bluuebunny/crossref_metadata_2025 huggingface dataset:
Major Histocompatibility Complex Class I and Class II Alleles May Confer Susceptibility to or Protection Against Morphea: Findings From the Morphea in Adults and Children Cohort
Authors: Jacobe Heidi , Ahn Chul , Arnett Frank C. , Reveille John D.
Published: September 2014

Objective

To determine the HLA class I and class II alleles of the human major histocompatibility complex showing an association with morphea (localized scleroderma) in the Morphea in Adults and Children (MAC) cohort, using a nested case–control association study.

Methods

Patients with morphea were identified from the MAC cohort, and matched controls were obtained from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases Scleroderma Family Registry and DNA Repository and from the Division of Rheumatology at the University of Texas Health Science Center at Houston. HLA class II genotyping and single‐strand conformational polymorphism typing were performed to identify HLA–A, B, and C alleles. Associations between HLA class I and class II alleles and morphea, as well as its subphenotypes, were determined.

Results

Two hundred eleven patients with morphea and 726 matched controls were available for HLA class I typing, and 158 patients with morphea and 1,008 matched controls were available for HLA class II typing. The strongest associations were found with DRB1*04:04 (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 1.4–4.0, P = 0.002), and HLA–B*37 conferred the highest OR among the class I alleles (OR 3.2, 95% CI 1.5–6.5, P = 0.001). Comparison of the risk allele profile in this cohort with the risk alleles previously identified in patients with systemic sclerosis, determined using the same methods and same control population, revealed one allele in common, DRB*04:04.

Conclusion

These results demonstrate that specific HLA class I and class II alleles are associated with morphea and are also likely to be associated with generalized and linear subtypes of morphea. The morphea‐associated alleles are different from those found in scleroderma, suggesting that morphea is immunogenetically distinct. Risk alleles in morphea are also associated with conditions such as rheumatoid arthritis (RA) and other autoimmune conditions. Population‐based studies have indicated that patients with RA have an increased risk of morphea, and therefore a common susceptibility allele may be implicated.
Effects of Fostamatinib, an Oral Spleen Tyrosine Kinase Inhibitor, in Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate: Results From a Phase III, Multicenter, Randomized, Double‐Blind, Placebo‐Controlled, Parallel‐Group Study
Authors: Weinblatt Michael E. , Genovese Mark C. , Ho Meilien , Hollis Sally , Rosiak‐Jedrychowicz Krystyna , Kavanaugh Arthur , Millson David S. , Leon Gustavo , Wang Millie , van der Heijde Désirée
Published: September 2014

Objective

This phase III, 52‐week study compared fostamatinib with placebo (for 24 weeks) in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) therapy.

Methods

Patients taking MTX were randomized (1:1:1) to receive fostamatinib 100 mg twice daily for 52 weeks (group A), fostamatinib 100 mg twice daily for 4 weeks and then 150 mg once daily (group B), or placebo for 24 weeks and then fostamatinib 100 mg twice daily (group C). At week 24, the co–primary end points were change from baseline in the American College of Rheumatology 20% (ACR20) improvement response rates and change in the modified total Sharp/van der Heijde score of radiographic damage (SHS).

Results

In this study, 918 patients were randomized and received ≥1 dose of study drug (fostamatinib or placebo); the demographic and baseline clinical characteristics were well balanced. Following treatment with both fostamatinib regimens, a statistically significant difference in the ACR20 improvement response was achieved at week 24 as compared with that in patients receiving placebo (49.0% [group A] and 44.4%, [group B] versus 34.2%; P < 0.001 and P = 0.006, respectively), but there was no statistically significant difference in the SHS between either fostamatinib group and placebo (P = 0.25 and P = 0.17, respectively). The most common adverse events in patients in groups A, B, and C were hypertension (15.8%, 15.1%, and 3.9%, respectively) and diarrhea (13.9%, 15.1%, and 3.9%, respectively). Elevated blood pressure (≥140/90 mm Hg) occurred at ≥1 visit in 44.2%, 41.6%, and 19.3% of patients in each respective group.

Conclusion

With the use of either fostamatinib regimen in patients with RA, statistically significant, but not clinically significant, improvements in the ACR20 improvement response over placebo were achieved at 24 weeks, whereas a significant difference in the SHS was not seen. The overall level of response to treatment with fostamatinib was lower than had been observed in the phase II program, but similar adverse events were reported.
Electrospun Cu/Sn/C Nanocomposite Fiber Anodes with Superior Usable Lifetime for Lithium‐ and Sodium‐Ion Batteries
Authors: Kim Jae‐Chan , Kim Dong‐Wan
Published: September 2014

Cu/Sn/C composite nanofibers were synthesized by using dual‐nozzle electrospinning and subsequent carbonization. The composite nanofibers are a homogeneous amorphous matrix comprised of Cu, Sn, and C with a trace of crystalline Sn. The Li‐ and Na‐ion storage performance of the Cu/Sn/C fiber electrodes were investigated by using cyclic voltammetry, galvanostatic cycling, and electrochemical impedance spectroscopy. Excellent, stable cycling performance indicates capacities of 490 and 220 mA h g−1 for Li‐ion (600 cycles) and Na‐ion (200 cycles) batteries, respectively. This is a significant improvement over other reported Sn/C nanocomposite devices. These superior electrochemical properties could be attributed to the advantages of incorporating one‐dimensional nanostructures into the electrodes, such as short electron diffusion lengths, large specific surface areas, ideal homogeneous structures for buffering volume changes, and better electronic conductivity that results from the amorphous copper and carbon matrix.
The stemness of neural crest cells and their derivatives
Authors: Kunisada Takahiro , Tezulka Ken‐Ichi , Aoki Hitomi , Motohashi Tsutomu
Published: September 2014

Neural crest cells (NCCs) are unique to vertebrates and emerge from the border of the neural plate and subsequently migrate extensively throughout the embryo after which they differentiate into many types of cells. This multipotency is the main reason why NCCs are regarded as a versatile tool for stem cell biology and have been gathering attention for their potential use in stem cell based therapy. Multiple sets of networks comprised of signaling molecules and transcription factors regulate every developmental phase of NCCs, including maintenance of their multipotency. Pluripotent stem cell lines, such as embryonic stem cells and induced pluripotent stem (iPS) cells, facilitate the induction of NCCs in combination with sophisticated culture systems used for neural stem cells, although at present, clinical experiments for NCC‐based cell therapy need to be improved. Unexpectedly, the multipotency of NCCs is maintained after they reach the target tissues as tissue neural crest stem cells (NCSCs) that may contribute to the establishment of NCC‐derived multipotential stem cells. In addition, under specific culture conditions, fate‐restricted unipotent descendants of NCCs, such as melanoblasts, show multipotency to differentiate into melanocytes, neurons, and glia cells. These properties contribute to the additional versatility of NCCs for therapeutic application and to better understand NCC development. Birth Defects Research (Part C) 102:251–262, 2014. © 2014 Wiley Periodicals, Inc.
Connecting teratogen‐induced congenital heart defects to neural crest cells and their effect on cardiac function
Authors: Karunamuni Ganga H. , Ma Pei , Gu Shi , Rollins Andrew M. , Jenkins Michael W. , Watanabe Michiko
Published: September 2014

Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol‐exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies. Birth Defects Research (Part C) 102:227–250, 2014. © 2014 Wiley Periodicals, Inc.
Characterization of apoptosis in PER.C6® batch and perfusion cultures
Authors: Mercier Sarah M. , Diepenbroek Bas , Martens Dirk , Wijffels Rene H. , Streefland Mathieu
Published: September 2014

Preventing or delaying cell death is a challenge in mammalian cell cultures for the development and optimization of production processes for biopharmaceuticals. Cell cultures need to be maintained highly viable for extended times in order to reach maximum production yields. Moreover, programmed cell death through apoptosis is often believed to occur without being detected by classical viability measurements. In this study, we characterized cell death in PER.C6® batch and perfusion cultures using three flow cytometry techniques measuring different steps of the apoptosis cascade: DNA fragmentation, caspases activation and phosphatidylserine externalization. We showed that apoptosis is the main pathway of PER.C6® cell death in batch cultures after depletion of main carbon sources. In high cell density perfusion cultures fed at a constant specific perfusion rate, both high viability and very limited apoptosis were observed. When extending this perfusion process far beyond standard operations, cultures were exposed to suboptimal process conditions, which resulted in an increase of apoptotic cell death. Moreover, we showed that the reference viability measurement using trypan blue exclusion properly assesses the level of cell death in PER.C6® cultures. This study is a first step in understanding the mechanisms of PER.C6® cell death, which will be helpful to support applications of the cell line. Biotechnol. Bioeng. 2015;112: 569–578. © 2014 Wiley Periodicals, Inc.
Spiral rectal valves: Anatomy, eponyms, and clinical significance
Authors: Ikard Robert W.
Published: September 2014

Rectal wall valves are obscure anatomic parts that rarely are considered in current medical practice. Yet from the seminal analysis of them in the early nineteenth century by the Irish anatomist and surgeon, John Houston, their structure, purpose, and clinical significance were topics of surprising disagreement. Were they true structures? What function might they have? Did disease originate in rectal valves? Were special operations required for any such diseases? Because Houston's anatomic analyses of rectal valves were substantiated, they came to be known in the English literature as the Spiral Rectal Valves of Houston. In the mid‐nineteenth century, a single mid‐rectal valve was described by the Hanoverian, Otto Kohlrausch., creating confusion with the established eponym “Houston's Valves.” Many hypotheses about rectal valves have been discredited; and their physiologic functions are still unknown. Clin. Anat. 28:436–441, 2015. © 2014 Wiley Periodicals, Inc.
Opportunities to address lung cancer disparities among African Americans
Authors: Coughlin Steven S. , Matthews‐Juarez Patricia , Juarez Paul D. , Melton Courtnee E. , King Mario
Published: September 2014

Race and socioeconomic status are well known to influence lung cancer incidence and mortality patterns in the U.S. Lung cancer incidence and mortality rates are higher among blacks than whites. In this article we review opportunities to address disparities in lung cancer incidence, mortality, and survivorship among African Americans. First, we summarize recent advances in the early detection and treatment of lung cancer. Then we consider black‐white disparities in lung cancer treatment including factors that may contribute to such disparities; the literature on smoking cessation interventions for patients with or without a lung cancer diagnosis; and the important roles played by cultural competency, patient trust in their physician, and health literacy in addressing lung cancer disparities, including the need for culturally competent lung cancer patient navigators. Intervention efforts should focus on providing appropriate quality treatment for lung cancer and educating African Americans about the value of having these treatments in order to reduce these disparities. Culturally competent, patient navigation programs are needed that support lung cancer patients, especially socioeconomically disadvantaged patients, from the point of diagnosis to the initiation and completion of treatment, including cancer staging.
A Membrane‐Bound Prenyltransferase Catalyzes the O‐Prenylation of 1,6‐Dihydroxyphenazine in the Marine Bacterium Streptomyces sp. CNQ‐509
Authors: Zeyhle Philipp , Bauer Judith S. , Steimle Marco , Leipoldt Franziska , Rösch Manuela , Kalinowski Jörn , Gross Harald , Heide Lutz
Published: September 2014

Streptomyces sp. CNQ‐509 produces the rare O‐prenylated phenazines marinophenazines A and B. To identify the enzyme catalyzing the O‐prenyl transfer in marinophenazine biosynthesis, we sequenced the genome of S. sp. CNQ‐509. This led to the identification of two genomic loci harboring putative phenazine biosynthesis genes. The first locus contains orthologues for all seven genes involved in phenazine‐1‐carboxylic acid biosynthesis in pseudomonads. The second locus contains two known phenazine biosynthesis genes and a putative prenyltransferase gene termed cnqPT1. cnqPT1 codes for a membrane protein with sequence similarity to the prenyltransferase UbiA of ubiquinone biosynthesis. The enzyme CnqPT1 was identified as a 1,6‐dihydroxyphenazine geranyltransferase, which catalyzes the CO bond formation between C‐1 of the geranyl moiety and O‐6 of the phenazine scaffold. CnqPT1 is the first example of a prenyltransferase catalyzing O‐prenyl transfer to a phenazine.
De novo acute myeloid leukemia with monocytoid blasts and erythrophagocytosis
Authors: Blieden Clifford , Fan Yao‐Shan , Chapman Jennifer Rose , Vega Francisco
Published: September 2014

Key Clinical Message

Acute myeloid leukemia (AML) with t(8:16) is an infrequent acute leukemia subtype. It can occur de novo or more frequently therapy‐related. The presence of blasts with monocytoid morphology and erythrophagocytosis suggest the presence of the t(8;16).
One‐Step Approach to 2,5‐Diformylfuran from Fructose by Proton‐ and Vanadium‐Containing Graphitic Carbon Nitride
Authors: Chen Jinzhu , Guo Yuanyuan , Chen Jiayi , Song Lu , Chen Limin
Published: September 2014

5‐Hydroxymethylfurfural (HMF) was selectively synthesized from fructose by using protonated graphitic carbon nitride [g‐C3N4(H+)] as a solid acid. With g‐C3N4 as the same precursor material, 2,5‐diformylfuran (DFF) was efficiently obtained from aerobic oxidation of HMF by using vanadium‐doped g‐C3N4 (V–g‐C3N4) as an environmentally benign heterogeneous catalyst with atmospheric pressure of molecular oxygen as the oxidant. In addition, a combination of g‐C3N4(H+) and V–g‐C3N4 successfully afforded the direct synthesis of DFF from fructose through g‐C3N4(H+)‐promoted fructose dehydration and V–g‐C3N4‐catalyzed successively aerobic oxidation of HMF to DFF in a one‐pot and two‐step process. Moreover, a bifunctional catalyst made of protonated V–g‐C3N4 [V–g‐C3N4(H+)] allowed one‐pot as well as one‐step direct transformation of fructose into DFF. Under optimized conditions, 80 % yield of HMF and 82 % yield of DFF were obtained from g‐C3N4(H+)‐promoted fructose dehydration and V–g‐C3N4‐catalyzed HMF oxidation, respectively. Stepwise addition of g‐C3N4(H+) and V–g‐C3N4 in the one‐pot process improved the DFF yield up to 63 % from fructose. In contrast, V–g‐C3N4(H+)‐catalyzed direct one‐step transformation of fructose into DFF led to a DFF yield of 45 %. The research highlights a one‐step approach to DFF from fructose with functional g‐C3N4 catalyst.
Supramolecular Complexation of Biological Phosphates with an Acyclic Triazolium‐Linked Anthracenyl‐1,3‐Diconjugate of Calix[4]Arene: Synthesis, Characterization, Spectroscopy, Microscopy, and Computational Studies
Authors: Sreenivasu Mummidivarapu V. V. , Kumar Hinge Vijaya , Samanta Kushal , Yarramala Deepthi S. , Pulla Rao Chebrolu
Published: September 2014

A triazolium‐anthracenyl calix[4]arene conjugate (L) was synthesized by methylating the precursor triazole derivative and then characterized. The potential of the cationic L to differentiate nucleoside triphosphates (NTPs) from their mono‐ and diphosphates was demonstrated. Due to its unique combination of arms with the calix‐platform, a fluorescence enhancement was observed for L with all the NTPs, whereas there is no report with such enhancement being exhibited in case of all the NTPs. This has been supported by the aggregation of L observed from microscopy. Selectivity of L towards NTPs over other phosphates was a result of specific weak interactions, namely, ion–ion, hydrogen bonding and π⋅⋅⋅π, present in the 1:2 complex of L and NTPs (based on ESI MS), which were absent in their congener‐phosphates as delineated by NMR and computational studies. Thus, L stands as a unique receptor for NTPs.
Diamine‐Catalyzed Addition of ZnEt2 to PhC(O)CF3: Two Mechanisms and Autocatalytic Asymmetric Enhancement
Authors: Calvillo‐Barahona Mercedes , Casares Juan A. , Cordovilla Carlos , Genov Miroslav N. , Martínez‐Ilarduya Jesús M. , Espinet Pablo
Published: September 2014

NMR spectroscopic studies of the catalytic addition reaction of ZnEt2 to PhC(O)CF3 in the presence of three very efficient catalysts [TMEDA, tBuBOX, and L; where L is a chiral diamine synthesized from optically pure (R,R)‐1,2‐diphenylethylenediamine and (S)‐2,2′‐bis‐(bromomethyl)‐1,1′‐binaphthalene] reveal large differences in their behavior. For the ligands TMEDA and tBuBOX, the catalysis shows no unusual features and proceeds via [(NN)Zn(Et){OC(CF3)(Et)Ph}]. For NNL, the observation of autocatalytic asymmetric enhancement during the catalysis, and unusual inverse concentration dependence on the reaction rate, indicate the participation of an additional novel catalytic cycle that goes through a dinuclear intermediate containing one ZnEt2 and one ZnEt fragment connected by NN and OR bridges. Interestingly, the 19F NMR signals of the main product of the reaction ([Zn(Et){OC*(CF3)(Et)Ph}]2) allowed us to assess the enantioselectivity of the processes in situ without the assistance of chiral chromatography.
Base‐Catalyzed Intramolecular Hydroamination of Cyclohexa‐2,5‐dienes: Insights into the Mechanism through DFT Calculations and Application to the Total Synthesis of epi‐Elwesine
Authors: Rousseau Géraldine , Lebeuf Raphaël , Schenk Kurt , Castet Frédéric , Robert Frédéric , Landais Yannick
Published: September 2014

The base‐catalyzed intramolecular hydroamination of 1‐ethylaminocyclohexa‐2,5‐dienes is described. The transformation proceeds through isomerization of the cyclohexa‐1,4‐dienyl fragment into the corresponding conjugated 1,3‐diene prior to the hydroamination step. Attaching a chiral glycinol ether auxiliary on the amino group allows the protonation to occur with complete diastereocontrol. The resulting lithium amide then adds onto the 1,3‐dienyl moiety, affording the desired fused pyrrolidine ring along with the corresponding lithium allylic anion. Protonation of the latter then proceeds with high regiocontrol to favor the resulting allylic amines. In contrast, when the reaction was performed on primary amines, fused pyrrolidines bearing a homoallylic amino group were obtained. The stereochemical course of the process and determination of the reaction pathways were established based on calculations performed at the DFT level. Finally, application of the methodology to the enantioselective synthesis of (+)‐epi‐elwesine, a crinane alkaloid, is described.
Mechanistic Insights into RNA Transphosphorylation from Kinetic Isotope Effects and Linear Free Energy Relationships of Model Reactions
Authors: Chen Haoyuan , Giese Timothy J. , Huang Ming , Wong Kin‐Yiu , Harris Michael E. , York Darrin M.
Published: September 2014

Phosphoryl transfer reactions are ubiquitous in biology and the understanding of the mechanisms whereby these reactions are catalyzed by protein and RNA enzymes is central to reveal design principles for new therapeutics. Two of the most powerful experimental probes of chemical mechanism involve the analysis of linear free energy relations (LFERs) and the measurement of kinetic isotope effects (KIEs). These experimental data report directly on differences in bonding between the ground state and the rate‐controlling transition state, which is the most critical point along the reaction free energy pathway. However, interpretation of LFER and KIE data in terms of transition‐state structure and bonding optimally requires the use of theoretical models. In this work, we apply density‐functional calculations to determine KIEs for a series of phosphoryl transfer reactions of direct relevance to the 2′‐O‐transphosphorylation that leads to cleavage of the phosphodiester backbone of RNA. We first examine a well‐studied series of phosphate and phosphorothioate mono‐, di‐ and triesters that are useful as mechanistic probes and for which KIEs have been measured. Close agreement is demonstrated between the calculated and measured KIEs, establishing the reliability of our quantum model calculations. Next, we examine a series of RNA transesterification model reactions with a wide range of leaving groups in order to provide a direct connection between observed Brønsted coefficients and KIEs with the structure and bonding in the transition state. These relations can be used for prediction or to aid in the interpretation of experimental data for similar non‐enzymatic and enzymatic reactions. Finally, we apply these relations to RNA phosphoryl transfer catalyzed by ribonuclease A, and demonstrate the reaction coordinate–KIE correlation is reasonably preserved. A prediction of the secondary deuterium KIE in this reaction is also provided. These results demonstrate the utility of building up knowledge of mechanism through the systematic study of model systems to provide insight into more complex biological systems such as phosphoryl transfer enzymes and ribozymes.
Understanding the Mechanisms of Unusually Fast HH, CH, and CC Bond Reductive Eliminations from Gold(III) Complexes
Authors: Nijamudheen A. , Karmakar Sharmistha , Datta Ayan
Published: September 2014

Carbon–carbon bond reductive elimination from gold(III) complexes are known to be very slow and require high temperatures. Recently, Toste and co‐workers have demonstrated extremely rapid CC reductive elimination from cis‐[AuPPh3(4‐F‐C6H4)2Cl] even at low temperatures. We have performed DFT calculations to understand the mechanistic pathway for these novel reductive elimination reactions. Direct dynamics calculations inclusive of quantum mechanical tunneling showed significant contribution of heavy‐atom tunneling (>25 %) at the experimental reaction temperatures. In the absence of any competing side reactions, such as phosphine exchange/dissociation, the complex cis‐[Au(PPh3)2(4‐F‐C6H4)2]+ was shown to undergo ultrafast reductive elimination. Calculations also revealed very facile, concerted mechanisms for HH, CH, and CC bond reductive elimination from a range of neutral and cationic gold(III) centers, except for the coupling of sp3 carbon atoms. Metal–carbon bond strengths in the transition states that originate from attractive orbital interactions control the feasibility of a concerted reductive elimination mechanism. Calculations for the formation of methane from complex cis‐[AuPPh3(H)CH3]+ predict that at −52 °C, about 82 % of the reaction occurs by hydrogen‐atom tunneling. Tunneling leads to subtle effects on the reaction rates, such as large primary kinetic isotope effects (KIE) and a strong violation of the rule of the geometric mean of the primary and secondary KIEs.
Hexameric MnII Dendrimer as MRI Contrast Agent
Authors: Zhu Jiang , Gale Eric M. , Atanasova Iliyana , Rietz Tyson A. , Caravan Peter
Published: September 2014

A MnII chelating dendrimer was prepared as a contrast agent for MRI applications. The dendrimer comprises six tyrosine‐derived [Mn(EDTA)(H2O)]2− moieties coupled to a cyclotriphosphazene core. Variable temperature 17O NMR spectroscopy revealed a single water co‐ligand per MnII that undergoes fast water exchange (kex=(3.0±0.1)×108 s−1 at 37 °C). The 37 °C per MnII relaxivity ranged from 8.2 to 3.8 mM−1 s−1 from 0.47 to 11.7 T, and is sixfold higher on a per molecule basis. From this field dependence a rotational correlation time was estimated as 0.45(±0.02) ns. The imaging and pharmacokinetic properties of the dendrimer were compared to clinically used [Gd(DTPA)(H2O)]2− in mice at 4.7 T. On first pass, the higher per ion relaxivity of the dendrimer resulted in twofold greater blood signal than for [Gd(DTPA)(H2O)]2−. Blood clearance was fast and elimination occurred through both the renal and hepatobiliary routes. This MnII containing dendrimer represents a potential alternative to Gd‐based contrast agents, especially in patients with chronic kidney disease where the use of current Gd‐based agents may be contraindicated.
Reverse Micelle Synthesis of Colloidal Nickel–Manganese Layered Double Hydroxide Nanosheets and Their Pseudocapacitive Properties
Authors: Sim Hwansu , Jo Changshin , Yu Taekyung , Lim Eunho , Yoon Songhun , Lee Jung Heon , Yoo Jibeom , Lee Jinwoo , Lim Byungkwon
Published: September 2014

Colloidal nanosheets of nickel–manganese layered double hydroxides (LDHs) have been synthesized in high yields through a facile reverse micelle method with xylene as an oil phase and oleylamine as a surfactant. Electron microscopy studies of the product revealed the formation of colloidal nanoplatelets with sizes of 50–150 nm, and X‐ray diffraction, energy dispersive X‐ray spectroscopy, and X‐ray photoelectron spectroscopy studies showed that the Ni–Mn LDH nanosheets had a hydrotalcite‐like structure with a formula of [Ni3Mn(OH)8](Cl−)⋅n H2O. We found that the presence of both Ni and Mn precursors was required for the growth of Ni‐Mn LDH nanosheets. As pseudocapacitors, the Ni–Mn LDH nanosheets exhibited much higher specific capacitance than unitary nickel hydroxides and manganese oxides.
Homo‐ and Heteroleptic Bismuth(III/V) Thiolates from N‐Heterocyclic Thiones: Synthesis, Structure and Anti‐Microbial Activity
Authors: Luqman Ahmad , Blair Victoria L. , Brammananth Rajini , Crellin Paul K. , Coppel Ross L. , Andrews Philip C.
Published: September 2014

Homo‐ and heteroleptic bismuth thiolato complexes have been synthesised and characterised from biologically relevant tetrazole‐, imidazole‐, thiadiazole‐ and thiazole‐based heterocyclic thiones (thiols): 1‐methyl‐1H‐tetrazole‐5‐thiol (1‐MMTZ(H)); 4‐methyl‐4H‐1,2,4‐triazole‐3‐thiol (4‐MTT(H)); 1‐methyl‐1H‐imidazole‐2‐thiol (2‐MMI(H)); 5‐methyl‐1,3,4‐thiadiazole‐2‐thiol (5‐MMTD(H)); 1,3,4‐thiadiazole‐2‐dithiol (2,5‐DMTD(H)2); and 4‐(4‐bromophenyl)thiazole‐2‐thiol (4‐BrMTD(H)). Reaction of BiPh3 with 1‐MMTZ(H) produced the rare BiV thiolato complex [BiPh(1‐MMTZ)4], which undergoes reduction in DMSO to give [BiPh(1‐MMTZ)2{(1‐MMTZ(H)}2]. Reactions with PhBiCl2 or BiPh3 generally produced monophenylbismuth thiolates, [BiPh(SR)2]. The crystal structures of [BiPh(1‐MMTZ)2{1‐MMTZ(H)}2], [BiPh(5‐MMTD)2], [BiPh{2,5‐DMTD(H)}2(Me2CO)] and [Bi(4‐BrMTD)3] were obtained. Evaluation of the bactericidal properties against M. smegmatis, S. aureus, MRSA, VRE, E. faecalis and E. coli showed complexes containing the anionic ligands 1‐ MMTZ, 4‐MTT and 4‐BrMTD to be most effective. The dithiolato dithione complexes [BiPh(4‐MTT)2{4‐MTT(H)}2] and [BiPh(1‐MMTZ)2{1‐MMTZ(H)}2] were most effective against all the bacteria: MICs 0.34 μM for [BiPh(4‐MTT)2{4‐MTT(H)}2] against VRE, and 1.33 μM for [BiPh(1‐MMTZ)2{1‐MMTZ(H)}2] against M. smegmatis and S. aureus. Tris‐thiolato BiIII complexes were least effective overall. All complexes showed little or no toxicity towards mammalian COS‐7 cells at 20 μg mL−1.
Rhodium(III)‐Catalyzed N‐Nitroso‐Directed CH Addition to Ethyl 2‐Oxoacetate for Cycloaddition/Fragmentation Synthesis of Indazoles
Authors: Chen Jinsen , Chen Pei , Song Chao , Zhu Jin
Published: September 2014

RhIII‐catalyzed N‐nitroso‐directed CH addition to ethyl 2‐oxoacetate allows subsequent construction of indazoles, a privileged heterocycle scaffold in synthetic chemistry, through the exploitation of reactivity between the directing group and installed group. The formal [2+2] cycloaddition/fragmentation reaction pathway identified herein, a unique reactivity pattern hitherto elusive for the N‐nitroso group, emphasizes the importance of forward reactivity analysis in the development of useful CH functionalization‐based synthetic tools. The synthetic utility of the protocol is demonstrated with the synthesis of a tricyclic‐fused ring system. The diversity of covalent linkages available for the nitroso group should enable the extension of the genre of reactivity reported herein to the synthesis of other types of heterocycles.
Total Synthesis of the Anti‐inflammatory and Pro‐resolving Lipid Mediator MaR1n−3 DPA Utilizing an sp3–sp3 Negishi Cross‐Coupling Reaction
Authors: Tungen Jørn Eivind , Aursnes Marius , Dalli Jesmond , Arnardottir Hildur , Serhan Charles Nicholas , Hansen Trond Vidar
Published: September 2014

The first total synthesis of the lipid mediator MaR1n−3 DPA (5) has been achieved in 12 % overall yield over 11 steps. The stereoselective preparation of 5 was based on a Pd‐catalyzed sp3–sp3 Negishi cross‐coupling reaction and a stereocontrolled Evans–Nagao acetate aldol reaction. LC‐MS/MS results with synthetic material matched the biologically produced 5. This novel lipid mediator displayed potent pro‐resolving properties stimulating macrophage efferocytosis of apoptotic neutrophils.
Photoresponsive DNA Nanocapsule Having an Open/Close System for Capture and Release of Nanomaterials
Authors: Takenaka Tomohiro , Endo Masayuki , Suzuki Yuki , Yang Yangyang , Emura Tomoko , Hidaka Kumi , Kato Takayuki , Miyata Tomoko , Namba Keiichi , Sugiyama Hiroshi
Published: September 2014

A photofunctionalized square bipyramidal DNA nanocapsule (NC) was designed and prepared for the creation of a nanomaterial carrier. Photocontrollable open/close system and toehold system were introduced into the NC for the inclusion and release of a gold nanoparticle (AuNP) by photoirradiation and strand displacement. The reversible open and closed states were examined by gel electrophoresis and atomic force microscopy (AFM), and the open behavior was directly observed by high‐speed AFM. The encapsulation of the DNA‐modified AuNP within the NC was carried out by hybridization of a specific DNA strand (capture strand), and the release of the AuNP was examined by addition of toehold‐containing complementary DNA strand (release strand). The release of the AuNP from the NC was achieved by the opening of the NC and subsequent strand displacement.
Ultrasound‐facilitated particle breakage: Estimation of kinetic parameters using population balance modelling
Authors: Bari Atul H. , Pandit Aniruddha B.
Published: September 2014

Ultrasound‐facilitated particle breakage has been proven to be a good technique for size reduction. However, because of the difficulties associated with the solution of population balance equation (PBE), there has been little attention on the estimation of kinetics of this process. In this paper an attempt has been made to develop a generic approach for solving PBE with a given particle size distribution (PSD) data to estimate the breakage kinetics. For this purpose, discretization technique along with gPROMS parameter estimation tool was used. This method was found to be a comprehensive method for the estimation of breakage kinetics in general and was subsequently used for the estimation of ultrasound‐facilitated breakage kinetics, using a simple model system. Potassium nitrate (KNO3) particles suspended in toluene was used as model system, and the effect of induced power on breakage strength was studied. The data obtained were used for the estimation of specific breakage rate with different particle size distribution function. The distribution function, for which simulated PSD was found to match with the experimental PSD, was considered for deriving energy‐size reduction law.
Demineralization of glucose solutions by electrodialysis: Influence of the ionic composition on the mass transfer and process performances
Authors: Galier Sylvain , Balmann Hélène Roux‐de
Published: September 2014

The aim of the present work was to investigate the influence of the ionic composition on the demineralization of a saccharide solution containing glucose. Experiments were carried out in order to evaluate the influence of the ionic composition on the solvent and solutes fluxes (glucose and electrolytes) through the membrane under different conditions (ionic compositions: NaCl, Na2SO4 and CaCl2; with or without current). From diffusion experiments (without current), it was shown that the glucose diffusion flux decreases for increasing ion hydration. These results are in agreement with those obtained in a previous work showing that the transfer modification reflects changes in the membrane properties associated with the hydration of its counter‐ion which is likely linked to swelling mechanisms at a microscopic scale.

From the experiments carried out in normal ED conditions (with current) an additional convective contribution was pointed out. This kind of result is rather scarce in the literature. The glucose flux was then the sum of two contributions: diffusion and convection, due to the electro‐osmotic flux which is proportional to the electrical current. The contribution of the glucose convection flux on the overall glucose transfer was ranged between 70 and 90 % according to the electrolyte nature (NaCl, Na2SO4 and CaCl2) and the electric current (150 or 300 A m−2). The variation of the convective flux has been further correlated to the hydration of the ions. Indeed increasing convection fluxes were obtained for decreasing anion (or cation) hydration. It was shown that the saccharide transfer increases in presence of salts and that this increase was correlated to the saccharide dehydration in presence of electrolyte. Finally, the solvent, ions and glucose fluxes were used to calculate the glucose loss factor versus the demineralization factor to evaluate the influence of the electrolyte nature on the demineralization process performances. It was observed that, for a fixed demineralization factor, the glucose loss factor (comprised between 4 and 5 % for a demineralization factor of 90 %) increased with the ion hydration due to the higher contribution of the glucose convection flux.
A Novel Dimeric BINOL for Enantioselective Recognition of 1,2‐Amino Alcohols
Authors: Velmurugan Krishnaswamy , Tang Lijun , Nandhakumar Raju
Published: September 2014

A novel auxillary chiral dimeric binol has been designed, synthesized, and used to enantioselectively recognize 1,2‐amino alcohols through the three point of interactions, the reversible imine bond, resonance assisted hydrogen bonding and the hydrogen bonding by the additional chiral moiety introduced at the receptor. The enantioselectivities were comparable to those of the previous reported receptors.
Recent Advances of the Combination of Au/Acid Catalysis
Authors: Zhang Shuo , Wei Fang , Song Chuangling , Jia Jiong , Xu Zhenghu
Published: September 2014

Recently, homogeneous gold catalysis has attracted tremendous attention and has also been widely used in multistep synthesis. The current reaction methodology starts from the gold activation of unsaturated carbon bond and subsequent nucleophilic attack. The combination of a gold catalyst with another acid catalyst, including Bronsted acid and Lewis acid, is possible to bring two distinctive catalytic systems together and deliver unprecedented new reactions. More essentially, it avoids the purification of unstable intermediates and improves the step and atom economy. Here, the recent progress in the Au/Acid combined catalysis is reviewed, including the scope of reactions, mechanism and synthetic applications.
Synthesis of Functionalized 1‐Benzamido‐1,4‐dihydropyridines via a One‐Pot Two‐Step Four‐Component Reaction
Authors: Sun Jing , Shen Guoliang , Xie Yajing , Yan Chaoguo
Published: September 2014

The one‐pot four‐component reaction of benzohydrazide, acetylenedicarboxylate, aromatic aldehydes and malononitrile in ethanol with triethylamine as base catalyst afforded functionalized 1‐benzamido‐1,4‐dihydropyridines in satisfactory yields. Under similar conditions, picolinohydrazide or nicotinohydrazide can also be successfully utilized in the reactions to give corresponding functionalized 1,4‐dihydropyridines. 1H NMR data indicated that an equilibrium of cis/trans‐conformations exist in 1‐benzamido‐1,4‐dihydropyridines.
Modern Obesity Pharmacotherapy: Weighing Cardiovascular Risk and Benefit
Authors: Cunningham Jonathan W. , Wiviott Stephen D.
Published: September 2014

Obesity is a major correlate of cardiovascular disease. Weight loss improves cardiovascular risk factors and has the potential to improve outcomes. Two drugs, phentermine plus topiramate and lorcaserin, have recently been approved by the US Food and Drug Administration for the indication of obesity; a third, bupropion plus naltrexone, is under consideration for approval. In clinical trials, these drugs cause weight loss and improve glucose tolerance, lipid profile, and, with the exception of bupropion plus naltrexone, blood pressure. However, their effect on cardiovascular outcomes is unknown. In defining appropriate roles for these drugs in preventive cardiology, it is important to remember the checkered history of drugs for obesity. New weight‐loss drugs share the serotonergic and sympathomimetic mechanisms that proved harmful in the cases of Fen‐Phen and sibutramine, respectively, albeit with significant differences. Given these risks, randomized cardiovascular outcomes trials are needed to establish the safety, and potential benefit, of these drugs. This review will discuss the history of pharmacotherapy for obesity, existing efficacy and safety data for the novel weight‐loss drugs, and issues in the design of postapproval clinical trials.
Elevated risks of subsequent primary malignancies in patients with thyroid cancer: A nationwide, population‐based study in Korea
Authors: Cho Yoon Young , Lim Jiwon , Oh Chang‐Mo , Ryu Junsun , Jung Kyu‐Won , Chung Jae Hoon , Won Young‐Joo , Kim Sun Wook
Published: September 2014

BACKGROUND

Thyroid cancer affects relatively young adults, and its overall survival is excellent. With long life expectancy, the development of subsequent cancers is an important concern for survivors of thyroid cancer. The objective of this study was to investigate the incidence and types of second primary malignancies in Korean patients with thyroid cancer.

METHODS

The study cohort included 178,844 registrants with thyroid cancer from the Korea Central Cancer Registry (KCCR) database between 1993 and 2010. Standardized incidence ratios (SIRs) were calculated using a statistical software program (SEER*Stat 8.0.4).

RESULTS

Among 178,844 patients with thyroid cancer, 2895 (1.6%) were diagnosed with subsequent second primary malignancies. The overall risks of a second primary cancer were elevated by 6% in patients who had thyroid cancer compared with the general population during the same period. The elevated risks for developing second cancers were observed in all sites except the stomach and cervix. The elevated risk of second primary cancers was observed within the first 10 years of follow‐up. Leukemia and cancers of the salivary gland, kidney, prostate, lung, and breast had the most significantly elevated risks as secondary cancers and presented as early as during the first 5 years after the initial diagnosis of thyroid cancer.

CONCLUSIONS

This is the largest, standardized, population‐based study to date using nationwide data from the entire Korean population. The risks of several cancers were elevated significantly during follow‐up, thus alerting physicians to pay special attention in their care of patients with thyroid cancer and long‐term survivors. Cancer 2015;121:259–68. © 2014 American Cancer Society.
Parent decision‐making around the genetic testing of children for germline TP53 mutations
Authors: Alderfer Melissa A. , Zelley Kristin , Lindell Robert B. , Novokmet Ana , Mai Phuong L. , Garber Judy E. , Nathan Deepika , Scollon Sarah , Chun Nicolette M. , Patenaude Andrea F. , Ford James M. , Plon Sharon E. , Schiffman Joshua D. , Diller Lisa R. , Savage Sharon A. , Malkin David , Ford Carol A. , Nichols Kim E.
Published: September 2014

BACKGROUND

Li‐Fraumeni syndrome is a rare genetic cancer predisposition syndrome caused by germline TP53 mutations. Up to 20% of mutation carriers develop cancer during childhood. The benefits of TP53 mutation testing of children are a matter of debate and knowledge of parent decision‐making around such testing is limited. The current study examined how parents make decisions regarding TP53 testing for their children.

METHODS

Families offered and those pursuing TP53 testing for their children were identified across the study sites. Qualitative interviews with 46 parents (39 families) were analyzed to describe decision‐making styles and perceived advantages and disadvantages of testing.

RESULTS

TP53 mutation testing uptake was high (92%). Three decision‐making styles emerged. Automatic decisions (44% of decisions) involved little thought and identified immediate benefit(s) in testing (100% pursued testing). Considered decisions (49%) weighed the risks and benefits but were made easily (77% pursued testing). Deliberated decisions (6%) were difficult and focused on psychosocial concerns (25% pursued testing). Perceived advantages of testing included promoting child health, satisfying a “need to know,” understanding why cancer(s) occurred, suggesting family member risk, and benefiting research. Disadvantages included psychosocial risks and privacy/discrimination/insurance issues.

CONCLUSIONS

Although empirical evidence regarding the benefits and risks of TP53 testing during childhood are lacking, the majority of parents in the current study decided easily in favor of testing and perceived a range of advantages. The authors conclude that in the context of a clinical diagnosis of Li‐Fraumeni syndrome, parents should continue to be offered TP53 testing for their children, counseled regarding potential risks and benefits, and supported in their decision‐making process. Cancer 2015;121:286–93. © 2014 American Cancer Society.
Synthesis and Visible‐Light Photocatalytic Performance of Cadmium Sulfide and Oxide Hexagonal Nanoplates
Authors: Lang Di , Liu Fan , Qiu Guohong , Feng Xionghan , Xiang Quanjun
Published: September 2014

Cadmium sulfide and oxide hexagonal nanoplates were prepared by a facile ion‐exchange strategy and crystal transformation process by using morphology‐analogous cadmium oxyhydroxide as a precursor. The precursors of uniform Cd(OH)2 hexagonal nanoplates was first synthesized by a simple ethylenediaminetetraacetic acid disodium salt assisted hydrothermal method. Then, through ion‐exchange reactions of the as‐prepared Cd(OH)2 precursors with S2− anions, cubic‐phase CdS was formed immediately on the surface of Cd(OH)2 nanoplates. The above intermediates could be further completely converted into CdS and CdO nanoplates without morphology changes through thermal treatment at 280 °C for 4 h under a sulfur atmosphere and under air, respectively. The photocatalytic activity of all samples was evaluated by the photocatalytic decolorization of an aqueous solution of methylene blue and photocatalytic hydrogen production under visible‐light irradiation. The results show that the CdS hexagonal nanoplates exhibit high visible‐light photocatalytic degradation properties and photocatalytic hydrogen production activity. The enhanced visible‐light photocatalytic activity can be related to several factors, including a suitable band gap, phase structure, and morphology of the hexagonal nanoplates.
Understanding the Change Process Involved in Solving Psychological Problems: A Model‐based Approach to Understanding How Psychotherapy Works
Authors: Marken Richard S. , Carey Timothy A.
Published: September 2014

A review of the literature on psychotherapy suggests that improvements in effectiveness, efficiency and accessibility have been hampered by a lack of understanding of how psychotherapy works. Central to gaining such understanding is an accurate description of the change process that occurs when someone solves a psychological problem. We describe the Perceptual Control Theory (PCT) model of human functioning, which can be used to understand the nature of psychological problems and how they are solved. PCT suggests that problems can be broadly grouped into two categories: those that can be solved using existing skills and those that require the generation of new skills. In general, psychological problems belong in the second category. PCT describes a fundamental form of learning in which existing structures and systems are reorganized to create new skills, perspective and insights. Psychotherapy based on PCT is aimed at directing reorganization to the source of the problem. Copyright © 2014 John Wiley & Sons, Ltd.

Key Practitioner Message

Understanding the phenomenon of control is central to understanding how psychotherapy works.

Conflict could be considered a general formulation for psychological distress.

Therapy will be efficient when the reorganization process is focused at the right level of the client's control hierarchy.

Therapy will be effective only when the client's reorganization system—not the therapist—has managed to come up with a solution to the client's problem.

What the client says about the nature and reason for their problem is less important than the point of view from which these problems are being discussed.
Rapid Conversion of Sorbitol to Isosorbide in Hydrophobic Ionic Liquids under Microwave Irradiation
Authors: Kamimura Akio , Murata Kengo , Tanaka Yoshiki , Okagawa Tomoki , Matsumoto Hiroshi , Kaiso Kouji , Yoshimoto Makoto
Published: September 2014

Sorbitol was effectively converted to isosorbide by treatment with [TMPA][NTf2] in the presence of catalytic amounts of TsOH under microwave heating at 180 °C. The reaction completed within 10 min and isosorbide was isolated to about 60 %. Ionic liquids were readily recovered by an extraction treatment and reused several times.