bluuebunny/crossref_metadata_2025_split huggingface dataset:
A long‐lived Aβ oligomer resistant to fibrillization
Authors: Nick Mimi , Wu Yibing , Schmidt Nathan W. , Prusiner Stanley B. , Stöhr Jan , DeGrado William F. 
Published: January 2018

AbstractThe hydrophobic Aβ peptide is highly aggregation prone; it first forms soluble oligomers, which then convert into the amyloid fibrils found in the cerebral plaques of Alzheimer's disease. It is generally understood that as the peptide concentration of Aβ increases, the fibrillization process is accelerated, but we examine the limits on this phenomenon. We found that once a threshold concentration of Aβ is exceeded, a stable oligomer is formed at the expense of fibril formation. The suppression of fibril formation was observed by amyloid‐binding dye Thioflavin T and solution nuclear magnetic resonance (NMR). Small‐angle X‐ray scattering, size exclusion chromatography, and analytical ultracentrifugation demonstrated that Aβ peptides form a range of compact species, with a dimer being an early highly populated oligomer. Solution NMR allowed us to define the secondary structure of this Aβ dimer, which shows interlocking contacts between C‐terminal peptide strands. Thus, we present a novel Aβ oligomer that resists conversion to fibrils and remains stable for more than one year.
Consolidated bioprocessing of lignocellulosic biomass to lactic acid by a synthetic fungal‐bacterial consortium
Authors: Shahab Robert L. , Luterbacher Jeremy S. , Brethauer Simone , Studer Michael H. 
Published: January 2018

AbstractConsolidated bioprocessing (CBP) of lignocellulosic feedstocks to platform chemicals requires complex metabolic processes, which are commonly executed by single genetically engineered microorganisms. Alternatively, synthetic consortia can be employed to compartmentalize the required metabolic functions among different specialized microorganisms as demonstrated in this work for the direct production of lactic acid from lignocellulosic biomass. We composed an artificial cross‐kingdom consortium and co‐cultivated the aerobic fungus Trichoderma reesei for the secretion of cellulolytic enzymes with facultative anaerobic lactic acid bacteria. We engineered ecological niches to enable the formation of a spatially structured biofilm. Up to 34.7 gL−1 lactic acid could be produced from 5% (w/w) microcrystalline cellulose. Challenges in converting pretreated lignocellulosic biomass include the presence of inhibitors, the formation of acetic acid and carbon catabolite repression. In the CBP consortium hexoses and pentoses were simultaneously consumed and metabolic cross‐feeding enabled the in situ degradation of acetic acid. As a result, superior product purities were achieved and 19.8 gL−1 (85.2% of the theoretical maximum) of lactic acid could be produced from non‐detoxified steam‐pretreated beech wood. These results demonstrate the potential of consortium‐based CBP technologies for the production of high value chemicals from pretreated lignocellulosic biomass in a single step.
Development of a temperature‐responsive yeast cell factory using engineered Gal4 as a protein switch
Authors: Zhou Pingping , Xie Wenping , Yao Zhen , Zhu Yongqiang , Ye Lidan , Yu Hongwei 
Published: January 2018

AbstractConflict between cell growth and product accumulation is frequently encountered in biosynthesis of secondary metabolites. Herein, a temperature‐dependent dynamic control strategy was developed by modifying the GAL regulation system to facilitate two‐stage fermentation in yeast. A temperature‐sensitive Gal4 mutant Gal4M9 was created by directed evolution, and used as a protein switch in ΔGAL80 yeast. After EGFP‐reported validation of its temperature‐responsive induction capability, the sensitivity and stringency of this system in multi‐gene pathway regulation was tested, using lycopene as an example product. When Gal4M9 was used to control the expression of PGAL‐driven pathway genes, growth and production was successfully decoupled upon temperature shift during fermentation, accumulating 44% higher biomass and 177% more lycopene than the control strain with wild‐type Gal4. This is the first example of adopting temperature as an input signal for metabolic pathway regulation in yeast cell factories.
Cooperate or not cooperate EEG, autonomic, and behavioral correlates of ineffective joint strategies
Authors: Balconi Michela , Gatti Laura , Vanutelli Maria Elide 
Published: January 2018

AbstractIntroductionThe neural activity in response to ineffective joint actions was explored in the present study. Subjects involved in a cooperative but frustrating task (poor performance as manipulated by an external feedback) were required to cooperate (T1) during an attentional task in a way to synchronize their responses and obtain better outcomes.MethodsWe manipulated their strategies by providing false feedbacks (T2) signaling the incapacity to create a synergy, which was reinforced by a general negative evaluation halfway through the game. A control condition was provided (no cooperation required, T0) as well as a check for possible learning effect (time series analysis). The effects of the feedback in modulating subjects' behavioral performance and electrocortical activity were explored by means of brain oscillations (delta, theta, alpha, beta) and autonomic activity (heart rate, HR; skin conductance activity, SCR).ResultsResults showed a specific pattern of behavioral, neural, and peripheral responses after the social feedback. In fact, within this condition, worse behavioral outcomes emerged, with longer response times with respect to the prefeedback one. In parallel, a specific right‐lateralized effect was observed over the dorsolateral prefrontal cortex (DLPFC), with increased delta and theta power compared to the previous condition. Moreover, increased SCR was observed with respect to the first part.ConclusionsTwo interpretations are put forward to explain the present findings: 1) the contribution of negative emotions in response to failing interactions or 2) a motivational disengagement toward goal‐oriented cooperation elicited by frustrating evaluations.
A feedback system to provide affective support to students
Authors: Jiménez Samantha , Juárez‐Ramírez Reyes , Castillo Víctor H. , Licea Guillermo , Ramírez‐Noriega Alan , Inzunza Sergio 
Published: January 2018

AbstractLearning support systems need to provide direct and affective interaction to students; it can encourage them and improve their motivation to learn. However, several systems do not include this kind of interaction between students and tutors. In those cases, the student learning interest and motivation to learn could be negatively affected, and student profits from the system could be impoverished. Only a few works have examined the influence of written affective feedback, but these studies focused on student learning outcomes, not in student motivation to learn. The objective of this work is to analyze the impact of an affective feedback system on the students’ perception of two aspects: (i) the degree to which study time is enjoyable and (ii) the motivation to learn. Results show that the affective feedback system makes more enjoyable study time and motivates students to learn, particularly to students with low academic performance. These system enhancements eventually would improve student‐learning outcomes.
Can therapeutic drug monitoring increase the safety of Imatinib in GIST patients?
Authors: Zhuang Wei , Xie Jing‐Dun , Zhou Shan , Zhou Zhi‐Wei , Zhou Yi , Sun Xiao‐Wei , Yuan Xiu‐Hong , Huang Min , Liu Si , Xin Shuang , Su Qi‐Biao , Qiu Hai‐Bo , Wang Xue‐Ding 
Published: January 2018

AbstractImatinib at 400 mg daily is the standard treatment for patients affected with CML and GIST. The intervariability in plasma concentration is very significant. In many reports, a good therapeutic effect is attributed to an adequate concentration of Imatinib. However, few studies have been conducted to investigate the association between plasma concentration and side effects. Besides, no upper concentration limit of Imatinib plasma concentration detection has been established. The correlation of Imatinib trough concentrations (Cmin) with adverse effects (AEs) was described here. Plasma samples were obtained from patients after 3 months treatment with Imatinib (steady state, n = 122). Liquid chromatography/ tandem mass spectrometry was used to determine the concentration of Imatinib and its metabolite NDI. The incidence of myelosuppression was increased significantly with the increased Imatinib trough plasma concentration. The plasma level of Imatinib and NDI in patients who developed myelosuppression are 1698.3 ± 598.6 ng/mL and 242.1 ng/mL, respectively, which were significantly higher than those in patients who did not (1327.2 ± 623.4 ng/mL, P = 1.75 × 10‐4; 206.3 ng/mL, P = 0.006). Estimated exposure thresholds of Imatinib and NDI were 1451.6 ng/mL with ROCAUC (95%CI) of 0.693 (0.597–0.789) and 207.1 ng/mL with ROCAUC (95%CI) of 0.646 (0.546–0.745), respectively. Multivariate regression confirmed the correlation of Imatinib Cmin with myelosuppression. Other side effects such as fluid retention and rash were not found to be correlated with Imatinib concentrations. These results suggest that trough concentration of Imatinib should be taken into consideration to increase the safety of Imatinib therapy in GIST patients.
Earth‐Friendly Seawater Desalination System Required in the 21st Century
Authors: Kurihara Masaru , Takeuchi Hiromu 
Published: January 2018

AbstractAlthough the distillation process was initially applied in seawater desalination plants to solve the current global water shortage, it has been replaced by the energy‐saving type reverse‐osmosis membrane process worldwide since the beginning of this century. Considering the population increase and economic development, the ‘Mega‐ton Water System' research project was conducted to identify the element technologies required for the 21st century in Japan. Enhancing the operational reliability of seawater desalination plants, these development technologies also enable the establishment of earth‐friendly seawater desalination plants anticipating considerable energy savings, lowering of the environmental impact, and reduction of water production costs.
Preparation of Hollow CeO2/CePO4 with Nitrogen and Phosphorus Co‐Doped Carbon Shells for Enhanced Oxygen Reduction Reaction Catalytic Activity
Authors: Yu Yue , He Bowen , Liao Yujia , Yu Xiaodan , Mu Zhongcheng , Xing Yan , Xing Shuangxi 
Published: January 2018

AbstractAchieving active and sustainable electrocatalysts for the oxygen reduction reaction with low cost and high performance attracts great interest in the field of fuel cells. Here, we report a facile route to prepare hollow CeO2/CePO4@N,P co‐doped carbon by pyrolyzing CeO2@polyaniline obtained in the presence of phytic acid. By virtue of the co‐doping of N and P elements as well as the existence of oxygen vacancies and the formation of a void, the product illustrated excellent catalytic activity towards the oxygen reduction reaction with onset and half‐wave potentials of 0.918 and 0.822 V, respectively, and a current density of 4.38 mA cm−2 at 0.565 V vs. RHE. Furthermore, it presented high durability and strong methanol tolerance, revealing its great potential for applications in energy conversion.
Epitope‐Targeted Macrocyclic Peptide Ligand with Picomolar Cooperative Binding to Interleukin‐17F
Authors: Lai Bert T. , Wilson Jeré A. , Malette Loredo Jacquie , Pitram Suresh M. , LaBerge Nicole A. , Heath James R. , Agnew Heather D. 
Published: January 2018

AbstractThe IL‐17 cytokine family is associated with multiple immune and autoimmune diseases and comprises important diagnostic and therapeutic targets. This work reports the development of epitope‐targeted ligands designed for differential detection of human IL‐17F and its closest homologue IL‐17A. Non‐overlapping and unique epitopes on IL‐17F and IL‐17A were identified by comparative sequence analysis of the two proteins. Synthetic variants of these epitopes were utilized as targets for in situ click screens against a comprehensive library of synthetic peptide macrocycles with 5‐mer variable regions. Single generation screens yielded selective binders for IL‐17F and IL‐17A with low cross‐reactivity. Macrocyclic peptide binders against two distinct IL‐17F epitopes were coupled using variable length chemical linkers to explore the physical chemistry of cooperative binding. The optimized linker length yielded a picomolar affinity binder, while retaining high selectivity. The presented method provides a rational approach towards targeting discontinuous epitopes, similar to what is naturally achieved by many B cell receptors.
Water–Tryptophan Interactions: Lone‐pair⋅⋅⋅π or O−H⋅⋅⋅π? Molecular Dynamics Simulations of β‐Galactosidase Suggest that Both Modes Can Co‐exist
Authors: Durec Matúš , Marek Radek , Kozelka Jiří 
Published: January 2018

AbstractIn proteins, the indole side chain of tryptophan can interact with water molecules either in‐plane, forming hydrogen bonds, or out‐of‐plane, with the water molecule contacting the aromatic π face. The latter interaction can be either of the lone pair⋅⋅⋅π (lp⋅⋅⋅π) type or corresponds to the O−H⋅⋅⋅π binding mode, an ambiguity that X‐ray structures usually do not resolve. Here, we report molecular dynamics (MD) simulations of a solvated β‐galactosidase monomer, which illustrate how a water molecule located at the π face of an indole side chain of tryptophan can adapt to the position of proximate residues and “select” its binding mode. In one such site, the water molecule is predicted to rapidly oscillate between the O−H⋅⋅⋅π and lp⋅⋅⋅π binding modes, thus gaining entropic advantage. Our MD simulations provide support for the role of lp⋅⋅⋅π interactions in the stabilization of protein structures.
Ultrafine and Ligand‐Free Precious Metal (Ru, Ag, Au, Rh and Pd) Nanoclusters Supported on Phosphorus‐Doped Carbon
Authors: Liu Ben , Jin Lei , Zhong Wei , Lopes Aaron , Suib Steven L. , He Jie 
Published: January 2018

AbstractWe report the use of phosphorus‐doped carbon (P‐C) as support to grow ultrasmall (1–3 nm) and ligand‐free precious metal nanocrystals (PMNCs) via chemical reduction. We show that the valence states of surface phosphorus species are critical in tuning the affinity between the carbon support and metal precursors, which rationally controls the loading size and uniformity of resultant PMNCs. Five kinds of PMNCs, including Ru, Ag, Au, Rh, and Pd, were grown in situ to demonstrate the key role of surface phosphorus sites on the P‐C support. As a proof‐of‐concept application, Ru nanocatalysts with an average diameter of 1.0±0.2 nm supported on P‐C were examined for the electrocatalytic hydrogen evolution reaction (HER). Ultrasmall and ligand‐free Ru nanocatalysts exhibited superior HER activity and stability compared to its counterparts with surface agents or larger sizes. An overpotential of 27.6 mV (vs. reversible hydrogen electrode) for Ru nanocatalysts was achieved at a current density of 10 mA cm−2. This novel method opens a new avenue to immobilize ligand‐free and well‐dispersed PMNCs on carbon; and, more importantly, it provides a new library of supported PMNCs with high catalytic activity.
Self‐Assembled Cofacial Zinc–Porphyrin Supramolecular Nanocapsules as Tuneable 1O2 Photosensitizers
Authors: Colomban Cédric , Fuertes‐Espinosa Carles , Goeb Sébastien , Sallé Marc , Costas Miquel , Blancafort Lluís , Ribas Xavi 
Published: January 2018

AbstractWe demonstrate the benefits of using cofacial Zn–porphyrins as structural synthons in coordination‐driven self‐assembled prisms to produce cage‐like singlet oxygen (1O2) photosensitizers with tunable properties. In particular, we describe the photosensitizing and emission properties of palladium‐ and copper‐based supramolecular capsules, and demonstrate that the nature of the bridging metal nodes in these discrete self‐assembled prisms strongly influences 1O2 generation at the Zn–porphyrin centers. The PdII‐based prism is a particularly robust photosensitizer, whereas the CuII self‐assembled prism is a dormant photosensitizer that could be switched to a ON state upon disassembly of the suprastructure. Furthermore, the well‐defined cavity within the prisms allowed encapsulation of pyridine‐based ligands and fullerene derivatives, which led to a remarkable guest tuning of the 1O2 production.
Effect of Crystal Packing on the Thermosalient Effect of the Pincer‐Type Diester Naphthalene‐2,3‐diyl‐bis(4‐fluorobenzoate): A New Class II Thermosalient Solid
Authors: Tamboli Majid I. , Karothu Durga Prasad , Shashidhar Mysore S. , Gonnade Rajesh G. , Naumov Panče 
Published: January 2018

AbstractThe pincer‐like double ester naphthalene‐2,3‐diyl‐bis(4‐fluorobenzoate) (2) is pentamorphic. Upon heating crystals of form I to below their melting point (441–443 K), they undergo a phase transition accompanied by a thermosalient effect, that is, rare and visually striking motility whereby the crystals jump or disintegrate. The phase transition and the thermosalient effect are reversible. Analysis of the crystal structure revealed that form I is a class II thermosalient solid. Crystals of form III also underwent a reversible phase transition in the temperature range of 160 to 170 K; however, they were not thermosalient. Comparison of the structures and the mechanical responses of the two polymorphs revealed that the thermosalient effect of form I was due to reversible closing and opening of the arms of the diester molecules in a tweezer‐like action.
A BODIPY‐Based Fluorescent Probe to Visually Detect Phosgene: Toward the Development of a Handheld Phosgene Detector
Authors: Sayar Melike , Karakuş Erman , Güner Tuğrul , Yildiz Busra , Yildiz Umit Hakan , Emrullahoğlu Mustafa 
Published: January 2018

AbstractA boron‐dipyrromethene (BODIPY)‐based fluorescent probe with a phosgene‐specific reactive motif shows remarkable selectivity toward phosgene, in the presence of which the nonfluorescent dye rapidly transforms into a new structure and induces a fluorescent response clearly observable to the naked eye under ultraviolet light. Given that dynamic, a prototypical handheld phosgene detector with a promising sensing capability that expedites the detection of gaseous phosgene without sophisticated instrumentation was developed. The proposed method using the handheld detector involves a rapid response period suitable for issuing early warnings during emergency situations.
Theoretical Investigations on the Mechanistic Aspects of O2 Activation by a Biomimetic Dinitrosyl Iron Complex
Authors: Banerjee Ambar , Sen Souloke , Paul Ankan 
Published: January 2018

AbstractThough dinitrosyl‐iron complexes (DNICs) are largely believed to act as NO carriers, several experiments on model DNICs have suggested that they can also act as nitrating agents in presence of dioxygen. Oxygen activation by DNICs has been implicated as a possible route for protein tyrosine nitration (PTN), which leads to neurodegenerative disorders. Herein using static and dynamic theoretical techniques we unravel a previously unknown dual state mechanistic paradigm for dioxygen activation of a biomimetic nitrating DNIC complex leading to phenolic nitration. Our computations reveal that the model DNIC, the ground electronic state of which is singlet, has a low‐lying triplet state and an inherent singlet–triplet spin‐crossover of DNICs can be triggered by fluxional changes in the bite angle of the two NO ligands. The presence of a low‐lying triplet state in the DNIC affords an avenue for O2 activation other than a direct O2 activation by O2‐induced spin‐crossover of the singlet ground state. These two low‐lying channels facilitate the formation of a peroxynitrite species. Nitration of phenolic substrates is facilitated by the release of NO2. The corresponding minimum energy crossing points (MECP) have been located. Along the reaction path, the changes in the electronic structure scenarios have been studied and interpreted. Our report also sheds light on the plausible mechanistic pathway of PTN by reactive species formed once O2 activation by DNICs have been achieved.
Formation of Cyanamide–Glyoxal Oligomers in Aqueous Environments Relevant to Primeval and Astrochemical Scenarios: A Spectroscopic and Theoretical Study
Authors: Lavado Nieves , García de la Concepción Juan , Babiano Reyes , Cintas Pedro 
Published: January 2018

AbstractThe condensation of cyanamide and glyoxal, two well‐known prebiotic monomers, in an aqueous phase has been investigated in great detail, demonstrating the formation of oligomeric species of varied structure, though consistent with generalizable patterns. This chemistry involving structurally simple substances also illustrates the possibility of building molecular complexity under prebiotically plausible conditions, not only on Earth, but also in extraterrestrial scenarios. We show that cyanamide–glyoxal reactions in water lead to mixtures comprising both acyclic and cyclic fragments, largely based on fused five‐ and six‐membered rings, which can be predicted by computation. Remarkably, such a mixture could be identified using high‐resolution electrospray ionization (ESI) mass spectrometry and spectroscopic methods. A few mechanistic pathways can be postulated, most involving the intermediacy of glyoxal cyanoimine and further chain growth, thus increasing the diversity of the observed products. This rationale is supported by theoretical analyses with clear‐cut identification of all of the stationary points and transition‐state structures. The properties and structural differences of oligomers obtained under thermodynamic conditions in water as opposed to those isolated by precipitation from organic media are also discussed.
Cp*Co(III)‐Catalyzed Coupling of Benzamides with α,β‐Unsaturated Carbonyl Compounds: Preparation of Aliphatic Ketones and Azepinones
Authors: Chirila Paula G. , Adams Joshua , Dirjal Amir , Hamilton Alex , Whiteoak Christopher J. 
Published: January 2018

AbstractA Cp*CoIII‐catalyzed C−H functionalization of benzamide substrates with α,β‐unsaturated ketones has been optimized, providing a facile route towards aliphatic ketone products. When employing α,β‐unsaturated aldehydes as coupling partners, under the optimized protocol, a cascade reaction forming azepinones has also been developed. Finally, DFT studies have demonstrated how stabilization of a metallo‐enol intermediate when employing α,β‐unsaturated ketones is the driving force leading to the observed aliphatic ketone product rather than olefinic products reported using α,β‐unsaturated esters as coupling partners.
Structural and Magnetic Variations in a Family of Isoskeletal, Oximate‐Bridged {MnIV2MIII} Complexes (MIII=Mn, Gd, Dy)
Authors: Alaimo Alysha A. , Worrell Anne , Gupta Sayak Das , Abboud Khalil A. , Lampropoulos Christos , Christou George , Stamatatos Theocharis C. 
Published: January 2018

AbstractThe self‐assembly reaction of MnCl2⋅4H2O, acenaphthenequinone dioxime (acndH2) and NEt3 has yielded an unprecedented, linear {MnIV2MnIII} complex with an S=5 spin ground state and non‐SMM behavior. The targeted replacement of the central MnIII ion with GdIII and DyIII ions has successfully increased the S and turned on the SMM dynamics without affecting the core structure and the nature of the magnetic exchange interactions.