bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of liquid ammonia yield using a novel deep learning‐based heterogeneous pruning ensemble model
Authors: Dai Min , Yang Fusheng , Zhang Zaoxiao , Liu Guilian , Feng Xiao , Hou Jianmin
Published: January 2020

Liquid ammonia yield is the main index characterizing the process output of ammonia synthesis, the prediction of which is crucial for process control and optimization. However, the industrial process of ammonia synthesis involves multiple variables and strong nonlinearity, making it difficult to be accurately predicted using conventional mechanism‐driven model, or a certain type of data‐driven model. Therefore, a deep learning‐based heterogeneous pruning ensemble (DL‐HPE) model is proposed to overcome the limitations of conventional models. In this model, a “VDiv” pruning strategy that trades off diversity and accuracy is proposed and successfully applied to select the optimal subset from nine representative base models. Finally, the deep learning is employed to integrate the outputs of the involving models to generate the final prediction. The DL‐HPE method was applied to modeling the UCI standard dataset and the historical dataset collected from an ammonia plant in China. The results show that the method is superior to single model or other ensemble models both in accuracy and in robustness.
Requirement of Mucosa‐Associated Lymphoid Tissue Lymphoma Translocation Protein 1 Protease Activity for Fcγ Receptor–Induced Arthritis, but Not Fcγ Receptor–Mediated Platelet Elimination, in Mice
Authors: Martin Kea , Touil Ratiba , Cvijetic Grozdan , Israel Laura , Kolb Yeter , Sarret Sophie , Valeaux Stéphanie , Degl'Innocenti Elena , Le Meur Thomas , Caesar Nadja , Bardet Maureen , Beerli Christian , Zerwes Hans‐Guenter , Kovarik Jiri , Beltz Karen , Schlapbach Achim , Quancard Jean , Régnier Catherine H. , Bigaud Marc , Junt Tobias , Wieczorek Grazyna , Isnardi Isabelle , Littlewood‐Evans Amanda , Bornancin Frédéric , Calzascia Thomas
Published: January 2020

Objective

Fcγ receptors (FcγR) play important roles in both protective and pathogenic immune responses. The assembly of the CBM signalosome encompassing caspase recruitment domain–containing protein 9, B cell CLL/lymphoma 10, and mucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT‐1) is required for optimal FcγR‐induced canonical NF‐κB activation and proinflammatory cytokine release. This study was undertaken to clarify the relevance of MALT‐1 protease activity in FcγR‐driven events and evaluate the therapeutic potential of selective MALT‐1 protease inhibitors in FcγR‐mediated diseases.

Methods

Using genetic and pharmacologic disruption of MALT‐1 scaffolding and enzymatic activity, we assessed the relevance of MALT‐1 function in murine and human primary myeloid cells upon stimulation with immune complexes (ICs) and in murine models of autoantibody‐driven arthritis and immune thrombocytopenic purpura (ITP).

Results

MALT‐1 protease function is essential for optimal FcγR‐induced production of proinflammatory cytokines by various murine and human myeloid cells stimulated with ICs. In contrast, MALT‐1 protease inhibition did not affect the Syk‐dependent, FcγR‐mediated production of reactive oxygen species or leukotriene B4. Notably, pharmacologic MALT‐1 protease inhibition in vivo reduced joint inflammation in the murine K/BxN serum–induced arthritis model (mean area under the curve for paw swelling of 45.42% versus 100% in control mice; P = 0.0007) but did not affect platelet depletion in a passive model of ITP.

Conclusion

Our findings indicate a specific contribution of MALT‐1 protease activity to FcγR‐mediated events and suggest that MALT‐1 protease inhibitors have therapeutic potential in a subset of FcγR‐driven inflammatory disorders.
Accretion‐induced collapse to third family compact stars as trigger for eccentric orbits of millisecond pulsars in binaries
Authors: Alvarez‐Castillo David Edwin , Antoniadis John , Ayriyan Alexander , Blaschke David , Danchev Victor , Grigorian Hovik , Largani Noshad Khosravi , Weber Fridolin
Published: January 2020

A numerical rotating neutron star solver is used to study the temporal evolution of accreting neutron stars using a multi‐polytrope model for the nuclear equation of state named ACB5. The solver is based on a quadrupole expansion of the metric, but confirms the results of previous works, revealing the possibility of an abrupt transition of a neutron star from a purely hadronic branch to a third‐family branch of stable hybrid stars, passing through an unstable intermediate branch. The accretion is described through a sequence of stationary rotating stellar configurations which lose angular momentum through magnetic dipole emission, while, at the same time, gaining angular momentum through mass accretion. The model has several free parameters which are inferred from observations. The mass accretion scenario is studied in dependence on the effectiveness of angular momentum transfer which determines at which spin frequency the neutron star will become unstable against gravitational collapse to the corresponding hybrid star on the stable third‐family branch. It is conceivable that the neutrino burst which accompanies the deconfinement transition may trigger a pulsar kick which results in the eccentric orbit. A consequence of the present model is the prediction of a correlation between the spin frequency of the millisecond pulsar in the eccentric orbit and its mass at birth.
Approaching Reactive KFePO4 Phase for Potassium Storage by Adopting an Advanced Design Strategy
Authors: Sultana Irin , Rahman M. Mokhlesur , Mateti Srikanth , Sharma Neeraj , Huang Shaoming , Chen Ying
Published: January 2020

Pristine KFePO4 is electrochemically inactive towards potassium, which suggests that K+ ion migration is unfavorable in the KFePO4 structure. Therefore, it is a challenge to create a reactive structure of KFePO4 towards reversible potassium insertion/extraction. In this study, we have fabricated reactive KFePO4 phase by adopting high‐energy ball milling technique where tiny nanoparticles (∼1.0‐1.5 nm) of KFePO4 are created and embedded in the Super P carbon black matrix, which provides conductivity and helps to stabilize the electrode structure. The combination of nano‐sizing and the conductive matrix appears to activate electrochemical reactivity. The obtained carbon incorporated KFePO4 material appears to be amorphous. The electrode produces an average operational potential of ∼2.5 V (vs K+/K) with high capacity retention of 90 mAh g−1. It is anticipated that this work could pave the way for further studies on cathodes and generate huge attention to the role of ball milling and particle size control on electrochemical activity of KFePO4 materials for the development of PIBs.
Production and purification of xylitol by Scheffersomyces amazonenses via sugarcane hemicellulosic hydrolysate
Authors: Silva Débora D.V. , Dussán Kelly J. , Idarraga Angela , Grangeiro Luana , Silva Silvio S. , Cardona Carlos A. , Quintero Julián , Felipe Maria G.A.
Published: January 2020

Xylitol was produced by Scheffersomyces amazonensis UFMG‐HMD‐26.3 in hemicellulosic hydrolysate obtained from a mixture of sugarcane bagasse and straw (1:1) in batch fermentation, and was recovered using supercritical fluid. The xylitol produced was 20.11 g L−1 and the extraction approach reached a xylitol recovery of 40.51% at a high purity level of 99.59%. An analysis of energy consumption for the xylitol production process showed that xylitol production from sugarcane biomass hemicellulosic hydrolysate is feasible, highlighting the potential use of this biomass in sustainable xylitol production and supercritical fluids as a robust proposal for xylitol separation. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd
“To hope was to expect”: The impact of perspective taking and forecast type on wishful thinking
Authors: Rose Jason P. , Aspiras Olivia
Published: January 2020

When forecasting future outcomes, people tend to believe that the outcomes they want to happen are also likely to happen. Despite numerous attempts, few systematic factors have been identified that consistently and robustly reduce wishful thinking (WT) effects. Using elections and sporting event outcomes as contexts, three experiments examined whether taking the perspective of a political rival or opposing fan reduced WT effects. We also examined whether making deliberative (vs. intuitive‐based) forecasts was associated with lower WT effects. Online adult samples of U.S. citizens from Mechanical Turk and U.S. college students provided their preferences and forecasts for the U.S. presidential election (Experiments 1 and 2) and a sports competition outcome (Experiment 3). Critically, some participants received perspective taking prompts immediately before providing forecasts. First, results revealed reductions in WT effects when participants engaged in perspective taking. Interestingly, this effect only emerged when intuitive‐based forecasts were made first (Experiment 3). Second, intuitive‐based forecasts revealed stronger evidence of WT effects. Finally, we found that perspective taking and forming forecasts deliberately promoted a shift in focus away from preferences and toward a consideration of the relative strengths and weaknesses of the entities (i.e., candidates and teams). Theoretical implications for understanding WT effects and applied implications for developing interventions are discussed.
Novel spectrofluorimetric quantification of linagliptin in biological fluids exploiting its interaction with 4‐chloro‐7‐nitrobenzofurazan
Authors: Aref Heba A. , Hammad Sherin F. , Elgawish Mohamed Saleh , Darwish Khaled M.
Published: January 2020

Direct determination of linagliptin (LIN) using fluorimetry has been limited because LIN releases a very weak fluorescence signal. Accordingly, it should be derivatized first with a fluorogenic reagent to enhance its fluorescence and consequentially the sensitivity required for its bioanalysis. This is the first description of a spectrofluorimetric method for LIN quantification in human plasma. The suggested method exploits the nucleophilic nature of its amino group to react with 4‐chloro‐7‐nitrobenzofurazan (NBD‐Cl) in borate buffer at pH 8.5 to yield a strong fluorescent product with excitation and emission wavelengths of 459 and 529 nm, respectively. Experimental variables concerning the conditions of reaction and fluorescence intensity were carefully investigated and optimized. The linearity range was from 1.0–100 ng ml−1 with a lower detection limit and a lower quantification limit of 0.60 ng ml−1 and 1.82 ng ml−1, respectively. Validation of the suggested method has been accomplished and the application to LIN analysis in commercial tablets as well as in human plasma resulted in a mean per cent recovery of 100.12 ± 1.57 and 99.65 ± 1.22, respectively. The developed method was proven to be a promising, simple and fast alternative bioanalytical method for LIN quantification in clinical and bioequivalence research.
Best Practices for Board Leadership During Times of Uncertainty and Instability
Authors: Aujla Sandeep
Published: January 2020

Sandeep Aujla is the president and founder of Multilevel Leadership Consulting, based in Brampton, Ontario, Canada. In this article, she explores the role of the board of directors during times of acute uncertainty, and lays out a series of best practices for corporate governance when organizations operate in an unstable and unpredictable political climate.
Insured Capacity: Owner‐Designee Directors Should Not Take Their D&O Coverage for Granted
Authors: Struck Daniel J.
Published: January 2020

Daniel J. Struck is partner at Culhane Meadows, a Dallas‐based law firm serving major corporations and emerging companies across industry. In this article, he discusses some of the complexities of directors and officers liability insurance and the protections and limitations it can offer corporate boards in light of a changing, and newly activist, corporate landscape.
Integrated analysis of a ceRNA network reveals potential prognostic lncRNAs in gastric cancer
Authors: Qi Mingran , Yu Bingxin , Yu Huiyuan , Li Fan
Published: January 2020

Long noncoding RNAs (lncRNAs) have important biological functions as competing endogenous RNAs (ceRNAs) in tumors, yet the functions and regulatory mechanisms of lncRNA‐related ceRNAs in gastric cancer have not been fully elucidated. In this study, we constructed a lncRNA‐miRNA‐mRNA ceRNA network and identified potential lncRNA biomarkers in gastric cancer. Basing on the RNA profiles downloaded from The Cancer Genome Atlas (TCGA) platform, the gastric cancer‐specific differentially expressed lncRNAs, miRNAs, and mRNAs were screened for constructing a ceRNA network using bioinformatic tools. The enrichment analysis of the biological processes in Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathways was performed on the ceRNA‐related DEmRNAs. According to the modularization of protein‐protein interaction (PPI) network, we extracted a ceRNA subnetwork and analyzed the correlation between the expression of the lncRNAs involved and specific clinical features of patients. Next, the expression of highly up‐regulated in liver cancer (HULC) and RP11‐314B1.2 showed significant changes in several pathological processes involved in gastric cancer, and nine lncRNAs were found to be correlated with the overall survival of patients with gastric cancer. Through the univariate and multivariate Cox regression analyses, two lncRNAs (LINC00106 and RP11‐999E24.3) were identified and utilized to establish a risk score model for assessing the prognosis of patients. The analysis results were also partially verified using quantitative real‐time PCR. The findings from this study indicate that HULC, RP11‐314B1.2, LINC00106, and RP11‐999E24.3 could be considered as potential therapeutic targets or prognostic biomarkers in gastric cancer, and provide a new perspective for cancer pathogenesis research.
The microRNA‐155 mediates hepatitis B virus replication by reinforcing SOCS1 signalling–induced autophagy
Authors: Chen Liyan , Ming Xiaoyu , Li Wensong , Bi Manru , Yan Bingzhu , Wang Xiaoren , Yang Pengfei , Yang Baoshan
Published: January 2020

As small conserved RNAs without a coding function, microRNAs are expressed in multicellular organisms and contribute to the modulation of multiple cellular reactions, such as viral replication, as well as autophagy. microRNAs can regulate host gene expression and inhibit or reinforce hepatitis B virus (HBV) replication. Hepatic cells express miR‐155 noticeably. Consequently, our study explored miR‐155 modulation of HBV replication and investigated the potential mechanism involved. miR‐155 was inhibited on HBV infection. miR‐155 transfection remarkably reinforced HBV replication, antigen expression, and progeny secretion in HepG2215 cells. Moreover, miR‐155 impaired the inhibition of the cytokine signalling 1 (SOCS1)/Akt/mTOR axis and reinforced HepG2215 autophagy. Additionally, the autophagy inhibitor (3‐MA) eliminated HBsAg secretion triggered by miR‐155. Taken together, miR‐155 reinforced HBV replication by reinforcing SOCS1‐triggered autophagy.

Significance of the study

The research studied the potential mechanism involved in HBV replication and miR‐155 that miR‐155 reinforces HBV replication by reinforcing the SOCS1/Akt/mTOR axis–stimulated autophagy, and therefore, it can provide medical practitioners with the inspiration that chronic HBV might be cured or improved by regulating the activation of miR‐155 in cells. In the study, the experiments show that autophagy inhibitors (3‐MA) counteracted miR‐155 contribution to HBV replication, and it might be a practicable way to improve HBV through some therapies that can repress the autophagy in related cells.
Quantitative MS‐Based Proteomics: Comparing the MCF‐7 Cellular Response to Hypoxia and a 2‐Oxoglutarate Analogue
Authors: Bush Jacob T. , Chan Mun Chiang , Mohammed Shabaz , Schofield Christopher J.
Published: January 2020

The hypoxia‐inducible factors (HIFs) are key transcription factors in determining cellular responses involving alterations in protein levels in response to limited oxygen availability in animal cells. 2‐Oxoglutarate‐dependent oxygenases play key roles in regulating levels of HIF and its transcriptional activity. We describe MS‐based proteomics studies in which we compared the results of subjecting human breast cancer MCF‐7 cells to hypoxia or treating them with a cell‐penetrating derivative (dimethyl N‐oxalylglycine; DMOG) of the stable 2OG analogue N‐oxalylglycine. The proteomic results are consistent with reported transcriptomic analyses and support the proposed key roles of 2OG‐dependent HIF prolyl‐ and asparaginyl‐hydroxylases in the hypoxic response. Differences between the data sets for hypoxia and DMOG might reflect context‐dependent effects or HIF‐independent effects of DMOG.
Percutaneous transluminal angioplasty with selective stenting for the treatment of renal artery stenosis caused by fibromuscular dysplasia: 18 years' experience from the China Center for Cardiovascular Disease
Authors: Chen Yang , Dong Hui , Jiang Xiongjing , Deng Yu , Zou Yubao , Che Wuqiang , Xiong Hongliang , Xu Bo , Yang Yuejin , Gao Runlin
Published: January 2020

Objectives

This study aimed to evaluate the safety and efficiency of percutaneous transluminal angioplasty (PTA) with selective stenting treating Chinese patients with renal artery stenosis (RAS) due to fibromuscular dysplasia (FMD).

Background

Endovascular data of patients with RAS caused by FMD are scarce in China.

Methods

Clinical data of 105 hypertensive patients with RAS caused by FMD underwent endovascular therapy at a single‐site between June 2001 and October 2018 were analyzed retrospectively. Baseline blood pressure, use of antihypertensive medications, renal function, and adverse events at a 1‐year follow‐up were evaluated.

Results

The patients were aged between 10 and 64 years (mean age 26.7 ± 8.2 years) and 52 (49.5%) were female. In total, 105 patients undergoing endovascular therapy involving 124 RASs. Thirty (24.2%), sixty‐four (51.6%), and thirty (24.2%) RASs were multifocal, unifocal, and tubular types, respectively. Ninety‐four (89.5%) and eleven (10.5%) patients underwent PTA alone and PTA plus stenting, respectively. The technical success rate for endovascular therapy was 95.2% (100/105) without severe complications. During 1‐year follow‐up (n = 100), the mean systolic and diastolic blood pressure decreased from 157.6 ± 17.5 and 102.3 ± 14.2 to 129.6 ± 12.3 and 81.3 ± 11.1 mmHg, respectively, and the number of antihypertensive medications reduced from 2.2 ± 1.2 to 0.8 ± 1.0 (all p < .001). The cure rate and improved rate of blood pressure was 49.0 and 40.0%, respectively. The serum creatinine levels remained stable. The primary and secondary restenosis rate was 13.4 and 5.8%, respectively.

Conclusion

Endovascular therapy for treating RAS caused by FMD was technically safe and effective for reducing blood pressure in Chinese patients.
Evaluation of a risk index for predicting short‐term and long‐term outcomes in patients with ST‐elevation myocardial infarction
Authors: Shao Chunli , Wang Jingjia , Li Ping , Yang Jingang , Wang Wenyao , Wang Yang , Zhao Yanyan , Ni Lin , Tian Jian , Zhang Kuo , Gao Jun , Tang Yi‐Da , Yang Yuejin
Published: January 2020

Objective

This study aimed to evaluate the usefulness of the admission risk index (RI) to predict short‐term and long‐term outcomes in a broad population with ST‐elevation myocardial infarction (STEMI) using data from the Chinese Acute Myocardial Infarction Registry.

Background

The RI was developed as a simple tool to predict risk of death in STEMI patients. The performance in predicting short‐term and long‐term risk of death in Chinese patients receiving percutaneous coronary intervention and conservative treatment for STEMI remains unclear.

Methods

Age, heart rate (HR), and systolic blood pressure (SBP) were used to calculate RI using (HR×[age/10]2)/SBP. We used the prediction tool to predict mortality over 12 months.

Results

TheC‐index of the admission RI for predicting in‐hospital, 1‐, 6‐, and 12‐months mortality were 0.78, 0.78, 0.78, and 0.77, respectively, compared with 0.75 of the Global Registry in Acute Coronary Events score. Based on the receiver operating characteristic curve analysis, the RI was categorized into quintiles for convenient clinical use, and it revealed a nearly 15‐fold gradient of increasing mortality from 2.29 to 32.5% (p < .0001) while RI >34 had the highest mortality. By categorizing into five different risk groups, the short‐term and long‐term mortality of patients receiving different treatments could be distinguished.

Conclusions

RI based on three routine variables and easily calculated by any medical practitioner is useful for predicting in‐hospital and long‐term mortality in patients with STEMI at the initial consultation with clinicians.
Northwell intracoronary brachytherapy for the treatment of recurrent drug eluting stent in‐stent restenosis (NITDI study group)
Authors: Meraj Perwaiz M. , Patel Krunalkumar , Patel Amitkumar , Doshi Rajkumar , Srinivas Guruprasad , Jauhar Rajiv , Kaplan Barry , Garzon Ruby , Sharma Anurag , Cao Yijian , Diaz Molina Ferney , Sharma Rajiv
Published: January 2020

Objective

The purpose of this study is to report on safety, short‐term and long‐term clinical efficacy following intracoronary brachytherapy (ICBT) for restenosis (ISR) in patients with drug eluting stents (DES).

Background

ICBT is an effective treatment for ISR of bare metal stents (BMS) but its utilization has waned due to the advent of DES. ISR following DES occurs at a frequency of 8% or greater.

Method

A retrospective analysis was performed on patients treated on an institutional review board (IRB) approved protocol using ICBT for DES ISR between January 2011 and October 2016. All patients were followed for 24 months for procedural complications, mortality, clinical ISR/target lesion revascularization (TLR) and stroke.

Results

A total of 290 patients were identified with a mean age of 66.6 years. All of them had high rates of typical coronary artery disease risk factors. Our primary outcome, composite of in‐hospital mortality, myocardial infarction (MI), safety outcomes and procedural failure was noted in 1(0.3%) patient who had a MI. No other secondary outcome was noted in‐hospital. At 1‐year follow up, 12.4% patients had ISR, 1.7% patients died, and 1 (0.3%) had ischemic stroke. At 2‐year, 14.7% had ISR, and total 6 (2.1%) patients had MI.

Conclusion

ICBT demonstrates excellent technical success rates for treatment, safety, and reasonable efficacy over 2‐years to be free from recurrent clinical ISR. This study represents the largest ICBT data for DES ISR to date among very complex lesion subsets, however, more prospective data will be needed to determine the optimal patient for treatment.
Organophotoredox‐Mediated Amide Synthesis by Coupling Alcohol and Amine through Aerobic Oxidation of Alcohol
Authors: Shah Sk. Sheriff , Shee Maniklal , Venkatesh Yarra , Singh Amit Kumar , Samanta Samya , Singh N. D. Pradeep
Published: January 2020

The combination of an organic photocatalyst [4CzIPN (1,2,3,5‐tetrakis(carbazol‐9‐yl)‐4,6 dicyanobenzene) or 5MeOCzBN (2,3,4,5,6‐pentakis(3,6‐dimethoxy‐9 H‐carbazol‐9‐yl)benzonitrile)], quinuclidine, and tetra‐n‐butylammonium phosphate (hydrogen‐bonding catalyst) was employed for amide bond formations. The hydrogen‐bonded OH group activated the adjacent C−H bond of alcohols towards hydrogen atom transfer (HAT) by a radical species. The quinuclidinium radical cation, generated through single‐electron oxidation of quinuclidine by the photocatalyst, employed to abstract a hydrogen atom from the α‐C−H bond of alcohols selectively due to a polarity effect‐produced α‐hydroxyalkyl radical, which subsequently converted to the corresponding aldehyde under aerobic conditions. Then the coupling of the aldehyde and an amine formed a hemiaminal intermediate that upon photocatalytic oxidation produced the amide.
Photo Cross‐Linking Probes Containing ϵ‐N‐Thioacyllysine and ϵ‐N‐Acyl‐(δ‐aza)lysine Residues
Authors: Bæk Michael , Martín‐Gago Pablo , Laursen Jonas S. , Madsen Julie L. H. , Chakladar Saswati , Olsen Christian A.
Published: January 2020

Posttranslational modifications (PTMs) are important in the regulation of protein function, trafficking, localization, and marking for degradation. This work describes the development of peptide activity/affinity‐based probes for the discovery of proteins that recognize novel acyl‐based PTMs on lysine residues in the proteome. The probes contain surrogates of ϵ‐N‐acyllysine by introduction of either hydrazide or thioamide functionalities to circumvent hydrolysis of the modification during the experiments. In addition to the modified PTMs, the developed chemotypes were analyzed with respect to the effect of peptide sequence. The photo cross‐linking conditions and subsequent functionalization of the covalent adducts were systematically optimized by applying fluorophore labeling and gel electrophoresis (in‐gel fluorescence measurements). Finally, selected probes, containing the ϵ‐N‐glutaryllysine and ϵ‐N‐myristoyllysine analogues, were successfully applied for the enrichment of native, endogenous proteins from cell lysate, recapitulating the expected interactions of SIRT5 and SIRT2, respectively. Interestingly, the latter mentioned was able to pull down two different splice variants of SIRT2, which has not been achieved with a covalent probe before. Based on this elaborate proof‐of‐concept study, we expect that the technology will have broad future applications for pairing of novel PTMs with the proteins that target them in the cell.
Hydrogen Atom Transfer‐Mediated Domino Cyclisation Reaction to Access (Spiro)Quinazolinones
Authors: Turner Oliver J. , Hirst David J. , Murphy John A.
Published: January 2020

A radical domino cyclisation reaction of N‐cyanamide alkenes, mediated by hydrogen atom transfer (HAT) has been developed. This method, using PhSiH3 and catalytic Fe(acac)3, allows for the synthesis of challenging (spiro)quinazolinone scaffolds from simple, tractable (hetero)aryl carboxylic acid and cyanamide building blocks.
Facile Access to AgOCF3 and Its New Applications as a Reservoir for OCF2 for the Direct Synthesis of N−CF3, Aryl or Alkyl Carbamoyl Fluorides
Authors: Turksoy Abdurrahman , Scattolin Thomas , Bouayad‐Gervais Samir , Schoenebeck Franziska
Published: January 2020

The development of innovative fluorination strategies is greatly dependent also on the availability, safety and practicability of available fluorinating reagents. We herein show a straightforward and quantitative strategy for the preparation of valuable AgOCF3 at room temperature and showcase its performance in trifluoromethoxylations or as reservoir for O=CF2. This enabled the direct, practical and safe synthesis of valuable N‐alkyl/aryl and N−CF3 carbamoyl fluorides from secondary amines and isothiocyanides, respectively. Our mechanistic data indicate that AgOCF3 does not liberate O=CF2 until it is activated by a nucleophilic co‐reagent, reinforcing the stability of the salt under our new preparation strategy.
Dynamics of the forced negative conductance series LCR circuit
Authors: Pitchaimuthu Megavarna Ezhilarasu , Kathamuthu Thamilmaran
Published: January 2020

In this paper, we make a revisit of a simple LCR circuit introduced earlier in 2005 by Thamilmaran et. al., and present the circuit simulation studies of its dynamics using the PSpice circuit simulator package. This is a simple sinusoidally forced series LCR circuit, employing an ordinary single PN junction diode in conjunction with a negative conductance as its nonlinearity. In circuit theoretic terms, this circuit is a modified form of the forced van der Pol type oscillator and is interesting because it exhibits a dual nature, namely, a forced van der Pol type circuit behaviour and an MLC circuit type behaviour for different parametric ranges. In addition, statistical studies have shown the circuit to possess strong chaoticity. Subsequent works on this circuit have shown the birth of strange nonchaos through four different routes, namely, the Heagy‐Hammel route, gradual fractalization route, intermittency route, and Bubbling route. In lieu of these, we look at the circuit afresh and study its dynamics in an exhaustive manner. These studies reveal many new bifurcations and routes to chaos. These results have been verified using hardware experiments in addition to numerical computations.
Circulating gluten‐specific, but not CMV‐specific, CD39+ regulatory T cells have an oligoclonal TCR repertoire
Authors: Cook Laura , Munier C Mee Ling , Seddiki Nabila , Hardy Melinda Y , Anderson Robert P , Zaunders John , Tye‐Din Jason A , Kelleher Anthony D , van Bockel David
Published: January 2020

Objectives

Understanding the T cell receptor (TCR) repertoire of regulatory CD4+ T‐cell (Treg) populations is important for strategies aiming to re‐establish tolerance in autoimmune diseases. We studied circulating deamidated gluten‐epitope‐specific CD39+ Tregs in patients with coeliac disease following an oral gluten challenge, and we used cytomegalovirus (CMV)‐specific CD39+ Tregs from healthy controls as a comparator population.

Methods

We used the OX40 assay to isolate antigen‐specific Tregs by induced surface co‐expression of CD25, OX40 and CD39. RACE PCR amplification and Sanger sequencing of the TCR β chain were used to analyse repertoire diversity.

Results

We found that, following oral gluten challenge, circulating gluten‐specific CD39+ Tregs had an oligoclonal TCR repertoire that contained public clonotypes. Conversely, the TCR repertoire of CMV‐epitope‐specific CD39+ Tregs from healthy controls was polyclonal.

Discussion

These data indicate that a biased TCR repertoire is not inherent to CD39+ Tregs, and, in this case, is apparently driven by the HLA‐DQ2.5‐restricted deamidated gluten peptide in coeliac disease patients.

Conclusion

This is the first assessment of the TCR repertoire within circulating human Tregs specific for foreign antigen. These data enhance our understanding of antigen‐specific CD4+ responses in the settings of chronic inflammation and infection and may help guide immunomonitoring strategies for CD4+ T cell‐based therapies, particularly for coeliac disease.
HDL cholesterol is an independent predictor of β‐cell function decline and incident type 2 diabetes: A longitudinal study
Authors: Fiorentino Teresa V. , Succurro Elena , Marini Maria A. , Pedace Elisabetta , Andreozzi Francesco , Perticone Maria , Sciacqua Angela , Perticone Francesco , Sesti Giorgio
Published: January 2020

Background

Experimental evidence indicates that high‐density lipoprotein (HDL) may stimulate glucose uptake and improve β‐cell function. The aim of this study was to evaluate whether lower levels of HDL may affect the risk to develop type 2 diabetes.

Methods

Incident rate of type 2 diabetes and changes in insulin sensitivity and β‐cell function over 5.5‐year follow‐up were examined in 670 non‐diabetic subjects stratified in tertiles according to basal HDL levels.

Results

As compared to the highest tertile of HDL, individuals with lower levels of HDL have an increased risk to develop type 2 diabetes independently from several cardiometabolic risk factors (odds ratio: 2.88, 95% confidence interval: 1.05‐7.91), and exhibited a greater deterioration of β‐cell function, estimated by the disposition index, over 5.5‐year follow‐up. Conversely, changes in Matsuda index of insulin sensitivity over the follow‐up were not significantly different amongst the three HDL groups. In a multivariable regression analysis model including age, sex, waist circumference, triglycerides, total cholesterol, C‐reactive protein, fasting and 2‐hour post‐load glucose, family history of type 2 diabetes and smoking habit, HDL concentration at baseline was an independent predictor of β‐cell function decline over the follow‐up (β = .30, P = .0001). Mediation analysis showed that the association between lower HDL levels at baseline and increased risk of incident diabetes was mediated by β‐cell function deterioration during the follow‐up (t = −3.32, P = .001).

Conclusions

Subjects with lower levels of HDL have an increased risk to develop type 2 diabetes likely due to a greater β‐cell function decline over time.
Wrangling with p‐values versus effect sizes to improve medical decision‐making: A tutorial
Authors: Kraemer Helena C. , Neri Eric , Spiegel David
Published: January 2020

The most pervasive and damaging myth in clinical research is that the smaller the p‐value, the stronger the hypothesis. In reality, the p‐value primarily reflects the quality of research design decisions. The most common proposal to avoid misleading conclusions from clinical research requires the appropriate use of effect sizes, but which effect size, used when and how, is an open question. A solution is proposed for perhaps the most common problem in clinical research, the comparison between two populations, for example, comparison of two treatments in a randomized clinical trial or comparison of high risk versus low risk individuals in an epidemiological study: the success rate difference or equivalently the number needed to treat/take (NNT).
Important role of genetic drift in rapid polygenic adaptation
Authors: John Sona , Stephan Wolfgang
Published: January 2020

We analyzed a model to determine the factors that facilitate or limit rapid polygenic adaptation. This model includes population genetic terms of mutation and both directional and stabilizing selection on a highly polygenic trait in a diploid population of finite size. First, we derived the equilibrium distribution of the allele frequencies of the multilocus model by diffusion approximation. This formula describing the equilibrium allele frequencies as a mutation‐selection‐drift balance was examined by computer simulation using parameter values inferred for human height, a well‐studied polygenic trait. Second, assuming that a sudden environmental shift of the fitness optimum occurs while the population is in equilibrium, we analyzed the adaptation of the trait to the new optimum. The speed at which the trait mean approaches the new optimum increases with the equilibrium genetic variance. Thus, large population size and/or large mutation rate may facilitate rapid adaptation. Third, the contribution of an individual locus i to polygenic adaptation depends on the compound parameter , where is the effect size, the equilibrium frequency of the trait‐increasing allele of this locus, and . Thus, only loci with large values of this parameter contribute coherently to polygenic adaptation. Given that mutation rates are relatively small, this is more likely in large populations, in which the effects of drift are limited.
Plant community assembly in suburban vacant lots depends on earthmoving legacy, habitat connectivity, and current mowing frequency
Authors: Tsuzuki Yoichi , Koyanagi Tomoyo F. , Miyashita Tadashi
Published: January 2020

In suburban regions, vacant lots potentially offer significant opportunities for biodiversity conservation. Recently, in Japan, due to an economic recession, some previously developed lands have become vacant. Little is known, however, about the legacy of earlier earthmoving, which involves topsoil removal and ground leveling before residential construction, on plant community composition in such vacant lots. To understand (dis)assembly processes in vacant lots, we studied 24 grasslands in a suburban region in Japan: 12 grasslands that had experienced earthmoving and 12 that had not. We surveyed plant community composition and species richness, and clarified compositional turnover (replacement of species) and nestedness (nonrandom species loss) by distance‐based β‐diversities, which were summarized by PCoA analysis. We used piecewise structural equation modeling to examine the effects of soil properties, mowing frequency, past and present habitat connectivities on compositional changes. As a result, past earthmoving, mowing frequency, soil properties, and past habitat connectivity were found to be the drivers of compositional turnover. In particular, we found legacy effects of earthmoving: earthmoving promoted turnover from native grassland species to weeds in arable lands or roadside by altering soil properties. Mowing frequency also promoted the same turnover, implying that extensive rather than intensive mowing can modify the negative legacy effects and maintain grassland species. Decrease in present habitat connectivity marginally enhanced nonrandom loss of native grassland species (nestedness). Present habitat connectivity had a positive effect on species richness, highlighting the important roles of contemporary dispersal. Our study demonstrates that community assembly is a result of multiple processes differing in spatial and temporal scales. We suggest that extensive mowing at local scale, as well as giving a high conservation priority to grasslands with high habitat connectivity at regional scale, is the promising actions to maintain endangered native grassland species in suburban landscapes with negative legacy effects of earthmoving.
Review on Recent Advances of Cathode Materials for Potassium‐ion Batteries
Authors: Sha Mo , Liu Long , Zhao Huaping , Lei Yong
Published: January 2020

Potassium‐ion batteries (PIBs) as a promising supplement to lithium‐ion batteries have drawn great attention attributing to the abundant potassium resources, the fast‐ionic conductivity of potassium ions in electrolyte, and the low standard redox potential of potassium. However, the development of PIBs is still in its infancy, which is largely restricted by the fact that the electrode materials, especially the cathode materials of PIBs, are far from satisfactory in practical applications regarding the capacity, voltage, and cycle life. Therefore, most of current research efforts have been devoted to exploring new and high‐performance electrode materials for achieving PIBs with high capacity and voltage as well as excellent cyclability. In this review, the recent advancements on cathode materials for PIBs are specially summarized. Besides, technological developments, scientific challenges, and future research opportunities of cathode materials for PIBs are also briefly outlooked.
Dynamic Gold(I) Complexes of Hexa‐tert‐butyl‐octaphosphane
Authors: Grell Toni , Hey‐Hawkins Evamarie
Published: January 2020

A facile synthesis for {cyclo‐(P4tBu3)}2 (1) is reported making the phosphane available for follow‐up chemistry. Octaphosphane 1 reacts with [AuCl(tht)] (tht = tetrahydrothiophene) to give a monometallic {[AuCl(1‐κ2P2,P4')], 2}, bimetallic {[(AuCl)2(1‐κ2P2,P4',κP2')], 3} and trimetallic complex {[(AuCl)3(1‐κ2P2,P4',κP2',κP4)], 4} in which up to four phosphorus atoms of the ligand are involved in coordination. In each of these complexes one gold(I) atom is chelated in an unusual distorted T‐shaped coordination mode which undergoes a rapid exchange between both donor atoms in solution. This mode of coordination in combination with the flexibility of the phosphane ligand moreover gives rise to an interesting dynamic behavior of the monometallic complex 2 which was elucidated by NMR spectroscopy, X‐ray crystallography and DFT calculations.
The Effects of Structural Modifications of Bis‐tert‐alcohol‐Functionalized Crown‐Calix[4]arenes as Nucleophilic Fluorination Promotors and Relations with Computational Predictions
Authors: Han Hae Ji , Lee Sung‐Sik , Kang Seok Min , Kim Yerin , Park Chanho , Yoo Suah , Kim Chul Hee , Oh Young‐Ho , Lee Sungyul , Kim Dong Wook
Published: January 2020

We prepared four structurally modified bis‐tert‐alcohol functionalized crown ether‐strapped calix[4]arene promoters, that is, bis‐tert‐alcohol functionalized crown‐5‐calix[4]arene (BA5C), bis‐tert‐alcohol functionalized crown‐7‐calix[4]arene (BA7C), bis‐1,1‐dimethylbutanol functionalized crown 6‐calix[4]arene (B3A6C), and bis‐1,1‐dimethylhexanol functionalized crown 6‐calix[4]arene (B5AC6C). Nucleophilic fluorinations were conducted using alkali metal fluorides to investigate phase‐transfer catalytic activities with respect to the sizes of crown ether‐strapped calix[4]arene (CEC) subunits and lengths of alkyl chain spacers between tert‐alcohol and CEC subunits. The reactivity of potassium fluoride was significantly enhanced by BA5C promoter because its crown‐5‐calix[4]arene subunit had cavity size appropriate for K+ capture. In contrast, BA7C did not efficiently enhance cesium fluoride SN2 fluorination because its crown‐7‐calix[4]arene cavity was too large to capture Cs+. The alkyl spacer of bis‐tert‐alcohol functionalized CEC provided sufficient distance between F– and Cs+. In particular, the three‐component alkyl carbon chain of B3A6C was optimal in terms of increasing CsF reactivity. Systematic quantum chemical analysis predicted that fluorination reactions facilitated by bis‐tert‐alcohol‐substituted crown‐6‐calix[4]arene (BACCA) and B3A6C might proceed via separated ion‐pair type pre‐reaction complexes, which suggested that these two promotors act as Lewis bases that essentially separate CsF ion‐pairs. The lower (by 0.4 kcal/mol) Gibbs free energy of activation for the reaction promoted by B3A6C than that facilitated by BACCA concurred with the experimentally observed slightly greater efficiency of B3A6C than BACCA.
Create monthly newsletter to engage graduate students
Authors: Pavlik Amelia
Published: January 2020

Lab, class, sleep — repeat. This phrase probably describes a daily routine for many of your graduate students. That's one of the reasons the University of Miami Graduate School created a newsletter to reach its target audience.
Persistent sodium current blockers can suppress seizures caused by loss of low‐threshold D‐type potassium currents: Predictions from an in silico study of Kv1 channel disorders
Authors: Du Jiaxin , Vegh Viktor , Reutens David C.
Published: January 2020

Objective

Ion channels belonging to subfamily A of voltage‐gated potassium channels (Kv1) are highly expressed on axons, where they play a key role in determining resting membrane potential, in shaping action potentials, and in modulating action potential frequency during repetitive neuronal firing. We aimed to study the genesis of seizures caused by mutations affecting Kv1 channels and searched for potential therapeutic targets.

Methods

We used a novel in silico model, the laminar cortex model (LCM), to examine changes in neuronal excitability and network dynamics associated with loss‐of‐function mutations in Kv1 channels. The LCM simulates the activities of a network of tens of thousands of interconnected neurons and incorporates the kinetics of 11 types of ion channel and three classes of neurotransmitter receptor. Changes in two types of potassium currents conducted by Kv1 channels were examined: slowly inactivating D‐type currents and rapidly inactivating A‐type currents. Effects on neuronal firing rate, action potential shape, and neuronal oscillation state were evaluated. A systematic parameter scan was performed to identify parameter changes that can reverse the effects of the changes.

Results

Reduced axonal D‐type currents led to lower firing threshold and widened action potentials, both lowering the seizure threshold. Two potential therapeutic targets for treating seizures caused by loss‐of‐function changes in Kv1 channels were identified: persistent sodium channels and NMDA receptors. Blocking persistent sodium channels restored the firing threshold and reduced action potential width. NMDA receptor antagonists reduced excitatory postsynaptic currents from excessive glutamate release related to widened action potentials.

Significance

Riluzole reduces persistent sodium currents and excitatory postsynaptic currents from NMDA receptor activation. Our results suggest that this FDA‐approved drug can be repurposed to treat epilepsies caused by mutations affecting axonal Kv1 channels.
Experimental study and application of medium‐length hole blasting technique in coal‐rock roadway
Authors: Ding Ziwei , Jia Jindui , Li Xiaofei , Li Ji , Li Yulong , Liao Jinglong
Published: January 2020

In this study, mechanical mechanism analyses of hole cut blasting and in situ hole cut blasting tests using different cutting programs were conducted to investigate the hole cut blasting mechanism under the influence of complicated geological conditions and its blasting excavation effect. The hole cut blasting mechanism was evaluated under the background of medium‐length hole cut blasting test in a typical coal‐rock roadway in Xiayukou coal mine of Hancheng mining area in Western China to improve the blasting excavation efficiency in coal mine roadways. Test results indicated that the rock clamping action is remarkably enhanced when the depth of medium‐length holes, which are impacted by various complicated geological factors, reaches more than 1.8 m under weak coal‐rock mass conditions. At the same time, the antidrag effect is good when double‐wedge cut blasting is selected, and its mitigation of rock clamping action is reflected through the reduction of rock resistance of phase I hole cut blasting. The enhanced blasting effect is embodied by the footage cycle and forming effect of blasting, and the footage cycle of single blasting increases from 1.6 to 2.0 m, thereby indicating its remarkable economic benefits. The results of this study can provide a reference for hole cut blasting design and mechanism study of weak coal‐rock masses under complicated geological conditions.
Auf verlässlichen Karrierewegen zu mehr forschenden Fachärzten
Authors: Deggerich Anke , Picht Eckard
Published: January 2020

An 13 Medizinischen Fakultäten fördert die DFG Clinician Scientist‐Programme / Neue Impulse durch wissenschaftliche Qualifizierung parallel zur Facharztweiterbildung
The genesis of high Ba‐Sr adakitic rocks: Insights from an Early Cretaceous volcanic suite in the central North China Craton
Authors: Xue Fei , Santosh M. , Tsunogae Toshiaki , Yang Fan , Zhou Hongying
Published: January 2020

The origin of high Ba‐Sr magmatic suites with adakitic features has remained controversial, although they provide important clues on the evolution of continental lithosphere. Here, we present petrological, geochemical, zircon U–Pb and Lu‐Hf data from an Early Cretaceous volcanic suite of andesitic‐dacitic composition in the Laiyuan complex of the central North China Craton, with a view to gain insights on the magma source, petrogenesis, and tectonic implications. The volcanic suite represented by rocks of andesitic‐dacitic composition shows enrichment in light rare earth elements (LREE) and large‐ion lithophile elements (LILE), and depletion in high‐field‐strength elements (HFSE) with no obvious Eu anomalies. They also show typical adakitic features such as high Sr/Y and La/Yb ratios, as well as high Ba‐Sr concentrations. Zircon U–Pb geochronology indicates that these rocks were formed in Early Cretaceous during 131 to 127 Ma, with εHf(t) values ranging from −23.5 to −19.4, suggesting enriched lithospheric mantle source. The geochemical and isotopic data show that the enriched lithospheric mantle source experienced fluid‐related subduction metasomatism. The distinct geochemical features of these identified in our study including high Ba‐Sr concentrations and adakitic affinities were not only inherited from their magma source, but are also a result of fractional crystallization during magma evolution including amphibole‐dominated fractional crystallization at depth and limited plagioclase removal. The volcanism in the Taihang Mountains occurred under extensional regime triggered by the subduction and rollback of the Paleo‐Pacific slab during Late Jurassic to Early Cretaceous and consequent thermal‐mechanical erosion of the lithospheric mantle.