204 research outputs found

    The financial crisis of 2008 in fixed income markets

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    We explore how a relatively small amount of heterogeneous securities created turmoil in financial markets in much of the world in 2007 and 2008. The drivers of the financial turmoil and the financial crisis of 2008 were heterogeneous securities that were hard to value. These securities created concerns about counterparty risk and ultimately created substantial uncertainty. The problems spread in ways that were hard to see in advance. The run on prime money market funds in September 2008 and the effects on commercial paper were an important aspect of the crisis itself and are discussed in some detail.

    Glycan analysis as biomarkers for testicular cancer

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    The U.S. Preventive Services Task Force does not recommend routine screening for testicular cancer (TC) in asymptomatic men, essentially because serological testicular cancer (TC) biomarkers are not reliable. The main reason is that two of the most important TC biomarkers, ?-fetoprotein (AFP) and human chorionic gonadotropin (hCG), are not produced solely due to TC. Moreover, up to 40% of patients with TC do not have elevated serological biomarkers, which is why serial imaging with CT is the chief means of monitoring progress. On the other hand, exposure to radiation can lead to an increased risk of secondary malignancies. This review provides the first comprehensive account of the applicability of protein glycoprofiling as a promising biomarker for TC with applications in disease diagnostics, monitoring and recurrence evaluation. The review first deals with the description and classification of TC. Secondly, the limitations of current TC biomarkers such as hCG, AFP and lactate dehydrogenase are provided together with an extensive overview of the glycosylation of hCG and AFP related to TC. The final part of the review summarises the potential of glycan changes on either hCG and AFP as TC biomarkers for diagnostics and prognostics purposes, and for disease recurrence evaluation. Finally, an analysis of glycans in serum and tissues as TC biomarkers is also provided. - 2019 by the authors.Funding: The authors wish to acknowledge the financial support received from the Slovak Research and Development Agency APVV 17-0300. This work was supported by the Ministry of Health of the Slovak Republic under project registration no. 2018/23-SAV-1. P.K. expresses thanks that this work was also made possible by NPRP grants NPRP 6-381-1-078 and NPRP-9-219-2-105 from the Qatar National Research Fund (A Member of The Qatar Foundation). The findings achieved herein are solely the responsibility of the authors.Scopu

    Electrochemical Impedance Spectroscopy Based Biosensors: Mechanistic Principles, Analytical Examples and Challenges towards Commercialization for Assays of Protein Cancer Biomarkers

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    Impedimetric affinity biosensors are, without any doubt, among the most sensitive analytical devices available, offering low limits of detection and wide linear response ranges. There are, however, only a few papers detailing the application of impedimetric biosensors for the analysis of clinically relevant samples with due clinical performance. The fact that these devices have not found their way to any commercial or clinical use to date might be surprising, since an electrochemical assay platform based on portable potentiostats is a success story for monitoring a range of clinical parameters such as ions, haematological indicators and glucose. This review discusses the reasons behind this discrepancy and addresses the barriers to be overcome in order to achieve the point-of-care diagnostics using such devices for detection of protein oncomarkers approved by FDA. The final part of the review covers the most recent progress in the area.The financial support received from the Slovak Scientific Grant Agency VEGA 2/0137/18 and 2/0090/16 and the Slovak Research and Development Agency APVV 17-0300 and APW-15-0227 is acknowledged. The research received funding from the European Research Council (no. 311532). This publication is the result of the project implementation: Centre for materials, layers and systems for applications and chemical processes under extreme conditions - Stage I, ITMS No.: 26240120007, supported by the ERDF

    A graphene-based glycan biosensor for electrochemical label-free detection of a tumor-associated antibody

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    The study describes development of a glycan biosensor for detection of a tumor-associated antibody. The glycan biosensor is built on an electrochemically activated/oxidized graphene screen-printed electrode (GSPE). Oxygen functionalities were subsequently applied for covalent immobilization of human serum albumin (HSA) as a natural nanoscaffold for covalent immobilization of Thomsen-nouvelle (Tn) antigen (GalNAc-O-Ser/Thr) to be fully available for affinity interaction with its analyte—a tumor-associated antibody. The step by step building process of glycan biosensor development was comprehensively characterized using a battery of techniques (scanning electron microscopy, atomic force microscopy, contact angle measurements, secondary ion mass spectrometry, surface plasmon resonance, Raman and energy-dispersive X-ray spectroscopy). Results suggest that electrochemical oxidation of graphene SPE preferentially oxidizes only the surface of graphene flakes within the graphene SPE. Optimization studies revealed the following optimal parameters: activation potential of +1.5 V vs. Ag/AgCl/3 M KCl, activation time of 60 s and concentration of HSA of 0.1 g L−1. Finally, the glycan biosensor was built up able to selectively and sensitively detect its analyte down to low aM concentration. The binding preference of the glycan biosensor was in an agreement with independent surface plasmon resonance analysis.The financial support received from the Slovak Scientific Grant Agency VEGA 2/0137/18 and 2/0090/16 from the Slovak Research and Development Agency APVV 17-0300 is acknowledged. This publication is the result of the project implementation: Centre for materials, layers and systems for applications and chemical processes under extreme conditions—Stage I, ITMS no.: 26240120007, supported by the ERDF. This publication was supported by Qatar University Collaborative Grant QUCG-CAM-19/20-2. The findings achieved herein are solely the responsibility of the authors.Scopu

    Identification of Molecular Fluorophore as a Component of Carbon Dots able to Induce Gelation in a Fluorescent Multivalent-Metal-Ion-Free Alginate Hydrogel

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    We introduce a simple approach to fabricate fluorescent multivalent metal ion-free alginate hydrogels, which can be produced using carbon dots accessible from natural sources (citric acid and L-cysteine). Molecular fluorophore 5-oxo-2,3-dihydro-5H-[1,3]-thiazolo[3,2-a] pyridine-3,7-dicarboxylic acid (TPDCA), which is formed during the synthesis of carbon dots, is identified as a key segment for the crosslinking of hydrogels. The crosslinking happens through dynamic complexation of carboxylic acid groups of TPDCA and alginate cages along with sodium ions. The TPDCA derived hydrogels are investigated regarding to their thermal, rheological and optical properties, and found to exhibit characteristic fluorescence of this aggregated molecular fluorophore. Moreover, gradient hydrogels with tunable mechanical and optical properties and controlled release are obtained upon immersion of the hydrogel reactors in solutions of divalent metal ions (Ca2+, Cu2+, and Ni2+) with a higher affinity to alginate. - 2019, The Author(s).This contribution was made possible by the NPRP award [8–878–1–172] from Qatar National Research Fund (a member of Qatar foundation), Qatar University grant QUCG-CAM-19/20-2 and by a grant from the Germany/ Hong Kong Joint Research Scheme sponsored by the Research Grants Council of Hong Kong and the Germany Academic Exchange Service of Germany (Reference No.: G-CityU103/16). M.D. thanks the VEGA Scientific Grant Agency for support through project no. 2/0158/17.Scopu

    In vivo 1H NMR spectroscopy of the human brain at 7 T

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    In vivo 1H NMR spectra from the human brain were measured at 7 T. Ultrashort echo-time STEAM was used to minimize J-modulation and signal attenuation caused by the shorter T2 of metabolites. Precise adjustment of higher-order shims, which was achieved with FASTMAP, was crucial to benefit from this high magnetic field. Sensitivity improvements were evident from single-shot spectra and from the direct detection of glucose at 5.23 ppm in 8-ml volumes. The linewidth of the creatine methyl resonance was at best 9 Hz. In spite of the increased linewidth of singlet resonances at 7 T, the ability to resolve overlapping multiplets of J-coupled spin systems, such as glutamine and glutamate, was substantially increased. Characteristic spectral patterns of metabolites, e.g., myo-inositol and taurine, were discernible in the in vivo spectra, which facilitated an unambiguous signal assignment. © 2001 Wiley-Liss, Inc

    Brain energy metabolism and neurotransmission at near-freezing temperatures: In vivo 1H MRS study of a hibernating mammal

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    The brain of a hibernating mammal withstands physiological extremes that would result in cerebral damage and death in a non-hibernating species such as humans. To examine the possibility that this neuroprotection results from alterations in cerebral metabolism, we used in vivo 1H NMR spectroscopy at high field (9.4 T) to measure the concentration of 18 metabolites (neurochemical profile) in the brain of 13-lined ground squirrels (Spermophilus tridecemlineatus) before, during, and after hibernation. Resolved in vivo1H NMR spectra were obtained even at low temperature in torpid hibernators (∌7°C). The phosphocreatine-to-creatine ratio was increased during torpor (+143%) indicating energy storage, and remained increased to a lesser extent during interbout arousal (IBA) (+83%). The total Îł-aminobutyric acid concentration was increased during torpor (+135%) and quickly returned to baseline during IBA. Glutamine (Gln) was decreased (-54%) during torpor but quickly returned to normal levels during IBA and after terminal arousal in the spring. Glutamate (Glu) was also decreased during torpor (-17%), but remained decreased during IBA (-20% compared with fall), and returned to normal level in the spring. Our observation that Glu and Gln levels are depressed in the brain of hibernators suggests that the balance between anaplerosis and loss of Glu and Gln (because of glutamatergic neurotransmission or other mechanisms) is altered in hibernation. © 2007 The Authors

    Stimulus-dependent maximum entropy models of neural population codes

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    Neural populations encode information about their stimulus in a collective fashion, by joint activity patterns of spiking and silence. A full account of this mapping from stimulus to neural activity is given by the conditional probability distribution over neural codewords given the sensory input. To be able to infer a model for this distribution from large-scale neural recordings, we introduce a stimulus-dependent maximum entropy (SDME) model---a minimal extension of the canonical linear-nonlinear model of a single neuron, to a pairwise-coupled neural population. The model is able to capture the single-cell response properties as well as the correlations in neural spiking due to shared stimulus and due to effective neuron-to-neuron connections. Here we show that in a population of 100 retinal ganglion cells in the salamander retina responding to temporal white-noise stimuli, dependencies between cells play an important encoding role. As a result, the SDME model gives a more accurate account of single cell responses and in particular outperforms uncoupled models in reproducing the distributions of codewords emitted in response to a stimulus. We show how the SDME model, in conjunction with static maximum entropy models of population vocabulary, can be used to estimate information-theoretic quantities like surprise and information transmission in a neural population.Comment: 11 pages, 7 figure
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