Search Results (10,902)

The expression of recombinant proteins in heterologous hosts is a common strategy to obtain larger quantities of the “protein of interest” (POI) for scientific, therapeutic or commercial purposes. However, the experimental success of such an approach critically depends on the choice of an appropriate host system to obtain biologically active forms of the POI. The correct folding of the molecule, mediated by disulfide bond formation, is one of the most critical steps in that process. Here we describe the recombinant expression of hirudin, a leech-derived anticoagulant and thrombin inhibitor, in the yeast Komagataella phaffii (formerly known and mentioned throughout this publication as Pichia pastoris) and in two different strains of Escherichia coli, one of them being especially designed for improved disulfide bond formation through expression of a protein disulfide isomerase. Cultivation of the heterologous hosts and expression of hirudin were performed at different temperatures, ranging from 22 to 42 °C for the bacterial strains and from 20 to 30 °C for the yeast strain, respectively. The thrombin-inhibitory potencies of all hirudin preparations were determined using the thrombin time coagulation assay. To our surprise, the hirudin preparations of P. pastoris were considerably less potent as thrombin inhibitors than the respective preparations of both E. coli strains, indicating that a eukaryotic background is not per se a better choice for the expression of a biologically active eukaryotic protein. The hirudin preparations of both E. coli strains exhibited comparable high thrombin-inhibitory potencies when the strains were cultivated at their respective optimal temperatures, whereas lower or higher cultivation temperatures reduced the inhibitory potencies. Full article

Background/Objectives: Targeting individuals with certain characteristics provides improved precision in many healthcare applications. An alert mechanism for COPD exacerbations has recently been validated. It has been argued that its efficacy improves considerably with stratification. This paper provides an in-depth analysis of the cough data of the stratified cohort to identify options for and the feasibility of improved precision in the alert mechanism for the intended patient group. Methods: The alert system was extended using a system complementary to the existing one to accommodate observed rapid changes in cough trends. The designed system was tested in a post hoc analysis of the data. The trend data were inspected to consider their meaningfulness for patients and caregivers. Results: While stratification was effective in reducing misses, the augmented alert system improved the sensitivity and number of early alerts for the acute exacerbation of COPD (AE-COPD). The combination of stratification and the augmented mechanism led to sensitivity of 86%, with a false alert rate in the order of 1.5 per year in the target group. The alert system is rule-based, operating on interpretable signals that may provide patients or their caregivers with better insights into the respiratory condition. Conclusions: The augmented alert system operating based on cough trends has the promise of increased precision in detecting AE-COPD in the target group. Since the design and testing of the augmented system were based on the same data, the system needs to be validated. Signals within the alert system are potentially useful for improved self-management in the target group. Full article

Humanoid robots have attracted considerable attention for their anthropomorphic structure, extended workspace, and versatile capabilities. This paper presents a novel humanoid upper-body robotic system comprising a pair of 8-degree-of-freedom (DOF) arms, a 3-DOF head, and a 3-DOF torso—yielding a 22-DOF architecture inspired by human biomechanics and implemented via standardized hollow joint modules. To overcome the critical reliance of zeroing neural network (ZNN)-based trajectory tracking on the Jacobian matrix derivative, we propose an integration-enhanced matrix derivative observer (IEMDO) that incorporates nonlinear feedback and integral correction. The observer is theoretically proven to ensure asymptotic convergence and enables accurate, real-time estimation of matrix derivatives, addressing a fundamental limitation in conventional ZNN solvers. Workspace analysis reveals that the proposed design achieves an 87.7% larger total workspace and a remarkable 3.683-fold expansion in common workspace compared to conventional dual-arm baselines. Furthermore, the observer demonstrates high estimation accuracy for high-dimensional matrices and strong robustness to noise. When integrated into the ZNN controller, the IEMDO achieves high-precision trajectory tracking in both simulation and real-world experiments. The proposed framework provides a practical and theoretically grounded approach for redundant humanoid arm control. Full article

While boreal forests constitute 30% of the Earth’s forested area and are responsible for 20% of the global carbon sink, there is considerable concern about their sustainability. This paper focuses on the role of elevated CO₂, examining whether wood volume in these forests has responded to increased CO₂ over the last 60 years. To accomplish this, we use a rich set of wood volume measurement data from the Province of Alberta, Canada, and deploy quasi-experimental techniques to determine the effect of elevated CO₂. While the few experimental studies that have examined boreal forests have found almost no effect of elevated CO₂, our results indicate that a 1.0% increase in lifetime exposure to CO₂ leads to a 1.1% increase in aboveground wood volume in these boreal forests. This study showcases the value of research designs that use natural settings to better account for the effects of prolonged exposure to elevated CO₂. Our results should enable improved delineation of the drivers of historical changes in wood volume and carbon storage in boreal forests. In addition, when combined with other studies, these results will likely aid policymakers in designing management or policy approaches that will enhance the sustainability of forests in boreal regions. Full article

Research on children’s singing development is extensive. Different ages, approaches, and variables have been taken into consideration. However, research on singing with text or a neutral syllable is scarce, and findings are inconclusive. This study investigated the influence of singing with text and a neutral syllable on children’s vocal performance. Children aged 4 to 9 (n = 135) participated in two periods of instruction and assessment. In Period One, Song 1 was taught with text and Song 2 with a neutral syllable, and in Period Two, the text was added to Song 2. In each period, children were individually audio-recorded singing both songs. Three independent raters scored the songs’ vocal performances using two researcher-designed rating scales, one for each song, which included the assessment of tonal and rhythm dimensions. Before data analysis, the validity and reliability of the rating scales used to assess vocal performance were examined and assured. The results revealed that 4-, 5-, and 7-year-olds sang Song 1 significantly better in Period One, and 4- and 5-year-olds sang Song 1 significantly better in Period Two. Thus, singing with text seems to favour younger children’s vocal performance. Findings also revealed that girls scored significantly higher than boys for Song 1 in both periods, but not for Song 2 in Period One. The implications of incorporating songs with text and neutral syllables into music programs, as well as the instruments used to assess vocal performances, are discussed. Full article

Sources of renewable energy have attracted considerable attention. Their expanded use will have a substantial impact on both the cost of energy production and climate change. Solar energy is one efficient and safe option; however, solar energy harvesting sites, irrespective of the location, can impact the ecosystem. This experimental study explores the energy available inside and outside of novel miniature energy harvesting cages by measuring light intensity and power generated. Varying light intensity outside the cage has been utilized to study the remaining energy inside the cage of a flexible design, where the heights of the harvesting panels are parameters. Cages are built from custom photovoltaic panels arranged in a staircase manner to provide access to growing plants. The balance between power generation and biological development is investigated. Two different structures are presented to explore the variation of illumination intensity inside the cages. The experimental results show a substantial reduction in energy inside the cages. The experimental results showed up to 24% reduction in illumination inside the cages in winter. The reduction is even larger in summer, up to 57%. The results from the models provide a framework to study the possible impact on a biological system residing inside the cages, paving the way for practical farming with sustainable energy harvesting. Full article

Aqueous organic redox flow batteries (AORFBs) represent an advancing class of electrochemical energy storage systems showing considerable promise for large-scale grid integration due to their unique aqueous organic chemistry. However, the use of small-molecule active materials in AORFBs is significantly limited by the issue of stability and crossover. To address these challenges, we designed a high-water-solubility polymer cathode material, P-T-S, which features a polyvinylimidazole backbone functionalized with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and sulfonate groups. P-T-S exhibits a solubility of 34 Ah L⁻¹ in water and 31 Ah L⁻¹ in 1.0 M NaCl aqueous solution (NaCl_aq). When paired with methyl viologen to assemble a pH-neutral AORFB with a theoretical capacity of 15 Ah L⁻¹, the system exhibits a material utilization rate of 92.0%, an average capacity retention rate of 99.74% per cycle (99.74% per hour), and an average Coulombic efficiency of 98.69% over 300 consecutive cycles at 30 mA cm⁻². This work provides a new design strategy for polymer materials for high-performance AORFBs. Full article

Introduction: Haglund’s deformity, characterized by bony enlargement at the back of the heel, often coincides with Achilles tendon pathology due to impingement on the retrocalcaneal bursa and tendon insertion. Surgical management of Haglund’s deformity with a preexisting Achilles tendon rupture is complex, and understanding the outcomes of this subset of patients is essential for optimizing treatment strategies. Methods: This retrospective study reviewed patients undergoing open surgical management for Haglund’s syndrome between January 2015 and December 2023. Patients with chronic degenerative changes secondary to Haglund’s deformity and a preoperative Achilles tendon rupture were compared to those without. Data on demographics, surgical techniques, weightbearing protocols, and complications were collected. Univariate analysis was performed using χ² or Fisher’s exact test for categorical variables, and the T-test or Wilcoxon rank-sum test for continuous and ordinal variables, with normality assessed via the Shapiro–Wilk test. Results: Four hundred and three patients were included, with 13 having a preoperative Achilles tendon rupture. There was a higher incidence of preoperative ruptures among males. Surgical repair techniques and postoperative weightbearing protocols varied, though were not randomized. Complications included persistent pain, wound breakdown, infection, plantar flexion weakness, and revision surgery. While patients with Haglund’s deformity and a preoperative Achilles tendon rupture demonstrated a trend toward higher complication rates, including postoperative rupture and wound breakdown, these differences were not statistically significant in our analysis. Conclusions: A cautious approach is warranted in managing these patients, with careful consideration of surgical planning and postoperative rehabilitation. While our findings provide valuable insights into managing patients with Haglund’s deformity and preoperative Achilles tendon rupture, the retrospective design, limited sample size of the rupture group, and short duration of follow-up restrict generalizability and the strength of the conclusions by limiting the power of the analysis and underestimating the incidence of long-term complications. Therefore, the results of this study should be interpreted with caution. Further studies with larger patient cohorts, validated functional outcome measures, and comparable follow-up durations between groups are needed to confirm these results and optimize treatment approaches. Full article

Direct electrification and hydrogen utilization represent two key pathways for decarbonizing the glass industry, with their effectiveness subject to adequate furnace design and renewable energy availability. This study presents a techno-economic assessment for optimal solar energy integration in a representative 300 t/d oxyfuel container glass furnace with a specific energy consumption of 4.35 GJ/t. A mixed-integer linear programming formulation is developed to evaluate specific melting costs, carbon emissions, and renewable energy self-consumption and self-production rates across three scenarios: direct solar coupling, battery storage, and a hydrogen-based infrastructure. Battery storage achieves the greatest reductions in specific melting costs and emissions, whereas hydrogen integration minimizes electricity export to the grid. By incorporating capital investment considerations, the study quantifies the cost premiums and capacity requirements under varying decarbonization targets. A combination of 30 MW of solar plant and 9 MW of electric boosting enables the realization of around 30% carbon reduction while increasing total costs by 25%. Deeper decarbonization targets require more advanced systems, with batteries emerging as a cost-effective solution. These findings offer critical insights into the economic and environmental trade-offs, as well as the technical constraints associated with renewable energy adoption in the glass industry, providing a foundation for strategic energy and decarbonization planning. Full article

Deep neural network (DNN) hardware (HW) accelerators have achieved great success in improving DNNs’ performance and efficiency. One key reason is the dataflow in executing a DNN layer, including on-chip data partitioning, computation parallelism, and scheduling policy, which have large impacts on latency and energy consumption. Unlike prior works that required considerable efforts from HW engineers to design suitable dataflows for different DNNs, this work proposes an efficient data-centric approach, named Dataflow Code Propagation (DCP), to automatically find the optimal dataflow for DNN layers in seconds without human effort. It has several attractive benefits that prior studies lack, including the following: (i) We translate the HW dataflow configuration into a code representation in a unified dataflow coding space, which can be optimized by back-propagating gradients given a DNN layer or network. (ii) DCP learns a neural predictor to efficiently update the dataflow codes towards the desired gradient directions to minimize various optimization objectives, e.g., latency and energy. (iii) It can be easily generalized to unseen HW configurations in a zero-shot or few-shot learning manner. For example, without using additional training data, Extensive experiments on several representative models such as MobileNet, ResNet, and ViT show that DCP outperforms its counterparts in various settings. Full article

The structural design of rail vehicle bodies significantly influences rail vehicle performance, passenger comfort, and operational efficiency. This study presents a comparative analysis of three key concepts of a rail vehicle body, namely a differential, an integral, and a hybrid structure, with a focus on their structural principles, material utilization, and implications for manufacturability and maintenance. Three rail vehicle body variants were developed, each incorporating a low-floor configuration to enhance accessibility and interior layout flexibility. The research explores the suitable placement of technical components such as a power unit and an air-conditioning system, and it evaluates interior layouts aimed at maximizing both passenger capacity and their travelling comfort. Key features, including door and window technologies, thermal comfort solutions, and seating arrangements, are also analyzed. The study emphasizes the importance of compromises between structural stiffness, reparability, production complexity, and passenger-oriented design considerations. A part of the research includes a proposal of three variants of a rail vehicle body frame, together with their strength analysis by means of the finite element method. These analyses identified that the maximal permissible stresses for the individual versions of the frame were not exceeded. Findings contribute to the development of more efficient, accessible, and sustainable regional passenger rail vehicles. Full article

Bearingless interior permanent magnet synchronous motors (BIPMSMs) have received considerable attention in recent research due to their advantages of high speed, high power density, and absence of mechanical wear. In order to improve the torque and suspension performance of the BIPMSM, an optimization design method of BIPMSM is proposed in this paper based on sensitivity analysis, response surface fitting, and the multi-objective whale optimization algorithm (MOWOA). Firstly, the structure and operation principle of the BIPMSM are introduced. Secondly, significant variables are extracted based on sensitivity analysis. Then, regression equations of the significant variables and optimization objectives are fitted by the response surface method, and global optimization is performed with MOWOA. Finally, the motor performance before and after optimization is compared. The results demonstrate that the proposed multi-objective optimization design scheme can significantly improve the performance of the BIPMSM and effectively shorten the design cycle. Full article

Τhe Greek Seas are one of the most favorable locations for offshore wind energy development in the Mediterranean basin. In 2023, the Hellenic Hydrocarbons & Energy Resources Management Company SA published the draft National Offshore Wind Farm Development Programme (NDP-OWF), including the main pillars for the design, development, siting, installation, and exploitation of offshore wind farms, along with the Strategic Environmental Impact Assessment. The NDP-OWF is under assessment by the relevant authorities and is expected to be finally approved through a Joint Ministerial Decision. In this work, the preliminary offshore wind energy assessment of the Greek Seas is performed using the CERRA wind reanalysis data and in situ measurements from six offshore locations of the Greek Seas. The in situ measurements are used in order to assess the performance of the reanalysis datasets. The results reveal that CERRA is a reliable source for preliminary offshore wind energy assessment studies. Taking into consideration the potential offshore wind farm organized development areas (OWFODA) according to the NDP-OWF, the study of the local wind characteristics is performed. The local wind speed and wind power density are assessed, and the wind energy produced from each OWFODA is estimated based on three different capacity density settings. According to the balanced setting (capacity density of 5.0 MW/km²), the annual energy production will be 17.5 TWh, which is equivalent to 1509.1 ktoe. An analysis of the wind energy correlation, synergy, and complementarity between the OWFODA is also performed, and a high degree of wind energy synergy is identified, with a very low degree of complementarity. Full article

Aims/Background: Polypharmacy, or the concurrent intake of five or more medications, is a significant issue in clinical practice, particularly in multimorbid elderly individuals. Despite its importance for patient safety, medical education often lacks systematic training in recognising and managing polypharmacy within the framework of patient-centred care. We investigated the impact of a structured learning intervention introducing polypharmacy as a chronic condition, assessing whether it enhances medical students’ diagnostic competence, confidence, and interprofessional collaboration. Methods: A prospective cohort study was conducted with 50 final-year medical students who received a three-phase educational intervention. Phase 1 was interactive workshops on the principles of polypharmacy, its dangers, and diagnostic tools. Phase 2 involved simulated patient consultations and medication review exercises with pharmacists. Phase 3 involved reflection through debriefing sessions, reflective diaries, and standardised patient feedback. Student knowledge, confidence, and attitudes towards polypharmacy management were assessed using pre- and post-intervention questionnaires. Quantitative data were analysed through paired t-tests, and qualitative data were analysed thematically from reflective diaries. Results: Students demonstrated considerable improvement after the intervention in identifying symptoms of polypharmacy, suggesting deprescribing strategies, and working in multidisciplinary teams. Confidence in prioritising polypharmacy as a primary diagnostic problem increased from 32% to 86% (p < 0.01), and knowledge of diagnostic tools increased from 3.1 ± 0.6 to 4.7 ± 0.3 (p < 0.01). Standardised patients felt communication and patient-centredness had improved, with satisfaction scores increasing from 3.5 ± 0.8 to 4.8 ± 0.4 (p < 0.01). Reflective diaries indicated a shift towards more holistic thinking regarding medication burden. The small sample size limits the generalisability of the results. Conclusions: Teaching polypharmacy as a chronic condition in medical school enhances diagnostic competence, interprofessional teamwork, and patient safety. Education is a structured way of integrating the management of polypharmacy into routine clinical practice. This model provides valuable insights for designing medical curricula. Future research must assess the impact of such training on patient outcomes and clinical decision-making in the long term. Full article

Frequency analysis is essential for designing hydraulic structures and managing water resources, as it helps assess hydrological extremes. However, changes in river basins can impact their accuracy, complicating the link between discharge and return periods. This study aims to comprehensively assess the probability characteristics of long-term M-day maximum/minimum discharges in the Carpathian region of Slovakia. We analyze the long-term data from 26 gauging stations covering 90 years of observation. Slovak rivers show considerable intra-annual variability, especially between the summer–autumn (SA) and winter–spring (WS) seasons. To allow consistent comparisons, we apply a uniform methodology to estimate T-year daily maximum and minimum specific discharges over durations of 1 and 7 days for both seasons. Our findings indicate that 1-day maximum specific discharges are generally higher during the SA season compared to the WS season. The 7-day minimum specific discharges are lower during the WS season compared to the SA season. Slovakia’s diverse orographic and climatic conditions cause significant spatial variability in extreme discharges. However, the estimated T-year 7-day minimum and 1-day maximum specific discharges, based on the mean specific discharge and the altitude of the water gauge, exhibit certain nonlinear dependences. These relationships could support the indirect estimation of T-year M-day discharges in regions with similar runoff characteristics. Full article