bluuebunny/crossref_metadata_2025 huggingface dataset:
Life Course Adiposity and Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study
Authors: Zhang Linjing , Tang Lu , Huang Tao , Fan Dongsheng
Published: January 2020

Objective

Observational studies have indicated that life course adiposity is associated with amyotrophic lateral sclerosis (ALS). However, whether such an association reflects causality remains unclear. We aimed to determine whether life course adiposity such as birth weight (BW), childhood body mass index (BMI), adult BMI, body fat percentage (BF%), and waist‐to‐hip ratio (WHR) have causal effects on ALS.

Methods

Single nucleotide polymorphisms (SNPs) significantly associated with life course adiposity were used as instrumental variables to estimate the causal effects on ALS. We used summary‐level data from a cohort of 20,806 cases and 59,804 controls in a Mendelian randomization (MR) framework.

Results

Genetically predicted one standard deviation (1‐SD) increase in BF% was associated with lower risk of ALS (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.54–0.83, p = 3.25E–04) after Bonferroni correction (p < 0.05/5). Genetically predicted 1‐SD higher childhood BMI was suggestively associated with lower risk of ALS (OR = 0.88, 95% CI = 0.78–0.99, p = 0.031). The weighted median method indicated a suggestive association between BMI and ALS (OR = 0.86, 95% CI = 0.69–0.96, p = 0.016). Neither a genetically predicted 1‐SD increase in BW (inverse variance weighted [IVW]: OR = 1.01, 95% CI = 0.87–1.17, p = 0.939) nor WHR adjusted for BMI (IVW: OR = 0.90, 95% CI = 0.76–1.05, p = 0.178) was associated with ALS.

Interpretation

Our findings provide novel evidence supporting a causal role of higher adiposity, taken as a whole, on lower risk of ALS. A deeper understanding of the energy metabolism of ALS is more likely to identify feasible nutritional interventions and even novel therapeutic targets that might improve the survival of ALS patients. Ann Neurol 2020;87:434–441
Visible‐Light Photochemical Reduction of CO2 to CO Coupled to Hydrocarbon Dehydrogenation
Authors: Yu Huijun , Haviv Eynat , Neumann Ronny
Published: January 2020

Research on the photochemical reduction of CO2, initiated already 40 years ago, has with few exceptions been performed by using amines as sacrificial reductants. Hydrocarbons are high‐volume chemicals whose dehydrogenation is of interest, so the coupling of a CO2 photoreduction to a hydrocarbon‐photodehydrogenation reaction seems a worthwhile concept to explore. A three‐component construct was prepared including graphitic carbon nitride (g‐CN) as a visible‐light photoactive semiconductor, a polyoxometalate (POM) that functions as an electron acceptor to improve hole–electron charge separation, and an electron donor to a rhenium‐based CO2 reduction catalyst. Upon photoactivation of g‐CN, a cascade is initiated by dehydrogenation of hydrocarbons coupled to the reduction of the polyoxometalate. Visible‐light photoexcitation of the reduced polyoxometalate enables electron transfer to the rhenium‐based catalyst active for the selective reduction of CO2 to CO. The construct was characterized by zeta potential, IR spectroscopy, thermogravimetry, scanning electron microscopy (SEM) and energy dispersive X‐ray spectroscopy (EDS). An experimental Z‐scheme diagram is presented based on electrochemical measurements and UV/Vis spectroscopy. The conceptual advance should promote study into more active systems.
Effective and Reversible Carbon Dioxide Insertion into Cerium Pyrazolates
Authors: Bayer Uwe , Werner Daniel , Maichle‐Mössmer Cäcilia , Anwander Reiner
Published: January 2020

The homoleptic pyrazolate complexes [CeIII4(Me2pz)12] and [CeIV(Me2pz)4]2 quantitatively insert CO2 to give [CeIII4(Me2pz⋅CO2)12] and [CeIV(Me2pz⋅CO2)4], respectively (Me2pz=3,5‐dimethylpyrazolato). This process is reversible for both complexes, as observed by in situ IR and NMR spectroscopy in solution and by TGA in the solid state. By adjusting the molar ratio, one molecule of CO2 per [CeIV(Me2pz)4] complex could be inserted to give trimetallic [Ce3(Me2pz)9(Me2pz⋅CO2)3(thf)]. Both the cerous and ceric insertion products catalyze the formation of cyclic carbonates from epoxides and CO2 under mild conditions. In the absence of epoxide, the ceric catalyst is prone to reduction by the co‐catalyst tetra‐n‐butylammonium bromide (TBAB).
A Flexible Rechargeable Zinc–Air Battery with Excellent Low‐Temperature Adaptability
Authors: Pei Zengxia , Yuan Ziwen , Wang Chaojun , Zhao Shenlong , Fei Jingyuan , Wei Li , Chen Junsheng , Wang Cheng , Qi Rongjie , Liu Zongwen , Chen Yuan
Published: January 2020

Flexible zinc–air batteries (ZAB) are a promising battery candidate for emerging flexible electronic devices, but the catalysis‐based working principle and unique semi‐opened structure pose a severe challenge to their overall performance at cold temperature. Herein, we report the first flexible rechargeable ZAB with excellent low‐temperature adaptability, based on the innovation of an efficient electrocatalyst to offset the electrochemical performance shrinkage caused by decreased temperature and a highly conductive hydrogel with a polarized terminal group to render the anti‐freezing property. The fabricated ZABs show excellent electrochemical performances that outperform those of many aqueous ZABs at room temperature. They also deliver a high capacity of 691 mAh g−1 and an energy density of 798 Wh kg−1 at −20 °C (92.7 % and 87.2 % retention of the room temperature counterparts, respectively), together with excellent flexibility and reverting capability.
Spectrofluorimetric Determination of Aflatoxin B1 in Winter Herbal Teas via Magnetic Solid Phase Extraction Method by using Metal–Organic Framework (MOF) Hybrid Structures Anchored with Magnetic Nanoparticles
Authors: Durmus Zehra , Zengin Kurt Belma , Gazioğlu Işıl , Sevgi Ece , Kizilarslan Hancer Cagla
Published: January 2020

MIL53(Al)‐SiO2@Fe3O4 composite was prepared by co‐precipitation route with a typical Stöber synthetic process and ultrasonic‐agitation, then subsequently utilized as a multi‐component novel sorbent in solid‐phase microextraction (SPME) of aflatoxin B1 in winter herbal teas. Microstructural properties of MIL53(Al)‐SiO2@Fe3O4 composite was characterized by using Fourier transform infrared (FTIR) spectroscopy, powder X‐ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) methods, and Brunauer–Emmett–Teller (BET) surface area measurement. The MIL53(Al)‐SiO2@Fe3O4 composite was found to be a very effective sorbent in spectrofluorimetric determination of aflatoxin B1 (AFB1) in winter herbal teas via magnetic solid‐phase extraction (SPE) route. The proposed method showed a wide linear range from 0.5 to 150 ng/ml, low limit of detection (LOD = 0.5 ng/ml), and an acceptable recovery values (70.7–96.5%) in real samples analysis. This study shows that the suggested method possesses an important potential to use for detecting AFB1 in quality control laboratories.
Iron oxide magnetic nanoparticles supported on amino propyl‐functionalized KCC‐1 as robust recyclable catalyst for one pot and green synthesis of tetrahydrodipyrazolopyridines and cytotoxicity evaluation
Authors: Azizi Sajjad , Soleymani Jafar , Hasanzadeh Mohammad
Published: January 2020

In this study, paramagnetic dendritic fibrous nano‐silica functionalized by aminopropyltriethoxysilan (Fe3O4@KCC‐1‐nPr‐NH2) was synthesized using a novel hydrothermal protocol and used as a highly efficient, recyclable and heterogeneous nanocatalyst for the synthesis of a wide range of tetrahydrodipyrazolopyridines derivatives (5a‐5 m). The influence of different reaction parameters, such as the effects of solvent, temperature, time and concentration of catalyst for the synthesis of tetrahydrodipyrazolopyridine (2a) were studied. This catalyst could be reused for ten consecutive recycles without any considerable loss in its catalytic activity. This novel synthesis method offers some advantages including short reaction time, high yield and simple work‐up procedure. Finally, the newly synthesized tetrahydrodipyrazolopyridines derivatives (5a‐5f) were characterized by 1H and 13C NMR, IR and CHN.
Copper iodide nanoparticles‐decorated porous polysulfonamide gel: As effective catalyst for decarboxylative synthesis of N‐Arylsulfonamides
Authors: Alavinia Sedigheh , Ghorbani‐Vaghei Ramin , Rakhtshah Jamshid , Yousefi Seyf Jaber , Ali Arabian Iman
Published: January 2020

A porous cross‐linked poly (ethyleneamine)‐polysulfonamide (PEA‐PSA) as a novel organic support system is synthesized in the presence of silica template by nanocasting technique. The paper demonstrates immobilization of CuI nanoparticles inside the pores (PEA‐PSA@CuI) for the facile recovery and recycling of these nanoparticles. The presence of porous PEA‐PSA and PEA‐PSA@CuI nanocomposites was confirmed using FT‐IR spectroscopy, FE‐SEM, EDX, TGA, XRD, TEM, BET, XPS, WDX, 1H NMR, and ICP‐OES techniques. The PEA‐PSA@CuI along with Ag(I)/K2S2O8 was implemented as a reusable cooperative catalyst‐oxidant system in the N‐arylation of p‐toluenesulfonamide with substituted carboxylic acids in mild condition. So, the novel decarboxylative cross‐coupling catalyzed by copper and silver has been developed. Aromatic, secondary and tertiary aliphatic acids underwent high efficient decarboxylative processes with p‐toluenesulfonamide to afford the corresponding products. This method provides a practical approach for the flexible synthesis of sulfonamides from the readily affordable substrates. The catalyst is highly reusable and efficient, especially in terms of time and yield of the desired product.
Design, synthesis, and biological evaluation of new 1,4‐diarylazetidin‐2‐one derivatives (β‐lactams) as selective cyclooxygenase‐2 inhibitors
Authors: Arefi Hadi , Naderi Nima , Shemirani Amir B. Irani , Kiani Falavarjani Mina , Azami Movahed Mahsa , Zarghi Afshin
Published: January 2020

A new series of 1,4‐diarylazetidin‐2‐one derivatives (β‐lactams) were designed and synthesized to evaluate their biological activities as selective cyclooxygenase‐2 (COX‐2) inhibitors. In vitro COX‐1 and COX‐2 inhibition studies showed that all compounds were selective inhibitors of the COX‐2 isozyme with IC50 values in the 0.05–0.11 µM range, and COX‐2 selectivity indexes in the range of 170–703.7. Among the synthesized β‐lactams, 3‐methoxy‐4‐(4‐(methylsulfonyl)phenyl)‐1‐(3,4,5‐trimethoxyphenyl)azetidin‐2‐one (4j) possessing trimethoxy groups at the N‐1 phenyl ring exhibited the highest COX‐2 inhibitory selectivity and potency, even more potent than the reference drug celecoxib. The analgesic activity of the synthesized compounds was also determined using the formalin test. Compound 4f displayed the best analgesic activity among the synthesized molecules. Molecular modeling studies indicated that the methylsulfonyl pharmacophore group can be inserted into the secondary pocket of the COX‐2 active site for interactions with Arg513. The structure–activity data acquired indicate that the β‐lactam ring moiety constitutes a suitable scaffold to design new 1,4‐diarylazetidin‐2‐ones with selective COX‐2 inhibitory activity.
Evidence for the contribution of COMT gene Val158/108Met polymorphism (rs4680) to working memory training‐related prefrontal plasticity
Authors: Zhao Wan , Huang Ling , Li Yang , Zhang Qiumei , Chen Xiongying , Fu Wenjin , Du Boqi , Deng Xiaoxiang , Ji Feng , Xiang Yu‐Tao , Wang Chuanyue , Li Xiaohong , Dong Qi , Chen Chuansheng , Jaeggi Susanne M. , Li Jun
Published: January 2020

Background

Genetic factors have been suggested to affect the efficacy of working memory training. However, few studies have attempted to identify the relevant genes.

Methods

In this study, we first performed a randomized controlled trial (RCT) to identify brain regions that were specifically affected by working memory training. Sixty undergraduate students were randomly assigned to either the adaptive training group (N = 30) or the active control group (N = 30). Both groups were trained for 20 sessions during 4 weeks and received fMRI scans before and after the training. Afterward, we combined the data from the 30 participants in the RCT study who received adaptive training with data from 71 additional participants who also received the same adaptive training but were not part of the RCT study (total N = 101) to test the contribution of the COMT Val158/108Met polymorphism to the interindividual difference in the training effect within the identified brain regions.

Results

In the RCT study, we found that the adaptive training significantly decreased brain activation in the left prefrontal cortex (TFCE‐FWE corrected p = .030). In the genetic study, we found that compared with the Val allele homozygotes, the Met allele carriers' brain activation decreased more after the training at the left prefrontal cortex (TFCE‐FWE corrected p = .025).

Conclusions

This study provided evidence for the neural effect of a visual–spatial span training and suggested that genetic factors such as the COMT Val158/108Met polymorphism may have to be considered in future studies of such training.
Anilate Tethered Neutral Tetrahedral Pd(II) Cages Exhibiting Selective Encapsulation of Xylenes and Mesitylene
Authors: Yadav Ashok , Sarkar Meghamala , Subrahmanyam Sappati , Chaudhary Atul , Hey‐Hawkins Evamarie , Boomishankar Ramamoorthy
Published: January 2020

The design of porous materials for the recognition of multiple hydrocarbons is highly desirable for the energy‐efficient separation and recognition of chemical feedstock. Herein, three new iso‐structural porous discrete metal–organic cages of formula {[Pd3(NiPr)3PO]4(R‐AN)6} (R‐AN=anilate linkers) for the selective recognition of substituted aromatic hydrocarbons are reported. The tetrahedral cages 1, 2, and 3 containing anilate, chloranilate, and bromanilate linkers exhibited selective encapsulation of mesitylene, o‐xylene, and p‐xylene, respectively, over other analogous aromatic hydrocarbons. These selective encapsulations were driven by the variations in the portal diameters present at each of these cages and their interactions with the hydrocarbon guests. These observations are supported by mass spectrometry, NMR studies, and theoretical binding‐energy calculations.
Reductive Hydroxymethylation of 4‐Heteroarylpyridines
Authors: Hepburn Hamish B. , Donohoe Timothy J.
Published: January 2020

The activation of pyridinium salts with electron‐withdrawing heterocycles enables an iridium‐catalyzed reductive hydroxymethylation reaction to proceed smoothly, facilitating the preparation of useful 3D heteroaryl‐substituted functionalized piperidines. The methodology is used to prepare 3‐hydroxymethylated analogues of pharmaceutical agents. Mechanistically, formaldehyde acts as both a hydride donor and the electrophile, leading to the formation of two new carbon–hydrogen bonds and one new carbon–carbon bond under relatively mild conditions.
Divalent Ytterbium Iodide Supported by β‐Diketiminato Based Tridentate Ligand: Synthesis, Structure and Small Molecule Activation†
Authors: Liu Xiaojuan , Xiang Li , Wang Chen , Wang Bingwu , Leng Xuebing , Chen Yaofeng
Published: January 2020

Summary of main observation and conclusion

Divalent ytterbium iodide [LYb(μ‐I)(THF)]2 (1; L = [MeC(NDIPP)CHC(Me)NCH2CH2NMe2]−, DIPP = 2,6‐(iPr)2C6H3) was synthesized and its reactivity was studied. Complex 1 was synthesized by salt metathesis of YbI2(THF)2 with the potassium salt of ligand (KL) in high yield. In the reactions with trimethylsilyl azide, azobenzene, sulfur and diphenyl disulfide, complex 1 acts as a 2e reductant. In the reaction with CO2, the central carbon atom of β‐diketiminato backbone in 1 nucleophilically attacks the CO2 molecule to give a divalent ytterbium carboxylate.
Frequent alterations in p16/CDKN2A identified by immunohistochemistry and FISH in chordoma
Authors: Cottone Lucia , Eden Nadia , Usher Inga , Lombard Patrick , Ye Hongtao , Ligammari Lorena , Lindsay Daniel , Brandner Sebastian , Pižem Jože , Pillay Nischalan , Tirabosco Roberto , Amary Fernanda , Flanagan Adrienne M
Published: January 2020

The expression of p16/CDKN2A, the second most commonly inactivated tumour suppressor gene in cancer, is lost in the majority of chordomas. However, the mechanism(s) leading to its inactivation and contribution to disease progression have only been partially addressed using small patient cohorts. We studied 384 chordoma samples from 320 patients by immunohistochemistry and found that p16 protein was lost in 53% of chordomas and was heterogeneously expressed in these tumours. To determine if CDKN2A copy number loss could explain the absence of p16 protein expression we performed fluorescence in situ hybridisation (FISH) for CDKN2A on consecutive tissue sections. CDKN2A copy number status was altered in 168 of 274 (61%) of samples and copy number loss was the most frequent alteration acquired during clinical disease progression. CDKN2A homozygous deletion was always associated with p16 protein loss but only accounted for 33% of the p16‐negative cases. The remaining immunonegative cases were associated with disomy (27%), monosomy (12%), heterozygous loss (20%) and copy number gain (7%) of CDKN2A, supporting the hypothesis that loss of protein expression might be achieved via epigenetic or post‐transcriptional regulatory mechanisms. We identified that mRNA levels were comparable in tumours with and without p16 protein expression, but other events including DNA promoter hypermethylation, copy number neutral loss of heterozygosity and expression of candidate microRNAs previously implicated in the regulation of CDKN2A expression were not identified to explain the protein loss. The data argue that p16 loss in chordoma is commonly caused by a post‐transcriptional regulatory mechanism that is yet to be defined.
A two steps method of resources utilization predication for large Hadoop data center
Authors: Yu Lei , Teng Fei , Ning Shangming , Li Yunshu , Cui Zhe , Du Shengdong
Published: January 2020

With the increase of data processing and Hadoop data center construction requirements, the performance of Hadoop data center is limited by inappropriate resources utilization. This paper introduces a new method to predict utilization for large‐scale Hadoop clusters. The new method adopts a two steps model, which includes Hadoop applications' performance simulation and resources utilization prediction. For performance simulation, a new simulator, which integrates baseline test and multilayered network model, is introduced and implemented. A resources utilization predictor is proposed in the second step. By analyzing the pattern of resources utilization, a single task model is proposed. A parallel‐batch‐task‐based (PBT) model, which represents the behavior of real Hadoop applications by integrating the single task model, is introduced. Two test scenarios are configured to verify the performance of our method. For the data center scenario, Terasort, Wordcount, and Hive are selected as benchmarks. In the virtual machines scenario, Terasort is used as benchmark. The experiments show that the error comparing between the simulator results and experimental environment results in most cases is less than 10%. The results confirm that we can locate the resource bottleneck for Hadoop clusters, meanwhile we can agilely configure clusters for applications with massive data.
Machine learning on Crays to optimize petrophysical workflows in oil and gas exploration
Authors: Brown Nick , Roubíčková Anna , Lampaki Ioanna , MacGregor Lucy , Ellis Michelle , Vera de Newton Paola
Published: January 2020

The oil and gas industry is awash with sub‐surface data, which is used to characterize the rock and fluid properties beneath the seabed. This drives commercial decision making and exploration, but the industry relies upon highly manual workflows when processing data. A question is whether this can be improved using machine learning, complementing the activities of petrophysicists searching for hydrocarbons. In this paper, we present work using supervised learning with the aim of decreasing the petrophysical interpretation time down from over 7 days to 7 minutes. We describe the use of mathematical models that have been trained using raw well log data, to complete each of the four stages of a petrophysical interpretation workflow, in addition to initial data cleaning. We explore how the predictions from these models compare against the interpretations of human petrophysicists, and numerous options and techniques that were used to optimize the models. The result of this work is the ability, for the first time, to use machine learning for the entire petrophysical workflow.
Cloud architecture for plant phenotyping research
Authors: Debauche Olivier , Mahmoudi Sidi Ahmed , De Cock Nicolas , Mahmoudi Saïd , Manneback Pierre , Lebeau Frédéric
Published: January 2020

Digital phenotyping is an emergent science mainly based on imagery techniques. The tremendous amount of data generated needs important cloud computing for their processing. The coupling of recent advance of distributed databases and cloud computing offers new possibilities of big data management and data sharing for the scientific research. In this paper, we present a solution combining a lambda architecture built around Apache Druid and a hosting platform leaning on Apache Mesos. Lambda architecture has already proved its performance and robustness. However, the capacity of ingesting and requesting of the database is essential and can constitute a bottleneck for the architecture, in particular, for in terms of availability and response time of data. We focused our experimentation on the response time of different databases to choose the most adapted for our phenotyping architecture. Apache Druid has shown its ability to respond to typical queries of phenotyping applications in times generally inferior to the second.
Corporate social responsibility leadership for sustainable development: An institutional logics perspective in Brazil
Authors: Pureza Alvaro Plinio , Lee Ki‐Hoon
Published: January 2020

This study investigates what drives the implementation of corporate social responsibility (CSR) practices in Brazil. It combines multiaspects of institutional forces and a multilevel analysis into one study to identify patterns of behaviour and leadership rationale. We use interviews to collect data from 16 top Brazilian corporations with good CSR reputations. Building on the institutional logics perspective, the study differentiates four CSR patterns of behaviour and identifies two leadership rationales behind those patterns: the reactionary and reputational self‐oriented rationale and the responsible and collaborative system‐oriented rationale. The “self‐oriented” rationale is linked to leaderships with predominantly egotistic values and short‐term thinking characteristics. Conversely, the “system‐oriented” rationale is linked to leaderships with predominantly altruistic values and long‐term thinking characteristics. These findings provide new insights into the sustainable development debate and help practitioners evaluate the appropriateness of their own CSR practices for the company's strategy and leadership rationale.
Cobalta‐Electrocatalyzed C−H Activation in Biomass‐Derived Glycerol: Powered by Renewable Wind and Solar Energy
Authors: Meyer Tjark H. , Chesnokov Gleb A. , Ackermann Lutz
Published: January 2020

Aqueous glycerol was identified as a renewable reaction medium for metalla‐electrocatalyzed C−H activation powered by sustainable energy sources. The renewable solvent was employed for cobalt‐catalyzed C−H/N−H functionalizations under mild conditions. The cobalta‐electrocatalysis manifold occurred with high levels of chemo‐ and positional selectivity and allowed for electrochemical C−H activations with broad substrate scope. The resource economy of this strategy was considerably substantiated by the direct use of renewable solar and wind energy.
An improved EAAP scheme for vehicular ad hoc networks
Authors: Gu Tianlong , Yuan Bin , Liu Yining , Wang Peng , Li Long , Chang Liang
Published: January 2020

Recently, Maria Azees et al proposed an “EAAP: efficient anonymous authentication with conditional privacy‐preserving scheme for Vehicular Ad Hoc Networks.” Their scheme is mainly to solve the problem of high computation time of anonymous certificate and signature authentication, as well as the tracking problem of malicious vehicles. However, some improvements are needed in the protection of anonymous identity and the effective tracking of malicious vehicles. In this paper, our scheme realizes mutual authentication between OBU and RSU, and the RSU is authenticated without using certificate. In order to prevent the anonymous identity of the vehicles from being monitored and tracked, we use the negotiated short‐time key to encrypt the anonymous identity in the vehicle certificates. In addition, our scheme uses a new tracking method for malicious vehicles. Then, we prove the scheme through BAN logic, and it has the properties of authentication, anonymity, unlinkability, privacy protection, and traceability. Finally, we compare the computation cost and communication cost with other schemes, and the scheme has been greatly improved.
A review of phenformin, metformin, and imeglimin
Authors: Yendapally Raghunandan , Sikazwe Donald , Kim Subin S. , Ramsinghani Sushma , Fraser‐Spears Rheaclare , Witte Amy P. , La‐Viola Brittany
Published: January 2020

Diabetes mellitus is a serious metabolic disorder affecting millions of people worldwide. Phenformin and metformin are biguanide antidiabetic agents that are conveniently synthesized in a single‐step chemical reaction. Phenformin was once used to lower blood glucose levels, but later withdrawn from the market in several countries because it was frequently associated with lactic acidosis. Metformin is still a widely prescribed medication for the treatment of type 2 diabetes despite the introduction of several newer antidiabetic agents. Metformin is administered orally and has desirable pharmacokinetics. Incidence of metformin‐induced lactic acidosis is serious but very rare. Imeglimin, a novel molecule being investigated by Poxel and Sumitomo Dainippon Pharma in Japan, is currently in clinical trials for the treatment of type 2 diabetes. Unlike metformin, imeglimin is a cyclic molecule containing a triazine ring. However, like metformin, imeglimin is also a basic small molecule. Imeglimin is synthesized from metformin as a precursor via a single step chemical reaction. Recent mechanism of action studies suggests that imeglimin improves mitochondria function, when given in combination with metformin it helps achieve better glycemic control in patients with type 2 diabetes. We herein describe and compare the current status, synthesis, physicochemical properties, pharmacokinetic parameters, mechanism of action, and preclinical/clinical studies of metformin and imeglimin.
Synthesis of novel flexible tamoxifen analogues to overcome CYP2D6 polymorphism and their biological evaluation on MCF‐7 cell line
Authors: Ahmed Nermin S. , Wober Jannette
Published: January 2020

Tamoxifen (TAM) is currently the endocrine treatment of choice for all stages of breast cancer; it has proven success in ER positive and ER negative patients. TAM is activated by endogenous CYP450 enzymes to the more biologically active metabolites 4‐hydroxytamoxifen and endoxifen mainly via CYP2D6 and CYP3A4/5. CYP2D6 has been investigated for polymorphism; there is a large interindividual variation in the enzyme activity, this drastically effects clinical outcomes of tamoxifen treatment. Here in we report the design and synthesis of 10 novel compounds bearing a modified tamoxifen skeleton, ring C is substituted with different ester groups to bypass the CYP2D6 enzyme metabolism and employ esterase enzymes for activation. All compounds endorse flexibility on ring A. Compounds (II–X) showed MCF‐7% growth inhibition >50% at a screening dose of 10 μM. These results were validated by yeast estrogen screen (YES) and E‐Screen assay combined with XTT assay. Compound II (E/Z 4‐[1–4‐(3‐Dimethylamino‐propoxy)‐phenyl)‐3‐(4‐methoxy‐phenyl)‐2‐methyl‐propenyl]‐phenol) showed nanomolar antiestrogenic activity (IC50 = 510 nM in YES assay) and was five times more potent in inhibiting the growth of MCF‐7 BUS (IC50 = 96 nM) compared to TAM (IC50 = 503 nM). Esterified analogues VI, VII were three times more active than TAM on MCF‐7 BUS (IC50 = 167 nM). Novel analogues are prodrugs that can ensure equal clinical outcomes to all breast cancer patients.
Communicating the consensus on climate change to college biology majors: The importance of preaching to the choir
Authors: Sloane Jeremy D. , Wiles Jason R.
Published: January 2020

College and university biology majors who are not climate change deniers may yet be unaware of the degree of scientific consensus on climate change and unprepared to communicate about climate science to others. This study reports on a population of climate change accepting biology majors at a large, private research university in the American northeast. Our students tended to greatly underestimate the degree of scientific consensus around climate change, to be only moderately worried about climate change, and to be unconfident in their ability to communicate about the state of the scientific consensus around climate change. After an introduction to the scholarly literature that substantiates and quantifies the scientific consensus on climate change in the context of a course on biological research literature, our students showed significant increases in their estimates of the consensus on climate change, and their estimates were more accurate. Additionally, they became more worried about climate change as well as more confident in their ability to communicate about the scientific consensus to others. These results are in line with the Gateway Belief Model, which positions perception of scientific agreement on climate change as an important driver of acceptance and motivation toward action.
Effects of climate change and crop planting structure on the abundance of cotton bollworm, Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae)
Authors: Huang Jian , Hao HongFei
Published: January 2020

The interactions between plants and insects play an important role in ecosystems. Climate change and cropping patterns can affect herbivorous pest insect dynamics. Understanding the reasons for population fluctuations can help improve integrated pest management strategies. Here, a 25‐year dataset on climate, cropping planting structure, and the population dynamics of cotton bollworms (Helicoverpa armigera) from Bachu County, south Xinjiang, China, was analyzed to assess the effects of changes in climate and crop planting structure on the population dynamics of H. armigera. The three generations of H. armigera showed increasing trends in population size with climate warming, especially in the third generation. The relative abundances of the first and second generations decreased, but that of the third generation increased. Rising temperature and precipitation produced different impacts on the development of different generations. The population numbers of H. armigera increased with the increase in the non‐Bacillus thuringiensis (Bt) cotton‐planted area. Asynchrony of abrupt changes existed among climate change, crop flowering dates, and the phenology of H. armigera moths. The asynchronous responses in crop flowering dates and phenology of H. armigera to climate warming would expand in the future. The primary factors affecting the first, second, and third generations of moths were Tmean in June, the last appearance date of the second generation of moths, and the duration of the third generation of moths, respectively. To reduce the harm to crops caused by H. armigera, Bt cotton should be widely planted.
Tick parasitism as a cost of sexual selection and male parental care in a Neotropical frog
Authors: Longo Ana V. , Rodríguez‐Gómez Carlos A. , Zegarra Jan P. , Monzón Omar , Claudio‐Hernández Héctor J. , Joglar Rafael L. , Zamudio Kelly R. , Burrowes Patricia A. , López‐Torres Alberto L.
Published: January 2020

Sexual selection can drive variation in conspicuous traits, providing signals to females about overall male health including their ability to fight parasites. Trait–parasite relationships have been extensively studied in fish and birds, but few records exist for amphibians. Here, we focused on a direct‐developing frog (Eleutherodactylus cooki) that exhibits variation in the extent of yellow coloration on the venter of males, a sexually selected trait that is correlated with reproductive success and parental care. We quantified the relationship between the color trait and the prevalence of two parasites, a tick (Carios undescribed sp.) and a fungal pathogen (Batrachochytrium dendrobatidis), across hosts, populations, and environmental contexts. We found that tick larvae were carried more frequently by males than females. Among males, ticks parasitized more those with a greater extent of yellow coloration. We did not detect any patterns associated with sex, habitat use, or male coloration with fungal infections. Co‐infections were low (5%) and predominantly occurred in males (71%). Our findings highlight the reproductive cost of tick parasitism for males and suggest that females may assess both the quality of parental care and overall health in areas of high tick exposure. Thus, yellow coloration in males of this nocturnal amphibian may have evolved as an honest signal of health and quality of parental care.
Management of Heart Failure with Reduced Ejection Fraction after ESC 2016 Heart Failure Guidelines: The Linx Registry
Authors: de Frutos Fernando , Mirabet Sonia , Ortega‐Paz Luis , Buera Irene , Darnés Sara , Farré Nuria , Perez Bernardo , Adeliño Raquel , Bascompte Ramón , Pérez‐Rodón Jordi , Aparicio Xavier , Sutil‐Vega Mario , Soto Adriana , Faraudo Mercedes , Cainzos‐Achirica Miguel , Manito Nicolás
Published: January 2020

Aims

In May 2016, a new version of the European Society of Cardiology (ESC) Guidelines for the management of heart failure (HF) was released. The aim of this study was to describe the management of HF with reduced ejection fraction after the publication of ESC Guidelines.

Methods and results

The Linx registry is a multicentre, observational, cross‐sectional study from 14 Catalan hospitals that enrolled 1056 patients with HF and reduced left ventricular ejection fraction (≤40%) from 1 February to 30 April 2017 in outpatient cardiology clinics. Results were compared between hospitals according to their level of complexity in our own registry and compared with previously published registries similar to ours. Sacubitril/valsartan was prescribed to 23.9% of patients in our population, as a consequence, use of angiotensin‐converting enzyme inhibitor and angiotensin receptor blockers in monotherapy decreased to 48.1% and 16.9%, respectively, and prescription of beta‐blockers (91.8%), mineralocorticoid receptor antagonists (72.7%), and ivabradine (21.4%) remained similar to previous registries. Target doses of beta‐blockers (25.4%), angiotensin‐converting enzyme inhibitors (24.9%), angiotensin receptor blockers (7.7%), sacubitril/valsartan (8.1%), and mineralocorticoid receptor antagonists (19.7%) were accomplished in a low proportion of patients. Our results also suggest that prescription and up‐titration of class I HF drugs were greater in hospitals with higher level of complexity.

Conclusions

The Linx registry shows an appropriate adherence to pharmacological recommendations from ESC HF Guidelines despite a low proportion of patients reached target doses. Almost one‐quarter of patients were under treatment with sacubitril/valsartan a few months after ESC HF Guidelines recommendations.
Carbene Bridging C–H Activation: Facile Isocoumarin Synthesis Through Palladium‐Catalyzed Reaction of 2‐Pseudohalobenzaldehydes with Aryl Diazoesters
Authors: Yan Chao , Yu Yinghua , Peng Bo , Huang Xueliang
Published: January 2020

A reaction mode on carbene bridging C–H activation (CBA) is described. In this reaction, metal carbene was produced prior to the event of C–H bond metallation. Readily available aryl dizaoesters were employed as the carbene precursors. Migratory insertion of the palladium carbene intermediate could create a modular bridging arm to promote the C–H bond palladation of tethered aldehyde moiety. Its synthetic potential was demonstrated by facile construction isocoumarin scaffold from easily accessible starting materials. Furthermore, this protocol is also amenable for late‐functionalization of complex molecules.
Characterization of sequence variation at 30 autosomal STRs in Chinese Han and Tibetan populations
Authors: Wang Zheng , Wang Le , Liu Jing , Ye Jian , Hou Yiping
Published: January 2020

Massively parallel sequencing (MPS) technologies have the ability to reveal sequence variations within STR alleles as well as their nominal allele lengths, which have traditionally been detected by CE instruments. Recently, Thermo Fisher Scientific has updated the MPS‐STR panel, named the Precision ID GlobalFiler next‐generation sequencing (NGS) STR Panel version 2, with primers redesigned to add two pentanucleotide tandem repeat loci and profile interpretation supported by the Converge software. Using the Ion Chef System, the Ion S5XL System, and the Converge software, genetic variations were characterized within STR repeat and flanking regions of 30 autosomal STR markers in 115 unrelated individuals from two Chinese population groups (58 Tibetans and 57 Hans). Nineteen STRs demonstrated a relative increase in diversity with the variant sequence alleles compared with those of traditional nominal length alleles. In total, 390 alleles were identified by their sequences compared with 258 alleles that were identified by length. Of these 92 sequence variants found within the STR repeat regions, 40 variants were located in STR flanking regions. Additionally, the agreement of the results with CE data was evaluated, as was the ability of this new MPS panel to analyze case‐type (11 samples) and artificially degraded samples (seven samples in triplicate). The results generated from this study illustrate that extensive sequence variation exists in commonly used STR markers in the selected population samples and indicate that this NGS STR panel has the potential to be used as an effective tool for human forensics.
Insecticides and ovarian functions
Authors: Sharma Rajnesh Kumar , Singh Priyanka , Setia Aarzoo , Sharma Aman Kumar
Published: January 2020

Insecticides, a heterogeneous group of chemicals, are widely used in agriculture and household practices to avoid insect‐inflicted damage. Extensive use of insecticides has contributed substantially to agricultural production and the prevention of deadly diseases by destroying their vectors. On the contrary, many of the insecticides are associated with several adverse health effects like neurological and psychological diseases, metabolic disorders, hormonal imbalance, and even cancer in non‐target species, including humans. Reproduction, a very selective process that ensures the continuity of species, is affected to a greater extent by the rampant use of insecticides. In females, exposure to insecticides leads to reproductive incapacitation primarily through disturbances in ovarian physiology. Disturbed ovarian activities encompass the alterations in hormone synthesis, follicular maturation, ovulation process, and ovarian cycle, which eventually lead to decline in fertility, prolonged time‐to‐conceive, spontaneous abortion, stillbirths, and developmental defects. Insecticide‐induced ovarian toxicity is effectuated by endocrine disruption and oxidative stress. Oxidative stress, which occurs due to suppression of antioxidant defense system, and upsurge of reactive oxygen and nitrogen species, potentiates DNA damage and expression of apoptotic and inflammatory markers. Insecticide exposure, in part, is responsible for ovarian malfunctioning through disruption of hypothalamic–pituitary–gonadal axis. The current article is focused on the adverse effects of insecticides on ovarian functioning, and consequently, on the reproductive efficacy of females. The possible strategies to combat insecticide‐induced toxicity are also discussed in the latter part of this review. Environ. Mol. Mutagen. 61:369–392, 2020. © 2020 Wiley Periodicals, Inc.
Cleaner strategies on the effective elimination of toxic chromium from wastewater using coupled electrochemical/biological systems
Authors: Pavithra Kirubanandam Grace , Jaikumar Vasudevan , Kumar Ponnusamy Senthil , Sundarrajan Panneerselvam
Published: January 2020

Hexavalent chromium is a toxic pollutant and carcinogen, which affects the organs internally as well as externally in our body. In this research, a combination of three‐dimensional (3D)‐electrochemical treatment followed by biological treatment was done for chromium removal in simulated wastewater. Surface‐modified Strychnos potatorum (SMSp) seeds and surface‐modified tamarind pod (SMTp) shell were used as particle electrodes, and the experiments were conducted for different pH, voltage, and particle electrode followed by biological treatment. In biological treatment, Enterobacter cloacae strain was isolated from a common effluent treatment plant (CETP) and it was utilized. The molecular characterization of E. cloacae (live biomass) was done using 16s rRNA sequencing. In 3D‐electrochemical treatment with SMSp, efficiency was found to be the best when compared with SMTp under optimum condition (6 V, 3 pH, 15 g of SMSp) at a working period of 60 min, and the removal of hexavalent chromium from aqueous solution using SMSp was successfully applied to semi‐empirical kinetic model, which is based on Fermi's equation. This semi‐empirical kinetic model effectively depicts the hexavalent chromium concentration evolution in 3D‐electrochemical treatment. The combined treatment reduced the amount of chemical oxygen demand as well as the hexavalent chromium‐ion concentration in aqueous solution.
Experimental study on the enhanced oil recovery by in situ foam formulation
Authors: Chen Hailong , Li Zhaomin , Wang Fei , Li Aixin , Wanambwa Silagi , Lu Teng
Published: January 2020

In situ CO2foams (ISCF) are studied systematically by combining in situ CO2gas reactants (carbonate anhydrous, hydrochloric acid) and bio‐based surfactant. Sandpack flooding experiments at 60°C along with PVT experiments were carried out to analyze the oil displacement mechanisms. The results showed that ISCF could increase oil recovery from heterogeneous multilayer formation of permeability ratio over 6, and displacement efficiency increased with the injection volume increased before the injection of 1 PV. The incremental oil recovery by ISCF was much greater than that of conventional foam or in situ CO2(ISC) without foam under the same injection conditions. The generated CO2foam could reduce the interfacial tension between displacement phase and displaced phase effectively which contributed to the great increase in capillary number. The CO2dissolution greatly reduced the viscosity of crude oil, and the highest viscosity reduction rate at 60°C could be as high as 98%. The Ca2+concentration of produced liquids analysis revealed the ISCF could distribute intelligently the acid in heterogeneous formations.
Geochemical characteristics and hydrocarbon expulsion of source rocks in the first member of the Qingshankou Formation in the Qijia‐Gulong Sag, Songliao Basin, Northeast China: Evaluation of shale oil resource potential
Authors: Huo Zhipeng , Hao Shibo , Liu Bo , Zhang Jinchuan , Ding Jianghui , Tang Xuan , Li Changrong , Yu Xiaofei
Published: January 2020

In recent years, there has been significant progress in shale oil exploration in the first member of the Qingshankou Formation (K2qn1) in the Qijia‐Gulong Sag, Songliao Basin, Northeast China: It shows good prospects for shale oil. However, the recognized lack of the geochemical and hydrocarbon generation and expulsion characteristics of K2qn1 source rocks limits an accurate evaluation of shale oil resource. This study systematically investigated the geological and geochemical characteristics, hydrocarbon generation and expulsion, and shale oil potential of the K2qn1 source rocks. The results show that the K2qn1 mudstones were mainly deposited in the semideep and deep lacustrine facies under reducing and weak reducing conditions. Compared with the southern Gulong Sag, the northern Qijia Sag has a higher salinity, more abundant prosperous aquatic organisms, and a greater paleoproductivity. The K2qn1 source rocks are pervasive and continuous in the entire sag, with maximum thicknesses greater than 110 m. They have a higher organic matter (OM) abundance (2.40% of the average TOC), are dominated by type I and II1 kerogen, and are mature (0.8%‐0.1.3% VR), which indicate that they are good to excellent source rocks and have significant hydrocarbon generation potential. The source rocks in the Qijia Sag have a higher OM abundance, a better OM type, and a lower OM maturity than those in the Gulong Sag. The threshold and peak hydrocarbon expulsion values for marlstone source rocks are 0.85% VR and 0.95% VR, respectively. The volumes of hydrocarbons generated and expulsed from the K2qn1 source rocks are 121.8 × 108 t and 46.9 × 108 t, respectively, with a retention efficiency of 61.5%. The in‐place and recoverable resources of shale oil are 74.9 × 108 t and (12.0‐13.5) × 108 t, respectively, indicating that the entire sag has a significant shale oil potential, especially the Qijia Sag.
Enhanced data communication models for real‐time power system monitoring in a distributed platform
Authors: Kannan Nithiyananthan , Thomas Sunil , Mobarak Youssef , Alharbi Fahd
Published: January 2020

The novelty behind this research is to develop enhanced models for real‐time power system monitoring in a platform‐independent and distributed platform. Distributed models for power system applications have been implemented using Remote Method Invocation (RMI), Common object Request Broker Architecture and. NET remoting technologies. The interoperability among the heterogeneous power system clients in a distributed platform has been achieved through XMLization of power system data which provides meaningful solution to the legacy issues associated with power systems. A RMI‐based model for real‐time power system monitoring in a distributed platform had been implemented and discussed in detail. A component model for real‐time power system monitoring has also been proposed and implemented to increase the reusability and scalability of the system. A location transparent model has been developed using Common object Request Broker Architecture with RMI‐Internet Inter‐Orb Protocol for load flow monitoring and the idea is extended to solve real‐time economic load dispatch and dynamic security monitoring. The detailed monitoring on performance of the proposed models has been done with load flow monitoring, dynamic security monitoring and economic load dispatch problems. A. NET remoting architectural model has been developed for real‐time economic load dispatch in a distributed platform. This research paper explores various issues in deploying power system applications in a distributed platform. It will serve the purpose of stimulating interest among power engineers and also will be extremely useful for electric power utilities.