bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enantioselective Catalyst Systems from Copper(II) Triflate and BINOL–Silanediol
Authors: Guan Yong , Attard Jonathan W. , Visco Michael D. , Fisher Thomas J. , Mattson Anita E. 
Published: March 2018

AbstractSilanediol and copper catalysis are merged, for the first time, to create an enhanced Lewis acid catalyst system for enantioselective heterocycle functionalization. The promise of this silanediol and copper catalyst combination is demonstrated in the enantioselective addition of indoles to alkylidene malonates to give rise to the desirable adducts in excellent yield and high enantiomeric excess. From these studies, 1,1′‐bi‐2‐naphthol (BINOL)‐based silanediols emerge as one‐of‐a‐kind cocatalysts. Their potential role in the reaction pathway is also discussed.
Catalytic Hydrodefluorination of C−F Bonds by an Air‐Stable PIII Lewis Acid
Authors: Chitnis Saurabh S. , Krischer Felix , Stephan Douglas W. 
Published: March 2018

AbstractCatalytic hydrodefluorination (HDF) of unactivated fluoroalkanes or CF3‐substituted aryl species is performed using the PIII Lewis acids, [(bipy)PPh]2+ (12+) and [(terpy)PPh]2+ (22+) under mild conditions (25 or 50 °C). Mechanistic studies indicate that activation of C−F bond by the PIII center is key. Particularly noteworthy is that the catalyst 2[B(C6F5)4]2 is air‐stable and readily accessible from bench‐stable, commercially available reagents in one‐step and can be used without isolation.
Amino acids as chiral derivatizing agents for antiproliferative substituted N‐benzyl isoindolinones
Authors: Grigoreva Tatyana A. , Novikova Daria S. , Gureev Maxim A. , Garabadzhiu Alexander V. , Tribulovich Vyacheslav G. 
Published: March 2018

AbstractThe absolute configurations of the diastereomers of novel amino acid ester derivatives of 2,3‐substituted isoindolinones, which are known as apoptosis activators due to their ability to inhibit the MDM2‐p53 PPI, were assigned using NMR and computational methods. Procedures for diastereomer separation and determining the absolute configuration were developed to perform the study. The high significance of N‐benzyl fragment for the determination of the diastereomer absolute configuration by NMR methods was established; it is determined by a number of factors inherent in this fragment and the structural features of the studied substrates. Analysis of the individual isomer activity showed that the target inhibitory effect of S‐ and R‐isoindolinone L‐valinates differs by less than 20%. It can be explained by the presence of a flexible linker between the isoindolinone core and amino acid fragment, which provides the optimal arrangement of the molecule in the hydrophobic cavity of MDM2 for both isomers.
Process Control and Yield Enhancement of the Galacto‐Oligosaccharide Formation
Authors: Mueller Ines , Kiedorf Gregor , Runne Eike , Pottratz Ines , Seidel‐Morgenstern Andreas , Hamel Christof 
Published: March 2018

AbstractAs lactose is an increasing by‐product of dairy industry, the selective conversion to prebiotic galacto‐oligosaccharides (GOSs) by the enzyme β‐galactosidase represents a highly attractive value creation. The synthesis of GOSs is characterized by an equilibrium‐limited reaction, which can be overcome by a coupling with an enzymatic reduction of the side product glucose to achieve an increase in product yield. Furthermore, the effect of substrate substitution based on sweet whey and the impact of whey‐dominating salt ions was examined, leading to a further process intensification of GOS synthesis.
Modeling and Design of a Catalytic Wall Reactor for the Methanation of Carbon Dioxide
Authors: Gruber Manuel , Wieland Christoph , Habisreuther Peter , Trimis Dimosthenis , Schollenberger Dominik , Bajohr Siegfried , vonMorstein Olaf , Schirrmeister Steffen 
Published: March 2018

AbstractMicroprocess engineering is an alternative approach to design reactors for CO2 methanation, which are used in power‐to‐gas applications. Microreactors offer advantages, e.g., in terms of heat removal. In the present work, design criteria evolved from transport phenomena are applied to derive preliminary reactor dimensions. The developed 1D model is used for parametric studies and reveals heat transport as limiting factor. More detailed 3D models confirm the results and demonstrate the effect of the metal matrix on heat transport. For further optimization a multi‐stage reactor design is proposed.
Abwarten und Bärentraubenblätter‐Tee trinken – mit Arbutin
Authors: Dietrich Corinna , Munzert Viola , Zeller Klaus‐Peter , Siehl Hans‐Ullrich , Berger Stefan , Sicker Dieter 
Published: March 2018

ZusammenfassungDie Blätter der Echten Bärentraube enthalten das Hydrochinon‐Glucosid Arbutin. Als Prodrug wird es erst im Körper zu einer pharmakologisch wirksamen Substanz metabolisiert, dem Aglykon Hydrochinon. Daher wirkt ein Bärentraubenblätter‐Kaltauszug als Hausmittel gegen einfache Formen der Blasenentzündung. Weniger bekannt ist, dass Arbutin auch in Kosmetika gegen Hyperpigmentierungs‐Störungen der Haut angewendet wird. Arbutin wurde frühzeitig strukturell aufgeklärt und synthetisiert. Wir beschreiben seine Isolierung und interpretieren den gesamten Spektrensatz als Musterbeispiel für ein einfaches β‐D‐Glucosid. Dieser Beitrag basiert auf einer Bachelorarbeit.
Dynamic control of arabinose and xylose utilization inE. coli
Authors: Choudhury Debika , Gayen Kalyan , Saini Supreet 
Published: March 2018

AbstractThe common bacteriumEscherichia coli(E. coli) can utilize the pentose sugars arabinose and xylose for growth and energy. When fed both these sugars, the bacterium preferentially utilizes arabinose and only when all the arabinose is exhausted from the media does it start to use xylose. This hierarchical utilization of the two sugars is dictated by two proteins: AraC and XylR. These proteins act as controllers of sugar utilization and dictate the timing and rate of utilization of these sugars. While the biochemical interactions defining individual arabinose and xylose utilization systems are well understood, it is not completely understood how the hierarchical utilization is maintained by the bacterium, and how the regulatory crosstalk between the two systems facilitates this hierarchy. To help answer these questions, in this work, we systematically experimentally characterize the regulatory crosstalk between the two sugar utilization systems.Our work demonstrates extensive interaction between the two sugar systems. Specifically, data from our experiments suggest that the xylose system can regulate arabinose gene expression and consequently, cellular physiology dynamically via promiscuous transport and maybe through cross interactions between regulator and non‐cognate sugar. Put together, we demonstrate that arabinose and xylose utilization networks exhibit an example of distributed control in a biological system. This design likely ensures that the system does not fail under perturbations (mutations). Our results help understand multi‐process control in biological systems and bring to light design criteria for synthetic biology applications.
Transport effects and chemical effects on NO removal by SCR with NH3over iron‐based catalyst in a magnetically fluidized bed
Authors: Yao Gui‐huan , Gui Ke‐ting , Ling Xiang 
Published: March 2018

AbstractSelective catalytic reduction (SCR) of NO by NH3on iron‐based catalysts was investigated with a magnetically fluidized bed (MFB). Magnetic fields promoted the NO conversion. The optimal efficiency of 95 % was attained under a magnetic field of 0.01–0.015 T at 250 °C. Magnetic fields yielded transport effects and chemical effects on SCR of NO over Fe2O3catalyst. The transport effects are reflected by the enhancement of physical transfer in a MFB. Magnetic fields can check and eliminate bubbles, increase gas‐solid contact probabilities, and thereby improve heat and mass transfer characteristics in a MFB. The chemical effects can be summarized into three points. First, the magnetization ofγ‐Fe2O3by uniform magnetic fields gives rise to boundary effects, which results in Faraday force on paramagnetic NO molecules and yields NO movement to the catalyst surface, and hence increases NO chemisorption. Second, the synergy of magnetic fields and ferrimagnetic iron‐based catalyst can boost the transformation of antimagnetic reactant into paramagnetic products, and accelerate electron transport in the reaction, which enhances the activation of NH3on magnetic Fe (III) sites. Third, magnetic fields can alter the energy dispersal of a free radicals reaction system, and thereby promotes the free radicals reaction between NH2· and NO·.
Homogeneous Light‐Driven Catalytic Direct Carboxylation with CO2
Authors: Tan Fen , Yin Guoyin 
Published: March 2018

AbstractCarbon dioxide is a ubiquitous and inexpensive one‐carbon source for chemical synthesis, and the efficient incorporation of CO2 into organic molecules is of widespread research interest both for economic and ecological reasons. The methodologies to employ carbon dioxide as a single‐carbon unit to construct molecules relevant for agrochemical and pharmaceutical research include many elegant approaches, including asymmetric transformations. Even though remarkable achievements have been made in the field of light‐driven catalysis, especially photoredox catalysis, homogeneous light‐driven catalytic carboxylation by employing CO2 as the key reagent has only become a subject of increasing attention in recent years. Therefore, this concise review will discuss the latest advances in this research area.
A defined, plant‐based diet utilized in an outpatient cardiovascular clinic effectively treats hypercholesterolemia and hypertension and reduces medications
Authors: Najjar Rami S. , Moore Carolyn E. , Montgomery Baxter D. 
Published: March 2018

BackgroundCardiovascular disease (CVD) is a major economic burden in the United States. CVD risk factors, particularly hypertension and hypercholesterolemia, are typically treated with drug therapy. Five‐year efficacy of such drugs to prevent CVD is estimated to be 5%. Plant‐based diets have emerged as effective mitigators of these risk factors.HypothesisThe implementation of a defined, plant‐based diet for 4 weeks in an outpatient clinical setting may mitigate CVD risk factors and reduce patient drug burden.MethodsParticipants consumed a plant‐based diet consisting of foods prepared in a defined method in accordance with a food‐classification system. Participants consumed raw fruits, vegetables, seeds, and avocado. All animal products were excluded from the diet. Participant anthropometric and hemodynamic data were obtained weekly for 4 weeks. Laboratory biomarkers were collected at baseline and at 4 weeks. Medication needs were assessed weekly. Data were analyzed using paired‐samples t tests and 1‐way repeated‐measures ANOVA.ResultsSignificant reductions were observed for systolic (−16.6 mmHg) and diastolic (−9.1 mmHg) blood pressure (P < 0.0005), serum lipids (P ≤ 0.008), and total medication usage (P < 0.0005). Other CVD risk factors, including weight (P < 0.0005), waist circumference (P < 0.0005), heart rate (P = 0.018), insulin (P < 0.0005), glycated hemoglobin (P = 0.002), and high‐sensitivity C‐reactive protein (P = 0.001) were also reduced.ConclusionA defined, plant‐based diet can be used as an effective therapeutic strategy in the clinical setting to mitigate cardiovascular risk factors and reduce patient drug burden.
Lipid profile and incidence of atrial fibrillation: A prospective cohort study in China
Authors: Li Xintao , Gao Lianjun , Wang Zhao , Guan Bo , Guan Xumin , Wang Binhao , Han Xu , Xiao Xianjie , Waleed Khalid Bin , Chandran Clarance , Wu Shouling , Xia Yunlong 
Published: March 2018

BackgroundThe association between dyslipidemia, a major risk factor for cardiovascular diseases, and atrial fibrillation (AF) is not clear because of limited evidence.Hypothesis.Dyslipidemia may be associated with increased risk of AF in a Chinese population.MethodsA total of 88 785 participants free from AF at baseline (2006–2007) were identified from the Kailuan Study. Fasting levels of total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), and triglycerides (TG) were measured at baseline using standard procedures. The study population was stratified based on quartiles of lipid profile. Incident AF was ascertained from electrocardiograms at biennial follow‐up visits (2008–2015). The associations between incident AF and the different lipid parameters (TC, LDL‐C, HDL‐C, and TG) were assessed by Cox proportional hazards regression analysis.ResultsOver a mean follow‐up period of 7.12 years, 328 subjects developed AF. Higher TC (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.43‐0.84) and LDL‐C (HR: 0.60, 95% CI: 0.43‐0.83) levels were inversely associated with incident AF after multivariable adjustment. HDL‐C and TG levels showed no association with newly developed AF. The results remained consistent after exclusion of individuals with myocardial infarction or cerebral infarction, or those on lipid‐lowering therapy. Both TC/HDL‐C and LDL‐C/HDL‐C ratios were inversely associated with risk of AF (per unit increment, HR: 0.88, 95% CI: 0.79‐0.98 and HR: 0.77, 95% CI: 0.66‐0.91, respectively).ConclusionsTC and LDL‐C levels were inversely associated with incident AF, whereas no significant association of AF with HDL‐C or TG levels was observed.
Low‐density lipoprotein‐cholesterol lowering in individuals at intermediate cardiovascular risk: Percent reduction or target level?
Authors: Cesena Fernando H. Y. , Laurinavicius Antonio Gabriele , Valente Viviane A. , Conceição Raquel D. , Santos Raul D. , Bittencourt Marcio S. 
Published: March 2018

BackgroundRecommendations for blood cholesterol management differ across different guidelines.HypothesisLipid‐lowering strategies based on low‐density lipoprotein‐cholesterol (LDL‐c) percent reduction or target concentration may have different effects on the expected cardiovascular benefit in intermediate‐risk individuals.MethodsWe selected individuals between 40 and 75 years of age with 10‐year risk for atherosclerotic cardiovascular disease (ASCVD) between 5.0% and <7.5% who underwent a routine health screening. For every subject, we simulated a strategy based on a 40% LDL‐c reduction (S40%) and another strategy based on achieving LDL‐c target ≤100 mg/dL (Starget‐100). The cardiovascular benefit was estimated assuming a 22% relative risk reduction in major cardiovascular events for each 39 mg/dL of LDL‐c lowered.ResultsThe study comprised 1756 individuals (94% men, 52 ± 5 years old). LDL‐c and predicted 10‐year ASCVD risk would be slightly lower in S40% compared to Starget‐100. The number needed to treat to prevent 1 major cardiovascular event in 10 years (NNT10) would be 56 with S40% and 66 with Starget‐100. S40% would prevent more events in individuals with lower baseline LDL‐c, whereas Starget‐100 would be more protective in those with higher LDL‐c. A dual‐target strategy (40% minimum LDL‐c reduction and achievement of LDL‐c ≤100 mg/dL) would be associated with outcomes similar to those expected with the S40% (NNT10 = 55).ConclusionsIn an intermediate‐risk population, cardiovascular benefit from LDL‐c lowering may be optimized by tailoring the treatment according to the baseline LDL‐c or by setting a dual‐target strategy (fixed dose statin plus achievement of target LDL‐c concentration).
Is exercise stress echocardiography useful in patients with suspected obstructive coronary artery disease who have resting left bundle branch block?
Authors: Xu Bo , Dobson Laura , Mottram Philip M. , Nasis Arthur , Cameron James , Moir Stuart 
Published: March 2018

BackgroundCurrent guidelines support exercise stress echocardiography (ESE) for evaluation of suspected obstructive coronary artery disease (OCAD) in ambulant patients with left bundle branch block (LBBB). Data regarding the diagnostic utility of ESE in patients with LBBB are limited.HypothesisWe hypothesized that the diagnostic performance of ESE for the assessment of suspected OCAD is reduced in the context of LBBB.MethodsWe studied 191 consecutive patients with resting LBBB undergoing ESE for the investigation of suspected OCAD between 2008 and 2015 at our center. The studies were categorized as inconclusive, normal, or abnormal. Patients with an abnormal response were subcategorized as regional ischemic response or globally abnormal.ResultsEighty‐two patients (43%) demonstrated a normal left ventricular contractile response (LVCR) to exercise; 92 (48%) developed an abnormal LVCR to exercise, including 70 patients with globally abnormal and 22 patients with regional ischemic responses. Of the patients with abnormal responses, 62 patients had anatomic imaging, only 29 of whom had significant OCAD, conferring an overall specificity of ESE for significant OCAD of 21% and accuracy of 52%. Of patients who developed a regionally abnormal response, 89% had significant OCAD.ConclusionsFor patients with LBBB who develop a globally abnormal LVCR during ESE, the specificity of ESE for reliably excluding significant OCAD is significantly reduced. ESE appears to be a suboptimal test for the evaluation of OCAD in patients with resting LBBB, as about 50% of patients will have an abnormal response, the majority due to globally abnormal contraction where OCAD cannot be reliably diagnosed. Alternative testing should be considered for the investigation of suspected OCAD in patients with resting LBBB.
Genetic diagnosis of familial hypercholesterolemia is associated with a premature and high coronary heart disease risk
Authors: Séguro Florent , Rabès Jean‐Pierre , Taraszkiewicz Dorota , Ruidavets Jean‐Bernard , Bongard Vanina , Ferrières Jean 
Published: March 2018

BackgroundFamilial hypercholesterolemia (FH) is a common autosomal dominant disease associated with premature coronary heart disease (CHD). Studies tend to show that patients with FH associated with an identified mutation (mutation+ FH) are at higher risk than patients without an identified mutation (mutation– FH). We compared the clinical and biological profile and the risk of CHD in patients with mutation+ FH and mutation– FH.HypothesisIn addition to LDL‐C, a pathogenic mutation predicts premature CHD in FH.MethodsWe successively included all patients with suspected FH (LDL‐C > 190 mg/dL if age > 18 years; LDL‐C > 160 mg/dL if age < 18 years) and compared patients with a pathogenic mutation with those without an identified pathogenic mutation.ResultsWe studied 179 patients with mutation+ FH and 147 with mutation– FH. The mean age was 44 (± 18) years. The lipid profile was more atherogenic in those with mutation+ FH, who had higher LDL‐C (254 ± 69 mg/dL vs 218 ± 35 mg/dL; P < 0.01) and lower HDL‐C (53 ± 14 mg/dL vs 58 ± 17 mg/dL; P < 0.01). Despite the more atherogenic nonlipid cardiovascular profile of patients with mutation– FH, the age of CHD onset was earlier in patients with mutation+ FH (48 vs 56 years; P = 0.026). After multiple adjustment, the presence of a positive mutation was significantly associated with premature CHD (OR: 3.0, 95% CI: 1.38‐6.55, P < 0.01).ConclusionsPatients with mutation+ FH have a more atherogenic lipid profile and a 3‐fold higher risk of premature CHD, as well as earlier onset of CHD, than patients with mutation– FH.
Natural Polyphenols Selectively Inhibit β‐Carbonic Anhydrase from the Dandruff‐Producing Fungus Malassezia globosa: Activity and Modeling Studies
Authors: Nocentini Alessio , Bua Silvia , Del Prete Sonia , Heravi Yeganeh Entezari , Saboury Ali A. , Karioti Anastasia , Bilia Anna Rita , Capasso Clemente , Gratteri Paola , Supuran Claudiu T. 
Published: March 2018

AbstractAround 50 % of the worldwide population is affected by dandruff, which is triggered by a variety of factors. The yeast Malassezia globosa has been labeled as the most probable causative agent for the onset of dandruff. The β‐carbonic anhydrase (CA) of MgCA was recently validated as an anti‐dandruff target, with its inhibition being responsible for in vivo growth defects in the fungus. As classical CA inhibitors of the sulfonamide type give rise to permeability problems through biological membranes, finding non‐sulfonamide alternatives for MgCA inhibition is of considerable interest in the cosmetic field. We recently screened a large library of human (h) CA inhibitors for MgCA inhibition, including different chemotypes, such as monothiocarbamates, dithiocarbamates, phenols, and benzoxaboroles. Herein, we expanded the research toward new MgCA inhibitors by considering a set of natural polyphenols (including flavones, flavonols, flavanones, flavanols, isoflavones, and depsides) that exhibited MgCA inhibitory activity in the micromolar range, as well as selectivity for the fungal isozyme over off‐target human isoforms. The binding mode of representative derivatives within the MgCA catalytic cleft was investigated by docking studies using a homology‐built model.
Synthesis, Pharmacological Evaluation, and Docking Studies of Novel Pyridazinone‐Based Cannabinoid Receptor Type 2 Ligands
Authors: Ragusa Giulio , Bencivenni Serena , Morales Paula , Callaway Tyra , Hurst Dow P. , Asproni Battistina , Merighi Stefania , Loriga Giovanni , Pinna Gerard A. , Reggio Patricia H. , Gessi Stefania , Murineddu Gabriele 
Published: March 2018

AbstractIn recent years, cannabinoid type 2 receptors (CB2R) have emerged as promising therapeutic targets in a wide variety of diseases. Selective ligands of CB2R are devoid of the psychoactive effects typically observed for CB1R ligands. Based on our recent studies on a class of pyridazinone 4‐carboxamides, further structural modifications of the pyridazinone core were made to better investigate the structure–activity relationships for this promising scaffold with the aim to develop potent CB2R ligands. In binding assays, two of the new synthesized compounds [6‐(3,4‐dichlorophenyl)‐2‐(4‐fluorobenzyl)‐cis‐N‐(4‐methylcyclohexyl)‐3‐oxo‐2,3‐dihydropyridazine‐4‐carboxamide (2) and 6‐(4‐chloro‐3‐methylphenyl)‐cis‐N‐(4‐methylcyclohexyl)‐3‐oxo‐2‐pentyl‐2,3‐dihydropyridazine‐4‐carboxamide (22)] showed high CB2R affinity, with Ki values of 2.1 and 1.6 nm, respectively. In addition, functional assays of these compounds and other new active related derivatives revealed their pharmacological profiles as CB2R inverse agonists. Compound 22 displayed the highest CB2R selectivity and potency, presenting a favorable in silico pharmacokinetic profile. Furthermore, a molecular modeling study revealed how 22 produces inverse agonism through blocking the movement of the toggle‐switch residue, W6.48.
Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of Macrophage Migration Inhibitory Factor
Authors: Trivedi‐Parmar Vinay , Robertson Michael J. , Cisneros José A. , Krimmer Stefan G. , Jorgensen William L. 
Published: March 2018

AbstractMacrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is implicated in the regulation of inflammation, cell proliferation, and neurological disorders. MIF is also an enzyme that functions as a keto–enol tautomerase. Most potent MIF tautomerase inhibitors incorporate a phenol, which hydrogen bonds to Asn97 in the active site. Starting from a 113‐μm docking hit, we report results of structure‐based and computer‐aided design that have provided substituted pyrazoles as phenol alternatives with potencies of 60–70 nm. Crystal structures of complexes of MIF with the pyrazoles highlight the contributions of hydrogen bonding with Lys32 and Asn97, and aryl–aryl interactions with Tyr36, Tyr95, and Phe113 to the binding.