bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selbstorganisation von funktionellen diskreten dreidimensionalen Architekturen in Wasser
Authors: Taylor Lauren L. K. , Riddell Imogen A. , Smulders Maarten M. J. 
Published: June 2018

AbstractDer Aufbau von diskreten, selbstorganisierten Architekturen in Wasser fand in den vergangenen Jahren erhebliches Interesse, da sich eine große Anzahl von Anwendungen aus ihrer definierten 3D‐Struktur ergibt. Dieser Aufsatz diskutiert die gemeinsamen Bemühungen von Chemikern aus der supramolekularen Chemie und von Biotechnologen zur Lösung fachspezifischer Aufgaben, die mit dem Aufbau von Anordnungen aus synthetischen bzw. biologisch abgeleiteten Komponenten verbunden sind. In Zukunft wird ein stärker interdisziplinärer Forschungsansatz die Entwicklung von Komplexen mit realen Anwendungen beschleunigen, welche die Vorteile der Kompartimentierung nutzen. Um dies zu unterstützen, sollen hier die Fortschritte zusammengefasst werden, die bei der Entwicklung diskreter, wasserlöslicher Anordnungen erzielt wurden, unter besonderer Berücksichtigung ihrer aktuellen und zukünftigen Anwendungen. Bereiche, in denen das Verständnis und die Methodik von einem auf das andere Gebiet übertragbar sind, werden hervorgehoben, mit der Hoffnung, dass dies zu Fortschritten führt, die auf beiden Gebieten allein nicht möglich wären.
Cobalt‐Catalyzed Cross‐Couplings between Alkenyl Acetates and Aryl or Alkenyl Zinc Pivalates
Authors: Li Jie , Knochel Paul 
Published: June 2018

AbstractCoBr2 (5 mol %) in the presence of 2,2′‐bipyridyl (5 mol %) enables electrophilic alkenylations between easily accessible alkenyl acetates or tosylates and various functionalized aryl zinc pivalates at ambient temperature. This cobalt‐catalyzed process was further applicable to alkenyl zinc pivalates to provide substituted 1,3‐dienes.
Stratification of Systemic Lupus Erythematosus Patients Into Three Groups of Disease Activity Progression According to Longitudinal Gene Expression
Authors: Toro‐Domínguez Daniel , Martorell‐Marugán Jordi , Goldman Daniel , Petri Michelle , Carmona‐Sáez Pedro , Alarcón‐Riquelme Marta E. 
Published: June 2018

ObjectiveThe highly heterogeneous clinical presentation of systemic lupus erythematosus (SLE) is characterized by the unpredictable occurrence of disease flares and organ damage. Attempts to stratify lupus patients have been limited to classification based on clinical information, leading to unsuccessful clinical trials and controversial research results. This study was undertaken to develop and validate a robust method to stratify patients with lupus according to longitudinal disease activity and whole‐genome gene expression data in order to establish subgroups of patients who share disease progression mechanisms.MethodsWe used a cluster‐based approach to stratify SLE patients based on the correlation between disease activity scores and longitudinal gene expression information. Clustering robustness was evaluated by the bootstrap method, and the clusters were characterized in terms of clinical and functional features.ResultsWe observed a clear partition into 3 different disease clusters in 2 independent sets of patients, one pediatric and one adult, which was not influenced by treatment, race, or other source of bias. Two of the clusters differentiated into a group showing a correlation between the percentage of neutrophils and disease activity progression and a group showing a correlation between the percentage of lymphocytes and disease activity progression. The third cluster, in which the percentage of neutrophils correlated to a lesser degree with disease activity, was functionally more heterogeneous. Patients in the neutrophil‐driven clusters had an increased risk of developing proliferative nephritis.ConclusionOur findings indicate that SLE patients can be stratified into 3 subgroups of patients who show different mechanisms of disease progression and are clinically differentiated. Our results have important implications for treatment options, the design of clinical trials, our understanding of the etiology of the disease, and the prediction of severe glomerulonephritis.
Improving the Performance of Batteries by Using Multi‐Pyrene PTMA Structures
Authors: Hergué Noémie , Ernould Bruno , Minoia Andrea , Lazzaroni Roberto , Gohy Jean‐François , Dubois Philippe , Coulembier Olivier 
Published: June 2018

AbstractWell‐defined pyrene‐based poly(2,2,6,6‐tetramethylpiperidinyloxy‐4‐yl methacrylate) (PTMA) (co)polymers have been synthesized and combined with multi‐wall carbon nanotubes (CNTs) as electrode material for organic radical batteries. The influence of the number of pyrene pendent groups on the electrochemical response of the nanocomposite materials has been assessed, focusing on the capacity retention upon charge/discharge cycling and on the cycling rate. In parallel, the interactions between the polymethacrylate chains and the CNT surface have been investigated with molecular modeling techniques, to shed light on the nature and stability of the functionalized PTMA/CNT interface.
Multispecies activity screening of microcin J25 mutants yields antimicrobials with increased specificity toward pathogenic Salmonella species relative to human commensal Escherichia coli
Authors: Ritter Seth C. , Yang Mike L. , Kaznessis Yiannis N. , Hackel Benjamin J. 
Published: June 2018

AbstractModern large‐scale agricultural practices that incorporate high density farming with subtherapeutic antibiotic dosing are considered a major contributor to the rise of antibiotic‐resistant bacterial infections of humans with species of Salmonella being a leading agriculture‐based bacterial infection. Microcin J25, a potent and highly stable antimicrobial peptide active against Enterobacteriaceae, is a candidate antimicrobial against multiple Salmonella species. Emerging evidence supports the hypothesis that the composition of the microbiota of the gastrointestinal tract prevents a variety of diseases by preventing infectious agents from proliferating. Reducing clearance of off‐target bacteria may decrease susceptibility to secondary infection. Of the Enterobacteriaceae susceptible to microcin J25, Escherichia coli are the most abundant within the human gut. To explore the modulation of specificity, a collection of 207 mutants encompassing 12 positions in both the ring and loop of microcin J25 was built and tested for activity against Salmonella and E. coli strains. As has been found previously, mutational tolerance of ring residues was lower than loop residues, with 22% and 51% of mutations, respectively, retaining activity toward at least one target within the target organism test panel. The multitarget screening elucidated increased mutational tolerance at position G2, G3, and G14 than previously identified in panels composed of single targets. Multiple mutations conferred differential response between the different targets. Examination of specificity differences between mutants found that 30% showed significant improvements to specificity toward any of the targets. Generation and testing of a combinatorial library designed from the point‐mutant study revealed that microcin J25I13T reduces off‐target activity toward commensal human‐derived E. coli isolates by 81% relative to Salmonella enterica serovar Enteritidis. These in vitro specificity improvements are likely to improve in vivo treatment efficacy by reducing clearance of commensal bacteria in the gastrointestinal tract of hosts.
Rational approach to improve ansamitocin P‐3 production by integrating pathway engineering and substrate feeding in Actinosynnema pretiosum
Authors: Du Zhi‐Qiang , Zhong Jian‐Jiang 
Published: June 2018

AbstractAnsamitocin P‐3 (AP‐3) produced by Actinosynnema pretiosum is an important antitumor agent for cancer treatment, but its market supply suffers from a low production titer. The role of AP‐3 unusual glycolate unit supply on its biosynthesis was investigated in this work by overexpressing the responsible gene cluster asm13‐17 in A. pretiosum (WT). As a result, the accumulation of AP‐3 and its intermediate glyceryl‐S‐ACP in the asm13‐17‐overexpressed strain (Oasm13‐17) versus WT was enhanced by 1.94 and 1.49‐fold, respectively. To provide a higher supply of another precursor 3‐amino‐5‐hydroxybenzoic acid, asmUdpg was also overexpressed in Oasm13‐17 (Oasm13‐17:asmUdpg), and an improved AP‐3 titer of 680.5 mg/L was achieved in shake flasks. To further enhance the AP‐3 titer, a rational fed‐batch strategy was developed in bioreactor fermentation of Oasm13‐17:asmUdpg; and by pulse feeding 15 g/L fructose and 1.64 g/L isobutanol at 60, 96, and 120 hr, the AP‐3 production level reached 757.7 mg/L, which is much higher than ever reported in bioreactors. This work demonstrated that a rational approach combining precursor pathway engineering with substrate feeding was very effective in enhancing the AP‐3 titer, and this enabling methodology would be helpful to industrial production of this eye‐catching drug.
Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications
Authors: Ortega‐Ribera Martí , Fernández‐Iglesias Anabel , Illa Xavi , Moya Ana , Molina Víctor , Maeso‐Díaz Raquel , Fondevila Constantino , Peralta Carmen , Bosch Jaume , Villa Rosa , Gracia‐Sancho Jordi 
Published: June 2018

AbstractMaintenance of the complex phenotype of primary hepatocytes in vitro represents a limitation for developing liver support systems and reliable tools for biomedical research and drug screening. We herein aimed at developing a biosystem able to preserve human and rodent hepatocytes phenotype in vitro based on the main characteristics of the liver sinusoid: unique cellular architecture, endothelial biodynamic stimulation, and parenchymal zonation. Primary hepatocytes and liver sinusoidal endothelial cells (LSEC) were isolated from control and cirrhotic human or control rat livers and cultured in conventional in vitro platforms or within our liver‐resembling device. Hepatocytes phenotype, function, and response to hepatotoxic drugs were analyzed. Results evidenced that mimicking the in vivo sinusoidal environment within our biosystem, primary human and rat hepatocytes cocultured with functional LSEC maintained morphology and showed high albumin and urea production, enhanced cytochrome P450 family 3 subfamily A member 4 (CYP3A4) activity, and maintained expression of hepatocyte nuclear factor 4 alpha (hnf4α) and transporters, showing delayed hepatocyte dedifferentiation. In addition, differentiated hepatocytes cultured within this liver‐resembling device responded to acute treatment with known hepatotoxic drugs significantly different from those seen in conventional culture platforms. In conclusion, this study describes a new bioengineered device that mimics the human sinusoid in vitro, representing a novel method to study liver diseases and toxicology.
A framework for the identification of promising bio‐based chemicals
Authors: Wu Wenzhao , Long Matthew R. , Zhang Xiaolin , Reed Jennifer L. , Maravelias Christos T. 
Published: June 2018

AbstractRecent progress in metabolic engineering and synthetic biology enables the use of microorganisms for the production of chemicals—“bio‐based chemicals.” However, it is still unclear which chemicals have the highest economic prospect. To this end, we develop a framework for the identification of such promising ones. Specifically, we first develop a genome‐scale constraint‐based metabolic modeling approach, which is used to identify a candidate pool of 209 chemicals (together with the estimated yield, productivity, and residence time for each) from the intersection of the high‐production‐volume chemicals and the KEGG and MetaCyc databases. Second, we design three screening criteria based on a chemical’s profit margin, market volume, and market size. The total process cost, including the downstream separation cost, is systematically incorporated into the evaluation. Third, given the three aforementioned criteria, we identify 32 products as economically promising if the maximum yields can be achieved, and 22 products if the maximum productivities can be achieved. The breakeven titer that renders zero profit margin for each product is also presented. Comparisons between extracellular and intracellular production, as well as Escherichia coli and Saccharomyces cerevisiae systems are also discussed. The proposed framework provides important guidance for future studies in the production of bio‐based chemicals. It is also flexible in that the databases, yield estimations, and criteria can be modified to customize the screening.
Lamellar Liquid Crystals of In‐Plane Lying Rod‐Like Mesogens with Designer Side‐Chains: The Case of Sliding versus Locked Layers
Authors: Prehm Marko , Enders Claudia , Mang Xiaobin , Zeng Xiangbing , Liu Feng , Ungar Goran , Baumeister Ute , Tschierske Carsten 
Published: June 2018

AbstractThe dimensionality of self‐assembled nanostructures plays an essential role for their properties and applications. Herein, an understanding of the transition from weakly to strongly coupled layers in soft matter systems is provided involving in‐plane organized π‐conjugated rods. For this purpose, bolaamphiphilic triblock molecules consisting of a rigid biphenyl core, polar glycerol groups at the ends, and a branched (swallow‐tail) or linear alkyl or semiperfluoroalkyl chain in lateral position have been synthesized and investigated. Besides weakly coupled lamellar isotropic (LamIso), lamellar nematic (LamN) and sliding lamellar smectic phases (LamSm), a sequence of three distinct types of strongly coupled (correlated) lamellar smectic phases with either centered (c2mm) or non‐centered rectangular (p2mm) lattice and an intermediate oblique lattices (p2) were observed depending on chain length, chain branching and degree of chain fluorination. This new sequence is explained by the strengthening of the layer coupling and the competition between energetic packing constraints and the entropic contribution of either longitudinal or tangential fluctuations. This example of directed side chain engineering of small generic model compounds provides general clues for morphological design of two‐dimensional and three‐dimensionally coupled lamellar systems involving larger π‐conjugated molecular rods and molecular or supramolecular polymers, being of actual interest in organic electronics and nanotechnology.
Strategies for Reversible Guest Uptake and Release from Metallosupramolecular Architectures
Authors: Kim Tae Y. , Vasdev Roan A. S. , Preston Dan , Crowley James D. 
Published: June 2018

AbstractThe cavities of metallosupramolecular cages can be used to mimic the central spaces of naturally occurring proteins and bind a wide variety of molecular guests. A range of potential applications have arisen from this capacity for host–guest chemistry. However, to truly harness the opportunities thus afforded, methodologies to controllably allow the release and reuptake of guests from the cavities of metallosupramolecular cages are required. Methods to accomplish this have centered upon reversibly altering the character of either the guest or host. This minireview outlines the current approaches used to carry out the binding and release of guests from metallosupramolecular hosts using important examples from the field.
KinITC—One Method Supports both Thermodynamic and Kinetic SARs as Exemplified on FimH Antagonists
Authors: Zihlmann Pascal , Silbermann Marleen , Sharpe Timothy , Jiang Xiaohua , Mühlethaler Tobias , Jakob Roman P. , Rabbani Said , Sager Christoph P. , Frei Priska , Pang Lijuan , Maier Timm , Ernst Beat 
Published: June 2018

AbstractAffinity data, such as dissociation constants (KD) or inhibitory concentrations (IC50), are widely used in drug discovery. However, these parameters describe an equilibrium state, which is often not established in vivo due to pharmacokinetic effects and they are therefore not necessarily sufficient for evaluating drug efficacy. More accurate indicators for pharmacological activity are the kinetics of binding processes, as they shed light on the rate of formation of protein–ligand complexes and their half‐life. Nonetheless, although highly desirable for medicinal chemistry programs, studies on structure–kinetic relationships (SKR) are still rare. With the recently introduced analytical tool kinITC this situation may change, since not only thermodynamic but also kinetic information of the binding process can be deduced from isothermal titration calorimetry (ITC) experiments. Using kinITC, ITC data of 29 mannosides binding to the bacterial adhesin FimH were re‐analyzed to make their binding kinetics accessible. To validate these kinetic data, surface plasmon resonance (SPR) experiments were conducted. The kinetic analysis by kinITC revealed that the nanomolar affinities of the FimH antagonists arise from both (i) an optimized interaction between protein and ligand in the bound state (reduced off‐rate constant koff) and (ii) a stabilization of the transition state or a destabilization of the unbound state (increased on‐rate constant kon). Based on congeneric ligand modifications and structural input from co‐crystal structures, a strong relationship between the formed hydrogen‐bond network and koff could be concluded, whereas electrostatic interactions and conformational restrictions upon binding were found to have mainly an impact on kon.
Excitation‐Wavelength‐Dependent Emission and Delayed Fluorescence in a Proton‐Transfer System
Authors: Berezin Alexey S. , Vinogradova Katerina A. , Krivopalov Viktor P. , Nikolaenkova Elena B. , Plyusnin Victor F. , Kupryakov Arkady S. , Pervukhina Natalia V. , Naumov Dmitrii Y. , Bushuev Mark B. 
Published: June 2018

AbstractManipulating the relaxation pathways of excited states and understanding mechanisms of photochemical reactions present important challenges in chemistry. Here we report a unique zinc(II) complex exhibiting unprecedented interplay between the excitation‐wavelength‐dependent emission, thermally activated delayed fluorescence (TADF) and excited state intramolecular proton transfer (ESIPT). The ESIPT process in the complex is favoured by a short intramolecular OH⋅⋅⋅N hydrogen bond. Synergy between the excitation‐wavelength‐dependent emission and ESIPT arises due to heavy zinc atom favouring intersystem crossing (isc). Reverse intersystem crossing (risc) and TADF are favoured by a narrow singlet–triplet gap, ΔEST≈10 kJ mol−1. These results provide the first insight into how a proton‐transfer system can be modified to show a synergy between the excitation‐wavelength‐dependent emission, ESIPT and TADF. This strategy offers new perspectives for designing ESIPT and TADF emitters exhibiting tunable excitation‐wavelength‐dependent luminescence.
Brønsted Base Assisted Photoredox Catalysis: Proton Coupled Electron Transfer for Remote C−C Bond Formation via Amidyl Radicals
Authors: Jia Jiaqi , Ho Yee Ann , Bülow Raoul F. , Rueping Magnus 
Published: June 2018

AbstractThe synthesis of alkyne‐ and alkene‐decorated lactams has been achieved through a photoredox‐initiated radical cascade reaction. The developed Brønsted base assisted, photoredox‐catalyzed, intramolecular 5‐exo‐trig cyclization/intermolecular radical addition/elimination reaction provides facile access to functionalized γ‐lactams, with good functional group tolerance and high yields.
Chemical Modification of Dehydrated Amino Acids in Natural Antimicrobial Peptides by Photoredox Catalysis
Authors: de Bruijn A. Dowine , Roelfes Gerard 
Published: June 2018

AbstractDehydroalanine (Dha) and dehydrobutyrine (Dhb) are remarkably versatile non‐canonical amino acids often found in antimicrobial peptides. This work presents the selective modification of Dha and Dhb in antimicrobial peptides through photocatalytic activation of organoborates under the influence of visible light. Ir(dF(CF3)ppy)2(dtbbpy)PF6 was used as a photoredox catalyst in aqueous solutions for the modification of thiostrepton and nisin. The mild conditions and high selectivity for the dehydrated residues show that photoredox catalysis is a promising tool for the modification of peptide‐derived natural products.
Perceptions of future health and cancer risk in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study
Authors: Gibson Todd M. , Li Chenghong , Armstrong Gregory T. , Srivastava Deo Kumar , Leisenring Wendy M. , Mertens Ann , Brinkman Tara M. , Diller Lisa , Nathan Paul C. , Hudson Melissa M. , Robison Leslie L. 
Published: June 2018

BACKGROUNDSurvivors of childhood cancer are at significant risk for serious chronic health conditions and subsequent cancers because of their prior treatment exposures. However, little is known about survivors' perceptions of their future health risks.METHODSThis study examined self‐reported levels of concern about future health and subsequent cancer in 15,620 adult survivors of childhood cancer (median age, 26 years; median time since diagnosis, 17 years) and 3991 siblings in the Childhood Cancer Survivor Study. The prevalence of concerns was compared between survivors and siblings, and the impact of participant characteristics and treatment exposures on concerns was examined with multivariable modified Poisson regression to estimate relative risks (RRs) and 95% confidence intervals (CIs).RESULTSA substantial proportion of survivors were not concerned about their future health (31%) or developing cancer (40%). The prevalence of concern in survivors was modestly higher (RR for future health, 1.12; 95% CI, 1.09‐1.15) or similar (RR for subsequent cancer, 1.02; 95% CI, 0.99‐1.05) in comparison with siblings. Survivors exposed to high doses of radiation (≥20 Gy) were more likely to report concern (RR for future health, 1.13; 95% CI, 1.09‐1.16; RR for subsequent cancer, 1.14; 95% CI, 1.10‐1.18), but 35% of these high‐risk survivors were not concerned about developing cancer, and 24% were not concerned about their future health.CONCLUSIONSA substantial subgroup of survivors were unconcerned about their future health and subsequent cancer risks, even after exposure to treatments associated with increased risk. These survivors may be less likely to engage in beneficial screening and risk‐reduction activities. Cancer 2018. © 2018 American Cancer Society.
Peptide‐Based Hydrogels as a Scaffold for In Situ Synthesis of Metal Nanoparticles: Catalytic Activity of the Nanohybrid System
Authors: Paul Subir , Basu Kingshuk , Das Krishna Sundar , Banerjee Arindam 
Published: June 2018

AbstractA tripeptide containing an oligo‐methylene group was found to form hydrogels at the two pH extremes (in presence of an acid or a base); however, it does not form a hydrogel at neutral pH. We use this property to obtain a hydrogel of the peptide in the presence of an organic acid, citric acid. The redox potential of citric acid is ideal to reduce Ag+ and Au3+ ions to form the corresponding nanoparticles. Keeping this in mind the hydrogel with citric acid was applied to fabricate silver and gold nanoparticles within the gel phase without the aid of external reducing and stabilising agents. The hydrogels and the peptide nanofiber‐metal nanoparticle based hybrid system were thoroughly characterized by UV‐visible spectroscopy, FEG‐TEM microscopy, FT‐IR spectroscopy, and powder X‐ray diffraction studies. From the FEG‐TEM images it is evident that a considerable amount of Au and Ag nanoparticles are found above the gel nanofibers. Interestingly, the hybrid hydrogel containing silver nanoparticles could be successfully employed as a catalyst in the transformation of p‐nitrophenol to p‐aminophenol and p‐nitroaniline to p‐phenylenediamine. It is also interesting to note that the native hydrogel (without Ag nanoparticles) is unable to act as a catalyst. Moreover, this hybrid hydrogel has been recycled a few times without significant loss of activity, showing the potential of this new nanohybrid system for catalysis.