bluuebunny/crossref_metadata_2025 huggingface dataset:
A Noncoding RNA Antisense to Moesin at 5p14.1 in Autism
Authors: Kerin Tara , Ramanathan Anita , Rivas Kasey , Grepo Nicole , Coetzee Gerhard A. , Campbell Daniel B.
Published: April 2012

An antisense RNA, transcribed from an autism-associated region on chromosome 5, is highly expressed in autism brains and could regulate the developmental brain protein moesin.
Preclinical Development and Clinical Translation of a PSMA-Targeted Docetaxel Nanoparticle with a Differentiated Pharmacological Profile
Authors: Hrkach Jeffrey , Von Hoff Daniel , Ali Mir Mukkaram , Andrianova Elizaveta , Auer Jason , Campbell Tarikh , De Witt David , Figa Michael , Figueiredo Maria , Horhota Allen , Low Susan , McDonnell Kevin , Peeke Erick , Retnarajan Beadle , Sabnis Abhimanyu , Schnipper Edward , Song Jeffrey J. , Song Young Ho , Summa Jason , Tompsett Douglas , Troiano Greg , Van Geen Hoven Tina , Wright Jim , LoRusso Patricia , Kantoff Philip W. , Bander Neil H. , Sweeney Christopher , Farokhzad Omid C. , Langer Robert , Zale Stephen
Published: April 2012

A targeted nanoparticle containing docetaxel displays antitumor activity in animals and differentiated pharmacological properties in patients with advanced solid tumors.
T Cells Gone Bad in Heart Disease
Authors: Baker Aaron B.
Published: April 2012

An unusual type of immune cell may hold the key to preventing heart attacks.
Tumors and Microbes, Sitting in a Tree…
Authors: Bettegowda Chetan
Published: April 2012

Tumor-targeting bacteria are imaged using bioluminescent technology, shedding light on the heterogeneity of the tumor microenvironment.
From Contagion to Outbreak: Host Susceptibility in Viral Pneumonia
Authors: Calfee Carolyn S.
Published: April 2012

A minor allele of the IFITM3 gene may partially explain why some exposed people develop severe influenza infection, whereas others remain healthy.
Multiple time period imputation technique for multiple missing traffic variables: nonparametric regression approach
Authors: Chang Hyunho , Park Dongjoo , Lee Younginn , Yoon Byoungjo
Published: April 2012

The objective of this study is to introduce an effective and practical model, based on non-parametric regression, to instantaneously estimate multivariate imputations replacing multiple missing variables during multiple time periods. The developed model was essentially designed for system-oriented, real-world applications. In an empirical study with real-world data, the proposed model, on the whole, outperformed the seasonal auto-regressive integrated moving average (ARIMA). The analysis of the results indicates that the introduced model was more applicable to multivariate imputation during multiple time intervals than that of ARIMA. In addition, it was revealed that ARIMA could somewhat deform the relationship between the volume (q) and speed (s), whereas the developed model reproduced the q–s relationship more similarly than ARIMA. Moreover, the proposed model is very simple and does not require system operators to input or recalibrate any external parameters because it was developed for applications of real data management systems.
Efficacy of acidic and basic electrolyzed water in eradicating Staphylococcus aureus biofilm
Authors: Sun Ji-Lu , Zhang Shao-Kang , Chen Jing-Yu , Han Bei-Zhong
Published: April 2012

Staphylococcus aureus is a major pathogen. It can form biofilm on the surfaces of medical devices and food equipment, which makes it more difficult to eradicate. To develop a novel method to eradicate S. aureus biofilm, the effects of electrolyzed water on removing and killing S. aureus biofilm were investigated in this study. By using a biofilm biomass assay with safranin staining and visualization of biofilm architecture with scanning electron microscopy, it was shown that basic electrolyzed water (BEW) could effectively remove established biofilm. The pH of electrolyzed water affected removal efficacy. Using a biofilm viability assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide staining, acidic electrolyzed water (AEW) efficiently killed biofilm-imbedded S. aureus. The available chlorine in AEW may be a main contributing factor for bactericidal activity. Additionally, BEW had a removal efficacy for S. aureus biofilm equivalent to 2% NaOH, and AEW had a bactericidal capability for S. aureus in biofilm equivalent to 2% HCl. These data suggested that AEW and BEW could be applied as a bactericide and removing agent for S. aureus in biofilm, respectively.
Detection of microcystin-producingMicrocystisin Guanqiao Lake using a sandwich hybridization assay
Authors: Zhu Jing Ping , Du Shi , Li Xian
Published: April 2012

Based on sequence analyses of the mcyJ gene from Microcystis strains, a probe pair TJF and TJR was designed and a sandwich hybridization assay (SHA) was established to quantitatively detect microcystin-producing Microcystis. Through BLAST and cyanobacterial culture tests, TJF and TJR were demonstrated to be specific for microcystin-producing Microcystis. A calibration curve for the SHA was established, and the lowest detected concentration was 100 cells·mL–1. Laboratory cultures and field samples from Guanqiao Lake were analyzed with both the SHA and microscopy. The cell number of microcystin-producing Microcystis and that of total Microcystis were compared. The biotic and abiotic components of the samples were of little disturbance to the SHA. In this study, a SHA was established to detect Microcystis, providing an alternative to PCR–ELISA and real-time PCR technology.
Interfering with hepatitis C virus assembly in vitro using affinity peptides directed towards core protein
Authors: Duvignaud Jean-Baptiste , Majeau Nathalie , Delisle Priscilla , Voyer Normand , Gagné Stéphane M. , Leclerc Denis
Published: April 2012

Viral assembly is a crucial key step in the life cycle of every virus. In the case of Hepatitis C virus (HCV), the core protein is the only structural protein to interact directly with the viral genomic RNA. Purified recombinant core protein is able to self-assemble in vitro into nucleocapsid-like particles upon addition of a structured RNA, providing a robust assay with which to study HCV assembly. Inhibition of self-assembly of the C170 core protein (first 170 amino acids) was tested using short peptides derived from the HCV core, from HCV NS5A protein, and from diverse proteins (p21 and p73) known to interact with HCV core protein. Interestingly, peptides derived from the core were the best inhibitors. These peptides are derived from regions of the core predicted to be involved in the interaction between core subunits during viral assembly. We also demonstrated that a peptide derived from the C-terminal end of NS5A protein moderately inhibits the assembly process.
Prospecting for ice association: characterization of freeze–thaw selected enrichment cultures from latitudinally distant soils
Authors: Wilson Sandra L. , Grogan Paul , Walker Virginia K.
Published: April 2012

Freeze–thaw stress has previously been shown to alter soil community structure and function. We sought to further investigate this stress on enriched microbial consortia with the aim of identifying microbes with ice-associating adaptations that facilitate survival. Enrichments were established to obtain culturable psychrotolerant microbes from soil samples from the latitudinal extremes of the Canadian Shield plateau. The resulting consortia were subjected to consecutive freeze–thaw cycles, and survivors were putatively identified by their 16S rRNA gene sequences. Even though the northerly site was exposed to longer, colder winters and large spring-time temperature fluctuations, the selective regime similarly affected both enriched consortia. Quantitative PCR and metagenomic sequencing were used to determine the frequency of a subset of the resistant microbes in the original enrichments. The metagenomes showed 22 initial genera, only 6 survived and these were not dominant prior to selection. When survivors were assayed for ice recrystallization inhibition and ice nucleation activities, over 60% had at least one of these properties. These phenotypes were not more prevalent in the northern enrichment, indicating that regarding these adaptations, the enrichment strategy yielded seemingly functionally similar consortia from each site.
Endophytic fungi associated with leaves of Betulaceae in Japan
Authors: Osono Takashi , Masuya Hayato
Published: April 2012

Diversity and species composition of endophytic fungi on leaves of 11 tree species in Betulaceae were studied, with reference to climatic, tree species, and seasonal variations. A total of 186 fungal isolates were obtained from 190 leaves collected in a subalpine forest, a cool temperate forest, and a subtropical forest in Japan, and were divided into 46 operational taxonomic units (OTUs) according to the base sequences of D1–D2 region of large subunit rDNA. The 2 most frequent OTUs were Muscodor sp. and Nemania sp. in Xylariaceae, followed by Gnomonia sp., Glomerella acutata , Apiosporopsis sp., Asteroma sp., and Cladosporium cladosporioides . The similarities of OTU composition in endophytic fungal assemblages on leaves of Betulaceae were generally low among the forests of different climatic regions. Fungal OTU compositions were relatively similar between 2 Betula species in the subalpine forest, whereas 7 tree species in the cool temperate forest were divided into 3 groups according to the similarity of endophytic fungal assemblages on the leaves, with 4 Carpinus species assigned into 2 of the 3 groups. The similarity of endophytic fungal assemblages between August and October was relatively high in the subalpine forest, whereas the seasonal changes were generally greater (i.e., the similarities among sampling dates were lower) in the cool temperate forest.
Role of Conical Intersections in Molecular Spectroscopy and Photoinduced Chemical Dynamics
Authors: Domcke Wolfgang , Yarkony David R.
Published: April 2012

This review describes how conical intersections affect measured molecular spectra and simple photofragmentation processes. We consider excitations that result in electron ejection, that is, photoionization or photodetachment, as well as photoinduced H-atom elimination. Section 1 presents a brief overview of the history of conical intersections and their rise from an arcane theoretical concept to a major paradigm in nonadiabatic chemistry. In Section 2, the generic properties of conical intersections are discussed, as well as their characterization with modern electronic-structure methods. Section 3 briefly discusses computational tools used to compute the nuclear motion involving conical intersections. Section 4 describes how the ideas of Sections 2 and 3 are combined to simulate molecular spectra impacted by conical intersections. Section 5 describes selected recent experimental and computational studies of photoelectron, photodetachment, and photofragment spectra. Rather than providing an encyclopedic bibliography of the previous and current literature, we illustrate significant problems currently being addressed and describe what can be accomplished with current computational techniques and how these results are achieved. Section 6 suggests future directions in this field.
Chemistry and Composition of Atmospheric Aerosol Particles
Authors: Kolb Charles E. , Worsnop Douglas R.
Published: April 2012

For more than two decades a cadre of physical chemists has focused on understanding the formation processes, chemical composition, and chemical kinetics of atmospheric aerosol particles and droplets with diameters ranging from a few nanometers to ∼10,000 nm. They have adapted or invented a range of fundamental experimental and theoretical tools to investigate the thermochemistry, mass transport, and chemical kinetics of processes occurring at nanoscale gas-liquid and gas-solid interfaces for a wide range of nonideal, real-world substances. State-of-the-art laboratory methods devised to study molecular spectroscopy, chemical kinetics, and molecular dynamics also have been incorporated into field measurement instruments that are deployed routinely on research aircraft, ships, and mobile laboratories as well as at field sites from megacities to the most remote jungle, desert, and polar locations. These instruments can now provide real-time, size-resolved aerosol particle physical property and chemical composition data anywhere in Earth's troposphere and lower stratosphere.
Free-Electron Lasers: New Avenues in Molecular Physics and Photochemistry
Authors: Ullrich Joachim , Rudenko Artem , Moshammer Robert
Published: April 2012

Free-electron lasers are fourth-generation light sources that deliver extremely intense (>1012 photons per pulse), ultrashort (∼10−14 s = 10 fs) light pulses at up to kilohertz repetition rates with unprecedented coherence properties and span a broad wavelength regime from soft (∼10 eV) to hard X-ray energies (∼15 keV). They thus enable a whole suite of novel experiments in molecular physics and chemistry: Inspecting radiation-induced reactions in cold molecular ions provides unprecedented insight into the photochemistry of interstellar clouds and upper planetary atmospheres; double core-hole photoelectron spectroscopy offers enhanced sensitivity for chemical analysis; the dynamics of highly excited molecular states, pumped by vacuum ultraviolet pulses, can be inspected; and vacuum ultraviolet or X-ray probe pulses generally hold the promise to trace chemical reactions along an entire reaction coordinate with atomic spatial and temporal resolution. This review intends to provide a first overview on upcoming possibilities, emerging technologies, pioneering results, and future perspectives in this exciting field.
Dipolar Recoupling in Magic Angle Spinning Solid-State Nuclear Magnetic Resonance
Authors: De Paëpe Gaël
Published: April 2012

Solid-state nuclear magnetic resonance (SSNMR) magic angle spinning (MAS) can be used to record high-resolution data dominated by site-specific information. Although MAS introduces high resolution by attenuating the anisotropic broadening, it also suppresses the nuclear dipole-dipole distance information that is the source of most structural data in the spectra. Such information can be reintroduced coherently and thus selectively by the application of a carefully chosen sequence of radiofrequency pulses, an approach that was introduced 20 years ago and is referred to as dipolar recoupling. This review presents the establishment of recoupling techniques in SSNMR and recalls the major steps achieved by the community throughout the last two decades. This review also presents emerging techniques and their corresponding new concepts. Finally, we present some recent developments based on second-order recoupling mechanisms and discuss their implications regarding dipolar truncation and the possibility to extract structural constraints in uniformly labeled systems.
Ultrathin Oxide Films on Metal Supports: Structure-Reactivity Relations
Authors: Shaikhutdinov S. , Freund H.-J.
Published: April 2012

Well-ordered, thin oxide films have drawn some attention in recent years as suitable oxide supports for modeling highly dispersed metal catalysts at the atomic scale. It turned out, however, that ultrathin oxide films may exhibit interesting catalytic properties in their own right. In this review, we discuss phenomena specifically connected to ultrathin oxide films to explain and understand the physicochemical basis of their reactivity in oxidation reactions. Two sets of systems are discussed, i.e., transition metal oxide films grown on metal substrates and native oxide films formed upon oxidation of metal surfaces.
Progress in Time-Dependent Density-Functional Theory
Authors: Casida M.E. , Huix-Rotllant M.
Published: April 2012

The classic density-functional theory (DFT) formalism introduced by Hohenberg, Kohn, and Sham in the mid-1960s is based on the idea that the complicated N-electron wave function can be replaced with the mathematically simpler 1-electron charge density in electronic structure calculations of the ground stationary state. As such, ordinary DFT cannot treat time-dependent (TD) problems nor describe excited electronic states. In 1984, Runge and Gross proved a theorem making TD-DFT formally exact. Information about electronic excited states may be obtained from this theory through the linear response (LR) theory formalism. Beginning in the mid-1990s, LR-TD-DFT became increasingly popular for calculating absorption and other spectra of medium- and large-sized molecules. Its ease of use and relatively good accuracy has now brought LR-TD-DFT to the forefront for this type of application. As the number and the diversity of applications of TD-DFT have grown, so too has our understanding of the strengths and weaknesses of the approximate functionals commonly used for TD-DFT. The objective of this article is to continue where a previous review of TD-DFT in Volume 55 of the Annual Review of Physical Chemistry left off and highlight some of the problems and solutions from the point of view of applied physical chemistry. Because doubly-excited states have a particularly important role to play in bond dissociation and formation in both thermal and photochemistry, particular emphasis is placed on the problem of going beyond or around the TD-DFT adiabatic approximation, which limits TD-DFT calculations to nominally singly-excited states.
Incomplete spinal cord injury promotes durable functional changes within the spinal locomotor circuitry
Authors: Martinez Marina , Delivet-Mongrain Hugo , Leblond Hugues , Rossignol Serge
Published: April 2012

While walking in a straight path, changes in speed result mainly from adjustments in the duration of the stance phase while the swing phase remains relatively invariant, a basic feature of the spinal central pattern generator (CPG). To produce a broad range of locomotor behaviors, the CPG has to integrate modulatory inputs from the brain and the periphery and alter these swing/stance characteristics. In the present work we raise the issue as to whether the CPG can adapt or reorganize in response to a chronic change of supraspinal inputs, as is the case after spinal cord injury (SCI). Kinematic data obtained from six adult cats walking at different treadmill speeds were collected to calculate the cycle and subphase duration at different stages after a first spinal hemisection at T10 and after a subsequent complete SCI at T13 respectively aimed at disconnecting unilaterally and then totally the spinal cord from its supraspinal inputs. The results show, first, that the neural control of locomotion is flexible and responsive to a partial or total loss of supraspinal inputs. Second, we demonstrate that a hemisection induces durable plastic changes within the spinal locomotor circuitry below the lesion. In addition, this study gives new insights into the organization of the spinal CPG for locomotion such that phases of the step cycle (swing, stance) can be independently regulated for adapting to speed and also that the CPGs controlling the left and right hindlimbs can, up to a point, be regulated independently.
Two-stage AMPA receptor trafficking in classical conditioning and selective role for glutamate receptor subunit 4 (tGluA4) flop splice variant
Authors: Zheng Zhaoqing , Sabirzhanov Boris , Keifer Joyce
Published: April 2012

Previously, we proposed a two-stage model for an in vitro neural correlate of eyeblink classical conditioning involving the initial synaptic incorporation of glutamate receptor A1 (GluA1)-containing α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid type receptors (AMPARs) followed by delivery of GluA4-containing AMPARs that support acquisition of conditioned responses. To test specific elements of our model for conditioning, selective knockdown of GluA4 AMPAR subunits was used using small-interfering RNAs (siRNAs). Recently, we sequenced and characterized the GluA4 subunit and its splice variants from pond turtles, Trachemys scripta elegans (tGluA4). Analysis of the relative abundance of mRNA expression by real-time RT-PCR showed that the flip/flop variants of tGluA4, tGluA4c, and a novel truncated variant tGluA4trc1 are major isoforms in the turtle brain. Here, transfection of in vitro brain stem preparations with anti-tGluA4 siRNA suppressed conditioning, tGluA4 mRNA and protein expression, and synaptic delivery of tGluA4-containing AMPARs but not tGluA1 subunits. Significantly, transfection of abducens motor neurons by nerve injections of tGluA4 flop rescue plasmid prior to anti-tGluA4 siRNA application restored conditioning and synaptic incorporation of tGluA4-containing AMPARs. In contrast, treatment with rescue plasmids for tGluA4 flip or tGluA4trc1 failed to rescue conditioning. Finally, treatment with a siRNA directed against GluA1 subunits inhibited conditioning and synaptic delivery of tGluA1-containing AMPARs and importantly, those containing tGluA4. These data strongly support our two-stage model of conditioning and our hypothesis that synaptic incorporation of tGluA4-containing AMPARs underlies the acquisition of in vitro classical conditioning. Furthermore, they suggest that tGluA4 flop may have a critical role in conditioning mechanisms compared with the other tGluA4 splice variants.
Capsule Endoscopy to Detect Normally Positioned Duodenal Papilla: Performance Comparison of SB and SB2
Authors: Park Sanghoon , Chun Hoon Jai , Keum Bora , Seo Yeon Seok , Kim Yong Sik , Jeen Yoon Tae , Lee Hong Sik , Um Soon Ho , Kim Chang Duck , Ryu Ho Sang
Published: April 2012

Purpose. PillCam SB2 capsule endoscopy, an upgraded version of widely used SB capsule endoscopy, was examined for its performance by comparing with SB.Methods. Examinees with various indications were enrolled for SB2 capsule endoscopy; subjects were also enlisted for the old SB capsule endoscopy. Number of photo images containing papilla of Vater was counted. Shape of the papilla seen in each image was evaluated by scoring 3 (fully observable papilla), 2 (more than half outline), or 1 (less than half outline) points. Images obtained from SB and SB2 were also subjectively compared; resolution and brightness were scored by six experienced endoscopists.Results. Baseline characteristics of two study groups (n=30each) were not significantly different. Number of images of the papilla revealed to show similar results between SB (3.1±1.1, range 1~5) and SB2 (3.1±1.5, range 1~8) (P=0.62). The maximum points of outline of papilla evaluated from each subject were also similar between two groups. New SB2 revealed to be superior to SB in terms of resolution but not significantly different in brightness.Conclusion. Our study showed that superiority of SB2 over SB is rather marginal on examining duodenal papilla.
Modeling of Current-Voltage Characteristics of the Photoactivated Device Based on SOI Technology
Authors: Abraham Doron , Chelly Avraham , Elbaz David , Schiff Shimron , Nabozny Michah , Zalevsky Zeev
Published: April 2012

An analytical model of the silicon on insulator photoactivated modulator (SOI-PAM) device is presented in order to describe the concept of this novel device in which the information is electronic while the modulation command is optical. The model, relying on the classic Shockley’s analysis, is simple and useful for analyzing and synthesizing the voltage-current relations of the device at low drain voltage. Analytical expressions were derived for the output current as function of the input drain and gate voltages with a parameterization of the physical values such as the doping concentrations, channel and oxide thicknesses, and the optical control energy. A prototype SOI-PAM device having an area of 4 μm × 3 μm with known parameters is used to experimentally validate and support the model. Finally, the model allows the understanding of the physical mechanisms inside the device for both dark and under illumination conditions, and it will be used to optimize and to find the performance limits of the device.
Progress in Dual (Piezoelectric-Magnetostrictive) Phase Magnetoelectric Sintered Composites
Authors: Adnan Islam Rashed , Priya Shashank
Published: April 2012

The primary aims of this review article are (a) to develop the fundamental understanding of ME behavior in perovskite piezoelectric-spinel magnetostrictive composite systems, (b) to identify the role of composition, microstructural variables, phase transformations, composite geometry, and postsintering heat treatment on ME coefficient, and (c) to synthesize, characterize, and utilize the high ME coefficient composite. The desired range of ME coefficient in the sintered composite is 0.5–1 V/cm⋅Oe. The studies showed that the soft piezoelectric phase quantified by smaller elastic modulus, large grain size of piezoelectric phase (~1 μm), and layered structures yields higher magnitude of ME coefficient. It is also found that postsintering thermal treatment such as annealing and aging alters the magnitude of magnetization providing an increase in the magnitude of ME coefficient. A trilayer composite was synthesized using pressure-assisted sintering with soft phase [0.9 PZT–0.1 PZN] having grain size larger than 1 μm and soft ferromagnetic phase of composition Ni0.8Cu0.2Zn0.2Fe2O4[NCZF]. The composite showed a high ME coefficient of 412 and 494 mV/cm⋅Oe after sintering and annealing, respectively. Optimized ferrite to PZT thickness ratio was found to be 5.33, providing ME coefficient of 525 mV/cm⋅Oe. The ME coefficient exhibited orientation dependence with respect to applied magnetic field. Multilayering the PZT layer increased the magnitude of ME coefficient to 782 mV/cm⋅Oe. Piezoelectric grain texturing and nanoparticulate assembly techniques were incorporated with the layered geometry. It was found that with moderate texturing,d33and ME coefficient reached up to 325 pC/N and 878 mV/cm⋅Oe, respectively. Nanoparticulate core shell assembly shows the promise for achieving large ME coefficient in the sintered composites. A systematic relationship between composition, microstructure, geometry, and properties is presented which will lead to development of high-performance magnetoelectric materials.
Biological Effect of Leaf Aqueous Extract ofCaesalpinia pyramidalisin Goats Naturally Infected with Gastrointestinal Nematodes
Authors: Borges-dos-Santos Roberto Robson , López Jorge A. , Santos Luciano C. , Zacharias Farouk , David Jorge Maurício , David Juceni Pereira , Lima Fernanda Washington de Mendonça
Published: April 2012

Forty-eight goats naturally infected with gastrointestinal nematodes were randomly divided into four groups (n=12): negative control (G1) (untreated), positive control (G2) (treated with doramectin, 1 mL/50 Kg b.w.), and G3 and G4 treated with 2.5 and 5 mg/Kg b.w. of a leaf aqueous extract ofCaesalpinia pyramidalis(CP). Fecal and blood samples were regularly collected for the evaluation of fecal egg count (FEC), hematological and immunological parameters to assess the anthelmintic activity. In treated animals with CP, there was noted a significant reduction of 54.6 and 71.2% in the mean FEC (P<0.05). An increase in IgA levels was observed in G3 and G4 (P<0.05), during the experimental period, suggesting that it was stimulated by the extract administration. In conclusion, the results showed that CP provoked a protective response in infected animals treated with them. This response could be partly explained by the CP chemical composition.
Cystoid Macular Edema in Acute Presentation of Central Retinal Artery Occlusion
Authors: Ng Wei Yan , Wong Doric W. K. , Yeo Ian Y. S. , Han Daphne C. Y.
Published: April 2012

A seventy-six-year-old lady with poor vision of the left eye due to previous retinal detachment presented with acute visual loss of her right eye secondary to central retinal artery occlusion. Clinical examination showed a pale right optic disc, macular edema, and a cherry red spot. Optical coherence tomography done four hours after onset showed right acute cystoid macular edema and diffuse inner retinal thickening. Subsequent treatment with intravenous carbonic anhydrase inhibitor resulted in some visual improvement. Central retinal artery occlusion has been known to produce diffuse intraretinal edema instead of cystoids changes. We would like to discuss a case of acute cystoid macular edema in acute central retinal artery occlusion.
Spectral Analysis of Sampled Signals in the Linear Canonical Transform Domain
Authors: Li Bing-Zhao , Xu Tian-Zhou
Published: April 2012

The spectral analysis of uniform or nonuniform sampling signal is one of the hot topics in digital signal processing community. Theories and applications of uniformly and nonuniformly sampled one‐dimensional or two‐dimensional signals in the traditional Fourier domain have been well studied. But so far, none of the research papers focusing on the spectral analysis of sampled signals in the linear canonical transform domain have been published. In this paper, we investigate the spectrum of sampled signals in the linear canonical transform domain. Firstly, based on the properties of the spectrum of uniformly sampled signals, the uniform sampling theorem of two dimensional signals has been derived. Secondly, the general spectral representation of periodic nonuniformly sampled one and two dimensional signals has been obtained. Thirdly, detailed analysis of periodic nonuniformly sampled chirp signals in the linear canonical transform domain has been performed.
Molecular Understanding of HIV-1 Latency
Authors: Abbas W. , Herbein G.
Published: April 2012

The introduction of highly active antiretroviral therapy (HAART) has been an important breakthrough in the treatment of HIV-1 infection and has also a powerful tool to upset the equilibrium of viral production and HIV-1 pathogenesis. Despite the advent of potent combinations of this therapy, the long-lived HIV-1 reservoirs like cells from monocyte-macrophage lineage and resting memory CD4+ T cells which are established early during primary infection constitute a major obstacle to virus eradication. Further HAART interruption leads to immediate rebound viremia from latent reservoirs. This paper focuses on the essentials of the molecular mechanisms for the establishment of HIV-1 latency with special concern to present and future possible treatment strategies to completely purge and target viral persistence in the reservoirs.
Occupational Asthma: New Low-Molecular-Weight Causal Agents, 2000–2010
Authors: Pralong J. A. , Cartier A. , Vandenplas O. , Labrecque M.
Published: April 2012

Background. More than 400 agents have been documented as causing occupational asthma (OA). The list of low-molecular-weight (LMW) agents that have been identified as potential causes of OA is constantly expanding, emphasizing the need to continually update our knowledge by reviewing the literature. Objective. The objective of this paper was to identify all new LMW agents causing occupational asthma reported during the period 2000–2010. Methods. A Medline search was performed using the keywords occupational asthma, new allergens, new causes, and low-molecular-weight agents. Results. We found 39 publications describing 41 new LMW causal agents, which belonged to the following categories: drugs (n=12), wood dust (n=11), chemicals (n=8), metals (n=4), biocides (n=3), and miscellaneous (n=3). The diagnosis of OA was confirmed through SIC for 35 of 41 agents, peak expiratory flow monitoring for three (3) agents, and the clinical history alone for three (3) agents. Immunological tests provided evidence supporting an IgE-mediated mechanism for eight (8) (20%) of the newly described agents. Conclusion. This paper highlights the importance of being alert to the occurrence of new LMW sensitizers, which can elicit OA. The immunological mechanism is explained by a type I hypersensitivity reaction in 20% of all newly described LMW agents.
Homoclinic Orbits for a Class of Nonperiodic Hamiltonian Systems
Authors: Qin Wenping , Zhang Jian , Zhao Fukun
Published: April 2012

We study the following nonperiodic Hamiltonian system , where H ∈ C1(ℝ × ℝ2N, ℝ) is the form H(t, z) = (1/2)B(t)z · z + R(t, z). We introduce a new assumption on B(t) and prove that the corresponding Hamiltonian operator has only point spectrum. Moreover, by applying a generalized linking theorem for strongly indefinite functionals, we establish the existence of homoclinic orbits for asymptotically quadratic nonlinearity as well as the existence of infinitely many homoclinic orbits for superquadratic nonlinearity.
Progress and Challenges in Colorectal Cancer Screening
Authors: Quintero Enrique , Hassan Cesare , Senore Carlo , Saito Yutaka
Published: April 2012

Although faecal and endoscopic tests appear to be effective in reducing colorectal cancer incidence and mortality, further technological and organizational advances are expected to improve the performance and acceptability of these tests. Several attempts to improve endoscopic technology have been made in order to improve the detection rate of neoplasia, especially in the proximal colon. Based on the latest evidence on the long-term efficacy of screening tests, new strategies including endoscopic and faecal modalities have also been proposed in order to improve participation and the diagnostic yield of programmatic screening. Overall, several factors in terms of both efficacy and costs of screening strategies, including the high cost of biological therapy for advanced colorectal cancer, are likely to affect the cost-effectiveness of CRC screening in the future.
High‐Level Synthesis under Fixed‐Point Accuracy Constraint
Authors: Menard Daniel , Herve Nicolas , Sentieys Olivier , Nguyen Hai-Nam
Published: April 2012

Implementing signal processing applications in embedded systems generally requires the use of fixed‐point arithmetic. The main problem slowing down the hardware implementation flow is the lack of high‐level development tools to target these architectures from algorithmic specification language using floating‐point data types. In this paper, a new method to automatically implement a floating‐point algorithm into an FPGA or an ASIC using fixed‐point arithmetic is proposed. An iterative process on high‐level synthesis and data word‐length optimization is used to improve both of these dependent processes. Indeed, high‐level synthesis requires operator word‐length knowledge to correctly execute its allocation, scheduling, and resource binding steps. Moreover, the word‐length optimization requires resource binding and scheduling information to correctly group operations. To dramatically reduce the optimization time compared to fixed‐point simulation‐based methods, the accuracy evaluation is done through an analytical method. Different experiments on signal processing algorithms are presented to show the efficiency of the proposed method. Compared to classical methods, the average architecture area reduction is between 10% and 28%.
An Investigation on the Formation of Carbon Nanotubes by Two‐Stage Chemical Vapor Deposition
Authors: Shamsudin M. S. , Achoi M. F. , Asiah M. N. , Ismail L. N. , Suriani A. B. , Abdullah S. , Yahya S. Y. S. , Rusop M.
Published: April 2012

High density of carbon nanotubes (CNTs) has been synthesized from agricultural hydrocarbon: camphor oil using a one‐hour synthesis time and a titanium dioxide sol gel catalyst. The pyrolysis temperature is studied in the range of 700–900°C at increments of 50°C. The synthesis process is done using a custom‐made two‐stage catalytic chemical vapor deposition apparatus. The CNT characteristics are investigated by field emission scanning electron microscopy and micro‐Raman spectroscopy. The experimental results showed that structural properties of CNT are highly dependent on pyrolysis temperature changes.
CCL2 Mediates Cross-talk between Cancer Cells and Stromal Fibroblasts That Regulates Breast Cancer Stem Cells
Authors: Tsuyada Akihiro , Chow Amy , Wu Jun , Somlo George , Chu Peiguo , Loera Sofia , Luu Thehang , Li Arthur Xuejun , Wu Xiwei , Ye Wei , Chen Shiuan , Zhou Weiying , Yu Yang , Wang Yuan-Zhong , Ren Xiubao , Li Hui , Scherle Peggy , Kuroki Yukio , Wang Shizhen Emily
Published: April 2012

Cancer stem cells (CSC) play critical roles in cancer initiation, progression, and therapeutic refractoriness. Although many studies have focused on the genes and pathways involved in stemness, characterization of the factors in the tumor microenvironment that regulate CSCs is lacking. In this study, we investigated the effects of stromal fibroblasts on breast cancer stem cells. We found that compared with normal fibroblasts, primary cancer-associated fibroblasts (CAF) and fibroblasts activated by cocultured breast cancer cells produce higher levels of chemokine (C-C motif) ligand 2 (CCL2), which stimulates the stem cell–specific, sphere-forming phenotype in breast cancer cells and CSC self-renewal. Increased CCL2 expression in activated fibroblasts required STAT3 activation by diverse breast cancer–secreted cytokines, and in turn, induced NOTCH1 expression and the CSC features in breast cancer cells, constituting a cancer-stroma-cancer signaling circuit. In a xenograft model of paired fibroblasts and breast cancer tumor cells, loss of CCL2 significantly inhibited tumorigenesis and NOTCH1 expression. In addition, upregulation of both NOTCH1 and CCL2 was associated with poor differentiation in primary breast cancers, further supporting the observation that NOTCH1 is regulated by CCL2. Our findings therefore suggest that CCL2 represents a potential therapeutic target that can block the cancer–host communication that prompts CSC-mediated disease progression. Cancer Res; 72(11); 2768–79. ©2012 AACR.
Increase in Cholesterol Predicts Survival Advantage in Renal Cell Carcinoma Patients Treated with Temsirolimus
Authors: Lee Chee Khoon , Marschner Ian C. , Simes R. John , Voysey Merryn , Egleston Brian , Hudes Gary , de Souza Paul
Published: April 2012

Purpose: Temsirolimus is an effective treatment for renal cell carcinoma. It is associated with increases in serum cholesterol, triglyceride, and glucose. We investigated whether changes of these biomarkers could predict its efficacy.

Experimental Design: We examined serial measurements of cholesterol, triglycerides, and glucose from patients randomized to IFN or temsirolimus in the Global Advanced Renal Cell Carcinoma Trial. Using time-dependent proportional hazards models, we quantified the association between changes in these biomarkers from baseline with overall survival (OS) and progression-free survival (PFS). We also assess the extent to which changes of these biomarkers predict the effects of temsirolimus on survival.

Results: Temsirolimus was associated with larger mean increases in cholesterol (1.02 mmol/L; P < 0.0001), triglycerides (0.32 mmol/L; P = 0.0008), and glucose (1.28 mmol/L; P < 0.0001) compared with IFN and improved survival rate (OS: HR = 0.76, P = 0.02; PFS: HR = 0.70, P = 0.001). Cholesterol increase during study was associated with longer survival (OS: HR = 0.77 per mmol/L, P < 0.0001; PFS: HR = 0.81 per mmol/L; P < 0.0001). Temsirolimus effect on cholesterol predicted its effect on survival with no additional survival advantage observed after adjusting for cholesterol change during study (OS: HR = 1.14, P = 0.37; PFS: HR = 0.88, P = 0.35). Temsirolimus effect on triglycerides or glucose did not predict its effect on survival, with survival advantage in favor of temsirolimus still observed after adjusting for these factors (P = 0.003 and P = 0.002).

Conclusion: Cholesterol increase is a potential predictor for temsirolimus efficacy. Longer survival in patients treated with temsirolimus was observed in those with larger increases in cholesterol. Prospectively designed biomarker studies of temsirolimus or other mTOR inhibitors are recommended. Clin Cancer Res; 18(11); 3188–96. ©2012 AACR.
Adenosine A2A and Beta-2 Adrenergic Receptor Agonists: Novel Selective and Synergistic Multiple Myeloma Targets Discovered through Systematic Combination Screening
Authors: Rickles Richard J. , Tam Winnie F. , Giordano Thomas P. , Pierce Laura T. , Farwell Melissa , McMillin Douglas W. , Necheva Antoaneta , Crowe David , Chen Mei , Avery William , Kansra Vikram , Nawrocki Steffan T. , Carew Jennifer S. , Giles Francis J. , Mitsiades Constantine S. , Borisy Alexis A. , Anderson Kenneth C. , Lee Margaret S.
Published: April 2012

The use of combination drug regimens has dramatically improved the clinical outcome for patients with multiple myeloma. However, to date, combination treatments have been limited to approved drugs and a small number of emerging agents. Using a systematic approach to identify synergistic drug combinations, combination high-throughput screening (cHTS) technology, adenosine A2A and β-2 adrenergic receptor (β2AR) agonists were shown to be highly synergistic, selective, and novel agents that enhance glucocorticoid activity in B-cell malignancies. Unexpectedly, A2A and β2AR agonists also synergize with melphalan, lenalidomide, bortezomib, and doxorubicin. An analysis of agonists, in combination with dexamethasone or melphalan in 83 cell lines, reveals substantial activity in multiple myeloma and diffuse large B-cell lymphoma cell lines. Combination effects are also observed with dexamethasone as well as bortezomib, using multiple myeloma patient samples and mouse multiple myeloma xenograft assays. Our results provide compelling evidence in support of development of A2A and β2AR agonists for use in multi-drug combination therapy for multiple myeloma. Furthermore, use of cHTS for the discovery and evaluation of new targets and combination therapies has the potential to improve cancer treatment paradigms and patient outcomes. Mol Cancer Ther; 11(7); 1432–42. ©2012 AACR.
Experience of Advate rAHF-PFM in previously untreated patients and minimally treated patients with haemophilia A
Authors: Auerswald Guenter , Thompson Alexis , Recht Michael , Brown Deborah , Liesner Raina , Guzmán-Becerra Norma , Dyck-Jones Jacqueline , Ewenstein Bruce , Abbuehl Brigitt
Published: April 2012

We report a prospective trial of 55 previously untreated patients (PUPs) and minimally treated patients (MTPs) with severe/moderately severe haemophilia A (baseline factor VIII [FVIII] ≤2%) treated with a single FVIII replacement product. It was the objective of this study to evaluate the immunogenicity, efficacy, and safety of rAHF-PFM (Advate®). Ondemand or prophylactic treatment regimens were determined at the discretion of the investigator. rAHF-PFM was also permitted for perioperative management. There were 633 bleeding episodes (BEs), including 517 treated, and 466 rated for efficacy. Haemostatic efficacy was considered excellent/good in 93% of 466 rated treatments. Of 517 treated BEs, 463/517 (90%) were managed with one (356/517 [69%]) or two infusions (107/517 [21%]). There were 27 surgeries. Intraoperative (n=22) and postoperative (n=25) haemostatic efficacies were considered excellent or good in 100% of rated surgeries. Related serious adverse events (SAEs) were inhibitor development in 16/55 (29.1%) subjects who received at least one infusion of rAHF-PFM. Nonserious, related adverse events (AEs) were few in number (14 in eight subjects). The odds ratio (OR [95% Confidence Interval, CI]) of developing inhibitors was significantly higher in subjects with a family history of inhibitor (4.95 [1.29–19.06]), non-Caucasian ethnicity (4.18, [1.18–14.82]), and intensive treatment at high dose (4.5 [1.05–19.25]) within ≤20 exposure days (EDs). In conclusion, rAHF-PFM was safe and effective for the management and perioperative coverage of PUPs/MTPs with severe/moderately severe haemophilia A. This report supports previous findings from studies in which family history of inhibitor, non-Caucasian ethnicity, and high intensity treatment were associated with high risk of inhibitor development.
Glycine Normalizes Hepatic Triglyceride-Rich VLDL Secretion by Triggering the CNS in High-Fat Fed Rats
Authors: Yue Jessica T.Y. , Mighiu Patricia I. , Naples Mark , Adeli Khosrow , Lam Tony K.T.
Published: April 2012

Rationale:

Dysregulation of hepatic triglyceride (TG)-rich very low-density lipoproteins (VLDL-TG) in obesity and type 2 diabetes contributes to the dyslipidemia that leads to cardiovascular morbidity. The central nervous system (CNS), particularly the hypothalamus, regulates hepatic lipid metabolism. Although the underlying neurocircuitry remains elusive, glycine has been documented to enhance CNS
N
-methyl-
d
-aspartate (NMDA) receptor-mediated transmission.

Objective:

We tested the hypothesis that glycine regulates hepatic VLDL-TG secretion by potentiating NMDA receptor-mediated transmission in the CNS.

Methods and Results:

Using 10-hour fasted male Sprague-Dawley rats implanted with stereotaxic cannulae into an extrahypothalamic region termed the dorsal vagal complex (DVC) and vascular catheters to enable direct DVC infusion and blood sampling, respectively, the rate of hepatic VLDL-TG secretion was measured following tyloxapol (an inhibitor of lipoprotein lipase) injection. Direct DVC infusion of glycine lowered VLDL-TG secretion, whereas NMDA receptor blocker MK-801 fully negated glycine's effect. NR1 subunit of NMDA receptor antagonist 7-chlorokynurenic acid, adenoviral injection of NR1 short hairpin RNA (shRNA), and hepatic vagotomy also nullified glycine's effect. Finally, DVC glycine normalized the hypersecretion of VLDL-TG induced by high-fat feeding.

Conclusions:

Molecular and pharmacological inhibition of the NR1-containing NMDA receptors in the DVC negated the ability of glycine to inhibit hepatic secretion of VLDL-TG in vivo. Importantly, the hypersecretion of VLDL-TG from the liver induced by a model of high-fat feeding was restored by the hepatic lipid control of CNS glycine sensing. These findings collectively suggest that glycine or glycine analogues may have therapeutic benefits in lowering plasma lipid levels in diabetes and obesity by triggering the CNS.
The Pediatric Stroke Outcome Measure
Authors: Kitchen Lisa , Westmacott Robyn , Friefeld Sharon , MacGregor Daune , Curtis Rosalind , Allen Anita , Yau Ivanna , Askalan Rand , Moharir Mahendranath , Domi Trish , deVeber Gabrielle
Published: April 2012

Background and Purpose—

The Pediatric Stroke Outcome Measure (PSOM) is an objective, disease-specific outcome measure containing 115 test items suitable for newborn to adult ages. The PSOM measures neurological deficit and function across 5 subscales: right sensorimotor, left sensorimotor, language production, language comprehension, and cognitive/behavior yielding a final 10-point deficit score. The goal of this study was to examine PSOM construct validity in measuring neurological outcome in pediatric stroke survivors and interrater reliability (IRR) for both prospective and retrospective scoring.

Methods—

For construct validity, PSOM subscale scores were correlated with scores on standardized neuropsychological measures matched by functional domain. We assessed IRR by comparing same-day “live” PSOM scores from 2 independent raters in 10 children (prospective IRR) and by comparing PSOM scores estimated from medical dictations across 5 raters in another 10 children (retrospective IRR).

Results—

We analyzed PSOM scores from 203 children with ischemic stroke. PSOM subscales show good construct validity (ρ=0.2–0.4;
P
<0.05). PSOM subscale scores of normal/abnormal demonstrate strong agreement for domain-matched neuropsychology scores (alternative chance-corrected statistic=0.4–0.8). IRR was excellent with the 2 prospective raters' scores in almost perfect agreement (intraclass correlation coefficient, 0.93; 95% CI, 0.76–0.98). Retrospective IRR demonstrated strong agreement with an intraclass correlation coefficient of 0.77 (95% CI, 0.56–0.92).

Conclusions—

The PSOM is a valid and reliable outcome measure for pediatric stroke. It is useful for retrospective scoring from health records and prospective serial longitudinal outcome assessments and is ideally suited for prospective clinical trials in pediatric stroke.