Sequential Function Research Articles

Sequential Targeted Enzyme-Instructed Self-Assembly Supramolecular Nanofibers to Attenuate Intervertebral Disc Degeneration.

As an age-related disease, intervertebral disc degeneration is closely related to inflammation and aging. Inflammatory cytokines and cellular senescence collectively contribute to the degradation of intervertebral disc. Blocking this synergy reduces disc extracellular matrix damage caused by inflammation and aging. In this study, drug-loaded nanofibers with sequential targeting functions are constructed through intelligent response, hydrophilicity, and in situ self-assembly empowerment of flurbiprofen. The peptide precursor responds to the cleavage of overexpressed MMP-2 in the degenerative intervertebral disc microenvironment (intracellular and extracellular), resulting in the formation of self-assembled nanofibers that enable the on-demand release of flurbiprofen and COX-2 response. In vitro, Comp. 1 (Flurbiprofen-GFFYPLGLAGEEEERGD) reduces the expression of inflammation-related genes and proteins and the polarization of M1 macrophages by competitively inhibiting COX-2 and increases the expression of extracellular matrix proteins COL-2 and aggrecan. Additionally, it can reduce the expression of Senescence-Associated Secretory Phenotype and DNA damage in aged nucleus pulposus cells and promote the recovery of proliferation and cell cycle. In vivo, drug-loaded nanofibers delay intervertebral disc degeneration by inhibiting inflammation and preventing the accumulation of senescent cells. Therefore, the sequentially targeted self-assembled drug-loaded nanofibers can delay intervertebral disc degeneration by blocking the synergistic effect of inflammatory cytokines and cellular senescence.

Programmed surface platform orchestrates anti-bacterial ability and time-sequential bone healing for implant-associated infection

Implant-associated infection (IAI) has become an intractable challenge in clinic. The healing of IAI is a complex physiological process involving a series of spatiotemporal connected events. However, existing titanium-based implants in clinic suffer from poor antibacterial effect and single function. Herein, a versatile surface platform based on the presentation of sequential function is developed. Fabrication of titania nanotubes and poly-γ-glutamic acid (γ-PGA) achieves the efficient incorporation of silver ions (Ag+) and the pH-sensitive release in response to acidic bone infection microenvironment. The optimized PGA/Ag platform exhibits satisfactory biocompatibility and converts macrophages from pro-inflammatory M1 to pro-healing M2 phenotype during the subsequent healing stage, which creates a beneficial osteoimmune microenvironment and promotes angio/osteogenesis. Furthermore, the PGA/Ag platform mediates osteoblast/osteoclast coupling through inhibiting CCL3/CCR1 signaling. These biological effects synergistically improve osseointegration under bacterial infection in vivo, matching the healing process of IAI. Overall, the novel integrated PGA/Ag surface platform proposed in this study fulfills function cascades under pathological state and shows great potential in IAI therapy.

Forecasting Lattice and Point Spatial Data: Comparison of Unilateral and Multilateral SAR Models

Spatial auto-regressive (SAR) models are widely used in geosciences for data analysis; their main feature is the presence of weight (W) matrices, which define the neighboring relationships between the spatial units. The statistical properties of parameter and forecast estimates strongly depend on the structure of such matrices. The least squares (LS) method is the most flexible and can estimate systems of large dimensions; however, it is biased in the presence of multilateral (sparse) matrices. Instead, the unilateral specification of SAR models provides triangular weight matrices that allow consistent LS estimates and sequential prediction functions. These two properties are strictly related and depend on the linear and recursive nature of the system. In this paper, we show the better performance in out-of-sample forecasting of unilateral SAR (estimated with LS), compared to multilateral SAR (estimated with maximum likelihood, ML). This conclusion is supported by numerical simulations and applications to real geological data, both on regular lattices and irregularly distributed points.

Weaning from mechanical ventilation during myasthenic crisis, a monocentric retrospective study

Mechanical ventilation in myasthenic crisis is not standardized and is at high risk of failure. We investigated liberation from mechanical ventilation during myasthenic crisis using a prolonged spontaneous breathing trials (SBT) and sequential pulmonary function tests (PFT). In this retrospective monocenter study, we included patients admitted for a first episode of myasthenic crisis between January 2001 and January 2018. The primary outcome was the incidence of weaning failure upon first extubation in our cohort of patients with MC. Secondary objectives were to determine risk factors and outcome associated with weaning failure upon first extubation in MC. We also compared the characteristics of patients with prolonged weaning. 126 episodes of MC were analyzed. Patient’s age was 64 [42–76] years with 72/126 (56.5%) being women. The median delay between weaning initiation and first extubation was 6 [3–10] days and the median total length of MV was 14 [10–23] days. 118/126 (93.7%) patients underwent prolonged SBT of 8 h or more prior to first extubation. The overall weaning failure rate was 18/126 (14.3%). Extubation was more often successful when the factor precipitating the myasthenic crisis was identified (86/108 (79.6%) vs. 8/18 (44.4%); p = 0.004), whereas PFT was similar in failure or successes. Most weaning failures upon first extubation attempt (11/18; 61%) were attributed to an insufficient stabilization of myasthenia gravis. Duration of mechanical ventilation, an infectious trigger and maximal inspiratory pressure upon intubation were independent risk factors for prolonged weaning. In myasthenic crisis, a standardized protocol including prolonged SBT and respiratory function tests might improve the success of first extubation without prolonging mechanical ventilation. The results of this single center study warrant further evaluation in interventional trials.

Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy

Autophagy is a highly conserved process from yeast to mammals in which intracellular materials are engulfed by a double-membrane organelle called autophagosome and degrading materials by fusing with the lysosome. The process of autophagy is regulated by sequential recruitment and function of autophagy-related (Atg) proteins. Genetic hierarchical analyses show that the ULK1 complex comprised of ULK1-FIP200-ATG13-ATG101 translocating from the cytosol to autophagosome formation sites as a most upstream ATG factor; this translocation is critical in autophagy initiation. However, how this translocation occurs remains unclear. Here, we show that ULK1 is palmitoylated by palmitoyltransferase ZDHHC13 and translocated to the autophagosome formation site upon autophagy induction. We find that the ULK1 palmitoylation is required for autophagy initiation. Moreover, the ULK1 palmitoylated enhances the phosphorylation of ATG14L, which is required for activating PI3-Kinase and producing phosphatidylinositol 3-phosphate, one of the autophagosome membrane’s lipids. Our results reveal how the most upstream ULK1 complex translocates to the autophagosome formation sites during autophagy.

An accelerated sequential function specification method based on LM gradient for transient inverse heat conduction problem

The sequential function specification method (SFSM) and the Levenberg-Marquardt method (LM) are two typical methods for inverse heat conduction problems (IHCP). However, these two methods have poor convergence and low convergence speed. Therefore, the combination of LM with SFSM is depended on to propose a modified Sequential Levenberg-Marquardt gradient method (SLM). The computation results of three shapes of heat fluxes with noise show the SLM is averagely improved over 16.3% more than SFSM in computation accuracy, but equally reduced over 39.9% less than in computation time. On other hand, when the emphasis is on the effect of the Aitken acceleration method, Tikhonov regularization and polynomial order on SLM, a neural network prediction model of the root mean square error is trained by regularization factor, polynomial order and the number of future time steps. Subsequently, the genetic algorithm optimization method is proposed for the minimum root mean square error so that it can improve the computation accuracy and efficiency of IHCP to the maximum extent. Finally, Second-order polynomial order and small order-of-magnitude regularization factor are highly recommended for parameter selection with multiple choices. The ASLM only needs to determine the optimal number of future time steps.

Synthesis of Singular Systems Walsh and Walsh-like Functions of Arbitrary Order

Functionally complete systems of Walsh functions (bases), a particular case of alternating piecewise constant sequential functions, are widely used in various scientific and technological fields. As applied to the tasks of spectral analysis of discrete signals, the most interesting are those Walsh bases that deliver linear coherence of the frequency scales of fast Fourier transform (FFT) processors. By the frequency scales of an FFT processor, we mean the scale on which the normalized frequencies of the input signal are arranged (input scale) and the scale on which the signal's spectral components are arranged (output scale). The frequency scales of the FFT processor are considered linearly coherent if the processor responses with maximum amplitudes and phases of the same sign are located on the bisector of the Cartesian coordinate system formed by the frequency scales of the processor. None of the known Walsh bases ordered by Hadamard, Kaczmage, or Paley provide linear coherence of the frequency scales of the FFT processor. In this study, we develop algorithms to synthesize two systems, called Walsh-Cooley and Walsh-Tukey systems, which turn out to be the only ones in the set of classical Walsh systems and sequents Walsh-like systems, respectively, that deliver linear coherence to the frequency scales of FFT processors.

Assessment of Bayesian guidance strategy to develop bake-hardening ferritic steel

ABSTRACT Developing alloys with optimal properties involves tuning several compositional and processing parameters. As the parametric space is often high-dimensional, doing so may require a prohibitively large number of experiments, which demand ample time and physical resources. In this study, we examine whether the method of Bayesian optimisation, which involves a sequential function evaluation scheme, applies to designing metallic alloys. We consider the example of bake-hardening ferritic steel and aim to maximise the extent of bake-hardening by tuning more than a dozen parameters while reducing the number of experimental fabrications and measurements. To this end, an existing dataset has been used to create a regression model, which acts as a surrogate for experimental measurements. The Bayesian optimiser has been implemented with three different covariance functions and two acquisition functions. Our results suggest that a design strategy guided by Bayesian optimisation has the potential to substantially reduce the time and cost of developing alloys through experimental routes.

Sequential organization and interactional functions of patient loyalty in routine chronic encounters

Doctor-patient communication is pivotal for the delivery of effective health care, patient satisfaction and retention, and the development of patient loyalty to the provider. However, the interactional dynamics of loyalty in real-life communication are left underexplored. In this regard, this study aims to examine and analyze loyalty in naturally occurring routine chronic encounters. Based on audio-recordings collected in a state-run tier-three hospital in China, the study uses conversation analysis to examine the sequential placement of loyalty display and its interactional functions in different environments. The findings report two sequential environments where loyalty display emerges: the opening and closing phases. The findings also show that loyalty is mainly produced by the patient to display affiliation and commitment, indicate their preferred treatment options, and rekindle a disconnected relationship. This work contributes to a more nuanced understanding of loyalty display in service and institutional encounters.

Characterization of a novel antioxidant byssal protein from Mytilus coruscus foot

Mussel byssal proteins are of biomimetic importance for the development of novel underwater bio-adhesive agents. It is important to maintain a reduced state during the process of byssus adhesion. There are 19 mussel foot proteins (MFPs) have been reported in previous studies, among which only MFP-6 had been confirmed as an antioxidant protein in mussel byssus due to the function of cysteines, and playing an essential role in the redox balance of mussel byssus during adhesion process. Although the other four MFPs (MFP-16 ~ MFP-19) also have abundant cysteines, their function is still unknown. In this study, a novel mussel foot protein, named MFP-20, was identified from Mytilus coruscus foot. The sequential features, expression profile, and function of recombinant MFP-20 were verified. The results showed that MFP-20 has more abundant cysteines than other MFPs, the relative expression of mfp-20 was upregulated in Fe3+ stress and low pH seawater. In addition, different adhesive substrates induced significant changes of expression level of mfp-20. Furthermore, rMFP-20 showed strong antioxidant capacity in the DPPH assay, and the abundant cysteines in its sequence may play vital roles in the antioxidation activity. Our findings revealed the possible function of MFP-20 with a totally different sequence from the reported MFP-6 and provided new clues for exploring the redox balance of mussel byssus during the adhesion process.

Design and simulation of a new QCA-based low-power universal gate

Quantum-dot Cellular Automata (QCA) is recognized in electronics for its low power consumption and high-density capabilities, emerging as a potential substitute for CMOS technology. GDI (Gate Diffusion Input) technology is featured as an innovative approach for enhancing power efficiency and spatial optimization in digital circuits. This study introduces an advanced four-input Improved Gate Diffusion Input (IGDI) design specifically for QCA technology as a universal gate. A key feature of the proposed 10-cell block is the absence of cross-wiring, which significantly enhances the circuit’s operational efficiency. Its universal cell nature allows for the carrying out of various logical gates by merely altering input values, without necessitating any structural redesign. The proposed design showcases notable advancements over prior models, including a reduced cell count by 17%, a 29% decrease in total energy usage, and a 44% reduction in average energy loss. This innovative IGDI design efficiently executes 21 combinational and various sequential functions. Simulations in 18 nm technology, accompanied by energy consumption analyses, demonstrate this design’s superior performance compared to existing models in key areas such as multiplexers, comparators, and memory circuits, alongside a significant reduction in cell count.

Characteristics and outcomes of patients admitted to intensive care units in Uganda: a descriptive nationwide multicentre prospective study

Intensive care unit (ICU) mortality rates have decreased over time. However, in low-and lower-middle income countries (LMICs), there remains an excess ICU mortality with limited understanding of patient characteristics, treatments, and outcomes from small single centre studies. We aimed therefore, to describe the characteristics, therapies and outcomes of patients admitted to all intensive care units in Uganda. A nationwide prospective observational study including all patients admitted Uganda’s ICUs with available daily charts was conducted from 8th January 2018 to 1st April 2018. Socio-demographics and clinical characteristics including worst vital signs in the first 24 h of admission were recorded with calculation of the National Early Warning Score (NEWS-2) and quick Sequential Organ Function Assessment (qSOFA) score. ICU interventions were recorded during the ICU stay and patients were followed up to 28 days in ICU. The primary outcome was 28 day ICU mortality. Three-hundred fifty-one patients were analysed with mean age 39 (24.1) years, 205 (58.4%) males with 197 (56%) surgical admissions. The commonest indication for ICU admission was postoperative care (42.9%), 214 (61%) had at least one comorbidity, with hypertension 104 (48.6%) most prevalent and 35 (10%) HIV positive. The 28 day ICU mortality was 90/351 (25.6%) with a median ICU stay of 3 (1–7) days. The highest probability of death occurred during the first 10 days with more non-survivors receiving mechanical ventilation (80% vs 34%; p < 0.001), sedation/paralysis (70% vs 50%; p < 0.001), inotropic/vasopressor support (56.7% vs 22.2%; p < 0.001) and renal replacement therapy (14.4% vs 4.2%; p < 0.001). Independent predictors of ICU mortality included mechanical ventilation (HR 3.34, 95% CI 1.48–7.52), sedation/paralysis (HR 2.68, 95% CI 1.39–5.16), inotropes/vasopressor (HR 3.17,95% CI 1.89–5.29) and an HIV positive status (HR 2.28, 95% CI 1.14–4.56). This study provides a comprehensive description of ICU patient characteristics, treatment patterns, and outcomes in Uganda. It not only adds to the global body of knowledge on ICU care in resource-limited settings but also serves as a foundation for future research and policy initiatives aimed at optimizing ICU care in Sub-Saharan Africa.

METHOD OF PROTOTYPING CONTROL UNITS BASED ON THE OPENPLC APPLICATION

The problem of designing control devices based on programmable logic controllers (PLCs) is their high cost and, as a rule, unavailability at the initial design stage. The purpose of the research is to reduce the time and cost of designing the system by creating prototypes of control units with the software implementation of control algorithms in the languages of the MEK 61131-3 standard and the execution of programs in the Arduino board. The research method consists in the decomposition of project models of operating and control automata of the control device and their implementation in the software environment of the OpenPLC application in the form of program organization components (POU) in Ladder Diagram, Function Block Diagram, Sequential Function Chart and Structured Text languages. The result of the study is a method of creating typical POU operating and control automata of the control system, which are executed in the Arduino board. An example of the application of the proposed methodology for the design of a prototype of the facility's temperature control system is given. The developed prototype was tested using a logical PLC and a physical prototype, which confirmed their functional compliance with the original and a reduction in the cost of the equipment by at least an order of magnitude.

Sequential control barrier functions for mobile robots with dynamic temporal logic specifications

We address a motion planning and control problem for mobile robots to satisfy rich, time-varying tasks expressed as Signal Temporal Logic (STL) specifications. The specifications may include tasks with nested temporal operators or time-conflicting requirements (e.g., achieving periodic tasks or tasks defined within the same time interval). Moreover, the tasks can be defined in locations changing with time (i.e., dynamic targets), and their future motions are not known a priori. This unpredictability requires an online control approach which motivates us to investigate the use of control barrier functions (CBFs). The proposed CBFs take into account the actuation limits of the robots and a feasible sequence of STL tasks. They define time-varying feasible sets of states the system must always stay inside. We show the feasible sequence generation process that even includes the decomposition of periodic tasks and alternative scenarios due to disjunction operators. The sequence is used to define CBFs, ensuring STL satisfaction. We also show some theoretical results on the correctness of the proposed method. We illustrate the benefits of the proposed method and analyze its performance via simulations and experiments with aerial robots.

Investigating the graphical IEC 61131-3 language impact on test case design and evaluation of mechatronic apprentices

Abstract Mechatronic on-site technicians are responsible for maintenance and thus adequate testing of automated production systems. Hence, they must derive test cases from the IEC 61131-3 control code, which requires systematic testing skills. But despite the industry’s high demand for such skills, testing is not established in mechatronic apprentices’ educational curriculum. For the design of a teaching strategy for mechatronic apprentices on testing, this paper investigates the impact of the IEC 61131-3 language on test case design and evaluation. Comparing Sequential Function Chart (SFC) and Function Block Diagram, a trend towards SFC in apprentices’ self-perceived and real competence is shown.

부모와의 상호작용과 또래애착에서 정신건강과 공동체의식의 매개효과

Objectives This study analyzed whether the mediating effect of mental health and sense of community was sig-nificant in the relationship between parents-children interaction and peer attachment of mid. adolescents, and whether having the multiple mediating effects of parents-children interaction on peer attachment through mental health and sense of community.&#x0D; Methods For the purposes, 6,429 cases, taken from the 7th wave data(high school 2nd year) of KELS2013 were used. A survey of parents-children interaction, mental health, sense of community, and peer attachment was conducted. Bootstrapping analysis was performed using the SPSS Macro Process to examine the mediating effects.&#x0D; Results The direct effects of parents-children interaction, mental health, and sense of community on peer at-tachment were significant. The each mediating effect of mental health and sense of community was significant in the relationship between parents-children interaction and peer attachment. As s result of analyzing the multiple mediators of mental health and sense of community in the effect of parents-children interaction on peer attach-ment, a sequential multi-mediation functions appeared between the two variables.&#x0D; Conclusions Parents-children interaction influences mid. adolescents’s peer attachment formation through bol-stering mental health and sense of community. This implies that mental health counseling and sense of commun-ity training helps the formation of the mid. adolescents’s peer attachment.

All-aqueous microfluidic printing of multifunctional bioactive microfibers promote whole-stage wound healing

Wound healing involves multi-stages of physiological responses, including hemostasis, inflammation, cell proliferation, and tissue remodeling. Satisfying all demands throughout different stages remains a rarely addressed challenge. Here we introduce an innovative all-aqueous microfluidic printing technique for fabricating multifunctional bioactive microfibers, effectively contributing to all four phases of the healing process. The distinctive feature of the developed microfibers lies in their capacity to be printed in a free-form manner in the aqueous-two phase system (ATPS). This is achieved through interfacial coacervation between alkyl-chitosan and alginate, with enhanced structural integrity facilitated by simultaneous crosslinking with calcium ions and alginate. The all-aqueous printed microfibers exhibit exceptional performance in terms of cell recruitment, blood cell coagulation, and hemostasis. The inclusion of a dodecyl carbon chain and amino groups in alkyl-chitosan imparts remarkable antimicrobial properties by anchoring to bacteria, complemented by potent antibacterial effects of encapsulated silver nanoparticles. Moreover, microfibers can load bioactive drugs like epidermal growth factor (EGF), preserving their activity and enhancing therapeutic effects during cell proliferation and tissue remodeling. With these sequential functions to guide the whole-stage wound healing, this work offers a versatile and robust paradigm for comprehensive wound treatment, holding great potential for optimal healing outcomes.

Group sequential two-stage preference designs.

The two-stage preference design (TSPD) enables inference for treatment efficacy while allowing for incorporation of patient preference to treatment. It can provide unbiased estimates for selection and preference effects, where a selection effect occurs when patients who prefer one treatment respond differently than those who prefer another, and a preference effect is the difference in response caused by an interaction between the patient's preference and the actual treatment they receive. One potential barrier to adopting TSPD in practice, however, is the relatively large sample size required to estimate selection and preference effects with sufficient power. To address this concern, we propose a group sequential two-stage preference design (GS-TSPD), which combines TSPD with sequential monitoring for early stopping. In the GS-TSPD, pre-planned sequential monitoring allows investigators to conduct repeated hypothesis tests on accumulated data prior to full enrollment to assess study eligibility for early trial termination without inflating type I error rates. Thus, the procedure allows investigators to terminate the study when there is sufficient evidence of treatment, selection, or preference effects during an interim analysis, thereby reducing the design resource in expectation. To formalize such a procedure, we verify the independent increments assumption for testing the selection and preference effects and apply group sequential stopping boundaries from the approximate sequential density functions. Simulations are then conducted to investigate the operating characteristics of our proposed GS-TSPD compared to the traditional TSPD. We demonstrate the applicability of the design using a study of Hepatitis C treatment modality.

Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients.

Coronavirus disease 2019 (COVID-19) caused a progress in research to find a solution to this pandemic. Also, various advances in pharmacotherapy against COVID-19 have emerged. Regarding antiviral therapy, casirivimab and imdevimab are antibodies combination against COVID-19. Standard antiviral therapy against COVID-19 includes remdesivir and favipiravir. The objectives were to compare progression and multi-organ function of hospitalized COVID-19 patients between these three antiviral groups. 265 COVID-19 hospitalized patients were included in this study and were divided into 3 groups (1:2:2), respectively, Group (A): casirivimab and imdevimab, group (B): remdesivir, and group (C): favipiravir. The design of the study is a single blind non-randomized controlled trial. This study is a phase IV clinical trial (post-marketing study). The duration of the study was about 6 months after receiving the ethical approval. Casirivimab and imdevimab achieved less case progression as presented by lower World Health Organization scale (P < 0.05 in comparing group A with B and C) and better multi-organ functions as presented by lower Sequential Organ Function Assessment score (P < 0.05 in comparing group A with B and C) than remdesivir and favipiravir. From all these results, it is concluded that Group A (casirivimab and imdevimab) produces better outcomes than B (remdesivir) and C (favipiravir) intervention groups.

Modelling a chain of command in the incident command system using sequential characteristic function games

Disaster response is a major challenge given the social and economic impact on the communities affected by disaster incidents. We investigate how coalition formation can be used for the problem of forming a hierarchy of resources (e.g., personnel responding to the incident). As a case study, we consider the roaring river flood scenario and model the Incident Command System (ICS) framework—providing guidelines on cooperatively responding to disaster incidents. Our approach is based on sequential characteristic-function games induced by size-based valuation structures. We show that this approach can deliver a hierarchy as required by the Operations Section of the ICS and provides a promising way to generate practical solutions for some realistic disaster scenarios.