Medicine by Alexandros G.Sfakianakis: 05/14/16

Σάββατο 14 Μαΐου 2016

Headspace-programmed temperature vaporization-mass spectrometry for the rapid determination of possible volatile biomarkers of lung cancer in urine

Abstract

We propose a new method for the rapid determination of five volatile compounds described in the literature as possible biomarkers of lung cancer in urine samples. The method is based on the coupling of a headspace sampler, a programmed temperature vaporizer in solvent-vent injection mode, and a mass spectrometer (HS-PTV-MS). This configuration is known as an electronic nose based on mass spectrometry. Once the method was developed, it was used for the analysis of urine samples from lung cancer patients and healthy individuals. Multivariate calibration models were employed to quantify the biomarker concentrations in the samples. The detection limits ranged between 0.16 and 21 μg/L. For the assignment of the samples to the patient group or the healthy individuals, the Wilcoxon signed-rank test was used, comparing the concentrations obtained with the median of a reference set of healthy individuals. To date, this is the first time that multivariate calibration and non-parametric methods have been combined to classify biological samples from profile signals obtained with an electronic nose. When significant differences in the concentration of one or more biomarkers were found with respect to the reference set, the sample is considered as a positive one and a new analysis was performed using a chromatographic method (HS-PTV-GC/MS) to confirm the result. The main advantage of the proposed HS-PTV-MS methodology is that no prior chromatographic separation and no sample manipulation are required, which allows an increase of the number of samples analyzed per hour and restricts the use of time-consuming techniques to only when necessary.

Graphical abstract

Schematic diagram of the developed methodology

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Ángela Molina and Joaquín GonzáIez: Pulse voltammetry in physical electrochemistry and electroanalysis: theory and applications

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Improved electrochemiluminescence labels for heterogeneous microbead immunoassay

Abstract

Ruthenium(II) complexes with carboxylic acid as a bioconjugatable group, i.e., [Ru(bathophenanthroline disulfonate)(2,2′-bipyridine)(4-methyl-4′-(3-carboxypropyl)-2,2′-bipyridine)]⁰, (C₄₉H₃₈N₆O₈S₂Ru), and [Ru(bathophenanthroline disulfonate)₂(4-methyl-4′-(3-carboxypropyl)-2,2′-bipyridine)]²⁻ · 2Na⁺, (C₆₃H₄₄N₆O₁₄S₄RuNa₂) were characterized spectroscopically and electrochemically. As potential labels for electrochemiluminescence (ECL) immunoassays, the ECL intensities of the free labels in homogenous aqueous buffer solutions were compared under a condition that is similar to the one employed by a commercial clinical immunoassay system. The two labels were found to be more emissive and, thus, can be detected at 10^{- 12} pM compared with 5× 10⁻¹² pM of the label currently used in the commercial ECL system. Furthermore, the improved ECL emission of the free labels in homogenous solutions was proven to be translated into more intense ECL signal in heterogeneous sandwich immunoassay and, thus, leading to a lower limit of detection in immunoassay. The data obtained from these ECL labels shed light on the further development of ECL-based clinical immunoassay technology.

Graphical abstract

Electrochemiluminescence immunoassays were carried out with three different ruthenium(II) complex labels. It was proved that the higher signal intensities found with the novel labels in homogeneous solutions were maintained in heterogeneous sandwich format.

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Determination of phthalate esters at trace level from environmental water samples by magnetic solid-phase extraction with Fe@SiO 2 @polyethyleneimine magnetic nanoparticles as adsorbent prior to high-performance liquid chromatography

Abstract

In this work, polyethyleneimine grafted silica-coated nanoscale zero valent iron (Fe@SiO₂@PEI) has been successfully synthesized and was investigated to be an effective adsorbent for efficient enrichment of five phthalate esters such as diphenyl phthalate, dibenzyl phthalate, butyl benzyl phthalate, diphenyl isophthalate, and dicyclohexyl phthalate (DPP, DBP, BBP, DPIP, and DCHP) from environmental water samples. The structure and morphology of the materials were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction(XRD). The parameters that influenced the enrichment performance such as amount of sorbent, sample pH, type of eluent, volume of eluent, salting-out effect, adsorption time, and desorption time were investigated. Under optimal conditions, excellent linear relationships were found in the concentration range from 0.5 to 100 μg L⁻¹, the limits of detection (S/N = 3) were in the range of 0.26–0.45 μg L⁻¹, and the intra-day and inter-day precisions (n = 6) were in the range of 3.7–4.8 and 3.2–4.3 %, respectively. The developed method was evaluated with real water samples, and satisfied spiked recoveries in the range of 99–104 % were achieved. The experimental results proved that Fe@SiO₂@PEI had good adsorption for phthalate esters, and would be a good adsorbent for the magnetic solid-phase extraction of important pollutants from environmental water samples.

ᅟ Graphical abstract

A flowchart of the synthesis of polyethyleneimine grafted silica coated nanoscale zero valent iron (Fe@SiO₂@PEI) and the process of the developed magnetic solid phase extraction of phthalate esters before the analysis by high performance liquid chromatography

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Structural analysis of the activation-induced deoxycytidine deaminase required in immunoglobulin diversification

Publication date: Available online 13 May 2016
Source:DNA Repair
Author(s): Phuong Pham, Samir A. Afif, Mayuko Shimoda, Kazuhiko Maeda, Nobuo Sakaguchi, Lars C. Pedersen, Myron F. Goodman
Activation-induced deoxycytidine deaminase (AID) initiates somatic hypermutation (SHM) and class-switch recombination (CSR) by deaminating C→U during transcription of Ig-variable (V) and Ig-switch (S) region DNA, which is essential to produce high-affinity antibodies. Here we report the crystal structure of a soluble human AID variant at 2.8Å resolution that favors targeting WRC motifs (W=A/T, R=A/G) in vitro, and executes Ig V SHM in Ramos B-cells. A specificity loop extending away from the active site to accommodate two purine bases next to C, differs significantly in sequence, length, and conformation from APOBEC proteins Apo3A and Apo3G, which strongly favor pyrimidines at −1 and −2 positions. Individual amino acid contributions to specificity and processivity were measured in relation to a proposed ssDNA binding cleft. This study provides a structural basis for residue contributions to DNA scanning properties unique to AID, and for disease mutations in human HIGM-2 syndrome.

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Sensors, Vol. 16, Pages 700: Extracting Objects for Aerial Manipulation on UAVs Using Low Cost Stereo Sensors

Giving unmanned aerial vehicles (UAVs) the possibility to manipulate objects vastly extends the range of possible applications. This applies to rotary wing UAVs in particular, where their capability of hovering enables a suitable position for in-flight manipulation. Their manipulation skills must be suitable for primarily natural, partially known environments, where UAVs mostly operate. We have developed an on-board object extraction method that calculates information necessary for autonomous grasping of objects, without the need to provide the model of the object's shape. A local map of the work-zone is generated using depth information, where object candidates are extracted by detecting areas different to our floor model. Their image projections are then evaluated using support vector machine (SVM) classification to recognize specific objects or reject bad candidates. Our method builds a sparse cloud representation of each object and calculates the object's centroid and the dominant axis. This information is then passed to a grasping module. Our method works under the assumption that objects are static and not clustered, have visual features and the floor shape of the work-zone area is known. We used low cost cameras for creating depth information that cause noisy point clouds, but our method has proved robust enough to process this data and return accurate results.

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Molecules, Vol. 21, Pages 647: Broadband Two-Photon Absorption Characteristics of Highly Photostable Fluorenyl-Dicyanoethylenylated [60]Fullerene Dyads

We synthesized four C60-(light-harvesting antenna) dyads C60 (>CPAF-Cn) (n = 4, 9, 12, or 18) 1-Cn for the investigation of their broadband nonlinear absorption effect. Since we have previously demonstrated their high function as two-photon absorption (2PA) materials at 1000 nm, a different 2PA wavelength of 780 nm was applied in the study. The combined data taken at two different wavelength ranges substantiated the broadband characteristics of 1-Cn. We proposed that the observed broadband absorptions may be attributed by a partial π-conjugation between the C60 > cage and CPAF-Cn moieties, via endinitrile tautomeric resonance, giving a resonance state with enhanced molecular conjugation. This transient state could increase its 2PA and excited-state absorption at 800 nm. In addition, a trend of concentration-dependent 2PA cross-section (σ2 ) and excited-state absorption magnitude was detected showing a higher σ value at a lower concentration that was correlated to increasing molecular separation with less aggregation for dyads C60(>CPAF-C18) and C60(>CPAF-C9), as better 2PA and excited-state absorbers.

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IJMS, Vol. 17, Pages 739: A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma

Malignant peritoneal mesothelioma (MPM) is an aggressive rare malignancy associated with asbestos exposure. A better understanding of the molecular pathogenesis of MPM will help develop a targeted therapy strategy. Oncogene targeted depth sequencing was performed on a tumor sample and paired peripheral blood DNA from a patient with malignant mesothelioma of the peritoneum. Four somatic base-substitutions in NOTCH2, NSD1, PDE4DIP, and ATP10B and 1 insert frameshift mutation in BAP1 were validated by the Sanger method at the transcriptional level. A 13-amino acids neo-peptide of the truncated Bap1 protein, which was produced as a result of this novel frameshift mutation, was predicted to be presented by this patient's HLA-B protein. The polyclonal antibody of the synthesized 13-mer neo-peptide was produced in rabbits. Western blotting results showed a good antibody-neoantigen specificity, and Immunohistochemistry (IHC) staining with the antibody of the neo-peptide clearly differentiated neoplastic cells from normal cells. A search of the Catalogue of Somatic Mutations in Cancer (COSMIC) database also revealed that 53.2% of mutations in BAP1 were frameshift indels with neo-peptide formation. An identified tumor-specific neo-antigen could be the potential molecular biomarker for personalized diagnosis to precisely subtype rare malignancies such as MPM.

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IJMS, Vol. 17, Pages 735: Sirolimus and Everolimus Pathway: Reviewing Candidate Genes Influencing Their Intracellular Effects

Sirolimus (SRL) and everolimus (EVR) are mammalian targets of rapamycin inhibitors (mTOR-I) largely employed in renal transplantation and oncology as immunosuppressive/antiproliferative agents. SRL was the first mTOR-I produced by the bacterium Streptomyces hygroscopicus and approved for several medical purposes. EVR, derived from SRL, contains a 2-hydroxy-ethyl chain in the 40th position that makes the drug more hydrophilic than SRL and increases oral bioavailability. Their main mechanism of action is the inhibition of the mTOR complex 1 and the regulation of factors involved in a several crucial cellular functions including: protein synthesis, regulation of angiogenesis, lipid biosynthesis, mitochondrial biogenesis and function, cell cycle, and autophagy. Most of the proteins/enzymes belonging to the aforementioned biological processes are encoded by numerous and tightly regulated genes. However, at the moment, the polygenic influence on SRL/EVR cellular effects is still not completely defined, and its comprehension represents a key challenge for researchers. Therefore, to obtain a complete picture of the cellular network connected to SRL/EVR, we decided to review major evidences available in the literature regarding the genetic influence on mTOR-I biology/pharmacology and to build, for the first time, a useful and specific "SRL/EVR genes-focused pathway", possibly employable as a starting point for future in-depth research projects.

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Sensors, Vol. 16, Pages 696: Stability-Aware Geographic Routing in Energy Harvesting Wireless Sensor Networks

A new generation of wireless sensor networks that harvest energy from environmental sources such as solar, vibration, and thermoelectric to power sensor nodes is emerging to solve the problem of energy limitation. Based on the photo-voltaic model, this research proposes a stability-aware geographic routing for reliable data transmissions in energy-harvesting wireless sensor networks (EH-WSNs) to provide a reliable routes selection method and potentially achieve an unlimited network lifetime. Specifically, the influences of link quality, represented by the estimated packet reception rate, on network performance is investigated. Simulation results show that the proposed method outperforms an energy-harvesting-aware method in terms of energy consumption, the average number of hops, and the packet delivery ratio.

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IJMS, Vol. 17, Pages 733: Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review

Major depressive disorder (MDD) is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Up to now, the exact pathogenesis of MDD remains poorly understood. Recent research has begun to reveal that the pro-inflammatory cytokines, particularly, tumor necrosis factor-α (TNF-α), play an integral role in the pathophysiology of depressive disorders and the mechanism of antidepressant treatment. On the base of several observations: it is found that subsets of MDD patients have enhanced plasma levels TNF-α; antidepressant treatments had linked with the decline of TNF-α; central administration of TNF-α gives rise to sickness behavior which shares features with depression; and a blockade of it can ameliorate depressive symptomatology in animal models and clinical trials. In this review article, we focus on recent evidence linking TNF-α and MDD looking at data from animal and clinical studies, illustrating the pathophysiological role, susceptibility and its therapeutic application in depression. We conclude by discussing future directions for research, in particular the opportunities for the development of novel therapeutics that target TNF-α. This will be very important for designing preventative strategies and for the identification of new drug targets and preventative strategies.

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Materials, Vol. 9, Pages 375: Formation of Aluminum Particles with Shell Morphology during Pressureless Spark Plasma Sintering of Fe–Al Mixtures: Current-Related or Kirkendall Effect?

A need to deeper understand the influence of electric current on the structure and properties of metallic materials consolidated by Spark Plasma Sintering (SPS) stimulates research on inter-particle interactions, bonding and necking processes in low-pressure or pressureless conditions as favoring technique-specific local effects when electric current passes through the underdeveloped inter-particle contacts. Until now, inter-particle interactions during pressureless SPS have been studied mainly for particles of the same material. In this work, we focused on the interactions between particles of dissimilar materials in mixtures of micrometer-sized Fe and Al powders forming porous compacts during pressureless SPS at 500–650 °C. Due to the chemical interaction between Al and Fe, necks of conventional shape did not form between the dissimilar particles. At the early interaction stages, the Al particles acquired shell morphology. It was shown that this morphology change was not related to the influence of electric current but was due to the Kirkendall effect in the Fe–Al system and particle rearrangement in a porous compact. No experimental evidence of melting or melt ejection during pressureless SPS of the Fe–Al mixtures or Fe and Al powders sintered separately was observed. Porous FeAl-based compacts could be obtained from Fe-40at.%Al mixtures by pressureless SPS at 650 °C.

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IJMS, Vol. 17, Pages 738: Effect of AQP9 Expression in Androgen-Independent Prostate Cancer Cell PC3

It is known that aquaporin 9 (AQP9) in the prostate was strictly upregulated by androgen and may represent a novel therapeutic target for several cancers, but whether AQP9 plays a role in the regulation of androgen-independent prostate cancer still remains unclear. In the present study, AQP9 was determined in prostate cancer and adjacent cancer tissues; AQP9-siRNA was applied to silencing AQP9 in androgen-independent prostate cancer cell PC3 cell line. Western blot and flow cytometry analysis were employed to detect changes in related-function of control and AQP9-siRNA groups. The results showed that AQP9 is significantly induced in cancer tissues than that in adjacent cancer tissues. Moreover, knockdown of AQP9 in PC3 androgen-independent prostate cancer cell prostate cancer cells increased inhibition rates of proliferation. In addition, knockdown of AQP9 resulted in a significant decrease in the expression of the Bcl-2 and with a notable increase in the expression of Bax and cleaved caspase 3, indicated that AQP9 knockdown promoted apoptosis in prostate cancer cells. From wound healing assay and matrigel invasion, we suggested that AQP9 expression affects the motility and invasiveness of prostate cancer cells. Moreover, In order to explore the pathway may be involved in AQP9-mediated motility and invasion of prostate cancer cells, the phosphorylation of ERK1/2 was significant suppressed in AQP9 siRNA-transfected cells compared with that in control cells, suggesting that AQP9 is involved in the activation of the ERK pathway in androgen-independent prostate cancer cells.

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IJMS, Vol. 17, Pages 733: Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review

IJMS, Vol. 17, Pages 739: A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma

IJMS, Vol. 17, Pages 735: Sirolimus and Everolimus Pathway: Reviewing Candidate Genes Influencing Their Intracellular Effects

IJMS, Vol. 17, Pages 737: Thrombin Receptor-Activating Protein (TRAP)-Activated Akt Is Involved in the Release of Phosphorylated-HSP27 (HSPB1) from Platelets in DM Patients

It is generally known that heat shock protein 27 (HSP27) is phosphorylated through p38 mitogen-activated protein (MAP) kinase. We have previously reported that HSP27 is released from human platelets associated with collagen-induced phosphorylation. In the present study, we conducted an investigation into the effect of thrombin receptor-activating protein (TRAP) on the release of HSP27 in platelets in type 2 diabetes mellitus (DM) patients. The phosphorylated-HSP27 levels induced by TRAP were directly proportional to the aggregation of platelets. The levels of phosphorylated-HSP27 (Ser-78) were correlated with the levels of phosphorylated-p38 MAP kinase and phosphorylated-Akt in the platelets stimulated by 10 µM TRAP but not with those of phosphorylated-p44/p42 MAP kinase. The levels of HSP27 released from the TRAP (10 µM)-stimulated platelets were correlated with the levels of phosphorylated-HSP27 in the platelets. The released platelet-derived growth factor-AB (PDGF-AB) levels were in parallel with the HSP27 levels released from the platelets stimulated by 10 µM TRAP. Although the area under the curve (AUC) of small aggregates (9–25 µm) induced by 10 µM TRAP showed no significant correlation with the released HSP27 levels, AUC of medium aggregates (25–50 µm), large aggregates (50–70 µm) and light transmittance were significantly correlated with the released HSP27 levels. TRAP-induced phosphorylation of HSP27 was truly suppressed by deguelin, an inhibitor of Akt, in the platelets from a healthy subject. These results strongly suggest that TRAP-induced activation of Akt in addition to p38 MAP kinase positively regulates the release of phosphorylated-HSP27 from human platelets, which is closely related to the platelet hyper-aggregation in type 2 DM patients.

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IJMS, Vol. 17, Pages 738: Effect of AQP9 Expression in Androgen-Independent Prostate Cancer Cell PC3

Toxins, Vol. 8, Pages 153: The Regulatory Networks That Control Clostridium difficile Toxin Synthesis

The pathogenic clostridia cause many human and animal diseases, which typically arise as a consequence of the production of potent exotoxins. Among the enterotoxic clostridia, Clostridium difficile is the main causative agent of nosocomial intestinal infections in adults with a compromised gut microbiota caused by antibiotic treatment. The symptoms of C. difficile infection are essentially caused by the production of two exotoxins: TcdA and TcdB. Moreover, for severe forms of disease, the spectrum of diseases caused by C. difficile has also been correlated to the levels of toxins that are produced during host infection. This observation strengthened the idea that the regulation of toxin synthesis is an important part of C. difficile pathogenesis. This review summarizes our current knowledge about the regulators and sigma factors that have been reported to control toxin gene expression in response to several environmental signals and stresses, including the availability of certain carbon sources and amino acids, or to signaling molecules, such as the autoinducing peptides of quorum sensing systems. The overlapping regulation of key metabolic pathways and toxin synthesis strongly suggests that toxin production is a complex response that is triggered by bacteria in response to particular states of nutrient availability during infection.

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Sensors, Vol. 16, Pages 701: Influences of Probe’s Morphology for Metal Ion Detection Based on Light-Addressable Potentiometric Sensors

The sensing mechanism of binding Hg2+ into thymine-thymine (T-T) mismatched base pairs was introduced into a light-addressable potentiometric sensor (LAPS) with anti-Hg2+ aptamer as the sensing units. Three kinds of T-rich single-strand DNA (ssDNA) chains with different spacer lengths, from 0 to 12 –CH2 groups, were designed to investigate surface charge and morphological effects on the LAPS' output. First, by comparing the responding of LAPS modified with three kinds of ssDNA, it was found that the best performance for Hg2+ sensing was exhibited by the probe without –CH2 groups. The detection limit of Hg2+ ion was 1 ppt under the optimal condition. Second, the cooperative effects of surface charge and morphology on the output were observed by the controlled experiments. The two effects were the negative charge balanced by metal cations and the morphological changing caused by the formation of T-Hg2+-T structure. In conclusion, not only the influences of the aptamer probe's morphology and surface charge was investigated on the platform of LAPS, but also sensing Hg2+ ions was achieved for the first time by the presented aptamer LAPS.

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Toxins, Vol. 8, Pages 153: The Regulatory Networks That Control Clostridium difficile Toxin Synthesis

Molecules, Vol. 21, Pages 636: The Suppression of Columnar π-Stacking in 3-Adamantyl-1-phenyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl

3-Adamantyl-1-phenyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (4) crystallizes as chains of radicals where the spin bearing benzotriazinyl moieties are isolated from each other. Magnetic susceptibility studies in the 5–300 K temperature region indicate that radical 4 demonstrates typical paramagnetic behavior stemming from non-interacting S = ½ spins.

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Molecules, Vol. 21, Pages 633: Recent Developments in Solid-Phase Extraction for Near and Attenuated Total Reflection Infrared Spectroscopic Analysis

A review with more than 100 references on the principles and recent developments in the solid-phase extraction (SPE) prior and for in situ near and attenuated total reflection (ATR) infrared spectroscopic analysis is presented. New materials, chromatographic modalities, experimental setups and configurations are described. Their advantages for fast sample preparation for distinct classes of compounds containing different functional groups in order to enhance selectivity and sensitivity are discussed and compared. This is the first review highlighting both the fundamentals of SPE, near and ATR spectroscopy with a view to real sample applicability and routine analysis. Most of real sample analyses examples are found in environmental research, followed by food- and bioanalysis. In this contribution a comprehensive overview of the most potent SPE-NIR and SPE-ATR approaches is summarized and provided.

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Molecules, Vol. 21, Pages 632: Antitumor Effect of the Mannich Base(1,3-bis-((3-Hydroxynaphthalen-2-yl)phenylmethyl)urea) on Hepatocellular Carcinoma

The present study was designed to evaluate the antitumor effects of the synthetic Mannich base 1,3-bis-((3-hydroxynaphthalen-2-yl)phenylmethyl)urea (1,3-BPMU) against HEP-G2 hepatoma cells and diethylnitrosamine (DEN)-induced hepatocarcinoma (HCC) in albino rats. In vitro analysis results revealed that 1,3-BPMU showed significant cytotoxicity and cell growth inhibition in HEP-G2 hepatoma cells in a concentration-dependent manner. Furthermore, flow cytometry results indicated that 1,3-BPMU enhanced early and late apoptosis. The maximum apoptosis was exhibited at a concentration of 100 μg/mL of 1,3-BPMU. In in vivo analysis, DEN treatment increased the content of nucleic acids, LPO and the activities of AST, ALT, ALP, LDH, γGT and 5'NT with decreased antioxidant activity as compared to control rats. However, 1,3-BPMU treatment to DEN-induced rats decreased the content of nucleic acids, LPO and the activities of AST, ALT, ALP, LDH, γGT and 5'NT and increased the activities of SOD, CAT, GPx, GST and GR (p < 0.05). Furthermore, 1,3-BPMU enhanced the apoptosis via upregulation of caspase-3 and caspase-9 and the downregulation of Bcl-2 and Bcl-XL mRNA expression as compared to DEN-induced rats. Histological and ultrastructural investigation showed that 1,3-BPMU treatment renovated the internal architecture of the liver in DEN-induced rats. In this study, the molecular and pre-clinical results obtained by treatment of DEN-induced rats with 1,3-BPMU suggested that 1,3-BPMU might be considered as an antitumor compound in the future.

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Molecules, Vol. 21, Pages 631: Characterization of the Principal Constituents of Danning Tablets, a Chinese Formula Consisting of Seven Herbs, by an UPLC-DAD-MS/MS Approach

Danning Tablets are a traditional Chinese formula showing broad clinical applications in hepatobiliary diseases and containing a diversity of bioactive chemicals. However, the chemical profiling of the formula, which serves as the material foundation of its efficacy, is really a big challenge as Danning Tablets consist of seven herbs from different origins. An ultra-performance liquid chromatography coupled to diode array detection and electrospray ionization mass spectrometry (UPLC-DAD-ESI-MS/MS) approach was developed to characterize the principal polyphenol constituents in the formula. As a result, a total of 32 constituents, including 14 anthraquinones and their glucosides, four anthrones, two naphthalene glycosides, two stilbenes and 10 flavonoids were identified based on their retention time, UV absorption and MS/MS fragmentation patterns. The sources of these compounds were also illustrated. Most of the bioactive anthraquinone derivatives were found in Rhei Radix et Rhizoma or Polygoni Cuspidati Rhizoma et Radix, which are the Emperor drugs in the formula for its clinic usage. These findings indicate the merit of using this integrated UPLC-DAD-ESI-MS/MS approach to rapidly illustrate the chemical foundation of complex formulas. The present study will facilitate the quality control of Danning Tablet formulas as well as the individual herbs.

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Molecules, Vol. 21, Pages 634: Synthesis and Biological Evaluation of Benzochromenopyrimidinones as Cholinesterase Inhibitors and Potent Antioxidant, Non-Hepatotoxic Agents for Alzheimer’s Disease

We report herein the straightforward two-step synthesis and biological assessment of novel racemic benzochromenopyrimidinones as non-hepatotoxic, acetylcholinesterase inhibitors with antioxidative properties. Among them, compound 3Bb displayed a mixed-type inhibition of human acetylcholinesterase (IC50 = 1.28 ± 0.03 μM), good antioxidant activity, and also proved to be non-hepatotoxic on human HepG2 cell line.

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IJMS, Vol. 17, Pages 737: Thrombin Receptor-Activating Protein (TRAP)-Activated Akt Is Involved in the Release of Phosphorylated-HSP27 (HSPB1) from Platelets in DM Patients

Cancers, Vol. 8, Pages 49: In Hyperthermia Increased ERK and WNT Signaling Suppress Colorectal Cancer Cell Growth

Although neoplastic cells exhibit relatively higher sensitivity to hyperthermia than normal cells, hyperthermia has had variable success as an anti-cancer therapy. This variable outcome might be due to the fact that cancer cells themselves have differential degrees of sensitivity to high temperature. We hypothesized that the varying sensitivity of colorectal cancer (CRC) cells to hyperthermia depends upon the differential induction of survival pathways. Screening of such pathways revealed that Extracellular Signal-Regulated Kinase (ERK) signaling is augmented by hyperthermia, and the extent of this modulation correlates with the mutation status of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS). Through clonal growth assays, apoptotic analyses and transcription reporter assays of CRC cells that differ only in KRAS mutation status we established that mutant KRAS cells are more sensitive to hyperthermia, as they exhibit sustained ERK signaling hyperactivation and increased Wingless/Integrated (WNT)/beta-catenin signaling. We propose that whereas increased levels of WNT and ERK signaling and a positive feedback between the two pathways is a major obstacle in anti-cancer therapy today, under hyperthermia the hyperinduction of the pathways and their positive crosstalk contribute to CRC cell death. Ascertaining the causative association between types of mutations and hyperthermia sensitivity may allow for a mutation profile-guided application of hyperthermia as an anti-cancer therapy. Since KRAS and WNT signaling mutations are prevalent in CRC, our results suggest that hyperthermia-based therapy might benefit a significant number, but not all, CRC patients.

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Molecules, Vol. 21, Pages 617: Imidazolium Ionic Liquid Functionalized Carbon Nanotubes for Improved Interfacial Charge Transfer and Simultaneous Determination of Dihydroxybenzene Isomers

In this paper; an imidazolium ionic liquid (IL) is used to functionalize multi-walled carbon nanotubes (MWNTs) by covalent bonding on the MWNT surface. The functionalization not only provides a hydrophilic surface for ion accessibility but also prevents the aggregation of MWNTs. The IL-functionalized MWNTs were then applied for the electrochemical determination of the dihydroxybenzene isomers hydroquinone (HQ); catechol (CC); and resorcinol (RC), exhibiting excellent recognition ability towards the three compounds. The linear calibration ranges for HQ; CC and RC are 0.9–150 μM; 0.9–150 μM and 1.9–145 μM and the detection limits are found to be 0.15 μM for HQ; 0.10 μM for CC and 0.38 μM for RC based on S/N of 3. The proposed electrochemical sensor was also found to be useful for the determination of the dihydroxybenzene isomers in Yellow River water with reliable recovery.

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IJERPH, Vol. 13, Pages 504: Epigenetic Effect of Environmental Factors on Autism Spectrum Disorders

Both environmental factors and genetic factors are involved in the pathogenesis of autism spectrum disorders (ASDs). Epigenetics, an essential mechanism for gene regulation based on chemical modifications of DNA and histone proteins, is also involved in congenital ASDs. It was recently demonstrated that environmental factors, such as endocrine disrupting chemicals and mental stress in early life, can change epigenetic status and gene expression, and can cause ASDs. Moreover, environmentally induced epigenetic changes are not erased during gametogenesis and are transmitted to subsequent generations, leading to changes in behavior phenotypes. However, epigenetics has a reversible nature since it is based on the addition or removal of chemical residues, and thus the original epigenetic status may be restored. Indeed, several antidepressants and anticonvulsants used for mental disorders including ASDs restore the epigenetic state and gene expression. Therefore, further epigenetic understanding of ASDs is important for the development of new drugs that take advantages of epigenetic reversibility.

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Nutrients, Vol. 8, Pages 295: Protein Intake and Muscle Health in Old Age: From Biological Plausibility to Clinical Evidence

The provision of sufficient amounts of dietary proteins is central to muscle health as it ensures the supply of essential amino acids and stimulates protein synthesis. Older persons, in particular, are at high risk of insufficient protein ingestion. Furthermore, the current recommended dietary allowance for protein (0.8 g/kg/day) might be inadequate for maintaining muscle health in older adults, probably as a consequence of "anabolic resistance" in aged muscle. Older individuals therefore need to ingest a greater quantity of protein to maintain muscle function. The quality of protein ingested is also essential to promoting muscle health. Given the role of leucine as the master dietary regulator of muscle protein turnover, the ingestion of protein sources enriched with this essential amino acid, or its metabolite β-hydroxy β-methylbutyrate, is thought to offer the greatest benefit in terms of preservation of muscle mass and function in old age.

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Electronics, Vol. 5, Pages 21: A Software Framework for Rapid Application-Specific Hybrid Photonic Network-on-Chip Synthesis

Network on Chip (NoC) architectures have emerged in recent years as scalable communication fabrics to enable high bandwidth data transfers in chip multiprocessors (CMPs). These interconnection architectures still need to conquer many challenges, e.g., significant power consumption and high data transfer latencies. Hybrid electro-photonic NoCs have been recently proposed as a solution to mitigate some of these challenges. However, with increasing application complexity, hardware dependencies, and performance variability, optimization of hybrid photonic NoCs requires traversing a massive design space. To date, prior work on software tools for rapid automated NoC synthesis have mainly focused on electrical NoCs. In this article, we propose a novel suite of software tools for effectively synthesizing hybrid photonic NoCs. We formulate and solve the synthesis problem using four search-based optimization heuristics: (1) Ant Colony Optimization (ACO); (2) Particle Swarm Optimization (PSO); (3) Genetic Algorithm (GA); and (4) Simulated Annealing (SA). Our experimental results show significant promise for the ACO and PSO based heuristics. Our novel implementation of PSO achieves an average of 64% energy-delay product improvements over GA and 53% improvement over SA; while our novel ACO implementation achieves 107% energy-delay product improvements over GA and 62% improvement over SA.

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Tissue-specific regulation of potassium homeostasis by high doses of cationic amino acids

The administration of l-arginine hydrochloride has been used for testing pituitary secretion in humans, and as an experimental model for induction of acute pancreatitis in rats and mice. Whereas in the first case...

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Advantages of L-3-[18F] fluoro-alpha-methyl tyrosine over 2-[18F]-fluoro-2-deoxyglucose in detecting liver metastasis during positron emission tomography scan

We aimed to assess the usefulness of positron emission tomography (PET) using the amino acid tracer L-3-[18F] fluoro-alpha-methyl tyrosine (FAMT) in detecting metastatic liver lesions compared with 2-[18F]-flu...

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Surgical treatment for lumbar tuberculosis by posterior transforaminal lumbar debridement, interbody fusion, and instrumentation in the aged

To evaluate the clinical efficacy and feasibility of single-stage posterior debridement, interbody fusion and posterior instrumentation for the treatment of lumbar tuberculosis in the aged and to discuss the s...

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Combined active and passive heat exposure induced heat acclimation in a soccer referee before 2014 FIFA World Cup

The 2014 FIFA World Cup was held in Brazil, where the climatic conditions presented a significant thermoregulatory and perceptual challenge to those unfamiliar with the heat and humidity.

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Skeletal muscle wasting and renewal: a pivotal role of myokine IL-6

Adult skeletal tissue is composed of heterogeneous population of cells that constantly self-renew by means of a controlled process of activation and proliferation of tissue-resident stem cells named satellite ...

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Sensors, Vol. 16, Pages 698: Erratum: Sutapun, B. et al. Development and Beam-Shape Analysis of an Integrated Fiber-Optic Confocal Probe for High-Precision Central Thickness Measurement of Small-Radius Lenses. Sensors, 2015, 15, 8512-8526

n/a

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Human tear proteomics and peptidomics in ophthalmology: Toward the translation of proteomic biomarkers into clinical practice

Publication date: Available online 13 May 2016
Source:Journal of Proteomics
Author(s): Mikel Azkargorta, Javier Soria, Arantxa Acera, Ibon Iloro, Tatiana Suarez, Felix Elortza
Tears are a complex biological mixture containing electrolytes, metabolites, lipids, mucins, some small organic molecules, and proteins. The film has various roles in the lubrication, protection from the external environment, and nutrition of the cornea; it is also involved in the modulation of the optical properties of the eye.Tear composition reflects the physiological condition of the underlying tissues. Therefore, the tear fluid is useful in the evaluation of health and disease statesand it is a valuable source of biomarkers for objective analysis of ocular and systemic diseases.The relatively high protein concentration of this fluid and the ease of noninvasive sample collection make it suitable for diagnostic and prognostic purposes. Efforts in proteomics research have positively affected to the field of ophthalmology, and the knowledge on the tear proteome has expanded considerably in the last few years. Nevertheless, despite a large amount of available data and the many biomarkers proposed for several eye and systemic diseases, the extent of translation to well-characterized and clinically useful tools has been largely insufficient. As for most of other biofluids, the road from discovery to clinical application is still long and full of pitfalls.In this review, we discuss the proteomic approaches used in the characterization of tear protein and peptide content, recapitulating the main studies and the progress done. We also present a brief summary of the path from discovery to clinical application of tear protein markers, with some representative examples of translation from the bench to the bedside.SignificanceIn this review we cover the most relevant proteomic approaches used in the characterization of tear proteome, and for the first time we also focus in advances performed in the nowadays emerging peptide content characterization. In this context, we recapitulate on the main studies and the progresses done in this field. We also present a concise overview of the course that may be happen from discovery to clinical application for tear protein markers. Finally we include some representative examples of translation from the bench to the bedside.

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Sensors, Vol. 16, Pages 697: Measurement of Moisture in Wood for Application in the Restoration of Old Buildings

There are many historic buildings whose construction is based on timber frame walls. Most buildings built during the nineteenth and early twentieth centuries were based on timber frame walls with vertical support elements. These timber frame elements are affected by their moisture content and by the passage of time. If the interaction of the timber frame walls with hygrothermal fluctuations were known, the maintenance of these buildings could be improved significantly. To determine the moisture content of wood there are two types of meters on the market: on the one hand, capacitance meters which consist of two side ends and where the moisture content is measured locally between two peaks. On the other hand, there are meters based on the variation of electromagnetic transmittance of timber, which depends on the moisture of timber. The second ones are very expensive and difficult to handle. This work presents a new non-intrusive capacitive sensor that measures the global moisture content in a section of the timber frame walls and therefore its accuracy is similar to the accuracy that can be obtained with electromagnetic transmittance meters. Additionally, as it is a capacitive sensor, it is low cost and easy to operate.

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Sustainability, Vol. 8, Pages 480: Spatial Assessment of Cancer Incidences and the Risks of Industrial Wastewater Emission in China

China's rapid economic growth and social transitions have deteriorated environmental conditions and caused further public health issues in last three decades. This study examines the complex mechanisms of how socioeconomic transitions and physical environmental conditions impact public health, especially with respect to increasing cancer incidences in mainland China from a spatial-temporal perspective. Specifically, (1) spatial variations of seven types of cancer incidences were analyzed in relation to heavy metal emissions from industrial wastewater at the prefecture-level city scale from 2004 to 2009. Additionally; (2) spatial statistical methods were employed to explore the associations between health outcome, heavy metal emissions from industrial wastewater (arsenic, chromium, cadmium, mercury, lead), as well as socioeconomic transitions (industrialization, urbanization, globalization) and physical environmental factors (hydrology and vegetation coverage). Results showed a significant increase of cancer incidences between 2004 and 2009. Consistent with the spatial pattern of heavy metal emissions, cancer patient clusters were identified in both traditional industrial bases and newly industrialized economic zones, especially in major cities located at downstream watersheds, including Beijing, Shanghai, Guangzhou, Shenyang, and Wuhan. The results also revealed the double-edged effects of industrialization, economic growth, and urbanization on natural environment and human health. The findings provide informative knowledge of heavy metal pollution and cancer outbreaks in China and therefore offer valuable reference for authorities formulating regulations.

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The Association between Openness and Physiological Responses to Recurrent Social Stress

Publication date: Available online 13 May 2016
Source:International Journal of Psychophysiology
Author(s): Wei Lü, Zhenhong Wang, Brian M. Hughes
The association between openness (assessed by shortened Chinese version of NEO Five-Factor Inventory, NEO-FFI) and physiological reactivity to, and recovery from, social stress (a video-recorded, timed public speaking task with evaluators present in the room), and physiological adaptation to repeated social stress was examined in the present study. Subjective and physiological data were collected from 70 college students across five laboratory stages: baseline, stress exposure period 1, post-stress period 1, stress exposure period 2, and post-stress period 2. Results indicated that higher openness was associated with lesser heart rate (HR) reactivity to the first and second stress exposure, and lesser systolic blood pressure (SBP) reactivity to the second stress exposure. Higher openness was associated with higher resting respiratory sinus arrhythmia (RSA), lesser RSA withdrawals to the first stress exposure, and more complete RSA recovery after the first stress exposure. Moreover, higher openness was associated with pronounced systolic and diastolic blood pressure (SBP, DBP) adaptation with greater decreases in SBP and DBP reactivity across the two successive stress exposures. These findings might shed light on the biological basis linking openness to health.

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Increased N250 amplitudes for other-race faces reflect more effortful processing at the individual level

Publication date: Available online 14 May 2016
Source:International Journal of Psychophysiology
Author(s): Grit Herzmann
The N250 and N250r (r for repetition, signaling a difference measure of priming) has been proposed to reflect the activation of perceptual memory representations for individual faces. Increased N250r and N250 amplitudes have been associated with higher levels of familiarity and expertise, respectively. In contrast to these observations, the N250 amplitude has been found to be larger for other-race than own-race faces in recognition memory tasks. This study investigated if these findings were due to increased identity-specific processing demands for other-race relative to own-race faces and whether or not similar results would be obtained for the N250 in a repetition priming paradigm. Only Caucasian participants were available for testing and completed two tasks with Caucasian, African-American, and Chinese faces. In a repetition priming task, participants decided whether or not sequentially presented faces were of the same identity (individuation task) or same race (categorization task). Increased N250 amplitudes were found for African-American and Chinese faces relative to Caucasian faces, replicating previous results in recognition memory tasks. Contrary to the expectation that increased N250 amplitudes for other-race face would be confined to the individuation task, both tasks showed similar results. This could be due to the fact that face identity information needed to be maintained across the sequential presentation of prime and target in both tasks. Increased N250 amplitudes for other-race faces are taken to represent increased neural demands on the identity-specific processing of other-race faces, which are typically processed less holistically and less on the level of the individual.

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Nutrients, Vol. 8, Pages 296: Diet Quality and Adequacy of Nutrients in Preschool Children: Should Rice Fortified with Micronutrients Be Included in School Meals?

Feeding is indicative of the nutritional status of children, however micronutrient deficiency is common in this age group. We evaluated the impact of inclusion of rice (Ultra Rice® (UR®)) fortified with iron, zinc, thiamin and folic acid on laboratory measurements and the nutrient intake of children. Ninety-nine preschoolers (2–6 years; 42.6% male) from two preschools participated, one of which received UR® added to polished rice as part of school meals (test preschool) and the other received only polished rice (control preschool). Biochemical evaluations were performed before and after four months of intervention. Feeding was assessed by direct weighing of food, complemented by 24-h recalls, and the diet was assessed by the Healthy Eating Index (HEI) adapted to the Brazilian reality. The fortified rice improved the levels of zinc (p < 0.001), thiamine (p < 0.001), folic acid (p = 0.003), mean corpuscular hemoglobin (p < 0.001) and mean corpuscular hemoglobin concentration (p < 0.001). The inadequacy percentages of thiamine, folic acid and iron were lower among preschoolers from the test preschool. This study demonstrated the effectiveness of using UR® on laboratory measurements of children. The inadequate intake of thiamine, folic acid and iron was also reduced, making the fortified rice an interesting strategy in school feeding programs.

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Sustainability, Vol. 8, Pages 479: Improving Freedom to Operate in Carrot Breeding through the Development of Eight Open Source Composite Populations of Carrot (Daucus carota L. var. sativus)

The intellectual property rights (IPR) landscape for plant germplasm has changed dramatically over the past 50 years, moving from the public domain into proprietary structures. Using carrot as a model crop, we explored the freedom to operate for plant breeding and research in relation to the diversity present in 140 commercially available cultivars in the United States. To determine freedom to operate, we characterized the phenotypic and genotypic diversity across cultivars and the IPR that were associated with each cultivar. With 87 of the 95 cultivars that were not restricted by IPR, we developed eight diverse composite populations of carrot through two cycles of breeding that are meant to encompass the available diversity in commercial germplasm. These populations are being released through the Open Source Seed Initiative (OSSI, www.osseeds.org). This is the first example of crop germplasm that has been collected, characterized, and bred specifically for entry into an open source commons.

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Molecules, Vol. 21, Pages 635: Mechanism of the Zn(II)Phthalocyanines’ Photochemical Reactions Depending on the Number of Substituents and Geometry

In this work, the synthesis and the nonlinear absorption and population dynamics investigation of a series of zinc phthalocyanines (ZnPcs) dissolved in chloroform are reported. In order to determine the relevant spectroscopic parameters, such as absorption cross-sections of singlet and triplet excited states, fluorescence relaxation times, intersystem crossing, radiative decay and internal conversion, different optical and spectroscopic techniques were used. By single pulse and pulse train Z-scan techniques, respectively, singlet and triplet excited states' absorption cross-section were determined at 532 nm. Furthermore, the intersystem crossing time was obtained by using both techniques combined with the fluorescence lifetime determined by time-resolved fluorescence. The radiative and internal conversion rates were determined from the fluorescence quantum yield of the samples. Such spectroscopy parameters are fundamental for selecting photosensitizers used in photodynamic therapy, as well as for many other applications.

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IJERPH, Vol. 13, Pages 503: Physiological and Molecular Response of Prorocentrum minimum to Tannic Acid: An Experimental Study to Evaluate the Feasibility of Using Tannic Acid in Controling the Red Tide in a Eutrophic Coastal Water

Bioassay and gene expression experiments were conducted in order to evaluate the growth and physiology of Prorocentrum minimum isolated from a eutrophic coastal water in response to tannic acid. In the bioassay experiments, variations in abundance, chlorophyll (chl) a concentration, maximum fluorescence (in vivo Fm), and photosynthetic efficiency (Fv/Fm) were measured over the course of a seven-day incubation. Moreover, stress-related gene expression in both the control and an experimental (2.5 ppm TA treatment) group was observed for 24 h and 48 h. The molecular markers used in this study were the heat shock proteins (Hsp70 and Hsp90) and cyclophilin (CYP). The findings show that P. minimum can thrive and grow at low concentrations (<2.5 ppm) of tannic acid, and, above this concentration, cells begin to slow down development. In addition, TA concentration of 10 ppm halted photosynthetic activity. At the molecular level, treatment with tannic acid increased the expression of Hsp70, Hsp90, and CYP, and heat shock proteins are more upregulated than the cyclophilin gene. Exposure to tannic acid increased the expression of stress factors over time (48 h) by 10- to 27-fold the expression level of the control group. These results suggest that tannic acid can be used to control harmful algal blooms such as those containing P. minimum in eutrophic coastal waters.

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Polymers, Vol. 8, Pages 195: Aerosol-Assisted Fast Formulating Uniform Pharmaceutical Polymer Microparticles with Variable Properties toward pH-Sensitive Controlled Drug Release

Microencapsulation is highly attractive for oral drug delivery. Microparticles are a common form of drug carrier for this purpose. There is still a high demand on efficient methods to fabricate microparticles with uniform sizes and well-controlled particle properties. In this paper, uniform hydroxypropyl methylcellulose phthalate (HPMCP)-based pharmaceutical microparticles loaded with either hydrophobic or hydrophilic model drugs have been directly formulated by using a unique aerosol technique, i.e., the microfluidic spray drying technology. A series of microparticles of controllable particle sizes, shapes, and structures are fabricated by tuning the solvent composition and drying temperature. It is found that a more volatile solvent and a higher drying temperature can result in fast evaporation rates to form microparticles of larger lateral size, more irregular shape, and denser matrix. The nature of the model drugs also plays an important role in determining particle properties. The drug release behaviors of the pharmaceutical microparticles are dependent on their structural properties and the nature of a specific drug, as well as sensitive to the pH value of the release medium. Most importantly, drugs in the microparticles obtained by using a more volatile solvent or a higher drying temperature can be well protected from degradation in harsh simulated gastric fluids due to the dense structures of the microparticles, while they can be fast-released in simulated intestinal fluids through particle dissolution. These pharmaceutical microparticles are potentially useful for site-specific (enteric) delivery of orally-administered drugs.

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Sensors, Vol. 16, Pages 693: The Real-Valued Sparse Direction of Arrival (DOA) Estimation Based on the Khatri-Rao Product

There is a problem that complex operation which leads to a heavy calculation burden is required when the direction of arrival (DOA) of a sparse signal is estimated by using the array covariance matrix. The solution of the multiple measurement vectors (MMV) model is difficult. In this paper, a real-valued sparse DOA estimation algorithm based on the Khatri-Rao (KR) product called the L1-RVSKR is proposed. The proposed algorithm is based on the sparse representation of the array covariance matrix. The array covariance matrix is transformed to a real-valued matrix via a unitary transformation so that a real-valued sparse model is achieved. The real-valued sparse model is vectorized for transforming to a single measurement vector (SMV) model, and a new virtual overcomplete dictionary is constructed according to the KR product's property. Finally, the sparse DOA estimation is solved by utilizing the idea of a sparse representation of array covariance vectors (SRACV). The simulation results demonstrate the superior performance and the low computational complexity of the proposed algorithm.

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Laws, Vol. 5, Pages 22: A Word of Caution: Human Rights, Disability, and Implementation of the Post-2015 Sustainable Development Goals

On 25 September 2015, the United Nations (UN) General Assembly unanimously voted for the post-2015 UN resolution on the post-2015 Sustainable Development Goal (SDG) agenda. This article argues that although the post-2015 SDG agenda is an advance on its precursor the Millennium Development Goals (MDGs)—especially for progressing the human rights of persons with disabilities in development settings, everywhere—it should nonetheless be approached with caution. This article will identify "three steps forward" for persons with disabilities within the broad content of the post-2015 SDGs, while also highlighting four potential "steps back". It concludes persons with disabilities, disability rights advocates and their supporters must remain vigilant as the post-SDG UN resolution is now operationalised and implemented by UN Member States and their many partners. This is particularly so if the content of the Convention on the Rights of Persons with Disabilities is to be effectively integrated into the post-2015 development policy and planning landscape.

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Σάββατο 14 Μαΐου 2016

Abstract

Abstract

Abstract