Development of innovative techniques, experimental devices and testing protocols for the measurement of muscle and neuromuscular junction functionality in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) remains an invariably fatal disease, in which neuromuscular junction (NMJ) functionality is strongly impaired. To this, the aim of this research project was to develop a series of novel testing tools for a precise assessment of the altered communication between muscle and nerve in ALS progression. A novel technique for the in-situ measurement of murine Tibialis Anterior (TA) NMJ functionality in isotonic conditions was developed and validated. A novel parameter, named Isotonic Neurotransmission Failure (INF), was proposed. Results showed an increase in INF of SOD1G93A mouse TA muscles at the end-stage of the disease, highlighting, for the first time, an increased impairment of NMJ functionality in isotonic conditions. An embedded system for the measurement of 3D engineered skeletal muscle tissues’ contractility with a non-invasive technique was proposed. Results showed the capability of the system to not impair tissue's contractility during the entire growth, and to discriminate healthy and pathological conditions. Finally, a 3D microfluidic device was designed and realized to promote the formation of NMJ between spinal cord-derived neuronal cells and 3D engineered skeletal muscle. Results showed a good attraction between these two cells populations, paving the basis for the development of a more comprehensive 3D NMJ in-vitro model. On the other hand, since extracellular vesicles (EVs) are involved in ALS pathological proteins transportation, a series of preliminary experiments with muscle cells’ populations was carried out, with the final aim of evaluating the role of SOD1G93A mice-derived EVs on the novel experimental models here proposed. Results showed that SOD1G93A mice-derived EVs increased in number during the ALS progression, and impaired C2C12 cells’ differentiation. In conclusion, a series of novel testing tools have been developed for a precise assessment of the NMJ functionality in different models which, of note, can be also employed to unravel the mechanism behind muscle-nerve impairments in other neurodegenerative pathologies

Hacer política para hacer negocios : la política paraguaya, la política borbónica y los comerciantes de yerba en Santa Fe (Siglo XVIII)

El presente trabajo se propone analizar las resistencias y estrategias llevadas adelante por un grupo de la elite santafesina, frente a los intentos de los agentes borbónicos de imponer el poder real por encima de las autonomías locales. A través del examen de una causa judicial sobre comercio ilícito entre algunos vecinos santafesinos y Joseph de Antequera (líder de las Revoluciones Comuneras del Paraguay), se intenta reflexionar respecto de los cambios en la política borbónica. Por otra parte, aportar evidencias que contribuyen a poner en cuestión la tesis tradicional sobre el absolutismo y la centralización de la monarquía borbónica. La administración colonial española se configuró como un sistema de equilibrios cambiantes entre las autonomías de las ciudades y del poder central. Estas autonomías sumadas a elites de poder constituidas a través de vínculos personales, de parentesco, de clientelismo, vecindad, paisanaje, entre otros, les permitieron cooptar el ejercicio de varias funciones frente al rey que, si bien no de manera monolítica, supusieron resistencias a la implementación de los cambios que proponían las reformas.This paper analyzes the resistances and strategies carried out by a group of Santa Fe’s elite, against the attempts of the Bourbon agents to impose royal power over local autonomies. Through examination of a court case on illegal trade, among some neighbors of Santa Fe and Joseph de Antequera (leader of the Commoner Revolutions of Paraguay), attempts to reflect on the changes in the Bourbon policy. On the other hand, provide evidence that contribute to question the traditional thesis on absolutism and centralization of the Bourbon monarchy. The Spanish colonial administration was configured as a system of changing balance between the autonomy of the cities and the central government. These coupled with power elites constituted through personal ties, kinship, patronage, neighborhood, peasantry, among others, autonomy allowed them to co-opt the exercise of various functions against the king, but not monolithically, supposed strengths the implementation of the changes proposed reforms.Fil: Forconi, María Celeste. Universidad Nacional de Rosari

Studio di potenziali acquiferi mediante indagini geoelettriche nel villaggio di itigi (Singida - Tanzania)

http://www.fe.infn.it/u/mantovani/CV/Proceedings/Colonna_08.pd

Do the Early Galaxies observed by JWST disagree with Planck's CMB polarization measurements?

The recent observations from the James Webb Space Telescope have led to a surprising discovery of a significant density of massive galaxies with masses of $M \ge 10^{10.5} M_{\odot}$ at redshifts of approximately $z\sim 10$. This corresponds to a stellar mass density of roughly $\rho_*\sim 10^6 M_{\odot} Mpc^{-3}$. Despite making conservative assumptions regarding galaxy formation, this finding may not be compatible with the standard $\Lambda$CDM cosmology that is favored by observations of CMB Anisotropies from the Planck satellite. In this paper, we confirm the substantial discrepancy with Planck's results within the $\Lambda$CDM framework. Assuming a value of $\epsilon=0.2$ for the efficiency of converting baryons into stars, we indeed find that the $\Lambda$CDM model is excluded at more than $99.7 \%$ confidence level (C.L.). An even more significant exclusion is found for $\epsilon \sim 0.1$, while a better agreement, but still in tension at more than $95 \%$, is obtained for $\epsilon =0.32$. This tension, as already discussed in the literature, could arise either from systematics in the JWST measurements or from new physics. Here, as a last-ditch effort, we point out that disregarding the large angular scale polarization obtained by Planck, which allows for significantly larger values of the matter clustering parameter $\sigma_8$, could lead to better agreement between Planck and JWST within the $\Lambda$CDM framework. Interestingly, the model compatible with Planck temperature-only data and JWST observation also favors a higher Hubble constant $H_0=69.0\pm1.1$ km/s/Mpc at $68\%$ C.L., in better agreement with observations based on SN-Ia luminosity distances.Comment: 5 pages, 2 Figures and a bunch of galaxie

Estratégias de melhorias do SLA (Service Level Agreement) através da criação de um documento de oferta básica de uma empresa

Orientador : Prof. Egon Walter Wildauer, Dr.Monografia (especialização) - Universidade Federal do Paraná, Curso de MBA Gerência em Sistemas LogísticosInclui referênciasResumo : Este projeto consiste na estruturação de um Service Level Agreement (SLA) ou Acordo de Nível de Serviço, que será utilizado como ferramenta através de um documento de Oferta Básica para a gestão no processo de Order To Cash. Por meio da utilização deste modelo de oferta de serviços, pretende-se apresentar, entre outros benefícios, maior transparência na relação com os clientes e possibilitar a melhoria continua desta relação, consequentemente, da operação. Para estruturação deste Nível de Serviço Acordado, é necessário entender as propriedades expostas nas referências bibliográficas apresentadas neste projeto e através dos conceitos revisados, trabalhar no desenvolvimento do documento considerando a capacidade operacional da empresa. Será definida a forma de como ocorrerá a gestão da rotina de serviço, contemplando cada parte do processo, detalhando o scopo do serviço e a amplitude, estabelecendo uma relação baseada na transparência com o cliente. Para finalizar, um alinhamento entre as áreas da empresa através de uma comunição acertiva, com o propósito de contribuir com a manutenção e aumento das vendas, consequemente o Market Share da empresa

Perfiles militares de la Tenencia de Gobernación santafesina en la era borbónica

The end of the war of Succession and the signing of the Utrecht peace treaty meant for the territories of the Río de la Plata a change in the geostrategic position in the territorial dispute. This article tries to analyze the reorganization in the political equipment taking like lookout a subordinate jurisdiction of the governorship of Buenos Aires, the city of Santa Fe. From the profiles of the lieutenants of governor it is tried to observe the articulation between dynamics local and Bourbon reforms of this process of reorganization of politico-military devices.La finalización de la guerra de Sucesión y la firma del tratado de Utrecht significó para los territorios del Río de la Plata un cambio en la posición geoestratégica en la disputa territorial. Este artículo intenta analizar la reorganización en sus equipamientos políticos tomando como mirador una jurisdicción subordinada de la gobernación de Buenos Aires, la ciudad de Santa Fe. A partir de los perfiles de los tenientes de gobernador se pretende observar la articulación entre dinámica local y reformas borbónicas de este proceso de reorganización de los dispositivos político-militares

Optimal force evaluation for isotonic fatigue characterization in mouse Tibialis Anterior muscle

Skeletal muscle fatigue is most often studied as a response to repeated stimulations in isometric conditions and it is usually quantified as the progressive loss of force generating capability over time. However, physical dynamic activity is based on the shortening of skeletal muscles. Therefore, the condition that best mimics body movements is the isotonic one, in which muscle is allowed to shorten against a constant load. In the literature, the isotonic fatigue test is performed allowing the muscle to lift a load corresponding to one-third of the maximal isometric force (reference optimal force), as best representative of the force at which the tissue develops its maximum power. The goal of this study was to devise a new testing protocol in which each muscle was tested for isotonic fatigue by shortening against its own optimal force, i.e. the force at which it really developed the maximum power. Our hypothesis was that testing all the muscle at a standard reference value would introduce significant errors in the parameters associated to muscle fatigue and in their variance. The proposed protocol was based on the real-time measurement of the maximum power a muscle was able to generate through the application of the after-load technique and a mathematical interpolation to the Hill's equation, that therefore allowed to determine the experimental optimal force to be applied during the fatigue test. Experimental results showed that the muscles tested with the experimental optimal force had a fatigue time significantly lower than the control muscles tested with the reference optimal force. A decrease, even if not statistically significant, was also measured for the power and work generated during the fatigue test. Of note, for all these parameters a huge decrease in the measurement variance was reported, confirming that a precise assessment of the muscle experimental optimal force was needed to increase the accuracy of the measurements. On the other hand, the application of the protocol proposed in this work required an increase in the test duration, due to the application of the after-load technique, and a real time measurement of the power generated by the tissue

Sensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia

Epstein Barr virus (EBV) is the etiologic agent involved in numerous human cancers. After infecting the host, EBV establishes a latent infection, with low levels of messenger RNA (mRNA) and protein expression, evolved to evade immune recognition. Conversely, EBV microRNAs (miRNA) are expressed ubiquitously and abundantly within infected cells. Their role in tumor biology and clinical outcomes across the spectrum of cancer is not fully explained. Here, we applied our bioinformatics pipeline for quantitative EBV miRNA detection to examine sequencing data of 8,955 individual tumor samples across 27 tumor types representing the breadth of cancer. We uncover an association of intermediate levels of viral miRNA with decreased survival in adult acute myeloid leukemia (AML) patients (P = 0.00013). Prognostic modeling of this association suggests that increased EBV miRNA levels represent an independent risk factor for poor patient outcomes. Furthermore, we explore differences in expression between elevated and absent viral miRNA loads in adult AML tumors finding that EBV positivity was associated with proinflammatory signals. Together, given no associations were found for pediatric AML, our analyses suggests EBV positivity has the potential for being a prognostic biomarker and might represent a surrogate measure related to immune impairment in adult patients

Distribution of the brown bear (Ursus arctos marsicanus) in the Central Apennines, Italy, 2005-2014

Despite its critical conservation status, no formal estimate of the Apennine brown bear (Ursus arctos marsicanus) distribution has ever been attempted, nor a coordinated effort to compile and verify all recent occurrences has ever been ensured. We used 48331 verified bear location data collected by qualified personnel from 20052014 in the central Apennines, Italy, to estimate the current distribution of Apennine brown bears. Data sources included telemetry relocations, scats and DNA-verified hair samples, sightings, indirect signs of presence, photos from camera traps, and damage to properties. Using a grid-based zonal analysis to transform raw data density, we applied ordinary kriging and estimated a 4923 km2 main bear distribution, encompassing the historical stronghold of the bear population, and including a smaller (1460 km2) area of stable occupancy of reproducing female bears. National and Regional Parks cover 38.8% of the main bear distribution, plus an additional 19.5% encompassed by the Natura 2000 network alone. Despite some methodological and sampling problems related to spatial and temporal variation in sampling effort at the landscape scale, our approach provides an approximation of the current bear distribution that is suited to frequently update the distribution map. Future monitoring of this bear population would benefit from estimating detectability across a range on environmental and sampling variables, and from intensifying the collection of bear presence data in the peripheral portions of the distribution