bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Hippocampal Atrophy With Cerebrospinal Fluid Antibodies Against the NR2 Subtype of the N‐Methyl‐D‐Aspartate Receptor in Patients With Systemic Lupus Erythematosus and Patients With Primary Sjögren's Syndrome
Authors: Lauvsnes Maria B. , Beyer Mona K. , Kvaløy Jan Terje , Greve Ole J. , Appenzeller Simone , Kvivik Ingeborg , Harboe Erna , Tjensvoll Anne B. , Gøransson Lasse G. , Omdal Roald
Published: August 2014

Objective

Cognitive dysfunction is common in both systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS). Antibodies against the NR2 subtype of the N‐methyl‐D‐aspartate receptor (anti‐NR2 antibodies) cause hippocampal atrophy and cognitive impairment in mice and have been associated with memory impairment in both patients with SLE and patients with primary SS. In addition, a reduced volume of hippocampal gray matter has been demonstrated in both SLE and primary SS. This study was undertaken to investigate whether there is a connection between the presence of anti‐NR2 antibodies and hippocampal atrophy in human diseases.

Methods

Fifty patients with SLE and 50 patients with primary SS underwent clinical examination and cerebral magnetic resonance imaging. Anti‐NR2 antibodies in cerebrospinal fluid (CSF) were measured, and hippocampal gray matter volumes were compared between patients who were positive for and those who were negative for anti‐NR2 antibodies.

Results

Patients with anti‐NR2 antibodies in CSF had less hippocampal gray matter than patients without these antibodies. No other differences regarding gray matter volumes in other parts of the brain were identified.

Conclusion

The present findings indicate that anti‐NR2 antibodies in patients with SLE and primary SS cause neuronal death manifested as reduced hippocampal gray matter, as has been previously demonstrated in mice with autoimmune disease.
Thermally Stable 3,6‐Dinitropyrazolo[4,3‐c]pyrazole‐based Energetic Materials
Authors: Zhang Jiaheng , Parrish Damon A. , Shreeve Jean'ne M.
Published: August 2014

3,6‐Dinitropyrazolo[4,3‐c]pyrazole was prepared using an efficient modified process. With selected cations, ten nitrogen‐rich energetic salts and three metal salts were synthesized in high yield based on the 3,6‐dinitropyrazolo[4,3‐c]pyrazolate anion. These compounds were fully characterized by IR and multinuclear NMR spectroscopies, as well as elemental analyses. The structures of the neutral compounds 4 and its salt 16 were confirmed by single‐crystal X‐ray diffraction showing extensive hydrogen‐bonding interactions. The neutral pyrazole precursor and its salts are remarkably thermally stable. Based on the calculated heats of formation and measured densities, detonation pressures (22.5–35.4 GPa) and velocities (7948–9005 m s−1) were determined, and they compare favorably with those of TNT and RDX. Their impact and friction sensitivities range from 12 to >40 J and 80 to 360 N, respectively. These properties make them competitive as insensitive and thermally stable high‐energy density materials.
Peptide Conjugates of a Nonsteroidal Anti‐Inflammatory Drug as Supramolecular Gelators: Synthesis, Characterization, and Biological Studies
Authors: Roy Rajdip , Deb Jolly , Jana Siddhartha Sankar , Dastidar Parthasarathi
Published: August 2014

Indomethacin (IND), which is a well‐known nonsteroidal anti‐inflammatory drug (NSAID), was conjugated with various naturally occurring amino acids. Most of these bioconjugates were capable of gelling pure water, a solution of NaCl (0.9 wt %), and phosphate‐buffered saline (pH 7.4), as well as a few organic solvents. The gels were characterized by table‐top and dynamic rheology, and electron microscopy. Variable‐temperature 1H NMR spectroscopy studies on a selected gel were performed to gain insights into the self‐assembly process during gel formation. Both 1D and 2D hydrogen‐bonded networks were observed in the single‐crystal structures of two of the gelators. Plausible biological applications of the hydrogelators were evaluated with the ultimate aim of drug delivery in a self‐delivery fashion. All hydrogelators were stable in phosphate‐buffered saline at pH 7.4 at 37 °C, and biocompatible in mouse macrophage RAW 264.7 cell line (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay). Two of the most biocompatible hydrogelators displayed an anti‐inflammatory response comparable to that of the parent drug IND in prostaglandin E2 assay. Release of the bioconjugates into the bulk solvent interfaced with the corresponding hydrogels indicated their plausible future application in drug delivery.
Reaction‐Based Fluorescent Probe for Detection of Endogenous Cyanide in Real Biological Samples
Authors: Long Lingliang , Wang Lin , Wu Yanjun , Gong Aihua , Da Zulin , Zhang Chi , Han Zhixiang
Published: August 2014

Herein, two compounds (1 a and 1 b) were rationally constructed as novel reaction‐based fluorescent probes for CN− by making use of the electron‐withdrawing ability of the cyano group that was formed from the sensing reaction. Notably, this design strategy was first employed for the development of fluorescent CN− probes. The experimental details showed that probe 1 a exhibited a fluorescence turn‐on response to CN−, whereas other anions, biological thiols, and hydrogen sulfide gave almost no interference. The detection limit of probe 1 a for CN− was found to be 0.12 μM. The sensing reaction product of 1 a with CN− was characterized by NMR spectroscopy and mass spectrometry. TD‐DFT calculations demonstrated that the formed cyano group drives the intramolecular charge transfer (ICT) process from coumarin dye to the cyano group and thus the original strong ICT from the coumarin dye to the 3‐position pyridyl vinyl ketone substituent is weakened, which results in recovery of coumarin fluorescence. The practical utility of 1 a was also examined. By fabricating paper strips, probe 1 a can be used as a simple tool to detect CN− in field measurements. Moreover, probe 1 a has been successfully applied for quantitative detection of endogenous CN− from cassava root.
Reaction of a Dialumene‐Benzene Adduct with Diphenylacetylene: Formation of 3,4‐Dialuminacyclobutene and 5,6‐Dialuminabicyclo[2.1.1]hex‐2‐ene Derivatives
Authors: Agou Tomohiro , Nagata Koichi , Sasamori Takahiro , Tokitoh Norihiro
Published: August 2014

Reaction of a dialumene‐benzene adduct bearing bulky aryl substituents with diphenylacetylene was found to give a novel 5,6‐dialuminabicyclo[2.1.1]hex‐2‐ene derivative in addition to the 3,4‐dialuminacyclobutene derivative, the formal [2+2]cycloadduct of an intermediary dialumene with diphenylacetylene. The molecular structure of the newly obtained 5,6‐dialuminabicyclo[2.1.1]hex‐2‐ene has been elucidated by X‐ray crystallographic analysis.
Robust Adaptive Fuzzy Control of Nonlinear Systems with Unknown and Time‐Varying Saturation
Authors: Lai Guanyu , Liu Zhi , Zhang Yun , Chen Xin , Philip Chen Chun Lung
Published: August 2014

In this paper, a robust adaptive fuzzy control approach is proposed for a class of nonlinear systems in strict‐feedback form with the unknown time‐varying saturation input. To deal with the time‐varying saturation problem, a novel controller separation approach is proposed in the literature to separate the desired control signal from the practical constrained control input. Furthermore, an optimized adaptation method is applied to the dynamic surface control design to reduce the number of adaptive parameters. By utilizing the Lyapunov synthesis, the fuzzy logic system technique and the Nussbaum function technique, an adaptive fuzzy control algorithm is constructed to guarantee that all the signals in the closed‐loop control system remain semiglobally uniformly ultimately bounded, and the tracking error is driven to an adjustable neighborhood of the origin. Finally, some numerical examples are provided to validate the effectiveness of the proposed control scheme in the literature.
Branched porphyrins as functional scaffolds for multisite bioconjugation
Authors: Engelen Mireille , Lombardi Angela , Vitale Rosa , Lista Liliana , Maglio Ornella , Pavone Vincenzo , Nastri Flavia
Published: August 2014

Bioconjugation is a rapidly expanding field because of the numerous potential applications of bioconjugate materials. We explored the usefulness of branched porphyrins as rigid scaffolds, bearing multiple sites for bioconjugation. To this end, we first selected the tetrakis(p‐[aminomethyl] phenyl) porphyrin (TAMPP) macrocycle and developed a straightforward synthetic protocol, able to provide the desired tetraphenylporphyrin, carrying four functional amino groups. The partially protection of the amino groups by tert‐butoxy‐carbonyl allowed the selective and specific decoration of the porphyrin with different peptide sequences. To explore the utility of the macrocycle as molecular scaffold for bioconjugation, we selected peptide sequences able to function as thrombin inhibitors. In particular, two peptide sequences, named CS3 and ES7, able to interact, respectively, with the thrombin catalytic site and the fibrinogen recognition exosite, were joined onto the porphyrin macrocycle, providing the multisite‐directed inhibitor CS3–TAMPP–ES7. This multisite inhibitor and its MnIII complex are able to inhibit α‐thrombin‐catalyzed hydrolysis of Tos–Gly–Pro–Arg–nitroanilide with inhibition constants in the micromolar range, as well as the hydrolysis of the natural substrate fibrinogen. The inhibitor is resistant against enzymatic degradation by thrombin and is highly selective. The MnIII complex is capable of interacting with clot‐bound thrombin and partially inhibits clot growth in the presence of fibrinogen. The results herein reported are very promising, suggesting the potential of the newly developed conjugate as new imaging agents for clot detection.
Coenzyme B12 can be produced by engineered Escherichia coli under both anaerobic and aerobic conditions
Authors: Ko Yeounjoo , Ashok Somasundar , Ainala Satish Kumar , Sankaranarayanan Mugesh , Chun Ah Yeong , Jung Gyoo Yeol , Park Sunghoon
Published: August 2014

Coenzyme B12 (Vitamin B12) is one of the most complex biomolecules and an essential cofactor required for the catalytic activity of many enzymes. Pseudomonas denitrificans synthesizes coenzyme B12 in an oxygen‐dependent manner using a pathway encoded by more than 25 genes that are located in six different operons. Escherichia coli, a robust and suitable host for metabolic engineering was used to produce coenzyme B12. These genes were cloned into three compatible plasmids and expressed heterologously in E. coli BL21 (DE3). Real‐time PCR, SDS–PAGE analysis and bioassay showed that the recombinant E. coli expressed the coenzyme B12 synthetic genes and successfully produced coenzyme B12. However, according to the quantitative determination by inductively coupled plasma‐mass spectrometry, the amount of coenzyme B12 produced by the recombinant E. coli (0.21 ± 0.02 μg/g cdw) was approximately 13‐fold lower than that by P. denitrificans (2.75 ± 0.22 μg/g cdw). Optimization of the culture conditions to improve the production of coenzyme B12 by the recombinant E. coli was successful, and the highest titer (0.65 ± 0.03 μg/g cdw) of coenzyme B12 was obtained. Interestingly, although the synthesis of coenzyme B12 in P. denitrificans is strictly oxygen‐dependent, the recombinant E. coli could produce coenzyme B12 under anaerobic conditions.
Insecticidal Metabolites from the Rhizomes of Veratrum album against Adults of Colorado Potato Beetle, Leptinotarsa decemlineata
Authors: Aydin Tuba , Cakir Ahmet , Kazaz Cavit , Bayrak Neslihan , Bayir Yasin , Taşkesenligil Yavuz
Published: August 2014

The dried rhizomes of Veratrum album were individually extracted with CHCl3, acetone, and NH4OH/benzene to test the toxic effects against the Colorado potato beetle, Leptinotarsa decemlineata, which is an important agricultural pest. Fifteen compounds in various amounts were isolated from the extracts using column and thin‐layer chromatography. The chemical structures of 14 compounds were characterized as octacosan‐1‐ol (1), β‐sitosterol (2), stearic acid (3), diosgenin (4), resveratrol (5), wittifuran X (6), oxyresveratrol (7), β‐sitosterol 3‐O‐β‐D‐glucopyranoside (8), diosgenin 3‐O‐α‐L‐rhamnopyranosyl‐(1→2)‐β‐D‐glucopyronoside (9), oxyresveratrol 3‐O‐β‐D‐glucopyranoside (10), jervine (11), pseudojervine (13), 5,6‐dihydro‐1‐hydroxyjervine (14), and saccharose (15) using UV, IR, MS, 1H‐ and 13C‐NMR, and 2D‐NMR spectroscopic methods. However, the chemical structure of 12, an oligosaccharide, has not fully been elucidated. Compounds 4, 6, 9, and 10 were isolated from V. album rhizomes for the first time in the current study. The toxic effects of three extracts (acetone, CHCl3, and NH4OH/benzene) and six metabolites, 2, 2+4, 5, 7, 8, and 11, were evaluated against the Colorado potato beetle. The assay revealed that all three extracts, and compounds 7, 8, and 11 exhibited potent toxic effects against this pest. This is the first report on the evaluation of the toxic effects of the extracts and secondary metabolites of V. album rhizomes against L. decemlineata. Based on these results, it can be concluded that the extracts can be used as natural insecticides.
Chemical Composition and Phytotoxic Effects of Essential Oils Obtained from Ailanthus altissima (Mill.)Swingle Cultivated in Tunisia
Authors: El Ayeb‐Zakhama Asma , Ben Salem Saoussen , Sakka‐Rouis Lamia , Flamini Guido , Ben Jannet Hichem , Harzallah‐Skhiri Fethia
Published: August 2014

Ailanthus altissima Mill. Swingle (Simaroubaceae), also known as tree of heaven, is used in the Chinese traditional medicine as a bitter aromatic drug for the treatment of colds and gastric diseases. In Tunisia, Ailanthus altissima is an exotic tree, which was introduced many years ago and used particularly as a street ornamental tree. Here, the essential oils of different plant parts of this tree, viz., roots, stems, leaves, flowers, and samaras (ripe fruits), were obtained by hydrodistillation. In total, 69 compounds, representing 91.0–97.2% of the whole oil composition, were identified in these oils by GC‐FID and GC/MS analyses. The root essential oil was clearly distinguishable for its high content in aldehydes (hexadecanal (1); 22.6%), while those obtained from flowers and leaves were dominated by oxygenated sesquiterpenes (74.8 and 42.1%, resp.), with caryophyllene oxide (4) as the major component (42.5 and 22.7%, resp.). The samara oil was rich in the apocarotenoid derivative hexahydrofarnesyl acetone (6; 58.0%), and the oil obtained from stems was characterized by sesquiterpene hydrocarbons (54.1%), mainly β‐caryophyllene (18.9%). Principal component and hierarchical cluster analyses separated the five essential oils into four groups, each characterized by the major oil constituents. Contact tests showed that the germination of lettuce seeds was totally inhibited by all the essential oils except of the samara oil at a dose of 1 mg/ml. The flower oil also showed a significant phytotoxic effect against lettuce germination at 0.04 and 0.4 mg/ml (−55.0±3.5 and −85.0±0.7%, resp.). Moreover, the root and shoot elongation was even more affected by the oils than germination. The inhibitory effect of the shoot and root elongation varied from −9.8 to −100% and from −38.6 to −100%, respectively. Total inhibition of the elongation (−100%) at 1 mg/ml was detected for all the oils, with the exception of the samara oil (−74.7 and −75.1% for roots and shoots, resp.).
Essential Oil from Blackcurrant Buds as Chemotaxonomy Marker and Antimicrobial Agent
Authors: Ðorđević Boban S. , Pljevljakušić Dejan S. , Šavikin Katarina P. , Stević Tatjana R. , Bigović Dubravka J.
Published: August 2014

Dormant buds are recognized as valuable side product of the blackcurrant cultivation. Four blackcurrant varieties cultivated in Serbia, i.e., Ben Sarek, Ometa, Ben Lomond, and Ben Nevis, were evaluated for the content, chemical composition, and antimicrobial activity of their bud essential oils. The oil yields of buds harvested during two different growth periods ranged from 1.2–2.0%, and the variety Ometa had the highest yield among the tested varieties. GC‐FID and GC/MS analysis of the oils allowed the identification of eight main components, i.e., α‐pinene (1.6–5.4%), sabinene (1.9–38.4%), δ‐car‐3‐ene (13.0–50.7%), β‐phellandrene (2.9–18.0%), terpinolene (6.6–11.9%), terpinen‐4‐ol (0.9–6.6%), β‐caryophyllene (3.8–10.4%), and α‐humulene (0.2–4.1%). In addition, the similarity degree of the essential‐oil compositions of buds harvested from the upper and lower parts of the shrubs was investigated by hierarchical clustering. All essential oils originating from the same genotype were grouped in the same cluster, indicating the reliability of essential oils as chemotaxonomic markers. For more detailed chemotaxonomic investigations, the three compounds with the greatest variance were chosen, i.e., sabinene, δ‐car‐3‐ene, and β‐phellandrene, which proved to be efficient for the variety distinction. Factor analysis showed that the essential‐oil composition as chemotaxonomic marker in blackcurrants was more reliable for variety Ben Sarek than for variety Ben Nevis. Moreover, it was demonstrated that the essential oils had very strong inhibitory activity against all tested microorganisms. Fungi were more sensitive than bacteria; indeed their growth was completely inhibited at much lower concentrations. In comparison to commercial antibiotics, significantly lower concentrations of the oils were necessary for the complete inhibition of fungal growth.
Binding Pockets and Pathways for Dioxygen through the KijD3 N‐Oxygenase in Complex with Flavin Mononucleotide Cofactor and a 3‐Aminoglucose Substrate: Predictions from Molecular Dynamics Simulations
Authors: Pietra Francesco
Published: August 2014

In this work, two protein systems, Kij3DFMNAKMO2 and Kij3DFMNO2, made of KijD3 N‐oxygenase, flavin mononucleotide (FMN) cofactor, dTDP‐3‐amino‐2,3,6‐trideoxy‐4‐keto‐3‐methyl‐D‐glucose (AKM) substrate, and dioxygen (O2), have been assembled by adding a molecule of O2, and removing (or not) AKM, to crystal data for the Kij3DFMNAKM complex. Egress of AKM and O2 from these systems was then investigated by applying a tiny external random force, in turn, to their center of mass in the course of molecular dynamics in explicit H2O. It turned out that the wide AKM channel, even when emptied, does not constitute the main route for O2 egress. Other routes appear to be also viable, while various binding pockets (BPs) outside the active center are prone to trap O2. By reversing the reasoning, these can also be considered as routes for uptake of O2 by the protein, before or after AKM uptake, while BPs may serve as reservoirs of O2. This shows that the small molecule O2 is capable of permeating the protein by exploiting all nearby interstices that are created on thermal fluctuations of the protein, rather than having necessarily to look for farther, permanent channels.
Total Mercury in Sediments, Macrophytes, and Fish from a Shallow Steppe Lake in Eastern Austria
Authors: Jirsa Franz , Pirker Daniel , Krachler Regina , Keppler Bernhard K.
Published: August 2014

During summer 2011, samples of sediment, macrophytes, and fish tissues from the shallow, slightly alkaline Lake Neusiedl, Austria, were evaluated for their total Hg content. This is the first report of Hg levels from this lake. Sediments displayed Hg contents between 0.025 and 0.113 μg g−1 dw (dry weight), significantly correlating with the proportion of organic components pointing to a small anthropogenic impact on the lake's Hg content. Hg Levels in plants and fish were unexpectedly high: both investigated submerged plant species, Potamogeton pectinatus and Myriophyllum spicatum, showed mean values of 0.245±0.152 and 0.298±0.115 μg g−1 dw, respectively. Biomagnification was evident when comparing muscle samples of the planktivorous fish species rudd Scardinus erythrophthalmus (n=10, mean=0.084 μg g−1 ww (wet weight)) with the piscivorous perch Perca fluviatilis (n=21, mean=0.184 μg g−1 ww) or pike‐perch Sander lucioperca (n=9, mean=0.205 μg g−1 ww). Significantly lower values were found in the muscle of the piscivorous pike Esox lucius (n=25, mean=0.135 μg g−1 ww), pointing to a specific Hg metabolism of this fish, presumably under the particular physicochemical properties of the lake. Hg Concentrations in fish could pose a risk to piscivorous birds in this protected wetland system.
Ribosylhopane, a Novel Bacterial Hopanoid, as Precursor of C35 Bacteriohopanepolyols in Streptomyces coelicolor A3(2)
Authors: Liu Wenjun , Sakr Elias , Schaeffer Philippe , Talbot Helen M. , Donisi Janina , Härtner Thomas , Kannenberg Elmar , Takano Eriko , Rohmer Michel
Published: August 2014

Wild‐type Streptomyces coelicolor A3(2) produces aminobacteriohopanetriol as the only elongated C35 hopanoid. The hopanoid phenotype of two mutants bearing a deletion of genes from a previously identified hopanoid biosynthesis gene cluster provides clues to the formation of C35 bacteriohopanepolyols. orf14 encodes a putative nucleosidase; its deletion induces the accumulation of adenosylhopane as it cannot be converted into ribosylhopane. orf18 encodes a putative transaminase; its deletion results in the accumulation of adenosylhopane, ribosylhopane, and bacteriohopanetetrol. Ribosylhopane was postulated twenty years ago as a precursor for bacterial hopanoids but was never identified in a bacterium. Absence of the transaminase encoded by orf18 prevents the reductive amination of ribosylhopane into aminobacteriohopanetriol and induces its accumulation. Its reduction by an aldose‐reductase‐like enzyme produces bacteriohopanetetrol, which is normally not present in S. coelicolor.
Earth‐Abundant Oxygen Evolution Catalysts Coupled onto ZnO Nanowire Arrays for Efficient Photoelectrochemical Water Cleavage
Authors: Jiang Chaoran , Moniz Savio J. A. , Khraisheh Majeda , Tang Junwang
Published: August 2014

ZnO has long been considered as a model UV‐driven photoanode for photoelectrochemical water splitting, but its performance has been limited by fast charge‐carrier recombination, extremely poor stability in aqueous solution, and slow kinetics of water oxidation. These issues were addressed by applying a strategy of optimization and passivation of hydrothermally grown 1D ZnO nanowire arrays. The length and diameter of bare ZnO nanowires were optimized by varying the growth time and precursor concentration to achieve optimal photoelectrochemical performance. The addition of earth‐abundant cobalt phosphate (Co‐Pi) and nickel borate (Ni‐B) oxygen evolution catalysts onto ZnO nanowires resulted in substantial cathodic shifts in onset potential to as low as about 0.3 V versus the reversible hydrogen electrode (RHE) for Ni‐B/ZnO, for which a maximum photocurrent density of 1.1 mA cm−2 at 0.9 V (vs. RHE) with applied bias photon‐to‐current efficiency of 0.4 % and an unprecedented near‐unity incident photon‐to‐current efficiency at 370 nm. In addition the potential required for saturated photocurrent was dramatically reduced from 1.6 to 0.9 V versus RHE. Furthermore, the stability of these ZnO nanowires was significantly enhanced by using Ni‐B compared to Co‐Pi due to its superior chemical robustness, and it thus has additional functionality as a stable protecting layer on the ZnO surface. These remarkable enhancements in both photocatalytic activity and stability directly address the current severe limitations in the use of ZnO‐based photoelectrodes for water‐splitting applications, and can be applied to other photoanodes for efficient solar‐driven fuel synthesis.
Aza‐Crown Ether Complex Cation Ionic Liquids: Preparation and Applications in Organic Reactions
Authors: Song Yingying , Cheng Chen , Jing Huanwang
Published: August 2014

Aza‐crown ether complex cation ionic liquids (aCECILs) were devised, fabricated, and characterized by using NMR spectroscopy, MS, thermogravimetric differential thermal analysis (TG‐DTA), elemental analysis and physical properties. These new and room‐temperature ILs were utilized as catalysts in various organic reactions, such as the cycloaddition reaction of CO2 to epoxides, esterification of acetic acid and alcohols, the condensation reaction of aniline and propylene carbonate, and Friedel–Crafts alkylation of indole with aldehydes were investigated carefully. In these reactions, the ionic liquid exhibited cooperative catalytic activity between the anion and cation. In addition, the aza‐[18‐C‐6HK][HSO4]2 was the best acidic catalyst in the reactions of esterification and Friedel–Crafts alkylation under mild reaction conditions.
Enzymatic Desymmetrising Redox Reactions for the Asymmetric Synthesis of Biaryl Atropisomers
Authors: Staniland Samantha , Yuan Bo , Giménez‐Agulló Nelson , Marcelli Tommaso , Willies Simon C. , Grainger Damian M. , Turner Nicholas J. , Clayden Jonathan
Published: August 2014

Atropisomeric biaryls carrying ortho‐hydroxymethyl and formyl groups were made enantioselectively by desymmetrisation of dialdehyde or diol substrates. The oxidation of the symmetrical diol substrates was achieved using a variant of galactose oxidase (GOase), and the reduction of the dialdehydes using a panel of ketoreductases. Either M or P enantiomers of the products could be formed, with absolute configurations assigned by time‐dependent DFT calculations of circular dichroism spectra. The differing selectivities observed with different biaryl structures offer an insight into the detailed structure of the active site of the GOase enzyme.
Structure‐Guided Design of Thiazolidine Derivatives as Mycobacterium tuberculosis Pantothenate Synthetase Inhibitors
Authors: Devi Parthiban Brindha , Samala Ganesh , Sridevi Jonnalagadda Padma , Saxena Shalini , Alvala Mallika , Salina Elena G. , Sriram Dharmarajan , Yogeeswari Perumal
Published: August 2014

The pantothenate biosynthetic pathway is essential for the persistent growth and virulence of Mycobacterium tuberculosis (Mtb) and one of the enzymes in the pathway, pantothenate synthetase (PS, EC: 6.3.2.1), encoded by the panC gene, has become an appropriate target for new therapeutics to treat tuberculosis. Herein, we report nanomolar thiazolidine inhibitors of Mtb PS developed by a rational inhibitor design approach. The thiazolidine compounds were discovered by using energy‐based pharmacophore modelling and subsequent in vitro screening, which resulted in compounds with a half maximal inhibitory concentration (IC50) value of (1.12±0.12) μM. These compounds were subsequently optimised by a combination of modelling and synthetic chemistry. Hit expansion of the lead by chemical synthesis led to an improved inhibitor with an IC50 value of 350 nM and an Mtb minimum inhibitory concentration (MIC) of 1.55 μM. Some of these compounds also showed good activity against dormant Mtb cells.
Position and Length of Fatty Acids Strongly Affect Receptor Selectivity Pattern of Human Pancreatic Polypeptide Analogues
Authors: Mäde Veronika , Bellmann‐Sickert Kathrin , Kaiser Anette , Meiler Jens , Beck‐Sickinger Annette G.
Published: August 2014

Pancreatic polypeptide (PP) is a satiety‐inducing gut hormone targeting predominantly the Y4 receptor within the neuropeptide Y multiligand/multireceptor family. Palmitoylated PP‐based ligands have already been reported to exert prolonged satiety‐inducing effects in animal models. Here, we suggest that other lipidation sites and different fatty acid chain lengths may affect receptor selectivity and metabolic stability. Activity tests revealed significantly enhanced potency of long fatty acid conjugates on all four Y receptors with a preference of position 22 over 30 at Y1, Y2 and Y5 receptors. Improved Y receptor selectivity was observed for two short fatty acid analogues. Moreover, [K30(E‐Prop)]hPP2−36 (15) displayed enhanced stability in blood plasma and liver homogenates. Thus, short chain lipidation of hPP at key residue 30 is a promising approach for anti‐obesity therapy because of maintained selectivity and a sixfold increased plasma half‐life.
Optoelectronic and Self‐assembly Properties of Porphyrin Derivatives with Click Chemistry Modification
Authors: Pengxia Liang , Du Zhengcai , Wang Dong , Yang Zhou , Sheng Huiyun , Liang Shuqiong , Cao Hui , He Wanli , Yang Huai
Published: August 2014

A series of functionalized porphyrin molecules containing electron‐rich alkynes, synthesized by means of the Sonogashira coupling reaction were further modified by reacting the ethynyl groups with click reagent through a formal [2+2] click reaction. The photophysical and electrochemical properties of the porphyrin derivatives were studied by UV/Vis spectroscopy and cyclic voltammetry. We show that the optoelectronic properties are affected by the click reagent groups and central metal ions. The functionalized porphyrin molecules show strong charge‐transfer (CT) bands in the visible region (near‐IR region) and potent redox activities. Through a phase‐exchange self‐assembly method, the highly organized morphologies were observed by scanning electron microscopy (SEM). The functionalized porphyrin molecules represent an interesting set of candidates for optoelectronic device components. The effect of the metal ions or click reagent groups on the self‐assembly properties were also studied by the UV/Vis spectroscopic titration experiments.
Optimization of rhabdomyosarcoma disseminated disease assessment by flow cytometry
Authors: Almazán‐Moga Ana , Roma Josep , Molist Carla , Vidal Isaac , Jubierre Luz , Soriano Aroa , Segura Miguel Francisco , Llort Anna , Sánchez de Toledo Josep , Gallego Soledad
Published: August 2014

Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. Circulating tumor cells in peripheral blood or disseminated to bone marrow, a concept commonly referred to as minimal residual disease (MRD), are thought to be key to the prediction of metastasis and treatment efficacy. To date, two MRD markers, MYOD and MYOGENIN, have been tested; however, MRD detection continues to be challenging mainly owing to the closeness of the detection limit and the discordance of both markers in some samples. Therefore, the addition of a third marker could be useful for more accurate MRD assessment. The PAX3 gene is expressed during embryo development in all myogenic precursor cells in the dermomyotome. As RMS cells are thought to originate from these muscle precursor cells, they are expected to be positive for PAX3. In this study, PAX3 expression was characterized in cancer cell lines and tumors, showing wide expression in RMS. Detection sensitivities by quantitative polymerase chain reaction (qPCR) of the previously proposed markers, MYOD and MYOGENIN, were similar to that of PAX3, thereby indicating the feasibility of its detection. Interestingly, the flow cytometry experiments supported the usefulness of this technique in the quantification of MRD in RMS using PAX3 as a marker. These results indicate that flow cytometry, albeit in some cases slightly less sensitive, can be considered a good approach for MRD assessment in RMS and more consistent than qPCR, especially owing to its greater specificity. Furthermore, fluorescence‐activated cell sorting permits the recovery of cells, thereby providing material for further characterization of circulating or disseminated cancer cells. © 2014 International Society for Advancement of Cytometry
The effect of call libraries and acoustic filters on the identification of bat echolocation
Authors: Clement Matthew J. , Murray Kevin L. , Solick Donald I. , Gruver Jeffrey C.
Published: August 2014

Quantitative methods for species identification are commonly used in acoustic surveys for animals. While various identification models have been studied extensively, there has been little study of methods for selecting calls prior to modeling or methods for validating results after modeling. We obtained two call libraries with a combined 1556 pulse sequences from 11 North American bat species. We used four acoustic filters to automatically select and quantify bat calls from the combined library. For each filter, we trained a species identification model (a quadratic discriminant function analysis) and compared the classification ability of the models. In a separate analysis, we trained a classification model using just one call library. We then compared a conventional model assessment that used the training library against an alternative approach that used the second library. We found that filters differed in the share of known pulse sequences that were selected (68 to 96%), the share of non‐bat noises that were excluded (37 to 100%), their measurement of various pulse parameters, and their overall correct classification rate (41% to 85%). Although the top two filters did not differ significantly in overall correct classification rate (85% and 83%), rates differed significantly for some bat species. In our assessment of call libraries, overall correct classification rates were significantly lower (15% to 23% lower) when tested on the second call library instead of the training library. Well‐designed filters obviated the need for subjective and time‐consuming manual selection of pulses. Accordingly, researchers should carefully design and test filters and include adequate descriptions in publications. Our results also indicate that it may not be possible to extend inferences about model accuracy beyond the training library. If so, the accuracy of acoustic‐only surveys may be lower than commonly reported, which could affect ecological understanding or management decisions based on acoustic surveys.
A Planar‐Chiral Phosphino(alkenyl)ferrocene for Suzuki–Miyaura C–C Coupling Reactions
Authors: Schaarschmidt Dieter , Grumbt Martin , Hildebrandt Alexander , Lang Heinrich
Published: August 2014

Planar‐chiral phosphinoferrocene [Fe(η5‐C5H3‐1‐PPh2‐2‐(E)‐CH=CHPh)(η5‐C5H5)] (4) was applied in the presence of palladium in Suzuki–Miyaura couplings for the synthesis of sterically congested biaryls. The catalytic activity arises from homogeneous palladium phosphine complexes, of which the potential pre‐catalyst [Pd(4)2Cl2] was characterized structurally. The catalytic system is excellently suited for the synthesis of tri‐ortho‐substituted biaryls under mild conditions (0.1 mol‐%, 50–100 °C), whereas its application towards the synthesis of tetra‐ortho‐substituted biaryls is quite limited. Comparing the performance of the reaction with 4 as catalyst and a range of substrates with differing ortho substituents suggests that transmetalation is rate determining. Complex (Sp)‐4 was used in atropselective couplings, wherein enantioenrichments of up to 36 % were achieved. The stereoselectivity depends to some extent on the steric properties of the boronic acids; however, slight changes at the aryl halides influence the enantioselectivity.
Design of a New Carbon Paste Electrode Modified with TiO2 Nanoparticles to Use in an Electrochemical Study of Codeine and Simultaneous Determination of Codeine and Acetaminophen in Human Plasma Serum Samples
Authors: Mashhadizadeh Mohammad Hossein , Rasouli Fatemeh
Published: August 2014

A new electrochemical sensor was fabricated via TiO2 nanoparticles onto a carbon paste electrode. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) studied the response of the modified electrode toward codeine. The effects of pH, modifier amount, pulse amplitude, and scan rate of potential have been examined. Using DPV, we could measure simultaneously codeine and acetaminophen in one mixture. The detection limits of 0.018 and 0.050 µmol L−1 were achieved for codeine and acetaminophen, respectively. The electrooxidation pathway, transfer coefficient, and standard rate constant, are estimated. The proposed voltammetric sensor was successfully applied to determination of codeine and acetaminophen in human plasma serum samples.
The identification of menstrual blood in forensic samples by logistic regression modeling of miRNA expression
Authors: Hanson Erin K. , Mirza Mohid , Rekab Kamel , Ballantyne Jack
Published: August 2014

We report the identification of sensitive and specific miRNA biomarkers for menstrual blood, a tissue that might provide probative information in certain specialized instances. We incorporated these biomarkers into qPCR assays and developed a quantitative statistical model using logistic regression that permits the prediction of menstrual blood in a forensic sample with a high, and measurable, degree of accuracy. Using the developed model, we achieved 100% accuracy in determining the body fluid of interest for a set of test samples (i.e. samples not used in model development). The development, and details, of the logistic regression model are described. Testing and evaluation of the finalized logistic regression modeled assay using a small number of samples was carried out to preliminarily estimate the limit of detection (LOD), specificity in admixed samples and expression of the menstrual blood miRNA biomarkers throughout the menstrual cycle (25–28 days). The LOD was <1 ng of total RNA, the assay performed as expected with admixed samples and menstrual blood was identified only during the menses phase of the female reproductive cycle in two donors.
Strategies for Accelerating the NEPA Process
Authors: Dunmire Carolyn
Published: August 2014

The National Environmental Policy Act (NEPA), signed by President Richard Nixon on January 1, 1970, instituted a decision‐making process that requires federal agencies to evaluate the environmental and social consequences of their actions and to notify the public of these consequences.
The role of liver fat and insulin resistance as determinants of plasma aminotransferase elevation in nonalcoholic fatty liver disease
Authors: Maximos Maryann , Bril Fernando , Portillo Sanchez Paola , Lomonaco Romina , Orsak Beverly , Biernacki Diane , Suman Amitabh , Weber Michelle , Cusi Kenneth
Published: August 2014

Plasma aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) are usually increased in patients with nonalcoholic fatty liver disease (NAFLD). However, the factors behind their elevation remain unclear. The aim of this study was to assess the role of insulin resistance (IR) and liver triglyceride content in relation to histology in patients with NAFLD/nonalcoholic steatohepatitis (NASH) with normal or elevated ALT levels. To this end, we enrolled 440 patients, divided into three groups: no NAFLD (n = 60); NAFLD with normal ALT (n = 165); and NAFLD with elevated ALT (n = 215). We measured: (1) liver fat by proton magnetic resonance spectroscopy (1H‐MRS); (2) severity of liver disease by biopsy (n = 293); and (3) insulin sensitivity in liver, muscle, and adipose tissue by a euglycemic hyperinsulinemic clamp with 3‐3H‐glucose. Patients with NAFLD and elevated ALT, even when well matched for body mass index to those with normal ALT, had worse adipose tissue insulin resistance (ATIR; P < 0.0001), higher liver triglyceride content (P < 0.0001), and lower plasma adiponectin (P < 0.05), but no differences in hepatic insulin resistance. Similar results were found when only patients with NASH were compared: both ATIR (P < 0.0001) and liver triglyceride content by 1H‐MRS (P < 0.0001) were worse in NASH with elevated ALT. Consistent with the 1H‐MRS data, steatosis on liver biopsy was also significantly increased in patients with NASH and elevated ALT levels (P < 0.0001). However, and most important, there were no differences in inflammation (P = 0.62), ballooning (P = 0.13), or fibrosis (P = 0.12). Conclusion: In patients with NAFLD or NASH, ATIR (but not HIR) and liver triglyceride content are major factors in the elevation of plasma aminotransferase levels. Patients with normal versus elevated ALT had similar severity of NASH, suggesting that plasma aminotransferase levels are misleading parameters for guiding clinical management. (Hepatology 2015;61:153–160)
The Assembly Specific Force Atlas
Authors: Schaub Karlheinz , Wakula Jurij , Berg Knut , Kaiser Bastian , Bruder Ralph , Glitsch Ulrich , Ellegast Rolf‐Peter
Published: August 2014

Even in hi‐tech industries, physical workload is partly considerable and cannot be avoided because of product and process requirements. Especially in automotive, aviation, and marine industries, the assembly of the product geometry requires force exertions in ergonomically unfavorable conditions. Unfortunately, internationally accepted methods for the evaluation of those types of force exertions are rare. Besides some traditional German methods and EN 1005‐3 hardly any evaluation methods exist. Even those methods refer to force exertions in primarily upright symmetric working postures. To overcome these problems the Assembly Specific Fore Atlas was created during the recent years. From a sample of automotive workers (n = 273), a set of 54 whole‐body forces (6 main force directions while standing, sitting, kneeling; in an upward, bent, and overhead posture) and a set of 38 types of finger‐hand forces (all at maximum voluntary contractions [MVC] levels) were measured in the field. The inputs for the types of force exertions required in practice were sampled from a consortium of major European car and truck companies. In addition, evaluation methods were developed that allow “calculating” maximum recommended force limits from the measured maximum static forces (i.e., MVC) and task and user group relevant parameters. This contribution gives a short overview on the data collected and focuses on the evaluation methods that had been realized. First, qualitative results are presented from the first field tests.
Reactions of Quino‐Ketenes with C‐Nucleophiles: Syntheses of (2‐Hydroxyphenyl)methanols and 2‐Hydroxyphenyl Ketones
Authors: Gündüz Hande , Kumbaraci Volkan , Talinli Naciye
Published: August 2014

In this study, we have developed a new, efficient, and one‐step protocol for the synthesis of derivatives of 2,4‐dihydroxyphenyl ketones and/or 2,4‐dihydroxyphenyl/naphthalenyl methanols starting from benzodioxinones/naphthodioxinones and organolithium compounds. Reactions have been performed under thermal conditions without catalyst. This work is the first example of the preparation of these products starting from 2‐hydroxy acids.
Copper‐Catalyzed N‐Arylation of 1,1,3,3‐TetramethylguanidinePhenyl Isocyanate Adduct
Authors: Yavari Issa , Nematpour Manijeh
Published: August 2014

The synthesis of a novel class of 3‐[bis(dimethylamino)methylidene]‐1,1‐diarylureas via a Cu‐catalyzed multicomponent reaction of phenyl isocyanate (PhNCO), 1,1,3,3‐tetramethylguanidine, and aryl halides is described.
Two New C‐seco Limonoids from the Fruit of Melia azedarach
Authors: Jin Qinghao , Lee Chul , Woo Lee Jin , Yeon Choi Jeong , Tae Hong Jin , Kim Youngsoo , Kyeong Lee Mi , Yeon Hwang Bang
Published: August 2014

A phytochemical investigation of the fruits of Melia azedarach led to the isolation of two new C‐seco‐nimbolinin‐type limonoids, 3α‐acetoxy‐1α,7α‐dihydroxy‐12α‐methoxynimbolinin (1) and 3α‐acetoxy‐1α,12α‐dihydroxy‐7α‐(2‐methylprop‐2‐enoyl)nimbolinin (2), together with eleven known compounds, 3–13. Their structures were elucidated on the basis of extensive spectroscopic analysis, including 1H‐ and 13C‐NMR, HMQC, HMBC, NOESY, and HR‐FAB‐MS.
Benzo[a]azulenediones and 10,10′‐Bibenzo[a]azulene
Authors: Sigrist Rolf , Hansen Hans‐Jürgen
Published: August 2014

The oxidation of benzo[a]azulene (4) with commercial MnO2 in dioxane/H2O leads to a number of products in low yield (Table 1). Treatment of 4 with ‘mild’ MnO2 (MnO2/C) in dioxane/5% H2O results in the formation of 10,10′‐bibenzo[a]azulene (18) in yields of up to 59% of isolated and purified material. Compound 18 exhibits atropisomerism and can be separated by HPLC on a Chiralcel column at room temperature into its stable antipodes (Fig.).
The New Belgian Act on Security Interests in Movable Property
Authors: Dirix Eric
Published: August 2014

The new Belgian Pledge Act of 11th July 2013 changes in a fundamental way the Belgian Civil Code as to security rights over movables. It contains a complete modernization of the legal framework regarding security rights over movables including the retention of title and the legal lien. The most important innovation is the possibility of a pledge over movable goods without dispossession of the pledger. It is expected that the new provisions will enter into force in 2015 when the new pledge register will be operational. The paper examines this reform from a comparative perspective against the background of legal harmonization in Europe.
Functional morphology of the copulatory system of box crabs with long second gonopods (Calappidae, Eubrachyura, Decapoda, Crustacea)
Authors: Ewers‐Saucedo Christine , Hayer Sarah , Brandis Dirk
Published: August 2014

Male True Crabs use two pairs of gonopods to deliver mating products during copulation. Commonly, the second pair is shorter than the first pair, and most research to date has focused on species with short second gonopods. We investigated male and female copulatory organs in Calappula saussurei and Calappa pelii, two species of box crabs (Calappidae) with second gonopods which are longer than the first pair. Scanning electron microscopy and histological cross sectioning show that the female copulatory system is unique in several aspects: the genital duct is part concave and part simple type. The seminal receptacle is divided into two chambers, a ventral chamber of ectodermal and mesodermal origin, and a dorsal chamber of ectodermal origin. This dorsal chamber is the location of spermatophore reception during copulation. A sperm plug closes the dorsal chamber off. We propose that long second gonopods deliver male mating products directly into the dorsal chamber. To date, spermatophore reception has been associated with the mesodermal tissue of the seminal receptacle. The copulatory system of box crabs with long second gonopods shows novel deviations from this general pattern. J. Morphol. 276:77–89, 2015. © 2014 Wiley Periodicals, Inc.
Prediction of survival for patients with advanced colorectal cancer using 1H High‐resolution magic angle spinning nuclear MR spectroscopy
Authors: Pacholczyk‐Sienicka Barbara , Fabiańska Anna , Pasz‐Walczak Grażyna , Kordek Radzisław , Jankowski Stefan
Published: August 2014

Purpose

To evaluate whether the metabolic profiles of colorectal cancer specimens can be used for prediction of survival.

Materials and Methods

The metabolic profiles of colorectal cancer tissues were determined using the high‐resolution magic angle spinning (HR MAS) nuclear magnetic resonance (NMR) technique (16.4 T). HR MAS analysis was performed for 52 tissues taken from patients classified as survivors and nonsurvivors (30). Quantitative analysis was performed for each spectrum. Receiver operating characteristic (ROC) curves were used to evaluate the potential to predict patient survival over 5.5 years.

Results

Analysis of 1H NMR spectra led to the identification and quantitative analysis of 30 metabolites. A significant increase in the Tau/Gly and Tau/MI ratios were associated with long‐term survival (P = 0.004 and P = 0.003, respectively). ROC analysis indicated that the Tau/MI ratio had the best predictive value for survival (sensitivity 64.7% and specificity 100%). Good predictive value of survival was found for Tau/Gly ratio (sensitivity 63.6% and specificity 96.3%). Moreover, the Glu/Gln metabolic ratio with a cutoff level of 1.74 was predictive of survival with a sensitivity of 83.3% and a specificity of 85.7%.

Conclusion

Our results indicate that HR MAS spectroscopy is potentially useful for survival prediction in advanced colorectal cancer. J. Magn. Reson. Imaging 2015;41:1669–1674. © 2014 Wiley Periodicals, Inc.