Multiple Replicas Research Articles

Performance Analysis of Grant-Free Random-Access NOMA in URLL IoT Networks

Internet-of-Things (IoT) networks have recently emerged to provide massive connectivity for many application scenarios and services. Additionally, developing spectrum-access strategies for a large number of nodes with sporadic data traffic behaviors in IoT networks has attracted much attention recently. However, developing such strategies becomes more challenging when ultra-reliable low-latency (URLL) transmissions are required. As IoT networks entail spectrum-efficient transmission schemes, non-orthogonal multiple-access (NOMA) has emerged as a key enabler for such networks. On the other hand, grant-free random-access (RA) techniques are particularly promising for high spectral-efficiency and massive connectivity, since they reduce signaling overhead, and packet latency. Therefore, in this paper, uplink RA-NOMA IoT networks with clustered IoT devices is studied, where short packet and diversity transmissions are adopted to meet the URLL requirements. To reduce the negative effect of diversity transmission on packet latency, multiple replicas of packets are accommodated within different resource blocks (RBs) in the same transmission time interval (TTI). The analytical expressions of network metrics, namely, average packet latency, reliability, and GoodPut are derived. Furthermore, the effect of the number of packet replicas, blocklength, and cluster size on the network metrics is evaluated. Finally, the analytical derivations are utilized to find the optimal values for the number of packet replicas, blocklength, and power control parameters, such that the network GoodPut is maximized, subject to URLL constraints.

In vitro evaluation of regional nasal drug delivery using multiple anatomical nasal replicas of adult human subjects and two nasal sprays.

Quantifying drug delivery to the site of action using locally-acting nasal suspension sprays is a challenging but important step toward understanding bioequivalence (BE) between test and reference products. The main objective of this study was to investigate the in vitro deposition pattern of two common but different locally-acting nasal suspension sprays using multiple nasal cavities. Twenty anatomically accurate nasal replicas were developed from high-resolution sinonasal computed tomography scans of adults with healthy nasal airways. The airways were segmented into two regions of anterior and posterior to the internal nasal valve. Both sides of the septum were considered separately; hence, 40 nasal cavities were studied. The positioning of the spray nozzle in all 40 cavities was characterized by the head angle, coronal angle, and the insertion depth. Despite using a controlled protocol to minimize the anterior losses, a wide range of variability in posterior drug delivery was observed. The observed intersubject variability using this in vitro method may have important implications for understanding BE of locally-acting nasal suspension sprays.

Design Principles for a Novel Lightweight Configurable PUF Using a Reconfigurable FET

This article presents a mixed signal-based novel configurable ring oscillator (CRO) physical unclonable function (PUF) architecture for resource constrained Internet of Things (IoT) devices. PUF can protect the IoT devices through their unique inherited fingerprints obtained from the manufacture variations. However, the conventional ring oscillator (RO) PUF need multiple replicas of ROs to produce a large set of challenge response pairs (CRPs) which invalidates its usage in an IoT environment. Using the concept of reconfigurable hetero material hetero dielectric FET (HM-HD-RFET) proposed in this manuscript, we have designed a novel CRO which allows 512 challenges and a sigma delta analog to digital converter (ADC) at the end generates a stream of response bits. HM-HD-RFET can be configured into four different combinations of transistors through two polarity gates (PGs) and their switching can be controlled using a control gate (CG). Next, we compare HM-HD-RFET with configurable silicon FET (Si-RFET) and homogenous dielectric FET (HM-RFET) to show that the proposed device performs well in all of the four configurations with negligible ambipolarity. The device characteristics is realized in Silvaco Atlas tool, circuit implementation is done in Cadence using Verilog-A based look table approach and properties of CRO PUF are computed in MATLAB.

Mutation-mediated influences on binding of anaplastic lymphoma kinase to crizotinib decoded by multiple replica Gaussian accelerated molecular dynamics

Anaplastic lymphoma kinase (ALK) has been thought to be a prospective target of anti-drug resistance design in treatment of tumors and specific neuron diseases. It is highly useful for the seeking of possible strategy alleviating drug resistance to probe the mutation-mediated effect on binding of inhibitors to ALK. In the current work, multiple replica Gaussian accelerated molecular dynamics (MR-GaMD) simulations, molecular mechanics generalized Born surface area (MM-GBSA) and free energy landscapes were coupled to explore influences of mutations L1198F, L1198F/C1156Y, and C1156Y on the binding of the first ALK inhibitor crizotinib to ALK. The results suggest that three mutations obviously affect structural flexibility, motion modes and conformational changes of ALKs. L1198F and L1198F/C1156Y strengthen the binding of crizotinib to the mutated ALKs but C1156Y induces evident drug resistance toward crizotinib. Analyses of free energy landscapes show that stability in the orientation and positions of crizotinib relative to ALK plays a vital role in alleviating drug resistance of mutations toward crizotinib. Residue-based free energy decomposition method was utilized to evaluate the contributions of separate residues to the binding of crizotinib. The results not only indicate that the tuning of point mutation L1198F on interaction networks of crizotinib with ALK can be regarded as a possible strategy to relieve drug resistance of the mutated ALK but also further verify that residues L1122, V1130, L1196, L1198, M1199, and L1256 can be used as efficient targets of anti-drug resistance design induced by mutations.

A Survey on Integrity Auditing for Data Storage in the Cloud: From Single Copy to Multiple Replicas

The rapid advancement of cloud computing has promoted the development of cloud storage services. One of the biggest concerns of cloud users is whether the completeness and recoverability of data can be guaranteed when cloud servers encounter problems. Only when the integrity of data is fully guaranteed can users consume cloud storage with confidence, especially in a complicated cloud environment with multiple clouds. However, the literature still lacks a thorough survey on cloud data integrity auditing for both single copy and multiple replicas. In this article, we survey and compare existing auditing schemes for single copy and multiple replicas based on a set of criteria. Based on our review and analysis, we discuss open issues, potential applications and future directions in the field of the integrity auditing in the cloud, including the implications of such trendy topics as merging blockchain and edge computing into data integrity auditing.

Optimal Irregular Repetition Slotted ALOHA Under Total Transmit Power Constraint in IoT-Oriented Satellite Networks

In this article, we propose an optimal irregular repetition slotted ALOHA (IRSA) under total transmit power constraint for random access (RA) in the Internet-of-Things (IoT)-oriented satellite networks, which is named as an optimal power-limited IRSA (PL-IRSA). In this proposal, the total transmit power for each satellite machine-type device (SMD) within a frame is considered to be the same and equally allocated into its multiple packet replicas. Due to a variant number of packet replicas, the transmit power of each packet replica for different SMDs may be different. The difference of transmit powers of packet replicas and path loss enhance the received power diversity, which is able to improve the throughput by using the capture effect. At the receiver side, we introduce a semi-analytical (SEA) model to approximate the physical-layer decoding and derive an asymptotic packet loss rate (PLR) based on this SEA model. From the derived results, an optimization problem is formulated and solved to find out the optimal degree distributions for different total transmit powers and code rates, which maximize the normalized system throughput. The simulation results demonstrate that the proposed optimal PL-IRSA can lead to significant performance improvement with respect to conventional ones.

Novel external-loop-airlift milliliter scale bioreactors for cell growth studies: Low cost design, CFD analysis and experimental characterization

Many researchers have limited access to fully equipped laboratory-scale batch bioreactors and chemostats due to their relatively high cost. This becomes particularly prohibitive when multiple replicas of the same experiment are required, but not enough bioreactors are available to operate simultaneously. Additionally, experiments using shaken flasks are common but show significant limitations in terms of maintaining homogeneous conditions in liquid cultures or installing instrumentation for monitoring. Here, we proposed to tackle this significant hurdle by providing a route to make available the manufacture of low-cost, milliliter-scale bioreactors. This approach seems plausible for enabling proof-of-concept experiments before moving to a larger scale without significant investments. The conceptually designed systems were based on external-loop bioreactors due to their flexibility, simplicity, and ease of assembling and testing. Designs were initially evaluated in silico with the aid of COMSOL Multiphysics. The successfully evaluated systems were then constructed via additive manufacturing and assembled for hydrodynamics testing via tracer methods. This was enabled by a newly home-made optical absorbance sensor (OAS) for in-line and real-time measurements. Both the in silico and experimental results indicated close to ideal mixing conditions and low shear stress. Cell growth curves were prepared by culturing Escherichia coli and following its cell density in real-time. Our cell growth rate and maximum cell density were similar to those previously obtained in closely related systems. Therefore, the proposed bioreactors are an affordable alternative for batch and continuous cell growth studies rapidly and inexpensively.

Dynamic Proof of Data Possession and Replication With Tree Sharing and Batch Verification in the Cloud

Cloud storage attracts a lot of clients to join the paradise. For a high data availability, some clients require their files to be replicated and stored on multiple servers. Because clients are generally charged based on the redundancy level required by them, it is critical for clients to obtain convincing evidence that all replicas are stored correctly and are updated to the up-to-date version. In this article, we propose a dynamic proof of data possession and replication (DPDPR) scheme, which is proved to be secure in the defined security model. Our scheme shares a single authenticated tree across multiple replicas, which reduces the tree's storage cost significantly. Our scheme allows for batch verification for multiple challenged leaves and can verify multiple replicas in a single batch way, which considerably save bandwidth and computation resources during audit process. We also evaluate the DPDPR's performance and compare it with the most related scheme. The evaluation results show that our scheme saves almost 66 percent tree's storage cost for three replicas, and obtains almost 60 and 80 percent efficiency improvements in terms of the overall bandwidth and computation costs, respectively, when three replicas are checked and each challenged with 460 blocks.

Anthropogenic soils and landscapes of European Russia: Summer school from sea to sea—A didactic prototype

AbstractField excursions and trainings are considered a key component of education programs in soil and environmental sciences. They allow mastering students’ practical skills in sampling and onsite assessments and improve understanding of ecosystem integrity and complexity. Urbanization has a substantial impact on soil properties and functions; however, field courses focused on urban soils are rare. We present a didactic prototype and the outcomes of the “Monitoring, Modeling, and Management of Urban Green Infrastructure and Soils (3MUGIS)” summer school—the first educational tour observing anthropogenic soils and landscapes along the bioclimatic gradient in European Russia, from tundra to dry steppes. Didactic learning was based on a studying‐by‐doing approach; students were involved in environmental assessment in multiple regions varying in climatic and socioeconomic features. Considering the high spatial heterogeneity of urban ecosystems, we used express techniques (portable X‐ray fluorescence, infrared gas analyzers) for onsite soil analysis at multiple replicas. The data collected were discussed with local and international experts from Russia, Germany, the United States, and France in the context of regional environmental problems (e.g., pollution, soil degradation, and urban expansion). Students discovered zonal changes in vegetation (e.g., increasing tree height and diversity from north taiga to forest steppes) and soil properties (e.g., a gradual increase in pH and changes in soil organic C), as well as urban‐specific processes and features (e.g., urban heat island effect or soil artifacts). The overall student feedback was very positive (50.8% excellent, 36% good); some specific organizational issues will be addressed for future 3MUGIS summer schools.

Quantum anomalous Hall effect in twisted bilayer graphene quasicrystal**Project supported by the National Natural Science Foundation of China (Grant Nos. 11774325 and 21603210), the National Key Research and Development Program of China (Grant No. 2017YFA0204904), and Fundamental Research Funds for the Central Universities, China.

The nontrivial topology is investigated in a dodecagonal quasicrystal made of 30° twisted bilayer graphene (TBG). Based on tight-binding model with both exchange field and Rashba spin–orbit coupling, the topological index, chiral edge states, and quantum conductance are calculated to distinguish its unique topological phase. A high Bott index (B = 4) quantum anomalous Hall effect (QAHE) is identified in TBG quasicrystal, which is robust to a finite perturbation without closing the nontrivial gap. Most remarkably, we have found that the multiple Dirac cone replicas in TBG quasicrystal are only a spectra feature without generating extra chiral edge states. Our results not only propose a possible way to realize the QAHE in quasicrystal, but also identify the continuity of nontrivial topology in TBG between crystal and quasicrystal.

Toward Highly Scalable Load Balancing in Kubernetes Clusters

Container-based virtualization has recently been flourishing due to its ease of deployment and flexibility of resource provisioning. Kubernetes, a well-known open source project, is an orchestration platform for containerized applications. Herein, applications can have multiple replicas to provide high scalability and availability, but some applications for stateful service require a leader to be elected to maintain consistency and coordinate tasks among the replicas. In this article, the Kubernetes architecture is first analyzed by focusing on load balancing, a leader election algorithm, and a leader-based consistency maintenance mechanism. Then we address the following challenges: the leader has heavy loads due to its inherent design, and the Kubernetes leader election algorithm cannot evenly distribute the leader throughout nodes. Finally, experimental results are provided to prove the importance of leader distribution throughout nodes in the cluster for highly scalable load balancing.

Generation and application of river network analogues for use in ecology and evolution.

Several key processes in freshwater ecology are governed by the connectivity inherent to dendritic river networks. These have extensively been analyzed from a geomorphological and hydrological viewpoint, yet structures classically used in ecological modeling have been poorly representative of the structure of real river basins, often failing to capture well‐known scaling features of natural rivers. Pioneering work identified optimal channel networks (OCNs) as spanning trees reproducing all scaling features characteristic of natural stream networks worldwide. While OCNs have been used to create landscapes for studies on metapopulations, biodiversity, and epidemiology, their generation has not been generally accessible.Given the increasing interest in dendritic riverine networks by ecologists and evolutionary biologists, we here present a method to generate OCNs and, to facilitate its application, we provide the R‐package OCNet. Owing to the stochastic process generating OCNs, multiple network replicas spanning the same surface can be built; this allows performing computational experiments whose results are irrespective of the particular shape of a single river network. The OCN construct also enables the generation of elevational gradients derived from the optimal network configuration, which can constitute three‐dimensional landscapes for spatial studies in both terrestrial and freshwater realms. Moreover, the package provides functions that aggregate OCNs into an arbitrary number of nodes, calculate several descriptors of river networks, and draw relevant network features.We describe the main functionalities of the package and its integration with other R‐packages commonly used in spatial ecology. Moreover, we exemplify the generation of OCNs and discuss an application to a metapopulation model for an invasive riverine species.In conclusion, OCNet provides a powerful tool to generate realistic river network analogues for various applications. It thereby allows the design of spatially realistic studies in increasingly impacted ecosystems and enhances our knowledge on spatial processes in freshwater ecology in general.

High-resolution (diffraction limited) single-shot multiplexed coded-aperture ptychography

We propose and numerically explore a method that upgrades a conventional single-shot microscope into a single-shot ptychographic microscope, without impairing its optical performance. It is based on splitting the microscope’s intermediate image plane into multiple replicas, and detecting a set of their coded Fourier transform magnitudes, using a different sensor for each replica. To code each beam, it is transmitted through a distinct coding mask. A ptychographic phase-retrieval algorithm is used to reconstruct the imaged object’s complex-valued transmission function. The proposed method also enables ultrahigh-speed imaging by using a pulse-burst as illumination and applying a multi-state reconstruction algorithm. This approach paves the way to both single-frame and ultrahigh-speed, diffraction-limited microscopy of complex-valued objects.

Effects of Disulfide Bonds on Binding of Inhibitors to β-Amyloid Cleaving Enzyme 1 Decoded by Multiple Replica Accelerated Molecular Dynamics Simulations.

The β-amyloid cleaving enzyme 1 (BACE1) has been thought to be an efficient target for treatment of Alzheimer's disease (AD). Deep insight into inhibitor-BACE1 binding mechanism is of significance for design of potent drugs toward BACE1. In this work, multiple replica accelerated molecular dynamics (MR-aMD) simulations, principal component (PC) analysis, and free energy landscapes were integrated to decode the effect of disulfide bonds (SSBs) in BACE1 on bindings of three inhibitors 3KO, 3KT, and 779 to BACE1. The results from cross-correlation analysis suggest that the breaking of SSBs exerts significant influence on structural flexibility and internal dynamics of inhibitor-bound BACE1. PC analysis and free energy landscapes reveal that the breaking of SSBs not only evidently induces the conformational rearrangement of BACE1 but also highly changes binding poses of three inhibitors in BACE1 and leads to more disordered binding of three inhibitors to BACE1, which is further supported by the increase in binding entropy of inhibitors to BACE1 due to the breaking of SSBs. Residue-based free energy decomposition method was utilized to evaluate contributions of separate residues to inhibitor-BACE1 binding. The results suggest that although the breaking of SSBs in BACE1 does not destroy the interaction network of inhibitors with BACE1 it changes interaction strength of some residues with inhibitors. Meanwhile, the information from residue-based free energy decomposition indicates that residues L91, S96, V130, Y132, Q134, W137, F169, I171, and I179 can be used as efficient targets of drug design toward BACE1.

Effective replica management for improving reliability and availability in edge-cloud computing environment

The multi-replica strategy can create multiple data replicas for the edge cloud system and store them in different DataNodes, which improves data availability and data service quality. However, the storage resources of DataNodes are limited and the user demand for data is time-varying, the unreasonable number of data replicas will cause a high storage burden on the file system or low data service quality. Therefore, the number of data replicas needs to be dynamically adjusted according to the actual situation. Based on this, a dynamic replica creation strategy based on the gray Markov chain is proposed. If the number of replicas needs to be increased, the newly added replicas need to be placed on the DataNodes. Considering the problem of load balancing of the DataNode during replica placement, this paper proposes a replica placement strategy based on the Fast Non-dominated Sorting Genetic algorithm. In addition, considering the problem of data replica synchronization and the data recovery of failed DataNodes in the edge cloud system, this paper proposes a delay-adaptive replica synchronization strategy and a load-balancing based replica recovery strategy. Finally, the experiments prove the effectiveness of the proposed strategies.

The design of Apache IoTDB distributed framework

Apache Internet of Things Database (IoTDB) is a new open-source timeseries database management system. A distributed data management system not only needs to solve the problem of metadata synchronization between nodes caused by data partition and multiple replicas, but also needs to support efficient query request processing. To solve the problem of metadata synchronization among nodes, we propose a dual-layer granularity metadata management strategy. Based on the consistency hash partitioning method and Raft protocol, we designed a distributed framework that supports both strong consistency query and eventual consistency query. Based on the single-machine version of Apache IoTDB, we carried out the system implementation and experimental test. Compared with the single-level granularity management strategy, the test results showed that the two-level granularity metadata management strategy takes less memory resources and improves the write performance by $5%\sim10%$. Also, the results showed that the read and write performance of the distributed Apache IoTDB increases linearly with the extension of cluster size.

Congestion-Aware Geocast Routing in Vehicular Delay-Tolerant Networks

Vehicular Delay-Tolerant Networks (VDTNs) are networks of vehicles that communicate wirelessly, where there are no permanent end-to-end connections. VDTNs have a highly variable topology, with frequent partitions, and possibly low node density. Thus, delay-tolerant routing adopts a store-carry-and-forward message transfer paradigm, where messages have a useful Time-To-Live (TTL) and are stored until a good contact opportunity arises. Multiple message replicas can be generated to improve delivery probability at the cost of increasing network congestion. In this paper, we propose the V-GRADIENT geocast routing protocol that monitors node density, buffer occupancy, and interest in geocast groups, to adapt the forwarding techniques used dynamically, to disseminate messages within the geographic region of interest. Simulation results show that the V-GRADIENT is capable of controlling network congestion and efficiently delivering messages resulting in better delivery ratios, lower latencies, and a small increase in overhead when compared with existing protocols.

Improving Temperature Generator in Parallel Tempering Simulation in the NPT Condition.

Parallel tempering (PT) simulations provide a powerful computational tool to accelerate conformational searches of complex molecular systems. In this method, multiple replica systems assigned to different temperatures run in parallel and undergo tandem replica exchange events to enhance conformational mixing in temperature space. Efficient PT simulations require a uniform acceptance ratio across all the replicas. In the context of a previous energy distribution-based temperature generation (TG) scheme, we propose an improved TG protocol to maintain such a uniform exchange probability in general PT simulations.

Reconstruction of ARNT PAS-B Unfolding Paths by Steered MD and Artificial Neural Network Reveals New Putative Binding Conformations

Several proteins have been identified that can switch between different folds, expanding their functional role through previously unknown binding interactions. In this context, experimental evidence suggests that the PAS-B domain of the Aryl Hydrocarbon Receptor Nuclear Translocator protein (ARNT) has a fragile β-sheet structure that can undergo a +3 register shift upon a single mutation, changing its dimerization surface. Both unfolding and interconversion mechanisms require the same uncharacterized partially-unfolded state. Single-molecule Atomic Force Microscopy measurements (AFM) confirmed that the ARNT PAS-B domain is mechanically labile and revealed two distinct unfolding pathways, one following a single-stage mechanism, and the other showing an intermediate state. An atomistic characterisation of unfolding paths and relevant intermediate states has been carried out to identify new ARNT conformations possibly involved in partner recruitment. The unfolding pathways for ARNT PAS-B were simulated by steered Molecular Dynamics. Multiple replicas were recorded to explore different paths at low pulling speed. The overall model of unfolding was then reconstructed using a self-organizing map (SOM), a type of artificial neural network with an explicit visual representation. The map was trained on inter-residue distances of native contacts. The SOM model clearly depicts two alternative pathways in a human-understandable two-dimensional map. Retracing of single replicas on the map highlights a two-stage mechanism with initial unfolding of the C-terminal strand in 1/3 of the simulations, in agreement with AFM findings. Shortest path analysis on the map correctly detects replicas with minimal steering work. The partially-folded states extracted from the map could have a role in selectivity for partner recruitment during ARNT transcriptional activity.

Destabilization and Resisting Growth of Alpha-Synuclein Fibril by Synuclean-D

Parkinson's disease (PD) is a major health condition, but current medications provide only symptomatic relief. The disease is associated with oligomerization of α-synuclein peptides into fibrils in neurons. An effective approach to prevent PD is to use molecular modalities that prevent the growth of nascent fibrils and/or destabilize pre-formed fibrils. Here, we explore the interactions of α-synuclein fibril with SynuClean-D (SCD), a newly discovered drug against PD, by docking, atomistic molecular dynamics (MD) simulations, and enhanced sampling techniques. Our aim is to investigate the mechanism by which SCD might destabilize and/or block the growth of α-synuclein fibrils. Initially, we performed SCD docking to the fibril and found that in the best predicted binding pose, SCD is completely inserted into the fibril core. Furthermore, to investigate the effect of SCD on the fibril, multiple replicas were simulated for 400 ns each in the presence and absence of SCD. The simulations showed that SCD significantly reduces the fibril-backbone H-bonding, thus affecting fibril stability. Next, in order to examine if SCD can enter the core spontaneously, we simulated 10 flooding simulations with 20 randomly distributed copies of SCD surrounding the fibril. In 20% cases, SCD arrived into the core through the end of the fibril and bound to the same domain found by docking. Steered MD simulations and umbrella sampling free energy calculations identified defects in the fibril, caused by loose inter-peptide interactions, through which SCD can enter the interior of the fibril. Moreover, detailed occupancy and clustering analyses of the flooding simulations revealed that SCD made strong interactions with the fibril end, demonstrating its potential to also inhibit fibril growth. These findings are novel in the context of drug-amyloid fibril interactions and offer a platform to design new drug molecules targeting α-synuclein fibrils.