473 research outputs found

    Detroit’s bankruptcy settlement will not solve the city’s problems

    Get PDF
    In December, a federal judge ruled that the city of Detroit’s bankruptcy proceedings could continue, and it is now likely to take years for the city to settle its creditors’ claims. Gary Sands, Laura A. Reese, and Mark Skidmore look at Detroit’s recent history which has been characterized by deindustrialization and depopulation, and public mismanagement and corruption. They argue that even after the city’s bankruptcy is concluded, Detroit’s underlying fundamental structural weaknesses mean that its problems are unlikely to go away

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

    Get PDF
    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

    The Holy Grail: A road map for unlocking the climate record stored within Mars' polar layered deposits

    Get PDF
    In its polar layered deposits (PLD), Mars possesses a record of its recent climate, analogous to terrestrial ice sheets containing climate records on Earth. Each PLD is greater than 2 ​km thick and contains thousands of layers, each containing information on the climatic and atmospheric state during its deposition, creating a climate archive. With detailed measurements of layer composition, it may be possible to extract age, accumulation rates, atmospheric conditions, and surface activity at the time of deposition, among other important parameters; gaining the information would allow us to “read” the climate record. Because Mars has fewer complicating factors than Earth (e.g. oceans, biology, and human-modified climate), the planet offers a unique opportunity to study the history of a terrestrial planet’s climate, which in turn can teach us about our own planet and the thousands of terrestrial exoplanets waiting to be discovered. During a two-part workshop, the Keck Institute for Space Studies (KISS) hosted 38 Mars scientists and engineers who focused on determining the measurements needed to extract the climate record contained in the PLD. The group converged on four fundamental questions that must be answered with the goal of interpreting the climate record and finding its history based on the climate drivers. The group then proposed numerous measurements in order to answer these questions and detailed a sequence of missions and architecture to complete the measurements. In all, several missions are required, including an orbiter that can characterize the present climate and volatile reservoirs; a static reconnaissance lander capable of characterizing near surface atmospheric processes, annual accumulation, surface properties, and layer formation mechanism in the upper 50 ​cm of the PLD; a network of SmallSat landers focused on meteorology for ground truth of the low-altitude orbiter data; and finally, a second landed platform to access ~500 ​m of layers to measure layer variability through time. This mission architecture, with two landers, would meet the science goals and is designed to save costs compared to a single very capable landed mission. The rationale for this plan is presented below. In this paper we discuss numerous aspects, including our motivation, background of polar science, the climate science that drives polar layer formation, modeling of the atmosphere and climate to create hypotheses for what the layers mean, and terrestrial analogs to climatological studies. Finally, we present a list of measurements and missions required to answer the four major questions and read the climate record. 1. What are present and past fluxes of volatiles, dust, and other materials into and out of the polar regions? 2. How do orbital forcing and exchange with other reservoirs affect those fluxes? 3. What chemical and physical processes form and modify layers? 4. What is the timespan, completeness, and temporal resolution of the climate history recorded in the PLD

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

    Get PDF
    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 SĂŁo Paulo, Dept Bioquim, Disciplina Biol Mol, BR-04044020 SĂŁo 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 SĂŁo Paulo, Dept Bioquim, Disciplina Biol Mol, BR-04044020 SĂŁo Paulo, BrazilWeb of Scienc

    Physiological Ecology of Microorgansisms in Subglacial Lake Whillans

    Get PDF
    Subglacial microbial habitats are widespread in glaciated regions of our planet. Some of these environments have been isolated from the atmosphere and from sunlight for many thousands of years. Consequently, ecosystem processes must rely on energy gained from the oxidation of inorganic substrates or detrital organic matter. Subglacial Lake Whillans (SLW) is one of more than 400 subglacial lakes known to exist under the Antarctic ice sheet; however, little is known about microbial physiology and energetics in these systems. When it was sampled through its 800 m thick ice cover in 2013, the SLW water column was shallow (~2 m deep), oxygenated, and possessed sufficient concentrations of C, N, and P substrates to support microbial growth. Here, we use a combination of physiological assays and models to assess the energetics of microbial life in SLW. In general, SLW microorganisms grew slowly in this energy-limited environment. Heterotrophic cellular carbon turnover times, calculated from 3H-thymidine and 3H-leucine incorporation rates, were long (60 to 500 days) while cellular doubling times averaged 196 days. Inferred growth rates (average ~0.006 d-1) obtained from the same incubations were at least an order of magnitude lower than those measured in Antarctic surface lakes and oligotrophic areas of the ocean. Low growth efficiency (8%) indicated that heterotrophic populations in SLW partition a majority of their carbon demand to cellular maintenance rather than growth. Chemoautotrophic CO2-fixation exceeded heterotrophic organic C-demand by a factor of ~1.5. Aerobic respiratory activity associated with heterotrophic and chemoautotrophic metabolism surpassed the estimated supply of oxygen to SLW, implying that microbial activity could deplete the oxygenated waters, resulting in anoxia. We used thermodynamic calculations to examine the biogeochemical and energetic consequences of environmentally imposed switching between aerobic and anaerobic metabolisms in the SLW water column. Heterotrophic metabolisms utilizing acetate and formate as electron donors yielded less energy than chemolithotrophic metabolisms when calculated in terms of energy density, which supports experimental results that showed chemoautotrophic activity in excess of heterotrophic activity. The microbial communities of subglacial lake ecosystems provide important natural laboratories to study the physiological and biogeochemical behavior of microorganisms inhabiting cold, dark environments

    19F labelled glycosaminoglycan probes for solution NMR and non-linear (CARS) microscopy

    Get PDF
    Studying polysaccharide-protein interactions under physiological conditions by conventional techniques is challenging. Ideally, macromolecules could be followed by both in vitro spectroscopy experiments as well as in tissues using microscopy, to enable a proper comparison of results over these different scales but, often, this is not feasible. The cell surface and extracellular matrix polysaccharides, glycosaminoglycans (GAGs) lack groups that can be detected selectively in the biological milieu. The introduction of 19F labels into GAG polysaccharides is explored and the interaction of a labelled GAG with the heparin-binding protein, antithrombin, employing 19F NMR spectroscopy is followed. Furthermore, the ability of 19F labelled GAGs to be imaged using CARS microscopy is demonstrated. 19F labelled GAGs enable both 19F NMR protein-GAG binding studies in solution at the molecular level and non-linear microscopy at a microscopic scale to be conducted on the same material, essentially free of background signals

    A method for successful collection of multicores and gravity cores from Antarctic subglacial lakes

    Get PDF
    During the 2018–2019 Antarctic field season, the Subglacial Antarctic Lakes Scientific Access project team cleanly accessed Mercer Subglacial Lake, West Antarctica, to sample water and sediments beneath 1087 m of overlying ice. A multicorer was successful in sampling the sediment–water interface, with 4 deployments retrieving 10 cores between 0.3 and 0.4 m in length. Gravity coring was also successful, retrieving cores of 0.97 and 1.78 m in glacial diamict. However, sediment cores retrieved by the gravity cores were shorter than the core barrel penetration (as measured by mud streaks on the outside of the coring system), indicating that the system can likely be improved. This manuscript describes the design, implementation, successes, and lessons learned while coring sediments in a subglacial lake

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

    Get PDF
    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
    • …
    corecore