bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxorubicin hinders DNA condensation promoted by the protein bovine serum albumin (BSA)
Authors: Lima C. H. M. , de Paula H. M. C. , da Silva L. H. M. , Rocha M. S. 
Published: October 2017

AbstractIn this work, we have studied the interaction between the anticancer drug doxorubicin (doxo) and condensed DNA, using optical tweezers. To perform this task, we use the protein bovine serum albumin (BSA) in the working buffer to mimic two key conditions present in the real intracellular environment: the condensed state of the DNA and the abundant presence of charged macromolecules in the surrounding medium. In particular, we have found that, when doxo is previously intercalated in disperse DNA, the drug hinders the DNA condensation process upon the addition of BSA in the buffer. On the other hand, when bare DNA is firstly condensed by BSA, doxo is capable to intercalate and to unfold the DNA condensates at relatively high concentrations. In addition, a specific interaction between BSA and doxo was verified, which significantly changes the chemical equilibrium of the DNA–doxo interaction. Finally, the presence of BSA in the buffer stabilizes the double‐helix structure of the DNA–doxo complexes, preventing partial DNA denaturation induced by the stretching forces.
Synthesis and structure analysis of ferrocene‐containing pseudopeptides
Authors: Angelici Gaetano , Górecki Marcin , Pescitelli Gennaro , Zanna Nicola , Monari Magda , Tomasini Claudia 
Published: October 2017

AbstractFerrocene with its aromaticity and facile redox properties is an attractive moiety to be incorporated into functional moieties. Medicinal applications of ferrocene are well known and ferrocene itself shows cytotoxic and antianemic properties. In this article, we will describe the synthesis and the structure analysis of two pseudopeptides containing a ferrocene moiety as N‐terminal group. After purification, Fc‐l‐Phe‐d‐Oxd‐OBn [l‐Phel‐phenylalanine; d‐Oxd(4R,5S)‐4‐Methyl‐5‐carboxy‐oxazolidin‐2‐one] appears as bright brown solid that spontaneously forms brown needles. The X‐ray diffraction of the crystals shows the presence of strong π interactions between the ferrocenyl moiety and the phenyl rings, while no NH•••OC hydrogen bonds are formed. This result is confirmed by FT‐IR and 1H NMR analysis. In contrast, both FT‐IR and 1H NMR analysis suggest that Fc‐(l‐Phe‐d‐Oxd)2‐OBn forms a turn conformation stabilized by intramolecular NH•••OC hydrogen bonds in solution. Chiroptical spectroscopies (ECD and VCD) substantially confirmed the absence of a well‐defined folded structure. The presence of the Fc moiety is responsible for specific ECD signals, one of which displayed pronounced temperature dependence and is directly related with the helicity assumed by the Fc core. Solid‐state ECD spectra were recorded and rationalized on the basis of the X‐ray geometry and quantum‐mechanical calculations.
Preparation and evaluation of a chiral HPLC stationary phase based on cone calix[4]arene functionalized at the upper rim with l‐alanine units
Authors: Yaghoubnejad Sadegh , Tabar Heydar Kourosh , Ahmadi Seyyed Hamid , Zadmard Reza 
Published: October 2017

AbstractHere we report a new chiral stationary phase (CSP) immobilized on silica gel based on cone calix[4]arene functionalized at the upper rim with two l‐alanine units as new chiral selector that has been used in high‐performance liquid chromatography. The CSP was prepared by covalently bonding the allyl groups at the lower rim of calix[4]arene to silica gel by thiol‐ene click chemistry reaction. Elemental analysis of the CSP showed that 120 μmol of chiral selector bonded per gram of silica gel. 1‐Hexene was used for end‐capping of unreacted mercapto groups on silica gel. Since the CSP is chemically bonded to the silica, it can be used in the normal‐phase and reversed‐phase mode and with halogenated solvents as mobile phases, if desired. The chromatographic performance of the CSP was evaluated in the enantioseparation of the 3,5‐dinitrobenzoyl derivatives of some amino acids, diclofop‐methyl and dl‐mandelic acid.
Lanthanoid Pseudo‐Grignard Reagents: A Major Untapped Resource
Authors: Ali Safaa H. , Deacon Glen B. , Junk Peter C. , Hamidi Shima , Wiecko Michal , Wang Jun 
Published: October 2017

AbstractPseudo‐Grignard reagents PhLnI (Ln=Yb, Eu), readily prepared by the oxidative addition of iodobenzene to ytterbium or europium metal at −78 °C in tetrahydrofuran (THF) or 1,2‐dimethoxyethane (DME), react with a range of bulky N,N′‐bis(aryl)formamidines to generate an extensive series of LnII or more rarely LnIII complexes, namely [Eu(DippForm)I(thf)4]⋅thf (1), [{EuI2(dme)2}2] (2), [Eu(XylForm)I(dme)2]⋅0.5 dme (3 a), [Eu(XylForm)I(dme)(μ‐dme)]n (3 b), [{Eu(XylForm)I(μ‐OH)(thf)2}2] (4), [Yb(DippForm)I(thf)3]⋅thf (5 a), [Yb(DippForm)I2(thf)3]⋅2 thf (5 b), [{Yb(MesForm)I(thf)2}2] (6), [{Yb(XylForm)I(thf)2}2] (7 a), and [Yb(XylForm)2I(dme)]⋅dme (7 b) {(Form=ArNCHNAr; XylForm (Ar=2,6‐Me2C6H3), MesForm (Ar=2,4,6‐Me3C6H2), DippForm (Ar=2,6‐iPr2C6H3)}. Reaction of PhEuI and MesFormH in DME consistently gave 2, and reaction with XylFormH in THF gave 4. Europium complexes 1 and 3 a are seven‐coordinate divalent monomers, whilst 3 b is a seven‐coordinate dme‐bridged polymer. Complex 5 a of the smaller YbII is a six‐coordinate monomer, but the related 6 and 7 a are six‐coordinate iodide‐bridged dimers. 4 is a trivalent seven‐coordinate hydroxide‐bridged dimer, whereas complexes 5 b and 7 b are seven‐coordinate monomeric YbIII derivatives. A characteristic structural feature is that iodide ligands are cisoid to the formamidinate ligand. To illustrate the synthetic scope of the pseudo‐Grignard reagents, [Yb(Ph2pz)I(thf)4] (Ph2pz=3,5‐diphenylpyrazolate) was oxidised with 1,2‐diiodoethane to afford seven‐coordinate monomeric pyrazolato‐ytterbium(III) iodide [Yb(Ph2Pz)I2(thf)3] (8) in high yield, whilst metathesis between [Yb(Ph2pz)I(thf)4] and NaCp (Cp=C5H5) gave [Yb(C5H5)(Ph2pz)(thf)]n (9), a nine‐coordinate η5:η5‐Cp‐bridged coordination polymer. Reaction of the pseudo‐Grignard reagent MeYbI with KN(SiMe3)2 gave [K(dme)4][Yb{N(SiMe3)2}3] (10) with a charge‐separated three‐coordinate homoleptic [Yb{N(SiMe3)2}3]− anion, a complex that could be obtained in high yield by deliberate synthesis from YbI2 and KN(SiMe3)2 in DME.
A Photo‐Responsive Organogel Based on Pyrene‐Substituted Acylhydrazone Derivative
Authors: Chai Qing , Wei Jue , Bai Binglian , Wang Haitao , Li Min 
Published: October 2017

AbstractA new simple pyrene‐substituted acylhydrazone derivative, 4‐(3,4‐dioctyloxy) phenyl‐1‐pyrene acylhydrazone (PAH‐8), was designed and synthesized. The PAH‐8 can form thermo‐reversible organogel in DMSO, and shows gelation‐induced enhanced fluorescence emission. Xerogel exhibits ribbon‐like fibrous aggregates with widths of 0.5‐1 μm. The PAH‐8 organogel indicates photo‐responsive behaviors due to the trans‐cis isomerizations of ‐C=N‐ bond upon exposure to visible or UV light. Upon visible light irradiation, the partial trans‐cis isomerization of the ‐C=N‐ bond causes the fiber morphology to disappear, resulting in gel‐sol transition, whereas the PAH‐8 organogel exhibits few photoisomerizations from trans to cis transition without breakage of the gel state upon UV light irradiation.
Comparison of Maximum Common Subgraph Isomorphism Algorithms for the Alignment of 2D Chemical Structures
Authors: Duesbury Edmund , Holliday John , Willett Peter 
Published: October 2017

AbstractThe identification of the largest substructure in common when two (or more) molecules are overlaid is important for several applications in chemoinformatics, and can be implemented using a maximum common subgraph (MCS) algorithm. Many such algorithms have been reported, and it is important to know which are likely to be the useful in operation. A detailed comparison was hence conducted of the efficiency (in terms of CPU time) and the effectiveness (in terms of the size of the MCS identified) of eleven MCS algorithms, some of which were exact and some of which were approximate in character. The algorithms were used to identify both connected and disconnected MCSs on a range of pairs of molecules. The fastest exact algorithms for the connected and disconnected problems were found to be the fMCS and MaxCliqueSeq algorithms, respectively, while the ChemAxon_MCS algorithm was the fastest approximate algorithm for both types of problem.
In Silico Prediction of Compounds Binding to Human Plasma Proteins by QSAR Models
Authors: Sun Lixia , Yang Hongbin , Li Jie , Wang Tianduanyi , Li Weihua , Liu Guixia , Tang Yun 
Published: October 2017

AbstractPlasma protein binding (PPB) is a significant pharmacokinetic property of compounds in drug discovery and design. Due to the high cost and time‐consuming nature of experimental assays, in silico approaches have been developed to assess the binding profiles of chemicals. However, because of unambiguity and the lack of uniform experimental data, most available predictive models are far from satisfactory. In this study, an elaborately curated training set containing 967 diverse pharmaceuticals with plasma‐protein‐bound fractions (fb) was used to construct quantitative structure–activity relationship (QSAR) models by six machine learning algorithms with 26 molecular descriptors. Furthermore, we combined all of the individual learners to yield consensus prediction, marginally improving the accuracy of the consensus model. The model performance was estimated by tenfold cross validation and three external validation sets comprising 242 pharmaceutical, 397 industrial, and 231 newly designed chemicals, respectively. The models showed excellent performance for the entire test set, with mean absolute error (MAE) ranging from 0.126 to 0.178, demonstrating that our models could be used by a chemist when drawing a molecular structure from scratch. Meanwhile, structural descriptors contributing significantly to the predictive power of the models were related to the binding mechanisms, and the trend in terms of their effects on PPB can serve as guidance for the structural modification of chemicals. The applicability domain was also defined to distinguish favorable predictions from unfavorable predictions.
Optimization of Substrate‐Analogue Furin Inhibitors
Authors: Ivanova Teodora , Hardes Kornelia , Kallis Stephanie , Dahms Sven O. , Than Manuel E. , Künzel Sebastian , Böttcher‐Friebertshäuser Eva , Lindberg Iris , Jiao Guan‐Sheng , Bartenschlager Ralf , Steinmetzer Torsten 
Published: October 2017

AbstractThe proprotein convertase furin is a potential target for drug design, especially for the inhibition of furin‐dependent virus replication. All effective synthetic furin inhibitors identified thus far are multibasic compounds; the highest potency was found for our previously developed inhibitor 4‐(guanidinomethyl)phenylacetyl‐Arg‐Tle‐Arg‐4‐amidinobenzylamide (MI‐1148). An initial study in mice revealed a narrow therapeutic range for this tetrabasic compound, while significantly reduced toxicity was observed for some tribasic analogues. This suggests that the toxicity depends at least to some extent on the overall multibasic character of this inhibitor. Therefore, in a first approach, the C‐terminal benzamidine of MI‐1148 was replaced by less basic P1 residues. Despite decreased potency, a few compounds still inhibit furin in the low nanomolar range, but display negligible efficacy in cells. In a second approach, the P2 arginine was replaced by lysine; compared to MI‐1148, this furin inhibitor has slightly decreased potency, but exhibits similar antiviral activity against West Nile and Dengue virus in cell culture and decreased toxicity in mice. These results provide a promising starting point for the development of efficacious and well‐tolerated furin inhibitors.
A Thorough QT Study to Evaluate the Effects of Supratherapeutic Doses of Ledipasvir on the QTc Interval in Healthy Subjects
Authors: German Polina , Mathias Anita , Brainard Diana M. , Song Qinghua , Ling John , Kearney Brian P. 
Published: October 2017

AbstractThis study evaluated the effect of supratherapeutic exposure of the anti‐HCV drug ledipasvir on the QTc interval in healthy subjects. Sixty healthy volunteers were randomized to receive twice‐daily blinded ledipasvir (120 mg) or placebo, administered for 10 days each, or single doses of open‐label moxifloxacin (400 mg). Serial plasma samples for ledipasvir concentration analysis were collected after each treatment. Triplicate time‐matched electrocardiograms were collected at baseline and after each treatment. Change from baseline in the QTc for ledipasvir or moxifloxacin versus placebo was determined using several correction formulas (primary: QTcF [Fridericia's]; secondary: QTcN [population] and QTcI [individual]). Pharmacokinetics and exposure–QTc relationships were evaluated. Ledipasvir AUC0–24 and Cmax achieved approximately 3.7‐fold and 4.2‐fold, respectively, above exposures observed following administration of ledipasvir/sofosbuvir (90/400 mg) to HCV‐infected patients. There was a lack of effect of supratherapeutic ledipasvir on QTc intervals using all correction methods (upper bound of the 2‐sided 90%CIs for the mean difference in time‐matched baseline‐corrected QTc between ledipasvir versus placebo < 10 milliseconds at all times). The lower bound of the 2‐sided 96.67%CI for the mean difference in moxifloxacin versus placebo was >5 milliseconds, thereby establishing assay sensitivity. Categorical analyses did not demonstrate clinically relevant effects of ledipasvir on QTc intervals or other electrocardiogram parameters. No relationships between ledipasvir plasma concentration and QTc interval were observed. Ledipasvir does not prolong QTc interval. Based on these results and a previous TQT evaluation for sofosbuvir, the fixed‐dose combination regimen of ledipasvir/sofosbuvir is not expected to prolong the QTc interval.
Lewis Rat Model of Experimental Autoimmune Encephalomyelitis
Authors: Pitarokoili Kalliopi , Ambrosius Bjoern , Gold Ralf 
Published: October 2017

AbstractIn this unit, we describe in detail the most common methods used to break immunological tolerance for central myelin antigens and induce experimental autoimmune encephalomyelitis (EAE) in Lewis rats as an animal model of multiple sclerosis. The resulting disease course ranges from an acute monophasic disease to a chronic relapsing or chronic progressive course, which strongly resembles the human disease. These models enable the study of cellular and humoral autoimmunity against major antigenic epitopes of the myelin basic protein, myelin oligodendrocyte glycoprotein, or proteolipid protein. We provide an overview of common immunization protocols for induction of active and passive EAE, assessment and analysis of clinical score, preparation and purification of myelin basic protein, and derivation of neuroantigen‐specific rat T cell lines. Finally, we describe the major clinical characteristics of these models. © 2017 by John Wiley & Sons, Inc.
Routing protocol development for quality of service optimization of video‐on‐demand system over mobile ad hoc networks
Authors: Ghalib Sadiq , Mishra Rajesh , Baghel Anurag Singh , Sharma Sandeep 
Published: October 2017

SummaryA video‐on‐demand (VoD) application system over mobile ad hoc networks typically requires particular quality of service (QoS) parameters to be achieved. In this paper, we have proposed a novel QoS‐based routing protocol called as mobile VoD protocol. This protocol has been developed for improving the QoS of the mobile VoD system (normal Mobi_VoD approach). The protocol uses customer caching scheme for storing the first fragment of the entire video in the mobile customers and thereafter broadcast them when the new mobile customers missed the portion of the already transmitted first fragment for reducing the service delay of the customer, consequently optimizing QoS parameters. Various scenarios have been studied, and the efficacy of simulation results proves that the proposed system architecture in which the mobile customers use an ad hoc network caching scheme (mobile VoD protocol) is more efficient and performs better than the existing system (ad hoc on‐demand distance vector protocol) when compared in terms of QoS parameters such as the end‐to‐end delay, energy consumption, packet delivery ratio, throughput, and overhead.
Performance analysis of load balancing in OFDMA cellular networks with inter‐cell relay
Authors: Lu Weifeng , Chen Siguang , Yang Lijun 
Published: October 2017

SummaryTo balance and improve the resource utilization of the orthogonal frequency division multiple access (OFDMA) cellular networks, we switch parts of the edge users in overloaded cell to the adjacent light‐loaded cells by using the inter‐cell relay. The efficiency of traditional load balancing method based on the cell switching is low and in some cases, will occur the collision load problem. In this paper, we propose a new load balancing scheme based on inter‐cell relay in downlink OFDMA cellular networks. Besides, we put forward a new spectrum division scheme to reduce interference and improve spectrum efficiency. According to the formulas derived from the model we established, we can obtain the signal interference ratio and further to calculate the amount of remaining subcarrier and the throughput of the system. Finally, through numerical calculation and simulation, the result shows that the load balancing and spectrum division schemes can remit the resource stress of the overloaded cell and improve the spectrum utilization in adjacent cells.
Potential paths for male‐mediated gene flow to and from an isolated grizzly bear population
Authors: Peck Christopher P. , van Manen Frank T. , Costello Cecily M. , Haroldson Mark A. , Landenburger Lisa A. , Roberts Lori L. , Bjornlie Daniel D. , Mace Richard D. 
Published: October 2017

AbstractFor several decades, grizzly bear populations in the Greater Yellowstone Ecosystem (GYE) and the Northern Continental Divide Ecosystem (NCDE) have increased in numbers and range extent. The GYE population remains isolated and although effective population size has increased since the early 1980s, genetic connectivity between these populations remains a long‐term management goal. With only ~110 km distance separating current estimates of occupied range for these populations, the potential for gene flow is likely greater now than it has been for many decades. We sought to delineate potential paths that would provide the opportunity for male‐mediated gene flow between the two populations. We first developed step‐selection functions to generate conductance layers using ecological, physical, and anthropogenic landscape features associated with non‐stationary GPS locations of 124 male grizzly bears (199 bear‐years). We then used a randomized shortest path (RSP) algorithm to estimate the average number of net passages for all grid cells in the study region, when moving from an origin to a destination node. Given habitat characteristics that were the basis for the conductance layer, movements follow certain grid cell sequences more than others and the resulting RSP values thus provide a measure of movement potential. Repeating this process for 100 pairs of random origin and destination nodes, we identified paths for three levels of random deviation (θ) from the least‐cost path. We observed broad‐scale concordance between model predictions for paths originating in the NCDE and those originating in the GYE for all three levels of movement exploration. Model predictions indicated that male grizzly bear movement between the ecosystems could involve a variety of routes, and verified observations of grizzly bears outside occupied range supported this finding. Where landscape features concentrated paths into corridors (e.g., because of anthropogenic influence), they typically followed neighboring mountain ranges, of which several could serve as pivotal stepping stones. The RSP layers provide detailed, spatially explicit information for land managers and organizations working with land owners to identify and prioritize conservation measures that maintain or enhance the integrity of potential areas conducive to male grizzly bear dispersal.
Raman, X‐Ray Fluorescence Spectroscopies and Graphene Oxide Modified Screen Printed Electrodes to Identify the Pigments and Earth Present in Ancient Leather Samples
Authors: Valentini Federica , Bicchieri Marina , Calcaterra Andrea , Talamo Maurizio 
Published: October 2017

AbstractMicro‐Raman and X‐Ray Fluorescence combined with electrochemical techniques proved to be suitable for the unambiguous identification of the green pigment in a very deteriorated historical leather. The colouring matter resulted in a mixture of blue and yellow. Raman identified the blue indigo, whereas iron and arsenic were identified by XRF. The redox status of these two elements was investigated by Square Wave Cathodic Stripping Voltammetry (SWCSV). Results demonstrated the presence of As(III), probably As2S3 (orpiment), and Fe(III), characterising the red earths. The quantitative results obtained by SWCSV were also confirmed for Fe and As by ICP‐MS (Inductively Coupled Plasma Mass spectrometry). Voltammetric techniques, applied here for the identification of the redox status of the elements, contained in pigments, are useful to understand two important aspects: the chemical‐physical composition of the colors and the best strategy to be applied for the preservation of the pigments in ancient/deteriorated artwork objects.
A Dendrimer Supported Electrochemical Immunosensor for the Detection of Alpha‐feto protein – a Cancer Biomarker
Authors: Idris Azeez O. , Mabuba Nonhlangabezo , Arotiba Omotayo A. 
Published: October 2017

AbstractThe electrochemical detection of alpha‐feto protein based on novel gold nanoparticles‐ poly(propylene imine) dendrimer platform is reported. The platform was prepared by co‐electrodeposition of gold nanoparticles and generation 3 poly (propylene imine) dendrimer on a glassy carbon electrode. Each modifying step was characterised by cyclic voltammetry and electrochemical impedance spectroscopy. The electrochemical measurements showed that the platform was stable, conducting and exhibited reversible electrochemistry. Results obtained from the electrochemical impedance spectroscopy interrogation in [Fe(CN)63−/4−] redox probe showed a marked reduction in charge transfer resistance (Rct) after each modification step. The immunosensor was prepared by immobilisation of a probe anti‐alpha feto protein (AFP) on the platform for 3 hrs at 35 °C followed by blocking the surface with bovine serum albumin to minimise non‐specific binding. The prepared immunosensor was used to detect AFP over a wide concentration range from 0.005 to 500 ng/mL and detection limits of 0.0022 and 0.00185 ng/mL were obtained for SWV and EIS measurements respectively. The immunosensor gave good stability over a period of fourteen days when stored at 4 °C.
Putative Risk Factors for Non‐Suicidal Self‐Injury in Eating Disorders
Authors: Vieira Ana Isabel , Machado Bárbara C. , Machado Paulo P.P. , Brandão Isabel , Roma‐Torres António , Gonçalves Sónia 
Published: October 2017

AbstractEvidence suggests a common association between eating disorders (EDs) and non‐suicidal self‐injury (NSSI). The present study aimed to investigate the potential risk factors for NSSI among ED patients. We assessed 245 ED patients with the Oxford Risk Factor Interview for ED. The results showed that 33% of ED patients reported NSSI in their lifetime. NSSI appeared to occur more frequently among binge eating/purging type ED patients than among patients with other ED and to be related to a more severe eating pathology. A younger age at the onset of eating problems, more negative self‐evaluation, suicide attempts, substance abuse, parents' low weight, family tension at mealtime, parental alcohol problems, childhood abuse, peer aggression, and negative antecedent life events were more common among patients with co‐occurring EDs and NSSI than among patients without NSSI. The results may inform the risk assessment and treatment of NSSI in EDs in the early detection period. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.