bluuebunny/crossref_metadata_2025 huggingface dataset:
Large‐Area Ultrathin Graphene Films by Single‐Step Marangoni Self‐Assembly for Highly Sensitive Strain Sensing Application
Authors: Li Xinming , Yang Tingting , Yang Yao , Zhu Jia , Li Li , Alam Fakhr E. , Li Xiao , Wang Kunlin , Cheng Huanyu , Lin Cheng‐Te , Fang Ying , Zhu Hongwei
Published: January 2016

Promoted by the demand for wearable devices, graphene has been proved to be a promising material for potential applications in flexible and highly sensitive strain sensors. However, low sensitivity and complex processing of graphene retard the development toward the practical applications. Here, an environment‐friendly and cost‐effective method to fabricate large‐area ultrathin graphene films is proposed for highly sensitive flexible strain sensor. The assembled graphene films are derived rapidly at the liquid/air interface by Marangoni effect and the area can be scaled up. These graphene‐based strain sensors exhibit extremely high sensitivity with gauge factor of 1037 at 2% strain, which represents the highest value for graphene platelets at this small deformation so far. This simple fabrication for strain sensors with highly sensitive performance of strain sensor makes it a novel approach to applications in electronic skin, wearable sensors, and health monitoring platforms.
Strain Control of Oxygen Vacancies in Epitaxial Strontium Cobaltite Films
Authors: Petrie Jonathan R. , Mitra Chandrima , Jeen Hyoungjeen , Choi Woo Seok , Meyer Tricia L. , Reboredo Fernando A. , Freeland John W. , Eres Gyula , Lee Ho Nyung
Published: January 2016

The ability to manipulate oxygen anion defects rather than metal cations in complex oxides can facilitate creating new functionalities critical for emerging energy and device technologies. However, the difficulty in activating oxygen at reduced temperatures hinders the deliberate control of important defects, oxygen vacancies. Here, strontium cobaltite (SrCoOx) is used to demonstrate that epitaxial strain is a powerful tool for manipulating the oxygen vacancy concentration even under highly oxidizing environments and at annealing temperatures as low as 300 °C. By applying a small biaxial tensile strain (2%), the oxygen activation energy barrier decreases by ≈30%, resulting in a tunable oxygen deficient steady‐state under conditions that would normally fully oxidize unstrained cobaltite. These strain‐induced changes in oxygen stoichiometry drive the cobaltite from a ferromagnetic metal towards an antiferromagnetic insulator. The ability to decouple the oxygen vacancy concentration from its typical dependence on the operational environment is useful for effectively designing oxides materials with a specific oxygen stoichiometry.
Scaffolded Thermally Remendable Hybrid Polymer Networks
Authors: Lyon Gayla Berg , Baranek Austin , Bowman Christopher N.
Published: January 2016

Step‐growth Diels–Alder (DA) networks using furan and maleimide groups are particularly useful in forming thermally remendable crosslinked polymers, due to the dramatic shift in equilibrium over a relatively low temperature range as compared with other diene‐dienophile pairs. However, the efficient healing observed in these materials at high temperature is directly tied to their ability to depolymerize and flow, and thermal treatment often results in deformation of the original shape. To overcome this limitation, a hybrid network material is developed, which consists of orthogonal Diels–Alder and polyurethane networks. Both step‐growth networks form simultaneously at elevated temperature without the presence of a catalyst. At high temperatures, the Diels–Alder network depolymerizes and flows into fractures through capillary action, while the polyurethane serves as a scaffold to maintain the overall shape of the sample. The DA network then repolymerizes at lower temperatures, creating a crosslinked, scar‐like “patch” throughout the crack. This healing process is repeatable without concern of monomer depletion. During heating through the glass transition, a shape memory “assist” is observed, which reverses some of the localized damage by bringing broken edges closer together. Samples are repeatedly damaged and then healed through temperature cycling, as evidenced through tensile fracture tests and electrochemical conductivity tests.
Palladium‐Catalyzed Divergent Arylation with Triazolopyridines: One‐Pot Synthesis of 6‐Aryl‐2‐α‐styrylpyridines
Authors: Moon Youngtaek , Kwon Soonhyung , Kang Dahye , Im Honggu , Hong Sungwoo
Published: January 2016

We have developed a new strategy for palladium‐catalyzed arylation reactions with triazolopyridines, wherein two different chemical transformations (C‐3 vs. C‐7) are observed by differentiating the substrates using different bases. The reactive palladium carbenoids were directly generated from triazolopyridines and underwent denitrogenative arylations with aryl bromides. Intriguingly, when potassium carbonate was replaced with potassium tert‐butoxide, direct CH arylation occurred at the most acidic position (C‐7). Moreover, two different catalytic arylation events were successfully performed in a one‐pot sequence, providing a convenient access to 6‐aryl‐2‐α‐styrylpyridines.

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Determining the Optimum Parting Direction in Plastic Injection Molds Based on Minimizing Rough Machining Time during Mold Manufacturing
Authors: Sarmiento‐Merida L. A. , Guevara‐Morales A. , Figueroa‐López U.
Published: January 2016

The versatility of plastic materials allows engineering components of very complex geometries and functionalities to be injection molded from them. Because the manufacturing cost of a mold increases with the complexity of the cavity, it is important to optimize the design of component and mold concurrently. In this study, a methodology for determining the optimum parting direction (PD) considering mold‐manufacturing factors such as tool accessibility and the amount of material to be removed is presented. The methodology starts with an accessibility analysis in which a three‐dimensional part is discretized, and candidate PDs are selected based on maximizing the accessible area, that is, the area that can be machined with a single workpiece orientation or setup. Then, the rough machining process is considered, and an optimum PD that minimizes the rough machining time for both the cavity and core plates is selected. The methodology is applied to four different automotive components: a mirror cover, an interior panel, a pillar, and a fender splash shield.
Operando Lithium Dynamics in the Li‐Rich Layered Oxide Cathode Material via Neutron Diffraction
Authors: Liu Haodong , Chen Yan , Hy Sunny , An Ke , Venkatachalam Subramanian , Qian Danna , Zhang Minghao , Meng Ying Shirley
Published: January 2016

Neutron diffraction under operando battery cycling is used to study the lithium and oxygen dynamics of high Li‐rich Li(Lix/3Ni(3/8‐3x/8)Co(1/4‐x/4)Mn(3/8+7x/24)O2 (x = 0.6, HLR) and low Li‐rich Li(Lix/3Ni(1/3‐x/3)Co(1/3‐x/3)Mn(1/3+x/3)O2 (x = 0.24, LLR) compounds that exhibit different degrees of oxygen activation at high voltage. The measured lattice parameter changes and oxygen position show largely contrasting changes for the two cathodes where the LLR exhibits larger movement of oxygen and lattice contractions in comparison to the HLR that maintains relatively constant lattice parameters and oxygen position during the high voltage plateau until the end of charge. Density functional theory calculations show the presence of oxygen vacancy during the high voltage plateau; changes in the lattice parameters and oxygen position are consistent with experimental observations. Lithium migration kinetics for the Li‐rich material is observed under operando conditions for the first time to reveal the rate of lithium extraction from the lithium layer, and transition metal layer is related to the different charge and discharge characteristics. At the beginning of charging, the lithium extraction predominately occurs within the lithium layer. Once the high voltage plateau is reached, the lithium extraction from the lithium layer slows down and extraction from the transition metal layer evolves at a faster rate.
Lithium Doping to Enhance Thermoelectric Performance of MgAgSb with Weak Electron–Phonon Coupling
Authors: Liu Zihang , Wang Yumei , Mao Jun , Geng Huiyuan , Shuai Jing , Wang Yuanxu , He Ran , Cai Wei , Sui Jiehe , Ren Zhifeng
Published: January 2016

Despite the unfavorable band structure with twofold degeneracy at the valence band maximum, MgAgSb is still an excellent p‐type thermoelectric material for applications near room temperature. The intrinsically weak electron–phonon coupling, reflected by the low deformation potential Edef ≈ 6.3 eV, plays a crucial role in the relatively high power factor of MgAgSb. More importantly, Li is successfully doped into Mg site to tune the carrier concentration, leading to the resistivity reduction by a factor of 3 and a consequent increase in power factor by ≈30% at 300 K. Low lattice thermal conductivity can be simultaneously achieved by all‐scale hierarchical phonon scattering architecture including high density of dislocations and nanoscale stacking faults, nanoinclusions, and multiscale grain boundaries. Collectively, much higher average power factor ≈25 μW cm−1 K−2 with a high average ZT ≈ 1.1 from 300 to 548 K is achieved for 0.01 Li doping, which would result in a high output power density ≈1.56 W cm−2 and leg efficiency ≈9.2% by calculations assuming cold‐side temperature Tc = 323 K, hot‐side temperature Th = 548 K, and leg length = 2 mm.
Reversed micelle synergistic extraction from phosphonium ionic liquid extractants in diluent for rare earth
Authors: Dong Yamin , Sun Xiaoqi , Wang Yanliang , Chai Yujun
Published: January 2016

The first synergistic extraction between quaternary phosphonium type ionic liquid extractants in toluene for rare earth was reported in this article. There were two different ion‐association mechanisms in the synergistic extraction system. The formed reversed micelles contributed to increase extractability of the synergistic extraction system to a considerable extent. On the one hand, million tons of saponification wastewater from acidic extractants may be avoided by developing the extraction system using bifunctional ionic liquid extractants. On the other hand, the novel synergistic extraction offers an effective strategy to increase the extractabilities of industrial extractants. This article reveals sustainable and efficient potentials for industrial rare earth separation. © 2016 American Institute of Chemical Engineers AIChE J, 62: 2163–2169, 2016
Inner ear morphology of the cioclovina early modern European calvaria from Romania
Authors: Uhl Alexandra , Reyes‐Centeno Hugo , Grigorescu Dan , Kranioti Elena F. , Harvati Katerina
Published: January 2016

Objectives

The morphology of the human bony labyrinth is thought to preserve a strong phylogenetic signal and to be minimally, if at all, affected by postnatal processes. The form of the semicircular canals is considered a derived feature of Neanderthals and different from the modern human anatomy. Among other hominins, European Middle Pleistocene humans have been found to be most similar to Neanderthals. Early modern humans have been proposed to show a pattern that is distinct, but most similar to that of Holocene people. Here we examine the inner ear structures of the Cioclovina calvaria, one of the earliest reliably dated and relatively complete modern human crania from Europe, in the context of recent and fossil human variation.

Materials and Methods

Bony labyrinths were virtually extracted from CT scans of recent Europeans and Cioclovina. Using univariate and multivariate methods, measurements of the semicircular canals were compared with published measurements of other fossil specimens.

Results

Our results show that Cioclovina's inner ear morphology falls within the range of modern variation, with affinities to both Late Pleistocene modern humans and recent Europeans. Using discriminant functions, the sex of the Cioclovina specimen is estimated as male.

Discussion

Results agree with previous work showing that Cioclovina exhibits fully modern cranial morphology. Am J Phys Anthropol 160:62–70, 2016. © 2016 Wiley Periodicals, Inc.
Z‐Shaped Pentaleno‐Acene Dimers with High Stability and Small Band Gap
Authors: Dai Gaole , Chang Jingjing , Luo Jie , Dong Shaoqiang , Aratani Naoki , Zheng Bin , Huang Kuo‐Wei , Yamada Hiroko , Chi Chunyan
Published: January 2016

Acene‐based materials have promising applications for organic electronics but the major constrain comes from their poor stability. Herein a new strategy to stabilize reactive acenes, by fusion of an anti‐aromatic pentalene unit onto the zigzag edges of two acene units to form a Z‐shaped acene dimer, is introduced. The Z‐shaped acene dimers are extremely stable and show a small energy gap resulting from intramolecular donor–acceptor interactions. X‐ray crystallographic analysis revealed their unique geometry and one‐dimensional slip‐stack columnar structure. Besides optical and electrochemical characterizations, solution‐processed field‐effect transistors were also fabricated.
Simple Peptide‐Tuned Self‐Assembly of Photosensitizers towards Anticancer Photodynamic Therapy
Authors: Liu Kai , Xing Ruirui , Zou Qianli , Ma Guanghui , Möhwald Helmuth , Yan Xuehai
Published: January 2016

Peptide‐tuned self‐assembly of functional components offers a strategy towards improved properties and unique functions of materials, but the requirement of many different functions and a lack of understanding of complex structures present a high barrier for applications. Herein, we report a photosensitive drug delivery system for photodynamic therapy (PDT) by a simple dipeptide‐ or amphiphilic amino‐acid‐tuned self‐assembly of photosensitizers (PSs). The assembled nanodrugs exhibit multiple favorable therapeutic features, including tunable size, high loading efficiency, and on‐demand drug release responding to pH, surfactant, and enzyme stimuli, as well as preferable cellular uptake and biodistribution. These features result in greatly enhanced PDT efficacy in vitro and in vivo, leading to almost complete tumor eradication in mice receiving a single drug dose and a single exposure to light.
The Enantioselective Dakin–West Reaction
Authors: Wende Raffael C. , Seitz Alexander , Niedek Dominik , Schuler Sören M. M. , Hofmann Christine , Becker Jonathan , Schreiner Peter R.
Published: January 2016

Here we report the development of the first enantioselective Dakin–West reaction, yielding α‐acetamido methylketones with up to 58 % ee with good yields. Two of the obtained products were recrystallized once to achieve up to 84 % ee. The employed methylimidazole‐containing oligopeptides catalyze both the acetylation of the azlactone intermediate and the terminal enantioselective decarboxylative protonation. We propose a dispersion‐controlled reaction path that determines the asymmetric reprotonation of the intermediate enolate after the decarboxylation.
Cooperative Reductive Elimination: The Missing Piece in the Oxidative‐Coupling Mechanistic Puzzle
Authors: Funes‐Ardoiz Ignacio , Maseras Feliu
Published: January 2016

The reaction between benzoic acid and methylphenylacetylene to form an isocoumarin is catalyzed by Cp*Rh(OAc)2 in the presence of Cu(OAc)2(H2O) as an oxidant and a leading example of oxidative‐coupling reactions. Its mechanism was elucidated by DFT calculations with the B97D functional. The conventional mechanism, with separate reductive‐elimination and reoxidation steps, was found to yield a naphthalene derivative as the major product by CO2 extrusion, contradicting experimental observations. The experimental result was reproduced by an alternative mechanism with a lower barrier: In this case, the copper acetate oxidant plays a key role in the reductive‐elimination step, which takes place through a transition state containing both rhodium and copper centers. This cooperative reductive‐elimination step would not be accessible with a generic oxidant, which, again, is in agreement with available experimental data.
Palladium‐Catalyzed Trifluoromethylation of (Hetero)Arenes with CF3Br
Authors: Natte Kishore , Jagadeesh Rajenahally V. , He Lin , Rabeah Jabor , Chen Jianbin , Taeschler Christoph , Ellinger Stefan , Zaragoza Florencio , Neumann Helfried , Brückner Angelika , Beller Matthias
Published: January 2016

The CF3 group is an omnipresent motif found in many pharmaceuticals, agrochemicals, catalysts, materials, and industrial chemicals. Despite well‐established trifluoromethylation methodologies, the straightforward and selective introduction of such groups into (hetero)arenes using available and less expensive sources is still a major challenge. In this regard, the selective synthesis of various trifluoromethyl‐substituted (hetero)arenes by palladium‐catalyzed C−H functionalization is herein reported. This novel methodology proceeds under comparably mild reaction conditions with good regio‐ and chemoselectivity. As examples, trifluoromethylations of biologically important molecules, such as melatonin, theophylline, caffeine, and pentoxifylline, are showcased.
Nanoplasmonic Photoluminescence Spectroscopy at Single‐Particle Level: Sensing for Ethanol Oxidation
Authors: Zheng Zhaoke , Majima Tetsuro
Published: January 2016

Surface plasmon resonances of metal nanoparticles have shown significant promise for the use of solar energy to drive catalytic chemical reactions. More importantly, understanding and monitoring such catalytic reactions at single‐nanoparticle level is crucial for the study of local reaction processes. Herein, using plasmonic photoluminescence (PL) spectroscopy, we describe a novel sensing method for catalytic ethanol oxidation reactions at the single‐nanoparticle level. The Au nanorod monitors the interfacial interaction with ethanol during the catalytic reaction through the PL intensity changes in the single‐particle PL spectra. The analysis of energy relaxation of excited electron–hole pairs indicates the relationship between the PL quenching and ethanol oxidation reaction on the single Au nanorod.
Mechanical Reversibility of Strain‐Promoted Azide–Alkyne Cycloaddition Reactions
Authors: Jacobs Monique J. , Schneider Guenter , Blank Kerstin G.
Published: January 2016

Mechanophores, that is, molecules that show a defined response to force, are crucial building blocks of mechanoresponsive materials. The possibility of mechanically induced cycloreversion for a series of triazoles formed via strain‐promoted azide–alkyne cycloaddition reactions was investigated by density functional theory calculations, and these triazoles were compared to the 1,4‐ and 1,5‐regioisomers formed in the reaction of an azide with a terminal alkyne. We show that cycloreversion is in principal possible and that the pulling geometry is the most important parameter that determines the probability of cycloreversion. We further compared triazole stability to the mechanical stability of polymers that are frequently used as force transducers in mechanochemical experiments and identified DIBAC (azadibenzylcyclooctyne) as a promising mechanophore for future applications.
Quantifying the Electrocatalytic Turnover of Vitamin B12‐Mediated Dehalogenation on Single Soft Nanoparticles
Authors: Cheng Wei , Compton Richard G.
Published: January 2016

We report the electrocatalytic dehalogenation of trichloroethylene (TCE) by single soft nanoparticles in the form of Vitamin B12‐containing droplets. We quantify the turnover number of the catalytic reaction at the single soft nanoparticle level. The kinetic data shows that the binding of TCE with the electro‐reduced vitamin in the CoI oxidation state is chemically reversible.
Traceless Synthesis of Asymmetrically Modified Bivalent Nucleosomes
Authors: Lechner Carolin C. , Agashe Ninad D. , Fierz Beat
Published: January 2016

Nucleosomes carry extensive post‐translational modifications (PTMs), which results in complex modification patterns that are involved in epigenetic signaling. Although two copies of each histone coexist in a nucleosome, they may not carry the same PTMs and are often differently modified (asymmetric). In bivalent domains, a chromatin signature prevalent in embryonic stem cells (ESCs), namely H3 methylated at lysine 4 (H3K4me3), coexists with H3K27me3 in asymmetric nucleosomes. We report a general, modular, and traceless method for producing asymmetrically modified nucleosomes. We further show that in bivalent nucleosomes, H3K4me3 inhibits the activity of the H3K27‐specific lysine methyltransferase (KMT) polycomb repressive complex 2 (PRC2) solely on the same histone tail, whereas H3K27me3 stimulates PRC2 activity across tails, thereby partially overriding the H3K4me3‐mediated repressive effect. To maintain bivalent domains in ESCs, PRC2 activity must thus be locally restricted or reversed.
New Potent SARS‐CoV 3C‐Like Protease Inhibitors Derived from Thieno[2,3‐d]‐pyrimidine Derivatives
Authors: Abd El‐All Amira S. , Atta Sanaa M. Sh. , Roaiah Hanaa M. F. , Awad Enas M. , Abdalla Mohamed M.
Published: January 2016

2‐Amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐3‐carboxamide (1) condensed with carbaldehydes 2a,b to give the respective thienopyrimidines (3a,b), which reacted with phosphoryl chloride and hydrazine hydrate to afford the respective pyrimidinohydrazines (4a,b). Compound 4a condensed with acetophenone under Vilsmeier conditions to afford the formylated pyrazolopyrimidine 6. Condensation of 4a with active methylenes produced the respective pyrazolopyrimidines (7–11). Besides, 4a condensed with succinic anhydride and with phthalic anhydride, yielding the pyrrolidine‐2,5‐dione 12 and the isoindoline‐1,3‐dione 13, respectively. Moreover, 4a reacted with isatin to afford the hydrazono‐indolin‐2‐one 14. Structural elucidations for the new thienopyrimidines were based upon compatible analytical and spectroscopic results. Eleven of the new compounds were tested and found active against influenza A neuraminidase virus (H3N2). Compounds 12 and 13 were the most potent.
Brief Report: Severe Inflammation Following Vaccination Against Streptococcus pneumoniae in Patients With Cryopyrin‐Associated Periodic Syndromes
Authors: Walker Ulrich A. , Hoffman Hal M. , Williams Rene , Kuemmerle‐Deschner Jasmin , Hawkins Philip N.
Published: January 2016

Objective

Pneumococcal vaccination is recommended for patients receiving immunosuppressive drugs. We describe unusually severe adverse reactions to pneumococcal vaccination in each of 7 consecutive patients with cryopyrin‐associated periodic syndromes (CAPS).

Methods

Seven consecutive patients with CAPS were vaccinated with pneumococcal polysaccharide or conjugate vaccines. Clinical information was collected retrospectively.

Results

Within a few hours after the vaccination, all 7 patients developed severe local reactions at the injection site. Two patients had to be hospitalized for systemic reactions including fever. All symptoms resolved in a period of 3–17 days.

Conclusion

Our findings indicate that pneumococcal vaccines can trigger a severe local and systemic inflammatory reaction in patients with CAPS and possibly patients with other autoinflammatory diseases. Careful consideration is warranted when implementing current European League Against Rheumatism immunization guidelines in this patient population.
A 3,7‐Dihydroxyphenoxazine‐based Fluorescent Probe for Selective Detection of Intracellular Hydrogen Peroxide
Authors: Han Zhiqiang , Liang Xiao , Ren Xuejiao , Shang Luqing , Yin Zheng
Published: January 2016

A novel N‐borylbenzyloxycarbonyl‐3,7‐dihydroxyphenoxazine fluorescent probe (NBCD) for detecting H2O2 in living cells is described. The probe could achieve high selectivity for detecting H2O2 over other biological reactive oxygen species (ROS). In addition, upon addition of H2O2, NBCD exhibited color change from colorless to pink, which makes it a “naked‐eye” probe for H2O2 detection. NBCD could not only be used to detect enzymatically generated H2O2 but also to detect H2O2 in living systems by using fluorescence spectroscopy, with a detection limit of 2 μm. Importantly, NBCD enabled the visualization of epidermal growth factor (EGF)‐stimulated H2O2 generation inside the cells.
Hybrid Coordination Networks Constructed from ɛ‐Keggin‐Type Polyoxometalates and Rigid Imidazole‐Based Bridging Ligands as New Carriers for Noble‐Metal Catalysts
Authors: Yang Xiao‐Jian , Sun Meng , Zang Hong‐Ying , Ma Yuan‐Yuan , Feng Xiao‐Jia , Tan Hua‐Qiao , Wang Yong‐Hui , Li Yang‐Guang
Published: January 2016

Three hybrid coordination networks that were constructed from ɛ‐Keggin polyoxometalate building units and imidazole‐based bridging ligands were prepared under hydrothermal conditions, that is, H[(Hbimb)2(bimb){Zn4PMoV8MoVI4O40}]⋅6 H2O (1), [Zn(Hbimbp)(bimbp)3{Zn4PMoV8MoVI4O40}]⋅DMF⋅3.5 H2O (2), and H[Zn2(timb)2(bimba)2Cl2{Zn4PMoV8MoVI4O40}]⋅7 H2O (3) (bimb=1,4‐bis(1‐imidazolyl)benzene, bimbp=4,4′‐bis(imidazolyl)biphenyl, timb=1,3,5‐tris(1‐imidazolyl)benzene, bimba=3,5‐bis(1‐imidazolyl)benzenamine). All three compounds were characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, and single‐crystal X‐ray diffraction. The mixed valence of the Mo centers was analyzed by XPS spectroscopy and bond‐valence sum calculations. In all three compounds, the ɛ‐Keggin polyoxometalate (POM) units acted as nodes that were connected by rigid imidazole‐based bridging ligands to form hybrid coordination networks. In compound 1, 1D zigzag chains extended to form a 3D supramolecular architecture through intermolecular hydrogen‐bonding interactions. Compound 2 consisted of 2D curved sheets, whilst compound 3 contained chiral 2D networks. Because of the intrinsic reducing properties of ɛ‐Keggin POM species, noble‐metal nanoparticles were loaded onto these POM‐based coordination networks. Thus, compounds 1–3 were successfully loaded with Ag nanoparticles, and the corresponding composite materials exhibited high catalytic activities for the reduction of 4‐nitrophenol.
Extremely low frequency magnetic fields regulate differentiation of regulatory T cells: Potential role for ROS‐mediated inhibition on AKT
Authors: Tang Ruijing , Xu Yujun , Ma Feiya , Ren Jing , Shen Sunan , Du Youwei , Hou Yayi , Wang Tingting
Published: January 2016

Our previous studies showed that extremely low frequency magnetic fields (ELF‐MFs) inhibited tumor growth and change proportion of splenic regulatory T cells (Treg cells). Here, we focus on the effect of ELF‐MFs on lung metastatic melanoma mouse model and the regulatory mechanism of ELF‐MFs on the differentiation of Treg cells. Tumor‐bearing mice were exposed to sham ELF‐MFs and ELF‐MFs (0.4 T, 7.5 Hz) 2 h/day for 27 days. Metastatic tumor burden of lung was significantly decreased after ELF‐MF treatment. Compared to the control group, expressions of matrix metalloproteinase (MMP2, MMP9) and forkhead box P3 (Foxp3) in lung nodules significantly decreased in the ELF‐MF group. Moreover, in vitro, after stimulated with anti‐CD3, anti‐CD28 antibodies and transforming growth factor‐β (TGF‐β) and treated with ELF‐MFs for 2 h, expression of Foxp3 in total T cells was significantly decreased. Differentiation rate of Treg cells was inhibited from 32.0% to 22.1% by ELF‐MFs. Furthermore, reactive oxygen species (ROS) was increased and phospho‐serine/threonine protein kinase (p‐AKT) was inhibited in both T cells and Jurkat cells. ROS scavenger N‐acetyl‐l‐cysteine reversed inhibition of AKT pathway and expression of Foxp3 from 18.6% to 26.6% in T cells. Taken together, our data show that ELF‐MF exposure promoted the inhibitory effect of ROS on AKT pathway and decreased Foxp3 expression, which provides an explanation for why ELF‐MF exposure can inhibit differentiation of Treg cells and enhance antitumor effect in metastatic melanoma mouse model. Bioelectromagnetics. 37:89–98, 2016. © 2016 Wiley Periodicals, Inc.
Europium‐activated rare earth fluoride (LnF3:Eu3+–Ln = La, Gd) nanocrystals prepared by using ionic liquid/NH4F as a fluorine source via hydrothermal synthesis
Authors: Kasturi S. , Sivakumar V. , Jeon Duk Young
Published: January 2016

Lanthanide (Ln) fluorides are considered exceptional luminescent rigid host matrices for various optical active Ln3+ ions due to their high refractive index, high chemical stability and low phonon energy, leading to the low probability of non‐radiative decay, which results in higher photoluminescence quantum yield (PLQY) (usually higher than oxide hosts). In this study, Eu3+‐activated Ln fluorides (LnF3:Eu3+–Ln = La, Gd) are synthesized by the hydrothermal method using 1‐butyl‐3‐methylimidazolium tertrafluoroborate [BMIBF4] and NH4F as fluorine precursors. The synthesized nanocrystals (NCs) are structurally and morphologically characterized, and their optical properties investigated using spectrofluorometry. The X‐ray diffraction (XRD) patterns of Eu3+‐substituted and ‐unsubstituted LnF3 (prepared from a different fluorine source) are indexed based on the hexagonal and orthorhombic crystal structure, respectively. Average crystalline sizes are calculated using the Scherrer equation and it is found that the synthesized NCs have an average crystalline size of 12–35 nm. Transmission electron microscopy (TEM) images reveal that the NCs are well dispersed and nearly ellipsoid, with an average size of ~ 5 nm. Eu3+‐activated NCs show characteristic excitation and emission spectra. The emission spectra show both magnetic (5D0–7F1) and electric (5D0–7F2) dipole transition with appropriate CIE color coordinates; however, the intensity of the magnetic dipole transition is high, which is in accordance with local site symmetry. Owing to their unique size and excellent optical properties, the synthesized NCs may have potential application in the fields bio‐imaging and solar concentrators. Copyright © 2016 John Wiley & Sons, Ltd.
Applications of microfluidics in microalgae biotechnology: A review
Authors: Juang Yi‐Je , Chang Jo‐Shu
Published: January 2016

Microalgae have been one of the important sources for biofuel production owing to their competitive advantages such as no need to tap into the global food supply chain, higher energy density, and absorbing carbon dioxide to mitigate global warming. One of the key factors to ensure successful biofuel production is that it requires not only bioprospecting of the microalgae with high lipid content, high growth rate and tolerance to environmental parameters but also on‐site monitoring of the cultivation process and optimization of the culturing conditions. However, as the conventional techniques usually involve in complicated procedures, or are time‐consuming or labor intensive, microfluidics technology offers an attractive alternative to resolve these issues. In this review, applications of microfluidics to bioprospecting in microalgae biotechnology were discussed such as cell identification, cell sorting/screening, cell culturing and cell disruption. In addition, utilization of microalgae in micro‐sized fuel cells and microfluidic platforms for biosensing was addressed. This review reports the recent studies and offers a look into how microfluidics is exploited to tackle the issues encountered in the microalgae biotechnology.
Scale‐up of industrial biodiesel production to 40 m3 using a liquid lipase formulation
Authors: Price Jason , Nordblad Mathias , Martel Hannah H. , Chrabas Brent , Wang Huali , Nielsen Per Munk , Woodley John M.
Published: January 2016

In this work, we demonstrate the scale‐up from an 80 L fed‐batch scale to 40 m3 along with the design of a 4 m3continuous process for enzymatic biodiesel production catalyzed by NS‐40116 (a liquid formulation of a modified Thermomyces lanuginosus lipase). Based on the analysis of actual pilot plant data for the transesterification of used cooking oil and brown grease, we propose a method applying first order integral analysis to fed‐batch data based on either the bound glycerol or free fatty acid content in the oil. This method greatly simplifies the modeling process and gives an indication of the effect of mixing at the various scales (80 L to 40 m3) along with the prediction of the residence time needed to reach a desired conversion in a CSTR. Suitable process metrics reflecting commercial performance such as the reaction time, enzyme efficiency, and reactor productivity were evaluated for both the fed‐batch and CSTR cases. Given similar operating conditions, the CSTR operation on average, has a reaction time which is 1.3 times greater than the fed‐batch operation. We also showed how the process metrics can be used to quickly estimate the selling price of the enzyme. Assuming a biodiesel selling price of 0.6 USD/kg and a one‐time use of the enzyme (0.1% (w/woil) enzyme dosage); the enzyme can then be sold for 30 USD/kg which ensures that that the enzyme cost is not more than 5% of the biodiesel revenue. Biotechnol. Bioeng. 2016;113: 1719–1728. © 2016 Wiley Periodicals, Inc.
A single short session of media perfusion induces osteogenesis in hBMSCs cultured in porous scaffolds, dependent on cell differentiation stage
Authors: Filipowska Joanna , Reilly Gwendolen C. , Osyczka Anna M.
Published: January 2016

Perfusing culture media through porous cell‐seeded scaffolds is now a common approach within many tissue engineering strategies. Human bone‐marrow derived mesenchymal stem cells (hBMSC) are a clinically valuable source of osteoprogenitors that respond to mechanical stimuli. However, the optimal mechanical conditions for their osteogenic stimulation in vitro have not been defined. Whereas the effects of short durations of media fluid flow have been studied in monolayers of osteoblastic cells, in 3D culture continuous or repeated perfusion is usually applied. Here, we investigated whether a short, single perfusion session applied to hBMSCs cultured in 3D would enhance their osteogenesis in vitro. We cultured hBMSCs on gelatine‐coated, porous polyurethane scaffolds with osteogenic supplements and stimulated them with a single 2‐h session of unidirectional, steady, 2.5 mL/min media perfusion, at either early or late stages of culture in 3D. Some cells were pre‐treated in monolayer with osteogenic supplements to advance cell differentiation, followed by 3D culture also with the osteogenic supplements. We report that this single, short session of media perfusion can markedly enhance the expression of bone‐related transcription and growth factors, and matrix components, by hBMSCs but that it is more effective when cells reach the pre‐osteoblast or osteoblast differentiation stage. These findings could aid in the optimization of 3D culture protocols for efficient bone tissue engineering. Biotechnol. Bioeng. 2016;113: 1814–1824. © 2016 Wiley Periodicals, Inc.
Efflux transporter engineering markedly improves amorphadiene production in Escherichia coli
Authors: Zhang Congqiang , Chen Xixian , Stephanopoulos Gregory , Too Heng‐Phon
Published: January 2016

Metabolic engineering aims at altering cellular metabolism to produce valuable products at high yields and titers. Achieving high titers and productivity can be challenging if final products are largely accumulated intracellularly. A potential solution to this problem is to facilitate the export of these substances from cells by membrane transporters. Amorphadiene, the precursor of antimalarial drug artemisinin, is known to be secreted from Escherichia coli overexpressing the biosynthetic pathway. In order to assess the involvement of various endogenous efflux pumps in amorphadiene transport, the effects of single gene deletion of 16 known multidrug‐resistant membrane efflux transporters were examined. The outer membrane protein TolC was found to be intimately involved in amorphadiene efflux. The overexpression of tolC together with ABC family transporters (macAB) or MFS family transporters (emrAB or emrKY) enhanced amorphadiene titer by more than threefold. In addition, the overexpression of transporters in the lipopolysaccharide transport system (msbA, lptD, lptCABFG) was found to improve amorphadiene production. As efflux transporters often have a wide range of substrate specificity, the multiple families of transporters were co‐expressed and synergistic benefits were observed in amorphadiene production. This strategy of screening and then rationally engineering transporters can be used to improve the production of other valuable compounds in E. coli. Biotechnol. Bioeng. 2016;113: 1755–1763. © 2016 Wiley Periodicals, Inc.
Solubilization and Iterative Saturation Mutagenesis of α1,3‐fucosyltransferase from Helicobacter pylori to enhance its catalytic efficiency
Authors: Choi Yun Hee , Kim Jong Hoon , Park Bum Seok , Kim Byung‐Gee
Published: January 2016

α1,3‐Fucosyltransferase (α1,3‐FucT) is essential for the biosynthesis of biologically active α1,3‐fucosyloligosacchairdes (3‐FOs) from human milk oligosaccharides (HMO), particularly 3‐fucosyllactose (3‐FL) trisaccharide. α1,3‐FucT from Helicobacter pylori 26695 (FutA) accepts lactose and LacNAc as glycan acceptors and has a very low level of expression in Escherichia coli, and it shows a low catalytic activity for lactose in the large‐scale synthesis of 3‐FL. To overcome the poor solubility of FutA, codon optimization, and systematic truncation of the protein at the C‐terminus with only one heptad repeat remaining (Δ52 FutA) were conducted to yield 150–200 mg/L of soluble protein of FutA and resulting in more than an 18‐fold increase in the 3‐FL yield. To improve the low level of enzyme catalytic activity for lactose, focused directed evolution was attempted using a semi‐rational approach that combines structure‐guided computational analysis and subsequent iterative saturation mutagenesis (ISM). In order to select the functional residues in active site/substrate binding site, docking simulation was used together with HotSpot Wizard to target evolutionarily variable amino acid positions. A128 site was selected from the key residue located in the active site, and A128N mutant displayed a 3.4‐fold higher catalytic activity than wild‐type Δ52 FutA. Considering that the A128N mutation is located in the deep cleft of the lactose binding site, the residues within the substrate binding sites, especially on the two α‐helices for lactose and one α‐helix for GDP‐fucose, were subjected to structure‐guided ISM. The selected residues from each helix were clustered, and ISM was performed for each cluster in parallel. In particular, the mutant with triple mutations (A128N/H129E/Y132I) located on the α5 helix exhibited a 9.6‐fold improvement in specific activity when compared to wild‐type Δ52 FutA. When such clustered mutations on two α‐helices (α5 and α2/loop) were combined, mutants with triple (A128N/H129E/S46F) and quadruple mutations (A128N/H129E/Y132I/S46F) were generated, which showed the synergistic effects, that is 14.5‐ and 15.5‐fold improvement in specific activity relative to wild‐type Δ52 FutA, respectively. The mutations increased their binding affinity for lactose and kcat values for lactose and GDP‐fucose. The Δ52 FutA quadruple mutant (A128N/H129E/Y132I/S46F) was successfully applied to in vitro synthesis of 3‐FL with an improved yield and productivity (>96% yield based on 5 mM of GDP‐Fuc within 1 h). Biotechnol. Bioeng. 2016;113: 1666–1675. © 2016 Wiley Periodicals, Inc.
Hydrogen‐fed biofilm reactors reducing selenate and sulfate: Community structure and capture of elemental selenium within the biofilm
Authors: Ontiveros‐Valencia Aura , Penton Christopher R. , Krajmalnik‐Brown Rosa , Rittmann Bruce E.
Published: January 2016

Remediation of selenate (SeO42−) contamination through microbial reduction is often challenging due to the presence of sulfate (SO42−), which can lead to competition for the electron donor and the co‐production of toxic H2S. Microbial reduction of SeO42− in the presence of SO42− was studied in two hydrogen‐based membrane biofilm reactors (MBfRs). One MBfR was initiated with SO42−‐reducing conditions and gradually shifted to SeO42− reduction. The second MBfR was developed with a SeO42−‐reducing biofilm, followed by SO42− introduction. Biofilms within both MBfRs achieved greater than 90% SeO42− reduction, even though the SeO42− concentration ranged from 1,000–11,000 μg/L, more than 20–200 times the maximum contaminant level for drinking water (50 μg/L). Biofilm microbial community composition, assessed by 16S rRNA gene‐based amplicon pyrosequencing, was distinct between the two MBfRs and was framed by alterations in SeO42− loading. Specifically, high SeO42− loading resulted in communities mainly composed of denitrifying bacteria (e.g., Denitratisoma and Dechloromonas). In contrast, low loading led to mostly sulfate‐reducing bacteria (i.e., Desulfovibrio) and sulfur‐oxidizing bacteria (i.e., Sulfuricurvum and Sulfurovum). SeO42− was reduced to elemental selenium (Se°), which was visualized within the biofilm as crystalloid aggregates, with its fate corresponding to that of biofilm solids. In conclusion, microbial biofilm communities initiated under either SeO42− or SO42−‐reducing conditions attained high SeO42− removal rates even though their microbial community composition was quite distinct. Biotechnol. Bioeng. 2016;113: 1736–1744. © 2016 Wiley Periodicals, Inc.
Fine tuning breath‐hold‐based cerebrovascular reactivity analysis models
Authors: van Niftrik Christiaan Hendrik Bas , Piccirelli Marco , Bozinov Oliver , Pangalu Athina , Valavanis Antonios , Regli Luca , Fierstra Jorn
Published: January 2016

Introduction

We elaborate on existing analysis methods for breath‐hold (BH)‐derived cerebrovascular reactivity (CVR) measurements and describe novel insights and models toward more exact CVR interpretation.

Methods

Five blood‐oxygen‐level‐dependent (BOLD) fMRI datasets of neurovascular patients with unilateral hemispheric hemodynamic impairment were used to test various BH CVR analysis methods. Temporal lag (phase), percent BOLD signal change (CVR), and explained variance (coherence) maps were calculated using three different sine models and two novel “Optimal Signal” model‐free methods based on the unaffected hemisphere and the sagittal sinus fMRI signal time series, respectively.

Results

All models showed significant differences in CVR and coherence between the affected—hemodynamic impaired—and unaffected hemisphere. Voxel‐wise phase determination significantly increases CVR (0.60 ± 0.18 vs. 0.82 ± 0.27; P < 0.05). Incorporating different durations of breath hold and resting period in one sine model (two‐task) did increase coherence in the unaffected hemisphere, as well as eliminating negative phase commonly obtained by one‐task frequency models. The novel model‐free “optimal signal” methods both explained the BOLD MR data similar to the two task sine model.

Conclusions

Our CVR analysis demonstrates an improved CVR and coherence after implementation of voxel‐wise phase and frequency adjustment. The novel “optimal signal” methods provide a robust and feasible alternative to the sine models, as both are model‐free and independent of compliance. Here, the sagittal sinus model may be advantageous, as it is independent of hemispheric CVR impairment.
Late rectal toxicity determined by dose–volume parameters in computed tomography‐based brachytherapy for locally advanced cervical cancer
Authors: Zhou Yong‐Chun , Zhao Li‐Na , Wang Ning , Hu Jing , Sun Xiao‐Huan , Zhang Ying , Li Jian‐Ping , Li Wei‐Wei , Liu Jun‐Yue , Wei Li‐Chun , Shi Mei
Published: January 2016

The aim of this study was to observe the relationship between dose–volume histogram (DVH) parameters and rectal late side effects (LSE) in computed tomography (CT)‐based brachytherapy (BT) for patients with locally advanced cervical cancer. In total, 144 cervical cancer patients received external beam radiotherapy and CT‐based BT. The data from 111 survival cases with pelvic local control (LC) were used to analyze the relationship between DVH parameters and rectal LSE. The total doses, manifesting 2, 1, and 0.1 cm3 (D2cc, D1cc, and D0.1cc) of the rectum, and D90 for high‐risk clinical target volume (HR CTV) were computed and normalized to 2 Gy fractions (EQD2) using a linear‐quadratic model. The rectal LSE were evaluated by the late effects in normal tissues‐subjective, objective, management, and analytic (LENT‐SOMA) scale. A dose–response relationship was evaluated by probit analyses. For all patients, the total rate of rectal LSE was 56%, and the rate of ≥Grade 2 LSE was 27.4%. For the 111 survival cases with pelvic LC, the total mean for D2cc was 71.23 ± 5.54 Gy for the rectum, and the D2cc, D1cc, and D0.1cc values for Grades 2 and 3 were higher than those for Grades 0 and 1. In addition, the number of complications increased, and the complications became more severe as the dose increased, with a dose of 73.5 Gy resulting in a 10% probability of ≥Grade 3 LSE. In conclusion, DVH parameters could predict the incidence and grades of rectal LSE in CT‐based BT. D2cc showed an excellent predictive value, and 73.5 Gy for D2cc of the rectum might be considered as an alternative dose limit.
Preliminary treatment results of proton beam therapy with chemoradiotherapy for stage I–III esophageal cancer
Authors: Takada Akinori , Nakamura Tatsuya , Takayama Kanako , Makita Chiyoko , Suzuki Motohisa , Azami Yusuke , Kato Takahiro , Tsukiyama Iwao , Hareyama Masato , Kikuchi Yasuhiro , Daimon Takashi , Toyomasu Yutaka , Ii Noriko , Nomoto Yoshihito , Sakuma Hajime , Fuwa Nobukazu
Published: January 2016

The effect of proton beam therapy (PBT) on various cancers is controversial. We aimed to evaluate the efficacy and safety of PBT with alternating chemoradiotherapy (ACRT) for patients with stage I–III esophageal cancer. Two cycles of systemic chemotherapy with a continuous infusion of 5‐fluorouracil (5‐FU) on days 1–5 and a 5h infusion of nedaplatin (NDP) on day 6 were accompanied by thoracic irradiation using X‐ray therapy and PBT. During the first half of the treatment, X‐rays were delivered to the prophylactic area. During the second half of the treatment, proton beams were used to irradiate the involved field. To reduce the dose of cardiac irradiation, proton beams were delivered with posterior and posterior oblique angles. Between January 2009 and December 2012, 47 patients were enrolled in this study. The median follow‐up duration was 29 months for all patients and 40 months for survivors. The 3 year overall survival rate, progression‐free survival rate, and local control rate were 59.2%, 56.3%, and 69.8%, respectively. With respect to grade 3–4 late toxicities, there were no pleural or pericardial effusions, but two patients (4.3%) had esophageal stenosis, one patient (2.1%) had fistula, and two patients (4.3%) developed radiation pneumonitis. PBT with ACRT might have the potential to reduce the risk of cardiac damage and might become one of the primary methods of esophageal cancer treatment.