Direct Switching Research Articles

Efficacy and Safety of Risankizumab in Patients with Psoriasis Showing Suboptimal Response to Secukinumab or Ixekizumab: Results from a Phase 3b, Open-Label, Single-Arm (aIMM) Study.

Risankizumab has demonstrated superior efficacy compared to other psoriasis treatments, including secukinumab, adalimumab, and ustekinumab; switching to risankizumab from other psoriasis treatments has shown superior clinical and quality of life (QoL) outcomes. We evaluated the efficacy and safety of directly switching patients with moderate-to-severe plaque psoriasis and a suboptimal response to interleukin (IL)-17 inhibitors (secukinumab or ixekizumab) to risankizumab. This 52-week, phase 3b study enrolled patients (≥ 18years) with moderate-to-severe plaque psoriasis who had previously been treated with the recommended dose of secukinumab or ixekizumab for ≥ 6months but did not achieve an optimal response (static Physician's Global Assessment [sPGA] 2/3; body surface are [BSA] 3- < 10%). Patients received subcutaneous risankizumab (150mg) without washout. The primary endpoint was the proportion of patients achieving sPGA of 0/1 at week 16. Secondary endpoints included sPGA 0/1 at week 52, sPGA 0, Dermatology Life Quality Index (DLQI) 0/1, and Psoriasis Symptoms Scale (PSS) 0 at weeks 16 and 52. Safety was monitored throughout the study. The study included 244 patients. sPGA 0/1 was achieved by 57.4% and 62.3% at week 16 and 52. At week 16, sPGA 0, DLQI 0/1, and PSS 0 were achieved by 20.5%, 40.2%, and 20.9%, respectively. At week 52, these proportions increased to 27.1% for sPGA 0, 47.2% for DLQI 0/1, and 27.5% for PSS 0. Most frequently reported adverse events (reported in ≥ 5% of patients) in risankizumab-treated patients were COVID-19 infection (8.6%) and nasopharyngitis (5.7%). No new safety signals were observed. Directly switching to risankizumab improved outcomes and QoL in patients with moderate-to-severe psoriasis who had suboptimal responses to anti-IL-17 inhibitors (secukinumab or ixekizumab). The safety results are consistent with previously reported safety of risankizumab. This study supports the efficacy of risankizumab in patients previously treated with biologics, including IL-17 inhibitors, and suggests a direct switch to risankizumab for improved clinical outcomes and QoL. ClinicalTrials.gov identifier: NCT04102007.

Novel modular multilevel matrix converter topology for efficient high-voltage AC-AC power conversion

Introduction. This paper delves into the practical application of multilevel technology, particularly focusing on the capacitor-clamped converter as a promising solution for medium-to-high voltage power conversion, with specific emphasis on direct AC-AC switching conditions. Problem. The limitations of conventional single-cell matrix converters (MC) in efficiency and performance for medium-to-high voltage power conversion applications are well-recognized. Goal. The primary objective is to investigate the performance of the 3 phase modular multilevel matrix converter (3MC) with three flying capacitors (FCs) modeling. This investigation utilizes the Venturini method for gate pulse generation, aiming to compare the performance of the 3MC with standard converter designs. Methodology. To achieve the research goal, the Venturini method is adopted for generating gate pulses for the 3MC, representing a departure from conventional approaches. Detailed simulations employing MATLAB/Simulink are conducted to comprehensively evaluate the performance of the 3MC in comparison to conventional converter designs. Results. The simulation outcomes reveal a significant reduction of 73 % in total harmonic distortion (THD) achieved by the 3MC. This reduction in THD indicates improved robustness and suitability for medium-to-high voltage power conversion systems necessitating direct AC-AC conversion. These results highlight the efficacy of the 3MC in enhancing power conversion efficiency and overall performance. Originality. This paper contributes novel insights into the practical implementation of multilevel technology, particularly within the realm of capacitor-clamped converters. Furthermore, the utilization of the Venturini method for gate pulse generation in the 3MC represents an original approach to enhancing converter performance. Practical value. The research findings present significant advancements in multilevel transformer technology, offering valuable guidance for optimizing transformer design in various industrial and renewable energy applications. These contributions serve to enhance the development of reliable and efficient power systems, addressing critical needs in the energy sector. References 54, tables 3, figures 4.

Enhanced reinforcement learning-based two-way transmit-receive directional antennas neighbor discovery in wireless ad hoc networks

The utilization of directional antennas for neighbor discovery in wireless ad hoc networks brings notable benefits, such as extended transmission range, reduced transmission interference, and enhanced antenna gain. However, when nodes use directional antennas for neighbor discovery, the communication range is limited, resulting in a lack of knowledge of potential neighbors. Hence, it is necessary to design a special antenna direction switching strategy for neighbor discovery based on directional antennas. Traditional methods of switching antenna directions are often random or follow predefined sequences, overlooking the historical knowledge of sector exploration for antenna directions. In contrast, existing machine learning approaches aim to leverage observed historical knowledge to adjust antenna directions for faster neighbor discovery. Nonetheless, the latency of neighbor discovery is still high because the node cannot fully utilize the observed historical knowledge (i.e., only using the knowledge observed by the node in transmission mode, ignoring the knowledge observed by the node in reception mode). Meanwhile, the corresponding reward and penalty mechanisms are still not detailed enough (i.e., these reward and penalty mechanisms only consider the sectors of discovered and undiscovered neighboring nodes, ignoring the scenario of sectors that have been rewarded). In this paper, the neighbor discovery process is modeled as a reinforcement learning-based learning automaton. We propose an enhanced reinforcement learning-based two-way transmit-receive directional antennas neighbor discovery algorithm, called ERTTND. The algorithm consists of a two-way transmit-receive reinforcement learning mechanism (TTRL) and an enhanced reward-and-penalty mechanism (ERAP). This algorithm leverages insights from nodes in transmission and reception modes to refine their tactical decisions. Then, through an enriched reward-and-penalty framework, nodes optimize their strategies, thus expediting neighbor discovery based on directional antennas in wireless ad hoc networks. Simulation results demonstrate that compared to existing representative algorithms, the proposed ERTTND algorithm can achieve over 30% savings in terms of average discovery delay and energy consumption.

Directional switching behavior of swarming systems with social and nonlinear interactions

Coordinated directional switching can occur among members of many mobile biological communities. Some studies show that self-propelled particle models can describe the directional switching behavior well. The key to understanding group movement is to determine the influential factors relevant to directional switching behavior. This paper focuses on the impact of social and nonlinear interactions on the directional switching behavior observed in swarming systems. In which, the nonlinear interaction is represented as a function of a trade-off between the velocity and velocity direction of its neighbors. Based on the framework of dimension reduction theory, the high-dimensional complex model is simplified into a one-dimensional simple model, and the stationary probability density and mean switching time are obtained by theoretical analysis of the one-dimensional model. It can be seen that social and nonlinear interactions play an important role in regulating the directional switching behaviors of swarming systems. Specifically, the increase of group density and nonlinear parameter can inhibit the directional switches. For Erdös-Rényi networks, the large mean degree can suppress the directional switching behavior. For scale-free networks, increasing the degree heterogeneity can reduce the mean switching time. The results reveal the underlying mechanisms by which social and nonlinear interactions influence the directional switching behaviors of swarming systems, and provide a theoretical foundation for the design of bio-inspired devices with specific functions.

Symmetry of loop extrusion by dimeric SMC complexes is DNA-tension-dependent.

Structural maintenance of chromosome (SMC) complexes organize and regulate genomes via DNA loop extrusion. During this process, the complexes increase the loop size by reeling in DNA from one or both sides of the loop. The factors governing this symmetry remain unclear. Here, we combine single-molecule analysis and molecular dynamic simulations to investigate the symmetry of loop extrusion of various SMC complexes. We find that whereas monomeric condensin and cohesin are one-sided extruders, the symmetry of dimeric SMCs, such as Smc5/6 and Wadjet, is DNA tension dependent. At low DNA tension (< 0.1pN), Smc5/6 and Wadjet extrude DNA from both sides of the loop. At higher tension, however, they transition to a behavior akin to one-sided extruders, yet still capable of extruding from one or the other side thereby switching the direction of extrusion. Our simulations further reveal that thermal fluctuations significantly influence loop extrusion symmetry, causing variations in DNA reeling rates between the two motors in the dimeric complexes and their direction switching at stalling tensions. Our findings challenge the previous view of loop extrusion symmetry as a fixed characteristic, revealing its dynamic nature and regulation by both intrinsic protein properties and extrinsic factors.

Real-world efficacy and safety of durvalumab-tremelimumab as second-line systemic therapy after atezolizumab-bevacizumab in unresectable hepatocellular carcinoma.

The efficacy and safety of immune-checkpoint inhibitors (ICI) for the treatment of unresectable hepatocellular carcinoma are known. We explored ICI rechallenges with direct switching from 1 ICI regimen to another. This retrospective study included 16 patients who received atezolizumab-bevacizumab (Atezo+Bev) and durvalumab-tremelimumab (Dur+Tre) as the first-line and second-line combination therapy, respectively, at Hiroshima University Hospital. The radiological response and adverse event were evaluated in all patients. Of the 16 patients, 12 were male, and the median age at Atezo+Bev induction was 71 years. The reasons for medication changes were disease progression in 11 patients and adverse events in 5 patients. With Atezo+Bev and Dur+Tre initiation, the Barcelona-Clinic Liver-Cancer stage (A/B/C) progressed in 9/6/3 and 3/4/9 patients and the Child-Pugh classification (A/B/C) progressed in 12/4/0 and 9/6/3 patients, respectively. The disease control rate and overall response rate of Atezo+Bev were 87.5% and 58.3%, respectively, and of Dur+Tre were 62.5% and 0%, respectively. The most common immune-related adverse event in both the Atezo+Bev and Dur+Tre groups was colitis; 3 of the 5 patients with colitis on Atezo+Bev treatment had colitis with Dur+Tre, and 2 had exacerbations. Regarding liver function, ALBI score significantly decreased during Atezo+Bev, but not Dur+Tre, treatment. In patients with colitis following Atezo+Bev, subsequent Dur+Tre treatment may induce colitis recurrence or exacerbation. For immune-related adverse events other than colitis, Dur+Tre could provide relatively safe disease control while maintaining liver function.

Structural basis of the bacterial flagellar motor rotational switching

The bacterial flagellar motor is a huge bidirectional rotary nanomachine that drives rotation of the flagellum for bacterial motility. The cytoplasmic C ring of the flagellar motor functions as the switch complex for the rotational direction switching from counterclockwise to clockwise. However, the structural basis of the rotational switching and how the C ring is assembled have long remained elusive. Here, we present two high-resolution cryo-electron microscopy structures of the C ring-containing flagellar basal body–hook complex from Salmonella Typhimurium, which are in the default counterclockwise state and in a constitutively active CheY mutant-induced clockwise state, respectively. In both complexes, the C ring consists of four subrings, but is in two different conformations. The CheY proteins are bound into an open groove between two adjacent protomers on the surface of the middle subring of the C ring and interact with the FliG and FliM subunits. The binding of the CheY protein induces a significant upward shift of the C ring towards the MS ring and inward movements of its protomers towards the motor center, which eventually remodels the structures of the FliG subunits and reverses the orientations and surface electrostatic potential of the αtorque helices to trigger the counterclockwise-to-clockwise rotational switching. The conformational changes of the FliG subunits reveal that the stator units on the motor require a relocation process in the inner membrane during the rotational switching. This study provides unprecedented molecular insights into the rotational switching mechanism and a detailed overall structural view of the bacterial flagellar motors.

Dynamic Line Rating for Congestion Management in Distribution Network

The growth of the demand because of the electrification of the heating system and the popularization of the use of electric vehicles added to an increase on the renewable energies generation connected to the distribution level, are responsible for an increase in the use of distribution network. This may lead to more congestions at this level that up to the date, are solved with direct switching actions which implies a negative economic impact and consequences for consumers and producers. Congestions can be solved also with market-based demand response which need the system to have flexibility to be applied effectively. On transmission network the usage of dynamic line rating (DLR) is more extended but on the distribution level, it is not common. This paper aims to show the use of DLR to provide flexibility to the distribution network, easing congestion management.

Synchronous and asynchronous updates of active Ising spins in one dimension

How do update rules affect the dynamical and steady state properties of a flock? In this study, we have explored the active Ising spins (s=±1) in one dimension, where spin updates its orientation according to the Metropolis algorithm (based on the neighbours) via two different update rules. (i) Parallel, and (ii) Random-sequential. We explore the effect of Parallel and Random-sequential updates on the dynamical properties of flocks in one dimension. Due to the inherent asynchronous nature of the Random-sequential update, the directional switching of the flock is increased compared to the Parallel one. The nature of phase transition is affected by the difference in the updating mechanism: discontinuous for Parallel and continuous for Random-sequential updates.

Prescription and switching patterns of direct oral anticoagulants in patients with atrial fibrillation

BackgroundThe patterns of direct oral anticoagulant (DOAC) selection and switching to a different oral anticoagulant (OAC) in patients with atrial fibrillation (AF) are unknown. ObjectivesTo describe temporal patterns in first DOAC prescriptions, estimate the incidence, and identify predictors of switching to a different OAC within 1 year in OAC-naive AF patients. MethodsIn this retrospective cohort study, using a near-nationwide prescription registry (IQVIA, the Netherlands), we determined the number of patients per month initiated on each DOAC and identified predictors of switching within 1 year with robust Poisson regression. ResultsWe included 94,874 patients. From November 2015 to November 2019, the monthly use of apixaban (n = 366 to n = 1066, +191%), rivaroxaban (n = 379 to n = 868, +129%), and edoxaban (n = 2 to n = 305, +15,150%) increased, whereas that of dabigatran decreased (n = 317 to n = 179, −44%). In the 66,090 patients with ≥1 year of available calendar time, 7% switched to a different OAC within 1 year. Strong predictors of switching to a different DOAC were using dabigatran (adjusted risk ratio [aRR], 3.33; 95% CI, 3.02-3.66) or edoxaban (aRR, 1.56; 95% CI, 1.34-1.82) rather than apixaban and using a standard DOAC dose (aRR, 2.54; 95% CI, 2.23-2.88). Strong predictors of switching to a vitamin K antagonist were using rivaroxaban (aRR, 1.36; 95% CI, 1.19-1.54 vs apixaban) and using a standard DOAC dose (aRR, 1.49; 95% CI, 1.26-1.77). ConclusionIn the Netherlands, factor Xa inhibitors are increasingly being selected for OAC-naive AF patients. Seven percent of patients switch to a different OAC within 1 year, and the initial DOAC type and dose are strong predictors of switching.

Decoding single-cell molecular mechanisms in astrocyte-to-iN reprogramming via Ngn2- and Pax6-mediated direct lineage switching

BackgroundThe limited regenerative capacity of damaged neurons in adult mammals severely restricts neural repair. Although stem cell transplantation is promising, its clinical application remains challenging. Direct reprogramming, which utilizes cell plasticity to regenerate neurons, is an emerging alternative approach.MethodsWe utilized primary postnatal cortical astrocytes for reprogramming induced neurons (iNs) through the viral-mediated overexpression of the transcription factors Ngn2 and Pax6 (NP). Fluorescence-activated cell sorting (FACS) was used to enrich successfully transfected cells, followed by single-cell RNA sequencing (scRNA-seq) using the 10 × Genomics platform for comprehensive transcriptomic analysis.ResultsThe scRNA-seq revealed that NP overexpression led to the differentiation of astrocytes into iNs, with percentages of 36% and 39.3% on days 4 and 7 posttransduction, respectively. CytoTRACE predicted the developmental sequence, identifying astrocytes as the reprogramming starting point. Trajectory analysis depicted the dynamic changes in gene expression during the astrocyte-to-iN transition.ConclusionsThis study elucidates the molecular dynamics underlying astrocyte reprogramming into iNs, revealing key genes and pathways involved in this process. Our research contributes novel insights into the molecular mechanisms of NP-mediated reprogramming, suggesting avenues for optimizing the efficiency of the reprogramming process.

Electrical properties determine the liquid flow direction in plasma–liquid interactions

During atmospheric pressure plasma impingement, plasma induced liquid flow will influence the transport and distribution of plasma generated charged and reactive species in liquids. We use particle image velocimetry and supplementary pH, conductivity and temperature measurements to investigate electrical properties of an AC kHz plasma jet interacting with water and electrolytes. We observe that the dominant driving mechanism in low conductive solutions are surface forces such as shear stresses and stagnation-pressure induced dimpling. These give upwards flows beneath the plasma–liquid interaction point. In highly conductive solutions, such as water with dissolved salts, the dominant driving mechanism is electro-hydrodynamic forces, with flows directed downwards underneath the plasma jet in our system. We therefore demonstrate that the direction of initial plasma induced liquid flows can be controlled through the addition of salt ions. In electrically grounded salt solutions, we also observe time resolved flow direction switching, possibly due to modification of salt solutions via electrolytic and plasma induced reactions changing the dominant flow mechanism over time.

Spatiotemporal changes in Netrin/Dscam1 signaling dictate axonal projection direction in Drosophila small ventral lateral clock neurons.

Axon projection is a spatial- and temporal-specific process in which the growth cone receives environmental signals guiding axons to their final destination. However, the mechanisms underlying changes in axonal projection direction without well-defined landmarks remain elusive. Here, we present evidence showcasing the dynamic nature of axonal projections in Drosophila's small ventral lateral clock neurons (s-LNvs). Our findings reveal that these axons undergo an initial vertical projection in the early larval stage, followed by a subsequent transition to a horizontal projection in the early-to-mid third instar larvae. The vertical projection of s-LNv axons correlates with mushroom body calyx expansion, while the s-LNv-expressed Down syndrome cell adhesion molecule (Dscam1) interacts with Netrins to regulate the horizontal projection. During a specific temporal window, locally newborn dorsal clock neurons secrete Netrins, facilitating the transition of axonal projection direction in s-LNvs. Our study establishes a compelling in vivo model to probe the mechanisms of axonal projection direction switching in the absence of clear landmarks. These findings underscore the significance of dynamic local microenvironments in the complementary regulation of axonal projection direction transitions.

Spin-Glass States Generated in a van der Waals Magnet by Alkali-Ion Intercalation.

Tuning magnetic properties in layered van der Waals (vdW) materials has captured significant attention due to the efficient control of ground states by heterostructuring and external stimuli. Electron doping by electrostatic gating, interfacial charge transfer, and intercalation is particularly effective in manipulating the exchange and spin-orbit properties, resulting in a control of Curie temperature (TC) and magnetic anisotropy. Here, an uncharted role of intercalation is discovered to generate magnetic frustration. As a model study, Na atoms are intercalated into the vdW gaps of pristine Cr2Ge2Te6 (CGT) where generated magnetic frustration leads to emerging spin-glass states coexisting with a ferromagnetic order. A series of dynamic magnetic susceptibility measurements/analysis confirms the formation of magnetic clusters representing slow dynamics with a distribution of relaxation times. The intercalation also modifies other macroscopic physical parameters including the significant enhancement of TC from 66 to 240K and the switching of magnetic easy-hard axis direction. This study identifies intercalation as a unique route to generate emerging frustrated spin states in simple vdW crystals.

Performance of capacitive deionizing membrane distillation (CDIMD) process for the organic sewage treatment and how operating parameters can affect it

To solve the fouling issue of traditional membrane distillation (MD) technique, a newly-designed hybrid purification system integrating capacitive deionization (CDI) with MD technology was established for the organic sewage treatment in this study, namely capacitive deionizing membrane distillation (CDIMD) technology. Complexes formation via cross-linking among protein, divalent cations, and polysaccharide, an archcriminal inducing MD fouling, was remarkably alleviated in the CDIMD system considering that negatively-charged organics were clearly divided away from those divalent cations in an electric field circumstance. The CDIMD performance was deeply explored in this study focusing on the impact mechanisms of core operational parameters. An appropriate increment of feed temperature (60–65 °C) and feed flow velocity (15.72–17.82 mm/s) contributed to the anti-fouling performance of CDIMD. Considering the side reactions at voltage >1.2 v, setting working voltage at around 1.2 v seemed to be optimal for CDIMD operation. With an overall consideration of pure water production and anti-fouling performance, a properly thicker CNTs layer (40–60 μm) efficiently enhanced the fouling mitigation of CDIMD. A frequent switching of electric field direction (9/1 min) facilitated the timely regeneration of electrode and composite membranes, accordingly promoting a reliable purification of organic wastewater by CDIMD technique.

Dynamic event-triggered time-varying formation control for heterogeneous unmanned swarm systems with scaling attacks

This paper addresses the problem of time-varying formation control for heterogeneous unmanned swarm systems (USSs) consisting of multiple unmanned aerial vehicles (UASs) and unmanned surface vehicles (USVs) based on a directional switching topology. Firstly, a novel USSs model is established, involving the effect of multiple network attacks, network bandwidth constraints and input saturation. In particular, a scaling attack model is proposed to account for denial-of-service (DoS) and deception attacks. Secondly, a distributed controller based on a dynamic event triggering mechanism is designed to reduce the communication load by adjusting the communication frequency between individuals, and the Zeno phenomenon is effectively avoided. Finally, the Lyapunov function is used to obtain sufficient conditions for system stability and bounds on the frequency and duration of network attacks. The experiments and comparison results verify the proposed strategy's effectiveness and superiority.

A dual-mode digital controller with a high accuracy load current estimator and Gaussian adaptive duty cycle switching for fast transient recovery in DC-DC buck converters

To improve the dynamic performance, this paper proposes a dual-mode digital controller with a high accuracy load current estimator and Gaussian adaptive duty cycle switching for DC-DC buck converters with an auxiliary power stage. The proposed digital controller has two operating modes: steady state and transient. In steady-state mode, a conventional PID control module is used to regulate the main power stage and the output voltage. In transient mode, a charge balance control module is responsible for controlling the auxiliary power stage to improve the dynamic performance. A long short-term memory (LSTM)-based load current estimator is proposed to obtain high accuracy load current. It employs a multiple-to-one structure and estimates the load current based on time series data (a sequence of data points indexed in time order). A Gaussian adaptive duty cycle switching is proposed to suppress the output voltage chattering when transitioning between the auxiliary and the main power stages. Simulation and experimental results demonstrate that the proposed controller has a superior dynamic performance when compared to controllers using linear-based load current estimator and direct duty cycle switching. The overshoot/undershoot and settling time can be reduced by over 50 % for a 1.9 A load transient in a 5 to 1.8 V buck converter operating switching at 2 MHz..

Selective directional liquid transport on shoot surfaces of Crassula muscosa.

Directional liquid transport has been widely observed in various species including cacti, spiders, lizards, the pitcher plant Nepenthes alata, and Araucaria leaves. However, in all these examples the liquid transport for a specific liquid is completely restricted in a fixed direction. We demonstrate that Crassula muscosa shoot surfaces have the ability to transport a specific liquid unidirectionally in either direction. This is accomplished through the presence of asymmetric reentrant leaves with varying reentrant angles, which yields the variation in liquid meniscus heterogeneity. These findings enable engineered biomimetic structures capable of selective directional liquid transport, with functions such as intelligent flow direction switching, liquid distribution, and mixing.

Topological Phase and Tunable Quantum State Transfer of Su–Schrieffer–Heeger Chain with an Embedded Quantum Ring

AbstractAn extended Su–Schrieffer–Heeger (SSH) model consisting of an SSH chain with an embedded quantum ring (QR) is investigated. In the case of two SSH chains with a symmetric distribution with respect to QR, by calculating the real‐space winding number and energy spectrum, the hopping amplitude‐induced topological phase is discovered. The probability distributions of gap states and the relationship between energy and magnetic flux prove the existence of the Aharonov–Bohm effect in the QR. Moreover, in the case of asymmetric distribution, the model possesses a zero‐energy mode within the energy gap, and it is found that it can realize quantum state transfer. By adjusting the connection site between the right SSH chain and QR, the direction of the output port can be flexibly engineered. Furthermore, it is shown that high‐fidelity quantum state transfer can still be achieved with the increasing of the system size. The tunable quantum state transfer based on the zero‐energy mode can be equivalent to a topological tunable directional switch with properties of non‐directional transfer. This work provides an approach for studying topological phase transition and tunable topological devices in an SSH chain with an embedded QR.

Reliability Analysis of Hinged Hydraulic System of Remanufactured EPB Shield Machine

Abstract To verify the reliability of the Earth Pressure Balance (EPB shield machine) hinged system, firstly, this paper analyses the reliability of the remanufactured EPB shield machine hinged system and then aims at the problem of the high failure rate of the hinged system in EPB shield machine. A fault tree model was established, and the qualitative and quantitative analysis of the fault tree was carried out. Finally, it is determined that the main cause of the oil cylinder malfunction in the hinged system is the insufficient pressure caused by the malfunction of the solenoid valve’s directional switching.