bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of quartz on crystallization behavior of mold fluxes and microstructural characteristics of flux film
Authors: Lei Liu , Xiuli Han , Mingduo Li , Di Zhang 
Published: September 2018

Background: Mold fluxes are mainly prepared using cement clinker, quartz, wollastonite, borax, fluorite, soda ash and other mineral materials. Quartz, as one of the most common and essential materials, was chosen for this study to analyze itseffects on crystallization temperature, critical cooling rate, crystal incubation time, crystallization ratio and phases of flux film. Methods: We used the research methods of process mineralogy with the application of the single hot thermocouple technique, heat flux simulator, polarizing microscope, X-ray diffraction, etc. Results: By increasing the quartz content from 16 mass% to 24 mass%, the crystallization temperature, critical cooling rate and crystallization ratio of flux film decreased, and the crystal incubation time was extended. Meanwhile, the mineralogical structure of the flux film changed, with a large amount of wollastonite precipitation and a significant decrease in the cuspidine content until it reached zero. This showed a steady decline in the heat transfer control capacity of the flux film. Conclusions: The reason for the results above is that, by increasing the quartz content, the silicon-oxygen tetrahedron network structure promoted a rise in viscosity and restrained ion migration, inhibiting crystal nucleation and growth, leading to the weakening of the crystallization and a decline in the crystallization ratio.
Using bioinformatics tools for the discovery of Dengue RNA-dependent RNA polymerase inhibitors
Authors: Nncube Nomagugu B. , Ramharack Pritika , Soliman Mahmoud E.S. 
Published: September 2018

BackgroundDengue fever has rapidly manifested into a serious global health concern. The emergence of various viral serotypes has prompted the urgent need for innovative drug design techniques. Of the viral non-structural enzymes, the NS5 RNA-dependent RNA polymerase has been established as a promising target due to its lack of an enzymatic counterpart in mammalian cells and its conserved structure amongst all serotypes. The onus is now on scientists to probe further into understanding this enzyme and its mechanism of action. The field of bioinformatics has evolved greatly over recent decades, with updated drug design tools now being publically available.MethodsIn this study, bioinformatics tools were used to provide a comprehensive sequence and structural analysis of the two most prominent serotypes of Dengue RNA-dependent RNA polymerase. A list of popularflavivirusinhibitors were also chosen to dock to the active site of the enzyme. The best docked compound was then used as a template to generate a pharmacophore model that may assist in the design of target-specific Dengue virus inhibitors.ResultsComparative sequence alignment exhibited similarity between all three domains of serotype 2 and 3.Sequence analysis revealed highly conserved regions at residues Meth530, Thr543 Asp597, Glu616, Arg659 and Pro671. Mapping of the active site demonstrated two highly conserved residues: Ser710 and Arg729. Of the active site interacting residues, Ser796 was common amongst all ten docked compounds, indicating its importance in the drug design process. Of the ten dockedflavivirusinhibitors, NITD-203 showed the best binding affinity to the active site. Further pharmacophore modeling of NITD-203 depicted significant pharmacophoric elements that are necessary for stable binding to the active site.DiscussionThis study utilized publically available bioinformatics tools to provide a comprehensive framework on Dengue RNA-dependent RNA polymerase. Based on docking studies, a pharmacophore model was also designed to unveil the crucial pharmacophoric elements that are required when constructing an efficacious DENV inhibitor. We believe that this study will be a cornerstone in paving the road toward the design of target-specific inhibitors against DENV RdRp.
Effectiveness of winter temperatures for satisfying chilling requirements for reproductive budburst of red alder (Alnus rubra)
Authors: Prevéy Janet S. , Harrington Constance A. 
Published: September 2018

Background
Experiencing an adequate amount of cold temperatures over winter is necessary for many temperate tree species to break dormancy and flower in spring. Thus, changes in winter and spring temperatures associated with climate change may influence when trees break dormancy and flower in the future. There have been several experimental studies that have quantified the effectiveness of cold temperatures for chilling requirements for vegetative budburst of temperate trees; however, there are few experimental studies addressing the chilling requirements for reproductive budburst of trees, as it is difficult to place reproductively mature trees in temperature-controlled environments.

Methods
To identify how changing temperatures associated with climate change may impact reproductive phenology, we completed a temperature-controlled growth chamber experiment using cuttings of reproductive branches of red alder (Alnus rubra), one of the most widespread hardwood tree species of the Pacific Northwest, USA. The purpose of this study was to examine how colder (4 °C) and warmer (9 °C) winter temperature regimes influenced the timing of reproductive budburst of red alder cuttings in spring. We also compared the date of budburst of cuttings to that of branches from intact trees.

Results
We found that cuttings flowered earlier after pretreatment with a 4 °C winter temperature regime than after a 9 °C winter temperature regime. We found no significant differences between the timing of male budburst of cuttings exposed to ambient conditions compared to male budburst of branches from intact trees. We used our experimental data to estimate a “possibility-line” that shows the accumulated chilling and forcing temperatures necessary prior to reproductive budburst of red alder.

Discussion
This study provides a preliminary indication that warmer winters with climate change may not be as effective as colder winters for satisfying chilling temperature requirements of a Northwest hardwood tree species.
In silico study of medical decision-making for rare diseases: heterogeneity of decision-makers in a population improves overall benefit
Authors: Wang Juan , Yamada Ryo 
Published: September 2018

BackgroundMedical decision-making is difficult when information is limited due to its rareness. For example, there are two treatment options for patients affected by a rare disease with high lethality. The information about both treatment effects is unavailable or very limited. Patients are inclined to accept one of the interventions rather than waiting for death, but they are reluctant to be assigned the inferior one. While a single patient selects one treatment that seems better based on the limited information, he or she loses the chance to select the other treatment, which may be the better option. This is the so-called dilemma between exploitation (enjoying the benefits of using current knowledge) and exploration (taking the risk to obtain new knowledge). In clinical settings, the statistical advice for individual patients seems to be the maximum expected success rate or something equivalent and patients’ selections tend to be homogeneous, which does not solve the dilemma. In this study, our aim is to investigate the effects of the heterogeneity of decision-makers in the decision process.MethodsHere, we proposed a decision strategy that introduced the heterogeneity of decision-makers by considering patients’ self-decisions where the patients’ heterogeneous attitudes towards the treatment are integrated into the probabilistic utility function based on the Beta Bayesian posterior. Based on the context of two-armed bandit treatment options with limited information, we compared the overall success rate of treatment between our heterogeneous decision strategy and a homogeneous decision strategy that is defined to select the treatment with the largest posterior mean.ResultsThe heterogeneity of decision-makers in a population improved the overall benefit of treatment under some conditions.DiscussionIn clinical settings, there exists heterogeneity of decision-making among patients. Our study investigated a targeting strategy by respecting the self-decision of all individuals and found that the heterogeneity of decision-making can improve the overall benefit under some conditions. In addition, this outperformance may suggest that heterogeneity of decision-making is of importance to human beings. Besides the ethical merit, our findings provide meaningful ideas for better strategies towards decision-making dilemmas in clinical settings for rare diseases or cases where only limited information is available. Furthermore, it is suggested to investigate the effects of heterogeneity of decision-making in other fashions, such as genetic heterogeneity and phenotypic heterogeneity.
NeurEx: digitalized neurological examination offers a novel high‐resolution disability scale
Authors: Kosa Peter , Barbour Christopher , Wichman Alison , Sandford Mary , Greenwood Mark , Bielekova Bibiana 
Published: September 2018

AbstractObjectiveTo develop a sensitive neurological disability scale for broad utilization in clinical practice.MethodsWe employed advances of mobile computing to develop an iPad‐based App for convenient documentation of the neurological examination into a secure, cloud‐linked database. We included features present in four traditional neuroimmunological disability scales and codified their automatic computation. By combining spatial distribution of the neurological deficit with quantitative or semiquantitative rating of its severity we developed a new summary score (called NeurEx; ranging from 0 to 1349 with minimal measurable change of 0.25) and compared its performance with clinician‐ and App‐computed traditional clinical scales.ResultsIn the cross‐sectional comparison of 906 neurological examinations, the variance between App‐computed and clinician‐scored disability scales was comparable to the variance between rating of the identical neurological examination by multiple sclerosis (MS)‐trained clinicians. By eliminating rating ambiguity, App‐computed scales achieved greater accuracy in measuring disability progression over time (n = 191 patients studied over 880.6 patient‐years). The NeurEx score had no apparent ceiling effect and more than 200‐fold higher sensitivity for detecting a measurable yearly disability progression (i.e., median progression slope of 8.13 relative to minimum detectable change of 0.25) than Expanded Disability Status Scale (EDSS) with a median yearly progression slope of 0.071 that is lower than the minimal measurable change on EDSS of 0.5.InterpretationNeurEx can be used as a highly sensitive outcome measure in neuroimmunology. The App can be easily modified for use in other areas of neurology and it can bridge private practice practitioners to academic centers in multicenter research studies.
Controllable Epitaxial Growth of Core–Shell PbSe@CsPbBr3 Wire Heterostructures
Authors: Fan Chao , Xu Xing , Yang Ke , Jiang Feng , Wang Songyang , Zhang Qinglin 
Published: September 2018

Abstract1D semiconductor core–shell wire heterostructures are crucial for high‐performance optical and optoelectronic device applications, but they are limited to the traditional semiconductor families. Here, the conformal epitaxy of CsPbBr3 shell on PbSe wire core is realized to form the core–shell PbSe@CsPbBr3 wire heterostructures via a chemical vapor deposition route. The Pb‐particle catalysts at the tips of the PbSe wires grown by vapor–liquid–solid provide the nucleation sites for the in situ rapid growth of CsPbBr3 cube crystals, which serve as the adatom collector for the following shell growth due to the faster adsorption of the evaporated source atoms on them than on the sidewalls of PbSe wires. This determines the directional growth of the shell along the PbSe wires from the tip to bottom. The spectral and transient photoluminescence reveals the efficient photogenerated carrier transfer from the shell to the core. Importantly, the photodetectors (PDs) based on the heterostructures show responsivity up to 4.7 × 104 A W−1 under 405 nm light illumination, and a wavelength‐dependent photocurrent polarity with the excitation of the light from near‐ to mid‐infrared (IR), which indicates potential applications in IR PDs and novel optoelectronic logical circuits.
Shift work, job strain, and metabolic syndrome: Cross‐sectional analysis of ELSA‐Brasil
Authors: Santos Aline E. , Araújo Larissa F. , Griep Rosane H. , Castro Moreno Claudia R. , Chor Dora , Barreto Sandhi M. , Giatti Luana 
Published: September 2018

AbstractBackgroundShift work and psychosocial stressors may contribute to higher metabolic syndrome (MetS) incidence. Few studies investigated whether the presence of both factors simultaneously has a synergic effect on risk of MetS.MethodsThis cross‐sectional analysis used baseline data (2008‐2010) for 10 960 current workers from ELSA‐Brasil. Multiple logistic regression was used to estimate independent associations between shift work and job strain and MetS. An interaction between these factors was tested by including a multiplicative term in the final model.ResultsExposure to three‐shifts a week (that is, three 12 h shifts of work followed by 36 h of rest) and high job‐strain were independently associated with greater risk of MetS. We found no indication (P > 0.05) of interaction between working in shifts and job strain on MetS.ConclusionsEfforts to reduce job strain and shift work should be considered as part of a primary prevention strategy to reduce the risk of MetS.
Electrocatalysis in Lithium Sulfur Batteries under Lean Electrolyte Conditions
Authors: Yang Yuxiang , Zhong Yiren , Shi Qiuwei , Wang Zhenhua , Sun Kening , Wang Hailiang 
Published: September 2018

AbstractThe presence of electrocatalysis in lithium–sulfur batteries has been proposed but not yet sufficiently verified. In this study, molybdenum phosphide (MoP) nanoparticles are shown to play a definitive electrocatalytic role for the sulfur cathode working under lean electrolyte conditions featuring a low electrolyte/active material ratio: the overpotentials for the charging and discharging reactions are greatly decreased. As a result, sulfur electrodes containing MoP nanoparticles show faster kinetics and more reversible conversion of sulfur species, leading to improvements in charging/discharging voltage profiles, capacity, rate performance, and cycling stability. Taking advantage of the electrocatalytic properties of MoP, high‐performance sulfur electrodes were successfully realized that are steadily cyclable at a high areal capacity of 5.0 mAh cm−2 with a challenging electrolyte/sulfur (E/S) ratio of 4 μLE mg−1S .
Enantioselective, Catalytic Vicinal Difluorination of Alkenes
Authors: Scheidt Felix , Schäfer Michael , Sarie Jérôme C. , Daniliuc Constantin G. , Molloy John J. , Gilmour Ryan 
Published: September 2018

AbstractThe enantioselective, catalytic vicinal difluorination of alkenes is reported by II/IIII catalysis using a novel, C2‐symmetric resorcinol derivative. Catalyst turnover via in situ generation of an ArIIIIF2 species is enabled by Selectfluor oxidation and addition of an inexpensive HF–amine complex. The HF:amine ratio employed in this process provides a handle for regioselective orthogonality as a function of Brønsted acidity. Selectivity reversal from the 1,1‐difluorination pathway (geminal) to the desired 1,2‐difluorination (vicinal) is disclosed (>20:1 in both directions). Validation with electron deficient styrenes facilitates generation of chiral bioisosteres of the venerable CF3 unit that is pervasive in drug discovery (20 examples, up to 94:06 e.r.). An achiral variant of the reaction is also presented using p‐TolI (up to >95 % yield).
Biocatalytic synthesis of lactones and lactams
Authors: Hollmann Frank , Kara Selin , Opperman Diederik J. , Wang Yonghua 
Published: September 2018

AbstractCyclic esters and amides (lactones and lactams) are important active ingredients and polymer building blocks. In recent years, numerous biocatalytic methods for their preparation have been developed including enzymatic and chemoenzymatic Baeyer–Villiger oxidations, oxidative lactonisation of diols, and reductive lactonisation and lactamisation of ketoesters. The current state of the art of these methods is reviewed.
Enantioselective Binding of Propranolol and Analogues Thereof to Cellobiohydrolase Cel7A
Authors: Hamark Christoffer , Pendrill Robert , Landström Jens , Dotson Fagerström Alexandra , Sandgren Mats , Ståhlberg Jerry , Widmalm Göran 
Published: September 2018

AbstractAt the catalytic site for the hydrolysis of cellulose the enzyme cellobiohydrolase Cel7A binds the enantiomers of the adrenergic beta‐blocker propranolol with different selectivity. Methyl‐to‐hydroxymethyl group modifications of propranolol, which result in higher affinity and improved selectivity, were herein studied by 1H,1H and 1H,13C scalar spin–spin coupling constants as well as utilizing the nuclear Overhauser effect (NOE) in conjunction with molecular dynamics simulations of the ligands per se, which showed the presence of all‐antiperiplanar conformations, except for the one containing a vicinal oxygen–oxygen arrangement governed by the gauche effect. For the ligand–protein complexes investigated by NMR spectroscopy using, inter alia, transferred NOESY and saturation‐transfer difference (STD) NMR experiments the S‐isomers were shown to bind with a higher affinity and a conformation similar to that preferred in solution, in contrast to the R‐isomer. The fact that the S‐form of the propranolol enantiomer is pre‐arranged for binding to the protein is also observed for a crystal structure of dihydroxy‐(S)‐propranolol and Cel7A presented herein. Whereas the binding of propranolol is entropy driven, the complexation with the dihydroxy analogue is anticipated to be favored also by an enthalpic term, such as for its enantiomer, that is, dihydroxy‐(R)‐propranolol, because hydrogen‐bond donation replaces the corresponding bonding from hydroxyl groups in glucosyl residues of the natural substrate. In addition to a favorable entropy component, albeit lesser in magnitude, this represents an effect of enthalpy‐to‐entropy compensation in ligand–protein interactions.
Photoswitchable Glycolipid Mimetics: Synthesis and Photochromic Properties of Glycoazobenzene Amphiphiles
Authors: Reise Franziska , Warias Jonas E. , Chatterjee Kuntal , Krekiehn Nicolai R. , Magnussen Olaf , Murphy Bridget M. , Lindhorst Thisbe K. 
Published: September 2018

AbstractGlycolipids as constituents of cell membranes play an important role in cell membrane functioning. To enable the structural modification of membranes on demand, embedding of photosensitive glycolipid mimetics was envisioned and novel amphiphilic glycolipid mimetics comprising a photoswitchable azobenzene unit were synthesized. In this study, the photochromic properties of these glycolipid mimetics were analyzed by means of UV/Vis spectroscopy and reversible photoswitching. The glycolipids were based on a racemic glycerolipid derivative to be comparable in DPPC (dipalmitoylphosphatidylcholine) phospholipid membrane monolayers. Carbohydrate head groups were altered between a β‐glucoside and a β‐lactosyl unit, as well as acyl chain lengths between C12 and C16, resulting in altered photoswitching. Langmuir isotherms showed that photoswitching of Langmuir films comprising the synthetic photosensitive glycoamphiphiles was successful.
Tuning the Binding Affinity and Selectivity of Perfluoroaryl‐Stapled Peptides by Cysteine‐Editing
Authors: Verhoork Sanne J. M. , Jennings Claire E. , Rozatian Neshat , Reeks Judith , Meng Jieman , Corlett Emily K. , Bunglawala Fazila , Noble Martin E. M. , Leach Andrew G. , Coxon Christopher R. 
Published: September 2018

AbstractA growing number of approaches to “staple” α‐helical peptides into a bioactive conformation using cysteine cross‐linking are emerging. Here, the replacement of l‐cysteine with “cysteine analogues” in combinations of different stereochemistry, side chain length and beta‐carbon substitution, is explored to examine the influence that the thiol‐containing residue(s) has on target protein binding affinity in a well‐explored model system, p53–MDM2/MDMX, which is constituted by the interaction of the tumour suppressor protein p53 and proteins MDM2 and MDMX, which regulate p53 activity. In some cases, replacement of one or more l‐cysteine residues afforded significant changes in the measured binding affinity and target selectivity of the peptide. Computationally constructed homology models indicate that some modifications, such as incorporating two d‐cysteine residues, favourably alter the positions of key functional amino acid side chains, which is likely to cause changes in binding affinity, in agreement with measured surface plasmon resonance data.
Insights into Cholesterol/Membrane Protein Interactions Using Paramagnetic Solid‐State NMR
Authors: Jaipuria Garima , Giller Karin , Leonov Andrei , Becker Stefan , Zweckstetter Markus 
Published: September 2018

AbstractCholesterol is an essential component of animal cell membranes and impacts the structure and function of membrane proteins. But how cholesterol exerts its functions remains often enigmatic. Here, high‐resolution solid‐state NMR in combination with paramagnetic cholesterol analogues was shown to be a powerful approach to study the interaction of membrane proteins with cholesterol. Application of the method to the 169‐residue translocator protein TSPO provides residue‐specific information about its interaction with cholesterol. Comparison with NMR signal perturbations induced by diamagnetic cholesterol furthermore supports changes in the structure of mammalian TSPO caused by cholesterol binding.
A requirement for Fgfr2 in middle ear development
Authors: Rigueur Diana , Roberts Ryan R. , Bobzin Lauren , Merrill Amy E. 
Published: September 2018

SummaryThe skeletal structure of the mammalian middle ear, which is composed of three endochondral ossicles suspended within a membranous air‐filled capsule, plays a critical role in conducting sound. Gene mutations that alter skeletal development in the middle ear result in auditory impairment. Mutations in fibroblast growth factor receptor 2 (FGFR2), an important regulator of endochondral and intramembranous bone formation, cause a spectrum of congenital skeletal disorders featuring conductive hearing loss. Although the middle ear malformations in multiple FGFR2 gain‐of‐function disorders are clinically characterized, those in the FGFR2 loss‐of‐function disorder lacrimo‐auriculo‐dento‐digital (LADD) syndrome are relatively undescribed. To better understand conductive hearing loss in LADD, we examined the middle ear skeleton of mice with conditional loss of Fgfr2. We find that decreased auditory function in Fgfr2 mutant mice correlates with hypoplasia of the auditory bulla and ectopic bone growth at sites of tendon/ligament attachment. We show that ectopic bone associated with the intra‐articular ligaments of the incudomalleal joint is derived from Scx‐expressing cells and preceded by decreased expression of the joint progenitor marker Gdf5. Together, these results identify a role for Fgfr2 in development of the middle ear skeletal tissues and suggest potential causes for conductive hearing loss in LADD syndrome.