Comparing Nonlinear Free Vibrations of Timoshenko Beams with Mechanical or Geometric Curvature Definition

Abstract The nonlinear free oscillations of a planar, initially straight Timoshenko beam are investigated by means of the asymptotic development method. Attention is focus on the difference in considering the "mechanical" vs the "geometric" curvature of the axis of the beam, which are different for extensible beams. A comparison of the results obtained by the two models is proposed, and it is shown when they are equivalent and when they give different nonlinear behaviours. A parametric analysis showing the effects of the slenderness (arbitrary, not necessarily large) and of the stiffness of the right-end axial spring is performed

Genetic rat manipulation as an efficient model to unravel the role of Nogo-A and Staufen 2 proteins in cognitive processes

Gene targeting technologies enabling a germline complete gene ablation mice had an enormous impact on the analysis of gene functions in vivo during the past two decades. However, the complete loss of a gene function often leads either to embryonic or early postnatal lethality or to molecular compensation that compensate for the function of the missing gene. Tissue or cell specific knockouts mostly avoid those drawbacks, but are currently confined mainly to mice as a model system. Indeed, development of gene inactivation technologies in rats is still far behind those available for mice, even if the elucidation of gene functions in transgenic rats would have several important advantages over using mice. The larger body size of a rat simplifies interventions such as microsurgery or multiple-electrode electrophysiological recording in vivo. Furthermore, higher order cognitive functions are more developed in this social rodent species than in the more solitarily living mice. Indeed, many behavioral tests are more advanced or validated for the rat, especially regarding the behavioral assessment of complex neuropsychiatric disease phenotypes, such as negative symptoms in schizophrenia or complex cognitive phenotypes. In the present study we used two different miRNA-based knockdown rat models to study the impact of those genes on emotional behavior and learning and memory processes. The first transgenic rat model is deficient for the Nogo-A protein within the entire animal. Nogo-A is expressed in CNS oligodendrocytes as well as in subpopulations of neurons and is known to suppress neurite growth and regeneration. In vivo studies in rats have shown successful regeneration of corticospinal tract axons over long distances and a significant enhancement of functional recovery using either neutralizing antibodies against Nogo-A or peptides blocking the Nogo receptor NgR. However, only few studies analyzed the role of Nogo-A on behavioral processes. Here, we show that Nogo-A deficient rats display behavioral phenotypes related to schizophrenia, such as difficulty in reversal learning, lower exploration and most importantly a reduced social contact behavior. Our behavior observations extend those described for Nogo-A knockout mice. In the second transgenic rat model were realized the first inducible tissue-specific gene inactivation rats described so far by knocking down Staufen2 (Stau2) protein production within excitatory neurons of the forebrain using an artificial miRNA targeting the respective protein. Staufen2 is a double-stranded RNA-binding protein essential for the localization of mRNAs in diverse cell types. In neurons, Stau2 regulates the dendritic localization and local translation of a subset of mRNAs that play a pivotal role in synaptic plasticity. In vitro experiments have shown that Stau2 is involved in the formation of dendritic spines, thereby modifying synaptic plasticity. However, no studies of Staufen function have been performed in vivo. Using our Stau2 deficient rats, we could show that the animals have an unaltered spatial reference memory and fear conditioning. However, Stau2 deficient rats have a highly significant impairment of spatial working memory. In addition, the transgenic animals have significant difficulties to detect spatial novelty. These behavioral finding fit very well to the in vivo electrophysiological data recorded by our collaborations, who could demonstrate that Stau2 deficient rats have an enhancement for LTP and an impairment of LTD. Together these findings suggest that Stau2 transported mRNAs are responsible for modulating synaptic plasticity at dendritic spines

Molecular epidemiology and pathogenic potential of underdiagnosed human papillomavirus types

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) tests are crucial diagnostic tools for the prevention of neoplastic lesions of the uterine cervix. However most commercial methods are designed to detect high-risk (HR) HPV types and a limited selection of low-risk ones, thus missing a fair number of intermediate/low-risk types. As a result, many HPV infections remain undiagnosed, generating distrust in virological diagnosis among gynaecologists, who continue to rely preferentially on cytological and colposcopic findings.</p> <p>Results</p> <p>In this study, we tested 6,335 consecutive clinical samples, most of them from Italian patients with cytological abnormalities. The samples, collected in 2000–2007, were analyzed using PCR amplification of a 173–206 bp (depending on HPV type) conserved region in the L1 open reading frame, restriction endonuclease analysis and, where required, sequence analysis for type determination. Analysis of a smaller male sample and long term follow-up of a few female subjects was also performed. A total of 2,161 samples tested positive for HPV DNA (32.1%); 21.3% of them were mixed infections. Overall, 59 known and 2 unknown HPV types were detected. Their relative prevalence was calculated; notably, types not clearly identifiable using the most common commercial method accounted for 36% of infections. Clinical findings associated with the underdiagnosed types ranged from H-SIL to low-grade abnormalities, although none of these infections resulted in invasive cancer.</p> <p>Conclusion</p> <p>Given the high prevalence of some underdiagnosed HPV types in the population (principally HPV53, HPV66, HPV84, and HPV87) and their frequent association with cytological abnormalities, techniques capable of detecting and typing them would prove extremely useful.</p

Impact of ART Use on Labour Force Participation among PLWHA Using ART in Southern Highlands HIV/AIDS Program in Tanzania

This is the retrospective cohort study which was conducted to analyse the impact of ART on labour force participation by 2829 PLWHA using ART at in Tanzania from 2005 to 2011. Quantitative method of research was applied and review of patients’ record was used to collect data. The results revealed that 92.4% of PLWHA registered on ART belong to working age group i.e. 15 – 65 years old (t-statistical value = 4.9 and p - value = 0.0002). There were 92.0% PLWHA who were able to work before ART, but labour force increased to 99.5% after PLWHA initiated on ART (correlation coefficient, r = 0.999, p-value &lt; 0.001). The researcher concluded that majority of PLWHA using ART belongs to the working age group, and ART increases PLWHA labour force participation .The researcher therefore recommended that ART is worth continuing on with the universal population coverage. The study has some limitations as it assessed only one benefits of ART that is labour force participation of PLWHA. Key words: PLWHA, Antiretroviral therapy, labour force participation, resource limited settin

Longitudinal–transversal internal resonances in Timoshenko beams with an axial elastic boundary condition

AbstractThe internal resonances between the longitudinal and transversal oscillations of a forced Timoshenko beam with an axial end spring are studied in depth. In the linear regime, the loci of occurrence of 1 : ir, $$ir \in \mathbb {N}$$ i r ∈ N , internal resonances in the parameters space are identified. Then, by means of the multiple time scales method, the 1 : 2 case is investigated in the nonlinear regime, and the frequency response functions and backbone curves are obtained analytically, and investigated thoroughly. They are also compared with finite element numerical simulations, to prove their reliability. Attention is paid to the system response obtained by varying the stiffness of the end spring, and it is shown that the nonlinear behaviour instantaneously jumps from hardening to softening by crossing the exact internal resonance value, in contrast to the singular (i.e. tending to infinity) behaviour of the nonlinear correction coefficient previously observed (without properly taking the internal resonance into account)

Crumbling of Amatrice clock tower during 2016 Central Italy seismic sequence: Advanced numerical insights

The dynamic behaviour and the seismic vulnerability of the ancient civic tower of Amatrice, dramatically damaged by the last shocks sequence of 2016 that occurred in Central Italy, have been studied in this paper by means of advanced 3D numerical analyses with the Discrete Element Method (DEM). Thus, a discontinuous approach has been used to assess the dynamic properties and the vulnerability of the masonry structure, through large deformations regulated by the Signorini's law, concerning the impenetrability between the rigid bodies, and by the Coulomb's law, regarding the dry-friction model. Afterward, different values have been assigned to the friction coefficient of the models and real seismic shocks have been applied in the nonlinear analyses. The major purpose of this study is to highlight that relevant data on the real structural behaviour of historical masonry can be provided through advanced numerical analyses. The comparison between the results of the numerical simulation and the survey of the existing crack pattern of the bell tower permitted to validate the approach used. Finally, from the results and conclusions of this case study, it is possible to affirm that the used methodology can be applied to a wide variety of historical masonry structure in Europe

Palliation with a multimodality treatment including hypoxic pelvic perfusion for unresectable recurrent rectal cancer: outcomes based on a retrospective study

Patients with unresectable recurrent rectal cancer that progresses after systemic chemotherapy and radiotherapy are candidates for palliation with hypoxic pelvic perfusion (HPP). The aim of this observational retrospective study was to evaluate if a multimodality treatment including HPP and targeted-therapy may be useful to prolong clinical responses and survival of these patients. From a cohort of 77 patients with unresectable recurrent rectal cancer in progression after standard treatments and submitted to HPP, 21 patients underwent repeat HPP using mitomycin C (MMC) at the dose of 25&nbsp;mg/m2. After the last HPP, 7 patients received a targeted-therapy with cetuximab according to overexpression of epidermal growth factor receptor in recurrence cancer cells. The median overall survival of these 21 patients from the diagnosis of unresectable recurrent rectal cancer was 23&nbsp;months (iqr 18-24). After the first HPP, the median survival of the 21 patients until death or end of follow-up was 10&nbsp;months (iqr 9-13). The 1-year and 2-year survival rates were 71.4%, and 4.8%, respectively. From the first HPP, age\u2009&gt;\u200960&nbsp;years, a recurrence shrinkage of at least 30% (partial response), and the addition of a post-HPP targeted-therapy with cetuximab significantly affected survival (P\u2009&lt;\u20090.04). In conclusion, repeated MMC-HPP followed by targeted-therapy seems to be an effective palliative treatment for patients with unresectable recurrent rectal cancer in progression after systemic chemotherapy and radiation but the results of this study have to be confirmed by a larger phase III trial

Parameters of flow in porous alluvial aquifers evaluated by tracers

Dye tracer tests, DNA biotracer, alluvial aquifer Marche, multiwell tests

Hydraulic contacts identification in the aquifers of limestone ridges: tracer tests in the Montelago pilot area (Central Apennines)

The investigated area, located in the inner part of the Marche region (central Italy) and belonging to the carbonate Umbria- Marche ridges in the central Apennines, is characterised by very complex geo-structural setting and widespread karst phenomena that make difficult the definition of the relation among the aquifers basing only on the hydrogeological survey. Hence, the presence of different flowpaths among aquifers of the Umbria-Marche hydrostratigraphic sequence and of tectonic contacts among the different structures is verified using tracer tests. In particular, the tests showed that the Calcare Massiccio and the Maiolica aquifers are connected under certain tectonic conditions. A new tracer given by a single stranded DNA molecule and traditional fluorescent dyes have been injected into the Montelago sinkhole in different periods (during the recharge and during the discharge) and recovered in several points along the expected hydrogeological basin, using either manual and automatic sampling. Fluorescent traps were positioned in creeks, rivers and springs. The DNA molecule is useful to trace surface water and groundwater, is detectable even at very low concentrations, no significant change in water density and viscosity can be observed and its use is not dangerous for the environment. The results stress the suitability of DNA as hydrogeological tracer, capable to identify connections among aquifers and study different flowpaths even in high flow conditions when traditional tracers are more and more diluted. Moreover, fluorescein tracer allowed for the transport parameter determination, giving mean velocities ranging from 100 to 3000 m/day and mean residence time from some tens to hundreds of hours, and determining the aquifer volumes

Damage Assessment by Numerical Modeling of Sant'Agostino's Sanctuary in Offida During the Central Italy 2016–2017 Seismic Sequence

The subject of this work is the Sant'Agostino Sanctuary in Offida (Italy); we investigated both the dynamic behavior and the seismic vulnerability of the complex, used nowadays in its parts as school building, oratory, and church. Offida is in central Italy; the village has been severely damaged by the last seismic events of 2016. The sanctuary was heavily damaged by the earthquake of 24 August 2016. We recurred to finite elements to estimate the vulnerability of the sanctuary and its dynamic response, considering masonry's non-linear behavior by means of proper constitutive assumptions. To estimate how the monastery bears the lateral loads related to the expected demands resulting from seismic actions (N2 method) using non-linear static analysis (Pushover), we recurred to a homogenized material and smeared cracking and crushing constitutive law. As may be remarked by observing buildings that share the same features of the sanctuary and, moreover, by comparing seismic demand vs. capacity, the structure is prone to massive damage leading to collapse. The paper underlines how advanced numerical analysis grants fundamental data on how historical masonry buildings behave under seismic action, providing a method that may easily be implemented at historic monasteries in Europe