Search

The satellite radar altimetry record of sea level has now surpassed 30 years in length. These observations have greatly improved our knowledge of the open ocean and are now an essential component of many operational marine systems and climate studies. But the use of altimetry close to the coast remains a challenge from both a technical and scientific point of view. Here, we take advantage of the recent availability of many new algorithms developed for altimetry sea level computation to quantify and analyze the uncertainties associated with the choice of algorithms when approaching the coast. To achieve this objective, we did a round-robin analysis of radar altimetry data, testing a total of 21 solutions for waveform retracking, correcting sea surface heights and finally deriving sea level variations. Uncertainties associated with each of the components used to calculate the altimeter sea surface heights are estimated by measuring the spread of sea level values obtained using the various algorithms considered in the round-robin for this component. We intercompare these uncertainty estimates and analyze how they evolve when we go from the open ocean to the coast. At regional scale, complementary analyses are performed through comparisons with independent tide gauge observations. The results show that tidal corrections and uncertainties in the mean sea surface can be significant contributors to uncertainties in sea level estimates in many coastal regions. However, improving the quality and robustness of the retracking algorithm used to derive both the range and the sea state bias correction is today the main factor to bring accurate altimetry sea level data closer to the shore than ever before.

In this work, the SrFe12–xZnxO19 (Zn-SrM, x = 0, 0.1, 0.4, and 1.0) samples were fabricated using a combination of ball milling and heat treatment methods, which was simple and low-cost. Interestingly, the Zn-SrM samples exhibited great microwave absorption performances with an absorption rate of more than 99.99% and very thin thicknesses. The x = 0.1 sample could reach an excellent RL value of −40.08 dB at f = 17.88 GHz for a thickness of 1.45 mm. The x = 0.4 sample achieved a great RL value of −42.51 dB at 17.86 GHz and an EAB value of 1.29 GHz for t = 1.50 mm. With a thickness of 5.1 mm, the x = 1.0 sample could achieve a great RL value of −51.20 dB and an EAB value of 1.58 GHz. This microwave absorption performance, low cost, and simplicity of fabrication could confirm that Zn-SrM samples could be used as high-efficiency MAMs. The great microwave dissipating characteristics could be attributed to the high values of imaginary parts of complex permeability and complex permittivity leading to the high loss tangent, high degree of impedance matching, high values of attenuation constant and conductivity, suitable values of eddy current factor, and large numbers of semicircles in their Cole-Cole plots.

Abstract Particle physics today faces the challenge of explaining the mystery of dark matter, the origin of matter over anti-matter in the Universe, the origin of the neutrino masses, the apparent fine-tuning of the electro-weak scale, and many other aspects of fundamental physics. Perhaps the most striking frontier to emerge in the search for answers involves new physics at mass scales comparable to familiar matter, below the GeV-scale, or even radically below, down to sub-eV scales, and with very feeble interaction strength. New theoretical ideas to address dark matter and other fundamental questions predict such feebly interacting particles (FIPs) at these scales, and indeed, existing data provide numerous hints for such possibility. A vibrant experimental program to discover such physics is under way, guided by a systematic theoretical approach firmly grounded on the underlying principles of the Standard Model. This document represents the report of the FIPs 2022 workshop, held at CERN between the 17 and 21 October 2022 and aims to give an overview of these efforts, their motivations, and the decadal goals that animate the community involved in the search for FIPs.

Abstract Background Implementation research is increasingly used to identify common implementation problems and key barriers and facilitators influencing efficient access to health interventions. Objective To develop and propose an equity-based framework for Implementation Research (EquIR) of health programs, policies and systems. Methods A systematic search of models and conceptual frameworks involving equity in the implementation of health programs, policies and systems was conducted in Medline (PubMed), Embase, LILACS, Scopus and grey literature. Key characteristics of models and conceptual frameworks were summarized. We identified key aspects of equity in the context of seven Latin American countries-focused health programs We gathered information related to the awareness of inequalities in health policy, systems and programs, the potential negative impact of increasing inequalities in disadvantaged populations, and the strategies used to reduce them. Results A conceptual framework of EquIR was developed. It includes elements of equity-focused implementation research, but it also links the population health status before and after the implementation, including relevant aspects of health equity before, during and after the implementation. Additionally, health sectors were included, linked with social determinants of health through the “health in all policies” proposal affecting universal health and the potential impact of the public health and public policies. Conclusion EquIR is a conceptual framework that is proposed for use by decision makers and researchers during the implementation of programs, policies or health interventions, with a focus on equity, which aims to reduce or prevent the increase of existing inequalities during implementation.

Abstract The small Ultra-Red Fluorescent Protein (smURFP) represents a new class of fluorescent protein with exceptional photostability and brightness derived from allophycocyanin in a previous directed evolution. Here, we report the smURFP crystal structure to better understand properties and enable further engineering of improved variants. We compare this structure to the structures of allophycocyanin and smURFP mutants to identify the structural origins of the molecular brightness. We then use a structure-guided approach to develop monomeric smURFP variants that fluoresce with phycocyanobilin but not biliverdin. Furthermore, we measure smURFP photophysical properties necessary for advanced imaging modalities, such as those relevant for two-photon, fluorescence lifetime, and single-molecule imaging. We observe that smURFP has the largest two-photon cross-section measured for a fluorescent protein, and that it produces more photons than organic dyes. Altogether, this study expands our understanding of the smURFP, which will inform future engineering toward optimal FPs compatible with whole organism studies.

AbstractGenus Penicillium comprising the most important and extensively studied fungi has been well-known as a rich source of secondary metabolites. Our study aimed to analyze and investigate biological activities, including in vitro anti-cancer, anti-inflammatory and anti-diabetic properties, of metabolites from a marine-derived fungus belonging to P. levitum. The chemical compounds in the culture broth of P. levitum strain N33.2 were extracted with ethyl acetate. Followingly, chemical analysis of the extract leaded to the isolation of three ergostane-type steroid components, namely cerevisterol (1), ergosterol peroxide (2), and (3β,5α,22E)-ergosta-6,8(14),22-triene-3,5-diol (3). Among these, (3) was the most potent cytotoxic against human cancer cell lines Hep-G2, A549 and MCF-7 with IC50 values of 2.89, 18.51, and 16.47 µg/mL, respectively, while the compound (1) showed no significant effect against tested cancer cells. Anti-inflammatory properties of purified compounds were evaluated based on NO-production in LPS-induced murine RAW264.7 macrophages. As a result, tested compounds performed diverse inhibitory effects on NO production by the macrophages, with the most significant inhibition rate of 81.37 ± 1.35% at 25 µg/mL by the compound (2). Interestingly, compounds (2) and (3) exhibited inhibitory activities against pancreatic lipase and α-glucosidase enzymes in vitro assays. Our study brought out new data concerning the chemical properties and biological activities of isolated steroids from a P. levitum fungus.

One of the most important units of Low-Density Parity-Check (LDPC) decoders is the Check-Node Unit. Its main task is to find the first two minimum values among incoming variable-to-check messages and return check-to-variable messages. This block significantly affects the decoding performance, as well as the hardware implementation complexity. In this paper, we first propose a modification to the check-node update rule by introducing two optimal offset factors applied to the check-to-variable messages. Then, we present the Check-Node Unit hardware architecture which performs the proposed algorithm. The main objective of this work aims to improve further the decoding performance for 5th Generation (5G) LDPC codes. The simulation results show that the proposed algorithm achieves essential improvements in terms of error correction performance. More precisely, the error-floor does not appear within Bit-Error-Rate (BER) of 10^(-8), while the decoding gain increases up to 0.21 dB compared to the baseline Normalized Min-Sum, as well as several state-of-the-art LDPC-based Min-Sum decoders.

Abstract Salivary gland (SG) dysfunction, due to radiotherapy, disease, or aging, is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life. Currently, the standard-of-care for this condition remains palliative. A variety of approaches have been employed to restore saliva production, but they have largely failed due to damage to both secretory cells and the extracellular matrix (niche). Transplantation of allogeneic cells from healthy donors has been suggested as a potential solution, but no definitive population of SG stem cells, capable of regenerating the gland, has been identified. Alternatively, mesenchymal stem cells (MSCs) are abundant, well characterized, and during SG development/homeostasis engage in signaling crosstalk with the SG epithelium. Further, the trans-differentiation potential of these cells and their ability to regenerate SG tissues have been demonstrated. However, recent findings suggest that the “immuno-privileged” status of allogeneic adult MSCs may not reflect their status post-transplantation. In contrast, autologous MSCs can be recovered from healthy tissues and do not present a challenge to the recipient’s immune system. With recent advances in our ability to expand MSCs in vitro on tissue-specific matrices, autologous MSCs may offer a new therapeutic paradigm for restoration of SG function.

Abstract An algorithm to describe patterns of intermittent oral corticosteroid use in the UK (n = 476,167) found that one-third of patients receiving intermittent oral corticosteroids for asthma only had short gaps (

The characterization of nickel (Ni)‐centred paramagnetic states relevant to [NiFe] hydrogenases is rare in mononuclear Ni hydrogen evolution catalysts. Here, the authors report the spectroscopic and synthetic characterization of NiI and NiIII states in an organometallic Ni hydrogen evolution catalyst.

Abstract Background The Harambee study is a cluster randomized trial in Western Kenya that tests the effect, mechanisms, and cost-effectiveness of integrating community-based HIV and non-communicable disease care within microfinance groups on chronic disease treatment outcomes. This paper documents the stages of our feasibility study conducted in preparation for the Harambee trial, which include (1) characterizing the target population and gauging recruitment capacity, (2) determining community acceptability of the integrated intervention and study procedures, and (3) identifying key implementation considerations prior to study start. Methods Feasibility research took place between November 2019 and February 2020 in Western Kenya. Mixed methods data collection included surveys administered to 115 leaders of 105 community-based microfinance groups, 7 in-person meetings and two workshops with stakeholders from multiple sectors of the health system, and ascertainment of field notes and geographic coordinates for group meeting locations and HIV healthcare facilities. Quantitative survey data were analyzed using STATA IC/13. Longitude and latitude coordinates were mapped to county boundaries using Esri ArcMap. Qualitative data obtained from stakeholder meetings and field notes were analyzed thematically. Results Of the 105 surveyed microfinance groups, 77 met eligibility criteria. Eligible groups had been in existence from 6 months to 18 years and had an average of 22 members. The majority (64%) of groups had at least one member who owned a smartphone. The definition of “active” membership and model of saving and lending differed across groups. Stakeholders perceived the community-based intervention and trial procedures to be acceptable given the minimal risks to participants and the potential to improve HIV treatment outcomes while facilitating care integration. Potential challenges identified by stakeholders included possible conflicts between the trial and existing community-based interventions, fear of group disintegration prior to trial end, clinicians’ inability to draw blood for viral load testing in the community, and deviations from standard care protocols. Conclusions This study revealed that it was feasible to recruit the number of microfinance groups necessary to ensure that our clinical trial was sufficient powered. Elicitation of stakeholder feedback confirmed that the planned intervention was largely acceptable and was critical to identifying challenges prior to implementation. Trial registration The original trial was prospectively registered with ClinicalTrials.gov (NCT04417127) on 4 June 2020.

Next-Generation Sequencing (NGS) has transformed clinical histocompatibility laboratories through its capacity to provide accurate, high-throughput, high-resolution typing of Human Leukocyte Antigen (HLA) genes, which is critical for transplant safety and success. As this technology becomes widely used for clinical genotyping, histocompatibility laboratories now have an increased capability to identify novel HLA alleles that previously would not be detected using traditional genotyping methods. Standard guidelines for the clinical verification and reporting of novelties in the era of NGS are greatly needed. Here, we describe the experience of a clinical histocompatibility laboratory’s use of NGS for HLA genotyping and its management of novel alleles detected in an ethnically-diverse population of British Columbia, Canada. Over a period of 18 months, 3,450 clinical samples collected for the purpose of solid organ or hematopoietic stem cell transplantation were sequenced using NGS. Overall, 29 unique novel alleles were identified at a rate of ∼1.6 per month. The majority of novelties (52%) were detected in the alpha chains of class II (HLA-DQA1 and -DPA1). Novelties were found in all 11 HLA classical genes except for HLA-DRB3, -DRB4, and -DQB1. All novelties were single nucleotide polymorphisms, where more than half led to an amino acid change, and one resulted in a premature stop codon. Missense mutations were evaluated for changes in their amino acid properties to assess the potential effect on the novel HLA protein. All novelties identified were confirmed independently at another accredited HLA laboratory using a different NGS assay and platform to ensure validity in the reporting of novelties. The novel alleles were submitted to the Immuno Polymorphism Database-Immunogenetics/HLA (IPD-IMGT/HLA) for official allele name designation and inclusion in future database releases. A nationwide survey involving all Canadian HLA laboratories confirmed the common occurrence of novel allele detection but identified a wide variability in the assessment and reporting of novelties. In summary, a considerable proportion of novel alleles were identified in routine clinical testing. We propose a framework for the standardization of policies on the clinical management of novel alleles and inclusion in proficiency testing programs in the era of NGS-based HLA genotyping.

The molecular mechanisms underlying deficits in Down syndrome remain unclear. Here, the authors show that copy number restoration of a chromatin remodeler in trisomic mice is sufficient to rescue epigenomic, physiological and cognitive deficits.

Abstract The propolis industry is well established in European, South American and East Asian countries. Within Australia, this industry is beginning to emerge with a few small-scale producers. To contribute to the development of the Australian propolis industry, the present study aimed to examine the quality and chemical diversity of propolis collected from various regions across Australia. The results of testing 158 samples indicated that Australian propolis had pure resin yielding from 2 to 81% by weight, total phenolic content and total flavonoid content in one gram of dry extract ranging from a few up to 181 mg of gallic acid equivalent and 145 mg of quercetin equivalent, respectively. Some Australian propolis showed more potent antioxidant activity than the well-known Brazilian green, Brazilian red, and Uruguayan and New Zealand poplar-type propolis in an in vitro DPPH assay. In addition, an HPLC–UV analysis resulted in the identification of 16 Australian propolis types which can be considered as high-grade propolis owing to their high total phenolic content. Chemometric analysis of their 1H NMR spectra revealed that propolis originating from the eastern and western coasts of Australia could be significantly discriminated based on their chemical composition.

Abnormal alpha-synuclein (α-SYN) protein deposition has long been recognized as one of the pathological hallmarks of Parkinson’s disease’s (PD). This study considers the potential utility of PD retinal biomarkers by investigating retinal changes in a well characterized PD model of α-SYN overexpression and how these correspond to the presence of retinal α-SYN. Transgenic A53T homozygous (HOM) mice overexpressing human α-SYN and wildtype (WT) control littermates were assessed at 4, 6, and 14 months of age (male and female, n = 15–29 per group). In vivo retinal function (electroretinography, ERG) and structure (optical coherence tomography, OCT) were recorded, and retinal immunohistochemistry and western blot assays were performed to examine retinal α-SYN and tyrosine hydroxylase. Compared to WT controls, A53T mice exhibited reduced light-adapted (cone photoreceptor and bipolar cell amplitude, p

Abstract Background Current treatments for salivary gland (SG) hypofunction are palliative and do not address the underlying cause or progression of the disease. SG-derived stem cells have the potential to treat SG hypofunction, but their isolation is challenging, especially when the tissue has been damaged by disease or irradiation for head and neck cancer. In the current study, we test the hypothesis that multipotent bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model are capable of trans-differentiating to the SG epithelial cell lineage when induced by a native SG-specific extracellular matrix (SG-ECM) and thus may be a viable substitute for repairing damaged SGs. Methods Rat BM-MSCs were treated with homogenates of decellularized rat SG-ECM for one hour in cell suspension and then cultured in tissue culture plates for 7 days in growth media. By day 7, the cultures contained cell aggregates and a cell monolayer. The cell aggregates were hand-selected under a dissecting microscope, transferred to a new tissue culture dish, and cultured for an additional 7 days in epithelial cell differentiation media. Cell aggregates and cells isolated from the monolayer were evaluated for expression of SG progenitor and epithelial cell specific markers, cell morphology and ultrastructure, and ability to form SG-like organoids in vivo. Results The results showed that this approach was very effective and guided the trans-differentiation of a subpopulation of CD133-positive BM-MSCs to the SG epithelial cell lineage. These cells expressed amylase, tight junction proteins (Cldn 3 and 10), and markers for SG acinar (Aqp5 and Mist 1) and ductal (Krt 14) cells at both the transcript and protein levels, produced intracellular secretory granules which were morphologically identical to those found in submandibular gland, and formed SG-like organoids when implanted in the renal capsule in vivo. Conclusions The results of this study suggest the feasibility of using autologous BM-MSCs as an abundant source of stem cells for treating SG hypofunction and restoring the production of saliva in these patients.

Abstract In addition to well characterized motor symptoms, visual disturbances are increasingly recognized as an early manifestation in Parkinson’s disease (PD). A better understanding of the mechanisms underlying these changes would facilitate the development of vision tests which can be used as preclinical biomarkers to support the development of novel therapeutics for PD. This study aims to characterize the retinal phenotype of a mouse model of dopaminergic dysfunction and to examine whether these changes are reversible with levodopa treatment. We use a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to characterize the neurotoxic effects of MPTP on in vivo retinal function (electroretinography, ERG), retinal structure (optical coherence tomography, OCT) and retinal dopaminergic cell number (tyrosine hydroxylase immunohistochemistry, IHC) at two time points (21 and 45 days) post MPTP model induction. We also investigate the effect of levodopa (L-DOPA) as a proof-of-principle chronic intervention against MPTP-induced changes in the retina. We show that MPTP decreases dopaminergic amacrine cell number (9%, p

Abstract From the end of 2019, one of the most serious and largest spread pandemics occurred in Wuhan (China) named Coronavirus (COVID-19). As reported by the World Health Organization, there are currently more than 100 million infectious cases with an average mortality rate of about five percent all over the world. To avoid serious consequences on people’s lives and the economy, policies and actions need to be suitably made in time. To do that, the authorities need to know the future trend in the development process of this pandemic. This is the reason why forecasting models play an important role in controlling the pandemic situation. However, the behavior of this pandemic is extremely complicated and difficult to be analyzed, so that an effective model is not only considered on accurate forecasting results but also the explainable capability for human experts to take action pro-actively. With the recent advancement of Artificial Intelligence (AI) techniques, the emerging Deep Learning (DL) models have been proving highly effective when forecasting this pandemic future from the huge historical data. However, the main weakness of DL models is lacking the explanation capabilities. To overcome this limitation, we introduce a novel combination of the Susceptible-Infectious-Recovered-Deceased (SIRD) compartmental model and Variational Autoencoder (VAE) neural network known as BeCaked. With pandemic data provided by the Johns Hopkins University Center for Systems Science and Engineering, our model achieves 0.98 $$R^2$$ R 2 and 0.012 MAPE at world level with 31-step forecast and up to 0.99 $$R^2$$ R 2 and 0.0026 MAPE at country level with 15-step forecast on predicting daily infectious cases. Not only enjoying high accuracy, but BeCaked also offers useful justifications for its results based on the parameters of the SIRD model. Therefore, BeCaked can be used as a reference for authorities or medical experts to make on time right decisions.