On the Role of Mechanics in Chronic Lung Disease.

Progressive airflow obstruction is a classical hallmark of chronic lung disease, affecting more than one fourth of the adult population. As the disease progresses, the inner layer of the airway wall grows, folds inwards, and narrows the lumen. The critical failure conditions for airway folding have been studied intensely for idealized circular cross-sections. However, the role of airway branching during this process is unknown. Here, we show that the geometry of the bronchial tree plays a crucial role in chronic airway obstruction and that critical failure conditions vary significantly along a branching airway segment. We perform systematic parametric studies for varying airway cross-sections using a computational model for mucosal thickening based on the theory of finite growth. Our simulations indicate that smaller airways are at a higher risk of narrowing than larger airways and that regions away from a branch narrow more drastically than regions close to a branch. These results agree with clinical observations and could help explain the underlying mechanisms of progressive airway obstruction. Understanding growth-induced instabilities in constrained geometries has immediate biomedical applications beyond asthma and chronic bronchitis in the diagnostics and treatment of chronic gastritis, obstructive sleep apnea and breast cancer

VALIDATION OF FULL-RESOLUTION DINSAR-DERIVED VERTICAL DISPLACEMENT IN CULTURAL HERITAGE MONITORING: INTEGRATION WITH GEODETIC LEVELLING MEASUREMENTS

Towards revealing the potential of satellite Synthetic Aperture Radar (SAR) Interferometry (InSAR) for efficient detection and monitoring of Cultural Heritage (CH) encouraging resilient built CH, this study is devoted to the validation of InSAR-derived vertical displacements with a full-resolution perspective taking advantage of high-precision geodetic levelling measurements. Considering the Cathedral of Como, northern Italy, as the case study, two different Persistent Scatterer Interferometry (PSI) techniques have been applied to Cosmo-SkyMed high-resolution SAR images acquired in both ascending and descending orbit tacks within the time interval of 2010–2012. Besides using the simplified approach for obtaining the vertical displacement velocity from Line of Sight (LOS) velocity, a weighted, localized, multi-track Vertical Displacement Extraction (VDE) approach is proposed and evaluated, which uses the technical outcome of Differential InSAR (DInSAR) and spatial information. The results, using a proper PSI technique, showed that the accuracy level of extracted vertical displacement velocities in a full-resolution application is ca. 0.6 [mm/year] with a dense concentration of InSAR-Levelling absolute errors lower than 0.3 [mm/year] which are reliable and reasonable levels based on the employed validation framework in this study. Also, the weighted localized VDE can significantly decrease the InSAR-Levelling errors, adding to the reliability of the InSAR application for CH monitoring and condition assessment in practice

Use of the Olympus endoArm for spinal and skull-based transsphenoidal neurosurgery

ManuscriptMinimally invasive surgical techniques have evolved to reduce soft-tissue injury associated with open surgical techniques. The use of endoscopic visualization allows the exposure of deep structures and provides a mechanism to perform all the components of an open surgical procedure through small portals, thus satisfying a basic requirement of minimally invasive surgical procedures. Surgeons in the field of skull-based and spine surgery are now taking advantage of the benefits of such endoscopes. The pneumatically powered EndoArm endoscopic holder has been used extensively in both cranial and spinal neurosurgical cases at the University of Utah. These cases include minimally invasive cervical and lumbar decompression procedures, as well as more recently for the resection of larger and more extensive pituitary tumors. In this paper, the multiple advantages of the Olympus EndoArm endoscopic holder are described in detail. As more surgeons gain experience with endoscopes in skull-based surgery, the hope is that operative times will be shorter and more extensive surgical resections will be possible with less patient morbidity

Bank Failure prediction: corporate governance and financial indicators

Most failure prediction studies have relied on using financial ratios as predictors. The most suitable financial predictors for banks are financial ratios following the CAMEL rating system. Also, corporate governance has been proven to be an important aspect of banks, especially after the financial crisis. Given its importance, we test the ability of corporate governance to enhance the prediction of bank failure. While there are only few studies that examine efficiency of corporate governance as a failure predictor, there are scarcely any studies that examine it as predictor of US banks failure. Using discriminant analysis, we predict the failure of banks insured by the Federal Deposit Insurance Corporation during the period from 2010 to 2018 using financial and non-financial predictors. We find that combining CAMEL ratios with corporate governance variables not only enhances the accuracy of prediction but also extends the time horizon of prediction to three years before failure. We also show that the earnings of banks are more significant in predicting bank failure than the capital structure and asset quality. The results further reveal that the CEO compensation, voting rights and institutional ownership are more significant predictors than the board characteristics. These results are robust when using logit regression. This paper provides insight to banks, regulators and shareholders by showing that corporate governance and banks earnings are strong predictors of bank failure

Gold nanorods functionalized with DNA oligonucleotide probes for biosensing and plasmon-enhanced fluorescence detection

Gold nanorods display plasmon resonances that are very sensitive to the refraction index close to the particle’s surface. The site-selective functionalization of Plasmon hot-spots with bioreceptors is crucial to develop plasmonic sensors with improved response bycapturing the target species at the most sensitive regions of the particle. Firstly, we used surface immobilized biotin-functionalized gold nanorods for streptavidin sensing.The selective functionalization of the nanorods’ tips was achieved with a CTAB bilayer and using a thiol linker to attach the desired biotin functionality. The sensor performance was characterized by measuring binding kinetic assays. In the recent years, Dengue virus DENV-2 has been reported as the largest dengue epidemic type and early stage detection of this virus would save the life of many patients. Thus, a plasmonic model biosensor was designed for the detection of RNA sequences proposed as disease biomarkers for Dengue virus.For this purpose, we have functionalized gold nanorods with thiolated DNA oligonucleotide probes complementary to a RNA sequence of Dengue virus.As a signal amplification strategy, we have used biotin-labeled oligonucleotide target sequences, in order to bind streptavidin or anti-biotin antibody to increase the surface plasmon response. Plasmon-enhanced fluorescence (PEF) microscopy provides fast, high-contrast, and lowbackground detection of single molecules. The interaction between the localized surface plasmon of gold nanorods and a fluorophore in their vicinity can induce the acceleration of excitation and decay rates thus leading to substantial fluorescence enhancements. In the third part of this Thesis, it was studied the interaction between gold nanorod antennas and a weakly fluorescence dye, TMPyP porphyrin. This interaction was mediated by electrostatic attraction between the tetracationic TMPyP and the DNA oligonucleotide coating on the nanorods’ surface. Preliminary measurements of optical spectroscopy were carried out to characterize the interaction in solution of TMPyP and single or double-stranded DNA oligonucleotides complementary to a RNA sequence of Dengue virus.The apparent equilibrium constants for the complex of TMPyP with single and double-stranded DNA were determined to be Ka= 3.9×107 M-1and 4.5×107 M-1respectively. The spectral changes show a strong specific intercalation of TMPyP with ds-DNA and ss-DNA because of GC-rich sites in the selected sequences. Next, the plasmon-enhanced fluorescence of TMPyP induced by gold nanorods was investigated using confocal fluorescence lifetime microscopy to perform measurements of nanoparticle emission intensity and spectrum, fluorescence correlation spectroscopy, emission intensity time trace and fluorescence decay. The gold nanorods were immobilized on glass and functionalized with a thiolated oligonucleotide coating, while TMPyP molecules are diffusing in solution and stochastically interact with the rod’s surface. The emission intensity traces measured on single particles show strong fluorescence bursts when TMPyP molecules come into close proximity of the nanorod. We have calculated the emission enhancement factors from a comparison with the non-enhanced emission of TMPyP in the same experimental conditions and found surprisingly large enhancement factors of around 60000-fold for TMPyP’s emission.These values of enhancement are two orders of magnitude larger than our calculated highest enhanced fluorescence expected for TMPyP molecule.Os nano-bastonetes de ouro são caracterizados por plasmões de superfície com frequências de ressonância bastante sensíveis ao índice de refração na proximidade da sua superfície. A funcionalização seletiva da superfície destas nanopartículas com bio-receptores é crucial para o desenvolvimento de sensores plasmónicos com resposta melhorada, pois permite a captura de analitos nas regiões mais sensíveis da nanopartícula. Em primeiro lugar foram preparadas superfícies com nano-bastonetes de ouro que depois foram funcionalizados com recetores biotina para ensaios modelo de deteção de estreptavidina. A funcionalização seletiva das extremidades dos nano-bastonetes foi conseguida através da proteção das suas paredes laterais com uma bicamada de tensioativo CTAB e usando uma biotina derivatizada com uma função tiól. O desempenho do sensor foi caracterizado por medidas da cinética de associação biotina-estreptavidina monitorizada por espectroscopia ótica de absorção. Em anos recentes, a infeção pelo vírus do Dengue DENV-2 tem sido relatada como a maior epidemia por este tipo de vírus, e a deteção precoce desta infeção poderia salvar a vida de muitos pacientes. Deste modo, foi desenhado um sensor plasmónico modelo para a deteção de sequências de ARN propostas como bio-marcadores para a infeção pelo vírus do Dengue. Para o efeito, foram funcionalizados nano-bastonetes de ouro com cadeias de oligonucleotídos de ADN complementares a uma sequência do ARN do vírus do Dengue. Como estratégia de amplificação de sinal foram usadas cadeias de oligonucleotídos alvo marcadas com biotina, de modo a ser possível num segundo passo ligar estreptavidina ou anticorpo anti-biotina com o objetivo de aumentar a resposta do plasmão de superfície dos nano-bastonetes de ouro. A fluorescência intensificada por efeito plasmónico permite a deteção rápida e com elevado contraste de molécula única em microscopia de fluorescência. A interação entre os modos localizados de plasmão de superfície de nano-bastonetes de ouro e moléculas fluorescentes na sua proximidade pode induzir a aceleração das taxas de excitação, decaimento radiativo e não-radiativo, e conduzir a uma intensificação de fluorescência.Na terceira parte desta Dissertação, foram investigadas as interações entre nano-antenas de ouro e um cromóforo pouco fluorescente, a porfirina TMPyP. Esta interação foi mediada pela atração eletrostática entre a porfirina tetra-catiónica e o revestimento de ADN na superfície dos nano-bastonetes de ouro. Ensaios preliminares de espectroscopia ótica foram realizados para caracterizar a interação em solução da TMPyP com sequências de ADN de cadeia simples ou duplacomplementares a uma sequência do ARN do vírus do Dengue. A constante aparente de equilíbrio para o complexo da TMPyP com as sequências de ADN de cadeia simples e dupla foram determinadas como sendo Ka= 3.9×107 M-1and 4.5×107 M-1, respetivamente. As alterações dos espectros de absorção e emissão mostram uma forte interação, provavelmente intercalação, daTMPyPcom ods-DNA,etambém com o ss-DNA, devido ao elevado conteúdo em pares GC nas sequências escolhidas. Em seguida, a fluorescência intensificada por efeito plasmónico na TMPyP induzida por nano-bastonetes de ouro foi investigada por microscopia confocal de tempos-de-vida, tendo sido realizadas medidas de intensidade e espectro de emissão de nanopartículas, espectroscopia de correlação de fluorescência, traços temporais de intensidade de emissão e de decaimento de fluorescência.Os nano-bastonetes de ouro foram imobilizados em vidro e funcionalizados com um revestimento de oligonucleotídostiolados, enquanto que as moléculas de TMPyP difundem-se em solução e podem interatuar estocasticamente com a superfície da nanopartícula. Os traços de intensidade de emissão medidos em nanopartículas individuais mostram picos de fluorescência intensos quando as moléculas de TMPyP se aproximam do nano-bastonete de ouro em resultado do efeito de nano-antena.Foram calculados os fatores de emissão intensificada por comparação com a emissão não-intensificada da TMPyP nas mesmas condições experimentais e obtiveram-se valores surpreendentemente elevados de cerca de 60000 vezes para a emissão intensificada da TMPyP. Estes fatores de intensificação são duas ordens de grandeza mais elevados do que as estimativas teóricas calculadas para a intensificação da emissão da TMPyP pelos nanobastonetes de ouro

New approaches to the study of sepsis

Models of sepsis have been instructive in understanding the sequence of events in animals and, to an extent, in humans with sepsis. Events developing early in sepsis suggest that a hyperinflammatory state exists, accompanied by a buildup of oxidants in tissues reflective of a redox imbalance. Development of immunosuppression and degraded innate and adaptive immune responses are well‐established complications of sepsis. In addition, there is robust activation of the complement system, which contributes to the harmful effects of sepsis. These events appear to be associated with development of multiorgan failure. The relevance of animal models of sepsis to human sepsis and the failure of human clinical trials are discussed, together with suggestions as to how clinical trial design might be improved. Currently there is no FDA‐approved drug for use in sepsis. This Review discusses the relevance of animal models to human sepsis and the failure of human clinical trials and provides suggestions as to how clinical trial design might be improved.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94452/1/1234_ftp.pd