A ‘Mouth-feel Wheel’: terminology for communicating the mouth-feel characteristics of red wine

Abstract A hierarchically structured vocabulary of mouth-feel sensations elicited by red wines has been produced. Represented as a wheel, this structured vocabulary should assist tasters in their interpretation and use of terminology relating to 'in mouth' sensations produced by red wines. These terms and their definitions were generated by consulting the opinions of experienced wine tasters following exposure to an extensive range of commercial red wines. Logical relationships among the derived terms were formulated by analysis of 'sorting data' provided by a combined group of experienced winemakers and wine-tasters

3D multi-robot patrolling with a two-level coordination strategy

Teams of UGVs patrolling harsh and complex 3D environments can experience interference and spatial conflicts with one another. Neglecting the occurrence of these events crucially hinders both soundness and reliability of a patrolling process. This work presents a distributed multi-robot patrolling technique, which uses a two-level coordination strategy to minimize and explicitly manage the occurrence of conflicts and interference. The first level guides the agents to single out exclusive target nodes on a topological map. This target selection relies on a shared idleness representation and a coordination mechanism preventing topological conflicts. The second level hosts coordination strategies based on a metric representation of space and is supported by a 3D SLAM system. Here, each robot path planner negotiates spatial conflicts by applying a multi-robot traversability function. Continuous interactions between these two levels ensure coordination and conflicts resolution. Both simulations and real-world experiments are presented to validate the performances of the proposed patrolling strategy in 3D environments. Results show this is a promising solution for managing spatial conflicts and preventing deadlocks

Selective superoxide generation within mitochondria by the targeted redox cycler MitoParaquat

Superoxide is the proximal reactive oxygen species (ROS) produced by the mitochondrial respiratory chain and plays a major role in pathological oxidative stress and redox signaling. While there are tools to detect or decrease mitochondrial superoxide, none can rapidly and specifically increase superoxide production within the mitochondrial matrix. This lack impedes progress, making it challenging to assess accurately the roles of mitochondrial superoxide in cells and in vivo. To address this unmet need, we synthesized and characterized a mitochondria-targeted redox cycler, MitoParaquat (MitoPQ) that comprises a triphenylphosphonium lipophilic cation conjugated to the redox cycler paraquat. MitoPQ accumulates selectively in the mitochondrial matrix driven by the membrane potential. Within the matrix, MitoPQ produces superoxide by redox cycling at the flavin site of complex I, selectively increasing superoxide production within mitochondria. MitoPQ increased mitochondrial superoxide in isolated mitochondria and cells in culture ~a thousand-fold more effectively than untargeted paraquat. MitoPQ was also more toxic than paraquat in the isolated perfused heart and in Drosophila in vivo. MitoPQ enables the selective generation of superoxide within mitochondria and is a useful tool to investigate the many roles of mitochondrial superoxide in pathology and redox signaling in cells and in vivo

Identification and Characterization of AES-135, a Hydroxamic Acid-Based HDAC Inhibitor That Prolongs Survival in an Orthotopic Mouse Model of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, incurable cancer with a 20% 1 year survival rate. While standard-of-care therapy can prolong life in a small fraction of cases, PDAC is inherently resistant to current treatments, and novel therapies are urgently required. Histone deacetylase (HDAC) inhibitors are effective in killing pancreatic cancer cells in in vitro PDAC studies, and although there are a few clinical studies investigating combination therapy including HDAC inhibitors, no HDAC drug or combination therapy with an HDAC drug has been approved for the treatment of PDAC. We developed an inhibitor of HDACs, AES-135, that exhibits nanomolar inhibitory activity against HDAC3, HDAC6, and HDAC11 in biochemical assays. In a three-dimensional coculture model, AES-135 kills low-passage patient-derived tumor spheroids selectively over surrounding cancer-associated fibroblasts and has excellent pharmacokinetic properties in vivo. In an orthotopic murine model of pancreatic cancer, AES-135 prolongs survival significantly, therefore representing a candidate for further preclinical testing

Zebrafish as a robust preclinical platform for screening plant-derived drugs with anticonvulsant properties—a review

Traditionally, selected plant sources have been explored for medicines to treat convulsions. This continues today, especially in countries with low-income rates and poor medical systems. However, in the low-income countries, plant extracts and isolated drugs are in high demand due to their good safety profiles. Preclinical studies on animal models of seizures/epilepsy have revealed the anticonvulsant and/or antiepileptogenic properties of, at least some, herb preparations or plant metabolites. Still, there is a significant number of plants known in traditional medicine that exert anticonvulsant activity but have not been evaluated on animal models. Zebrafish is recognized as a suitable in vivo model of epilepsy research and is increasingly used as a screening platform. In this review, the results of selected preclinical studies are summarized to provide credible information for the future development of effective screening methods for plant-derived antiseizure/antiepileptic therapeutics using zebrafish models. We compared zebrafish vs. rodent data to show the translational value of the former in epilepsy research. We also surveyed caveats in methodology. Finally, we proposed a pipeline for screening new anticonvulsant plant-derived drugs in zebrafish (“from tank to bedside and back again”)

Community-based in situ simulation: bringing simulation to the masses

Simulation-based methods are regularly used to train inter-professional groups of healthcare providers at academic medical centers (AMC). These techniques are used less frequently in community hospitals. Bringing in-situ simulation (ISS) from AMCs to community sites is an approach that holds promise for addressing this disparity. This type of programming allows academic center faculty to freely share their expertise with community site providers. By creating meaningful partnerships community-based ISS facilitates the communication of best practices, distribution of up to date policies, and education/training. It also provides an opportunity for system testing at the community sites. In this article, we illustrate the process of implementing an outreach ISS program at community sites by presenting four exemplar programs. Using these exemplars as a springboard for discussion, we outline key lessons learned discuss barriers we encountered, and provide a framework that can be used to create similar simulation programs and partnerships. It is our hope that this discussion will serve as a foundation for those wishing to implement community-based, outreach ISS

Escherichia coli Frameshift Mutation Rate Depends on the Chromosomal Context but Not on the GATC Content Near the Mutation Site

Different studies have suggested that mutation rate varies at different positions in the genome. In this work we analyzed if the chromosomal context and/or the presence of GATC sites can affect the frameshift mutation rate in the Escherichia coli genome. We show that in a mismatch repair deficient background, a condition where the mutation rate reflects the fidelity of the DNA polymerization process, the frameshift mutation rate could vary up to four times among different chromosomal contexts. Furthermore, the mismatch repair efficiency could vary up to eight times when compared at different chromosomal locations, indicating that detection and/or repair of frameshift events also depends on the chromosomal context. Also, GATC sequences have been proved to be essential for the correct functioning of the E. coli mismatch repair system. Using bacteriophage heteroduplexes molecules it has been shown that GATC influence the mismatch repair efficiency in a distance- and number-dependent manner, being almost nonfunctional when GATC sequences are located at 1 kb or more from the mutation site. Interestingly, we found that in E. coli genomic DNA the mismatch repair system can efficiently function even if the nearest GATC sequence is located more than 2 kb away from the mutation site. The results presented in this work show that even though frameshift mutations can be efficiently generated and/or repaired anywhere in the genome, these processes can be modulated by the chromosomal context that surrounds the mutation site