bluuebunny/crossref_metadata_2025 huggingface dataset:
Fractal Dimension of Microbead Assemblies Used for Protein Detection
Authors: Hecht Ariel , Commiskey Patrick , Lazaridis Filippos , Argyrakis Panos , Kopelman Raoul
Published: September 2014

We use fractal analysis to calculate the protein concentration in a rotating magnetic assembly of microbeads of size 1 μm, which has optimized parameters of sedimentation, binding sites and magnetic volume. We utilize the original Forrest–Witten method, but due to the relatively small number of bead particles, which is of the order of 500, we use a large number of origins and also a large number of algorithm iterations. We find a value of the fractal dimension in the range 1.70–1.90, as a function of the thrombin concentration, which plays the role of binding the microbeads together. This is in good agreement with previous results from magnetorotation studies. The calculation of the fractal dimension using multiple points of reference can be used for any assembly with a relatively small number of particles.
Averaging Techniques for Reaction Barriers in QM/MM Simulations
Authors: Cooper April M. , Kästner Johannes
Published: September 2014

Herein, we test and compare different techniques to obtain averaged reaction barriers from quantum mechanics/molecular mechanics (QM/MM) simulations based on snapshots taken from molecular dynamics. Reasonable values can be obtained from a fairly small sample of well‐chosen snapshots if an exponential averaging, also called Boltzmann averaging, is used. Snapshots with geometries close to the expected transition state are to be picked preferentially. Exponential averaging, arithmetic averaging, and simply taking the minimum barrier are compared to free‐energy calculations from umbrella sampling. Three reactions within a protein in a water environment are used as test cases.
Low temperature Hydrogen Reduction of High Surface Area Anatase and Anatase/β‐TiO2 for High‐Charging‐Rate Batteries
Authors: Ventosa Edgar , Tymoczko Anna , Xie Kunpeng , Xia Wei , Muhler Martin , Schuhmann Wolfgang
Published: September 2014

There are several strategies to improve the electrochemical performance of TiO2 as negative electrode material for Li‐ion batteries. Introducing oxygen vacancies through hydrogen reduction leads to an enhancement in electrical conductivity. However, this strategy does not improve the low lithium‐ion mobility. Herein, we show that by decreasing the temperature of hydrogen annealing the improved lithium‐ion mobility of high‐surface‐area TiO2 and β‐TiO2 can be combined with the enhanced electrical conductivity of oxygen deficiencies. Annealing at only 275–300 °C in pure hydrogen atmosphere successfully creates oxygen vacancies in TiO2, as confirmed by UV/Vis spectroscopy, whereas the temperature is low enough to maintain a high specific surface area and prevent β‐to‐anatase phase transformation. The hydrogen reduction of high‐surface‐area anatase or anatase/β‐TiO2 at these temperatures leads to improvements in the performance, achieving charge capacities of 142 or 152 mAh g−1 at 10C, respectively.
Homologous recombination efficiency enhanced by inhibition of MEK and GSK3β
Authors: Lin Zhaoyu , Zhang Yanli , Gao Tianyun , Wang Liudi , Zhang Qing , Zhou Juan , Zhao Jing
Published: September 2014

Homologous recombination in embryonic stem cells (ESCs) is widely utilized in genome engineering, particularly in the generation of gene targeted mice. However, genome engineering is often plagued by the problem of low homologous recombination efficiency. In this study, we developed a novel method to increase the efficiency of homologous recombination in ESCs by changing its culture conditions. By comparing the efficiency of different ESCs in various culture conditions, we determined that chemicals that inhibit the MEK and GSK3β pathways (2i condition) enhance homologous recombination and eliminate differences in efficiencies among cell lines. Analysis of gene expression patterns in ESCs maintained in different culture conditions has identified several homologous recombination‐related candidates, including the pluripotent markers Eras and Tbx3. The results of this study suggest that homologous recombination is associated with ESC pluripotency. genesis 52:889–896, 2014. © 2014 Wiley Periodicals, Inc.
Population structure and diversity of an invasive pine needle pathogen reflects anthropogenic activity
Authors: Barnes Irene , Wingfield Michael J. , Carbone Ignazio , Kirisits Thomas , Wingfield Brenda D.
Published: September 2014

Dothistroma septosporum is a haploid fungal pathogen that causes a serious needle blight disease of pines, particularly as an invasive alien species on Pinus radiata in the Southern Hemisphere. During the course of the last two decades, the pathogen has also incited unexpected epidemics on native and non‐native pine hosts in the Northern Hemisphere. Although the biology and ecology of the pathogen has been well documented, there is a distinct lack of knowledge regarding its movement or genetic diversity in many of the countries where it is found. In this study we determined the global population diversity and structure of 458 isolates of D. septosporum from 14 countries on six continents using microsatellite markers. Populations of the pathogen in the Northern Hemisphere, where pines are native, displayed high genetic diversities and included both mating types. Most of the populations from Europe showed evidence for random mating, little population differentiation and gene flow between countries. Populations in North America (USA) and Asia (Bhutan) were genetically distinct but migration between these continents and Europe was evident. In the Southern Hemisphere, the population structure and diversity of D. septosporum reflected the anthropogenic history of the introduction and establishment of plantation forestry, particularly with Pinus radiata. Three introductory lineages in the Southern Hemisphere were observed. Countries in Africa, that have had the longest history of pine introductions, displayed the greatest diversity in the pathogen population, indicating multiple introductions. More recent introductions have occurred separately in South America and Australasia where the pathogen population is currently reproducing clonally due to the presence of only one mating type.
EpsinR, a target for pyrenocine B, role in endogenous MHC‐II‐restricted antigen presentation
Authors: Shishido Tatsuya , Hachisuka Masami , Ryuzaki Kai , Miura Yuko , Tanabe Atsushi , Tamura Yasuaki , Kusayanagi Tomoe , Takeuchi Toshifumi , Kamisuki Shinji , Sugawara Fumio , Sahara Hiroeki
Published: September 2014

While the presentation mechanism of antigenic peptides derived from exogenous proteins by MHC class II molecules is well understood, relatively little is known about the presentation mechanism of endogenous MHC class II‐restricted antigens. We therefore screened a chemical library of 200 compounds derived from natural products to identify inhibitors of the presentation of endogenous MHC class II‐restricted antigens. We found that pyrenocine B, a compound derived from the fungus Pyrenochaeta terrestris, inhibits presentation of endogenous MHC class II‐restricted minor histocompatibility antigen IL‐4 inducible gene 1 (IL4I1) by primary dendritic cells (DCs). Phage display screening and surface plasmon resonance (SPR) analysis were used to investigate the mechanism of suppressive action by pyrenocine B. EpsinR, a target molecule for pyrenocine B, mediates endosomal trafficking through binding of soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors (SNAREs). Lentiviral‐mediated short hairpin (sh) RNA downregulation of EpsinR expression in DCs resulted in a decrease in the responsiveness of CD4+ T cells. Our data thus suggest that EpsinR plays a role in antigen presentation, which provides insight into the mechanism of presentation pathway of endogenous MHC class II‐restricted antigen.
Synthesis and Structure of [Et3NH][Fe(HL)2] [H3L =L‐2‐(3,5‐Di‐tert‐butyl‐2‐hydroxybenzylamino)succinic Acid] and Its Catalytic Activity towards Efficient Photodegradation of Dyes in the Presence of H2O2
Authors: Dasgupta Sohaham , Atta Sanghamitra , Singh N. D. Pradeep , Deb Dibakar , Kassel W. Scott , Bhattacharjee Manish
Published: September 2014

A new biogenic potentially tetradentate ligand,L‐2‐(3,5‐di‐tert‐butyl‐2‐hydroxybenzylamino)succinic acid, has been synthesized. Upon reaction with FeCl3in the presence of triethylamine, it afforded the complex [Et3NH][Fe(HL)2] (1). The complex was structurally characterized and was used for homogeneous photocatalytic degradation of methylene blue (MB), malachite green (MG), crystal violet (CV) and rhodamine B (RhB) under visible‐light irradiation in aqueous solution in the presence of H2O2.
Reactivity of Bis(organoamino)phosphanes with Aluminum(III) Compounds: Straightforward Access to Diiminophosphinates by Means of Hydrogen‐Atom Migration – An Experimental and Theoretical Study
Authors: Vrána Jan , Jambor Roman , Růžička Aleš , Alonso Mercedes , De Proft Frank , Dostál Libor
Published: September 2014

The reactivity of bis(organoamino)phosphanes PhP(NHR)(NHR′) (1a–1c, in which R, R′ = tBu for 1a; tBu, Dip for 1b; and Ph for 1c; Dip = C6H3–2,6‐iPr2) and tBuP(NHDip)2 (1d) with Me3Al was investigated. The reaction of 1a or 1b gave in the first step compounds [PhP(NHR)(NR′)]AlMe2 (in which R, R′ = tBu for 2a; tBu, Dip for 2b) as a result of methane elimination that upon heating underwent nitrogen‐to‐phosphorus hydrogen‐atom migration under the formation of diiminophosphinates [Ph(H)P(NR)(NR′)]AlMe2 (in which R, R′ = tBu for 3a; tBu, Dip for 3b). In contrast, phosphane 1c showed a reversed reaction sequence that yielded an intermediate [Ph(H)P(NHPh)(=NPh)]AlMe3 (2c) first as a consequence of hydrogen‐atom migration followed by the methane elimination and formation of diiminophosphinate [Ph(H)P(NPh)2]AlMe2 (3c). The partial deprotonation of 1a,b,d using one molar equivalent of nBuLi followed by the treatment with AlCl3 smoothly produced compounds [Ph(H)P(NR)(NR′)]AlCl2 (in which R, R′ = tBu for 4a; tBu, Dip for 4b) and [tBu(H)P(NDip)2]AlCl2 (4d), in which the hydrogen atom was again shifted from the nitrogen to the phosphorus atom. All studied compounds were characterized with the help of elemental analysis; 1H, 13C{1H}, 31P, and 31P{1H} NMR spectra; and in the case of 3c, 4a, 4b, and 4d by using single‐crystal X‐ray diffraction analysis. The phenomenon of the hydrogen‐atom migration was subjected also to a theoretical survey with particular emphasis on the influence of the phosphane used.
Monomeric Germanium(II) Amides Bearing β‐Diketiminato Ligands: Synthesis, Structural Characterization, and Thermal Properties
Authors: Ballestero‐Martínez Ernesto , Klosin Jerzy , Fahlman Bradley D. , Pineda Leslie W.
Published: September 2014

Germanium(II) compounds featuring β‐diketiminate‐type ligands are attractive for applications as nanoparticle precursors, imaging agents, and components of electronic devices. In this work, we report the synthesis of β‐diketiminatogermanium(II) amides L′Ge(NHPh) [1, L′ = {HC(CMeN–2,4,6‐Me3C6H2)2}–], L′Ge(4‐NHPy) (2), L′Ge(2‐NHPy) (3), and LGe(2‐NHPy) (4), L = {HC(CMeN–2,6‐iPr2C6H3)2}–], which were obtained by the reaction of a low‐valent organogermanium halide (L′GeCl or LGeCl) with a lithium salt of the respective aromatic amine (LiNHPh) or aminopyridine [Li(4‐NHPy) and Li(2‐NHPy)]. Compounds 1–4 were characterized with several techniques such as melting point, FTIR, 1H and 13C NMR spectroscopy, elemental analysis, X‐ray diffraction, and thermogravimetric analysis (TGA). Compounds 1–3 and 4 crystallized in the orthorhombic (space group Pnma) and monoclinic (space group P21/c) crystal systems, respectively. In all cases, the geometry around the central germanium atom was highly tetrahedrally distorted. According to TGA data, 1–4 do not sublime intact but rather exhibit thermal decomposition.
Core‐shell structure microcapsules with dual pH‐responsive drug release function
Authors: Yang Chih‐Hui , Wang Chih‐Yu , Grumezescu Alexandru Mihai , Wang Andrew H.‐J. , Hsiao Ching‐Ju , Chen Zu‐Yu , Huang Keng‐Shiang
Published: September 2014

Electrophoresis 2014, 35, 2673–2680. DOI: 10.1002/elps.201400210

pH‐responsive microcapsules manufactured by combining electrostatic droplets (ESD) and microfluidic droplets (MFD) techniques to produce mono‐disperse core (alginate) ‐ shell (chitosan) structure with controlled drug release behavior. The fabricated core‐shell microcapsules have a pH‐controlled drug delivery function according to acidic and alkaline environment, and present positive biocompatibility, indicating their potential use in biological and biomedical applications, such as pH‐responsive drug‐delivery systems, scaffolding for bone tissues, and as an oral drug‐delivery vehicle.

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Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals
Authors: Møller Peter , Jensen Ditte Marie , Christophersen Daniel Vest , Kermanizadeh Ali , Jacobsen Nicklas Raun , Hemmingsen Jette Gjerke , Danielsen Pernille Høgh , Karottki Dorina Gabriela , Roursgaard Martin , Cao Yi , Jantzen Kim , Klingberg Henrik , Hersoug Lars‐Georg , Loft Steffen
Published: September 2014

Increased levels of oxidatively damaged DNA have been documented in studies of metal, metal oxide, carbon‐based and ceramic engineered nanomaterials (ENMs). In particular, 8‐oxo‐7,8‐dihydroguanine‐2'‐deoxyguanosine (8‐oxodG) is widely assessed as a DNA nucleobase oxidation product, measured by chromatographic assays, antibody‐based methods or the comet assay with DNA repair enzymes. However, spurious oxidation of DNA has been a problem in certain studies applying chromatographic assays, yielding high baseline levels of 8‐oxodG. Antibody‐based assays detect high 8‐oxodG baseline levels, related to cross‐reactivity with other molecules in cells. This review provides an overview of efforts to reliably detect oxidatively damaged DNA and a critical assessment of the published studies on DNA damage levels. Animal studies with high baseline levels of oxidatively damaged DNA are more likely to show positive associations between exposure to ENMs and oxidized DNA in tissue than studies showing acceptable baseline levels (odds ratio = 12.1, 95% confidence interval: 1.2–124). Nevertheless, reliable studies indicate that intratracheal instillation of nanosized carbon black is associated with increased levels of oxidatively damaged DNA in lung tissue. Oral exposure to nanosized carbon black, TiO2, carbon nanotubes and ZnO is associated with elevated levels of oxidatively damaged DNA in tissues. These observations are supported by cell culture studies showing concentration‐dependent associations between ENM exposure and oxidatively damaged DNA measured by the comet assay. Cell culture studies show relatively high variation in the ability of ENMs to oxidatively damage DNA; hence, it is currently impossible to group ENMs according to their DNA damaging potential. Environ. Mol. Mutagen. 56:97–110, 2015. © 2014 Wiley Periodicals, Inc.
Influence of EC7 design approaches on the design of deep excavations with FEM
Authors: Schweiger Helmut F.
Published: September 2014

In the current version of EC7, three different design approaches are defined, which differ in their application of partial factors on actions, soil strength and resistance. When analysing deep excavations two problems arise, first the fact that soil can act as both load and resistance, and second that, when employing numerical methods, earth pressures are not an input into the analysis, which can be factored accordingly, but are a result of the analysis. By comparing the results obtained from simple examples it will be shown that different design approaches can be readily employed in combination with numerical methods although some differences in the results may be expected. From the studies performed, another preliminary conclusion can be drawn, namely that the influence of the design approach seems to be less significant when employing advanced elasto‐plastic constitutive models incorporating strain hardening behaviour as compared to elastic‐perfectly plastic failure criteria. However, further studies are required to confirm these findings.

Einfluss des Nachweisverfahrens auf die Bemessung von Baugruben mit FEM. In der derzeit gültigen Fassung des EC7 sind drei Nachweisverfahren definiert, die sich in der Anwendung der Teilsicherheitsfaktoren auf Einwirkungen, Widerstände und Bodenkennwerte unterscheiden. Wesentliche Aspekte bei der Berechnung von Baugruben sind einerseits, dass der Baugrund sowohl Einwirkung als auch Widerstand sein kann und andererseits, dass sich bei Anwendung numerischer Methoden die Größe des Erddruckes aus der Berechnung ergibt und somit keine Eingabegröße darstellt, die mit einem entsprechenden Teilsicherheitsbeiwert beaufschlagt werden kann. In dem Beitrag wird an Hand von einfachen Beispielen gezeigt, dass die unterschiedlichen Nachweisverfahren auch mit numerischen Verfahren angewendet werden können, wobei die sich ergebenden Unterschiede in den Ergebnissen aufgezeigt werden. Bei den durchgeführten Studien zeigte sich auch, dass die Unterschiede aus den Nachweisverfahren bei Anwendung hochwertiger elasto‐plastischer Stoffgesetze mit Verfestigung im Vergleich zu elastisch‐ideal plastischen Bruchkriterien geringer ausfallen; jedoch sind weitere Studien zur Bestätigung dieser Erkenntnisse erforderlich.
Grenzen der Anwendbarkeit der DIN 4019 für geschichtete Böden
Authors: Vrettos Christos , Merz Kai
Published: September 2014

Konventionelle Berechnungen von Setzungen und Verdrehungen von Fundamentkörpern erfolgen auf der Basis von Lösungen der Elastizitätstheorie. Das Verfahren der DIN 4019 basiert auf der Annahme, dass die Verteilung der vertikalen Spannungen im Boden unabhängig vom Steifemodul und der Poissonzahl ist. Bei Böden mit unregelmäßiger Schichtung und einer steiferen oberen Schicht, wie diese bei Baugrundverbesserungsmaßnahmen auftreten kann, führen die Lösungsalgorithmen zu ungenauen Ergebnissen, die zu einer unwirtschaftlichen Bemessung führen. Der Beitrag erläutert die Hintergründe anhand eines Rechenbeispiels.

Limits of the applicability of DIN 4019 for layered soils. Conventional calculations of settlement and rotation of foundations are based on solution of linear elasticity. It is assumed that the distribution of vertical stresses in the soil is independent of the constrained modulus and the Poisson's ratio. For soils with irregular stratigraphy and a stiffer upper layer, as this may occur after ground improvement, these solution algorithms yield inaccurate results leading to uneconomical design. The paper elucidates the background by means of a calculation example.
Pan evaporation modelling and changing attribution analysis on the Tibetan Plateau (1970–2012)
Authors: Xie Hong , Zhu Xuan , Yuan Dao‐Yang
Published: September 2014

Pan evaporation (Ep) is an important indicator of water and energy and the decline of Ep has been reported in many regions over the last decades. The climate and Ep are dependent on each other. In this study, the temporal trends of Ep and main Ep drivers, namely mean air temperature (Ta), wind speed (u), global solar radiation (Rs), net long‐wave radiation(Rnl) and vapour pressure deficit (D) from 1970 to 2012, were calculated on the basis of 26 meteorological stations on the Tibetan Plateau. The arithmetic average of Ep from 26 stations decreased with the rate of −11.91 mm a−2; the trends of Rs, Rnl, Ta, u and D were −1.434 w m−2 decade−1, 0.2511 w m−2 decade−1, 0.3590°C decade−1, −0.2376 m s−1 decade−1 and 9.523 Pa decade−1, respectively. The diffuse irradiance is an essential parameter to model Ep and quantify the contribution of climatic factors to changing Ep. 60 724 observations of Rs and diffuse solar irradiance (Rd) from seven of the 26 stations were used to develop the correlation between the diffuse fraction (Rd/Rs), and the clearness index (Rs/Ro). On the basis of the estimation of the diffuse component of Rs and climatic data, we modified the PenPan model to estimate Chinese micro‐pan evaporation (Ep) and assess the attribution of Ep dynamics using partial derivatives. The results showed that there was a good agreement between the observed and calculated daily Ep values. The observed decrease in Ep was mostly due to declining wind speed (−13.7 mm a−2) with some contributions from decreasing solar irradiance (−3.1 mm a−2); and the increase of temperature had a large positive effect (4.55 mm a−2) in total whilst the increase of Rnl had insignificant effect (0.35 mm a−2) on Ep rates. The change of Ep is the net result of all the climatic variables. Copyright © 2014 John Wiley & Sons, Ltd.
The strength of aversive and appetitive associations and maladaptive behaviors
Authors: Itzhak Yossef , Perez‐Lanza Daniel , Liddie Shervin
Published: September 2014

Certain maladaptive behaviors are thought to be acquired through classical Pavlovian conditioning. Exaggerated fear response, which can develop through Pavlovian conditioning, is associated with acquired anxiety disorders such as post‐traumatic stress disorders (PTSDs). Inflated reward‐seeking behavior, which develops through Pavlovian conditioning, underlies some types of addictive behavior (e.g., addiction to drugs, food, and gambling). These maladaptive behaviors are dependent on associative learning and the development of long‐term memory (LTM). In animal models, an aversive reinforcer (fear conditioning) encodes an aversive contextual and cued LTM. On the other hand, an appetitive reinforcer results in conditioned place preference (CPP) that encodes an appetitive contextual LTM. The literature on weak and strong associative learning pertaining to the development of aversive and appetitive LTM is relatively scarce; thus, this review is particularly focused on the strength of associative learning. The strength of associative learning is dependent on the valence of the reinforcer and the salience of the conditioned stimulus that ultimately sways the strength of the memory trace. Our studies suggest that labile (weak) aversive and appetitive LTM may share similar signaling pathways, whereas stable (strong) aversive and appetitive LTM is mediated through different pathways. In addition, we provide some evidence suggesting that extinction of aversive fear memory and appetitive drug memory is likely to be mediated through different signaling molecules. We put forward the importance of studies aimed to investigate the molecular mechanisms underlying the development of weak and strong memories (aversive and appetitive), which would ultimately help in the development of targeted pharmacotherapies for the management of maladaptive behaviors that arise from classical Pavlovian conditioning. © 2014 IUBMB Life, 66(8):559–571, 2014
Photocatalytic ozonation of clopyralid, picloram and triclopyr. Kinetics, toxicity and influence of operational parameters
Authors: Solís Rafael R , Rivas F Javier , Gimeno Olga , Pérez‐Bote José Luis
Published: September 2014

BACKGROUND

Photolysis, photocatalysis, ozonation and photocatalytic ozonation in the presence of titania have been applied to the elimination of three pyridine carboxylic acids herbicides (clopyralid, picloram and triclopyr) in water.

RESULTS

Photocatalytic ozonation led to the best results in terms of herbicide elimination rate and mineralization. The herbicides were relatively recalcitrant to direct ozonation (rate constants: 20 M−1 min−1 for clopyralid and triclopyr, and 105 M−1 min−1 in the case of picloram). Herbicides degradation proceeds by hydroxyl radicals attack (rate constants: 0.73, 3.80 and 1.73 × 109 M−1 s−1 for clopyralid, picloram and triclopyr, respectively). Monitoring of chloride and nitrates suggests dechlorination as the primary stage in the process. Further ring opening led to the accumulation of nitrates and the appearance of some low weight carboxylic acids. Toxicity decreased at the end of the process.

CONCLUSION

Tested herbicides slowly react with ozone. Photocatalytic ozonation shows different degrees of synergism, leading to 80% mineralization in less than 1 h. Small amounts of TiO2 (i.e. 0.005 g L−1) maintains the efficiency of the photocatalytic ozonation. Quantitative free chloride and nitrates rapidly appear in the O3/UVA/TiO2 system. First intermediates in the photocatalytic ozonation of clopyralid show higher toxicity than the parent compound. © 2014 Society of Chemical Industry
Sonographic evaluation of the medial aspect of the knee in a population‐based cohort study
Authors: Yanagisawa Shinya , Kobayashi Tsutomu , Ohsawa Takashi , Saito Kenichi , Yamamoto Atsushi , Tajika Tsuyoshi , Takagishi Kenji
Published: September 2014

Purpose

The aim of this study was to evaluate the medial aspect of the knee with ultrasound (US).

Methods

This study included 71 men and 154 women (450 knees) with a mean age of 65 years. US was used to evaluate the medial joint space of both knees with and without weight‐bearing. In each subject, the medial radial displacement of the medial meniscus, the peripheral joint space, and the number of osteophytes were evaluated. The subjects were stratified by age into five groups: 40–49 years, 50–59 years, 60–69 years, 70–79 years, and 80 years and older, and the US findings in each group were compared.

Results

Statistically significant differences were noted between the 60–69 and over‐80 age groups in medial radial displacements and peripheral joint spaces (p < 0.01 for both). The number of osteophytes significantly increased after 60 years of age (p < 0.01).

Conclusions

We believe that US is a useful tool for making a simple evaluation of the intra‐articular components in population‐based studies. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:318–321, 2015
Synthesis of carbon‐14 and stable isotope labeled Avagacestat: a novel gamma secretase inhibitor for the treatment of Alzheimer's disease
Authors: Burrell Richard C. , Easter John A. , Cassidy Michael P. , Gillman Kevin W. , Olson Richard E. , Bonacorsi Samuel J.
Published: September 2014

Bristol‐Myers Squibb and others are developing drugs that target novel mechanisms to combat Alzheimer's disease. γ‐Secretase inhibitors are one class of potential therapies that have received considerable attention. (R)‐2‐(4‐Chloro‐N‐(2‐fluoro‐4‐(1,2,4‐oxadiazol‐3‐yl)benzyl)phenylsulfonamido)‐5,5,5‐trifluoropentanamide (Avagacestat) is a γ‐secretase‐inhibiting drug that has been investigated by Bristol‐Myers Squibb in preclinical and clinical studies. An important step in the development process was the synthesis of a carbon‐14‐labeled analog for use in a human absorption, distribution, metabolism, and excretion study and a stable isotope labeled analog for use as a standard in bioanalytical assays to accurately quantify the concentration of the drug in biological samples.

Carbon‐14 labeled Avagacestat was synthesized in seven steps in a 33% overall yield from carbon‐14 labeled potassium cyanide. A total of 5.95 mCi was prepared with a specific activity of 0.81 μCi/mg and a radiochemical purity of 99.9%. 13C6‐Labeled Avagacestat was synthesized in three steps in a 15% overall yield from 4‐chloro[13C6]aniline. A total of 585 mg was prepared with a ultraviolet purity of 99.9%.
Characteristics of dysphagia in older patients evaluated at a tertiary center
Authors: Kocdor Pelin , Siegel Eric R. , Giese Rachel , Tulunay‐Ugur Ozlem E.
Published: September 2014

Objective

To determine laryngoscopic and videofluoroscopic swallowing study (VFSS) findings in geriatric patients with dysphagia; to evaluate management.

Study Design

Retrospective chart review.

Methods

Patients over 65 years old complaining of dysphagia, seen at a tertiary laryngology clinic, were included. Head and neck cancer and stroke patients were excluded. Demographics, laryngoscopic findings, swallowing studies, and treatment modalities were reviewed.

Results

Sixty‐five patients were included. Mean age was 75 years old (range = 66–97) with female predominance of 67.6%. Weight loss was seen in 9.2% of the patients. Whereas 52.3% of the patients complained of solid food dysphagia, 53.8% were choking on food. On laryngoscopy, 15.3% of the patients had pooling in the pyriform sinuses, 30.7% had glottic gap, 18.4% had vocal fold immobility, and 3% had hypomobility. VFSS showed that 38.4% of the patients had pharyngoesophageal dysphagia, 20% had oropharyngeal dysphagia, 20% had pharyngeal dysphagia, and 20% had a normal study. In addition, 41.5% of the patients showed laryngeal penetration and 18.4% showed aspiration. Surgical intervention was employed in 29.2% of the patients in the form of botulinum toxin injection, esophageal dilatation, cricopharyngeal myotomy, vocal fold injection, diverticulectomy, and percutaneous endoscopic gastrostomy. Whereas 21.5% of the patients received swallowing therapy, 61.5% underwent diet modification. As a result, 80% of the patients needed some type of treatment.

Conclusions

Swallowing problems in older patients are not uncommon. The clinician needs to be diligent to inquire about dysphagia because a large number of these patients will require treatment.

Level of Evidence

4. Laryngoscope, 125:400–405, 2015
On the discontinuous second‐order deviated Dirichlet problem with non‐monotone conditions
Authors: Figueroa Rubén
Published: September 2014

We provide a new result on the existence of extremal solutions for second‐order Dirichlet problems with deviation argument. As a novelty in this work, the nonlinearity need not be continuous or monotone. In order to obtain this new result, we use a generalized monotone method coupled with lower and upper solutions.
Anticholinergic drugs rescue synaptic plasticity in DYT1 dystonia: Role of M1 muscarinic receptors
Authors: Maltese Marta , Martella Giuseppina , Madeo Graziella , Fagiolo Irene , Tassone Annalisa , Ponterio Giulia , Sciamanna Giuseppe , Burbaud Pierre , Conn P. Jeffrey , Bonsi Paola , Pisani Antonio
Published: September 2014

Broad‐spectrum muscarinic receptor antagonists have represented the first available treatment for different movement disorders such as dystonia. However, the specificity of these drugs and their mechanism of action is not entirely clear. We performed a systematic analysis of the effects of anticholinergic drugs on short‐ and long‐term plasticity recorded from striatal medium spiny neurons from DYT1 dystonia knock‐in (Tor1a+/Δgag) mice heterozygous for ΔE‐torsinA and their controls (Tor1a+/+ mice). Antagonists were chosen that had previously been proposed to be selective for muscarinic receptor subtypes and included pirenzepine, trihexyphenydil, biperiden, orphenadrine, and a novel selective M1 antagonist, VU0255035. Tor1a+/Δgag mice exhibited a significant impairment of corticostriatal synaptic plasticity. Anticholinergics had no significant effects on intrinsic membrane properties and on short‐term plasticity of striatal neurons. However, they exhibited a differential ability to restore the corticostriatal plasticity deficits. A complete rescue of both long‐term depression (LTD) and synaptic depotentiation (SD) was obtained by applying the M1‐preferring antagonists pirenzepine and trihexyphenidyl as well as VU0255035. Conversely, the nonselective antagonist orphenadrine produced only a partial rescue of synaptic plasticity, whereas biperiden and ethopropazine failed to restore plasticity. The selectivity for M1 receptors was further demonstrated by their ability to counteract the M1‐dependent potentiation of N‐methyl‐d‐aspartate (NMDA) current recorded from striatal neurons. Our study demonstrates that selective M1 muscarinic receptor antagonism offsets synaptic plasticity deficits in the striatum of mice with the DYT1 dystonia mutation, providing a potential mechanistic rationale for the development of improved antimuscarinic therapies for this movement disorder. © 2014 International Parkinson and Movement Disorder Society
Plug‐and‐play distributed model predictive control with coupling attenuation
Authors: Riverso Stefano , Ferrari‐Trecate Giancarlo
Published: September 2014

We consider the control of a large‐scale system composed of state‐coupled linear subsystems that can be added or removed offline. In this paper, we present plug‐and‐play (PnP) design methods based on model predictive control, meaning that (i) the design of a local controller requires information from parent subsystems only, (ii) the plugging in/out of a subsystem triggers at most the redesign of controllers associated to subsystems coupled to it, and (iii) plug‐in/out operations are automatically denied if they compromise the stability of the overall system or constraint satisfaction. We advance previously proposed PnP decentralized control schemes by introducing a distributed control architecture that exploits communication between coupled subsystems. New controllers embody coupling attenuation terms that make PnP design applicable even when existing synthesis method are not. The main features of our approach are illustrated considering the PnP design of controllers for regulating the frequency of multiple generators in power networks. Copyright © 2014 John Wiley & Sons, Ltd.
Lung function in adult survivors of very low birth weight, with and without bronchopulmonary dysplasia
Authors: Gibson Anne‐Marie , Reddington Charlotte , McBride Lucy , Callanan Catherine , Robertson Colin , Doyle Lex W
Published: September 2014

Introduction

The lung function outcome of cohorts of very low birth weight (VLBW; birth weight <1501 g) survivors born in the late 1970s or early 1980s into adulthood at an age when lung growth would be expected to have ceased is not well described. The aim of this study was to report lung function data in adulthood of VLBW survivors compared with normal birth weight controls (>2499 g), and in those who had bronchopulmonary dysplasia (BPD) compared with those without BPD.

Materials and Methods

Spirometry and lung volumes were measured according to standard guidelines when subjects were in their mid‐20s; there were 47 survivors of birth weight <1000 g, 40 of birth weight 1000–1500 g, and 20 controls of birth weight >2499 g. Results were converted to z‐scores.

Results

Both subgroups with birth weight <1501 g had significant reductions in airflow compared with controls, but not compared with each other. There were no significant differences between groups in variables reflecting air trapping. Within the VLBW cohort, those with BPD (n = 24) had reductions in airflow, including the z‐score for the forced expired volume in 1 sec (FEV1), compared with those without BPD (n = 63). Within the VLBW cohort, there were positive relationships between FEV1 measurements earlier in childhood with those obtained at 25 years of age; these relationships were stronger in those who had BPD in the newborn period, and increased over time.

Conclusions

VLBW survivors continue to have airways obstruction in their mid‐20s compared with controls, particularly those who had BPD in the newborn period. Pediatr Pulmonol. 2015; 50:987–994. © 2014 Wiley Periodicals, Inc.
Molybdenum nano‐precipitates in silicon: A TEM and DLTS study
Authors: Leonard Simon , Markevich Vladimir P. , Peaker Anthony R. , Hamilton Bruce , Youssef Khaled , Rozgonyi George
Published: September 2014

The quest for low cost solar cells has resulted in attempts to use lower purity silicon rather than conventional electronic grade material. The metallic content of such ‘solar silicon’ is usually much higher than electronic grade material and this compromises the efficiency of photovoltaic conversion via a variety of recombination mechanisms. Molybdenum is a common metallic contaminant in Si which is difficult to getter because of its low diffusivity. It is known that Mo incorporates into the Si lattice as single interstitial atoms, introducing a deep donor level into the gap. In this work, we show that Mo in silicon can also form nano‐precipitates which may represent a new general class of efficient recombination centres. We have observed the Mo precipitates by TEM as 5–10 nm clusters in Si samples into which molybdenum was introduced during growth or by ion implantation and annealing. In general, such precipitates can form in Si samples containing metals with low diffusivity during high‐temperature treatments and subsequent cooling. We report the carrier capture and emission properties of Mo nano‐precipitates, which show that these could be very effective recombination centres for minority carriers in p‐type Si. In particular we present data and analysis of minority carrier charge exchange at these nano‐dimension metallic defects.
Use of the ocean surface wind direction signal in microwave radiance assimilation
Authors: Kazumori Masahiro , English Stephen J.
Published: September 2014

We developed an empirical relative wind direction (RWD) model function to represent azimuthal variations of oceanic microwave radiances of vertical and horizontal polarizations. The RWD model function was based on radiance measurements from the Advanced Microwave Scanning Radiometer and Special Sensor Microwave Imager/Sounder (SSMIS). Ocean surface wind vector data from SeaWinds on board the Advanced Earth Observing Satellite‐II and European Centre for Medium‐range Weather Forecasts (ECMWF) Integrated Forecasting System were utilized for the RWD model function development. The RWD model function was introduced to a microwave ocean emissivity model: a FAST microwave Emissivity Model (FASTEM) in a radiative transfer model for satellite radiance assimilation. Performances of the RWD model function were much more realistic than present azimuthal model functions in FASTEM for low wind speed and high‐frequency channels. Assimilation experiments using the RWD model function were performed in the ECMWF system. The experiment demonstrated reductions of first‐guess departure biases arising from modelling of the azimuthal variations in areas of high wind‐speed and low variability of wind direction. For example, bias reductions in ascending and descending SSMIS 19 GHz vertically polarized radiance in the Somali jet over the Arabian Sea were approximately 0.6 and 0.7 K. The bias reductions were found for all assimilated microwave imager channels in a wide wind‐speed range. Moreover, analysis increments of specific humidity in the lower troposphere were reduced (e.g. 0.2 g kg−1 reduction at 1000 hPa in the Somali jet). We found improvements of relative humidity and temperature in short‐range forecasts in the lower troposphere. The experiment results clearly showed the importance of modelling the azimuthal variation of emissivity for assimilation of microwave imager observations. The new RWD model function, combined with the other components of FASTEM, will be available as FASTEM‐6.
Accounting for model error due to unresolved scales within ensemble Kalman filtering
Authors: Mitchell Lewis , Carrassi Alberto
Published: September 2014

We propose a method to account for model error due to unresolved scales in the context of the ensemble transform Kalman filter (ETKF). The approach extends to this class of algorithms the deterministic model error formulation recently explored for variational schemes and extended Kalman filter. The model error statistic required in the analysis update is estimated using historical reanalysis increments and a suitable model error evolution law. Two different versions of the method are described; a time‐constant model error treatment where the same model error statistical description is time‐invariant, and a time‐varying treatment where the assumed model error statistics is randomly sampled at each analysis step. We compare both methods with the standard method of dealing with model error through inflation and localization, and illustrate our results with numerical simulations on a low‐order nonlinear system exhibiting chaotic dynamics. The results show that the filter skill is significantly improved through the proposed model error treatments, and that both methods require far less parameter tuning than the standard approach. Furthermore, the proposed approach is simple to implement within a pre‐existing ensemble‐based scheme. The general implications for the use of the proposed approach in the framework of square‐root filters such as the ETKF are also discussed.
A provably secure smart card‐based authenticated group key exchange protocol
Authors: Chang Chin‐Chen , Le Hai‐Duong
Published: September 2014

A password‐based authenticated group key exchange protocol assists group participants who possess low‐entropy, human‐memorable passwords in establishing a secure communication channel. In this type of scheme, the server needs to store the users' verifiers in a database. Therefore, it is susceptible to stolen‐verifier attacks. In this paper, we propose a new authenticated group key protocol that eliminates the need of verifier database at the server side. Our protocol is based on a two‐factor authentication that employs both smart card and password. Copyright © 2014 John Wiley & Sons, Ltd.
Modelling changes in small area disability free life expectancy: trends in London wards between 2001 and 2011
Authors: Congdon Peter
Published: September 2014

Existing analyses of trends in disability free life expectancy (DFLE) are mainly at aggregate level (national or broad regional). However, major differences in DFLE, and trends in these expectancies, exist between different neighbourhoods within regions, so supporting a small area perspective. However, this raises issues regarding the stability of conventional life table estimation methods at small area scales. This paper advocates a Bayesian borrowing strength technique to model trends in mortality and disability differences across 625 small areas in London, using illness data from the 2001 and 2011 population Censuses, and deaths data for two periods centred on the Census years. From this analysis, estimates of total life expectancy and DFLE are obtained. The spatio‐temporal modelling perspective allows assessment of whether significant compression or expansion of morbidity has occurred in each small area. Appropriate models involve random effects that recognise correlation and interaction effects over relevant dimensions of the observed deaths and illness data (areas, ages), as well as major spatial trends (e.g. gradients in health and mortality according to area deprivation category). Whilst borrowing strength is a primary consideration (and demonstrated by raised precision for estimated life expectancies), so also is model parsimony. Therefore, pure borrowing strength models are compared with models allowing selection of random age‐area interaction effects using a spike‐slab prior, and in fact borrowing strength combined with random effects selection provides better fit. Copyright © 2014 John Wiley & Sons, Ltd.
Is Any Alleged Truthmaker for Negatives Explanatorily Deficient?
Authors: Kitamura Naoaki ,   Philosophy Documentation Center
Published: September 2014

Some truthmaker theorists posit a distinctive kind of entity to solve the problem of providing ontological grounding for negative truths. Recently, A. M. Griffith has raised a general objection against these alleged truthmakers based on an explanatory constraint on truthmaking and the existence condition of these entities. This paper counters the objection by placing it on the horns of a dilemma: the argument must either specify that the existence condition in question is a conceptual matter or insist that the condition is of properly metaphysical substance. I first argue that the former horn cannot be pursued because it makes the objection irrelevant to the alleged claims of truthmaking. I then argue that the latter horn is also highly problematic because simply insisting on the claim begs the question; appreciating this point leads proponents and opponents of the alleged truthmakers to a substantial debate about the metaphysical nature of these entities and the overall theoretical benefit of their postulation. The discussion shows that Griffith’s argument fails to establish its conclusion and reveals what is actually required to argue for/against a particular proposal to provide ontological grounding for negative truths.
Mercosur After Chavez
Authors: Gouvea Raul , Montoya Manuel
Published: September 2014

A redesigned “Tordesillas Line” is being drawn in Latin America that will divide “Atlantic” and “Pacific” nations. Atlantic nations are rapidly turning into protectionist nations plagued by heavy bureaucracy, heavy taxes, and an intervening and expanding state. Pacific nations, however, are embracing transparency and market‐driven policies, bringing a new dynamism to their economies. The legacy of Hugo Chavez (“Chavismo”) is capable of perpetuating Chavez's legacy in Mercosur, impregnating the trading bloc with a strong political and economic bias, further moving the trading bloc away from mainstream globalization forces. This article will elaborate on the main challenges and opportunities permeating Mercosur after Chavez. The recently created “Alliance of the Pacific” (AP) revives the economic agenda for Latin American trading blocs, and provides a comparison to Mercosur's agenda, impregnated with ideologies and political agendas. © 2014 Wiley Periodicals, Inc.
Facial profile markers in second‐ and third‐trimester fetuses with trisomy 18
Authors: Vos F. I. , de Jong‐Pleij E. A. P. , Bakker M. , Tromp E. , Manten G. T. R. , Bilardo C. M.
Published: September 2014

Objectives

To evaluate nasal bone length (NBL), maxilla–nasion–mandible (MNM) angle, fetal profile (FP) line, prenasal thickness (PT), prenasal thickness to nasal bone length (PT:NBL) ratio and prefrontal space ratio (PFSR) as markers of trisomy 18 in the second and third trimesters of pregnancy.

Methods

The NBL, MNM angle, FP line, PT, PT:NBL ratio and PFSR were measured retrospectively from stored two‐dimensional images or three‐dimensional volumes of trisomy‐18 fetuses, and were compared with our previously reported normal ranges for euploid fetuses. Additional ultrasound findings were noted at initial routine second‐trimester scan and at subsequent advanced ultrasound examination performed after referral for karyotyping.

Results

A total of 43 trisomy‐18 fetuses were included in the analysis. At initial examination, median gestational age was 21 + 2 weeks. NBL and PT were correlated with gestational age (P < 0.001), but the other markers were not. Mean NBL, MNM angle, PT, PT:NBL ratio and PFSR were 3.76 mm, 16.67°, 4.25 mm, 1.39 and 0.87, respectively. The FP line was zero (normal) in 53.7% of cases and negative (abnormal) in 46.3%. All markers were significantly associated with trisomy 18, with the PT:NBL ratio yielding the highest detection rate (88.4%) followed by NBL (83.7%), MNM angle (56.4%), FP line (46.3%), PT (27.9%) and the PFSR (20.5%) (for a 5% false‐positive rate for the continuous variables). Various combinations of the four best markers (NBL, FP line, MNM angle and PT:NBL ratio) yielded detection rates of between 72% and 95%. Structural anomalies were not detected in 22% of fetuses at the initial scan and in 2% at the advanced scan.

Conclusions

The PT:NBL ratio and NBL are robust second‐ and third‐trimester markers for trisomy 18. A negative FP line has a 0% false‐positive rate and the potential to differentiate between trisomy 18 and Down syndrome, as in the latter the FP line is often positive. No major anomaly was observed at the initial scan in about a quarter of trisomy‐18 fetuses, underlining the role of second‐trimester facial marker evaluation. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.