Loop Network Research Articles

Dystonia

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements or postures. Currently, dystonia is defined as a network disorder involving the basal ganglia, cerebellum, thalamus, and sensorimotor cortex. Considering that it is refractory to medical therapy, functional neurosurgery is indispensable in the treatment strategy for dystonia. Functional neurosurgery may improve dystonic symptoms by suppressing abnormal neuronal activity in the motor loop network. Deep brain stimulation(DBS)of the globus pallidus internus(GPi)is a useful surgical treatment for genetically defined and primary dystonia involving the axial musculature. Thalamic ventral oral(Vo)nucleus surgery is recommended for cases of peripheral dystonia, such as writer's cramp and other occupational types of dystonia. However, pallidal DBS is less effective in cases of secondary dystonia, with the exception of tardive dystonia. Recent studies have reevaluated that ablation surgery is the last-resort treatment when DBS must be discontinued for certain conditions. Magnetic resonance-guided focused ultrasound(MRgFUS), a novel, incision-free, ablation technique, is currently used for the treatment of focal hand dystonia.

Simulasi Modifikasi Konfigurasi Jaringan Spindel Menjadi Loop Tertutup Untuk Meningkatkan Keandalan Sistem Distribusi Menggunakan Software ETAP

Distribution reliability network rely on to any factor such as material quality, maintenance, operational pattern, protection device and also network configuration. In the spindle network the level of network reliability is level 3 (SPLN 52-3, 1983: 5). In order to leveling up the network reliability from level 3 to level 5 (zero down time)[2][3] we need to modify the protection system from overcurrent relay and ground fault relay to line differential relay in each distribution substation. Beside that Load Break Switch in each customer cubicle substation and in the connection substation should replaced by circuit breaker. Spindle network which operated open loop in the connection substation switch to normally close operated, so it can be called as closed loop network. This modification purpose is ther is no down time in case off ground fault or phase to phase sort circuit on the network cable. Before this kind of modification and the setting applied into real network, we make a simulation using an application called ETAP and no missmatch trip from 7 time experiment consist of ground fault and phase to phase short circuit in 7 cable

Clocking cancer: the circadian clock as a target in cancer therapy.

Disruption of the cellular pathway modulating endogenous 24-h rhythms, referred to as "the circadian clock", has been recently proven to be associated with cancer risk, development, and progression. This pathway operates through a complex network of transcription-translation feedback loops generated by a set of interplaying proteins. The expression of core circadian clock genes is frequently dysregulated in human tumors; however, the specific effects and underlying mechanisms seem to vary depending on the cancer types and are not fully understood. In addition, specific oncogenes may differentially induce the dysregulation of the circadian clock in tumors. Pharmacological modulation of clock components has been shown to result in specific lethality in certain types of cancer cells, and thus holds great promise as a novel anti-cancer therapeutic approach. Here we present an overview of the rationale and current evidence for targeting the clock in cancer treatment.

Experimental phase control of a 100 laser beam array with quasi-reinforcement learning of a neural network in an error reduction loop.

An innovative scheme is proposed for the dynamic phase control of a laser beam array. It is based on a simple neural network included in a phase correction loop that predicts the complex field array from the intensity of the induced scattered pattern through a phase intensity transformer made of a diffuser. A crucial feature is the use of a kind of reinforcement learning approach for the neural network training which takes account of the iterated corrections. Experiments on a proof-of-concept system demonstrated the high performance and scalability of the scheme with an array of up to 100 laser beams and a phase setting at λ/30.

Cusp properties of high harmonic loops

In determining the gravitational signal of cusps from a network of cosmic string loops, a number of key parameters have to be assumed. These include the typical number of cusps per period of string oscillation and the typical values of the sharpness parameters of left- and right-moving waves on the string, evaluated at the cusp event. Both of these are important, as the power stored in the gravitational waves emitted from the loops of string is proportional to the number of cusps per period and inversely proportional to the product of the sharpness parameters associated with the left- and right-moving modes on the string. In suitable units, both of these quantities are usually thought to be of order unity. To try and place these parameters on a more robust footing, we analyze in detail a large number of randomly chosen loops of string that can have high harmonics associated with them, such as one might expect to form by chopping off an infinite string in the early Universe. This allows us to analyze tens of thousands of loops and obtain detailed statistics on these crucial parameters. While we find in general the sharpness parameters are indeed close to unity, as assumed in previous work [with occasional exceptions where they can become $O({10}^{\ensuremath{-}2})$], the cusp number per period scales directly with the number of harmonics on the loop and can be significantly larger than unity. This opens up the possibility of larger signals than would have otherwise been expected, potentially leading to tighter bounds on the dimensionless cosmic string tension $G\ensuremath{\mu}$.

Stormwater hydrographs simulated for different structures of urban drainage network: dendritic and looped sewer networks

ABSTRACT Despite urban drainage pipe networks being of great significance to urban flood control, few studies have focused on the influence of urban drainage pipe network structure on hydrological response. We studied two areas in downtown Dongying, Shandong Province, China, which have dendritic and loop drainage pipe networks, respectively. The loop network was converted to a dendritic system for scenario analysis using numerical simulation. Comparing the hydrological response of the original drainage system and the converted system showed that although the dendritic network could reduce node flood volume, the dendritic pipe overload situation was inferior to the loop network. Runoff in the former network was predominantly concentrated in the main pipes and near the outlets and the discharge-peak at the outlet was 47.0% greater than that of the loop. Thus, the loop drainage pipe network is more likely to reduce peak runoff at the outlet, which helps decrease flood risk.

Adaptation and convergence in circadian\u2010related genes in Iberian freshwater fish

BackgroundThe circadian clock is a biological timing system that improves the ability of organisms to deal with environmental fluctuations. At the molecular level it consists of a network of transcription-translation feedback loops, involving genes that activate (bmal and clock – positive loop) and repress expression (cryptochrome (cry) and period (per) – negative loop). This is regulated by daily alternations of light but can also be affected by temperature. Fish, as ectothermic, depend on the environmental temperature and thus are good models to study its integration within the circadian system. Here, we studied the molecular evolution of circadian genes in four Squalius freshwater fish species, distributed across Western Iberian rivers affected by two climatic types with different environmental conditions (e.g., light and temperature). S. carolitertii and S. pyrenaicus inhabit the colder northern region under Atlantic climate type, while S. torgalensis, S. aradensis and some populations of S. pyrenaicus inhabit the warmer southern region affected by summer droughts, under Mediterranean climate type.ResultsWe identified 16 circadian-core genes in the Squalius species using a comparative transcriptomics approach. We detected evidence of positive selection in 12 of these genes using methods based on dN/dS. Positive selection was mainly found in cry and per genes of the negative loop, with 55 putatively adaptive substitutions, 16 located on protein domains. Evidence for positive selection is predominant in southern populations affected by the Mediterranean climate type. By predicting protein features we found that changes at sites under positive selection can impact protein thermostability by changing their aliphatic index and isoelectric point. Additionally, in nine genes, the phylogenetic clustering of species that belong to different clades but inhabit southern basins with similar environmental conditions indicated evolutionary convergence. We found evidence for increased nonsynonymous substitution rate in convergent lineages, likely due to positive selection at 27 sites, mostly in cry genes.ConclusionsOur results support that temperature may be a selective pressure driving the evolution of genes involved in the circadian system. By integrating sequence-based functional protein prediction with dN/dS-based methods to detect selection we uncovered adaptive convergence in the southern populations, probably related to their similar thermal conditions.

Dynamic Optimization Method of Transmission Line Parameters Based on Grey Support Vector Regression

Aiming at the problem of insufficient accuracy and timeliness of transmission line parameters in the grid energy management system (EMS) parameter library, a dynamic optimization method of transmission line parameters based on grey support vector regression is proposed. Firstly, the influence of operating conditions and meteorological factors on the changes of parameters is analyzed. Based on this, the correlation quantification method of transmission line parameters is designed based on Pearson coefficient, and the influence coefficient value is obtained. Then, with the influence coefficient as the constraint condition, a method for selecting strong influence characteristics of line parameters based on improved Elastic Net is proposed. Finally, based on the grey prediction theory, a grey support vector regression (GM-SVR) parameter optimization model is constructed to realize the dynamic optimization of line parameter values under the power grid operation state. The effectiveness and feasibility of the proposed method is verified through the commissioning of the reactance parameters of the actual local loop network transmission line.

Optimal Design of Pipe Networks Accounting for Future Demands and Phased Expansion using Integrated Dynamic Programming and Differential Evolution Approach

The water distribution network (WDN) design comprises determining optimal pipe sizes to achieve minimum cost pipe network to meet the required demands and performance levels. However, with time, the water demand for any region changes due to population, migration, and lifestyles, so interventions need to be made to the existing WDNs. Therefore, the capacity expansion problem consists of determining the suitable interventions at various stages such that the required demands are met at minimum cost. The present study proposed a novel methodology for planning such interventions based on Dynamic Programming (DP) formulation and presented a combined Self-Adaptive Differential Evolution and DP (SADE-DP) methodology for solving the WDN expansion problems considering life cycle costs. The methodology is applied and tested on three benchmark WDNs, namely New York Tunnel (NYT), Two loop (TL), and Blacksburg (BLA) networks, and also for a real case study of the Badlapur WDN in Maharashtra, India. The proposed model solutions are validated by comparing them with other WDN expansion methods taken from the literature. The results indicate that the proposed SADE-DP approach is computationally efficient and provides cost-effective solutions by meeting desired performance levels at various stages, and can serve as a potential alternative for solving real-world WDN expansion problems.

Four-Port Symmetrical Reflectionless Lumped Filter/Diplexer: Prototype and Design Table

It is shown that a well-designed lumped $LC$ loop network with a phase inverter can exhibit perfect reflectionless filtering response at its all four ports. The network is composed of two pairs of symmetrical $LC$ ladder circuits, in which one pair is obtained from lowpass transformation at a prescribed frequency based on a special lowpass prototype, and the other pair is from highpass transformation based on the same prototype at the same frequency. The input power, at any port, is divided into the two adjacent ports in the frequency domain through different paths of the loop. Each path between any two ports nearby can be treated as a mono-functional filter, whereas the adjacent two paths work as two filters with complementary responses. The overall circuit performs as a generalized diplexer without a specified “common” or “separation/combination” port. By using a numerical equation solver, the element values of the reflectionless lowpass/highpass prototype filter of order one, three, five, and seven are given. Then, the values of order nine, eleven, thirteen, and fifteen are obtained by using the optimization method. Other filtering functions such as bandpass/bandstop or dual-band can be easily implemented with the proposed prototype by using the standard frequency transformation method. For verification, two sample filters are fabricated and measured. The experimental data agree well with the predictions.

DStudy on small interference analysis and transmission capacity of UHVAC loop power grid of Shandong–Hebei

This paper studies the main operation characteristics, small interference analysis and transmission capacity of UHVAC in Shandong- Hebei loop power grid. It mainly includes the small interference characteristics and section transmission limit analysis of the certain area under the typical mode and maintenance mode, then the operation limit would be defined, so as to provide basic work for the safety and stability calculation of the loop network in the next stage.

Construction of a TF\u2013miRNA\u2013gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease and the most common type of neuromuscular disease. Genes and miRNAs associated with MG have been widely studied; however, the molecular mechanisms of transcription factors (TFs) and the relationship among them remain unclear. A TF–miRNA–gene network (TMGN) of MG was constructed by extracting six regulatory pairs (TF–miRNA, miRNA–gene, TF–gene, miRNA–TF, gene–gene and miRNA–miRNA). Then, 3/4/5-node regulatory motifs were detected in the TMGN. Then, the motifs with the highest Z-score, occurring as 3/4/5-node composite feed-forward loops (FFLs), were selected as statistically significant motifs. By merging these motifs together, we constructed a 3/4/5-node composite FFL motif-specific subnetwork (CFMSN). Then, pathway and GO enrichment analyses were performed to further elucidate the mechanism of MG. In addition, the genes, TFs and miRNAs in the CFMSN were also utilized to identify potential drugs. Five related genes, 3 TFs and 13 miRNAs, were extracted from the CFMSN. As the most important TF in the CFMSN, MYC was inferred to play a critical role in MG. Pathway enrichment analysis showed that the genes and miRNAs in the CFMSN were mainly enriched in pathways related to cancer and infections. Furthermore, 21 drugs were identified through the CFMSN, of which estradiol, estramustine, raloxifene and tamoxifen have the potential to be novel drugs to treat MG. The present study provides MG-related TFs by constructing the CFMSN for further experimental studies and provides a novel perspective for new biomarkers and potential drugs for MG.

Cellular clocks in hyperoxia effects on [Ca2+]i regulation in developing human airway smooth muscle.

Supplemental O2 (hyperoxia) is necessary for preterm infant survival but is associated with development of bronchial airway hyperreactivity and childhood asthma. Understanding early mechanisms that link hyperoxia to altered airway structure and function are key to developing advanced therapies. We previously showed that even moderate hyperoxia (50% O2) enhances intracellular calcium ([Ca2+]i) and proliferation of human fetal airway smooth muscle (fASM), thereby facilitating bronchoconstriction and remodeling. Here, we introduce cellular clock biology as a novel mechanism linking early oxygen exposure to airway biology. Peripheral, intracellular clocks are a network of transcription-translation feedback loops that produce circadian oscillations with downstream targets highly relevant to airway function and asthma. Premature infants suffer circadian disruption whereas entrainment strategies improve outcomes, highlighting the need to understand relationships between clocks and developing airways. We hypothesized that hyperoxia impacts clock function in fASM and that the clock can be leveraged to attenuate deleterious effects of O2 on the developing airway. We report that human fASM express core clock machinery (PER1, PER2, CRY1, ARNTL/BMAL1, CLOCK) that is responsive to dexamethasone (Dex) and altered by O2. Disruption of the clock via siRNA-mediated PER1 or ARNTL knockdown alters store-operated calcium entry (SOCE) and [Ca2+]i response to histamine in hyperoxia. Effects of O2 on [Ca2+]i are rescued by driving expression of clock proteins, via effects on the Ca2+ channels IP3R and Orai1. These data reveal a functional fASM clock that modulates [Ca2+]i regulation, particularly in hyperoxia. Harnessing clock biology may be a novel therapeutic consideration for neonatal airway diseases following prematurity.

Short loop functional commonality identified in leukaemia proteome highlights crucial protein sub-networks.

Direct drug targeting of mutated proteins in cancer is not always possible and efficacy can be nullified by compensating protein–protein interactions (PPIs). Here, we establish an in silico pipeline to identify specific PPI sub-networks containing mutated proteins as potential targets, which we apply to mutation data of four different leukaemias. Our method is based on extracting cyclic interactions of a small number of proteins topologically and functionally linked in the Protein–Protein Interaction Network (PPIN), which we call short loop network motifs (SLM). We uncover a new property of PPINs named ‘short loop commonality’ to measure indirect PPIs occurring via common SLM interactions. This detects ‘modules’ of PPI networks enriched with annotated biological functions of proteins containing mutation hotspots, exemplified by FLT3 and other receptor tyrosine kinase proteins. We further identify functional dependency or mutual exclusivity of short loop commonality pairs in large-scale cellular CRISPR–Cas9 knockout screening data. Our pipeline provides a new strategy for identifying new therapeutic targets for drug discovery.

N-terminal domain mutations of the spike protein are structurally implicated in epitope recognition in emerging SARS-CoV-2 strains

During the past two years, the world has been ravaged by a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acquired mutations in the SARS-CoV-2 genome affecting virus infectivity and/or immunogenicity have led to a number of novel strains with higher transmissibility compared to the original Wuhan strain. Mutations in the receptor binding domain (RBD) of the SARS-CoV-2 spike protein have been extensively studied in this context. However, mutations and deletions within the N-terminal domain (NTD) located adjacent to the RBD are less studied. Many of these are found within certain β sheet-linking loops, which are surprisingly long in SARS-CoV-2 in comparison to SARS-CoV and other related β coronaviruses. Here, we perform a structural and epidemiological study of novel strains carrying mutations and deletions within these loops. We identify short and long-distance interactions that stabilize the NTD loops and form a critical epitope that is essential for the recognition by a wide variety of neutralizing antibodies from convalescent plasma. Among the different mutations/deletions found in these loops, Ala 67 and Asp 80 mutations as well as His 69/Val 70 and Tyr 144 deletions have been identified in different fast-spreading strains. Similarly, deletions in amino acids 241–243 and 246–252 have been found to affect the network of NTD loops in strains with high transmissibility. Our structural findings provide insight regarding the role of these mutations/deletions in altering the epitope structure and thus affecting the immunoreactivity of the NTD region of spike protein.

Prepare for the Worst - Using Facility Location to Alleviate Product Recall Risks

This paper is motivated by major food product recall events in recent years, especially how the timely and effective response using post-recall management can make a difference. We consider the rare but very influential major product recalls as disruptions to the supply chain and incorporate locating reprocessing centers for the returned products to mitigate expected operational costs. We adopt the closed loop network design framework and assume the location decisions for reprocessing center take place after the product recall events. Our scenario-based analysis shows the approach is effective in both absolute and relative measures.

Double Loop Network for Combined Heating and Cooling in Low Heat Density Areas

This study investigated a double loop network operated with ultra-low supply/return temperatures of 45/25 °C as a novel solution for low heat-density areas in Denmark and compared the proposed concept with a typical tree network and with individual heat pumps to each end-users rather than district networks. It is a pump-driven system, where the separate circulation of supply and return flow increased the flexibility of the system to integrate and displace heating and cooling energy along the network. Despite the increased use of central and local water pumps to operate and control the system, the simulated overall pump energy consumption was 0.9% of the total energy consumption. This was also an advantage at the design stage as the larger pressure gradient, up to 570 Pa/m, allowed minimal pipe diameters. In addition, the authors proposed the installation of electrically heated vacuum-insulated micro tanks of 10 L on the primary side of each building substation as a supplementary heating solution to meet the comfort and hygiene requirements for domestic hot water (DHW). This, combined with supply water circulation in the loop network, served as a technical solution to remove the need for bypass valves during summer periods with no load in the network. The proposed double loop system reduced distribution heat losses from 19% to 12% of the total energy consumption and decreased average return temperatures from 33 °C to 23 °C compared to the tree network. While excess heat recovery can be limited due to hydraulic issues in tree networks, the study investigated the double loop concept for scenarios with heat source temperatures of 30 °C and 45 °C. The double loop network was cost-competitive when considering the required capital and operating costs. Furthermore, district networks outperformed individual heat pump solutions for low-heat density areas when waste heat was available locally. Finally, although few in Denmark envisage residential cooling as a priority, this study investigated the potential of embedding heating and cooling in the same infrastructure. It found that the return line could deliver cold water to the end-users and that the maximum cooling power was 1.4 kW to each end-user, which corresponded to 47% of the total peak heat demand used to dimension the double loop network.

Deciphering the dynamics of lamellipodium in a fish keratocytes model

Motile cells depend on an intricate network of feedback loops that are essential in driving cell movement. Integrin-based focal adhesions (FAs) along with actin are the two key factors that mediate such motile behaviour. Together, they generate excitable dynamics that are essential for forming protrusions at the leading edge of the cell and, in certain cases, traveling waves along the membrane. A partial differential equation (PDE) model of a self-organizing lamellipodium in crawling keratocytes has been previously developed to understand how the three spatiotemporal patterns of activity observed in such cells, namely, stalling, waving and smooth motility, are produced. The model consisted of three key variables: the density of barbed actin filaments, newly formed FAs called nascent adhesions (NAs) and VASP, an anti-capping protein that gets sequestered by NAs during maturation. Using parameter sweeping techniques, the distinct regimes of behaviour associated with the three activity patterns were identified. In this study, we convert the PDE model into an ordinary differential equation (ODE) model to examine its excitability properties and determine all the patterns of activity exhibited by this system. Our results reveal that there are two additional regimes not previously identified, including bistability and oscillatory-like type IV excitability (generated by three steady states and their manifolds, rather than limit cycles). These regimes are also present in the PDE model. Applying slow-fast analysis on the ODE model shows that it exhibits a canard explosion through a folded-saddle and that rough motility seen in keratocytes is likely due to noise-dependent motility governed by dynamics near the interface of bistability and type IV excitability. The two parameter bifurcation suggests that the increase in the proportion of rough motion is due to a shift in activity towards the bistable and type IV excitable regimes induced by a decrease in NA maturation rate. Our results thus provide important insight into how microscopic mechanical effects are integrated to produce the observed modes of motility.

How Retroactivity Affects the Behavior of Incoherent Feedforward Loops.

SummaryAn incoherent feedforward loop (IFFL) is a network motif known for its ability to accelerate responses and generate pulses. It remains an open question to understand the behavior of IFFLs in contexts with high levels of retroactivity, where an upstream transcription factor binds to numerous downstream binding sites. Here we study the behavior of IFFLs by simulating and comparing ODE models with different levels of retroactivity. We find that increasing retroactivity in an IFFL can increase, decrease, or keep the network's response time and pulse amplitude constant. This suggests that increasing retroactivity, traditionally considered an impediment to designing robust synthetic systems, could be exploited to improve the performance of IFFLs. In contrast, we find that increasing retroactivity in a negative autoregulated circuit can only slow the response. The ability of an IFFL to flexibly handle retroactivity may have contributed to its significant abundance in both bacterial and eukaryotic regulatory networks.

All Digital Phase-Locked Loop Networks for Clock Generation and Distribution: Network Stability, Convergence and Performance

In this paper, we study networks of coupled oscillators applied to the distributed synthesis of clock signals for large systems-on-chip. The oscillators are implemented as interconnected all-digital phase-locked loops (ADPLLs), which are asynchronous control systems. We address the issue of modelling, synchronization and stability of both a single ADPLL and interconnected ADPLLs. We prove that the stability domain is universal for large Cartesian networks, and it related to the domain for a single ADPLL. We show that within the stability domain the network synchronises to the reference signal both in frequency and phase. A hardware verification of Cartesian networks is presented, and it is consistent with our theoretical findings. The proposed design may be useful for multiples engineering and physics applications, including clock generation, distributed computations, beamforming, and other applications, where the control over time synchronicity is crucially important for the system performance.