CHRONIC EXPOSURE TO OPIOIDS DOWN-REGULATES GENOMIC HISTONE MODIFICATIONS AND DISRUPTS STAT3 GENE EXPRESSION IN HUMAN INDUCED PLURIPOTENT STEM CELLS

Examining epigenetic (EG) manifestations and genomic heterogeneity is a novel perspective to understand opioid induced toxicity. Aberrations in histone protein post-translational modifications (HP-PTM) induce perturbations in chromatin integrity resulting in consequences for genomic expression patterns. In the current study, we hypothesize that chronic exposure to morphine sulfate (MS) alters histone-3-protein (H3)-PTM and disrupts STAT3 gene expression in human induced pluripotent stem cells (iPSC). We analyzed 21 genomic H3-PTM following exposure to 1 and 10 uM MS for 2 and 5 days. The results showed decreases in levels of repressive H3-PTM, namely H3K9me1 (2 day) and H3K27me3 (5 day). To confirm if these changes were reversible, cells were allowed to recover for 3 days in the absence of MS; genomic levels of both H3K9me1 and H3K27me3 rebounded to control levels, suggesting that MS induced EG effects are reversible and not heritable. Additionally, decreases in levels of H3K9me1 and H3K27me3 were concentration dependent and were not antagonized by pre-exposure of iPSC to naltrexone indicating that EG effects are independent of opioid receptor antagonism. Continuous chronic MS exposure for through 10 passages rendered the levels of histone modifications to increase by day 26. In addition, exposure for 2 days resulted in significant up-regulation of STAT3 gene expression which plunged with continuing MS exposure. This characteristic transcriptional up-regulation coupled with translational downregulation of STAT3 demonstrates the ability of MS mediated gene expression disruption. Interestingly, STAT3 protein levels remained at control levels when iPSC were pretreated with naltrexone prior to MS exposure. Controlled regulation of STAT3 signaling pathway is pivotal in sustaining and propagating pluripotency phenotype in stem cells. Furthermore, the levels of phosphorylated STAT3 at residues –tyrosine705 (STAT3-pTyr-705) and –serine727 (STAT3-pSer-727) were down-regulated on day 5 and day 2, correspondingly, following MS exposure. Together, the results indicate that MS alters pre-programmed genomic H3-PTM and induces STAT3 gene expression perturbations in iPSC

Single-test evaluation of directional elastic properties of anisotropic structured materials

When the elastic properties of structured materials become direction-dependent, the number of their descriptors increases. For example, in two-dimensions, the anisotropic behavior of materials is described by up to 6 independent elastic stiffness parameters, as opposed to only 2 needed for isotropic materials. Such high number of parameters expands the design space of structured materials and leads to unusual phenomena, such as materials that can shear under uniaxial compression. However, an increased number of properties descriptors and the coupling between shear and normal deformations render the experimental evaluation of material properties more challenging. In this paper, we propose a methodology based on the virtual fields method to identify six separate stiffness tensor parameters of two-dimensional anisotropic structured materials using just one tension test, thus eliminating the need for multiple experiments, as it is typical in traditional methods. The approach requires no stress data and uses full-field displacement data and global force data. We show the accuracy of our method using synthetic data generated from finite element simulations as well as experimental data from additively manufactured specimen

Evaluation of Physical and Chemical Pretreatment Methods to Improve Efficiency of Anaerobic Digestion of Waste Streams from Grain Processing

Globally, Anaerobic Digestion (AD) industry is booming and biogas, the most sustainable biofuel, produced via AD is in an exponential market growth curve. According to a November 2020 report from US Energy Information Administration (EIA), “25 large dairies and livestock operations in the United States produced a total of about 224 million kWh (or 0.2 billion kWh) of electricity from biogas”. However, the growth of AD and the cost-effective use of the generated biogas are hindered by the inconsistencies (composition, suspended solids, flow rate, etc.) of the incoming waste stream and the associated biogas quality (due to the presence of hydrogen sulfide gas). A pretreatment step prior to an AD unit can promote consistency in the incoming stream, minimize the suspended solids; and thereby insures the efficiency of AD. In this study, we evaluated the method of pretreatment of waste streams from three grain processing industries, where 1) we adjusted the pH of a stream corresponding to its isoelectric point (zero zeta-potential), 2) removed solids (and their corresponding COD) that precipitated, and 3) produced a consistent composition stream to feed the AD process. For grain processing industry, the precipitated solids can be returned to their process – thus integrating the pretreatment with the rest of the process. The pH pre-treatment should not add any additional cost to the plant since the pH of the waste streams from grain processing plant needs to be raised per plant permits prior to disposal. Our lab and pilot AD studies showed a positive effect of such pretreatment on these waste streams in terms of increased biogas production (11–60%) and COD removal (12–60%), and in some instances reduction in H2S content in biogas (8%). This study clearly demonstrated that such a pretreatment method is economical and is effective to improve AD performance on waste waters from grain processing industries

Single-test evaluation of directional elastic properties of anisotropic structured materials

When the elastic properties of structured materials become direction-dependent, the number of their descriptors increases. For example, in two-dimensions, the anisotropic behavior of materials is described by up to 6 independent elastic stiffness parameters, as opposed to only 2 needed for isotropic materials. Such high number of parameters expands the design space of structured materials and leads to unusual phenomena, such as materials that can shear under uniaxial compression. However, an increased number of properties descriptors and the coupling between shear and normal deformations render the experimental evaluation of material properties more challenging. In this paper, we propose a methodology based on the virtual fields method to identify six separate stiffness tensor parameters of two-dimensional anisotropic structured materials using just one tension test, thus eliminating the need for multiple experiments, as it is typical in traditional methods. The approach requires no stress data and uses full-field displacement data and global force data. We show the accuracy of our method using synthetic data generated from finite element simulations as well as experimental data from additively manufactured specimen

Shear-Normal Coupled Deformations in Anisotropic Structured Materials

The advent of additive manufacturing has allowed the design and engineering of a new class of materials known as metamaterials, or structured/architected materials. These metamaterials exhibit unique functionalities, such as ultrahigh strength-to-density ratios, which their base materials cannot achieve. Often designed to exhibit near-isotropic behavior, metamaterials derive their special properties from the distinctive deformation, dynamic motion, and elastic energy distribution of their micro- and meso-architectures. However, designing metamaterials for anisotropy, despite their ability to attain unique properties, is challenging. Fully characterizing anisotropic stiffness in planar loading requires six independent elastic tensor moduli. This high number of independent elastic stiffness parameters also expands the design space of structured materials and leads to unusual phenomena, such as materials that can shear under uniaxial compression. This direction-dependent shear-axial coupling is crucial for many applications such as shape-morphing, elastic wave manipulation devices and impact redirection. This thesis aims to understand the fundamental limits of shear-normal coupled deformations in anisotropic structured materials. Currently, there are no established upper and lower bounds on anisotropic moduli achieving extreme elastic anisotropy, similar to the Hashin-Shtrikman bounds in isotropic composites. This range is known as G-closure and provides limits for the achievable tensors. To date, there are no experimental methods that can measure the stiffness parameters of fully anisotropic structured materials from a single experiment. To address these challenges, we first introduce a method to generate two-phase periodic anisotropic unit cell geometries and construct a database of unit cells with a diverse range of effective elasticity tensors. The constructed database is compared with the properties achieved by hierarchical laminates and identify the regions where hierarchical designs are necessary to reach a specific extreme elasticity tensor. We then propose an experimental methodology to evaluate the anisotropic material properties. Our technique, which utilizes the virtual fields method, allows for the determination of six separate stiffness tensor parameters of two-dimensional structured materials using just one tension test. This method thus eliminates the need for multiple experiments as is typical in traditional methods. We show the accuracy of our method using synthetic data generated from finite element simulations as well as by conducting experiments on four additively manufactured specimens. The approach requires no stress data and uses the full-field displacement data measured using digital image correlation and global force data. We present a method for creating functionally graded anisotropic structures that smoothly transition between unit cells with distinct patterns. Isotropic materials with spatially varying density gradients have been shown to exhibit unique characteristics such as superior energy absorption. However, achieving smooth spatial gradients in the anisotropic mechanical properties while ensuring the connectivity of adjacent meso-architectures is non-trivial. This method allows for independent control of several functional gradients, such as porosity, anisotropic moduli, and symmetry. We show that certain nonlinearly graded structures when designed with unit cells positioned at distinct corners of the property space boundary exhibit novel mechanical behaviors. We conclude by designing specific functionally graded structures that demonstrate peculiar behaviors such as selective strain energy localization, localized rotations, compressive strains under tension, and longitudinal-shear wave mode conversion.</p

A Survey of Graph-based Deep Learning for Anomaly Detection in Distributed Systems

Anomaly detection is a crucial task in complex distributed systems. A thorough understanding of the requirements and challenges of anomaly detection is pivotal to the security of such systems, especially for real-world deployment. While there are many works and application domains that deal with this problem, few have attempted to provide an in-depth look at such systems. In this survey, we explore the potentials of graph-based algorithms to identify anomalies in distributed systems. These systems can be heterogeneous or homogeneous, which can result in distinct requirements. One of our objectives is to provide an in-depth look at graph-based approaches to conceptually analyze their capability to handle real-world challenges such as heterogeneity and dynamic structure. This study gives an overview of the State-of-the-Art (SotA) research articles in the field and compare and contrast their characteristics. To facilitate a more comprehensive understanding, we present three systems with varying abstractions as use cases. We examine the specific challenges involved in anomaly detection within such systems. Subsequently, we elucidate the efficacy of graphs in such systems and explicate their advantages. We then delve into the SotA methods and highlight their strength and weaknesses, pointing out the areas for possible improvements and future works.Comment: The first two authors (A. Danesh Pazho and G. Alinezhad Noghre) have equal contribution. The article is accepted by IEEE Transactions on Knowledge and Data Engineerin

(1,4,7,10-Tetra­oxacyclo­dodeca­ne)(trideuteroacetonitrile)lithium perchlorate

In the title compound, [Li(C8H16O4)(CD3CN)]ClO4, the Li atom is penta­coordinate. The O atoms of the 12-crown-4 ether form the basal plane, whereas the N atom of the trideutero­aceto­nitrile occupies the apical position. The Li+ atom is displaced by 0.794 (6) Å toward the apical position from the plane formed by the O atoms because the Li+ atom is too large to fit in the cavity of the 12-crown-4 ether, resulting in a distorted square-pyramidal geometry about the Li+ atom