Space biology initiative program definition review. Trade study 1: Automation costs versus crew utilization

A significant emphasis upon automation within the Space Biology Initiative hardware appears justified in order to conserve crew labor and crew training effort. Two generic forms of automation were identified: automation of data and information handling and decision making, and the automation of material handling, transfer, and processing. The use of automatic data acquisition, expert systems, robots, and machine vision will increase the volume of experiments and quality of results. The automation described may also influence efforts to miniaturize and modularize the large array of SBI hardware identified to date. The cost and benefit model developed appears to be a useful guideline for SBI equipment specifiers and designers. Additional refinements would enhance the validity of the model. Two NASA automation pilot programs, 'The Principal Investigator in a Box' and 'Rack Mounted Robots' were investigated and found to be quite appropriate for adaptation to the SBI program. There are other in-house NASA efforts that provide technology that may be appropriate for the SBI program. Important data is believed to exist in advanced medical labs throughout the U.S., Japan, and Europe. The information and data processing in medical analysis equipment is highly automated and future trends reveal continued progress in this area. However, automation of material handling and processing has progressed in a limited manner because the medical labs are not affected by the power and space constraints that Space Station medical equipment is faced with. Therefore, NASA's major emphasis in automation will require a lead effort in the automation of material handling to achieve optimal crew utilization

Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability

Epilepsy is the most common neurological disorder, with over 50 million people worldwide affected. Recent evidence suggests that the transient receptor potential cation channel subfamily V member 1 (TRPV1) may contribute to the onset and progression of some forms of epilepsy. Since the two nonpsychotropic cannabinoids cannabidivarin (CBDV) and cannabidiol (CBD) exert anticonvulsant activity in vivo and produce TRPV1-mediated intracellular calcium elevation in vitro, we evaluated the effects of these two compounds on TRPV1 channel activation and desensitization and in an in vitro model of epileptiform activity. Patch clamp analysis in transfected HEK293 cells demonstrated that CBD and CBDV dose-dependently activate and rapidly desensitize TRPV1, as well as TRP channels of subfamily V type 2 (TRPV2) and subfamily A type 1 (TRPA1). TRPV1 and TRPV2 transcripts were shown to be expressed in rat hippocampal tissue. When tested on epileptiform neuronal spike activity in hippocampal brain slices exposed to a Mg2+-free solution using multielectrode arrays (MEAs), CBDV reduced both epileptiform burst amplitude and duration. The prototypical TRPV1 agonist, capsaicin, produced similar, although not identical effects. Capsaicin, but not CBDV, effects on burst amplitude were reversed by IRTX, a selective TRPV1 antagonist. These data suggest that CBDV antiepileptiform effects in the Mg2+-free model are not uniquely mediated via activation of TRPV1. However, TRPV1 was strongly phosphorylated (and hence likely sensitized) in Mg2+-free solution-treated hippocampal tissue, and both capsaicin and CBDV caused TRPV1 dephosphorylation, consistent with TRPV1 desensitization. We propose that CBDV effects on TRP channels should be studied further in different in vitro and in vivo models of epilepsy

Remote heart rate monitoring - Assessment of the Facereader rPPg by Noldus

Remote photoplethysmography (rPPG) allows contactless monitoring of human cardiac activity through a video camera. In this study, we assessed the accuracy and precision for heart rate measurements of the only consumer product available on the market, namely the Facereader™ rPPG by Noldus, with respect to a gold standard electrocardiograph. Twenty-four healthy participants were asked to sit in front of a computer screen and alternate two periods of rest with two stress tests (i.e. Go/No-Go task), while their heart rate was simultaneously acquired for 20 minutes using the ECG criterion measure and the Facereader™ rPPG. Results show that the Facereader™ rPPG tends to overestimate lower heart rates and underestimate higher heart rates compared to the ECG. The Facereader™ rPPG revealed a mean bias of 9.8 bpm, the 95% limits of agreement (LoA) ranged from almost -30 up to +50 bpm. These results suggest that whilst the rPPG Facereader™ technology has potential for contactless heart rate monitoring, its predictions are inaccurate for higher heart rates, with unacceptable precision across the entire range, rendering its estimates unreliable for monitoring individuals

Transcriptional Profiling of Human Liver Identifies Sex-Biased Genes Associated with Polygenic Dyslipidemia and Coronary Artery Disease

Sex-differences in human liver gene expression were characterized on a genome-wide scale using a large liver sample collection, allowing for detection of small expression differences with high statistical power. 1,249 sex-biased genes were identified, 70% showing higher expression in females. Chromosomal bias was apparent, with female-biased genes enriched on chrX and male-biased genes enriched on chrY and chr19, where 11 male-biased zinc-finger KRAB-repressor domain genes are distributed in six clusters. Top biological functions and diseases significantly enriched in sex-biased genes include transcription, chromatin organization and modification, sexual reproduction, lipid metabolism and cardiovascular disease. Notably, sex-biased genes are enriched at loci associated with polygenic dyslipidemia and coronary artery disease in genome-wide association studies. Moreover, of the 8 sex-biased genes at these loci, 4 have been directly linked to monogenic disorders of lipid metabolism and show an expression profile in females (elevated expression of ABCA1, APOA5 and LDLR; reduced expression of LIPC) that is consistent with the lower female risk of coronary artery disease. Female-biased expression was also observed for CYP7A1, which is activated by drugs used to treat hypercholesterolemia. Several sex-biased drug-metabolizing enzyme genes were identified, including members of the CYP, UGT, GPX and ALDH families. Half of 879 mouse orthologs, including many genes of lipid metabolism and homeostasis, show growth hormone-regulated sex-biased expression in mouse liver, suggesting growth hormone might play a similar regulatory role in human liver. Finally, the evolutionary rate of protein coding regions for human-mouse orthologs, revealed by dN/dS ratio, is significantly higher for genes showing the same sex-bias in both species than for non-sex-biased genes. These findings establish that human hepatic sex differences are widespread and affect diverse cell metabolic processes, and may help explain sex differences in lipid profiles associated with sex differential risk of coronary artery disease

Predicting Academic Performance: A Systematic Literature Review

The ability to predict student performance in a course or program creates opportunities to improve educational outcomes. With effective performance prediction approaches, instructors can allocate resources and instruction more accurately. Research in this area seeks to identify features that can be used to make predictions, to identify algorithms that can improve predictions, and to quantify aspects of student performance. Moreover, research in predicting student performance seeks to determine interrelated features and to identify the underlying reasons why certain features work better than others. This working group report presents a systematic literature review of work in the area of predicting student performance. Our analysis shows a clearly increasing amount of research in this area, as well as an increasing variety of techniques used. At the same time, the review uncovered a number of issues with research quality that drives a need for the community to provide more detailed reporting of methods and results and to increase efforts to validate and replicate work.Peer reviewe

Current and Future Drug Targets in Weight Management

Obesity will continue to be one of the leading causes of chronic disease unless the ongoing rise in the prevalence of this condition is reversed. Accumulating morbidity figures and a shortage of effective drugs have generated substantial research activity with several molecular targets being investigated. However, pharmacological modulation of body weight is extremely complex, since it is essentially a battle against one of the strongest human instincts and highly efficient mechanisms of energy uptake and storage. This review provides an overview of the different molecular strategies intended to lower body weight or adipose tissue mass. Weight-loss drugs in development include molecules intended to reduce the absorption of lipids from the GI tract, various ways to limit food intake, and compounds that increase energy expenditure or reduce adipose tissue size. A number of new preparations, including combinations of the existing drugs topiramate plus phentermine, bupropion plus naltrexone, and the selective 5-HT2C agonist lorcaserin have recently been filed for approval. Behind these leading candidates are several other potentially promising compounds and combinations currently undergoing phase II and III testing. Some interesting targets further on the horizon are also discussed

The thiosemicarbazone Me2NNMe2 induces paraptosis by disrupting the ER thiol redox homeostasis based on protein disulfide isomerase inhibition

Due to their high biological activity, thiosemicarbazones have been developed for treatment of diverse diseases, including cancer, resulting in multiple clinical trials especially of the lead compound Triapine. During the last years, a novel subclass of anticancer thiosemicarbazones has attracted substantial interest based on their enhanced cytotoxic activity. Increasing evidence suggests that the double-dimethylated Triapine derivative Me2NNMe2 differs from Triapine not only in its efficacy but also in its mode of action. Here we show that Me2NNMe2- (but not Triapine)-treated cancer cells exhibit all hallmarks of paraptotic cell death including, besides the appearance of endoplasmic reticulum (ER)-derived vesicles, also mitochondrial swelling and caspase-independent cell death via the MAPK signaling pathway. Subsequently, we uncover that the copper complex of Me2NNMe2 (a supposed intracellular metabolite) inhibits the ER-resident protein disulfide isomerase, resulting in a specific form of ER stress based on disruption of the Ca2+ and ER thiol redox homeostasis. Our findings indicate that compounds like Me2NNMe2 are of interest especially for the treatment of apoptosis-resistant cancer and provide new insights into mechanisms underlying drug-induced paraptosis. © 2018, The Author(s)