bluuebunny/crossref_metadata_2025 huggingface dataset:
Rational Manipulation of DNA Methylation by Using Isotopically Reinforced Cytosine
Authors: Woodcock Clayton B. , Ulashchik Egor A. , Poopeiko Nikolai E. , Shmanai Vadim V. , Reich Norbert O. , Shchepinov Mikhail S.
Published: September 2016

The human DNA methyltransferase 3A (DNMT 3A) is responsible for de novo epigenetic regulation, which is essential for mammalian viability and implicated in diverse diseases. All DNA cytosine C5 methyltransferases follow a broadly conserved catalytic mechanism. We investigated whether C5 β‐elimination contributes to the rate‐limiting step in catalysis by DNMT3A and the bacterial M.HhaI by using deuterium substitutions of C5 and C6 hydrogens. This substitution caused a 1.59–1.83 fold change in the rate of catalysis, thus suggesting that β‐elimination is partly rate‐limiting for both enzymes. We used a multisite substrate to explore the consequences of slowing β‐elimination during multiple cycles of catalysis. Processive catalysis was slower for both enzymes, and deuterium substitution resulted in DNMT 3A dissociating from its substrate. The decrease in DNA methylation rate by DNMT 3A provides the basis of our ongoing efforts to alter cellular DNA methylation levels without the toxicity of currently used methods.
Interleukin‐4‐Clicked Surfaces Drive M2 Macrophage Polarization
Authors: Lühmann Tessa , Spieler Valerie , Werner Vera , Ludwig Marie‐Gabrielle , Fiebig Juliane , Mueller Thomas D. , Meinel Lorenz
Published: September 2016

Driving macrophage (Mϕ) polarization into the M2 phenotype provides potential against inflammatory diseases. Interleukin‐4 (IL‐4) promotes polarization into the M2‐Mϕ phenotype, but its systemic use is constrained by dose‐limiting toxicity. Consequently, we developed IL‐4‐decorated surfaces aiming at sustained and localized activity. IL‐4 muteins were generated by genetic code expansion; Lys42 was replaced by unnatural amino acids (uAAs). Both muteins showed cell‐stimulation ability and binding affinity to IL4Rα similar to those of wt‐IL‐4. Copper‐catalyzed (CuAAC) and copper‐free strain‐promoted (SPAAC) 1,3‐dipolar azide–alkyne cycloadditions were used to site‐selectively anchor IL‐4 to agarose surfaces. These surfaces had sustained IL‐4 activity, as demonstrated by TF‐1 cell proliferation and M2, but not M1, polarization of M‐CSF‐generated human Mϕ. The approach provides a blueprint for the engineering of cytokine‐activated surfaces profiled for sustained and spatially controlled activity.
MiR‐125b regulates SFRP5 expression to promote growth and activation of cardiac fibroblasts
Authors: Bie Zi‐dong , Sun Li‐ye , Geng Chuan‐liang , Meng Qing‐guo , Lin Xiao‐jing , Wang Yu‐feng , Wang Xue‐ban , Yang Jun
Published: September 2016

Myocardial fibrosis (MF), which typically occurs after a myocardial infarction (MI), is a major factor involved in the process of ventricular remodeling and subsequent progression to heart failure. Current studies have found that various microRNAs (miRNAs), such as miR‐125b, play an important role in this process. However, few studies have investigated the specific mechanism of miR‐125b. Transfection of miR‐125b mimics into cardiac fibroblasts (CFs) resulted in significantly increased expression of the myofibroblast marker alpha‐smooth muscle actin (α‐SMA) and vinculin by Western blot analysis, while transfection of miR‐125b inhibitors resulted in the opposite effect. Analysis of putative CF target genes for miR‐125b revealed that miR‐125b specifically inhibits expression of secreted frizzled‐related protein 5 (SFRP5). SFRP5 inhibited expression of α‐SMA and collagen I and III in CFs, while miR‐125b promoted the expression of these proteins. Cotransfection of the SFRP5 overexpression vector and miR‐125b mimics did not result in significant upregulation of SFRP5 expression or downregulation of α‐SMA and collagen I and III. Further analysis revealed that miR‐125b promotes the proliferation and migration of CFs and inhibits their apoptosis, while SFRP5 exhibits the opposite effects. These results indicate that miR‐125b can regulate SFRP5 expression and thus influence the growth and activation of CFs. Hence, this study provides important insight into possible approaches for the prevention and treatment of MF after an MI.
Incorporation of N‐Methyl‐d‐glucamine Functionalized Oligomer into MIL‐101(Cr) for Highly Efficient Removal of Boric Acid from Water
Authors: Wang Jiawei , Bao Zongbi , Xing Huabin , Su Baogen , Zhang Zhiguo , Yang Qiwei , Yang Yiwen , Ren Qilong , Chen Banglin
Published: September 2016

Polymeric resins are practically important adsorbents in a wide variety of applications, but they generally suffer from low surface areas and limited functionalized adsorption sites owing to their closely compacted and tangled polymeric chains. A metal–organic framework (MOF)–polymer composite with enhanced adsorption capacity against the compacted polymeric resins was reported. The strategy to incorporate functionalized oligomer within the cavities of the MOF was demonstrated by the preparation of MIL‐101(Cr) incorporated with N‐methyl‐d‐glucamine‐based organosiloxane polymer. The resulting MOF composite shows high efficiency for the removal of boric acid from water because of exceptionally high loading of functional groups responsible for the boron adsorption. This material offers promising perspectives for boron removal applications in seawater desalination.
Utilizing a pH‐Sensitive Dye in the Selective Fluorescent Recognition of Sulfate
Authors: Agafontsev Aleksandr M. , Shumilova Tatiana A. , Panchenko Pavel A. , Janz Sharon , Fedorova Olga A. , Kataev Evgeny A.
Published: September 2016

A receptor containing amidopyrrole binding subunits and free amino groups, conjugated to a naphthalimide dye, has been designed and synthesized. The intrinsic selectivity of the binding motif for phosphate present in DMSO completely disappears in 10 % DMSO aqueous buffer at pH 3.6, at which the receptor is protonated. The electrostatic interactions between the receptor and an anion start to dominate, thus leading to selectivity for sulfate. The ability of the HSO4− anion to transfer the proton to the amino group during the recognition event suppresses the photoinduced electron transfer (PET) on the dye, resulting in a selective turn‐on fluorescent response. The choice of pH of the solution for sensing is dictated by the pKa value of the dye.
Charge Control in Two Isostructural Anionic/Cationic CoII Coordination Frameworks for Enhanced Acetylene Capture
Authors: Chen Di‐Ming , Tian Jia‐Yue , Liu Chun‐Sen , Chen Min , Du Miao
Published: September 2016

Two isostructural CoII‐based metal–organic frameworks (MOFs) with the opposite framework charges have been constructed, which can be simply controlled by changing the tetrazolyl or triazolyl terminal in two bifunctional ligands. Notably, the cationic MOF 2 can adsorb much more C2H2 than the anionic MOF 1 with an increase of 88 % for C2H2 uptake at 298 K in spite of more active nitrogen sites in 1. Theoretical calculations indicate that both nitrate and triazolyl play vital roles in C2H2 binding and the C2H2 adsorption isotherm confirms that the enhanced C2H2 uptake for 2 (225 and 163 cm3g−1 at 273 and 298 K) is exceptionally high for MOF materials without open metal sites or uncoordinated polar atom groups on the frameworks.
Cyano‐Bridged Trimetallic Coordination Polymer Nanoparticles and Their Thermal Decomposition into Nanoporous Spinel Ferromagnetic Oxides
Authors: Zakaria Mohamed B. , Hossain Md. Shahriar A. , Shiddiky Muhammad J. A. , Shahabuddin Mohammed , Yanmaz Ekrem , Kim Jung Ho , Belik Alexei A. , Ide Yusuke , Hu Ming , Tominaka Satoshi , Yamauchi Yusuke
Published: September 2016

The synthesis of a novel family of cyano‐bridged trimetallic coordination polymers (CPs) with various compositions and shapes has been reported by changing the compositional ratios of Fe, Co, and Ni species in the reaction system. In order to efficiently control the nucleation rate and the crystal growth, trisodium citrate dihydrate plays an important role as a chelating agent. After the obtained cyano‐bridged trimetallic CPs undergo thermal treatment in air at three different temperatures (250, 350, and 450 °C), nanoporous spinel metal oxides are successfully obtained. Interestingly, the obtained nanoporous metal oxides are composed of small crstalline grains, and the grains are oriented in the same direction, realizing pseudo‐single crystals with nanopores. The resultant nanoporous spinel oxides feature interesting magnetic properties. Cyano‐bridged multimetallic CPs with various sizes and shapes can provide a pathway toward functional nanoporous metal oxides that are not attainable from simple cyano‐bridged CPs containing single metal ions.
The Recently Synthesized Dimagnesiabutadiene and the Analogous Dimetalla‐Beryllium, ‐Calcium, ‐Strontium, and ‐Barium Compounds
Authors: Li Huidong , Feng Hao , Xie Yaoming , Schaefer III Henry F.
Published: September 2016

The 2014 synthesis of the remarkable dimagnesium compound Mg2[C4(CH3)2(Si(CH3)3)2](C3H7)2(C4H8O)2 may point the way to a new chapter in alkaline earth organometallic chemistry. Accordingly, we have studied the known Mg compound and the analogous Be, Ca, Sr, and Ba structures. Although most of our theoretical predictions come from density functional methods, the latter have been benchmarked using coupled cluster theory including single, double, and perturbative triplet excitations, CCSD(T) using cc‐pVTZ basis sets. Among our most important predictions are the energies for dissociation to the butadiene plus the RM−MR [R=(C3H7)2(C4H8O)2; M=Be, Mg, Ca, Si, and Ba] entities. The most reliable predictions for the dissociation energies are 99–104 (Be), 85–93 (Mg), 90–99 (Ca), 83–92 (Sr), and 83–94 (Ba) kcal mol−1. Thus, there is reason to anticipate that the four unknown compounds should be achievable synthetically. The predicted metal–metal distances (not single bonds) are 2.89 Å (Mg⋅⋅⋅Mg), 3.46 Å (Ca⋅⋅⋅Ca), 3.75 Å (Sr⋅⋅⋅Sr), and 4.04 Å (Ba⋅⋅⋅Ba). The separated RM−MR compounds have longer M−M distances but genuine metal–metal single bonds. This perhaps counter intuitive result is due to the presence of the bridging carbons in the alkaline earth butadiene compounds. All five compounds incorporate metal–carbon ionic interactions.
Modulare Verfahrenstechnik: Apparateentwicklung für wandlungsfähige Produktionssysteme
Authors: Lier Stefan , Paul Sarah , Ferdinand Dennis , Grünewald Marcus
Published: September 2016

Die Prozessindustrie steht im intensivierten, globalen Wettbewerb der Herausforderung zunehmender Marktdynamiken gegenüber. Modular aufgebaute, wandlungsfähige Produktionskonzepte versprechen eine verbesserte Anpassung an diese in den Dimensionen Mengenausbringung, Produktmix und Produktionsort. Um das gesamte Potenzial entfalten zu können, bedarf es nicht nur einer Modularisierung und Wandlungsbefähigung auf der Anlagen‐ und Logistikebene, sondern auch auf der Apparateebene. Charakteristika wie Aufbau und Skalierungskonzepte werden diskutiert. Beispiele für modulare Apparate aus den Bereichen Mischen, Wärmeübertragung, Reaktion und Trennung werden vorgestellt und weiterer Forschungsbedarf abgeleitet.
Relationship between Electron Affinity and Half‐Wave Reduction Potential: A Theoretical Study on Cyclic Electron‐Acceptor Compounds
Authors: Calbo Joaquín , Viruela Rafael , Ortí Enrique , Aragó Juan
Published: September 2016

A high‐level ab initio protocol to compute accurate electron affinities and half‐wave reduction potentials is presented and applied for a series of electron‐acceptor compounds with potential interest in organic electronics and redox flow batteries. The comprehensive comparison between the theoretical and experimental electron affinities not only proves the reliability of the theoretical G3(MP2) approach employed but also calls into question certain experimental measurements, which need to be revised. By using the thermodynamic cycle for the one‐electron attachment reaction A+e−→A−, theoretical estimates for the first half‐wave reduction potential have been computed along the series of electron‐acceptor systems investigated, with maximum deviations from experiment of only 0.2 V. The precise inspection of the terms contributing to the half‐wave reduction potential shows that the difference in the free energy of solvation between the neutral and the anionic species (ΔΔGsolv) plays a crucial role in accurately estimating the electron‐acceptor properties in solution, and thus it cannot be considered constant even in a family of related compounds. This term, which can be used to explain the occasional lack of correlation between electron affinities and reduction potentials, is rationalized by the (de)localization of the additional electron involved in the reduction process along the π‐conjugated chemical structure.
Orientation‐Dependent Thermogenesis of Assembled Magnetic Nanoparticles in the Presence of an Alternating Magnetic Field
Authors: Sun Jianfei , Fan Fengguo , Wang Peng , Ma Siyu , Song Lina , Gu Ning
Published: September 2016

Thanks to thermogenesis in the presence of an alternating magnetic field, magnetic nanoparticles could play a promising role in local heating in vivo. However, the flexible control of thermogenesis for the given nanomaterials remains challenging. Here, we propose that the thermogenesis of assembled magnetic nanoparticles can be controlled by orientation of the film relative to an external field. This idea arises from the principle of energy conservation that is formulated by Poynting′s theorem in electromagnetics. We firstly prove that the thermogenesis of magnetic nanoparticles under an alternating magnetic field is directly related to the energy flux of the field rather than to the field′s intensity. Then, alteration of the orientation can lead to different incident electromagnetic energies for the nanoparticle film, where the cross‐section of the energy absorption plays a crucial role. We developed a method to directly measure the complex susceptibility of an assembled film to confirm this point. This work could be of great importance for applications based on the electromagnetic energy conversion of nanomaterials.
Competition between Halogen, Hydrogen and Dihydrogen Bonding in Brominated Carboranes
Authors: Fanfrlík Jindřich , Holub Josef , Růžičková Zdeňka , Řezáč Jan , Lane Paul D. , Wann Derek A. , Hnyk Drahomír , Růžička Aleš , Hobza Pavel
Published: September 2016

Halogen bonds are a subset of noncovalent interactions with rapidly expanding applications in materials and medicinal chemistry. While halogen bonding is well known in organic compounds, it is new in the field of boron cluster chemistry. We have synthesized and crystallized carboranes containing Br atoms in two different positions, namely, bound to C‐ and B‐vertices. The Br atoms bound to the C‐vertices have been found to form halogen bonds in the crystal structures. In contrast, Br atoms bound to B‐vertices formed hydrogen bonds. Quantum chemical calculations have revealed that halogen bonding in carboranes can be much stronger than in organic architectures. These findings open new possibilities for applications of carboranes, both in materials and medicinal chemistry.
Impact of routine cell block preparation on results of head and neck fine needle aspirates
Authors: Carter Michael D. , Moore David P. , MacIntosh Rebecca F. , Bullock Martin J.
Published: September 2016

Background

Fine needle aspiration (FNA) of head and neck masses is a common technique for providing cytology specimens to guide patient management. Cell blocks made from these specimens can be beneficial. Policy at our institution was changed from production of cell blocks only when requested by the pathologist to routine production for all non‐parotid gland head and neck FNAs. The program was evaluated in terms of its impact on diagnosis and specimen turnaround time (TAT).

Methods

A retrospective study was carried out using electronic records at our institution. The Intervention group consisted of FNAs obtained in the 15‐month period following implementation of routine cell block preparation (n = 391). The Control group consisted of the same specimens obtained in the 15 months prior to implementation (n = 403). The groups were compared with regards to diagnostic distribution into five categories—Unsatisfactory, Negative/Benign, Abnormal, Suggestive of Malignancy, and Malignant. Cytological‐histological correlation and TAT were also compared. Chi square and t tests with P < 0.05 threshold were used.

Results

There was no difference in diagnostic distribution between the two groups (P = 0.59) and TAT was unchanged (P = 0.74). Cytological‐histological correlation was borderline improved in the Intervention group, with fewer false negatives (33.0% Intervention, 44.3% Control, P = 0.050). The cost of the program was estimated at CAD$53.60/cell block, or CAD$16,771/year.

Conclusion

Implementation of routine cell blocks for head and neck FNAs did not result in a difference in diagnostic distribution or improve case turnaround time despite incurring substantial cost. Correlation with final histology, however, was borderline improved, with fewer false negatives. Diagn. Cytopathol. 2016;44:880–887. © 2016 Wiley Periodicals, Inc.
The Molecular Basis of Insomnia: Implication for Therapeutic Approaches
Authors: Wang Zi‐Jun , Liu Jian‐Feng
Published: September 2016

Preclinical Research

Insomnia is one of the most common sleep disorders that is characterized by difficulty in sleep initiation, sleep maintenance, and/or poor sleep quality. Treatment for insomnia includes both pharmacological and non‐pharmacological interventions. Recently, the development of pharmacological treatment for insomnia has been prompted by the understanding of the molecular neurobiology of sleep‐wake regulation. For pharmacological treatment, benzodiazepines that target GABAergic system are the most widely used hypnotics. Besides GABA, the hypocretin/orexin system, and the hypothalamic–pituitary–adrenal (HPA) axis are involved in sleep‐wake regulation and may also play important role in the pathogenesis of insomnia. Genetic studies have revealed the critical role of several important genes related to the above‐mentioned systems in the regulation and function of sleep, suggesting the genetic/epigenetic factors could also contribute to the development and regulation of insomnia. Non‐pharmacological interventions include cognitive behavioral therapy for insomnia (CBT‐I) that is an effective insomnia treatment with less risk and side effects of drug therapy. Here the current treatments for insomnia based on the molecular mechanisms underlying sleep‐wake regulation, were reviewed and some newer targets that may be beneficial in the development of new treatments for insomnia were discussed. Drug Dev Res 77 : 427–436, 2016. © 2016 Wiley Periodicals, Inc.
Epigenetic Mechanisms in Psychiatric Diseases and Epigenetic Therapy
Authors: Karsli‐Ceppioglu Seher
Published: September 2016

Preclinical Research

Epigenetic mechanisms refer covalent modification of DNA and histone proteins that control transcriptional regulation of gene expression. Epigenetic regulation is involved in the development of the nervous system and plays an important role in the pathophysiology of psychiatric disorders, including depression, bipolar disorder, and schizophrenia. Epigenetic drugs, including histone deacetylation and DNA methylation inhibitors have received increased attention for the management of psychiatric diseases. The purpose of this review is to discuss the potential of epigenetic drugs to treat these disorders and to clarify the mechanisms by which they regulate the dysfunctional genes in the brain. Drug Dev Res 77 : 407–413, 2016. © 2016 Wiley Periodicals, Inc.
Child cortisol moderates the association between family routines and emotion regulation in low‐income children
Authors: Miller Alison L. , Song Ju‐Hyun , Sturza Julie , Lumeng Julie C. , Rosenblum Katherine , Kaciroti Niko , Vazquez Delia M.
Published: September 2016

Biological and social influences both shape emotion regulation. In 380 low‐income children, we tested whether biological stress profile (cortisol) moderated the association among positive and negative home environment factors (routines; chaos) and emotion regulation (negative lability; positive regulation). Children (M age = 50.6, SD = 6.4 months) provided saliva samples to assess diurnal cortisol parameters across 3 days. Parents reported on home environment and child emotion regulation. Structural equation modeling was used to test whether cortisol parameters moderated associations between home environment and child emotion regulation. Results showed that home chaos was negatively associated with emotion regulation outcomes; cortisol did not moderate the association. Child cortisol level moderated the routines‐emotion regulation association such that lack of routine was most strongly associated with poor emotion regulation among children with lower cortisol output. Findings suggest that underlying child stress biology may shape response to environmental influences.
Urinary human chorionic gonadotropin isoform concentrations in doping control samples
Authors: Butch Anthony W. , Woldemariam Getachew A.
Published: September 2016

Anti‐doping laboratories routinely use immunoassays to measure urinary concentrations of human chorionic gonadotropin (hCG). To minimize immunoassay differences and false positive screen results from inactive isoforms (free β‐subunit (hCGβ), β‐subunit core fragment (hCGβcf)) laboratories now use intact hCG instead of total hCG immunoassays to measure hCG. To determine the distribution of hCG isoforms in urine, we determined the concentrations of intact hCG, hCGβ, and hCGβcf in male urine samples based on immunoassay total hCG concentrations using a sequential immunoextraction and a liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method. hCG was isolated using antibody‐conjugated magnetic beads and unique tryptic peptides were quantified by LC‐MS/MS. Negative samples with detectable but low total hCG concentrations (1.2–3.5 pmol/L) had intact and hCGβ concentrations <1.2 pmol/L, and hCGβcf concentrations <2.3 pmol/L by LC‐MS/MS. Urine samples from an athlete receiving hCG had intact hCG concentrations ranging from 18.8 to 57.6 pmol/L, hCGβ concentrations <0.7 pmol/L, and hCGβcf concentrations ranging from 94 to 243% of the intact hCG concentration. In 27 atypical samples with total hCG concentrations ranging from 16.7 to 412.7 pmol/L with intact hCG <2.7 pmol/L by immunoassay, all samples had intact hCG concentrations <3.8 pmol/L and hCGβ concentrations <6.2 pmol/L by LC‐MS/MS. hCGβcf concentrations by LC‐MS/MS varied widely and ranged from 1.03 to 21.9 pmol/L. In summary, total hCG immunoassays significantly overestimate hCG concentrations and can produce false positive results. Although the intact hCG immunoassay slightly overestimates hCG concentrations compared to LC‐MS/MS, it can distinguish between cases of hCG use and atypical cases with elevated total hCG concentrations. Copyright © 2016 John Wiley & Sons, Ltd.
Bioanalysis for cocaine, opiates, methadone, and amphetamines exposure detection during pregnancy
Authors: Concheiro Marta , Lendoiro Elena , de Castro Ana , Gónzalez‐Colmenero Eva , Concheiro‐Guisan Ana , Peñas‐Silva Patricia , Macias‐Cortiña Manuel , Cruz‐Landeira Angelines , López‐Rivadulla Manuel
Published: September 2016

Drug exposure during pregnancy constitutes a major legal issue and a public health concern. Drug and metabolite determination in biological matrices from mother and newborn is an objective indication of prenatal drug exposure. However, limited data are available regarding the interpretation of these analytical results in terms of window of detection and degree of exposure. We collected paired maternal hair, meconium, placenta, and umbilical cord from 727 mother‐newborn dyads. We analyzed these specimens by liquid chromatography‐tandem mass spectrometry for the determination of cocaine, opioids, methadone, and amphetamines, and compared the analytical results from the four different matrices. The cases were divided in non‐exposure, low, and frequent exposure, based on maternal hair concentrations and segmental analysis by trimesters. For cocaine, 62 cases tested positive in hair, 9 in meconium, 6 in placenta and 7 in umbilical cord. In the case of opioids, 14 maternal hair cases were positive, 11 meconium and umbilical cord and 9 placenta samples. For methadone, 11 cases were positive in hair, 9 in meconium and 6 in placenta and umbilical cord. For amphetamines, 18 cases were positive according to maternal hair, but all meconium, placenta, and umbilical cord tested negative. Maternal hair was the most sensitive specimen to detect drug exposure during pregnancy. Meconium, placenta, and umbilical cord tested positive if hair concentrations showed frequent drug use during the whole pregnancy, especially during the third trimester. Meconium, placenta, and umbilical cord also tested positive for morphine and metabolites, if this drug was administered during labour and delivery. Copyright © 2016 John Wiley & Sons, Ltd.
Negative correlation between altitudes and oxygen isotope ratios of seeds: exploring its applicability to assess vertical seed dispersal
Authors: Naoe Shoji , Tayasu Ichiro , Masaki Takashi , Koike Shinsuke
Published: September 2016

Vertical seed dispersal, which plays a key role in plant escape and/or expansion under climate change, was recently evaluated for the first time using negative correlation between altitudes and oxygen isotope ratio of seeds. Although this method is innovative, its applicability to other plants is unknown. To explore the applicability of the method, we regressed altitudes on δ18O of seeds of five woody species constituting three families in temperate forests in central Japan. Because climatic factors, including temperature and precipitation that influence δ18O of plant materials, demonstrate intensive seasonal fluctuation in the temperate zone, we also evaluated the effect of fruiting season of each species on δ18O of seeds using generalized linear mixed models (GLMM). Negative correlation between altitudes and δ18O of seeds was found in four of five species tested. The slope of regression lines tended to be lower in late‐fruiting species. The GLMM analysis revealed that altitudes and date of fruiting peak negatively affected δ18O of seeds. These results indicate that the estimation of vertical seed dispersal using δ18O of seeds can be applicable for various species, not just confined to specific taxa, by identifying the altitudes of plants that produced seeds. The results also suggest that the regression line between altitudes and δ18O of seeds is rather species specific and that vertical seed dispersal in late‐fruiting species is estimated at a low resolution due to their small regression slopes. A future study on the identification of environmental factors and plant traits that cause a difference in δ18O of seeds, combined with an improvement of analysis, will lead to effective evaluation of vertical seed dispersal in various species and thereby promote our understanding about the mechanism and ecological functions of vertical seed dispersal.
Severity of renal impairment in patients with heart failure and atrial fibrillation: implications for non‐vitamin K antagonist oral anticoagulant dose adjustment
Authors: Hawkins Nathaniel M. , Jhund Pardeep S. , Pozzi Andrea , O'Meara Eileen , Solomon Scott D. , Granger Christopher B. , Yusuf Salim , Pfeffer Marc A. , Swedberg Karl , Petrie Mark C. , Virani Sean , McMurray John J.V.
Published: September 2016

Aims

The non‐vitamin K antagonist oral anticoagulants (NOACs) have varying degrees of renal elimination which may be challenging in patients with heart failure (HF) and atrial fibrillation (AF). We examined the severity and variation in renal impairment, and the proportion of patients requiring NOAC cessation or dose reduction.

Methods and results

A retrospective analysis of patients with HF and AF in the Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity programme was carried out. Trends in renal impairment over 26 months were defined using Cockcroft–Gault (CG), simplified Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equations. Mean estimated glomerular filtration rate (eGFR) was worse at every time point in patients with AF compared with those without AF, the difference being ∼11 mL/min (CG), 9 mL/min (CKD‐EPI), and 7 mL/min (MDRD). As renal function declined, CG classified a greater proportion of patients as having moderate or severe CKD and agreement with MDRD/CKD‐EPI declined. At least moderate renal impairment was present in a quarter of patients with AF at baseline, a third by study completion, and approaching a half at least once during follow‐up. The projected need for NOAC dose reduction was accordingly high, though it varied between individual NOACs due to different criteria for adjustment.

Conclusions

Renal impairment in patients with HF and AF is common, fluctuates, progresses, and frequently mandates NOAC dose reduction, though the need for cessation is rare. Baseline renal function, the method of estimating GFR, and intensity of monitoring should be considered when commencing oral anticoagulation.
Aging of the immune system: Focus on inflammation and vaccination
Authors: Pinti Marcello , Appay Victor , Campisi Judith , Frasca Daniela , Fülöp Tamas , Sauce Delphine , Larbi Anis , Weinberger Birgit , Cossarizza Andrea
Published: September 2016

Major advances in preventing, delaying, or curing individual pathologies are responsible for an increasingly long life span in the developed parts of our planet, and indeed reaching eight to nine decades of life is nowadays extremely frequent. However, medical and sanitary advances have not prevented or delayed the underlying cause of the disparate pathologies occurring in the elderly: aging itself. The identification of the basis of the aging processes that drives the multiple pathologies and loss of function typical of older individuals is a major challenge in current aging research. Among the possible causes, an impairment of the immune system plays a major role, and indeed numerous studies have described immunological changes which occur with age. Far from the intention of being exhaustive, this review will focus on recent advances and views on the role that modifications of cell signalling and remodelling of the immune response play during human aging and longevity, paying particular attention to phenomena which are linked to the so called inflammaging process, such as dysregulation of innate immunity, altered T‐cell or B‐cell maturation and differentiation, as well as to the implications of immune aging for vaccination strategies in the elderly.
IL‐33 delivery induces serous cavity macrophage proliferation independent of interleukin‐4 receptor alpha
Authors: Jackson‐Jones Lucy H. , Rückerl Dominik , Svedberg Freya , Duncan Sheelagh , Maizels Rick M. , Sutherland Tara E. , Jenkins Stephen J. , McSorley Henry J. , Bénézech Cécile , MacDonald Andrew S. , Allen Judith E.
Published: September 2016

IL‐33 plays an important role in the initiation of type‐2 immune responses, as well as the enhancement of type 2 effector functions. Engagement of the IL‐33 receptor on macrophages facilitates polarization to an alternative activation state by amplifying IL‐4 and IL‐13 signaling to IL‐4Rα. IL‐4 and IL‐13 also induce macrophage proliferation but IL‐33 involvement in this process has not been rigorously evaluated. As expected, in vivo delivery of IL‐33 induced IL‐4Rα‐dependent alternative macrophage activation in the serous cavities. IL‐33 delivery also induced macrophages to proliferate but, unexpectedly, this was independent of IL‐4Rα signaling. In a filarial nematode infection model in which IL‐4Rα‐dependent alternative activation and proliferation in the pleural cavity is well described, IL‐33R was essential for alternative activation but not macrophage proliferation. Similarly, during Alternaria alternata induced airway inflammation, which provokes strong IL‐33 responses, we observed that both IL‐4Rα and IL‐33R were required for alternative activation, while macrophage proliferation in the pleural cavity was still evident in the absence of either receptor alone. Our data show that IL‐33R and IL‐4Rα promote macrophage proliferation independently of each other, but both are essential for induction of alternative activation.
Thermal and Magnetic Diversity in the Behaviour of the CuII‐bdc‐bpa System: 1D, 2D and Interpenetrated 3D Frameworks
Authors: Bravo‐García Laura , Barandika Gotzone , Fidalgo‐Marijuan Arkaitz , Bazan Begoña , Urtiaga Miren Karmele , Lezama Luis , Arriortua María Isabel
Published: September 2016

Metal organic frameworks (MOFs) are crystalline materials based on connections between metal ions through organic ligands. The combination of polycarboxylate anions and dipyridyl ligands is an effective strategy for producing extended structures. In this sense, the combination of bpa with m‐bdc [bpa = 1,2‐bis(4‐pyridyl)ethane, m‐bdc = 1,3‐benzenedicarboxylate] has produced three new CuII‐based networks with different dimensionalities, namely the 1D [Cu(m‐bdc)(bpa)0.5(H2O)dmf]·0.5H2O (1, synthesis based on sonication and slow evaporation), the 2D [Cu6(m‐bdc)6(bpa)6(dmf)3]·8dmf (2, microwave synthesis) and the 3D [Cu4(m‐bdc)4(bpa)2dmf]·dmf (3, microwave synthesis). The three compounds have been structurally characterized by means of single‐crystal X‐ray diffraction, IR and UV/Vis spectroscopy and elemental analysis. An unprecedented CuII dimer has been observed for compound 3. The thermal behaviour of the compounds was analysed by thermogravimetry (TG/DSC) and X‐ray thermodifractometry (TDX), and it was concluded that the dimensionality plays an important role in their thermal properties. Electronic paramagnetic resonance and magnetic susceptibility measurements for compounds 1 and 3 showed that antiferromagnetic interactions exist between the metal ions.
Difluorotriorganylphosphoranes for the Synthesis of Fluorophosphonium and Bismuthonium Salts
Authors: Solyntjes Sven , Neumann Beate , Stammler Hans‐Georg , Ignat'ev Nikolai , Hoge Berthold
Published: September 2016

Invited for the cover of this issue is the group of Berthold Hoge at Universität Bielefeld, Germany. The cover image shows a musical “triad” symbolizing the three phosphorus(V) species discussed in the paper.
I2/CHP‐Mediated Oxidative Coupling of 2‐Aminobenzamides and Isocyanides: Access to 2‐Aminoquinazolinones
Authors: Wei Tian‐Qi , Xu Pei , Wang Shun‐Yi , Ji Shun‐Jun
Published: September 2016

An oxidative coupling of 2‐aminobenzamides 1 and isocyanides 2 mediated by I2 and cumyl hydroperoxide (CHP) leads to the formation of 2‐aminoquinazolinones 3 in moderate to excellent yields. This method provides an efficient approach to 2‐aminoquinazolinones with high atom economy under metal‐free conditions through two C–N bond‐formation reactions. The products can be further transformed to give benzo[4,5]imidazo[2,1‐b]quinazolin‐12(6H)‐one (4).
Agarose bioplastic‐based drug delivery system for surgical and wound dressings
Authors: Awadhiya Ankur , Tyeb Suhela , Rathore Kalpana , Verma Vivek
Published: September 2016

We have developed an agarose‐based biocompatible drug delivery vehicle. The vehicle is in the form of thin, transparent, strong and flexible films. The biocompatibility and haemocompatibility of the films is confirmed using direct and indirect contact biological assay. Contact angle measurement exhibits hydrophilic nature of the films, and protein adsorption test shows low protein adsorption on the film surface. Drugs, antibiotics and antiseptics, retain their potency after their incorporation into the films. Our bioplastic films can be a versatile medium for drug delivery applications, especially as wound and surgical dressings where a fast drug release rate is desired.
5GEx: realising a Europe‐wide multi‐domain framework for software‐defined infrastructures
Authors: Bernardos Carlos J. , Gerö Balázs Péter , Di Girolamo Marco , Kern András , Martini Barbara , Vaishnavi Ishan
Published: September 2016

Market fragmentation has resulted in a multitude of network and cloud/data center operators, each focused on different countries, regions and technologies. This makes it difficult and costly to create infrastructure services spanning multiple domains, such as virtual connectivity or compute resources. In this article, we discuss the goals and work being done within the 5GEx (5G Exchange) project in realising a Europe‐wide multi‐domain platform. This platform aims at enabling cross‐domain orchestration of services over multiple administrations or over multi‐domain single administrations in the context of emerging 5G networking. The 5GEx vision is based on introducing a unification via network function virtualisation/software‐defined networking compatible multi‐domain orchestration for networks, clouds and services. We describe the motivation and 5GEx vision, the adopted architecture and the next steps in terms of implementation and experimentation. Copyright © 2016 John Wiley & Sons, Ltd.
An adaptive 5G multiservice and multitenant radio access network architecture
Authors: Droste Heinz , Rost Peter , Doll Mark , Berberana Ignacio , Mannweiler Christian , Breitbach Markus , Banchs Albert , Puente Miguel A.
Published: September 2016

This article provides an overview on objectives and first results of the Horizon 2020 project 5G NOvel Radio Multiservice adaptive network Architecture (5GNORMA). With 5G NORMA, leading players in the mobile ecosystem aim to underpin Europe's leadership position in 5G. The key objective of 5G NORMA is to develop a conceptually novel, adaptive and future‐proof 5G mobile network architecture. This architecture will allow for adapting the network to a wide range of service specific requirements, resulting in novel service‐aware and context‐aware end‐to‐end function chaining. The technical approach is based on an innovative concept of adaptive (de)composition and allocation of mobile network functions based on end‐user requirements and infrastructure capabilities. At the same time, cost savings and faster time to market are to be expected by joint deployment of logically separated multiservice and multitenant networks on common hardware and other physical resources making use of traffic multiplexing gains. In this context architectural enablers such as network function virtualization and software‐defined mobile networking will play a key role for introducing the needed flexible resource assignment to logical networks and specific virtual network functions. Copyright © 2016 John Wiley & Sons, Ltd.
Efficient signal detection for cognitive radio relay networks under imperfect channel estimation
Authors: Sadough Seyed Mohammad Sajad , Chamideh Zahra , Khalighi Mohammad‐Ali
Published: September 2016

Assuming imperfect channel knowledge at the destination, we propose an improved detector for an underlay cognitive (secondary) amplify‐and‐forward wireless relay network coexisting with a primary transmission system. At first, we adjust the amplify‐and‐forward relay amplification factors by taking into account the interference temperature constraint at the primary receiver. In a second step, for the case of coherent distributed space‐time coding at the relays and maximum a posteriori signal detection at the destination, we propose a modified detector formulation. The proposed scheme reduces the impact of channel uncertainty on the receiver performance by appropriately exploiting the statistics of the channel estimation errors. Furthermore, it takes into account the interference level limitation imposed by the primary transmission system on the relays. Through some numerical results, we show that the proposed detector reduces significantly the required power level to achieve a target performance at the destination, which is of special interest for underlay cognitive radio systems. This way, the proposed receiver allows a reduction of the required protection area around the primary transmitter, leading to the increased of flexibility of the cognitive radio network design. Copyright © 2016 John Wiley & Sons, Ltd.
Implementing Pre‐Post Test Designs in Higher Education Evaluations
Authors: Tesch Aaron
Published: September 2016

This chapter outlines the implementation of a pilot project to evaluate courses and an education program with pre‐post designs in an undergraduate psychology program. This plan of evaluation incorporates a variety of pre‐post test designs to measure the change in student performance across different contexts—including traditional and online courses—rather than rely solely on outcome measures without controls as is common in higher education evaluation. In addition to building on the essential value of this design, this chapter examines a largely faculty‐directed evaluation program, which examines the need for expertise in instrument development and pedagogical scholarship, and demonstrates the importance of administrative support.
Evaluating a General Education Program in Transition
Authors: Stevenson John F. , Hicks Sandy Jean , Hubbard Anne
Published: September 2016

This reflective case study uses one public university example to explore the role of student learning outcomes assessment in the improvement of general education programs. These programs are a universal feature of higher education in the United States, requiring learning experiences for all students at an institution—but with little likely commitment from the faculty. Our university's efforts to overcome faculty apathy and resistance, build a responsive assessment system, and direct it toward transformation of our program are instructive beyond the higher education context. We take a participatory, utilization‐focused approach and reflect on what we have learned as it illuminates both the relevance of evaluation concepts to our work in assessment and the contributions from our context to the broader domains of evaluation conceptualization and practice.
Engaging Faculty in an Evaluative Conversation
Authors: Rickards William H. , Abromeit Jeana , Mentkowski Marcia , Mernitz Heather
Published: September 2016

Higher education evaluation or assessment plans generally look to key assessments within the curriculum for critical demonstrations of students’ learning. Increasingly, accreditation agencies (e.g., Southern Association of Schools and Colleges, National Council on Accreditation of Teacher Education) have asked for evidence of how faculty have made use of student outcome data in their own ongoing planning. This is a condition that expands the notion of evaluation as a collection of data from which to examine the merit or worth of a program to the collaborative and analytic meaning making of evaluative action. This has been an area of traditional complication where evaluators work to support the use of evaluation findings while maintaining appropriate independence from the program administrators with operational responsibility. However, this combination of instructional needs, accountability expectations, and insight into evaluative outcomes amplifies the need for evaluator expertise for collaborating in these dimensions of practice. This study then examines the work of a faculty and its assessment team—including evaluation researchers—to (a) implement and evaluate a general education program through a midprogram assessment, (b) analyze the faculty's engagement with the results and (c) adapt the reporting and meaning‐making processes to further invest the faculty as coinvestigators in the evaluation and its use in improving the program.
Beyond the Rhetoric: Evaluation Practices in Higher Education
Authors: Stitt‐Bergh Monica , Rickards William H. , Bertrand Jones Tamara
Published: September 2016

North American higher education institutions have been developing their own systems of learning outcomes assessment that are not part of the public rhetoric on higher education. Evaluators have new opportunities in higher education and evaluator–faculty partnerships are a key to their success. Evaluator knowledge of the institution‐specific context and evaluator cultural competence can help evaluators overcome faculty resistance and design appropriate assessment systems. In higher education, the evaluators’ roles include documenting and facilitating use of results, leveraging technology and existing data, negotiating what becomes public information, and coauthoring with faculty.
Rückverankerung einer Spritzbetonschale im Rahmen einer Tunnelsanierung
Authors: von Havranek Frank
Published: September 2016

Der Effolderbacher Eisenbahntunnel wurde im Jahr 1870 erbaut. Bereits kurz nach Inbetriebnahme musste das Gewölbe teilweise überfirstet und verstärkt werden. In jüngeren Sanierungen wurden in Teilabschnitten Gitterbögen mit Spritzbetonrippen eingebaut und der Sandsteinausbau örtlich mit Ziegelmauerwerk erneuert. Bereits in den 1950er‐Jahren wurde eine Absenkung der Firste um bis zu 0,35 m infolge sich ablösender Gebirgsbereiche festgestellt. Infolge von Wasserzutritt und Frost witterte das ursprünglich 0,25 bis 0,50 m starke Sandsteingewölbe teils stark ab, was dessen Tragfähigkeit stark reduzierte. Deshalb fand eine erste Sofortsicherung mit rückverankertem Spritzbeton bereits im Jahr 2009 statt. Im Rahmen verschiedener Variantenuntersuchungen und Wirtschaftlichkeitsanalysen entschied sich die DB Netz AG für die Sanierung des bestehenden Bauwerks und für den Einbau einer dauerhaften rückverankerten Innenschale. Die Auswahl eines geeigneten Ankersystems ist ein komplexes Thema. Neben der Wahl des Einbauverfahrens, ist die Vielzahl geänderter Baubestimmungen durch Einführung der europäischen Normung, die teils neu herausgegebenen oder an die europäische Normung angepassten eisenbahnspezifischen Regelungen und der aktuelle Stand der Zulassungen zu beachten. Im Beitrag werden anhand der konkreten Baumaßnahme die Gründe diskutiert, die bei der Auswahl eines dauerhaften Ankersystems maßgebend sein können.
What is the therapeutic value of antidepressants in dementia? A narrative review
Authors: Farina Nicolas , Morrell Lucy , Banerjee Sube
Published: September 2016

Objectives

Antidepressants are commonly used in dementia. Depression is a frequent and important co‐morbidity in dementia, and antidepressants are often used to treat depression and more widely. However, there are questions about their utility in depression in dementia and other behavioural and psychological symptoms of dementia. The aim of this narrative review is to summarize the evidence on whether there is therapeutic value in prescribing antidepressants to people with dementia.

Methods

A PubMed search was performed to identify randomized controlled trials that prescribed antidepressants to people with dementia, either in the treatment of behavioural and psychological symptoms of dementia (depression, anxiety, agitation/aggression, psychosis and apathy) or for secondary outcomes (quality of life, carer burden, activities of daily living, cognition, clinical severity and adverse events).

Results

Thirty‐six randomized controlled trials were identified (participant n = 3386). A consistent finding in well‐designed blinded placebo controlled trials in dementia is the lack of positive effect of antidepressants on outcomes of interest, including depression. One large well‐designed study has reported a significant reduction in agitation in people with dementia, but at the expense of clinically significant adverse events. Otherwise, change observed in open trials is also seen in the placebo group, suggesting that any effect is not attributable to the prescription of antidepressants.

Conclusions

It is striking how few data there are on indications other than depression. We should question the use of antidepressants in dementia. Definitive trials of clinical effectiveness of specific indications such as anxiety and agitation in dementia and discontinuation of antidepressants in dementia are needed. Copyright © 2016 John Wiley & Sons, Ltd.