bluuebunny/crossref_metadata_2025 huggingface dataset:
Visible‐Light‐Mediated Dearomatisation of Indoles and Pyrroles to Pharmaceuticals and Pesticides
Authors: Schilling Waldemar , Zhang Yu , Riemer Daniel , Das Shoubhik
Published: October 2019

Dearomatisation of indole derivatives to the corresponding isatin derivatives has been achieved with the aid of visible light and oxygen. It should be noted that isatin derivatives are highly important for the synthesis of pharmaceuticals and bioactive compounds. Notably, this chemistry works excellently with N‐protected and protection‐free indoles. Additionally, this methodology can also be applied to dearomatise pyrrole derivatives to generate cyclic imides in a single step. Later this methodology was applied for the synthesis of four pharmaceuticals and a pesticide called dianthalexin B. Detailed mechanistic studies revealed the actual role of oxygen and photocatalyst.
Alkaline Earth Metal Template (Cross‐)Coupling Reactions with Hybrid Disila‐Crown Ether Analogues
Authors: Dankert Fabian , Donsbach Carsten , Rienmüller Julia , Richter Roman M. , von Hänisch Carsten
Published: October 2019

Alkaline earth metal iodides were used as templates for the synthesis of novel silicon‐based ligands. Siloxane moieties were (cross‐)coupled and ion‐specific, silicon‐rich crown ether analogues were obtained. The reaction of 1,2,7,8‐tetrasila[12]crown‐4 (I) and 1,2‐disila[9]crown‐3 (II) with MgI2 yielded exclusively [Mg(1,2,7,8‐tetrasila[12]crown‐4)I2] (1). The larger Ca2+ ion was then employed for cross‐coupling of I and II and yielded the complex [Ca(1,2,7,8‐tetrasila[15]crown‐5)I2] (2). Cross‐coupling of I and 1,2,4,5‐tetrasila[9]crown‐3 (III) with SrI2 enables the synthesis of the silicon‐dominant 1,2,4,5,10,11‐hexasila[15]crown‐5 ether complex of SrI2 (3). Further, the compounds [Sr(1,2,10,11‐tetrasila[18]crown‐6)I2] (4), [Sr(1,2,13,14‐tetrasila[24]crown‐8)I2] (5), and [Sr(1,2,13,14‐tetrasila‐dibenzo[24]crown‐8)I2] (6) were obtained by coupling I, 1,2‐disila[12]crown‐4 (IV) or 1,2‐disila‐benzo[12]crown‐4 (V), respectively. Using various anions, the (cross‐)coupled ligands were also observed in an X‐ray structure within the mentioned complexes. These template‐assisted (cross‐)couplings of various ligands are the first of their kind and a novel method to obtain macrocycles and/or their metal complexes to be established. Further, the Si−O bond activations presented herein might be of importance for silane or even organic functionalization.
Ultrafine PtRu Dilute Alloy Nanodendrites for Enhanced Electrocatalytic Methanol Oxidation
Authors: Zhang Shuping , Rong Hongpan , Yang Tianyi , Bai Bing , Zhang Jiatao
Published: October 2019

Dilute alloy nanostructures have been demonstrated to possess distinct catalytic properties. Noble‐metal‐induced reduction is one effective synthesis strategy to construct dilute alloys and modify the catalytic performance of the host metal. Herein, we report the synthesis of ultrafine PtRu dilute alloy nanodendrites (PtRu NDs, molar ratio Ru/Pt is 1:199) by the reduction of RuIII ions induced by Pt metal. For the methanol oxidation reaction, PtRu NDs showed the highest forward peak current density (2.66 mA cm−2, 1.14 A/mgPt) and the best stability compared to those of pure‐Pt nanodendrites (pure‐Pt NDs), commercial PtRu/C and commercial Pt/C catalysts.
Time Evolution of Local pH Around a Photo‐Acid in Water and a Polymer Hydrogel: Time Resolved Fluorescence Spectroscopy of Pyranine
Authors: Chakraborty Subhajit , Nandi Somen , Bhattacharyya Kankan , Mukherjee Saptarshi
Published: October 2019

In this work, we propose a new analysis of the time resolved emission spectra of a photo‐acid, HA, pyranine (8‐hydroxypyrene‐1,3,6‐trisulphonic acid, HPTS) based on time resolved area normalized emission spectra (TRANES). Presence of an isoemissive point in TRANES confirms the presence of two emissive species (HA and A−) inside the system in bulk water and inside a co‐polymer hydrogel [F127, (PEO)100–(PPO)70–(PEO)100]. We show that following electronic excitation, the local pH around HPTS, is much lower than the bulk pH presumably because of ejection of proton from the photo‐acid in the excited state. With increase in time, the local pH increases and reaches the bulk value. We further, demonstrate that the excited state pKa of HPTS may be estimated from the emission intensities of HA and A− at long time. The time constant for time evolution of pH is ∼630 ps in water, ∼1300 ps in F127 gel and ∼4700 ps in CTAB micelle. The location and local viscosity sensed by the probe is ascertained using fluorescence correlation spectroscopy (FCS) and fluorescence anisotropy decay. The different values of the local viscosity reported by these two methods are reconciled.
Performance of Density Functional Theory for Transition Metal Oxygen Bonds
Authors: Moltved Klaus A. , Kepp Kasper P.
Published: October 2019

The accuracy of density functional theory (DFT) limits predictions in theoretical catalysis, and strong chemical bonds between transition metals and oxygen pose a particular challenge. We benchmarked 30 diverse density functionals against the bond dissociation enthalpies (BDE) of the 30 MO and 30 MO+ diatomic systems of all the 3d, 4d, and 5d metals, to test universality across the d‐block as required in comparative studies. Seven functionals, B98, B97‐1, B3P86, B2PLYP, TPSSh, B3LYP, and B97‐2, display mean absolute errors (MAE) <30 kJ/mol. In contrast, many commonly used functionals such as PBE and RPBE overestimate M−O bonding by +30 kJ/mol and display MAEs from 48–76 kJ/mol. RPBE and OPBE reduce the over‐binding of PBE but remain very inaccurate. We identify a linear relationship (p‐value 7.6 ⋅ 10−5) between the precision and accuracy of DFT, i. e. inaccurate functionals tend to produce larger, unpredictable random errors. Some functionals commonly deviate from this relationship: Thus, M06‐2X is very precise but not very accurate, whereas B3LYP* and MN15‐L are more accurate but less precise than M06‐2X. The best‐performing hybrids have 10–30 % HF exchange, but this can be relieved by double hybrids (B2PLYP). Most functionals describe trends well, but errors comparing 5d to 4d/3d are ∼10 kJ/mol larger than group‐wise errors, due to uncertainties in the spin‐orbit coupling corrections for effective core potentials, affecting e. g. Pt/Pd or Au/Ag comparisons.
Erweiterung des Anwendungsbereichs von DIN EN 1996‐3/NA für hohe Wände
Authors: Förster Valentin , Graubner Carl‐Alexander
Published: October 2019

According to Eurocode 6, unreinforced masonry walls can be designed using different verification methods, whereby the simplified calculation methods are contained in Part 3 of DIN EN 1996 [1]. If the associated application limits and boundary conditions are fulfilled, a large part of the usual problems occurring in masonry construction can be dealt with without great effort. A limiting condition for the application of the simplified calculation methods is a maximum clear wall height of h = 2.75 m or h = 12 • t. Changes in user requirements for modern buildings with masonry walls nowadays often require greater wall heights, wherefore a verification according to the general rules from DIN EN 1996‐1‐1/NA [2] is necessary. This means a considerably higher effort for the structural engineer.

A considerable amount of calculations was done to verify whether the results of the simplified calculation methods are also valid for greater wall heights. The results were transferred into a consistent standardization proposal with regard to extended application limits of DIN EN 1996‐3/NA, which is contained in a new draft Amendment A3 for the National Application Document for Germany.
Comparison of fish detections, community diversity, and relative abundance using environmental DNA metabarcoding and traditional gears
Authors: Sard Nicholas M. , Herbst Seth J. , Nathan Lucas , Uhrig Genelle , Kanefsky Jeannette , Robinson John D. , Scribner Kim T.
Published: October 2019

Background

Detecting species at low abundance, including aquatic invasive species (AIS), is critical for making informed management decisions. Environmental DNA (eDNA) methods have become a powerful tool for rare or cryptic species detection; however, many eDNA assays offer limited utility for community‐level analyses due to their use of species‐specific (presence/absence) ‘barcodes’. Metabarcoding methods provide information on entire communities based on sequencing of all taxon‐specific barcodes within an eDNA sample.

Aims

Evaluate measures of fish species detections, community diversity, and estimates of relative abundance based on eDNA metabarcoding and traditional fisheries sampling approaches in the context of fish community characterization and AIS survellience.

Materials and Methods

In 2016, eight limnologically diverse lakes (surface area range: 13 – 1,728 ha) in Michigan, USA were sampled using a variety of traditional fisheries gears to characterize fish community composition. Environmental DNAs from surface (33 ± 6, mean ± 1 SD) and benthic (14 ± 2) water samples from each lake were isolated and amplified for two metabarcoding markers (mitochondrial 12S and 16S rDNA loci) using fish‐specific primers. Fish species detected within each lake were determined by comparing the sequencing data to a database of sequences from native Michigan fish species and 19 AIS on the Michigan's Watch List.

Results

Analysis of species accumulation curves indicated multi‐locus eDNA metabarcoding assays can enhance species detection capacities and characterize 95% of a fish community in fewer sampling efforts than traditional gear (range: 2 – 62, median: 14). In addition, all AIS detected in traditional gear samples were also detected by eDNA, while some AIS detected by eDNA assays were absent from traditional gear samples.

Discussion

Results reported here are, in part, driven by the lack of species‐selectivity during eDNA sampling events. Given the efficacy of eDNA assays, we suggest multi‐locus eDNA metabarcoding assays be implemented in early detection efforts.
Mononuclear Lanthanide Complexes Containing [O‐O]‐Chelating Sulfonylamidophosphate Type Ligands
Authors: Prytula‐Kurkunova Angelina Y. , Pichon Céline , Duhayon Carine , Amirkhanov Vladimir M. , Sutter Jean‐Pascal
Published: October 2019

The ability of a sulfonyl amidophosphate (SAPh) compounds having the structural fragment RSO2NHP(O)R to act as a β‐diketone homologue for the complexation of Ln(III) ions has been explored. We report the synthesis and magnetic properties of five mononuclear complexes of formula LnL3Phen (L stands for deprotonated bis(methyl(phenyl)amino)phosphoryl)benzenesulfonamide, C6H5SO2NP(O)[N(CH3)(C6H5)]2, and Phen for phenanthroline) with Ln = TbIII, DyIII, HoIII, ErIII, and YbIII, along with the X‐ray structure of the Dysprosium and Ytterbium compounds. In‐field SMM behaviors were observed for the Dy and Er derivatives.
Aroma‐Relevant Volatile Compounds as Markers for the Sensory Quality of Argan Oil
Authors: Matthäus Bertrand , Bonte Anja , Sinning Bernadette , Charrouf Zoubida
Published: October 2019

The aim of the present work is to identify and characterize the most important aroma active compounds of argan oil from unroasted and roasted argan almonds as well as roasted almonds obtained from goat‐digested fruits by dynamic headspace GC and GC‐olfactometry with aroma dilution analysis to classify samples from the market according to their processing. While fresh ground argan almonds are characterized by only seven aroma active compounds, in argan oil from unroasted and roasted almonds, 22 and 35 aroma active compounds are found, respectively. As a result of the roasting process, 14 aroma active compounds with dilution factors >64 are detected in the oil by GC‐olfactometry. 17 aroma active compounds show significant differences between the three different argan oil qualities. These compounds are used to differentiate the quality of argan oil from the market.

Practical Application: Argan oil belongs to the high‐price oils on the market but sometimes the sensory quality of the oil contradicts the positive image that has been built up for oil by unpleasant cheese‐like and fusty sensory attributes. Although some information about the composition of the volatile compounds of cold‐pressed argan oil from unroasted and roasted kernels is available, the knowledge about compounds that are typical for the aroma of argan oil is important in order to develop analytical methods for the classification of different argan oil qualities. This reduces the work for a panel group that is often time and labor consuming and sometimes the results are not reliable. The present paper demonstrates which volatile compounds show significant differences between argan oil from unroasted and roasted argan almonds as well as roasted almonds obtained from goat‐digested fruits allowing a differentiation of these oils.
Thermodynamic Analysis of High‐Temperature Carnot Battery Concepts
Authors: Steinmann Wolf-Dieter , Jockenhöfer Henning , Bauer Dan
Published: October 2019

Within the thermal energy storage initiative, National Demonstrator for IseNtropic Energy (NADINE) storage, three projects are carried out focusing on thermal energy storage at different temperature levels. Thermal storage units are key components of Carnot batteries, which are based on the intermediate conversion of electric energy into heat. Pumped thermal energy storage (PTES) is an emerging Carnot battery concept variant for the flexible management of supply and demand of electricity, heat, and cold. A counterclockwise thermodynamic cycle operated by surplus electricity is used to charge a thermal storage, which delivers heat to operate a power cycle during discharge. The absence of geographic constraints, a theoretical roundtrip efficiency of 100%, and a small environmental footprint are promising features of PTES. PTES is also able to provide low‐cost backup capacity in case of shortages in available renewable energy. Various options are proposed for the technical implementation of PTES, using various combinations of engines, thermal storage units, and working fluids. The resulting systems differ in efficiency, costs, maturity, and complexity. Herein, a thermodynamic analysis of five different PTES variants is presented. The results should help to identify priorities in the further development of the PTES variants.
Trading risk control model of electricity retailers in multi‐level power market of China
Authors: Yu Xiaobao , Sun Yixin
Published: October 2019

The decision‐making and risk assessment of electricity purchase and sales is the key to adapt to the electricity market for independent electricity retailers in China. This research carried out the purchase and sales risks of electricity for electricity retailers and constructed the multi‐level market purchase and sales combination optimization model. Based on the portfolio optimization theory, the conditional value at risk theory (CVaR) was proposed. Based on the evaluation index about the conditional risk profit and CVaR, electricity retailers purchase and sales combined optimization model has been constructed to explore the impact of purchase and sales risks by different factors in multi‐level electricity market. The example analysis was carried out by the fixed spread mode and the linkage spread mode. The results showed that the mathematical mean and variance of market spread had great influence on the electricity purchase and sales combination. Especially in the mature electricity market, the mathematical mean of spread and risk in medium‐ and long‐term market was smaller than that in spot market, and the best point of the electricity purchase and sales combination was shown on the smallest value of CVaR, while the electricity purchase and sales combination was optimal under limited conditions.
A National-Scale Framework for Visualizing Riverine Concentrations of Microplastics Released from Municipal Wastewater Treatment Incorporating Generalized Instream Losses
Authors: Holmes Christopher M. , Dyer Scott D. , Vamshi Raghu , Maples-Reynolds Nikki , Davies Iain A.
Published: October 2019

Down-the-drain exposure models provide a valuable tool for estimating environmental exposure to substances which are treated and discharged by municipal wastewater-treatment plants (WWTPs). Microplastics may enter WWTPs from consumer activities and disposal. An exposure framework was developed using the iSTREEM® model, which estimates spatially explicit concentrations of substances in riverine systems across the United States and portions of Ontario, Canada. One hundred simulations covering a range of WWTP removal and instream loss rates (proxy for net sedimentation) were incorporated into a Web-based visualization tool for user exploration of relative concentrations across simulations. Surface water concentrations specific to user-supplied tonnage were examined via interactive heat maps and cumulative distributions. Exploring the spatial aspect of iSTREEM results showed that modeling 90% WWTP removal and no instream loss resulted in 8.5% of the mass entering WWTPs discharged to marine estuaries (7.4%) or Great Lakes (1.1%) environments, with the remainder of the mass discharged (1.5%) in inland sinks or exiting the United States via rivers. Modeling an example instream loss of k = 0.1 d–1 (i.e., half-life = 7 d), terminal river segments contained 3.3% of influent mass (2.3% marine estuaries, 1.0% Great Lakes). Varying instream loss rates had substantial impacts on the total mass exported. The Web-based tool provided a user-based mechanism to visualize relative freshwater concentrations of microplastics across a large geographic area by varying simplified particle fate assumptions. Environ Toxicol Chem 2019;39:210–219. © 2019 SETAC

Abstract

Hypothetical microplastic particles emitted from municipal wastewater treatment were modeled to estimate relative environmental concentrations in rivers when wastewater and in-stream removal rates were varied. Comparisons of marine and Great Lakes discharge reaches were made with the overall set of more than 28 000 river segments in the conterminous United States and portions of Ontario, Canada. WWTP = wastewater-treatment plant.
Inhibition of Piezo1 attenuates demyelination in the central nervous system
Authors: Velasco‐Estevez María , Gadalla Kamal K. E. , Liñan‐Barba Núria , Cobb Stuart , Dev Kumlesh K. , Sheridan Graham K.
Published: October 2019

Piezo1 is a mechanosensitive ion channel that facilitates the translation of extracellular mechanical cues to intracellular molecular signaling cascades through a process termed, mechanotransduction. In the central nervous system (CNS), mechanically gated ion channels are important regulators of neurodevelopmental processes such as axon guidance, neural stem cell differentiation, and myelination of axons by oligodendrocytes. Here, we present evidence that pharmacologically mediated overactivation of Piezo1 channels negatively regulates CNS myelination. Moreover, we found that the peptide GsMTx4, an antagonist of mechanosensitive cation channels such as Piezo1, is neuroprotective and prevents chemically induced demyelination. In contrast, the positive modulator of Piezo1 channel opening, Yoda‐1, induces demyelination and neuronal damage. Using an ex vivo murine‐derived organotypic cerebellar slice culture model, we demonstrate that GsMTx4 attenuates demyelination induced by the cytotoxic lipid, psychosine. Importantly, we confirmed the potential therapeutic effects of GsMTx4 peptide in vivo by co‐administering it with lysophosphatidylcholine (LPC), via stereotactic injection, into the cerebral cortex of adult mice. GsMTx4 prevented both demyelination and neuronal damage usually caused by the intracortical injection of LPC in vivo; a well‐characterized model of focal demyelination. GsMTx4 also attenuated both LPC‐induced astrocyte toxicity and microglial reactivity within the lesion core. Overall, our data suggest that pharmacological activation of Piezo1 channels induces demyelination and that inhibition of mechanosensitive channels, using GsMTx4, may alleviate the secondary progressive neurodegeneration often present in the latter stages of demyelinating diseases.
The microglial NLRP3 inflammasome is activated by amyotrophic lateral sclerosis proteins
Authors: Deora Vandana , Lee John D. , Albornoz Eduardo A. , McAlary Luke , Jagaraj Cyril J. , Robertson Avril A. B. , Atkin Julie D. , Cooper Matthew A. , Schroder Kate , Yerbury Justin J. , Gordon Richard , Woodruff Trent M.
Published: October 2019

Microglial NLRP3 inflammasome activation is emerging as a key contributor to neuroinflammation during neurodegeneration. Pathogenic protein aggregates such as β‐amyloid and α‐synuclein trigger microglial NLRP3 activation, leading to caspase‐1 activation and IL‐1β secretion. Both caspase‐1 and IL‐1β contribute to disease progression in the mouse SOD1G93A model of amyotrophic lateral sclerosis (ALS), suggesting a role for microglial NLRP3. Prior studies, however, suggested SOD1G93A mice microglia do not express NLRP3, and SOD1G93A protein generated IL‐1β in microglia independent to NLRP3. Here, we demonstrate using Nlrp3‐GFP gene knock‐in mice that microglia express NLRP3 in SOD1G93A mice. We show that both aggregated and soluble SOD1G93A activates inflammasome in primary mouse microglia leading caspase‐1 and IL‐1β cleavage, ASC speck formation, and the secretion of IL‐1β in a dose‐ and time‐dependent manner. Importantly, SOD1G93A was unable to induce IL‐1β secretion from microglia deficient for Nlrp3, or pretreated with the specific NLRP3 inhibitor MCC950, confirming NLRP3 as the key inflammasome complex mediating SOD1‐induced microglial IL‐1β secretion. Microglial NLRP3 upregulation was also observed in the TDP‐43Q331K ALS mouse model, and TDP‐43 wild‐type and mutant proteins could also activate microglial inflammasomes in a NLRP3‐dependent manner. Mechanistically, we identified the generation of reactive oxygen species and ATP as key events required for SOD1G93A‐mediated NLRP3 activation. Taken together, our data demonstrate that ALS microglia express NLRP3, and that pathological ALS proteins activate the microglial NLRP3 inflammasome. NLRP3 inhibition may therefore be a potential therapeutic approach to arrest microglial neuroinflammation and ALS disease progression.
Short‐term plasticity following motor sequence learning revealed by diffusion magnetic resonance imaging
Authors: Tavor Ido , Botvinik‐Nezer Rotem , Bernstein‐Eliav Michal , Tsarfaty Galia , Assaf Yaniv
Published: October 2019

Current noninvasive methods to detect structural plasticity in humans are mainly used to study long‐term changes. Diffusion magnetic resonance imaging (MRI) was recently proposed as a novel approach to reveal gray matter changes following spatial navigation learning and object‐location memory tasks. In the present work, we used diffusion MRI to investigate the short‐term neuroplasticity that accompanies motor sequence learning. Following a 45‐min training session in which participants learned to accurately play a short sequence on a piano keyboard, changes in diffusion properties were revealed mainly in motor system regions such as the premotor cortex and cerebellum. In a second learning session taking place immediately afterward, feedback was given on the timing of key pressing instead of accuracy, while participants continued to learn. This second session induced a different plasticity pattern, demonstrating the dynamic nature of learning‐induced plasticity, formerly thought to require months of training in order to be detectable. These results provide us with an important reminder that the brain is an extremely dynamic structure. Furthermore, diffusion MRI offers a novel measure to follow tissue plasticity particularly over short timescales, allowing new insights into the dynamics of structural brain plasticity.
Cost‐Effectiveness of Noninvasive Screening for Alcohol‐Related Liver Fibrosis
Authors: Asphaug Lars , Thiele Maja , Krag Aleksander , Melberg Hans Olav ,   on behalf of the GALAXY Consortium
Published: October 2019

Background and Aims

Alcohol‐related liver disease is often undetected until irreversible late‐stage decompensated disease manifests. Consequently, there is an unmet need for effective and economically reasonable pathways to screen for advanced alcohol‐related fibrosis.

Approach and Results

We used real‐world data from a large biopsy‐controlled study of excessive drinkers recruited from primary and secondary care, to evaluate the cost‐effectiveness of four primary care initiated strategies: (1) routine liver function tests with follow‐up ultrasonography for test‐positives, (2) the enhanced liver fibrosis (ELF) test with hospital liver stiffness measurement (LSM) for positives, (3) a three‐tier strategy using the Forns Index to control before strategy 2, and (4) direct referral of all to LSM. We used linked decision trees and Markov models to evaluate outcomes short term (cost‐per‐accurate diagnosis) and long term (quality‐adjusted life‐years [QALYs]). For low‐prevalence populations, ELF with LSM follow‐up was most cost‐effective, both short term (accuracy 96%, $196 per patient) and long term (incremental cost‐effectiveness ratio [ICER] $5,387‐$8,430/QALY), depending on whether diagnostic testing had lasting or temporary effects on abstinence rates. Adding Forns Index decreased costs to $72 per patient and accuracy to 95%. The strategy resulted in fewer QALYs due to more false negatives but an ICER of $3,012, making this strategy suited for areas with restricted access to ELF and transient elastography or lower willingness‐to‐pay. For high‐prevalence populations, direct referral to LSM was highly cost‐effective (accuracy 93%, $297 per patient), with ICERs between $490 and $1,037/QALY.

Conclusions

Noninvasive screening for advanced alcohol‐related fibrosis is a cost‐effective intervention when different referral pathways are used according to the prevalence of advanced fibrosis. Patients in the primary health care sector should be tested with the ELF test followed by LSM if the test was positive, whereas direct referral to LSM is highly cost‐effective in high‐prevalence cohorts.
Molecular expression profiles of morphologically defined hippocampal neuron types: Empirical evidence and relational inferences
Authors: White Charise M. , Rees Christopher L. , Wheeler Diek W. , Hamilton David J. , Ascoli Giorgio A.
Published: October 2019

Gene and protein expressions are key determinants of cellular function. Neurons are the building blocks of brain circuits, yet the relationship between their molecular identity and the spatial distribution of their dendritic inputs and axonal outputs remains incompletely understood. The open‐source knowledge base Hippocampome.org amasses such transcriptomic data from the scientific literature for morphologically defined neuron types in the rodent hippocampal formation: dentate gyrus, CA3, CA2, CA1, subiculum, and entorhinal cortex. Positive, negative, or mixed expression reports were initially obtained from published articles directly connecting molecular evidence to neurons with known axonal and dendritic patterns across hippocampal layers. Here, we supplement this information by collating, formalizing, and leveraging relational expression inferences that link a gene or protein expression or lack thereof to that of another molecule or to an anatomical location. With these additional interpretations, we freely release online a comprehensive human‐ and machine‐readable molecular profile for more than 100 neuron types in Hippocampome.org. Analysis of these data ascertains the ability to distinguish unequivocally most neuron types in each of the major subdivisions of the hippocampus based on currently known biochemical markers. Moreover, grouping neuron types by expression similarity reveals eight superfamilies characterized by a few defining molecules.
Changes in event‐based streamflow magnitude and timing after suburban development with infiltration‐based stormwater management
Authors: Hopkins Kristina G. , Bhaskar Aditi S. , Woznicki Sean A. , Fanelli Rosemary M.
Published: October 2019

Green stormwater infrastructure implementation in urban watersheds has outpaced our understanding of practice effectiveness on streamflow response to precipitation events. Long‐term monitoring of experimental suburban watersheds in Clarksburg, Maryland, USA, provided an opportunity to examine changes in event‐based streamflow metrics in two treatment watersheds that transitioned from agriculture to suburban development with a high density of infiltration‐focused stormwater control measures (SCMs). Urban Treatment 1 has predominantly single family detached housing with 33% impervious cover and 126 SCMs. Urban Treatment 2 has a mix of single family detached and attached housing with 44% impervious cover and 219 SCMs. Differences in streamflow‐event magnitude and timing were assessed using a before‐after‐control‐reference‐impact design to compare urban treatment watersheds with a forested control and an urban control with detention‐focused SCMs. Streamflow and precipitation events were identified from 14 years of sub‐daily monitoring data with an automated approach to characterize peak streamflow, runoff yield, runoff ratio, streamflow duration, time to peak, rise rate, and precipitation depth for each event. Results indicated that streamflow magnitude and timing were altered by urbanization in the urban treatment watersheds, even with SCMs treating 100% of the impervious area. The largest hydrologic changes were observed in streamflow magnitude metrics, with greater hydrologic change in Urban Treatment 2 compared with Urban Treatment 1. Although streamflow changes were observed in both urban treatment watersheds, SCMs were able to mitigate peak flows and runoff volumes compared with the urban control. The urban control had similar impervious cover to Urban Treatment 2, but Urban Treatment 2 had more than twice the precipitation depth needed to initiate a flow response and lower median peak flow and runoff yield for events less than 20 mm. Differences in impervious cover between the Urban Treatment watersheds appeared to be a large driver of differences in streamflow response, rather than SCM density. Overall, use of infiltration‐focused SCMs implemented at a watershed‐scale did provide enhanced attenuation of peak flow and runoff volumes compared to centralized‐detention SCMs.
Risk of being born preterm in offspring of survivors with childhood or adolescent central nervous system tumor in Sweden
Authors: Huang Wuqing , Sundquist Kristina , Sundquist Jan , Crump Casey , Ji Jianguang
Published: October 2019

An increasing number of patients with central nervous system (CNS) tumor could survive to reproductive age. However, it is largely unknown whether the history of CNS tumor might affect pregnancy outcome. We aimed to explore the risk of being born preterm among children of CNS tumor survivors. By linking several nationwide registers in Sweden, we identified 1,369 children whose parents were childhood or adolescent CNS tumor survivors. Children whose parents did not have CNS tumor were matched randomly with a 5:1 ratio to generate the reference group. Conditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI). The prevalence of preterm birth (PTB) was 6.9% among children of survivors with CNS tumor and 5.2% among the matched controls. Children of survivors had an increased risk of PTB (adjusted OR = 1.29, 95%CI 1.01–1.65) compared to the matched controls. This risk was increased specifically among offspring of those diagnosed in childhood (adjusted OR = 1.53, 95%CI 1.14–2.06) but not adolescence (adjusted OR = 0.89, 95%CI 0.56–1.41). For families with more than one child, the risk was slightly lower among the second child as compared to the first child. The risk was negatively associated with time interval between parental diagnosis and childbirth. Parental medulloblastoma and ependymoma were most strongly associated with a higher risk of PTB. Children of survivors with CNS tumor experienced an elevated risk of PTB. However, the risk diminishes gradually after parental diagnosis of CNS tumor. Offspring of childhood CNS tumor survivors and medulloblastoma or ependymoma survivors may have the highest risk of PTB.
FTIR spectra signatures reveal different cellular effects of EGFR inhibitors on nonsmall cell lung cancer cells
Authors: Tabtimmai Lueacha , Srisook Pimonwan , Kuaprasert Buabarn , Thumanu Kanjana , Choowongkomon Kiattawee
Published: October 2019

ATP‐analogue inhibitors, Gefitinib (Iressa) and Erlotinib (Tarceva) had been approved for advanced and metastatic nonsmall cell lung cancer (NSCLC) cells against tyrosine kinase domain of epidermal growth factor receptor (EGFR). Many techniques have been developed to better understand the drug mechanism which is multistep, time‐consuming and expensive. Herein, we performed Fourier‐transform infrared (FTIR) microscopy for evaluating the biochemical change on NSCLC (A549) cells after treatment. At levels that produced equivalent effects, Gefitinib dramatically induced cell apoptosis via impaired mitochondrial transmembrane potential. Whereas, Erlotinib had a slight effect on A549. Principal component analysis was performed to distinguish the effect of EGFR inhibitors on A549. FTIR spectra regions were divided into three regions: lipids (3000‐2800 cm−1), proteins (1700‐1500 cm−1) and carbohydrates and nuclei acids (1200‐1000 cm−1). Biochemical changes can be evaluated by these spectral regions. This work may be a novel concept for utilizing FTIR spectroscopy for high‐throughput discriminative effects of a drug or compound and its derivatives on cells.
Aberrant expression of a five‐microRNA signature in breast carcinoma as a promising biomarker for diagnosis
Authors: Bitaraf Amirreza , Babashah Sadegh , Garshasbi Masoud
Published: October 2019

Background

Breast cancer (BC) is the most common malignancy among females with dismal quality of life in patients. It has been proven that epigenetic factors, especially microRNAs, are involved in breast carcinogenesis and progression. This study aimed to assess the expression and clinical performances of a five‐microRNA signature (miR‐127‐3p, miR‐133a‐3p, miR‐155‐5p, miR‐199b‐5p, and miR‐342‐5p) in breast cancer and adjacent normal tissues to identify a potential biomarker for BC and investigate the relationship between their expression and clinicopathological features of BC patients as well.

Methods

In this case‐control investigation, we recruited 50 pairs of tumor and matched non‐tumor surgical specimens from patients diagnosed with BC. Expression levels of miR‐127‐3p, miR‐133a‐3p, miR‐155‐5p, miR‐199b‐5p, and miR‐342‐5p were measured in BC and adjacent normal tissues by RT‐qPCR.

Results

We found that miR‐127‐3p, miR‐133a‐3p, miR‐199b‐5p, and miR‐342‐5p were significantly down‐regulated, while miR‐155‐5p was significantly up‐regulated in BC tumor tissues compared with the corresponding adjacent normal tissues. The decreased expression of miR‐127‐3p, miR‐133a‐3p, miR‐342‐5p, and up‐regulation of miR‐155‐5p showed a significant correlation with disease stage. We also found a significant down‐regulation of miR‐127‐3p, miR‐199b‐5p, and miR‐342‐5p compared in HER‐2‐negative patients. Our results indicated that miR‐155‐5p had a higher expression level in HER‐2‐positive patients. Receiver operating characteristic (ROC) curve analysis demonstrated that all these five microRNAs can serve as potential biomarkers to distinguish between tumor and non‐tumor breast tissue samples.

Conclusions

The present findings suggested that dysregulation of this five‐miRNA signature might be considered as a promising and functional biomarker for BC diagnosis.
Justice and rule of law failure in Haiti: A view from the Shanties
Authors: Marcelin Louis H. , Cela Toni
Published: October 2019

Since 1995, significant investments have been made in justice reform initiatives in Haiti. The results, however, have been meager. Drawing upon data from a longitudinal study conducted in Cité Soleil between 2008 and 2011, this article illuminates the short‐sightedness of top‐down reforms that fail to meet the demands of the population, leaving them to fend for themselves. In the absence of a viable justice system Cité Soleil residents have resorted to alternative, and at times pathological, measures to exact some level of “justice”. In this article, we contend that an empirically grounded base of knowledge of the demand side of justice and the promotion of trust‐building strategies that engage the active participation of citizens in the country are necessary to enact and sustain justice and rule of law reform. Such an approach will create a venue to channel civil society's demands, build political will and facilitate coordination between stakeholders and Haitian society for self‐sustained rule of law institutions and long‐term peace building in Haiti.
HSP90 regulates osteosarcoma cell apoptosis by targeting the p53/TCF‐1‐mediated transcriptional network
Authors: Yang Jie , Li Yu‐Hang , He Ming‐Tang , Qiao Ju‐Feng , Sang Yuan , Cheang Lek Hang , Gomes Fernando Cardoso , Hu Yang , Li Zhen‐Yan , Liu Ning , Zhang Huan‐Tian , Zha Zhen‐Gang
Published: October 2019

Osteosarcoma (OS) is the most common bone tumor that occurs predominantly in children and teenagers. Although many genes, such as p53 and Rb1, have been shown to be mutated, deregulation of the canonical Wnt/β‐catenin signaling pathway is frequently observed in OS. We recently demonstrated that heat shock protein 90 (HSP90) is involved in the regulation of runt‐related transcription factor 2 via the AKT/GSK‐3β/β‐catenin signaling pathway in OS. However, the precise role of T cell factors/lymphoid enhancer‐binding factor (TCFs/LEF) family members, which are the major binding complex of β‐catenin, in OS is poorly understood. In the present study, we first demonstrated that TCF‐1 is overexpressed in OS compared with other bone tumors. Knockdown of TCF‐1 significantly induced cell cycle arrest, severe DNA damage, and subsequent caspase‐3‐dependent apoptosis. Interestingly, coexpression of HSP90 and TCF‐1 was observed in OS, and mechanistically, we demonstrated that TCF‐1 expression is regulated by HSP90 either through a β‐catenin‐dependent mechanism or a direct degradation of the proteasome. We also found that overexpression of TCF‐1 partially abolishes the apoptosis induced by HSP90 inhibition. Furthermore, we provided evidence that p53, but not miR‐34a, plays a crucial role in the HSP90‐regulated TCF‐1 expression and subsequent apoptosis. Given the diverse combination regimens of HSP90 inhibition with some other treatments, we propose that the p53 status and the expression level of TCF‐1 should be taken into consideration to enhance the therapeutic efficacy of HSP90 inhibition.
LINC01342 promotes the progression of ovarian cancer by absorbing microRNA‐30c‐2‐3p to upregulate HIF3A
Authors: Zhang Chu , Liu Jie , Zhang Yang , Luo Chengyan , Zhu Tong , Zhang Rongrong , Yao Ruiqin
Published: October 2019

Ovarian cancer (OC) is a highly prevalent gynecologic malignancy and its mortality is extremely high. Therefore, the development of novel therapeutic approaches for OC is of great significance. In this study, LINC01342 was upregulated in OC tissue in the GSE38666 microarray and in tumor tissue samples collected in our center. The silencing of LINC01342 suppressed the proliferative and metastatic capacities of A2780 and HO8910 cells. Subcellular distribution assays showed that LINC01342 was mainly enriched in the cytoplasm. Subsequently, the downregulation of microRNA‐30c‐2‐3p was proven to be the target of LINC01342. The silencing of microRNA‐30c‐2‐3p enhanced the clonality and migratory capacity of OC cells. Moreover, the silencing of microRNA‐30c‐2‐3p could reverse the inhibited migration and clonality in OC cells caused by LINC01342 knockdown. In addition, hypoxia‐inducible factor 3 subunit α (HIF3A) was proven to be the target gene of microRNA‐30c‐2‐3p, which was upregulated. HIF3A was negatively regulated by microRNA‐30c‐2‐3p but positively regulated by LINC01342 in OC cells. An RNA binding protein immunoprecipitation assay showed that microRNA‐30c‐2‐3p, LINC01342, and HIF3A could bind to argonaute RISC catalytic component 2. The overexpression of HIF3A reversed the inhibited migration and clonality in OC cells with LINC01342 knockdown. By analyzing the follow‐up data from the enrolled OC patients, the LINC01342 and HIF3A levels were negatively correlated with prognosis, while the microRNA‐30c‐2‐3p level was positively correlated with the same. In short, the upregulated LINC01342 in OC absorbs microRNA‐30c‐2‐3p to release HIF3A. Thus, upregulated HIF3A expression accelerates the progression of OC.
A Population Pharmacokinetic Model of Oral Docetaxel Coadministered With Ritonavir to Support Early Clinical Development
Authors: Yu Huixin , Janssen Julie M. , Sawicki Emilia , van Hasselt J. G. Coen , de Weger Vincent A. , Nuijen Bastiaan , Schellens Jan H. M. , Beijnen Jos H. , Huitema Alwin D. R.
Published: October 2019

Oral administration of docetaxel is an attractive alternative for conventional intravenous (IV) administration. The low bioavailability of docetaxel, however, hinders the application of oral docetaxel in the clinic. The aim of the current study was to develop a population pharmacokinetic (PK) model for docetaxel and ritonavir based on the phase 1 studies and to support drug development of this combination treatment. PK data were collected from 191 patients who received IV docetaxel and different oral docetaxel formulations (drinking solution, ModraDoc001 capsule, and ModraDoc006 tablet) coadministered with ritonavir. A PK model was first developed for ritonavir. Subsequently, a semiphysiological PK model was developed for docetaxel, which incorporated the inhibition of docetaxel metabolism by ritonavir. The uninhibited intrinsic clearance of docetaxel was estimated based on data on IV docetaxel as 1980 L/h (relative standard error, 11%). Ritonavir coadministration extensively inhibited the hepatic metabolism of docetaxel to 9.3%, which resulted in up to 12‐fold higher docetaxel plasma concentrations compared to oral docetaxel coadministered without ritonavir. In conclusion, a semiphysiological PK model for docetaxel and ritonavir was successfully developed. Coadministration of ritonavir resulted in increased plasma concentrations of docetaxel after administration of the oral formulations of ModraDoc. Furthermore, the oral ModraDoc formulations showed lower variability in plasma concentrations between and within patients compared to the drinking solution. Comparable exposure could be reached with the oral ModraDoc formulations compared to IV administration.
Cultivation of Chlorella sorokiniana using wastewaters from different processing units of the silk industry for enhancing biomass production and nutrient removal
Authors: Deng Xiangyuan , Li Da , Xue Chunye , Chen Biao , Dong Jingwei , Tetteh Pius A , Gao Kun
Published: October 2019

Background

Previous studies have documented that searching for wastewaters with appropriate nutrient profiles to cultivate microalgae directly was an effective measure to reduce the cost of algae cultivation. In this work, wastewaters collected from different processing units of the silk industry were used to cultivate Chlorella sorokiniana directly or after preliminary pretreatment for producing algal biomass and removing nutrients.

Results

The data showed that C. sorokiniana could grow on reeling wastewater and cooking cocoon wastewater with a maximum biomass of 0.26 and 0.49 g L−1, respectively, but could not grow on frigon wastewater because of high salinity and turbidity. Furthermore, the binary mixed wastewaters were used to cultivate this alga, which were mixed according to the algal nutritional requirements. Results indicated that the highest algal biomass (0.56 g L−1), and total nitrogen and phosphorus removal efficiencies (71.7% and 97.1%) were obtained when frigon wastewater was diluted with reeling wastewater (v/v) at a dilution multiple of eight, which was used as the algal culture media. Additionally, contents of protein, lipids, carbohydrates, and pigments in the algal cells varied with the changes in nutrient profiles of wastewaters.

Conclusions

It is concluded that (i) reeling wastewater and cooking cocoon wastewater were rich in nutrients for the growth of C. sorokiniana, which could be used as algal culture medium directly; and (ii) growing C. sorokiniana on mixed wastewaters could enhance biomass production and nutrient removal. Thus, the silk industry wastewaters could be considered as suitable media to cultivate microalgae directly or by simply mixing. © 2019 Society of Chemical Industry
Point‐of‐care gastrointestinal ultrasound in inflammatory bowel disease: An accurate alternative for disease monitoring
Authors: Sathananthan Dharshan , Rajagopalan Arvind , Van De Ven Lucinda , Martin Serena , Fon James , Costello Samuel , Bryant Robert V
Published: October 2019

Background and Aim

Point‐of‐care ultrasound (POCUS) is a noninvasive alternative to ileocolonoscopy for monitoring disease activity in inflammatory bowel disease (IBD) but is underutilized in practice. Accuracy data are needed to engender clinician confidence in POCUS and increase uptake. The aim of this study was to evaluate the accuracy of POCUS compared to ileocolonoscopy in detecting active disease and extent in patients with IBD.

Methods

A prospective, blinded study was performed at a single tertiary center in South Australia between May 2017 and May 2018. Consecutive patients with a formal diagnosis of IBD who underwent both POCUS and ileocolonoscopy within 30 days of one another, performed to evaluate IBD disease activity, were eligible for participation. The accuracy of POCUS compared to ileocolonoscopy was assessed using sensitivity, specificity, and Cohen's kappa coefficient analyses.

Results

A total of 74 patients were included in the final analysis, 35 (47%) of whom had Crohn's disease and 39 (53%) ulcerative colitis; 37 subjects (50%) underwent a POCUS and ileocolonoscopy on the same day. POCUS demonstrated 91% sensitivity and 83% specificity for detecting endoscopically active IBD, correlating with a positive predictive value (PPV) of 89%, a negative predictive value (NPV) of 86%, and a kappa coefficient of 0.74 (88%). POCUS defined disease extent with 87% sensitivity and 81% specificity, correlating with a PPV of 85% and NPV of 83% and a kappa coefficient of 0.70 (85%).

Conclusion

POCUS is accurate in defining disease activity and extent in IBD compared to ileocolonoscopy. POCUS represents an appealing, noninvasive alternative to ileocolonoscopy for monitoring disease activity in IBD.