Time series feature engineering is a time-consuming process because scientists and engineers have to consider the multifarious algorithms of signal processing and time series analysis for identifying ...and extracting meaningful features from time series. The Python package tsfresh (Time Series FeatuRe Extraction on basis of Scalable Hypothesis tests) accelerates this process by combining 63 time series characterization methods, which by default compute a total of 794 time series features, with feature selection on basis automatically configured hypothesis tests. By identifying statistically significant time series characteristics in an early stage of the data science process, tsfresh closes feedback loops with domain experts and fosters the development of domain specific features early on. The package implements standard APIs of time series and machine learning libraries (e.g. pandas and scikit-learn) and is designed for both exploratory analyses as well as straightforward integration into operational data science applications.
Dysfunction of autophagy and disturbed protein homeostasis are linked to the pathogenesis of human neurodegenerative diseases and the modulation of autophagy as the protein clearance process has ...become one key pharmacological target. Due to the role of sigma-1 receptors (Sig-1R) in learning and memory, and the described pleiotropic neuroprotective effects in various experimental paradigms, Sig-1R activation is recognized as one potential approach for prevention and therapy of neurodegeneration and, interestingly, in amyotrophic lateral sclerosis associated with mutated Sig-1R, autophagy is disturbed. Here we analyzed the effects of tetrahydro-
,
-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73), a muscarinic receptor ligand and Sig-1R agonist, on autophagy and proteostasis. We describe, at the molecular level, for the first time, that pharmacological Sig-1R activation a) enhances the autophagic flux in human cells and in
and b) increases proteostasis capacity, ultimately ameliorating paralysis caused by protein aggregation in
. ANAVEX2-73 is already in clinical investigation for the treatment of Alzheimer's disease, and the novel activities of this compound on autophagy and proteostasis described here may have consequences for the use and further development of the Sig-1R as a drug target in the future. Moreover, our study defines the Sig-1R as an upstream modulator of canonical autophagy, which may have further implications for various conditions with dysfunctional autophagy, besides neurodegeneration.
Neurodegenerative diseases are linked to dysfunctional proteostasis and disturbed autophagy. Here, we discuss how the sigma-1 receptor (Sig-1R) may act at the intersection of this interaction, as ...loss-of-function mutations of this unique chaperone are associated with defective autophagy and its pharmacological activation induces autophagic activity.
The monitoring of real-time objects such as steel billets during their casting process creates myriads of events. Complex Event Processing (CEP) is the technology to analyze resulting event streams ...as fast as possible. But classic CEP is not able to consider events that did not happen yet. It is not clear how to transform CEP from a technology, which reacts on past events, to one, which anticipates near future events. Conditional density estimation allows to combine both estimation and expected uncertainty about the next occurrence of a given event in one mathematical object. Moreover, it allows to calculate the probability of event patterns, which are the basis for CEP. Hence, we are introducing the concept of Conditional Event Occurrence Density Estimation (CEODE) to CEP. We present a reference architecture for combining CEP engines with predictive analytics using CEODEs. On basis of concrete guidelines for transforming classical event processing rules to proactive ones, we are demonstrating how CEP evolves from being reactive to becoming both predictive and prescriptive.
The all-relevant problem of feature selection is the identification of all strongly and weakly relevant attributes. This problem is especially hard to solve for time series classification and ...regression in industrial applications such as predictive maintenance or production line optimization, for which each label or regression target is associated with several time series and meta-information simultaneously. Here, we are proposing an efficient, scalable feature extraction algorithm for time series, which filters the available features in an early stage of the machine learning pipeline with respect to their significance for the classification or regression task, while controlling the expected percentage of selected but irrelevant features. The proposed algorithm combines established feature extraction methods with a feature importance filter. It has a low computational complexity, allows to start on a problem with only limited domain knowledge available, can be trivially parallelized, is highly scalable and based on well studied non-parametric hypothesis tests. We benchmark our proposed algorithm on all binary classification problems of the UCR time series classification archive as well as time series from a production line optimization project and simulated stochastic processes with underlying qualitative change of dynamics.
Toll-like receptor (TLR) activation induces inflammatory responses in macrophages by activating temporally defined transcriptional cascades. Whether concurrent changes in the cellular metabolism that ...occur upon TLR activation influence the quality of the transcriptional responses remains unknown. Here, we investigated how macrophages adopt their metabolism early after activation to regulate TLR-inducible gene induction. Shortly after TLR4 activation, macrophages increased glycolysis and tricarboxylic acid (TCA) cycle volume. Metabolic tracing studies revealed that TLR signaling redirected metabolic fluxes to generate acetyl-Coenzyme A (CoA) from glucose resulting in augmented histone acetylation. Signaling through the adaptor proteins MyD88 and TRIF resulted in activation of ATP-citrate lyase, which in turn facilitated the induction of distinct LPS-inducible gene sets. We postulate that metabolic licensing of histone acetylation provides another layer of control that serves to fine-tune transcriptional responses downstream of TLR activation. Our work highlights the potential of targeting the metabolic-epigenetic axis in inflammatory settings.
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•Macrophages adopt a transient metabolic state in response to TLR4 activation•MyD88 and TRIF synergistically facilitate signaling-driven changes in metabolism•Increases in glycolysis and ATP-citrate lyase activity foster histone acetylation•ATP-citrate lyase governs gene induction of a distinct LPS responsive gene set
TLR4 activation by LPS induces defined transcriptional cascades. Lauterbach et al. provide evidence that TLR activation induces a transient metabolic state that supports the transcriptional response. Mechanistically, they show that concerted increases in glycolytic flux and ATP-citrate lyase activity foster histone acetylation.
Surgical adhesions are bands of scar tissues that abnormally conjoin organ surfaces. Adhesions are a major cause of post-operative and dialysis-related complications, yet their patho-mechanism ...remains elusive, and prevention agents in clinical trials have thus far failed to achieve efficacy. Here, we uncover the adhesion initiation mechanism by coating beads with human mesothelial cells that normally line organ surfaces, and viewing them under adhesion stimuli. We document expansive membrane protrusions from mesothelia that tether beads with massive accompanying adherence forces. Membrane protrusions precede matrix deposition, and can transmit adhesion stimuli to healthy surfaces. We identify cytoskeletal effectors and calcium signaling as molecular triggers that initiate surgical adhesions. A single, localized dose targeting these early germinal events completely prevented adhesions in a preclinical mouse model, and in human assays. Our findings classifies the adhesion pathology as originating from mesothelial membrane bridges and offer a radically new therapeutic approach to treat adhesions.
Abstract
Stable jet electrospinning (SJES) is a special form of optical fiber generation that prevents chaotic fiber whipping typical for conventional electrospinning procedures. Incorporation of ...highly emissive semiconductor nanoplatelets (NPLs) in such fibers has very high potential in optical data transmission, optological circuits, fiber lasers, solar light concentrators and many other fields because NPLs exhibit strongly directed emission from their surface plane due to various in‐plane transition dipole moments. However, potential orientation control of 2D‐NPLs in SJES is entirely unknown as electric fields and various mechanical forces contribute in a complex manner simultaneously. Here, the observation of counter‐intuitive yet very beneficial orientation of rectangular CdSe/CdS 2D‐NLP in SJES perpendicular to the fiber drawing axis is reported. Scanning electron microscopy, 3D‐single particle excitation polarization microscopy, 3D‐photogoniometry, polarized emission spectroscopy and small angle X‐ray scattering (SAXS) demonstrate aggregation free perpendicular alignment of the NPLs in poly(methyl methacrylate) (PMMA) fibers, resulting in dominant emission in directions parallel to the fiber. It is suggested that the observed vertical alignment is due to normal forces resulting from viscoelastic expansion when the polymer solution leaves the cannula (Barus effect) and that using such perpendicular nano‐emitter alignment forces allows for the generation of novel materials also beyond fibers.
Hot Jupiters are rarely accompanied by other planets within a factor of a few in orbital distance. Previously, only two such systems have been found. Here, we report the discovery of a third system ...using data from the Transiting Exoplanet Survey Satellite (TESS). The host star, TOI-1130, is an eleventh magnitude K-dwarf in Gaia G-band. It has two transiting planets: a Neptune-sized planet (3.65 0.10 ) with a 4.1 days period, and a hot Jupiter ( ) with an 8.4 days period. Precise radial-velocity observations show that the mass of the hot Jupiter is . For the inner Neptune, the data provide only an upper limit on the mass of 0.17 (3 ). Nevertheless, we are confident that the inner planet is real, based on follow-up ground-based photometry and adaptive-optics imaging that rule out other plausible sources of the TESS transit signal. The unusual planetary architecture of and the brightness of the host star make TOI-1130 a good test case for planet formation theories, and an attractive target for future spectroscopic observations.
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