bluuebunny/crossref_metadata_2025 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

In 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

Ferrocene 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

Here 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.
The development of a core syllabus for the teaching of oral anatomy, histology, and embryology to dental students via an international ‘Delphi Panel’
Authors: Moxham Bernard John , McHanwell Stephen , Berkovitz Barry
Published: October 2017

The formulation of core syllabuses for the biomedical sciences within medical and dental courses is partially driven by the need to cope with decreased time allocations for these subjects as a result of major curricular changes taking place worldwide. There is also a requirement to deal with the request for increased clinical relevance. In response to such demands, the International Federation of Associations of Anatomists (IFAA) is devising core syllabuses for the anatomical sciences relating to the education and training of both scientific and clinical professions. The process initially involves using Delphi Panels consisting of a team of anatomists, scientists, and clinicians who evaluate syllabus content in detail and accord each element/topic ‘essential,’ ‘important,’ ‘acceptable,’ or ‘not required’ status. Their conjectures, published on the IFAA website, provide merely a framework to enable other stakeholders to comment. The approach is international in scope, is conceptually ‘democratic,’ and is developmentally fluid in being readily available for amendment. The aim is to set internationally recognized standards and thus to provide guidelines concerning anatomical knowledge when engaged in course development. This article presents the deliberations of an IFAA Delphi Panel into a core syllabus for oral anatomy, histology, and embryology within the dental curriculum. Clin. Anat. 31:231–249, 2018. © 2017 Wiley Periodicals, Inc.
Conduct effective threat assessment to prevent violence
Authors: Hope Joan
Published: October 2017

OCALA, Fla. — After a campus shooting or other violent act, many people ask, “What made him snap?” “People don't just snap,” said Rebecca Bolante, Ph.D., C.R.C., C.T.M., director of threat management resources at Chemeketa Community College in Oregon. She spoke at a Campus Safety Symposium sponsored by the Association of Florida Colleges, along with Dave Benson, principal/owner at D.J. Benson & Associates; Rick Parfitt, chief of police and director of public safety at Florida SouthWestern State College; and Ryan Woods, captain of the Police Department at Santa Fe College in Florida.
Manage impact of marijuana legislation on your campus
Authors: McCarthy Claudine
Published: October 2017

JACKSONVILLE, Fla. — After several states passed legislation permitting recreational use of marijuana, college campuses in those states and beyond felt the impact. Private and public colleges and universities must rethink how they communicate community standards, educate students and staff, and address conduct violations, while clarifying mixed messages stemming from conflicting state and federal laws and the fluid environment of the emerging pot industry.
Be aware of suicide risk among female student‐veterans
Authors: Sutton Halley
Published: October 2017

Female veterans are 250 percent more likely to commit suicide than their civilian peers, according to a report from the Department of Veterans Affairs. The report, which analyzed more than 55 million veteran records from 1970–2014, found that female veterans aged 18–29 were the most likely to commit suicide, a prime age demographic for student‐veterans on campus. According to the report, an average of 20 veterans, both male and female, died from suicide each day in 2014, and the states with the highest suicide rates were Montana, Utah, Nevada, and New Mexico.
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

Pseudo‐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

A 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.
Traffic ‐and Industry‐Related Air Pollution Exposure Assessment in an Asian Megacity
Authors: Alvi Muhammad Usman , Chishtie Farrukh , Shahid Imran , Mahmud Tariq , Hussain Riaz
Published: October 2017

Like other Asian countries, Pakistan is facing the issue of air pollution due to rapid urbanization, enormous transportation increases, and other related human activities. Moreover, continuously increasing emission sources have not only raised pollutant concentrations but also their types, thus damaging both human health and the environment. Faisalabad is the third largest megacity of Pakistan and its state of air quality is getting worse due to factors such as industrialization, high traffic volumes, and extensive fossil‐fuel‐burning activities. This review article aims to highlight the present status of air pollution in this city with special reference to particulate matter, elemental profiles, gaseous pollutants, organic–inorganic particulate contents as well as their sources. The concentration levels of these entities were also compared with other national and international cities, and related environmental standards. It is found that current levels of these pollutants are beyond safety limits as specified by various environment protection agencies and organizations. Several weak aspects and gaps are also identified along with suggestions for improvements of the present situation and directions for future research.
Microbial Activity in Marine Sediments Exposed to Hexadecane: A Laboratory Study
Authors: Gamboa‐Muñoz Abril M. , García‐Cruz N. Ulises , Ramos‐Castillo Alejandra , Gold‐Bouchot Gerardo , Aguirre‐Macedo M. Leopoldina
Published: October 2017

Bacteria have developed metabolic pathways that allow them to use hydrocarbons as the source of carbon and energy, so that they now play a key role throughout the degradation of petroleum in natural environments. However, knowledge regarding the degradation of petroleum by microorganisms is far larger in soils than in marine environments. Hexadecane (HXD) is one of the most representative alkanes present in petroleum, and one of the most frequently used in laboratory trials to evaluate the degradation of hydrocarbons by microorganisms. In this study, the capacity for HXD degradation by microorganisms present in marine sediments collected at 15 and 200 m depth is determined experimentally. For 42 days, kinetics studies are carried out to measure the consumption of HXD. Every 7 days the number of colony forming units (CFU) and HXD concentration are determined. Additionally, a biomass sample for pyrosequencing is collected at the beginning of the experiment (t0), the time of maximum bacterial growth (t7ort21) and at the end of the experiment (t42). A higher HXD consumption rate is observed in sediments from 15 m with respect to sediments from 200 m depth. The major HXD consumption occurs within the first 7 days for the sediments from 15 m and within 21 days for the sediments from 200 m depth; the biomass concentration CFU follows the same profile. The non‐metric multidimensional scaling analysis of the non‐cultivable bacteria indicates differences between bacteria species composition at different depths, which is confirmed by bacterial identification by pyrosequencing.
Comparison of Maximum Common Subgraph Isomorphism Algorithms for the Alignment of 2D Chemical Structures
Authors: Duesbury Edmund , Holliday John , Willett Peter
Published: October 2017

The 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

Plasma 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

The 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

This 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

In 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

A 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

To 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

For 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.
Synthesis, Electrochemical and Photophysical Properties of 2,4,6‐Tripyridyl‐1,3,5‐Triazine‐Bridged Trinuclear Diimine Rhenium(I) Tricarbonyl Complexes
Authors: Lee Mandy M. , Lin Ju‐Ling , Chang Che‐Wei , Hung Chen‐Yen , Chen Chih‐Wei , Hsu Chao‐Ping , Sun Shih‐Sheng
Published: October 2017

Two series of trinuclear diimine ReI tricarbonyl complexes bridged by 2,4,6‐tri(pyridin‐4‐yl)‐1,3,5‐triazine (L1) or 2,4,6‐tri(pyridin‐3‐yl)‐1,3,5‐triazine (L2) have been synthesized and characterized. These two series of trinuclear complexes show distinctly different photophysical and electrochemical properties. The L2‐bridged complexes exhibit strong luminescence and relatively long emission lifetimes in room‐temperature solution, which are typical of decay from 3MLCT excited states, whereas L1‐bridged complexes show only very weak luminescence and short lifetimes under the same experimental conditions. The prominent differences in photophysical behavior between these two groups of trinuclear complexes has been rationalized by energy gap law, which has been supported by detailed analysis of the steady state and time‐resolved luminescence of these complexes. Moreover, computational results indicated that a low‐lying excited state locates below 3MLCT states in the series of L1‐bridged complexes.
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

Micro‐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

The 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

Evidence 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.
The ketone body metabolite β‐hydroxybutyrate induces an antidepression‐associated ramification of microglia via HDACs inhibition‐triggered Akt‐small RhoGTPase activation
Authors: Huang Chao , Wang Peng , Xu Xing , Zhang Yaru , Gong Yu , Hu Wenfeng , Gao Minhui , Wu Yue , Ling Yong , Zhao Xi , Qin Yibin , Yang Rongrong , Zhang Wei
Published: October 2017

Abstact

Direct induction of macrophage ramification has been shown to promote an alternative (M2) polarization, suggesting that the ramified morphology may determine the function of immune cells. The ketone body metabolite β‐hydroxybutyrate (BHB) elevated in conditions including fasting and low‐carbohydrate ketogenic diet (KD) can reduce neuroinflammation. However, how exactly BHB impacts microglia remains unclear. We report that BHB as well as its producing stimuli fasting and KD induced obvious ramifications of murine microglia in basal and inflammatory conditions in a reversible manner, and these ramifications were accompanied with microglial profile toward M2 polarization and phagocytosis. The protein kinase B (Akt)‐small RhoGTPase axis was found to mediate the effect of BHB on microglial shape change, as (i) BHB activated the microglial small RhoGTPase (Rac1, Cdc42) and Akt; (ii) Akt and Rac1‐Cdc42 inhibition abolished the pro‐ramification effect of BHB; (iii) Akt inhibition prevented the activation of Rac1‐Cdc42 induced by BHB treatment. Incubation of microglia with other classical histone deacetylases (HDACs) inhibitors, but not G protein‐coupled receptor 109a (GPR109a) activators, also induced microglial ramification and Akt activation, suggesting that the BHB‐induced ramification of microglia may be triggered by HDACs inhibition. Functionally, Akt inhibition was found to abrogate the effects of BHB on microglial polarization and phagocytosis. In neuroinflammatory models induced by lipopolysaccharide (LPS) or chronic unpredictable stress (CUS), BHB prevented the microglial process retraction and depressive‐like behaviors, and these effects were abolished by Akt inhibition. Our findings for the first time showed that BHB exerts anti‐inflammatory actions via promotion of microglial ramification.
Functional rhythmogenic domains defined by astrocytic networks in the trigeminal main sensory nucleus
Authors: Condamine Steven , Lavoie Raphaël , Verdier Dorly , Kolta Arlette
Published: October 2017

Stimuli that induce rhythmic firing in trigeminal neurons also increase astrocytic coupling and reveal networks that define the boundaries of this particular population. Rhythmic firing depends on astrocytic coupling which in turn depends on S100β. In many nervous functions that rely on the ability of neuronal networks to generate a rhythmic pattern of activity, coordination of firing is an essential feature. Astrocytes play an important role in some of these networks, but the contribution of astrocytic coupling remains poorly defined. Here we investigate the modulation and organization of astrocytic networks in the dorsal part of the trigeminal main sensory nucleus (NVsnpr), which forms part of the network generating chewing movements. Using whole‐cell recordings and the dye coupling approach by filling a single astrocyte with biocytin to reveal astrocytic networks, we showed that coupling is limited under resting conditions, but increases importantly under conditions that induce rhythmic firing in NVsnpr neurons. These are: repetitive electrical stimulation of the sensory inputs to the nucleus, local application of NMDA and decrease of extracellular Ca2+. We have previously shown that rhythmic firing induced in NVsnpr neurons by these stimuli depends on astrocytes and their Ca2+‐binding protein S100β. Here we show that extracellular blockade of S100β also prevents the increase in astrocytic coupling induced by local application of NMDA. Most of the networks were small and remained confined to the functionally distinct area of dorsal NVsnpr. Disrupting coupling by perfusion with the nonspecific gap junction blocker, carbenoxolone or with GAP26, a selective inhibitor of connexin 43, mostly expressed in astrocytes, abolished NMDA‐induced rhythmic firing in NVsnpr neurons. These results suggest that astrocytic coupling is regulated by sensory inputs, necessary for neuronal bursting, and organized in a region specific manner.
Multichannel wearable fNIRS‐EEGsystem for long‐term clinical monitoring
Authors: Kassab Ali , Le Lan Jérôme , Tremblay Julie , Vannasing Phetsamone , Dehbozorgi Mahya , Pouliot Philippe , Gallagher Anne , Lesage Frédéric , Sawan Mohamad , Nguyen Dang Khoa
Published: October 2017

Continuous brain imaging techniques can be beneficial for the monitoring of neurological pathologies (such as epilepsy or stroke) and neuroimaging protocols involving movement. Among existing ones, functional near‐infrared spectroscopy (fNIRS) and electroencephalography (EEG) have the advantage of being noninvasive, nonobstructive, inexpensive, yield portable solutions, and offer complementary monitoring of electrical and local hemodynamic activities. This article presents a novel system with 128 fNIRS channels and 32 EEG channels with the potential to cover a larger fraction of the adult superficial cortex than earlier works, is integrated with 32 EEG channels, is light and battery‐powered to improve portability, and can transmit data wirelessly to an interface for real‐time display of electrical and hemodynamic activities. A novel fNIRS‐EEG stretchable cap, two analog channels for auxiliary data (e.g., electrocardiogram), eight digital triggers for event‐related protocols and an internal accelerometer for movement artifacts removal contribute to improve data acquisition quality. The system can run continuously for 24 h. Following instrumentation validation and reliability on a solid phantom, performance was evaluated on (1) 12 healthy participants during either a visual (checkerboard) task at rest or while pedalling on a stationary bicycle or a cognitive (language) task and (2) 4 patients admitted either to the epilepsy (n = 3) or stroke (n = 1) units. Data analysis confirmed expected hemodynamic variations during validation recordings and useful clinical information during in‐hospital testing. To the best of our knowledge, this is the first demonstration of a wearable wireless multichannel fNIRS‐EEG monitoring system in patients with neurological conditions.Hum Brain Mapp 39:7–23, 2018. ©2017 Wiley Periodicals, Inc.
Partial splenic artery embolization for severe hepatic myelopathy in cirrhosis
Authors: Philips Cyriac Abby , Kumar Lijesh , Augustine Philip
Published: October 2017

Hepatic myelopathy (HM) is a devastating but rare complication of cirrhosis and portal hypertension that profoundly affects quality of life and improves only with liver transplantation. We present a case where progressive severe spastic paraparesis due to HM was substantially reversed with partial splenic artery emobilization (PSAE). (Hepatology 2018;67:1169–1171)
Fat‐free muscle mass in magnetic resonance imaging predicts acute‐on‐chronic liver failure and survival in decompensated cirrhosis
Authors: Praktiknjo Michael , Book Marius , Luetkens Julian , Pohlmann Alessandra , Meyer Carsten , Thomas Daniel , Jansen Christian , Feist Andreas , Chang Johannes , Grimm Jochen , Lehmann Jennifer , Strassburg Christian P. , Abraldes Juan Gonzalez , Kukuk Guido , Trebicka Jonel
Published: October 2017

Muscle mass seems to be a prognostic marker in patients with liver cirrhosis. However, reported methods to quantify muscle mass are heterogeneous, consented cutoff values are missing, and most studies have used computed tomography. This study evaluated fat‐free muscle area (FFMA) as a marker of sarcopenia using magnetic resonance imaging (MRI) in patients with decompensated cirrhosis with transjugular intrahepatic portosystemic shunt (TIPS). The total erector spinae muscle area and the intramuscular fat tissue area were measured and subtracted to calculate the FFMA in 116 patients with cirrhosis by TIPS and MRI. The training cohort of 71 patients compared computed tomography–measured transversal psoas muscle thickness with FFMA. In 15 patients MRI was performed before and after TIPS, and in 12 patients follistatin serum measurements were carried out. The results on FFMA were confirmed in a validation cohort of 45 patients. FFMA correlated with follistatin and transversal psoas muscle thickness and showed slightly better association with survival than transversal psoas muscle thickness. Gender‐specific cutoff values for FFMA were determined for sarcopenia. Decompensation (ascites, overt hepatic encephalopathy) persisted after TIPS in the sarcopenia group but resolved in the nonsarcopenia group. Sarcopenic patients showed no clinical improvement after TIPS as well as higher mortality, mainly due to development of acute‐on‐chronic liver failure. FFMA was an independent predictor of survival in these patients. Conclusion: This study offers an easy‐to‐apply MRI‐based measurement of fat‐free muscle mass as a marker of sarcopenia in decompensated patients; while TIPS might improve sarcopenia and thereby survival, persistence of sarcopenia after TIPS is associated with a reduced response to TIPS and a higher risk of acute‐on‐chronic liver failure development and mortality. (Hepatology 2018;67:1014–1026)
Three variants in the nicotinamide adenine dinucleotide phosphate oxidase complex are associated with HCV‐related liver damage
Authors: Page Sandra J. , Rivera Maria M. , Kleiner David E. , Zhao Xiongce , Auh Sungyoung , Remmers Elaine F. , Heller Theo
Published: October 2017

Approximately 71 million people are chronically infected with the hepatitis C virus (HCV), a potentially lethal pathogen. HCV generates oxidative stress correlating with disease severity. HCV proteins increase reactive oxygen species production by stimulating nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity. Reactive oxygen species are necessary for host defense and cell signaling; however, elevated NOX activity contributes to cancer, and NOX overexpression is associated with hepatic fibrosis. Our aim was to investigate whether single nucleotide polymorphisms (SNPs) in NOX family members are associated with HCV‐related liver damage. Three hundred and thirty‐one individuals of European ancestry and 90 individuals of African ancestry, all diagnosed with HCV, were genotyped for 243 tagSNPs in NOX enzymes and their regulatory factors. Pathology scores were available for 288 Caucasians and 71 Africans, and mortality status was determined for all subjects. SNPs were tested for association with pathology scores and as predictors of mortality. In Africans, homozygosity for the A allele of rs12753665 (neutrophil cytosolic factor 2) and homozygosity for the T allele of rs760519 (neutrophil cytosolic factor 4) were associated with and predictive of higher rates of advanced fibrosis and cirrhosis compared to other genotypes after controlling for age and sex. In Caucasians, homozygosity for the T allele of rs2292464 (dual oxidase 1) was associated with and predictive of decreased periportal inflammation after controlling for age and sex. No SNPs were significant predictors of mortality. Conclusion: In this exploratory study, three NOX‐related polymorphisms in two ethnic groups were significantly associated with hepatic inflammation and fibrosis. Future studies investigating these SNPs in larger cohorts of patients with HCV are warranted. (Hepatology Communications 2017;1:973–982)
Regional economic impact assessment: Evaluating remedial alternatives for the Portland Harbor Superfund Site, Portland, Oregon, USA
Authors: Harrison David , Coughlin Conor , Hogan Dylan , Edwards Deborah A , Smith Benjamin C
Published: October 2017

The present paper describes a methodology for evaluating impacts of Superfund remedial alternatives on the regional economy in the context of a broader sustainability evaluation. Although economic impact methodology is well established, some applications to Superfund remedial evaluation have created confusion because of seemingly contradictory results. This confusion arises from failure to be explicit about 2 opposing impacts of remediation expenditures: 1) positive regional impacts of spending additional money in the region and 2) negative regional impacts of the need to pay for the expenditures (and thus forgo other expenditures in the region). The present paper provides a template for economic impact assessment that takes both positive and negative impacts into account, thus providing comprehensive estimates of net impacts. The paper also provides a strategy for identifying and estimating major uncertainties in the net impacts. The recommended methodology was applied at the Portland Harbor Superfund Site, located along the Lower Willamette River in Portland, Oregon, USA. The US Environmental Protection Agency (USEPA) developed remedial alternatives that it estimated would cost up to several billion dollars, with construction durations possibly lasting decades. The economic study estimated regional economic impacts—measured in terms of gross regional product (GRP), personal income, population, and employment—for 5 of the USEPA alternatives relative to the “no further action” alternative. Integr Environ Assess Manag 2018;14:32–42. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

Key Points

This study illustrates a methodology for evaluating the regional economic impacts of Superfund remediation activities, a methodology that can be used along with environmental and social analyses to develop a broad assessment of Superfund remedial alternatives. The economic impact assessment should include the 2 opposing impacts of remediation expenditures: 1) the positive impacts of spending additional money in the region and 2) the negative effects of the need to pay for the expenditures. Detailed estimates of the expenditures—including the time they are incurred, the sectors they involve, and their location—are important to provide accurate assessments of regional economic impacts. The recommended methodology includes a dynamic regional economic impact model, inputs that account for both positive and negative effects, and qualitative assessments of impacts excluded from empirical estimates (such as potential disruption to river businesses).
Identification of novel inhibitors against UDP‐galactopyranose mutase to combat leishmaniasis
Authors: Kashif Mohammad , Tabrez Shams , Husein Atahar , Arish Mohd , Kalaiarasan Ponnusamy , Manna Partha P. , Subbarao Naidu , Akhter Yusuf , Rub Abdur
Published: October 2017

Leishmania, a protozoan parasite that causes leishmaniasis, affects 1‐2 million people every year worldwide. Leishmaniasis is a vector born disease and characterized by a diverse group of clinical syndromes. Current treatment is limited because of drug resistance, high cost, poor safety, and low efficacy. The urgent need for potent agents againstLeishmaniahas led to significant advances in the development of novel antileishmanial drugs. β‐galactofuranose (β‐Galf) is an important component ofLeishmanialcell surface matrix and plays a critical role in the pathogenesis of parasite. UDP‐galactopyranose mutase (UGM) converts UDP‐galactopyranose (UDP‐Galp) to UDP‐galactofuranose (UDP‐Galf) which acts as the precursor for β‐Galf synthesis. Due to its absence in human, this enzyme is selected as the potential target in search of new antileishmanial drugs. Three dimensional protein structure model ofLeishmania majorUGM (LmUGM) has been homology modeled usingTrypanosoma cruziUGM (TcUGM) as a template. The stereochemistry was validated further. We selected already reported active compounds from PubChem database to target theLmUGM. Three compounds (6064500, 44570814, and 6158954) among the top hit occupied the UDP binding site of UGM suggested to work as a possible inhibitor for it. In vitro antileishmanial activity assay was performed with the top ranked inhibitor, 6064500. The 6064500 molecule has inhibited the growth ofLeishmania donovanipromastigotes significantly. Further, at similar concentrations it has exhibited significantly lesser toxicity than standard drug miltefosine hydrate in mammalian cells.