2,615 research outputs found
Mitochondrial targeting in LRRK2-associated parkinsonism (PARK8)
No full textAmong monogenic forms of Parkinson's disease (PD), the most frequent is associated with the leucine-rich repeat kinase2 (LRRK2) mutation, named PARK8 and the most common G2019S mutation. LRRK2 is expressed in the dopamine (DA) neurons of the substantia nigra compacta, suggesting a role in PD degeneration. In PD, mitochondrial complex I is impaired thus inhibitors of this complex and 6-OHDA are used to lesion the DA nigrostriatal system and induce experimental parkisonism. To study the role of LRRK2, models carrying LRRK2 pathogenic mutations have been developed. LRRK2 mutants cause neurodegeneration impairing mitochondrial activity indicating a prominent role of this structure in LRRK2-mediated death signals. Kinase regulation of mitochondrial dynamics are pivotal in these processes in relation to PD onset and expression of G2019S mutation alters the homeostasis of mitochondrial Ca2+. Drugs able to correct LRRK2-associated mitochondrial dysfunction may attenuate parkinsonism in mice. Aim 1.
We will investigate whether the G2019S mutation renders dopamine (DA) neurons more prone to death over aging or following exposure to parkinsonian toxins, ultimately making mice more susceptible to develop parkinsonism. Therefore, our first main goal is to provide behavioral, electrophysiological (striatal slices), biochemical (cell lines and mesencephalic/cerebrocortical neurons) and neurochemical (microdyalisis/synaptosomes) characterization of i) mice over-expressing human LRRK2 carrying the G2019S mutation; ii) LRRK2 Knock-Out (KO) mice; iii) LRKK2 G2019S Knock-In (KI) mice and iv) mice expressing a LRRK2 mutation (D1994S) associated with null kinase activity (Kinase Dead; KD mice). Aim 2. We will take advantage of these multiple genetic models and expertises available, to evaluate: i) the relation between mouse phenotype and age (3, 6 and 12 months); ii) the effect of exposure to various parkinsonian toxins such as MPTP, 6-OHDA and rotenone. Aim 3. In addition, mitochondrial drugs will be administered to correct behavioral and biochemical deficits in LRKK2 mice in vivo and ex vivo, as well as in cell lines. In particular, drugs specific for mitochondrial targets (permeability transition pore, radical oxygen production, dynamin-related GTPases) will be used in order to protect from in vitro and in vivo degeneration DA neurons carrying the characterized LRRK2 mutations
Urban goods movements in a sensitive context: The case of Parma
No full textThis paper focuses on the efficiency of one-to-many distribution processes in urban environments. An in-depth 8-month survey of commercial vehicle tours leaving from an Urban Distribution Centre (UDC) located on the outskirts of the city of Parma (Italy), was carried out, merging information from a GPS-based dataset and a wider operation dataset. Tours were classified according to UDC-customer distances in order to prove the clear correlation between the efficiency of the distribution process and the size (and the network characteristics) of the area being served. When such area covers the city center, available data highlighted how vehicle routing is affected by constraints which strongly prevent the optimization of routes and occupancy rate. Through continuous approximation models, the relative impact of the time-dependent parameters of the delivery process, particularly maximum tour travel times and preferred time slots for deliveries, was analyzed along with the effects of traffic congestion on commercial vehicle tours. The resulting scenario analysis allowed to assess a significant increase in the number of tours needed (+34,3%) and the total distance travelled (+9%), to serve a given set of customers in the city center, when travel time variability and tour duration constraint become stricter. © 2014 Elsevier Ltd
Michele Taruffo: el magisterio y la obra ejemplares del genial procesalista «todoterreno»
No full textThe author reflects on Michele Taruffo’s extraordinarily important contribution to the renewal of both conventional procedural law scholarship and the theoretical background of law-court professionals. Taruffo’s contribution was achieved by means of introducing to mainstream culture in those circles the necessary knowledge of the underlying epistemic dimension, which was traditionally suppressed by the strictly legal one.El autor discurre acerca de la importantísima contribución de Michele Taruffo a la renovación del procesalismo convencional y del bagaje teórico de los profesionales de la jurisdicción, mediante la incorporación a la cultura dominante en tales medios del imprescindible conocimiento de la dimensión epistémica subyacente y tradicionalmente sofocada por la propiamente jurídica
Looking for Japan in contemporary Italy
No full textPh. D.Includes bibliographical referencesIncludes vitaby Michele Monserrat
Flexural resistance of CAD-CAM blocks. Part 3: Polymer-based restorative materials for permanent restorations
No full textPurpose: Concurrently with the growing interest in CAD-CAM systems, several new materials of different chemical nature have become available. As an alternative to ceramics, numerous polymer-based materials have recently been proposed for permanent prosthetic restorations. Aim of this study was to test the CAD-CAM polymer-based materials available on the market, comparing mean flexural strength, Weibull characteristic strength and Weibull modulus. Methods: Seven types of polymer-based blocks were tested: Lava Ultimate, 3M; Brilliant Crios, Coltene; Cerasmart, GC; Block HC, Shofu; Katana Avencia, Noritake; Grandio Blocs, Voco; Tetric CAD, and Ivoclar-Vivadent. Specimens were cut out from blocks, finished, polished, and tested in a three-point bending test apparatus until failure (n=30). Flexural strength, Weibull characteristic strength, and Weibull modulus were calculated. Flexural strength data were statistically analyzed. ANOVA on Ranks was applied, followed by the Dunn's test for post hoc comparisons (P= 0.05). Results: Flexural strength values (MPa) were measured (mean±standard deviation). Different letters in parentheses label statistically significant differences: Grandio Blocs 266±24(a), Brilliant Crios 259±21(ab); Tetric CAD 254±15(ab); Katana Avencia 241±29(bc); Cerasmart 221±24(cd); Lava Ultimate 196±23(de); Block HC 139±10(e). All the tested materials had flexural strengths greater than 100 MPa, thereby satisfying the requirements of ISO standards for polymer-based materials. For all the tested materials the Weibull characteristic strength was greater than 100 MPa. Weibull modulus ranged between 21.20 (Tetric CAD) and 9.09 (Katana Avencia). Clinical significance: Even though all the CAD-CAM polymer-based materials marketed in blocks tested in the present study satisfy the requirements of ISO standard for polymer-based materials, their flexural resistance differs significantly. The data presented in the study may be helpful to clinicians for selecting the most appropriate materials for each clinical case
FROM VIRTUAL PROTOTYPING TO DIGITAL TWIN
No full textThe virtual prototyping of the ship has been used for many years, starting at the beginning of the century. The main idea was to implement a Virtual representation of the ship and her systems able to behave reliably through simulation. A 3D virtual reality environment was the background for this virtual prototype which behaved realistically to verify and assess functionalities of the designed ship. This was primarily focused on the design phase, but the idea of reusing this virtual prototype in different ship lifecycle phases was already in place: reuse in training, operations, maintenance, dismantling... Many development and research activities have been performed building and reusing much technology: multibody simulations, virtual reality, HLA...
But a crucial ingredient was missing: the interaction with the real ship. Meanwhile, onboard automation systems, sensors and actuators, and networks become essential parts of the ship. Nowadays, IoT, global communications, cloud technologies, A.I. pave the way for connecting the Virtual world with the Real one.
The naval industry has witnessed a significant transformation, transitioning from traditional virtual prototyping applications to the more sophisticated paradigm of digital twins.
This paper presents a comprehensive review of this evolutionary journey through examples of the implementation of virtual prototypes and their reuse in a Digital Twin environment under implementation and evolution, tracing the key technological advancements, challenges, and opportunities that have propelled this transition
The Author Reply. Letter to the Editor
No full textThe Author reply to the Letter sent to the Editor about a previus article on low anterior resection
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