An open-label multi-center phase 1 safety study of BXQ-350 in children and young adults with relapsed solid tumors, including recurrent malignant brain tumors

BACKGROUND: BXQ-350 is a novel anti-neoplastic agent composed of saposin C (SapC) and phospholipid dioleoylphosphatidyl-serine sodium (DOPS) that selectively binds tumor cell phosphatidylserine (PS), inducing apoptosis. BXQ-350 has demonstrated preclinical antitumor effects in high-grade gliomas (HGG) and clinical activity in adult patients with recurrent HGG. METHODS: A phase 1 study was conducted in pediatric patients with relapsed/refractory solid tumors, including recurrent brain tumors. Primary objectives were to characterize safety and determine maximum tolerated dose (MTD) and preliminary antitumor activity. Sequential dose cohorts were assessed up to 3.2 mg/kg using an accelerated titration design. Each cycle was 28 days; dosing occurred on days 1-5, 8, 10, 12, 15, and 22 of cycle 1, and day 1 of subsequent cycles, until disease progression or toxicity. RESULTS: Nine patients, median age 10 years (range: 4-23), were enrolled. Seven patients (78%) had central nervous system (CNS) and two (22%) had non-CNS tumors. Eight patients completed cycle 1. No dose limiting toxicity (DLT) or BXQ-350-related serious adverse events (SAEs) were observed. Six patients experienced at least one adverse event (AE) considered possibly BXQ-350-related, most were grade ≤2. One patient with diffuse intrinsic pontine glioma experienced stable disease for 5 cycles. The study was terminated after part 1 to focus development on the frontline setting. CONCLUSION: No DLTs or BXQ-350-related SAEs were reported, and the maximal planned dose of 3.2 mg/kg IV was tolerable. Limited safety and efficacy data support continued BXQ-350 development in pediatric HGG; however, early discontinuations for progression suggest novel therapies be assessed at earlier disease stages

Análisis de la generación eléctrica distribuida en la localidad de Tres Lagos, provincia de Santa Cruz, Argentina

Fil: Lorenzetti, D. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: Moyano, H. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: León, H. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: Fernández, C. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: Abdelbaki, A. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: Rodríguez, R. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Matemática; Argentina.Fil: Leiva, E.P.M. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Matemática y Física; Argentina.Fil: Leiva, E.P.M. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Físico-Química de Córdoba; Argentina.Se presenta en este trabajo el diseño de un sistema de generación de energía eléctrica distribuida (GD) para la localidad de Tres Lagos, ubicada en la provincia de Santa Cruz, Argentina. El sistema de GD utiliza en su diseño recursos eólicos, solares y convencional (generador diesel) como fuentes primarias de energía, en una configuración de red eléctrica autónoma.http://www.hyfusen.com/libro.htmlFil: Lorenzetti, D. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: Moyano, H. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: León, H. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: Fernández, C. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: Abdelbaki, A. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: Rodríguez, R. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Matemática; Argentina.Fil: Leiva, E.P.M. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Matemática y Física; Argentina.Fil: Leiva, E.P.M. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Físico-Química de Córdoba; Argentina.Otras Ingeniería Eléctrica, Ingeniería Electrónica e Ingeniería de la Informació

Análisis de la producción y distribución de hidrógeno en un circuito patagónico

Se presenta en este trabajo un estudio comparativo de la factibilidad técnica y económica de la producción central de hidrógeno mediante fuentes renovables. Dicha comparación se llevó a cabo de manera simulada mediante la utilización de las herramientas de software libre, las cuales funcionan bajo entorno Windows, por una parte y valores reales obtenidos de datos de la Planta Experimental de Hidrógeno de PicoTruncado.http://www.hyfusen.com/libro.htmlFil: MacDonald, E. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: Lorenzetti, D. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: Moyano, H. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: León, H. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: Fernández, C. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: Abdelbaki, A. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Laboratorio de Energías Renovables; Argentina.Fil: Rodríguez, R. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Matemática; Argentina.Otras Ingeniería de los Materiale

The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial

\ua9 2023, The Author(s).BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 (n = 77) of the ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated the efficacy of the oral, selective, central nervous system–penetrant, type II RAF inhibitor tovorafenib (420 mg m−2 once weekly; 600 mg maximum) in patients with BRAF-altered, relapsed/refractory pLGG. Arm 2 (n = 60) is an extension cohort, which provided treatment access for patients with RAF-altered pLGG after arm 1 closure. Based on independent review, according to Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, the overall response rate (ORR) of 67% met the arm 1 prespecified primary endpoint; median duration of response (DOR) was 16.6 months; and median time to response (TTR) was 3.0 months (secondary endpoints). Other select arm 1 secondary endpoints included ORR, DOR and TTR as assessed by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO) criteria and safety (assessed in all treated patients and the primary endpoint for arm 2, n = 137). The ORR according to RAPNO criteria (including minor responses) was 51%; median DOR was 13.8 months; and median TTR was 5.3 months. The most common treatment-related adverse events (TRAEs) were hair color changes (76%), elevated creatine phosphokinase (56%) and anemia (49%). Grade ≥3 TRAEs occurred in 42% of patients. Nine (7%) patients had TRAEs leading to discontinuation of tovorafenib. These data indicate that tovorafenib could be an effective therapy for BRAF-altered, relapsed/refractory pLGG. ClinicalTrials.gov registration: NCT04775485

Multi-sensor spectral synergies for crop stress detection and monitoring in the optical domain: A review

Remote detection and monitoring of the vegetation responses to stress became relevant for sustainable agriculture. Ongoing developments in optical remote sensing technologies have provided tools to increase our understanding of stress-related physiological processes. Therefore, this study aimed to provide an overview of the main spectral technologies and retrieval approaches for detecting crop stress in agriculture. Firstly, we present integrated views on: i) biotic and abiotic stress factors, the phases of stress, and respective plant responses, and ii) the affected traits, appropriate spectral domains and corresponding methods for measuring traits remotely. Secondly, representative results of a systematic literature analysis are highlighted, identifying the current status and possible future trends in stress detection and monitoring. Distinct plant responses occurring under short-term, medium-term or severe chronic stress exposure can be captured with remote sensing due to specific light interaction processes, such as absorption and scattering manifested in the reflected radiance, i.e. visible (VIS), near infrared (NIR), shortwave infrared, and emitted radiance, i.e. solar-induced fluorescence and thermal infrared (TIR). From the analysis of 96 research papers, the following trends can be observed: increasing usage of satellite and unmanned aerial vehicle data in parallel with a shift in methods from simpler parametric approaches towards more advanced physically-based and hybrid models. Most study designs were largely driven by sensor availability and practical economic reasons, leading to the common usage of VIS-NIR-TIR sensor combinations. The majority of reviewed studies compared stress proxies calculated from single-source sensor domains rather than using data in a synergistic way. We identified new ways forward as guidance for improved synergistic usage of spectral domains for stress detection: (1) combined acquisition of data from multiple sensors for analysing multiple stress responses simultaneously (holistic view); (2) simultaneous retrieval of plant traits combining multi-domain radiative transfer models and machine learning methods; (3) assimilation of estimated plant traits from distinct spectral domains into integrated crop growth models. As a future outlook, we recommend combining multiple remote sensing data streams into crop model assimilation schemes to build up Digital Twins of agroecosystems, which may provide the most efficient way to detect the diversity of environmental and biotic stresses and thus enable respective management decisions

Imports and isotopes: a modern baseline study for interpreting Iron Age and Roman trade in fallow deer antlers

The European Fallow deer (Dama dama dama) became extinct in the British Isles and most of continental Europe at the time of the Last Glacial Maximum, with the species becoming restricted to an Anatolian refugium (Masseti et al. 2008). Human-mediated reintroductions resulted in fallow populations in Rhodes, Sicily, Mallorca, Iberia and other parts of western Europe (Sykes et al. 2013). Eventually, the species was brought to Britain by the Romans during the 1st century AD, with a breeding population being established at Fishbourne Roman Palace (Sykes et al. 2011). The human influence on the present-day distribution of the species makes it particularly interesting from a zooarchaeological perspective. This paper describes my MSc research, as part of the AHRC-funded project Dama International: Fallow Deer and European Society 6000 BC–AD 1600, looking at antlers from Iron Age and Roman sites in Britain for evidence of trade in body parts and whether this can be elucidated by a parallel stable isotope study of modern fallow antlers of known provenance

Decision support system for the management of water distribution networks a case study of Tourville, Algeria

The analysis of the current situation of water distribution networks (WDNs) is based on many alternatives that are technically feasible and implemented by decision makers. Taking the WDN of Tourville city as a case study, this paper combines a set of decision support systems (DSSs), including geographic information systems (GISs), multicriteria analysis and hydraulic simulation models, to establish a multicriteria decision-making aid method for the renovation and rehabilitation of water distribution networks. This combination creates an expert management system based on multicriteria decision making that strengthens the optimization of the management of water distribution networks in terms of renovation and rehabilitation. After dividing the water distribution network into three emergency levels, it was concluded that 26% of the network is in urgent need of rehabilitation

Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus

Aurora A kinase (AURKA) is a major regulator of mitosis and an important driver of cancer progression. The roles of AURKA outside of mitosis, and how these might contribute to cancer progression, are not well understood. Here, we show that a fraction of cytoplasmic AURKA is associated with mitochondria, co-fractionating in cell extracts and interacting with mitochondrial proteins by reciprocal co-immunoprecipitation. We have also found that the dynamics of the mitochondrial network are sensitive to AURKA inhibition, depletion or overexpression. This can account for the different mitochondrial morphologies observed in RPE-1 and U2OS cell lines, which show very different levels of expression of AURKA. We identify the mitochondrial fraction of AURKA as influencing mitochondrial morphology, because an N-terminally truncated version of the kinase that does not localize to mitochondria does not affect the mitochondrial network. We identify a cryptic mitochondrial targeting sequence in the AURKA N-terminus and discuss how alternative conformations of the protein may influence its cytoplasmic fate

Platinum degradation mechanisms in proton exchange membrane fuel cell (PEMFC) system: A review

Proton Exchange Membrane Fuel Cells (PEMFCs) have the perspective to intensely decrease global emission through environmentally-friendly potential. This review paper summarizes the degradation of platinum catalyst layer that has become a significant issue in the improvement of PEMFCs. The review intends to categorise and provide a clear understanding between disintegration and agglomerate that occurs during platinum degradation. In each process, different degradation mechanisms and their migration processes are presented. The improvement in platinum degradation as a function of increasing the performance of PEMFC is established. Prospects for addressing platinum degradation through the exploration of further experimental and numerical research are recommended. Lastly, this paper through recommendation attempts to prevent platinum degradation and reduces high costs associated with the replacement of catalysts in the PEMFCs