Cellular Mode Research Articles

Throughput of Hybrid UAV Networks With Scale-Free Topology

Unmanned Aerial Vehicles (UAVs) hold great potential to support a wide range of applications due to the high maneuverability and flexibility. Compared with single UAV, UAV swarm carries out tasks efficiently in harsh environment, where the network resilience is of vital importance to UAV swarm. The network topology has a fundamental impact on the resilience of UAV network. It is discovered that scale-free network topology, as a topology that exists widely in nature, has the ability to enhance the network resilience. Besides, increasing network throughput can enhance the efficiency of information interaction, improving the network resilience. Facing these facts, this paper studies the throughput of UAV network with scale-free topology. Introducing the hybrid network structure combining both ad hoc transmission mode and cellular transmission mode into UAV network, the throughput of UAV network is improved compared with that of pure ad hoc UAV network. Furthermore, this work also investigates the optimal setting of the hop threshold for the selection of ad hoc or cellular transmission mode. It is discovered that the optimal hop threshold is related with the number of UAVs and the parameters of scale-free topology. This paper may motivate the application of hybrid network structure into UAV network.

Effect of cellular regeneration and viral transmission mode on viral spread

Illness negatively affects all aspects of life and one major cause of illness is viral infections. Some viral infections can last for weeks; others, like influenza (the flu), can resolve quickly. During infections, uninfected cells can replicate in order to replenish the cells that have died due to the virus. Many viral models, especially those for short-lived infections like influenza, tend to ignore cellular regeneration since many think that uncomplicated influenza resolves much faster than cells regenerate. This research accounts for cellular regeneration, using an agent-based framework, and varies the regeneration rate in order to understand how cell regeneration affects viral infection dynamics under assumptions of different modes of transmission. We find that although the general trends in peak viral load, time of viral peak, and chronic viral load as regeneration rate changes are the same for cell-free or cell-to-cell transmission, the changes are more extreme for cell-to-cell transmission due to limited access of infected cells to newly generated cells.

Resource Allocation and Mode Selection in 5G Networks Based on Energy Efficient Game Theory Approach

With the advent of next-generation cellular networks, energy efficiency is becoming increasingly important. To tackle this issue, this paper investigates energy efficiency in D2D-enabled heterogeneous cellular networks. Boosting the longterm energy efficiency of wireless 5G communication networks is being explored through mode selection and resource allocation. The study proposed a three-stage process for energy-efficient mode selection and resource allocation. The process starts with cellular users who switch to D2D emitting a beacon and cellular users within close proximity reacting to it. A proposed auction mechanism will be enacted inside the group in the second state ( in this paper, the group size will be four). Next, each cellular user was classified according to SINR values, distance, and battery life, so that they could dynamically transition between standard cellular mode and D2D mode. For stage three, direct-hop hybrid D2D communication, we developed a TAMM double auction game model that efficiently splits resources. To identify the true bidders in our game model, we compute the median and mode values of the ASK and BID values received by both seller and buyer cellular users. A simulation study shows that the proposed method is energy-efficient in a heterogeneous network enabled by D2D.

Discovery of Potent Inhibitors of Cyclin-Dependent Kinases 7 and 9: Design, Synthesis, Structure-Activity Relationship Analysis and Biological Evaluation.

Cyclin-dependent kinases (CDKs) 7 and 9 are deregulated in various types of human cancer and are thus viewed as therapeutic targets. Accordingly, small-molecule inhibitors of both CDKs are highly sought-after. Capitalising on our previous discovery of CDKI-73, a potent CDK9 inhibitor, medicinal chemistry optimisation was pursued. A number of N-pyridinylpyrimidin-2-amines were rationally designed, chemically synthesised and biologically assessed. Among them, N-(6-(4-cyclopentylpiperazin-1-yl)pyridin-3-yl)-4-(imidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-amine was found to be one of the most potent inhibitors of CDKs 7 and 9 as well as the most effective anti-proliferative agent towards multiple human cancer cell lines. The cellular mode of action of this compound was investigated in MV4-11 acute myeloid leukaemia cells, revealing that the compound dampened the kinase activity of cellular CDKs 7 and 9, arrested the cell cycle at sub-G1 phase and induced apoptosis.

Abstract B054: Histone lysine methyltransferase NSD3 governs transcriptional programs that drive pancreatic neuroendocrine tumors

Abstract Pancreatic Neuroendocrine Tumors (PanNETs) are the most common and lethal neuroendocrine malignancies. For decades, standard chemotherapeutic regimens and targeted therapeutics have been used in advanced patients with little to no avail. Thus, there is a critical unmet need to develop novel and effective precision therapeutics. Additionally, pre-clinical models that faithfully recapitulate disease are urgently needed for translational studies. Here, we directly address these challenges by characterizing a novel genetically engineered mouse model of PanNETs as well as identifying histone lysine methyltransferase (KMT) NSD3 as a critical oncogenic driver. We identified KMT NSD3 to be upregulated through a meta-analysis of human PanNET RNA-Seq data. Previous literature indicates that NSD3 canonically di-methylates Histone H3 lysine residue 36 (H3K36me2) selecting transcriptional and gene expression programs with potential cancer implications. Thus, we sought to identify the role of NSD3 and H3K36 di-methylation dynamics in PanNET tumorigenesis. Our initial findings indicate that loss of NSD3 decreases proliferation and di-methylation of H3K36 in vitro using PanNET PDX cell lines. Additionally, we generated a novel in vivo model focusing on the pancreatic islet-specific loss of conditional Men1Lox/Lox, AtrxLox/Lox, and PtenLox/Lox alleles, alterations of which are representative of human disease. Proof-of-concept studies were done comparing time-matched wild-type and our PanNET model, revealing that our model has increased islet hyperplasia and proliferation. Additionally, to analyze the role of NSD3 in vivo, we generated a conditional Nsd3Lox/Lox knockout mouse which I have crossed to our PanNET model. Preliminary studies suggest that Nsd3 depletion significantly attenuates tumor growth in vivo. Furthermore, our lab conducted in vitro methylation assays that identified a gain-of-function point mutation NSD3T1232A that increases the catalytic activity of NSD3 at H3K36me2. Thus, to understand the role of the enzymatic activity of NSD3 in PanNET tumorigenesis, we conducted studies in vitro where we reconstituted NSD3 wild-type, NSD3Y1174A enzymatically deficient, and NSD3T1232A in NSD3 depleted cells. Preliminary findings indicate that NSD3T1232A increases H3K36me2 and significantly increases proliferation, while NSD3WT rescues H3K36me2 and proliferation, and NSD3Y1174A does not rescue H3K36me2 and the phenotype observed. Lastly, to leverage NSD3 hyperactivity in vivo, we generated an NSD3T1232A mouse (Rosa26LSL-NSD3T1232A) and crossed with our initial PanNET model. Our results demonstrate that NSD3T1232A significantly decreases survival, accelerates tumor burden, and proliferation when compared to time-matched control and NSD3 deficient mice. Together, these studies provide insights into the role of NSD3 in PanNET tumorigenesis. Future portions of testing will establish the specific cellular and molecular modes of action of NSD3 and establish a potential therapeutic target. Citation Format: Mary E. Fuentes, Simone C. Hausmann, Natasha M. Flores, Xiaoyin Lu, Pawel K. Mazur. Histone lysine methyltransferase NSD3 governs transcriptional programs that drive pancreatic neuroendocrine tumors [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B054.

Benzimidazoles cause lethality by inhibiting the function of Caenorhabditis elegans neuronal beta-tubulin

Parasitic nematode infections cause an enormous global burden to both humans and livestock. Resistance to the limited arsenal of anthelmintic drugs used to combat these infections is widespread, including benzimidazole (BZ) compounds. Previous studies using the free-living nematode Caenorhabditis elegans to model parasitic nematode resistance have shown that loss-of-function mutations in the beta-tubulin gene ben-1 confer resistance to BZ drugs. However, the mechanism of resistance and the tissue-specific susceptibility are not well known in any nematode species. To identify in which tissue(s) ben-1 function underlies BZ susceptibility, transgenic strains that express ben-1 in different tissues, including hypodermis, muscles, neurons, intestine, and ubiquitous expression were generated. High-throughput fitness assays were performed to measure and compare the quantitative responses to BZ compounds among different transgenic lines. Significant BZ susceptibility was observed in animals expressing ben-1 in neurons, comparable to expression using the ben-1 promoter. This result suggests that ben-1 function in neurons underlies susceptibility to BZ. Subsetting neuronal expression of ben-1 based on the neurotransmitter system further restricted ben-1 function in cholinergic neurons to cause BZ susceptibility. These results better inform our current understanding of the cellular mode of action of BZs and also suggest additional treatments that might potentiate the effects of BZs in neurons.

An overview of PAX1: Expression, function and regulation in development and diseases.

Transcription factors play multifaceted roles in embryonic development and diseases. PAX1, a paired-box transcription factor, has been elucidated to play key roles in multiple tissues during embryonic development by extensive studies. Recently, an emerging role of PAX1 in cancers was clarified. Herein, we summarize the expression and functions of PAX1 in skeletal system and thymus development, as well as cancer biology and outline its cellular and molecular modes of action and the association of PAX1 mutation or dysregulation with human diseases, thus providing insights for the molecular basis of congenital diseases and cancers.

Computational simulation of thermo-mechanical field and fluid flow and their effect on the solidification process in TWIP steel welds

The primary austenitic solidification mode of Twinning Induced Plasticity (TWIP) steel weld joints is one of the most important issues limiting its weldability. In order to gain knowledge on this topic, a comprehensive study was carried out through numerical simulation of diffusive-convective phenomena of fluid flow and heat transfer of the melted material in the weld pool of TWIP steel weld joints. Weldments were performed using different heat inputs and constraint conditions. The predictions of convective motion, thermal history and cooling rates estimated by finite element (FE) and finite volume (FV) simulations were correlated with chemical species segregation (Mn, C, Al and Si) and the solidification mode in the fusion zone. The microstructural characterization of weld joints and the numerical results provided a full analysis of the weld pool solidification process. Results revealed a relationship between both the dendrite size and Mn segregation with the estimated velocity field of liquid material in the melted zone. Moreover, the presence of δ-ferrite was experimentally detected in some weld joints and associated with the convective movement of melted material and chemical segregation. The cellular dendritic growth mode found in some weld joints contributed to the formation of δ-ferrite and promoted the transition of the solidification mode from austenitic to ferritic-austenitic. As well δ-ferrite allowed to mitigate hot-cracking and interrupted the Mn-enriched liquid film migration towards the heat-affected zone, avoiding the formation of liquation cracks. The presence of δ-ferrite phase maintained a high mechanical strength providing improved elongation regarding the welded material mechanical properties.

Numerical simulation of detonation wave propagation through a rigid permeable barrier

The results of calculation of the detonation propagation in a porous medium for hydrogen-air mixture are presented. The porous medium was specified explicitly and consisted of sets of individual obstacles in the form of solid walls or the sets of finite-size plates. Various modes of detonation propagation depending on obstacle parameters are obtained: propagation in a cellular mode, stationary propagation with destruction of the cellular structure of the detonation front, propagation of a monotonically attenuating detonation wave with destruction of the cellular structure of the front. The possibility of reducing the detonation propagation velocity by replacing solid plates with finite-size ones was shown. The effect of the geometrical parameters of the plates and the step of it installation on the degree of detonation attenuation was estimated. It was determined that an increase in the number of plates leads to a stronger attenuation of the detonation.

Endocannabinoids at the synapse and beyond: implications for neuropsychiatric disease pathophysiology and treatment.

Endocannabinoids (eCBs) are lipid neuromodulators that suppress neurotransmitter release, reduce postsynaptic excitability, activate astrocyte signaling, and control cellular respiration. Here, we describe canonical and emerging eCB signaling modes and aim to link adaptations in these signaling systems to pathological states. Adaptations in eCB signaling systems have been identified in a variety of biobehavioral and physiological process relevant to neuropsychiatric disease states including stress-related disorders, epilepsy, developmental disorders, obesity, and substance use disorders. These insights have enhanced our understanding of the pathophysiology of neurological and psychiatric disorders and are contributing to the ongoing development of eCB-targeting therapeutics. We suggest future studies aimed at illuminating how adaptations in canonical as well as emerging cellular and synaptic modes of eCB signaling contribute to disease pathophysiology or resilience could further advance these novel treatment approaches.

Kinase Inhibitor Screening Displayed ALK as a Possible Therapeutic Biomarker for Gastric Cancer.

Despite advances in cancer chemotherapy, gastric cancer (GC) continues to have high recurrence rates and poor prognosis with limited treatment options. Understanding the etiology of GC and developing more effective, less harmful therapeutic approaches are vital and urgent. Therefore, this work describes a novel kinase target in malignant gastric cells as a potential therapeutic strategy. Our results demonstrate that among 147 kinase inhibitors (KI), only three molecules were significantly cytotoxic for the AGP-01 cell line. Hence, these three molecules were further characterized in their cellular mode of action. There was significant cell cycle impairment due to the expression modulation of genes such as TP53, CDKN1A, CDC25A, MYC, and CDK2 with subsequent induction of apoptosis. In fact, the Gene Ontology analysis revealed a significant enrichment of pathways related to cell cycle regulation (GO:1902749 and GO:1903047). Moreover, the three selected KIs significantly reduced cell migration and Vimentin mRNA expression after treatment. Surprisingly, the three KIs share the same target, ALK and INSR, but only the ALK gene was found to have a high expression level in the gastric cancer cell line. Additionally, lower survival rates were observed for patients with high ALK expression in TCGA-STAD analysis. In summary, we hypothesize that ALK gene overexpression can be a promising biomarker for prognosis and therapeutic management of gastric adenocarcinoma.

Cellular modes of action of the methanol extract from the aerial parts of Psychotria sycophylla (K.Schum.) Petit (Rubiaceae) against multidrug-resistant bacteria

Background: Infectious diseases caused by multidrug-resistant bacteria (MDR) remain a global health issue. The population uses several plants from the Cameroonian pharmacopeia to treat bacterial infections. The methanol extract from the aerial parts of Psychotria sycophylla (K.Schum.) Petit (Rubiaceae) (PSA) previously showed antibacterial activities against MDR bacteria. In the present study, the antibacterial activities of PSA were determined in the presence of an efflux pump inhibitor (EPI), phenylalanine-arginine β-naphthylamide (PAβN). The effects of PSA on the bacterial membrane and its ability to inhibit the bacterial biofilm were also assessed. Methods: The evaluation of antibacterial activity of PSA in the presence of PAβN was evaluated using the microdilution method. The modification of the bacterial membrane permeability as well as the inhibition of biofilm were evaluated using spectrophotometric methods. Results: When tested with PAβN, the inhibitory effects of PSA increased vis à vis all the tested bacteria. PSA also destroyed the bacterial membrane and showed significant inhibition of biofilms of Escherichia coli AG102 strain. Conclusion: The reported data provide complementary information on the antibacterial effect of Psychotria sycophylla and might be helpful in formulating a phytomedicine to combat infections due to multidrug-resistant bacteria. Keywords: Bacteria; modes of action; multidrug resistance; Psychotria sycophylla; Rubiaceae.

The BEHAV3D Platform Demonstrates Cellular Immunotherapy Modes of Action.

An organoid-based, 3D imaging-transcriptomic platform was developed to investigate immunotherapy modes of action.

Routing protocols for hybrid wireless networks: a brief review

Hybrid <span>wireless networks (HWNs) are resulted from the integration of a mobile Ad hoc networks (MANET) and an infrastructure wireless networks. These networks have received increasing interest from researchers for their superior performance and reliability. Packet routing protocols in hybrid wireless networks are important to increase the capacity and scalability of these networks, therefore, several routing protocols have been proposed. Routing protocols in HWNs are designed and implemented from combining <span>the cellular transmission mode with the Ad hoc transmission mode. To route a message to the intended recipient of the sender, hybrid wireless networks use multi-hop technology. However, the source node needs relay nodes, which may be either adjacent nodes or base stations depending on set of parameters like bandwidth, load balancing, or the nearest node. This paper explores routing protocols for hybrid wireless networks and the techniques to enhance the security, performance, and capacity of these routing protocols.</span></span>

Modeling D2D Underlaying Cellular Network for Hotspot Communications with Poisson Cluster and Hole Processes

This paper develops a new approach to the modeling and analysis of device-to-device (D2D) underlaying multi-tier cellular network for dense hotspot communications, which consists of macro base stations (MBSs), pico BSs (PBSs), femto BSs (FBSs). A typicl user equipment (UE) can work either in D2D mode or cellular mode. Considering the dense hotspot communications, this work employs Poisson point process (PPP) to model the locations of MBSs and PBSs, and uses Poisson cluster process (PCP) to model the ones of UEs and FBSs. The locations of PBSs are also modeled as the centers of hotspots, referred to as the centers of PCPs. UEs and FBSs cluster around the common parent process PBSs. To guard the cluster-edge UEs, the clustered-UE classification and modified fractional frequency reuse (FFR) are jointly used, by which both the UEs and FBSs are classified two sets, cluster-center UEs and cluster-edge UEs, cluster-center FBSs and cluster-edge FBSs, respectively. The total frequency band is divided into two orthogonal segments, one of which is shared by D2D devices, cluster-edge FBSs, and PBSs, and the other segment of which is shared by cluster-center FBSs and MBSs. For such clustered multi-tier network, by using the methods from PPP, PCP, and PHP, this paper presents a tractable approach for modeling and analyzing the performance of cellular and D2D networks and gives the statistical descriptions of the experienced interferences at a typical D2D or cellular receiver by using the approximated Poisson hole processes (PHP) theory. This yields the derivations of the coverage probabilities of both the D2D receivers and cellular destinations. In additon, during the analysis of cellular UEs, to derive the coverage probabilities, this paper specially constructs one UE association criterion as well as the derivations of both the association probabilities and the statistical descriptions of association distances for cluster-center and cluster-edge UEs. The simulations results exploit the effect of various network parameters on the network performance and give the insights in terms of the proposed schemes as well as the comparison between cluster-center and cluster-edge UEs.

Myelinated axons are the primary target of hemin-mediated oxidative damage in a model of the central nervous system

Iron released from oligodendrocytes during demyelination or derived from haemoglobin breakdown products is believed to amplify oxidative tissue injury in multiple sclerosis (MS). However, the pathophysiological significance of iron-containing haemoglobin breakdown products themselves is rarely considered in the context of MS and their cellular specificity and mode of action remain unclear. Using myelinating cell cultures, we now report the cytotoxic potential of hemin (ferriprotoporphyrin IX chloride), a major degradation product of haemoglobin, is 25-fold greater than equimolar concentrations of free iron in myelinating cultures; a model that reproduces the complex multicellular environment of the CNS. At low micro molar concentrations (3.3 - 10 μM) we observed hemin preferentially binds to myelin and axons to initiate a complex detrimental response that results in targeted demyelination and axonal loss but spares neuronal cell bodies, astrocytes and the majority of oligodendroglia. Demyelination and axonal loss in this context are executed by a combination of mechanisms that include iron-dependent peroxidation by reactive oxygen species (ROS) and ferroptosis. These effects are microglial-independent, do not require any initiating inflammatory insult and represent a direct effect that compromises the structural integrity of myelinated axons in the CNS. Our data identify hemin-mediated demyelination and axonal loss as a novel mechanism by which intracerebral degradation of haemoglobin may contribute to lesion development in MS.

Unveiling the cellular and molecular mode of action of Melaleuca cajuputi Powell. essential oil against aflatoxigenic strains of Aspergillus flavus isolated from stored maize samples

This study aimed to reveal the bio-efficacy of Melaleuca cajuputi essential oil (McEO) against aflatoxigenic fungi and lipid peroxidation causing deterioration of stored maize samples. Three different toxigenic strains of Aspergillus flavus, namely AF-LHP-M2, AF-LHP-SP2, and AF-LHP-VS8 were investigated. Gas chromatography-mass spectrometry (GC-MS) analysis of EO revealed the presence of α-pinene (49.24%) as major compound. Investigation on efficacy showed that McEO exhibited remarkable inhibitory activity against growth and AFB1 production by AF-LHP-M2 (2.0 and 1.4 μL mL−1, respectively), AF-LHP-SP2 (1.2 and 1.0 μL mL−1, respectively), and AF-LHP-VS8 (0.8 μL mL−1) (p < 0.05). The McEO inhibited fungal growth via inhibition of ergosterol biosynthesis, cellular constituents' leakage, and damage of mitochondrial membrane potential, while AFB1 production by inhibition of intracellular methylglyoxal. Further, molecular docking study was carried out to unveil the binding affinities of major compounds with the target protein Nor-1 (primarily catalyze an important step in AFB1 biosynthesis), and the results revealed good correlation with the experimental findings. In addition, McEO showed significantly (p < 0.05) higher DPPH• and ABTS•+ scavenging activity with IC50 values 3.16 and 4.29 μL mL−1, respectively. Interestingly, McEO inhibited AFB1 production, and malondialdehyde content in fumigated maize samples without significantly (p < 0.05) changing their sensory attributes, ascertaining its efficacy in food system with high safety profile (LD50 = 1800 mg kg−1 body weight) on mice model. The overall results proved McEO's potential as natural food preservative of stored food products.

Deep Reinforcement Learning-Based Resource Allocation for Cellular Vehicular Network Mode 3 with Underlay Approach.

Vehicle-to-vehicle (V2V) communication has attracted increasing attention since it can improve road safety and traffic efficiency. In the underlay approach of mode 3, the V2V links need to reuse the spectrum resources preoccupied with vehicle-to-infrastructure (V2I) links, which will interfere with the V2I links. Therefore, how to allocate wireless resources flexibly and improve the throughput of the V2I links while meeting the low latency requirements of the V2V links needs to be determined. This paper proposes a V2V resource allocation framework based on deep reinforcement learning. The base station (BS) uses a double deep Q network to allocate resources intelligently. In particular, to reduce the signaling overhead for the BS to acquire channel state information (CSI) in mode 3, the BS optimizes the resource allocation strategy based on partial CSI in the framework of this article. The simulation results indicate that the proposed scheme can meet the low latency requirements of V2V links while increasing the capacity of the V2I links compared with the other methods. In addition, the proposed partial CSI design has comparable performance to complete CSI.

Biological system considerations for application of toxicogenomics in next-generation risk assessment and predictive toxicology

There is increasing interest in using modern ‘omics technologies, such as whole transcriptome sequencing, to inform decisions about human health safety and chemical toxicity hazard. High throughput methodologies using in vitro assays offer a path forward in reducing or eliminating animal testing. However, many aspects of these technologies need assessment before they will gain the trust of regulators and the public as viable alternative test methods for human health and safety. We used a high throughput whole transcriptome sequence assay (TempO-Seq) to assess the use of three widely used cancer cell lines (HepG2, MCF7, and Ishikawa cells) as in vitro systems for determination of cellular modes of action for two well studied compounds with canonical liver responses: ketoconazole and phenobarbital. We evaluated transcriptomic data to infer points of departure for use in risk analyses of compounds. Both compounds displayed shortcomings in evidence for canonical liver-related responses in any cell line, despite a strong dose response in all three. This raises questions about the competence of simple, mono-cultured cancer cell lines as appropriate surrogates for some adverse effects or toxic endpoints. Points of departure derived from benchmark doses were highly consistent across all three cell lines however, indicating the use of transcriptomic BMD analyses for such purposes would be a reliable and consistent approach.

A Reliable Self-Adaptive Scheduling Control Protocol for Cellular V2X Mode 4

A Reliable Self-Adaptive Scheduling Control Protocol for Cellular V2X Mode 4