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Κυριακή 26 Ιουνίου 2016

Sensors, Vol. 16, Pages 969: Sensor Network-Based and User-Friendly User Location Discovery for Future Smart Homes

User location is crucial context information for future smart homes where many location based services will be proposed. This location necessarily means that User Location Discovery (ULD) will play an important role in future smart homes. Concerns about privacy and the need to carry a mobile or a tag device within a smart home currently make conventional ULD systems uncomfortable for users. Future smart homes will need a ULD system to consider these challenges. This paper addresses the design of such a ULD system for context-aware services in future smart homes stressing the following challenges: (i) users' privacy; (ii) device-/tag-free; and (iii) fault tolerance and accuracy. On the other hand, emerging new technologies, such as the Internet of Things, embedded systems, intelligent devices and machine-to-machine communication, are penetrating into our daily life with more and more sensors available for use in our homes. Considering this opportunity, we propose a ULD system that is capitalizing on the prevalence of sensors for the home while satisfying the aforementioned challenges. The proposed sensor network-based and user-friendly ULD system relies on different types of inexpensive sensors, as well as a context broker with a fuzzy-based decision-maker. The context broker receives context information from different types of sensors and evaluates that data using the fuzzy set theory. We demonstrate the performance of the proposed system by illustrating a use case, utilizing both an analytical model and simulation.

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Sensors, Vol. 16, Pages 924: Verification of Geometric Model-Based Plant Phenotyping Methods for Studies of Xerophytic Plants

This paper presents the results of verification of certain non-contact measurement methods of plant scanning to estimate morphological parameters such as length, width, area, volume of leaves and/or stems on the basis of computer models. The best results in reproducing the shape of scanned objects up to 50 cm in height were obtained with the structured-light DAVID Laserscanner. The optimal triangle mesh resolution for scanned surfaces was determined with the measurement error taken into account. The research suggests that measuring morphological parameters from computer models can supplement or even replace phenotyping with classic methods. Calculating precise values of area and volume makes determination of the S/V (surface/volume) ratio for cacti and other succulents possible, whereas for classic methods the result is an approximation only. In addition, the possibility of scanning and measuring plant species which differ in morphology was investigated.

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Sensors, Vol. 16, Pages 944: A Tightly-Coupled GPS/INS/UWB Cooperative Positioning Sensors System Supported by V2I Communication

This paper investigates a tightly-coupled Global Position System (GPS)/Ultra-Wideband (UWB)/Inertial Navigation System (INS) cooperative positioning scheme using a Robust Kalman Filter (RKF) supported by V2I communication. The scheme proposes a method that uses range measurements of UWB units transmitted among the terminals as augmentation inputs of the observations. The UWB range inputs are used to reform the GPS observation equations that consist of pseudo-range and Doppler measurements and the updated observation equation is processed in a tightly-coupled GPS/UWB/INS integrated positioning equation using an adaptive Robust Kalman Filter. The result of the trial conducted on the roof of the Nottingham Geospatial Institute (NGI) at the University of Nottingham shows that the integrated solution provides better accuracy and improves the availability of the system in GPS denied environments. RKF can eliminate the effects of gross errors. Additionally, the internal and external reliabilities of the system are enhanced when the UWB observables received from the moving terminals are involved in the positioning algorithm.

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Endoxifen, a New Treatment Option for Mania: A Double-Blind, Active-Controlled Trial Demonstrates the Antimanic Efficacy of Endoxifen

The protein kinase C (PKC) signaling system plays a role in mood disorders and PKC inhibitors such as endoxifen may be an innovative medicine for bipolar disorder (BP) patients. In this study we show for the first time the antimanic properties of endoxifen in patients with bipolar I disorder (BPD I) with current manic or mixed episode. In a double-blind, active-controlled study, 84 subjects with BPD I were randomly assigned to receive endoxifen (4 mg/day or 8 mg/day) or divalproex in a 2:1 ratio. Patients orally administered 4 mg/day or 8 mg/day endoxifen showed significant improvement in mania assessed by the Young Mania Rating Scale as early as 4 days. The effect remained significant throughout the 21-day period. At study end point, response rates were 44.44% and 64.29% at 4 mg/day and 8 mg/day of endoxifen treatment, respectively. Thus, endoxifen has been shown as a promising novel antimanic or mood stabilizing agent.



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Studying the Role of Alveolar Macrophages in Breast Cancer Metastasis

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Here we describe the model and approach to study functions of pulmonary alveolar macrophages in cancer metastasis. To demonstrate the role of these cells in metastasis, the syngeneic (4T1) model of breast cancer in conjunction with the depletion of alveolar macrophage with clodronate liposomes was used.

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Circulating MicroRNA Quantification Using DNA-binding Dye Chemistry and Droplet Digital PCR

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A sensitive and accurate method for cell-free microRNAs quantification using a dye-based chemistry and droplet digital PCR technology is described.

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Cutaneous Surgical Denervation: A Method for Testing the Requirement for Nerves in Mouse Models of Skin Disease

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This article includes detailed protocols for genetic labeling of mouse skin, surgical denervation, skin biopsy and visualizing labeled epithelia by whole-mount β-galactosidase staining. These methods can be used to test the requirement for nerves in mouse models of normal and pathological skin.

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Novel synthetic lethality screening method identifies TIP60-dependent radiation sensitivity in the absence of BAF180

Publication date: Available online 25 June 2016
Source:DNA Repair
Author(s): Suzanna Hopkins, Grant McGregor, Joanne M. Murray, Jessica A. Downs, Velibor Savic
In recent years, research into synthetic lethality and how it can be exploited in cancer treatments has emerged as major focus in cancer research. However, the lack of a simple to use, sensitive and standardised assay to test for synthetic interactions has been slowing the efforts. Here we present a novel approach to synthetic lethality screening based on co-culturing two syngeneic cell lines containing individual fluorescent tags. By associating shRNAs for a target gene or control to individual fluorescence labels, we can easily follow individual cell fates upon siRNA treatment and high content imaging. We have demonstrated that the system can recapitulate the functional defects of the target gene depletion and is capable of discovering novel synthetic interactors and phenotypes. In a trial screen, we show that TIP60 exhibits synthetic lethality interaction with BAF180, and that in the absence of TIP60, there is an increase micronuclei dependent on the level of BAF180 loss, significantly above levels seen with BAF180 present. Moreover, the severity of the interactions correlates with proxy measurements of BAF180 knockdown efficacy, which may expand its usefulness to addressing synthetic interactions through titratable hypomorphic gene expression.



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The Effect of Teriparatide on Fracture Healing of Osteoporotic Patients: A Meta-Analysis of Randomized Controlled Trials

Purpose. This meta-analysis is to assess the effectiveness of teriparatide in fracture healing and clinical function improvement of the osteoporotic patients. Methods. We searched PubMed, Embase, Web of Science, and the Cochrane databases for randomized and quasi-randomized controlled trials comparing teriparatide to placebo, no treatment, or comparator interventions in the osteoporotic patients. Results. Five studies with 251 patients were included. Patients treated with teriparatide therapy had a significant shorter radiological fracture healing time compared with those in the control group (mean difference [MD] −4.54 days, 95% confidence interval [CI] −8.80 to −0.28). Stratified analysis showed that lower limb group had significant shorter healing time (MD −6.24 days, 95% CI −7.20 to −5.29), but upper limb group did not (MD −1 days, 95% CI −2.02 to 0.2). Patients treated with teriparatide therapy showed better functional outcome than those in the control group (standardized mean difference [SMD] −1.02, 95% CI −1.81 to −0.22). Patients with therapy duration over 4 weeks would have better functional outcome (SMD −1.68, 95% CI −2.07 to −1.29). Conclusions. Teriparatide is effective in accelerating fracture healing and improving functional outcome of osteoporotic women. However, more clinical studies are warranted in order to determine whether the results are applicable to males and the clinical indications for teriparatide after osteoporotic fractures.

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MicroRNA-21 Promotes Proliferation of Fibroblast-Like Synoviocytes through Mediation of NF-κB Nuclear Translocation in a Rat Model of Collagen-Induced Rheumatoid Arthritis

MicroRNA-21 (miR-21) is overexpressed in patients with rheumatoid arthritis (RA). This study was designed to investigate the effect and mechanism of miR-21 on cell proliferation in fibroblast-like synoviocytes (FLS) of RA. FLS were primary-cultured from a rat RA model. RA-FLS and normal FLS were infected with lentivirus (anti-miR-21 or pro-miR-21) for overexpression or downregulation of miR-21, respectively. The effects of miR-21 overexpression or inhibition on nucleoprotein NF-κB levels and FLS cell proliferation were evaluated by western blotting and MTT assays. The effects of an inhibitor of NF-κB nuclear translocation (BAY 11-7082) were also evaluated. The results showed that the levels of miR-21 and nucleoprotein NF-κB were increased in FLS of RA model rats compared to the control group. Downregulation of miR-21 in RA FLS led to a significant decrease in nucleoprotein NF-κB levels and cell proliferation rates compared to the antinegative control (NC) group. However, miR-21 overexpression in normal FLS resulted in a significant increase of nucleoprotein NF-κB levels and cell proliferation rates compared to the pro-NC group. The effects of miR-21 overexpression were reversed by BAY 11-7082. We concluded that upregulated miR-21 in FLS in RA model rats may promote cell proliferation by facilitating NF-κB nuclear translocation, thus affecting the NF-κB pathway.

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Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer’s Disease

The failure of several Phase II/III clinical trials in Alzheimer's disease (AD) with drugs targeting β-amyloid accumulation in the brain fuelled an increasing interest in alternative treatments against tau pathology, including approaches targeting tau phosphatases/kinases, active and passive immunization, and anti-tau aggregation. The most advanced tau aggregation inhibitor (TAI) is methylthioninium (MT), a drug existing in equilibrium between a reduced (leuco-methylthioninium) and oxidized form (MT+). MT chloride (methylene blue) was investigated in a 24-week Phase II clinical trial in 321 patients with mild to moderate AD that failed to show significant positive effects in mild AD patients, although long-term observations (50 weeks) and biomarker studies suggested possible benefit. The dose of 138 mg/day showed potential benefits on cognitive performance of moderately affected AD patients and cerebral blood flow in mildly affected patients. Further clinical evidence will come from the large ongoing Phase III trials for the treatment of AD and the behavioral variant of frontotemporal dementia on a new form of this TAI, more bioavailable and less toxic at higher doses, called TRx0237. More recently, inhibitors of tau acetylation are being actively pursued based on impressive results in animal studies obtained by salsalate, a clinically used derivative of salicylic acid.

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Effect of Water-Glass Coating on HA and HA-TCP Samples for MSCs Adhesion, Proliferation, and Differentiation

Ca-P and silicon based materials have become very popular as bone tissue engineering materials. In this study, water-glass (also known as sodium silicate glass) was coated on sintered hydroxyapatite (HA) and HA-TCP (TCP stands for tricalcium phosphate) samples and subsequently heat-treated at 600°C for 2 hrs. X-rays diffraction showed the presence of β- and α-TCP phases along with HA in the HA-TCP samples. Samples without coating, with water-glass coating, and heat-treated after water-glass coating were used to observe the adhesion and proliferation response of bone marrow derived-mesenchymal stem cells (MSCs). Cell culture was carried out for 4 hrs, 1 day, and 7 days. Interestingly, all samples showed similar response for cell adhesion and proliferation up to 7-day culture but fibronectin, E-cadherin, and osteogenic differentiation related genes (osteocalcin and osteopontin) were significantly induced in heat-treated water-glass coated HA-TCP samples. A water-glass coating on Ca-P samples was not found to influence the cell proliferation response significantly but activated some extracellular matrix genes and induced osteogenic differentiation in the MSCs.

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Phytochemical, Antimicrobial, and Toxicological Evaluation of Traditional Herbs Used to Treat Sore Throat

The in vitro antibacterial activities of 29 traditional medicinal plants used in respiratory ailments were assessed on multidrug resistant Gram-positive and Gram-negative bacteria isolated from the sore throat patients and two reference strains. The methanolic, n-hexane, and aqueous extracts were screened by the agar well diffusion assay. Bioactive fractions of effective extracts were identified on TLC coupled with bioautography, while their toxicity was determined using haemolytic assay against human erythrocytes. Qualitative and quantitative phytochemical analysis of effective extracts was also performed. Methanolic extract of 18 plants showed antimicrobial activity against test strains. Adhatoda vasica (ZI = 17–21 mm, MIC: 7.12–62.5 μg/mL), Althaea officinalis (ZI = 16–20 mm, MIC: 15.62–31.25 μg/mL), Cordia latifolia (ZI = 16–20 mm, MIC: 12.62–62.5 μg/mL), Origanum vulgare (ZI = 20–22 mm, MIC: 3–15.62 μg/mL), Thymus vulgaris (ZI = 21–25 mm, MIC: 7.81–31.25 μg/mL), and Ziziphus jujuba (ZI = 14–20 mm, MIC: 7.81–31.25 μg/mL) showed significant antibacterial activity. Alkaloid fractions of Adhatoda vasica, Cordia latifolia, and Origanum vulgare and flavonoid fraction of the Althaea officinalis, Origanum vulgare, Thymus Vulgaris, and Ziziphus jujuba exhibited antimicrobial activity. Effective plant extracts show 0.93–0.7% erythrocyte haemolysis. The results obtained from this study provide a scientific rationale for the traditional use of these herbs and laid the basis for future studies to explore novel antimicrobial compounds.

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Synthesis and Potent Antiprotozoal Activity of Mono/Di amidino 2-Anilinobenz-imidazoles versus Plasmodium falciparum and Trypanosoma brucei rhodesiense

Publication date: Available online 25 June 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Cigdem Karaaslan, Marcel Kaiser, Reto Brun, Hakan Göker
A series of mono and dicationic new 2-anilinobenz- imidazole carboxamidines were prepared in a four step process starting from 4- amino-3nitrobenzonitrile and corresponding o-phenylenediamines. Their antiparasitic activity against Plasmodium falciparum (P. falciparum) and Trypanosoma brucei rhodesiense (T.b. rhodesiense) were evaluated in vitro. Some of the dicationic compounds (10,12,14) showed equal or very close activity against T.b. rhodesiense with Melarsoprol and also showed promising activity against P. falciparum as compared to Chloroquine. Among the monocationic derivatives compound 21 exhibited best inhibitory activity against P. falciparum.

Graphical abstract

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Complementary Medicine Health Literacy among a Population of Older Australians Living in Retirement Villages: A Mixed Methods Study

Background. Older Australians are consumers of high levels of complementary medicines. The aim of this study was to examine health literacy in a population of older Australians related to their use of complementary medicine. Methods. A two-phase sequential mixed method design incorporating quantitative and qualitative methods was used in this study. The first phase consisted of a cross-sectional survey using a validated health literacy questionnaire and follow-up interviews with 11 residents of retirement villages. Interviews explored low scoring domains on the health literacy questionnaire. Results. Health literacy competencies scored higher for the domains of having sufficient information to manage their health; felt understood and supported by health care providers; actively managed their health; and having social support for health. Three health literacy domains scored low including appraisal of health information; ability to find good information; and navigating the health care system. The findings suggest that participants had different experiences navigating the health care system to access information and services relating to complementary medicines. Two themes of "trust" and "try and see" provide insight into how this group of older Australians appraised health information in relation to complementary medicines. Conclusions. With a focus on self-care there is a need for improved health literacy skills.

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Identification of Plants That Inhibit Lipid Droplet Formation in Liver Cells: Rubus suavissimus Leaf Extract Protects Mice from High-Fat Diet-Induced Fatty Liver by Directly Affecting Liver Cells

Fatty liver disease is a condition in which abnormally large numbers of lipid droplets accumulate in liver cells. Fatty liver disease induces inflammation under conditions of oxidative stress and may result in cancer. To identify plants that protect against fatty liver disease, we examined the inhibitory effects of plant extracts on lipid droplet formation in mouse hepatoma cells. A screen of 98 water extracts of plants revealed 4 extracts with inhibitory effects. One of these extracts, Rubus suavissimus S. Lee (Tien-cha or Chinese sweet tea) leaf extract, which showed strong inhibitory effects, was tested in a mouse fatty liver model. In these mouse experiments, intake of the plant extract significantly protected mice against fatty liver disease without affecting body weight gain. Our results suggest that RSE directly affects liver cells and protects them from fatty liver disease.

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Paeoniflorin and Albiflorin Attenuate Neuropathic Pain via MAPK Pathway in Chronic Constriction Injury Rats

Neuropathic pain remains as the most frequent cause of suffering and disability around the world. The isomers paeoniflorin (PF) and albiflorin (AF) are major constituents extracted from the roots of Paeonia (P.) lactiflora Pall. Neuroprotective effect of PF has been demonstrated in animal models of neuropathologies. However, only a few studies are related to the biological activities of AF and no report has been published on analgesic properties of AF about neuropathic pain to date. The aim of this study was to compare the effects of AF and PF against CCI-induced neuropathic pain in rat and explore the underlying mechanism. We had found that both PF and AF could inhibit the activation of p38 mitogen-activated protein kinase (p38 MAPK) pathway in spinal microglia and subsequent upregulated proinflammatory cytokines (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)). AF further displayed remarkable effects on inhibiting the activation of astrocytes, suppressing the overelevated expression of phosphorylation of c-Jun N-terminal kinases (p-JNK) in astrocytes, and decreasing the content of chemokine CXCL1 in the spinal cord. These results suggest that both PF and AF are potential therapeutic agents for neuropathic pain, which merit further investigation.

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Expressions of Matrix Metalloproteinases 2, 7, and 9 in Carcinogenesis of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease, usually diagnosed in an advanced stage which gives a slight chance of recovery. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that participate in tissue remodeling and stimulate neovascularization and inflammatory response. The aim of the study was to evaluate the expression of MMP-2, MMP-7, and MMP-9 in normal ducts, tumor pancreatic adenocarcinoma cells, and peritumoral stroma in correlation with clinicohistopathological parameters. The study material was obtained from 29 patients with pancreatic ductal adenocarcinoma. The expressions of MMP-2, MMP-7, and MMP-9 were performed by immunohistochemical technique. Microvessel density (MVD) was visualized by special immunostaining. The expressions of MMP-2, MMP-7, and MMP-9 were mainly observed in tumor cells and peritumoral stroma. MMP-2 expression in cancer cells was correlated with female gender, stronger inflammation, and histopathological type of cancer (, ; , ; , , resp.). The expression of MMP-7 in tumor cells was found to positively correlate with the presence of necrosis and negatively correlate with MVD (, ; , ). We also showed that positive MMP-9 expression in tumor cells was associated with MVD (, ); however, it was not statistically significant. Our results demonstrate that MMP-2, MMP-7, and MMP-9 expressions correlate with various morphological features of the PDAC tumor such as inflammation, necrosis, and formation of the new blood vessels.

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High Expression of PTGR1 Promotes NSCLC Cell Growth via Positive Regulation of Cyclin-Dependent Protein Kinase Complex

Lung cancer has been the most common cancer and the main cause of cancer-related deaths worldwide for several decades. PTGR1 (prostaglandin reductase 1), as a bifunctional enzyme, has been involved in the occurrence and progression of cancer. However, its impact on human lung cancer is rarely reported. In this study, we found that PTGR1 was overexpressed in lung cancer based on the analyses of Oncomine. Moreover, lentivirus-mediated shRNA knockdown of PTGR1 reduced cell viability in human lung carcinoma cells 95D and A549 by MTT and colony formation assay. PTGR1 depletion led to G2/M phase cell cycle arrest and increased the proportion of apoptotic cells in 95D cells by flow cytometry. Furthermore, silencing PTGR1 in 95D cells resulted in decreased levels of cyclin-dependent protein kinase complex (CDK1, CDK2, cyclin A2, and cyclin B1) by western blotting and then PTGR1 is positively correlated with cyclin-dependent protein by using the data mining of the Oncomine database. Therefore, our findings suggest that PTGR1 may play a role in lung carcinogenesis through regulating cell proliferation and is a potential new therapeutic strategy for lung cancer.

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Focal Segmental Glomerulosclerosis: Genetics, Mechanism, and Therapies



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Glia-Neuron Interactions in the Retina Can Be Studied in Cocultures of Müller Cells and Retinal Ganglion Cells

Glia-neuron partnership is important for inner retinal homeostasis and any disturbances may result in retinal ganglion cell (RGC) death. Müller cells support RGCs with essential functions such as removing excess glutamate and providing energy sources. The aim was to explore the impact of Müller cells on RGC survival. To investigate the Müller cell/RGC interactions we developed a coculture model, in which primary Müller cells were grown in inserts on top of pure primary RGC cultures. The impact of starvation and mitochondrial inhibition on the Müller cell ability to protect RGCs was studied. Moreover, the ability of Müller cells to remove glutamate from the extracellular space was investigated. RGC survival was evaluated by cell viability assays and glutamate uptake was assessed by kinetic uptake assays. We demonstrated a significantly increased RGC survival in presence of untreated and prestarved Müller cells. Additionally, prestarved Müller cells significantly increased RGC survival after mitochondrial inhibition. Finally, we revealed a significantly increased ability to take up glutamate in starved Müller cells. Overall, our study confirms essential roles of Müller cells in RGC survival. We suggest that targeting Müller cell function could have potential for future treatment strategies to prevent blinding neurodegenerative retinal diseases.

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