Universal Adapter Research Articles

Shared structural features of Miro binding control mitochondrial homeostasis

Miro proteins are universally conserved mitochondrial calcium-binding GTPases that regulate a multitude of mitochondrial processes, including transport, clearance, and lipid trafficking. The exact role of Miro in these functions is unclear but involves binding to a variety of client proteins. How this binding is operated at the molecular level and whether and how it is important for mitochondrial health, however, remains unknown. Here, we show that known Miro interactors—namely, CENPF, Trak, and MYO19—all use a similar short motif to bind the same structural element: a highly conserved hydrophobic pocket in the first calcium-binding domain of Miro. Using these Miro-binding motifs, we identified direct interactors de novo, including MTFR1/2/1L, the lipid transporters Mdm34 and VPS13D, and the ubiquitin E3-ligase Parkin. Given the shared binding mechanism of these functionally diverse clients and its conservation across eukaryotes, we propose that Miro is a universal mitochondrial adaptor coordinating mitochondrial health.

Designer Small-Molecule Control System Based on Minocycline-Induced Disruption of Protein-Protein Interaction.

A versatile, safe, and effective small-molecule control system is highly desirable for clinical cell therapy applications. Therefore, we developed a two-component small-molecule control system based on the disruption of protein-protein interactions using minocycline, an FDA-approved antibiotic with wide availability, excellent biodistribution, and low toxicity. The system comprises an anti-minocycline single-domain antibody (sdAb) and a minocycline-displaceable cyclic peptide. Here, we show how this versatile system can be applied to OFF-switch split CAR systems (MinoCAR) and universal CAR adaptors (MinoUniCAR) with reversible, transient, and dose-dependent suppression; to a tunable T cell activation module based on MyD88/CD40 signaling; to a controllable cellular payload secretion system based on IL12 KDEL retention; and as a cell/cell inducible junction. This work represents an important step forward in the development of a remote-controlled system to precisely control the timing, intensity, and safety of therapeutic interventions.

Damage localisation using disparate damage states via domain adaptation

Abstract A significant challenge of structural health monitoring (SHM) is the lack of labeled data collected from damage states. Consequently, the collected data can be incomplete, making it difficult to undertake machine learning tasks, to detect or predict the full range of damage states a structure may experience. Transfer learning is a helpful solution, where data from (source) structures containing damage labels can be used to transfer knowledge to (target) structures, for which damage labels do not exist. Machine learning models are then developed that generalize to the target structure. In practical applications, it is unlikely that the source and the target structures contain the same damage states or experience the same environmental and operational conditions, which can significantly impact the collected data. This is the first study to explore the possibility of transfer learning for damage localisation in SHM when the damage states and the environmental variations in the source and target datasets are disparate. Specifically, using several domain adaptation methods, this article localizes severe damage states at a target structure, using labeled information from minor damage states at a source structure. By minimizing the distance between the marginal and conditional distributions between the source and the target structures, this article successfully localizes damage states of disparate severities, under varying environmental and operational conditions. The effect of partial and universal domain adaptation—where the number of damage states in the source and target datasets differ—is also explored in order to mimic realistic industrial applications of these methods.

SGDA: Towards 3-D Universal Pulmonary Nodule Detection via Slice Grouped Domain Attention.

Lung cancer is the leading cause of cancer death worldwide. The best solution for lung cancer is to diagnose the pulmonary nodules in the early stage, which is usually accomplished with the aid of thoracic computed tomography (CT). As deep learning thrives, convolutional neural networks (CNNs) have been introduced into pulmonary nodule detection to help doctors in this labor-intensive task and demonstrated to be very effective. However, the current pulmonary nodule detection methods are usually domain-specific, and cannot satisfy the requirement of working in diverse real-world scenarios. To address this issue, we propose a slice grouped domain attention (SGDA) module to enhance the generalization capability of the pulmonary nodule detection networks. This attention module works in the axial, coronal, and sagittal directions. In each direction, we divide the input feature into groups, and for each group, we utilize a universal adapter bank to capture the feature subspaces of the domains spanned by all pulmonary nodule datasets. Then the bank outputs are combined from the perspective of domain to modulate the input group. Extensive experiments demonstrate that SGDA enables substantially better multi-domain pulmonary nodule detection performance compared with the state-of-the-art multi-domain learning methods.

Universal Adaptive Stream-Based Entropy Coding

Universal Adaptive Stream-Based Entropy Coding

Development of the Centering-Based Group Care Adaptation Framework, a supporting tool when implementing Centering-Based Group Care

Background: Centering-Based Group Care (CBGC) is an alternative way of delivering antenatal and/or postnatal care, and includes three core components: (1) health assessment, (2) interactive learning, and (3) community building. Despite the increasing interest in CBGC worldwide, implementation can be challenging and adaptations are required for sustainable implementation while maintaining the core components. Examples of site-specific adaptations for implementation are documented but are scattered and a hands-on tool for practice has not been created. This study aims to develop a CBGC adaptation framework that supports sustainable implementation within and across different contexts.
 Methods: We conducted a context-analysis using a Rapid Qualitative Inquiry (RQI) approach in 26 sites in seven participating countries (Belgium, Ghana, Kosovo, South Africa, Suriname, The Netherlands, and United Kingdom) during the pre-implementation phase. We conducted 335 semi-structured interviews with service users (n=150) and with key stakeholders such as politicians, health care managers, health care providers, religious leaders (n=185). 10 focus group discussions with service users and 56 review meetings with the local research teams were included. In addition, national guidelines and documents were analysed for their CBGC-relevant content. RQI included data triangulation and investigator triangulation. We incorporated data from the RQI into the iteratively evolving adaptation framework and systematically discussed preliminary versions with country-specific research teams. Insights and feedback from these teams were incorporated to create the final version of the CBGC adaptation framework. 
 Results: We identified six universal surface adaptations categories (content, materials, timing, location, group composition, facilitators), and five universal deep structure adaptations categories (self-assessment/medical check-up, scheduling CBGC into regular care, enrolment, (possible) partner organisations, financials). The CBGC Adaptation Framework provides an overview of the site’s adaptation needs, expected barriers and facilitators, and encourages the development of an action plan to apply these adaptations in practice.
 Conclusion: The Adaptation Framework is a useful tool to identify surface and deep structure adaptation categories. In this way, it serves as a useful tool to provide the necessary support during the complex implementation of CBGC. Completing the framework raises awareness of multiple levels of adaptations that must be considered if sustainable implementation of CBGC is to be achieved.

Cross-domain fault diagnosis method for rolling bearings based on contrastive universal domain adaptation

To address the unknown spatial relationship between source and target domain labels, which leads to poor fault diagnosis accuracy, a contrastive universal domain adaptation model and rolling bearing fault diagnosis approach are proposed. The approach introduces bootstrap your own latent network to mine the data-specific structure of the target domain and proposes rejecting unknown class samples using an entropy separation strategy. Simultaneously, a source class weighting mechanism is designed to improve the transferable semantics augmentation method by assigning various class-level weights to source categories, which improves the alignment of the feature distributions in the shared label space to further construct fault diagnosis models. Experimental validation on two rolling bearing datasets confirmed the superior fault diagnosis accuracy of the proposed method under diverse working conditions.

General feature spatial location and distance-based unknown Detection: A universal domain adaptation fault diagnosis framework of rotating Machinery

Recently, domain adaptation (DA) based cross-domain fault diagnosis of rotating machinery has gained much attention, where a target domain with only unlabeled data can be diagnosed by transferring diagnosis knowledge from a labeled source domain. In industrial applications, the target domain may occur only limited types of faults contained in the source domain, or even novel faults unseen in the source domain. Moreover, since the target domain is unlabeled in reality, the prior label space relationship between two domains is hard to know. Therefore, not only domain shift, it is also essential to tackle the uncertainty of both the category shift and the unknown space in actual cross-domain scenarios, which can be abstracted as a universal domain adaptation (UniDA) problem. This paper proposes a cross-domain diagnosis framework for rotating machinery under UniDA to handle the uncertainty dilemma by converting it to certainty. Specifically, a feature spatial location principle general for different label space relationships is designed, where the known classes form a hypersphere and the central region of the hypersphere is left for the possible target domain unknown samples. Then, a novel distance-based unknown detection strategy is proposed, which is friendly to different “open” degrees of the unknown space. The diagnosis results of three case studies show the effectiveness of the proposed framework under all possible label space relationships, including close set DA, partial set DA, open set DA and open-partial set DA. Further discussions demonstrate the superiority of the proposed framework in known class recognition and possible unknown detection. The proposed diagnosis framework provides a new insight for solving the uncertainty dilemma laid in actual cross-domain diagnosis scenarios under UniDA setting, which is more potential to practical engineering applications compared with many DA-based diagnosis methods tailored for specific label space relationship.

A novel sample selection approach based universal unsupervised domain adaptation for fault diagnosis of rotating machinery

A novel sample selection approach based universal unsupervised domain adaptation for fault diagnosis of rotating machinery

ELEMENTS OF GAME TECHNOLOGIES AS A MOTIVATION FACTOR OF AN INCLUSIVE EDUCATIONAL ENVIRONMENT

The article describes the effectiveness of the mechanisms of practical use of game technologies in the environment of inclusive education. The search for optimal ways and the effectiveness of the educational process will be as successful as possible if learning is exciting, interesting, informative, motivating and creative. In connection with today's challenges, the issue of optimization, innovation and availability of knowledge has become relevant. The game as a means of sensory influence for the field of inclusion is extremely important, because it allows people with special needs to adapt to life's difficulties in the future. The paradigm of gaming practices grew as a result of the fact that digital education was institutionalized rather quickly and impulsively. An important transition took place in the system of educational values: the acquisition of experience in the form of informative blocks, the possession of a number of facts, statistics were replaced by the ability to effectively apply the necessary knowledge in the field of practical activity, that is, in life; to be able to choose the main thing, to find the necessary information and to be capable of its practical application. The issue of selecting original methodical practices that would be effective for comprehensive training of students with disabilities remains relevant. Participants of the educational process, who are included in the inclusive platform, are forced to undergo another, universal adaptation in the difficult realities of today. The method of pedagogical observation in combination with a Google Form survey made it possible to analyze the functional significance of game elements in classes in the disciplines of the philological cycle and to prove the effectiveness of the game as a sensory tool among people with special educational needs.

Insulin-like Growth Factor 2 (IGF2)-Fused Lysosomal Targeting Chimeras for Degradation of Extracellular and Membrane Proteins.

Targeted degradation of the cell-surface and extracellular proteins via the endogenous lysosomal degradation pathways, such as lysosome-targeting chimeras (LYTACs), has recently emerged as an attractive tool to expand the scope of extracellular chemical biology. Herein, we report a series of recombinant proteins genetically fused to insulin-like growth factor 2 (IGF2), which we termed iLYTACs, that can be conveniently obtained in high yield by standard cloning and bacterial expression in a matter of days. We showed that both type-I iLYTACs, in which IGF2 was fused to a suitable affibody or nanobody capable of binding to a specific protein target, and type-II iLYTAC (or IGF2-Z), in which IGF2 was fused to the IgG-binding Z domain that served as a universal antibody-binding adaptor, could be used for effective lysosomal targeting and degradation of various extracellular and membrane-bound proteins-of-interest. These heterobifunctional iLYTACs are fully genetically encoded and can be produced on a large scale from conventional E. coli expression systems without any form of chemical modification. In the current study, we showed that iLYTACs successfully facilitated the cell uptake, lysosomal localization, and efficient lysosomal degradation of various disease-relevant protein targets from different mammalian cell lines, including EGFR, PD-L1, CD20, and α-synuclein. The antitumor properties of iLYTACs were further validated in a mouse xenograft model. Overall, iLYTACs represent a general and modular strategy for convenient and selective targeted protein degradation, thus expanding the potential applications of current LYTACs and related techniques.

Designer Adaptor Proteins for Functional Conversion of Peptides to Small-Molecule Ligands toward In-Cell Catalytic Protein Modification.

Peptides are privileged ligands for diverse biomacromolecules, including proteins; however, their utility is often limited due to low membrane permeability and in-cell instability. Here, we report peptide ligand-inserted eDHFR (PLIED) fusion protein as a universal adaptor for targeting proteins of interest (POI) with cell-permeable and stable synthetic functional small molecules (SFSM). PLIED binds to POI through the peptide moiety, properly orienting its eDHFR moiety, which then recruits trimethoprim (TMP)-conjugated SFSM to POI. Using a lysine-acylating BAHA catalyst as SFSM, we demonstrate that POI (MDM2 and chromatin histone) are post-translationally and synthetically acetylated at specific lysine residues. The residue-selectivity is predictable in an atomic resolution from molecular dynamics simulations of the POI/PLIED/TMP-BAHA (MTX was used as a TMP model) ternary complex. This designer adaptor approach universally enables functional conversion of impermeable peptide ligands to permeable small-molecule ligands, thus expanding the in-cell toolbox of chemical biology.

From evidence-based health prevention registers to best practices in implementation: how to succeed and tailor an effective prevention program?

Abstract The role of evidence-based prevention registers and “best practice portals”, aiming at health enhancing behaviour changes and reducing social inequalities, are even more important in the post COVID era. Evidence-based practices are interventions for which there is consistent scientific evidence asserting that they improve health outcomes for a specific population at time T in setting S. Adaptation and dissemination are the next challenges for decision-makers whereas there is no scientific consensus on a universal dissemination and adaptation model. Best practice portals should help to disseminate evidence-based interventions in health prevention. Therefore specific skills for adapting and implementing programs in local settings are needed. Models for dissemination remain complex for field practitioners and local stakeholders. Nevertheless, effective implementation can be achieved by supporting the local practitioners and stakeholders with scientific standards in prevention research including a delivery system, an organizational capacity, a support system and a strong training and technical assistance. In this workshop, we will briefly present: 1. The implementation of evidence-based interventions (Unplugged, ICAPS Intervention centred on adolescents’ physical activity and sedentary behavior) or experimented for adaptation (Panjo: Nurse-family partnership, PSFP: Strengthening Families Program, Good Behavior Game, MBCP: Mindfulness-based childbirth and parenting). 2. The lessons learned from the implementation of these interventions. The required conditions for dissemination include readiness assessment, affordability of training and manuals, targeted audience, materials, supportive training and assistance. Fidelity monitoring tools must be provided for field practitioners who face the dilemma to adapt evidence-based program respecting its unchangeable core components (fidelity vs. flexibility in adapting an evidence-based intervention).

70 Purpose-built Catheters for Minimally Invasive Surfactant Therapy – Experience from a Canadian Tertiary Level Neonatal Intensive Care Unit

Abstract Background Surfactant delivery via a thin endotracheal catheter during spontaneous breathing (a technique called minimally invasive surfactant therapy [MIST]), is an increasingly popular alternative to intubation and surfactant administration. Procedural details among different centres vary, with marked differences in the choice of catheter to instill surfactant. Studies report use of feeding catheters, multiaccess catheters and vascular catheters for this purpose. Recently, purpose-built catheters for MIST received regulatory approval in Canada and became available for use. Procedural differences and user experiences between such catheters have not been described. Objectives The aim of this study was to describe procedural success, procedural adverse effects and user experience pertaining to two different types of purpose-build catheters (BLEScath™ and Surfcath™) for surfactant administration. Design/Methods This was a retrospective review of prospectively collected data at a tertiary care neonatal intensive care unit (NICU) in Southwestern Ontario. Neonates who received MIST using purpose-built catheters between January 1, 2021 and March 31, 2022 were included. Two types of purpose-built catheters were used in this time period: Surfcath™ and BLEScath™. Relevant baseline characteristics and data on procedural details (premedication, type of catheter) were collected. The procedural success, number of attempts and adverse effects among neonates who received MIST via Surfcath™ and those who received surfactant via BLEScath™ were compared, using chi-square tests or Fisher’s tests, as appropriate. User experience was described using an ease-of-use scale. Descriptive reports of user experience were collected and explored for themes/patterns. P-values <0.05 were considered statistically significant. Results 37 neonates met eligibility criteria; 22 received MIST via Surfcath™, whereas 15 received MIST via BLEScath™. Success rates were 91% in SurfCath™ and 93% in BLES-Cath (P> 0.994). Failed attempts were lower in Surfcath™ (23%) compared with BLEScath™ (33%), but the difference was not statistically significant (p=0.708). Upon analyzing ease-of-use by operators, we found that 90% of operators found Surfcath™ very easy or relatively easy to use, compared with 43% of users reflecting the same degree of use with BLEScath™ (P=.021). Users described difficulty in ‘maneuvering’ the BLEScath™ and reported it to be ‘pliable/ flimsy’. There was no difference in adverse events between groups. Conclusion This is the first study in Canada to report the experience of MIST with purpose-built catheters. Overall success rate was equally high for both catheters. Users subjectively reported higher ease of use with SurfCath™. Commercially available purpose-built catheters should facilitate universal adaptation of the MIST method. Our reports regarding operator experience may help with optimizing future product design to improve ease-of-use.

Universal primer multiplex PCR assay for detection and genotyping of porcine astroviruses

Porcine astroviruses (PAstV) are members of the family Astroviridae, Mamastravirus genus and have been identified to have five genotypes (PAstV1–5). These viruses are highly prevalent in pigs and can cause enteric disease as well as neurological or respiratory symptoms depending on their genotypes. At present, the epidemiological impacts of some PAstV genotypes on pigs are largely unknown and hence continuously monitoring of these PAstVs may be needed. The purpose of this research was to develop an improved and efficient detection tool for PAstVs and to evaluate the developed method using clinical samples. Initially, a set of five chimeric primers (CP), each comprising genotype specific primer pairs with an identical universal adapter at the 5’ end, and a universal primer (UP) that is identical to universal adapter sequence, were designed. With these tools in place, a novel multiplex PCR system with universal primer was established for the simultaneous detection of the five types of PAstV. This method can specifically detect PAstV genotypes, with a limit of detection (LOD) of 5 copies/μL for each genotype irrespective of single or mixed target template. Using this new assay, 273 pig fecal samples were investigated for further assay evaluation. Among all samples, the positive rate was 70.0% with PAstV4 in 56.8% of the samples, PAstV2 in 38.8%, PAstV1 in 16.8%, and PAstV5 in 11.0%. More than one PAstV in a sample were detected in 39.2% of the samples. The consistency rate between the novel multiplex PCR and singleplex PCRs was 96.4–100%. Given its rapidity, specificity and sensitivity, the novel multiplex PCR is a useful approach for demonstrating single or mixed genotype infections of PAstV.

Advances in TEE-Centric Intraprocedural Multimodal Image Guidance for Congenital and Structural Heart Disease.

Percutaneous interventions are gaining rapid acceptance in cardiology and revolutionizing the treatment of structural heart disease (SHD). As new percutaneous procedures of SHD are being developed, their associated complexity and anatomical variability demand a high-resolution special understanding for intraprocedural image guidance. During the last decade, three-dimensional (3D) transesophageal echocardiography (TEE) has become one of the most accessed imaging methods for structural interventions. Although 3D-TEE can assess cardiac structures and functions in real-time, its limitations (e.g., limited field of view, image quality at a large depth, etc.) must be addressed for its universal adaptation, as well as to improve the quality of its imaging and interventions. This review aims to present the role of TEE in the intraprocedural guidance of percutaneous structural interventions. We also focus on the current and future developments required in a multimodal image integration process when using TEE to enhance the management of congenital and SHD treatments.

Identification and functional analysis of myeloid differentiation factor 88 (MyD88) in early development of Haliotis diversicolor

Myeloid differentiation factor 88 (MyD88) is a universal adaptor protein and plays an important role in the signal transduction of Toll like receptors (TLR) family. In this study, the MyD88 gene from the Haliotis diversicolor (hdMyD88) was identified. The full-length cDNA of hdMyD88 has a 1927 base pairs (bp), with an open reading frame of 1314 bp encoding 437 amino acids including a death domain (DD) at the N-terminus and TIR domain at the C-terminus which are typical features of MyD88 family proteins. Three conserved boxes are also found in the hdMyD88, which are similar to MyD88 in vertebrates. The expression levels of hdMyD88 mRNA at different early embryonic developmental stages of abalone were measured by qPCR revealed that their constitutive expression at all developmental stages analyzed with the considerably highest values at 8 cell stage and the lowest level at the trochosphere stage. Additionally, the mRNA expression of hdMyD88 decreased significantly (P < 0.05) after MyD88-dsRNA soak in the stage of trochosphere and veliger than EGFP-dsRNA group and blank control group. Whole embryo in situ hybridization showed that the positive signals of hdMyD88 were in visceral mass of trochophore larvae and veliger larvae. These results indicate hdMyD88 may could respond to pathogenic infection and may play an important role in early innate immunity in the process of abalone larval development.

Domain consensual contrastive learning for few-shot universal domain adaptation

Domain consensual contrastive learning for few-shot universal domain adaptation

Efficient active contours with optical physical parameters for shoreline extraction: a general method and novel framework

ABSTRACT Accurate shoreline extraction is important for global climate change, land-sea interactions, and ocean dynamics. However, many current shoreline extraction methods have limitations in accuracy and efficiency when applied to different data, resulting from either empirical model parameters or limited image types. Considering the advantages of active contour in applying variational ideas to solve energy generalizations and the universal adaptability of optical physical parameters, an active contours with optical physical parameters (ACOPP) method that rapidly converges for shoreline extraction is proposed in this study. This model uses active contours to calculate the pixel-level energy generalization function of the image and combines the energy of the optical physical parameters to accelerate the process of contour curve approximation to the target edge by energy confrontation through iterative fitting, and improve the accuracy and efficiency of the target curves. Different images with multiple time phases in different regions were selected as experimental data, including GF2, SPOT-5, Sentinel-2, and Landsat-8, to demonstrate the accuracy, efficiency, and universality, while shoreline complexity coefficient was proposed for the study area division, which was used for shoreline extraction by ACOPP. Finally, the extraction results were analysed and validated, and the conclusions are as follows: ACOPP has a faster convergence speed in the extraction process than traditional methods, and the extraction results have a higher spatial resolution. The extraction results were highly accurate, and the mean absolute error (MAE) compared with the validation sets was < 2 pixels. The model is applicable to remote sensing images in which the normalized difference water index (NDWI) can be calculated, that is, optical remote sensing images containing green and near-infrared (or mid-infrared) bands. The experimental results prove the feasibility of ACOPP and a novel framework that combines ACOPP to extract target feature edge information for remote sensing images is proposed, the feasible and extensible of the frame have been verified.

Multistage Approach for Securing Data of Returned Disk On Data Center Environment

Once disk was either proactively or correctively replaced in a data center, it still contained data. With warranty or contractual agreement, the disk will be sent back to disk vendor outside of data center. Data with sensitive and confidential information will be risky leaved on disk sent outside data center without any effort to anticipate. By using sophisticated and latest technique, this information can be extracted for misused or criminal activity. We propose RAID striping, disk encryption, and dedicated shredding machine as multistage approach to secure the information. RAID striping will augment data while encryption will scramble information. Dedicated shredding machine will erase data by implementing simple machine and universal adaptor. By applying these combined multistage approaches, stakeholder will be no worried about the replaced disk sent outside their data center. By applying these three methods, accessible replaced disk’s data will be meaningless, unreadable then erased. Hence leaving disk with useless bits. For customer’s view on inaccessible disk, RAID striping and encryption will be more enough without erasing due to limited access on it. This approach shows three of four simulation which data on disk sent outside data center is secured.