4,813 research outputs found

    Munterville: A New Soil Series in Iowa

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    Before 2009, the Natural Resources Conservation Service (NRCS) staff noticed plant roots and argillans deep within the B horizon of Gosport polypedons (a fine, illitic, mesic Oxyaquic Dystrudept) while updating Major Land Resource Area (MLRA) 108 (Illinois and Iowa deep loess and drift) and 109 (Iowa and Missouri heavy till plain) in the central United States. In 2009, Gosport soils in MLRAs 108 and 109 were remapped and reclassified. Both map unit transects and the relevƩ method were used to identify pedons for detailed laboratory analyses. Eight pedons representing Gosport soils were collected from eight counties in southern Iowa, USA (Davis, Jefferson, Keokuk, Lucas, Mahaska, Marion, Monroe, and Van Buren). All of the pedons were described, analyzed, and classified. The results revealed two groups of soils, which are different than that of Gosport: Alfisols, newly named as the Munterville series (fine, mixed, smectitic or kaolinitic, active or superactive, mesic Oxyaquic Hapludalfs), and Ultisols (fine, mixed or kaolinitic, active, mesic Oxyaquic Hapludults) that have not yet been assigned a series name. The aims of this work were to reclassify the Gosport soils and detect the lithologic discontinuities within their sola

    Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial

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    Brain penetration; Mutant; OlutasidenibPenetraciĆ³ cerebral; Mutant; OlutasidenibPenetraciĆ³n cerebral; Mutante; OlutasidenibBackground Olutasidenib (FT-2102) is a highly potent, orally bioavailable, brain-penetrant and selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aim of the study was to determine the safety and clinical activity of olutasidenib in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation. Methods This was an open-label, multicenter, nonrandomized, phase Ib/II clinical trial. Eligible patients (ā‰„18 years) had histologically confirmed IDH1R132X-mutated glioma that relapsed or progressed on or following standard therapy and had measurable disease. Patients received olutasidenib, 150 mg orally twice daily (BID) in continuous 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs) (cycle 1) and safety in phase I and objective response rate using the Modified Response Assessment in Neuro-Oncology criteria in phase II. Results Twenty-six patients were enrolled and followed for a median 15.1 months (7.3ā€’19.4). No DLTs were observed in the single-agent glioma cohort and the pharmacokinetic relationship supported olutasidenib 150 mg BID as the recommended phase II dose. In the response-evaluable population, disease control rate (objective response plus stable disease) was 48%. Two (8%) patients demonstrated a best response of partial response and eight (32%) had stable disease for at least 4 months. Grade 3ā€’4 adverse events (ā‰„10%) included alanine aminotransferase increased and aspartate aminotransferase increased (three [12%], each). Conclusions Olutasidenib 150 mg BID was well tolerated in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation and demonstrated preliminary evidence of clinical activity in this heavily pretreated population.This study was funded by Forma Therapeutics, Inc., Watertown, MA, USA

    Leafroof

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    Conventional solar energy collection technologies have a lot of limitations with respect to their applicability in the urban environment. The PV cells of the buildings need to be oriented towards the South at a specific angle causing restrictions on urban planning. Moreover, the aesthetics of PV cells are not well suited for building design, creating a generally dull and industrial look in urban environment.The 3TU Lighthouse Leafroof project focuses on creating a roof design, inspired by the natural shape of leaves. By incorporating the Luminescent Solar Concentrator (LSC) technology the system can collect and ā€œtrapā€ solar irradiation and concentrate it to a much smaller area of PV cells located at the centre or the edge of the leaf tiles.This approach allows more freedom of building orientation and roof inclination compared to the conventional PV system. Subsequently, it enhances freedom in urban planning. The goal of this project is to create a ā€œleaf roofā€ prototype and form a feasible solar energy collection technology that is competitive to conventional systems

    Suitability of faecal near-infrared reflectance spectroscopy (NIRS) predictions for estimating gross calorific value

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    A total of 220 faecal pig and poultry samples, collected from different experimental trials were employed with the aim to demonstrate the suitability of Near Infrared Reflectance Spectroscopy (NIRS) technology for estimation of gross calorific value on faeces as output products in energy balances studies. NIR spectra from dried and grounded faeces samples were analyzed using a Foss NIRSystem 6500 instrument, scanning over the wavelength range 400-2500 nm. Validation studies for quantitative analytical models were carried out to estimate the relevance of method performance associated to reference values to obtain an appropriate, accuracy and precision. The results for prediction of gross calorific value (GCV) of NIRS calibrations obtained for individual species showed high correlation coefficients comparing chemical analysis and NIRS predictions, ranged from 0.92 to 0.97 for poultry and pig. For external validation, the ratio between the standard error of cross validation (SECV) and the standard error of prediction (SEP) varied between 0.73 and 0.86 for poultry and pig respectively, indicating a sufficiently precision of calibrations. In addition a global model to estimate GCV in both species was developed and externally validated. It showed correlation coefficients of 0.99 for calibration, 0.98 for cross-validation and 0.97 for external validation. Finally, relative uncertainty was calculated for NIRS developed prediction models with the final value when applying individual NIRS species model of 1.3% and 1.5% for NIRS global prediction. This study suggests that NIRS is a suitable and accurate method for the determination of GCV in faeces, decreasing cost, timeless and for convenient handling of unpleasant samples

    Elevated expression of the chemokine-scavenging receptor D6 is associated with impaired lesion development in psoriasis

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    D6 is a scavenging-receptor for inflammatory CC chemokines that are essential for resolution of inflammatory responses in mice. Here, we demonstrate that D6 plays a central role in controlling cutaneous inflammation, and that D6 deficiency is associated with development of a psoriasis-like pathology in response to varied inflammatory stimuli in mice. Examination of D6 expression in human psoriatic skin revealed markedly elevated expression in both the epidermis and lymphatic endothelium in "uninvolved" psoriatic skin (ie, skin that was more than 8 cm distant from psoriatic plaques). Notably, this increased D6 expression is associated with elevated inflammatory chemokine expression, but an absence of plaque development, in uninvolved skin. Along with our previous observations of the ability of epidermally expressed transgenic D6 to impair cutaneous inflammatory responses, our data support a role for elevated D6 levels in suppressing inflammatory chemokine action and lesion development in uninvolved psoriatic skin. D6 expression consistently dropped in perilesional and lesional skin, coincident with development of psoriatic plaques. D6 expression in uninvolved skin also was reduced after trauma, indicative of a role for trauma-mediated reduction in D6 expression in triggering lesion development. Importantly, D6 is also elevated in peripheral blood leukocytes in psoriatic patients, indicating that upregulation may be a general protective response to inflammation. Together our data demonstrate a novel role for D6 as a regulator of the transition from uninvolved to lesional skin in psoriasis

    Structural basis for CRISPR RNA-guided DNA recognition by Cascade

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    The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and low-resolution structure of Cascade and show how it recognizes double-stranded DNA (dsDNA) targets in a sequence-specific manner. Cascade is a 405-kDa complex comprising five functionally essential CRISPR-associated (Cas) proteins (CasA1B2C6D1E1) and a 61-nucleotide CRISPR RNA (crRNA) with 5ā€²-hydroxyl and 2ā€²,3ā€²-cyclic phosphate termini. The crRNA guides Cascade to dsDNA target sequences by forming base pairs with the complementary DNA strand while displacing the noncomplementary strand to form an R-loop. Cascade recognizes target DNA without consuming ATP, which suggests that continuous invader DNA surveillance takes place without energy investment. The structure of Cascade shows an unusual seahorse shape that undergoes conformational changes when it binds target DNA.

    A kinematic study of Open Clusters: implications for their origin

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    The Galactic population of open clusters provides an insight into star formation in the Galaxy. The open cluster catalogue by Dias et al.(2002b) is a rich source of data, including kinematic information. This large sample made it possible to carry out a systematic analysis of 481 open cluster orbits, using parameters based on orbit eccentricity and separation from the Galactic plane. These two parameters may be indicative of origin, and we find them to be correlated. We also find them to be correlated with metallicity, another parameter suggested elsewhere to be a marker for origin in that high values of any of these two parameters generally indicates a low metallicity ([Fe/H] Solar<āˆ’<-0.2 dex). The resulting analysis points to four open clusters in the catalogue being of extra-Galactic origin by impact of high velocity cloud on the disk: Berkeley21, 32, 99, and Melotte66, with a possible further four due to this origin (NGC2158, 2420, 7789, IC1311). A further three may be due to Galactic globular cluster impact on the disk i.e of internal Galactic origin (NGC6791, 1817, and 7044).Comment: 14 pages, 816 figures, accepted for publication in MNRAS 14-May-201

    Political Regimes and Sovereign Credit Risk in Europe, 1750-1913

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    This article uses a new panel data set to perform a statistical analysis of political regimes and sovereign credit risk in Europe from 1750 to 1913. Old Regime polities typically suffered from fiscal fragmentation and absolutist rule. By the start of World War I, however, many such countries had centralized institutions and limited government. Panel regressions indicate that centralized and?or limited regimes were associated with significant improvements in credit risk relative to fragmented and absolutist ones. Structural break tests also reveal close relationships between major turning points in yield series and political transformations

    Abnormally high risk of stroke in Brugada syndrome

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    BACKGROUND The present study sought to evaluate the incidence of cerebrovascular events in a large cohort of patients with Brugada syndrome (BrS) analysing possible predictors, clinical characteristics and prognosis of cardioembolic events secondary to atrial fibrillation. METHODS A total of 671 consecutive patients (age 42.1ā€ŠĀ±ā€Š17.0 years; men 63%) with a diagnosis of BrS were retrospectively analysed over a mean follow-up period of 10.8ā€ŠĀ±ā€Š5.5 years. The diagnosis of ischemic stroke was made according to the AHA/ASA guidelines using computed tomography (CT) and angio-CT in the emergency department. RESULTS Among 671 patients with BrS, 79 (11.8%) had atrial fibrillation. The incidence of cardioembolic stroke in patients with BrS and atrial fibrillation was 13.9% (11 events). These patients had a low CHA2DS2Vasc score (82%, 0 and 1). Patients with transient ischemic attack/stroke were more frequently asymptomatic (91 vs. 25%; Pā€Š<ā€Š0.0001) and older (59.4ā€ŠĀ±ā€Š11.2 vs. 43.9ā€ŠĀ±ā€Š16.7; Pā€Š=ā€Š0.004) as compared with those without cerebrovascular events. CONCLUSION The incidence of cardioembolic stroke in patients with BrS and atrial fibrillation was unexpectedly high. The cerebrovascular accidents were often the presenting clinical manifestation and were significantly associated with asymptomatic atrial fibrillation and older age. CHADS2 and CHA2DS2Vasc scores did not predict the unexpectedly high risk of thromboembolic events in this group of patients. The use of more invasive diagnostic tools might be useful in order to increase the rate of atrial fibrillation detection

    The Impact of Pandemic Influenza H1N1 on Health-Related Quality of Life: A Prospective Population-Based Study

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    BACKGROUND: While the H1N1v influenza pandemic in 2009 was clinically mild, with a low case-fatality rate, the overall disease burden measured in quality-adjusted life years (QALY) lost has not been estimated. Such a measure would allow comparison with other diseases and assessment of the cost-effectiveness of pandemic control measures. METHODS AND FINDINGS: Cases of H1N1v confirmed by polymerase chain reaction (PCR) and PCR negative cases with similar influenza-like illness (ILI controls) in 7 regions of England were sent two questionnaires, one within a week of symptom onset and one two weeks later, requesting information on duration of illness, work loss and antiviral use together with EQ-5D questionnaires. Results were compared with those for seasonal influenza from a systematic literature review. A total QALY loss for the 2009 pandemic in England was calculated based on the estimated total clinical cases and reported deaths. A total of 655 questionnaires were sent and 296 (45%) returned. Symptoms and average illness duration were similar between confirmed cases and ILI controls (8.8 days and 8.7 days respectively). Days off work were greater for cases than ILI controls (7.3 and 4.9 days respectively, pā€Š = ā€Š0.003). The quality-adjusted life days lost was 2.92 for confirmed cases and 2.74 for ILI controls, with a reduction in QALY loss after prompt use of antivirals in confirmed cases. The overall QALY loss in the pandemic was estimated at 28,126 QALYs (22,267 discounted) of which 40% was due to deaths (24% with discounting). CONCLUSION: Given the global public health significance of influenza, it is remarkable that no previous prospective study of the QALY loss of influenza using standardised and well validated methods has been performed. Although the QALY loss was minor for individual patients, the estimated total burden of influenza over the pandemic was substantial when compared to other infectious diseases
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