bluuebunny/crossref_metadata_2025 huggingface dataset:
Sodium‐Ion Battery Electrolytes: Modeling and Simulations
Authors: Åvall Gustav , Mindemark Jonas , Brandell Daniel , Johansson Patrik
Published: February 2018

The authors review the efforts made from a modeling and simulation perspective in order to assist both the fundamental understanding as well as the development of higher performance sodium‐ion battery (SIB) electrolytes. Depending on the type of the electrolyte studied, liquid, ionic liquid, polymer, glass, solid‐state, etc., the simulation methods applied and the research questions in focus differ, but all contribute to more rational progress. Furthermore, the authors create cases of meta‐analysis using literature data. A historical perspective is applied and the focus clearly is on more recent work and novel electrolyte materials. Finally, the authors outline a few prospective areas for where SIB electrolyte simulations can/should be extended for maximum impact in the field.
Dramatic Enhancement of CO2 Photoreduction by Biodegradable Light‐Management Paper
Authors: Wang Yangang , Li Tian , Yao Yonggang , Li Xi , Bai Xia , Yin Chaochuang , Williams Nicholas , Kang Shifei , Cui Lifeng , Hu Liangbing
Published: February 2018

Photocatalytic reduction of CO2 with H2O vapor is gaining increased interest because it is a promising “green chemistry” route for the direct conversion of CO2 to value‐added chemicals driven by solar energy. To increase the efficiency of photocatalytic conversion, most efforts are made by exploring various photocatalysts while little effort on advanced light management. For the first time, it is demonstrated that bio‐degradable transparent paper with excellent light diffusivity can effectively enhance the light utilization of photocatalytic reactions when attached on the device surface, and thus greatly increase the conversion efficiency. As a proof‐of‐concept, a graphitic carbon nitride (g‐C3N4) photocatalyst with transparent paper attached, exhibited 1.5 times higher photocatalytic activity than bare g‐C3N4 in the reduction of CO2 under visible light irradiation. The improved catalytic performance can be ascribed to the (1) refractive index matching and (2) enhanced light absorption via prolonged light traveling path in transparent paper, which decreases the light reflection at surface and traps the absorbed light inside, leading to an increased light absorption at the active layer of the device. The transparent paper with a controllable light management behavior has an unprecedented potential for applications in photocatalysis as a general method for improved light utilization.
Hierarchical Fabric Decorated with Carbon Nanowire/Metal Oxide Nanocomposites for 1.6 V Wearable Aqueous Supercapacitors
Authors: Fu Wenbin , Zhao Enbo , Ren Xiaolei , Magasinski Alexandre , Yushin Gleb
Published: February 2018

Aqueous asymmetric supercapacitors (ASCs) may offer comparable or higher energy density than electric double‐layer capacitors (EDLCs) based on organic electrolytes. As such, ASCs may be more suitable for integration into smart textiles, where the use of flammable organic solvents is not acceptable. However, reported ASC devices typically suffer from poor rate capability and low areal loadings. This study demonstrates the development of nitrogen‐doped carbon (N‐C) nanowire/metal oxide (Fe2O3 and MnO2) nanocomposite electrodes directly produced on the internal surface of a conductive fabric for use as high‐rate electrodes for solid‐state ASCs. The N‐C nanowires provide fast and efficient pathways for electrons, while short diffusion paths within nanosized metal oxides enable fast ion transport, leading to greatly enhanced performance at high rates. The porous structure of the fabric enables high areal capacitance loading in each electrode (≈150 mF cm−2). Both electrodes show high specific capacitance of ≈180 F g−1 (Fe2O3) and ≈250 F g−1 (MnO2) and excellent rate capability. Solid‐state ASCs assembled by using an aqueous gel electrolyte operate at 1.6 V and deliver over 60 mF cm−2 during ≈50 s charging/discharging time and over 30 mF cm−2 for ≈5 s discharge.
The effect of particle rotation on the motion and rejection of capsular particles in slit pores
Authors: Delavari Armin , Agasanapura Basavaraju , Baltus Ruth E.
Published: February 2018

The results from a two‐dimensional computational model describing the motion of capsule‐shaped particles in a slit pore under small Re conditions are reported. Average particle velocities and particle rejection coefficients were determined for capsules with aspect ratios of 2 and 4. Two different approaches were used to characterize particle rotation and hydrodynamic particle‐pore wall interactions. In one approach, all sterically allowed particle orientation angles had equal probability, i.e., infinite rotational diffusion was assumed. In the second approach, particles were allowed to freely rotate in the pore; particle orientations were dictated by hydrodynamic forces acting on the particle surface and rotational particle diffusion was neglected. Minimal lateral migration across the pore was observed for the freely rotating particles. Although particle alignment was observed for the freely rotating particles, rejections predicted from the two approaches were found to be in close agreement. © 2018 American Institute of Chemical Engineers AIChE J, 64: 2828–2836, 2018
Mutations in SCN3A cause early infantile epileptic encephalopathy
Authors: Zaman Tariq , Helbig Ingo , Božović Ivana Babić , DeBrosse Suzanne D. , Bergqvist A. Christina , Wallis Kimberly , Medne Livija , Maver Aleš , Peterlin Borut , Helbig Katherine L. , Zhang Xiaohong , Goldberg Ethan M.
Published: February 2018

Objective

Voltage‐gated sodium (Na+) channels underlie action potential generation and propagation and hence are central to the regulation of excitability in the nervous system. Mutations in the genes SCN1A, SCN2A, and SCN8A, encoding the Na+ channel pore‐forming (α) subunits Nav1.1, 1.2, and 1.6, respectively, and SCN1B, encoding the accessory subunit β1, are established causes of genetic epilepsies. SCN3A, encoding Nav1.3, is known to be highly expressed in brain, but has not previously been linked to early infantile epileptic encephalopathy. Here, we describe a cohort of 4 patients with epileptic encephalopathy and heterozygous de novo missense variants in SCN3A (p.Ile875Thr in 2 cases, p.Pro1333Leu, and p.Val1769Ala).

Methods

All patients presented with treatment‐resistant epilepsy in the first year of life, severe to profound intellectual disability, and in 2 cases (both with the variant p.Ile875Thr), diffuse polymicrogyria.

Results

Electrophysiological recordings of mutant channels revealed prominent gain of channel function, with a markedly increased amplitude of the slowly inactivating current component, and for 2 of 3 mutants (p.Ile875Thr and p.Pro1333Leu), a leftward shift in the voltage dependence of activation to more hyperpolarized potentials. Gain of function was not observed for Nav1.3 variants known or presumed to be inherited (p.Arg1642Cys and p.Lys1799Gln). The antiseizure medications phenytoin and lacosamide selectively blocked slowly inactivating over transient current in wild‐type and mutant Nav1.3 channels.

Interpretation

These findings establish SCN3A as a new gene for infantile epileptic encephalopathy and suggest a potential pharmacologic intervention. These findings also reinforce the role of Nav1.3 as an important regulator of neuronal excitability in the developing brain, while providing additional insight into mechanisms of slow inactivation of Nav1.3. Ann Neurol 2018;83:703–717
Herstellung direkt nutzbarer Durchflussreaktorkartuschen durch 3D‐Druck von thermostabilen Enzymen
Authors: Maier Manfred , Radtke Carsten P. , Hubbuch Jürgen , Niemeyer Christof M. , Rabe Kersten S.
Published: February 2018

Die Kompartimentierung chemischer Reaktionen ist ein grundlegendes Prinzip des Lebens und daher ein wichtiger Ausgangspunkt für Innovationen bei der Entwicklung neuer Ansätze in der Biokatalyse. Zur Implementierung von Biotransformationen in räumlich getrennten Kompartimenten werden daher Herstellungsmethoden benötigt, die die schnelle Produktion von in Flusssystemen einsetzbaren Biokatalysatoren erlauben. Dreidimensionale (3D) Drucktechniken bieten eine solche hohe Durchsatzleistung, sind aber normalerweise nicht mit der empfindlichen Natur von Enzymen kompatibel, die physiologische Verarbeitungsparameter erfordern. Wir zeigen hier die Anwendung thermostabiler Enzyme zur Realisierung biokatalytischer, Agarose‐basierter Tinten, die in einem einfachen temperaturgesteuerten 3D‐Druckprozess angewendet werden können. Als Beispiele haben wir eine Esterase (EstII) und eine Alkoholdehydrogenase (ADH) aus thermophilen Organismen verwendet sowie eine Decarboxylase, die durch gerichtete Proteinevolution thermostabilisiert wurde. Die resultierenden 3D‐gedruckten Kartuschen wurden anschließend für eine kontinuierliche, zweistufige sequentielle Biotransformation in einem fluidischen Setup angewendet.
Strukturelle Untersuchung subviraler Partikel durch die Kombination von zellfreier Proteinherstellung mit 110 kHz MAS‐NMR‐Spektroskopie
Authors: David Guillaume , Fogeron Marie‐Laure , Schledorn Maarten , Montserret Roland , Haselmann Uta , Penzel Susanne , Badillo Aurélie , Lecoq Lauriane , André Patrice , Nassal Michael , Bartenschlager Ralf , Meier Beat H. , Böckmann Anja
Published: February 2018

Virale Membranproteine sind vorrangige Ziele bei der Bekämpfung von Infektionen. Ihre Strukturbestimmung bleibt jedoch eine Herausforderung, sowohl in Bezug auf die Probenvorbereitung als auch auf die Methodologie der Strukturanalyse von Proteinen in einer Lipidmembranumgebung. Zellfreie Proteinherstellung und Festkörper‐NMR‐Spektroskopie sind vielversprechende Ansätze in diesem Zusammenhang, der erstere in Bezug auf das hohe Potenzial, komplexe Proteine in nativer Form herzustellen und der letztere für die Fähigkeit, Proteine in Lipiden analysieren zu können. Wir zeigen hier, dass mg‐Mengen des kleinen Hüllproteins des Enten‐Hepatitis‐B‐Virus (DHBV) mittels zellfreier Herstellung produziert werden können, und dass die Proteine zu subviralen Partikeln zusammenlagern. Protonendetektierte 2D‐NMR‐Spektren, die bei 110 kHz schneller Probenrotation um den magischen Winkel und mit <500 μg Protein aufgenommen wurden, zeigen eine Reihe von isolierten Signalen mit Linienbreiten, die vergleichbar zu denen von Modellmembranproteinen sind. Dies ebnet den Weg für strukturelle Studien dieser komplexen supramolekularen Proteinsysteme, die Homologe eines wichtigen Zielproteins für Arzneimittel in der HBV‐Infektion sind.
NiH‐Catalyzed Reductive Relay Hydroalkylation: A Strategy for the Remote C(sp3)−H Alkylation of Alkenes
Authors: Zhou Fang , Zhu Jin , Zhang Yao , Zhu Shaolin
Published: February 2018

The terminal‐selective, remote C(sp3)−H alkylation of alkenes was achieved by a relay process combining NiH‐catalyzed hydrometalation, chain walking, and alkylation. This method enables the construction of unfunctionalized C(sp3)−C(sp3) bonds under mild conditions from two simple feedstock chemicals, namely olefins and alkyl halides. The practical value of this transformation is further demonstrated by the large‐scale and regioconvergent alkylation of isomeric mixtures of olefins at low catalyst loadings.
Lewis Acid Catalyzed Enantioselective Desymmetrization of Donor–Acceptor meso‐Diaminocyclopropanes
Authors: Perrotta Daniele , Wang Ming‐Ming , Waser Jérôme
Published: February 2018

The first Lewis acid catalyzed enantioselective ring‐opening desymmetrization of a donor–acceptor meso‐diaminocyclopropane is reported. The copper(II)‐catalyzed Friedel–Crafts alkylation of indoles and one pyrrole with an unprecedented meso‐diaminocyclopropane delivered enantioenriched, diastereomerically pure urea products, which are structurally related to natural and synthetic bioactive compounds. The development of a new ligand through the investigation of an underexplored subclass of bis(oxazoline) ligands was essential for achieving high enantioselectivities.
Direct Formation of C−C Triple‐Bonded Structural Motifs by On‐Surface Dehalogenative Homocouplings of Tribromomethyl‐Substituted Arenes
Authors: Sun Qiang , Yu Xin , Bao Meiling , Liu Mengxi , Pan Jinliang , Zha Zeqi , Cai Liangliang , Ma Honghong , Yuan Chunxue , Qiu Xiaohui , Xu Wei
Published: February 2018

On‐surface synthesis shows significant potential in constructing novel nanostructures/nanomaterials, which has been intensely studied in recent years. The formation of acetylenic scaffolds provides an important route to the fabrication of emerging carbon nanostructures, including carbyne, graphyne, and graphdiyne, which feature chemically vulnerable sp‐hybridized carbon atoms. Herein, we designed and synthesized a tribromomethyl‐substituted compound. By using a combination of high‐resolution scanning tunneling microscopy, non‐contact atomic force microscopy, and density functional theory calculations, we demonstrated that it is feasible to convert these compounds directly into C−C triple‐bonded structural motifs by on‐surface dehalogenative homocoupling reactions. Concurrently, sp3‐hybridized carbon atoms are converted into sp‐hybridized ones, that is, an alkyl group is transformed into an alkynyl moiety. Moreover, we achieved the formation of dimer structures, one‐dimensional molecular wires, and two‐dimensional molecular networks on Au(111) surfaces, which should inspire further studies towards two‐dimensional graphyne structures.
Wirklich grüne Synthese von Artemisinin aus Pflanzenextrakt
Authors: Triemer Susann , Gilmore Kerry , Vu Giang T. , Seeberger Peter H. , Seidel‐Morgenstern Andreas
Published: February 2018

Durch den Einsatz von Pflanzenextrakten als Reaktionsmedium für chemische Synthesen können hocheffiziente und nachhaltige Prozesse erzielt werden. Dieses Prinzip wird auf die Partialsynthese von Artemisinin angewendet, ein sekundärer Metabolit der Pflanze Artemisia annua und eine wichtige Vorstufe von hochwirksamen Malariamedikamenten. Extrakte von A. annua enthalten außer Artemisinin auch als Abfallprodukte angesehene Komponenten, wie Dihydroartemisininsäure, die letzte Vorstufe von Artemisinin in der Biosynthese, und Chlorophyll, das als Photosensibilisator wirkt. Durch intensive Beleuchtung des unaufgearbeiteten Extrakts mit sichtbarem Licht wird Artemisinin in einem kontinuierlichen Durchflussreaktor in hoher Ausbeute aus dem Extrakt erzeugt. Dieser an der Biosynthese angelehnte Prozess ist dabei hocheffizient und nachhaltiger als etablierte Prozesse auf der Basis reiner Substanzen.
Dioxygen Sensitivity of [Fe]‐Hydrogenase in the Presence of Reducing Substrates
Authors: Huang Gangfeng , Wagner Tristan , Ermler Ulrich , Bill Eckhard , Ataka Kenichi , Shima Seigo
Published: February 2018

Mono‐iron hydrogenase ([Fe]‐hydrogenase) reversibly catalyzes the transfer of a hydride ion from H2 to methenyltetrahydromethanopterin (methenyl‐H4MPT+) to form methylene‐H4MPT. Its iron guanylylpyridinol (FeGP) cofactor plays a key role in H2 activation. Evidence is presented for O2 sensitivity of [Fe]‐hydrogenase under turnover conditions in the presence of reducing substrates, methylene‐H4MPT or methenyl‐H4MPT+/H2. Only then, H2O2 is generated, which decomposes the FeGP cofactor; as demonstrated by spectroscopic analyses and the crystal structure of the deactivated enzyme. O2 reduction to H2O2 requires a reductant, which can be a catalytic intermediate transiently formed during the [Fe]‐hydrogenase reaction. The most probable candidate is an iron hydride species; its presence has already been predicted by theoretical studies of the catalytic reaction. The findings support predictions because the same type of reduction reaction is described for ruthenium hydride complexes that hydrogenate polar compounds.
Iron‐Catalyzed Cross‐Couplings in the Synthesis of Pharmaceuticals: In Pursuit of Sustainability
Authors: Piontek Aleksandra , Bisz Elwira , Szostak Michal
Published: February 2018

The scarcity of precious metals has led to the development of sustainable strategies for metal‐catalyzed cross‐coupling reactions. The establishment of new catalytic methods using iron is attractive owing to the low cost, abundance, ready availability, and very low toxicity of iron. In the last few years, sustainable methods for iron‐catalyzed cross‐couplings have entered the critical area of pharmaceutical research. Most notably, iron is one of the very few metals that have been successfully field‐tested as highly effective base‐metal catalysts in practical, kilogram‐scale industrial cross‐couplings. In this Minireview, we critically discuss the strategic benefits of using iron catalysts as green and sustainable alternatives to precious metals in cross‐coupling applications for the synthesis of pharmaceuticals. The Minireview provides an essential introduction to the fundamental aspects of practical iron catalysis, highlights areas for improvement, and identifies new fields to be explored.
Revealing the Active Species for Aerobic Alcohol Oxidation by Using Uniform Supported Palladium Catalysts
Authors: Xin Pingyu , Li Jia , Xiong Yu , Wu Xi , Dong Juncai , Chen Wenxing , Wang Yu , Gu Lin , Luo Jun , Rong Hongpan , Chen Chen , Peng Qing , Wang Dingsheng , Li Yadong
Published: February 2018

The active species in supported metal catalysts are elusive to identify, and large quantities of inert species can cause significant waste. Herein, using a stoichiometrically precise synthetic method, we prepare atomically dispersed palladium–cerium oxide (Pd1/CeO2) and hexapalladium cluster–cerium oxide (Pd6/CeO2), as confirmed by spherical‐aberration‐corrected transmission electron microscopy and X‐ray absorption fine structure spectroscopy. For aerobic alcohol oxidation, Pd1/CeO2 shows extremely high catalytic activity with a TOF of 6739 h−1 and satisfactory selectivity (almost 100 % for benzaldehyde), while Pd6/CeO2 is inactive, indicating that the true active species are single Pd atoms. Theoretical simulations reveal that the bulkier Pd6 clusters hinder the interactions between hydroxy groups and the CeO2 surface, thus suppressing synergy of Pd‐Ce perimeter.
Propylene polymerization over supported Ziegler–Natta catalysts: Effect of internal and external donors on distribution of active sites according to stereospecificity
Authors: Nikolaeva Marina , Matsko Mikhail , Zakharov Vladimir
Published: February 2018

Data on the content of fractions with different microtacticities for polypropylene (PP) samples produced over three catalysts [the “donor‐free” titanium–magnesium catalyst and catalysts with dibutyl phthalate and 1,3‐diether(fluorene) used as internal donors] upon polymerization in the absence/presence of an external donor (ED) have been obtained by preparative temperature rising elution fractionation method. The effect of internal and EDs on the distribution of PP fractions with different microtacticity is discussed. Data on molecular weight and thermophysical characteristics were obtained for individual fractions with different microtacticities. Correlations were found between microtacticity, molecular weight, and the melting points of these fractions. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46291.
Global biomass trade for energy— Part 2: Production and trade streams of wood pellets, liquid biofuels, charcoal, industrial roundwood and emerging energy biomass
Authors: Proskurina Svetlana , Junginger Martin , Heinimö Jussi , Tekinel Beysin , Vakkilainen Esa
Published: February 2018

Many countries have limited low‐cost biomass resources to satisfy their own demand for bioenergy; consequently, international trade in biomass in various liquid and solid forms is increasing. The aim of this study is to present a quantitative overview of the development of international biomass trade for energy purposes. This paper focuses on the main biomass producing and consuming countries, as well as exporters and importers of liquid and solid biofuels, such as wood pellets, biodiesel, and bio‐ethanol, and biomass products, for example industrial roundwood. The study discusses changes in trends that have occurred over the past decade, and investigates emerging energy biomass trade streams. Due to increased demand for wood pellets from the heating and industrial sectors, global wood pellet markets and international trade have increased significantly in the past decade. The United States and Brazil remain leaders in bio‐ethanol production with about 45 Mt and 24 Mt respectively. In recent years, Asian markets such as China (industrial roundwood), South Korea (wood pellets), Malaysia, and Indonesia (palm oil) have developed considerably. In the EU‐28, more than 60% of total palm oil consumption is used for energy purposes. The EU is the global leader in biomass for energy utilization and also the main importer of most biomass products, particularly wood pellets. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd
Microalgae cultivation and metabolites production: a comprehensive review
Authors: Vuppaladadiyam Arun K. , Prinsen Pepijn , Raheem Abdul , Luque Rafael , Zhao Ming
Published: February 2018

Microalgae have important potential in the bio‐based industry. However, their light‐utilization mechanisms are still not fully understood. Together with knowledge of their metabolic pathways and their responses in carbon partitioning to different primary metabolites (carbohydrates, lipids and proteins), this information is essential if their potential and profitability are to be better exploited. The first part of this review describes the techniques used for microalgae cultivation and the growth factors that determine their productivity, one of the most important factors in techno‐economic assessment studies of microalgae production systems. In the second part, a closer look is taken at their chemical composition in relation to the biosynthesis of primary and secondary metabolites. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd
Enzymatic Production of Biodiesel: Strategies to Overcome Methanol Inactivation
Authors: Lotti Marina , Pleiss Jürgen , Valero Francisco , Ferrer Pau
Published: February 2018

Lipase‐catalyzed transesterification of triglycerides and alcohols to obtain biodiesel is an environmentally friendly and sustainable route for fuels production since, besides proceeding in mild reaction conditions, it allows for the use of low‐cost feedstocks that contain water and free fatty acids, for example non‐edible oils and waste oils. This review article reports recent advances in the field and focus in particular on a major issue in the enzymatic process, the inactivation of most lipases caused by methanol, the preferred acyl acceptor used for alcoholysis. The recent results about immobilization of enzymes on nano‐materials and the use of whole‐cell biocatalysts, as well as the use of cell‐surface display technologies and metabolic engineering strategies for microbial production of biodiesel are described. It is discussed also insight into the effects of methanol on lipases obtained by modeling approaches and report on studies aimed at mining novel alcohol stable enzymes or at improving robustness in existing ones by protein engineering.
“Cooperative collapse” of the denatured state revealed through Clausius‐Clapeyron analysis of protein denaturation phase diagrams
Authors: Tischer Alexander , Machha Venkata R. , Rösgen Jörg , Auton Matthew
Published: February 2018

Protein phase diagrams have a unique potential to identify the presence of additional thermodynamic states even when non‐2‐state character is not readily apparent from the experimental observables used to follow protein unfolding transitions. Two‐state analysis of the von Willebrand factor A3 domain has previously revealed a discrepancy in the calorimetric enthalpy obtained from thermal unfolding transitions as compared with Gibbs‐Helmholtz analysis of free energies obtained from the Linear Extrapolation Method (Tischer and Auton, Prot Sci 2013; 22(9):1147‐60). We resolve this thermodynamic conundrum using a Clausius‐Clapeyron analysis of the urea‐temperature phase diagram that defines how
and the urea m‐value interconvert through the slope of cm versus T,
. This relationship permits the calculation of
at low temperature from m‐values obtained through iso‐thermal urea denaturation and high temperature m‐values from
obtained through iso‐urea thermal denaturation. Application of this equation uncovers sigmoid transitions in both cooperativity parameters as temperature is increased. Such residual thermal cooperativity of
and the m‐value confirms the presence of an additional state which is verified to result from a cooperative phase transition between urea‐expanded and thermally‐compact denatured states. Comparison of the equilibria between expanded and compact denatured ensembles of disulfide‐intact and carboxyamidated A3 domains reveals that introducing a single disulfide crosslink does not affect the presence of the additional denatured state. It does, however, make a small thermodynamically favorable free energy (∼–13 ± 1 kJ/mol) contribution to the cooperative denatured state collapse transition as temperature is raised and urea concentration is lowered. The thermodynamics of this “cooperative collapse” of the denatured state retain significant compensations between the enthalpy and entropy contributions to the overall free energy.
Engineered CRISPR/Cas9 system for multiplex genome engineering of polyploid industrial yeast strains
Authors: Lian Jiazhang , Bao Zehua , Hu Sumeng , Zhao Huimin
Published: February 2018

The CRISPR/Cas9 system has been widely used for multiplex genome engineering of Saccharomyces cerevisiae. However, its application in manipulating industrial yeast strains is less successful, probably due to the genome complexity and low copy numbers of gRNA expression plasmids. Here we developed an efficient CRISPR/Cas9 system for industrial yeast strain engineering by using our previously engineered plasmids with increased copy numbers. Four genes in both a diploid strain (Ethanol Red, 8 alleles in total) and a triploid strain (ATCC 4124, 12 alleles in total) were knocked out in a single step with 100% efficiency. This system was used to construct xylose‐fermenting, lactate‐producing industrial yeast strains, in which ALD6, PHO13, LEU2, and URA3 were disrupted in a single step followed by the introduction of a xylose utilization pathway and a lactate biosynthetic pathway on auxotrophic marker plasmids. The optimized CRISPR/Cas9 system provides a powerful tool for the development of industrial yeast based microbial cell factories.
Enhancing cytochrome P450‐mediated non‐natural cyclopropanation by mutation of a conserved second‐shell residue
Authors: Gober Joshua G. , Rydeen Amy E. , Schwochert Timothy D. , Gibson‐O'Grady Evan J. , Brustad Eric M.
Published: February 2018

Engineered cytochrome P450s are emerging as powerful synthetic tools due to their ability catalyze non‐native metallocarbenoid and ‐nitrenoid insertion reactions. P450‐mediated cyclopropanation has garnered particular interest due to the high selectivity demonstrated by engineered scaffolds and their application towards the synthesis of therapeutic agents. We previously reported that mutation of a conserved, first‐shell heme‐ligating Cys to Ser led to significant improvements in cyclopropanation activity in a model enzyme, P450BM3h. Here, we demonstrate that mutation of a ubiquitously conserved second‐shell Phe (F393) to His or Ala, provides complementary increases in the P450 heme reduction potential and conversion to cyclopropanation products when compared to first‐shell Cys to Ser mutations. Furthermore, we show that these mutations confer improved non‐natural catalysis in 4 diverse P450 scaffolds.
Metabolic responses and pathway changes of mammalian cells under different culture conditions with media supplementations
Authors: Park Seo‐Young , Reimonn Thomas M. , Agarabi Cyrus D. , Brorson Kurt A. , Yoon Seongkyu
Published: February 2018

Amino acids and glucose consumption, cell growth and monoclonal antibody (mAb) production in mammalian cell culture are key considerations during upstream process and particularly media optimization. Understanding the interrelations and the relevant cellular physiology will provide insight for setting strategy of robust and effective mAb production. The aim of this study was to further our understanding of nutrient consumption metabolism, since this could have significant impact on enhancing mAb titer, cell proliferation, designing feeding strategies, and development of feed media. The nutrient consumption pattern, mAb concentration, and cell growth were analyzed in three sets of cell cultures with media supplementation of glucose, methionine, threonine, tryptophan, and tyrosine. The amino acids metabolism and its impact on cell growth and mAb production during the batch and fed‐batch culture were closely analyzed. It was shown that the phenylalanine, tyrosine and tryptophan biosynthesis pathways were significantly altered under different culture conditions with different media. These changes were more apparent in the fed‐batch process in which higher mAb titer was observed due to the metabolic changes than mAb titer in the batch process. The pathway analysis approach was well utilized for evaluating the impact on the relevant pathways involved under different cell culture conditions to improve cell growth and mAb titer. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:793–805, 2018
Microbial lipid extraction from Lipomyces starkeyi using irreversible electroporation
Authors: Karim Ahasanul , Yousuf Abu , Islam M. Amirul , Naif Yasir H. , Faizal Che Ku Mohammad , Alam Md. Zahangir , Pirozzi Domenico
Published: February 2018

The aim of the study was to investigate the feasibility of using irreversible electroporation (EP) as a microbial cell disruption technique to extract intracellular lipid within short time and in an eco‐friendly manner. An EP circuit was designed and fabricated to obtain 4 kV with frequency of 100 Hz of square waves. The yeast cells of Lipomyces starkeyi (L. starkeyi) were treated by EP for 2‐10 min where the distance between electrodes was maintained at 2, 4, and 6 cm. Colony forming units (CFU) were counted to observe the cell viability under the high voltage electric field. The forces of the pulsing electric field caused significant damage to the cell wall of L. starkeyi and the disruption of microbial cells was visualized by field emission scanning electron microscopic (FESEM) image. After breaking the cell wall, lipid was extracted and measured to assess the efficiency of EP over other techniques. The extent of cell inactivation was up to 95% when the electrodes were placed at the distance of 2 cm, which provided high treatment intensity (36.7 kWh m−3). At this condition, maximum lipid (63 mg g−1) was extracted when the biomass was treated for 10 min. During the comparison, EP could extract 31.88% lipid while the amount was 11.89% for ultrasonic and 16.8% for Fenton's reagent. The results recommend that the EP is a promising technique for lowering the time and solvent usage for lipid extraction from microbial biomass. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:838–845, 2018
A blood tumor marker combination assay produces high sensitivity and specificity for cancer according to the natural history
Authors: Kobayashi Tsuneo
Published: February 2018

Diagnosis using a specific tumor marker is difficult because the sensitivity of this detection method is under 20%. Herein, a tumor marker combination assay, combining growth‐related tumor marker and associated tumor marker (Cancer, 73(7), 1994), was employed. This double‐blind tumor marker combination assay (TMCA) showed 87.5% sensitivity as the results, but a low specificity, ranging from 30 to 76%. To overcome this low specificity, we exploited complex markers, a multivariate analysis and serum fractionation by biochemical biopsy. Thus, in this study, a combination of new techniques was used to re‐evaluate these serum samples. Three serum panels, containing 90, 120, and 97 samples were obtained from the Mayo Clinic. The final results showed 80‐90% sensitivity, 84‐85% specificity, and 83‐88% accuracy. We demonstrated a notable tumor marker combination assay with high accuracy. This TMCA should be applicable for primary cancer detection and recurrence prevention.
The efficacy of adding targeted agents to neoadjuvant therapy for locally advanced rectal cancer patients: a meta‐analysis
Authors: Zhong Xi , Wu Zhonghua , Gao Peng , Shi Jinxin , Sun Jingxu , Guo Zhexu , Wang Zhenning , Song Yongxi
Published: February 2018

Patients with locally advanced rectal cancer (LARC) are at tremendous risk of metastatic diseases. To improve the prognoses of LARC patients, the efficacy of adding targeted agents to neoadjuvant therapy has been investigated by many researchers but remains controversial. A literature search of relevant databases was conducted through December 2016, 804 studies were identified and 32 investigations were ultimately included. A total of 1196 patients from 31 cohorts of 29 studies were eligible for quantitative synthesis in this single‐arm setting meta‐analysis. As pathologic complete response (pCR) shows promise as a prognosis indicator, we focused on pCR rates to evaluate whether adding targeted agents to neoadjuvant therapies improves the outcome of LARC patients. In our study, we revealed pooled estimates of pCR of 27% (95%CI, 21–34%) and 14% (95%CI, 9–21%) for bevacizumab‐relevant cohorts and cetuximab‐relevant cohorts, respectively. The safety of adding targeted agents to neoadjuvant therapy was also evaluated by pooling the data of Grade 3/4 toxicity. In conclusion, our study revealed that adding bevacizumab to the neoadjuvant therapy regimens provides appreciable pCR for LARC patients. Meanwhile, the efficacy of cetuximab remains inconclusive, RCTs with larger scale and better study design that stress more on mutational status are needed.
Forkhead box C2 promotes the invasion ability of human trophoblast cells through Hedgehog (Hh) signaling pathway
Authors: Zhang Yuhong , Zhang Yangjia
Published: February 2018

Embryonic development depends on the normal invasion of trophoblast cells. Forkhead box C2 (FOXC2) is a member of Forkhead box family, which is involved in the tumor cells invasion. The aim of this study was to explore the roles of FOXC2 on the invasion of human trophoblast cells, and further study its molecular mechanism. The mRNA and protein levels of FOXC2 in human normal trophoblast and choriocarcinoma cell lines were analyzed by quantitative real‐time PCR (qRT‐PCR) and Western blot assays, respectively. Methylthiazolyldiphenyl‐tetrazo lium bromide (MTT) and transwell assays were separately performed to detect the adhesion and invasion of normal trophoblast cells treated with exogenous FOXC2 and FOXC2 siRNA. QRT‐PCR and Western blot assays were used to test levels of the epithelial‐mesenchymal transition (EMT)‐related and Hedgehog (Hh) signaling pathway‐related factors, respectively. Herein, our results found that the expression levels of FOXC2 in normal trophoblast cells were lower than choriocarcinoma cells. FOXC2 over‐expression remarkably strengthened the adhesion and invasion abilities of normal trophoblast cells. Moreover, over‐expression of FOXC2 significantly promoted the expression of human leukocyte antigen‐G (HLA‐G), matrix metalloproteinase‐2 (MMP‐2), Vimentin, sonic hedgehog (Shh), Glioma‐associated oncogene homolog 1 (Gli1), and Snail, and inhibited E‐cadherin expression. However, it showed the opposite tendency in FOXC2 siRNA group. In addition, there was no significant change in the expression of MMP9 among different groups. Above results illustrated that FOXC2 could promote the invasion ability of normal trophoblast cells by EMT‐mediated Hh pathway.
Neonatal adrenal findings: significance and diagnostic approach. Description of two cases
Authors: Angelis Dimitrios , Mudduluru Manjula , Joseph Sonia , Ching Christopher , Hughes Amanda , Bennett Robert
Published: February 2018

Key Clinical Message

Abnormal adrenal findings such as hemorrhage or calcifications in the neonate can stem from a variety of etiologies. Clinical presentation can vary significantly based on the degree of hemorrhage or the associated condition. Thorough work‐up is important to rule out critical underlying conditions as well as adrenal insufficiency.
Renal cyst infection: a diagnostic dilemma
Authors: Kamboj Mayanka , Zeng Xu , Koratala Abhilash
Published: February 2018

Key Clinical Message

Cyst infection is a common complication of autosomal dominant polycystic kidney disease. It presents with vague clinical features and imaging findings which make the diagnosis challenging. Imaging findings can be misinterpreted as renal cell carcinoma, and biopsy of the lesion is often required for definitive diagnosis.
Claramines: A New Class Of Broad‐Spectrum Antimicrobial Agents With Bimodal Activity
Authors: Blanchet Marine , Borselli Diane , Rodallec Anne , Peiretti Franck , Vidal Nicolas , Bolla Jean‐Michel , Digiorgio Carole , Morrison Kelly R. , Wuest William M. , Brunel Jean Michel
Published: February 2018

The emergence of multidrug‐resistant bacteria and pathogens has created an urgent need for the development of new antibiotics. Herein we report our investigations into the broad‐spectrum activity of an easily prepared water‐soluble polyaminosterol compound, namely claramine A1, against both drug‐sensitive and drug‐resistant Gram‐negative and Gram‐positive bacterial strains. We also report its peculiar mechanism of action, which differs from that of all the other well‐known classes of antibiotics, toward Gram‐negative and Gram‐positive bacteria. Given their low cytotoxicity, this class of compounds based on claramine A1 could constitute an effective response to combat the emergence of multidrug‐resistant bacteria and nosocomial diseases.
Research Directions in the Clinical Implementation of Pharmacogenomics: An Overview of US Programs and Projects
Authors: Volpi Simona , Bult Carol J. , Chisholm Rex L. , Deverka Patricia A. , Ginsburg Geoffrey S. , Jacob Howard J. , Kasapi Melpomeni , McLeod Howard L. , Roden Dan M. , Williams Marc S. , Green Eric D. , Rodriguez Laura Lyman , Aronson Samuel , Cavallari Larisa H. , Denny Joshua C. , Dressler Lynn G. , Johnson Julie A. , Klein Teri E. , Leeder J. Steven , Piquette‐Miller Micheline , Perera Minoli , Rasmussen‐Torvik Laura J. , Rehm Heidi L. , Ritchie Marylyn D. , Skaar Todd C. , Wagle Nikhil , Weinshilboum Richard , Weitzel Kristin W. , Wildin Robert , Wilson John , Manolio Teri A. , Relling Mary V.
Published: February 2018

Response to a drug often differs widely among individual patients. This variability is frequently observed not only with respect to effective responses but also with adverse drug reactions. Matching patients to the drugs that are most likely to be effective and least likely to cause harm is the goal of effective therapeutics. Pharmacogenomics (PGx) holds the promise of precision medicine through elucidating the genetic determinants responsible for pharmacological outcomes and using them to guide drug selection and dosing. Here we survey the US landscape of research programs in PGx implementation, review current advances and clinical applications of PGx, summarize the obstacles that have hindered PGx implementation, and identify the critical knowledge gaps and possible studies needed to help to address them.
Fluorescent Flavoprotein Heterodimers: Combining Photostability with Singlet Oxygen Generation
Authors: Rodríguez‐Pulido Alberto , Torra Joaquim , Mejías Sara H. , Cortajarena Aitziber L. , Ruiz‐González Rubén , Nonell Santi , Flors Cristina
Published: February 2018

Flavoproteins that combine stable fluorescence emission with the ability to photosensitize reactive oxygen species (ROS) have great potential for advanced imaging techniques, such as correlative light and electron microscopy (CLEM). However, ROS photosensitization results in substantial fluorescence photobleaching in flavoproteins, limiting their application as genetically encoded microscopy tags. To address this issue, we have engineered two novel flavoprotein heterodimers from monomers with complementary properties, and show that a good compromise between photostability and singlet oxygen photosensitization can be achieved. The potential of the heterodimers as tags for CLEM is also investigated and discussed. Since the size of the tandem heterodimers is still small, similar to that of a single green fluorescent protein, these novel tags are a useful addition to the flavoprotein toolbox for a growing number of advanced imaging techniques.
A Lion‐Whale optimization‐based migration of virtual machines for data centers in cloud computing
Authors: Venkata Krishna J. , Apparao Naidu G. , Upadhayaya Niraj
Published: February 2018

The scalability, reliability, and flexibility in the cloud computing services are the obligations in the growing demand of computation power. To sustain the scalability, a proper virtual machine migration (VMM) approach is needed with apt balance on quality of service and service‐level agreement violation. In this paper, a novel VMM algorithm based on Lion‐Whale optimization is developed by integrating the Lion optimization algorithm and the Whale optimization algorithm. The optimal virtual machine (VM) migration is performed by the Lion‐Whale VMM based on a new fitness function in the regulation of the resource use, migration cost, and energy consumption of VM placement. The experimentation of the proposed VM migration strategy is performed over 4 cloud setups with a different configuration which are simulated using CloudSim toolkit. The performance of the proposed method is validated over existing optimization‐based VMM algorithms, such as particle swarm optimization and genetic algorithm, using the performance measures, such as energy consumption, migration cost, and resource use. Simulation results reveal the fact that the proposed Lion‐Whale VMM effectively outperforms other existing approaches in optimal VM placement for cloud computing environment with reduced migration cost of 0.01, maximal resource use of 0.36, and minimal energy consumption of 0.09.
Immediate biopsy of cervical cytology‐negative and non‐HPV‐16/18 oncogenic types positive patients
Authors: Karaca İbrahim , Öztürk Mustafa , Comba Cihan , Demirayak Gökhan , Alay İsmail , Erdoğan Volkan Şakir , Hoşgören Murat , Yaşar Levent
Published: February 2018

Background

According to the American Society of Colposcopy and Cervical Pathology (ASCCP), a co‐test is recommended for patients one year after the detection of non‐HPV 16/18 viral types in association with a negative cervical cytology. In this study, we used immediate colposcopy to evaluate the risks to the patient during the one year waiting period.

Methods

We included 544 Hpv‐positive/cervical cytology‐negative patients who underwent cervical cancer screening from June 2015 to June 2017. Cytological specimens were classified using the Bethesta method on a liquid based preparation. We used the Hybrid Capture 2 system to define HPV DNA. Biopsies were performed on all patients under colposcopy.

Results

Three hundred and seventy‐five patients had HPV types 16/18 and 169 had non‐HPV‐16/18 oncogenic types. Of the 169 patients who had non‐HPV‐16/18 oncogenic types, 151 (89%) had no dysplasia, 16 (9.4%) had CIN 1, and 2 (1.1%) had CIN 2/CIN 3.

Conclusion

For the patients who had cervical cytology negative/non‐HPV‐16/18 positive, we detected that 1.1% of these women had CIN 2‐3. For this reason, by chasing the algorithm recommended by guidelines, gynecologists take risk missing a diagnosis of CIN 2 plus lesion in 1.1% of patients.
Evaluation of nuclear chromatin using grayscale intensity and thresholded percentage area in liquid‐based cervical cytology
Authors: Lee Hyekyung , Han Myungein , Yoo Taejo , Jung Chanho , Son Hyun‐Jin , Cho Migyung
Published: February 2018

Objectives

Development of computerized image analysis techniques has opened up the possibility for the quantitative analysis of nuclear chromatin in pathology. We hypothesized that the features extracted from digital images could be used to determine specific cytomorphological findings for nuclear chromatin that may be applicable for establishing a medical diagnosis.

Methods

Three parameters were evaluated from nuclear chromatin images obtained from the liquid‐based cervical cytology samples of patients with biopsy‐proven high‐grade squamous intraepithelial lesion (HGSIL), and compared between non‐neoplastic squamous epithelia and dysplastic epithelia groups: (1) standard deviation (SD) of the grayscale intensity; (2) difference between the maximum and minimum grayscale intensity (M‐M); and (3) thresholded area percentage. Each parameter was evaluated at the mean, mean‐1SD, and mean‐2SD thresholding intensity levels.

Results

Between the mean and mean‐1SD levels, the thresholded nuclear chromatin pattern was most similar to the chromatin granularity of the unthresholded grayscale images. The SD of the gray intensity and the thresholded area percentage differed significantly between the non‐neoplastic squamous epithelia and dysplastic epithelia of HGSIL images at all three thresholding intensity levels (mean, mean‐1SD, and mean‐2SD). However, the M‐M significantly differed between the two sample types for only two of the thresholding intensity levels (mean‐1SD and mean‐2SD).

Conclusions

The digital parameters SD and M‐M of the grayscale intensity, along with the thresholded area percentage could be useful in automated cytological evaluations. Further studies are needed to identify more valuable parameters for clinical application.
Trajectories of frontal brain activity and socio‐emotional development in children
Authors: Poole Kristie L. , Santesso Diane L. , Van Lieshout Ryan J. , Schmidt Louis A.
Published: February 2018

Asymmetric frontal brain activity is thought to reflect individual differences in approach‐ and avoidance‐oriented motivation and emotional experience. Using a prospective longitudinal design, the authors investigated whether trajectories of frontal electroencephalogram (EEG) asymmetry in children (Mage = 6.39 years at enrollment) predicted subjective, behavioral, and autonomic indices of socioemotional processes. Resting frontal EEG activity was measured across four separate repeated assessments spanning approximately 2 years. Children's EEG asymmetry across assessments was best characterized by two trajectories: a stable right frontal asymmetry class (48.65%), and a stable left frontal asymmetry class (51.35%). At visit 4, children in the stable right frontal asymmetry displayed more avoidance‐related tendencies and children in the stable left frontal asymmetry class exhibited more approach‐related tendencies across social, emotional, and autonomic measures. These findings suggest that developmental patterns of resting frontal brain activity across the early school years may underlie approach‐ and avoidance‐related motivation and predict socio‐emotional processes in some children.