bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of non‐covalent interaction of natural flexible cyclic molecules with telomeric RNA G‐quadruplexes by electrospray ionization mass spectrometry
Authors: Cui Xiaojie , Lin Sen , Zhou Jiang , Yuan Gu
Published: July 2012

RATIONALE

Recently, human telomeric DNA was found to be transcribed into RNA transcripts composing of tandem repeats of r(UUAGGG) which can form G‐quadruplex structures. Studies have shown that human telomeric RNA is associated with the telomerase activity in vitro. Finding high affinity small molecule ligands binding to the telomeric RNA G‐quadruplex may facilitate the regulation of the telomerase activity.

METHODS

The 12‐mer and 24‐mer telomeric RNA sequences, r(UAGGGUUAGGGU) and r(UAGGGUUAGGGUUAGGGUUAGGGU), were synthesized by TaKaRa Biotechnology (Dalian) Co., Ltd. (TaKaRa, Dalian) with high‐performance liquid chromatography (HPLC) purification. Electrospray ionization ion‐trap mass spectrometry was used to evaluate the binding affinities of three natural flexible cyclic molecules, tetrandrine, fangchinoline and cepharanthine, with the telomeric RNA G‐quadruplexes. The fragmentation pathways of the G‐quadruplexes and G‐quadruplex‐ligand complexes were investigated by tandem mass spectrometry.

RESULTS

the natural flexible cyclic molecules were found to have high binding affinities to the 12‐mer and 24‐mer RNA G‐quadruplexes with stoichiometry of 1:1 to 3:1. Collision‐induced dissociation tandem mass spectrometry shows that the G‐quadruplex‐ligand complexes lose neutral ammoniums first and the small molecule ligand subsequently. Besides, among the three flexible cyclic molecules, cepharanthine binds most tightly to the RNA G‐quadruplexes than tetandrine and fangchinoline.

CONCLUSIONS

Three flexible cyclic small molecules were found to be potential telomeric RNA G‐quadruplex ligands, especially cepharanthine, which has high affinity and binds most tightly to the RNA G‐quadruplexes. These findings may provide further implications in the regulation of telomeric RNA and telomerase activity. Copyright © 2012 John Wiley & Sons, Ltd.
Moving object detection with laser scanners
Authors: Mertz Christoph , Navarro‐Serment Luis E. , MacLachlan Robert , Rybski Paul , Steinfeld Aaron , Suppé Arne , Urmson Christopher , Vandapel Nicolas , Hebert Martial , Thorpe Chuck , Duggins David , Gowdy Jay
Published: July 2012

The detection and tracking of moving objects is an essential task in robotics. The CMU‐RI Navlab group has developed such a system that uses a laser scanner as its primary sensor. We will describe our algorithm and its use in several applications. Our system worked successfully on indoor and outdoor platforms and with several different kinds and configurations of two‐dimensional and three‐dimensional laser scanners. The applications vary from collision warning systems, people classification, observing human tracks, and input to a dynamic planner. Several of these systems were evaluated in live field tests and shown to be robust and reliable. © 2012 Wiley Periodicals, Inc.
Etching of polyethylene terephthalate thin films by neutral oxygen atoms in the late flowing afterglow of oxygen plasma
Authors: Vesel Alenka , Kolar Metod , Doliska Ales , Stana‐Kleinschek Karin , Mozetic Miran
Published: July 2012

Films of polyethylene terephthalate were deposited on quartz crystals and exposed to oxygen atoms to study their etching characteristics and quantify the etching rate. Oxygen (O) atoms were created by passing molecular oxygen through plasma created in a microwave discharge. The discharge power was fixed at 250 W, while the pressure of oxygen was 50 Pa. Before exposure to oxygen atoms, a thin polymer film of polyethylene terephthalate (PET) was deposited uniformly over a crystal with a diameter of 12 mm. The crystal was mounted on a quartz crystal microbalance to accurately determine the thickness of the polymer film. The polymer film was exposed to O atoms in the flowing afterglow. The density of O atoms was measured with a cobalt catalytic probe mounted next to the sample and was determined to be 1.2 × 1021 m–3. Samples were treated with O atoms for different periods of up to 120 min. The thickness of the film decreased linearly with treatment time. After 90 min of treatment, a 65‐nm‐thick polymer film was completely removed. Therefore, the etching rate was 0.5 nm/min, so the interaction probability between an O atom and an atom in the sample was extremely low, just 1.4 × 10–6. Samples treated for different periods were investigated by atomic force microscopy and X‐ray photoelectron spectroscopy to examine the etching characteristics of O atoms in the flowing afterglow. Copyright © 2012 John Wiley & Sons, Ltd.
The role of electron temperature dynamics for secondary ion formation
Authors: Weidtmann B. , Hanke S. , Duvenbeck A. , Wucher A.
Published: July 2012

The ionization probabilities of particles emitted from a silver (111) surface after bombardment with 5‐keV silver atoms are calculated by means of a hybrid computer simulation model combining molecular dynamics with kinetic electronic excitation. The simulations produce a four‐dimensional electron excitation profile parameterized by an effective electron temperature which is then used to calculate an individual ionization probability α+ for each sputtered atom. The results demonstrate the significant role of the time structure of the electron temperature profile. Copyright © 2012 John Wiley & Sons, Ltd.
Preliminary characterization of Palaeogene European ambers using ToF‐SIMS
Authors: Sodhi Rana N. S. , Mims Charles A. , Goacher Robyn E. , McKague Bruce , Wolfe Alexander P.
Published: July 2012

Amber comprises polymerized plant resins that have a remarkable capacity for survival in a range of geological environments. Most ambers can be traced to coniferous trees and typically combine a broad array of plant natural products including terpenoids, carboxylic acids, and associated alcohols. Because amber may entomb various organisms at the time of production and preserve them with unmatched fidelity, it has been studied for centuries. Despite extensive geochemical profiling of amber‐derived extracts using techniques such as gas‐chromatography mass spectrometry, to date amber compositional variability has not been investigated by time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS). We conducted a series of scans on microtomed surfaces of Baltic and Bitterfeld ambers, representing two of Europe's major deposits, both of Palaeogene age. We exploited authentic standards of mono‐methyl succinate and diterpene resin acids to guide interpretation of the results. The ToF‐SIMS spectra are highly reproducible for each amber type considered and highlight subtle differences that are likely underscored by differences in age, botanical provenance, and post‐depositional history. Importantly, the abundance of succinate is consistently higher in Baltic amber relative to Bitterfeld amber, suggesting they are distinct deposits and not regional variants of each other. Copyright © 2012 John Wiley & Sons, Ltd.
Direct Visualization of Symmetry Breaking During Janus Nanoparticle Formation
Authors: Loget Gabriel , Lee Tung C. , Taylor Richard W. , Mahajan Sumeet , Nicoletti Olivia , Jones Samuel T. , Coulston Richard J. , Lapeyre Véronique , Garrigue Patrick , Midgley Paul A. , Scherman Oren A. , Baumberg Jeremy J. , Kuhn Alexander
Published: July 2012

The straight‐forward synthesis of Janus nanoparticles composed of Ag and AgBr is reported. For their formation, cucurbit[n]uril (CB)‐stabilized AgBr nanoparticles are first generated in water by precipitation. Subsequent irradiation with an electron beam transforms a fraction of each AgBr nanoparticle into Ag0, leading to well‐defined Janus particles, stabilized by the binding of CB to the surface of both AgBr and Ag0. With the silver ion reduction being triggered by the electron beam, the progress of the transformation can be directly monitored with a transmission electron microscope.
Nanolattices of Switchable DNA‐Based Motors
Authors: Saccà Barbara , Siebers Benjamin , Meyer Rebecca , Bayer Manfred , Niemeyer Christof M.
Published: July 2012

Miniaturization is an important aspect of device fabrication. Despite the advancements of modern top‐down approaches, scaling‐down to the sub‐nanometer size is still a challenge. As an alternative, bottom‐up approaches, such as the use of DNA as an engineering material, are therefore emerging, allowing control of matter at the single‐molecule level. A DNA‐based self‐assembly method for the construction of switchable DNA devices is descrbied here based on G‐quadruplex moieties, which are patterned on quasi‐planar DNA arrays with nanoscale precision. The reversible switching of the devices is triggered by addition of DNA sequences (‘fuels’) and translated into linear extension/contractile movements. The conformational change of the devices was visualized by atomic force microscopy and FRET spectroscopy. Steady state fluorescence spectroscopy indicated that scaffolding of the G4 motors to either individual tiles or extended superlattices had no significant impact on the switching and optical performance of the system. However, time‐resolved spectroscopy revealed that ordering in the microstructural environment enhances the fraction of molecules subject to FRET. Altogether, our study confirms that DNA superstructures are well‐suited scaffolds for accommodation of mechanically switchable units and thus opens the door to the development of more sophisticated nanomechanical devices.
Plasmonic Nanogap‐Enhanced Raman Scattering Using a Resonant Nanodome Array
Authors: Wu Hsin‐Yu , Choi Charles J. , Cunningham Brian T.
Published: July 2012

The optical properties and surface‐enhanced Raman scattering (SERS) of plasmonic nanodome array (PNA) substrates in air and aqueous solution are investigated. PNA substrates are inexpensively and uniformly fabricated with a hot spot density of 6.25 × 106 mm−2 using a large‐area nanoreplica moulding technique on a flexible plastic substrate. Both experimental measurement and numerical simulation results show that PNAs exhibit a radiative localized surface plasmon resonance (LSPR) due to dipolar coupling between neighboring nanodomes and a non‐radiative surface plasmon resonance (SPR) resulting from the periodic array structure. The high spatial localization of electromagnetic field within the ∼10 nm nanogap together with the spectral alignment between the LSPR and excited and scattered light results in a reliable and reproducible spatially averaged SERS enhancement factor (EF) of 8.51 × 107 for Au‐coated PNAs. The SERS enhancement is sufficient for a wide variety of biological and chemical sensing applications, including detection of common metabolites at physiologically relevant concentrations.
A Review of the Relationship between Viscosity and the Structure of Calcium‐Silicate‐Based Slags in Ironmaking
Authors: Sohn Il , Min Dong Joon
Published: July 2012

This review focuses on elucidating the viscosity of ironmaking slags and the effect of various components in the multi‐component calcium‐silicate‐based slag system on the viscosity. Using various widely used spectroscopic techniques including Fourier transform infrared (FTIR), Raman, X‐ray photoelectron spectroscopy (XPS), and nuclear magnetic resonance (NMR), the viscous behavior and the slag structure of this system were correlated. In particular, the review begins with an introduction to the viscous behavior of binary silicate systems and an identification of the intricate details of the slag structure. Using the binary system as a basis, the compounded effect of typical ironmaking slag components such as Al2O3, MgO, alkali oxides, and TiO2 on the viscosity is introduced through expansion to a quinary slag system. Using a combination of the aforementioned spectroscopic methods, the meticulous details of the slag structure were ascertained, and the depolymerization or polymerization mechanisms of the silicate and alumino‐silicate structures were subsequently identified. This review also compares well‐known viscosity prediction models with experimentally measured values and identifies potential fields of research in the ironmaking industry associated with slag viscosities.
A Bayesian model for inference on population proportions
Authors: Okafor R. O. , Mbata U. A.
Published: July 2012

In recent times and even up to now, traffic congestion and parking difficulties, especially during morning and evening rush hours, have become a major concern to members of the University of Lagos (UNILAG) community and visitors alike. UNILAG has witnessed unprecedented growth in student enrollment during the past 10 years or so culminating in the current total enrollment of more than 35,000 students, of which about 25,000 are undergraduates. In order to study the worrisome traffic situation at UNILAG in the wake of these large numbers, independent, although similar, sample surveys of undergraduate students of the eight faculties on the main campus of UNILAG were conducted in 2007. The purpose of the surveys was to collect data on undergraduate students who owned or used motor vehicles on campus. Furthermore, to investigate possible temporal trends, the surveys were repeated in 2009. The types of data obtained from the surveys provided veritable impetus for the application of empirical Bayes (EB) analysis to estimate the proportions of students of individual faculties who used motor vehicles on campus roads during the periods under reference. The EB technique, being a Bayesian method, combines prior information and sample information in a manner that ‘shrinks’ an EB estimator toward the sample estimator if a vague prior (proper prior with a large variance) is used. The main result is that in 2007 about one in four students used motor vehicles, and this result held almost across the eight faculties. Although results of the 2009 surveys were generally similar there were faculties that recorded some reduction in the estimated proportions of students who used motor vehicles. WIREs Comput Stat 2012 doi: 10.1002/wics.1218

This article is categorized under:

Statistical and Graphical Methods of Data Analysis > Bayesian Methods and Theory
Smart polymersomes for therapy and diagnosis: fast progress toward multifunctional biomimetic nanomedicines
Authors: De Oliveira Hugo , Thevenot Julie , Lecommandoux Sébastien
Published: July 2012

Rising from the shortcomings of modern day therapeutics there is a need for a controlled approach in carrier‐mediated drug delivery. Polymeric vesicles, also called polymersomes, are powerful tools to address issues of efficacy, specificity, and controlled release of drugs to diseased tissues. These recent, biomimetic structures are able to overcome the body's natural defences, remaining stable for extended time in circulation, have tuneable membrane properties, allowing the control of membrane permeability and therefore of drug release, and have the potential to be functionalized for active targeting of specific tissues, reducing undesirable side effects. Extensive work has been carried out in order to attain multifunctional polymeric vesicles that respond to precise triggers (e.g., temperature, pH, redox, magnetic field, etc) with a spatial and temporal monitoring what may enable unprecedented control of drug release in the body. These versatile structures can be loaded with different type of (bio)molecules and nanoparticles, from drugs to contrast agents for medical imaging, and are able to accommodate them in different subcompartments of the vesicle (i.e., hydrophobic membrane and hydrophilic core). Multimodal targeted delivery system could be obtained from this unique platform, with abilities in both drug delivery and medical imaging contrast enhancement, widening the perspectives toward theranostics. Polymersomes offer a promising route toward more effective treatments with fewer side effects and superior outcomes. WIREs Nanomed Nanobiotechnol 2012, 4:525–546. doi: 10.1002/wnan.1183

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Emerging Technologies

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

Biology-Inspired Nanomaterials > Peptide-Based Structures
Schizosaccharomyces pombe reporter strains for relative quantitative assessment of heterochromatin silencing
Authors: Shimada Yukiko , Bühler Marc
Published: July 2012

The fission yeast Schizosaccharomyces pombe has been emerging as an important model organism for studying the formation and repression of heterochromatin. To enable simple and relative quantitative assessment of heterochromatin silencing, we have created bioluminescence‐based reporter strains. A green‐emitting click beetle luciferase (CBG68) gene was inserted within pericentromeric heterochromatin or at the silent mating‐type locus via homologous recombination. In the same strains, a red‐emitting click beetle luciferase (CBR) gene is expressed from the euchromatic leu1+ locus and can be used as a reference in dual‐colour assays. Our reporter strains are suitable for performing Chroma‐Glo™ assays, which can be carried out directly in the culture medium without prior cell lysis and in a multiwell format. Our reporter system reliably reflects the state of chromatin and can be easily adapted for use in high‐throughput screening approaches. Copyright © 2012 John Wiley & Sons, Ltd.
The New International Treaties in the Context of the European Union: A Temporary Solution for the Current Political Challenges or a Risk to the Institutional Future of the Union?
Authors: Casini Carlo
Published: July 2012

The Treaty of Lisbon is a stage in a process—not a final outcome, but rather an intermediate result. The EU can be seen as a building that is currently under construction; but now for various reasons this project is facing a major crisis, especially in the economic area. Two treaties have recently been signed with the hope that they are the tools needed to overcome this obstacle. Although anomalous, they may, under certain conditions, return us to the correct path.
Lovastatin‐induced apoptosis is modulated by geranylgeraniol in a neuroblastoma cell line
Authors: Marcuzzi Annalisa , Zanin Valentina , Piscianz Elisa , Tricarico Paola Maura , Vuch Josef , Girardelli Martina , Monasta Lorenzo , Bianco Anna Monica , Crovella Sergio
Published: July 2012

Mevalonic aciduria (MA), the most severe form of mevalonate kinase deficiency (MKD), is still an orphan drug disease and the pathogenetic mechanisms underlying neuronal dysfunction is still poorly understood. In our study we have investigated the apoptotic mechanism mediated by the exposure of the cultured neuroblastoma cell line, SH‐SY5Y, to lovastatin in absence or in presence of the isoprenoid, geranylgeraniol, with the aim of unraveling the pathogenesis of MA. Lovastatin, blocks the mevalonate pathway inhibiting the 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMG‐CR), an enzyme of the mevalonate pathway upstream the mevalonate kinase enzyme, reproducing biochemical features similar to those found in MKD.

We demonstrate that apoptosis in neuronal lovastatin treated‐cells is induced by the mitochondrial pathway, with caspase‐9 as the initiator and caspase‐3 as the effector caspase. The presence of geranylgeraniol modulates both the caspase‐9 and caspase‐3 activity in a dose‐dependent way, confirming that this isoprenoid enters the mevalonate pathway, is metabolized and finally is able to by‐pass the statin biochemical block reconstituting the mevalonate pathway. According to our findings, it should not be the time course adopted that modulates the apoptotic response but rather the isoprenoid itself.

Being aware that our results have been obtained using a biochemical model of MKD, and not cells from patients with the disease, we believe our findings increase the knowledge of MA pathogenesis, and may possibly contribute to the development of novel therapeutic strategies.
An investigation of PreMCI: Subtypes and longitudinal outcomes
Authors: Loewenstein David A. , Greig Maria T. , Schinka John A. , Barker Warren , Shen Qian , Potter Elizabeth , Raj Ashok , Brooks Larry , Varon Daniel , Schoenberg Michael , Banko Jessica , Potter Huntington , Duara Ranjan
Published: July 2012

Background/Aims

To investigate the clinical features and rates of progression of conditions that are not considered to be normal, but do not fulfill criteria for mild cognitive impairment (MCI).

Methods

We longitudinally evaluated 269 elderly subjects who did not meet formal criteria for MCI at baseline but had: (1) a clinical history suggesting MCI without neuropsychological deficits (PreMCI‐Clinical); or (2) neuropsychological deficits on one or more memory measures in conjunction with a negative clinical examination (amnestic PreMCI‐NP) or were normal on both neuropsychological and clinical examination.

Results

The rate of progression to MCI or dementia over an average of 2‐ to 3 years was 3.7% for no cognitive impairment subjects, whereas it was significantly greater for all PreMCI subtypes (22.0% for PreMCI‐Clinical, 38.9% for amnestic PreMCI‐NP subjects with two or more memory impairments). Among PreMCI subjects as a whole, lower baseline scores on object memory and category fluency tests were the best predictors of progression to MCI or dementia. Cardiovascular risk factors, Parkinsonian symptoms, and hippocampal atrophy were not associated with progression.

Conclusion

Distinct PreMCI subtypes defined on the basis of clinical and neuropsychological evaluations were found to have distinct characteristics, but both subtypes demonstrated elevated risk for progression to MCI or dementia. Despite the lack of evidence of clinical impairment, subjects with neuropsychological deficits in two memory domains were particularly at increased risk for progression of their deficits.
Nonsteroidal anti‐inflammatory drug use and the risk of cognitive impairment and Alzheimer's disease
Authors: Côté Sharlène , Carmichael Pierre‐Hugues , Verreault René , Lindsay Joan , Lefebvre Jean , Laurin Danielle
Published: July 2012

Background

Some observational studies have established an association between exposure to nonsteroidal anti‐inflammatory drugs (NSAIDs) and a decreased risk of subsequently developing Alzheimer's disease (AD). Mild cognitive impairment or cognitive impairment, not dementia (CIND) is more likely to convert to AD, and no specific preventive method is currently available. The objective of this study was to determine the association of NSAID use in 5276 cognitively normal subjects of the Canadian Study of Health and Aging, a 10‐year population‐based cohort study, with the incidence of CIND, AD, and all‐cause dementia.

Methods

Hazard ratios were calculated from Cox proportional hazards models with age as the time scale according to three study samples including 824 cases of dementia (563 cases of AD), 630 cases of dementia (435 cases of AD), and 883 cases of CIND, respectively. Adjustments were made for gender, education, lifestyle factors, comorbid diseases, and vascular risk factors.

Results

Lower risks for AD and all‐cause dementia were significantly associated with the use of any NSAIDs and the salicylates without barbiturates subgroup in the study sample including subjects with CIND at baseline. There was a weak association between any NSAIDs and the risk of CIND (hazard ratio, 0.87; 95% confidence interval, 0.76–1.00).

Conclusion

These results suggest that there is an association between NSAID use and a lower incidence of AD and, to a lesser extent, of CIND.
Risk of dementia in an elderly population of Parkinson's disease patients: A 15‐year population‐based study
Authors: Perez Florian , Helmer Catherine , Foubert‐Samier Alexandra , Auriacombe Sophie , Dartigues Jean‐François , Tison François
Published: July 2012

Background

The incidence of dementia in Parkinson's disease (PD) is not fully known, and previous studies have provided a wide range of rates owing to variations in diagnostic criteria and methodologies used. We estimated the risk of dementia in newly diagnosed cases of PD in a population‐based cohort of subjects aged >65 years.

Methods

We performed repetitive systematic screening of PD diagnosis, cognitive performances, and clinical dementia during 15 years (at year 0, 3, 5, 8, 10, and 15) in 3726 elderly subjects living at home in southwestern France (PAQUID). Two sets of diagnostic criteria for dementia in PD were considered: Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria and Movement Disorders Society criteria.

Results

Forty‐four incident cases of PD occurred in the cohort; of these, 18 (41%) developed dementia during a mean follow‐up of 6.8 ± 3.6 years. Incidence rate of dementia associated with PD was 74 per 1000 patient‐years. The cumulative risk of dementia was approximately 25% and 50% after 5 and 10 years of follow‐up, respectively. The relative risk for developing dementia in incident PD subjects compared with non‐PD subjects was 2.47 (1.55–3.95). Equivalent estimations were obtained with Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria or Movement Disorders Society criteria.

Conclusion

PD represents a high‐risk stage for dementia in the general population.
Predictors for cognitive decline in patients with confluent white matter hyperintensities
Authors: Mok Vincent , Xiong Yunyun , Wong Kelvin K. , Wong Adrian , Schmidt Reinhold , Chu Winnie W.C. , Hu Xintao , Lung Leung Eric Yim , Chen Sirong , Chen Yangkun , Tang Wai Kwong , Chen Xiangyan , Ho Chi Lai , Wong Ka Sing , Wong Stephen T.C.
Published: July 2012

Background

Although patients harboring confluent white matter hyperintensities (WMH) are at high risk of cognitive decline, this risk varies among individuals. We investigated the predictors for cognitive decline in stroke patients with confluent WMH.

Methods

We followed up 100 stroke patients with confluent WMH who were participants of the VITAmins TO Prevent Stroke study for 2 years.

We investigated the association between clinical features, apolipoprotein E status, imaging measures (infarcts, microbleeds, volumes of WMH, cortical gray matter [cGM], lateral ventricles, and hippocampi), and B vitamins with changes in cognitive measures (clinical dementia rating scale, Mini‐Mental State Examination, Mattis dementia rating scale—initiation/perseveration subscale). We performed Pittsburgh compound B imaging among dementia converters.

Results

Multivariate regression analysis showed that increase in clinical dementia rating scale grade was associated with cGM atrophy, absence of hyperlipidemia, and lower diastolic blood pressure at baseline. cGM atrophy and absence of hyperlipidemia were also associated with deterioration in Mini‐Mental State Examination and Mattis dementia rating scale—initiation/perseveration subscale scores. Pittsburgh compound B retention typical of Alzheimer's disease was found only in 10% of dementia converters. Incident stroke and B vitamins were not associated with cognitive decline.

Conclusions

Among stroke patients with confluent WMH, cGM atrophy and absence of hyperlipidemia are important predictors for cognitive decline. Significant cognitive decline can occur in the absence of incident stroke or Alzheimer's pathology.
The epidemiology of Alzheimer's disease: Laying the foundation for drug design, conduct, and analysis of clinical trials
Authors: Yaffe Kristine , Tocco Michael , Petersen Ronald C. , Sigler Catherine , Burns Leah C. , Cornelius Christel , Khachaturian Ara S. , Irizarry Michael C. , Carrillo Maria C.
Published: July 2012

Epidemiological studies increasingly inform Alzheimer's disease (AD) public health impact, prevention strategies, drug targets, therapeutic interventions, and clinical trial design. For this reason, the Alzheimer's Association Research Roundtable convened an international group of AD experts with experience in conducting both observational and clinical trials for a meeting on October 19 and 20, 2010, in Washington, DC, to discuss the role of epidemiologic studies in AD research and therapeutic advances. Topics included wellness markers and risk factors, with a focus on special populations such as those at elevated risk, super agers, and underserved populations. Discussions also highlighted lessons learned from observational studies of aging, cardiovascular disease, and other disease areas, as well as how new technologies have enabled the gathering of data relevant to drug development and clinical trial conduct.
The draft “National Plan” to address Alzheimer's disease ‐ National Alzheimer's Project Act (NAPA)
Authors: Khachaturian Zaven S. , Khachaturian Ara S. , Thies William
Published: July 2012

This perspective updates the status of the “National Plan to Address Alzheimer's Disease” and the recommendations of the NAPA Advisory Council's Sub‐committee on Research. Here, we identify some of the critical issues the future reiterations of the National Plan should consider during implementation phase of the plan. The Journal invites the scientific community to contribute additional ideas and suggestions towards a national research initiative.
Streaming-potential phenomena in the thin-Debye-layer limit. Part 2. Moderate Péclet numbers
Authors: Schnitzer Ory , Frankel Itzchak , Yariv Ehud
Published: July 2012

Macroscale description of streaming-potential phenomena in the thin-double-layer limit, and in particular the associated electro-viscous forces, has been a matter of long-standing controversy. In part 1 of this work (Yariv, Schnitzer & Frankel,J. Fluid Mech., vol. 685, 2011, pp. 306–334) we identified that the product of the Hartmann ($\lambda $) and Péclet ($\mathit{Pe}$) numbers is$O({\delta }^{\ensuremath{-} 2} )$,$\delta $being the dimensionless Debye thickness. This scaling relationship defines a one-family class of limit processes appropriate to the consistent analysis of this singular problem. In that earlier contribution we focused on the generic problems associated with moderate$\lambda $and large$\mathit{Pe}$, where the streaming-potential magnitude is comparable to the thermal voltage. Here we consider the companion generic limit of moderate Péclet numbers and large Hartmann numbers, deriving the appropriate macroscale model wherein the Debye-layer physics is represented by effective boundary conditions. Since the induced electric field is asymptotically smaller, calculation of these conditions requires higher asymptotic orders in analysing the Debye-scale transport. Nonetheless, the leading-order electro-viscous forces are of the same$O({\delta }^{2} )$relative magnitude as those previously obtained in the large-$\mathit{Pe}$limit. The structure of these forces is different, however, first because the small Maxwell stresses do not contribute at leading order, and second because salt polarization results in a dominant diffuso-osmotic slip. Since the salt distribution is governed by an advection–diffusion equation, this slip gives rise to electro-viscous forces which are nonlinear in the driving flow. The resulting scheme is illustrated by the calculation of the electro-viscous excess drag in the prototype problem of a translating sphere.
Gene expression analysis of the liver and skeletal muscle of psyllium-treated mice
Authors: Togawa Naoyuki , Takahashi Rumiko , Hirai Shizuka , Fukushima Tatsunobu , Egashira Yukari
Published: July 2012

Psyllium, a dietary fibre rich in soluble components, has both cholesterol- and TAG-lowering effects. Many studies have verified these actions using liver samples, whereas little information is available on the effects of psyllium treatment on other organs. The purpose of the present study was to evaluate the possible beneficial effects of psyllium. We investigated the gene expression profiles of both liver and skeletal muscle using DNA microarrays. C57BL/6J mice were fed a low-fat diet (LFD; 7 % fat), a high-fat diet (HFD; 40 % fat) or a HFD with psyllium (40 % fat+5 % psyllium; HFD+Psy) for 10 weeks. Body weights and food intake were measured weekly. After 10 weeks, the mice were killed and tissues were collected. Adipose tissues were weighed, and plasma total cholesterol and TAG blood glucose levels were measured. The expression levels of genes involved in glycolysis, gluconeogenesis, glucose transport and fatty acid metabolism were measured by DNA microarray in the liver and skeletal muscle. In the HFD+Psy group, plasma total cholesterol, TAG and blood glucose levels significantly decreased. There was a significant reduction in the relative weight of the epididymal and retroperitoneal fat tissue depots in mice fed the HFD+Psy. The expression levels of genes involved in fatty acid oxidation and lipid transport were significantly up-regulated in the skeletal muscle of the HFD+Psy group. This result suggests that psyllium stimulates lipid transport and fatty acid oxidation in the muscle. In conclusion, the present study demonstrates that psyllium can promote lipid consumption in the skeletal muscle; and this effect would create a slightly insufficient glucose state in the liver.
Fenugreek seed affects intestinal microbiota and immunological variables in piglets after weaning
Authors: Zentek Jürgen , Gärtner Stefanie , Tedin Lydia , Männer Klaus , Mader Anneluise , Vahjen Wilfried
Published: July 2012

Fenugreek seed has been shown to affect the intestinal microbiota and immunological responses in animals. A feeding trial with male castrated piglets was performed over 28 d without or with the addition of 1·5 g fenugreek seeds/kg complete diet in ten and eleven piglets, weaned at 21 d. In the intestinal tract, pH, lactate and SCFA were measured as major bacterial metabolites. Immune cell phenotypes, phagocytic activity and lymphocyte proliferation after stimulation with pokeweed mitogen, concanavalin A and phytohaemagglutinin M were measured by flow cytometry. Health status and performance of the piglets were not affected by fenugreek. The pH in the caecum and colon were reduced compared with the control (P< 0·05). Higher concentrations ofl-lactic acid were recorded in the small-intestinal digesta (average concentrations from the duodenum, jejunum and ileum;P< 0·05), while the concentrations of SCFA remained unchanged except an increase inn-butyric acid in colon contents (P< 0·05). The piglets fed the fenugreek diet had higherLactobacillusand clostridium cluster I concentrations and lowerEscherichia,HafniaandShigellaconcentrations in the small intestine. The addition of fenugreek increased the relative concentration of the γδ T-cell population (TCR1+CD8α−) in the blood with a simultaneous reduction of antigen-presenting cells (MHCII+CD5−) (P< 0·05). Proliferation rate and phagocytosis activity of monocytes were not affected by the additive. In conclusion, fenugreek seeds might be interesting as a feed ingredient for young piglets due to their effects on the intestinal microbiota and immunological variables. The impact on performance and animal health has to be further evaluated.
Is There a Secret Ballot? Ballot Secrecy Perceptions and Their Implications for Voting Behaviour
Authors: Gerber Alan S. , Huber Gregory A. , Doherty David , Dowling Conor M.
Published: July 2012

Do people believe the votes they cast are truly secret? Novel items added to a nationally representative survey show that 25 per cent of respondents report not believing their ballot choices are kept secret and over 70 per cent report sharing their vote choices with others. These findings suggest that standard models of candidate choice should account for the potential effects of doubts about ballot secrecy. Consistent with this view, regression analysis shows that social forces appear to have a greater effect on vote choices among people who doubt the formal secrecy of the ballot. This analysis supports the broader claim that the intended benefits of institutional rules may not be realized if people's perceptions of these rules differ from their formal characteristics.
Arbitrary amplitude dust-acoustic double-layers in an electron-depleted dusty plasma with two high-energy tail ion distributions
Authors: MAYOUT SALIHA , TRIBECHE MOULOUD
Published: July 2012

Arbitrary amplitude dust-acoustic double-layers (DA-DLs) in two high-energy tail ion distributions are investigated. The electron number density has been assumed sufficiently depleted during the charging of dust grains on account of the attachment of background plasma electrons on the surface of dust grains. It is found that under certain conditions DA-DLs may be admitted. The degree of suprathermality of the low-temperature component has a sensitive role on their formation and a small change in this degree can even prevent the DL formation. The ‘Maxwellianization’ of the high-temperature component involves a suprathermalization process of the low-temperature component for the existence of localized DA-DLs. Our results may be relevant to a number of space dusty plasma systems, particularly the Saturn's F-ring where electron depletion and suprathermality are thought to come into play.
Efficient generation of proton bunches by intense laser pulse with a double-slice-foil target
Authors: ZHENG JUN , SHENG ZHENG-MING , LIU JIN-LU , ZHOU WEI-MIN , XU HAN , ZHANG JIE
Published: July 2012

A double-slice-foil target is proposed for the generation of quasi-monoenergetic proton bunches by intense laser pulses. In this new target structure, two symmetrical solid slices are adjoined obliquely to the front side of a plane double-layer target. Two-dimensional particle-in-cell simulations show that a large number of hot electrons are pulled out from solid slices and accelerated forward by direct laser acceleration, which lead to significant enhancement of the sheath field and the produced proton beam energy as compared with the normal plane double-layer target and some other modified targets. It appears that well-collimated proton bunches with energy larger than 200 MeV can be produced at the focused laser intensity of about 1021W/cm2 with the proposed target design.
Effect of RF on RF nitrogen discharge with induced argon plasma at high pressure
Authors: WANG YINAN , LIU YUE , ZHENG SHU , LIN GUOQIANG
Published: July 2012

A one-dimensional fluid model is built to study the effect of radio frequency (RF) on the characteristics of RF nitrogen discharge with induced argon plasma at high pressure. The model is solved by a finite difference method, and the numerical results are obtained. The numerical results show that by modulating driven frequency, the discharge can obtain higher plasma density. Moreover, the discharge is operated in a stable α mode in a range of 100 MHz of driven frequency.
Dust-ion-acoustic solitary waves in a dusty plasma with arbitrarily charged dust and non-thermal electrons
Authors: KUNDU N. R. , MAMUN A. A.
Published: July 2012

The dust-ion-acoustic solitary waves (DIA SWs) in an unmagnetized dusty plasma containing non-thermal electrons, cold mobile positive ions, and stationary arbitrarily (positively and negatively) charged static dust have been theoretically studied. The reductive perturbation technique has been employed to derive the Korteweg-de Vries equation, which admits SW solutions under certain conditions. It has been also shown that the basic features (amplitude, width, speed, etc.) of DIA SWs are significantly modified by the polarity of dust and non-thermal electrons. The implications of our results in space and laboratory dusty plasma situations are briefly discussed.
Rotavirus genotypes in children in the Basque Country (North of Spain): rapid and intense emergence of the G12[P8] genotype
Authors: CILLA G. , MONTES M. , GOMARIZ M. , ALKORTA M. , ITURZAETA A. , PEREZ-YARZA E. G. , PEREZ-TRALLERO E.
Published: July 2012

Between July 2009 and June 2011, rotavirus was detected in 507 of 4597 episodes of acute gastroenteritis in children aged <3 years in Gipuzkoa (Basque Country, Spain), of which the G-type was determined in 458 (90·3%). During the annual seasonal epidemic of 2010–2011, the unusual G-type 12 was predominant, causing 65% (145/223) of cases of rotavirus gastroenteritis. All the G12 strains were clustered in lineage III and were preferentially associated with P-type 8. This epidemic was characterized by broad geographical distribution (rural and urban) and, over 7 months, affected both infants and children, the most frequently affected being children between 4 and 24 months. Of children with rotavirus G12, 16% required hospital admission, the admission rate in children aged <2 years being 20·7 cases/10 000 children. The sudden emergence and predominance of G12 rotaviruses documented in this winter outbreak suggest that they may soon become a major human rotavirus genotype.
Seismic stratigraphy of the late Quaternary sedimentary infill of Lac d'Armor (Kerguelen archipelago): a record of glacier retreat, sedimentary mass wasting and southern Westerly intensification
Authors: Heirman Katrien , De Batist Marc , Arnaud Fabien , De Beaulieu Jacques-Louis
Published: July 2012

Lac d'Armor (49°27′S, 69°42′E) is a medium-sized, fjord-type lake located on the ‘Grande Terre’ island of the Kerguelen archipelago. A dense grid of high-resolution reflection seismic profiles was collected from this lake basin. The seismic stratigraphic facies reveal a last deglaciation to Holocene infill comparable to the seismic facies found in other glacigenic lakes all over the world. Remarkable features in the seismic stratigraphy are mounded structures found at the southern edge of both sub-basins. The sediment mounds can be interpreted as sediment drifts created by wind-induced bottom currents. The onset of the build-up of these drifts initiated at some point in the Holocene and indicates a strengthening of the southern Westerlies, which are currently the dominant winds on this island.
A Generalization of the Erdős–Turán Law for the Order of Random Permutation
Authors: GNEDIN ALEXANDER , IKSANOV ALEXANDER , MARYNYCH ALEXANDER
Published: July 2012

We consider random permutations derived by sampling from stick-breaking partitions of the unit interval. The cycle structure of such a permutation can be associated with the path of a decreasing Markov chain onnintegers. Under certain assumptions on the stick-breaking factor we prove a central limit theorem for the logarithm of the order of the permutation, thus extending the classical Erdős–Turán law for the uniform permutations and its generalization for Ewens' permutations associated with sampling from the PD/GEM(θ)-distribution. Our approach is based on using perturbed random walks to obtain the limit laws for the sum of logarithms of the cycle lengths.
THE MORAL SIGNIFICANCE OF RISKING
Authors: Oberdiek John
Published: July 2012

What makes careless conduct careless is easily one of the deepest and most contested questions in negligence law, tort theory, and moral theory. Answering it involves determining the conditions that make the imposition of risk unjustifiable, wrong, or impermissible. Yet there is a still deeper as well as overlooked and undertheorized question: Why does subjecting others to risk of harm call for justification in the first place? That risk can be impermissibly imposed upon others—that is, the very possibility of negligence—presupposes that imposing risk is the kind of thing that can be impermissible. Unless imposing risk can be impermissible after all, unjustified risking is literally impossible. In this discussion, I explore what I call the moral significance of risking, arguing that the moral significance of risking resides in a certain kind of nonmaterial autonomy interest that is implicated whenever one imposes risk of harm on another.
FINANCIAL GLOBALIZATION AND ECONOMIC GROWTH
Authors: Neto Delfim Gomes
Published: July 2012

Using a two-sector endogenous growth model, the speed of convergence is determined primarily by the gap in rates of return between physical and human capital. In closed economies, for a typical situation of having relatively less physical capital than in a steady state, the return on physical capital will be significantly high, whereas the return on human capital will be relatively low. This gap in rates of return is quite large when the economy is not at its steady state. In open economies, where human capital is nontradable, the gap in rates of return is small, as is the gap between the international interest rate (which is less than the closed economies return on physical capital) and the return on human capital. Convergence in open economies will be relatively slow, and convergence in closed economies will be relatively fast, and therefore there is little gain from financial liberalization.
Trade and the political economy of standards
Authors: SWINNEN JOHAN , VANDEMOORTELE THIJS
Published: July 2012

This paper reviews the emerging literature on the political economy of public standards in an open economy to explain why standards are set at certain levels, and how this affects trade. We use a simple framework to illustrate how interest groups may influence the standard-setting process, and which factors may affect the political equilibria. We analyze the relation between trade and standards, and their potential protectionist nature. We argue that standards may act as barriers or catalysts to trade, that both under- or over-standardization may occur, and that standards may serve as protectionist instruments, or not.
Global Public-Private Partnerships in International Law
Authors: AZIZ Davinia
Published: July 2012

Over the last decade, public-private partnerships between states and a variety of non-state actors have proliferated as vehicles for functional co-operation at the global level. In parallel, there has been an emerging trend to accord such partnerships the privileges and immunities normally reserved for intergovernmental organizations (“IO-type privileges and immunities”). After identifying the legal and normative issues associated with this trend, this article argues that IO-type privileges and immunities should be restricted to entities that are clearly established under and governed by international law, and that any approach to IO-type privileges and immunities as a uniform package deal, regardless of the precise functional requirements of the global public-private partnership and its different categories of staff, or the specific conditions in the relevant national jurisdiction where a given privilege or immunity is sought, should be avoided.
Schulbegleitende Förderung von Kindern mit einer LRS beim Englischlernen
Authors: Dorsch Ursula , Dreßler Johannes
Published: July 2012

Zusammenfassung: In diesem Artikel möchte ich die von mir entwickelte Förderung für legasthene und lese-rechtschreibschwache Kinder in der Fremdsprache Englisch vorstellen. Nach einem kurzen Überblick über Herkunft und Besonderheiten der gesprochenen und geschriebenen englischen Sprache an sich, gehe ich näher auf die Schwierigkeiten ein, die sich bei den Legasthenikern eigenen audio-visuellen Diskriminationsproblemen auftun. Auf dieser Basis, und die bisher vorhandenen Fördermaterialien in Deutschland und England einbeziehend, erläutere ich meinen systematischen, strukturierten, handlungsorientierten, schulartbezogenen und unterrichtsparallelen Förderansatz mit Individualisierungsmöglichkeiten für spätere Jahrgangsstufen und Lernniveaus. Zur Effektivitätsprüfung wählte ich die Falldarstellungen, die exemplarisch am Beispiel Julian hier Eingang finden und maßgeblich die Entwicklung meines Programms beeinflussten. Ein Ausblick auf die in Zukunft anstehenden Evaluationen schließt diesen Artikel ab.