bluuebunny/crossref_metadata_2025 huggingface dataset:
Insertion of CO2 Mediated by a (Xantphos)NiI–Alkyl Species
Authors: Diccianni Justin B. , Hu Chunhua T. , Diao Tianning
Published: July 2019

The incorporation of CO2 into organometallic and organic molecules represents a sustainable way to prepare carboxylates. The mechanism of reductive carboxylation of alkyl halides has been proposed to proceed through the reduction of NiII to NiI by either Zn or Mn, followed by CO2 insertion into NiI‐alkyl species. No experimental evidence has been previously established to support the two proposed steps. Demonstrated herein is that the direct reduction of (tBu‐Xantphos)NiIIBr2 by Zn affords NiI species. (tBu‐Xantphos)NiI‐Me and (tBu‐Xantphos)NiI‐Et complexes undergo fast insertion of CO2 at 22 °C. The substantially faster rate, relative to that of NiII complexes, serves as the long‐sought‐after experimental support for the proposed mechanisms of Ni‐catalyzed carboxylation reactions.
Synthesis of Homoallylic Alcohols with Acyclic Quaternary Centers through CoIII‐Catalyzed Three‐Component C−H Bond Addition to Internally Substituted Dienes and Carbonyls
Authors: Dongbang Sun , Shen Zican , Ellman Jonathan A.
Published: July 2019

An efficient CoIII‐catalyzed three‐component strategy to prepare homoallylic alcohols containing acyclic quaternary centers is disclosed. This transformation enables the introduction of two C−C σ bonds through C−H bond activation and sequential addition to internally substituted dienes and a wide range of aldehydes and activated ketones. Isoprene and other internally monosubstituted dienes are effective inputs, with the reaction proceeding with high diastereoselectivity for those substrate combinations that result in more than one stereogenic center. Moreover, the opposite relative stereochemistry can be achieved by employing 1,2‐disubstituted dienes. A mechanism for the transformation is proposed based upon the relative stereochemistry of the products and studies with isotopically labeled starting materials.
Topotactic Synthesis of Phosphabenzene‐Functionalized Porous Organic Polymers: Efficient Ligands in CO2Conversion
Authors: Yang Zhenzhen , Chen Hao , Li Bo , Guo Wei , Jie Kecheng , Sun Yifan , Jiang De‐en , Popovs Ilja , Dai Sheng
Published: July 2019

Progress toward the preparation of porous organic polymers (POPs) with task‐specific functionalities has been exceedingly slow—especially where polymers containing low‐oxidation phosphorus in the structure are concerned. A two‐step topotactic pathway for the preparation of phosphabenzene‐based POPs (Phos‐POPs) under metal‐free conditions is reported, without the use of unstable phosphorus‐based monomers. The synthetic route allows additional functionalities to be introduced into the porous polymer framework with ease. As an example, partially fluorinated Phos‐POPs (F‐Phos‐POPs) were obtained with a surface area of up to 591 m2 g−1. After coordination with Ru species, a Ru/F‐Phos‐POPs catalyst exhibited high catalytic efficiency in the formylation of amines (turnover frequency up to 204 h−1) using a CO2/H2mixture, in comparison with the non‐fluorinated analogue (43 h−1) and a Au/TiO2heterogeneous catalysts reported previously (<44 h−1). This work describes a practical method for synthesis of porous organic phosphorus‐based polymers with applications in transition‐metal‐based heterogeneous catalysis.
Synthesis of Indolines and Derivatives by Aza‐Heck Cyclization
Authors: Xu Feiyang , Korch Katerina M. , Watson Donald A.
Published: July 2019

For the first time, an aza‐Heck cyclization that allows the preparation of indoline scaffolds is described. Using N‐hydroxy anilines as electrophiles, which can be easily accessed from the corresponding nitroarenes, this method provides indolines bearing pendant functionality and complex ring topologies. Synthesis of challenging indolines, such as those bearing fully substituted carbon atoms at C2, is also possible using this method.
What Level of Inflammation Leads to Structural Damage in the Sacroiliac Joints? A Four‐Year Magnetic Resonance Imaging Follow‐Up Study of Low Back Pain Patients
Authors: Arnbak Bodil , Jensen Tue S. , Schiøttz‐Christensen Berit , Pedersen Susanne J. , Østergaard Mikkel , Weber Ulrich , Hendricks Oliver , Zejden Anna , Manniche Claus , Jurik Anne G.
Published: July 2019

Objective

Sacroiliac (SI) joint bone marrow edema (BME) is considered to be pivotal in the detection of early spondyloarthritis. However, the link between BME and development of spondyloarthritis‐related bone remodeling remains unclear. This study was undertaken to investigate the evolution of BME and structural lesions in the SI joints over time.

Methods

Baseline and 4‐year follow‐up magnetic resonance imaging scans were conducted in 604 patients ages 18–40 years who were referred with low back pain to an outpatient spine clinic. Eight SI joint regions were scored for BME and categorized as absent, limited (<25% of subcortical bone region), intermediate (25–50%), or extensive (>50%). Structural lesions including erosions and fat lesions were scored as absent or present.

Results

SI joint BME was seen at either time point (baseline or at 4 years) in 41% of participants but was persistent at both time points in only 16% of participants. Structural SI joint lesions developed according to the extent of BME at baseline: limited, intermediate, and extensive BME (as compared to absent BME) were independently associated with erosion at follow‐up with odds ratios (ORs) of 3, 5, and 46, respectively, and with fat lesions (ORs 3, 7, and 33, respectively). In regions with limited and intermediate BME at baseline, 60% and 50% had resolved by follow‐up, respectively, while only 2% and 7% had evolved into extensive BME by follow‐up.

Conclusion

While extensive SI joint BME was a strong independent predictor of development of structural lesions, limited and intermediate BME were mostly transient and only rarely evolved into extensive BME or structural lesions. These findings enhance our understanding of the natural development of SI joint lesions and indicate different progression patterns for limited/intermediate versus extensive BME, possibly due to different etiologies.
Regulation of Fibroblast Apoptosis and Proliferation by MicroRNA‐125b in Systemic Sclerosis
Authors: Kozlova Anastasiia , Pachera Elena , Maurer Britta , Jüngel Astrid , Distler Jörg H. W. , Kania Gabriela , Distler Oliver
Published: July 2019

Objective

To analyze the expression, regulation, and role of microRNA‐125b (miR‐125b) in systemic sclerosis (SSc).

Methods

MiR‐125b expression was assessed by quantitative polymerase chain reaction (qPCR) of RNA from dermal fibroblasts and whole skin biopsy specimens from healthy controls and SSc patients. To identify downstream effectors, RNA from healthy control fibroblasts was sequenced after miR‐125b knockdown and further validated using qPCR and Western blotting. Fibrosis, apoptosis, and proliferation were assessed by Caspase‐Glo 3/7 assay, Western blotting, immunofluorescence staining for cleaved caspase 3, and annexin V real‐time assay in dermal fibroblasts.

Results

Expression of miR‐125b was significantly down‐regulated in SSc skin biopsy specimens by 53% (median fold change 0.47 [interquartile range 0.35–0.69]; P < 0.001) and in SSc dermal fibroblasts by 47% (median fold change 0.53 [interquartile range 0.36–0.58]; P < 0.001) compared to healthy control skin biopsy specimens and fibroblasts, respectively (n = 10 samples per group). Treatment with the histone deacetylase inhibitors trichostatin A and tubastatin A significantly decreased the expression of miR‐125b in dermal fibroblasts. MiR‐125b knockdown significantly reduced cell proliferation and α‐smooth muscle actin (α‐SMA) expression at the messenger RNA (mRNA) and protein levels. RNA‐Seq identified BAK1, BMF, and BBC3 as potential targets of miR‐125b. Quantitative PCR confirmed that knockdown of miR‐125b up‐regulated these genes (P < 0.01; n = 12). Bcl‐2 homologous antagonist killer 1 showed the strongest induction confirmed at the protein level (P < 0.01; n = 10). Consequently, miR‐125b knockdown increased apoptosis compared to scrambled control. Accordingly, miR‐125b overexpression decreased apoptosis.

Conclusion

Our findings indicate that miR‐125b is down‐regulated in SSc skin and primary dermal fibroblasts. MiR‐125b down‐regulation increases apoptosis and decreases proliferation and α‐SMA expression in dermal fibroblasts, indicating that its compensatory, antifibrotic mechanism may be a potential novel therapeutic option.
The iterated extended set membership filter applied to relative localization between autonomous vehicles based on GNSS and UWB ranging
Authors: Bolting Jan , Fergani Soheib
Published: July 2019

This paper presents a novel Iterated Extended Set Membership Filter (IESMF) with an application to relative localization. For safe operation of formations of automatic vehicles, consistent uncertainty estimates are of crucial importance. Here, a localization filter that provides ellipsoidal regions that are guaranteed to contain another vehicles position is presented. The proposed iterative update step can appreciably reduce the size of the a posteriori state ellipsoid. The idea of using SIVIA as a baseline to quantify conservativeness is introduced. Another novelty is that we take into account parametric uncertainty of the observation equation.

The proposed filter is applied to a two unmanned aircraft systems (UAS) localization problem in simulation with observation noise obtained from real sensors. Simulation results illustrate the effective reduction of filter conservativeness by a small number of iterative updates.
Mechanism and Inhibitor Exploration with Binuclear Mg Ketol‐Acid Reductoisomerase: Targeting the Biosynthetic Pathway of Branched‐Chain Amino Acids
Authors: Yu Ming‐Jia , Wu Jue , Chen Shi‐Lu
Published: July 2019

Binuclear Mg ketol‐acid reductoisomerase (KARI), which converts (S)‐2‐acetolactate into (R)‐2,3‐dihydroxyisovalerate, is responsible for the second step of the biosynthesis of branched‐chain amino acids in plants and microorganisms and thus serves as a key inhibition target potentially without effects on mammals. Here, through the use of density functional calculations and a chemical model, the KARI‐catalyzed reaction has been demonstrated to include the initial deprotonation of the substrate C2 hydroxy group, bridged by the two Mg ions, alkyl migration from the C2‐alkoxide carbon atom to the C3‐carbonyl carbon atom, and hydride transfer from a nicotinamide adenine dinucleotide phosphate [NAD(P)H] cofactor to C2. A dead‐end mechanism with a hydride transferred to the C3 carbonyl group has been ruled out. The nucleophilicity (migratory aptitude) of the migrating carbon atom and the provision of additional negative charge to the di‐Mg coordination sphere have significant effects on the steps of alkyl migration and hydride transfer, respectively. Other important mechanistic characteristics are also revealed. Inspired by the mechanism, an inhibitor (2‐carboxylate‐lactic acid) was designed and predicted by barrier analysis to be effective in inactivating KARI, hence probably enriching the antifungal and antibacterial library. Two types of slow substrate analogues (2‐trihalomethyl acetolactic acids and 2‐glutaryl lactic acid) were also found.
Exotic Bonding Regimes Uncovered in Excited States
Authors: Casals‐Sainz José Luis , Jara‐Cortés Jesús , Hernández‐Trujillo Jesús , Guevara‐Vela José Manuel , Francisco Evelio , Pendás Ángel Martín
Published: July 2019

Real‐space tools were employed to show that the chemical bonding scenario used routinely to understand ground states lacks the necessary flexibility in excited states. It is shown that, even for two‐center, two‐electron bonds, the real‐space bond orders have exotic values that have never been reported. The nature of these situations was uncovered by using electron‐counting techniques that provide an appealing statistical interpretation of bonding descriptors, together with simple physical models. Bond orders greater than one as well as negative bond orders for a single bonding electron pair emerge in situations in which the electrons in the pair show a gregarious (bosonic) instead of the usual lonely (fermionic) behavior. In the first case the gregarious pair is intra‐atomic, whereas the coupling is interatomic in the second. A number of examples are used to substantiate these claims.
Gold‐Catalyzed Regiospecific Annulation of Unsymmetrically Substituted 1,5‐Diynes for the Precise Synthesis of Bispentalenes
Authors: Tavakkolifard Sara , Sekine Kohei , Reichert Lisa , Ebrahimi Mina , Museridz Ketevan , Michel Elena , Rominger Frank , Babaahmadi Rasool , Ariafard Alireza , Yates Brian F. , Rudolph Matthias , Hashmi A. Stephen K.
Published: July 2019

Precise control of the selectivity in organic synthesis is important to access the desired molecules. We demonstrate a regiospecific annulation of unsymmetrically substituted 1,2‐di(arylethynyl)benzene derivatives for a geometry‐controlled synthesis of linear bispentalenes, which is one of the promising structures for material science. A gold‐catalyzed annulation of unsymmetrically substituted 1,2‐di(arylethynyl)benzene could produce two isomeric pentalenes, but both electronic and steric effects on the aromatics at the terminal position of the alkyne prove to be crucial for the selectivity; especially a regiospecific annulation was achieved with sterically blocked substituents; namely, 2,4,6‐trimetyl benzene or 2,4‐dimethyl benzene. This approach enables the geometrically controlled synthesis of linear bispentalenes from 1,2,4,5‐tetraethynylbenzene or 2,3,6,7‐tetraethynylnaphthalene. Moreover, the annulation of a series of tetraynes with a different substitution pattern regioselectively provided the bispentalene scaffolds. A computational study revealed that this is the result of a kinetic control induced by the bulky NHC ligands.
A Chemical Proteomic Analysis of Illudin‐Interacting Proteins
Authors: Le Philipp , Nodwell Matthew B. , Eirich Jürgen , Sieber Stephan A.
Published: July 2019

The illudin natural product family are fungal secondary metabolites with a characteristic spirocyclopropyl‐substituted fused 6,5‐bicyclic ring system. They have been extensively studied for their cytotoxicity in various tumor cell types, and semisynthetic derivatives with improved therapeutic characteristics have progressed to clinical trials. Although it is believed that this potent alkylating compound class acts mainly through DNA modification, little is known about its binding to protein sites in a cellular context. To reveal putative protein targets of the illudin family in live cancer cells, we employed a semisynthetic strategy to access a series of illudin‐based probes for activity‐based protein profiling (ABPP). While the probes largely retained potent cytotoxicity, proteomic profiling studies unraveled multiple protein hits, suggesting that illudins exert their mode of action not from addressing a specific protein target but rather from DNA modification and unselective protein binding.
Allosteric Modulators of Potential Targets Related to Alzheimer's Disease: a Review
Authors: Silva Guilherme Martins , Barcelos Mariana Pegrucci , Poiani João Gabriel Curtolo , Hage‐Melim Lorane Izabel da Silva , da Silva Carlos Henrique Tomich de Paula
Published: July 2019

Among neurodegenerative disorders, Alzheimer's disease (AD) is the most common type of dementia, and there is an urgent need to discover new and efficacious forms of treatment for it. Pathological patterns of AD include cholinergic dysfunction, increased β‐amyloid (Aβ) peptide concentration, the appearance of neurofibrillary tangles, among others, all of which are strongly associated with specific biological targets. Interactions observed between these targets and potential drug candidates in AD most often occur by competitive mechanisms driven by orthosteric ligands that sometimes result in the production of side effects. In this context, the allosteric mechanism represents a key strategy; this can be regarded as the selective modulation of such targets by allosteric modulators in an advantageous manner, as this may decrease the likelihood of side effects. The purpose of this review is to present an overview of compounds that act as allosteric modulators of the main biological targets related to AD.
Gene expression correlates of facultative predation in the blow fly Chrysomya rufifacies (Diptera: Calliphoridae)
Authors: Pimsler Meaghan L. , Sze Sing‐Hoi , Saenz Sunday , Fu Shuhua , Tomberlin Jeffery K. , Tarone Aaron M.
Published: July 2019

Effects of intraguild predation (IGP) on omnivores and detritivores are relatively understudied when compared to work on predator guilds. Functional genetic work in IGP is even more limited, but its application can help answer a range of questions related to ultimate and proximate causes of this behavior. Here, we integrate behavioral assays and transcriptomic analysis of facultative predation in a blow fly (Diptera: Calliphoridae) to evaluate the prevalence, effect, and correlated gene expression of facultative predation by the invasive species Chrysomya rufifacies. Field work observing donated human cadavers indicated facultative predation by C. rufifacies on the native blow fly Cochliomyia macellaria was rare under undisturbed conditions, owing in part to spatial segregation between species. Laboratory assays under conditions of starvation showed predation had a direct fitness benefit (i.e., survival) to the predator. As a genome is not available for C. rufifacies, a de novo transcriptome was developed and annotated using sequence similarity to Drosophila melanogaster. Under a variety of assembly parameters, several genes were identified as being differentially expressed between predators and nonpredators of this species, including genes involved in cell‐to‐cell signaling, osmotic regulation, starvation responses, and dopamine regulation. Results of this work were integrated to develop a model of the processes and genetic regulation controlling facultative predation.
When the “selfish herd” becomes the “frozen herd”: spatial dynamics and population persistence in a colonial seabird
Authors: McDowall Philip S. , Lynch Heather J.
Published: July 2019

Aggregations are common in ecological systems at a range of scales and may be driven by exogenous constraints such as environmental heterogeneity and resource availability or by “self‐organizing” interactions among individuals. One mechanism leading to self‐organized animal aggregations is captured by Hamilton's “selfish herd” hypothesis, which suggests that aggregations may be driven by an individual's effort to minimize their risk of predation by surrounding themselves with conspecifics. We demonstrate that aggregations observed in Adélie Penguin (Pygoscelis adeliae) colonies are a convolution of both self‐organized dynamics and external forcing arising from landscape terrain. In fluid, highly mobile aggregations, individuals are constantly moving in response to changing environmental conditions, the locations of predators, or the movements of conspecifics. However, when the ability to rearrange is limited and spatial reconfiguration occurs on slower time scales than changes in population size, systems may become trapped in suboptimal arrangements. We use simulated annealing to demonstrate that Adélie Penguin colonies are frozen in suboptimal spatial arrangements, and employ an individual‐based modeling approach to demonstrate that this suboptimal spatial configuration is driven by a convolution of nest site fidelity and stochastic events at the level of individual nests. The resulting spatial dynamics are responsible for a hysteretic response to long‐term changes in abundance. We find that declining abundance leads to fragmentation even in a homogeneous environment, which has population‐level consequences for reproductive success because predation is biased towards colony edges. Strong edge effects from heterogeneous predation coupled with fragmentation in response to population declines create a positive feedback cycle that can accelerate population decline. This work provides a mechanistic understanding of complex spatial structuring in penguin colonies, provides a link between current spatial patterning and past dynamics, and suggests the possibility of critical collapse in seabird populations.
The Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure (DAPA‐HF) trial: baseline characteristics
Authors: McMurray John J.V. , DeMets David L. , Inzucchi Silvio E. , Køber Lars , Kosiborod Mikhail N. , Langkilde Anna Maria , Martinez Felipe A. , Bengtsson Olof , Ponikowski Piotr , Sabatine Marc S. , Sjöstrand Mikaela , Solomon Scott D. ,   on behalf of the DAPA‐HF Committees and Investigators
Published: July 2019

Background

The aims of this study were to: (i) report the baseline characteristics of patients enrolled in the Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure (DAPA‐HF) trial, (ii) compare DAPA‐HF patients to participants in contemporary heart failure (HF) registries and in other recent HF trials, and (iii) compare individuals with diabetes, pre‐diabetes and a normal glycated haemoglobin (HbA1c) in DAPA‐HF.

Methods and results

Adults with HF in New York Heart Association functional class ≥ II, a left ventricular ejection fraction ≤ 40%, an elevated N‐terminal pro‐B‐type natriuretic peptide concentration and receiving standard treatment were eligible for DAPA‐HF, which is comparing dapagliflozin 10 mg once daily to matching placebo. In patients without a history of diabetes, previously undiagnosed diabetes was defined as a confirmed HbA1c ≥ 6.5%. Among patients without known or undiagnosed diabetes, pre‐diabetes was defined as a HbA1c ≥ 5.7% The remainder of patients, with a HbA1c < 5.7%, were defined as normoglycaemic. Of the 4744 patients (mean age 66 years; 23% women) randomized, 42% had known diabetes and 3% undiagnosed diabetes. Of the remainder, 67% had pre‐diabetes and 33% normal HbA1c. Overall, DAPA‐HF patients were generally similar to those in recent registries and in relevant trials and had high levels of background therapy: 94% angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor–neprilysin inhibitor, 96% beta‐blocker, and 71% mineralocorticoid receptor antagonist; 26% had a defibrillator. Patients with diabetes had worse HF status, more co‐morbidity, and greater renal impairment but received similar HF therapy. Patients with diabetes received non‐insulin hypoglycaemic therapy alone in 49%, insulin alone in 11%, both in 14%, and none in 26%.

Conclusions

Patients randomized in DAPA‐HF were similar to those in other contemporary HF with reduced ejection fraction (HFrEF) registries and trials. These patients were receiving recommended HFrEF therapy and those with diabetes were also treated with conventional glucose‐lowering therapy. Consequently, DAPA‐HF will test the incremental efficacy and safety of dapagliflozin in HFrEF patients with and without diabetes.

Clinical Trial Registration: ClinicalTrials.gov Identifier NCT03036124
Monofunctional PtII Complexes Based on 8‐Aminoquinoline: Synthesis and Pharmacological Characterization
Authors: Facchetti Giorgio , Ferri Nicola , Lupo Maria Giovanna , Giorgio Lucchini , Rimoldi Isabella
Published: July 2019

Among the heterocyclic compounds, 8‐aminoquinoline and its derivatives have become important candidates for the preparation of new antiproliferative metallo‐drugs. Here, we reported the synthesis and cytotoxicity evaluation of a series of platinum complexes using 8‐aminoquinoline and its chiral 5,6,7,8‐tetrahydro‐derivatives as chelating ligands. In the proposed complexes, a differently and opportunely alkylated imidazole was used to prepare the corresponding monofunctional platinum complexes. The preliminary cytotoxicity evaluation was carried out on the highly aggressive MDA‐MB‐231, invasive and poorly differentiated triple‐negative breast cancer (TNBC) cell line, furnishing a significant IC50 10.9 ± 1.3 µM for Pt‐IV. This series of complexes revealed an induction of p53, interfering with the progression of the G0/G1 phase of the cell cycle.
Convergent Synthesis of the Hexasaccharide Repeating Unit of the O‐Antigenic OPS of Escherichia coli O133
Authors: Mitra Ankita , Mukhopadhyay Balaram
Published: July 2019

Synthesis of the hexasaccharide repeating unit of the O‐antigen from E. coli O133 has been accomplished with rational protecting group manipulations on commercially available monosaccharides and stereoselective glycosylations through a convergent protocol. A late stage TEMPO mediated oxidation is used to install the required uronic acid moiety. Chloroacetate group is used extensively as a temporary protecting group.
Effective and Sustainable Access to Quinolines and Acridines: A Heterogeneous Imidazolium Salt Mediates C–C and C–N Bond Formation
Authors: Gisbert Patricia , Albert‐Soriano María , Pastor Isidro M.
Published: July 2019

Quinoline and acridine derivatives have been prepared using a functionalized imidazolium salt as heterogeneous catalyst. Different ketones have been coupled with 2‐aminobenzaldehydes and 2‐aminoaryl ketones under solvent‐free conditions, employing 1,3‐bis(carboxymethyl)‐imidazolium chloride as a catalyst. The protocol is simple and effective for the synthesis of a variety of nitrogen containing heterocycles (> 35 examples) with moderate to excellent yields (up to 96 %), being possible to perform the reaction in preparative scale. Additionally, 3‐acetylquinolines have been transformed, under solvent‐free conditions, into quinolyl chalcone derivatives by means of the same catalyst. Thus, the catalytic system mediates both reactions effectively in a tandem procedure. Furthermore, the catalyst is easily separated from the reaction mixture and can be reused without loss of activity (up to 8 cycles) which remarks its sturdiness. The E‐factors are in the range of 14–23, both for the formation of quinolines and for the tandem reaction, which demonstrates the sustainability of the protocols described.
Direct Decarboxylative Allylation and Arylation of Aliphatic Carboxylic Acids Using Flavin‐Mediated Photoredox Catalysis
Authors: Ramirez Nieves P. , Lana‐Villarreal Teresa , Gonzalez‐Gomez Jose C.
Published: July 2019

We describe herein a direct decarboxylative allylation of aliphatic carboxylic acids with allylsulfones using visible light and riboflavin tetraacetate (RFTA) as photocatalyst. The reaction proceeds at room temperature tolerating a wide range of functionalities, avoiding the use of external bases or additives. Mechanistic studies support that alkyl radicals are involved in the reaction and that a true photocatalytic cycle is operating. It is proposed that the carboxylic acid is deprotonated by [RFTA]·–, and the corresponding carboxylate acts as a reductive quencher of RFTA*, which after decarboxylation produces the alkyl radical. The methodology was adapted to prepare benzothiazoles substituted at C2, by reacting some carboxylic acids with 2‐(phenylsulfonyl)benzothiazole. The number of carboxylic acids suitable for this arylation was lower than for the allylation and this different reactivity was briefly commented.
Voltammetric Electronic Tongue Based on Carbon Paste Electrodes Modified with Biochar for Phenolic Compounds Stripping Detection
Authors: Kalinke Cristiane , de Oliveira Paulo Roberto , Bonet San Emeterio Marta , González‐Calabuig Andreu , del Valle Manel , Salvio Mangrich Antonio , Humberto Marcolino Junior Luiz , Bergamini Márcio F.
Published: July 2019

Biochar is a charcoal produced from the biomass pyrolysis process that presents a highly porous and functionalized surface. In the present work an array of carbon paste electrodes (CPE) made of different forms of carbon (graphite, carbon nanotubes and activated biochar) was evaluated in the development of an electronic tongue for discrimination and stripping voltammetric determination of catechol (CAT), 4‐ethylcatechol (4‐EC) and 4‐ethylguaiacol (4‐EG) phenolic compounds. Morphological characterization of carbon materials and electrodes surfaces was performed by scanning electron microscopy (SEM) and semi‐quantitative elemental composition by energy dispersive spectroscopy (EDS). Electrochemical Impedance Spectroscopy (EIS) measurements were used for electrochemical characterization of electrodes. Cyclic voltammetry measurements were performed for the phenolic compounds evaluated using different concentrations. Principal component analysis (PCA) was performed to evaluate the qualitative analysis. Quantitative data modeling was done using artificial neural networks (ANN). The proposed sensor array presented analytical potentiality allowing the distinction and determination of CAT, 4‐EC and 4‐EG by using chemometric processing. The method showed sensibility, reproducibility and a good linearity (R2>0.9940) for three compounds evaluated. Spontaneous preconcentration of three compounds was possible using all three sensors, which can allow the application of these as passive samplers for remote determinations of phenolic compounds in wine and food samples.
Batch Injection Analysis with Amperometric Detection for DNA Biosensing Applications
Authors: Svitková Veronika , Labuda Ján , Vyskočil Vlastimil
Published: July 2019

In this work, batch injection analysis with the amperometric detection (BIA‐AD), employing a detection cell designed to adapt a screen‐printed carbon electrode (SPCE) was used for the first time as a robust electroanalytical system for DNA biosensing applications. The sensitive amperometric detection was used to evaluate the structural changes in double‐stranded DNA (dsDNA) after UV‐C irradiation of its solution for a given time. Batching of DNA samples was performed by precise electronic pipette microinjection of an irradiated sample aliquot onto the unmodified activated SPCE surface incorporated in the BIA‐AD system. Using the optimized experimental conditions (40 μL of 1 mg mL−1 dsDNA in a 0.1 M phosphate buffer of pH 7.4 sampled at the injection speed degree of 6 and detected at the potential of +1.5 V vs silver pseudo‐reference electrode), a time‐dependent response (gradual decrease of amperometric signal up to 58 % after 10 min of the irradiation) was found for the detection of damage to low molecular weight salmon sperm dsDNA. The advantages of this low‐dimensional and cost‐effective measuring system can be utilized not only for the quantification of DNA damage/degradation by UV irradiation, but they are also promising for studying other types of DNA interactions.
Electroanalysis of the Anthelmintic Drug Bithionol at Edge Plane Pyrolytic Graphite Electrode
Authors: Brycht Mariola , Konecka Kinga , Sipa Karolina , Skrzypek Sławomira , Mirčeski Valentin
Published: July 2019

An electrochemical study of the anthelmintic drug bithionol using edge plane pyrolytic graphite electrode (EPPGE) is presented for the first time by applying different electrochemical techniques, such as cyclic voltammetry (CV), square‐wave voltammetry (SWV), square‐wave adsorptive stripping voltammetry (SWAdSV), and alternating current (AC) impedance spectroscopy. Mechanistic aspects of the electrode reaction were studied implying a quasireversible electrode reaction from an adsorbed state of the reactant, coupled with a follow‐up chemical reaction to a final electroinactive product. The overall mechanism appears totally irreversible under conditions of CV at moderate scan rate, while being quasireversible under conditions of the fast SWV. Furthermore, an optimisation of the analytical procedure for quantitative determination of bithionol was conducted by applying SWV in an adsorptive stripping mode. The calibration curve was constructed in the concentration range of 0.1–1.0 μmol L−1 (R2=0.9984) with a sensitivity of 3.6 μA L μmol−1 and LOD of 26.7 nmol L−1. The simple and sensitive SWAdSV procedure was proved to be suitable for the analysis of spiked urine samples.
Coupling Electrochemical Adsorption and Long‐range Electron Transfer: Label‐free DNA Mismatch Detection with Ultramicroelectrode (UME)
Authors: Basu Nivedita , Ho Thu Huong , Guillon François‐Xavier , Zhang Yuanyuan , Bigey Pascal , Navakanta Bhat , Bedioui Fethi , Lazerges Mathieu
Published: July 2019

A new electrochemical hybridization transduction pathway, obtained by coupling electrochemical adsorption and long‐range electron transfer through double‐stranded DNA, was investigated using ultramicroelectrode (UME). The results show that long‐range electron transfer does not occurs exclusively throws well‐packed and organized self‐assembled DNA monolayers. This approach is used to investigate long‐range electron transfer properties of both single‐ and double‐ stranded short synthetic DNA and DNA plasmids. Single mismatch electrochemical detection protocol of non‐labelled short synthetic DNA, without heating or probe labelling, in a 10 minutes protocol, was in fine performed.
Maximization of piezoelectric vibration energy harvesting of vehicle based on double‐gear drive
Authors: Li Yang , Xie Changjun , Quan Shuhai , Li Wenlian , Shi Ying
Published: July 2019

A cantilever‐based piezoelectric energy harvesting generator driven by an automatically ‐switchable double‐gear is designed, to assemble the linear‐to‐rotary motion translation and achieve a continuous recovery efficiently by piecewise harvesting. On the basis of identifying the road tolerance grade, an investigation is conducted into the relationship between the gear pitch, vehicle speeds and the energy. A value‐taking method and switching principle are proposed for the gear pitch of the double‐gear under comprehensive driving conditions. According to the tests of two road sections, the results of the simulations show that the automatically ‐switchable double gear can maximize the piezoelectric vibration energy harvesting efficiency under comprehensive driving conditions and road surface with varying tolerances. Meanwhile, results concerning the device experiments indicate that the harvesting efficiency could be improved by 131.66% (76.70%) and 9.37% (22.38%) compared with the single gear with its pitch of 3 mm and 10 mm, respectively.
Genomics of rapid ecological divergence and parallel adaptation in four tidal marsh sparrows
Authors: Walsh Jennifer , Benham Phred M. , Deane-Coe Petra E. , Arcese Peter , Butcher Bronwyn G. , Chan Yvonne L. , Cheviron Zachary A. , Elphick Chris S. , Kovach Adrienne I. , Olsen Brian J. , Shriver W. Gregory , Winder Virginia L. , Lovette Irby J.
Published: July 2019

Theory suggests that different taxa having colonized a similar, challenging environment will show parallel or lineage-specific adaptations to shared selection pressures, but empirical examples of parallel evolution in independent taxa are exceedingly rare. We employed comparative genomics to identify parallel and lineage-specific responses to selection within and among four species of North American sparrows that represent four independent, post-Pleistocene colonization events by an ancestral, upland subspecies and a derived salt marsh specialist. We identified multiple cases of parallel adaptation in these independent comparisons following salt marsh colonization, including selection of 12 candidate genes linked to osmoregulation. In addition to detecting shared genetic targets of selection across multiple comparisons, we found many novel, species-specific signatures of selection, including evidence of selection of loci associated with both physiological and behavioral mechanisms of osmoregulation. Demographic reconstructions of all four species highlighted their recent divergence and small effective population sizes, as expected given their rapid radiation into saline environments. Our results highlight the interplay of both shared and lineage-specific selection pressures in the colonization of a biotically and abiotically challenging habitat and confirm theoretical expectations that steep environmental clines can drive repeated and rapid evolutionary diversification in birds.
Lactobacillus paracasei Jlus66 extenuate oxidative stress and inflammation via regulation of intestinal flora in rats with non alcoholic fatty liver disease
Authors: Wang Wei , Li Qian , Chai Wenhui , Sun Chunyan , Zhang Tiehua , Zhao Changhui , Yuan Yuan , Wang Xinyu , Liu Huiqin , Ye Haiqing
Published: July 2019

The nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease that affects the health of people in an increasing rate. In the current research, we investigated the beneficial effect of a novel probiotic strain L. paracasei Jlus66 (Jlus66) on rats with high‐fat diet (HFD)‐induced NAFLD. The intestinal flora of rats was analyzed based on V3‐V4 region 16S rDNA sequencing. Moreover, we measured the oxidative stress and inflammation factors in the liver using commercial ELISA kit, and the lipopolysaccharide (LPS) in serum with chromogenic end‐point tachypheus amebocyte lysate. Compared with the HFD‐induced group, Jlus66 treatment significantly decreased the malondialdehyde (MDA) level in the serum (p < 0.05). Additionally, Jlus66 significantly enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) in the liver and serum (p < 0.05). Jlus66 administration also reduced the levels of tumor necrosis factor (TNF‐α) and interleukin‐6 (IL‐6), and inversely increased the interleukin‐10 (IL‐10) level in serum (p < 0.05). Intestinal flora analysis results showed that Jlus66 can improve intestinal flora structure by increasing the abundance of gram‐positive flora such as Firmicutes, and decreasing gram‐negative flora such as Bacteroidetes, Proteobacteria, and Fusobacteria, and then reduced LPS concentration in the serum. So we concluded that Jlus66 can improve NAFLD by modulating the intestinal flora and followed reduction of oxidative stress (OxS) and inflammation.
Development of quantitative metrics of plume migration at geologic CO2 storage sites
Authors: Harp Dylan , Onishi Tsubasa , Chu Shaoping , Chen Bailian , Pawar Rajesh
Published: July 2019

We develop plume migration metrics based on spatial moment analysis methods that quantify the spatio‐temporal evolution of plumes at geologic CO2 storage sites. The metrics are generalized to handle any 3‐D scalar attribute field values. Within the geologic CO2 storage context, these can be parameters such as CO2 saturation, effective pressure, overpressure, dissolved CO2 concentration, total dissolved solids, pH, and other attributes that are critical for assessing risks. The metrics are comprehensive in that they can effectively handle and account for complex continuous and discontinuous plumes and intra‐plume migration. We demonstrate the metrics on simulated CO2 plumes injected into flat and tilted reservoirs with homogeneous and heterogeneous permeability fields. Using these idealized reservoir scenarios, we demonstrate the information that the metrics extract, showing that the metrics elucidate nuances in plume migration not apparent by standard approaches to the scalar fields values. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
The Roots of Bio‐Molecular Simulation: The Eight‐Week CECAM Workshop ‘Models for Protein Dynamics’ of 1976
Authors: van Gunsteren Wilfred F.
Published: July 2019

This year, the Centre Européen de Calcul Atomique et Moléculaire (CECAM) celebrates its 50‐th anniversary. Founded in 1969 in Orsay near Paris, it later moved to Lyon and in 2008 to Lausanne. It is an organization devoted to the promotion of fundamental research on advanced computational methods and their application in condensed matter science. Its main vehicle to this end is the organization of workshops. The key role of an eight‐week workshop held forty‐three years ago, characterized by an open exchange of scientific ideas and a foresight regarding the topics relevant to a proper dynamic simulation of bio‐molecules such as proteins, is remembered, together with the issues discussed at the time. These are still relevant today.
A Probabilistic Co-Occurrence Approach for Estimating Likelihood of Spatial Overlap Between Listed Species Distribution and Pesticide Use Patterns
Authors: Richardson Leif , Bang JiSu , Budreski Katherine , Dunne Jonnie , Winchell Michael , Brain Richard A , Feken Max
Published: July 2019

Characterizing potential spatial overlap between federally threatened and endangered (“listed”) species distributions and registered pesticide use patterns is important for accurate risk assessment of threatened and endangered species. Because accurate range information for such rare species is often limited and agricultural pesticide use patterns are dynamic, simple spatial co-occurrence methods may overestimate or underestimate overlap and result in decisions that benefit neither listed species nor the regulatory process. Here, we demonstrate a new method of co-occurrence analysis that employs probability theory to estimate spatial distribution of rare species populations and areas of pesticide use to determine the likelihood of potential exposure. Specifically, we 1) describe a probabilistic method to estimate pesticide use based on crop production patterns; 2) construct species distribution models for 2 listed insect species whose ranges were previously incompletely described, the rusty-patched bumble bee (Bombus affinis) and the Poweshiek skipperling (Oarisma poweshiek); and 3) develop a probabilistic co-occurrence methodology and assessment framework. Using the principles of the Bayes' theorem, we constructed probabilistic spatial models of pesticide use areas by integrating information from land-cover spatial data, agriculture statistics, and remote-sensing data. We used maximum entropy methods to build species distribution models for 2 listed insects based on species collection and observation records and predictor variables relevant to the species' biogeography and natural history. We further developed novel methods for refinement of these models at spatial scales relevant to US Fish and Wildlife Service (FWS) regulatory priorities (e.g., critical habitat areas). Integrating both probabilistic assessments and focusing on USFWS priority management areas, we demonstrate that spatial overlap (i.e., potential for exposure) is not deterministic but instead a function of both species distribution and land use patterns. Our work serves as a framework to enhance the accuracy and efficiency of threatened and endangered species assessments using a data-driven likelihood analysis of species co-occurrence. Integr Environ Assess Manag 2019;00:1–12. © 2019 SETAC
Evaluation of neuroprotective activity of digoxin and semisynthetic derivatives against partial chemical ischemia
Authors: de Souza Gonçalves Bruno , de Moura Valadares Jéssica M. , Alves Silmara L. G. , Silva Simone C. , Rangel Luciana P. , Cortes Vanessa F. , Villar José A. F. P. , Barbosa Leandro A. , de Lima Santos Hérica
Published: July 2019

Recently, cardiotonic steroids (CTS) have been shown to lead to the activation of Na,K‐ATPase at low concentrations in brain, promoting neuroprotection against ischemia. We report here the results of the use of digoxin and its semisynthetic derivatives BD‐14, BD‐15, and BD‐16 against partial chemical ischemic induction followed by reperfusion in murine neuroblastoma cells neuro‐2a (N2a). For chemical ischemic induction, sodium azide (5 mM) was used for 5 hours, and then reperfusion was induced for 24 hours. Na,K‐ATPase activity and protein levels were analyzed in membrane preparation of N2a cells pretreated with the compounds (150 nM), in the controls and in induced chemical ischemia. In the Na,K‐ATPase activity and protein levels assays, the steroids digoxin and BD‐15 demonstrated a capacity to modulate the activity of the enzyme directly, increasing its levels of expression and activity. Oxidative parameters, such as superoxide dismutase (SOD) activity, lipid peroxidation (thiobarbituric acid reactive substance), glutathione peroxidase (GPx), glutathione (GSH) levels, hydrogen peroxide content, and the amount of free radicals (reactive oxygen species) during induced chemical ischemia were also evaluated. Regarding the redox state, lipid peroxidation, hydrogen peroxide content, and GPx activity, we have observed an increase in the chemical ischemic group, and a reduction in the groups treated with CTS. SOD activity increased in all treated groups when compared to control and GSH levels decreased when treated with sodium azide and did not change with CTS treatments. Regarding the lipid profile, we saw a decrease in the content of phospholipids and cholesterol in the chemical ischemic group, and an increase in the groups treated with CTS. In conclusion, the compounds used in this study demonstrate promising results, since they appear to promote neuroprotection in cells exposed to chemical ischemia.
Molecular docking studies of chloroquine and its derivatives against P23pro‐zbd domain of chikungunya virus: Implication in designing of novel therapeutic strategies
Authors: Kumar Maneesh , Topno Roshan Kamal , Dikhit Manas Ranjan , Bhawana  , Sahoo Ganesh Chandra , Madhukar Major , Pandey Krishna , Das Pradeep
Published: July 2019

The arthropod‐transmitted chikungunya virus has emerged as an epidemic menace that causes debilitating polyarthritis. With this life‐threatening impact on humans, the possible treatment requires to cure the viral infectivity. But, devoid of any vaccine against the chikungunya virus (CHIKV), there is a need to develop a novel chemotherapeutic strategy to treat this noxious infection. CHIKV carries highly compact P23pro‐zbd structure that possesses potential RNA‐binding surface domains which extremely influences the use of RNA template during genome replication at the time of infection and pathogenesis. Therefore, computational approaches were used to explore the novel small molecule inhibitors targeting P23pro‐zbd domain. The tertiary structure was modeled and optimized using in silico approaches. The results obtained from PROCHECK (93.1% residues in favored regions), ERRAT (87.480 overall model quality) and ProSA (Z‐score: −11.72) revealed the reliability of the proposed model. Interestingly, a previously reported inhibitor, chloroquine possesses good binding affinities with the target domain. In‐depth analysis revealed that chloroquine derivatives such as didesethyl chloroquine hydroxyacetamide, cletoquine, hydroxychloroquine exhibited a better binding affinity. Notably, MD simulation analysis exhibited that Thr1312, Ala1355, Ala1356, Asn1357, Asp1364, Val1366, Cys1367, Ala1401, Gly1403, Ser1443, Tyr1444, Gly1445, Asn1459, and Thr1463 residues are the key amino acid responsible for stable ligand‐protein interaction. The results obtained from this study provide new insights and advances the understanding to develop a new approach to consider effective and novel drug against chikungunya. However, a detailed in vivo study is required to explore its drug likeliness against this life‐threatening disease.