Neuroplastin genetically interacts with Cadherin 23 and the encoded isoform Np55 is sufficient for cochlear hair cell function and hearing

Mammalian hearing involves the mechanoelectrical transduction (MET) of sound-induced fluid waves in the cochlea. Essential to this process are the specialised sensory cochlear cells, the inner (IHCs) and outer hair cells (OHCs). While genetic hearing loss is highly heterogeneous, understanding the requirement of each gene will lead to a better understanding of the molecular basis of hearing and also to therapeutic opportunities for deafness. The Neuroplastin (Nptn) gene, which encodes two protein isoforms Np55 and Np65, is required for hearing, and homozygous loss-of-function mutations that affect both isoforms lead to profound deafness in mice. Here we have utilised several distinct mouse models to elaborate upon the spatial, temporal, and functional requirement of Nptn for hearing. While we demonstrate that both Np55 and Np65 are present in cochlear cells, characterisation of a Np65-specific mouse knockout shows normal hearing thresholds indicating that Np65 is functionally redundant for hearing. In contrast, we find that Nptn-knockout mice have significantly reduced maximal MET currents and MET channel open probabilities in mature OHCs, with both OHCs and IHCs also failing to develop fully mature basolateral currents. Furthermore, comparing the hearing thresholds and IHC synapse structure of Nptn-knockout mice with those of mice that lack Nptn only in IHCs and OHCs shows that the majority of the auditory deficit is explained by hair cell dysfunction, with abnormal afferent synapses contributing only a small proportion of the hearing loss. Finally, we show that continued expression of NEUROPLASTIN in OHCs of adult mice is required for membrane localisation of Plasma Membrane Ca2+ ATPase 2 (PMCA2), which is essential for hearing function. Moreover, Nptn haploinsufficiency phenocopies Atp2b2 (encodes PMCA2) mutations, with heterozygous Nptn-knockout mice exhibiting hearing loss through genetic interaction with the Cdh23ahl allele. Together, our findings provide further insight to the functional requirement of Neuroplastin for mammalian hearing.

A GRAPH PARTITIONING TECHNIQUE TO OPTIMIZE THE PHYSICAL INTEGRATION OF FUNCTIONAL REQUIREMENTS FOR AXIOMATIC DESIGN

According to the concept of physical integration as understood in Axiomatic Design, design parameters of a product should be integrated into a single physical part or a few parts with the aim of reducing the information content, while still satisfying the independence of functional requirement. However, no specific method is suggested in the literature for determining the optimal degree of physical integration in a given design. This is particularly important with the current advancement in technologies such as additive manufacturing. As new manufacturing technologies allow physical elements to be integrated in new ways, new methods are needed to help designers optimize physical integration given the specific constraints and conflicts of each design. This study proposes an algorithm which uses graph partitioning to allow a designer to optimize the integration of functional requirements into a target number of parts, with the goal of minimizing the co-allocation of incompatible functional requirements in the same part. The operation and viability of the algorithm is demonstrated via two numerical examples and a practical example of designing a pencil.

3D-Printed Collagen-Based Waveform Microfibrous Scaffold for Periodontal Ligament Reconstruction

Reconstruction of the periodontal ligament (PDL) to fulfill functional requirement remains a challenge. This study sought to develop a biomimetic microfibrous system capable of withstanding the functional load to assist PDL regeneration. Collagen-based straight and waveform microfibers to guide PDL cell growth were prepared using an extrusion-based bioprinter, and a laminar flow-based bioreactor was used to generate fluidic shear stress. PDL cells were seeded on the respective microfibers with 0 or 6 dynes/cm2 fluidic shear stress for 1–4 h. The viability, morphology, adhesion pattern, and gene expression levels of PDL cells were assessed. The results revealed that upon bioprinting optimization, collagen-based microfibers were successfully fabricated. The straight microfibers were 189.9 ± 11.44 μm wide and the waveform microfibers were 235.9 ± 11.22 μm wide. Under 6 dynes/cm2 shear stress, PDL cells were successfully seeded, and cytoskeleton expansion, adhesion, and viability were greater. Cyclin D, E-cadherin, and periostin were upregulated on the waveform microfibers. In conclusion, 3D-printed collagen-based waveform microfibers preserved PDL cell viability and exhibited an enhanced tendency to promote healing and regeneration under shear stress. This approach is promising for the development of a guiding scaffold for PDL regeneration.

Archive Records Management System (ARMS): Functional Requirement

Background of the Study: This paper present the functional requirement in Archive Records Management System (ARMS) that provide a comprehensive record keeping management system based on the organization function according to the business activities and process. Purpose: The purpose of this article is to describe the core functional requirement for record keeping system to support users in performing their task that related to electronic record management system. Method: The method used in this article are based on the previous research, guidelines and standards. Findings: Furthermore, this article similarly aim to evaluate and identify the core functional requirement of archive records management system based on the standards use. This article intent to make user aware towards the core functional requirement in managing electronic records system to fulfil the needs and meet based on proper requirements. Subsequently, through completion this article, the research limitation and difficulties in this study is there are too many requirement of electronic record keeping system available that make users are confused to differentiate between requirements. Meanwhile, the user does not know to choose the right requirement that meet organization function and activities. Other than that, it is quite hard to keep core functional requirement sustain in line with the compliance in organization. Conclusion: The originality this article is to provide a clear content and original requirement based on Archive Records Management System implementation for record professional to recognize the high levels of competencies as well as effectiveness reflection in handling Archive Record Management System (ARMS).

High-Resolution Pixel LED Headlamps: Functional Requirement Analysis and Research Progress

High-resolution pixel LED headlamps are lighting devices that can produce high-resolution light distribution to adapt to road and traffic conditions, intelligently illuminate traffic areas, and assist drivers. Due to the complexity of roads and traffic conditions, the functional diversity of high-resolution pixel LEDs headlamps and traffic safety has come into question and is the subject of in-depth research conducted by car manufacturers and regulators. We summarize the current possible functions of high-resolution pixel LED headlamps and analyze ways in which they could be improved. This paper also discusses the prospect of new technologies in the future.