hybrids. The PEGylation improves their biocompatibility, water solubility, and increases blood circulation. CNTs-Fe3O4-PEG was used as T2-contrat agent for magnetic resonance imaging (MRI). In addition, doxorubicin (DOX) was loaded onto CNTs-Fe3O4-PEG. The release of DOX from DOX-loaded CNTs-Fe3O4-PEG was tested under different pH conditions (7.4, 6.3 and 5.2). The release increased at acidic pH compared to neutral pH, which shows the sensitivity of the system to pH change. Triggering the release by Near Infra-Red (NIR) irradiation was furthermore investigated. The release increased after irradiation with NIR compared to control sample. These result prove that the designed system can be triggered by an internal stimuli (pH) and external stimuli (NIR irradiation) making it a promising candidate to be used for biomedical applications.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第19019号 / 農博第2097号 / 新制||農||1029(附属図書館) / 学位論文||H27||N4901(農学部図書室) / 31970 / 京都大学大学院農学研究科地域環境科学専攻 / (主査)教授 近藤 直, 教授 清水 浩, 准教授 小川 雄一 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

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Multiple object tracking (MOT) can be an efficient tool for finding patterns in video monitoring data. In this thesis, we investigate which type of video data works best for MOT in an indoor combat training scenario. The three types of camera data evaluated are color data, near-infrared (NIR) data, and depth data. In order to evaluate which of these lend themselves best for MOT, we develop object tracking models based on YOLOv5 and DeepSORT, and train the models on the respective types of data. In addition to the individual models, ensembles of the three models are also developed, to see if any increase in performance can be gained. The models are evaluated using the well-established MOT evaluation metrics, as well as studying the frame rate performance of each model. The results are rigorously analyzed using statistical significance tests, to ensure only well-supported conclusions are drawn. These evaluations and analyses show mixed results. Regarding the MOT metrics, the performance of most models were not shown to be significantly different from most other models, so while a difference in performance was observed, it cannot be assumed to hold over larger sample sizes. Regarding frame rate, we find that the ensemble models are significantly slower than the individual models on their own.