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Introduction. In the actual era, the integration of decentralized generation in radial distribution networks is becoming important for the reasons of their environmental and economic benefits. Purpose. This paper investigate the optimal size, location and kind of decentralized generation connected in radial distribution networks using a new optimization algorithm namely bald eagle search. Methods. The authors check the optimal allocation of two kinds of decentralized generation the first is operated at unity power factor and the second is operated at 0.95 power factor, a multi-objective functions are minimized based on reduction of voltage deviation index, active and reactive power losses, while taking into consideration several constraints. Results. Simulation results obtained on Standard IEEE-33 bus and IEEE-69 bus radial distribution networks demonstrate the performance and the efficiency of bald eagle search compared with the algorithms existing in literature and radial distribution networks performances are improved in terms of voltage profile and notably active and reactive power losses reduction, decentralized generation operated at 0.95 power factor are more perfect than those operated at unit power factor.

Introduction. The over-current relay is widely used to protect distribution and transmission electrical systems against excessive currents occurring due to short circuit or overload conditions. Many works have been carried out in the field of models simulation design of digital over-current relays in the literature, but unfortunately many of them are more complex design models, have very slow execution time and only work in simple faults cases. Purpose. The purpose of this work is to present the performance of a modified and improved model of a digital over-current relay designed in Simulink/MATLAB environment with more simplified design, faster execution time, and able to operate under more complex fault conditions. Methodology. Before starting tests, modelling of over-current relay is presented in details, of which the basic logics of the proposed model to implement inverse and instantaneous characteristics are well explained. Afterwards, various tests are carried out for the performance analysis of the enhanced designed relay model in terms of: operating speed for eliminating faults that has arisen, ability to distinguish between a fault current and load starting current, capacity distinguish between real and temporary fault currents, the way to manage variable faults over time, and the degree of harmony between primary protection relay and back-up protection relay. Originality. The originality of our proposed work consists in the development and improvement of a digital over-current relay model designed in Simulink/MATLAB environment in such way that it becomes able to operate under new harsh test conditions. This developed designed model is implemented and applied in a 400V radial distribution power system with a load that causes a starting current. Results. The obtained values of simulation are compared with the theoretically calculated values and known existing models. The obtained results after various tests validate the good performance of our enhanced designed model.

Introduction. The railway Traction Power Supply System (TPSS) encounters a common challenge related to high-frequency harmonic resonance, especially when employing AC-DC-AC traction drive systems in high-speed trains. This resonance issue arises when the harmonic elements introduced by the traction AC-DC converter on the grid side of trains align with the innate resonance frequency of the TPSS. The novelty the proposed work focuses on the challenges associated with resonance elevation and high-frequency harmonics in high-speed trains, while simultaneously enhancing energy quality. This is achieved by integrating a pulse-width-modulated converter on the grid side with a single-phase configuration and incorporating an LCL filter. Methodology. In order to optimize the system’s efficiency, a robust control system is employed, taking advantage of the capabilities of a fuzzy logic controller (FLC). The choice of the FLC is justified by its straightforward design and reliability, emphasizing the dedication to precise control, as fuzzy logic excels in handling complex, nonlinear systems. Through the use of linguistic variables and heuristic reasoning, the FLC adjusts to dynamic changes in the system, demonstrating its efficacy in enhancing both transient and steady-state responses. Practical value. A grid-side LCL filter-based converter was meticulously designed and rigorously simulated using the MATLAB/Simulink platform. The inclusion of an advanced FLC in the system introduced a novel approach to control strategies, surpassing the traditional PI controller. Through a comprehensive comparative analysis, the simulation results showcased the remarkable efficacy of the proposed solution in an effectively mitigating high-frequency resonance within the TPSS. This outcome underscores the potential of FLC as a sophisticated control mechanism for enhancing the performance systems in railway applications, showcasing its superiority over conventional control methods. The study contributes in shedding light on innovative approaches for optimizing the control and efficiency of grid-side LCL filter-based converters in high-speed train systems.

The paper aims to identify the optimum size and location of photovoltaic distributed generation systems and distribution static synchronous compensators (DSTATCOMs) systems to minimize active power losses in the distribution network and enhance the voltage profile. The methodology employed in this article begins by thoroughly discussing various acceleration algorithms used in Particle Swarm Optimization (PSO) and their variations with each iteration. Subsequently, a range of PSO algorithms, each incorporating different variations of acceleration coefficients was verified to solve the problem of active power losses and voltage improvement. Simulation results attained on Standard IEEE-33 bus radial distribution network prove the efficiency of acceleration coefficients of PSO; it was evaluated and compared with other methods in the literature for improving the voltage profile and reducing active power. Originality. Consists in determining the most effective method among the various acceleration coefficients of PSO in terms of minimizing active power losses and enhancing the voltage profile, within the power system. Furthermore, demonstrates the superiority of the selected method over others for achieving significant improvements in power system efficiency. Practical value of this study lies on its ability to provide practical solutions for the optimal placement and sizing of distributed generation and DSTATCOMs. The proposed optimization method offers tangible benefits for power system operation and control. These findings have practical implications for power system planners, operators, and policymakers, enabling them to make informed decisions on the effective integration of distributed generation and DSTATCOM technologies.

Purpose Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. Methods After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 μg/kg/day. Results In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. Conclusion Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.

This phase 1b trial investigated several doses and schedules of midostaurin in combination with daunorubicin and cytarabine induction and high-dose cytarabine post-remission therapy in newly diagnosed patients with acute myeloid leukemia (AML). The discontinuation rate on the 50-mg twice-daily dose schedule was lower than 100 mg twice daily, and no grade 3/4 nausea or vomiting was seen. The complete remission rate for the midostaurin 50-mg twice-daily dose schedule was 80% (FMS-like tyrosine kinase 3 receptor (FLT3)–wild-type: 20 of 27 (74%), FLT3-mutant: 12 of 13 (92%)). Overall survival (OS) probabilities of patients with FLT3-mutant AML at 1 and 2 years (0.85 and 0.62, respectively) were similar to the FLT3–wild-type population (0.78 and 0.52, respectively). Midostaurin in combination with standard chemotherapy demonstrated high complete response and OS rates in newly diagnosed younger adults with AML, and was generally well tolerated at 50 mg twice daily for 14 days. A phase III prospective trial is ongoing (CALGB 10603, NCT00651261).

There are no effective therapies for achondroplasia. An open-label study suggested that vosoritide administration might increase growth velocity in children with achondroplasia. This phase 3 trial was designed to further assess these preliminary findings. This randomised, double-blind, phase 3, placebo-controlled, multicentre trial compared once-daily subcutaneous administration of vosoritide with placebo in children with achondroplasia. The trial was done in hospitals at 24 sites in seven countries (Australia, Germany, Japan, Spain, Turkey, the USA, and the UK). Eligible patients had a clinical diagnosis of achondroplasia, were ambulatory, had participated for 6 months in a baseline growth study and were aged 5 to less than 18 years at enrolment. Randomisation was done by means of a voice or web-response system, stratified according to sex and Tanner stage. Participants, investigators, and trial sponsor were masked to group assignment. Participants received either vosoritide 15·0 μg/kg or placebo, as allocated, for the duration of the 52-week treatment period administered by daily subcutaneous injections in their homes by trained caregivers. The primary endpoint was change from baseline in mean annualised growth velocity at 52 weeks in treated patients as compared with controls. All randomly assigned patients were included in the efficacy analyses (n=121). All patients who received one dose of vosoritide or placebo (n=121) were included in the safety analyses. The trial is complete and is registered, with EudraCT, number, 2015-003836-11. All participants were recruited from Dec 12, 2016, to Nov 7, 2018, with 60 assigned to receive vosoritide and 61 to receive placebo. Of 124 patients screened for eligibility, 121 patients were randomly assigned, and 119 patients completed the 52-week trial. The adjusted mean difference in annualised growth velocity between patients in the vosoritide group and placebo group was 1·57 cm/year in favour of vosoritide (95% CI [1·22–1·93]; two-sided p<0·0001). A total of 119 patients had at least one adverse event; vosoritide group, 59 (98%), and placebo group, 60 (98%). None of the serious adverse events were considered to be treatment related and no deaths occurred. Vosoritide is an effective treatment to increase growth in children with achondroplasia. It is not known whether final adult height will be increased, or what the harms of long-term therapy might be. BioMarin Pharmaceutical.

Microorganisms in the atmosphere comprise a small fraction of the Earth's microbiome. A significant portion of this aeromicrobiome consists of bacteria that typically remain airborne for a few days before being deposited. Unlike bacteria in other spheres (e.g., litho-, hydro-, phyllo-, cryospheres), atmospheric bacteria are aerosolized, residing in individual particles and separated from each other. In the atmosphere, bacteria encounter chemical and physical conditions that affect their stress levels and survival. This article goes beyond previous overviews by placing these conditions in the context of fundamental chemical and microphysical concepts related to atmospheric aerosols. We provide ranges of water amounts surrounding bacterial cells both inside and outside clouds and suggest that the small volumes of individual cloud droplets lead to nutrient and oxidant limitations. This may result in greater nutrient limitation but lower oxidative stress in clouds than previously thought. Various chemical and microphysical factors may enhance or reduce microbial stress (e.g., oxidative, osmotic, UV-induced), affecting the functioning and survival of atmospheric bacteria. We illustrate that these factors could impact stress levels under polluted conditions, indicating that conclusions about the role of pollutants in directly causing changes to microbial abundance can be erroneous. The perspectives presented here aim to motivate future experimental and modeling studies to disentangle the complex interplay of chemical and microphysical factors with the atmospheric microbiome. Such studies will help to comprehensively characterize the role of the atmosphere in modifying the Earth' microbiome, which regulates the stability of global ecosystems and biodiversity.

Background and Objective Vosoritide, an analog of C-type natriuretic peptide, has been developed for the treatment of children with achondroplasia. The pharmacokinetics of vosoritide and relationships between plasma exposure and efficacy, biomarkers, and safety endpoints were evaluated in a phase II, open-label, dose-escalation study ( N = 35 patients aged 5–14 years who received daily subcutaneous injections for 24 months) and a phase III, double-blind, placebo-controlled study ( N = 60 patients aged 5–18 years randomized to receive daily subcutaneous injections for 52 weeks). Methods Pharmacokinetic parameters for both studies were obtained from non-compartmental analysis. Potential correlations between vosoritide exposure and changes in annualized growth velocity, collagen type X marker (CXM; a biomarker of endochondral ossification), cyclic guanosine monophosphate (cGMP; a biomarker of pharmacological activity), heart rate, and systolic and diastolic blood pressures were then evaluated. Results The exposure–response relationships for changes in both annualized growth velocity and the CXM biomarker saturated at 15 μg/kg, while systemic pharmacological activity, as measured by urinary cGMP, was near maximal or saturated at exposures obtained at the highest dose studied (i.e. 30 μg/kg). This suggested that the additional bioactivity was likely in tissues not related to endochondral bone formation. In the phase III study, following subcutaneous administration at the recommended dose of 15 μg/kg to patients with achondroplasia aged 5–18 years, vosoritide was rapidly absorbed with a median time to maximal plasma concentration ( C max ) of 15 minutes, and cleared with a mean half-life of 27.9 minutes after 52 weeks of treatment. Vosoritide exposure ( C max and area under the concentration-time curve [AUC]) was consistent across visits. No evidence of accumulation with once-daily dosing was observed. Total anti-vosoritide antibody (TAb) responses were detected in the serum of 25 of 60 (42%) treated patients in the phase III study, with no apparent impact of TAb development noted on annualized growth velocity or vosoritide exposure. Across the exposure range obtained with 15 µg/kg in the phase III study, no meaningful correlations between vosoritide plasma exposure and changes in annualized growth velocity or CXM, or changes from predose heart rate, and systolic or diastolic blood pressures were observed. Conclusions The results support the recommended dose of vosoritide 15 µg/kg for once-daily subcutaneous administration in patients with achondroplasia aged ≥ 5 years whose epiphyses are not closed. Clinical Trials Registration NCT02055157, NCT03197766, and NCT01603095.

In 2022, wilting, yellowing of leaves, vascular discoloration of roots and stems, and plant death, indicative of fusarium wilt, were observed in vetch fields in Constantine Province (northeastern Algeria). The two obtained isolates were confirmed as Fusarium redolens based on morphological and molecular analyses and found to be pathogenic on vetch plants. This study is the first report of F. redolens as a pathogen on Vicia sativa causing fusarium wilt.