An Inexpensive, Pulsed, and Multiple Wavelength Bench-Top Light Source for Biological Spectroscopy

Since signal/noise ratios are proportional to the square root of the intensity, high intensity light sources are advantageous for many forms of UV–Vis and IR spectroscopy particularly with very low or high absorbance samples. We report the construction of a low-cost (˜ £6500 GBP, ca. 2016) bench-top spectrometer suitable for biological spectroscopy, which utilizes a hot plasma, generated with a pulsed Nd:YAG laser (? = 1064 nm). The properties (reliability, intensity, and spectral profiles) of light generated with the plasma in different gaseous media (helium, neon, argon, and krypton) were investigated. Argon provided high intensity broadband light and was the most cost effective. The instrument was compared for spectral accuracy to a commercially available spectrometer (Thermo Scientific, GENESYS 10S) by measurement of the absorbance spectrum of the UV–Vis calibration standard holmium (III) oxide (4%, w/v) in perchloric acid (10%, w/v) and accurately replicated the results of the commercial spectrometer. This economical instrument can record consecutive absorbance spectra (between ? = 380 and 720 nm) for each laser pulse (6 Hz; ~160 ms/pulse), evinced by investigations into lysozyme aggregation in the presence of heparin. This instrument is suitablefor use with lasers of a higher pulse power and repetition rates that would induce higher temperature plasmas. Higher temperature plasma sources offer increased signal to noise ratios due to the higher intensity emission generated

The potential for circular dichroism as an additional facile and sensitive method of monitoring low-molecular-weight heparins and heparinoids

The ultraviolet circular dichroism (CD) spectra of commercial low-molecular-weight heparins, heparinoids and other anticoagulant preparations have been recorded between 180 and 260 nm. Principal component analysis of the spectra allowed their differentiation into a number of groups related to the means of their production reflecting the structural changes introduced by each process. The findings suggest that CD provides a complementary technique for the rapid analysis of heparin preparations

Jetstream: A self-provisoned, scalable science and engineering cloud environment

The paper describes the motivation behind Jetstream, its functions, hardware configuration, software environment, user interface, design, use cases, relationships with other projects such as Wrangler and iPlant, and challenges in implementation.Funded by the National Science Foundation Award #ACI - 144560

Laboratory for Essential Biodiversity Variables (EBV) Concepts – The “Data Pool Initiative for the Bohemian Forest Ecosystem”

Forest ecosystems respond very sensitively to climate and atmospheric changes. Feedback mechanisms can be measured via changes in albedo, energy balance and carbon storage. The Bavarian Forest National Park is a unique forest ecosystem with large non-intervention zones, which promote a large scale re-wilding process with low human interference. It provides important ecosystem services of clear water, carbon sequestration and recreation, and has fragile habitats with endangered forest species. The national park is therefore a very suitable field of research to study natural and near natural ecosystem processes. Under the leadership of the national park authority, experts from various European research institutions have joined forces to systematically establish a remote sensing data pool on the Bavarian Forest as a resource for their research. This collaborative effort provides an opportunity to combine various methodological approaches and data and to optimize products by sharing knowledge and expertise. The first objective of the data pool is to develop methods for the establishment of Essential Biodiversity Variables (EBV) based on a very sound and comprehensive data base. The recent advances in tighter collaboration of remote sensing and biodiversity science, especially with regard to the newly established EBV and RS-EBV concepts will help to improve the interdisciplinary research. However, such concepts and especially the underlying remote sensing data need to be developed, adapted and validated against biodiversity patterns. Such process needs an extensive set of in-situ and remotely sensed data in order to allow a thorough analysis. The Bavarian data pool fits these requirements through the commitment of all members and hence provides a variety of remote sensing data sets such as hyperspectral, Lidar as well as CIR and multispectral data, as well as a wealth of in-situ data of zoological and botanical transects. This combination allows setting sensor-specific, as well as species-specific analysis on different aspects, i.e. different processes between managed and natural forest, impact of climate change or species distribution mapping. The second objective is to develop concepts for EBV using Sentinel mission data combined with data from future contributing hyperspectral missions such as EnMAP. Spaceborne hyperspectral data has been identified by the remote sensing related biodiversity community as an important data source. However, the acquisition of airborne data is very expensive for regular coverage of forest stands and the entire forest ecosystem. This drawback will be overcome by the launch of the space-borne imaging spectroscopy mission EnMAP. It is a contributing mission to the Copernicus program and will be launched in 2018. EnMAP is expected to provide high quality imaging spectroscopy data on an operational basis and will be suitable for the retrieval of high resolution plant traits at local scales. First studies within the data pool have been focused on e.g. derivation of plant traits like chlorophyll, LAI and nitrogen and tree species classification with a special focus on rare species within the national park, just to name a few. Objective, purpose and content of the data pool will be shown as well as first selective developments

Cyberinfrastructure Deployments on Public Research Clouds Enable Accessible Environmental Data Science Education

Modern science depends on computers, but not all scientists have access to the scale of computation they need. A digital divide separates scientists who accelerate their science using large cyberinfrastructure from those who do not, or who do not have access to the compute resources or learning opportunities to develop the skills needed. The exclusionary nature of the digital divide threatens equity and the future of innovation by leaving people out of the scientific process while over-amplifying the voices of a small group who have resources. However, there are potential solutions: recent advancements in public research cyberinfrastructure and resources developed during the open science revolution are providing tools that can help bridge this divide. These tools can enable access to fast and powerful computation with modest internet connections and personal computers. Here we contribute another resource for narrowing the digital divide: scalable virtual machines running on public cloud infrastructure. We describe the tools, infrastructure, and methods that enabled successful deployment of a reproducible and scalable cyberinfrastructure architecture for a collaborative data synthesis working group in February 2023. This platform enabled 45 scientists with varying data and compute skills to leverage 40,000 hours of compute time over a 4-day workshop. Our approach provides an open framework that can be replicated for educational and collaborative data synthesis experiences in any data- and compute-intensive discipline

High-sensitivity visualisation of contaminants in heparin samples by spectral filtering of H-1 NMR spectra

A novel application of two-dimensional correlation analysis has been employed to filter H-1 NMR heparin spectra distinguishing acceptable natural variation and the presence of foreign species. Analysis of contaminated heparin samples, compared to a dataset of accepted heparin samples using two-dimensional correlation spectroscopic analysis of their 1-dimensional H-1 NMR spectra, allowed the spectral features of contaminants to be recovered with high sensitivity, without having to resort to more complicated NMR experiments. Contaminants, which exhibited features distinct from those of heparin and those with features normally hidden within the spectral mass of heparin could be distinguished readily. A heparin sample which had been pre-mixed with a known contaminant, oversulfated chondroitin sulfate (OSCS), was tested against the heparin reference library. It was possible to recover the 1 H NMR spectrum of the OSCS component through difference 2D-COS power spectrum analysis of as little as 0.25% (w/w) with ease, and of 2% (w/w) for more challenging contaminants, whose NMR signals fell under those of heparin. the approach shows great promise for the quality control of heparin and provides the basis for greatly improved regulatory control for the analysis of heparin, as well as other intrinsically heterogeneous and varied products.Wellcome TrustRoyal SocietyBBSRCFinlambardia SPA 'Fondo per la promozione di Accordi Istituzionali'Univ Liverpool, Sch Biol Sci, Liverpool L69 3BX, Merseyside, EnglandIst Ric Chim & Biochim G Ronzoni, I-20133 Milan, ItalyUNIFESP Universidade Federal de São Paulo, Dept Bioquim, Disciplina Biol Mol, BR-04044020 São Paulo, BrazilKeele Univ, Inst Sci & Technol Med, Keele ST5 5BG, Staffs, EnglandNatl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, EnglandUNIFESP Universidade Federal de São Paulo, Dept Bioquim, Disciplina Biol Mol, BR-04044020 São Paulo, BrazilWeb of Scienc

Identification of heparin modifications and polysaccharide inhibitors of Plasmodium falciparum merozoite invasion that have potential for novel drug development

Despite recent successful control efforts, malaria remains a leading global health burden. Alarmingly, resistance to current antimalarials is increasing and the development of new drug families is needed to maintain malaria control. Current antimalarials target the intraerythrocytic developmental stage of the Plasmodium falciparum life cycle. However, the invasive extracellular parasite form, the merozoite, is also an attractive target for drug development. We have previously demonstrated that heparin-like molecules, including those with low molecular weights and low anticoagulant activities, are potent and specific inhibitors of merozoite invasion and blood-stage replication. Here we tested a large panel of heparin-like molecules and sulfated polysaccharides together with various modified chemical forms for their inhibitory activity against P. falciparum merozoite invasion. We identified chemical modifications that improve inhibitory activity and identified several additional sulfated polysaccharides with strong inhibitory activity. These studies have important implications for the further development of heparin-like molecules as antimalarial drugs and for understanding merozoite invasion

The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding

Many pathogens take advantage of the dependence of the host on the interaction of hundreds of extracellular proteins with the glycosaminoglycans heparan sulphate to regulate homeostasis and use heparan sulphate as a means to adhere and gain access to cells. Moreover, mucosal epithelia such as that of the respiratory tract are protected by a layer of mucin polysaccharides, which are usually sulphated. Consequently, the polydisperse, natural products of heparan sulphate and the allied polysaccharide, heparin have been found to be involved and prevent infection by a range of viruses including S-associated coronavirus strain HSR1. Here we use surface plasmon resonance and circular dichroism to measure the interaction between the SARS-CoV-2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) and heparin. The data demonstrate an interaction between the recombinant surface receptor binding domain and the polysaccharide. This has implications for the rapid development of a first-line therapeutic by repurposing heparin and for next-generation, tailor-made, GAG-based antivirals

A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the beta Secretase Implicated in Alzheimer's Disease

Therapeutic options for Alzheimer’s disease, the most common form of dementia, are currently restricted to palliative treatments. The glycosaminoglycan heparin, widely used as a clinical anticoagulant, has previously been shown to inhibit the Alzheimer’s disease-relevant β-secretase 1 (BACE1). Despite this, the deployment of pharmaceutical heparin for the treatment of Alzheimer’s disease is largely precluded by its potent anticoagulant activity. Furthermore, ongoing concerns regarding the use of mammalian-sourced heparins, primarily due to prion diseases and religious beliefs hinder the deployment of alternative heparin-based therapeutics. A marine-derived, heparan sulphate-containing glycosaminoglycan extract, isolated from the crab Portunus pelagicus, was identified to inhibit human BACE1 with comparable bioactivity to that of mammalian heparin (IC50 = 1.85 μg mL−1 (R2 = 0.94) and 2.43 μg mL−1 (R2 = 0.93), respectively), while possessing highly attenuated anticoagulant activities. The results from several structural techniques suggest that the interactions between BACE1 and the extract from P. pelagicus are complex and distinct from those of heparin