Achondroplasia is a genetic disorder that inhibits endochondral ossification, resulting in disproportionate short stature and clinically significant medical complications. Vosoritide is a biologic ...analogue of C-type natriuretic peptide, a potent stimulator of endochondral ossification.
In a multinational, phase 2, dose-finding study and extension study, we evaluated the safety and side-effect profile of vosoritide in children (5 to 14 years of age) with achondroplasia. A total of 35 children were enrolled in four sequential cohorts to receive vosoritide at a once-daily subcutaneous dose of 2.5 μg per kilogram of body weight (8 patients in cohort 1), 7.5 μg per kilogram (8 patients in cohort 2), 15.0 μg per kilogram (10 patients in cohort 3), or 30.0 μg per kilogram (9 patients in cohort 4). After 6 months, the dose in cohort 1 was increased to 7.5 μg per kilogram and then to 15.0 μg per kilogram, and in cohort 2, the dose was increased to 15.0 μg per kilogram; the patients in cohorts 3 and 4 continued to receive their initial doses. At the time of data cutoff, the 24-month dose-finding study had been completed, and 30 patients had been enrolled in an ongoing long-term extension study; the median duration of follow-up across both studies was 42 months.
During the treatment periods in the dose-finding and extension studies, adverse events occurred in 35 of 35 patients (100%), and serious adverse events occurred in 4 of 35 patients (11%). Therapy was discontinued in 6 patients (in 1 because of an adverse event). During the first 6 months of treatment, a dose-dependent increase in the annualized growth velocity was observed with vosoritide up to a dose of 15.0 μg per kilogram, and a sustained increase in the annualized growth velocity was observed at doses of 15.0 and 30.0 μg per kilogram for up to 42 months.
In children with achondroplasia, once-daily subcutaneous administration of vosoritide was associated with a side-effect profile that appeared generally mild. Treatment resulted in a sustained increase in the annualized growth velocity for up to 42 months. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov numbers, NCT01603095, NCT02055157, and NCT02724228.).
The potential of green nanomaterials for environmental and agricultural fields is emerging due to their biocompatible, eco-friendly, and cost-effective performance. We report the use of Canna indica ...flowers extract as new capping and stabilizing source to bio-fabricate ZnO nanoparticles (ZnO NPs for dyes removal, seed germination. ZnO NPs was biosynthesized by ultrasound-assisted alkaline-free route to reach the critical green strategy. The physicochemical findings of ZnO revealed small crystallite size (27.82 nm), sufficient band-gap energy (3.08 eV), and diverse functional groups. Minimum‑run resolution IV approach found the most pivotal factors influencing on removal of Coomassie Brilliant Blue G-250. Uptake studies pointed out that pseudo second-order, and Langmuir were the best fitted models. Dye molecules behaved monolayer adsorption on ZnO surface layers, and controlled by chemisorption. Natural solar light was used as effective source for photocatalytic degradation of methylene blue (94.23% of removal and 31.09 mg/g of uptake capacity). Compared with H2O and ZnSO4, ZnO NPs positively affected the growth of shoot and root lengths (10.2–27.8%) of bean seedlings in most cases. ZnO acts an agrochemical for boosting weight gain, and germination ratio. This study may be promising for developing the recyclable, multifunctional ZnO nanoparticles for environmental and agricultural applications.
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•ZnO nanoparticles were biosynthesized from Canna indica L. flowers.•Minimum–run resolution IV was used to screen and optimize the adsorption parameters.•Photodegradation of methylene blue was conducted under solar light illumination.•ZnO nanoparticles boosted shoot and root lengths of green and red bean seedlings.•Good recyclability and high removal efficiency were obtained.
Emerging applications in brain-machine interface systems require high-resolution, chronic multisite cortical recordings, which cannot be obtained with existing technologies due to high power ...consumption, high invasiveness, or inability to transmit data wirelessly. In this paper, we describe a microsystem based on electrocorticography (ECoG) that overcomes these difficulties, enabling chronic recording and wireless transmission of neural signals from the surface of the cerebral cortex. The device is comprised of a highly flexible, high-density, polymer-based 64-channel electrode array and a flexible antenna, bonded to 2.4 mm × 2.4 mm CMOS integrated circuit (IC) that performs 64-channel acquisition, wireless power and data transmission. The IC digitizes the signal from each electrode at 1 kS/s with 1.2 μV input referred noise, and transmits the serialized data using a 1 Mb/s backscattering modulator. A dual-mode power-receiving rectifier reduces data-dependent supply ripple, enabling the integration of small decoupling capacitors on chip and eliminating the need for external components. Design techniques in the wireless and baseband circuits result in over 16× reduction in die area with a simultaneous 3× improvement in power efficiency over the state of the art. The IC consumes 225 μW and can be powered by an external reader transmitting 12 mW at 300 MHz, which is over 3× lower than IEEE and FCC regulations.
This article presents a reconfigurable single-inductor multi-stage (SIMS) hybrid step-down converter that efficiently provides a wide range of voltage conversion ratios (VCRs) needed for 1-cell ...battery charging across a wide input voltage range of 5-24 V while moving the inductor away from the high-output current path. The inductor is used to couple two synchronous switched-capacitor stages to provide soft charging benefits to each stage. A prototype was implemented in a 0.18 <inline-formula> <tex-math notation="LaTeX">\mu</tex-math> </inline-formula>m bipolar, complimentary metal-oxide semiconductor, double-diffused metal-oxide semiconductor (BCD) process with a die area of 9.4 mm<inline-formula> <tex-math notation="LaTeX">^{2}</tex-math> </inline-formula>. It extends reconfigurable switched-capacitor and merged multi-stage operation concepts to deliver a maximum output current of 5 A and achieves peak efficiencies of 94.8% and 92.4% from 5-and 24-V input supplies, respectively.
The animal gut microbiota evolves quickly towards a complex community and plays crucial roles in its host's health and development. Factors such as host genetics and environmental changes are ...regarded as important for controlling the dynamics of animal gut microbiota. Migratory animals are an important group for studying how these factors influence gut microbiota because they experience strong environmental perturbations during migration. The commercially important grey mullet, Mugil cephalus, is a cosmopolitan species complex that display reproductive migration behaviour. There are three cryptic species of M. cephalus fish distributed across the Northwest Pacific, and their spawning sites overlap in the Taiwan Strait. This extraordinary natural occurrence makes the grey mullet an ideal model organism for exploring the nature of wild animal-gut microbiota relationships and interactions. This study investigates the diversity and structure of the gut microbial community in three cryptic M. cephalus species using 16S rRNA amplicon sequencing. Gut microbial compositions from adult and juvenile fish samples were analysed. Our results indicate that gut microbial communities within the grey mullet share a core microbiome dominated by Proteobacteria, Firmicutes and Actinobacteria. However, the structures of gut microbial communities were more distinct between adult mullet groups than they were between juvenile ones. Intriguingly, we found that adult fish that migrate to different geographical tracts harbour gut microbiota similar to historical records of seawater microflora, along their respective migration routes. This observation provides new insights into the interaction between aquatic animal gut microbial communities and the environments along their hosts' migratory routes, and thus warrants future study.
Gate driver circuits to ensure proper turn- on and turn- off for power switches are essential parts of a power converter design. They become significantly challenging for multilevel converters, where ...multiple switches are operated at active voltage domains. The recent favorable use of gallium nitride devices for power switches makes gate driving even more difficult as the switch performance and reliability are very sensitive to the variations of the gate driving signals and power rails compared with traditional power MOSFETs. This article discusses gate driving methods using a multilevel multi-inductor hybrid (MIH) converter as the demonstration prototype to address two key challenges in designing gate drivers: 1) providing level-shifted pulsewidth modulation signals to active voltage domains and 2) powering schemes for gate driver circuits. To solve the first challenge, an optimal use of available half-bridge drivers is proposed to eliminate the need for separate signal isolator chips. This method was implemented and verified in an MIH converter prototype for 48-V point-of-load applications using three different powering schemes for gate drivers, including isolated power modules, regulated supplies from switch blocking voltages, and cascaded bootstrap power rails with regulations. The gate driver techniques and powering schemes are compared experimentally in terms of performance to illustrate their benefits and tradeoffs.
This paper describes design techniques to maximize the efficiency and power density of fully integrated switched-capacitor (SC) DC-DC converters. Circuit design methods are proposed to enable ...simplified gate drivers while supporting multiple topologies (and hence output voltages). These methods are verified by a proof-of-concept converter prototype implemented in 0.374 mm 2 of a 32 nm SOI process. The 32-phase interleaved converter can be configured into three topologies to support output voltages of 0.5 V-1.2 V from a 2 V input supply, and achieves 79.76% efficiency at an output power density of 0.86 W/mm 2 .
This paper describes the topology, fundamental operations, and key characteristics of a Dual-Phase Multi-Inductor Hybrid (DP-MIH) Converter for Point of Load (POL) telecommunication and data center ...applications. The circuit topology employs a unique configuration of switched inductor and capacitor pairs to achieve complete soft charging and native voltage balancing of flying capacitors regardless of mismatches and variations in capacitor and inductor values. The converter topology and its operation are verified by a five-level DP-MIH converter prototype capable of delivering maximum load of 100A at 1V-5V regulated output voltages from a 48V input supply. It achieves 90.9% peak efficiency and 440 w/in 3 power density for 48V-to-1V conversion and 95.3% and 2200W/in 3 for a 48V-to-5V conversion.
This paper presents a new highly integrable hybrid step-down converter that merges switched-inductor and switched-capacitor operations and significantly reduces onboard loss by using the input ...cable's parasitic inductance as its main inductor. This converter has the inductor placed at the input with a smaller voltage swing, leading to possible use of a smaller inductor and low-voltage rating switches that generally translate to reduced conduction losses. Analyses of converter operation and losses to reveal its original characteristics and design guidelines are presented to facilitate the components optimization. The converter architecture is verified by a proof-of-concept 15-W inductor-less lithium-ion battery charger prototype that uses a 1-m USB 3.0 cable as inductor. The converter, switched at 2 MHz from a 5-V input, experimentally achieves 89.7% peak efficiency and 6% higher efficiency at full load than a Buck converter counterpart. This high efficiency and zero onboard inductor yield a relative 45.7% onboard loss reduction at full load, promising excellent integration feasibility and superior system thermal management.
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