bluuebunny/crossref_metadata_2025 huggingface dataset:
Stereoselective Synthesis of Piperidines by Iridium‐Catalyzed Cyclocondensation
Authors: Sandmeier Tobias , Krautwald Simon , Carreira Erick M.
Published: July 2017

An iridium‐catalyzed cyclocondensation of amino alcohols and aldehydes is reported. Intramolecular allylic substitution by an enamine intermediate and subsequent in situ reduction furnishes 3,4‐disubstituted piperidines with high enantiospecificity and good diastereoselectivity. The modular approach and the broad functional group tolerance provide access to diverse piperidine derivatives, which were further functionalized to give a versatile set of products.
Copper‐Catalyzed Decarboxylative Radical Silylation of Redox‐Active Aliphatic Carboxylic Acid Derivatives
Authors: Xue Weichao , Oestreich Martin
Published: July 2017

A decarboxylative silylation of aliphatic N‐hydroxyphthalimide (NHPI) esters using Si−B reagents as silicon pronucleophiles is reported. This C(sp3)−Si cross‐coupling is catalyzed by copper(I) and follows a radical mechanism, even with exclusion of light. Both primary and secondary alkyl groups couple effectively, whereas tertiary alkyl groups are probably too sterically hindered. The functional‐group tolerance is generally excellent, and α‐heteroatom‐substituted substrates also participate well. This enables, for example, the synthesis of α‐silylated amines starting from NHPI esters derived from α‐amino acids. The new method extends the still limited number of C(sp3)−Si cross‐couplings of unactivated alkyl electrophiles.
Anti‐proliferative activity of newly synthesized Cd(II), Cu(II), Zn(II),Ni(II), Co(II), VO(II), and Mn(II) complexes of 2‐((4,9‐dimethoxy‐5‐oxo‐5H‐furo[3,2‐g]chromen‐6‐yl)methylene) hydrazinecarbothioamide on three human cancer cells
Authors: Shakdofa Mohamad M.E. , Mousa Hanan A. , Elseidy Ahmed M.A. , Labib Ammar A. , Ali Mamdouh M. , Abd‐El‐All Amira S.
Published: July 2017

Thiosemicarbazone ligand, 2‐((4,9‐dimethoxy‐5‐oxo‐5H‐furo[3,2‐g]chromen‐6‐yl)methylene) hydrazinecarbothioamide and its Cd(II), Cu(II), Zn(II), Ni(II), Co(II), VO(II), and Mn(II) complexes have been prepared and characterized by various spectroscopic and analytical techniques. Complexes molar conductance measurements displayed that all complexes (2–8) are non‐electrolyte. With general composition [M(H3L)(CH3COO)2H2O].nH2O, where M = Cd(II), Cu(II), Zn(II), Ni(II), Co(II) and Mn(II) while complex (8) has [VO(H3L)(SO4)H2O].2H2O formula. Based on analytical and spectral measurements, the octahedral or distorted octahedral geometries suggested for complexes. Ligand and complexes anti‐proliferative activities were assessed against three various human tumor cell lines including breast cancer (MCF‐7), liver cancer (HepG2) and lung cancer (A549) using SRB fluorometric assay and cis‐platin as positive control. The anti‐proliferative activity result indicated that the ligand and its complexes have considerable anti‐proliferative activity analogous to that of ordinarily utilized anti‐cancer drug (cis‐platin). They do their anti‐cancer activities by modifying free radical's generation via raising the superoxide dismutase activity and depletion of intracellular reduced glutathione level, catalase, glutathione peroxidase activities, escorted by highly generation of hydrogen peroxide, nitric oxide and other free radicals leading to tumor cells death, as monitoring by decreasing the protein and nucleic acids synthesis.
A comparative study on the catalytic performance of heme and non‐heme catalysts: Metal porphyrins versus metal Schiff bases
Authors: Talaeizadeh Atefeh , Tofighi Mahdi , Zakavi Saeed
Published: July 2017

Catalytic activity and oxidative stability of a series of iron and manganese porphyrins with 2‐chlorophenyl, phenyl and 4‐methoxyphenyl at the meso positions and metallosalens (Mn‐ and Fe‐salens) including N,N′‐bis(salicylidene)ethylenediamine, N,N′‐bis(5‐ chlorosalicylidene)ethylenediamine and N,N′‐bis(2,4‐dihydroxysalicylidene)ethylenediamine for the oxidation of olefins with tetra‐n‐butylammonium periodate (TBAP) and tetra‐n‐butyl‐ammonium Oxone (TBAO) have been investigated and compared. Although the metalloporphyrins showed an increased catalytic activity relative to the Schiff base complexes, the former provided no significant catalytic advantage over the latter. Also, a comparable or slightly higher oxidative stability was observed for the Schiff base complexes under the reaction conditions. Furthermore, in spite of large difference between the oxidizing ability of TBAO and TBAP, similar patterns were observed for the order of catalytic activity and oxidative stability of the used heme and non‐heme catalysts. The introduction of a methyl group at the ɑ position of styrene led to an increase in its reactivity, indicating the dominance of electronic effects over the steric ones in these catalytic systems.
Impact of the hard‐segment concentration on highly resilient polyurethane foams based on palm olein polyol
Authors: Adnan Srihanum , Tuan Noor Maznee T. I. , ‘Ain Nurul H. , Devi Kosheela P. P. , Mohd Norhisham S. , Shoot Kian Yeong , Idris Zainab B. , Campara Irma , Schiffman Christi M. , Pietrzyk Karol , Sendijarevic Vahid , Sendijarevic Ibrahim
Published: July 2017

The impact of replacing polyether polyol with different levels of a palm‐olein‐based natural oil polyol (NOP) was systematically correlated with the changes in the foaming reactivities, cell structures, physicomechanical properties, and morphologies of highly resilient (HR) polyurethane foams. Replacing the polyether polyol with the NOP did not require us to significantly modify the formulation to obtain stabile foams with uniform and open cell structures. The incorporation of the NOP increased the tear strength and load‐bearing capacity of the HR polyurethane foams; this was attributed to the high functionality and lower equivalent weight of the NOP. The addition of the NOP increased the energy‐absorbing properties of the molded HR foams; this correlated with the increased phase mixing of hard and soft segments, as determined via dynamic mechanical analysis and Fourier transform infrared analyses. The HR‐molded foams’ hysteresis and compression sets, which are inversely correlated with the durability of HR‐molded foams in automotive seating applications, were found to increase with the addition of the NOP. However, it was demonstrated that the changes in the hysteresis and compression set could be partially offset by the reduction of the isocyanate index, which could allow for the increased incorporation of the NOPs in the HR foams without a notable loss of key performance characteristics. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45440.
Poly(lactic acid)/starch composites: Effect of microstructure and morphology of starch granules on performance
Authors: Khalid Saud , Yu Long , Meng Linghan , Liu Hongsheng , Ali Amjad , Chen Ling
Published: July 2017

Starches used to develop biodegradable composites belong to different botanical sources that exhibit different microstructures and morphologies. This results in confused relationship and no comparison of data for applications. In this work, the most popular ten different starches were used as model materials to investigate the relationship between starch microstructure and the performance of poly(lactic acid) (PLA)/starch composites. It was found that: (a) composites filled with either well‐sized (small‐sized and non‐agglomerated) starch granules or those containing high amylose content (G‐50 and G‐80) improves the reinforcing ability of PLA, with least reduction in deformation; (b) aggregation tendency of small‐sized starch granules can be controlled using surface modification approach that not only reduces the phase‐separation between starch and PLA but also improves the dispersion; and (c) no discernible relationship exists between the starches, from different botanical sources, and the thermal performance of PLA/starch composites. The results provide practical guidelines to develop starch‐based biodegradable composites for commercial applications. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45504.
Investigation of the microstructures, properties, and toughening mechanism of polypropylene/calcium carbonate toughening masterbatch composites
Authors: Lu Qi‐Cheng , Dou Qiang
Published: July 2017

The morphologies, crystallization and melting behaviors, and mechanical, thermal and processing properties of polypropylene (PP)/CaCO3 toughening masterbatch (CTM) composites were investigated. The good dispersion of CaCO3 particles via appropriate surface encapsulation in the composites is proven by density measurements and scanning electron microscopy images. The crystallinity and tensile strength of PP decrease with the addition of CTM. The flexural modulus and storage modulus (E′) at 23 °C increase with CTM content, implying improved stiffness. A sharp increase in the Izod notched impact strength can be observed for the composites, and the critical ligament thickness (τc) is calculated to be 1.31 and 2.46 μm for PP (S1003) and PP (001 G) composites, respectively. The morphologies of the impact‐fractured surfaces of the specimens were observed, and the shear deformation is enhanced by the addition of CTM. The presence of CTM also increases the melt flowability and decreases the shrinkage of the composites. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45515.
Induction of stress‐ and immune‐associated genes in the Indian meal moth Plodia interpunctella against envenomation by the ectoparasitoid Bracon hebetor
Authors: Shafeeq Tahir , UlAbdin Zain , Lee Kyeong‐Yeoll
Published: July 2017

Envenomation is an important process in parasitism by parasitic wasps; it suppresses the immune and development of host insects. However, the molecular mechanisms of host responses to envenomation are not yet clear. This study aimed to determine the transcription‐level responses of the Indian meal moth Plodia interpunctella against envenomation of the ectoparasitoid Bracon hebetor. Quantitative real‐time reverse‐transcription PCR was used to determine the transcriptional changes of 13 selected genes, which are associated with development, metabolism, stress, or immunity, in the feeding and wandering fifth instar larvae over a 4‐day period after envenomation. The effects of envenomation on the feeding‐stage larvae were compared with those of starvation in the transcriptional levels of the 13 genes. Most selected genes were altered in their expression by either envenomation or starvation. In particular, a heat shock protein, hsp70, was highly upregulated in envenomated larvae in both the feeding and wandering stages as well as in starved larvae. Further, some genes were upregulated by envenomation in a stage‐specific manner. For example, hsp25 was upregulated after envenomation in the feeding larvae, but hsp90 and an immune‐associated gene, hemolin, were upregulated in the wandering larvae. However, both envenomation and starvation resulted in the downregulation of genes associated with development and metabolism. Taken together, P. interpunctella upregulated stress‐ and immune‐responsive genes, but downregulated genes associated with development and metabolism after envenomation. This study provides important information for understanding the molecular mechanisms of host responses to parasitism.
Über ein elastoplastisches Stoffgesetz für zyklisch beanspruchten Sand
Authors: Carow Christian , Rackwitz Frank , Savidis Stavros
Published: July 2017

Die numerische Simulation aktueller Problemstellungen in der Geotechnik erfordert Stoffgesetze, die das Spannungs‐Dehnungsverhalten von Sand realitätsnah beschreiben. In Bezug auf monotone Lasten sind mit bestehenden Modellierungsansätzen bereits sehr gute Ergebnisse zu erzielen. Das Materialverhalten bei zyklischer Beanspruchung ist jedoch außerordentlich komplex. Selbst die derzeit leistungsfähigsten Stoffgesetze können nur einzelne Aspekte abbilden. Daher ist weitere Forschungsarbeit dringend erforderlich.

Vor diesem Hintergrund stellt der Beitrag ein Stoffgesetz für Sand vor, das auf der Grenzflächenplastizität sowie dem Konzept kritischer Zustände basiert. Es kann das Verhalten des Bodens für komplexe zyklische Belastungspfade über eine breite Spanne von Dichte‐ und Spannungszuständen mit einem einzigen Parametersatz abbilden. Die Funktionsweise des Stoffgesetzes wird im Beitrag konzeptionell dargestellt. Die Ergebnisse der numerischen Simulation zyklischer undränierter Triaxialversuche werden den Ergebnissen entsprechender Laborversuche gegenübergestellt. Der Vergleich liefert eine gute Übereinstimmung. Die Eignung des Stoffgesetzes für den Einsatz in komplexen numerischen Simulationen wird anhand eines Berechnungsbeispiels gezeigt. Hierfür wurde ein Staudamm gewählt, der durch einen Erdbebenzeitverlauf an der Basis angeregt wird. Abschließend werden im Beitrag Ansätze zur Weiterentwicklung des Stoffgesetzes aufgezeigt.
Differences in Stem Cell Processing Lead to Distinct Secretomes Secretion—Implications for Differential Results of Previous Clinical Trials of Stem Cell Therapy for Myocardial Infarction
Authors: Wernly Bernhard , Gonçalves Inês , Kiss Attila , Paar Vera , Mösenlechner Tobias , Leisch Michael , Santer David , Motloch Lukas Jaroslaw , Klein Klaus U. , Tretter Eva V. , Kretzschmar Daniel , Podesser Bruno , Jung Christian , Hoppe Uta C. , Lichtenauer Michael
Published: July 2017

Stem cell therapy for acute myocardial infarction (AMI) seemed to be a promising therapy, however, large clinical trials brought differential outcome. It has been shown that paracrine effects of secretomes of stem cells rather than cell therapy might play a fundamental role. The present study seeks to compare cell processing protocols of clinical trials and investigate effects of differential cell culture conditions on chemokine secretion and functional effects. Different secretomes are compared regarding IL‐8, VEGF, MCP‐1, and TNF‐alpha secretion. Secretome mediated effects are evaluated on endothelial cell (HUVEC) tube formation and migration. Cardioprotective signaling kinases in human cardiomyocytes are determined by Western immunoblotting. Cells processed according to the REPAIR‐AMI protocol secrete significantly higher amounts of IL‐8 (487.3 ± 1231.1 vs 9.1 ± 8.2 pg mL−1; p < 0.05). REAPIR‐AMI supernatants lead to significantly pronounced tube formation and migration on HUVEC and enhance the phosphorylation of Akt, ERK, and CREB. Cell processing conditions have a major impact on the composition of the secretome. The REPAIR‐AMI secretome significantly enhances proangiogenic chemokine secretion, angiogenesis, cell migration, and cardioprotective signaling pathways. These results might explain differential outcomes between clinical trials. Optimizing cell processing protocols with special regards to paracrine factors, might open a new therapeutic concept for improving patient outcome.
Improving Succinate Productivity by Engineering a Cyanobacterial CO2 Concentrating System (CCM) in Escherichia coli
Authors: Xiao Mengyong , Zhu Xinna , Bi Changhao , Ma Yanhe , Zhang Xueli
Published: July 2017

Biologically fixation of CO2 has great potential as a significant carbon source for biosynthesis, which is also a major way to reduce CO2 accumulation in atmosphere. Phosphoenolpyruvate (PEP) carboxylation is the key step of anaerobic succinate production in Escherichia coli. In this reaction, one mole CO2 is assimilated with PEP to form oxaloacetate by PEP carboxykinase (PCK). The preferred substrate of PCK is CO2, which is very limited in cytoplasm. In this study, the carbon concentration mechanism (CCM) of cyanobacteria was introduced into Escherichia coli to enhance the intracellular inorganic carbon concentration for improving carboxylation velocity. Overexpression of the bicarbonate transporter (BT) or carbonic anhydrase (CA) gene from Synechococcus sp. PCC7002 led to a 22 or 35% increase in succinate titer at 36 h, respectively. The carboxylation rate of PCK increased from 2.46 to 3.92 µmol min−1 mg−1 protein by overexpression of the CA gene. In addition, co‐overexpression of BT and CA genes had a synergetic effect, leading to a 44% increase in succinate titer at 36 h. This work is the first attempt to increase carbon fixation involved in microbial biosynthesis by engineering a biological CO2 delivery system, which provides new direction and strategies for improving industrial fermentations based on biological CO2 assimilation pathways.
Solvent‐Free Off–On Detection of the Improvised Explosive Triacetone Triperoxide (TATP) with Fluorogenic Materials
Authors: Calvo‐Gredilla Patricia , García‐Calvo José , Cuevas José V. , Torroba Tomás , Pablos Jesús‐Luis , García Félix C. , García José‐Miguel , Zink‐Lorre Nathalie , Font‐Sanchis Enrique , Sastre‐Santos Ángela , Fernández‐Lázaro Fernando
Published: July 2017

A fluorogenic perylenediimide‐functionalized polyacrylate capable of generating color and fluorescence changes in the presence of triacetone triperoxide TATP), an improvised explosive used in terrorist attacks, under solvent‐free, solid‐state conditions has been developed. The material works by accumulating volatile TATP until it reaches a threshold; therefore, triggering colorimetric and fluorescent responses.
Discrepancy Between Experimental and Theoretical Predictions of the Adiabaticity of Ti++CH3OH
Authors: Sweeny Brendan C. , Ard Shaun G. , McDonald David C. , Martinez Oscar , Viggiano Albert A. , Shuman Nicholas S.
Published: July 2017

The reaction between Ti+ and methanol (CH3OH) is a model system for competition between activation of C−O, C−H, and O−H bonds and of the role of excited electronic pathways in catalytic processes. Herein, we use experimental kinetics, quantum chemical calculations, and statistical modeling to identify the critical features of the reaction's potential energy surface. Experimental kinetics data between 300 and 600 K shows the reaction largely proceeds through C−O bond activation, yielding TiOH+ and TiO+. Products of the O−H activation pathway, TiOCH2+ and TiOCH3+ are minor, whereas C−H bond activation is not observed at thermal energies. Statistical modeling well‐reproduces the experimental results and offers insight into the reaction mechanism. Notably, efficient spin‐crossing along the C−O activation pathway is required to produce the observed product distribution, in contrast to a previous estimate of inefficient crossing based on calculation of a small spin‐orbit coupling constant. This discrepancy highlights a potential limitation of simple models within the Landau–Zener framework, which are commonly used to calculate surface‐crossing probabilities in reactive systems.
Exploiting the MeDbz Linker To Generate Protected or Unprotected C‐Terminally Modified Peptides
Authors: Arbour Christine A. , Saraha Hasina Y. , McMillan Timothy F. , Stockdill Jennifer L.
Published: July 2017

C‐terminally modified peptides are important targets for pharmaceutical and biochemical applications. Known methods for C‐terminal diversification are limited mainly in terms of the scope of accessible modifications or by epimerization of the C‐terminal amino acid. In this work, we present a broadly applicable approach that enables access to a variety of C‐terminally functionalized peptides in either protected or unprotected form. This chemistry proceeds without epimerization of C‐terminal Ala and tolerates nucleophiles of varying nucleophilicity. Finally, unprotected peptides bearing nucleophilic side chain groups can be selectively functionalized by strong nucleophiles, whereas macrocyclization is observed for weaker nucleophiles. The potential utility of this method is demonstrated through the divergent synthesis of the conotoxin conopressin G and GLP‐1(7‐36) and analogs.
Targeting of a Helix‐Loop‐Helix Transcriptional Regulator by a Short Helical Peptide
Authors: Roschger Cornelia , Neukirchen Saskia , Elsässer Brigitta , Schubert Mario , Maeding Nicole , Verwanger Thomas , Krammer Barbara , Cabrele Chiara
Published: July 2017

The Id proteins (Id1–4) are cell‐cycle regulators that play a key role during development, in cancer and vascular disorders. They contain a conserved helix‐loop‐helix (HLH) domain that folds into a parallel four‐helix bundle upon self‐ or hetero‐association with basic‐HLH transcription factors. By using such protein–protein interactions, the Id proteins inhibit cell differentiation and promote cell‐cycle progression. Accordingly, their supporting role in cancer has been convincingly demonstrated, which makes these proteins interesting therapeutic targets. Herein we present a short peptide containing an (i,i+4)‐lactam bridge and a hydrophobic (Φ) three‐residue motif Φ(i)−Φ(i+3)−Φ(i+6), which adopts a helical conformation in water, shows Id protein binding in the low‐micromolar range, penetrates into breast (MCF‐7 and T47D) and bladder (T24) cancer cells, accumulates in the nucleus, and decreases cell viability to ∼50 %. Thus, this cyclopeptide is a promising scaffold for the development of Id protein binders that impair cancer cell viability.
Contemporary use trends and survival outcomes in patients undergoing radical cystectomy or bladder‐preservation therapy for muscle‐invasive bladder cancer
Authors: Cahn David B. , Handorf Elizabeth A. , Ghiraldi Eric M. , Ristau Benjamin T. , Geynisman Daniel M. , Churilla Thomas M. , Horwitz Eric M. , Sobczak Mark L. , Chen David Y. T. , Viterbo Rosalia , Greenberg Richard E. , Kutikov Alexander , Uzzo Robert G. , Smaldone Marc C.
Published: July 2017

BACKGROUND

The current study was performed to examine temporal trends and compare overall survival (OS) in patients undergoing radical cystectomy (RC) or bladder‐preservation therapy (BPT) for muscle‐invasive urothelial carcinoma of the bladder.

METHODS

The authors reviewed the National Cancer Data Base to identify patients with AJCC stage II to III urothelial carcinoma of the bladder from 2004 through 2013. Patients receiving BPT were stratified as having received any external‐beam radiotherapy (any XRT), definitive XRT (50‐80 grays), and definitive XRT with chemotherapy (CRT). Treatment trends and OS outcomes for the BPT and RC cohorts were evaluated using Cochran‐Armitage tests, unadjusted Kaplan‐Meier curves, adjusted Cox multivariate regression, and propensity score matching, using increasingly stringent selection criteria.

RESULTS

A total of 32,300 patients met the inclusion criteria and were treated with RC (22,680 patients) or BPT (9620 patients). Of the patients treated with BPT, 26.4% (2540 patients) and 15.5% (1489 patients), respectively, were treated with definitive XRT and CRT. Improved OS was observed for RC in all groups. After adjustments with more rigorous statistical models controlling for confounders and with more restrictive BPT cohorts, the magnitude of the OS benefit became attenuated on multivariate (any XRT: hazard ratio [HR], 2.115 [95% confidence interval [95% CI], 2.045‐2.188]; definitive XRT: HR, 1.870 [95% CI, 1.773‐1.972]; and CRT: HR, 1.578 [95% CI, 1.474‐1.691]) and propensity score (any XRT: HR, 2.008 [95% CI, 1.871‐2.154]; definitive XRT: HR, 1.606 [95% CI, 1.453‐1.776]; and CRT: HR, 1.406 [95% CI, 1.235‐1.601]) analyses.

CONCLUSIONS

In the National Cancer Data Base, receipt of BPT was associated with decreased OS compared with RC in patients with stage II to III urothelial carcinoma. Increasingly stringent definitions of BPT and more rigorous statistical methods adjusting for selection biases attenuated observed survival differences. Cancer 2017;123:4337‐45. © 2017 American Cancer Society.
Structure and development of the subesophageal zone of the Drosophila brain. I. Segmental architecture, compartmentalization, and lineage anatomy
Authors: Hartenstein Volker , Omoto Jaison J. , Ngo Kathy T. , Wong Darren , Kuert Philipp A. , Reichert Heinrich , Lovick Jennifer K. , Younossi‐Hartenstein Amelia
Published: July 2017

The subesophageal zone (SEZ) of the Drosophila brain houses the circuitry underlying feeding behavior and is involved in many other aspects of sensory processing and locomotor control. Formed by the merging of four neuromeres, the internal architecture of the SEZ can be best understood by identifying segmentally reiterated landmarks emerging in the embryo and larva, and following the gradual changes by which these landmarks become integrated into the mature SEZ during metamorphosis. In previous works, the system of longitudinal fibers (connectives) and transverse axons (commissures) has been used as a scaffold that provides internal landmarks for the neuromeres of the larval ventral nerve cord. We have extended the analysis of this scaffold to the SEZ and, in addition, reconstructed the tracts formed by lineages and nerves in relationship to the connectives and commissures. As a result, we establish reliable criteria that define boundaries between the four neuromeres (tritocerebrum, mandibular neuromere, maxillary neuromere, labial neuromere) of the SEZ at all stages of development. Fascicles and lineage tracts also demarcate seven columnar neuropil domains (ventromedial, ventro‐lateral, centromedial, central, centrolateral, dorsomedial, dorsolateral) identifiable throughout development. These anatomical subdivisions, presented in the form of an atlas including confocal sections and 3D digital models for the larval, pupal and adult stage, allowed us to describe the morphogenetic changes shaping the adult SEZ. Finally, we mapped MARCM‐labeled clones of all secondary lineages of the SEZ to the newly established neuropil subdivisions. Our work will facilitate future studies of function and comparative anatomy of the SEZ.
Evaluating the Renal Safety of Investigational New Drugs: Where Should We Be Going?
Authors: Stockbridge N , Blank M , Hausner EA , Thompson A
Published: July 2017

We the authors work in the US Food and Drug Administration (FDA) review division responsible for the therapeutic agents for primary renal disease. We also field consultative inquiries regarding off‐target adverse renal effects of drugs intended to treat other diseases. We do neither basic science research on renal diseases nor clinical studies of new drugs, but we are professional spectators of both. We offer here our thoughts on the challenge of identifying renal safety signals in the preclinical space and in the earliest phases of clinical development.
Stabilizing the Performance of High‐Capacity Sulfur Composite Electrodes by a New Gel Polymer Electrolyte Configuration
Authors: Agostini Marco , Lim Du Hyun , Sadd Matthew , Fasciani Chiara , Navarra Maria Assunta , Panero Stefania , Brutti Sergio , Matic Aleksandar , Scrosati Bruno
Published: July 2017

Increased pollution and the resulting increase in global warming are drawing attention to boosting the use of renewable energy sources such as solar or wind. However, the production of energy from most renewable sources is intermittent and thus relies on the availability of electrical energy‐storage systems with high capacity and at competitive cost. Lithium–sulfur batteries are among the most promising technologies in this respect due to a very high theoretical energy density (1675 mAh g−1) and that the active material, sulfur, is abundant and inexpensive. However, a so far limited practical energy density, life time, and the scaleup of materials and production processes prevent their introduction into commercial applications. In this work, we report on a simple strategy to address these issues by using a new gel polymer electrolyte (GPE) that enables stable performance close to the theoretical capacity of a low cost sulfur–carbon composite with high loading of active material, that is, 70 % sulfur. We show that the GPE prevents sulfur dissolution and reduces migration of polysulfide species to the anode. This functional mechanism of the GPE membranes is revealed by investigating both its morphology and the Li‐anode/GPE interface at various states of discharge/charge using Raman spectroscopy.
Adopt 10 key strategies for successful leadership
Authors: Hope Joan
Published: July 2017

NEW ORLEANS — If you're looking for higher‐level leadership opportunities, showing leadership in your current position can get you noticed. Chemene Crawford, vice president for student services and enrollment management at El Centro College in the Dallas County Community College District; and Ann Johnson, vice president for student success at Lone Star College, Tomball, explained how to lead from any position at a session at the American Association of Community Colleges annual convention.
Autoantibodies against PFDN2 are associated with an increased risk of type 2 diabetes: A case‐control study
Authors: Chang Douglas C. , Piaggi Paolo , Hanson Robert L. , Knowler William C. , Bogardus Clifton , Krakoff Jonathan
Published: July 2017

Background

The adaptive immune system is involved in type 2 diabetes mellitus (T2DM), indicating the presence of unidentified autoantibodies that might be useful biomarkers for emerging immunomodulatory therapy. A prior microarray study with a small number of participants suggested the association of novel autoantibodies with T2DM in Southwest American Indians. We therefore sought to determine whether antibodies against 14 target proteins are associated with T2DM in a large case‐control study.

Methods

Participants were adults (age 20‐59 y) of Southwest American Indian heritage. Plasma antibodies against 14 possible target proteins were measured in 476 cases with T2DM of less than 5 years duration and compared with 424 controls with normal glucose regulation.

Results

Higher levels of antibodies against prefoldin subunit 2 (PFDN2) were associated with T2DM (P = .0001; Bonferroni‐corrected threshold for multiple tests = 0.0036 [α = 0.05]). The association between anti‐PFDN2 antibodies and T2DM remained in multivariable logistic regression (odds ratio 1.27; 95% confidence interval, 1.09‐1.49; per one SD difference in anti‐PFDN2 antibody). The odds of T2DM were increased in the highest anti‐PFDN2 antibody quintile by 66% compared with the lowest quintile. Differences in anti‐PFDN2 antibodies were most prominent among cases with earlier onset of disease (ie, age 20‐39 y) compared with controls.

Conclusions

Anti‐PFDN2 antibodies are associated with T2DM and might be a useful biomarker. These findings indicate that autoimmunity may play a role in T2DM in Southwest American Indians, especially among adults presenting with young onset of disease.
Alkaloid profiling of herbal drugs using high resolution mass spectrometry
Authors: Nardin Tiziana , Piasentier Edi , Barnaba Chiara , Larcher Roberto
Published: July 2017

Herbal infusions are consumed worldwide thanks to their “natural” beneficial effects, also due to the presence of alkaloids, although these compounds can have poisonous effects. A method combining online solid‐phase purification with high resolution mass spectrometry was used to define the alkaloid profiles of 117 herbs and 7 commercial blends. Forty‐one alkaloids were quantified in reference to analytical standards, while the presence of a further 116 was confirmed based on accurate mass, retention time, and fragmentation profile. The targeted study showed that 52% of herbs and 42% of commercial blends contained at least one alkaloid. Pyrrolizidines were the most commonly present (26% of samples), with concentrations generally ranging from the quantification limit to roughly 100 μg kg−1. Moreover, a homemade infusion was studied, finding on average 45% and 6% lower extraction for pyrrolizidine and steroidal alkaloids, respectively. Nevertheless, the migration of pyrrolizidines was confirmed. The study confirmed the frequent presence, natural or accidental, of alkaloids in commercial infusion herbs, highlighting the urgent need for routine and accurate controls.
The thermal niche of Neotropical nectar‐feeding bats: Its evolution and application to predict responses to global warming
Authors: Ortega‐García Stephanie , Guevara Lázaro , Arroyo‐Cabrales Joaquín , Lindig‐Cisneros Roberto , Martínez‐Meyer Enrique , Vega Ernesto , Schondube Jorge E.
Published: July 2017

The thermal niche of a species is one of the main determinants of its ecology and biogeography. In this study, we determined the thermal niche of 23 species of Neotropical nectar‐feeding bats of the subfamily Glossophaginae (Chiroptera, Phyllostomidae). We calculated their thermal niches using temperature data obtained from collection records, by generating a distribution curve of the maximum and minimum temperatures per locality, and using the inflection points of the temperature distributions to estimate the species optimal (STZ) and suboptimal (SRZ) zones of the thermal niche. Additionally, by mapping the values of theSTZandSRZon a phylogeny of the group, we generated a hypothesis of the evolution of the thermal niches of this clade of nectar‐feeding bats. Finally, we used the characteristics of their thermal niches to predict the responses of these organisms to climate change. We found a large variation in the width and limits of the thermal niches of nectar‐feeding bats. Additionally, while the upper limits of the thermal niches varied little among species, their lower limits differ wildly. The ancestral reconstruction of the thermal niche indicated that this group of Neotropical bats evolved under cooler temperatures. The two clades inside the Glossophaginae differ in the evolution of their thermal niches, with most members of the clade Choeronycterines evolving “colder” thermal niches, while the majority of the species in the clade Glossophagines evolving “warmer” thermal niches. By comparing thermal niches with climate change models, we found that all species could be affected by an increase of 1°C in temperature at the end of this century. This suggests that even nocturnal species could suffer important physiological costs from global warming. Our study highlights the value of scientific collections to obtain ecologically significant physiological data for a large number of species.
Topographic, edaphic, and vegetative controls on plant‐available water
Authors: Dymond Salli F. , Bradford John B. , Bolstad Paul V. , Kolka Randall K. , Sebestyen Stephen D. , DeSutter Thomas M.
Published: July 2017

Soil moisture varies within landscapes in response to vegetative, physiographic, and climatic drivers, which makes quantifying soil moisture over time and space difficult. Nevertheless, understanding soil moisture dynamics for different ecosystems is critical, as the amount of water in a soil determines a myriad ecosystem services and processes such as net primary productivity, runoff, microbial decomposition, and soil fertility. We investigated the patterns and variability in in situ soil moisture measurements converted to plant‐available water across time and space under different vegetative cover types and topographic positions at the Marcell Experimental Forest (Minnesota, USA). From 0‐ to 228.6‐cm soil depth, plant‐available water was significantly higher under the hardwoods (12%), followed by the aspen (8%) and red pine (5%) cover types. Across the same soil depth, toeslopes were wetter (mean plant‐available water = 10%) than ridges and backslopes (mean plant‐available water was 8%), although these differences were not statistically significant (p < .05). Using a mixed model of fixed and random effects, we found that cover type, soil texture, and time were related to plant‐available water and that topography was not significantly related to plant‐available water within this low‐relief landscape. Additionally, during the 3‐year monitoring period, red pine and quaking aspen sites experienced plant‐available water levels that may be considered limiting to plant growth and function. Given that increasing temperatures and more erratic precipitation patterns associated with climate change may result in decreased soil moisture in this region, these species may be sensitive and vulnerable to future shifts in climate.
Ambidentate Ligand Reactivity with the Rhenium(I) Compounds [BrRe(CO)4]2 and cis‐BrRe(CO)4L: A Kinetic and Mechanistic Study
Authors: Mayberry Darrell D. , Nesterov Vladimir N. , Richmond Michael G.
Published: July 2017

The reaction of the halo‐bridged dimer [BrRe(CO)4]2 with the ambidentate donor 2‐(diphenylphosphanyl)pyridine (PN) has been investigated. The substitution reaction is rapid at room temperature and regioselective for phosphorus coordination to yield exclusively cis‐BrRe(CO)4(κP‐PN) (1). Thermolysis of 1 furnishes the PN‐chelated product fac‐BrRe(CO)3(κP,N‐PN) (2) and CO. The kinetics for the conversion of 1 → 2 + CO have been measured by UV/Vis spectroscopy in toluene over the temperature range of 323–343 K. On the basis of the activation parameters [ΔH‡ = 28.0(0.9) kcal/mol and ΔS‡ = 31(3) eu], a dissociative process is supported, and this was corroborated by electronic structure calculations. The regioselectivity in the ligand‐substitution reaction involving [BrRe(CO)4]2 and the tridentate donor 6‐(diphenylphosphanyl)‐2‐formylpyridine (PON) was also studied, and consistent with the PN donor, only the κP‐product, cis‐BrRe(CO)4(κP‐PON) (3) is formed. The reaction of the dimer [BrRe(CO)4]2 with 2‐(diphenylphosphanyl)pyridine (PN) has been computationally modeled by DFT calculations. The energetics for the creation of an unsaturated intermediate through the cleavage of one of the bridging bromide ligands, followed by the addition of the donor to the unsaturated rhenium center versus the direct attack of the pnictogen donor on the dimer have been evaluated. The latter process is computed as the preferred route for dimer activation, with an attack of the pyridyl moiety slightly favored compared to the phosphine moiety. The computed pnictogen preference agrees with the kinetic data published by Zingales and coworkers. Concerning the reaction of the PN ligand with [BrRe(CO)4]2, we predict the initial formation of the κN‐isomer of 1 as the kinetic product of substitution, which in turn undergoes a rapid isomerization to furnish the thermodynamically more stable κP‐isomer through a reversible ligand dissociation process. The intramolecular linkage isomerization of κN‐1 to κP‐1 in 1 was also investigated by DFT, and the concerted process was found to lie 6.5 kcal/mol above the two‐step process involving ligand dissociation.
Luminescent 1,8‐Naphthalimide‐Derived ReI Complexes: Syntheses, Spectroscopy, X‐ray Structure and Preliminary Bioimaging in Fission Yeast Cells
Authors: Langdon‐Jones Emily E. , Williams Catrin F. , Hayes Anthony J. , Lloyd David , Coles Simon J. , Horton Peter N. , Groves Lara M. , Pope Simon J. A.
Published: July 2017

A series of picolyl‐functionalised, fluorescent 1,8‐naphthalimide ligands (L) have been synthesised and coordinated to ReI to form luminescent cationic complexes of the general form fac‐[Re(phen)(CO)3(L)]BF4. The complexes were characterised by using a range of spectroscopic and analytical techniques. One example of a complex was also characterised in the solid‐state by using single‐crystal X‐ray diffraction, revealing a distorted octahedral coordination sphere at ReI and Re–C/Re–N bond lengths within the expected ranges. All ligands were shown to be fluorescent, with the 4‐amino derivatives showing intramolecular charge transfer in the visible region (511–534 nm). The complexes generally showed a mixture of ligand‐centred and/or 3MLCT emission depending upon the nature of the coordinated 1,8‐naphthalimide ligand. For selected complexes, confocal fluorescence microscopy was undertaken by using fission yeast cells (Schizosaccharomyces pombe) and showed that the structure of the 1,8‐naphthalimide ligand influences the uptake and localisation of the rhenium complex.
Polyborate Anions Partnered with Large Nonmetal Cations: Triborate(1–), Pentaborate(1–) and Heptaborate(2–) Salts
Authors: Beckett Michael A. , Coles Simon J. , Horton Peter N. , Jones Charlotte L.
Published: July 2017

New polyborate salts containing bulky nonmetal cations have been prepared from either the free organic base or the [nonmetal cation][OH] in an aqueous solution with methanol: 1‐adamantylammonium pentaborate [C10H18N][B5O6(OH)4] (1), 2‐adamantylammonium pentaborate dihydrate [C10H18N][B5O6(OH)4]·2H2O (2), N,N‐dimethyl‐1‐adamantylammonium pentaborate boric acid monohydrate [C12H22N][B5O6(OH)4]·B(OH)3·H2O (3), N,N,N‐trimethyl‐1‐adamantylammonium pentaborate trihydrate [C13H24N][B5O6(OH)4]·3H2O (4), N,N,N‐trimethyl‐2‐adamantylammonium pentaborate trihydrate [C13H24N][B5O6(OH)4]·3H2O (5), dibenzylammonium pentaborate sesquihydrate [C14H16N][B5O6(OH)4]·1.5H2O (6), bis(triphenylphosphine)iminium pentaborate sesquihydrate [C36H30NP2][B5O6(OH)4]·1.5H2O (7), bis(triphenylphosphine)iminium triborate·2.5hydrate [C36H30NP2][B3O3(OH)4]·2.5H2O (8), 4,4′‐bipiperidinium heptaborate dihydrate [C10H22N2][B7O9(OH)5]·2H2O (9). All compounds were characterized by thermal (TGA/DSC) and spectroscopic (NMR, IR) analysis. Compounds 3–5 and 9 were characterized by single‐crystal XRD studies. The waters of crystallization in 3–6 and the boric acid of crystallization in 3 play important structural roles in expanding the supramolecular pentaborate(1–) lattices to accommodate the bulkier cations.
Switchable Dielectric Constant in the Cyanometalate‐Based Hydrogen‐Bonded [(CH3)2NH2]2(H3O)[Co(CN)6] Framework
Authors: Shi Chao , Wang Ya , Han Xiang‐Bin , Zhang Wen
Published: July 2017

Invited for the cover of this issue is the group of Wen Zhang from Southeast University, Nanjing, China. The cover image shows host–guest type organic–inorganic frameworks that have switchable dielectric constants.
Flow‐Assisted Synthesis: A Key Fragment of SR 142948A
Authors: Kitching Matthew O. , Dixon Olivia E. , Baumann Marcus , Baxendale Ian R.
Published: July 2017

We report a series of multi‐step flow operations to deliver an advanced hydrazine intermediate used in the assembly of the neurotensin modulator SR 142948A. Several new reactor configurations have enabled chemical transformations that would be otherwise difficult or dangerous to perform at scale. Overall the flow approach has allowed the preparation of kilogram quantities of the required hydrazine through a short and efficient route.
Sensors for disposable bioreactors
Authors: Busse Christoph , Biechele Philipp , de Vries Ingo , Reardon Kenneth F. , Solle Dörte , Scheper Thomas
Published: July 2017

Modern bioprocess monitoring demands sensors that provide on‐line information about the process state. In particular, sensors for monitoring bioprocesses carried out in single‐use bioreactors are needed because disposable systems are becoming increasingly important for biotechnological applications. Requirements for the sensors used in these single‐use bioreactors are different than those used in classical reusable bioreactors. For example, long lifetime or resistance to steam and cleaning procedures are less crucial factors, while a requirement of sensors for disposable bioreactors is a cost that is reasonable on a per‐use basis. Here, we present an overview of current and emerging sensors for single‐use bioreactors, organized by the type of interface of the sensor systems to the bioreactor. A major focus is on non‐invasive, in‐situ sensors that are based on electromagnetic, semiconducting, optical, or ultrasonic measurements. In addition, new technologies like radio‐frequency identification sensors or free‐floating sensor spheres are presented. Notably, at this time there is no standard interface between single‐use bioreactors and the sensors discussed here. In the future, manufacturers should address this shortcoming to promote single‐use bioprocess monitoring and control.
Bio-nano interface and environment: A critical review
Authors: Pulido-Reyes Gerardo , Leganes Francisco , Fernández-Piñas Francisca , Rosal Roberto
Published: July 2017

The bio–nano interface is the boundary where engineered nanomaterials (ENMs) meet the biological system, exerting the biological function for which they have been designed or inducing adverse effects on other cells or organisms when they reach nontarget scenarios (i.e., the natural environment). Research has been performed to determine the fate, transport, and toxic properties of ENMs, but much of it is focused on pristine or so-called as-manufactured ENMs, or else modifications of the materials were not assessed. We review the most recent progress regarding the bio–nano interface and the transformations that ENMs undergo in the environment, paying special attention to the adsorption of environmental biomolecules on the surface of ENMs. Whereas the protein corona has received considerable attention in the fields of biomedics and human toxicology, its environmental analogue (the eco-corona) has been much less studied. A section dedicated to the analytical methods for studying and characterizing the eco-corona is also presented. We conclude by presenting and discussing the key problems and knowledge gaps that need to be resolved in the near future regarding the bio–nano interface and the eco-corona. Environ Toxicol Chem 2017;36:3181–3193. © 2017 SETAC

Abstract
Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell line
Authors: Morgado Patrícia I. , Jose Sílvia , Wanke Riccardo , M. Antunes Alexandra M. , Cardoso Ana Sofia , Jordao Luisa
Published: July 2017

Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants present in the environment with known mutagenic and carcinogenic properties. In the present study the effects of exposure to single or multiple doses of benzo[a]anthracene (BaA), pyrene (Pyr), and 3 halogenated derivatives of these compounds (1-chloropyrene, 1-bromopyrene [1-BrPyr], and 7-chlorobenzo[a]anthracene [7-ClBaA]) were evaluated in a liver-derived human cell line (HepG2). Cytotoxicity as assessed by the classic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red assays showed a mild toxic effect in response to single or multiple dose exposure for up to 72 h, except for multiple dose exposure to BaA and 7-ClBaA (1 μM/d for 4 d) and single exposure to 10 μM BaA. Furthermore, selective mitochondrial and lysosomal toxicity was observed for Pyr and BaA series, respectively. To understand the underlying molecular mechanisms responsible for this effect, reactive oxygen species production, mitochondrial membrane depolarization, lysosomal pH, DNA fragmentation, and early and late apoptosis mediators were evaluated after exposure to single doses of the compounds. All compounds were able to trigger oxidative stress after 24 h as measured by catalase activity, and a good correlation was found between mitochondrial membrane depolarization, lysosomal pH increase, and MTT and neutral red assays. Evaluation of cell death mediators showed that caspase-3/7, but not annexin-V, pathways were involved in toxicity triggered by the studied compounds. The integration of all results showed that 1-BrPyr and BaA have a higher toxicity potential. Environ Toxicol Chem 2017;36:3404–3414. © 2017 SETAC