Cryogenic Ion Vibrational Spectroscopy of Gas-Phase Clusters: Structure, Anharmonicity and Fluxionality

Gas-phase clusters are aggregates of a countable number of particles, which exhibit size-dependent physical and chemical properties that typically lie in the non-scalable size regime. These properties can be systematically characterized at a molecular level with respect to composition, size and charge state. This allows studying how macroscopic properties of condensed matter, e.g. phase transitions or metallic behavior, emerge from the atomic or molecular properties as a function of cluster size. Furthermore, smaller clusters are also amenable to high-level quantum chemical calculations, making them ideal model systems for understanding phenomena in more complex heterogeneous matter. The main advantage here is that clusters can be studied with a very high degree of selectivity and sensitivity, under well-defined conditions and in the absence of perturbing interaction with an environment. The studies presented in this theses focus on the structure characterization of ionic clusters using cryogenic ion vibrational spectroscopy. This technique combines cryogenic ion trapping with mass spectrometric schemes and infrared photodissociation (IRPD) spectroscopy. It makes use of an ion-trap triple mass spectrometer in combination with various light sources that grant access to a wide range of the infrared spectrum (210-4000 cm-1). Structures are typically assigned by comparing experimental IRPD spectra with computed vibrational spectra. The structures of aluminum oxide clusters and their interaction with water are studied in the framework of the collaborative research center CRC1109 "Understanding of Metal Oxide / Water Systems at the Molecular Scale: Structural Evolution, Interfaces, and Dissolution". This project aims at gaining a molecular level understanding of the mechanisms involved in oxide formation and dissolution. Section 4.1 and 4.2 present results of IRPD spectroscopy experiments on small mono and dialuminum oxide anions and on the anionic cluster series (Al2O3)nAlO2- with n = 0 to 6. These studies discuss the effects of the distribution of the excess charge on the cluster structure, analyze how structural properties evolve with size and how these relate to those of nanoparticles and crystal surfaces. The dissociative adsorption of water by Al-oxide clusters is investigated in Section 4.3.2. Boron exhibits a rich variety of polymorphs with the B12 icosahedron as a common building block. This three dimensional (3D) structure is retained in the halogenated closo-dodecaborate dianions (B12X122-). On the other hand, small pure boron clusters are essentially planar. The study presented in Section 5.2 investigates the 3D to 2D structural transition by probing the vibrational spectra of partially deiodinated B12In2- clusters as a function of decreasing n. The results presented in Section 5.1 show that B13+ has a planar structure consisting of two concentric rings. As a result of delocalized aromatic bonding, this structure is particularly stable without being rigid as it permits an almost free rotation of the inner ring. Protonated water clusters are model systems for understanding protons in aqueous solutions. The interpretation of their vibrational spectra is a challenge for state-of-the-art electronic structure calculations and therefore often prone to controversies. The results presented in Chapter 6 clear existing doubts over the assignment of the protonated water pentamer structure and the vibrational fingerprints of the embedded distorted H3O+. This study laid the foundation for a subsequent series of measurements which provided crucial new insights into the proton transfer mechanism in water

Targeting dementias through cancer kinases inhibition

The failures in Alzheimer's disease (AD) therapy strongly suggest the importance of reconsidering the research strategies analyzing other mechanisms that may take place in AD as well as, in general, in other neurodegenerative dementias. Taking into account that in AD a variety of defects result in neurotransmitter activity and signaling efficiency imbalance, neuronal cell degeneration and defects in damage/repair systems, aberrant and abortive cell cycle, glial dysfunction, and neuroinflammation, a target may be represented by the intracellular signaling machinery provided by the kinome. In particular, based on the observations of a relationship between cancer and AD, we focused on cancer kinases for targeting neurodegeneration, highlighting the importance of targeting the intracellular pathways at the intersection between cell metabolism control/duplication, the inhibition of which may stop a progression in neurodegeneration

PMI: A Delta Psi(m) Independent Pharmacological Regulator of Mitophagy

Mitophagy is central to mitochondrial and cellular homeostasis and operates via the PINK1/Parkin pathway targeting mitochondria devoid of membrane potential (ΔΨm) to autophagosomes. Although mitophagy is recognized as a fundamental cellular process, selective pharmacologic modulators of mitophagy are almost nonexistent. We developed a compound that increases the expression and signaling of the autophagic adaptor molecule P62/SQSTM1 and forces mitochondria into autophagy. The compound, P62-mediated mitophagy inducer (PMI), activates mitophagy without recruiting Parkin or collapsing ΔΨm and retains activity in cells devoid of a fully functional PINK1/Parkin pathway. PMI drives mitochondria to a process of quality control without compromising the bio-energetic competence of the whole network while exposing just those organelles to be recycled. Thus, PMI circumvents the toxicity and some of the nonspecific effects associated with the abrupt dissipation of ΔΨm by ionophores routinely used to induce mitophagy and represents a prototype pharmacological tool to investigate the molecular mechanisms of mitophagy

Tactile perception by friction induced vibrations

Cataloged from PDF version of article.When a finger moves to scan the surface of an object (haptic sensing), the sliding contact generates vibrations that propagate in the finger skin activating the receptors (mechanoreceptors) located in the skin, allowing the brain to identify objects and perceive information about their properties. The information about the surface of the object is transmitted through vibrations induced by friction between the skin and the object scanned by the fingertip. The mechanoreceptors transduce the stress state into electrical impulses that are conveyed to the brain. A clear understanding of the mechanisms of the tactile sensing is fundamental to numerous applications, like the development of artificial tactile sensors for intelligent prostheses or robotic assistants, and in ergonomics. While the correlation between surface roughness and tactile sensation has already been reported in literature, the vibration spectra induced by the finger-surface scanning and the consequent activation of the mechanoreceptors on the skin have received less attention. In this paper, frequency analysis of signals characterizing surface scanning is carried out to investigate the vibration spectrum measured on the finger and to highlight the changes shown in the vibration spectra as a function of characteristic contact parameters such as scanning speed, roughness and surface texture. An experimental set-up is developed to recover the vibration dynamics by detecting the contact force and the induced vibrations; the bench test has been designed to guarantee reproducibility of measurements at the low amplitude of the vibrations of interest, and to perform measurements without introducing external noise. Two different perception mechanisms, as a function of the roughness wavelength, have been pointed out. The spectrum of vibration obtained by scanning textiles has been investigated. (C) 2011 Elsevier Ltd. All rights reserved

Significados y estrategias de cuidados desarrollados en la vida cotidiana por madres de niños con trastornos del espectro autista en Las Piedras

La presente tesis es la sistematización de una investigación, que busca conocer los significados y estrategias de cuidados desarrollados en la vida cotidiana por madres de niños de 8 a 14 años con Trastorno del Espectro Autista (TEA), en la ciudad de Las Piedras. Enmarcada en una metodología cualitativa exploratoria, se realiza una Etnografía, utilizando Entrevistas Etnográficas, Observación Participante y Análisis de Documento, para la recolección de datos, posteriormente se efectúa análisis de contenido. Obtenidos los resultados preliminares, se organiza un encuentro de Devolución Creativa con las participantes, siete mujeres de la Asociación de Padres de niños con TEA (APTEA). Se pretende realizar una mirada crítica a la vida cotidiana (Hetler,1977; Pichón Riviére, Pampliega de Quiroga 1985), visibilizando los modos de adjudicación-asunción de roles, y las formas de producción y reproducción de la vida. A partir del diagnóstico como mojón que obliga a la reorganización familiar, se trabaja conceptos de cuidados y sus fuentes de aprendizajes, y las estrategias que crean estas mujeres para llevarlo adelante. Se analizan las dimensiones de cuidados, proceso diagnóstico, educación, trabajo, salud, tiempo libre, redes, necesidades y fortalezas identificadas en el cuidado. Se revisaron los documentos de APTEA, para identificar las posturas colectivas en torno a los cuidados. Como conclusiones se visualiza que la vida familiar gira entorno al niño con discapacidad, siendo la madre la cuidadora principal, tarea que está atravesada fuertemente por estereotipos de género. En consecuencia en la vida cotidiana se despliegan múltiples estrategias de cuidados, que repercuten en las áreas laborales, sociales y salud de estas mujeres. Se identifica a APTEA como un nodo importante en la red personal, como espacio de contención, donde se comparten estrategias de cuidado, frustraciones y alegrías

A Statistical Framework for Automatic Leakage Detection in Smart Water and Gas Grids

In the last few years, due to the technological improvement of advanced metering infrastructures, water and natural gas grids can be regarded as smart-grids, similarly to power ones. However, considering the number of studies related to the application of computational intelligence to distribution grids, the gap between power grids and water/gas grids is notably wide. For this purpose, in this paper, a framework for leakage identification is presented. The framework is composed of three sections aimed at the extraction and the selection of features and at the detection of leakages. A variation of the Sequential Feature Selection (SFS) algorithm is used to select the best performing features within a set, including, also, innovative temporal ones. The leakage identification is based on novelty detection and exploits the characterization of a normality model. Three statistical approaches, The Gaussian Mixture Model (GMM), Hidden Markov Model (HMM) and One-Class Support Vector Machine (OC-SVM), are adopted, under a comparative perspective. Both residential and office building environments are investigated by means of two datasets. One is the Almanac of Minutely Power dataset (AMPds), and it provides water and gas data consumption at 1, 10 and 30 min of time resolution; the other is the Department of International Development (DFID) dataset, and it provides water and gas data consumption at 30 min of time resolution. The achieved performance, computed by means of the Area Under the Curve (AUC), reaches 90 % in the office building case study, thus confirming the suitability of the proposed approach for applications in smart water and gas grids

Contact of a Finger on Rigid Surfaces and Textiles: Friction Coefficient and Induced Vibrations

The tactile information about object surfaces is obtained through perceived contact stresses and frictioninduced vibrations generated by the relative motion between the fingertip and the touched object. The friction forces affect the skin stress-state distribution during surface scanning, while the sliding contact generates vibrations that propagate in the finger skin activating the receptors (mechanoreceptors) and allowing the brain to identify objects and perceive information about their properties. In this article, the friction coefficient between a real human finger and both rigid surfaces and fabrics is retrieved as a function of the contact parameters (load and scanning speed). Then, the analysis of the vibration spectra is carried out to investigate the features of the induced vibrations, measured on the fingernail, as a function of surface textures and contact parameters. While the friction coefficient measurements on rigid surfaces agree with empirical laws found in literature, the behaviour of the friction coefficient when touching a fabric is more complex, and is mainly the function of the textile constructional properties. Results show that frequency spectrum distribution, when touching a rigid surface, is mainly determined by the relative geometry of the two contact surfaces and by the contact parameters. On the contrary, when scanning a fabric, the structure and the deformation of the textile itself largely affect the spectrum of the induced vibration. Finally, some major features of the measured vibrations (frequency distribution and amplitude) are found to be representative of tactile perception compared to psychophysical and neurophysiologic works in literature

An immature B cell population from peripheral blood serves as surrogate marker for monitoring tumor angiogenesis and anti-angiogenic therapy in mouse models

Tumor growth depends on the formation of new blood vessels (tumor angiogenesis) either from preexisting vessels or by the recruitment of bone marrow-derived cells. Despite encouraging results obtained with preclinical cancer models, the therapeutic targeting of tumor angiogenesis has thus far failed to deliver an enduring clinical response in cancer patients. One major obstacle for improving anti-angiogenic therapy is the lack of validated biomarkers, which allow patient stratification for suitable treatment and a rapid assessment of therapy response. Toward these goals, we have employed several mouse models of tumor angiogenesis to identify cell populations circulating in their blood that correlated with the extent of tumor angiogenesis and therapy response. Flow cytometry analyses of different combinations of cell surface markers that define subsets of bone marrow-derived cells were performed on peripheral blood mononuclear cells from tumor-bearing and healthy mice. We identified one cell population, CD45dimVEGFR1⁻CD31low, that was increased in levels during active tumor angiogenesis in a variety of transgenic and syngeneic transplantation mouse models of cancer. Treatment with various anti-angiogenic drugs did not affect CD45dimVEGFR1⁻CD31low cells in healthy mice, whereas in tumor-bearing mice, a consistent reduction in their levels was observed. Gene expression profiling of CD45dimVEGFR1⁻CD31low cells characterized these cells as an immature B cell population. These immature B cells were then directly validated as surrogate marker for tumor angiogenesis and of pharmacologic responses to anti-angiogenic therapies in various mouse models of cancer