Gestão da informação: implantação de um sistema de informações gerenciais para o sistema de bibliotecas da UFMG

It describes the implementation proposal of a managerial information system for the System of Libraries of the Federal University of Minas Gerais (SB/UFMG). It also reports on the current situation of the information management in the System of Libraries and emphasizes the importance of the information technology as an innovation in the reports management, with the purposes of optimizing processes and supporting managers during decision-making processes

Formación de docentes en procesos de enseñanza y aprendizaje en y para la virtualidad - SIED UNSJ : nuevos desafíos en épocas de pandemia

En este trabajo presentamos la experiencia desarrollada por el Equipo de Mediación Pedagógica y Comunicacional del área de Educación a Distancia de la Universidad Nacional de San Juan, (SIED-UNSJ), que consistió en cuatro seminarios talleres de posgrado virtuales. Estuvieron dirigidos a docentes de todas las unidades académicas de la UNSJ en el contexto de educación remota en emergencia sanitaria COVID-19, durante el primer semestre de 2021. En relación a aspectos pedagógicos didácticos, los profesores lograron optimizar el uso de sus aulas virtuales e incorporaron nuevas herramientas que repercutieron en sus estrategias metodológicas y de evaluación. En relación con el aspecto comunicacional lograron una participación activa entre docentes de distintas unidades académicas generando un intercambio interdisciplinario que favoreció la conformación de comunidades de aprendizaje que se consolidaron posteriormente en proyectos integradores y de articulación. En el aspecto emocional mostraron cambios desde la incertidumbre, preocupación y angustia hacia la seguridad, desafío y aprendizaje compartido. Esta experiencia visibilizó, por un lado, problemáticas que inciden en las prácticas de enseñanza y la relevancia del contexto como obstaculizador o favorecedor. Por otro lado, el papel del docente como generador de cambios desde la formación continua, el trabajo colaborativo y en redes que potencien soluciones innovadoras.Fil: Carmona, Emilse Elizabeth. Universidad Nacional de San Juan.Fil: Guirado, Ana María . Universidad Nacional de San Juan.Fil: Espósito, Rosa María . Universidad Nacional de San Juan

TeraHertz Exploration and Zooming-in for Astrophysics (THEZA): ESA Voyage 2050 White Paper

This paper presents the ESA Voyage 2050 White Paper for a concept of TeraHertz Exploration and Zooming-in for Astrophysics (THEZA). It addresses the science case and some implementation issues of a space-borne radio interferometric system for ultra-sharp imaging of celestial radio sources at the level of angular resolution down to (sub-) microarcseconds. THEZA focuses at millimetre and sub-millimetre wavelengths (frequencies above $\sim$300~GHz), but allows for science operations at longer wavelengths too. The THEZA concept science rationale is focused on the physics of spacetime in the vicinity of supermassive black holes as the leading science driver. The main aim of the concept is to facilitate a major leap by providing researchers with orders of magnitude improvements in the resolution and dynamic range in direct imaging studies of the most exotic objects in the Universe, black holes. The concept will open up a sizeable range of hitherto unreachable parameters of observational astrophysics. It unifies two major lines of development of space-borne radio astronomy of the past decades: Space VLBI (Very Long Baseline Interferometry) and mm- and sub-mm astrophysical studies with "single dish" instruments. It also builds upon the recent success of the Earth-based Event Horizon Telescope (EHT) -- the first-ever direct image of a shadow of the super-massive black hole in the centre of the galaxy M87. As an amalgam of these three major areas of modern observational astrophysics, THEZA aims at facilitating a breakthrough in high-resolution high image quality studies in the millimetre and sub-millimetre domain of the electromagnetic spectrum.Comment: White Paper submitted in response to the ESA Call Voyage 205

The science case and challenges of space-borne sub-millimeter interferometry

Ultra-high angular resolution in astronomy has always been an important vehicle for making fundamental discoveries. Recent results in direct imaging of the vicinity of the supermassive black hole in the nucleus of the radio galaxy M87 by the millimeter VLBI system Event Horizon Telescope and various pioneering results of the Space VLBI mission RadioAstron provided new momentum in high angular resolution astrophysics. In both mentioned cases, the angular resolution reached the values of about 10–20 microarcseconds (0.05–0.1 nanoradian). Further developments towards at least an order of magnitude “sharper” values, at the level of 1 microarcsecond are dictated by the needs of advanced astrophysical studies. The paper emphasis that these higher values can only be achieved by placing millimeter and submillimeter wavelength interferometric systems in space. A concept of such the system, called Terahertz Exploration and Zooming-in for Astrophysics, has been proposed in the framework of the ESA Call for White Papers for the Voyage 2050 long term plan in 2019. In the current paper we present new science objectives for such the concept based on recent results in studies of active galactic nuclei and supermassive black holes. We also discuss several approaches for addressing technological challenges of creating a millimeter/sub-millimeter wavelength interferometric system in space. In particular, we consider a novel configuration of a space-borne millimeter/sub-millimeter antenna which might resolve several bottlenecks in creating large precise mechanical structures. The paper also presents an overview of prospective space-qualified technologies of low-noise analogue front-end instrumentation for millimeter/sub-millimeter telescopes. Data handling and processing instrumentation is another key technological component of a sub-millimeter Space VLBI system. Requirements and possible implementation options for this instrumentation are described as an extrapolation of the current state-of-the-art Earth-based VLBI data transport and processing instrumentation. The paper also briefly discusses approaches to the interferometric baseline state vector determination and synchronisation and heterodyning system. The technology-oriented sections of the paper do not aim at presenting a complete set of technological solutions for sub-millimeter (terahertz) space-borne interferometers. Rather, in combination with the original ESA Voyage 2050 White Paper, it sharpens the case for the next generation microarcsecond-level imaging instruments and provides starting points for further in-depth technology trade-off studies.</p

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Roles of the Phosphate-regulating Proteins, PHEX and DMP1, in the Dentin Matrix of XLH

X-linked hypophosphatemia (XLH) is the most common hereditary hypophosphatemic disorder resulting from loss-of-function of the phosphate-regulating endopeptidase, PHEX. Although the mineralization defects observed in XLH patients have been solely attributed to decreased serum phosphate levels, the local disruption in the organization of the dentin matrix that precedes and sustains mineralization has not been studied. Nevertheless, disruption of extracellular matrix (ECM) factors necessary for the maturation and mineralization of cartilage, bone and cementum have been reported, suggesting that PHEX mutations and/or hypophosphatemia may indeed disrupt ECM deposition. The studies herein were undertaken to elucidate the local effects of PHEX mutations on the deposition and mineralization of dentin matrix. By manipulating in vitro conditions, we evaluated the effect of phosphate donors on the differentiation of XLH dental pulp cells. We found that XLH dental pulp cells are sensitive to the phosphate source used during in vitro differentiation experiments and that XLH cells have an impaired differentiation response when compared to healthy control cells. By generating cell lines with constitutive DMP1 expression we showed that full-length DMP1(FL-DMP1) was able to reverse the impaired mineralization in XLH cells. Furthermore, induction of differentiation resulted in the upregulation of inhibitors of the canonical Wnt pathway, altered ECM protein processing and elevated levels of MMP2 and MMP3 in XLH cells. DMP1 expression was sufficient to reverse these patterns. We generated a tooth-specific DMP1-overexpressing PHEX-deficient mouse. DMP1 expression resulted in decreased Col.I protein expression in the predentin and periodontal ligament space relative to their wild-type(WT) and XLH/Hyp counterparts. Although DMP1 expression was associated with decreased WNT5A expression in DMP1-overxpressing mice, DMP1 was unable to effect the same response in the Phex-deficient background. Likewise, DMP1 overexpression failed to rescue the dentin phenotype of Hyp mice. In summary, our studies suggest that deregulation of the differentiation process may be occurring in XLH cells. DMP1 has the potential to modulate these differentiation pathways but requires a functional PHEX protein to function. These findings suggest that PHEX and DMP1 may interact and/or that DMP1 may function upstream of PHEX in many of these pathways

Constitutively Active MAVS Inhibits HIV-1 Replication via Type I Interferon Secretion and Induction of HIV-1 Restriction Factors.

Type I interferon is known to inhibit HIV-1 replication through the induction of interferon stimulated genes (ISG), including a number of HIV-1 restriction factors. To better understand interferon-mediated HIV-1 restriction, we constructed a constitutively active form of the RIG-I adapter protein MAVS. Constitutive MAVS was generated by fusion of full length MAVS to a truncated form of the Epstein Barr virus protein LMP1 (ΔLMP1). Supernatant from ΔLMP1-MAVS-transfected 293T cells contained high levels of type I interferons and inhibited HIV replication in both TZM-bl and primary human CD4+ T cells. Supernatant from ΔLMP1-MAVS-transfected 293T cells also inhibited replication of VSV-G pseudotyped single cycle SIV in TZM-bl cells, suggesting restriction was post-entry and common to both HIV and SIV. Gene array analysis of ΔLMP1-MAVS-transfected 293T cells and trans-activated CD4+ T cells showed significant upregulation of ISG, including previously characterized HIV restriction factors Viperin, Tetherin, MxB, and ISG56. Interferon blockade studies implicated interferon-beta in this response. In addition to direct viral inhibition, ΔLMP1-MAVS markedly enhanced secretion of IFN-β and IL-12p70 by dendritic cells and the activation and maturation of dendritic cells. Based on this immunostimulatory activity, an adenoviral vector (Ad5) expressing ΔLMP1-MAVS was tested as a molecular adjuvant in an HIV vaccine mouse model. Ad5-Gag antigen combined with Ad5-ΔLMP1-MAVS enhanced control of vaccinia-gag replication in a mouse challenge model, with 4/5 animals showing undetectable virus following challenge. Overall, ΔLMP1-MAVS is a promising reagent to inhibit HIV-1 replication in infected tissues and enhance vaccine-mediated immune responses, while avoiding toxicity associated with systemic type I interferon administration

Abstract B062: Immune activation by LMP1 CD40 pathway and LMP1-IPS-1 STING pathway activators

Abstract The strongest CD8+ T cell responses ever recorded in humans occur as a result of infection by the Epstein-Barr Virus (EBV). Following a massive CD8+ T cell response during acute EBV infection, ∼5.5% of the total CD8+ T cell repertoire in blood is thereafter committed to the life-long suppression of viral replication. The key to this response is the EBV Latent Membrane Protein-1 (LMP1) which functions as a constitutively activated form of the CD40 receptor. LMP1 consists of an N-terminal domain that clusters in cell membranes and a C-terminal domain that engages the proteins of the CD40 signalosome. Studies to determine if LMP1 could be used for immunotherapy led to the following conclusions: (1) LMP1 mRNA directly activated human dendritic cells (DCs), showing its potential as an adjuvant for mRNA vaccines; (2) Adenovirus (Ad)-delivered LMP1 strongly enhanced vaccine-induced CD8+ T cell responses in mice, indicating that LMP1 may enhance Ad-based oncolytic therapies; (3) lentiviruses incorporating LMP1 became strong activators of DCs in vitro; and (4) DNA vaccines incorporating LMP1 protected mice from tumor challenge in a B16F10 melanoma metastasis model. These data show that the LMP1 nucleic acid sequence is a portable genetic adjuvant with broad applicability to tumor immunotherapy. In related studies, the membrane clustering N-terminal domain of LMP1 was fused to Interferon-beta Promoting Stimulator-1 (IPS-1, also called MAVS, VISA, or Cardif), a protein that requires membrane clustering to become activated. This fusion protein acts independently of cyclic dinucleotides (CDN) to activate downstream mediators of the STING pathway. Vaccination of mice with Ad expressing antigen plus LMP1-IPS-1 resulted in complete protection from challenge with Vaccinia-antigen virus (&amp;gt;1 million-fold protection). These data suggest that LMP1-IPS-1 combined with gene delivery technologies may supplant the need for small molecule CDNs for STING pathway activation in immuno-oncology. Citation Format: Richard S. Kornbluth, Sachin Gupta, James M. Termini, Elizabeth Guirado, Geoffrey W. Stone. Immune activation by LMP1 CD40 pathway and LMP1-IPS-1 STING pathway activators [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B062.</jats:p

ΔLMP1-MAVS enhances anti-Gag immune responses as an Ad5 viral vector vaccine adjuvant.

<p>BALB/c mice were left untreated or vaccinated with a combination of Ad5-Gag and either Ad5-GFP (control), Ad5-ΔLMP1-MAVS, or Ad5-LMP1. Two weeks following vaccination, mice were challenged with vaccinia-gag virus. Vaccinia titers were measured from ovaries after 5 days. NT: no treatment.</p

Gene array analysis of transfected 293T cells and primary CD4+ T cells cultured with 293T supernatant.

<p>Three independent wells of 293T cells were transfected with pcDNA3.1 empty vector or ΔLMP1-MAVS plasmid and total RNA isolated 36 hours later. Primary CD4+ T cells from 3 independent donors were cultured with 293T supernatant (collected 24 hours following pcDNA3.1 or ΔLMP1-MAVS transfection). Total CD4+ T cell RNA was isolated 36 hours later. (A) Venn Diagrams of the number of probe sets upregulated and down-regulated (>2-fold change) by ΔLMP1-MAVS. (B) Differential gene expression of 293T cells and CD4+ T cells. (C) List of genes upregulated by ΔLMP1-MAVS in both 293T cells and CD4+ T cells. Fold-change and P-values for each probe set are shown for CD4+ T cells following ΔLMP1-MAVS treatment. (D) List of genes upregulated by CD4+ T cells but not 293T cells. Fold-change between pcDNA3.1 and pΔLMP1-MAVS and P-values for each probe set are shown. (E) Gen Go networks analysis of pathways significantly upregulated by ΔLMP1-MAVS in transfected 293T cells, or CD4+ T cells cultured with ΔLMP1-MAVS transfected 293T supernatant.</p