Advancing Vibrational Spectroscopy for Cellular and Sub Cellular Analysis: Raman Spectroscopy as an in Vitro Chemotherapeutic Screeening and Assessment Protocol

Vibrational spectroscopy, including Raman micro-spectroscopy, has attracted considerable attention over the last few years, as a powerful, non-invasive tool for clinical applications, especially in cancer diagnosis, in vivo and ex vivo. As a molecular fingerprinting technique with optical resolution, Raman micro-spectroscopy is able to monitor biochemical processes, drug uptake, efficacy and mode of action and mechanisms of interaction of chemotherapeutic drugs at a subcellular level. In vitro applications may be more strategically achievable, and can help guide drug design and discovery, and eventually evaluate To this end, different lung cell lines were used and Raman micro-spectroscopy was coupled to valuable other techniques such as Confocal Laser Scanning Fluorescence Microscopy, Flow Cytometry and Atomic Force Microscopy, in order to explore itssignatures of drug resistance, towards potential applications in personalised therapy and as a companion diagnostic tool. However, to evaluate accurately the potential of Raman micro-spectroscopy for such applications, it is essential to optimise measurement and data processing protocols associated with subcellular analysis in order to extract all valuable spectroscopic information and to demonstrate the ability of this technique to distinguish not only between normal and cancer cells but also between cancer cell lines before exploring its potential as a chemotherapeutic screening and assessment protocol using commercially available chemotherapeutic agents. To be considered as an in vitro companion diagnostics technique to screen for personalised therapies, Raman micro-spectroscopy should be able to monitor subcellular interaction with chemotherapeutic drugs and to characterise cellular resistance. To this end, different lung cell lines were used and Raman micro-spectroscopy was coupled to valuable other techniques such as Confocal Laser Scanning Fluorescence Microscopy, Flow Cytometry and Atomic Force Microscopy, in order to explore its potential to elucidate drug pathways, chemical binding signature, mechanisms of action and efficacy and physiological cellular responses to the drug exposure. As chemotherapeutic agents, Doxorubicin and Actinomycin D, both anthracyclines widely used in clinics especially for lung cancer were employed as pilot molecules. Multivariate data analysis, consisting of Principal Component Analysis, Linear discriminant and Partial Least Square Regression analysis were employed to deeply investigate the spectral features related to drug effects and cellular responses. Investigations demonstrate the ability of Raman micro-spectroscopy not only to track the subcellular accumulation of the drug as function of time but also to identify its mechanism of action, the subsequent cellular response and to differentiate cellular resistance. Moreover, despite the fact that different cell lines show different chemotherapeutic resistance, the chemical binding signature appears to be identical from anti-cancer drugs which belongs to same chemotherapeutic group with implications of different mechanisms of action function of time and dose. In human lung cancer cell lines which show different cytotoxic sensitivities to the drugs, different spectroscoic response profiles to the drugs are observed, which can be potentially linked to cellular defence mechanisms, such as the expression of anti-apoptotic proteins, and DNA repair

Coding of the dimension group

AbstractWe study an aspect of dimension group theory, linked to coding. The dimension group that we consider is built on a given square primitive integer matrix M satisfying the conditions that |detM|⩾2 and that the characteristic polynomial of M is irreducible. The coding is based on iteration of what could be seen as a generalization to Zd of the Euclidean algorithm induced by the matrix M and in a natural way we define a binary operation of addition in the coding group.The set B of symbols is a subset of Zd, and if we denote by ρ the Perron–Frobenius eigenvalue of M and by v a left eigenvector associated to ρ, we define a function Zd×BN*→R which assigns to the element (p,b1,b2,…) the series〈v,p〉+1ρ〈v,b1〉+1ρ2〈v,b2〉+⋯ (in case M=(10), this is the decimal expansion) and the restriction of this function to finite codes is the classical embedding of the dimension group into R.Finally, and under some suitable conditions, we prove that the last function is surjective and this allows the coding of real numbers and consequently the dimension group embedded into R appears as the set of decimal numbers

Study of Harnessing Raindrop Energy Potential in Perak, Malaysia

The main objective of this project is to determine the potential electrical power that can be generated from raindrop impact on piezoelectric material. Previous studies show that the fossil fuel production is depleting and with the rapid growth of population, the remainder supply could not keep up with the energy demand. Therefore, new alternative energy is required to avoid full dependency on fossil fuel. This is a preliminary study focus on rainfall records of Perak, Malaysia to obtain the significant of this new source of energy. By referring to previous study and finite element method, the mathematical model in developed and simulate to define the vibratory movement, strain and potential energy exerted from raindrop impact on polyvinylidene fluoride. The finding shows that the energy output from100m² PVDF plate area was very low in the range of 0.49mJ .The detail of this project are discussed in this paper

Smart Algorithms to Control a Variable Speed Wind Turbine

In this paper, a robust adaptive fuzzy neural network sliding mode (AFNNSM) control design is proposed to maximize the captured energy for a variable speed wind turbine and to minimize the efforts of the drive shaft. Fuzzy neural network (FNN) is used to improve the mathematical system model, by the prediction of model unknown function, which is used by the Sliding mode control approach (SMC) and enables a lower switching gain to be used despite the presence of large uncertainties. As a result, the used robust control action did not exhibit any chattering behavior. This FNN is trained on-line using the backpropagation algorithm (BP). The particle swarm optimization (PSO) algorithm is used in this study to optimize the learning rate of BP algorithm in order to improve the network performance in term of the speed of convergence. The stability is shown by the Lyapunov theory and the trajectory tracking errors converge to zero without any oscillatory behavior. Simulations illustrate the effectiveness of the designed method

Spectroscopic studies of anthracyclines: Structural characterization and in vitro tracking

A broad spectroscopic characterization, using ultraviolet-visible (UV-vis) and Fourier transform infrared absorption as well as Raman scattering, of two commonly used anthracyclines antibiotics (DOX) daunorubicin (DNR), their epimers (EDOX, EDNR) and ten selected analogs is presented. The paper serves as a comprehensive spectral library of UV-vis, IR and Raman spectra of anthracyclines in the solid state and in solution. The particular advantage of Raman spectroscopy for the measurement and analysis of individual antibiotics is demonstrated. Raman spectroscopy can be used to monitor the in vitro uptake and distribution of the drug in cells, using both 488 nm and 785 nm as source wavelengths, with submicrometer spatial resolution, although the cellular accumulation of the drug is different in each case. The high information content of Raman spectra allows studies of the drug-cell interactions, and so the method seems very suitable for monitoring drug uptake and mechanisms of interaction with cellular compartments at the subcellular level

A Novel Development in Three-Dimensional Analytical Solutions for Air Pollution Dispersion Modeling

A novel analytical solution has been developed for the three-dimensional dispersion of atmospheric pollutants, providing a new approach to understanding and addressing this important environmental issue. The central concept of the study is to divide the planetary boundary layer into multiple vertical sub-layers, each characterized by its own average wind speed and eddy diffusivity. This allows for a more comprehensive and nuanced examination of atmospheric processes within the boundary layer. The validity of the model is thoroughly evaluated through a comparison of its predictions with data collected from the Copenhagen Diffusion and Prairie Grass experiments. This approach ensures that the model accurately reflects the complexities of atmospheric dispersion in real-world scenarios. The results of the study demonstrate a strong correlation between the predicted and measured crosswind-integrated concentrations. Furthermore, the statistical indices computed for the model fall within an acceptable range, indicating a high level of accuracy in the model’s predictions. These findings reinforce the validity of the analytical solution for modeling atmospheric pollutant dispersion

Gliosarcome: tumeur rare du système nerveux central - présentation de deux cas

Le gliosarcome est une tumeur primitive mixte du système nerveux central, caractérisée par une prolifération biphasique associant un contingent glial de type glioblastome et un contingent sarcomateux. L'âge moyen de survenue de cette tumeur varie de 40 à 60 ans, avec un sex-ratio homme/femme de 1,8/1. Nous rapportons ici deux cas de gliosarcome traités dans notre service Le traitement standard consiste en une résection chirurgicale de la tumeur suivie d'une radiothérapie externe et parfois d'une chimiothérapie.Pan African Medical Journal 2015; 2

A classification of finite rank dimension groups by their representations in ordered real vector spaces

Peer reviewedPostprin

Psychological wellbeing in chronic disease from a gender perspective: psychosocial variables and brief psychological interventions

La transición epidemiológica en occidente ha supuesto grandes cambios en los patrones de morbi-mortalidad, con un aumento exponencial de las enfermedades no transmisibles (ENT). Esto provocó un cambio en la concepción de salud hacia una perspectiva más integradora, en la que los factores biopsicosociales eran necesarios para explicar los procesos de salud-enfermedad y las personas por tanto se convertían en agentes activos, en responsables más que meros sujetos pasivos a la espera de recibir medicación. Las enfermedades cardiovasculares (ECV) son el conjunto de ENT más prevalente y con una mayor tasa de mortalidad a nivel mundial. Históricamente han sido consideradas enfermedades masculinas, aunque las estadísticas muestran una mayor mortalidad en mujeres. Esta brecha de sexo en las ECV parece venir determinada por un sesgo de género que afecta al diagnóstico e intervención y hace necesaria una perspectiva de género a la hora de abordarlas. Estas enfermedades son el claro ejemplo de la necesidad de entender la salud de manera integral, ya que los principales factores de riesgo cardiovascular son modificables y, por tanto, prevenibles. Uno de los objetivos de la Psicología de la Salud es precisamente conocer los factores subyacentes que influyen en el comportamiento saludable de este tipo de pacientes con el fin de promoverlo. En esta dirección, numerosas investigaciones han relacionado las conductas saludables con variables psicológicas como la autoeficacia, una regulación emocional adecuada o el bienestar psicológico, que se vinculan con un mayor compromiso terapéutico y cambios saludables en el estilo de vida. A su vez, las ECV se han encontrado relacionadas con unos niveles altos de ansiedad, estrés y depresión, y estas se relacionan asimismo con un peor pronóstico de la enfermedad y una peor calidad de vida en estos pacientes. Por esta relación entre factores psicológicos y determinantes de salud cardiovascular, se necesitan intervenciones dirigidas a intentar promover estas variables psicológicas con el objetivo de mejorar su ajuste a la enfermedad y la reducción del riesgo cardiovascular. En esta línea, y partiendo de los prometedores resultados de la telemedicina para promover conductas saludables, es necesario conocer si este tipo de intervenciones serían eficaces para mejorar las variables psicológicas antes mencionadas en pacientes con ECV. De igual modo, la brecha de salud entre mujeres y hombres hace necesaria la implementación de una perspectiva de género en la investigación e intervención sobre la misma. Por todo lo anterior, la presente Tesis Doctoral tiene como objetivo profundizar en el análisis de los factores psicosociales que afectan a la salud y que se relacionan con la ECV, así como poner a prueba la eficacia de intervenciones mHealth para promover las variables psicológicas que se relacionan con los comportamientos saludables y el bienestar psicológico de esta población. Se proponen, por tanto, una serie de investigaciones que se han materializado en la publicación de tres artículos científicos independientes e interrelacionados, los cuales se presentan a continuación. El primer estudio es una revisión sistemática que tiene como objetivo explorar los factores psicosociales que se han estudiado para explicar la vulnerabilidad diferencial del bienestar psicológico en mujeres y hombres. Partiendo de un modelo biopsicosocial, complementado con la perspectiva de género, se incluyeron estudios que evaluaban las diferencias de sexo y género en la ansiedad y su comorbilidad. Siguiendo la metodología PRISMA, se realizó una búsqueda sistemática en las bases de datos electrónicas PubMed y PsycInfo, incorporando estudios empíricos y revisiones publicadas entre 2008 - 2021. Tras la búsqueda, 44 estudios fueron incluidos, los cuales se analizaron y clasificaron en función del objeto de estudio. Finalmente, se realizó una síntesis narrativa cualitativa de los resultados. Los resultados de los estudios incluidos mostraron que las diferencias en la vulnerabilidad psicológica entre sexos se han analizado históricamente a partir de factores biológicos o factores de corte psicosocial; sin embargo, estudios que abordasen la problemática aludiendo de manera conjunta a ambos factores fueron escasos El segundo estudio tiene como objetivo evaluar la efectividad de una intervención psicológica mHealth en regulación emocional para mejorar el afecto positivo y la autoeficacia en personas con ECV. Para ello, se diseñó un ensayo controlado no aleatorizado de dos brazos, en el que la muestra de 69 pacientes cardiovasculares participó en un grupo experimental o un grupo control o de tratamiento habitual. La intervención, basada en el proceso de regulación emocional (Gross, 1998; Leahy, 2011), está conformada por dos fases. La primera consistió en una sesión presencial y la segunda en una intervención basada en mHealth de 14 días. Ambos grupos fueron evaluados en múltiples ocasiones en afecto positivo y autoeficacia (crónica y cardíaca), incluyendo dos follow-ups, lo que permitió un análisis de medidas repetidas. Los resultados indican que la intervención psicológica mHealth fue efectiva para mejorar el afecto positivo y la autoeficacia en pacientes con ECV, encontrándose diferencias intragrupo y entre grupos. El tercer estudio es un ensayo clínico piloto no aleatorizado, que tiene como objetivo diseñar y evaluar la efectividad de una intervención mHealth multicomponente en autoeficacia para mejorar el bienestar subjetivo y la autoeficacia para el manejo de la enfermedad cardíaca y crónica, analizando además posibles diferencias entre hombres y mujeres. Para este estudio, la muestra estaba compuesta por 42 pacientes cardiovasculares, que participaron equitativamente en un grupo experimental o control. Esta intervención multicomponente fue diseñada en base a la autoeficacia (Bandura, 1986a) e incluye una sesión presencial personalizada y una intervención mHealth de 14 días. Al igual que en el segundo estudio, ambos grupos fueron evaluados en repetidas ocasiones, con dos evaluaciones follow-ups que permitieron hacer comparaciones entre grupos e intragrupo, y ofrecer información más precisa acerca de la efectividad de la intervención. Los resultados mostraron que esta fue efectiva para mejorar el afecto positivo y la autoeficacia para el manejo de la enfermedad en pacientes cardiovasculares. Sin embargo, cuando se analizaron los datos por sexo, se observó que esta efectividad se daba únicamente en la población masculina. En conjunto, los resultados derivados de los tres estudios que conforman la presente tesis doctoral ponen de manifiesto la necesidad de incorporar el modelo biopsicosocial, así como la perspectiva de género, para comprender los procesos de salud enfermedad y abordar el diagnóstico y tratamiento de enfermedades de largo alcance como lo son las ECV, y su relación con la salud mental. Por su parte, los estudios empíricos aportan evidencia en favor de las vertientes terapéuticas que demandan la inclusión de la psicología en la rehabilitación cardíaca, además de la incorporación de nuevas estrategias de intervención que garanticen la accesibilidad de la atención sanitaria a este tipo de pacientes. Se considera que investigaciones futuras, por otro lado, deberían poner el foco en cómo establecer intervenciones online sin perder el contacto humano, así como tratar de adentrarse completamente en la personalización de estas intervenciones buscando evitar las diferencias en efectividad para las mujeres y la obtención de mejores resultados terapéuticos.The epidemiological transition in Western countries has led to major changes in morbidity and mortality patterns, with an exponential increase in non-communicable diseases (NCDs). This led to a change in the conception of health towards a more integrative perspective, in which biopsychosocial factors were necessary to explain the health disease processes and people, therefore, became active agents, responsible rather than mere passive subjects waiting to receive medication. Cardiovascular diseases (CVD) are the most prevalent set of NCDs with the highest mortality rate worldwide. They have historically been considered male diseases, although statistics show a higher mortality in women. This gender gap in CVD seems to be determined by a gender bias that affects diagnosis and intervention and makes a gender perspective necessary when addressing them. These diseases are a clear example of the need for a holistic approach to health, as the main cardiovascular risk factors are modifiable and, therefore, preventable. One of the objectives of Health Psychology is precisely to understand the underlying factors that influence healthy behaviour of these patients in order to promote them. In this direction, numerous investigations have related healthy behaviours to psychological variables, such as self-efficacy, adequate emotional regulation or psychological well-being, which are linked to greater therapeutic commitment and healthy lifestyle changes. In turn, CVD has been found to be associated with high levels of anxiety, stress and depression, which are also related to a worse prognosis of the disease and a poorer quality of life in these patients. Due to this relationship between psychological factors and cardiovascular health determinants, interventions aimed at promoting these psychological variables with the objective of improving their adjustment to the disease and reducing cardiovascular risk are deemed necessary. In this line, and based on the promising results of telemedicine to promote healthy behaviours, it is necessary to know whether this type of intervention would be effective in improving the aforementioned psychological variables in patients with CVD. Similarly, the health gap between women and men makes it necessary to implement a gender perspective in research and intervention. For all of the above reasons, the aim of this doctoral thesis is to deepen the analysis of the psychosocial factors that affect health and are related to CVD, as well as to test the effectiveness of mHealth interventions to promote the psychological variables related to healthy behaviours and psychological well-being in these patients. Thus, a series of investigations are proposed. These investigations have materialised in the publication of three independent and interrelated scientific articles, which are presented below. The first study is a systematic review that aims to explore the psychosocial factors that have been studied to explain the differential vulnerability of psychological well-being in women and men. Based on a biopsychosocial model, complemented by the gender perspective, studies assessing sex and gender differences in anxiety and its comorbidity were included. Following the PRISMA methodology, a systematic search was conducted in the electronic databases PubMed and PsicInfo, incorporating empirical studies and reviews published between 2008 - 2021. Following the search, 44 studies were included, which were analysed and classified according to the object of study. Finally, a qualitative narrative synthesis of the results was conducted. The results of the included studies showed that differences in psychological vulnerability between the sexes have historically been analysed on the basis of biological factors or psychosocial factors, but few studies have addressed the problem by alluding to both factors together. The second study aims to evaluate the effectiveness of an mHealth psychological intervention in emotional regulation to improve positive affect and self-efficacy in patients with CVD. To this end, a two-arm, non-randomised controlled trial was designed, in which the sample of 69 CVD patients was assigned to either the experimental group or the control or treatment-as-usual group. The intervention, based on the emotional regulation process (Gross, 1998; Leahy, 2011), consists of two phases, a face-to-face session and a second 14-day mHealth phase. Both groups were assessed multiple times on positive affect and self-efficacy (chronic and cardiac), including two follow-ups, which allowed for a repeated measures analysis. The results indicate that the mHealth psychological intervention was effective in improving positive affect and self-efficacy in patients with cardiovascular disease, with intra-group and between-group differences found. The third study is another pilot non-randomised clinical trial, which aims to design and evaluate the effectiveness of a multicomponent mHealth intervention on self-efficacy in improving subjective well-being and self-efficacy for the management of cardiac and chronic disease, also analysing possible differences between men and women. For this study, the sample consisted of 42 cardiovascular patients, who were equally assigned to the control or experimental group. This multicomponent intervention was designed on the basis of self-efficacy (Bandura, 1986a) and included a face-to-face one-to-one session and a 14-day mHealth intervention. As in the second study, both groups were repeatedly evaluated, with two follow-up assessments allowing for between-group and within-group comparisons and providing more accurate information about the effectiveness of the intervention. The results showed that the intervention was effective in improving positive affect and self-efficacy for disease management in cardiovascular patients. However, when the data were analysed by gender, this effectiveness was found to occur only in the male population. Taken together, the results derived from the three studies that constitute this doctoral thesis highlight the need to incorporate the biopsychosocial model, as well as a gender perspective, in order to understand health-disease processes and to address the diagnosis and treatment of long-term diseases, such as CVD, and their relation with mental health. With regards to the empirical studies, they provide evidence in favor of the therapeutic aspects that demand the inclusion of psychology in cardiac rehabilitation, as well as the incorporation of new intervention strategies that guarantee the accessibility of health care for these patients. Future research, on the other hand, should focus on how to establish online interventions without losing human contact, as well as try to fully explore the personalization of these interventions in order to avoid differences in effectiveness for women and to obtain better therapeutic results