Spatio-temporal patterns and trends in MODIS-retrieved radiative forcing by snow impurities over the Western U.S. from 2001 - 2022

Seasonal mountain snowpack of the western US (WUS) is a key water resource to millions of people. Impurities at the snow surface directly affect snowmelt timing and rate, as they contribute to earlier peak streamflow, snow disappearance, and less water availability in dry months. Predicting the locations, timing, and intensity of impurities is challenging, and little is known concerning how RF has changed over the past decades. Here we contribute a novel analysis of the magnitude and spatio-temporal variability of snow radiative forcing (RF) across the WUS at 3 distinct spatial scales using remotely sensed RF from MODIS data sets (MODSCAG/DRFS) from 2001-2022. To establish spatial patterns, we calculated a single pixel-integrated value of RF from March 1st - June 30th for the 22 years. A Mann-Kendall significance test was used to detect long-term trends, and Theil-Sen's slope analysis was used to determine trend magnitude. We found the greatest snow RF in the Upper Colorado region, with notable RF in less-studied regions, (such as the Great Basin and Pacific Northwest), that watersheds with greater temporal variability tend to have greater spatial variability, and that these watersheds are more associated with arid regions. Trends of snow RF are largely stable in the WUS; only a small percent of mountain ecoregions (0.03-8%) had significant trends in RF, and these were typically negative. All mountain ecoregions exhibited a net decline in RF on snow, with the most ubiquitous and widespread decline seen in the Sierra Nevadas. This study helps inform where and when RF impacts on snowmelt may need to be considered in hydrologic models

Outliers, Extreme Events and Multiscaling

Extreme events have an important role which is sometime catastrophic in a variety of natural phenomena including climate, earthquakes and turbulence, as well as in man-made environments like financial markets. Statistical analysis and predictions in such systems are complicated by the fact that on the one hand extreme events may appear as "outliers" whose statistical properties do not seem to conform with the bulk of the data, and on the other hands they dominate the (fat) tails of probability distributions and the scaling of high moments, leading to "abnormal" or "multi"-scaling. We employ a shell model of turbulence to show that it is very useful to examine in detail the dynamics of onset and demise of extreme events. Doing so may reveal dynamical scaling properties of the extreme events that are characteristic to them, and not shared by the bulk of the fluctuations. As the extreme events dominate the tails of the distribution functions, knowledge of their dynamical scaling properties can be turned into a prediction of the functional form of the tails. We show that from the analysis of relatively short time horizons (in which the extreme events appear as outliers) we can predict the tails of the probability distribution functions, in agreement with data collected in very much longer time horizons. The conclusion is that events that may appear unpredictable on relatively short time horizons are actually a consistent part of a multiscaling statistics on longer time horizons.Comment: 11 pages, 14 figures included, PRE submitte

Enzyme prodrug therapy achieves site-specific, personalized physiological responses to the locally produced nitric oxide

Nitric oxide (NO) is a highly potent but short-lived endogenous radical with a wide spectrum of physiological activities. In this work, we developed an enzymatic approach to the site-specific synthesis of NO mediated by biocatalytic surface coatings. Multilayered polyelectrolyte films were optimized as host compartments for the immobilized β-galactosidase (β-Gal) enzyme through a screen of eight polycations and eight polyanions. The lead composition was used to achieve localized production of NO through the addition of β-Gal–NONOate, a prodrug that releases NO following enzymatic bioconversion. The resulting coatings afforded physiologically relevant flux of NO matching that of the healthy human endothelium. The antiproliferative effect due to the synthesized NO in cell culture was site-specific: within a multiwell dish with freely shared media and nutrients, a 10-fold inhibition of cell growth was achieved on top of the biocatalytic coatings compared to the immediately adjacent enzyme-free microwells. The physiological effect of NO produced via the enzyme prodrug therapy was validated ex vivo in isolated arteries through the measurement of vasodilation. Biocatalytic coatings were deposited on wires produced using alloys used in clinical practice and successfully mediated a NONOate concentration-dependent vasodilation in the small arteries of rats. The results of this study present an exciting opportunity to manufacture implantable biomaterials with physiological responses controlled to the desired level for personalized treatment

Metabolic network analysis predicts efficacy of FDA-approved drugs targeting the causative agent of a neglected tropical disease

<p>Abstract</p> <p>Background</p> <p>Systems biology holds promise as a new approach to drug target identification and drug discovery against neglected tropical diseases. Genome-scale metabolic reconstructions, assembled from annotated genomes and a vast array of bioinformatics/biochemical resources, provide a framework for the interrogation of human pathogens and serve as a platform for generation of future experimental hypotheses. In this article, with the application of selection criteria for both <it>Leishmania major </it>targets (e.g. <it>in silico </it>gene lethality) and drugs (e.g. toxicity), a method (MetDP) to rationally focus on a subset of low-toxic Food and Drug Administration (FDA)-approved drugs is introduced.</p> <p>Results</p> <p>This metabolic network-driven approach identified 15 <it>L. major </it>genes as high-priority targets, 8 high-priority synthetic lethal targets, and 254 FDA-approved drugs. Results were compared to previous literature findings and existing high-throughput screens. Halofantrine, an antimalarial agent that was prioritized using MetDP, showed noticeable antileishmanial activity when experimentally evaluated <it>in vitro </it>against <it>L. major </it>promastigotes. Furthermore, synthetic lethality predictions also aided in the prediction of superadditive drug combinations. For proof-of-concept, double-drug combinations were evaluated <it>in vitro </it>against <it>L. major </it>and four combinations involving the drug disulfiram that showed superadditivity are presented.</p> <p>Conclusions</p> <p>A direct metabolic network-driven method that incorporates single gene essentiality and synthetic lethality predictions is proposed that generates a set of high-priority <it>L. major </it>targets, which are in turn associated with a select number of FDA-approved drugs that are candidate antileishmanials. Additionally, selection of high-priority double-drug combinations might provide for an attractive and alternative avenue for drug discovery against leishmaniasis.</p

Synthesis and pharmacological characterization of the selective GluK1 radioligand (S)-2-amino-3-(6-[³H]-2,4-dioxo-3,4-dihydrothieno.3,2-d] pyrimidin1(2H)- yl) propanoic acid ([³H]-NF608)

The kainic acid receptors belong to the class of ionotropic glutamate receptors and comprise five subunits named GluK1-5. Radioligands are essential tools for use in binding assays aimed at ligand-receptor structure-activity-relationship studies. Previous work has led to the synthesis of GluK1 radioligands [3H]-SYM2081, [3H]-UBP310 and [3H]-ATPA, however all strategies were work-intensive and thus not attractive. Herein, we report the synthesis of [3H]-NF608 and subsequent pharmacological evaluation at homomeric recombinant rat GluK1 receptors. Binding affinities of a series of standard GluK1 ligands were shown to be in line with previously reported affinities obtained by use of already reported radioligands

A study on African vernacular mosque: A lesson from tradition

Mosques as a symbol of Islamic cities have a significant place in Islamic Architecture and it prompts architects to create admirable, magnificent buildings. While several studies have done on features and prototypes in this field but mainly it leaded to exaggerate dominance of dome as inseparable component of mosques. Although dome construction is costly, it is not that much adaptable to different climates and even it is not a good culture indicator of different countries, still there is a strong insist on presence of dome in mosques everywhere. This paper aims to study African mosque example which deeply relied on vernacular architecture. Various styles of design in Mali as case study investigated in terms of material, design concept, to arrive at concrete results

Evaluation of an in-clinic Serum Amyloid A (SAA) assay and assessment of the effects of storage on SAA samples

<p>Abstract</p> <p>Background</p> <p>An in-clinic assay for equine serum amyloid A (SAA) analysis, Equinostic EVA1, was evaluated for use in a clinical setting. Stability of SAA in serum samples was determined.</p> <p>Methods</p> <p>Intra- and inter- assay variation of the in-clinic method was determined. The in-clinic method (EVA1) results were compared to a reference method (Eiken LZ SAA) with 62 patient samples. For samples with SAA concentrations within the assay range of EVA1 (10-270 mg/L), differences between the methods were evaluated in a difference plot. Linearity under dilution was evaluated in two samples. Stability of SAA in three serum pools stored at 4°C and approximately 22°C was evaluated with the reference method day 0, 1, 2, 4, 7, 17 and analysed with a two-way ANOVA.</p> <p>Results</p> <p>The imprecision (coefficient of variation, CV) for the in-clinic method was acceptable at higher SAA concentrations with CV values of 7,3-12%, but poor at low SAA concentrations with CV values of 27% and 37% for intra- and inter-assay variation respectively. Recovery after dilution was 50-138%. The in-clinic assay and the reference method identified equally well horses with low (<10 mg/L) and high (>270 mg/L) SAA concentrations. Within the assay range of the in-clinic method, 10-270 mg/L, the difference between the two methods was slightly higher than could be explained by the inherent imprecision of the assays. There were no significant changes of serum SAA concentrations during storage.</p> <p>Conclusions</p> <p>The in-clinic assay identified horses with SAA concentrations of <10 mg/L and >270 mg/L in a similar way as the reference method, and provided an estimate of the SAA concentration in the range of 10-270 mg/L. The imprecision of the in-clinic method was acceptable at high SAA concentrations but not at low concentrations. Dilution of samples gave inconsistent results. SAA was stable both at room temperature and refrigerated, and thus samples may be stored before analysis with the reference method.</p

Association between antibodies to Coxiella burnetii in bulk tank milk and perinatal mortality of Danish dairy calves

<p>Abstract</p> <p>Background</p> <p><it>Coxiella burnetii </it>is a well-known cause of placentitis and subsequent abortion in ruminants, but there are no reports on the relationship with perinatal mortality. The study was performed to determine the influence of level and change of bulk tank milk (BTM) antibodies to <it>C. burnetii </it>on two outcomes associated with parturition in cattle: a) stillbirth; and b) stillbirth and neonatal mortality combined (perinatal death).</p> <p>Methods</p> <p>Twenty-four Danish dairy herds were tested repeatedly for antibodies to <it>C. burnetii </it>in BTM using a commercial ELISA. Samples were collected monthly from July 2008 to July 2009. Information on the 2,362 calvings occurring in the study period was obtained from the Danish Cattle Database. Two multilevel logistic regression models were created for the two outcomes stillbirth and perinatal mortality. One model included the level of BTM antibodies in a specified period before or after the outcome had occurred. The other model included the change in antibodies over time. These predictors were included both at herd and animal level. Furthermore, all models included parity and breed.</p> <p>Results</p> <p>The individual monthly BTM antibody levels were highly correlated within herds. Consequently, changes in BTM antibody levels were not found to be associated with neither risk of stillbirth nor the risk of perinatal mortality. However, the risk of stillborn calves and perinatal death was higher with high level of BTM antibodies 8 to 9 months after the incident, but not outside this period.</p> <p>Conclusion</p> <p>We conclude that the level of antibodies to <it>C. burnetii </it>in BTM may be associated with perinatal mortality, but the association was not persistent and should be investigated further.</p