Critical Constituents Research Articles

Active free secretory component and secretory IgA in human milk: do maternal vaccination, allergy, infection, mode of delivery, nutrition and active lifestyle change their concentrations?

Free secretory component (free SC) in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion, but its concentration in human milk is unknown. To evaluate the relationship between free SC and SIgA, the influence of maternal factors (vaccination during pregnancy, allergy, previous infections, nutrition, mode of delivery and active lifestyle) on the concentrations of those secretory immune components in human milk was investigated. Concentration of active free SC and SIgA in 124 milk samples from 91 mothers were measured via ELISA. Free SC in milk from Tdap-vaccinated mothers was lower than the Tdap-flu-vaccinated, flu-vaccinated or Rhogam-vaccinated mothers. Free SC in mothers who had a cesarean delivery was higher than mothers who had a vaginal delivery. Free SC in the nonallergic group was higher than the allergic group. Free SC was higher in mothers who rarely/never eat junk food, than in mothers who always/frequently eat junk food. Free SC also was higher in the moderate exercise group (active lifestyle) compared with the group who rarely/never exercise (sedentary lifestyle). Free SC in human milk was not affected by previous maternal infection or probiotic supplementation whereas SIgA was not changed by all investigated maternal factors. This study suggests that active free SC is more impacted by maternal factors than active SIgA in human milk. Active free secretory component (free SC) is more impacted by maternal factors than active secretory IgA (SIgA) in human milk. Vaccination during pregnancy, allergy, nutrition, type of delivery and active lifestyle affect the secretion of free SC in human milk, but not SIgA secretion. Free SC in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion against pathogens and its active concentration in milk strongly varies between mothers, partially due to their specific maternal background.

Deformation and fracture evolution of FeAl-based metallic-intermetallic laminate (MIL) composites

FeAl-based Metallic-Intermetallic Laminate (MIL) composites exhibit enhanced strength and ductility compared to previously studied MIL composites. The deformation and fracture evolution of the FeAl-based MIL composites are investigated here via incremental compression testing. Microstructure assessment via electron backscatter diffraction suggests that deformation proceeds in a fairly homogeneous manner across gradients in the microstructure. Eventual failure is mainly induced by normal stresses, whereas other MIL composites typically fail by shear induced localizations. Geometrically necessary dislocation analysis indicates the FeAl regions deform in similar manners for the three MIL composites (Fe-FeAl-MIL, 430SS-FeAl-MIL, and 304SS-FeAl-MIL), and each fails in a similar mode. While the FeAl phase is the majority constituent of the composites, the mechanical properties are significantly influenced by the softer metal layers. The transition layer formed between the Fe-based metal layers and FeAl regions is the most critical constituent of the composites. Although the volume fraction of the transition layer is only ∼15%, a stronger transition layer can improve the work hardening behavior of the FeAl phase, increasing MIL composite strength by as much as 1 GPa. The findings can guide the design of the MIL composites to achieve even better mechanical properties.

Snai2 Maintains Bone Marrow Niche Cells by Repressing Osteopontin Expression

Bone marrow (BM) mesenchymal stem and progenitor cells (MSPCs) are a critical constituent of the hematopoietic stem cell (HSC) niche. Previous studies have suggested that the zinc-finger epithelial-mesenchymal transition transcription factor Snai2 (also known as Slug) regulated HSCs autonomously. Here, we show that Snai2 expression in the BM is restricted to the BM stromal compartment where it regulates the HSC niche. Germline or MSPC-selective Snai2 deletion reduces the functional MSPC pool and their mesenchymal lineage output and impairs HSC niche function during homeostasis and after stress. RNA sequencing analysis revealed that Spp1 (osteopontin) expression is markedly upregulated in Snai2-deficient MSPCs. Genetic deletion of Spp1 in Snai2-deficient mice rescues MSPCs' functions. Thus, SNAI2 is a critical regulator of the transcriptional network maintaining MSPCs by the suppression of osteopontin expression.

RNA Droplets.

Liquid-liquid phase separation is emerging as the universal mechanism by which membraneless cellular granules form. Despite many previous studies on condensation of intrinsically disordered proteins and low complexity domains, we lack understanding about the role of RNA, which is the essential component of all ribonucleoprotein (RNP) granules. RNA, as an anionic polymer, is inherently an excellent platform for achieving multivalency and can accommodate many RNA binding proteins. Recent findings have highlighted the diverse function of RNA in tuning phase-separation propensity up or down, altering viscoelastic properties and thereby driving immiscibility between different condensates. In addition to contributing to the biophysical properties of droplets, RNA is a functionally critical constituent that defines the identity of cellular condensates and controls the temporal and spatial distribution of specific RNP granules. In this review, we summarize what we have learned so far about such roles of RNA in the context of in vitro and in vivo studies.

(Invited) High Temperature Smart Sensor Systems for Venus and Aerospace Applications

(Invited) High Temperature Smart Sensor Systems for Venus and Aerospace Applications

Cannabis Inflorescence for Medical Purposes: USP Considerations for Quality Attributes.

There is an active and growing interest in cannabis female inflorescence (Cannabis sativa) for medical purposes. Therefore, a definition of its quality attributes can help mitigate public health risks associated with contaminated, substandard, or adulterated products and support sound and reproducible basic and clinical research. As cannabis is a heterogeneous matrix that can contain a complex secondary metabolome with an uneven distribution of constituents, ensuring its quality requires appropriate sampling procedures and a suite of tests, analytical procedures, and acceptance criteria to define the identity, content of constituents (e.g., cannabinoids), and limits on contaminants. As an independent science-based public health organization, United States Pharmacopeia (USP) has formed a Cannabis Expert Panel, which has evaluated specifications necessary to define key cannabis quality attributes. The consensus within the expert panel was that these specifications should differentiate between cannabis chemotypes. Based on the secondary metabolite profiles, the expert panel has suggested adoption of three broad categories of cannabis. These three main chemotypes have been identified as useful for labeling based on the following cannabinoid constituents: (1) tetrahydrocannabinol (THC)-dominant chemotype; (2) intermediate chemotype with both THC and cannabidiol (CBD); and (3) CBD-dominant chemotype. Cannabis plants in each of these chemotypes may be further subcategorized based on the content of other cannabinoids and/or mono- and sesquiterpene profiles. Morphological and chromatographic tests are presented for the identification and quantitative determination of critical constituents. Limits for contaminants including pesticide residues, microbial levels, mycotoxins, and elemental contaminants are presented based on toxicological considerations and aligned with the existing USP procedures for general tests and assays. The principles outlined in this review should be able to be used as the basis of public quality specifications for cannabis inflorescence, which are needed for public health protection and to facilitate scientific research on cannabis safety and therapeutic potential.

DHA Sensor GPR120 in Host Defense Exhibits the Dual Characteristics of Regulating Dendritic Cell Function and Skewing the Balance of Th17/Tregs.

In addition to functioning as an antioxidant, anti-inflammatory and age-defying cellular component, DHA impacts the immune system by facilitating the pathogen invasion. The mechanism through which DHA regulates immune suppression remains obscure. In our study, we postulated that DHA might interact with GPR120 to shape the dendritic cell (DC) differentiation and subsequently drive T cell proliferation during the virus infection. In vitro, the proportion of costimulatory molecules and HLA-DR on DC that generated from exogenous and endogenous (fad3b expression) DHA supplemented mice were significantly lower than wild-type mice. Given the importance of FAs, DHA is not only a critical cellular constituent but also a cell signaling molecule and FA deficiency reduces DC generation; we used GPR120-/- mice to determine whether DHA receptor deficiency disorders DC maturation processing. Novelty, the expression of GPR120 on DC from wild-type (WT) mice was inversely related to DC activation and DC from the GPR120-/- mice maintained a spontaneous maturation status. In vivo, both the excessive activation of GPR120 by DHA and the deletion of GPR120 effectively skewed the balance of Th17/Tregs and reduced the production of VNA and protection of vaccination. Overall, our results revealed a mechanism that the GPR120 self-regulation plays a crucial role in sensing DHA variation, which provides a new prospect for therapeutic manipulation in autoimmune diseases and the design of a vaccine adjuvant.

Intron 1–Mediated Regulation of EGFR Expression in EGFR-Dependent Malignancies Is Mediated by AP-1 and BET Proteins

The epidermal growth factor receptor (EGFR) is overexpressed in numerous solid tumors and is the subject of extensive therapeutic efforts. Much of the research on EGFR is focused on protein dynamics and downstream signaling; however, few studies have explored its transcriptional regulation. Here, we identified two enhancers (CE1 and CE2) present within the first intron of the EGFR gene in models of glioblastoma (GBM) and head and neck squamous cell carcinoma (HNSCC). CE1 and CE2 contain open chromatin and H3K27Ac histone marks, enhance transcription in reporter assays, and interact with the EGFR promoter. Enhancer genetic deletion by CRISPR/Cas9 significantly reduces EGFR transcript levels, with double deletion exercising an additive effect. Targeted repression of CE1 and CE2 by dCas9-KRAB demonstrates repression of transcription similar to that of genomic deletion. We identify AP-1 transcription factor family members in concert with BET bromodomain proteins as modulators of CE1 and CE2 activity in HNSCC and GBM through de novo motif identification and validate their presence. Genetic inhibition of AP-1 or pharmacologic disruption of BET/AP-1 binding results in downregulated EGFR protein and transcript levels, confirming a role for these factors in CE1 and CE2. Our results identify and characterize these novel enhancers, shedding light on the role that epigenetic mechanisms play in regulating EGFR transcription in EGFR-dependent cancers. IMPLICATIONS: We identify critical constituent enhancers present in the first intron of the EGFR gene, and provide a rationale for therapeutic targeting of EGFR intron 1 enhancers through perturbation of AP-1 and BET in EGFR-positive malignancies.

Neuromorphic Photonics With Coherent Linear Neurons Using Dual-IQ Modulation Cells

Neuromorphic photonics aims to transfer the high-bandwidth and low-energy credentials of optics into neuromorphic computing architectures. In this effort, photonic neurons are trying to combine the optical interconnect segments with optics that can realize all critical constituent neuromorphic functions, including the linear neuron stage and the activation function. However, aligning this new platform with well-established neural network training models in order to allow for the synergy of the photonic hardware with the best-in-class training algorithms, the following requirements should apply: i) the linear photonic neuron has to be able to handle both positive and negative weight values, ii) the activation function has to closely follow the widely used mathematical activation functions that have already shown an enormous performance in demonstrated neural networks so far. Herein, we demonstrate a coherent linear neuron architecture that relies on a dual-IQ modulation cell as its basic neuron element, introducing distinct optical elements for weight amplitude and weight sign representation and exploiting binary optical carrier phase-encoding for positive/negative number representation. We present experimental results of a typical IQ modulator performing as an elementary two-input linear neuron cell and successfully implementing all-optical linear algebraic operations with 104-ps long optical pulses. We also provide the theoretical proof and formulation of how to extend a dual-IQ modulation cell into a complete $N$ -input coherent linear neuron stage that requires only a single-wavelength optical input and avoids the resource-consuming Wavelength Division Multiplexing (WDM) weighting schemes. An 8-input coherent linear neuron is then combined with an experimentally validated optical sigmoid activation function into a physical layer simulation environment, with respective training and physical layer simulation results for the MNIST dataset revealing an average accuracy of 97.24% and 94.37%, respectively.

An efficient 3D DEM-FEM contact detection algorithm for tire-sand interaction

The combined discrete-finite element method is often used for dynamic interaction simulations, in which contact detection is the most time-consuming but critical constituent. Therefore, it is significant to develop an accurate and efficient contact detection algorithm. In this study, an efficient contact detection algorithm termed TSC (tire-sand contact) is developed for dealing with the interactions between spherical discrete elements and hexahedral finite elements. The global search of TSC is suitable for the contact detection of tire-sand interaction. In the global search phase, according to the contact characteristics of tire movement on granular terrain, the potential contact pairs are quickly determined by using the method of dynamically changing the slave nodes and master segments within a moving contact region. The local search is based on the principle of inside-outside algorithm, and the contact region is divided into three types, i.e. surface contact region, edge contact region and node contact region. In the local search phase, the invalid contact pairs and repeated contact pairs can be quickly excluded from the multiple potential contact pairs of one particle according to the relevant judgment conditions. And the Hertz-Mindlin contact model is used in corresponding contact force calculation. As a result, the quick contact search and accurate evaluation of contact force are accomplished. Finally, several numerical examples are presented to validate the accuracy and efficiency of the TSC algorithm in 3D contact analysis, which also demonstrates the advantages of the proposed algorithm in tire-sand interaction simulations.

Design of Security System Based on Raspberry-PI

Abstract As a critical constituent of many associations’ protection and security precedence, video surveillance has set up its importance and benefits numerous instances with the aid of imparting immediate supervising of possessions, people, surroundings and property. This paper deals with the diagram strategy of an embedded real-time surveillance gadget based totally on Raspberry-Pi single board computer (SBC) for intruder detection which is reinforcing technology of surveillance to supply fundamental security to our life and associated control and alert operations. The suggested safety solution is hinging on our novel integration of cameras and action detectors into application of web. Raspberry-Pi is operating and controlling action detectors and video cameras for far flung sensing and surveillance, streams live video and files it for future playback. Also, this paper is focusing on growing a surveillance machine that detects strangers and to response speedily through taking pictures and relaying photos to proprietor based totally wireless module. This Raspberry-Pi based clever surveillance machine presents the concept of monitoring a region in a far-flung area. The suggested solution offers a fee advantageous ubiquitous surveillance solution, environment friendly and convenient to implement. Furthermore, the paper presents the idea of motion detection and tracking using image processing. This type of technology is of great importance when it comes to surveillance and security. Live video streams therefore be used to show how objects can be detected then tracked. The detection and tracking process are based on pixel threshold.

Deubiquitination and stabilization of estrogen receptor α by ubiquitin-specific protease 7 promotes breast tumorigenesis.

Breast cancer is the most common malignancy in women around the world. Estrogen receptor α (ERα) is expressed in approximately 70% of breast tumors, and considered as one of most effective targets in breast cancer therapy. It has been reported that the degradation of ERα protein is mediated by ubiquitin-proteasome system. However, little is known about the regulation of ERα deubiquitination, a critical constituent of its degradation control. The current study first reports that there is a positive correlation between ERα and ubiquitin specific protease 7 (USP7) protein levels in human breast tumor tissues. Subsequent studies showed that USP7 physically interacted with the ERα, thereby mediating the deubiquitination and stabilization of ERα. In addition, USP7 inhibition or silencing led to growth inhibition and apoptosis of ERα-positive breast cancer cells both in vitro and in vivo. Furthermore, overexpression of ERα rescued the USP7 silencing-induced cell cycle arrest and apoptosis, supporting that ERα status is essential to the function of USP7 in breast carcinogenesis. Overall, this study suggests that targeting USP7-ERα complex could be a potential strategy to treat ERα-positive breast cancer.

The Political-Economic Foundations of Representative Government

The dominant interpretation of the Glorious Revolution portrays it as an innovative compromise that used clever institutional design to solve a coordination problem between rival elites. In contrast, I argue that it was neither innovative nor a compromise and that it was the product of structural change rather than institutional design. Following Barrington Moore, I focus on the rise of agrarian capitalism and economically autonomous elites, who, in contrast to rent-seeking elites, do not depend on favor from the state for their income. They have an interest in the creation of a political system that ensures their equal rights under the law, open access to markets, and opportunities to form broad coalitions against rent-seeking. This makes them a critical constituency for representative government. I test this argument through an analysis of patterns of allegiance for Crown and Parliament at the outset of the English Civil War and address its relevance to the Glorious Revolution.

Abstract 106: Cardiac Fibroblast as a Critical Constituent of the Cellular Niche Driving Cardiac Maturation

Rationale: Cardiac maturation lays the foundation of postnatal heart development and disease, yet little is known about the contributions of the microenvironment to cardiomyocyte maturation. Objective: To identify non-cardiomyocyte cell types and important signaling pathways central to cardiomyocyte maturation. Methods and Results: Through building cell-cell interactomes and signaling regulatory networks from single-cell RNA-sequencing data of mouse hearts at various postnatal stages, we identified switching of fibroblast subclusters state as a key driving force behind cardiac maturation. Molecular and functional maturation of immature (neonatal) mouse cardiomyocytes or human embryonic stem cell-derived cardiomyocytes were considerably enhanced when co-cultured with their corresponding adult cardiac fibroblasts in vitro . Further, single-cell analysis of the cardiac maturation trajectory revealed highly conserved signaling pathways and ligands in fibroblast-induced cardiomyocyte maturation in vivo and in vitro . Targeting these signaling pathways using inhibitors significantly delayed cardiac maturation in postnatal hearts, and markedly induced cardiomyocyte proliferation in infarcted hearts. Conclusions: Our study unveiled cardiac fibroblasts as a major constituent in the microenvironment driving cardiac maturation. Targeting signaling pathways and ligand-receptor interactions involved in their crosstalk with cardiomyocytes may yield useful strategies to modulate cardiomyocyte maturation state in cardiac diseases and for regeneration purposes. Keywords: Cardiac Maturation, Fibroblast, Single-Cell RNA-Sequencing

Evangelical globalism and the internationalization of Sudan’s second civil war

The roles played by evangelical Christians in the internationalization of Sudan’s second civil war (1983–2005) illustrate the multidirectional effects of faith-based interventions into the global south. Evangelicalism is one of the most rapidly expanding contemporary religious forms in the world. The engagement of South Sudan by evangelicals of the global north has been a major moment in its formation as a unique and critical international constituency. This work unsettles deeply rooted assumptions about these types of actors, their emergent politics and their locations in global governance relations. I argue that the politics of Sudan’s civil war represents a global moment in faith-based advocacy and humanitarianism, which is deeply implicated in a globalizing and globally-engaged evangelicalism.

Graphene nanosheets assisted carbon hollow cylinder for high-performance field emission applications

Electron sources are critical constituents for myriad many electronic applications including electron imaging, mass spectroscopy etc. Here, we report the realization of high-performance field emission from graphene assisted carbon hollow cylinders (Gr-CHCs) composed of multi-stacked radially aligned CNTs. These CHCs have built-in synthesis related Fe nanoparticles (NPs). This engineered nano-structure exhibits excellent field emission properties such as one of the ultra-low turn-on field (0.64 V μm−1 at 10 μA cm−2), low threshold field (0.74 V μm−1 at 100 μA cm−2), very high current density (15.49 mA cm−2 at 1.32 V μm−1) which is nearly double the current density obtained in our previous study. High field enhancement factor (0.72 × 104) with highly stable emission current at 100 μA was observed for more than 3 hrs at the base pressure of ∼1 × 10−8 mbar. This study suggests an approach to enhance the current density using the proposed innovative nanostructure and forms the basic theme of this communication. Highly efficient and stable field emissions observed are attributed to the geometry of cylinder and the production of the high density of sharp protrusions within the graphene sheets which enhance the local electric field and dramatically enhance field emission. This innovative cylindrical geometry associated with graphene assisted on Fe bearing aligned CNTs along with the periphery of the bulk cylinder provides an easy injection of electrons from the conduction band of CHCs into the vacuum in the presence of an external electric field. The tunability of field emission properties of these CHCs can be easily achieved by tailoring their diameter (10 and 20 mm) and different concentrations of the precursor. This new approach of the graphene assisted cylindrical geometry-based field emitter source provides enormous prospects and demand for next-generation high resolutions display devices.

A Two-Step Approach to Optimal Selection of Alerts for Investigation in a CSOC

A Cyber Security Operations Center (CSOC) is responsible for investigating all the alerts generated from the intrusion detection systems to identify suspicious activities in a timely manner. There exists a critical gap between the time needed (demand) and the time available (limited analyst resource) for alert investigation at a CSOC. Hence, alert prioritization is important, for which CSOCs employ ad-hoc filtering methods to prune and triage the alerts that are presented to the analysts for investigation. One of the major drawbacks of the ad-hoc methods is that they do not comprehensively take into consideration the organization-specific factors such as mission and asset criticality, CSOC resource availability, demand variations, and the desired CSOC performance metrics. Hence, an ad-hoc triaging (or prioritization) method is insufficient, and an intelligent method for optimal selection of alerts that considers the above-mentioned organization-specific factors must be developed, which is described as a two-step process in this paper. First, a composite risk score of each alert is determined using a quantitative value function hierarchy process, which takes into account several organization-specific factors. Second, an optimization model selects a list of alerts for investigation that optimizes the CSOC performance metrics for a given demand subject to its resource constraints. Experimental results show that the alerts that pertain to mission criticalities are handled in a timelier manner as compared to current practices at the CSOCs. The average persistence time of an alert in the CSOC system is also shown to significantly reduce with this new approach, which is a paradigm shift in providing a stronger cyber-defense system by protecting the critical constituents of an organization.

Naturally Fermented Acid Slurry of Soy Whey: High-Throughput Sequencing-Based Characterization of Microbial Flora and Mechanism of Tofu Coagulation.

Tofu processing generates large quantities of whey as waste water. Although naturally fermented whey serves as a coagulant, the critical constituents remain unknown. High-throughput sequencing identified predominant Lactobacillus in the naturally fermented acid slurry. Lactobacillus casei YQ336 with high coagulating ability and lactic acid production was isolated and its soy protein coagulating mechanism was determined. The acid in YQ336 fermented acid slurry lowered soy milk pH and reduced negatively charged groups of denatured soy protein, leading to coagulation. Acid slurry metal ions also promoted pH decline; moreover, YQ336-produced protease might partially hydrolyse soy protein, further promoting coagulation. Thus, organic acids, metal ions, and enzymes together promote coagulation, with the former acting as the main contributing factor. This study will pave the way for future industrial application of L. casei YQ336 in acid slurry tofu processing and food manufacturing, thereby potentially reducing resource waste and environmental pollution.

Ultra-Clean Pure Shift 1H-NMR applied to metabolomics profiling

Even though Pure Shift NMR methods have conveniently been used in the assessment of crowded spectra, they are not commonly applied to the analysis of metabolomics data. This paper exploits the recently published SAPPHIRE-PSYCHE methodology in the context of plant metabolome. We compare single pulse, PSYCHE, and SAPPHIRE-PSYCHE spectra obtained from aqueous extracts of Physalis peruviana fruits. STOCSY analysis with simplified SAPPHIRE-PSYCHE spectra of six types of Cape gooseberry was carried out and the results attained compared with classical STOCSY data. PLS coefficients analysis combined with 1D-STOCSY was performed in an effort to simplify biomarker identification. Several of the most compromised proton NMR signals associated with critical constituents of the plant mixture, such as amino acids, organic acids, and sugars, were more cleanly depicted and their inter and intra correlation better reveled by the Pure Shift methods. The simplified data allowed the identification of glutamic acid, a metabolite not observed in previous studies of Cape gooseberry due to heavy overlap of its NMR signals. Overall, the results attained indicated that Ultra-Clean Pure Shift spectra increase the performance of metabolomics data analysis such as STOCSY and multivariate coefficients analysis, and therefore represent a feasible and convenient additional tool available to metabolomics.

Practical Reliability Analysis and Approximate Design of Arithmetic Circuits

Critical constituent gates are first detected and graded based on their individual impact of an error in the outputs. This brings in the idea of practical reliability analysis metric. Then, the approximation of arithmetic circuits by random logic applied to least significant gates is introduced. The 74283 fast adder is used as an example to illustrate the feasibility of the proposed methods. Simulation results show the potential efficient application of the proposed reliability analysis metric and approximation method.