Current Platforms Research Articles

Development and application of a miniature mass spectrometer with continuous sub-atmospheric pressure interface and integrated ionization source

For the miniature mass spectrometer (MS) with a continuous atmospheric pressure interface (CAPI), the gas in the multi-stage chambers directly affects the performance of the instrument. In this study, a sealed ionization chamber is designed to couple with a conventional mini CAPI-MS. In this configuration, the gas environment in the first ionization chamber can be flexibly changed to regulate the gas conditions throughout the entire instrument. By studying the effect of gas pressure on the performance of the instrument, we found that the instrument shows some unique advantages when the first ionization chamber is under sub-atmospheric pressure (SAP) conditions, such as reducing the load of the vacuum pump by 40%, achieving pump-free injection for gas and liquid samples, and improving the resolution by a factor of 2 without loss of detection sensitivity. Therefore, we propose a new integrated interface called continuous sub-atmospheric pressure interface (CSAPI) for building a miniature ion trap mass spectrometer. The CSAPI specially integrates sample introduction, gas/ions interface, and ionizations, including electrospray ionization (ESI) and secondary electrospray ionization (SESI), making this system more convenient for non-professional handlers to rapidly identify or monitor target analytes in gaseous- and solution-phase samples. We also use this system to study gas composition to further improve performance, being able to achieve a 5-fold sensitivity and 2-fold resolution improvement. At last, some custom applications of the current CSAPI-MS platform are explored and demonstrated, including real-time monitoring of chemical reactions in solution and long-distance sampling and analysis of dried Chinese herbs. In conclusion, this study provides a new approach to constructing a complete, versatile and practical miniature MS instrument.

Carob extract induces spermatogenesis in an infertile mouse model via upregulation of Prm1, Plzf, Bcl-6b, Dazl, Ngn3, Stra8, and Smc1b

Ethnopharmacological relevanceEthnopharmacological studies for drug discovery from natural compounds play an important role for developing current therapeutical platforms. Plants are a group of natural sources which have been served as the basis in the treatment of many diseases for centuries. In this regard, Ceratonia siliqua (carob) is one of the herbal medicine which is traditionally used for male infertility treatments. But so far the main mechanisms for effects of carob are unknown. Here, we intend to investigate the ability of carob extract to induce spermatogenesis in an azoospermia mouse model and determine the mechanisms that underlie its function. Aim of the studyThis is a pre-clinical animal model study to evaluate the effect of carob extract in spermatogenesis recovery. MethodsWe established an infertile mouse model with the intent to examine the ability of carob extract as a potential herbal medicine for restoration of male fertility. Sperm parameters, as well as gene expression dynamics and levels of spermatogenesis hormones, were evaluated 35 days after carob administration. ResultsSignificant enhanced sperm parameters (P < 0.05) showed that the carob extract could induce spermatogenesis in the infertile mouse model. Our data suggested an anti-apototic and inducer role in the expressions of cell cycle regulating genes. Carob extract improved the spermatogenesis niche by considerable affecting Sertoli and Leydig cells (P < 0.05). The carob-treated mice were fertile and contributed to healthy offspring that matured. Our data confirmed that this extract triggered the hormonal system, the spermatogenesis-related gene expression network, and signaling pathways to induce and promote sperm production with notable level (P < 0.05). We found that the aqueous extract consisted of a polar and mainly well water-soluble substance. Carob extract might upregulate spermatogenesis hormones via its amino acid components, which were detected in the extract by liquid chromatography-mass spectrometry (LC-MS). ConclusionOur results strongly suggest that carob extract might be a promising future treatment option for male infertility. This finding could pave the way for clinical trials in infertile men. This is the first study that has provided reliable, strong pre-clinical evidence for carob extract as an effective candidate for fertility recovery in cancer-related azoospermia.

Defining A Liquid Biopsy Profile of Circulating Tumor Cells and Oncosomes in Metastatic Colorectal Cancer for Clinical Utility.

Simple SummaryMetastatic colorectal cancer (mCRC) is typified by its tumor heterogeneity and changing disease states, suggesting that personalized medicine approaches could be vital to improving clinical practice. As a minimally invasive approach, the liquid biopsy has the potential to be a powerful longitudinal prognostic tool. We investigated mCRC patients’ peripheral blood samples using an enrichment-free single-cell approach to capture the broader rare-event population beyond the conventionally detected epithelial-derived circulating tumor cell (CTC). Our analysis reveals a heterogenous profile of CTCs and oncosomes not commonly found in normal donor samples. We identified select rare cell types based on their distinct immunofluorescence expression and morphology across multiple assays. Lastly, we highlight correlations between enumerations of the blood-based analytes and progression-free survival. This study clinically validates an unbiased rare-event approach in the liquid biopsy, motivating future studies to further investigate these analytes for their prognostic potential.Metastatic colorectal cancer (mCRC) is characterized by its extensive disease heterogeneity, suggesting that individualized analysis could be vital to improving patient outcomes. As a minimally invasive approach, the liquid biopsy has the potential to longitudinally monitor heterogeneous analytes. Current platforms primarily utilize enrichment-based approaches for epithelial-derived circulating tumor cells (CTC), but this subtype is infrequent in the peripheral blood (PB) of mCRC patients, leading to the liquid biopsy’s relative disuse in this cancer type. In this study, we evaluated 18 PB samples from 10 mCRC patients using the unbiased high-definition single-cell assay (HDSCA). We first employed a rare-event (Landscape) immunofluorescence (IF) protocol, which captured a heterogenous CTC and oncosome population, the likes of which was not observed across 50 normal donor (ND) samples. Subsequent analysis was conducted using a colorectal-targeted IF protocol to assess the frequency of CDX2-expressing CTCs and oncosomes. A multi-assay clustering analysis isolated morphologically distinct subtypes across the two IF stains, demonstrating the value of applying an unbiased single-cell approach to multiple assays in tandem. Rare-event enumerations at a single timepoint and the variation of these events over time correlated with progression-free survival. This study supports the clinical utility of an unbiased approach to interrogating the liquid biopsy in mCRC, representing the heterogeneity within the CTC classification and warranting the further molecular characterization of the rare-event analytes with clinical promise.

Achieving high intracellular trehalose in hRBCs by reversible membrane perturbation of maltopyranosides with synergistic membrane protection of macromolecular protectants.

Trehalose is considered as a biocompatible cryoprotectant for solvent-free cryopreservation of cells, but the difficulty of the current trehalose delivery platforms to human red blood cells (hRBCs) limits its wide applications. Due to cell injuries caused by incubation at 37°C and low intracellular loading efficiency, development of novel methods to facilitate trehalose entry in hRBCs is essential. Herein, a reversible membrane perturbation and synergistic membrane stabilization system based on maltopyranosides and macromolecular protectants was constructed, demonstrating the ability of efficient trehalose loading in hRBCs at 4 °C. Results of confocal laser scanning microscopy exhibited that the intracellular loading with the assistance of maltopyranosides was a reversible process, while the membrane protective effect of macromolecular protectants on trehalose loading in hRBCs was necessary. It was suggested that introduction of 30mM poly(vinyl pyrrolidone) 8000 combined with 1mM dodecyl-β-D-maltopyranoside and 0.8M trehalose could increase the intracellular trehalose to 84.0±11.3mM in hRBCs, whereas poly(ethylene glycol), dextran, human serum albumin or hydroxyethyl starch had a weak effect. All the macromolecular protectants could promote the cryosurvival of hRBCs, exhibiting membrane stabilization, and incubation and followed by cryopreservation did not change the basic functions and normal morphology of hRBCs substantially. This study provided an alternative strategy for glycerol-free cryopreservation of cells and the delivery of membrane-impermeable cargos.

Streaming steam

Building its present identity from the reimagined recollections of a past age of industry, the steampunk movement’s array of antiquated yet spectacular machines have become hallmarks of our fascination with technology’s history. In this article, I will trace the movement’s retrofuturistic sensibilities through a wave of short films and web series that set themselves within worlds that are constructed from anachronistic devices that belong to neither the past nor the present. Instead, these are texts that, whether constructed by amateur filmmakers, professionals - and a range of practices in-between - use their science fictional identities to disrupt the seemingly linear trajectory of our media’s historical progress. Through them, the aesthetics of nineteenth-century photographic techniques and special effects are reimagined through the lens of current streaming platforms, modern computer-generated imagery and a new breed of maker cultures who desire to conflate cutting-edge innovation with the first wave of invention and experimentation that breathed life into our visual media. Most significantly, however, by exploring the proliferation and popularization of neo-Victorian machinery within the vast array of short films that have been both distributed and produced through highly digitized practices, the steampunk genre will be used to examine representations of craftsmanship and “making” that have become embedded within contemporary popular culture.

CCi-CLOUD: A framework for community based remote cochlear implant user experiments based on the CCi-MOBILE research platform

The speech processing field has recently developed a critical need for conducting listener experiments remotely versus traditional in-person methods due to social distancing measures enforced by COVID-19 pandemic. CCi-MOBILE is our current hardware research platform created to support the Cochlear Implant research community, facilitating the development of new strategies &amp; algorithms for improving sound quality and scientific investigation for CI users/systems. In this study, CCi-CLOUD, a virtual platform, is proposed and developed to expand the functionality of CCi-MOBILE to allow for both subject testing and scientific studies to be performed remotely. CCi-CLOUD portal is established with three support categories: (i) Remote Desktop: with direct connect support for CI user remote experimentation; (ii) Cloud Data Storage: for data sharing among researchers &amp; subjects; (iii) Online Web App: serves as a portal which connects CI subjects with the CI research community. Three multimodal sound experiments are considered in this study as a virtual experimental framework including speech recognition, speaker identification, and sound type classification for both CI and normal hearing (NH) users. Experimental evaluation is performed for both In-Lab and Remote/Online scenarios to benchmark experimental protocols and infrastructure validity for CI/NH subjects. Results on consistency between the two modalities are also discussed.

Knowledge of SARS-CoV-2 Epitopes and Population HLA Types Is Important in the Design of COVID-19 Vaccines.

The COVID-19 pandemic has caused extensive loss of lives and economic hardship. In response, infectious disease experts and vaccine developers promptly responded by bringing forth candidate vaccines, some of which have been listed in the World Health Organization’s Emergency Use Listing. Notwithstanding the diverse worldwide population genetics, the vaccines thus far developed are generic in nature for use worldwide. Differences in the human leukocyte antigen (HLA) in different populations, variation of the T cell epitopes, and the propensity of SARS-CoV-2 genetic mutations left room for improvement of the vaccines. Here, we discussed the implications of COVID-19 vaccination and SARS-CoV-2 infection by taking into consideration SARS-CoV-2 mutations, T cell epitopes, risk factors, and current platforms of candidate vaccines based on the HLA types that are commonly present in Peninsular Malaysia Chinese, Indian, and Malay populations. The HLA types associated with protection against and susceptibility to severe SARS-CoV-2 infection were identified based on reported case-control and cohort studies. The relevance of including the non-spike SARS-CoV-2 proteins in the future COVID-19 vaccines is also highlighted. This review is meant to trigger researchers to acknowledge the importance of investigating the possible relationships between the HLA haplotype and the SARS-CoV-2 strains circulating in different populations.

Dual-path inscription of plasmonic nano-Ag moiré fringes.

Construction of moiré surface patterns has attracted considerable attention due to the fascinating function of photoelectric manipulation. Holographic inscription offers superposition of two or more sinusoidal gratings to form moiré structures. However, the current material platforms primarily depend on a single process of photoinduced physical property change to build up multicomponent gratings. Herein, we demonstrate a strategy of bidirectional photochemical reaction on mesoporous TiO2 matrices to form plasmonic nano-Ag moiré fringes. This consists of a photoreduction grating from in situ growth of Ag nanoparticles (NPs) and a photooxidation grating utilizing the Schottky interface of Ag/TiO2. The pattern obtained under the superposition of double spatial frequencies exhibits non-equidistant moiré fringes. This Letter provides a pathway for implementing complex surface structures.

Label-free detection of DNA methylation by surface-enhanced Raman spectroscopy using zirconium-modified silver nanoparticles

DNA methylation is an important feature of gene epigenetics that affects the metabolic process of organisms. Although surface-enhanced Raman spectroscopy (SERS) has demonstrated great potential in label-free DNA detection, discriminating the various processes involved in DNA methylation remains a challenge. DNA molecules fold themselves, wrapping the hydrophobic bases, thus making it difficult for traditional methods to detect single-base signals. In this study, we develop a SERS platform for detecting DNA via modifying silver nanoparticles by zirconium ions to obtain the DNA fingerprint information of base methylations (N6-methylated adenine and 5-methylated cytosine). Zirconium ions open the folded DNA molecules, enabling SERS signals of the four DNA bases (A, C, G, T) to be obtained as well as identification of the subtle differences between normal and methylated DNA with single base-level sensitivity. Moreover, the identifying information of DNA methylation was obtained by combining principal component analysis (PCA) with 2D correlation spectroscopy analysis. The findings of this study provide a substantial progress for current platforms for DNA sequencing, genetic testing, and gene-disease treatment.

Quality measurement and surveillance platforms in critically ill children: A scoping review

Background/aimThe objective of this study was to describe current surveillance platforms which support routine quality measurement in paediatric critical care. MethodScoping review. The search strategy consisted of a traditional database and grey literature search as well as expert consultation. Surveillance platforms were eligible for inclusion if they collected measures of quality in critically ill children. ResultsThe search strategy identified 21 surveillance platforms, collecting 57 unique outcome (70%), process (23%), and structural (7%) quality measures. Hospital-associated infections were the most commonly collected outcome measure across all platforms (n = 11; 52%). In general, case definitions were not harmonised across platforms, with the exception of nationally mandated hospital-associated infections (e.g., central line–associated blood stream infection). Data collection relied on manual coding. Platforms typically did not provide an evidence-based rationale for measures collected, with no identifiable reports of co-designed, consensus-derived measures or consumer involvement in measure selection or prioritisation. ConclusionsQuality measurement in critically ill children lacks uniformity in definition which limits local and international benchmarking. Current surveillance activities for critically ill children focus heavily on outcome measurement, with process, structural, and patient-reported measures largely overlooked. Long-term outcome measures were not routinely collected. Harmonisation of paediatric intensive care unit quality measures is needed and can be achieved using prioritisation and consensus/co-design methods.

Constraining China's land carbon sink from emerging satellite CO2 observations: Progress and challenges.

Land carbon sink is a vital component for the achievement of China's ambitious carbon neutrality goal, but its magnitude is poorly known. Atmospheric observations and inverse models are valuable tools to constrain the China's land carbon sink. Space-based CO2 measurements from satellites form an emerging data stream for application of such atmospheric inversions. Here, we reviewed the satellite missions that is dedicated to the monitoring of CO2 , and the recent progresses on the inversion of China's land carbon sink using satellite CO2 measurements. We summarized the limitations and challenges in current space platforms, retrieval algorithms, and the inverse modeling. It is shown that there are large uncertainties of contemporary satellite-based estimates of China's land carbon sink. We discussed future opportunities of continuous improvements in three aspects to better constrain China's land carbon sink with space-based CO2 measurements.

Controlled Rehydration of Dried Reagents for Robust Multiplex Digital PCR.

Digital polymerase chain reaction (dPCR) is emerging as a powerful method for nucleic acid detection due to its unprecedented sensitivity and precision. However, most current dPCR platforms are inherently limited by their low multiplexing ability due to primer-pair cross interactions and spectral overlap of available fluorophores. Here, we present a novel and robust method for multiplexing dPCR that is free from primer dimerization and fluorescence channel number limitation, enabling highly precise and multiplexed detection of nucleic acid targets. By prestoring target-specific primers and probes in different storage chambers, the method physically separates reactions and thus avoids the primer-pair cross interactions and spectral overlap of different fluorescent probes that usually occur within a single-tube reaction. Furthermore, a dissolvable delay valve (DDV) is embedded between each pair of the reagent prestorage chamber and reaction microwell array. Such a DDV configuration allows full reconstitution of the prestored reagents and then generates a uniform concentration distribution of the reconstituted reagents across the entire reaction microwell array, which is favorable for achieving reliable and robust multiplex dPCR assays. We demonstrated the feasibility of this method by performing an eight-plex dPCR assay targeting the seven most common point mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) and a reference sequence (wild-type KRAS allele).

Design and Application of e-Commerce Platform System Based on Blockchain Technology on the Internet of Things

Focusing on the problems of platform monopoly, power rent-seeking and high cost in the current Internet e-commerce platform system, a new method and paradigm of e-commerce platform is introduced in this paper based on the blockchain, smart contract technology, tokenomics thought, and e-commerce professional theory. The interconnection of e-commerce information value chain can be realized by means of blockchain related technology and the construction of circulation system, payment system, and credit system in the core module of e-commerce platform. From the perspective of users of e-commerce platform, the optimizing of the application process and operation structure of e-commerce operation can significantly improve users’ service experience, avoid information disclosure risk, and reduce process redundancy as well. The prominent advantages of this e-commerce platform include data security, data sharing, shopping cost reduction, monopoly elimination, community construction, and commercial form innovation. The e-commerce function was originally defined as building an e-commerce platform, optimizing and promoting various search products, maintaining, refactoring and extending the e-commerce platform, and developing and monetizing online products. It has 6 operating modes: direct sales model, yellow pages model, coupon model, brokerage model, reservation model, and market model.

Cryopreservation of Human Bone Marrow Derived Mesenchymal Stem Cells at High Concentration Is Feasible.

Introduction: For stem cell therapies to be adopted in mainstream health care, robust, reliable, and cost-effective storage and transport processes must be developed. Cryopreservation remains the best current platform for this purpose, and freezing cells at high concentration may have many benefits, including savings on cost and storage space, facilitating transport logistics, and reducing cryoprotectant volume. Cells, such as mesenchymal stem cells (MSCs), are typically frozen at 1 million cells per milliliter (mL), but the aim of this study is to examine the post-thaw attributes of human bone marrow derived MSCs (hBM-MSCs) frozen at 1, 5, and 10 million cells per mL. Methods: Thawed cells were assessed for their morphology, phenotypic marker expression, viability, apoptosis level, metabolic activity, proliferation, and osteogenic and adipogenic differentiation. Results: In this study, for the first time, it is shown that all assessed cells expressed the typical MSC markers (CD90, CD105, and CD73) and lacked the expression of CD14, CD20, CD34, CD45, and HLA-DR. In addition, all cells showed elongated fibroblastic morphology. Post-thaw viability was retained with no difference among the three concentrations. Moreover, no significant statistical difference was observed in the post-thaw apoptosis level, metabolic activity, proliferation, and osteogenic potential, indicating that these cells are amenable to cryopreservation at higher concentrations. Conclusion: The results of this study are of paramount importance to the development of manufacturing processes around a useful freezing concentration when cells are targeted to be stored for at least 6 months.

Resonant Plasmonic-Biomolecular Chiral Interactions in the Far-Ultraviolet: Enantiomeric Discrimination of sub-10 nm Amino Acid Films.

Resonant plasmonic-molecular chiral interactions are a promising route to enhanced biosensing. However, biomolecular optical activity primarily exists in the far-ultraviolet regime, posing significant challenges for spectral overlap with current nano-optical platforms. We demonstrate experimentally and computationally the enhanced chiral sensing of a resonant plasmonic-biomolecular system operating in the far-UV. We develop a full-wave model of biomolecular films on Al gammadion arrays using experimentally derived chirality parameters. Our calculations show that detectable enhancements in the chiroptical signals from small amounts of biomolecules are possible only when tight spectral overlap exists between the plasmonic and biomolecular chiral responses. We support this conclusion experimentally by using Al gammadion arrays to enantiomerically discriminate ultrathin (<10 nm thick) films of tyrosine. Notably, the chiroptical signals of the bare films were within instrumental noise. Our results demonstrate the importance of using far-UV active metasurfaces for enhancing natural optical activity.

Satellite multi-beam multicast support for an efficient community-based CDN

The design and implementation of an efficient end-to-end IP-based infrastructure for the delivery of multimedia content is of paramount importance in current public networks, dominated by the constant growth of video streaming traffic. Content Delivery Networks (CDNs) represent the main technological solution to manage the huge volumes of traffic involved, by guaranteeing high quality levels to applications and low impact to the core networks, thanks to the efficient distribution of content among edge caches that are located as close as possible to end-users. Nonetheless, the hierarchical data distribution associated with CDNs can be in principle subject to inefficiencies, as well as performance limitations in case of congested segments along the end-to-end delivery path. In this context, we propose the exploitation of satellite multicast capabilities offered by modern high throughput satellite (HTS) platforms, in a virtualized-compatible model, to compensate for flaws of terrestrial networks. The role of satellite communication is to offer multicast support (as a complement to landline connectivity) with wide geographical service areas based on the available satellite beams, enabling a popularity-based content distribution support. In addition, multi-beam satellite technology allows for a more fine-grained approach to popularity evaluation based on user location. The proposed service and the related network configuration are described in the paper, in relation with current and future SatCom platforms. We then present the results of the proposed CDN caching algorithms in a simulated environment, showing promising results associated with a preliminary performance evaluation.

Evaluation of a High-Temperature Pre-Heating System Design for a Large-Scale Additive Manufacturing System

Additive Manufacturing (AM) of titanium (Ti6Al4V) material using Selective Laser Melting (SLM) may generate significant residual stresses of a tensile nature, which can cause premature component failure. The Aeroswift platform is a large volume AM machine where a high-temperature substrate preheating system is used to mitigate high thermal gradients. The current machine platform is unable to achieve a target build-plate temperature of 600 °C. This study focuses on the analysis of the preheating system design to determine the cause of its inefficiency, and the experimental testing of key components such as the heater and insulation materials. A Finite Element Analysis (FEA) model shows the ceramic heater achieves a maximum temperature of 395 °C, while the substrates (build-plates) only attain 374 °C. Analysis showed that having several metal components in contact and inadequate insulation around the heater caused heat loss, resulting in the preheating system’s inefficiency. Additionally, experimental testing shows that the insulation material used was 44% efficient, and a simple insulated test setup was only able to obtain a maximum temperature of 548.8 °C on a 20 mm thick stainless steel 304 plate, which illustrated some of the challenges faced by the current pre-heating design. New design options have been developed and FEA analysis indicates that a reduction in heat loss through improved sub-component configurations can obtain 650 °C degrees above the substrate without changing the heating element power. The development and challenges associated with the large-scale preheating system for AM are discussed, giving an insight into improving its performance.

The The Study of UX on Students’ Perception and Attitude of Using Zoom During Covid-19 Pandemic Using User Centered Design Method

The pandemic of COVID-19 resulted in the physical shutdown which has now transformed education into an exclusive "online learning" model. Zoom is being used to evaluate the perceived usability as the reference platform. The students find it less collaborative, less interactive, boring, and less collaborative. From this perspective, the Usability of the current online learning platforms is an important factor, particularly because no physical classes are present. The User-Centered Design (UCD) approach was chosen for this study and using the Usability Scale (SUS) method to evaluate the interface. The objective of this study is to analyze user experience, design solutions and evaluate user interfaces that can meet user needs. A pre-survey to evaluate the difficulties of the Zoom application based on user experience, and a post-survey to see if the upgraded design can help the students using the Zoom application for online learning. Then, use the System Usability Scale (SUS) questionnaire approach to measure the system's usability. After the UCD approach was completed, the researcher did a follow-up survey. The results showed that SUS ratings went up to 85.12. As a result, the previously low acceptability ranges have been raised to acceptable. Additionally, the grade scale has been reclassified B. The Zoom program now has more features and is easier to use, and fulfills the students' needs.

TCT-428 Outcomes of Patients Undergoing TAVI for Purely Regurgitant Native Aortic Valves With the Current Generation Transcatheter Aortic Valve Platforms

TCT-428 Outcomes of Patients Undergoing TAVI for Purely Regurgitant Native Aortic Valves With the Current Generation Transcatheter Aortic Valve Platforms

Optimal QoE-Fair Resource Allocation in Multipath Video Delivery Network

A steadily increasing number of users consume videos over the Internet. In current video platforms, players run a control algorithm that dynamically chooses the video bitrate to match the time-varying network bandwidth. Such an algorithm strives to improve the quality individually perceived by users. Consequently, this control architecture leads, in the optimal case, to maximize the average quality perceived collectively by all users rather than to a quality-fair distribution of resources, possibly leading to user abandonment for those users receiving a lower quality. Therefore, we argue that well-designed video delivery networks should gracefully degrade the perceived quality equally for all users when resources become scarce. In this paper, we propose the Multi-Commodity Flow Problem (MCFP) optimization framework to address the issue of designing a QoE-fair optimal allocation strategy. We show how to make the resulting problem tractable for video platforms serving massive audiences. The performance of the proposed optimal fair resource allocation strategy is tested through realistic simulations involving thousands of concurrent users on two real networks by varying both the total load on the network and the system parameters.