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Copyright of Automatisierungstechnik is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Stevia plant is one of the most important medicinal plants used to control diabetes due to its sweetening properties and low calories. Stevia is cultivated in many parts of the world, and to increase its sweetening properties, the effects of many different factors have been tested on this plant. In this research, we investigated the effect of elements related to metal oxidants on the induction of molecular levels and transcription. Thus, the activity of 3 key genes named CPPS, HDS, and GGDPS in response to six different metal oxidants named Cro3, Pbo, Fe2O3, Ag2O, Bao, and Tio2 was carried out in this research. The results showed that the increased concentration of metal oxides, especially Fe2O3 and TiO2, escalates gene expression in the biosynthesis of sweeteners extracted from stevia leaves. Also, related to all treatments, the higher the concentration, the higher the gene expression. Among all metal oxide treatments, Pbo and Bao resulted in low gene expression for CPPS, HDS, and GGDPS genes. On the other side, control showed the lowest expression regarding all three surveyed genes, indicating that using metal oxides can achieve higher production of sweeteners in stevia plants. The results of this research determined that physiological characteristics are affected by metal oxide treatments. Also, the expression of genes effective in the production of steviol glycosides, which is one of the important sweetening factors of this plant in the leaves, increases under the influence of these treatments. As a result, it can be said that the use of these treatments can have an increasing effect on the amount of sweetening of the plant. [ABSTRACT FROM AUTHOR]

Stevia plant is one of the most important medicinal plants used to control diabetes due to its sweetening properties and low calories. Stevia is cultivated in many parts of the world, and to increase its sweetening properties, the effects of many different factors have been tested on this plant. In this research, we investigated the effect of elements related to metal oxidants on the induction of molecular levels and transcription. Thus, the activity of 3 key genes named CPPS, HDS, and GGDPS in response to six different metal oxidants named Cro3, Pbo, Fe2O3, Ag2O, Bao, and Tio2 was carried out in this research. The results showed that the increased concentration of metal oxides, especially Fe2O3 and TiO2, escalates gene expression in the biosynthesis of sweeteners extracted from stevia leaves. Also, related to all treatments, the higher the concentration, the higher the gene expression. Among all metal oxide treatments, Pbo and Bao resulted in low gene expression for CPPS, HDS, and GGDPS genes. On the other side, control showed the lowest expression regarding all three surveyed genes, indicating that using metal oxides can achieve higher production of sweeteners in stevia plants. The results of this research determined that physiological characteristics are affected by metal oxide treatments. Also, the expression of genes effective in the production of steviol glycosides, which is one of the important sweetening factors of this plant in the leaves, increases under the influence of these treatments. As a result, it can be said that the use of these treatments can have an increasing effect on the amount of sweetening of the plant.

With advancements in communication systems and measurement technologies, smart grids have become more observable and controllable, evolving into cyberphysical-power systems (CPPS). The impact of network security and secondary equipment on power system stability has become more evident. To support the existing grid toward a smart grid scenario, smart metering plays a vital role at the customer end side. Cyber-Physical systems are vulnerable to cyber-attacks and various techniques have been evolved to detect a cyber attack in the smart grid. Weighted trust-based models are suggested as one of the most effective security mechanisms. A hardware-in-loop CPPS co-simulation platform is established to facilitate the theoretical study of CPPS and the formulation of grid operation strategies. This paper examines current co-simulation platform schemes and highlights the necessity for a real-time hard-ware-in-the-loop platform to accurately simulate cyber-attack processes. This consideration takes into account the fundamental differences in modeling between power and communication systems. The architecture of the co-simulation platform based on RT-LAB and OPNET is described, including detailed modeling of the power system, communication system, and security and stability control devices. Additionally, an analysis of the latency of the co-simulation is provided. The paper focuses on modeling and implementing methods for addressing DDOS attacks and man-in-the-middle at-tacks in the communication network. The results from simulating a 7-bus system show the effectiveness and rationality of the co-simulation platform that has been designed. [ABSTRACT FROM AUTHOR]

The thermostability of vaccines, particularly enveloped viral vectored vaccines, remains a challenge to their delivery wherever needed. The freeze-drying of viral vectored vaccines is a promising approach but remains challenging due to the water removal process from the outer and inner parts of the virus. In the case of enveloped viruses, freeze-drying induces increased stress on the envelope, which often leads to the inactivation of the virus. In this study, we designed a method to freeze-dry a recombinant vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike glycoprotein. Since the envelope of VSV is composed of 50% lipids and 50% protein, the formulation study focused on both the protein and lipid portions of the vector. Formulations were prepared primarily using sucrose, trehalose, and sorbitol as cryoprotectants; mannitol as a lyoprotectant; and histidine as a buffer. Initially, the infectivity of rVSV-SARS-CoV-2 and the cake stability were investigated at different final moisture content levels. High recovery of the infectious viral titer (~0.5 to 1 log loss) was found at 3–6% moisture content, with no deterioration in the freeze-dried cakes. To further minimize infectious viral titer loss, the composition and concentration of the excipients were studied. An increase from 5 to 10% in both the cryoprotectants and lyoprotectant, together with the addition of 0.5% gelatin, resulted in the improved recovery of the infectious virus titer and stable cake formation. Moreover, the secondary drying temperature of the freeze-drying process showed a significant impact on the infectivity of rVSV-SARS-CoV-2. The infectivity of the vector declined drastically when the temperature was raised above 20 °C. Throughout a long-term stability study, formulations containing 10% sugar (sucrose/trehalose), 10% mannitol, 0.5% gelatin, and 10 mM histidine showed satisfactory stability for six months at 2–8 °C. The development of this freeze-drying process and the optimized formulation minimize the need for a costly cold chain distribution system. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chronic prostatitis/chronic pelvic pain syndrome CP/CPPS is a rather common condition and in recent years many studies have shown contradictory results regarding its impact on semen quality. This prospective cohort study set out to investigate how CP/CPPS affected the parameters of semen in a prospective cohort of patients compared with the WHO 2021 reference group. Methods: From 2013 to 2022, a total of 1071 patients with suspicion of CP/CPPS received a comprehensive andrological examination. Complete semen analysis was carried out in compliance with WHO 2010 guidelines, comparing every study population semen variable to the WHO 2021 reference group (n~3500). Results: All evaluated semen parameters had median values that fell within a normal range. Nonetheless, approximately 25% of patients had values for each semen variable that were lower than the WHO reference group's fifth percentile. In particular, bacteriospermia was associated with a negative impact on semen volume. Conclusions: This is the largest study that compares all standard semen parameters in patients suffering from CP/CPPS to WHO 2021 reference values. It provides evidence of an impairment of conventional semen parameters. [ABSTRACT FROM AUTHOR]

In recent years cepstral analysis and specific cepstrum-based measures such as smoothed cepstral peak prominence (CPPS) has become increasingly researched and utilized in attempts to determine the extent of overall dysphonia in voice signals. Yet, few studies have extensively examined how specific voice-source parameters affect CPPS values. Using a range of synthesized tones, this exploratory study sought to systematically analyze the effect of fundamental frequency (f o), vibrato extent, source-spectrum tilt, and the amplitude of the voice-source fundamental on CPPS values. A series of scales were synthesised using the freeware Madde. Fundamental frequency, vibrato extent, source-spectrum tilt, and the amplitude of the voice-source fundamental were systematically and independently varied. The tones were analysed in PRAAT , and statistical analyses were conducted in SPSS. CPPS was significantly affected by both f o and source-spectrum tilt, independently. A nonlinear association was seen between vibrato extent and CPPS, where CPPS values increased from 0 to 0.6 semitones (ST), then rapidly decreased approaching 1.0 ST. No relationship was seen between the amplitude of the voice-source fundamental and CPPS. The large effect of f o should be taken into account when analyzing the voice, particularly in singing-voice research, when comparing pre and posttreatment data, and when comparing inter-subject CPPS data. [ABSTRACT FROM AUTHOR]

In digital product and ion scheduling centers, order–factory allocation, factory–mold allocation, and mold routing can be performed centrally and efficiently to maximize the utilization of manufacturing resources (molds). Therefore, in this paper, a manufacturing resource (molds)-sharing mechanism based on the Internet of Things (IoT) and a cyber-physical production system (CPPS) is designed to realize the coordinated allocation of molds and production scheduling. A mixed-integer mathematical model is developed to optimize the cost structure and obtain a reasonable profit solution. A heuristic algorithm based on evolutionary reversal is used to solve the problem. The numerical results show that based on the digital coordinated production scheduling method, distributed two-stage assembly manufacturing with shared molds can effectively reduce the order delay time and increase potential benefits for distributed production enterprises. [ABSTRACT FROM AUTHOR]

Recent advancements in communication technology have transformed the way the industrial system works. This digitalization has improved the way of communication between different actors involved in cyber physical production systems (CPPS), such as users, suppliers, and manufacturers, thus making the whole process transparent. The utilization of emerging new technologies in CPPS can cause vulnerable spots that can be exploited by attackers to launch sophisticated distributed denial of service (DDoS) attacks, hence threatening the availability of the production systems. Existing machine learning based intrusion detection systems (IDS) often rely on unrealistic datasets for training and validation, thus missing the crucial testing phase with real-time scenarios. The results generated by the ML models are based on predictions at each flow level and cannot provide summarized information about malicious entities. To address this limitation, this study proposed an efficient IDS system that uses both rule-based detection and ML-based approaches to detect DDoS attacks damaging the infrastructure of CPPS. For training and validation of the system, we use real-time network traffic extracted from a real industrial scenario, referred to as Farm-to-Fork (F2F) supply chain system. Both, attacks and normal traffic were captured, and bidirectional features were extracted through CIC-FLOWMETER. We make use of 8 ML supervised and unsupervised approaches to detect the malicious flows; and then a rule-based detection mechanism is used to calculate the frequency of the malicious flows and to assign different severity levels based on the computed frequency. The overall results show that supervised models outperform unsupervised approaches and achieve an accuracy 99.97% and TPR 99.96%. Overall, the weighted accuracy when tested and deployed in a real-time scenario is around 98.71%. The results prove that the system works better when considering real-time scenarios and provides comprehensive information about the detected results that can be used to take different mitigation actions.

The growing prominence of Industry 4.0 necessitates the increased utilization and complexity of Cyber-Physical Production Systems (CPPS). However, challenges persist in the systematic application of the RAMI 4.0 reference architecture for CPPS and the lack of standardization. To address these issues, we propose a novel process-based methodology leveraging RAMI 4.0 for analyzing, evaluating, and enhancing system interoperability within CPPS. By examining two exemplary CPPS in this study, we demonstrate the significance of minimizing interfaces and adaptations. The results reveal a reduction in required hardware, interfaces, information, and protocols between the systems. Our findings contribute to the advancement of standardized approaches for achieving holistic interoperability among individual systems within the RAMI 4.0 framework. [ABSTRACT FROM AUTHOR]

Real-time performance and reliability are two critical indicators in cyber–physical production systems (CPPS). To meet strict requirements in terms of these indicators, it is necessary to solve complex job-shop scheduling problems (JSPs) and reserve considerable redundant resources for unexpected jobs before production. However, traditional job-shop methods are difficult to apply under dynamic conditions due to the uncertain time cost of transmission and computation. Edge computing offers an efficient solution to this issue. By deploying edge servers around the equipment, smart factories can achieve localized decisions based on computational intelligence (CI) methods offloaded from the cloud. Most works on edge computing have studied task offloading and dispatching scheduling based on CI. However, few of the existing methods can be used for behavior-level control due to the corresponding requirements for ultralow latency (10 ms) and ultrahigh reliability (99.9999% in wireless transmission), especially when unexpected computing jobs arise. Therefore, this paper proposes a dynamic resource prediction scheduling (DRPS) method based on CI to achieve real-time localized behavior-level control. The proposed DRPS method primarily focuses on the schedulability of unexpected computing jobs, and its core ideas are (1) to predict job arrival times based on a backpropagation neural network and (2) to perform real-time migration in the form of human–computer interaction based on the results of resource analysis. An experimental comparison with existing schemes shows that our DRPS method improves the acceptance ratio by 25.9 % compared to the earliest deadline first scheme. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic Pelvic Pain Syndrome (CPPS) is the occurrence of chronic pelvic pain when there is no proven infection or other obvious local pathology that may account for the pain. It is often associated with negative cognitive, behavioural, sexual or emotional consequences, as well as with symptoms of lower urinary tract, sexual or bowel dysfunction. As there is a close link between psychosocial factors and the development of myofascial pain syndromes it is important for healthcare professionals to have knowledge of how the pain begins and the activities at the debut of the symptoms. Aim The aim of the study was to explore men’s experiences of the process leading to CPPS and healthcare received. Methods Information was obtained from semi-structured video interviews with 14 men with CPPS. Interviews were audio-recorded and transcribed. The text was then abstracted into codes and analysed with inductive content analysis. Results The age of the informants ranged between 22 and 73 (median 48), and the duration with CPPS ranged from 1 to 46 years. Two themes emerged, one with the heading Struggling to pin it down with four subthemes and The helpful and unhelpful healthcare with two subthemes. The four subthemes show that the informants experienced difficulties in their lives in the months before the debut of symptoms, for some it was several years. They had specific triggers for the onset of pain. These included cold, trauma to the perineum, chlamydia infection and possibly secondary to a symptomatic urethral stricture. Confusion and frustration were an important element in the informants’ overall experience of CPPS. Healthcare varied widely. The two subthemes about healthcare show expressions of being overlooked or wasting the doctor’s time, but also the experience of being validated and being thoroughly examined. Conclusion The informants in our study described clear and specific triggers for CPPS such as being cold, having digestive issues and trauma to the perineum. Stressful events seemed to have a big impact on these informants and very possibly affected the start of symptoms. This information should be helpful healthcare professionals to understand the patient and his needs.

An external disruptor to a manufacturing process (e.g., a supply chain failure, or a cyber‐attack) can affect more than a factory's output; it can have wider societal concerns, raising the issue of industrial resilience at different levels. In this work, manufacturing resilience is revisited, reviewing the applicability of the resilience concept to the industrial domain, particularly the smart factories enabled by newer digital technologies. The meaning of resilience within manufacturing is shown to be composed of several factors that operate at three levels (macro, meso, and micro). The factors have been united from a variety of sources to unify the traits within manufacturing resilience. Furthermore, a summary of the advanced digital technologies that can aid (or detract) from resilience is discussed, along with some of their challenges around digital complexity, legacy equipment support, high‐performance wireless communications, and cybersecurity. Although it is seen that digital manufacturing systems can aid resilience within the industrial sector and contribute to wider societal goals, the biggest impact is likely to be at the lowest (micro) level. Opportunities exist to quantify resilience factors and their use within manufacturing systems support software, and how to influence the resilience requirements of the wider stakeholders. [ABSTRACT FROM AUTHOR]

In a constantly changing world, information stands as one of the most valuable assets for a manufacturing site. However, exchanging information is not a straightforward process among factories, and concerns regarding the trustability and validation of transactions between various stakeholders have emerged within the context of micro-factories. This work presents an architecture designed to enable information exchange among heterogeneous stakeholders, taking advantage of the cloud infrastructure. It was designed to enable the use of several tools, connected through a middleware system deployed on the cloud. To demonstrate the potential of this architecture, a platform was instantiated, and two use cases—designed to accurately represent real manufacturing sites—were implemented. [ABSTRACT FROM AUTHOR]

ObjectivesDoxorubicin (Dox) is one of the most well-known chemotherapeutics that are commonly applied for a wide range of cancer treatments. However, in most cases, efflux pumps like P-glycoprotein (P-gp), expel the taken drugs out of the cell and decrease the Dox bioavailability. Expression of P-gp is associated with elevated mRNA expression of the ATP-binding cassette B1 (ABCB1) gene.Materials and methodsIn the current study, different sequences of cell-penetrating peptides (CPPs) containing tryptophan, lysine, and arginine and their nano-complexes were synthesized and their impact on the expression and activity of the ABCB1 gene was evaluated in the A549 lung carcinoma cell line. Furthermore, the cellular uptake of designed CPPs in the A549 cell line was assessed.ResultsThe designed peptides, including [W4K4], [WR]3-QGR, R10, and K10 increased Dox cytotoxicity after 48 hr. Furthermore, arginine-rich peptides showed higher cellular uptake. Rhodamin123 accumulation studies illustrated that all the obtained peptides could successfully inhibit the P-gp pump. The designed peptides inhibited the ABCB1 gene expression, of which, [W4K4] resulted in the lowest expression ratio.Conclusion[W4K4], [WR]3-QGR, R10, and K10 could successfully increase the Dox cytotoxicity by decreasing the efflux pump gene expression.

Methotrexate (MTX) is one of the most effective therapeutics to treat different types of solid tumors; however, it suffers low permeability limiting its bioavailability and cellular uptake. To tackle this, we aim to design and fabricate different types of cell-penetrating peptides (CPPs) to improve the intracellular uptake of MTX without causing any immunogenic response. CPPs were synthesized by the solid-phase peptide synthesis method. Peptide-MTX conjugates were prepared via covalent binding of peptide and drug molecule. CPPs and peptide-E8 nanoparticles were characterized using zeta-sizer and scanning electron microscopy. Cytotoxicity of CPPs and peptide-MTX conjugates was evaluated by MTT assay. An enzyme-linked immunosorbent assay was employed to assess the IL-6 and TNF-α cytokine release profile. Amongst all sequences, W4R4-MTX possessed the highest loading efficiency (97%) and drug to peptide percentage (24.02%). The lowest loading efficiency (36%) and drug to peptide percentage (8.76%) were seen for NGRWK-MTX conjugates. The NGRWR peptide and NGRWR-E8 nanoparticles had acceptable size (~100 nm) with spherical and rod-like structures, respectively. The selected CPPs and peptide-MTX conjugates did not show any cytotoxicity or immunogenicity. The fabricated peptides are represented as promising carriers to improve the intracellular delivery of MTX to cancer cells with low immunogenic and cytotoxic effects on normal cells.

In digital product and ion scheduling centers, order–factory allocation, factory–mold allocation, and mold routing can be performed centrally and efficiently to maximize the utilization of manufacturing resources (molds). Therefore, in this paper, a manufacturing resource (molds)-sharing mechanism based on the Internet of Things (IoT) and a cyber-physical production system (CPPS) is designed to realize the coordinated allocation of molds and production scheduling. A mixed-integer mathematical model is developed to optimize the cost structure and obtain a reasonable profit solution. A heuristic algorithm based on evolutionary reversal is used to solve the problem. The numerical results show that based on the digital coordinated production scheduling method, distributed two-stage assembly manufacturing with shared molds can effectively reduce the order delay time and increase potential benefits for distributed production enterprises.

Peptides and proteins, two important classes of biomacromolecules, play important roles in the biopharmaceuticals field. As compared with traditional drugs based on small molecules, peptide- and protein-based drugs offer several advantages, although most cannot traverse the cell membrane, a natural barrier that prevents biomacromolecules from directly entering cells. However, drug delivery via cell-penetrating peptides (CPPs) is increasingly replacing traditional approaches that mediate biomacromolecular cellular uptake, due to CPPs' superior safety and efficiency as drug delivery vehicles. In this review, we describe the discovery of CPPs, recent developments in CPP design, and recent advances in CPP applications for enhanced cellular delivery of peptide- and protein-based drugs. First, we discuss the discovery of natural CPPs in snake, bee, and spider venom. Second, we describe several synthetic types of CPPs, such as cyclic CPPs, glycosylated CPPs, and D-form CPPs. Finally, we summarize and discuss cell membrane permeability characteristics and therapeutic applications of different CPPs when used as vehicles to deliver peptides and proteins to cells, as assessed using various preclinical disease models. Ultimately, this review provides an overview of recent advances in CPP development with relevance to applications related to the therapeutic delivery of biomacromolecular drugs to alleviate diverse diseases. [ABSTRACT FROM AUTHOR]

With the development of power technology and communication technology, the power grid and power communication network have become interdependent and closely coupled. The load shedding operation of the power grid is an important means to reduce the occurrence of chain faults and ensure the safe and stable operation of the power grid. Based on the transmission of load control services in the communication network, this paper establishes a model for a dual-network coupled cyber physical power system (CPPS). Considering communication edge faults, the associated load capacity of the communication edge and the expected load loss of the power grid are defined. On this basis, the paper proposes a complete information zero-sum game mechanism called "defense attack defense" for communication edge failures, which takes the expected loss of load from the power grid as the benefit. The paper studies the optimal attack and defense game strategies and provides the algorithm implementation process for the three stages of the game. Considering the bandwidth capacity of the communication edge, this paper uses the Dijkstra algorithm or k shortest paths (KSP) algorithm with the cost factor of the communication edge as the weight to plan the main and backup communication channels for multiple load control services. The simulation results show that the game mechanism proposed in this paper can effectively reduce the expected load loss from the power grid and improve the stability of the CPPS. [ABSTRACT FROM AUTHOR]

Background: Chronic Pelvic Pain Syndrome (CPPS) is the occurrence of chronic pelvic pain when there is no proven infection or other obvious local pathology that may account for the pain. It is often associated with negative cognitive, behavioural, sexual or emotional consequences, as well as with symptoms of lower urinary tract, sexual or bowel dysfunction. As there is a close link between psychosocial factors and the development of myofascial pain syndromes it is important for healthcare professionals to have knowledge of how the pain begins and the activities at the debut of the symptoms. Aim: The aim of the study was to explore men's experiences of the process leading to CPPS and healthcare received. Methods: Information was obtained from semi-structured video interviews with 14 men with CPPS. Interviews were audio-recorded and transcribed. The text was then abstracted into codes and analysed with inductive content analysis. Results: The age of the informants ranged between 22 and 73 (median 48), and the duration with CPPS ranged from 1 to 46 years. Two themes emerged, one with the heading Struggling to pin it down with four subthemes and The helpful and unhelpful healthcare with two subthemes. The four subthemes show that the informants experienced difficulties in their lives in the months before the debut of symptoms, for some it was several years. They had specific triggers for the onset of pain. These included cold, trauma to the perineum, chlamydia infection and possibly secondary to a symptomatic urethral stricture. Confusion and frustration were an important element in the informants' overall experience of CPPS. Healthcare varied widely. The two subthemes about healthcare show expressions of being overlooked or wasting the doctor's time, but also the experience of being validated and being thoroughly examined. Conclusion: The informants in our study described clear and specific triggers for CPPS such as being cold, having digestive issues and trauma to the perineum. Stressful events seemed to have a big impact on these informants and very possibly affected the start of symptoms. This information should be helpful healthcare professionals to understand the patient and his needs. [ABSTRACT FROM AUTHOR]

Copyright of Automatisierungstechnik is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Introduction Nearly one in seven women worldwide suffers from chronic pelvic pain syndrome (CPPS) each year. Often, CPPS necessitates a combination of treatments. Studies have shown the good therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) upon CPPS. We wish to undertake a randomized controlled trial (RCT) to observe the effect of high-frequency rTMS at different intensities upon CPPS. Methods and analyses In this prospective, double-blinded RCT, 63 female CPPS participants will be recruited and randomized (1:1:1) to high-intensity rTMS, low-intensity rTMS, or sham rTMS. The control group will receive a 10-day course of conventional pelvic floor (PF) rehabilitation (neuromuscular stimulation, magnetic therapy, or light therapy of the PF). On the basis of conventional treatment, participants in the high-intensity rTMS group will receive pulses of 10 Hz with a resting motor threshold (RMT) of 110% for a total of 15,000 pulses. Participants in the low-intensity rTMS group will receive pulses of 10 Hz with an RMT of 80% with 15,000 pulses. The sham rTMS group will be subjected to sham stimulation with the same sound as produced by the real magnetic stimulation coil. The primary outcome will be determined using a visual analog scale, the Genitourinary Pain Index, Zung Self-Rating Anxiety Scale, and Zung Self-Rating Depression Scale. The secondary outcome will be determined by electromyography of the surface of PF muscles at baseline and after treatment completion. Ethics and dissemination This study is approved by the Ethics Committee of Bao’an People’s Hospital, Shenzhen, Guangdong Province (approval number: BYL20211203). The results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences (Protocol version 1.0-20220709). Trial registration Chictr.org.cn, ID: ChiCTR2200055615. Registered on 14 January 2022, http://www.chictr.org.cn/showproj.aspx?proj=146720 . Protocol version 1.0-20220709.

Cloud manufacturing (CM) is a service-oriented business model which is being adopted for industry 4.0 (i4.0). African-based small-to-medium manufacturing enterprises (SMMEs) are yet to adopt the collaborative business manufacturing model, due to challenges associated with vagueness to new manufacturing technologies adoption. However, technological advancements have led to industry 5.0 (i5.0), which present multiple favorable opportunities for manufacturing organizations in Africa. Technology adoption was identified as a key accelerator towards sustainable manufacturing and successful implementation of sustainable development goals (SDGs). This paper aims to conscientise on the future of the manufacturing industry for an African digital economy. Adoption of new manufacturing technologies is disrupting traditional business models and creating new business models which are collaborative, and technology centered. A system of systems methodology was used to address multiple challenges affecting advancing technologies in the transport manufacturing industry in Africa. The result is a strategic system mapping for developing a cognitive manufacturing system for the transport manufacturing system. [ABSTRACT FROM AUTHOR]

Cyber-physical production systems (CPPS) are highly complex and difficult to manage systems. To address these issues, sensors have to be integrated to collect data and monitor processes, and thus provide in-depth intelligence for decision-making processes. The integration of sensors is a major challenge due to the infrastructure required for connectivity and flexibility. However, in existing manufacturing systems, the infrastructure for comprehensive data acquisition does not exist. Expanding the cable infrastructure to a sufficient level leads to high individual deployment and maintenance efforts. Approaches to implement different wireless infrastructure for different use cases lead to a high heterogeneity of communication technologies. 5G meets the networking requirements for many industrial use cases. This enables the flexible, wireless realization of process-integrated sensors. However, currently no implemented 5G-based data acquisition and utilization for a machine tool exists. In this paper, a framework for 5G-enabled sensors is developed and implemented for a machine tool. An existing digital twin for a milling machine is adapted to implement data-driven analysis. An accelerometer is 5G-enabled to transfer data in real-time for evaluation and visualization. Moreover, a smartphone-based sensor with 5G capability collects data of the machining process. This paper outlines the components needed for 5G-enabled data acquisition and analysis and aims to elaborate the benefits, potentials, and transferability of 5G sensors for further use cases. [ABSTRACT FROM AUTHOR]

Real-time performance and reliability are two critical indicators in cyber–physical production systems (CPPS). To meet strict requirements in terms of these indicators, it is necessary to solve complex job-shop scheduling problems (JSPs) and reserve considerable redundant resources for unexpected jobs before production. However, traditional job-shop methods are difficult to apply under dynamic conditions due to the uncertain time cost of transmission and computation. Edge computing offers an efficient solution to this issue. By deploying edge servers around the equipment, smart factories can achieve localized decisions based on computational intelligence (CI) methods offloaded from the cloud. Most works on edge computing have studied task offloading and dispatching scheduling based on CI. However, few of the existing methods can be used for behavior-level control due to the corresponding requirements for ultralow latency (10 ms) and ultrahigh reliability (99.9999% in wireless transmission), especially when unexpected computing jobs arise. Therefore, this paper proposes a dynamic resource prediction scheduling (DRPS) method based on CI to achieve real-time localized behavior-level control. The proposed DRPS method primarily focuses on the schedulability of unexpected computing jobs, and its core ideas are (1) to predict job arrival times based on a backpropagation neural network and (2) to perform real-time migration in the form of human–computer interaction based on the results of resource analysis. An experimental comparison with existing schemes shows that our DRPS method improves the acceptance ratio by 25.9% compared to the earliest deadline first scheme.

Cyber-Physical Production Systems increasingly use semantic information to meet the grown flexibility requirements. Ontologies are often used to represent and use this semantic information. Existing systems focus on mapping knowledge and less on the exchange with other relevant IT systems (e.g., ERP systems) in which crucial semantic information, often implicit, is contained. This article presents an approach that enables the exchange of semantic information via adapters. The approach is demonstrated by a use case utilizing an MES system and an ERP system. [ABSTRACT FROM AUTHOR]

Introduction: Nearly one in seven women worldwide suffers from chronic pelvic pain syndrome (CPPS) each year. Often, CPPS necessitates a combination of treatments. Studies have shown the good therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) upon CPPS. We wish to undertake a randomized controlled trial (RCT) to observe the effect of high-frequency rTMS at different intensities upon CPPS. Methods and analyses: In this prospective, double-blinded RCT, 63 female CPPS participants will be recruited and randomized (1:1:1) to high-intensity rTMS, low-intensity rTMS, or sham rTMS. The control group will receive a 10-day course of conventional pelvic floor (PF) rehabilitation (neuromuscular stimulation, magnetic therapy, or light therapy of the PF). On the basis of conventional treatment, participants in the high-intensity rTMS group will receive pulses of 10 Hz with a resting motor threshold (RMT) of 110% for a total of 15,000 pulses. Participants in the low-intensity rTMS group will receive pulses of 10 Hz with an RMT of 80% with 15,000 pulses. The sham rTMS group will be subjected to sham stimulation with the same sound as produced by the real magnetic stimulation coil. The primary outcome will be determined using a visual analog scale, the Genitourinary Pain Index, Zung Self-Rating Anxiety Scale, and Zung Self-Rating Depression Scale. The secondary outcome will be determined by electromyography of the surface of PF muscles at baseline and after treatment completion. Ethics and dissemination: This study is approved by the Ethics Committee of Bao'an People's Hospital, Shenzhen, Guangdong Province (approval number: BYL20211203). The results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences (Protocol version 1.0-20220709). Trial registration: Chictr.org.cn, ID: ChiCTR2200055615. Registered on 14 January 2022, http://www.chictr.org.cn/showproj.aspx?proj=146720. Protocol version 1.0-20220709. [ABSTRACT FROM AUTHOR]

Myotonic dystrophy type 1 is a debilitating neuromuscular disease causing muscle weakness, myotonia, and cardiac dysfunction. The phenotypes are caused by muscleblind-like (MBNL) protein sequestration by toxic RNA in the DM1 protein kinase (DMPK) gene. DM1 patients exhibit a pathogenic number of repetitions in DMPK, which leads to downstream symptoms. Another disease characteristic is altered microRNA (miRNA) expression. It was previously shown that miR-23b regulates the translation of MBNL1 into protein. Antisense oligonucleotide (AON) treatment targeting this miRNA can improve disease symptoms. Here, we present a refinement of this strategy targeting a miR-23b binding site on the MBNL1 3ʹ UTR in DM1 model cells and mice by using AONs called blockmiRs. BlockmiRs linked to novel cell-penetrating peptide chemistry showed an increase in MBNL1 protein in DM1 model cells and HSALR mice. They also showed an increase in muscle strength and significant rescue of downstream splicing and histological phenotypes in mice without disturbing the endogenous levels of other miR-23b target transcripts.

Developing safe and effective methods for intracellular miRNA delivery remains a challenge. This study used the MR peptide-based carrier for miRNA delivery into liver cells (Huh7) followed by assessment of gene expression and cellular uptake mechanisms. The MR peptide is a fusion of R9 with two membrane-active peptides, namely cecropin and melittin. This fusion peptide possesses cell-penetrating properties. Huh7 cells were cultured and transfected with pLenti-III-miR-124-GFP plasmid containing pre-miR-124. MR- and R9-formulated complexes with plasmid were added to cells and GFP and miR-124 expression were assessed using fluorescence microscopy, flow cytometry and Real time-PCR (RT-PCR). Fluorescence microscopy confirmed the transfection of plasmid by R9 and MR carrier peptides. RT-PCR also showed the overexpression of miR-124 expression by R9 (2.5-fold) and MR (1.7-fold) respectively. However, no difference between the peptides was found. Hemolysis assays showed that MR and R9 induced less lysis compared with Triton X-100, demonstrating their low cytotoxicity. In flow cytometry assay we observed higher transfection of MR mediated delivery than R9. The cellular uptake mechanism studies found that both MR and R9 peptides rely on energy-dependent pathways, as transfection was significantly reduced at low temperatures. Macropinocytosis inhibition substantially decreased transfection for both peptides, suggesting it represents an important route of cellular entry. Clathrin- and caveolin-dependent endocytosis inhibitions also reduced transfection levels to a significant degree for each peptide. This implies that, in addition to macropinocytosis, these receptor-mediated pathways also contribute substantially to intracellular delivery. No clear predominant mechanism could be identified, as no single inhibitor entirely blocked transfection. Overall, the results point to the peptides having flexibility to utilize multiple co-existing endocytic pathways rather than solely relying on one mechanism. Further studies are needed to more precisely define each pathway's relative contribution to peptide-mediated miRNA delivery. [Display omitted] [ABSTRACT FROM AUTHOR]

• Cell-penetrating peptides (CPPs) transport molecular cargos across cell membrane. • CPPs are commonly used in pharmaceuticals and medical products. • CPPs with nanoparticles hybrid delivery vectors and their uptake pathways are crucial. • Preclinical and clinical applications of CPPS hybrid systems are promising. Cell-penetrating peptides (CPPs) are molecules that improve the cellular uptake of various molecular payloads that do not easily traverse the cellular membrane. CPPs can be found in pharmaceutical and medical products. The vast majority of cell-penetrating chemicals that are discussed in published research are peptide based. The paper also delves into the various applications of hybrid vectors. Because CPPs are able to carry cargo across the cellular membrane, they are a viable candidate for use as a suitable carrier for a wide variety of cargoes, such as siRNA, nanoparticles, and others. In which we discuss the CPPs, their classification, uptake mechanisms, hybrid vector systems, nanoparticles and their uptake mechanisms, etc. Further in this paper, we discuss CPPs conjugated to Nanoparticles, Combining CPPs with lipids and polymeric Nanoparticles in A Conjugated System, CPPs conjugated to nanoparticles for therapeutic purposes, and potential therapeutic uses of CPPs as delivery molecules. Also discussed the preclinical and clinical use of CPPS, intracellular trafficking of nanoparticles, and activatable and bioconjugated CPPs. [ABSTRACT FROM AUTHOR]

In a constantly changing world, information stands as one of the most valuable assets for a manufacturing site. However, exchanging information is not a straightforward process among factories, and concerns regarding the trustability and validation of transactions between various stakeholders have emerged within the context of micro-factories. This work presents an architecture designed to enable information exchange among heterogeneous stakeholders, taking advantage of the cloud infrastructure. It was designed to enable the use of several tools, connected through a middleware system deployed on the cloud. To demonstrate the potential of this architecture, a platform was instantiated, and two use cases—designed to accurately represent real manufacturing sites—were implemented.

Purpose: Speech-language pathologists (SLPs) work with individuals with communication disorders. Their work can strain their voice, resulting in dysphonia, adversely affecting their career and quality of life. Laryngeal hydration can prevent vocal damage and improve vocal performance in SLPs. However, there is limited research on the effects of laryngeal hydration in SLPs using longitudinal studies. Hence, the present study aims to assess the longitudinal impact of laryngeal hydration in SLPs using multiparametric acoustic and self-perceptual measures., Method: The research method lasted for 6 consecutive days, with each day lasting 2-3 hours for each participant. Ten SLPs, aged 18-30 years, were recruited. On alternate days, laryngeal hydration treatment (systemic, surface, and combined hydration) was given while participants performed vocal loading tasks. Prerecording and postrecording of the Acoustic Voice Quality Index (AVQI) and its consistent parameters (smoothed cepstral peak prominence [CPPs], harmonics-to-noise ratio [HNR], shimmer%, shimmer local, long-term average spectrum [LTAS] slope, and LTAS tilt) and self-perceptual measures (perceived phonatory effort [PPE], perceived vocal tiredness [PVT]) were taken. Kruskal-Wallis test and the Wilcoxon signed-rank test were used to assess vocal changes in SLPs with laryngeal hydration., Results: No significant differences in overall AVQI scores were found between pretests and posttests for all types of laryngeal hydration treatment. However, there was a significant increase in CPPs and the LTAS slope for combined hydration and a decrease in HNR with an increase in shimmer local for systemic hydration in the posttest compared with the pretest. Only systemic hydration in the posttest showed a rise in PPE and PVT compared with the pretest, compared with surface and combined hydration., Conclusion: Voice outcome measures of the present study demonstrated the immediate beneficial effects of surface hydration and combined hydration in SLPs by preserving voice quality during vocal loading. Systemic hydration had less of an immediate impact on voice quality. This study suggests empirical evidence for laryngeal hydration, which can enhance vocal performance and preserve voice quality in SLPs., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)