Efficiency Evaluation and Applications of Finite-Time ZNN Designs Using Constant/Fuzzy Variables for TVQPEI.
  Our analysis suggests that SUGP1 mutations in cancers can induce missplicing identical or similar to that observed in mutant SF3B1 cancers.Nucleoli, the sites of ribosome biogenesis and the largest structures in human nuclei, form around nucleolar organizer regions (NORs) comprising ribosomal DNA (rDNA) arrays. NORs are located on the p-arms of the five human acrocentric chromosomes. Defining the rules of engagement between these p-arms and nucleoli takes on added significance as describing the three-dimensional organization of the human genome represents a major research goal. Here we used fluorescent in situ hybridization (FISH) and immuno-FISH on metaphase chromosomes from karyotypically normal primary and hTERT-immortalized human cell lines to catalog NORs in terms of their relative rDNA content and activity status. We demonstrate that a proportion of acrocentric p-arms in cell lines and from normal human donors have no detectable rDNA.  https://www.selleckchem.com/products/decursin.html  Surprisingly, we found that all NORs with detectable rDNA are active, as defined by upstream binding factor loading. We determined the nucleolar association status of all NORs during interphase, and found that nucleolar association of acrocentric p-arms can occur independently of rDNA content, suggesting that sequences elsewhere on these chromosome arms drive nucleolar association. In established cancer lines, we characterize a variety of chromosomal rearrangements involving acrocentric p-arms and observe silent, rDNA-containing NORs that are dissociated from nucleoli. In conclusion, our findings indicate that within human nuclei, positioning of all 10 acrocentric chromosomes is dictated by nucleolar association. Furthermore, these nucleolar associations are buffered against interindividual variation in the distribution of rDNA. Copyright © 2020 the Author(s). Published by PNAS.Barrier-to-autointegration factor (BAF) is a highly conserved protein in metazoans that has multiple functions during the cell cycle. We found that BAF is SUMOylated at K6, and that this modification is essential for its nuclear localization and function, including nuclear integrity maintenance and DNA replication. K6-linked SUMOylation of BAF promotes binding and interaction with lamin A/C to regulate nuclear integrity. K6-linked SUMOylation of BAF also supports BAF binding to DNA and proliferating cell nuclear antigen and regulates DNA replication. SENP1 and SENP2 catalyze the de-SUMOylation of BAF at K6. Disrupting the SUMOylation and de-SUMOylation cycle of BAF at K6 not only disturbs nuclear integrity, but also induces DNA replication failure. Taken together, our findings demonstrate that SUMOylation at K6 is an important regulatory mechanism that governs the nuclear functions of BAF in mammalian cells. Copyright © 2020 the Author(s). Published by PNAS.The phenomenon of benign overfitting is one of the key mysteries uncovered by deep learning methodology deep neural networks seem to predict well, even with a perfect fit to noisy training data. Motivated by this phenomenon, we consider when a perfect fit to training data in linear regression is compatible with accurate prediction. We give a characterization of linear regression problems for which the minimum norm interpolating prediction rule has near-optimal prediction accuracy. The characterization is in terms of two notions of the effective rank of the data covariance. It shows that overparameterization is essential for benign overfitting in this setting the number of directions in parameter space that are unimportant for prediction must significantly exceed the sample size. By studying examples of data covariance properties that this characterization shows are required for benign overfitting, we find an important role for finite-dimensional data the accuracy of the minimum norm interpolating prediction rule approaches the best possible accuracy for a much narrower range of properties of the data distribution when the data lie in an infinite-dimensional space vs. when the data lie in a finite-dimensional space with dimension that grows faster than the sample size.The management of harmful species, including invasive species, pests, parasites, and diseases, is a major global challenge. Harmful species cause severe damage to ecosystems, biodiversity, agriculture, and human health. In particular, managing harmful species often requires cooperation among multiple agents, such as landowners, agencies, and countries. Each agent may have incentives to contribute less to the treatment, leaving more work for other agents, which may result in inefficient treatment.  https://www.selleckchem.com/products/decursin.html  A central question is, therefore, how should a policymaker allocate treatment duties among the agents? Specifically, should the agents work together in the same area, or should each agent work only in a smaller area designated just for her/him? We consider a dynamic game-theoretic model, where a Nash equilibrium corresponds to a possible set of contributions that the agents could adopt over time. In turn, the allocation by the policymaker determines which of the Nash equilibria could be adopted, which allows us to compare the outcome of various allocations. Our results show that fewer agents can abate the harmful species population faster, but more agents can better control the population to keep its density lower. We prove this result in a general theorem and demonstrate it numerically for two case studies. Therefore, following an outbreak, the better policy would be to split and assign one or a few agents to treat the species in a given location, but if controlling the harmful species population at some low density is needed, the agents should work together in all of the locations.A sustained increase in intracellular Ca2+ concentration (referred to herein as excitotoxicity), brought on by chronic metabolic stress, may contribute to pancreatic β-cell failure. To determine the additive effects of excitotoxicity and overnutrition on β-cell function and gene expression, we analyzed the impact of a high fat diet (HFD) on Abcc8 knock-out mice. Excitotoxicity caused β-cells to be more susceptible to HFD-induced impairment of glucose homeostasis, and these effects were mitigated by verapamil, a Ca2+ channel blocker. Excitotoxicity, overnutrition and the combination of both stresses caused similar but distinct alterations in the β-cell transcriptome, including additive increases in genes associated with mitochondrial energy metabolism, fatty acid β-oxidation and mitochondrial biogenesis, and their key regulator Ppargc1a Overnutrition worsened excitotoxicity-induced mitochondrial dysfunction, increasing metabolic inflexibility and mitochondrial damage. In addition, excitotoxicity and overnutrition, individually and together, impaired both β-cell function and identity by reducing expression of genes important for insulin secretion, cell polarity, cell junction, cilia, cytoskeleton, vesicular trafficking, and regulation of β-cell epigenetic and transcriptional program.