Anomalous transport in disordered fracture networks: Spatial Markov model for dispersion with variable injection modes

We investigate tracer transport on random discrete fracture networks that are characterized by the statistics of the fracture geometry and hydraulic conductivity. While it is well known that tracer transport through fractured media can be anomalous and particle injection modes can have major impact on dispersion, the incorporation of injection modes into effective transport modeling has remained an open issue. The fundamental reason behind this challenge is that-even if the Eulerian fluid velocity is steady-the Lagrangian velocity distribution experienced by tracer particles evolves with time from its initial distribution, which is dictated by the injection mode, to a stationary velocity distribution. We quantify this evolution by a Markov model for particle velocities that are equidistantly sampled along trajectories. This stochastic approach allows for the systematic incorporation of the initial velocity distribution and quantifies the interplay between velocity distribution and spatial and temporal correlation. The proposed spatial Markov model is characterized by the initial velocity distribution, which is determined by the particle injection mode, the stationary Lagrangian velocity distribution, which is derived from the Eulerian velocity distribution, and the spatial velocity correlation length, which is related to the characteristic fracture length. This effective model leads to a time-domain random walk for the evolution of particle positions and velocities, whose joint distribution follows a Boltzmann equation. Finally, we demonstrate that the proposed model can successfully predict anomalous transport through discrete fracture networks with different levels of heterogeneity and arbitrary tracer injection modes. © 2017 Elsevier Ltd.PKK and SL acknowledge a grant (16AWMP- B066761-04) from the AWMP Program funded by the Ministry of Land, Infrastructure and Transport of the Korean government and the support from Future Research Program (2E27030) funded by the Korea Institute of Science and Technology (KIST). PKK and RJ acknowledge a MISTI Global Seed Funds award. MD acknowledges the support of the European Research Council (ERC) through the project MHetScale (617511). TLB acknowledges the support of European Research Council (ERC) through the project Re- activeFronts (648377). RJ acknowledges the support of the US Department of Energy through a DOE Early Career Award (grant DE-SC0009286). The data to reproduce the work can be obtained from the corresponding author.N

Newly identified climatically and environmentally significant high-latitude dust sources

Peer reviewe

Newly identified climatically and environmentally significant high-latitude dust sources

Dust particles from high latitudes have a potentially large local, regional, and global significance to climate and the environment as short-lived climate forcers, air pollutants, and nutrient sources. Identifying the locations of local dust sources and their emission, transport, and deposition processes is important for understanding the multiple impacts of high-latitude dust (HLD) on the Earth\u27s systems. Here, we identify, describe, and quantify the source intensity (SI) values, which show the potential of soil surfaces for dust emission scaled to values 0 to 1 concerning globally best productive sources, using the Global Sand and Dust Storms Source Base Map (G-SDS-SBM). This includes 64 HLD sources in our collection for the northern (Alaska, Canada, Denmark, Greenland, Iceland, Svalbard, Sweden, and Russia) and southern (Antarctica and Patagonia) high latitudes. Activity from most of these HLD sources shows seasonal character. It is estimated that high-latitude land areas with higher (SI ≥0.5), very high (SI ≥0.7), and the highest potential (SI ≥0.9) for dust emission cover >1 670 000 km$^{2}$, >560 000 km$^{2}$, and >240 000 km$^{2}$, respectively. In the Arctic HLD region (≥60$^{∘}$ N), land area with SI ≥0.5 is 5.5 % (1 035 059 km$^{2}$), area with SI ≥0.7 is 2.3 % (440 804 km$^{2}$), and area with SI ≥0.9 is 1.1 % (208 701 km$^{2}$). Minimum SI values in the northern HLD region are about 3 orders of magnitude smaller, indicating that the dust sources of this region greatly depend on weather conditions. Our spatial dust source distribution analysis modeling results showed evidence supporting a northern HLD belt, defined as the area north of 50$^{∘}$ N, with a “transitional HLD-source area” extending at latitudes 50–58∘ N in Eurasia and 50–55$^{∘}$ N in Canada and a “cold HLD-source area” including areas north of 60$^{∘}$ N in Eurasia and north of 58$^{∘}$ N in Canada, with currently “no dust source” area between the HLD and low-latitude dust (LLD) dust belt, except for British Columbia. Using the global atmospheric transport model SILAM, we estimated that 1.0 % of the global dust emission originated from the high-latitude regions. About 57 % of the dust deposition in snow- and ice-covered Arctic regions was from HLD sources. In the southern HLD region, soil surface conditions are favorable for dust emission during the whole year. Climate change can cause a decrease in the duration of snow cover, retreat of glaciers, and an increase in drought, heatwave intensity, and frequency, leading to the increasing frequency of topsoil conditions favorable for dust emission, which increases the probability of dust storms. Our study provides a step forward to improve the representation of HLD in models and to monitor, quantify, and assess the environmental and climate significance of HLD

Classification of Inhibitors of Hepatic Organic Anion Transporting Polypeptides (OATPs): Influence of Protein Expression on Drug–Drug Interactions

ABSTRACT: The hepatic organic anion transporting poly-peptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug−drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1. The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors

Utvärdering av instrumentet UF-5000 för automatiserad urinpartikelanalys i en metodjämförelse med manuell mikroskopering av urinsediment

Inledning: Mikroskopisk analys av urinsediment anses i dagsläget vara gold standard inom urinsedimentdiagnostik, trots att metoden ofta är otillräckligt standardiserad. En rad automatiserade instrument, såsom UF-5000, finns idag tillgängliga och kompenserar för problematiken med den gamla metoden. Analys av urinsediment är avgörande vid flertal njursjukdomar, där bland annat erytrocyter, leukocyter, epitelceller, cylindrar och kristaller är av stort diagnostiskt värde. Syfte: Syftet var att utvärdera det automatiserade urinpartikelinstrumentet UF-5000 samt att jämföra metoden med manuell ljusmikroskopering av urinsediment. Metod: Vid metodjämförelse analyserades 69 prover med instrumentet UF-5000 samt i mikroskop. Data bearbetades med Passing Bablok-regression, Bland-Altman differensanalys samt Spearmans rangkorrelationkoefficient. Resultat: Statistisk signifikant skillnad förekom vid metodjämförelsen. Utvärderingen av instrumentet visade hög mätnoggrannhet med undantag för variationskoefficienten vid låg leukocytkoncentration samt avvikelser för instrumentets linjäritet. Diskussion: Då ljusmikroskopering av urinsediment är en otillräckligt standardiserad metod kunde statistiskt signifikanta skillnader ses, vilket kan bero på den bristande referensmetoden. Fortsatta studier där automatiserad metod jämförs med en mer standardiserad manuell mikroskopi är av stor vikt. Även reducering av cut-off för diverse parametrar kan vara aktuellt. Instrumentutvärdering visade en generell mätnoggrannhet med enstaka undantag vilket kan bero på felhantering vid analys. För vidare analys av linjäritet skulle ett ytterligare instrument som komplement kunna användas.Introduction: Microscopy is gold standard for urine sediment analysis, although the method is often insufficiently standardized. Several automated instruments, such as UF-5000, are commercially available on the market. Urine sediment analysis is crucial for diagnosis of kidney and urinary tract diseases where elements such as erythrocytes, leukocytes, epithelial cells, casts and crystals can be identified. Aim: The aim was to evaluate the performance of UF-5000 and compare the method with manual microscopic analysis of urine sediment. Method: Analysis with UF-5000 and microscopy was conducted on 69 samples. Data were processed with Passing Bablok-regression, Bland-Altman bias plot and Spearman's rank order correlation. Result: Comparison showed statistical significance between the two methods. Performance evaluation showed high accuracy apart from the coefficient of variation for low concentration of leukocytes and systematic error for linearity. Discussion: Since microscopy of urine sediment is an insufficiently standardized method, differences were acknowledged caused by discrepancies in the reference method. Further studies where UF-5000 is compared to a more standardized manual microscopy with a larger amount of pathological urine samples is of great importance. Reduction for cut-off may also be relevant. For further analysis of linearity, an additional instrument should be used as a complement

Quarz und Cristobalit aus Allchar als Monitore fuer kosmogenes

Allchar, Sb-As-Tl- Au Lagerstätte, befindet sich in Süd-West Teil von Mazedonien an der Grenze mit Griechenland. Wir haben eine ausführliche Untersuchungen, mit verschiedenen komparativen und komplementären Methoden (wie OM, Rö- Beugung, SEM, SEM-EDX, EPMA, ICP – MS, AMS) an den Quarz und Cristobalit aus Allchar durchgeführt. Zwei verschieden Art der Proben wurde untersucht: einmal als erz- bzw. petrographische Schliefe und nach Mineralogische Separation und mineralogisch – chemische Extraktion, als sogen. feinpulverliche stöchiometrische Minerale

Triplet-driven chemical reactivity of β\beta-carotene and its biological implications

The endoperoxides of β-carotene (βCar-EPOs) are regarded as main products of the chemical deactivation of (1)O(2) by β-carotene, one of the most important antioxidants, following a concerted singlet-singlet reaction. Here we challenge this view by showing that βCar-EPOs are formed in the absence of (1)O(2) in a non-concerted triplet-triplet reaction: (3)O(2) + (3)β-carotene → βCar-EPOs, in which (3)β-carotene manifests a strong biradical character. Thus, the reactivity of β-carotene towards oxygen is governed by its excited triplet state. βCar-EPOs, while being stable in the dark, are photochemically labile, and are a rare example of nonaromatic endoperoxides that release (1)O(2), again not in a concerted reaction. Their light-induced breakdown triggers an avalanche of free radicals, which accounts for the pro-oxidant activity of β-carotene and the puzzling swap from its anti- to pro-oxidant features. Furthermore, we show that βCar-EPOs, and carotenoids in general, weakly sensitize (1)O(2). These findings underlie the key role of the triplet state in determining the chemical and photophysical features of β-carotene. They shake up the prevailing models of carotenoid photophysics, the anti-oxidant functioning of β-carotene, and the role of (1)O(2) in chemical signaling in biological photosynthetic systems. βCar-EPOs and their degradation products are not markers of (1)O(2) and oxidative stress but of the overproduction of extremely hazardous chlorophyll triplets in photosystems. Hence, the chemical signaling of overexcitation of the photosynthetic apparatus is based on a (3)chlorophyll-(3)β-carotene relay, rather than on extremely short-lived (1)O(2)

Intention-to-treat analysis may be more conservative than per protocol analysis in antibiotic non-inferiority trials: a systematic review

Abstract Background In non-inferiority trials, there is a concern that intention-to-treat (ITT) analysis, by including participants who did not receive the planned interventions, may bias towards making the treatment and control arms look similar and lead to mistaken claims of non-inferiority. In contrast, per protocol (PP) analysis is viewed as less likely to make this mistake and therefore preferable in non-inferiority trials. In a systematic review of antibiotic non-inferiority trials, we compared ITT and PP analyses to determine which analysis was more conservative. Methods In a secondary analysis of a systematic review, we included non-inferiority trials that compared different antibiotic regimens, used absolute risk reduction (ARR) as the main outcome and reported both ITT and PP analyses. All estimates and confidence intervals (CIs) were oriented so that a negative ARR favored the control arm, and a positive ARR favored the treatment arm. We compared ITT to PP analyses results. The more conservative analysis between ITT and PP analyses was defined as the one having a more negative lower CI limit. Results The analysis included 164 comparisons from 154 studies. In terms of the ARR, ITT analysis yielded the more conservative point estimate and lower CI limit in 83 (50.6%) and 92 (56.1%) comparisons respectively. The lower CI limits in ITT analysis favored the control arm more than in PP analysis (median of − 7.5% vs. -6.9%, p = 0.0402). CIs were slightly wider in ITT analyses than in PP analyses (median of 13.3% vs. 12.4%, p < 0.0001). The median success rate was 89% (interquartile range IQR 82 to 93%) in the PP population and 44% (IQR 23 to 60%) in the patients who were included in the ITT population but excluded from the PP population (p < 0.0001). Conclusions Contrary to common belief, ITT analysis was more conservative than PP analysis in the majority of antibiotic non-inferiority trials. The lower treatment success rate in the ITT analysis led to a larger variance and wider CI, resulting in a more conservative lower CI limit. ITT analysis should be mandatory and considered as either the primary or co-primary analysis for non-inferiority trials. Trial registration PROSPERO registration number CRD42020165040