Gaussian graphical modeling for spectrometric data analysis

Motivated by the analysis of spectrometric data, we introduce a Gaussian graphical model for learning the dependence structure among frequency bands of the infrared absorbance spectrum. The spectra are modeled as continuous functional data through a B-spline basis expansion and a Gaussian graphical model is assumed as a prior specification for the smoothing coefficients to induce sparsity in their precision matrix. Bayesian inference is carried out to simultaneously smooth the curves and to estimate the conditional independence structure between portions of the functional domain. The proposed model is applied to the analysis of infrared absorbance spectra of strawberry purees

Primary Macrophage Chemotaxis Induced by Cannabinoid Receptor 2 Agonists Occurs Independently of the CB2 Receptor

Activation of CB(2) has been demonstrated to induce directed immune cell migration. However, the ability of CB2 to act as a chemoattractant receptor in macrophages remains largely unexplored. Using a real-time chemotaxis assay and a panel of chemically diverse and widely used CB(2) agonists, we set out to examine whether CB(2) modulates primary murine macrophage chemotaxis. We report that of 12 agonists tested, only JWH133, HU308, L-759,656 and L-759,633 acted as macrophage chemoattractants. Surprisingly, neither pharmacological inhibition nor genetic ablation of CB(2) had any effect on CB(2) agonist-induced macrophage chemotaxis. As chemotaxis was pertussis toxin sensitive in both WT and CB(2)(-/-) macrophages, we concluded that a non-CB(1)/CB(2), G(i/o)-coupled GPCR must be responsible for CB(2) agonist-induced macrophage migration. The obvious candidate receptors GPR18 and GPR55 could not mediate JWH133 or HU308-induced cytoskeletal rearrangement or JWH133-induced β-arrestin recruitment in cells transfected with either receptor, demonstrating that neither are the unidentified GPCR. Taken together our results conclusively demonstrate that CB(2) is not a chemoattractant receptor for murine macrophages. Furthermore we show for the first time that JWH133, HU308, L-759,656 and L-759,633 have off-target effects of functional consequence in primary cells and we believe that our findings have wide ranging implications for the entire cannabinoid field

Un'analisi empirica delle determinanti del partenariato pubblico-privato nei governi locali in Svizzera

The concept of public-private partnership (PPP) has been developed in several countries, in the context of ground-breaking reforms related to the emergent paradigm of public management. A common characteristic among the PPP models developed around the world comprises the possibility for the public sector to bring in management processes from the private sector, such as privatization, decentralization, contract in and out, and PPPs. In opposition to the traditional model whereby the production function is carried out either by governmental institutions or by private companies, a third path is emerging whereby the public and the private sectors join hands to deliver a good or service to citizens. Along these lines, PPP is defined as a durable collaboration between public and private actors, where the partners collaborate to develop products and services, thus sharing risks, costs, and benefits. The primary objective of the present work is to identify a series of conditions whereby a Swiss municipality should bring about a PPP. Thus, an empirical analysis tests five hypotheses with the purpose to understand what is, or what are, the conditions with a major bearing over the constitution of the PPP.Il partenariato pubblico-privato è stato sviluppato in differenti Paesi del mondo in un contesto di radicali cambiamenti facenti riferimento alle riforme del public management. Tra i diversi Stati che hanno adottato questi programmi di riforma vi sono delle caratteristiche comuni, una delle quali include la possibilità per l’ente pubblico di introdurre dei sistemi di gestione dal settore privato, quali: la privatizzazione, la decentralizzazione delle funzioni e delle responsabilità, il contracting out e contracting in dei servizi e, per finire, il partenariato tra lo Stato ed il settore privato. Si viene dunque a creare una terza via in cui, a differenza del modello tradizionale che prevede la produzione dei beni interamente da parte del settore privato oppure da parte di quello pubblico, lo Stato e le imprese private (le quali sono costituite sia da imprese for profit, sia da imprese no profit) collaborano per fornire un bene o servizio pubblico ai cittadini. Pertanto il partenariato pubblico-privato è definito come una collaborazione tra attori pubblici e privati con un carattere di durabilità, in cui gli attori sviluppano insieme prodotti e servizi ed in cui i rischi, i costi ed i benefici sono condivisi. Questo lavoro si prefigge come obiettivo fondamentale l'identificazione di una serie di condizioni per cui un Comune svizzero dovrebbe attivare un partenariato pubblico-privato. Successivamente, attraverso un’analisi empirica, si intendono testare cinque ipotesi per verificare qual è o quali sono le condizioni che maggiormente influenzano la creazione del partenariato

The identification & optimisation of endogenous signalling pathway modulators

Chapter 1 Provides an overview of drug discovery with particular emphasis on library selection and hit identification methods using virtual based approaches. Chapter 2 Gives an outline of the bone morphogenetic protein (BMP) signalling pathway and literature BMP pathway modulators. The association between the regulation of BMP pathway and cardiomyogenesis is also described. Chapter 3 Describes the use of ligand based virtual screening to discover small molecule activators of the BMP signalling pathway. A robust cell based BMP responsive gene activity reporter assay was developed to test the libraries of small molecules selected. Hit molecules from the screen were synthesised to validate activity. It was found that a group of known histone deacetylase (HDAC) inhibitors displayed most promising activity. These were evaluated in a secondary assay measuring the expression of two BMP pathway regulated genes, hepcidin and Id1, using reverse transcription polymerase chain reaction (RT-PCR). 188 was discovered to increase expression of both BMP-responsive genes. Chapter 4 Provides an overview of existing cannabinoid receptor (CBR) modulating molecules and their connection to progression of atherosclerosis. Chapter 5 Outlines the identification and optimisation of selective small molecule agonists acting at the cannabinoid 2 receptor (CB2R). Ligand based virtual screen was undertaken and promising hits were synthesised to allow structure activity relationship (SAR) to be developed around the hit molecule providing further information of the functional groups tolerated at the active site. Subsequent studies led to the investigation and optimisation of physicochemical properties around 236 leading to the development of a suitable compound for in vivo testing. Finally, a CB2R selective compound with favourable physicochemical properties was evaluated in vivo in a murine inflammation model and displayed reduced recruitment of monocytes to the site of inflammation.</p

Indagine di customer satisfaction presso l'istituto Romano Bruni

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The identification & optimisation of endogenous signalling pathway modulators

Chapter 1 Provides an overview of drug discovery with particular emphasis on library selection and hit identification methods using virtual based approaches. Chapter 2 Gives an outline of the bone morphogenetic protein (BMP) signalling pathway and literature BMP pathway modulators. The association between the regulation of BMP pathway and cardiomyogenesis is also described. Chapter 3 Describes the use of ligand based virtual screening to discover small molecule activators of the BMP signalling pathway. A robust cell based BMP responsive gene activity reporter assay was developed to test the libraries of small molecules selected. Hit molecules from the screen were synthesised to validate activity. It was found that a group of known histone deacetylase (HDAC) inhibitors displayed most promising activity. These were evaluated in a secondary assay measuring the expression of two BMP pathway regulated genes, hepcidin and Id1, using reverse transcription polymerase chain reaction (RT-PCR). 188 was discovered to increase expression of both BMP-responsive genes. Chapter 4 Provides an overview of existing cannabinoid receptor (CBR) modulating molecules and their connection to progression of atherosclerosis. Chapter 5 Outlines the identification and optimisation of selective small molecule agonists acting at the cannabinoid 2 receptor (CB2R). Ligand based virtual screen was undertaken and promising hits were synthesised to allow structure activity relationship (SAR) to be developed around the hit molecule providing further information of the functional groups tolerated at the active site. Subsequent studies led to the investigation and optimisation of physicochemical properties around 236 leading to the development of a suitable compound for in vivo testing. Finally, a CB2R selective compound with favourable physicochemical properties was evaluated in vivo in a murine inflammation model and displayed reduced recruitment of monocytes to the site of inflammation.This thesis is not currently available in OR

Functional graphical model for spectrometric data analysis

Motivated by the analysis of spectrographic data, we introduce a functional graphical model for learning the conditional independence structure of spectra. Absorbance spectra are modeled as continuous functional data through a cubic B-spline basis expansion. A Gaussian graphical model is assumed for basis ex- pansion coefficients, where a sparse structure is induced for the precision matrix. Bayesian inference is carried out, providing an estimate of the precision matrix of the coefficients, which translates into an estimate of the conditional independence structure between frequency bands of the spectrum. The proposed model is applied to the analysis of the infrared absorbance spectra of strawberry purees

Understanding Social Behaviour in a Health-Care Facility from Localization Data: A Case Study

The most frequent form of dementia is Alzheimer’s Disease (AD), a severe progressive neurological pathology in which the main cognitive functions of an individual are compromised. Recent studies have found that loneliness and living in isolation are likely to cause an acceleration in the cognitive decline associated with AD. Therefore, understanding social behaviours of AD patients is crucial to promote sociability, thus delaying cognitive decline, preserving independence, and providing a good quality of life. In this work, we analyze the localization data of AD patients living in assisted care homes to gather insights about the social dynamics among them. We use localization data collected by a system based on iBeacon technology comprising two components: a network of antennas scattered throughout the facility and a Bluetooth bracelet worn by the patients. We redefine the Relational Index to capture wandering and casual encounters, these being common phenomena among AD patients, and use the notions of Relational and Popularity Indexes to model, visualize and understand the social behaviour of AD patients. We leverage the data analyses to build predictive tools and applications to enhance social activities scheduling and sociability monitoring and promotion, with the ultimate aim of providing patients with a better quality of life. Predictions and visualizations act as a support for caregivers in activity planning to maximize treatment effects and, hence, slow down the progression of Alzheimer’s disease. We present the Community Behaviour Prediction Table (CBPT), a tool to visualize the estimated values of sociability among patients and popularity of places within a facility. Finally, we show the potential of the system by analyzing the Coronavirus Disease 2019 (COVID-19) lockdown time-frame between February and June 2020 in a specific facility. Through the use of the indexes, we evaluate the effects of the pandemic on the behaviour of the residents, observing no particular impact on sociability even though social distancing was put in place

Critical review on the usage of antimicrobials and on the restoration of the intestinal environment in canine acute and chronic diarrhea

Antimicrobials (AMs) are used in many cases of acute and chronic diarrhea in the dog. The aim of the present Manuscript is to critically review the current literature trying to define how frequently bacteria effectively cause acute and chronic diarrhea and which are the most frequent clinical effects of antimicrobials’ use. In addition, a brief overview of the main approaches to restore the intestinal environment is given. It resulted that antimicrobials do not always improve the clinical condition, unless bacteria are an established cause of the observed clinical signs (e.g. diarrhea), as rarely happens, or the related complications (e.g. sepsis). ). AMs should not be used empirically as a tool in the diagnostic work-up, neither in acute nor in chronic diarrhea and the presence of fresh blood in stools should not necessarily imply the obligation to resort to antimicrobials use