Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer

Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response

OBJECTIVE: To analyse predictors for relapses and number of attacks under different immunotherapies in patients with neuromyelitis optica spectrum disorder (NMOSD). DESIGN: This is a retrospective cohort study conducted in neurology departments at 21 regional and university hospitals in Germany. Eligible participants were patients with aquaporin-4-antibody-positive or aquaporin-4-antibody-negative NMOSD. Main outcome measures were HRs from Cox proportional hazard regression models adjusted for centre effects, important prognostic factors and repeated treatment episodes. RESULTS: 265 treatment episodes with a mean duration of 442 days (total of 321 treatment years) in 144 patients (mean age at first attack: 40.9 years, 82.6% female, 86.1% aquaporin-4-antibody-positive) were analysed. 191 attacks occurred during any of the treatments (annual relapse rate=0.60). The most common treatments were rituximab (n=77, 111 patient-years), azathioprine (n=52, 68 patient-years), interferon-beta (n=32, 61 patient-years), mitoxantrone (n=34, 32.1 patient-years) and glatiramer acetate (n=17, 10 patient-years). Azathioprine (HR=0.4, 95% CI 0.3 to 0.7, p=0.001) and rituximab (HR=0.6, 95% CI 0.4 to 1.0, p=0.034) reduced the attack risk compared with interferon-beta, whereas mitoxantrone and glatiramer acetate did not. Patients who were aquaporin-4-antibody-positive had a higher risk of attacks (HR=2.5, 95% CI 1.3 to 5.1, p=0.009). Every decade of age was associated with a lower risk for attacks (HR=0.8, 95% CI 0.7 to 1.0, p=0.039). A previous attack under the same treatment tended to be predictive for further attacks (HR=1.5, 95% CI 1.0 to 2.4, p=0.065). CONCLUSIONS: Age, antibody status and possibly previous attacks predict further attacks in patients treated for NMOSD. Azathioprine and rituximab are superior to interferon-beta

Implementación del Proyecto Planta de Alimentos para la Integración Social de la Universidad Nacional de La Plata (PAIS-UNLP)

En el marco de la crisis alimentaria global, durante el bienio 2016-2018 cerca de 14.2 millones de argentinos padecían inseguridad alimentaria, moderada o grave, valor que duplicaba lo registrado para el bienio anterior (FAO, 2019). En este aspecto el INDEC informó que, para 2021, existían en nuestro país casi 12 millones de personas por debajo de la línea de pobreza, de los cuales 3 millones se encontraban por debajo de la línea de indigencia. En la ciudad de La Plata, entre 2018 y 2019, el Consejo Social llevó adelante un relevamiento de Sitios de Distribución de Alimentos del Gran La Plata, encontrando también datos alarmantes: casi un 41% de la población por debajo de la línea de pobreza y un 13.5% por debajo de la línea de indigencia. Frente a este panorama, la Universidad Nacional de La Plata (UNLP) priorizó la necesidad de un accionar urgente planteando nuevas herramientas. Por este motivo, en el marco del Plan Argentina Contra el Hambre, en 2019, la UNLP puso a disposición toda su capacidad científica y técnica y se propuso como objetivo principal la creación de la Planta de Alimentos para la Integración Social (P.A.I.S) con el propósito de generar productos de alta calidad nutricional, de fácil acceso para las personas más vulnerables, que permitan articular las capacidades productivas del Cinturón Hortícola Platense fortaleciendo el sistema productivo local y en particular la cadena de valor alimentaria.Facultad de Ingenierí

The 2018 GaN power electronics roadmap

Gallium nitride (GaN) is a compound semiconductor that has tremendous potential to facilitate economic growth in a semiconductor industry that is silicon-based and currently faced with diminishing returns of performance versus cost of investment. At a material level, its high electric field strength and electron mobility have already shown tremendous potential for high frequency communications and photonic applications. Advances in growth on commercially viable large area substrates are now at the point where power conversion applications of GaN are at the cusp of commercialisation. The future for building on the work described here in ways driven by specific challenges emerging from entirely new markets and applications is very exciting. This collection of GaN technology developments is therefore not itself a road map but a valuable collection of global state-of-the-art GaN research that will inform the next phase of the technology as market driven requirements evolve. First generation production devices are igniting large new markets and applications that can only be achieved using the advantages of higher speed, low specific resistivity and low saturation switching transistors. Major investments are being made by industrial companies in a wide variety of markets exploring the use of the technology in new circuit topologies, packaging solutions and system architectures that are required to achieve and optimise the system advantages offered by GaN transistors. It is this momentum that will drive priorities for the next stages of device research gathered here

Characterization and application of 600 V normally-off GaN transistors in hard switching DC/DC converters

As GaN power devices emerge from research to industry, the characterization of these novel devices itself and its application in power electronic converters is essential. The purpose of this paper is to prove the capabilities of GaN technology using a novel 600 V normally-off GaN-on-Si transistor which shows no dynamic behavior of its on-resistance. A hard switching DC/DC converter prototype reveals efficiencies up to 99.3 % and switching frequencies up to 1 MHz incorporating a high power density up to 28 kW/l