Chaperoning junior faculty: Institutional support and guidance can relieve challenges for early-career group leaders and imporove academic performance

The initial excitement of finally leading an independent research group is quickly followed by the realization that it comes with novel challenges. The first day as a principal investigator sets the clock ticking on limited time and opportunities to publish and apply for grants and awards that all are required for tenure or the next job. Expectations are high: PIs must be outstanding scholars who establish their own research program, excel in teaching, and are helpful colleagues and mentors for their students and postdocs. Meeting such high expectations with little experience can cause anxiety and stress. Moreover, we are often our own worst critics; meeting high self‐expectations can be demanding even without external pressure. Based on our experiences as junior faculty, we herewith suggest a set of measures that could help early‐career group leaders to better handle this stress and allow them—and their host institutes—to flourish

Prototipo de sistema inteligente basado en patrones de ondas cerebrales para prevenir accidentes de tránsito

This article presents the prototype of an intelligent system based on patterns of brain waves to prevent traffic accidents,by which, through a sensor, placed on the driver's head, monitors the patterns of brain waves that are sent in real time via Bluetoothto a Raspberry Pi to be processed with machine learning strategies. In this way it allows to send a visual and sound warning when itdetects the state of drowsiness in the driver. For the prototype construction, data of four people were collected while they were awake,drowsy and asleep. The data set was processed with four supervised learning algorithms: nearest neighbors, support vector machine,decision trees and random forests; the last one was the one that obtained the best result, reaching 82.05% accuracy whendifferentiating the three different states. The estimated cost of the system is 210 USD, resulting an economic system in relation toothers existing in the market.Este artículo presenta el prototipo de sistema inteligente basado en patrones de ondas cerebrales para prevenir accidentesde tránsito, que, mediante un sensor colocado en la cabeza del conductor, monitoriza los patrones de ondas cerebrales los cuales sonenviados en tiempo real vía Bluetooth a una placa Raspberry Pi para ser procesados con estrategias de aprendizaje automático y deesta forma enviar una alerta visual y sonora cuando detecta el estado de somnolencia en el conductor. Para la construcción delprototipo se recogieron datos de cuatro personas en tres estados distintos, mientras estaban despiertas, somnolientas y dormidas. Elconjunto de datos fue procesado con cuatro algoritmos de aprendizaje supervisado: vecinos más cercanos, máquina de soportevectorial, árboles de decisión, bosques aleatorios; siendo este último el que mejores resultados mostró alcanzando un 82.05% deprecisión al diferenciar los tres estados anteriormente mencionados. El costo estimado del sistema es de 210 USD, resultando unsistema económico con relación a otros existentes en el mercado

Prototipo de mano robótica controlada mediante el procesamiento de señales cerebrales utilizando redes neuronales recurrentes

The mapping of electrical activity in the human brain is not only useful in the medical field for the diagnosis of diseases but can also be of great help in other fields such as computer science. This research proposes the use of brain signals as a control mechanism using artificial intelligence techniques. Its main objective is to build a prototype of a 3D printed robotic hand prosthesis monitored through the processing of brain signals using recurrent neural networks. Three different recurrent network architectures were trained and compared using a prototyping methodology (Simple RNN, LSTM, and GRU). This prototyping methodology was trained using a sample size of thirteen people and the non-invasive sensor Mindwave Mobile 2 was used to record the data. The first version, which was in development approximately 3 months, achieved 77% accuracy in classifying new samples using the GRU network model. With further research and development, this prototype may prove very useful in the future for providing people in need of such technology with a higher quality of life.Las señales generadas por la actividad eléctrica producida en el cerebro humano, además de ser utilizadas en el área de medicina para el diagnóstico de enfermedades, pueden ser de gran ayuda en otros campos, como lo son las ciencias computacionales. Esta investigación propone la utilización de señales cerebrales como mecanismo de control, empleando técnicas de inteligencia artificial. La misma tiene como objetivo principal construir un prototipo de una prótesis de mano robótica impresa en 3D, controlada a través del procesamiento de señales cerebrales, utilizando redes neuronales recurrentes. Mediante una metodología de prototipado se entrenaron y compararon tres arquitecturas distintas de redes recurrentes (RNN simple, LSTM y GRU), entrenadas a partir de datos de trece personas, utilizando el sensor no invasivo Mindwave Mobile 2 para la adquisición de estos. La primera versión, desarrollada en un periodo aproximado de tres meses, alcanzó una precisión del 77% al clasificar nuevas muestras utilizando el modelo de red GRU. Este prototipo, al ser una primera aproximación y requerir mayor tiempo de investigación y desarrollo, puede ser de gran utilidad a futuro para personas que así lo necesiten, brindándoles una mayor calidad de vida

Personalizing dental screening and prevention protocols in dentulous patients with oropharyngeal cancer undergoing radiotherapy:A retrospective cohort study

Objectives:Patients with head and neck cancer are routinely screened for dental foci prior to radiotherapy (RT) to prevent post- RT tooth extractions associated with an increased risk of osteoradionecrosis. We evaluated the risk factors for post-RT tooth extraction to personalise dental screening and prevention protocols prior to RT. Materials and methods: This retrospective cohort study included dentulous patients diagnosed with oropharyngeal cancer who had undergone radiation therapy at doses 60–70 Gy and achieved a disease-free survival of ≥ 1 year (N = 174). Risk factors were assessed using Cox regression models. Results: The cumulative incidence of post-RT tooth extraction was 30.7 % at 5 years. Main indications for extraction (n = 62) were radiation caries (n = 20) and periodontal disease (n = 27). Risk factors associated (p &lt; 0.05) with radiation caries-related extractions included active smoking, alcohol abuse, poor oral hygiene, parotid gland irradiation, and mandibular irradiation. A high-dose volume in the mandible was associated with periodontal disease events. Conclusion: Post-RT extractions due to radiation caries were influenced by lifestyle factors and RT dose in the mandible and parotid glands. Periodontal disease-related extractions were primarily associated with the mandibular dose. During dental screening these post-RT risk factors should be taken into account to prevent osteoradionecrosis.</p

Insect Cells for High-Yield Production of SARS-CoV-2 Spike Protein: Building a Virosome-Based COVID-19 Vaccine Candidate.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) homotrimeric spike (S) protein is responsible for mediating host cell entry by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, thus being a key viral antigen to target in a coronavirus disease 19 (COVID-19) vaccine. Despite the availability of COVID-19 vaccines, low vaccine coverage as well as unvaccinated and immune compromised subjects are contributing to the emergence of SARS-CoV-2 variants of concern. Therefore, continued development of novel and/or updated vaccines is essential for protecting against such new variants. In this study, we developed a scalable bioprocess using the insect cells-baculovirus expression vector system (IC-BEVS) to produce high-quality S protein, stabilized in its pre-fusion conformation, for inclusion in a virosome-based COVID-19 vaccine candidate. By exploring different bioprocess engineering strategies (i.e., signal peptides, baculovirus transfer vectors, cell lines, infection strategies and formulation buffers), we were able to obtain ~4 mg/L of purified S protein, which, to the best of our knowledge, is the highest value achieved to date using insect cells. In addition, the insect cell-derived S protein exhibited glycan processing similar to mammalian cells and mid-term stability upon storage (up to 90 days at -80 and 4 °C or after 5 freeze-thaw cycles). Noteworthy, antigenicity of S protein, either as single antigen or displayed on the surface of virosomes, was confirmed by ELISA, with binding of ACE2 receptor, pan-SARS antibody CR3022 and neutralizing antibodies to the various epitope clusters on the S protein. Binding capacity was also maintained on virosomes-S stored at 4 °C for 1 month. This work demonstrates the potential of using IC-BEVS to produce the highly glycosylated and complex S protein, without compromising its integrity and antigenicity, to be included in a virosome-based COVID-19 vaccine candidate

Initial activation of EpCAM cleavage via cell-to-cell contact

<p>Abstract</p> <p>Background</p> <p>Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein, which is frequently over-expressed in simple epithelia, progenitors, embryonic and tissue stem cells, carcinoma and cancer-initiating cells. Besides functioning as a homophilic adhesion protein, EpCAM is an oncogenic receptor that requires regulated intramembrane proteolysis for activation of its signal transduction capacity. Upon cleavage, the extracellular domain EpEX is released as a soluble ligand while the intracellular domain EpICD translocates into the cytoplasm and eventually into the nucleus in combination with four-and-a-half LIM domains protein 2 (FHL2) and β-catenin, and drives cell proliferation.</p> <p>Methods</p> <p>EpCAM cleavage, induction of the target genes, and transmission of proliferation signals were investigated under varying density conditions using confocal laser scanning microscopy, immunoblotting, cell counting, and conditional cell systems.</p> <p>Results</p> <p>EpCAM cleavage, induction of the target genes, and transmission of proliferation signals were dependent on adequate cell-to-cell contact. If cell-to-cell contact was prohibited EpCAM did not provide growth advantages. If cells were allowed to undergo contact to each other, EpCAM transmitted proliferation signals based on signal transduction-related cleavage processes. Accordingly, the pre-cleaved version EpICD was not dependent on cell-to-cell contact in order to induce <it>c-myc </it>and cell proliferation, but necessitated nuclear translocation. For the case of contact-inhibited cells, although cleavage of EpCAM occurred, nuclear translocation of EpICD was reduced, as were EpCAM effects.</p> <p>Conclusion</p> <p>Activation of EpCAM's cleavage and oncogenic capacity is dependent on cellular interaction (juxtacrine) to provide for initial signals of regulated intramembrane proteolysis, which then support signalling via soluble EpEX (paracrine).</p

Time Delay Lens Modelling Challenge

In recent years, breakthroughs in methods and data have enabled gravitational time delays to emerge as a very powerful tool to measure the Hubble constant $H_0$. However, published state-of-the-art analyses require of order 1 year of expert investigator time and up to a million hours of computing time per system. Furthermore, as precision improves, it is crucial to identify and mitigate systematic uncertainties. With this time delay lens modelling challenge we aim to assess the level of precision and accuracy of the modelling techniques that are currently fast enough to handle of order 50 lenses, via the blind analysis of simulated datasets. The results in Rung 1 and Rung 2 show that methods that use only the point source positions tend to have lower precision ($10 - 20\%$) while remaining accurate. In Rung 2, the methods that exploit the full information of the imaging and kinematic datasets can recover $H_0$ within the target accuracy ($|A| < 2\%$) and precision ($< 6\%$ per system), even in the presence of poorly known point spread function and complex source morphology. A post-unblinding analysis of Rung 3 showed the numerical precision of the ray-traced cosmological simulations to be insufficient to test lens modelling methodology at the percent level, making the results difficult to interpret. A new challenge with improved simulations is needed to make further progress in the investigation of systematic uncertainties. For completeness, we present the Rung 3 results in an appendix, and use them to discuss various approaches to mitigating against similar subtle data generation effects in future blind challenges.Comment: 23 pages, 12 figures, 6 tables, MNRAS accepte

Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer

The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested in parallel at three sites, and all results are published. We report the effects of lifelong treatment of mice with four agents not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and metformin – the latter with and without rapamycin, and two drugs previously examined: 17-α-estradiol and nordihydroguaiaretic acid (NDGA), at doses greater and less than used previously. 17-α-estradiol at a threefold higher dose robustly extended both median and maximal lifespan, but still only in males. The male-specific extension of median lifespan by NDGA was replicated at the original dose, and using doses threefold lower and higher. The effects of NDGA were dose dependent and male specific but without an effect on maximal lifespan. Protandim, a mixture of botanical extracts that activate Nrf2, extended median lifespan in males only. Metformin alone, at a dose of 0.1% in the diet, did not significantly extend lifespan. Metformin (0.1%) combined with rapamycin (14 ppm) robustly extended lifespan, suggestive of an added benefit, based on historical comparison with earlier studies of rapamycin given alone. The α-glucosidase inhibitor, acarbose, at a concentration previously tested (1000 ppm), significantly increased median longevity in males and 90th percentile lifespan in both sexes, even when treatment was started at 16 months. Neither fish oil nor UDCA extended lifespan. These results underscore the reproducibility of ITP longevity studies and illustrate the importance of identifying optimal doses in lifespan studies