2,089 research outputs found

    Use of Kriging Technique to Study Roundabout Performance

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    Road intersections are dangerous places because of the many conflicting points between motorized and nonmotorized vehicles. In the case of defined traffic volume, several research groups have proved that roundabouts reduced the number of injuries and fatal accident cases. In recent years, many countries have adopted roundabouts as a standard design solution for both urban and rural roads. Several recent studies have investigated the performance of roundabouts, including some with models that calculated the entering flow (Q sub e) as a function of the circulating flow (Q sub c). Most existing models have been constructed with the use of linear or exponential statistical regression. The interpolative techniques in classical statistics are based on the use of canonical forms (linear or polynomial) that completely ignore the correlation law between collected data. As such, the determined interpolation stems from the assumption that the data represent a random sample. In the research reported in this paper, a geostatistical approach was considered: the relationship Q sub e versus Q sub c is supposed to be a regionalized phenomenon. According to that supposition, collected data do not represent a random sample of values but are supposed to be related to each other with a defined law. This recognition allows the realization of interpolation on the basis of the real law of the phenomenon. This paper discusses the fundamental theories, the applied operating procedures, and the first results obtained in modeling the Q sub e versus Q sub c relationship with the application of geostatistics

    The issue of stereochemical control in multicomponent reactions and glycosylation processes.

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    Multicomponent reactions (MCRs) are processes that show high atom and step economy; two different parts of my thesis were linked by MCRs. In the first part, levulinic acid was converted into a variety of bicyclic nitrogen heterocycles passing by an Ugi reaction. The obtained intermediate was then converted in the final product via a simple SN2 cyclization. The second part, instead, was dedicated to the obtainment of organo-catalysts structurally based on secondary and tertiary amine groups. First attempts, to get the latter in bicyclic structures, involved a starting MCR with L-prolinol, but the reaction showed low diastereoselectivity and the cyclization failed. A different strategy was aimed to obtain secondary amines and resulted to be more efficient. The involvement of a seven-membered cyclic imine, with a chiral center in C-3, in a Ugi-Joulli\ue9 reaction resulted in a very diastereoselective process. Using a silyl oxy derived carboxylic acid, an Ugi adduct with a protected alcohol is obtained. Thus, an intramolecular cyclization can be performed producing the final free amine group. The obtained amine was used to perform the first catalysis tests in Michael and aldol reactions. Although no catalytic activity was detected, different reaction conditions and structures have still to been tested. Finally, the reaction mechanism in self-promoted glycosylations was investigated. They involve a trichloroacetimidate as glycosyl donor which is activated by an acceptor that contains an acid sulfonamide portion. An alcoholic function was added to the acceptor with a consecutive possible production of both O- and N-glycosides. Dissociative mechanism favors the first while an associative mechanism brings to the second. The study showed the chemoselectivity and, to some extent, the stereoselectivity of the reaction to be controlled by tuning the parameters e.g. the polarity of the solvent, the concentration of donor and acceptor and the use of additives such as lithium salts

    Analysis of heat kernel highlights the strongly modular and heat-preserving structure of proteins

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    In this paper, we study the structure and dynamical properties of protein contact networks with respect to other biological networks, together with simulated archetypal models acting as probes. We consider both classical topological descriptors, such as the modularity and statistics of the shortest paths, and different interpretations in terms of diffusion provided by the discrete heat kernel, which is elaborated from the normalized graph Laplacians. A principal component analysis shows high discrimination among the network types, either by considering the topological and heat kernel based vector characterizations. Furthermore, a canonical correlation analysis demonstrates the strong agreement among those two characterizations, providing thus an important justification in terms of interpretability for the heat kernel. Finally, and most importantly, the focused analysis of the heat kernel provides a way to yield insights on the fact that proteins have to satisfy specific structural design constraints that the other considered networks do not need to obey. Notably, the heat trace decay of an ensemble of varying-size proteins denotes subdiffusion, a peculiar property of proteins

    Geostatistical Approach for Operating Speed Modelling on Italian Roads

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    Injuries are one of the main causes of death according to W.H.O. For this reason the attention of road safety researchers especially regards the study of the relationship between driver and road environment. Several research works show that operating speed is an excellent driver behavior parameter. This article describes a different approach to the classical definition of prediction models for operating speed on horizontal curves. In this paper, the fundamental theories, the applied operating procedures and the first results obtained with the application of Geostatistics are discussed. The mathematical models expressing operating speed in function of horizontal curves characteristics found in International scientific literature, have mainly been built on the basis of Classical Statistics. For this reason, it needs to be pointed out that the interpolative techniques found in Classical Statistics are based upon the use of canonical forms (linear or polynomial regressions) that completely ignore the correlation law between collected data. As such, the determined interpolation stems from the assumption that the data represent a random sample. The models described in this article have instead been created with the geostatistical interpolation technique (i.e. Kriging). This technique allows to obtain the "best" estimates possible because it considers the true correlation law between the measured data. The applied methods are then described along with the results obtained in the field of road safety by applying Geostatistics which, for several years, have been used, with positive results, in all scientific and engineering fields dealing with empirical data analysis and processing

    Feminizing adrenocortical carcinoma with distant metastases: can surgery be considered?

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    Functioning adrenocortical carcinomas are rare diseases with dismal prognosis. A 41-yearold man presenting with gynecomastia had a giant feminizing adrenocortical carcinoma at stage IV. Although surgical resection was controversial, we removed the primary tumor to reduce the mass effects. He lived for 12 months with an acceptable quality of life. Gynecomastia may be the first sign of feminizing adrenal malignancies. Surgery may ameliorate the quality of life in selected patients with metastatic disease

    The neurometabolic basis of mood instability: the parvalbumin interneuron link — a systematic review and meta-analysis

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    The neurobiological bases of mood instability are poorly understood. Neuronal network alterations and neurometabolic abnormalities have been implicated in the pathophysiology of mood and anxiety conditions associated with mood instability and hence are candidate mechanisms underlying its neurobiology. Fast-spiking parvalbumin GABAergic interneurons modulate the activity of principal excitatory neurons through their inhibitory action determining precise neuronal excitation balance. These interneurons are directly involved in generating neuronal networks activities responsible for sustaining higher cerebral functions and are especially vulnerable to metabolic stress associated with deficiency of energy substrates or mitochondrial dysfunction. Parvalbumin interneurons are therefore candidate key players involved in mechanisms underlying the pathogenesis of brain disorders associated with both neuronal networks’ dysfunction and brain metabolism dysregulation. To provide empirical support to this hypothesis, we hereby report meta-analytical evidence of parvalbumin interneurons loss or dysfunction in the brain of patients with Bipolar Affective Disorder (BPAD), a condition primarily characterized by mood instability for which the pathophysiological role of mitochondrial dysfunction has recently emerged as critically important. We then present a comprehensive review of evidence from the literature illustrating the bidirectional relationship between deficiency in mitochondrial-dependent energy production and parvalbumin interneuron abnormalities. We propose a mechanistic explanation of how alterations in neuronal excitability, resulting from parvalbumin interneurons loss or dysfunction, might manifest clinically as mood instability, a poorly understood clinical phenotype typical of the most severe forms of affective disorders. The evidence we report provides insights on the broader therapeutic potential of pharmacologically targeting parvalbumin interneurons in psychiatric and neurological conditions characterized by both neurometabolic and neuroexcitability abnormalities

    Tools to discriminate between targets of CK2 vs PLK2/PLK3 acidophilic kinases

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    While the great majority of Ser/Thr protein kinases are basophilic or proline directed, a tiny minority is acidophilic. The most striking example of such "acidophilic" kinases is CK2, whose sites are specified by numerous acidic residues surrounding the target one. However PLK2 and PLK3 kinases recognize an acidic consensus similar to CK2 when tested on peptide libraries. Here we describe optimal buffer conditions for PLK2 and 3 kinase activity assays and tools such as using GTP as a phosphate donor and the specific inhibitors CX-4945 and BI 2536, useful to discriminate between acidic phosphosites generated either by CK2 or by PLK2/PLK

    Verifica in opera dei requisiti acustici passivi: applicazione a un caso studio di procedure BIM per la determinazione dei componenti piĂą critici da indagare

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    La metodologia del Building Information Modelling richiede, per poter essere messa in pratica, l’utilizzo di software moderni in grado di gestire in maniera interoperabile un edificio in ogni sua parte ed elemento, compresi i dati analitici associati ad essi, lungo tutto il suo arco di vita, dalla progettazione alla demolizione. Tali capacità permettono di sfruttare la geometria per eseguire calcoli di diversa natura, tra cui quelli acustici sulla base di un modello correttamente modellato e con dati associati, ma non sempre si ha accesso ad un modello simile. Questo lavoro considera l’utilizzo di un modello puramente geometrico privo di dati acustici, al quale sono state assegnate le informazioni mancanti in fase di analisi, attraverso il quale ricercare quali elementi risultano maggior-mente critici ai fini della scelta degli elementi per le verifiche in opera. Infine i diversi metodi implementati, tra i quali il calcolo acustico previsionale eseguito sul modello, sono stati comparati fra loro per valutarne la percentuale di corrispondenza

    Assessment Of Circulating Endothelial Cells And Their Progenitors As Potential Biomarkers Of Disease Activity And Damage Accrual In Behçet's Syndrome

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    PURPOSE: To explore the potential role of circulating endothelial cells (CECs) and their progenitors (EPCs) as biomarkers of disease activity and damage accrual in patients with Behçet's syndrome (BS), by using a standardised and reliable flow cytometry protocol. PATIENTS AND METHODS: CECs and EPCs were assessed in 32 BS patients and 11 gender/age/smoking habits matched healthy controls (HC). They were identified by flow cytometry as alive/nucleated/CD45-negative/CD34-bright/CD146-positive and alive/nucleated/CD45-negative/CD34-bright/CD309-positive events, respectively. In BS patients, demographic and clinical features, including disease activity (assessed by Behçet's disease current disease activity form, BDCAF) and irreversible damage accrual (by the vasculitis damage index, VDI) were recorded. Uni- and multivariate analysis were performed to compare the CECs and EPCs concentrations in BS vs HC and to identify potential associations with demographic or clinical features. RESULTS: The CECs concentration was significantly higher in the BS patients than HCs [median (IQR) 15.0 (7.5-23.0) vs 6.0 (2.0-13.0) CECs/mL, p=0.024]. In BS patients, no significant associations were found between CECs and demographic features, present and past clinical manifestations, BDCAF score and ongoing treatment. A significant association was observed between CECs and organ damage, as assessed by the VDI (rho 0.356, p=0.045). Higher levels of CECs were especially associated with vascular damage [median (IQR) 23.0 (14.0-47.0) vs 13.0 (6.0-19.0) CECs/mL, p=0.011], including arterial aneurysm and stenosis, complicated venous thrombosis, cerebrovascular accident. The concentration of EPCs did not significantly differ between the BS and HC [median 26.5 (13.0-46.0) vs 19.0 (4.0-42.0) EPCs/mL, p=0.316] and no significant associations were observed between their levels and any clinical characteristic. CONCLUSION: Our study suggests that the CECs concentration is significantly higher in BS than healthy subjects, and it mainly correlates with vascular damage. A longitudinal extension of the present study on a wider cohort would be useful to validate the potential role of CECs as a marker or, hopefully, predictor of vascular damage in BS
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