Thanks to their simplicity and interpretable structure, autoregressive processes are widely used to model time series data. However, many real time series data sets exhibit non-linear patterns, requiring nonlinear modeling. The threshold Auto-Regressive (TAR) process provides a family of non-linear auto-regressive time series models in which the process dynamics are specific step functions of a thresholding variable. While estimation and inference for low-dimensional TAR models have been investigated, high-dimensional TAR models have received less attention. In this article, we develop a new framework for estimating high-dimensional TAR models, and propose two different sparsity-inducing penalties. The first penalty corresponds to a natural extension of classical TAR model to high-dimensional settings, where the same threshold is enforced for all model parameters. Our second penalty develops a more flexible TAR model, where different thresholds are allowed for different auto-regressive coefficients. We show that both penalized estimation strategies can be utilized in a three-step procedure that consistently learns both the thresholds and the corresponding auto-regressive coefficients. However, our theoretical and empirical investigations show that the direct extension of the TAR model is not appropriate for high-dimensional settings and is better suited for moderate dimensions. In contrast, the more flexible extension of the TAR model leads to consistent estimation and superior empirical performance in high dimensions.
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http://dx.doi.org/10.1214/22-EJS1982 | DOI Listing |
J Phys Chem B
December 2024
Department of Chemistry, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pune 411008, India.
Understanding RNA-protein interactions is crucial for uncovering the mechanisms of cellular processes and can provide insights into the basis of various diseases, paving the way for the development of targeted therapeutic interventions. Exposure to stress conditions, such as hypoxia, leads to a drop in intracellular pH, which, in turn, alters the ionization states of amino acid residues and RNA bases, affecting the charge distribution and electrostatic interactions between RNA and proteins. In addition, pH also perturbs the structure and dynamics of proteins via the disruption of H-bonds and ionic interactions.
View Article and Find Full Text PDFActa Neuropathol Commun
December 2024
Brain Science Institute, Johns Hopkins University School of Medicine, Johns Hopkins University, 855 N. Wolfe St., Rangos 275, Baltimore, MD, 21205, USA.
The GC hexanucleotide repeat expansion in C9ORF72 is the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 GC hexanucleotide repeats.
View Article and Find Full Text PDFPLoS Comput Biol
December 2024
HUN-REN Institute of Experimental Medicine, Budapest, Hungary.
Finding optimal parameters for detailed neuronal models is a ubiquitous challenge in neuroscientific research. In recent years, manual model tuning has been gradually replaced by automated parameter search using a variety of different tools and methods. However, using most of these software tools and choosing the most appropriate algorithm for a given optimization task require substantial technical expertise, which prevents the majority of researchers from using these methods effectively.
View Article and Find Full Text PDFThe GC hexanucleotide repeat expansion in the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 GC hexanucleotide repeats.
View Article and Find Full Text PDFJ Ethnopharmacol
December 2024
Department of Anesthesiology, Affiliated hospital of Guilin Medical University, China. Electronic address:
Ethnopharmacological Relevance: Taraxasterol (TAR), a compound highly abundant and easily obtainable from Tibetan medicine Ixeridium gramineum (Fisch.) Tzvel., exhibits a variety of biological effects, including hepatoprotective, anti-inflammatory, and antioxidant activities.
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