bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increase of hyperpolarization‐activated cyclic nucleotide‐gated current in the aberrant excitability of spinal muscular atrophy
Authors: Lai Hsing‐Jung , Chen Chien‐Lin , Tsai Li‐Kai 
Published: February 2018

ObjectiveThe pathophysiology of spinal muscular atrophy (SMA) is still unclear.MethodsThe nerve excitability test in SMA patients and a mouse model of SMA was carried out to explore the pathophysiology of nodal and internodal currents, and quantitative PCR, western blotting, and whole‐cell patch‐clamp recording were used for the identified hypothesis.ResultsThe nerve excitability test in SMA patients showed increased inward rectification in the current‐threshold relationship and increased overshoot after hyperpolarizing threshold electrotonus, which indicates increased hyperpolarization‐activated cyclic nucleotide‐gated (HCN) current; these findings correlated with disease severity. Increased inward rectification in the current‐threshold relationship was reproducible in a mouse model of mild SMA, and the abnormality preceded the decline of compound motor action potential amplitudes. Furthermore, quantitative PCR of spinal cord tissues and western blotting of the spinal cord and sciatic nerves showed increased HCN1 and HCN2 expression in SMA mice, and voltage‐clamp recording in dissociated spinal motor neurons from SMA mice also showed increased HCN current density. Treatment with ZD7288, an HCN channel blocker, also reduced early mortality, improved motor function, and restored neuromuscular junction architecture in a mouse model of severe SMA.InterpretationThis study shows that increased HCN current underlies the pathophysiology of SMA and can be a novel non‐SMN target for SMA therapy. Ann Neurol 2018;83:494–507
The Weinberg‐Salam Model of Electroweak Interactions: Ingenious Discovery or Lucky Hunch?
Authors: Borrelli Arianna 
Published: February 2018

AbstractThis contribution looks back at the papers published fifty years ago by Abdus Salam and Steven Weinberg, which are today regarded as marking the coming‐to‐be of the Weinberg‐Salam model of electroweak interactions. Despite their present fame, at the time of their publication the papers went largely unnoticed. Reconstructing the historical context from which they emerged will show how, against the traditional image of theoretical physicists as “lone geniuses,” the Weinberg‐Salam model actually came to be thanks to the interplay of many different actors and ideas.
Acute Modulation of Mycobacterial Cell Envelope Biogenesis by Front‐Line Tuberculosis Drugs
Authors: Rodriguez‐Rivera Frances P. , Zhou Xiaoxue , Theriot Julie A. , Bertozzi Carolyn R. 
Published: February 2018

AbstractFront‐line tuberculosis (TB) drugs have been characterized extensively in vitro and in vivo with respect to gene expression and cell viability. However, little work has been devoted to understanding their effects on the physiology of the cell envelope, one of the main targets of this clinical regimen. Herein, we use metabolic labeling methods to visualize the effects of TB drugs on cell envelope dynamics in mycobacterial species. We developed a new fluorophore–trehalose conjugate to visualize trehalose monomycolates of the mycomembrane using super‐resolution microscopy. We also probed the relationship between mycomembrane and peptidoglycan dynamics using a dual metabolic labeling strategy. Finally, we found that metabolic labeling of both cell envelope structures reports on drug effects on cell physiology in two hours, far faster than a genetic sensor of cell envelope stress. Our work provides insight into acute drug effects on cell envelope biogenesis in live mycobacteria.
Templatsynthese dreidimensionaler Hexakisimidazolium‐Käfige
Authors: Sun Li‐Ying , Sinha Narayan , Yan Tao , Wang Yi‐Shou , Tan Tristan T. Y. , Yu Le , Han Ying‐Feng , Hahn F. Ekkehardt 
Published: February 2018

AbstractEine Strategie für die Synthese dreidimensionaler Hexakisimidazolium‐Käfigverbindungen wurde entwickelt. Die Reaktion von trigonalen Trisimidazolium‐Salzen H3L(PF6)3 mit drei terminalen N‐Olefin‐Substituenten und Silberoxid ergibt molekulare Trisilber‐Hexacarben‐Zylinder des Typs [Ag3(L)2]3+, in denen die N‐Olefin‐Substituenten von zwei unterschiedlichen Tricarben‐Liganden paarweise angeordnet sind. UV‐Bestrahlung führt über drei [2+2]‐Cycloadditionen zu drei Cyclobutan‐Brücken zwischen den beiden Tris‐NHC‐Liganden und damit zu einem dreidimensionalen Hexakis‐NHC‐Liganden. Das Entfernen der Metallionen ergibt dreidimensionale Hexakisimidazolium‐Käfigkationen mit einem großen inneren Hohlraum; dies sind die ersten Beispiele für derartige Verbindungen.
Biocatalytic Conversion of Cyclic Ketones Bearing α‐Quaternary Stereocenters into Lactones in an Enantioselective Radical Approach to Medium‐Sized Carbocycles
Authors: Morrill Charlotte , Jensen Chantel , Just‐Baringo Xavier , Grogan Gideon , Turner Nicholas J. , Procter David J. 
Published: February 2018

AbstractCyclic ketones bearing α‐quaternary stereocenters underwent efficient kinetic resolution using cyclohexanone monooxygenase (CHMO) from Acinetobacter calcoaceticus. Lactones possessing tetrasubstituted stereocenters were obtained with high enantioselectivity (up to >99 % ee) and complete chemoselectivity. Preparative‐scale biotransformations were exploited in conjunction with a SmI2‐mediated cyclization process to access complex, enantiomerically enriched cycloheptan‐ and cycloctan‐1,4‐diols. In a parallel approach to structurally distinct products, enantiomerically enriched ketones from the resolution with an α‐quaternary stereocenter were used in a SmI2‐mediated cyclization process to give cyclobutanol products (up to >99 % ee).
Contra‐Thermodynamic, Photocatalytic E→Z Isomerization of Styrenyl Boron Species: Vectors to Facilitate Exploration of Two‐Dimensional Chemical Space
Authors: Molloy John J. , Metternich Jan B. , Daniliuc Constantin G. , Watson Allan J. B. , Gilmour Ryan 
Published: February 2018

AbstractDesigning strategies to access stereodefined olefinic organoboron species is an important synthetic challenge. Despite significant advances, there is a striking paucity of routes to Z‐α‐substituted styrenyl organoborons. Herein, this strategic imbalance is redressed by exploiting the polarity of the C(sp2)−B bond to activate the neighboring π system, thus enabling a mild, traceless photocatalytic isomerization of readily accessible E‐α‐substituted styrenyl BPins to generate the corresponding Z‐isomers with high fidelity. Preliminary validation of this contra‐thermodynamic E→Z isomerization is demonstrated in a series of stereoretentive transformations to generate Z‐configured trisubstituted alkenes, as well as in a concise synthesis of the anti‐tumor agent Combretastatin A4.
Hierarchical Assembly of an Interlocked M8L16 Container
Authors: Bloch Witold M. , Holstein Julian J. , Dittrich Birger , Hiller Wolf , Clever Guido H. 
Published: February 2018

AbstractThe self‐assembly of eight PdII cations and sixteen phenanthrene‐derived bridging ligands with 60° bite angles yielded a novel M8L16 metallosupramolecular architecture composed of two interlocked D4h‐symmetric barrel‐shaped containers. Mass spectrometry, NMR spectroscopy, and X‐ray analysis revealed this self‐assembled structure to be a very large “Hopf link” catenane featuring channel‐like cavities, which are occupied by NO3− anions. The importance of the anions as catenation templates became imminent when we observed the nitrate‐triggered structural rearrangement of a mixture of M3L6 and M4L8 assemblies formed in the presence of BF4− anions into the same interlocked molecule. Furthermore, the densely packed structure of the M8L16 catenane was exploited in the preparation of a hexyloxy‐functionalized analogue, which further self‐assembled into vesicle‐like aggregates in a reversible manner.
Process optimization of the extraction condition of β‐amylase from brewer's malt and its application in the maltose syrup production
Authors: Niu Chengtuo , Zheng Feiyun , Li Yongxian , Liu Chunfeng , Li Qi 
Published: February 2018

Abstractβ‐Amylase is of important biotechnological aid in maltose syrup production. In this study, the extraction condition of β‐amylase from brewer's malt and the optimal dosage of β‐amylase in maltose syrup production were optimized using response surface methodology and uniform design method. The optimal extraction condition of β‐amylase from brewer's malt was composed of 1:17 (g/v) material/liquid ratio, 44°C extraction temperature, pH 6.4 buffer pH, 2.3 H extraction time, and 1.64 g L−1 NaSO3 dosage with a predicted β‐amylase activity of 1,290.99 U g−1, which was close to the experimental β‐amylase activity of 1,230.22 U g−1. The optimal dosages of β‐amylase used in maltose syrup production were 455.67 U g−1 starch and its application in maltose syrup production led to a 68.37% maltose content in maltose syrup, which was 11.2% and 28.9% higher than those using β‐amylases from soybean and microbe (P < 0.01). Thus, β‐amylase from brewer's malt was beneficial for production of high maltose syrup.
Mechanism‐Based Inhibitor of DNA Cytosine‐5 Methyltransferase by a SNAr Reaction with an Oligodeoxyribonucleotide Containing a 2‐Amino‐4‐Halopyridine‐C‐Nucleoside
Authors: Sato Kousuke , Kunitomo Yuma , Kasai Yukiko , Utsumi Shohei , Suetake Isao , Tajima Shoji , Ichikawa Satoshi , Matsuda Akira 
Published: February 2018

AbstractIn chromatin, 5‐methylcytosine (mC), which represents the fifth nucleobase in genomic DNA, plays a role as an inducer of epigenetic changes. Tumor cells exhibit aberrant DNA methylation patterns, and inhibition of human DNA cytosine‐5 methyltransferase (DNMT), which is responsible for generating mC in CpG sequences, is an effective strategy to treat various cancers. Here, we describe the design, synthesis, and evaluation of the properties of 2‐amino‐4‐halopyridine‐C‐nucleosides (dXP) and oligodeoxyribonucleotides (ODNs) containing dXP as a novel mechanism‐based inhibitor of DNMTs. The designed ODN containing XPpG forms a complex with DNMTs by covalent bonding through a nucleophilic aromatic substitution (SNAr) reaction, and its cell proliferation activity is investigated. This study suggests that dXP in a CpG sequence of DNA could serve as a potential nucleic acid drug lead in cancer chemotherapy and a useful chemical probe for studies of epigenetics. Our molecular design using a SNAr reaction would be useful for DNMTs and other protein–DNA interactions.
Flue‐Gas Desulfurization by Using a HiGee Electric‐Field Device
Authors: Zou Hai-Kui , Arowo Moses , Zhang Qiang , Zhang Liangliang , Sun Baochang , Chu Guang-Wen , Shao Lei , Chen Jian-Feng 
Published: February 2018

AbstractAn innovative technique to remove SO2 from flue gas, comprising a rotating packed bed (RPB) coupled with an electric‐field device, is presented herein. The effects of operating conditions, such as packing type, rotation speed, gas‐liquid volumetric ratio, Na2SO3 content, and voltage supply on SO2 removal efficiency (η), as well as the gas‐phase overall volumetric mass‐transfer coefficient (KGa), were systematically investigated. Results indicate that a high η can be achieved under certain operating conditions. A correlation to predict KGa was also established and results show that the predicted values are in agreement with the experimental results. This work generally provides a feasible means of intensification for flue gas desulfurization.
Hierarchical Nanostructures of Metal‐Organic Frameworks Applied in Gas Separating ZIF‐8‐on‐ZIF‐67 Membranes
Authors: Knebel Alexander , Wulfert‐Holzmann Paul , Friebe Sebastian , Pavel Janet , Strauß Ina , Mundstock Alexander , Steinbach Frank , Caro Jürgen 
Published: February 2018

AbstractMembranes from metal‐organic frameworks (MOFs) are highly interesting for industrial gas separation applications. Strongly improved performances for carbon capture and H2 purification tasks in MOF membranes are obtained by using highly reproducable and very accuratly, hierarchically grown ZIF‐8‐on‐ZIF‐67 (ZIF‐8@ZIF‐67) nanostructures. To forgo hardly controllable solvothermal synthesis, particles and layers are prepared by self‐assembling methods. It was possible for the first time to confirm ZIF‐8‐on‐ZIF‐67 membrane growth on rough and porous ceramic supports using the layer‐by‐layer deposition. Additionally, hierarchical particles are made in a fast RT synthesis with high monodispersity. Characterization of the hierarchical and epitaxial grown layers and particles is performed by SEM, TEM, EDXM and gas permeation. The system ZIF‐8@ZIF‐67 shows a nearly doubled H2/CO2 separation factor, regardless of whether neat membrane or mixed‐matrix‐membrane in comparison to other MOF materials.
CHIPMUNK: A Virtual Synthesizable Small‐Molecule Library for Medicinal Chemistry, Exploitable for Protein–Protein Interaction Modulators
Authors: Humbeck Lina , Weigang Sebastian , Schäfer Till , Mutzel Petra , Koch Oliver 
Published: February 2018

AbstractA common issue during drug design and development is the discovery of novel scaffolds for protein targets. On the one hand the chemical space of purchasable compounds is rather limited; on the other hand artificially generated molecules suffer from a grave lack of accessibility in practice. Therefore, we generated a novel virtual library of small molecules which are synthesizable from purchasable educts, called CHIPMUNK (CHemically feasible In silico Public Molecular UNiverse Knowledge base). Altogether, CHIPMUNK covers over 95 million compounds and encompasses regions of the chemical space that are not covered by existing databases. The coverage of CHIPMUNK exceeds the chemical space spanned by the Lipinski rule of five to foster the exploration of novel and difficult target classes. The analysis of the generated property space reveals that CHIPMUNK is well suited for the design of protein–protein interaction inhibitors (PPIIs). Furthermore, a recently developed structural clustering algorithm (StruClus) for big data was used to partition the sub‐libraries into meaningful subsets and assist scientists to process the large amount of data. These clustered subsets also contain the target space based on ChEMBL data which was included during clustering.
Treatment of co‐occurring food avoidance and alcohol use disorder in an adult: Possible avoidant restrictive food intake disorder?
Authors: Steen Eloisa , Wade Tracey D. 
Published: February 2018

AbstractObjectiveThis case report details the presentation and treatment of a 42‐year‐old male self‐presenting for treatment who reported having been a restrictive eater since childhood; since adolescence he had failed to meet appropriate nutritional intake with one meal at night followed by around 10–20 standard alcoholic drinks.MethodTen sessions of cognitive behavioral therapy were offered emphasizing the need to adhere to regular eating patterns in conjunction with significant reduction of binge drinking.ResultsAt the end of treatment, and 1‐month follow‐up, improvements in nutritional intake and alcohol intake were observed, accompanied by improvements in depression, anxiety, and stress.DiscussionHowever, excessive alcohol intake had reoccurred at 3‐month follow‐up, accompanied by increases in negative affect and impairment due to eating, indicating that longer‐term therapy may be required for this group of people.
Robust, Bridge‐less Ion‐selective Electrodes with Significantly Reduced Need for Pre‐ and Post‐application Handling
Authors: Schazmann B. , Demey S. , Ali Z. Waqar , Plissart M‐S. , Brennan E. , Radu A. 
Published: February 2018

AbstractWe are demonstrating robust, single‐layer ion‐selective electrode (ISE) utilizing simple Ag/AgCl electrode as solid support without the need for intermediate polymer layer. We have created and chemically linked a family of imidazolium ionic liquids (ILs) with poly (vinyl chloride) (PVC) using click chemistry, resulting in hybrid materials with tunable characteristics. The resultant material inherently contains chloride ion thus offering the ability to stabilize interfacial potential. This allowed us to construct very simple, single‐layer membranes with significantly reduced need for conditioning as an added bonus compared to traditional sensors. Chemical immobilization of ISE membrane components also led to extended lifetime as the potential for material loss is reduced and detection limits are lowered. In our characterization we focused on perchlorate as a model ion. It's levels of around 10−7 M could be repeatedly quantified over a 100 day period despite constant exposure of ISEs to aqueous solution over this time. Most importantly, the electrodes exhibited stable and reproducible signal with significantly simplified pre‐ and post‐operation handling protocols. This offers potential for in situ applications as well as to advanced fabrication techniques and miniaturization. Simplicity of construction and operation, and low cost of the solid substrate allows for disposable ISE formats.
Numerical Study of Solid Oxide Fuel Cell Contacting Mechanics
Authors: Chen Z. , Wang X. , Brandon N. , Atkinson A. 
Published: February 2018

AbstractAssembly of a planar solid oxide fuel cell (SOFC) or solid electrolyzer (SOE) stack involves the lamination of cells and interconnect plates under an applied load. In most designs a pattern of ribs on the interconnector makes contact with a porous ceramic current collector layer on the air side. These localized contacts are regions of increased stress on the cells and can cause damage if the stresses become too large. In this paper the mechanical response of an anode‐supported cell to localized loads from interconnector ribs is simulated. The simulations show that the critical stress for initiating and propagating a crack in the electrolyte (∼300MPa for a 10 μm thick electrolyte) is reached when the interconnector displacement reaches 20 μm (after touching the cathode) with reduced support, or 30 μm when in an oxidized state. The difference is due to the lower stiffness of the reduced support. The residual compressive stress in the electrolyte layer has a major protective effect for the electrolyte. It is concluded that fracture is very unlikely for a geometrically perfect contact, but if the contact is non‐uniform due to manufacturing variability in the contact plate or cell, local displacements >∼20 μm can be dangerous. The simulations are used in an example of contacting geometry optimization.
Berechnung von Gleitkreisen mit dem Lamellenverfahren und die Berücksichtigung von Zuggliedern
Authors: Goldscheider Michael 
Published: February 2018

AbstractDas in der Praxis übliche vereinfachte Verfahren nach Bishop für Gleitkreisberechnungen mit Lamellen wird hergeleitet und die zugrundeliegenden Annahmen und die Lösungsmethode erläutert. Die für alle Berechnungsverfahren mit Lamellen geltenden statischen Gesetzmäßigkeiten, die für eine statisch mögliche, widerspruchsfreie und eindeutige Lösung notwendig sind, werden dargestellt. Ferner werden die Publikationen anderer Autoren, die durch genauere Berechnungen zur Entwicklung und Begründung und zum Nachweis der Genauigkeit des vereinfachten Verfahrens entscheidend beigetragen haben, in den Grundzügen wiedergegeben und bewertet. Auf der Grundlage der Annahmen des vereinfachten Verfahrens werden Ansätze zur Berücksichtigung von Verpressankern und Bodennägeln entwickelt.
Identifying Early Carboniferous bimodal volcanic rocks and geochemical characteristics in the Atengtao Mountain, Yili Block (Chinese western Tianshan)
Authors: Wang Zuopeng , Li Yongjun , Tong Lili , Yang Gaoxue , Ren Pengfei , Wang Ran , Li Hai 
Published: February 2018

The Early Carboniferous bimodal volcanic rocks are firstly recognized in the Atengtao Mountain, Yili Block (Chinese Western Tianshan). The bimodal volcanic rocks are composed of dominant rhyolite and subordinate basaltic andesite. The SiO2 contents of basaltic andesites span a range of 52.08 to 60.44 wt.%, whereas those of the rhyolites range from 72.50 to 76.78 wt.%, showing a sharp gap between 60.44 and 72.50 wt.% for SiO2 content. Zircon U–Pb dating of rhyolitic sample yielded crystallization age of 340 ± 6 Ma, which is interpreted as the extrusive age of the bimodal volcanic rocks. Basaltic andesite samples belong to the calc‐alkaline series, whereas rhyolites are peraluminous. The basaltic andesite samples display enrichment in LREE ((La/Yb)N = 3.16–6.27), and nearly no obvious Eu anomalies (δEu = 0.86–1.21), with relative enrichment in large ion lithophile elements (Rb, K, Sr, U) and depletion in high field strength elements (Nb, Ta). Compared to the basaltic andesites, the rhyolites show enriched LREE patterns ((La/Yb)N = 7.05–9.27) and significantly negative Eu anomalies (δEu = 0.36–0.62), with remarkably negative Nb, Ta, P, Ti, and Sr anomalies, which is consistent with A‐type granites. The rhyolites have positive εHf(t) values from 1.5 to 4.8 and TDM2(Hf) values from 1,036 to 1,247 Ma. The basaltic andesites are interpreted as resulting from partial melting of an enriched lithospheric mantle source that was metasomatized by subduction‐related components, whereas the rhyolites were derived from basaltic melt‐induced reworking of Proterozoic juvenile crustal material. Based on our data, and taking into account the regional geology, a model of back‐arc setting was proposed for the Early Carboniferous formation of the bimodal volcanic rocks in the Atengtao Mountain. Therefore, we suggest that the volcanic rocks were likely induced by the northward subduction of the South Tianshan Ocean. The subduction resulted in opening of a back‐arc basin in Atengtao Mountain, leading to upwelling of mantle that had produced the basaltic andesites. Moreover, this process provided heat to remelt the crustal materials and form the rhyolites.
Sixty‐Two‐Year‐Old Male Suffering From Uremic Leontiasis Ossea Caused by Severe Secondary Hyperparathyroidism
Authors: Purrunsing Yogendranath , Zhang Jingjing , Cui Ying , Liu Wei , Xu Yi , Hong Xunning , Xing Changying , Zha Xiaoming , Wang Ningning 
Published: February 2018

ABSTRACTSecondary hyperparathyroidism (SHPT) is a long‐term complication of chronic kidney disease–mineral and bone disorder (CKD‐MBD). SHPT is characterized by hyperplasia of the parathyroid glands and abnormal secretion of parathyroid hormones (PTH), calcium and phosphorous metabolic disorders, renal osteodystrophy, vascular and soft tissue calcification, malnutrition, and other multiple system complications, which can seriously affect the quality of life of the patient and increase the risk of cardiovascular disease and mortality rate. Uremic leontiasis ossea (ULO) is a medical condition only rarely encountered clinically. SHPT causes craniofacial bone deformity accompanied by lesions of the nerve, cardiovascular, respiratory, bone, or other systems within the body. The case discussed here is related to severe SHPT. A 62‐year‐old male patient was suffering from leontiasis ossea, pectus excavatum, vascular calcification, spontaneous bone fractures, and lower limb deformities. He was undergoing hemodialysis and given total parathyroidectomy (TPTX) with autotransplantation (AT). We further analyzed the multivariate therapeutic effects of TPTX on this patient in order to provide clinical data for standardized treatment of individuals with CKD‐MBD. © 2018 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.