bluuebunny/crossref_metadata_2025 huggingface dataset:
Symptomatic and Electrodiagnostic Features of Peripheral Neuropathy in Scleroderma
Authors: Paik Julie J. , Mammen Andrew L. , Wigley Fredrick M. , Shah Ami A. , Hummers Laura K. , Polydefkis Michael
Published: December 2015

Objective

To determine the prevalence of peripheral neuropathy in scleroderma.

Methods

The prevalence of length‐dependent peripheral neuropathy was rigorously assessed using signs and symptoms of neuropathy derived from the Total Neuropathy Score (TNS), and standardized nerve conduction study (NCS). All subjects underwent TNS and NCS. Those who were symptomatic or had NCS evidence of peripheral neuropathy underwent laboratory evaluation for secondary causes of neuropathy.

Results

A total of 130 subjects were approached for participation and 60 enrolled. Of the 60 subjects, 50 (83.3%) were female and 37 (61.7%) were of the limited cutaneous subtype. The mean ± SD age was 55 ± 11.1 years, and mean ± SD disease duration was 15.3 ± 10.1 years. A total of 17 of 60 (28%) had evidence of a peripheral neuropathy as defined by the presence of neuropathic symptoms on the TNS (12 of 60) and/or electrophysiologic evidence of neuropathy (5 subjects with neuropathic symptoms and 5 without neuropathic symptoms). Subjects with neuropathy were more likely to be male (60% versus 40%; P = 0.02), African American (41% versus 4.6%; P = 0.001), have diabetes mellitus (17.7% versus 0%; P = 0.02), have limited cutaneous scleroderma (82.3% versus 53.5%; P = 0.04), and have anti‐U1 RNP antibodies (23.5% versus 0%; P = 0.009) than those without neuropathy. A potential nonscleroderma etiology for the peripheral neuropathy such as diabetes mellitus was found in 82.3% (14 of 17) of subjects with neuropathy.

Conclusion

While symptoms or objective evidence of peripheral neuropathy are common among patients with scleroderma, the cause may often be attributed to comorbid nonscleroderma‐related conditions.
Iron–Nitrogen‐Doped Vertically Aligned Carbon Nanotube Electrocatalyst for the Oxygen Reduction Reaction
Authors: Yasuda Satoshi , Furuya Atom , Uchibori Yosuke , Kim Jeheon , Murakoshi Kei
Published: December 2015

A highly active iron–nitrogen‐doped carbon nanotube catalyst for the oxygen reduction reaction (ORR) is produced by employing vertically aligned carbon nanotubes (VA‐CNT) with a high specific surface area and iron(II) phthalocyanine (FePc) molecules. Pyrolyzing the composite easily transforms the adsorbed FePc molecules into a large number of iron coordinated nitrogen functionalized nanographene (Fe–N–C) structures, which serve as ORR active sites on the individual VA‐CNT surfaces. The catalyst exhibits a high ORR activity, with onset and half‐wave potentials of 0.97 and 0.79 V, respectively, versus reversible hydrogen electrode, a high selectivity of above 3.92 electron transfer number, and a high electrochemical durability, with a 17 mV negative shift of E
1/2 after 10 000 cycles in an oxygen‐saturated 0.5 m H2SO4 solution. The catalyst demonstrates one of the highest ORR performances in previously reported any‐nanotube‐based catalysts in acid media. The excellent ORR performance can be attributed to the formation of a greater number of catalytically active Fe–N–C centers and their dense immobilization on individual tubes, in addition to more efficient mass transport due to the mesoporous nature of the VA‐CNTs.
Contact Doping for Vertical Organic Field‐Effect Transistors
Authors: Günther Alrun A. , Sawatzki Michael , Formánek Petr , Kasemann Daniel , Leo Karl
Published: December 2015

Doping is a powerful tool to overcome contact limitations in short‐channel organic field‐effect transistors (OFETs) and has been successfully used in the past to improve the charge carrier injection in OFETs. The present study applies this familiar concept to the architecture of vertical organic field‐effect transistors (VOFETs), which are often severely limited by injection due to their very short channel lengths. The present study shows that the performance of p‐type VOFETs with pentacene as an active material can be significantly enhanced by the addition of the common p‐dopant C60F36 as a thin injection layer underneath the VOFET source electrode, resulting in an increase of On‐state current and On/Off ratio by one order of magnitude. The present study further investigates mixed injection layers of pentacene and the p‐dopant and finds that the improvement is less pronounced than for the pure dopant layers and depends on the concentration of dopant molecules in the injection layer. Through application of the transfer length method to equivalent OFET geometries, the present study is finally able to link the observed improvement to a decrease in transfer length and can thus conclude that this length is a crucial parameter onto which further improvement efforts have to be concentrated to realize true short‐channel VOFETs.
Ultrahigh‐Q Fano Resonances in Terahertz Metasurfaces: Strong Influence of Metallic Conductivity at Extremely Low Asymmetry
Authors: Srivastava Yogesh Kumar , Manjappa Manukumara , Cong Longqing , Cao Wei , Al‐Naib Ibraheem , Zhang Weili , Singh Ranjan
Published: December 2015

Fano resonances in metasurfaces are important due to their low loss subradiant behavior that allows excitation of high‐quality (Q) factor resonances extending from the microwave to the optical regime. High‐Q Fano resonances have recently enabled applications in the areas of sensing, modulation, filtering, and efficient cavities for lasing spasers. Highly conducting metals are the most commonly used materials for fabricating the metasurfaces, especially at the low‐frequency terahertz region where the DC, Drude, and perfect electric conductivity show similar resonant behavior of the subwavelength meta‐atoms. Here, it is experimentally and theoretically demontrated that the Q factor of a low asymmetry Fano resonance is extremely sensitive to the conducting properties of the metal at terahertz frequencies. Large differences in the Q factor and figure of merit of the Fano resonance is observed for perfect electric conductors, Drude metal, and a DC‐conducting metal, which is in sharp contrast to the behavior of the inductive–capacitive resonance of meta‐atoms at terahertz frequency. Identification of such a low asymmetry regime in Fano resonances is the key to engineer the radiative and nonradiative losses in plasmonic and metamaterial‐based devices that have potential applications in the microwave, terahertz, infrared, and the optical regimes.
Electronic Structure, Bandgap, and Thermal Quenching of Sr[Mg3SiN4]:Eu2+ in Comparison to Sr[LiAl3N4]:Eu2+
Authors: Tolhurst Thomas M. , Schmiechen Sebastian , Pust Philipp , Schmidt Peter J. , Schnick Wolfgang , Moewes Alexander
Published: December 2015

In this study the band gap and electronic structure of the next‐generation, red phosphor Sr[Mg3SiN4]:Eu2+ (SMS) are explored through a combination of soft X‐ray spectroscopy, density functional theory calculations, and thermal quenching data for the Eu2+ 5d→4f emissions. The results will be compared to those for the high‐efficiency phosphor Sr[LiAl3N4]:Eu2+ (SLA), which shows different, yet exceptional emission characteristics in the red‐spectral region. It is found that SMS has an indirect band gap of 3.28 ± 0.20 eV, strong uniformity in the density of states of its nonequivalent nitrogen sites, and an estimated energetic separation between the lowest Eu2+ 5d state and the conduction band of ≈0.13 eV. The Eu2+ 5d–conduction band separation in SLA is found to be ≈0.28 eV, which points to why the visible emissions of SLA, and not SMS, show outstanding thermal stability. A bonding scheme explaining the band gap difference of SMS and SLA is proposed based on the density of states of SMS. Modifications to each lattice are put forward for achieving optimized phosphor characteristics for use in pc‐LEDs.
Routes to High Energy Cathodes of Sodium‐Ion Batteries
Authors: Fang Chun , Huang Yunhui , Zhang Wuxing , Han Jiantao , Deng Zhe , Cao Yuliang , Yang Hanxi
Published: December 2015

Sodium‐ion batteries (SIBs) are now being actively developed as low cost and sustainable alternatives to lithium‐ion batteries (LIBs) for large‐scale electric energy storage applications. In recent years, various inorganic and organic Na compounds, mostly mimicked from their Li counterparts, have been synthesized and tested for SIBs, and some of them indeed demonstrate comparable specific capacity to the presently developed LIB electrodes. However, the lack of suitable cathode materials is still a major obstacle to the commercial development of SIBs. Here, we present a brief review on the recent developments of SIB cathodes, with a focus on low cost and high energy density materials (> 450 Wh kg−1 vs Na) together with discussion of their Na‐storage mechanisms. The considerable differences in the structural requirements for Li‐ and Na‐storage reactions mean that it is not sufficient to design SIB cathode materials by simply mimicking LIB materials, and therefore great efforts are needed to discover new materials and reaction mechanisms to further develop variable cathodes for advanced SIB technology. Some directions for future research and possible strategies for building advanced cathode materials are also proposed here.
Optimal design of renewable energy systems with flexible inputs and outputs using the P‐graph framework
Authors: Szlama Adrian , Heckl Istvan , Cabezas Heriberto
Published: December 2015

The P‐graph framework introduced by Friedler et al. (Chem Eng Sci. 1992;47:1973–1988) is a general mathematical methodology based on Graph Theory which is applicable to many process design problems. We propose an extension of the P‐graph framework and the associated MILP model to account for operating units and systems where the inputs and outputs are variable. This is important because the P‐graph framework in its current form would otherwise apply only to systems where the ratios of inputs to outputs are fixed. Consequently, it is difficult to apply the method to many emerging systems without the new mathematical model presented here. We discuss and develop the model in detail, and we then illustrate its application with the case study of an energy system. We establish a structure with optimal cost for a baseline heat demand, and we further explore how the energy system structure and the feedstocks change as the heat demand increases. © 2015 American Institute of Chemical Engineers AIChE J, 62: 1143–1153, 2016
N‐Bromosuccinimide‐Mediated Thiocyanation of Cyclohexene‐Fused Isoxazoline N‐Oxides
Authors: Ichake Sachin S. , Rajawinslin R. R. , Kavala Veerababurao , Villuri Bharath Kumar , Yang Huei‐Ting , Kuo Chun‐Wei , Yao Ching‐Fa
Published: December 2015

An efficient, metal‐free, NBS‐mediated thiocyanation protocol has been developed for the synthesis of (6‐(hydroxyimino)‐2‐thiocyanatocyclohex‐1‐en‐1‐yl)(phenyl)methanone derivatives from cyclohexene‐fused isoxazoline N‐oxides under mild conditions. This rapid, one‐pot transformation is achieved in acetonitrile, and provides access to diverse SCN‐containing compounds bearing a wide range of functional groups in good to excellent yields. Moreover, an SCN containing product was further utilized for the synthesis of cyclohexanone ring‐fused isothiazole derivatives.
An Ethyne‐Bridged Porphyrin‐Hexaphyrin‐Porphyrin Triad That Undergoes a Thermal Transannular Cyclization
Authors: Honjo Kazuma , Mori Hirotaka , Osuka Atsuhiro
Published: December 2015

An ethyne‐bridged Ni2+ porphyrin‐[26]hexaphyrin‐Ni2+ porphyrin triad (4) has been prepared and shown to adopt a dumbbell‐like conformation despite the two bulky porphyrinylethynyl groups at the hinge positions of the hexaphyrin. The 1H NMR and UV/vis/NIR spectra of 4 revealed that the aromatic nature of the [26]hexaphyrin unit was significantly mitigated via conjugative interaction with the porphyrinylethynyl substituents. Thermal transannular cyclization of 4 proceeded smoothly to give vinylene‐bridged triad 12, in which the π‐systems of the Ni2+ porphyrins and [26]hexaphyrin are not conjugated and the aromatic character of the latter is enhanced.
Platinfreie Nanomaterialien für die Sauerstoffreduktion
Authors: Xia Wei , Mahmood Asif , Liang Zibin , Zou Ruqiang , Guo Shaojun
Published: December 2015

Der Ersatz von Platin (Pt) durch billigere, unedle Elemente in Elektrokatalysatoren für die Sauerstoffreduktionsreaktion (ORR) ist für die Entwicklung nachhaltiger, leistungsfähiger Brennstoffzellen zur Energieumwandlung von größtem Interesse. Platinfreie Materialien bergen jedoch eine Reihe von Herausforderungen, wie eine geringe intrinsische katalytische Aktivität, eine begrenzte Zahl aktiver Zentren und schlechte Stofftransporteigenschaften. Jüngste Fortschritte in den Materialwissenschaften und der Nanotechnologie ermöglichen nun ein rationales Design von neuen Materialien mit unedlen Elementen mit optimierter Zusammensetzung und präziser Nanostruktur. Dies eröffnet neue Möglichkeiten zur Verbesserung der ORR‐Leistung auf molekularer Ebene. Dieser Aufsatz beleuchtet die aktuellen Durchbrüche bei der Entwicklung von Nanokatalysatoren für die ORR.
Controlling the Assembly of Coiled–Coil Peptide Nanotubes
Authors: Thomas Franziska , Burgess Natasha C. , Thomson Andrew R. , Woolfson Derek N.
Published: December 2015

An ability to control the assembly of peptide nanotubes (PNTs) would provide biomaterials for applications in nanotechnology and synthetic biology. Recently, we presented a modular design for PNTs using α‐helical barrels with tunable internal cavities as building blocks. These first‐generation designs thicken beyond single PNTs. Herein we describe strategies for controlling this lateral association, and also for the longitudinal assembly. We show that PNT thickening is pH sensitive, and can be reversed under acidic conditions. Based on this, repulsive charge interactions are engineered into the building blocks leading to the assembly of single PNTs at neutral pH. The building blocks are modified further to produce covalently linked PNTs via native chemical ligation, rendering ca. 100 nm‐long nanotubes. Finally, we show that small molecules can be sequestered within the interior lumens of single PNTs.
Brook Rearrangement as a Trigger for the Ring Opening of Strained Carbocycles
Authors: Zhang Fa‐Guang , Eppe Guillaume , Marek Ilan
Published: December 2015

The combined regio‐ and stereoselective carbometalation of cyclopropenyl amides, followed by the addition of an acyl silane, led to the formation of polysubstituted cyclopropyl derivatives as unique diastereoisomers. Upon warming of the reaction mixture to room temperature, a Brook rearrangement proceeded with inversion of configuration to provide ready access to δ‐ketoamides possessing a quaternary carbon center with high enantiomeric ratios through selective CC bond cleavage of the ring.
What a Difference an OH Makes: Conformational Dynamics as the Basis for the Ligand Specificity of the Neomycin‐Sensing Riboswitch
Authors: Duchardt‐Ferner Elke , Gottstein‐Schmidtke Sina R. , Weigand Julia E. , Ohlenschläger Oliver , Wurm Jan‐Philip , Hammann Christian , Suess Beatrix , Wöhnert Jens
Published: December 2015

To ensure appropriate metabolic regulation, riboswitches must discriminate efficiently between their target ligands and chemically similar molecules that are also present in the cell. A remarkable example of efficient ligand discrimination is a synthetic neomycin‐sensing riboswitch. Paromomycin, which differs from neomycin only by the substitution of a single amino group with a hydroxy group, also binds but does not flip the riboswitch. Interestingly, the solution structures of the two riboswitch–ligand complexes are virtually identical. In this work, we demonstrate that the local loss of key intermolecular interactions at the substitution site is translated through a defined network of intramolecular interactions into global changes in RNA conformational dynamics. The remarkable specificity of this riboswitch is thus based on structural dynamics rather than static structural differences. In this respect, the neomycin riboswitch is a model for many of its natural counterparts.
Enantioselective Catalysts for the Synthesis of α‐Substituted Allylboronates—An Accelerated Approach towards Isomerically Pure Homoallylic Alcohols
Authors: Brauns Marcus , Muller Frédéric , Gülden Daniel , Böse Dietrich , Frey Wolfgang , Breugst Martin , Pietruszka Jörg
Published: December 2015

The use of a convenient protecting group for boronates allows a selective, catalyzed SN2′ reaction to generate allylboronates which are applied for the synthesis of enantiomerically pure homoallylic alcohols. Depending on the configuration of both catalyst and the protecting group any of the four possible stereoisomers can be formed. The rationale behind the selective addition is supported by density functional theory calculations.
Identification of a Systemic Lupus Erythematosus Risk Locus Spanning ATG16L2, FCHSD2, and P2RY2 in Koreans
Authors: Lessard Christopher J. , Sajuthi Satria , Zhao Jian , Kim Kwangwoo , Ice John A. , Li He , Ainsworth Hannah , Rasmussen Astrid , Kelly Jennifer A. , Marion Miranda , Bang So‐Young , Bin Joo Young , Choi Jeongim , Lee Hye‐Soon , Mo Kang Young , Suh Chang‐Hee , Tae Chung Won , Lee Soo‐Kon , Choe Jung‐Yoon , Cheol Shim Seung , Hee Oh Ji , Jin Kim Young , Han Bok‐Ghee , Shen Nan , Siew Howe Hwee , Wakeland Edward K. , Li Quan‐Zhen , Wook Song Yeong , Gaffney Patrick M. , Alarcón‐Riquelme Marta E. , Criswell Lindsey A. , Jacob Chaim O. , Kimberly Robert P. , Vyse Timothy J. , Harley John B. , Sivils Kathy L. , Bae Sang‐Cheol , Langefeld Carl D. , Tsao Betty P.
Published: December 2015

Objective

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder whose etiology is incompletely understood, but likely involves environmental triggers in genetically susceptible individuals. Using an unbiased genome‐wide association (GWA) scan and replication analysis, we sought to identify the genetic loci associated with SLE in a Korean population.

Methods

A total of 1,174 SLE cases and 4,246 population controls from Korea were genotyped and analyzed with a GWA scan to identify single‐nucleotide polymorphisms (SNPs) significantly associated with SLE, after strict quality control measures were applied. For select variants, replication of SLE risk loci was tested in an independent data set of 1,416 SLE cases and 1,145 population controls from Korea and China.

Results

Eleven regions outside the HLA exceeded the genome‐wide significance level (P = 5 × 10−8). A novel SNP–SLE association was identified between FCHSD2 and P2RY2, peaking at rs11235667 (P = 1.03 × 10−8, odds ratio [OR] 0.59) on a 33‐kb haplotype upstream of ATG16L2. In the independent replication data set, the SNP rs11235667 continued to show a significant association with SLE (replication meta‐analysis P = 0.001, overall meta‐analysis P = 6.67 × 10−11; OR 0.63). Within the HLA region, the SNP–SLE association peaked in the class II region at rs116727542, with multiple independent effects observed in this region. Classic HLA allele imputation analysis identified HLA–DRB1*1501 and HLA–DQB1*0602, each highly correlated with one another, as most strongly associated with SLE. Ten previously established SLE risk loci were replicated: STAT1–STAT4, TNFSF4, TNFAIP3, IKZF1, HIP1, IRF5, BLK, WDFY4, ETS1, and IRAK1–MECP2. Of these loci, previously unreported, independent second risk effects of SNPs in TNFAIP3 and TNFSF4, as well as differences in the association with a putative causal variant in the WDFY4 region, were identified.

Conclusion

Further studies are needed to identify true SLE risk effects in other loci suggestive of a significant association, and to identify the causal variants in the regions of ATG16L2, FCHSD2, and P2RY2.
Computational Characterization of the Origin of Selectivity in Cycloaddition Reactions Catalyzed by Phosphoric Acid Derivatives
Authors: Liu Chunhui , Besora Maria , Maseras Feliu
Published: December 2015

The mechanism of the organocatalyzed [4+2] cycloaddition of ο‐hydroxybenzaldimines to 2,3‐dihydro‐2 H‐furan (DHF) to form furanobenzopyrans has been investigated by using computational methods. Experiments have shown that this reaction produces different products (trans‐fused or cis‐fused) if different phosphoric acid derivatives are applied. Our study shows the reaction proceeds through a mechanism in which the imine re‐arranges into an amine, which subsequently reacts with DHF with mediation from the catalyst. The rate‐limiting step in this process is the formation of two new bonds, which is also the key step in determining the reaction selectivity. The selectivity is controlled by a balance of noncovalent interactions between the catalyst and the substrates. The discriminating factor between the two catalysts is the presence of a triflyl substituent on one of catalysts, which constraints the relative orientations of the substrates.
2D l‐Di‐toluoyl‐tartaric acid Lanthanide Coordination Polymers: Toward Single‐component White‐Light and NIR Luminescent Materials
Authors: Niu Wan‐Ying , Sun Jing‐Wen , Yan Peng‐Fei , Li Yu‐Xin , An Guang‐Hui , Li Guang‐Ming
Published: December 2015

A series of five l‐di‐p‐toluoyl‐tartaric acid (l‐DTTA) lanthanide coordination polymers, namely {[Ln4K4 L6(H2O)x]⋅yH2O}n, [Ln=Dy (1), x=24, y=12; Ln=Ho (2), x=23, y=12; Ln=Er (3), x=24, y=12; Ln=Yb (4), x=24, y=11; Ln=Lu (5), x=24, y=12] have been isolated by simple reactions of H2L (H2L= L‐DTTA) with LnCl3⋅6 H2O at ambient temperature. X‐ray crystallographic analysis reveals that complexes 1–5 feature two‐dimensional (2D) network structures in which the Ln3+ ions are bridged by carboxylate groups of ligands in two unique coordinated modes. Luminescent spectra demonstrate that complex 1 realizes single‐component white‐light emission, while complexes 2–4 exhibit a characteristic near‐infrared (NIR) luminescence in the solid state at room temperature.
Elevated body mass index and decreased diet quality among women and risk of birth defects in their offspring
Authors: Carmichael Suzan L. , Yang Wei , Gilboa Suzanne , Ailes Elizabeth , Correa Adolfo , Botto Lorenzo D. , Feldkamp Marcia L. , Shaw Gary M. ,   the National Birth Defects Prevention Study
Published: December 2015

Background

We examined whether risks of 32 birth defects were higher than expected in the presence of overweight or obese body mass index (BMI) and low diet quality, based on estimating individual and joint effects of these factors and calculating relative excess risk due to interaction.

Methods

Analyses included mothers of 20,250 cases with birth defects and 8617 population‐based controls without birth defects born from 1997 to 2009 and interviewed for the National Birth Defects Prevention Study. We used logistic regression to generate adjusted odds ratios (AORs) reflecting the combined effects of BMI and diet quality. We focused analyses on 16 birth defects (n = 11,868 cases, 8617 controls) for which initial results suggested an association with BMI or diet quality.

Results

Relative to the reference group (normal weight women with not low diet quality, i.e., >lowest quartile), AORs for low diet quality among normal weight women tended to be >1, and AORs for overweight and obese women tended to be stronger among women who had low diet quality than not low diet quality. For 9/16 birth defects, AORs for obese women who had low diet quality—the group we hypothesized to have highest risk—were higher than other stratum‐specific AORs. Most relative excess risk due to interactions were positive but small (<0.5), with confidence intervals that included zero.

Conclusion

These findings provide evidence for the hypothesis of highest birth defect risks among offspring to women who are obese and have low diet quality but insufficient evidence for an interaction of these factors in their contribution to risk. Birth Defects Research (Part A) 106:164–171, 2016. © 2015 Wiley Periodicals, Inc.
Metabolic engineering of acid resistance elements to improve acid resistance and propionic acid production of Propionibacterium jensenii
Authors: Guan Ningzi , Li Jianghua , Shin Hyun‐dong , Du Guocheng , Chen Jian , Liu Long
Published: December 2015

Propionic acid (PA) and its salts are widely used in the food, pharmaceutical, and chemical industries. Microbial production of PA by propionibacteria is a typical product‐inhibited process, and acid resistance is crucial in the improvement of PA titers and productivity. We previously identified two key acid resistance elements—the arginine deaminase and glutamate decarboxylase systems—that protect propionibacteria against PA stress by maintaining intracellular pH homeostasis. In this study, we attempted to improve the acid resistance and PA production of Propionibacterium jensenii ATCC 4868 by engineering these elements. Specifically, five genes (arcA, arcC, gadB, gdh, and ybaS) encoding components of the arginine deaminase and glutamate decarboxylase systems were overexpressed in P. jensenii. The activities of the five enzymes in the engineered strains were 26.7–489.0% higher than those in wild‐type P. jensenii. The growth rates of the engineered strains decreased, whereas specific PA production increased significantly compared with those of the wild‐type strain. Among the overexpressed genes, gadB (encoding glutamate decarboxylase) increased PA resistance and yield most effectively; the PA resistance of P. jensenii‐gadB was more than 10‐fold higher than that of the wild‐type strain, and the production titer, yield, and conversion ratio of PA reached 10.81 g/L, 5.92 g/g cells, and 0.56 g/g glycerol, representing increases of 22.0%, 23.8%, and 21.7%, respectively. We also investigated the effects of introducing these acid resistance elements on the transcript levels of related enzymes. The results showed that the expression of genes in the engineered pathways affected the expression of the other genes. Additionally, the intracellular pools of amino acids were altered as different genes were overexpressed, which may further contribute to the enhanced PA production. This study provides an effective strategy for improving PA production in propionibacteria; this strategy may be useful for the production of other organic acids. Biotechnol. Bioeng. 2016;113: 1294–1304. © 2015 Wiley Periodicals, Inc.
A novel strategy for selective gene delivery by using the inhibitory effect of blue light on jetPRIME‐mediated transfection
Authors: Dateki Minori , Imamura Osamu , Arai Masaaki , Shimizu Hidehisa , Takishima Kunio
Published: December 2015

Photodynamic control of gene delivery is a new technology with growing applications in gene therapy and basic cell research. Main approaches of light‐selective gene delivery rely on the light‐dependent enhancement of transfection efficiency. Studies focused on light‐stimulated inhibitory regulation of transfection have rarely been reported. Here, we tried to establish a novel procedure of light‐dependent inhibition of transfection. Our experiments, conducted with several types of commercial transfection reagents, revealed that jetPRIME‐mediated transfection was strongly inhibited by blue light. Although the uptake of reagent–DNA complex was drastically reduced, preliminary exposure of cells or reagent–DNA complex to blue light had no inhibitory effect on the transfection efficiency. The inhibitory effect was wavelength‐dependent and mediated by reactive oxygen species. Partial exposure of a culture vessel to blue light resulted in selective gene delivery into cells grown on the unexposed area of the vessel. By using this approach, different types of plasmid DNA were delivered into different areas in the culture vessel. This novel approach to the inhibitory control of transfection provides practical options for research and therapeutics. Biotechnol. Bioeng. 2016;113: 1560–1567. © 2015 Wiley Periodicals, Inc.
Kidney and liver transplantation in the elderly
Authors: Sutherland A I , IJzermans J N M , Forsythe J L R , Dor F J M F
Published: December 2015

Background

Transplant surgery is facing a shortage of deceased donor organs. In response, the criteria for organ donation have been extended, and an increasing number of organs from older donors are being used. For recipients, the benefits of transplantation are great, and the growing ageing population has led to increasing numbers of elderly patients being accepted for transplantation.

Methods

The literature was reviewed to investigate the impact of age of donors and recipients in abdominal organ transplantation, and to highlight aspects of the fine balance in donor and recipient selection and screening, as well as allocation policies fair to young and old alike.

Results

Overall, kidney and liver transplantation from older deceased donors have good outcomes, but are not as good as those from younger donors. Careful donor selection based on risk indices, and potentially biomarkers, special allocation schemes to match elderly donors with elderly recipients, and vigorous recipient selection, allows good outcomes with increasing age of both donors and recipients. The results of live kidney donation have been excellent for donor and recipient, and there is a trend towards inclusion of older donors. Future strategies, including personalized immunosuppression for older recipients as well as machine preservation and reconditioning of donor organs, are promising ways to improve the outcome of transplantation between older donors and older recipients.

Conclusion

Kidney and liver transplantation in the elderly is a clinical reality. Outcomes are good, but can be optimized by using strategies that modify donor risk factors and recipient co-morbidities, and personalized approaches to organ allocation and immunosuppression.
miR‐548d‐3p/TP53BP2 axis regulates the proliferation and apoptosis of breast cancer cells
Authors: Song Qiong , Song Jiangqiang , Wang Qimin , Ma Yanling , Sun Nai , Ma Jieyu , Chen Qiu , Xia Guishan , Huo Yanping , Yang Longqiu , Li Baolin
Published: December 2015

Fast growth and hardly any apoptosis are important characteristics of breast cancer, which assure the spread via invasion and metastasis of breast cancer cells. Inhibition of fast proliferation and induction of apoptosis are critical way to cure this cancer. microRNAs (miRNAs) had been increasingly reported to be the critical regulator of tumorigenesis. In our study, we found that increasing copy number of miR‐548d‐2‐3p is critically involved poor prognosis. We overexpressed miR‐548d‐3p in MDA‐MB‐231cells and found that the proliferation was promoted significantly, whereas the inhibition of miR‐548d‐3p repressed the proliferation of MDA‐MB‐231 cells and also induced the increase in apoptosis. Additionally, we found that miR‐548d‐3p downregulated the expression of TP53BP2 by directly targeting the 3′UTR. We also found that knockdown of TP53BP2 significantly resorted the proliferation and apoptosis regulated by miR‐548d‐3p inhibitor. Our study showed that miR‐548d‐3p/TP53BP2 pathway is critically involved in the proliferation and apoptosis of breast cancer cells and may be new therapeutic target of breast cancer cells.
Inhibitors of the Polo‐Box Domain of Polo‐Like Kinase 1
Authors: Berg Angela , Berg Thorsten
Published: December 2015

Polo‐like kinase 1 (Plk1), a key player in mitosis, is overexpressed in a wide range of tumor types and has been validated as a target for tumor therapy. In addition to its N‐terminal kinase domain, Plk1 harbors a C‐terminal protein–protein interaction domain, referred to as the polo‐box domain (PBD). Because the PBD is unique to the five‐member family of polo‐like kinases, and its inhibition is sufficient to inhibit the enzyme, the Plk1 PBD is an attractive target for the inhibition of Plk1 function. Although peptide‐based inhibitors are invaluable tools for elucidating the nature of the binding interface, small molecules are better suited for the induction of mitotic arrest and apoptosis in tumor cells by Plk1 inhibition. This review describes the considerable progress that has been made in developing small‐molecule and peptide‐based inhibitors of the Plk1 PBD.
Biologically Induced Hydrogen Production Drives High Rate/High Efficiency Microbial Electrosynthesis of Acetate from Carbon Dioxide
Authors: Jourdin Ludovic , Lu Yang , Flexer Victoria , Keller Jurg , Freguia Stefano
Published: December 2015

Electron‐transfer pathways occurring in biocathodes are still unknown. We demonstrate here that high rates of acetate production by microbial electrosynthesis are mainly driven by an electron flux from the electrode to carbon dioxide, occurring via biologically induced hydrogen, with (99±1) % electron recovery into acetate. Nevertheless, acetate production is shown to occur exclusively within the biofilm. The acetate producers, putatively Acetoanaerobium, showed the remarkable ability to consume a high H2 flux before it could escape from the biofilm. At zero wastage of H2 gas, it allows superior production rates and lesser technical bottlenecks over technologies that rely on mass transfer of H2 to microorganisms suspended in aqueous solution. This study suggests that bacterial modification of the electrode surface (possibly via synthesis of Cu nanoparticles) is directly involved in the significant enhancement of the hydrogen production.
Cation–π Interactions Contribute to Substrate Recognition in γ‐Butyrobetaine Hydroxylase Catalysis
Authors: Kamps Jos J. A. G. , Khan Amjad , Choi Hwanho , Lesniak Robert K. , Brem Jürgen , Rydzik Anna M. , McDonough Michael A. , Schofield Christopher J. , Claridge Timothy D. W. , Mecinović Jasmin
Published: December 2015

γ‐Butyrobetaine hydroxylase (BBOX) is a non‐heme FeII‐ and 2‐oxoglutarate‐dependent oxygenase that catalyzes the stereoselective hydroxylation of an unactivated C−H bond of γ‐butyrobetaine (γBB) in the final step of carnitine biosynthesis. BBOX contains an aromatic cage for the recognition of the positively charged trimethylammonium group of the γBB substrate. Enzyme binding and kinetic analyses on substrate analogues with P and As substituting for N in the trimethylammonium group show that the analogues are good BBOX substrates, which follow the efficiency trend N+>P+>As+. The results reveal that an uncharged carbon analogue of γBB is not a BBOX substrate, thus highlighting the importance of the energetically favorable cation–π interactions in productive substrate recognition.
Synthesis of Spirocyclic Indolenines
Authors: James Michael J. , O'Brien Peter , Taylor Richard J. K. , Unsworth William P.
Published: December 2015

This Review provides an in‐depth account of the synthesis of spirocyclic indolenines. Over the last 77 years, a wide array of diverse synthetic methods has been developed in order to generate these synthetically useful and biologically important spirocyclic scaffolds. The main synthetic strategies discussed are grouped into three main categories, namely interrupted Fischer indolisations, dearomatisation reactions of indoles and condensation reactions. The historical background, common synthetic challenges, current state‐of‐the‐art and future perspectives of this field are examined.
Understanding social change through catalytic innovation: Empirical findings in Mexican social entrepreneurship
Authors: Auvinet Caroline , Lloret Antonio
Published: December 2015

Christensen, Baumann, Ruggles, and Sadtler (2006) proposed that organizations addressing social problems may use catalytic innovation as a strategy to create social change. These innovations aim to create scalable, sustainable, and systems‐changing solutions. This empirical study examines: (a) whether catalytic innovation applies to Mexican social entrepreneurship; (b) whether those who adopt Christensen et al.’s (2006) strategy generate more social impact; and (c) whether they demonstrate economic success. We performed a survey of 219 Mexican social entrepreneurs and found that catalytic innovation does occur within social entrepreneurship, and that those social entrepreneurs who use catalytic innovations not only maximize their social impact but also maximize their profits, and that they do so with diminishing returns to scale. Copyright © 2015 ASAC. Published by John Wiley & Sons, Ltd.
Identifying factors key to encouraging entrepreneurial intentions among seniors
Authors: Sahut Jean‐Michel , Gharbi Sami , Mili Mehdi
Published: December 2015

Using the theory of planned behaviour (TPB), we examined the impact of age on entrepreneurial intention, with special focus on seniors. Using samples from France reflecting a broad age range, a negative relationship involving age and entrepreneurial intent was found. Consistent with TPB, attitude, social norms, and perceived behavioural control were all significantly associated with intent. Importantly however, the relative weight seniors gave these components differed from that of prime age participants. For seniors, the belief that they had the requisite competencies and resources needed to own a business was especially important. Seniors also expressed greater relative interest in social entrepreneurship. The implications of these findings for both researchers and public policy makers are considered. Copyright © 2015 ASAC. Published by John Wiley & Sons, Ltd.
NOISE REMOVAL BASED ON FILTERED PRINCIPAL COMPONENT RECONSTRUCTION
Authors: Ling‐Qun WANG , Bing‐Bing LI , Jun LIN , Bin XIE , Qi WANG , Yu‐Qi CHENG , Kai‐Guang ZHU
Published: December 2015

Principal component analysis solves the overlap between the signal and noise in spectra, however the low‐order components still contain high frequency spatial noise. To tackle this problem, a denosing approach based on filtered principal component reconstruction is proposed. This method designs a low pass filter group which is based on adaptive width smoothing algorithm to remove the noise of the low‐order components. And then the electromagnetic data are reconstructed by the filtered low‐order components. This approach can not only remove the high frequency spatial noise of low‐order components, but also remove uncorrelated noise of high‐order components. The experimental results of the simulation data show that the SNR is improved by 10.96 dB and 2.52 dB relative to the traditional profile filter and principal component reconstruction, respectively. The results of conductivity‐depth imaging also prove that the filtered principal component reconstruction can improve the ability to identify deep targets. Finally the conductivity‐depth imaging for the survey profile data indicates that noise removal based on filtered principal component reconstruction is very effective.
Determination and Monitoring of Tetracycline and Degradation Products in Landfill Leachate
Authors: Topal Murat , Arslan Topal Emine Işıl
Published: December 2015

Tetracyclines (TCs) have importance because of their common usage, high potential to reach the receiving environments, and toxicity for the organisms. The aim of this study is the determination of concentrations of TC and degradation products (DPs) as anhydrotetracycline (ATC), 4‐epitetracycline (ETC), and 4‐epianhydrotetracycline (EATC) in the leachate basin of landfill located in Elazığ City, Turkey. For this aim, leachate samples are taken from the leachate basin every week (wk) during March and April 2014. Maximum TC, ETC, EATC, and ATC concentrations in leachate samples are 2.47 ± 0.12 (wk 3), 10.3 ± 0.5 (wk 3), 37.1 ± 1.8 (wk 1), and 6.43 ± 0.32 μg/L (wk 8). The concentrations of TC and DPs followed the decreasing order of EATC > ETC > ATC > TC. As a result, it is determined that the concentrations of TC and DPs are at μg/L levels in the leachate basin of landfill.
Thrombin‐Inhibiting Anticoagulant Liposomes: Development and Characterization
Authors: Endreas Wegderes , Brüßler Jana , Vornicescu Doru , Keusgen Michael , Bakowsky Udo , Steinmetzer Torsten
Published: December 2015

Many peptides and peptidomimetic drugs suffer from rapid clearance in vivo; this can be reduced by increasing their size through oligomerization or covalent conjugation with polymers. As proof of principle, an alternative strategy for drug oligomerization is described, in which peptidomimetic thrombin inhibitors are incorporated into the liposome surface. For this purpose, the inhibitor moieties were covalently coupled to a palmitic acid residue through a short bifunctionalized ethylene glycol spacer. These molecules were directly added to the lipid mixture used for liposome preparation. The obtained liposomes possess strong thrombin inhibitory potency in enzyme kinetic measurements and anticoagulant activity in plasma. Their strong potency and positive ζ potential indicate that large amounts of the benzamidine‐derived inhibitors are located on the surface of the liposomes. This concept should be applicable to other drug molecules that suffer from rapid elimination and allow covalent modification with a suitable fatty acid residue.
Skeletal Ni Catalysts Prepared from Amorphous Ni–Zr Alloys: Enhanced Catalytic Performance for Hydrogen Generation from Ammonia Borane
Authors: Nozaki Ai , Tanihara Yasutomo , Kuwahara Yasutaka , Ohmichi Tetsutaro , Mori Kohsuke , Nagase Takeshi , Yasuda Hiroyuki Y. , Yamashita Hiromi
Published: December 2015

Skeletal Ni catalysts were prepared from Ni–Zr alloys, which possess different chemical composition and atomic arrangements, by a combination of thermal treatment and treatment with aqueous HF. Hydrogen generation from ammonia borane over the skeletal Ni catalysts proceeded efficiently, whereas the amorphous Ni–Zr alloy was inactive. Skeletal Ni prepared from amorphous Ni30Zr70 alloy had a higher catalytic activity than that prepared from amorphous Ni40Zr60 and Ni50Zr50 alloys. The atomic arrangement of the Ni–Zr alloy also strongly affected the surface structure and catalytic activities. Thermal treatment of the amorphous Ni–Zr alloys at a temperature slightly lower than the crystallization temperature led to an increase of the number of surface‐exposed Ni atoms and an enhancement of the catalytic activities for hydrogen generation from ammonia borane. The skeletal Ni catalysts also showed excellent durability and recyclability.
Hyperconjugative and Electrostatic Interactions as Anomeric Triggers in Archetypical 1,4‐Dioxane Derivatives
Authors: Ortega Pilar Gema Rodríguez , Montejo Manuel , López González Juan Jesús
Published: December 2015

The anomeric effect accounts for the greater thermodynamic stability of axially arranged six‐membered heterocycles holding an electronegative substituent at the C1 position. Within a frame of no general consensus, two different theories are typically claimed to justify this effect mostly based on either hyperconjugative or electrostatic factors. Here we report a theoretical‐experimental study of the role of both as anomeric triggers in two archetypical 1,4‐dioxane derivatives, using a suitable combination of spectroscopic (IR and vibrational circular dichroism) and computational techniques for the analysis of the solvation environment effect in their anomeric choices. VCD and IR spectroscopies are used as conformer‐discriminating tools: a detailed analysis of the evolution of the spectral profiles allows assessing the theoretically predicted changes in the experimental α/β ratios when changing the polar solvent, which are fully explained on the basis of an extensive NBO energy partition scheme that provides a detailed view of the role of hyperconjugative and electrostatic interactions as anomeric regulators. Our results suggest that the anomeric equilibrium cannot be described by a single stereoelectronic effect but by the combined contribution of hyperconjugation and electrostatic repulsions, so that the β‐anomeric choice in polar solvents is markedly driven by the strong attenuation of electrostatic repulsive interactions that occurs in solution.
Perchlorination of Coronene Enhances its Propensity for Self‐Assembly on Graphene
Authors: Conti Simone , del Rosso Maria G. , Ciesielski Artur , Weippert Jürgen , Böttcher Artur , Shin Yuyoung , Melinte Georgian , Ersen Ovidiu , Casiraghi Cinzia , Feng Xinliang , Müllen Klaus , Kappes Manfred M. , Samorì Paolo , Cecchini Marco
Published: December 2015

Providing a quantitative understanding of the thermodynamics involved in molecular adsorption and self‐assembly at a nanostructured carbon material is of fundamental importance and finds outstanding applications in the graphene era. Here, we study the effect of edge perchlorination of coronene, which is a prototypical polyaromatic hydrocarbon, on the binding affinity for the basal planes of graphite. First, by comparing the desorption barrier of hydrogenated versus perchlorinated coronene measured by temperature‐programmed desorption, we quantify the enhancement of the strength of physisorption at the single‐molecule level though chlorine substitution. Then, by a thermodynamic analysis of the corresponding monolayers based on force‐field calculations and statistical mechanics, we show that perchlorination decreases the free energy of self‐assembly, not only enthalpically (by enhancing the strength of surface binding), but also entropically (by decreasing the surface concentration). The functional advantage of a chemically modulated 2D self‐assembly is demonstrated in the context of the molecule‐assisted liquid‐phase exfoliation of graphite into graphene.
Integrating electronic health record genotype and phenotype datasets to transform patient care
Authors: Roden DM , Denny JC
Published: December 2015

The Health Information Technology for Economic and Clinical Health (HITECH) Act of 2009 mandates the development and implementation of electronic health record (EHR) systems across the country. While a primary goal is to improve the care of individual patients, EHRs are also key enabling resources for a vision of individualized (or personalized or precision) medicine: the aggregation of multiple EHRs within or across healthcare systems should allow discovery of patient subsets that have unusual and definable clinical trajectories that deviate importantly from the expected response in a “typical” patient. The spectrum of such personalized care can then extend from prevention to choice of medication to intensity or nature of follow‐up.
Parallel assessment of Th17 cell frequencies by surface marker co‐expression versus ex vivo IL‐17 production in HIV‐1 infection
Authors: Dunay Gábor A. , Tóth Ilona , Eberhard Johanna M. , Degen Olaf , Tolosa Eva , van Lunzen Jan , Hauber Joachim , Schulze zur Wiesch Julian
Published: December 2015

Introduction

Th17 cells can either be identified by co‐staining of surface markers or by intracellular cytokine staining (ICS) for IL‐17 production. Discrepancies regarding the published frequencies of Th17 cells in peripheral blood mononuclear cells (PBMC) of HIV patients may partly be due to the different methodologies used.

Methods

Cryopreserved PBMC from healthy controls and HIV‐infected subjects, including treated (cART) and viremic patients, were split and analyzed side‐by‐side by flow cytometry for expression of surface markers CCR6, CXCR3, CCR4, and CD161, or for intracellular expression of IL‐17A and IFNγ after stimulation.

Results

The characterization of Th17 cells as CXCR3 − CCR6 + CCR4 + CD161+ yielded considerably higher frequencies than the corresponding frequencies obtained by characterization via cytokines (IL‐17 + IFNγ–), regardless of the HIV status. However, the overall frequencies delivered by the two methods significantly correlated. The relative frequency of Th17 cells within the CD4+ T cell compartment was preserved in HIV infection but there was a significant decrease in the absolute Th17 number, which was restored after initiation of cART, paralleling CD4+ T cell recovery. Absolute Th17 numbers inversely correlated with HIV viral load.

Conclusion

The definition of Th17 cells by surface markers might overestimate their frequency in comparison to functional assessment of IL‐17 production by ICS, regardless of the HIV infection status. However, both methods yield proportionate results with reduced absolute numbers of Th17 cells in untreated HIV disease, reflecting the depletion of total CD4+ T cells in viremic HIV patients, and restoration with cART. © 2016 International Clinical Cytometry Society