Use of water-Cherenkov detectors to detect Gamma-Ray-Bursts at the Large Aperture GRB Observatory (LAGO)

The Large Aperture GRB Observatory (LAGO) project aims at the detection of high energy photons from Gamma Ray Bursts (GRB) using the single particle technique in ground-based water-Cherenkov detectors (WCD). To reach a reasonable sensitivity, high altitude mountain sites have been selected in Mexico (Sierra Negra, 4550 m a.s.l.), Bolivia (Chacaltaya, 5300 m a.s.l.) and Venezuela (Me´ rida, 4765 m a.s.l.). We report on detector calibration and operation at high altitude, search for bursts in 4 months of preliminary data, as well as search for signal at ground level when satellites report a burst.Fil: Allard, D.. Université Paris Diderot - Paris 7; FranciaFil: Allekotte, Ingomar. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Alvarez, C.. Facultad de Ciencias Fısico-Matematicas; MéxicoFil: Asorey, Hernán Gonzalo. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Barros, H.. Universidad Simon Bolivar; VenezuelaFil: Bertou, Xavier Pierre Louis. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Burgoa, O.. Instituto de Investigaciones Fisicas; BoliviaFil: Gomez Berisso, Mariano. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Martinez, O.. Facultad de Ciencias Fısico-Matematicas; MéxicoFil: Miranda Loza, P.. Instituto de Investigaciones Fısicas; BoliviaFil: Murrieta, T.. Facultad de Ciencias Fısico-Matematicas; MéxicoFil: Perez, G.. Facultad de Ciencias Fısico-Matematicas; MéxicoFil: Rivera, H.. Instituto de Investigaciones Fısicas; BoliviaFil: Rovero, Adrian Carlos. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Saavedra, O.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Salazar, H.. Facultad de Ciencias Fısico-Matematicas ; MéxicoFil: Tello, J. C.. Universidad Simon Bolıvar; VenezuelaFil: Ticona Peralda, R.. Instituto de Investigaciones Fısicas; BoliviaFil: Velarde, A.. Instituto de Investigaciones Fısicas; BoliviaFil: Villaseñor, L.. Universidad de Michoacan; MéxicoFil: Areso, Omar Antonio. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Arnaldi, Luis Horacio. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Dasso, Sergio Ricardo. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Gonzalez, M.. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Gulisano, Adriana Maria. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Martin, R.. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. Dirección Nacional del Antártico. Instituto Antártico Argentino; ArgentinaFil: Masías Meza, Jimmy Joel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Sidelnik, Iván Pedro. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Alvarez, W.. Universidad de San Carlos; GuatemalaFil: The LAGO Collaboration

Potent pro-apoptotic combination therapy is highly effective in a broad range of cancers

Primary or acquired therapy resistance is a major obstacle to the effective treatment of cancer. Resistance to apoptosis has long been thought to contribute to therapy resistance. We show here that recombinant TRAIL and CDK9 inhibition cooperate in killing cells derived from a broad range of cancers, importantly without inducing detectable adverse events. Remarkably, the combination of TRAIL with CDK9 inhibition was also highly effective on cancers resistant to both, standard-of-care chemotherapy and various targeted therapeutic approaches. Dynamic BH3 profiling revealed that, mechanistically, combining TRAIL with CDK9 inhibition induced a drastic increase in the mitochondrial priming of cancer cells. Intriguingly, this increase occurred irrespective of whether the cancer cells were sensitive or resistant to chemo- or targeted therapy. We conclude that this pro-apoptotic combination therapy has the potential to serve as a highly effective new treatment option for a variety of different cancers. Notably, this includes cancers that are resistant to currently available treatment modalities

Kv7 Channels Can Function without Constitutive Calmodulin Tethering

M-channels are voltage-gated potassium channels composed of Kv7.2-7.5 subunits that serve as important regulators of neuronal excitability. Calmodulin binding is required for Kv7 channel function and mutations in Kv7.2 that disrupt calmodulin binding cause Benign Familial Neonatal Convulsions (BFNC), a dominantly inherited human epilepsy. On the basis that Kv7.2 mutants deficient in calmodulin binding are not functional, calmodulin has been defined as an auxiliary subunit of Kv7 channels. However, we have identified a presumably phosphomimetic mutation S511D that permits calmodulin-independent function. Thus, our data reveal that constitutive tethering of calmodulin is not required for Kv7 channel function

Changing environments during the Middle-Upper Palaeolithic transition in the eastern Cantabrian Region (Spain): direct evidence from stable isotope studies on ungulate bones

Environmental change has been proposed as a factor that contributed to the extinction of the Neanderthals in Europe during MIS3. Currently, the different local environmental conditions experienced at the time when Anatomically Modern Humans (AMH) met Neanderthals are not well known. In the Western Pyrenees, particularly, in the eastern end of the Cantabrian coast of the Iberian Peninsula, extensive evidence of Neanderthal and subsequent AMH activity exists, making it an ideal area in which to explore the palaeoenvironments experienced and resources exploited by both human species during the Middle to Upper Palaeolithic transition. Red deer and horse were analysed using bone collagen stable isotope analysis to reconstruct environmental conditions across the transition. A shift in the ecological niche of horses after the Mousterian demonstrates a change in environment, towards more open vegetation, linked to wider climatic change. In the Mousterian, Aurignacian and Gravettian, high inter-individual nitrogen ranges were observed in both herbivores. This could indicate that these individuals were procured from areas isotopically different in nitrogen. Differences in sulphur values between sites suggest some variability in the hunting locations exploited, reflecting the human use of different parts of the landscape. An alternative and complementary explanation proposed is that there were climatic fluctuations within the time of formation of these archaeological levels, as observed in pollen, marine and ice cores.This research was funded by the European Commission through a Marie Curie Career Integration Grant (FP7- PEOPLE-2012-CIG-322112), by the Spanish Ministry of Economy and Competitiveness (HAR2012-33956 and Ramon y Cajal-2011-00695), the University of Cantabria and Campus International to ABMA. Radiocarbon dating at ORAU was funded by MINECO-HAR2012-33956 project. J.J was supported initially by the FP7- PEOPLE-2012-CIG-322112 and later by a Marie Curie Individual Fellowship (H2020-MSCA-IF-2014-656122). Laboratory work, associated research expenses and isotopic analysis were kindly funded by the Max Planck Society to M.R

Calibración del detector de rayos cósmicos instalado en la Base Antártica Argentina Marambio

Durante 2019 el grupo LAMP (Laboratorio Argentino de Meteorología del esPacio) dasarrolló el laboratorio Antártico de Meteorología del Espacio en la base Argentina Marambio, en la Península Antártica. El principal instrumento instalado fue un detector de rayos cósmicos basado en el efecto Cherenkov en agua. Este detector es el primer nodo antártico permanente de la colaboración LAGO (Latin American Giant Observatory). El transporte de rayos cósmicos galácticos de baja energía se ve afectado por estructuras transitorias en la heliósfera. Por lo tanto, estudiar las variaciones temporales del flujo de partículas cósmicas secundarias observadas en tierra es de relevancia para la Meteorología del Espacio. En este trabajo presentamos y analizamos el primer año de observaciones del flujo de rayos cósmicos secundarios de este detector.In 2019 an Antarctic Space Weather laboratory was deployed by the LAMP group (Laboratorio Argentino de Meteorología del esPacio) at Marambio base, in the Antarctic Peninsula. The main instrument installed was a cosmic ray detector based on water Cherenkov radiation. This detector is the first permanent antarctic node of the LAGO Collaboration (Latin American Giant Observatory). Transient heliospheric structures affect lowest-energy galactic cosmic rays transport. Thus, study temporal variations of the observed flux at Earth is relevant for Space Weather. We present and analyze one-year observations of the flux of secondary cosmic rays observed by this detector.Asociación Argentina de Astronomí