bluuebunny/crossref_metadata_2025_split huggingface dataset:
Covalent or Non‐Covalent? A Mechanistic Insight into the Enantioselective Brønsted Acid Catalyzed Dearomatization of Indoles with Allenamides
Authors: Giacinto Pietro , Bottoni Andrea , Garelli Andrea , Miscione Gian Pietro , Bandini Marco 
Published: April 2018

AbstractThe reaction mechanism of the enantioselective Brønsted acid catalyzed dearomatization of C(2),C(3)‐disubstituted indoles with allenamides is investigated by means of density functional theory (DFT) calculations and ESI‐MS analysis. The first step of the process (rate‐determining step) is the formation of a covalent adduct between allenamide and the chiral organo‐promoter. The resulting chiral α‐amino allylic phosphate undergoes dearomative condensation with indoles. In the first step, the indole moiety remains bonded to the catalyst through strong hydrogen contacts. It can take on two different orientations that make the Re or Si prochiral face available to the subsequent electrophilic attack of allenamide. The attack on the indole faces originates two reaction paths leading to different stereoisomeric products, which differ in the configuration of the new stereocenter at the C3‐indole position.
Quantifying the Sub‐Cellular Distributions of Gold Nanospheres Taken Up by Cells through Stepwise, Site‐Selective Etching
Authors: Huo Da , Xia Younan 
Published: April 2018

AbstractA quantitative understanding of the sub‐cellular distributions of nanospheres taken up by cells is of key importance to the development of effective nanomedicine. With gold nanospheres as a model system, here we demonstrate, for the first time, how to quantify the numbers of nanospheres bound to plasma membrane, accumulated in cytosol, and entrapped in endo‐lysosomes, respectively, through stepwise, site‐selective etching. Our results indicate that the chance for nanospheres to escape from endo‐lysosomes is insensitive to the presence of targeting ligand although ligand–receptor binding has been documented as a critical factor in triggering internalization. Furthermore, the presence of serum proteins is shown to facilitate the binding of nanospheres to plasma membrane lacking the specific receptor. Collectively, these findings confirm the potential of stepwise etching in quantitatively analyzing the sub‐cellular distributions of nanospheres taken up by cells in an effort to optimize the therapeutic effect.
Porous Single‐Crystalline CdSe Nanobelts: Cation‐Exchange Synthesis and Highly Selective Photoelectric Sensing toward Cu2+
Authors: Guo Zheng , Su Yao , Li Yi‐Xiang , Li Gang , Huang Xing‐Jiu 
Published: April 2018

AbstractPorous single‐crystalline nanostructures are of tremendous interest for their application in the catalytic, electronic and sensing fields due to their large active surfaces, favorable diffusion, and good electronic transport. Despite the recent advances of various other components, photoelectric chalcogenides remain almost undeveloped. The present study contributes a facile strategy to prepare porous single‐crystalline CdSe nanobelts through a cation‐exchange reaction, in which ZnSe⋅0.5 N2H4 hybrid nanobelts are employed as precursors. The detailed characterizations indicate the preservation of the belt‐like morphology of the precursors due to the spatial confinement effect, which arises from the coated surfactant layer during the cation‐exchange process. Simultaneously, CdSe nanobelts with porous and single‐crystalline structures are formed following a complete exchange between Zn2+ and Cd2+, the release of N2H4, and the atomic arrangement. The native photoelectric properties of the as‐prepared porous single‐crystalline CdSe nanobelts are systematically addressed based on the nanodevices fabricated with a single nanobelt and assembled nanobelt array. The results indicate that they present a rapid, stable, and repeatable photoelectric response. Moreover, as‐prepared nanobelts exhibit highly selective photoelectric sensing toward Cu2+ with a low detection limit down to 0.1 ppm. To illuminate this phenomenon, a possible sensing mechanism is also discussed.
Group 9 Metallacyclopentadienes as Key Intermediates in [2+2+2] Alkyne Cyclotrimerizations. Insight from Activation Strain Analyses
Authors: Dalla Tiezza Marco , Bickelhaupt F. Matthias , Orian Laura 
Published: April 2018

AbstractThe intramolecular oxidative coupling converting a bis‐acetylene complex of formula CpM (C2H2)2 (Cp=C5H5−; M=Co, Rh, Ir) into a 16‐electron metallacycle is studied in silico. This reaction is paradigmatic in acetylene [2+2+2] cycloaddition to benzene catalyzed by CpM fragments, being the step with the highest activation energy, and thus affecting the whole catalysis. Our activation strain and quantitative molecular orbital (MO) analyses elucidate the mechanistic details and reveal why cobalt performs better than rhodium and iridium catalysts outlining general principles for rational design of catalysts to be used in these processes.
Oral insulin does not alter gut microbiota composition of NOD mice
Authors: Kihl Pernille , Krych Lukasz , Buschard Karsten , Wesley Johnna D. , Kot Witold , Hansen Axel Kornerup , Nielsen Dennis S. , von Herrath Matthias G. 
Published: April 2018

AbstractBackgroundOral insulin as a preventive strategy and/or treatment of type 1 diabetes has been the target of much research. Producing oral insulins is a complex and challenging task, with numerous pitfalls, due to physiological, physical, and biochemical barriers. Our aim was to determine the impact of oral insulin on the delicate gut microbiota composition.MethodsFemale nonobese diabetic mice were given oral porcine insulin 2 times a week from 5 weeks of age for 4 weeks, and then subsequently once a week for 21 weeks, or until euthanized. The mice were divided into groups on a gluten‐reduced diet or a standard diet. Gut microbiota composition was analysed based on faecal samples, and the type 1 diabetes incidence of the mice was monitored.ResultsWe observed no influence of the oral porcine insulin on the gut microbiota composition of mice on a gluten‐reduced or a standard diet at 9 weeks of age. Also, the administration of oral insulin did not influence the incidence of type 1 diabetes at 30 weeks of age.ConclusionsOral porcine insulin does not alter the gut microbiota composition of nonobese diabetic mice on either a gluten‐reduced diet or standard diet. Also, the oral porcine insulin did not influence the incidence of type 1 diabetes in the groups.
Interfacial Thermal Resistance in Magnetocaloric Epoxy‐Bonded La‐Fe‐Co‐Si Composites
Authors: Sellschopp Kai , Weise Bruno , Krautz Maria , Cugini Francesco , Solzi Massimo , Helmich Lars , Hütten Andreas , Waske Anja 
Published: April 2018

AbstractMagnetocaloric composites made from La−Fe−Co−Si particles and an epoxy binder matrix exhibit mechanical stability and good magnetocaloric properties, but also a large characteristic time for thermal transport. Here, the origin of this large time constant is examined by comparing two measurement techniques, direct and contactless, to finite‐element simulations based on a tomographic dataset of the sample. The combination of the low thermal conductivity of the epoxy matrix and a thermal resistance at the interface between epoxy and La−Fe−Co−Si is shown to be in good agreement in simulations and experiments. The findings help to disentangle the role of the thermal conductivity and the interfacial thermal resistance for the heat flow in magnetocaloric composites. It is shown that the low thermal conductivity of the epoxy alone cannot explain the large time constant and possibilities for using the interfacial thermal resistance to tailor anisotropic thermal conductivity for directional heat transfer in magnetocaloric composites are presented.
The response strategy and the place strategy in a plus‐maze have different sensitivities to devaluation of expected outcome
Authors: Kosaki Yutaka , Pearce John M. , McGregor Anthony 
Published: April 2018

AbstractPrevious studies have suggested that spatial navigation can be achieved with at least two distinct learning processes, involving either cognitive map‐like representations of the local environment, referred to as the “place strategy”, or simple stimulus‐response (S‐R) associations, the “response strategy”. A similar distinction between cognitive/behavioral processes has been made in the context of non‐spatial, instrumental conditioning, with the definition of two processes concerning the sensitivity of a given behavior to the expected value of its outcome as well as to the response‐outcome contingency (“goal‐directed action” and “S‐R habit”). Here we investigated whether these two versions of dichotomist definitions of learned behavior, one spatial and the other non‐spatial, correspond to each other in a formal way. Specifically, we assessed the goal‐directed nature of two navigational strategies, using a combination of an outcome devaluation procedure and a spatial probe trial frequently used to dissociate the two navigational strategies. In Experiment 1, rats trained in a dual‐solution T‐maze task were subjected to an extinction probe trial from the opposite start arm, with or without prefeeding‐induced devaluation of the expected outcome. We found that a non‐significant preference for the place strategy in the non‐devalued condition was completely reversed after devaluation, such that significantly more animals displayed the use of the response strategy. The result suggests that the place strategy is sensitive to the expected value of the outcome, while the response strategy is not. In Experiment 2, rats with hippocampal lesions showed significant reliance on the response strategy, regardless of whether the expected outcome was devalued or not. The result thus offers further evidence that the response strategy conforms to the definition of an outcome‐insensitive, habitual form of instrumental behavior. These results together attest a formal correspondence between two types of dual‐process accounts of animal learning and behavior.
Hyperglycaemia is inversely correlated with live M. bovis BCG‐specific CD4+ T cell responses in Tanzanian adults with latent or active tuberculosis
Authors: Boillat‐Blanco Noémie , Tumbo Anneth‐Mwasi N. , Perreau Matthieu , Amelio Patrizia , Ramaiya Kaushik L. , Mganga Maliwaza , Schindler Christian , Gagneux Sebastien , Reither Klaus , Probst‐Hensch Nicole , Pantaleo Giuseppe , Daubenberger Claudia , Portevin Damien 
Published: April 2018

AbstractIntroductionThe rising prevalence of Diabetes mellitus (DM) in high TB‐endemic countries may adversely affect sustainability of TB control since DM constitutes a risk factor for development of active tuberculosis (TB). The impact of DM on TB specific adaptive immune responses remains poorly addressed, particularly in people living in Sub‐Saharan countries. We performed a functional characterization of TB specific cellular immune response in Tanzanian subjects with active or latent Mycobacterium tuberculosis (Mtb) infection stratified by their diabetic status.MethodsHIV negative active TB patients (≥18 years) with Xpert MTB/RIF positive pulmonary TB were included before starting TB treatment in Dar es Salaam, Tanzania between April and December 2013. HIV negative healthy controls latently infected with TB but without past TB history were also included. Active and latent TB patients were stratified in two groups according to their diabetic status. Peripheral Blood Mononuclear cells were stimulated with either live M. bovis BCG or Mtb‐specific peptide pools and analyzed by intracellular cytokine staining and polychromatic flow cytometry.ResultsOur results show a lower frequency of IFN‐γ CD4+ T cells in patients with active TB and DM compared to patients with active TB only after live M. bovis BCG (p = 0.04) but not after Mtb peptide pools re‐stimulation. Irrespective of TB status, level of glycaemia is selectively inversely correlated with IFN‐γ and TNF‐α CD4+ T cell production (p = 0.02 and p = 0.03) after live M. bovis BCG stimulation.ConclusionsThese results support the hypothesis that hyperglycaemia negatively impacts antigen processing and/or presentation of whole mycobacteria delaying secretion of key cytokines involved in TB immunity.
TOWARDS A QUANTITATIVE FRAMEWORK FOR EVALUATING THE EXPRESSIVE POWER OF CONCEPTUAL SYSTEM MODELS
Authors: Mordecai Yaniv , Dori Dov 
Published: April 2018

ABSTRACTConceptual models describe, explain, and specify the function, concept, structure, and behavior of complex systems. Quantifying the contribution of conceptual models to stakeholder understanding of the systems‐of‐interest has been a great challenge. This difficulty hinders justifying the use of formal modeling and simulation of complex systems and the adoption of a holistic model‐based systems engineering (MBSE) approach. The informativity of a model is the value of the information it conveys. Conceptual system model informativity is a key performance indicator for MBSE. We introduce MIA – Model Informativity Analysis – a quantitative, utility‐based, prescriptive approach for boosting conceptual models’ expressive power and measuring the value of the information they provide. We define an integrated informativity index, “I3”, which aggregates model scores of diverse informativity‐enhancing factors. We demonstrate various aspects of MIA with Object Process Methodology, OPM – a model‐based systems engineering paradigm and ISO‐19450 standard. OPM caters to quantitative informativity analysis due its formality, comprehensive function‐structure‐behavior modeling, and bimodal equivalent graphical‐textual representation.
In vitro degradation and in vivo toxicity of NanoMatrix3D® polycaprolactone and poly(lactic acid) nanofibrous scaffolds
Authors: Pogorielov Maksym , Hapchenko Andrii , Deineka Volodymyr , Rogulska Larysa , Oleshko Olexandr , Vodseďálková Kateřina , Berezkinová Liliana , Vysloužilová Lucie , Klápšťová Andrea , Erben Jakub 
Published: April 2018

AbstractNanofibrous materials present unique properties favorable in many biomedicine and industrial applications. In this research we evaluated biodegradation, tissue response and general toxicity of nanofibrous poly(lactic acid) (PLA) and polycaprolactone (PCL) scaffolds produced by conventional method of electrospinning and using NanoMatrix3D® (NM3D®) technology.Mass density, scanning electron microscopy and in vitro degradation (static and dynamic) were used for material characterization, and subcutaneous, intramuscular and intraperitoneal implantation – for in vivo tests. Biochemical blood analysis and histology were used to assess toxicity and tissue response. Pore size and fiber diameter did not differ in conventional and NM3D® PLA and PCL materials, but mass density was significantly lower in NM3D® ones. Scaffolds made by conventional method showed toxic effect during the in‐vivo tests due to residual concentration of chloroform that released with material degradation. NM3D® method allowed cleaning scaffolds from residual solutions that made them nontoxic and biocompatible. Subcutaneous, intramuscular and intraperitoneal implantation of PCL and PLA NM3D® electrospun nanofibrous scaffolds showed their appropriate cell conductive properties, tissue and vessels formation in all sites. Thus, NM3D® PCL and PLA nanofibrous electrospun scaffolds can be used in the field of tissue engineering, surgery, wound healing, drug delivery, and so forth, due to their unique properties, nontoxicity and biocompatibility. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2200‐2212, 2018.
A collagen based cryogel bioscaffold coated with nanostructured polydopamine as a platform for mesenchymal stem cell therapy
Authors: Razavi Mehdi , Hu Sophia , Thakor Avnesh S. 
Published: April 2018

AbstractCryo‐hydrogels (cryogels) are polymer hydrogels formed at sub‐zero temperatures. Bioscaffolds created from cryogels have interconnected macropores which allow for cell migration, tissue‐ingrowth, unhindered diffusion of solutes and mass transport of therapeutics. In this study, we developed collagen based cryogel bioscaffolds and coated them with polydopamine using a simple two‐step technique. Cryogel bioscaffolds were synthesized by collagen crosslinking at −20°C and exhibited a macroporous interconnected architecture with 75% ± 3% porosity. Two groups of pore sizes were observed: 300 ± 50 µm and 30 ± 10 µm in diameter. The addition of a polydopamine coating to cryogel bioscaffolds was confirmed using composition analysis. This resulted in a 41% ± 5% decrease in water uptake, 81% ± 10% decrease in swelling rate and 12% ± 3% decrease in their degree of dissolution (p < 0.05), with a 48% ± 2% increase in stiffness and 57% ± 5% increase in compressive strength (p < 0.05). Seeding adipose tissue‐derived mesenchymal stem cells (AD‐MSCs) into polydopamine coated‐cryogel bioscaffolds resulted in cells demonstrating a 52% ± 4% increase in viability and 33% ± 3% increase in proliferation when compared to AD‐MSCs seeded into uncoated‐cryogel bioscaffolds (p < 0.05). In summary, our novel polydopamine coated‐cryogel bioscaffold represents an efficient and low‐cost bioscaffold platform to support MSC therapies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2213‐2228, 2018.
Hypomagnesemia During Teriparatide Treatment in Osteoporosis: Incidence and Determinants
Authors: Bégin Marie-Josée , Ste-Marie Louis-Georges , Coupal Louis , Ethier Jean , Räkel Agnès 
Published: April 2018

ABSTRACT

In our clinical experience, we have encountered patients who developed hypomagnesemia after the introduction of teriparatide. Some trials have reported hypomagnesemia as an adverse event during teriparatide treatment, but this issue had never been studied specifically. Our objective was twofold: 1) determine the incidence of hypomagnesemia (serum magnesium &lt;0.7 mmol/L) associated with teriparatide in a retrospective cohort and 2) identify the predisposing factors to hypomagnesemia in this cohort. We reviewed the files of 53 patients treated for severe osteoporosis with teriparatide for 6 to 24 months between May 2008 and January 2016. Serum magnesium levels were measured at 0, 3, 6, 12, 18, and 24 months. In the full cohort, we observed an average decrease of serum magnesium of 0.075 mmol/L, 0.069 mmol/L, 0.085 mmol/L, 0.086 mmol/L (p &lt; 0.001) at 3, 6, 12 months, and at the end of the treatment, respectively. The cumulative incidence of hypomagnesemia during treatment with teriparatide was 35.9% (19 patients). Patients’ older age (71.1 versus 65.1 years; p = 0.05) and lower baseline level of magnesium before teriparatide treatment (0.81 mmol/L versus 0.85 mmol/L; p = 0.03) were significant risk factors for teriparatide-induced hypomagnesemia. The average decrease of serum magnesium was greater in the patients who developed hypomagnesemia compared with normomagnesemic patients at 3 months (0.110 mmol/L versus 0.054 mmol/L; p = 0.02), 6 months (0.139 mmol/L versus 0.036 mmol/L; p &lt; 0.001), and 12 months (0.156 mmol/L versus 0.048 mmol/L; p &lt; 0.001). Serum calcium, creatinine, and parathyroid hormone remained normal throughout the treatment period. We observed a statistically significant decrease in the serum magnesium levels in patients treated with teriparatide for severe osteoporosis. Older age and lower baseline magnesium were significant determinants of hypomagnesemia. Closer monitoring of serum magnesium level should be considered in these patients. © 2018 American Society for Bone and Mineral Research.
The caveolar membrane system in endothelium: From cell signaling to vascular pathology
Authors: Filippini Antonio , Sica Gigliola , D'Alessio Alessio 
Published: April 2018

AbstractCaveolae are 50‐ to 100‐nm cholesterol and glycosphingolipid‐rich flask‐shaped invaginations commonly observed in many terminally differentiated cells. These organelles have been described in many cell types and are particularly abundant in endothelial cells, where they have been involved in the regulation of certain signaling pathways. Specific scaffolding proteins termed caveolins, along with the more recently discovered members of the cavin family, represent the major protein components during caveolae biogenesis. In addition, multiple studies aimed to investigate the expression and the regulation of these proteins significantly contributed to elucidate the role of caveolae and caveolins in endothelial cell physiology and disease. The aim of this review is to survey recent evidence of the involvement of the caveolar network in endothelial cell biology and endothelial cell dysfunction.
4D flow MRI quantification of mitral and tricuspid regurgitation: Reproducibility and consistency relative to conventional MRI
Authors: Feneis Jennifer F. , Kyubwa Espoir , Atianzar Kimberly , Cheng Joseph Y. , Alley Marcus T. , Vasanawala Shreyas S. , Demaria Anthony N. , Hsiao Albert 
Published: April 2018

BackgroundIn patients with mitral or tricuspid valve regurgitation, evaluation of regurgitant severity is essential for determining the need for surgery. While transthoracic echocardiography is widely accessible, it has limited reproducibility for grading inlet valve regurgitation. Multiplanar cardiac MRI is the quantitative standard but requires specialized local expertise, and is thus not widely available. Volumetric 4D flow MRI has potential for quantitatively grading the severity of inlet valve regurgitation in adult patients.PurposeTo evaluate the accuracy and reproducibility of volumetric 4D flow MRI for quantification of inlet valvular regurgitation compared to conventional multiplanar MRI, which may simplify and improve accessibility of cardiac MRI.Study TypeThis retrospective, HIPAA‐compliant imaging‐based comparison study was conducted at a single institution.SubjectsTwenty‐one patients who underwent concurrent multiplanar and 4D flow cardiac MRI between April 2015 and January 2017.Field Strength/Sequences3T; steady‐state free‐precession (SSFP), 2D phase contrast (2D‐PC), and postcontrast 4D flow.AssessmentWe evaluated the intertechnique (4D flow vs. 2D‐PC), intermethod (direct vs. indirect measurement), interobserver and intraobserver reproducibility of measurements of regurgitant flow volume (RFV), fraction (RF), and volume (RVol).Statistical TestsStatistical analysis included Pearson correlation, Bland–Altman statistics, and intraclass correlation coefficients.ResultsThere was high concordance between 4D flow and multiplanar MRI, whether using direct or indirect methods of quantifying regurgitation (r = 0.813–0.985). Direct interrogation of the regurgitant jet with 4D flow showed high intraobserver consistency (r = 0.976–0.999) and interobserver consistency (r = 0.861–0.992), and correlated well with traditional indirect measurements obtained as the difference between stroke volume and forward outlet valve flow.Data Conclusion4D flow MRI provides highly reproducible measurements of mitral and tricuspid regurgitant volume, and may be used in place of conventional multiplanar MRI.Level of Evidence: 4Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2018;48:1147–1158.
How the influx of Chinese tourists affects national tourism behaviors: Evidence from Taiwan
Authors: Yang Chih‐Hai , Lo Pei‐Ling 
Published: April 2018

AbstractTaiwan implemented its tourism open policy for Chinese tourists in 2008, thereby inducing a skyrocketing‐growth of tourist arrivals from China in subsequent years. This paper examines the influence of Chinese tourist arrivals on national tourism in Taiwan. Based on individual‐level data in 2006–2013, empirical estimations find no crowding‐out effect on national tourism, whereas Taiwan's residents exhibit an increasing frequency of domestic trips. Crucially, residents lower their willingness to visit most of famous tourism sites that Chinese tourists prefer to visit, suggesting the increasing domestic tourists are crowded out from famous tourist attractions and, instead, visiting some local scenic sites.