Drug Delivery Micropump with Built-In Monitoring

AbstractWe report on the fabrication of the first MEMS micropump including an integrated pressure sensor. The signal of this sensor allows direct insight into the pump's operating dynamics and enables real-time self-monitoring. We demonstrate the changes in the sensor signal under different pumping conditions, including the presence of air in the pumping chamber and a downstream occlusions. Deviations from normal operating conditions create clear and characteristic deviations from the normal signal. These deviations will be exploited to detect extraordinary or faulty pumping conditions during use

Preclinical testing of an oncolytic parvovirus in Ewing sarcoma : protoparvovirus H-1 induces apoptosis and lytic infection in vitro but fails to improve survival in vivo

About 70% of all Ewing sarcoma (EWS) patients are diagnosed under the age of 20 years. Over the last decades little progress has been made towards finding effective treatment approaches for primarily metastasized or refractory Ewing sarcoma in young patients. Here, in the context of the search for novel therapeutic options, the potential of oncolytic protoparvovirus H-1 (H-1PV) to treat Ewing sarcoma was evaluated, its safety having been proven previously tested in adult cancer patients and its oncolytic efficacy demonstrated on osteosarcoma cell cultures. The effects of viral infection were tested in vitro on four human Ewing sarcoma cell lines. Notably evaluated were effects of the virus on the cell cycle and its replication efficiency. Within 24 h after infection, the synthesis of viral proteins was induced. Efficient H-1PV replication was confirmed in all four Ewing sarcoma cell lines. The cytotoxicity of the virus was determined on the basis of cytopathic effects, cell viability, and cell lysis. These in vitro experiments revealed efficient killing of Ewing sarcoma cells by H-1PV at a multiplicity of infection between 0.1 and 5 plaque forming units (PFU)/cell. In two of the four tested cell lines, significant induction of apoptosis by H-1PV was observed. H-1PV thus meets all the in vitro criteria for a virus to be oncolytic towards Ewing sarcoma. In the first xenograft experiments, however, although an antiproliferative effect of intratumoral H-1PV injection was observed, no significant improvement of animal survival was noted. Future projects aiming to validate parvovirotherapy for the treatment of pediatric Ewing sarcoma should focus on combinatorial treatments and will require the use of patient-derived xenografts and immunocompetent syngeneic animal models

Energy or information? The role of seed availability for reproductive decisions in edible dormice

The edible dormouse is a specialized seed predator which is highly adapted to the fluctuations of food availability caused by mast seeding of beech and oak trees. Dormice produce young just in time with maximum food availability, and can completely skip reproduction in years with a lack of seeding. Because their decision to reproduce or not in any particular year is made long before the ripe seeds are available, it seems that dormice can anticipate the upcoming mast situation. We tested the hypothesis that the presence of high caloric food in spring affects their reproductive decision. Therefore, we supplementary fed dormice in a field experiment from spring to early summer with sunflower seeds, which also contain a high amount of energy. Supplemental feeding caused significant increases in the proportion of reproducing females and reproductively active males. These results suggest that edible dormice may use the occurrence of an energy rich food resource to predict the autumnal mast situation. Further, our data indicate that the decision to reproduce was not the result of an increased body mass due to the consumption of surplus food, but that sufficient seed abundance acts as an environmental signal to which dormice adjust their reproduction

Earth System Model Evaluation Tool (ESMValTool) v2.0 - An extended set of large-scale diagnostics for quasi-operational and comprehensive evaluation of Earth system models in CMIP

The Earth System Model Evaluation Tool (ESMValTool) is a community diagnostics and performance metrics tool designed to improve comprehensive and routine evaluation of Earth system models (ESMs) participating in the Coupled Model Intercomparison Project (CMIP). It has undergone rapid development since the first release in 2016 and is now a well-tested tool that provides end-to-end provenance tracking to ensure reproducibility. It consists of (1) an easy-to-install, well-documented Python package providing the core functionalities (ESMValCore) that performs common preprocessing operations and (2) a diagnostic part that includes tailored diagnostics and performance metrics for specific scientific applications. Here we describe large-scale diagnostics of the second major release of the tool that supports the evaluation of ESMs participating in CMIP Phase 6 (CMIP6). ESMValTool v2.0 includes a large collection of diagnostics and performance metrics for atmospheric, oceanic, and terrestrial variables for the mean state, trends, and variability. ESMValTool v2.0 also successfully reproduces figures from the evaluation and projections chapters of the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5) and incorporates updates from targeted analysis packages, such as the NCAR Climate Variability Diagnostics Package for the evaluation of modes of variability, the Thermodynamic Diagnostic Tool (TheDiaTo) to evaluate the energetics of the climate system, as well as parts of AutoAssess that contains a mix of top-down performance metrics. The tool has been fully integrated into the Earth System Grid Federation (ESGF) infrastructure at the Deutsches Klimarechenzentrum (DKRZ) to provide evaluation results from CMIP6 model simulations shortly after the output is published to the CMIP archive. A result browser has been implemented that enables advanced monitoring of the evaluation results by a broad user community at much faster timescales than what was possible in CMIP5

Verbal instructions override the meaning of facial expressions

Psychological research has long acknowledged that facial expressions can implicitly trigger affective psychophysiological responses. However, whether verbal information can alter the meaning of facial emotions and corresponding response patterns has not been tested. This study examined emotional facial expressions as cues for instructed threat-of-shock or safety, with a focus on defensive responding. In addition, reversal instructions were introduced to test the impact of explicit safety instructions on fear extinction. Forty participants were instructed that they would receive unpleasant electric shocks, for instance, when viewing happy but not angry faces. In a second block, instructions were reversed (e.g., now angry faces cued shock). Happy, neutral, and angry faces were repeatedly presented, and auditory startle probes were delivered in half of the trials. The defensive startle reflex was potentiated for threat compared to safety cues. Importantly, this effect occurred regardless of whether threat was cued by happy or angry expressions. Although the typical pattern of response habituation was observed, defense activation to newly instructed threat cues remained significantly enhanced in the second part of the experiment, and it was more pronounced in more socially anxious participants. Thus, anxious individuals did not exhibit more pronounced defense activation compared to less anxious participants, but their defense activation was more persistent

Pantropical variability in tree crown allometry

Aim: Tree crowns determine light interception, carbon and water exchange. Thus, understanding the factors causing tree crown allometry to vary at the tree and stand level matters greatly for the development of future vegetation modelling and for the calibration of remote sensing products. Nevertheless, we know little about large‐scale variation and determinants in tropical tree crown allometry. In this study, we explored the continental variation in scaling exponents of site‐specific crown allometry and assessed their relationships with environmental and stand‐level variables in the tropics. / Location: Global tropics. / Time period: Early 21st century. / Major taxa studied: Woody plants. / Methods: Using a dataset of 87,737 trees distributed among 245 forest and savanna sites across the tropics, we fitted site‐specific allometric relationships between crown dimensions (crown depth, diameter and volume) and stem diameter using power‐law models. Stand‐level and environmental drivers of crown allometric relationships were assessed at pantropical and continental scales. / Results: The scaling exponents of allometric relationships between stem diameter and crown dimensions were higher in savannas than in forests. We identified that continental crown models were better than pantropical crown models and that continental differences in crown allometric relationships were driven by both stand‐level (wood density) and environmental (precipitation, cation exchange capacity and soil texture) variables for both tropical biomes. For a given diameter, forest trees from Asia and savanna trees from Australia had smaller crown dimensions than trees in Africa and America, with crown volumes for some Asian forest trees being smaller than those of trees in African forests. / Main conclusions: Our results provide new insight into geographical variability, with large continental differences in tropical tree crown allometry that were driven by stand‐level and environmental variables. They have implications for the assessment of ecosystem function and for the monitoring of woody biomass by remote sensing techniques in the global tropics

Related to Anxiety: Arbitrarily Applicable Relational Responding and Experimental Psychopathology Research on Fear and Avoidance

Humans have an unparalleled ability to engage in arbitrarily applicable relational responding (AARR). One of the consequences of this ability to spontaneously combine and relate events from the past, present, and future may, in fact, be a propensity to suffer. For instance, maladaptive fear and avoidance of remote or derived threats may actually perpetuate anxiety. In this narrative review, we consider contemporary AARR research on fear and avoidance as it relates to anxiety. We first describe laboratory-based research on the emergent spread of fear- and avoidance-eliciting functions in humans. Next, we consider the validity of AARR research on fear and avoidance and address the therapeutic implications of the work. Finally, we outline challenges and opportunities for a greater synthesis between behavior analysis research on AARR and experimental psychopathology

Pantropical variability in tree crown allometry

Aim Tree crowns determine light interception, carbon and water exchange. Thus, understanding the factors causing tree crown allometry to vary at the tree and stand level matters greatly for the development of future vegetation modelling and for the calibration of remote sensing products. Nevertheless, we know little about large‐scale variation and determinants in tropical tree crown allometry. In this study, we explored the continental variation in scaling exponents of site‐specific crown allometry and assessed their relationships with environmental and stand‐level variables in the tropics. Location Global tropics. Time period Early 21st century. Major taxa studied Woody plants. Methods Using a dataset of 87,737 trees distributed among 245 forest and savanna sites across the tropics, we fitted site‐specific allometric relationships between crown dimensions (crown depth, diameter and volume) and stem diameter using power‐law models. Stand‐level and environmental drivers of crown allometric relationships were assessed at pantropical and continental scales. Results The scaling exponents of allometric relationships between stem diameter and crown dimensions were higher in savannas than in forests. We identified that continental crown models were better than pantropical crown models and that continental differences in crown allometric relationships were driven by both stand‐level (wood density) and environmental (precipitation, cation exchange capacity and soil texture) variables for both tropical biomes. For a given diameter, forest trees from Asia and savanna trees from Australia had smaller crown dimensions than trees in Africa and America, with crown volumes for some Asian forest trees being smaller than those of trees in African forests. Main conclusions Our results provide new insight into geographical variability, with large continental differences in tropical tree crown allometry that were driven by stand‐level and environmental variables. They have implications for the assessment of ecosystem function and for the monitoring of woody biomass by remote sensing techniques in the global tropics

Tallo: A global tree allometry and crown architecture database.

This is the final version. Available from Wiley via the DOI in this record. Data capturing multiple axes of tree size and shape, such as a tree's stem diameter, height and crown size, underpin a wide range of ecological research-from developing and testing theory on forest structure and dynamics, to estimating forest carbon stocks and their uncertainties, and integrating remote sensing imagery into forest monitoring programmes. However, these data can be surprisingly hard to come by, particularly for certain regions of the world and for specific taxonomic groups, posing a real barrier to progress in these fields. To overcome this challenge, we developed the Tallo database, a collection of 498,838 georeferenced and taxonomically standardized records of individual trees for which stem diameter, height and/or crown radius have been measured. These data were collected at 61,856 globally distributed sites, spanning all major forested and non-forested biomes. The majority of trees in the database are identified to species (88%), and collectively Tallo includes data for 5163 species distributed across 1453 genera and 187 plant families. The database is publicly archived under a CC-BY 4.0 licence and can be access from: https://doi.org/10.5281/zenodo.6637599. To demonstrate its value, here we present three case studies that highlight how the Tallo database can be used to address a range of theoretical and applied questions in ecology-from testing the predictions of metabolic scaling theory, to exploring the limits of tree allometric plasticity along environmental gradients and modelling global variation in maximum attainable tree height. In doing so, we provide a key resource for field ecologists, remote sensing researchers and the modelling community working together to better understand the role that trees play in regulating the terrestrial carbon cycle.Natural Environment Research Council (NERC)Natural Environment Research Council (NERC); Ministry of Education, Youth and Sports of the Czech RepublicFAPEMIGUniversidad Nacional Autónoma de MéxicoUniversidad Nacional Autónoma de MéxicoConsejo Nacional de Ciencia y TecnologíaSwedish Energy AgencyUKRIFederal Ministry of Education and ResearchNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Science FoundationNational Science FoundationInternational Foundation for ScienceP3FACDynAfForNanjing Forestry UniversityJiangsu Science and Technology Special ProjectHebei UniversityAgence Nationale de la RechercheAgence Nationale de la RechercheAgua Salud ProjectU.S. Department of EnergyCAPE