A robust approach to sharp multiplier theorems for Grushin operators

We prove a multiplier theorem of Mihlin-Hörmander-type for operators of the form -Δx-V (x) Δy on Rd1 x ×Rd2 y , where V (x) = Σd1 j=1 Vj (xj ), the Vj are perturbations of the power law t → |t|2σ, and σ ∈ (1/2,∞). The result is sharp whenever d1 ≥ σd2. The main novelty of the result resides in its robustness: This appears to be the first sharp multiplier theorem for nonelliptic subelliptic operators allowing for step higher than two and perturbation of the coefficients. The proof hinges on precise estimates for eigenvalues and eigenfunctions of one-dimensional Schrödinger operators, which are stable under perturbations of the potential

Effect of integration time on the morphometric, densitometric and mechanical properties of the mouse tibia

Micro-Computed Tomography (microCT) images are used to measure morphometric and densitometric properties of bone, and to develop finite element (FE) models to estimate mechanical properties. However, there are concerns about the invasiveness of microCT imaging due to the X-rays ionising radiation induced by the repeated scans on the same animal. Therefore, the best compromise between radiation dose and image quality should be chosen for each preclinical application. In this study, we investigated the effect of integration time (time the bone is exposed to radiation at each rotation step during microCT imaging) on measurements performed on the mouse tibia. Four tibiae were scanned at 10.4 µm voxel size using four different procedures, characterized by decreasing integration time (from 200 ms to 50 ms) and therefore decreasing nominal radiation dose (from 513 mGy to 128 mGy). From each image, trabecular and cortical morphometric parameters, spatial distribution of bone mineral content (BMC) in the whole tibia and FE-based estimations of stiffness and strength were obtained. A high-resolution scan (4.3 µm voxel size) was used to quantify measurement errors. Integration time had the largest effect on trabecular morphometric parameters (7-28%). Lower effects were observed on cortical parameters (1-3%), BMC (1-10%) distribution, and FE-based estimations of mechanical properties (1-3%). In conclusion, the effect of integration time on image-based measurements has been quantified. This data should be considered when defining the in vivo microCT scanning protocols in order to find the best compromise between nominal radiation exposure and accuracy in the estimation of bone parameters

Development of a protocol to quantify local bone adaptation over space and time: quantification of reproducibility

In vivo micro-computed tomography (μCT) scanning of small rodents is a powerful method for longitudinal monitoring of bone adaptation. However, the life-time bone growth in small rodents makes it a challenge to quantify local bone adaptation. Therefore, the aim of this study was to develop a protocol, which can take into account large bone growth, to quantify local bone adaptations over space and time. The entire right tibiae of eight 14-week-old C57BL/6J female mice were consecutively scanned four times in an in vivo μCT scanner using a nominal isotropic image voxel size of 10.4 μm. The repeated scan image datasets were aligned to the corresponding baseline (first) scan image dataset using rigid registration. 80% of tibia length (starting from the endpoint of the proximal growth plate) was selected as the volume of interest and partitioned into 40 regions along the tibial long axis (10 divisions) and in the cross-section (4 sectors). The bone mineral content (BMC) was used to quantify bone adaptation and was calculated in each region. All local BMCs have precision errors (PE%CV) of less than 3.5% (24 out of 40 regions have PE%CV of less than 2%), least significant changes (LSCs) of less than 3.8%, and 38 out of 40 regions have intraclass correlation coefficients (ICCs) of over 0.8. The proposed protocol allows to quantify local bone adaptations over an entire tibia in longitudinal studies, with a high reproducibility, an essential requirement to reduce the number of animals to achieve the necessary statistical power

Traditional Approaches and Emerging Biotechnologies in Grapevine Virology

Environmental changes and global warming may promote the emergence of unknown viruses, whose spread is favored by the trade in plant products. Viruses represent a major threat to viticulture and the wine industry. Their management is challenging and mostly relies on prophylactic measures that are intended to prevent the introduction of viruses into vineyards. Besides the use of virus-free planting material, the employment of agrochemicals is a major strategy to prevent the spread of insect vectors in vineyards. According to the goal of the European Green Deal, a 50% decrease in the use of agrochemicals is expected before 2030. Thus, the development of alternative strategies that allow the sustainable control of viral diseases in vineyards is strongly needed. Here, we present a set of innovative biotechnological tools that have been developed to induce virus resistance in plants. From transgenesis to the still-debated genome editing technologies and RNAi-based strategies, this review discusses numerous illustrative studies that highlight the effectiveness of these promising tools for the management of viral infections in grapevine. Finally, the development of viral vectors from grapevine viruses is described, revealing their positive and unconventional roles, from targets to tools, in emerging biotechnologies

Uncertainties of synchrotron microCT-based digital volume correlation bone strain measurements under simulated deformation

Digital Volume Correlation (DVC) is used to measure internal displacements and strains in bone. Recent studies have shown that synchrotron radiation micro-computed tomography (SR-microCT) can improve the accuracy and precision of DVC. However, only zero-strain or virtually-moved test have been used to quantify the DVC uncertainties, leading to potential underestimation of the measurement errors. In this study, for the first time, the uncertainties of a global DVC approach have been evaluated on repeated SR-microCT scans of bovine cortical bone (voxel size: 1.6μm), which were virtually deformed for different magnitudes and along different directions. The results showed that systematic and random errors of the normal strain components along the deformation direction were higher than the errors along unstrained directions. The systematic percentage errors were smaller for larger virtual deformations. The random percentage error was in the order of 10% of the virtual deformation. However, higher errors were localized at the boundary of the volumes of interest, perpendicular to the deformation direction. When only the central region of the samples was considered (100 micrometers layers removed from the borders where the deformation was applied), the errors in the direction of virtual deformation were comparable to the errors in the unstrained directions. In conclusion, the method presented to estimate the uncertainties of DVC is suitable for testing anisotropic specimens as cortical bone. The good agreement between the uncertainties in measurements of strain components obtained with this approach and with the simpler zero-strain-test suggests that the latter is adequate in the tested deformation scenarios

Variability in strain distribution in the mice tibia loading model: A preliminary study using digital volume correlation

It is well known that bone has an enormous adaptive capacity to mechanical loadings, and to this extent, several in vivo studies on mouse tibia use established cyclic compressive loading protocols to investigate the effects of mechanical stimuli. In these experiments, the applied axial load is well controlled but the positioning of the hind-limb between the loading endcaps may dramatically affect the strain distribution induced on the tibia. In this study, the full field strain distribution induced by a typical in vivo setup on mouse tibiae was investigated through a combination of in situ compressive testing, µCT scanning and a global digital volume correlation (DVC) approach. The precision of the DVC method and the effect of repositioning on the strain distributions were evaluated. Acceptable uncertainties of the DVC approach for the analysis of loaded tibiae (411 ± 58µɛ) were found for nodal spacing of approximately 50 voxels (520 µm). When pairs of in situ preloaded and loaded images were registered, low variability of the strain distributions within the tibia were seen (range of mean differences in principal strains: 585-1800µɛ). On contrary, larger differences were seen after repositioning (range of mean differences in principal strains: 2500-5500µɛ). To conclude, these preliminary results on thee specimens showed that the DVC approach applied to the mouse tibia can be precise enough to evaluate local strain distributions under loads, and that repositioning of the hind-limb within the testing machine can induce large differences in the strain distributions that should be accounted for when modelling this system

Ripartire dalla bellezza. Gestione e marketing delle opportunit\ue0 d\ub4innovazione nell\ub4albergo diffuso nei centri storici e nelle aree rurali

Questo libro propone un percorso di lavoro utile per creare un Albergo Diffuso remunerativo e per rendere visibili tutte le opportunit\ue0 imprenditoriali esistenti in un dato luogo. Si presentano alcune tendenze di mercato in atto in Europa importanti per il rilancio di aree fino a poco tempo fa considerate \u2018marginali'. Seguono alcuni dei programmi di finanziamento europei utilizzabili dagli operatori dell'Ospitalit\ue0 Diffusa, nonch\ue9 una short-list dei tranelli in cui si potrebbe rischiare di cadere nel progettare un'opportunit\ue0 d'impresa come l'AD. Segue un elenco delle opportunit\ue0 imprenditoriali pi\uf9 attuali e interessanti. Si sviluppa poi il lavoro necessario per gestire e per fare marketing delle opportunit\ue0. Si presentano la cornice teorica necessaria, gli strumenti di lavoro, un percorso \u2018originale' e il metodo per progettare insieme (co-progettare) le opportunit\ue0. Il testo offre in sintesi un metodo collaudato per far emergere tutte le opportunit\ue0 di soddisfazione e di spesa per i clienti, di reddito, di occupazione, d'impresa e d'investimento per gli operatori interessati

A Guide to Cannabis Virology: From the Virome Investigation to the Development of Viral Biotechnological Tools

Cannabis sativa cultivation is experiencing a period of renewed interest due to the new opportunities for its use in different sectors including food, techno-industrial, construction, pharmaceutical and medical, cosmetics, and textiles. Moreover, its properties as a carbon sequestrator and soil improver make it suitable for sustainable agriculture and climate change mitigation strategies. The increase in cannabis cultivation is generating conditions for the spread of new pathogens. While cannabis fungal and bacterial diseases are better known and characterized, viral infections have historically been less investigated. Many viral infection reports on cannabis have recently been released, highlighting the increasing threat and spread of known and unknown viruses. However, the available information on these pathogens is still incomplete and fragmentary, and it is therefore useful to organize it into a single structured document to provide guidance to growers, breeders, and academic researchers. This review aims to present the historical excursus of cannabis virology, from the pioneering descriptions of virus-like symptoms in the 1940s/50s to the most recent high-throughput sequencing reports. Each of these viruses detected in cannabis will be categorized with an increasing degree of threat according to its potential risk to the crop. Lastly, the development of viral vectors for functional genetics studies will be described, revealing how cannabis virology is evolving not only for the characterization of its virome but also for the development of biotechnological tools for the genetic improvement of this crop