Boosting Fronthaul Capacity: Global Optimization of Power Sharing for Centralized Radio Access Network

The limited fronthaul capacity imposes a challenge on the uplink of centralized radio access network (C-RAN). We propose to boost the fronthaul capacity of massive multiple-input multiple-output (MIMO) aided C-RAN by globally optimizing the power sharing between channel estimation and data transmission both for the user devices (UDs) and the remote radio units (RRUs). Intuitively, allocating more power to the channel estimation will result in more accurate channel estimates, which increases the achievable throughput. However, increasing the power allocated to the pilot training will reduce the power assigned to data transmission, which reduces the achievable throughput. In order to optimize the powers allocated to the pilot training and to the data transmission of both the UDs and the RRUs, we assign an individual power sharing factor to each of them and derive an asymptotic closed-form expression of the signal-to-interference-plus-noise for the massive MIMO aided C-RAN consisting of both the UD-to-RRU links and the RRU-to-baseband unit (BBU) links. We then exploit the C-RAN architecture's central computing and control capability for jointly optimizing the UDs' power sharing factors and the RRUs' power sharing factors aiming for maximizing the fronthaul capacity. Our simulation results show that the fronthaul capacity is significantly boosted by the proposed global optimization of the power allocation between channel estimation and data transmission both for the UDs and for their host RRUs. As a specific example of 32 receive antennas (RAs) deployed by RRU and 128 RAs deployed by BBU, the sum-rate of 10 UDs achieved with the optimal power sharing factors improves 33\% compared with the one attained without optimizing power sharing factors

Transcriptome and venom proteome of the box jellyfish Chironex fleckeri

Background: The box jellyfish, Chironex fleckeri, is the largest and most dangerous cubozoan jellyfish to humans. It produces potent and rapid-acting venom and its sting causes severe localized and systemic effects that are potentially life-threatening. In this study, a combined transcriptomic and proteomic approach was used to identify C. fleckeri proteins that elicit toxic effects in envenoming. Results: More than 40,000,000 Illumina reads were used to de novo assemble ~34,000 contiguous cDNA sequences and ~20,000 proteins were predicted based on homology searches, protein motifs, gene ontology and biological pathway mapping. More than 170 potential toxin proteins were identified from the transcriptome on the basis of homology to known toxins in publicly available sequence databases. MS/MS analysis of C. fleckeri venom identified over 250 proteins, including a subset of the toxins predicted from analysis of the transcriptome. Potential toxins identified using MS/MS included metalloproteinases, an alpha-macroglobulin domain containing protein, two CRISP proteins and a turripeptide-like protease inhibitor. Nine novel examples of a taxonomically restricted family of potent cnidarian pore-forming toxins were also identified. Members of this toxin family are potently haemolytic and cause pain, inflammation, dermonecrosis, cardiovascular collapse and death in experimental animals, suggesting that these toxins are responsible for many of the symptoms of C. fleckeri envenomation. Conclusions: This study provides the first overview of a box jellyfish transcriptome which, coupled with venom proteomics data, enhances our current understanding of box jellyfish venom composition and the molecular structure and function of cnidarian toxins. The generated data represent a useful resource to guide future comparative studies, novel protein/peptide discovery and the development of more effective treatments for jellyfish stings in humans. (Length: 300)

BioClojure: A functional library for the manipulation of biological sequences

Motivation: BioClojure is an open-source library for the manipulation of biological sequence data written in the language Clojure. BioClojure aims to provide a functional framework for the processing of biological sequence data that provides simple mechanisms for concurrency and lazy evaluation of large data sets. Results: BioClojure provides parsers and accessors for a range of biological sequence formats, including UniProtXML, Genbank XML, fasta and fastq. In addition it provides wrappers for key analysis programs, including BLAST, SignalP, TMHMM and InterProScan, and parsers for analyzing their output. All interfaces leverage Clojure\u27s functional style and emphasize laziness and composability, so that BioClojure, and user-defined, functions can be chained into simple pipelines that are thread-safe and seamlessly integrate lazy evaluation. Availability: BioClojure is distributed under the Lesser GPL (LGPL) and the source code is freely available from GitHub (https://github.com/s312569/clj-biosequence). Contact: [email protected]

A complicated complex: ion channels, voltage sensing, cell membranes and peptide inhibitors

Voltage-gated ion channels (VGICs) are specialised ion channels that have a voltage dependent mode of action, where ion conduction, or gating, is controlled by a voltage-sensing mechanism. VGICs are critical for electrical signalling and are therefore important pharmacological targets. Among these, voltage-gated sodium channels (Nas) have attracted particular attention as potential analgesic targets. Nas, however, comprise several structurally similar subtypes with unique localisations and distinct functions, ranging from amplification of action potentials in nociception (e.g. Na1.7) to controlling electrical signalling in cardiac function (Na1.5). Understanding the structural basis of Na function is therefore of great significance, both to our knowledge of electrical signalling and in development of subtype and state selective drugs. An important tool in this pursuit has been the use of peptides from animal venoms as selective Na modulators. In this review, we look at peptides, particularly from spider venoms, that inhibit Nas by binding to the voltage sensing domain (VSD) of this channel, known as gating modifier toxins (GMT). In the first part of the review, we look at the structural determinants of voltage sensing in VGICs, the gating cycle and the conformational changes that accompany VSD movement. Next, the modulation of the analgesic target Na1.7 by GMTs is reviewed to develop bioinformatic tools that, based on sequence information alone, can identify toxins that are likely to inhibit this channel. The same approach is also used to define VSD sequences, other than that from Na1.7, which are likely to be sensitive to this class of toxins. The final section of the review focuses on the important role of the cellular membrane in channel modulation and also how the lipid composition affects measurements of peptide-channel interactions both in binding kinetics measurements in solution and in cell-based functional assays

A microRNA profile associated with Opisthorchis viverrini-induced cholangiocarcinoma in tissue and plasma

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive tumor of the bile duct, and a significant public health problem in East Asia, where it is associated with infection by the parasite Opisthorchis viverrini. ICC is often detected at an advanced stage and with a poor prognosis, making a biomarker for early detection a priority. Methods: We have comprehensively profiled miRNA expression levels in ICC tumor tissue using small RNA-Seq and validated these profiles using quantitative PCR on matched plasma samples. Results: Distinct miRNA profiles were associated with increasing histological differentiation of ICC tumor tissue. We also observed that histologically normal tissue adjacent to ICC tumor displayed miRNA expression profiles more similar to tumor than liver tissue from healthy donors. In plasma samples, an eight-miRNA signature associated with ICC, regardless of the degree of histological differentiation of its matched tissue, forming the basis of a circulating miRNA-based biomarker for ICC. Conclusions: The association of unique miRNA profiles with different ICC subtypes suggests the involvement of specific miRNAs during ICC tumor progression. In plasma, an eight-miRNA signature associated with ICC could form the foundation of an accessible (plasma-based) miRNA-based biomarker for the early detection of ICC

Cannabinoid biosynthesis using non-canonical enzymes

Please click Additional Files below to see the full abstract

Development of 5G-based Remote Ultrasound Education: Current Status and Future Trends

The rapid advancement of 5G technology has opened new possibilities for remote ultrasound education, offering the potential to enhance training, real-time consultation, and quality control for primary ultrasound doctors. The 5G remote ultrasound education has the potential to revolutionize the way primary ultrasound doctors are trained and supported, ultimately leading to improved patient care and outcomes. By understanding the current status and development trends of this cutting-edge educational approach, the medical community can better prepare for and contribute to its ongoing evolution. Looking towards the future, the development trends in 5G remote ultrasound education are expected to revolve around continuous improvement and innovation in educational methods and technologies. This includes the exploration of artificial intelligence and machine learning applications, the expansion of telemedicine and telementoring programs, and the development of personalized learning plans tailored to individual learners\u27 needs. This article aims to offer an overview of the current status and applications of 5G remote ultrasound education, including the development of theoretical courses and network construction within our institutes, and to discuss future trends in this field

Elucidating the Lipid Binding Properties of Membrane-Active Peptides Using Cyclised Nanodiscs

The lipid composition of the cellular membrane plays an important role in a number of biological processes including the binding of membrane-active peptides. Characterization of membrane binding remains challenging, due to the technical limitations associated with the use of standard biophysical techniques and available membrane models. Here, we investigate the lipid binding properties of two membrane-active peptides, VSTx1, a well characterized ion-channel inhibitor, identified from spider venom, that preferentially binds to anionic lipid mixtures, and AA139 an antimicrobial β-hairpin peptide with uncharacterised lipid binding properties, currently in pre-clinical development. The lipid binding properties of these peptides are elucidated using nanodiscs formed by both linear and circularized (sortase-mediated) forms of a membrane scaffold protein (MSP1D1ΔH5). We find that nanodiscs formed by circularized MSPs—in contrast to those formed by linear MSPs—are sufficiently stable under sample conditions typically used for biophysical measurements (including lipid composition, a range of buffers, temperatures and concentrations). Using these circularized nanodiscs, we are able to extract detailed thermodynamic data using isothermal titration calorimetry (ITC) as well as atomic resolution mapping of the lipid binding interfaces of our isotope labeled peptides using solution-state, heteronuclear, nuclear magnetic resonance (NMR) spectroscopy. This represents a novel and general approach for elucidating the thermodynamics and molecular interface of membrane-active peptides toward flat lipid bilayers of variable composition. Our approach is validated by first determining the thermodynamic parameters and binding interface of VSTx1 toward the lipid bilayer, which shows good agreement with previous studies using lipid micelles and liposomes. The method is then applied to AA139, where the membrane binding properties are unknown. This characterization, involved solving the high-resolution structure of AA139 in solution using NMR spectroscopy and the development of a suitable expression system for isotope labeling. AA139 was found to bind exclusively to anionic membranes with moderate affinity (Kd~low μM), and was found to have a lipid binding interface involving the termini of the β-hairpin structure. The preference of AA139 for anionic lipids supports a role for membrane binding in the mode-of-action of this peptide, which is also consistent with its higher inhibitory activity against bacterial cells compared to mammalian cells. The described approach is a powerful method for investigation of the membrane binding properties of this important class of molecules

Semienzymatic cyclization of disulfide-rich peptides using sortase A

Background: Sortase A (SrtA) is a transpeptidase capable of catalyzing the formation of amide bonds. Results: SrtA was used to backbone-cyclize disulfide-rich peptides, including kalata B1, -conotoxin Vc1.1, and SFTI-1. Conclusion: SrtA-mediated cyclization is applicable to small disulfide-rich peptides. Significance: SrtA-mediated cyclization is an alternative to native chemical ligation for the cyclization of small peptides of therapeutic interest