Reusing Data and Metadata to Create New Metadata Through Machine-Learning & Other Programmatic Methods

Recent improvements in natural language processing (NLP) enable metadata to be created programmatically from reused original metadata or even the dataset itself. Transfer-learning applied to NLP has greatly improved performance and reduced training data requirements. In this talk, well compare machine-generated metadata to human-generated metadata and discuss characteristics of metadata and data archives that affect suitability for machine-learning reuse of metadata. Where as human-generated metadata is often populated once, populated from the perspective of data supplier, populated by many individuals with different words for the same thing, and limited in length, machine-generated metadata can be updated any number of times, generated from the perspective of any user, constrained to a standardized set of terms that can be evolved over time, and be any length required. Machine-learning generated metadata offers benefits but also additional needs in terms of version control, process transparency, human-computer interaction, and IT requirements. As a successful example, well discuss how a dataset of abstracts and associated human-tagged keywords from a standardized list of several thousand keywords were used to create a machine-learning model that predicted keyword metadata for open-source code projects on code.nasa.gov. Well also discuss a less successful example from data.nasa.gov to show how data archive architecture and characteristics of initial metadata can be strong controls on how easy it is to leverage programmatic methods to reuse metadata to create additional metadata

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Salicylic acid:old and new implications for the treatment of type 2 diabetes?

Efficacy of salicylic acid as a treatment for diabetes was first established well over a century ago. Antihyperglycaemic effects are thought to include improved peripheral insulin sensitivity and suppression of hepatic glucose production. For most of this period, the molecular mechanisms underlying these effects have been poorly understood and these are still a focus of considerable research, which is reviewed here. Antihyperglycaemic effects are observed only at much higher concentrations than analgesic, antipyretic and antithrombotic properties, suggesting that different targets underlie the antidiabetic aspects of salicylate pharmacology. In the 1950s, antihyperglycaemic responses were linked to mitochondrial uncoupling effects of the drug. Then at the beginning of this century, antihyperglycaemic effects were linked to anti-inflammatory effects of the drug on NF-κB signalling. More recently, new work suggests that direct activation of AMPK may contribute to antihyperglycaemic/antihyperlipidemic actions of salicylates. Better understanding of the mechanism of salicylate’s anthyperglycaemic effects may ultimately accelerate the development of new drugs for human use