bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring health disparities: a comparison of absolute and relative disparities
Authors: Moonesinghe Ramal , Beckles Gloria L.A.
Published: November 2015

Monitoring national trends in disparities in different diseases could provide measures to evaluate the impact of intervention programs designed to reduce health disparities. In the US, most of the reports that track health disparities provided either relative or absolute disparities or both. However, these two measures of disparities are not only different in scale and magnitude but also the temporal changes in the magnitudes of these measures can occur in opposite directions. The trends for absolute disparity and relative disparity could move in opposite directions when the prevalence of disease in the two populations being compared either increase or decline simultaneously. If the absolute disparity increases but relative disparity declines for consecutive time periods, the absolute disparity increases but relative disparity declines for the combined time periods even with a larger increase in absolute disparity during the combined time periods. Based on random increases or decreases in prevalence of disease for two population groups, there is a higher chance the trends of these two measures could move in opposite directions when the prevalence of disease for the more advantaged group is very small relative to the prevalence of disease for the more disadvantaged group. When prevalence of disease increase or decrease simultaneously for two populations, the increase or decrease in absolute disparity has to be sufficiently large enough to warrant a corresponding increase or decrease in relative disparity. When absolute disparity declines but relative disparity increases, there is some progress in reducing disparities, but the reduction in absolute disparity is not large enough to also reduce relative disparity. When evaluating interventions to reduce health disparities using these two measures, it is important to consider both absolute and relative disparities and consider all the scenarios discussed in this paper to assess the progress towards reducing or eliminating health disparities.
The taxonomic status of Hypsela sessiliflora E.Wimm. (Campanulaceae)
Authors: Albrecht David , Walsh Neville G , Jobson Richard W , Knox Eric B
Published: November 2015

The taxonomic status of Hypsela sessiliflora, a threatened NSW endemic, was examined using morphological and molecular data. Although the Type specimen appears to be missing and the protologue is of limited value, available evidence suggests that it is best included within a slightly broadened circumscription of the highly variable Isotoma fluviatilis subsp. fluviatilis.
Two new species of Prostanthera (Lamiaceae) in New South Wales
Authors: Conn Barry John , Wilson Trevor C
Published: November 2015

Prostanthera gilesii and P. makinsonii (Lamiaceae) are described as new for New South Wales, Australia. These descriptions are accompanied by illustrations and general notes, including distribution and conservation status. A new identification key is provided for the species of Prostanthera in New South Wales.
Li partitioning in the benthic foraminifera Amphistegina lessonii
Authors: Langer Gerald , Sadekov Aleksey , Thoms Silke , Mewes Antje , Nehrke Gernot , Greaves Mervyn , Misra Sambuddha , Bijma Jelle , Elderfield Henry
Published: November 2015

The shallow water benthic foraminifer Amphistegina lessonii was grown in seawater of variable Li and Ca concentration and shell Li/Ca was determined by means of LA‐ICPMS. Shell Li/Ca is positively correlated to seawater Li/Ca only when the Li concentration of seawater is changed. If the seawater Ca concentration is changed, shell Li/Ca remains constant. This indicates that Li does not compete with Ca for incorporation in the shell of A. lessonii. A recently proposed calcification model can be applied to divalent cations (e.g., Mg and Sr), which compete for binding sites of ion transporters and positions in the calcite lattice. By contrast, the transport pathway of monovalent cations such as Li is probably diffusion based (e.g., ion‐channels), and monovalent cations do not compete with Ca for a position in the calcite lattice. Here we present a new model for Li partitioning into foraminiferal calcite which predicts our experimental results and should also be applicable to other alkali metals.
West wall structuring of equatorial plasma bubbles simulated by three‐dimensional HIRB model
Authors: Yokoyama T. , Jin H. , Shinagawa H.
Published: November 2015

Plasma density depletions in the equatorial ionosphere, or so‐called equatorial plasma bubbles (EPBs), are generated in the postsunset period and tend to have a very complex spatial structure. Especially, the east‐west asymmetry of EPBs has been reported by various observations. Using a high‐resolution bubble (HIRB) model, which is a newly developed three‐dimensional numerical model for the equatorial ionosphere, small‐scale structuring at the west wall of large‐scale F layer upwelling is clearly reproduced for the first time. It is not an eastward neutral wind but a vertical shear of zonal plasma drift velocity at the bottomside of the F region that plays an important role in accelerating the instability growth at the west wall and generating the east‐west asymmetry of EPBs.
Multiyear applications of WRF/Chem over continental U.S.: Model evaluation, variation trend, and impacts of boundary conditions
Authors: Yahya Khairunnisa , He Jian , Zhang Yang
Published: November 2015

Multiyear applications of an online‐coupled meteorology‐chemistry model allow an assessment of the variation trends in simulated meteorology, air quality, and their interactions to changes in emissions and meteorology, as well as the impacts of initial and boundary conditions (ICONs/BCONs) on simulated aerosol‐cloud‐radiation interactions over a period of time. In this work, the Weather Research and Forecasting model with Chemistry version 3.4.1 (WRF/Chem v. 3.4.1) with the 2005 Carbon Bond mechanism coupled with the Volatility Basis Set module for secondary organic aerosol formation (WRF/Chem‐CB05‐VBS) is applied for multiple years (2001, 2006, and 2010) over continental U.S. This work also examines the changes in simulated air quality and meteorology due to changes in emissions and meteorology and the model's capability in reproducing the observed variation trends in species concentrations from 2001 to 2010. In addition, the impacts of the chemical ICONs/BCONs on model predictions are analyzed. ICONs/BCONs are downscaled from two global models, the modified Community Earth System Model/Community Atmosphere model version 5.1 (CESM/CAM v5.1) and the Monitoring Atmospheric Composition and Climate model (MACC). The evaluation of WRF/Chem‐CB05‐VBS simulations with the CESM ICONs/BCONs for 2001, 2006, and 2010 shows that temperature at 2 m (T2) is underpredicted for all three years likely due to inaccuracies in soil moisture and soil temperature, resulting in biases in surface relative humidity, wind speed, and precipitation. With the exception of cloud fraction, other aerosol‐cloud variables including aerosol optical depth, cloud droplet number concentration, and cloud optical thickness are underpredicted for all three years, resulting in overpredictions of radiation variables. The model performs well for O3 and particulate matter with diameter less than or equal to 2.5 (PM2.5) for all three years comparable to other studies from literature. The model is able to reproduce observed annual average trends in O3 and PM2.5 concentrations from 2001 to 2006 and from 2006 to 2010 but is less skillful in simulating their observed seasonal trends. The 2006 and 2010 results using CESM and MACC ICONs/BCONs are compared to analyze the impact of ICONs/BCONs on model performance and their feedbacks to aerosol, clouds, and radiation. Comparing to the simulations with MACC ICONs/BCONs, the simulations with the CESM ICONs/BCONs improve the performance of O3 mixing ratios (e.g., the normalized mean bias for maximum 8 h O3 is reduced from −17% to −1% in 2010), PM2.5 in 2010, and sulfate in 2006 (despite a slightly larger normalized mean bias for PM2.5 in 2006). The impacts of different ICONs/BCONs on simulated aerosol‐cloud‐radiation variables are not negligible, with larger impacts in 2006 compared to 2010.
LC
–
MS
Applications in Environmental and Food Analysis
Authors: Gentili Alessandra , Caretti Fulvia , Fernández Virginia Pérez
Published: November 2015

This chapter offers a comprehensive overview of the main application fields of liquid chromatography–mass spectrometry (
LC
–
MS
) technology, highlighting practical aspects, advantages, and shortcomings. The areas covered include environmental and food applications. Emphasis is placed on potentiality and pitfalls of the different
LC
–
MS
approaches to perform both confirmation analysis and large‐scale screening analysis of pesticides, drugs, and toxins using both low‐ and high‐resolution mass spectrometry. The key role of
LC
–
MS
in the emerging
omics
technologies (proteomics, metabolomics, and lipidomics) will also be discussed along with “global” or “targeted” strategies to identify a huge number of proteins or metabolites. Latest advances and potential trends using
LC
–
MS
are also outlined in the several branches of the analytical chemistry.
Inline Detectors
Authors: Rao Ramisetti Nageswara , Rao Pothuraju Nageswara
Published: November 2015

A detector is considered one of the most important components of LC and regarded as an input transducer which translates the changes in the chemical composition of the column effluents into electrical signals. The UV‐Visible absorbance detector, fluorescence detector, refractive index (RI) detector, conductivity detector, and mass detectors are most successful. Refractive index is a property of both the solute and the mobile phase. Alternatively, the detectors such as UV‐Vis and electrochemical based on the property of a solute but not solvent are called solute property detectors. The RI detector is widely used in exclusion chromatography but is less sensitive compared to UV. The chapter also overviews the photodiode array detector (PDA), electrochemical detector (ECD), carona charged aerosol detection (CAD), and conductivity detector. The important characteristics required for an ideal detector include sensitivity, linearity, universal or selectivity, low dead volume, and nondestructive.
ChiralGC
Authors: Schurig Volker
Published: November 2015

In enantioselective gas chromatography (enantio‐GC), the chiral stationary phases (CSPs) are coated on deactivated capillary columns in bulk as nonvolatile liquids or as solution in a conventional achiral stationary phase (squalane, polyethylene glycol, and various polysiloxanes). In Chirasil‐type CSPs, the chiral selector is chemically bonded to a polysiloxane backbone and thermally immobilized on the capillary inner surface. Three different approaches of mixed binary selector systems in enantio‐GC have been described in this chapter. The separation of enantiomers on chiral nonracemic selectors by enantio‐GC is entirely governed by thermodynamics. It is brought about by the fast and reversible formation of transient and energetically distinct diastereomeric association complexes (DD′ and LD′) between the select and enantiomers (arbitrarily denoted D and L) and the enantiopure selector (arbitrarily denoted D′). The chapter ends with a note on the mechanisms of chirality recognition.
Chip‐Based Gas Chromatography
Authors: Shakeel Hamza , Agah Masoud
Published: November 2015

The implementation of microfabrication and nanotechnology methods for gas chromatography (GC) components has opened up new applications and design paradigms. These new methods have enabled the realization of a low‐cost, field‐portable, and low‐power GC platform. In this chapter, microfabricated GC (µGC) components (separation columns and detectors) are described. A brief introduction about the established microfabrication techniques is followed by an overview of µGC history dating back to 1979. The main focus of this chapter is the review of different aspects of µGC separation column design, fabrication, coating, and characterization. It touches upon the different aspects of cutting‐edge µGC detectors. The chapter concludes with the state‐of‐the‐art portable µGC systems and an outlook describing the future challenges of this technology.
Modern Injection Modes (Stacking) for
CE
Authors: Quirino Joselito P.
Published: November 2015

The development of assays for real samples using capillary electrophoresis (
CE
) normally involves some form of sample treatment to remove interfering compounds and/or to enrich the target analytes. Sample concentration is performed to overcome the poor detection sensitivity in
CE
using photometric or on‐capillary detection schemes. This chapter will cover some of the recent (from 2010) or modern approaches for online sample concentration or stacking in
CE
. The mechanism of selected stacking approaches will be highlighted.
Detectors in Capillary Electrophoresis
Authors: Tůma Petr , Opekar František
Published: November 2015

This chapter presents a fundamental overview over current detection systems used in capillary electrophoresis with the focus on modern trends. Attention is paid mainly to
UV
‐
Vis
absorption spectrometric, fluorescence, amperometric, contactless conductivity, and electrochemiluminiscence detectors. Each detection technique is characterized by fundamental physical–chemical principle, designs of detection cells, and examples of typical applications are presented. Special attention is given to combinations of detection techniques used in multidimensional detection systems.
Two‐Dimensional Liquid Chromatography
Authors: Sarrut Morgan , Marchetti Nicola , Heinisch Sabine
Published: November 2015

Two‐dimensional liquid chromatography saw significant developments in handling the need to separate a rising number of highly complex samples. 2
D
‐
LC
is the coupling of the separation of a complex sample by a first
LC
method to a second different
LC
method. This chapter details the different ways to perform such coupling 2
D
‐
LC
methods: heart‐cutting method; offline, online, and stop‐flow methods, and comprehensive
LC
 × 
LC
. The critical parameter is peak capacity that is defined and calculated in classical
LC
and 2
D
‐
LC
methods. It is linked to the orthogonality of the separation power of the two coupled
LC
methods. From a practical point of view, the effective peak capacity is compared with the theoretical one. Analysis time and dilution are also two critical parameters in 2
D
‐
LC
that need to be considered. All parameters are presented describing a practical method development.
Sampling Strategies: Statistics of Sampling
Authors: Bodnar Małgorzata , Konieczka Piotr , Namieśnik Jacek
Published: November 2015

Each step of the analytical procedure has a significant influence on the final result of the analysis. In the majority of cases the analytical procedure encompasses sampling because the analysis of the entire object (material) is usually not possible. Thus it is necessary to include the uncertainty related to sampling procedure in the uncertainty budget calculations. In the paper:

the most important properties of the analysed object, which influence the method of sample collection and handling,

elements of the sampling strategy,

methods of estimating uncertainty is presented in the EURACHEM Guide and also in the Theory of Sampling (TOS),

were described.
Solid‐Phase Microextraction
Authors: Mehdinia Ali , Aziz‐Zanjani Mohammad Ovais
Published: November 2015

Since its introduction in 1990, solid phase microextraction (SPME) method has been widely applied as a convenient and rapid sample preparation technique. The developments in SPME which make it flexible for different applications could be divided into the following categories: (i) emergence of novel SPME configurations and devices, (ii) application of manifold homemade materials as SPME coatings or sorbents, and (iii) development of different techniques for preparing SPME coatings. The aim of this chapter is to discuss about the fundamentals of the SPME as well as its recent advances. These advances were oriented to address the needs for an efficient, rapid, reproducible and selective extraction, suitable for laboratory and in‐vivo analysis, and on‐site sampling.
Novel Approach for Modeling the Dynamics of Fiber Breakage in Polymer Matrix Composites during Capillary Extrusion
Authors: Sporleder F. , Carella J. M. , Dorao C. A. , Ludueña L. N.
Published: November 2015

In this work, a population balance equation (PBE) model is used to predict the evolution of the fiber breakage in thermoplastic polymer/short‐fiber composites during capillary extrusion. The least squares spectral method was used to solve the resulting integrodifferential equation. The differences found between the experimental and simulated data were attributed to the selected breakage and redistribution functions. An experimental setup is proposed to find accurate breakage functions for this problem. The results indicate that the application of the PBE for such a breakage process could be a powerful tool for the design of injection molding molds.
Telomere longitudinal shortening as a biomarker for dementia status of adults with Down syndrome
Authors: Jenkins Edmund C. , Ye Lingling , Krinsky‐McHale Sharon J. , Zigman Warren B. , Schupf Nicole , Silverman Wayne P.
Published: November 2015

Previous studies have suggested that Alzheimer's disease (AD) causes an accelerated shortening of telomeres, the ends of chromosomes consisting of highly conserved TTAGGG repeats that, because of unidirectional 5′–3′ DNA synthesis, lose end point material with each cell division. Our own previous work suggested that telomere length of T‐lymphocytes might be a remarkably accurate biomarker for “mild cognitive impairment” in adults with Down syndrome (MCI‐DS), a population at dramatically high risk for AD. To verify that the progression of cognitive and functional losses due to AD produced this observed telomere shortening, we have now examined sequential changes in telomere length in five individuals with Down syndrome (3F, 2M) as they transitioned from preclinical AD to MCI‐DS (N = 4) or dementia (N = 1). As in our previous studies, we used PNA (peptide nucleic acid) probes for telomeres and the chromosome 2 centromere (as an “internal standard” expected to be unaffected by aging or dementia status), with samples from the same individuals now collected prior to and following development of MCI‐DS or dementia. Consistent shortening of telomere length was observed over time. Further comparisons with our previous cross‐sectional findings indicated that telomere lengths prior to clinical decline were similar to those of other adults with Down syndrome (DS) who have not experienced clinical decline while telomere lengths following transition to MCI‐DS or dementia in the current study were comparable to those of other adults with DS who have developed MCI‐DS or dementia. Taken together, findings indicate that telomere length has significant promise as a biomarker of clinical progression of AD for adults with DS, and further longitudinal studies of a larger sample of individuals with DS are clearly warranted to validate these findings and determine if and how factors affecting AD risk also influence these measures of telomere length. © 2015 Wiley Periodicals, Inc.
RDoC and translational perspectives on the genetics of trauma‐related psychiatric disorders
Authors: Montalvo‐Ortiz Janitza L. , Gelernter Joel , Hudziak James , Kaufman Joan
Published: November 2015

Individuals with a history of child abuse are at high risk for depression, anxiety disorders, aggressive behavior, and substance use problems. The goal of this paper is to review studies of the genetics of these stress‐related psychiatric disorders. An informative subset of studies that examined candidate gene by environment (GxE) predictors of these psychiatric problems in individuals maltreated as children is reviewed, together with extant genome wide association studies (GWAS). Emerging findings on epigenetic changes associated with adverse early experiences are also reviewed. Meta‐analytic support and replicated findings are evident for several genetic risk factors; however, extant research suggests the effects are pleiotropic. Genetic factors are not associated with distinct psychiatric disorders, but rather diverse clinical phenotypes. Research also suggests adverse early life experiences are associated with changes in gene expression of multiple known candidate genes, genes involved in DNA transcription and translation, and genes necessary for brain circuitry development, with changes in gene expression reported in key brain structures implicated in the pathophysiology of psychiatric and substance use disorders. The finding of pleiotropy highlights the value of using the Research Domain Criteria (RDoC) framework in future studies of the genetics of stress‐related psychiatric disorders, and not trying simply to link genes to multifaceted clinical syndromes, but to more limited phenotypes that map onto distinct neural circuits. Emerging work in the field of epigenetics also suggests that translational studies that integrate numerous unbiased genome‐wide approaches will help to further unravel the genetics of stress‐related psychiatric disorders. © 2015 Wiley Periodicals, Inc.
Dose‐Dependent Response of Personal Glucose Meters to Nicotinamide Coenzymes: Applications to Point‐of‐Care Diagnostics of Many Non‐Glucose Targets in a Single Step
Authors: Zhang Jingjing , Xiang Yu , Wang Miao , Basu Ananda , Lu Yi
Published: November 2015

We report a discovery that personal glucose meters (PGMs) can give a dose‐dependent response to nicotinamide coenzymes, such as the reduced form of nicotinamide adenine dinucleotide (NADH). We have developed methods that take advantage of this discovery to perform one‐step homogeneous assays of many non‐glucose targets that are difficult to recognize by DNAzymes, aptamers, or antibodies, and without the need for conjugation and multiple steps of sample dilution, separation, or fluid manipulation. The methods are based on the target‐induced consumption or production of NADH through cascade enzymatic reactions. Simultaneous monitoring of the glucose and L‐lactate levels in human plasma from patients with diabetes is demonstrated and the results are comparable to those from current standard test methods. Since a large number of commercially available enzymatic assay kits utilize NADH in their detection, this discovery will allow the transformation of almost all of these clinical lab tests into POC tests that use a PGM.
Total Synthesis and Structural Reassignment of Aspergillomarasmine A
Authors: Liao Daohong , Yang Shaoqiang , Wang Jianyu , Zhang Jian , Hong Benke , Wu Fan , Lei Xiaoguang
Published: November 2015

The increase and spread of Gram‐negative bacteria that resistant are to almost all currently available β‐lactam antibiotics is a major global health problem. The primary cause for drug resistance is the acquisition of metallo‐β‐lactamases such as metallo‐β‐lactamase‐1 (NDM‐1). The fungal natural product aspergillomarasmine A (AMA), a fungal natural product, is an inhibitor of NDM‐1 and has shown promising in vivo therapeutic potential in a mouse model infected with NDM‐1‐expressing Gram‐negative bacteria. The first total synthesis and stereochemical configuration reassignment of aspergillomarasmine A is reported. The synthesis highlights a flexible route and an effective strategy to achieve the required oxidation state at a late stage. This modular route is amenable to the efficient preparation of analogues for the development of metallo‐β‐lactamase inhibitors to potentiate β‐lactam antibiotics.
Accelerated weathering properties of compatibilized composites made from recycled HDPE and nonmetallic printed circuit board waste
Authors: Muniyandi Shantha Kumari , Sohaili Johan , Hassan Azman
Published: November 2015

The main aim of this work is to examine the influence of the contents of nonmetallic printed circuit board (PCB) waste component on the photodegradation of recycled high‐density polyethylene (rHDPE) composites. The properties tested were chemical changes, flexural properties, color stability, water absorption, leaching properties, and crystallinity changes of the composites after exposure to 2,000 h of accelerated weathering. Surface degradation for composites with nonmetallic PCB was less compared to unfilled rHDPE mainly because glass fibers covered almost the whole surface of specimens, acting as a protective layer, thus, slowing down the photodegradation reaction. Incorporation of compatibilizer in rHDPE/PCB composites had played an important role in resisting degradation due to UV exposure. All the composite samples became lighter in the early stages of weathering exposure; however, compatibilized composites showed less lightening and reduction on strength and modulus. Carbonyl index increases with exposure time indicating that the oxidation reaction continuously occurred during the aging process. Incorporation of compatibilizer had successfully reduced the water absorption uptake by the composites and effectively delayed some degradation properties of weathering. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43110.
Behavioral Variability in the Play of Children With Autism and Their Typically Developing Peers
Authors: Bancroft Stacie L. , Thompson Rachel H. , Peters Lindsay C. , Dozier Claudia L. , Harper Amy M.
Published: November 2015

Invariable or repetitive behavior is a defining feature of autism and can limit a child's exposure to varying consequences and subsequent learning opportunities. We compared the variability in play material selection between 30 children with autism and 30 typically developing children, aged 2‐8 years, across three different activities: selecting paper outfits to dress dolls, selecting beads to place on a string, and choosing marker colors for coloring shapes. Selections of materials could be varied or identical to previous selections within the session. Although there was some overlap between the two groups, children with autism were more likely to respond invariably than typically developing children. Two‐year‐old children in both groups tended to display invariable play material selection, but variability increased across increasing age groups for typical children and remained relatively stable across increasing age groups for children with autism. Implications regarding the divergence in variable behavior across children with autism and typically developing children as a function of age are discussed. Copyright © 2015 John Wiley & Sons, Ltd.
Assessment of learning gains in a flipped biochemistry classroom
Authors: Ojennus Deanna Dahlke
Published: November 2015

The flipped classroom has become an increasingly popular pedagogical approach to teaching and learning. In this study, learning gains were assessed in a flipped biochemistry course and compared to gains in a traditional lecture. Although measured learning gains were not significantly different between the two courses, student perception of learning gains did differ and indicates a higher level of satisfaction with the flipped lecture format. © 2015 by The International Union of Biochemistry and Molecular Biology, 44:20–27, 2016.
Effects of physical exercise training in DNA damage and repair activity in humans with different genetic polymorphisms of hOGG1 (Ser326Cys)
Authors: Soares Jorge Pinto , Silva Ana Inês , Silva Amélia M. , Almeida Vanessa , Teixeira João Paulo , Matos Manuela , Gaivão Isabel , Mota Maria Paula
Published: November 2015

The main purpose of this pilot study was to investigate the possible influence of genetic polymorphisms of the hOGG1 (Ser326Cys) gene in DNA damage and repair activity by 8‐oxoguanine DNA glycosylase 1 (OGG1 enzyme) in response to 16 weeks of combined physical exercise training. Thirty‐two healthy Caucasian men (40–74 years old) were enrolled in this study. All the subjects were submitted to a training of 16 weeks of combined physical exercise. The subjects with Ser/Ser genotype were considered as wild‐type group (WTG), and Ser/Cys and Cys/Cys genotype were analysed together as mutant group (MG). We used comet assay in conjunction with formamidopyrimidine DNA glycoslyase (FPG) to analyse both strand breaks and FPG‐sensitive sites. DNA repair activity were also analysed with the comet assay technique. Our results showed no differences between DNA damage (both strand breaks and FPG‐sensitive sites) and repair activity (OGG1) between genotype groups (in the pre‐training condition). Regarding the possible influence of genotype in the response to 16 weeks of physical exercise training, the results revealed a decrease in DNA strand breaks in both groups, a decrease in FPG‐sensitive sites and an increase in total antioxidant capacity in the WTG, but no changes were found in MG. No significant changes in DNA repair activity was observed in both genotype groups with physical exercise training. This preliminary study suggests the possibility of different responses in DNA damage to the physical exercise training, considering the hOGG1 Ser326Cys polymorphism. Copyright © 2015 John Wiley & Sons, Ltd.
Flexibility of C3h‐Symmetrical Linkers in Tris‐oligonucleotide‐Based Tetrahedral Scaffolds
Authors: Panagiotidis Christos , Kath‐Schorr Stephanie , von Kiedrowski Günter
Published: November 2015

Flexibility of tris‐oligonucleotides is determined by the length of their connecting hydrocarbon chains. Tris‐oligonucleotides are branched DNA building blocks with three oligonucleotide arms attached to a C3h‐symmetrical linker core at these chains. Four tris‐oligonucleotides hybridise into a tetrahedral nanocage by sequence‐determined self‐assembly. The influence of methylene, ethylene and propylene chains was studied by synthesising sets of tris‐oligonucleotides and analysing the relative stability of the hybridisation products against digestion by mung bean nuclease by using gel electrophoresis. Linkers with ethylene chains showed sufficient flexibility, whereas methylene‐chain linkers were too rigid. Tris‐oligonucleotides based on the latter still formed tetrahedral scaffolds in intermixing experiments with linkers of higher flexibility. Thus, a new generation of versatile isocyanurate‐based linkers was established.
Bottom‐Up Fabrication of Single‐Layered Nitrogen‐Doped Graphene Quantum Dots through Intermolecular Carbonization Arrayed in a 2D Plane
Authors: Li Rui , Liu Yousong , Li Zhaoqian , Shen Jinpeng , Yang Yuntao , Cui Xudong , Yang Guangcheng
Published: November 2015

A single‐layered intermolecular carbonization method was applied to synthesize single‐layered nitrogen‐doped graphene quantum dots (N‐GQDs) by using 1,3,5‐triamino‐2,4,6‐trinitrobenzene (TATB) as the only precursor. In this method, the gas produced in the pyrolysis of TATB assists with speeding up of the reactions and expanding the layered distance, so that it facilitates the formation of single‐layered N‐GQDs (about 80 %). The symmetric intermolecular carbonizations of TATB arrayed in a plane and six nitrogen‐containing groups ensure small, uniform sizes (2–5 nm) of the resulting products, and provide high nitrogen‐doping concentrations (N/C atomic ratio ca. 10.6 %). In addition to release of the produced gas, TATB is almost completely converted into aggregated N‐GQDs; thus, relatively higher production rates are possible with this approach. Investigations show that the as‐produced N‐GQDs have superior fluorescent characteristics; high water solubility, biocompatibility, and low toxicity; and are ready for potential applications, such as biomedical imaging and optoelectronic devices.
Tuning the Electron Acceptor in Phthalocyanine‐Based Electron Donor–Acceptor Conjugates
Authors: Sekita Michael , Jiménez Ángel J. , Marcos M. Luisa , Caballero Esmeralda , Rodríguez‐Morgade M. Salomé , Guldi Dirk M. , Torres Tomás
Published: November 2015

Zinc phthalocyanines (ZnPc) have been attached to the peri‐position of a perylenemonoimide (PMI) and a perylenemonoanhydride (PMA), affording electron donor–acceptor conjugates 1 and 2, respectively. In addition, a perylene‐monoimide‐monoanhydride (PMIMA) has been connected to a ZnPc through its imido position to yield the ZnPc‐PMIMA conjugate 10. The three conjugates have been studied for photoinduced electron transfer. For ZnPc‐PMIMA 10, electron transfer occurs upon both ZnPc and PMIMA excitation, giving rise to a long‐lived (340 ps) charge‐separated state. For ZnPc‐PMI 1 and ZnPc‐PMA 2, stabilization of the radical ion pair states by using polar media is necessary. In THF, photoexcitation of either ZnPc or PMI/PMA produces charge‐separated states with lifetimes of 375 and 163 ps, respectively.
Discovery of 3‐Hydroxy‐3‐phenacyloxindole Analogues of Isatin as Potential Monoamine Oxidase Inhibitors
Authors: Tripathi Rati K. P. , Krishnamurthy Sairam , Ayyannan Senthil R.
Published: November 2015

A series of 3‐hydroxy‐3‐phenacyloxindole analogues of isatin were designed, synthesized, and evaluated in vitro for their inhibitory activity toward monoamine oxidase (MAO) A and B. Most of the synthesized compounds proved to be potent and selective inhibitors of MAO‐A rather than MAO‐B. 1‐Benzyl‐3‐hydroxy‐3‐(4′‐hydroxyphenacyl)oxindole (compound 18) showed the highest MAO‐A inhibitory activity (IC50: 0.009±0.001 μm, Ki: 3.69±0.003 nm) and good selectivity (selectivity index: 60.44). Kinetic studies revealed that compounds 18 and 16 (1‐benzyl‐3‐hydroxy‐3‐(4′‐bromophenacyl)oxindole) exhibit competitive inhibition against MAO‐A and MAO‐B, respectively. Structure–activity relationship studies suggested that the 3‐hydroxy group is an essential feature for these analogues to exhibit potent MAO‐A inhibitory activity. Computational studies revealed the possible molecular interactions between the inhibitors and MAO isozymes. The computational data obtained are congruent with experimental results. Further studies on the lead inhibitors, including co‐crystallization of inhibitor–MAO complexes and in vivo evaluations, are essential for their development as potential therapeutic agents for the treatment of MAO‐associated neurological disorders.
Identification of HDAC6‐Selective Inhibitors of Low Cancer Cell Cytotoxicity
Authors: Gaisina Irina N. , Tueckmantel Werner , Ugolkov Andrey , Shen Sida , Hoffen Jessica , Dubrovskyi Oleksii , Mazar Andrew , Schoon Renee A. , Billadeau Daniel , Kozikowski Alan P.
Published: November 2015

The histone deacetylases (HDACs) occur in 11 different isoforms, and these enzymes regulate the activity of a large number of proteins involved in cancer initiation and progression. The discovery of isoform‐selective HDAC inhibitors (HDACIs) is desirable, as it is likely that such compounds would avoid some of the undesirable side effects found with the first‐generation inhibitors. A series of HDACIs previously reported by us were found to display some selectivity for HDAC6 and to induce cell‐cycle arrest and apoptosis in pancreatic cancer cells. In the present work, we show that structural modification of these isoxazole‐based inhibitors leads to high potency and selectivity for HDAC6 over HDAC1–3 and HDAC10, while unexpectedly abolishing their ability to block cell growth. Three inhibitors with lower HDAC6 selectivity inhibit the growth of cell lines BxPC3 and L3.6pl, and they only induce apoptosis in L3.6pl cells. We conclude that HDAC6 inhibition alone is insufficient for disruption of cell growth, and that some degree of class 1 HDAC inhibition is required. Moreover, the highly selective HDAC6Is reported herein that are weakly cytotoxic may find use in cancer immune system reactivation.
Structure–Activity Relationship Studies of Amino Acid Substitutions in Radiolabeled Neurotensin Conjugates
Authors: Mascarin Alba , Valverde Ibai E. , Mindt Thomas L.
Published: November 2015

Radiolabeled derivatives of the peptide neurotensin (NT) and its binding sequence NT(8–13) have been studied as potential imaging probes and therapeutics for NT‐1‐receptor‐positive cancer. However, a direct comparison of reported NT analogues, even if radiolabeled with the same radionuclide, is difficult because different techniques and models have been used for preclinical evaluations. In an effort to identify a suitable derivative of NT(8–13) for radiotracer development, we herein report a side‐by‐side in vitro comparison of radiometallated NT derivatives bearing some of the most commonly reported amino acid substitutions in their sequence. Performed investigations include cell internalization experiments, determinations of receptor affinity, measurements of the distribution coefficient, and blood serum stability studies. Of the [177Lu]‐1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA)‐labeled examples studied, analogues of NT(8–13) containing a short hydrophilic tetraethylene glycol (PEG4) spacer between the peptide and the radiometal complex, and a minimum number of substitutions of amino acid residues, exhibited the most promising properties in vitro.
Photoinduced Isomerization and Hepatoxicities of Semaxanib, Sunitinib and Related 3‐Substituted Indolin‐2‐ones
Authors: Ngai Mun Hong , So Choon Leng , Sullivan Michael B. , Ho Han Kiat , Chai Christina L. L.
Published: November 2015

3‐Substituted indolin‐2‐ones are an important class of compounds that display a wide range of biological activities. Sunitinib is an orally available multiple tyrosine kinase inhibitor that has been approved by the US Food and Drug Administration (FDA) for the treatment of renal cell cancer. Sunitinib and a related compound, semaxanib, exist as thermodynamically stable Z isomers, which photoisomerize to E isomers in solution. In this study, 17 3‐substituted indolin‐2‐ones were synthesized, and the kinetics of their photoisomerization were studied by 1H NMR spectroscopy. The rate constants for photoisomerization ranged from 0.009 to 0.048 h−1. Selected compounds were tested for cytotoxicity in the TAMH liver cell line. E/Z mixtures of four compounds were also assessed for toxicity in the TAMH and HepG2 cell lines. In some cases, the stereochemically pure drug was more toxic than the E/Z mixtures, but a general statement cannot be made. Our studies show that each stereoisomer could contribute differently to toxicity, suggesting that stereochemical purity issues that could arise from isomerization cannot be ignored.
Improved Electrochemical Performance of a ZnFe2O4 Nanoflake‐Based Supercapacitor Electrode by Using Thiocyanate‐Functionalized Ionic Liquid Electrolytes
Authors: Vadiyar Madagonda M. , Patil Sandip K. , Bhise Sagar C. , Ghule Anil V. , Han Sung‐Hwan , Kolekar Sanjay S
Published: November 2015

Thiocyanate‐functionalized ionic liquids (ILs) 1‐butyl‐3‐methylimidazolium thiocyanate [BMIM][SCN], 1‐ethyl‐3‐methylimidazolium thiocyanate [EMIM][SCN], and 3‐methylimidazolium thiocyanate [MIM][SCN], with varying chain lengths, were synthesized by using metathesis followed by ion exchange under reflux conditions. These ILs were investigated for their application as electrolyte with a ZnFe2O4 nanoflake‐based supercapacitor electrode; they exhibited significantly better performance than any other previously reported ILs used as electrolytes. [BMIM][SCN] showed higher specific capacitance (781 F g–1), cycle stability (95 % retention, 3000 cycle), and energy density (156 W h kg–1) than [EMIM][SCN] (590 F g–1, 86 % retention, and 78 W h kg–1) and [MIM][SCN] (250 F g–1, 80 % retention, and 50 W h kg–1). The ZnFe2O4 nanoflake electrodes were able to deliver an energy density of 156 W h kg–1 even at an extra high power density of 7.11 kW kg–1 in [BMIM][SCN] electrolyte, justifying its utility as a potential electrolyte. Furthermore, the effect of how the hydrated ions of the ILs in aqueous media influence the overall performance of the supercapacitor was studied systematically and found to be contrary to the reported trend and use of pure ILs as electrolytes.
Synthesis of the Spiroketal Core of the Pinnatifinoside Family of Natural Products
Authors: Chorley Daniel F. , Furkert Daniel P. , Brimble Margaret A.
Published: November 2015

Synthesis of the benzannulated spiroketal core of the pinnatifinoside family of natural products, via Sonagashira cross‐coupling and gold‐catalysed spirocyclisation of functionalised flavone derivatives is described. These investigations lay the framework for ongoing synthetic studies towards the pinnatifinoside family, and related biologically active derivatives.
Linear and Branched Pyridyl–Oxazole Oligomers: Synthesis and Circular Dichroism Detectable Effect on c‐Myc G‐Quadruplex Helicity
Authors: Rizeq Natalia , Georgiades Savvas N.
Published: November 2015

Five unprecedented pyridyl–oxazole oligomers exhibiting either linear or branched connectivity of their subunits were developed as a family of potential G‐quadruplex‐interacting ligands. Our synthesis employed variations of a key Pd/Cu‐mediated C–C cross‐coupling/C–H activation reaction to gain access to the oligomer products from a small set of substituted pyridine building blocks. The effect of the compounds on the conformation of a c‐myc oncogene promoter G‐quadruplex was investigated by circular dichroism under various conditions. Some or all of the compounds induced detectable helicity enhancement in low‐cation and Na+‐rich Tris‐HCl (pH 7.4) buffers, respectively, in which the helix was only partially prefolded.
Synthesis of Functionalized Ring C of Escobarines
Authors: Lechuga‐Eduardo Harim , Romero‐Ortega Moises , Olivo Horacio F.
Published: November 2015

A synthetic strategy was developed for the preparation of α‐ethynyl‐α,β‐epoxy‐β‐formyl‐ and α‐ethynyl‐α,β‐epoxy‐β‐(hydroxymethyl)cyclohexanone from cyclohexenone as a model study in a proposed synthesis of escobarines. This highly functionalized ring is found in the anti‐TB cassane‐type diterpenes escobarines A and B. Introduction of the β‐hydroxymethyl group was carried out by reversing the chemical reactivity of the enone using the anion of a sulfonyl group and electrophilic attack of paraformaldehyde. Further functionalization of the β‐(hydroxymethyl)cyclohexenone delivered the desired compounds.
Impact of lifestyle‐related disease on conversion and reversion in patients with mild cognitive impairment: after 12 months of follow‐up
Authors: Osone Akira , Arai Reiko , Hakamada Rina , Shimoda Kazutaka
Published: November 2015

Objective

The objective of the study is to investigate whether the lifestyle‐related disease (LSRD) hypertension, type II diabetes mellitus, and lipid abnormality are associated with conversion and reversion in patients with mild cognitive impairment (MCI) over 12 months of follow‐up.

Methods

One hundred and thirteen patients with MCI were prospectively enrolled and longitudinally assessed. Methods used include mini‐mental state examination, the Japanese version of the cognitive subscale of the Alzheimer's Disease Assessment Scale, the Clinical Dementia Rating, the Frontal Assessment Battery, the Neuropsychiatric Inventory, magnetic resonance imaging, and quantitative single‐photon emission computed tomography. In addition, laboratory examinations of glucose and lipids were also performed. All measurements were performed at first intake and again at the end of the 12‐month follow‐up. Conversion was identified as a change in Clinical Dementia Rating from 0.5 to 1 and reversion as a change from 0.5 to 0.

Results

Patients with MCI with reversion had lower comorbid lipid abnormality at baseline and higher cognitive and behaviour function across the 12‐month follow‐up compared with those with no change or conversion. Patients without comorbid LSRD had lower systolic pressure and lower glucose and triglyceride levels at baseline, as well as less cognitive decline compared with other groups across the follow‐up period.

Conclusions

The absence of lipid abnormality at baseline may contribute to reversion in patients with MCI. The presence of multiple LSRD was associated with cognitive decline. Our results highlight the contribution of multiple LSRD on increasing conversion and decreasing reversion in patients with MCI. Copyright © 2015 John Wiley & Sons, Ltd.
A novel method for identifying settings for well‐motivated ecologic studies of cancer
Authors: Stang Andreas , Kowall Bernd , Rusner Carsten , Trabert Britton , Bray Freddie , Schüz Joachim , McGlynn Katherine A. , Kuss Oliver
Published: November 2015

A low within‐country variability and a large between‐country variability in cancer incidence may indicate that ecologic factors are involved in the etiology of the disease. The aim of this study is to explore the within‐ and between‐country variability of cancer incidence to motivate high‐quality ecologic studies. We extracted age‐standardized incidence rate estimates (world standard population) from 135 regions for the ten most frequent invasive cancers in Europe for non‐Hispanic white populations from Cancer Incidence in Five Continents, Volume X. We fitted weighted multilevel Poisson regression models with random country effects for each cancer and sex. We estimated intraclass correlation coefficients (ICCs) and 95% confidence intervals (95% CIs). A high ICC indicates a low within‐ and a high between‐country variability of rates. The two cancer sites with the highest ICC among men were prostate cancer (0.96, 95% CI: 0.92–0.99) and skin melanoma (0.78, 0.64–0.93). Among women, high ICCs were observed for lung cancer (0.84, 0.73–0.95) and breast cancer (0.80, 0.69–0.91). The two most prominent sex differences for ICC occurred for cancers of the head and neck (men: 0.70, 0.55–0.85, women: 0.19, 0.08–0.30) and breast cancer (men: 0.04, 0.01–0.07, women: 0.80, 0.69–0.91). ICCs were relatively low for pancreatic cancer (men: 0.23, 0.10–0.35; women: 0.13, 0.04–0.21) and leukemia (men: 0.12, 0.04–0.21; women: 0.08, 0.02–0.14). For cancers with high ICC for which systematic factors of the health care system, screening and diagnostic activities are not plausible explanations for between‐country variations in incidence, cross‐country sex‐specific ecologic studies may be especially promising.
Non‐invasive in vivo imaging of early metabolic tumor response to therapies targeting choline metabolism
Authors: Mignion Lionel , Danhier Pierre , Magat Julie , Porporato Paolo E. , Masquelier Julien , Gregoire Vincent , Muccioli Giulio G. , Sonveaux Pierre , Gallez Bernard , Jordan Bénédicte F.
Published: November 2015

The cholinic phenotype, characterized by elevated phosphocholine and a high production of total‐choline (tCho)‐containing metabolites, is a metabolic hallmark of cancer. It can be exploited for targeted therapy. Non‐invasive imaging biomarkers are required to evaluate an individual's response to targeted anticancer agents that usually do not rapidly cause tumor shrinkage. Because metabolic changes can manifest at earlier stages of therapy than changes in tumor size, the aim of the current study was to evaluate 1H‐MRS and diffusion‐weighted MRI (DW‐MRI) as markers of tumor response to the modulation of the choline pathway in mammary tumor xenografts. Inhibition of choline kinase activity was achieved with the direct pharmacological inhibitor H‐89, indirect inhibitor sorafenib and down‐regulation of choline‐kinase α (ChKA) expression using specific short‐hairpin RNA (shRNA). While all three strategies significantly decreased tCho tumor content in vivo, only sorafenib and anti‐ChKA shRNA significantly repressed tumor growth. The increase of apparent‐diffusion‐coefficient of water (ADCw) measured by DW‐MRI, was predictive of the induced necrosis and inhibition of the tumor growth in sorafenib treated mice, while the absence of change in ADC values in H89 treated mice predicted the absence of effect in terms of tumor necrosis and tumor growth. In conclusion, 1H‐choline spectroscopy can be useful as a pharmacodynamic biomarker for choline targeted agents, while DW‐MRI can be used as an early marker of effective tumor response to choline targeted therapies. DW‐MRI combined to choline spectroscopy may provide a useful non‐invasive marker for the early clinical assessment of tumor response to therapies targeting choline signaling.