Single-cell transcriptomics of human iPSC differentiation dynamics reveal a core molecular network of Parkinson’s disease

Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder, characterized by the loss of dopaminergic neurons (mDA) in the midbrain. The underlying mechanisms are only partly understood and there is no treatment to reverse PD progression. Here, we investigated the disease mechanism using mDA neurons differentiated from human induced pluripotent stem cells (hiPSCs) carrying the ILE368ASN mutation within the PINK1 gene, which is strongly associated with PD. Single-cell RNA sequencing (RNAseq) and gene expression analysis of a PINK1-ILE368ASN and a control cell line identified genes differentially expressed during mDA neuron differentiation. Network analysis revealed that these genes form a core network, members of which interact with all known 19 protein-coding Parkinson’s disease-associated genes. This core network encompasses key PD-associated pathways, including ubiquitination, mitochondrial function, protein processing, RNA metabolism, and vesicular transport. Proteomics analysis showed a consistent alteration in proteins of dopamine metabolism, indicating a defect of dopaminergic metabolism in PINK1-ILE368ASN neurons. Our findings suggest the existence of a network onto which pathways associated with PD pathology converge, and offers an inclusive interpretation of the phenotypic heterogeneity of PD.

An Efficient 5G Data Plan Approach Based on Partially Distributed Mobility Architecture

Reaching a flat network is the main target of future evolved packet core for the 5G mobile networks. The current 4th generation core network is centralized architecture, including Serving Gateway and Packet-data-network Gateway; both act as mobility and IP anchors. However, this architecture suffers from non-optimal routing and intolerable latency due to many control messages. To overcome these challenges, we propose a partially distributed architecture for 5th generation networks, such that the control plane and data plane are fully decoupled. The proposed architecture is based on including a node Multi-session Gateway to merge the mobility and IP anchor gateway functionality. This work presented a control entity with the full implementation of the control plane to achieve an optimal flat network architecture. The impact of the proposed evolved packet Core structure in attachment, data delivery, and mobility procedures is validated through simulation. Several experiments were carried out by using NS-3 simulation to validate the results of the proposed architecture. The Numerical analysis is evaluated in terms of total transmission delay, inter and intra handover delay, queuing delay, and total attachment time. Simulation results show that the proposed architecture performance-enhanced end-to-end latency over the legacy architecture.

Transmission of Q-signaling by the tunneling procedure in the automatic telephone network of integrated services of the Serbian Armed Forces

Introduction/purpose: To specify the practical application of ECMA355 and ECMA-336 Standards for Q-SIG tunneling and the implementation of mapping functions via the existing IP (Internet Protocol) network of the Serbian Armed Forces (Intranet SAF), in the Private Automatic Telephone Network SAF (PATN SAF), as the main part of the Private telecommunication-information networks of integrated services SAF (PISN SAF). Methods: Description of the implemented solution and analysis of the software parameters of the established transmission SIP route, with the display of the results obtained in the fight with jitter and echo in the network. Results: With such a solution, it was achieved that participants from the peripheral parts of the PISN SAF, which operate on the principle of transmission and circuit switching by TDM (Time Division Multiplexing), can connect with each other via the newly established central IP network SAF (Core network) which operates on the principle of transmission and switching packets with the SIP (Session Initiation Protocol), without losing the functionality of QSIG from the framework of the digital telecommunication network of integrated services ISDN (Integrated Services Digital Network). Conclusion: The article deals with the modern IP PINX (Private Integrated Services Network Exchange) manufactured by Mitel, type MX-ONE Service Node 6.0, which is implemented at the transit level PATN SAF and which successfully implements the process of tunneling Q-SIG through the IP network and the necessary functions for mapping the transmission of tunneled QSIG messages and mapping voice (and other audio) information to VoIP (Voice over IP) communication media streams through that network. Also, the basic elements for its software preparation during the introduction of a new SIP route, with a capacity of 30 IP trunks in a transmission beam realized with 100 Mb/s-T Ethernet, are given, and the fight with the present jitter and echo in the network is described. Finally, the paper presents the experience-based values of the parameters for reducing the influence of jitter and suppressing echo.

An efficient anonymous group handover authentication protocol for MTC devices for 5G networks

Machine Type Communication (MTC) has been emerging for a wide range of applications and services for the Internet of Things (IoT). In some scenarios, a large group of MTC devices (MTCDs) may enter the communication coverage of a new target base station simultaneously. However, the current handover mechanism specified by the Third Generation Partnership Project (3GPP) incur high signalling overhead over the access network and the core network for such scenario. Moreover, other existing solutions have several security problems in terms of failure of key forward secrecy (KFS) and lack of mutual authentication. In this paper, we propose an efficient authentication protocol for a group of MTCDs in all handover scenarios. By the proposal, the messages of two MTCDs are concatenated and sent by an authenticated group member to reduce the signalling cost. The proposed protocol has been analysed on its security functionality to show its ability to preserve user privacy and resist from major typical malicious attacks. It can be expected that the proposed scheme is applicable to all kinds of group mobility scenarios such as a platoon of vehicles or a high-speed train. The performance evaluation demonstrates that the proposed protocol is efficient in terms of computational and signalling cost.

A Study of 5G Edge-Central Core Network Split Options

With the wide adoption of edge compute infrastructures, an opportunity has arisen to deploy part of the functionality at the edge of the network to enable a localized connectivity service. This development is also supported by the adoption of “on-premises” local 5G networks addressing the needs of different vertical industries and by new standardized infrastructure services such as Mobile Edge Computing (MEC). This article introduces a comprehensive set of deployment options for the 5G network and its network management, complementing MEC with the connectivity service and addressing different classes of use cases and applications. We have also practically implemented and tested the newly introduced options in the form of slices within a standard-based testbed. Our performed validation proved their feasibility and gave a realistic perspective on their impact. The qualitative assessment of the connectivity service gives a comprehensive overview on which solution would be viable to be deployed for each vertical market and for each large-scale operator situation, making a step forward towards automated distributed 5G deployments.

Connectomic Analysis of Alzheimer’s Disease using Percolation Theory

Alzheimer’s disease (AD) is a severe neurodegenerative disorder that affects a growing worldwide elderly population. Identification of brain functional biomarkers is expected to help determine preclinical stages for targeted mechanistic studies and development of therapeutic interventions to deter disease progression. Connectomic analysis, a graph theory-based methodology used in the analysis of brain-derived connectivity matrices was used in conjunction with percolation theory targeted attack model to investigate the network effects of AD-related amyloid deposition. We used matrices derived from resting state functional magnetic resonance imaging collected on mice with extracellular amyloidosis (TgCRND8 mice, n = 17) and control littermates (n = 17). Global, nodal, spatial, and percolation-based analysis was performed comparing AD and control mice. These data indicate a short-term compensatory response to neurodegeneration in the AD brain via a strongly connected core network with highly vulnerable or disconnected hubs. Targeted attacks demonstrated a greater vulnerability of AD brains to all types of attacks and identified progression models to mimic AD brain functional connectivity through betweenness centrality and collective influence metrics. Furthermore, both spatial analysis and percolation theory identified a key disconnect between the anterior brain of the AD mice to the rest of the brain network.

Large-scale genomic study reveals robust activation of the immune system following advanced Inner Engineering meditation retreat

The positive impact of meditation on human well-being is well documented, yet its molecular mechanisms are incompletely understood. We applied a comprehensive systems biology approach starting with whole-blood gene expression profiling combined with multilevel bioinformatic analyses to characterize the coexpression, transcriptional, and protein–protein interaction networks to identify a meditation-specific core network after an advanced 8-d Inner Engineering retreat program. We found the response to oxidative stress, detoxification, and cell cycle regulation pathways were down-regulated after meditation. Strikingly, 220 genes directly associated with immune response, including 68 genes related to interferon signaling, were up-regulated, with no significant expression changes in the inflammatory genes. This robust meditation-specific immune response network is significantly dysregulated in multiple sclerosis and severe COVID-19 patients. The work provides a foundation for understanding the effect of meditation and suggests that meditation as a behavioral intervention can voluntarily and nonpharmacologically improve the immune response for treating various conditions associated with excessive or persistent inflammation with a dampened immune system profile.

Signalling load reduction in 5G network based on cloud radio access network architecture

The rapid growth of both mobile users and application numbers has caused a huge load on the core network (CN). This is attributed to the large numbers of control messages circulating between CN entities for each communication or service request, however, making it imperative to develop innovative designs to handle this load. Consequently, a variety of proposed architectures, including a software defined network (SDN) paradigm focused on the separation of control and data plans, have been implemented to make networks more flexible. Cloud radio access network (C-RAN) architecture has been suggested for this purpose, which is based on separating base band units (BBU) from several base stations and assembling these in one place. In this work, a novel approach to realize this process is based on SDN and C-RAN, which also distributes the control elements of the CN and locates them alongside the BBU to obtain the lowest possible load. The performance of this proposed architecture was evaluated against traditional architecture using MATLAB simulation, and. the results of this assessment indicated a major reduction in signalling load as compared to that seen in the traditional architecture. Overall, the number of signalling messages exchanged between control entities was decreased by 53.19 percent as compared to that seen in the existing architecture.

Beyond private 5G networks: applications, architectures, operator models and technological enablers

Private networks will play a key role in 5G and beyond to enable smart factories with the required better deployment, operation and flexible usage of available resource and infrastructure. 5G private networks will offer a lean and agile solution to effectively deploy and operate services with stringent and heterogeneous constraints in terms of reliability, latency, re-configurability and re-deployment of resources as well as issues related to governance and ownership of 5G components, and elements. In this paper, we present a novel approach to operator models, specifically targeting 5G and beyond private networks. We apply the proposed operator models to different network architecture options and to a selection of relevant use cases offering mixed private–public network operator governance and ownership. Moreover, several key enabling technologies have been identified for 5G private networks. Before the deployment, stakeholders should consider spectrum allocation and on-site channel measurements in order to fully understand the propagation characteristic of a given environment and to set up end-to-end system parameters. During the deployment, a monitoring tools will support to validate the deployment and to make sure that the end-to-end system meet the target KPI. Finally, some optimization can be made individually for service placement, network slicing and orchestration or jointly at radio access, multi-access edge computing or core network level.

Interactions of host defense and hyper-keratinization in psoriasis

Objectives: To understand the crosstalk between the host and microbiota in psoriatic skin, using a systems biology approach based on transcriptomics and microbiome profiling. Methods: We collected the skin tissue biopsies and swabs in both lesion and non-lesion skin of 13 patients with psoriasis (PsO), 15 patients with psoriatic arthritis (PsA), and healthy skin from 12 patients with ankylosing spondylitis (AS). We performed transcriptome sequencing and metagenomics profiling on the local skin sites to study the similarities and differences in the molecular profiles between the three conditions, and the associations between the host defense and microbiota dynamic. Results: We found that lesion and non-lesional samples were remarkably different in terms of their transcriptome profiles. Functional annotation of differentially expressed genes (DEGs) showed a major enrichment in neutrophil activation. By using co-expression gene networks, we identified a gene module that was associated with local psoriasis severity at the site of biopsy. From this module, we extracted a "core" set of genes that were functionally involved in neutrophil activation, epidermal cell differentiation and response to bacteria. Skin microbiome analysis revealed that the abundance of Enhydrobacter, Micrococcus and Leptotrichia were significantly correlated with the "core network" of genes. Conclusions: We identified a core network that regulates inflammation and hyper-keratinization in psoriatic skin, and is associated with local disease severity and microbiome composition.