I brevetti delle Universit\ue0 regionali e la rete degli accademici inventori

Come differiscono le reti di collaborazione generate dai brevetti quando si considerino congiuntamente i brevetti Univerity Owned e quelli Unvieristy Invented? Le diverse configurazioni che si generano sono influenzate delle strategie delle singole Universit\ue0?\u2019 E qual \ue8 la loro importanza come canali di trasferimento della conoscenza nel territorio pi\uf9 prossimo? .Lo studio contribuisce all\u2019esame di questi problemi attraverso l\u2019analisi del caso studio delle Universit\ue0 di Trieste e di Udine. I risultati della Social Network Analysis evidenziano significative differenze tra le due Universit\ue0: in particolare. nel caso di Trieste, le reti generate dai due tipi di brevetti mostrano una sovrapposizione nettamente pi\uf9 marcata. Il legame con il territorio locale appare, invece, sempre piuttosto debole sia per i brevetti Univerity Owned che per quelli Univerity Invented., Sotto il profilo metodologico, l\u2019analisi micro, condotta a livello delle sottoreti e di regioni specifiche della rete, si dimostra quella pi\uf9 fruttuosa

Hybrid reduced-order modeling and particle-Kalman filtering for the health monitoring of flexible structures

MEMS-based, surface-mounted structural health monitoring systems were recently proposed to locate possible damage events in lightweight composite structures. To track the structural dynamics induced by the external actions and identify in real-time the inception of drifts from the virgin, or undamaged state, recursive Bayesian filters are here adopted. As the main drawback of any on-line identification method might be linked to the excessive computational costs, two solutions are jointly enforced: an order-reduction of the numerical model used to track the structural behavior, through the proper orthogonal decomposition in its snapshot-based version; an improved particle filtering strategy, which features an extended Kalman updating of each evolving particle before the resampling stage. While the former method alone can reduce the number of effective degrees-of-freedom of the structure to a few only (depending on the excitation), the latter allows to track the evolution of damage and also locate it thanks to an intricate formulation. To assess the proposed procedure, the case of a thin plate subject to bending is investigated; it is shown that, when the procedure is fed by measurements gathered by a network of inertial MEMS sensors appropriately deployed over the plate, damage is efficiently and accurately estimated and located

An optimal sensor placement method for SHM based on Bayesian experimental design and polynomial chaos expansion

We present an optimal sensor placement methodology for structural health monitoring (SHM) purposes, relying on a Bayesian experimental design approach. The unknown structural properties, e.g. the residual strength and stiffness, are inferred from data collected through a network of sensors, whose architecture, i.e., type and position may largely affect the accuracy of the monitoring system. In tackling this issue, an optimal network configuration is herein sought by maximizing the expected information gain between prior and posterior probability distributions of the parameters to be estimated. Since the objective function linked to the network topology cannot be analytically computed, a numerical approximation is provided by means of a Monte Carlo analysis, wherein each realization is obtained via finite element modeling. Since the computational burden linked to this procedure often grows infeasible, a Polynomial Chaos Expansion (PCE) approach is adopted for accelerating the computation of the forward problem. The analysis expands over joint samples covering both structural state and design variables, i.e., sensor locations. Via increase of the number of deployed sensors in the network, the optimization procedure soon turns computationally costly due to the curse of dimensionality. To this end, a stochastic optimization method is adopted for accelerating the convergence of the optimization process and thereby the damage detection capability of the SHM system. The proposed method is applied to thin flexible structures, and the resulting optimal sensor configuration is shown. The effects of the number of training samples, the polynomial degree of the approximation expansion and the optimization settings are also discussed

Detection of prions in skin punch biopsies of Creutzfeldt–Jakob disease patients

Prion real-time quaking-induced conversion (RT-QuIC) is an ultrasensitive assay detecting pathological aggregates of misfolded prion protein in biospecimens. We studied 71 punch biopsy skin samples of 35 patients with Creutzfeldt–Jakob disease (CJD), including five assessed in vitam. The results confirmed the high value of skin prion RT-QuIC for CJD diagnosis (89% sensitivity and 100% specificity) and support its use in clinical practice. Preliminary data based on a limited number of cases suggest that prion-seeding activity in the skin varies according to the prion strain, being higher in sporadic CJD subtypes linked to the V2 strain (VV2 and MV2K) than in typical CJDMM1

Antemortem CSF Aβ42/Aβ40 ratio predicts Alzheimer's disease pathology better than Aβ42 in rapidly progressive dementias

Objective: Despite the critical importance of pathologically confirmed samples for biomarker validation, only a few studies have correlated CSF Aβ42 values in vivo with postmortem Alzheimer's disease (AD) pathology, while none evaluated the CSF Aβ42/Aβ40 ratio. We compared CSF Aβ42 and Aβ42/Aβ40 ratio as biomarkers predicting AD neuropathological changes in patients with a short interval between lumbar puncture and death. Methods: We measured CSF Aβ40 and Aβ42 and assessed AD pathology in 211 subjects with rapidly progressive dementia (RPD) and a definite postmortem diagnosis of Creutzfeldt-Jakob disease (n = 159), AD (n = 12), dementia with Lewy bodies (DLB, n = 4), AD/DLB mixed pathologies (n = 5), and various other pathologies (n = 31). Results: The score reflecting the severity of Aβ pathology showed a better correlation with ln(Aβ42/Aβ40) (R 2  = 0.506, β = −0.713, P < 0.001) than with ln(Aβ42) (R 2  = 0.206, β = −0.458, P < 0.001), which was confirmed after adjusting for covariates. Aβ42/Aβ40 ratio showed significantly higher accuracy than Aβ42 in the distinction between cases with or without AD pathology (AUC 0.818 ± 0.028 vs. 0.643 ± 0.039), especially in patients with Aβ42 levels ≤495 pg/mL (AUC 0.888 ± 0.032 vs. 0.518 ± 0.064). Using a cut-off value of 0.810, the analysis of Aβ42/Aβ40 ratio yielded 87.0% sensitivity, 88.2% specificity in the distinction between cases with an intermediate-high level of AD pathology and those with low level or no AD pathology. Interpretation: The present data support the use of CSF Aβ42/Aβ40 ratio as a biomarker of AD pathophysiology and noninvasive screener for Aβ pathology burden, and its introduction in the research diagnostic criteria for AD

Identification of recurrent genetic patterns from targeted sequencing panels with advanced data science: a case-study on sporadic and genetic neurodegenerative diseases

open8noThis work is funded by the University of Bologna, the IRCCS Institute of Neurological sciences of Bologna, and by the European Grants H2020 GenoMed4All [AM1] (Grant N. 101017549) and H2020 MSCA-ITN IMforFUTURE (Grant N. 721815).Background Targeted Next Generation Sequencing is a common and powerful approach used in both clinical and research settings. However, at present, a large fraction of the acquired genetic information is not used since pathogenicity cannot be assessed for most variants. Further complicating this scenario is the increasingly frequent description of a poli/oligogenic pattern of inheritance showing the contribution of multiple variants in increasing disease risk. We present an approach in which the entire genetic information provided by target sequencing is transformed into binary data on which we performed statistical, machine learning, and network analyses to extract all valuable information from the entire genetic profile. To test this approach and unbiasedly explore the presence of recurrent genetic patterns, we studied a cohort of 112 patients affected either by genetic Creutzfeldt–Jakob (CJD) disease caused by two mutations in the PRNP gene (p.E200K and p.V210I) with different penetrance or by sporadic Alzheimer disease (sAD). Results Unsupervised methods can identify functionally relevant sources of variation in the data, like haplogroups and polymorphisms that do not follow Hardy–Weinberg equilibrium, such as the NOTCH3 rs11670823 (c.3837 + 21 T > A). Supervised classifiers can recognize clinical phenotypes with high accuracy based on the mutational profile of patients. In addition, we found a similar alteration of allele frequencies compared the European population in sporadic patients and in V210I-CJD, a poorly penetrant PRNP mutation, and sAD, suggesting shared oligogenic patterns in different types of dementia. Pathway enrichment and protein–protein interaction network revealed different altered pathways between the two PRNP mutations. Conclusions We propose this workflow as a possible approach to gain deeper insights into the genetic information derived from target sequencing, to identify recurrent genetic patterns and improve the understanding of complex diseases. This work could also represent a possible starting point of a predictive tool for personalized medicine and advanced diagnostic applications.openTarozzi, M.; Bartoletti-Stella, A.; Dall’Olio, D.; Matteuzzi, T.; Baiardi, S.; Parchi, P.; Castellani, G.; Capellari, S.Tarozzi, M.; Bartoletti-Stella, A.; Dall’Olio, D.; Matteuzzi, T.; Baiardi, S.; Parchi, P.; Castellani, G.; Capellari, S

CSF SerpinA1 in Creutzfeldt\u2013Jakob disease and frontotemporal lobar degeneration

Objective: SerpinA1 (alpha-1 antitrypsin) is an acute inflammatory protein, which seems to play a role in neurodegeneration and neuroinflammation. In Alzheimer\u2019s disease and synucleinopathies, SerpinA1 is overexpressed in the brain and the cerebrospinal fluid (CSF) showing abnormal patterns of its charge isoforms. To date, no comprehensive studies explored SerpinA1 CSF isoforms in Creutzfeldt\u2013Jakob disease (CJD) and frontotemporal lobar degeneration (FTLD). Methods: Using a capillary isoelectric focusing immunoassay, we analyzed CSF SerpinA1 isoforms in control cases (n = 31) and patients with a definite or probable diagnosis of CJD (n=77) or FTLD (n = 30), belonging to several disease subtypes. Results: The overall SerpinA1 signal was significantly higher than in controls in CJD subtypes linked to abnormal prion protein (PrPSc) type 1, such as sporadic CJD (sCJD) MM(V)1, and in FTLD-TDP. Moreover, CJD linked to PrPSc type 1 and FTLD-TAU groups showed a significant relative increase of acidic and basic isoforms in comparison with controls, thereby forming two distinct SerpinA1 isoform profiles. Interpretation: CJD linked to PrPSc type 1 and FTLD show a differential upregulation and post-translational modifications of CSF SerpinA1. Further studies are needed to clarify whether these findings may reflect a common, albeit disease-specific, pathogenetic mechanism related to neurodegeneration

The characterization of AD/PART co-pathology in CJD suggests independent pathogenic mechanisms and no cross-seeding between misfolded Aβ and prion proteins

Current evidence indicating a role of the human prion protein (PrP) in amyloid-beta (Aβ) formation or a synergistic effect between Aβ and prion pathology remains controversial. Conflicting results also concern the frequency of the association between the two protein misfolding disorders and the issue of whether the apolipoprotein E gene (APOE) and the prion protein gene (PRNP), the major modifiers of Aβ- and PrP-related pathologies, also have a pathogenic role in other proteinopathies, including tau neurofibrillary degeneration. Here, we thoroughly characterized the Alzheimer's disease/primary age-related tauopathy (AD/PART) spectrum in a series of 450 cases with definite sporadic or genetic Creutzfeldt-Jakob disease (CJD). Moreover, we analyzed: (i) the effect of variables known to affect CJD pathogenesis and the co-occurring Aβ- and tau-related pathologies; (II) the influence of APOE genotype on CJD pathology, and (III) the effect of AD/PART co-pathology on the clinical CJD phenotype. AD/PART characterized 74% of CJD brains, with 53.3% and 8.2% showing low or intermediate-high levels of AD pathology, and 12.4 and 11.8% definite or possible PART. There was no significant correlation between variables affecting CJD (i.e., disease subtype, prion strain, PRNP genotype) and those defining the AD/PART spectrum (i.e., ABC score, Thal phase, prevalence of CAA and Braak stage), and no difference in the distribution of APOE ε4 and ε2 genotypes among CJD subtypes. Moreover, AD/PART co-pathology did not significantly affect the clinical presentation of typical CJD, except for a tendency to increase the frequency of cognitive symptoms. Altogether, the present results seem to exclude an increased prevalence AD/PART co-pathology in sporadic and genetic CJD, and indicate that largely independent pathogenic mechanisms drive AD/PART and CJD pathology even when they coexist in the same brain

Terneza, grasa intramuscular y de cobertura en carne de novillos faenados en Corrientes (Argentina)

La terneza de la carne es el atributo más apreciado por los consumidores, encontrándose condicionada por muchos factores. El objetivo de este trabajo fue generar información sobre terneza objetiva post maduración de la carne bovina y determinar valores de grasa intramuscular y de cobertura en animales de diferentes biotipos y edades faenados en Corrientes. El trabajo se realizó en un frigorífico tipo A y en la Facultad de Ciencias Veterinarias de la UNNE. Se evaluó el músculo longisimus dorsi de novillos tipo Brangus y Braford, de 4, 6 y 8 dientes. Se registró el peso individual de res caliente, así como la conformación y terminación. Las muestras divididas en dos fueron maduradas durante 7 y 14 días envasadas al vacío. La terneza se evaluó por la cizalla de Warner-Bratzler, la grasa total por el método de Soxhlet y la grasa de cobertura con un escalímetro. Se utilizó el análisis de la covarianza a tres vías incluyendo el peso de la res como covariable. El periodo de maduración afectó la terneza. Se registraron diferencias estadísticas entre tratamientos a los 14 días, no así a los 7 días. Durante este periodo, la diferencia de peso lograda se atribuyó al número de dientes y la covariable. El espesor de grasa dorsal se vio afectado por el número de dientes al igual que en la grasa intramuscular, donde además afectó la covariable. La maduración al vacío mejoró la terneza de la carne, siendo este efecto manifiesto en individuos más jóvenes, incrementándose la grasa de cobertura con la edad, no así la grasa intramuscular. La carne producto de animales faenados en la Provincia de Corrientes debe ser considerada de buena calidad, ya que según características de terneza y porcentajes de grasa intramuscular y de cobertura encontradas, responde a las más altas exigencias del mercado

Analysis of RNA Expression Profiles Identifies Dysregulated Vesicle Trafficking Pathways in Creutzfeldt-Jakob Disease

Functional genomics applied to the study of RNA expression profiles identified several abnormal molecular processes in experimental prion disease. However, only a few similar studies have been carried out to date in a naturally occurring human prion disease. To better characterize the transcriptional cascades associated with sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, we investigated the global gene expression profile in samples from the frontal cortex of 10 patients with sCJD and 10 non-neurological controls by microarray analysis. The comparison identified 333 highly differentially expressed genes (hDEGs) in sCJD. Functional enrichment Gene Ontology analysis revealed that hDEGs were mainly associated with synaptic transmission, including GABA (q value = 0.049) and glutamate (q value = 0.005) signaling, and the immune/inflammatory response. Furthermore, the analysis of cellular components performed on hDEGs showed a compromised regulation of vesicle-mediated transport with mainly up-regulated genes related to the endosome (q value = 0.01), lysosome (q value = 0.04), and extracellular exosome (q value < 0.01). A targeted analysis of the retromer core component VPS35 (vacuolar protein sorting-associated protein 35) showed a down-regulation of gene expression (p value= 0.006) and reduced brain protein levels (p value= 0.002). Taken together, these results confirm and expand previous microarray expression profile data in sCJD. Most significantly, they also demonstrate the involvement of the endosomal-lysosomal system. Since the latter is a common pathogenic pathway linking together diseases, such as Alzheimer’s and Parkinson’s, it might be the focus of future studies aimed to identify new therapeutic targets in neurodegenerative diseases