Crosstalk Analysis Research Articles

Comparative crosstalk performance analysis of different configurations of heterogeneous multicore fiber

Abstract In order to select the heterogeneous multicore fiber (MCF) configuration with ultra-low crosstalk and low peak bending radius, comparative crosstalk analysis have been done for the three possible core configurations, namely, Configuration 1 - different refractive index (R.I.) and different radius, Configuration 2 - different R.I., and Configuration 3 - different radius. Using the coupled mode equation and the simplified expressions of mode coupling coefficient (MCC) for different configurations of heterogeneous cores, the crosstalk performance of all the heterogeneous MCF configurations along with the homogeneous MCF have been investigated analytically with respect to core pitch (D) and fiber bending radius ( R b ${R}_{b}$ ). Further, these expressions of MCC have been extended to obtain the simplified expressions of MCC for the estimation of crosstalk levels in respective trench-assisted (TA) heterogeneous MCF configurations. It is observed from the analysis that in Configuration 1, crosstalk level is lowest and the rate of decrease in the crosstalk with respect to the core pitch is highest compared to the other configurations of heterogeneous MCF. The values of crosstalk obtained analytically have been validated by comparing it with the values obtained from finite element method (FEM) based numerical simulation results. Further, we have investigated the impact of a fixed percent change (5%) in the core parameters (radius and/or R.I.) of one of the core of a homogeneous MCF, to realize the different heterogeneous MCF configurations, on the variations in crosstalk levels, difference in the mode effective refractive index of the core 1 and core 2 ( Δ n e f f = n e f f 1 − n e f f 2 $\Delta {n}_{eff}={n}_{eff1}-{n}_{eff2}$ ), and the peak bending radius ( R p k ${R}_{pk}$ ). For the same percent variations (5%) in the core parameters (radius and/or R.I.) of different configurations of cores (Config. 1-Config. 3), Config. 1 MCF has highest variation in Δ n e f f $\Delta {n}_{eff}$ value compared to other configurations of MCF. Further, this highest variation in Δ n e f f $\Delta {n}_{eff}$ value of Config. 1 MCF results in smallest peak bending radius. The smaller value of peak bending radius allows MCF to bend into smaller radius. Therefore, Configuration 1 is the potential choice for the design of MCF with smaller peak bending radius and ultra-low crosstalk level compared to the other configurations of SI-heterogeneous MCF.

Abstract 6103: Absence of Mitsuokella multacida is associated with early onset of colorectal cancer

Abstract Colorectal cancer (CRC) is a global burden, with an expected 2.2 million annual cases and 1.1 million deaths by 2030. Nearly 90% of CRC cases occur in people over the age of 50. However, early onset (<50 years) of CRC is increasing in Egypt. Prior studies suggest that alteration in microbiome composition (dysbiosis) disturbs the symbiotic relationship between the colorectum and resident micro-organisms and promotes CRC. We hypothesize that, for Egyptians, microbiome dysbiosis is responsible for early-onset of CRC. We further hypothesize that there is cross-talk between the microbiome, tumor molecular features, and the immune microenvironment. Thus, we investigated the molecular profiling of these patients via integrated transcriptional-microbiome analysis. We assessed the colonic microbiota and the expression of specific host response genes in normal colonic mucosal samples from 8 healthy individuals and samples from 20 Egyptian CRC patients. A retrospective convenience sample design was employed. Colonoscopy was performed on these patients at Alexandria University Hospital, Alexandria, Egypt. Microbiota composition was determined by 16S rRNA amplicon sequencing. A panel of 784 genes involved in tumor, microenvironment, and immune response were used to characterize differential expression across patient groups by the Nanostring method. This panel facilitates the estimation of immune cell abundance for 15 tumor-infiltrating immune cell types. Differential abundance and cross-talk between the relative abundance of microbiota and tumor RNA expression were evaluated using negative binomial model fitting and Wald statistics. One third of our CRC patient population was under 50 years old at the time of diagnosis with CRC, and most were female. Healthy controls were even younger than CRC cases, and most were females. There were differences in relative abundances of bacteria between healthy controls and those with CRCs. Analysis showed a low abundance of Mitsuokella multacida, a short-chain fatty acid (SCFA)-producing bacterium, in CRC patients when compared to healthy individuals. In particular, this trend was evident for older CRC patients (≥ 50 years); of note, this bacterium was absent in younger patients (<50 years) (adj. p-value = 0.01). Further, there was a high abundance of Fusobacterium nucleatum in all CRC patients compared to healthy individuals (adj. p-value = 0.04). In cross-talk analysis for healthy controls, elevated abundance of M. multacida was inversely associated with macrophage abundance (global p-value =0.055).For Egyptian patients, the absence of SCFA-producing multacida in younger patients may be a reason for early onset of CRC. These findings suggest that the oncoprotective effect of Mitsuokella multacida should be further investigated. These studies are supported by the US-Egypt STDF grants (NAS 2000007148 and 144/17) and the Impact funds of University of Alabama at Birmingham. Citation Format: Amr Elkholy, Michael Behring, Mohammed Mohsen, Prachi Bajpai, Amira Embaby, Doaa Header, Reham Abo Elwafa, Hesham Saeed, Mona Fouad, Waleed Arafat, Upender Manne. Absence of Mitsuokella multacida is associated with early onset of colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6103.

Crosstalk Analysis and Suppression of GaN Driving Circuit in Bridge Converter

Enhancement mode Gallium-Nitride power transistors (GaN HEMT) have emerged as promising devices for high frequency, high efficiency and high power density switch m ode power supplies. However, when GaN device works in high frequency, the dv/dt and di/dt slopes are increased due to stray inductances and parasitic capacitances, which leads to oscillations and overshoots in gate-source voltage and affect the stability of driving circuits. Especially in the phase-bridge circuit, the crosstalk between the upper and lower switch seriously limits the performance of the device. In order to solve the short circuit problem of bridge arms generated by oscillation and crosstalk, an improved design of gate driving circuit was proposed, which could eliminate the parasitic oscillation and voltage spikes, suppress crosstalk and higher harmonics effectively. In addition, A double pulse test prototype is built and the simulation and experimental results verify the effectiveness of this driving circuit.

Phosphoproteomic Analysis of Spiroplasma eriocheiris and Crosstalk with Acetylome Reveals the Role of Post-Translational Modifications in Metabolism

Background: Post-translational modifications (PTMs) such as phosphorylation are an essential regulatory mechanism of protein function and associated with a range of biological processes beyond genome and transcriptome. Spiroplasma eriocheiris, a wall-less helical bacterium, is one of the smallest known self-replicating bacteria and a novel pathogen of freshwater crustacean. Methods: To study the physiological characteristics and regulatory mechanism of S. eriocheiris, the protein phosphorylation in the bacterium were systematically investigated by iTRAQ analyzed by LC-MS/MS. Data are available via ProteomeXchange with identifier PXD015055. Results: We identified 465 phosphorylation sites in 246 proteins involved in a broad spectrum of fundamental biological process ranging from regulation of metabolic pathways to protein synthesis. Notably, most proteins in glycolysis and all proteins in the arginine deiminase system were phosphorylated. Meanwhile, the cytoskeleton proteins (Fibril, Mrebs and ET-Tu) were all phosphorylated suggest that the phosphorylation also may play a crucial role in cell skeleton formation. We have got a lot of highly conserved proteins and phosphorylation sites by analysis, and those proteins or phosphorylation sites were mainly participated in glucose metabolism and protein synthesis. Crosstalk analysis with protein-protein interaction networks in relation to phosphorylated proteins and acetylated proteins found that the two PTMs are required for playing crucial roles in many physiological processes in S. eriocheiris. By comparing the relative positions of acetylation versus phosphorylation, we found that the two modifications often found close to proximity on the same protein. Conclusions: The results imply that there is previously unreported hidden role of phosphorylation that define the functional state of Spiroplasma.

A Computational Study of Graphene as a Prospective Material for Microelectrodes in Retinal Prosthesis and Electric Crosstalk Analysis.

The computational model plays a vital role in the design and optimization of microelectrodes for efficient electrical stimulation and recording in the retinal prosthesis. Moreover, the material choice acts decisively in ensuring that the electronic device delivers sufficient stimulating current to the retina without harming the neighboring tissue. Recently, due to the enhanced electrical and electrochemical properties of graphene, it has become a viable material in biomedical applications. In this study, we analyzed the computational model for the retinal prosthesis by the novel use of graphene-based microelectrodes. For this, different topologies of the electrode arrangement were investigated. The most suitable configuration involves the arrangement of electrodes serving as the ground in a hexagonal fashion around the central stimulating electrode. We observed that the performance of graphene as the stimulating electrodes is comparable to the existing noble metal-based electrodes. Moreover, we found that optimizing the microelectrode design resulted in uniform electric potential distribution, and this eventually led to an increased electric field intensity at the desired activation point. Additionally, we analyzed the crosstalk phenomenon, and we observed from the results that it is better to implant such an electrode array in the vicinity of the targeted volume to minimize the effect of crosstalk.Clinical relevance- The present study can help in the improvement of the retinal prosthesis by analyzing the quantitative and qualitative effects of graphene-based microelectrodes on producing the threshold electric field in the retina tissue. The results obtained can be used to optimize the implantable microelectrode design and thus is a step forward in finding a cure to vision impairment diseases.

Identification of hydatidosis-related modules and key regulatory genes.

BackgroundEchinococcosis caused by larval of Echinococcus is prevalent all over the world. Although clinical experience showed that the presence of tapeworms could not be found in liver lesions, the repeated infection and aggravation of lesions still occur in the host. Here, this study constructed a multifactor-driven disease-related dysfunction network to explore the potential molecular pathogenesis mechanism in different hosts after E.multilocularis infection.MethodFirst, iTRAQ sequencing was performed on human liver infected with E.multilocularis. Second, obtained microRNAs(miRNAs) expression profiles of humans and canine infected with Echinococcus from the GEO database. In addition, we also performed differential expression analysis, protein interaction network analysis, enrichment analysis, and crosstalk analysis to obtain genes and modules related to E.multilocularis infection. Pivot analysis is used to calculate the potential regulatory effects of multiple factors on the module and identify related non-coding RNAs(ncRNAs) and transcription factors(TFs). Finally, we screened the target genes of miRNAs of Echinococcus to further explore its infection mechanism.ResultsA total of 267 differentially expressed proteins from humans and 3,635 differentially expressed genes from canine were obtained. They participated in 16 human-related dysfunction modules and five canine-related dysfunction modules, respectively. Both human and canine dysfunction modules are significantly involved in BMP signaling pathway and TGF-beta signaling pathway. In addition, pivot analysis found that 1,129 ncRNAs and 110 TFs significantly regulated human dysfunction modules, 158 ncRNAs and nine TFs significantly regulated canine dysfunction modules. Surprisingly, the Echinococcus miR-184 plays a role in the pathogenicity regulation by targeting nine TFs and one ncRNA in humans. Similarly, miR-184 can also cause physiological dysfunction by regulating two transcription factors in canine.ConclusionThe results show that the miRNA-184 of Echinococcus can regulate the pathogenic process through various biological functions and pathways. The results laid a solid theoretical foundation for biologists to further explore the pathogenic mechanism of Echinococcosis.

PM fiber based sensing tapes with automated 45° birefringence axis alignment for distributed force/pressure sensing.

Polarization maintaining (PM) fibers can be used for distributed force/pressure sensing in which the birefringence axis of the PM fiber should preferably be oriented 45° from the direction of the force/pressure for the maximum sensitivity. However, it is a challenge to achieve such 45° axis orientation for a long length of PM fiber in practice. In this paper, we report the development of what we believe the first equipment and process for making PM fiber based sensing tapes, capable of automatically adjusting the fiber axis orientation 45° with respect to the tape surface. In particular, we develop a machine vision system with the ability of continuously determining fiber axis orientation in real time as the fiber passes by and feeding back the orientation information to a fiber rotation apparatus to automatically adjust its orientation before fixing the fiber on a transparent PET tape with UV epoxy. We show the results of a successfully fabricated 70-m-long PM fiber sensing tape achieving an axis orientation accuracy of 45 ± 3° throughout the whole length of the tape, which is further validated with a distributed polarization crosstalk analyzer (DPXA). Finally, we demonstrate distributed transversal load sensing with 14 force applying weights randomly distributed along the sensing tape using the DPXA, with a polarization crosstalk measurement uniformity of 0.62 dB (standard deviation) using the same applied weight of 100 grams. The same sensing tape can also be used for pressure sensing with properly designed fixtures.

Crosstalk reduction in copper on‐chip interconnects with graphene barrier for ternary logic applications

SummaryThis paper presents the investigations of crosstalk effects in ternary logic‐based coupled interconnects. The crosstalk analysis is investigated for coupled copper interconnects and copper‐multilayer graphene (Cu‐MLG) interconnects. In Cu‐MLG interconnects, the Cu interconnect is enclosed with MLG barrier and standard ternary inverter is used to drive the interconnect. Based on the industry standard HSPICE simulation results, the crosstalk effects such as noise peak and delay are lower compared with conventional Cu interconnects. Moreover, the Cu‐MLG interconnects show reduced power dissipation, power delay product (PDP), and energy delay product (EDP) over the Cu interconnects. From the simulation results, it is observed that the Cu‐MLG interconnects provides the performance improvements up to 30.67% compared with the Cu interconnects. Thus, the Cu‐MLG interconnects are more compatible for ternary logic integrated circuits compared with traditional Cu interconnects.

Abstract B24: A multicellular, microfluidic model of the human bone marrow niche in metastatic cancers

Abstract Bone metastases cause significant morbidity in solid tumors, with prostate, breast, lung, and kidney cancers representing the most common primary sources. Understanding the landscape of stromal interactions in bone and bone marrow would facilitate development of novel therapies targeting this unique metastatic niche. Mesenchymal stromal cells (MSCs) are multipotent cells in bone marrow that differentiate into osteoblasts, adipocytes, and fibroblasts and regulate immune and inflammatory responses. MSC recruitment into primary tumors enhances invasiveness of prostate adenocarcinoma, which suggests that bone marrow MSCs impact development of bone metastases in prostate cancer and promote treatment resistance. We hypothesize that multicellular interactions drive a permissive bone marrow environment for outgrowth of metastatic lesions. The goal of this study is to develop a multicellular bone stromal model from patients with solid tumors for functional and molecular analysis of cellular crosstalk. We have recently published a reconfigurable, microfluidic platform that enables culture of up to 6 different cell types in 3-dimensional matrices and multi-endpoint analysis of limited patient samples. In this study, we have modified this platform to culture patient-derived tissue, by using primary bone marrow cells from patients consented to provide bone marrow aspirate at time of radical prostatectomy. This technology allows spatiotemporal control of individual treatment conditions, enabling culture and differentiation of primary human cells in separate chips that can be reconfigured into defined microenvironments. Subsequently, specific compartments can be isolated for gene expression analysis and in-device imaging. Using this platform, we present two distinct bone marrow models. In the first model, we cultured primary human bone marrow MSCs that were induced into osteoblastic and adipocytic lineages in 3D microculture. MSCs induced invasion of prostate cancer cell lines, and paracrine crosstalk between MSCs and prostate cancer cells increased expression of IL-6, IL-8, CXCL12, and MMP-9 in MSCs. In the second model, we generated a multicellular mixed 3D culture in which osteoblasts and adipocytes spontaneously differentiate in coculture with stromal cells, osteoclasts, and leukocytes. The mixed 3D cultures generated spheroid structures that resemble stem cell components with self-renewal capability, previously called mesenspheres. Overall, we have recapitulated cellular compartments in the bone marrow niche using two complementary methods. The impact of defined molecular subtypes of cancer is now being tested to understand if specific genetic alterations promote development of invasive cancer in bone marrow. Future directions include analysis of paracrine signaling and functional interactions between disseminated cancer cells and bone marrow cellular stroma as potential therapeutic targets. Citation Format: Nan Sethakorn, David Kosoff, Erika Heninger, Jasmine Martinez Soto, Jiaquan Yu, Rahul Das, David Jarrard, Jacques Galipeau, Peiman Hematti, Scott Dehm, David J. Beebe, Joshua M. Lang. A multicellular, microfluidic model of the human bone marrow niche in metastatic cancers [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B24.

Efficient time‐domain numerical modelling of crosstalk between coaxial cables incorporating frequency‐dependent parameters

This study presents an analysis of time-domain crosstalk between two parallel coaxial cables from 10 MHz − 1 GHz. Although such coupling has been extensively studied in the frequency domain, it is advantageous to evaluate the coupling in the time-domain for the analysis of signal integrity-related issues. The near-end crosstalk is modelled using one dimensional transmission line modelling (TLM) approach, which is validated against practical measurements and commercial simulation software. A prony approximation method and equivalent circuit approach were used to account for frequency-dependent parameters such as surface transfer impedance and skin effect in the TLM simulations.

ZFAT and smart sensor promotes the progression of cervical cancer through mitotic pathway

Abstract Cervical cancer is one of the leading causes of cancer death in women worldwide, which poses a serious threat to the lives of patients and normal life. Tumor activator ZFAT plays an important role in regulating gene expression and cancer development. This study explored the core driving role of ZFAT in the regulation of cervical cancer disease through comprehensive analysis based on smart sensor. Therefore, we downloaded the expression profile data of cervical cancer from NCBI-GEO database to identify the relevant modules by weighted gene co-expression analysis, and then used cross talk analysis to observe the interaction between the modules. Then, the GO function and KEGG pathway enrichment analysis of related dysfunction modules are carried out using R language Cluster Profiler package. Finally, key transcription factors and non-coding RNA of regulatory module were identified based on hypergeometric test, and related drugs were predicted according to the principle of drug target action. It was found that seven modules participated in the development of cervical cancer, while ZFAT differentially expressed and significantly regulated the core functional modules, which played an important regulatory role in the disease. At the same time, the mitotic pathway of ZFAT significantly regulates seven functional modules of cervical cancer. Secondly, 483 transcription factors, such as let-7a-5p and miR-6840-3p, and TP53, play an important role in regulating the co-expression module. In addition, drugs such as Felodipine and Theophylline have potential effects on cervical cancer. In conclusion, this study identified ZFAT as the core driver gene of cervical cancer, which promotes the development of cervical cancer through mitotic pathway. In addition, it can also be used as a biomarker of disease for further in-depth study and discussion. Exploring the strategy of driver-mediated dysfunction module provides a new way to discover the potential pathogenesis and treatment strategy of cervical cancer. These studies also provide a good reference for the study of reproductive system related diseases such as complications.

Temperature‐dependent analysis of crosstalk and delay uncertainty in multilayer graphene nanoribbon interconnects

SummaryIn this article, we have analyzed delay uncertainty due to crosstalk in multilayer graphene nanoribbon (MLGNR) interconnects. Crosstalk is a challenging problem in deep‐sub‐micron and nanometer designs. In this work, we have analyzed the crosstalk delay with a wide variation in chip operating temperature. The mean free path is modeled as a function of temperature. Furthermore, the resistance of MLGNR interconnect system is modeled. Crosstalk delay analysis is performed for both top‐contact MLGNR and side‐contact MLGNR (SC‐MLGNR) interconnects and compared the results with that of the traditional Cu interconnects. The analysis has been carried out for different interconnect widths 11, 16, and 22 nm and lengths 10, 50, and 100 μm for three different chip operating temperatures 233, 300, and 398K. The decrease in rise/fall delay (speed up) and increase in rise/fall time delay (slow down) are modeled. Finally, the delay uncertainty is modeled for different interconnect systems. The percentage change in delay values for speed up and slow down cases are −23.4%, −29.8% and 114.4%, 161.9%, respectively, for 10μm SC‐MLGNR interconnect. It is shown that the delay uncertainty is significantly less in SC‐MLGNR interconnects and with the advancement of technology the performance is improved as compared with copper interconnects.

A novel pancreatic tumour and stellate cell 3D co-culture spheroid model

BackgroundPancreatic ductal adenocarcinoma is a devastating disease with poor outcome, generally characterized by an excessive stroma component. The purpose of this study was to develop a simple and reproducible in vitro 3D-assay employing the main constituents of pancreatic ductal adenocarcinoma, namely pancreatic stellate and cancer cells.MethodA spheroid assay, directly co-culturing human pancreatic stellate cells with human pancreatic tumour cells in 3D was established and characterized by electron microscopy, immunohistochemistry and real-time RT-PCR. In order to facilitate the cell type-specific crosstalk analysis by real-time RT-PCR, we developed a novel in vitro 3D co-culture model, where the participating cell types were from different species, human and mouse, respectively. Using species-specific PCR primers, we were able to investigate the crosstalk between stromal and cancer cells without previous cell separation and sorting.ResultsWe found clear evidence for mutual influence, such as increased proliferation and a shift towards a more mesenchymal phenotype in cancer cells and an activation of pancreatic stellate cells towards the myofibroblast phenotype. Using a heterospecies approach, which we coined virtual sorting, confirmed the findings we made initially in the human-human spheroids.ConclusionsWe developed and characterized different easy to set up 3D models to investigate the crosstalk between cancer and stroma cells for pancreatic cancer.

Metabolomic analysis of animal models of depression.

Our understanding of the molecular mechanisms of depression remains largely unclear. Previous studies have shown that the prefrontal cortex (PFC) is among most important brain regions that exhibits metabolic changes in depression. A comprehensive analysis based on candidate metabolites in the PFC of animal models of depression will provide valuable information for understanding the pathogenic mechanism underlying depression. Candidate metabolites that are potentially involved in the metabolic changes of the PFC in animal models of depression were retrieved from the Metabolite Network of Depression Database. The significantly altered metabolic pathways were revealed by canonical pathway analysis, and the relationships among altered pathways were explored by pathway crosstalk analysis. Additionally, drug-associated pathways were investigated using drug-associated metabolite set enrichment analysis. The interrelationships among metabolites, proteins, and other molecules were analyzed by molecular network analysis. Among 88 candidate metabolites, 87 altered canonical pathways were identified, and the top five ranked pathways were tRNA charging, the endocannabinoid neuronal synapse pathway, (S)-reticuline biosynthesis II, catecholamine biosynthesis, and GABA receptor signaling. Pathway crosstalk analysis revealed that these altered pathways were grouped into three interlinked modules involved in amino acid metabolism, nervous system signaling/neurotransmitters, and nucleotide metabolism. In the drug-associated metabolite set enrichment analysis, the main enriched drug pathways were opioid-related and antibiotic-related action pathways. Furthermore, the most significantly altered molecular network was involved in amino acid metabolism, molecular transport, and small molecule biochemistry. This study provides important clues for the metabolic characteristics of the PFC in depression.

Insights into Mcl-1 Conformational States and Allosteric Inhibition Mechanism from Molecular Dynamics Simulations, Enhanced Sampling, and Pocket Crosstalk Analysis.

In this study, we explored the structural dynamics of Mcl-1, an anti-apoptotic protein. On the basis of structural ensembles, the essential dynamics was extracted and showed two major axes of variability: a breathing motion at the binding interface and a correlated motion through the internal loops. A free energy surface characterizing the breathing motion at the binding interface was generated and suggested an equilibrium between a closed conformation and a "ready to bind" conformation as the predominant states of Mcl-1 in solution. Moreover, the analysis of the dynamics along the internal loops revealed a hidden communication network of transient and cryptic pockets controlling the allosteric inhibition of Mcl-1. A detailed model joining the pocket crosstalk and salt bridge networks along the internal loops was proposed and allowed us to shed light on the key interactions governing Mcl-1's allosteric inhibition.

The Integrated Landscape of Biological Candidate Causal Genes in Coronary Artery Disease.

BackgroundGenome-wide association studies (GWASs) have identified more than 150 genetic loci that demonstrate robust association with coronary artery disease (CAD). In contrast to the success of GWAS, the translation from statistical signals to biological mechanism and exploration of causal genes for drug development remain difficult, owing to the complexity of gene regulatory and linkage disequilibrium patterns. We aim to prioritize the plausible causal genes for CAD at a genome-wide level.MethodsWe integrated the latest GWAS summary statistics with other omics data from different layers and utilized eight different computational methods to predict CAD potential causal genes. The prioritized candidate genes were further characterized by pathway enrichment analysis, tissue-specific expression analysis, and pathway crosstalk analysis.ResultsOur analysis identified 55 high-confidence causal genes for CAD, among which 15 genes (LPL, COL4A2, PLG, CDKN2B, COL4A1, FES, FLT1, FN1, IL6R, LPA, PCSK9, PSRC1, SMAD3, SWAP70, and VAMP8) ranked the highest priority because of consistent evidence from different data-driven approaches. GO analysis showed that these plausible causal genes were enriched in lipid metabolic and extracellular regions. Tissue-specific enrichment analysis revealed that these genes were significantly overexpressed in adipose and liver tissues. Further, KEGG and crosstalk analysis also revealed several key pathways involved in the pathogenesis of CAD.ConclusionOur study delineated the landscape of CAD potential causal genes and highlighted several biological processes involved in CAD pathogenesis. Further studies and experimental validations of these genes may shed light on mechanistic insights into CAD development and provide potential drug targets for future therapeutics.

Modeling and Analysis of Crosstalk for Time-Interleaved Photonic ADCs

We build a model of channel response for time-interleaved photonic analog-to-digital converters (TIPADCs) including interchannel and intrachannel crosstalks. The characteristic of the channel magnitude responses of TIPADCs in the cases with and without mismatch are analyzed under different backend bandwidths. When a backend bandwidth is less than half of the overall sampling rate, interchannel crosstalk will cause a periodical variation on the corresponding channel magnitude response in mismatch-free TIPADCs, with the period being the overall sampling rate. The periodicity caused by interchannel crosstalk will be disrupted by time mismatch in TIPADCs. The theoretical analyses are verified by the simulation results of 2- and 4-channel TIPADCs and experimental measurements of a 2-channel TIPADC system.

Molecular dissection of pheromone selectivity in the competence signaling system ComRS of streptococci

Competence allows bacteria to internalize exogenous DNA fragments for the acquisition of new phenotypes such as antibiotic resistance or virulence traits. In most streptococci, competence is regulated by ComRS signaling, a system based on the mature ComS pheromone (XIP), which is internalized to activate the (R)RNPP-type ComR sensor by triggering dimerization and DNA binding. Cross-talk analyses demonstrated major differences of selectivity between ComRS systems and raised questions concerning the mechanism of pheromone-sensor recognition and coevolution. Here, we decipher the molecular determinants of selectivity of the closely related ComRS systems from Streptococcus thermophilus and Streptococcus vestibularis Despite high similarity, we show that the divergence in ComR-XIP interaction does not allow reciprocal activation. We perform the structural analysis of the ComRS system from S. vestibularis. Comparison with its ortholog from S. thermophilus reveals an activation mechanism based on a toggle switch involving the recruitment of a key loop by the XIP C terminus. Together with a broad mutational analysis, we identify essential residues directly involved in peptide binding. Notably, we generate a ComR mutant that displays a fully reversed selectivity toward the heterologous pheromone with only five point mutations, as well as other ComR variants featuring XIP bispecificity and/or neofunctionalization for hybrid XIP peptides. We also reveal that a single XIP mutation relaxes the strictness of ComR activation, suggesting fast adaptability of molecular communication phenotypes. Overall, this study is paving the way toward the rational design or directed evolution of artificial ComRS systems for a range of biotechnological and biomedical applications.

Влияние газотрансмиттера сероводорода на микрореологические свойства эритроцитов здоровых лиц и больных сахарным диабетом второго типа

Цель исследования: изучение влияния донора газотрансмиттера (ГТ) сероводорода (NaНS) и активатора его внутриклеточного синтеза (Lцистеина) на микрореологические характеристики эритроцитов в норме и при сахарном диабете 2-го типа (СД2). Материалы и методы. Эритроциты 16 здоровых лиц и 16 больных СД2 инкубировали с донором сероводорода гидросульфидом натрия (NaHS) в концентрации 10, 50 и 100 мкмоль и стимулятором его эндогенного синтеза Lцистеином в концентрации 10, 50 и 100 мкмоль. Блокировали АТФзависимые калиевые каналы глибенкламидом (50 мкмоль). Ингибировали растворимую гуанилатциклазу с помощью 0,5 мкмоль ODQ (1H-1,2,4-oxadiazolo4,3-a quinoxalin-l-one). Регистрировали деформируемость (ИУЭ) и агрегацию эритроцитов. Результаты. Под влиянием NaHS наблюдали дозозависимые положительные изменения микрореологии эритроцитов. Микрореологические ответы эритроцитов на NaHS были более выраженными у здоровых лиц, чем у больных СД2. Сходную картину наблюдали и при воздействии на эритроциты Lцистеином. Прединкубация с глибенкламидом не устраняла положительного влияния донора ГТ на микрореологию эритроцитов, тогда как ингибирование растворимой гуанилатциклазы с помощью ODQ полностью устраняло положительные изменения ИУЭ под действием ГТ и существенно уменьшало его влияние на агрегацию клеток. Заключение. Таким образом, сероводород как газотрансмиттер улучшает микрореологию эритроцитов. При одинаковой концентрации донора сероводорода (NaHS) и стимулятора его синтеза (Lцистеина) более выраженные сдвиги микрореологических параметров эритроцитов наблюдаются у здоровых лиц по сравнению с больными СД2. Aim: to study the effect of donor gasotransmitter (GT) hydrogen sulphide (NaHS) and the activator of its intracellular synthesis (Lcysteine) on the red blood cells (RBCs) microrheological characteristics in normal and diabetes mellitus type 2 (DM2). Materials and methods. RBCs of 16 healthy individuals and 16 patients with DM2 were incubated with hydrogen sulfide donor sodium hydrosulfide (NaHS) in concentrations of 10, 50 and 100 mol and a stimulator of its endogenous synthesis Lcysteine (10, 50 and 100 mol). ATPdependent potassium channels were blocked by glibenclamide (50 mol). Soluble guanylate cyclase was inhibited using 0.5 mol ODQ (1H-1,2,4-oxadiazolo4,3-a quinoxalin-l-one). Deformability (RBCD) and RBCs aggregation were recorded. Results. Under the influence of NaHS, dose-dependent positive changes in RBCs microrheology were observed. Cellular microrheological responses to GT donor were more pronounced in healthy individuals than in patients with DM2. A similar pattern was observed when RBCs were exposed to Lcysteine. Preincubation with glibenclamide did not eliminate the positive effect of GT donor on RBCs microrheology. Whereas inhibition of soluble guanylate cyclase with the help of ODQ completely eliminated positive changes in RBCD under the action of GT and significantly reduced its effect on aggregation. Conclusion. Thus, hydrogen sulfide as a gasotransmitter improves RBCs microrheology. With the same concentration of hydrogen sulphide donor (NaHS) and its synthesis stimulator (Lcysteine), more pronounced shifts in the microrheological parameters of erythrocytes are observed in healthy individuals as compared with DM2 patients.

Comprehensive gene and pathway analysis of cervical cancer progression.

Cervical Cancer is one of the leading causes of cancer-associated mortality in women. The present study aimed to identify key genes and pathways involved in cervical cancer (CC) progression, via a comprehensive bioinformatics analysis. The GSE63514 dataset from the Gene Expression Omnibus database was analyzed for hub genes and cancer progression was divided into four phases (phases I–IV). Pathway enrichment, protein-protein interaction (PPI) and pathway crosstalk analyses were performed, to identify key genes and pathways using a criterion nodal degree ≥5. Gene pathway analysis was determined by mapping the key genes into the key pathways. Co-expression between key genes and their effect on overall survival (OS) time was assessed using The Cancer Genome Atlas database. A total of 3,446 differentially expressed genes with 107 hub genes were identified within the four phases. A total of 14 key genes with 11 key pathways were obtained, following extraction of ≥5 degree nodes from the PPI and pathway crosstalk networks. Gene pathway analysis revealed that CDK1 and CCNB1 regulated the cell cycle and were activated in phase I. Notably, the following terms, ‘pathways in cancer’, ‘focal adhesion’ and the ‘PI3K-Akt signaling pathway’ ranked the highest in phases II–IV. Furthermore, FN1, ITGB1 and MMP9 may be associated with metastasis of tumor cells. STAT1 was indicated to predominantly function at the phase IV via cancer-associated signaling pathways, including ‘pathways in cancer’ and ‘Toll-like receptor signaling pathway’. Survival analysis revealed that high ITGB1 and FN1 expression levels resulted in significantly worse OS. CDK1 and CCNB1 were revealed to regulate proliferation and differentiation through the cell cycle and viral tumorigenesis, while FN1 and ITGB1, which may be developed as novel prognostic factors, were co-expressed to induce metastasis via cancer-associated signaling pathways, including PI3K-Art signaling pathway, and focal adhesion in CC; however, the underlying molecular mechanisms require further research.