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Δευτέρα 5 Σεπτεμβρίου 2016

IJERPH, Vol. 13, Pages 882: Associations of Cholesteryl Ester Transfer Protein TaqIB Polymorphism with the Composite Ischemic Cardiovascular Disease Risk and HDL-C Concentrations: A Meta-Analysis

Background: Previous studies have evaluated the associations between the cholesteryl ester transfer protein (CETP) TaqIB polymorphism (rs708272), the risk of developing composite ischemic cardiovascular disease (CVD) and the concentration of high-density lipoprotein cholesterol (HDL-C), but results remain controversial. The objective of this study was to investigate whether a relationship exists between these factors. Methods: We conducted a meta-analysis of available studies to clarify the associations of the CETP TaqIB polymorphism with HDL-C concentration and the composite ischemic CVD risk in both Asians and Caucasians. All statistical analyses were done with Stata 12.0. Results: Through utilization of the Cochrane Library, Embase, PubMed, Web of Science, Springer, China Science and Technology Journal Database, China National Knowledge Infrastructure, Google Scholar, and Baidu Library, a total of 45 studies from 44 papers with 20,866 cases and 21,298 controls were combined showing a significant association between the CETP TaqIB variant and composite ischemic CVD risk. Carriers of allele TaqIB-B1 were found to have a higher risk of composite ischemic CVD than non-carriers: OR = 1.15, 95% CI = 1.09–1.21, p < 0.001. Meanwhile, 28 studies with 23,959 subjects were included in the association between the CETP TaqIB polymorphism and the concentration of HDL-C. Results suggested that carriers of the B1B1 genotype had lower concentrations of HDL-C than those of the B2B2 genotype: SMD = 0.50, 95% CI = 0.36–0.65, p < 0.001. Conclusions: The synthesis of available evidence demonstrates that the CETP TaqIB polymorphism protects against composite ischemic CVD risk and is associated with a higher HDL-C concentration in both Asians and Caucasians.

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Water, Vol. 8, Pages 378: Assessment of Drought Evolution Characteristics and Drought Coping Ability of Water Conservancy Projects in Huang-Huai-Hai River Basin, China

Based on the national precipitation dataset in the Huang-Huai-Hai River Basin of China for the 1961–2011 period, the China-Z growing season index was calculated to analyze the characteristics of the evolution of meteorological droughts. Data from statistical droughts (the droughts which are defined and classified by the actual statistic data) were compared with those of meteorological droughts during the 2000–2011 period. Nine indexes were selected to evaluate the drought coping ability of water conservancy projects based on the fuzzy comprehensive assessment model. The results showed that the China-Z growing season index was a downward trend with a rate of −0.063 per decade from 1961 to 2011, which indicates an increasing trend in drought intensity. Droughts were more frequent than average during the 1961–1979 period and returned to normal frequency during the 1980–2011 period. Both the ratio of drought affected area (RDAA) and the ratio of drought suffering area (RDSA) of statistical droughts decreased more quickly than those of meteorological droughts (2000–2011). The indexes of water conservancy projects were lower than the average all-China indexes. Half of the 59 three-level water resources districts exhibited a relatively poor drought coping ability, which means that enhancing the drought coping ability of the water conservancy project was quite important.

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Religions, Vol. 7, Pages 115: Psalms 111–112: Big Story, Little Story

This study argues that the juxtaposition of Psalms 111–112 offers wisdom for life. Psalm 111, in stressing God's mighty deeds of redemption for his people, focuses on the "big story" for the whole people; Psalm 112, in stressing "wisdom," encourages each member of God's people in a day-to-day walk, a "little story," that contributes to the big story of the whole people.

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Angiogenic Effects of Collagen/Mesoporous Nanoparticle Composite Scaffold Delivering VEGF165

Vascularization is a key issue for the success of tissue engineering to repair damaged tissue. In this study, we report a composite scaffold delivering angiogenic factor for this purpose. Vascular endothelial growth factor (VEGF) was loaded on mesoporous silica nanoparticle (MSN), which was then incorporated within a type I collagen sponge, to produce collagen/MSN/VEGF (CMV) scaffold. The CMV composite scaffold could release VEGF sustainably over the test period of 28 days. The release of VEGF improved the cell proliferation. Moreover, the in vivo angiogenesis of the scaffold, as studied by the chick chorioallantoic membrane (CAM) model, showed that the VEGF-releasing scaffold induced significantly increased number of blood vessel complexes when compared with VEGF-free scaffold. The composite scaffold showed good biocompatibility, as examined in rat subcutaneous tissue. These results demonstrate that the CMV scaffold with VEGF-releasing capacity can be potentially used to stimulate angiogenesis and tissue repair.

http://ift.tt/2cmdhy7

Micromachines, Vol. 7, Pages 157: Neural Circuits on a Chip

Neural circuits are responsible for the brain's ability to process and store information. Reductionist approaches to understanding the brain include isolation of individual neurons for detailed characterization. When maintained in vitro for several days or weeks, dissociated neurons self-assemble into randomly connected networks that produce synchronized activity and are capable of learning. This review focuses on efforts to control neuronal connectivity in vitro and construct living neural circuits of increasing complexity and precision. Microfabrication-based methods have been developed to guide network self-assembly, accomplishing control over in vitro circuit size and connectivity. The ability to control neural connectivity and synchronized activity led to the implementation of logic functions using living neurons. Techniques to construct and control three-dimensional circuits have also been established. Advances in multiple electrode arrays as well as genetically encoded, optical activity sensors and transducers enabled highly specific interfaces to circuits composed of thousands of neurons. Further advances in on-chip neural circuits may lead to better understanding of the brain.

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IJMS, Vol. 17, Pages 1482: Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses.

http://ift.tt/2c1Jbjc

IJMS, Vol. 17, Pages 1479: Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7 in Diabetes and Painful Diabetic Neuropathy

Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and incompletely understood. Voltage-gated sodium channels (VGSCs) link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, NaV1.3 and NaV1.7, which are encoded by the sodium voltage-gated channel alpha subunit 3 and 9 (Scn3A and Scn9A) genes, respectively, have been identified in both peripheral nociceptive neurons of dorsal root ganglion (DRG) and pancreatic islet cells. Recent advances in our understanding of tetrodotoxin-sensitive (TTX-S) sodium channels NaV1.3 and NaV1.7 lead to the rational doubt about the cause–effect relation between diabetes and painful neuropathy. In this review, we summarize the roles of NaV1.3 and NaV1.7 in islet cells and DRG neurons, discuss the link between DM and painful neuropathy, and present a model, which may provide a starting point for further studies aimed at identifying the mechanisms underlying diabetes and painful neuropathy.

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Energies, Vol. 9, Pages 711: Chemical Flooding in Heavy-Oil Reservoirs: From Technical Investigation to Optimization Using Response Surface Methodology

Heavy-oil resources represent a large percentage of global oil and gas reserves, however, owing to the high viscosity, enhanced oil recovery (EOR) techniques are critical issues for extracting this type of crude oil from the reservoir. According to the survey data in Oil & Gas Journal, thermal methods are the most widely utilized in EOR projects in heavy oil fields in the US and Canada, and there are not many successful chemical flooding projects for heavy oil reported elsewhere in the world. However, thermal methods such as steam injection might be restricted in cases of thin formations, overlying permafrost, or reservoir depths over 4500 ft, for which chemical flooding becomes a better option for recovering crude oil. Moreover, owing to the considerable fluctuations in the oil price, chemical injection plans should be employed consistently in terms of either technical or economic viewpoints. The numerical studies in this work aim to clarify the predominant chemical injection schemes among the various combinations of chemical agents involving alkali (A), surfactant (S) and polymer (P) for specific heavy-oil reservoir conditions. The feasibilities of all potential injection sequences are evaluated in the pre-evaluation stage in order to select the most efficient injection scheme according to the variation in the oil price which is based on practical market values. Finally, optimization procedures in the post-evaluation stage are carried out for the most economic injection plan by an effective mathematic tool with the purpose of gaining highest Net Present Value (NPV) of the project. In technical terms, the numerical studies confirm the predominant performances of sequences in which alkali-surfactant-polymer (ASP) solution is injected after the first preflushing water whereby the recovery factor can be higher than 47%. In particular, the oil production performances are improved by injecting a buffering viscous fluid right after the first chemical slug rather than using a water slug in between. The results of the pre-evaluation show that two sequences of the ASP group have the highest NPV corresponding to the dissimilar applied oil prices. In the post-evaluation, the successful use of response surface methodology (RSM) in the estimation and optimization procedures with coefficients of determination R2 greater than 0.97 shows that the project can possibly gain 4.47 $MM at a mean oil price of 46.5 $/bbl with the field scale of a quarter five-spot pattern. Further, with the novel assumption of normal distribution for the oil price variation, the chemical flooding sequence of concurrent alkali-surfactant-polymer injection with a buffering polymer solution is evaluated as the most feasible scheme owing to the achievement of the highest NPV at the highly possible oil price of 40–55 $/bbl compared to the other scheme.

http://ift.tt/2bNCQXD

IJFS, Vol. 4, Pages 17: Spatially-Aggregated Temperature Derivatives: Agricultural Risk Management in China

In this paper, a new form of weather derivative contract, namely the climatic zone-based growth degree-day (GDD) contract, is introduced. The objective is to increase the risk management efficiency in the agricultural sector of China and to reduce the model dimension of multi-regional temperature-based weather derivatives pricing. Since the proposed contract serves as a risk management tool for all of the cities in the same climatic zone, we compare the risk hedging power between the climatic zone-based and the city-based GDD contracts. As a result, we find that the differences between the two types of temperature-based weather contracts are maintained within a certain range.

http://ift.tt/2bNTrj3

Sustainability, Vol. 8, Pages 898: Factors Promoting Environmental Responsibility in European SMEs: The Effect on Performance

There is increasing social and political awareness of the importance of developing environmental responsibility at a corporate level. When focusing on issues of responsibility, large companies are frequently perceived to be more responsible for driving climate change and resource depletion. However, small and medium enterprises (SMEs) contribute significantly to the use of resources such as material and energy and produce approximately 64% of the pollution in Europe. Drawing on evidence from "The Eurobarometer 381 Survey on SMEs, Resource Efficiency and Green Markets", we analyze the environmental responsibility of European SMEs, studying their compliance with environmental legislation and how several factors drive environmental orientation among SMEs. Our sample consists of 3647 SMEs operating in 38 countries. Only around a fifth of the firms go beyond environmental regulations, showing the highest levels of environmental responsibility. We conduct OLS regressions to analyze the factors that affect a positive environmental attitude among European SMEs (internal drivers being more significant than external ones) and then, to observe the positive effect of environmental responsibility and firm's experience in offering green services/products on performance, although a conjoint effect was not found. Implications for practitioners, academics, and policy-makers are outlined.

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Energies, Vol. 9, Pages 708: Innovative Calibration Method for System Level Simulation Models of Internal Combustion Engines

The paper outlines a procedure for the computer-controlled calibration of the combined zero-dimensional (0D) and one-dimensional (1D) thermodynamic simulation model of a turbocharged internal combustion engine (ICE). The main purpose of the calibration is to determine input parameters of the simulation model in such a way as to achieve the smallest difference between the results of the measurements and the results of the numerical simulations with minimum consumption of the computing time. An innovative calibration methodology is based on a novel interaction between optimization methods and physically based methods of the selected ICE sub-systems. Therein physically based methods were used for steering the division of the integral ICE to several sub-models and for determining parameters of selected components considering their governing equations. Innovative multistage interaction between optimization methods and physically based methods allows, unlike the use of well-established methods that rely only on the optimization techniques, for successful calibration of a large number of input parameters with low time consumption. Therefore, the proposed method is suitable for efficient calibration of simulation models of advanced ICEs.

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IJMS, Vol. 17, Pages 1476: MRI Dynamically Evaluates the Therapeutic Effect of Recombinant Human MANF on Ischemia/Reperfusion Injury in Rats

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As an endoplasmic reticulum (ER) stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to protect dopaminergic neurons and nondopaminergic cells. Our previous studies had shown that MANF protected against ischemia/reperfusion injury. Here, we developed a magnetic resonance imaging (MRI) technology to dynamically evaluate the therapeutic effects of MANF on ischemia/reperfusion injury. We established a rat focal ischemic model by using middle cerebral artery occlusion (MCAO). MRI was performed to investigate the dynamics of lesion formation. MANF protein was injected into the right lateral ventricle at 3 h after reperfusion following MCAO for 90 min, when the obvious lesion firstly appeared according to MRI investigation. T2-weighted imaging for evaluating the therapeutic effects of MANF protein was performed in ischemia/reperfusion injury rats on Days 1, 2, 3, 5, and 7 post-reperfusion combined with histology methods. The results indicated that the administration of MANF protein at the early stage after ischemia/reperfusion injury decreased the mortality, improved the neurological function, reduced the cerebral infarct volume, and alleviated the brain tissue injury. The findings collected from MRI are consistent with the morphological and pathological changes, which suggest that MRI is a useful technology for evaluating the therapeutic effects of drugs.

http://ift.tt/2bXVGgN

IJMS, Vol. 17, Pages 1482: Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

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Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses.

http://ift.tt/2c1Jbjc

Epstein-Barr virus-positive mucocutaneous ulcer

Publication date: Available online 4 September 2016
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Bo-Jung Chen, Chia-Lang Fang, Shih-Sung Chuang




http://ift.tt/2csRLes

Gasterophilus (Diptera, Gasterophilidae) infestation of equids in the Kalamaili Nature Reserve, China

Authors: Heqing Huang, Boru Zhang, Hongjun Chu, Dong Zhang and Kai Li.<br />Parasite Vol. 23 , page 36<br />Published online: 05/09/2016<br /> Keywords: Gasterophilus ; Equids ; Przewalski's horses ; Epidemiology ; Differential analysis.<img src="http://ift.tt/2bYYlFk" height="1" width="1" alt=""/>

http://ift.tt/2bRspp6

Sandflies in an urban area of transmission of visceral leishmaniasis in midwest Brazil

Authors: Maria Elizabeth Cavalheiros Dorval, Elisa Teruya Oshiro, Andreia Fernandes Brilhante, Vânia Lúcia Brandão Nunes, Geucira Cristaldo, Manoel Sebastião Costa Lima Júnior and Eunice Aparecida Bianchi Galati.<br />Parasite Vol. 23 , page 35<br />Published online: 05/09/2016<br /> Keywords: Bichromomyia flaviscutellata ; Leishmania infantum ; Lutzomyia longipalpis ; Phlebotomine ; Natural infection.<img src="http://ift.tt/2bYYbxQ" height="1" width="1" alt=""/>

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Entropy, Vol. 18, Pages 320: Using Graph and Vertex Entropy to Compare Empirical Graphs with Theoretical Graph Models

Over the years, several theoretical graph generation models have been proposed. Among the most prominent are: the Erdős–Renyi random graph model, Watts–Strogatz small world model, Albert–Barabási preferential attachment model, Price citation model, and many more. Often, researchers working with real-world data are interested in understanding the generative phenomena underlying their empirical graphs. They want to know which of the theoretical graph generation models would most probably generate a particular empirical graph. In other words, they expect some similarity assessment between the empirical graph and graphs artificially created from theoretical graph generation models. Usually, in order to assess the similarity of two graphs, centrality measure distributions are compared. For a theoretical graph model this means comparing the empirical graph to a single realization of a theoretical graph model, where the realization is generated from the given model using an arbitrary set of parameters. The similarity between centrality measure distributions can be measured using standard statistical tests, e.g., the Kolmogorov–Smirnov test of distances between cumulative distributions. However, this approach is both error-prone and leads to incorrect conclusions, as we show in our experiments. Therefore, we propose a new method for graph comparison and type classification by comparing the entropies of centrality measure distributions (degree centrality, betweenness centrality, closeness centrality). We demonstrate that our approach can help assign the empirical graph to the most similar theoretical model using a simple unsupervised learning method.

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Econometrics, Vol. 4, Pages 37: Generalized Fractional Processes with Long Memory and Time Dependent Volatility Revisited

In recent years, fractionally-differenced processes have received a great deal of attention due to their flexibility in financial applications with long-memory. This paper revisits the class of generalized fractionally-differenced processes generated by Gegenbauer polynomials and the ARMA structure (GARMA) with both the long-memory and time-dependent innovation variance. We establish the existence and uniqueness of second-order solutions. We also extend this family with innovations to follow GARCH and stochastic volatility (SV). Under certain regularity conditions, we give asymptotic results for the approximate maximum likelihood estimator for the GARMA-GARCH model. We discuss a Monte Carlo likelihood method for the GARMA-SV model and investigate finite sample properties via Monte Carlo experiments. Finally, we illustrate the usefulness of this approach using monthly inflation rates for France, Japan and the United States.

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Sustainability, Vol. 8, Pages 895: Temporal Effects of Environmental Characteristics on Urban Air Temperature: The Influence of the Sky View Factor

This study examines the relationship between air temperature and urban environment indices, mainly focusing on sky view factor (SVF) in Seoul, Korea. We use air temperature data observed from 295 automatic weather stations (AWS) during the day and night in Seoul. We conduct a spatial regression analysis to capture the effect of spatial autocorrelation in our data and identify changes in the effects of SVF on air temperature, while conducting the regression model for each dataset according to the floor area ratio (FAR). The findings of our study indicate that SVF negatively affects air temperature during both day and night when other effects are controlled through spatial regression models. Moreover, we address the environmental indices associated with day-time and night-time air temperatures and identify the changing effects of SVF on air temperature according to the areal floor area ratio of the analysis datasets. This study contributes to the literature on the relationship between SVF and air temperature in high-density cities and suggests policy implications for improving urban thermal environments with regard to urban design and planning.

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Coatings, Vol. 6, Pages 39: Deposition and Characterization of Si-Doped Diamond Films Using Tetraethoxysilane onto a WC-Co Substrate

Silicon-doped (Si-doped) diamond films were deposited on a Co-cemented tungsten carbide (WC-Co) substrate using the hot filament chemical vapor deposition (HFCVD) method with a mixture of acetone, tetraethoxysilane (TEOS), and hydrogen as the recant source. The as-deposited doped diamond films were characterized with field emission scanning electron microscopy (FE-SEM), Raman spectrum, and X-ray diffraction (XRD). Furthermore, Rockwell C indentation tests were conducted to evaluate the adhesion of the Si-doped diamond films grown on the WC-Co substrate. The results demonstrated that the silicon concentration in the reactant source played an important role in the surface morphology and adhesion of diamond films. The size of diamond grain varied from 3 μm to 500 nm with silicon concentration increasing from 0 to 1.41 atom %. When the silicon concentration rose to 1.81 atom %, the grain size became bigger than that of the lower concentration. The ratio of diamond peak {220}/{111} varied with different silicon concentrations. Raman study features revealed high purity of as-deposited diamond films. The Raman spectra also demonstrated the presence of silicon in the diamond films with Si–Si, Si–C and Si–O bonds. Si-doped diamond films with strong adhesive strength on the WC-Co substrate was beneficial for diamond films applied on cutting tools and wear resistance components.

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Polymers, Vol. 8, Pages 331: PLA with Intumescent System Containing Lignin and Ammonium Polyphosphate for Flame Retardant Textile

Using bio-based polymers to replace of polymers from petrochemicals in the manufacture of textile fibers is a possible way to improve sustainable development for the textile industry. Polylactic acid (PLA) is one of the available bio-based polymers. One way to improve the fire behavior of this bio-based polymer is to add an intumescent formulation mainly composed of acid and carbon sources. In order to optimize the amount of bio-based product in the final material composition, lignin from wood waste was selected as the carbon source. Different formulations of and/or ammonium polyphosphate (AP) were prepared by melt extrusion and then hot-pressed into sheets. The thermal properties (thermogravimetric analyses (TGA) and differential scanning calorimetry (DSC)) and fire properties (UL-94) were measured. The spinnability of the various composites was evaluated. The mechanical properties and physical aspect (microscopy) of PLA multifilaments with lignin (LK) were checked. A PLA multifilament with up to 10 wt % of intumescent formulation was processed, and the fire behavior of PLA fabrics with lignin/AP formulation was studied by cone calorimeter.

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Sensors, Vol. 16, Pages 1427: Continuous Indoor Positioning Fusing WiFi, Smartphone Sensors and Landmarks

To exploit the complementary strengths of WiFi positioning, pedestrian dead reckoning (PDR), and landmarks, we propose a novel fusion approach based on an extended Kalman filter (EKF). For WiFi positioning, unlike previous fusion approaches setting measurement noise parameters empirically, we deploy a kernel density estimation-based model to adaptively measure the related measurement noise statistics. Furthermore, a trusted area of WiFi positioning defined by fusion results of previous step and WiFi signal outlier detection are exploited to reduce computational cost and improve WiFi positioning accuracy. For PDR, we integrate a gyroscope, an accelerometer, and a magnetometer to determine the user heading based on another EKF model. To reduce accumulation error of PDR and enable continuous indoor positioning, not only the positioning results but also the heading estimations are recalibrated by indoor landmarks. Experimental results in a realistic indoor environment show that the proposed fusion approach achieves substantial positioning accuracy improvement than individual positioning approaches including PDR and WiFi positioning.

http://ift.tt/2bXXc2k

Sensors, Vol. 16, Pages 1429: Neural Network-Based Self-Tuning PID Control for Underwater Vehicles

For decades, PID (Proportional + Integral + Derivative)-like controllers have been successfully used in academia and industry for many kinds of plants. This is thanks to its simplicity and suitable performance in linear or linearized plants, and under certain conditions, in nonlinear ones. A number of PID controller gains tuning approaches have been proposed in the literature in the last decades; most of them off-line techniques. However, in those cases wherein plants are subject to continuous parametric changes or external disturbances, online gains tuning is a desirable choice. This is the case of modular underwater ROVs (Remotely Operated Vehicles) where parameters (weight, buoyancy, added mass, among others) change according to the tool it is fitted with. In practice, some amount of time is dedicated to tune the PID gains of a ROV. Once the best set of gains has been achieved the ROV is ready to work. However, when the vehicle changes its tool or it is subject to ocean currents, its performance deteriorates since the fixed set of gains is no longer valid for the new conditions. Thus, an online PID gains tuning algorithm should be implemented to overcome this problem. In this paper, an auto-tune PID-like controller based on Neural Networks (NN) is proposed. The NN plays the role of automatically estimating the suitable set of PID gains that achieves stability of the system. The NN adjusts online the controller gains that attain the smaller position tracking error. Simulation results are given considering an underactuated 6 DOF (degrees of freedom) underwater ROV. Real time experiments on an underactuated mini ROV are conducted to show the effectiveness of the proposed scheme.

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Crystals, Vol. 6, Pages 108: Crystallography of Representative MOFs Based on Pillared Cyanonickelate (PICNIC) Architecture

The pillared layer motif is a commonly used route to porous coordination polymers or metal organic frameworks (MOFs). Materials based on the pillared cyano-bridged architecture, [Ni'(L)Ni(CN)4]n (L = pillar organic ligands), also known as PICNICs, have been shown to be especially diverse where pore size and pore functionality can be varied by the choice of pillar organic ligand. In addition, a number of PICNICs form soft porous structures that show reversible structure transitions during the adsorption and desorption of guests. The structural flexibility in these materials can be affected by relatively minor differences in ligand design, and the physical driving force for variations in host-guest behavior in these materials is still not known. One key to understanding this diversity is a detailed investigation of the crystal structures of both rigid and flexible PICNIC derivatives. This article gives a brief review of flexible MOFs. It also reports the crystal structures of five PICNICS from our laboratories including three 3-D porous frameworks (Ni-Bpene, NI-BpyMe, Ni-BpyNH2), one 2-D layer (Ni-Bpy), and one 1-D chain (Ni-Naph) compound. The sorption data of BpyMe for CO2, CH4 and N2 is described. The important role of NH3 (from the solvent of crystallization) as blocking ligands which prevent the polymerization of the 1-D chains and 2-D layers to become 3D porous frameworks in the Ni-Bpy and Ni-Naph compounds is also addressed.

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IJMS, Vol. 17, Pages 1476: MRI Dynamically Evaluates the Therapeutic Effect of Recombinant Human MANF on Ischemia/Reperfusion Injury in Rats

As an endoplasmic reticulum (ER) stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to protect dopaminergic neurons and nondopaminergic cells. Our previous studies had shown that MANF protected against ischemia/reperfusion injury. Here, we developed a magnetic resonance imaging (MRI) technology to dynamically evaluate the therapeutic effects of MANF on ischemia/reperfusion injury. We established a rat focal ischemic model by using middle cerebral artery occlusion (MCAO). MRI was performed to investigate the dynamics of lesion formation. MANF protein was injected into the right lateral ventricle at 3 h after reperfusion following MCAO for 90 min, when the obvious lesion firstly appeared according to MRI investigation. T2-weighted imaging for evaluating the therapeutic effects of MANF protein was performed in ischemia/reperfusion injury rats on Days 1, 2, 3, 5, and 7 post-reperfusion combined with histology methods. The results indicated that the administration of MANF protein at the early stage after ischemia/reperfusion injury decreased the mortality, improved the neurological function, reduced the cerebral infarct volume, and alleviated the brain tissue injury. The findings collected from MRI are consistent with the morphological and pathological changes, which suggest that MRI is a useful technology for evaluating the therapeutic effects of drugs.

http://ift.tt/2bXVGgN

Cosmetics, Vol. 3, Pages 32: Packaging Evaluation Approach to Improve Cosmetic Product Safety

In the Regulation 1223/2009, evaluation of packaging has become mandatory to assure cosmetic product safety. In fact, the safety assessment of a cosmetic product can be successfully carried out only if the hazard deriving from the use of the designed packaging for the specific product is correctly evaluated. Despite the law requirement, there is too little information about the chemical-physical characteristics of finished packaging and the possible interactions between formulation and packaging; furthermore, different from food packaging, the cosmetic packaging is not regulated and, to date, appropriate guidelines are still missing. The aim of this work was to propose a practical approach to investigate commercial polymeric containers used in cosmetic field, especially through mechanical properties' evaluation, from a safety point of view. First of all, it is essential to obtain complete information about raw materials. Subsequently, using an appropriate full factorial experimental design, it is possible to investigate the variables, like polymeric density, treatment, or type of formulation involved in changes to packaging properties or in formulation-packaging interaction. The variation of these properties can greatly affect cosmetic safety. In particular, mechanical properties can be used as an indicator of pack performances and safety. As an example, containers made of two types of polyethylene with different density, low-density polyethylene (LDPE) and high-density polyethylene (HDPE), are investigated. Regarding the substances potentially extractable from the packaging, in this work the headspace solid-phase microextraction method (HSSPME) was used because this technique was reported in the literature as suitable to detect extractables from the polymeric material here employed.

http://ift.tt/2cAY4xZ

Buildings, Vol. 6, Pages 36: Thermal Assessment of Low-Cost Rural Housing—A Case Study in the Ecuadorian Andes

The aim of this research is to assess the indoor thermal performance of rural dwellings in the Ecuadorian highlands through both experimental and numerical analysis. A three-step methodology was applied to conduct the research: (a) field data collection, (b) building thermal model development and calibration, and (c) comparison analysis and assessment of traditional improvement strategies. Qualitative and quantitative data were collected from two representative rural dwellings under typical usage conditions. The first is a traditional construction, medium-exposed thermal mass dwelling (Case A). The second is a local common, uninsulated, lightweight construction (Case B). The thermal model was calibrated by comparing hourly temperature values of the observed and the predicted indoor air temperature. A high correlation level (R2) was achieved between the observed and predicted data; 0.89 in Case A and 0.94 in Case B. The results show that the roof, floor, and the airtightness are the critical building parameters affecting the indoor thermal environment. Likewise, the indoor air temperature is increased up to 4 °C through the implementation of traditional strategies. However, despite the rise in indoor air temperature, acceptable thermal comfort ranges were only reached for 25% of the total hours.

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Viruses, Vol. 8, Pages 245: Analysis of the Prevalence of HTLV-1 Proviral DNA in Cervical Smears and Carcinomas from HIV Positive and Negative Kenyan Women

The oncogenic retrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in some countries although its prevalence and relationship with other sexually transmitted infections in Sub-Saharan Africa is largely unknown. A novel endpoint PCR method was used to analyse the prevalence of HTLV-1 proviral DNA in genomic DNA extracted from liquid based cytology (LBC) cervical smears and invasive cervical carcinomas (ICCs) obtained from human immunodeficiency virus-positive (HIV+ve) and HIV-negative (HIV−ve) Kenyan women. Patient sociodemographic details were recorded by structured questionnaire and these data analysed with respect to HIV status, human papillomavirus (HPV) type (Papilocheck®) and cytology. This showed 22/113 (19.5%) of LBC's from HIV+ve patients were positive for HTLV-1 compared to 4/111 (3.6%) of those from HIV−ve women (p = 0.0002; odds ratio (OR) = 6.42 (2.07–26.56)). Only 1/37 (2.7%) of HIV+ve and none of the 44 HIV−ve ICC samples were positive for HTLV-1. There was also a significant correlation between HTLV-1 infection, numbers of sexual partners (p < 0.05) and smoking (p < 0.01). Using this unique method, these data suggest an unexpectedly high prevalence of HTLV-1 DNA in HIV+ve women in this geographical location. However, the low level of HTLV-1 detected in HIV+ve ICC samples was unexpected and the reasons for this are unclear.

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Molecules, Vol. 21, Pages 1174: Recent Advances in Recoverable Systems for the Copper-Catalyzed Azide-Alkyne Cycloaddition Reaction (CuAAC)

The explosively-growing applications of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition reaction between organic azides and alkynes (CuAAC) have stimulated an impressive number of reports, in the last years, focusing on recoverable variants of the homogeneous or quasi-homogeneous catalysts. Recent advances in the field are reviewed, with particular emphasis on systems immobilized onto polymeric organic or inorganic supports.

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Molecules, Vol. 21, Pages 1177: Palladium(II) Catalyzed Cyclization-Carbonylation-Cyclization Coupling Reaction of (ortho-Alkynyl Phenyl) (Methoxymethyl) Sulfides Using Molecular Oxygen as the Terminal Oxidant

An efficient PdII/Pd0-p-benzoquinone/hydroquinone-CuCl2/CuCl catalyst system was developed that uses environmentally friendly molecular oxygen as the terminal oxidant to catalyze the cyclization-carbonylation-cyclization coupling reaction (CCC-coupling reaction) of (o-alkynyl phenyl) (methoxymethyl) sulfides.

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Energies, Vol. 9, Pages 712: Influence of Insulating Materials on Green Building Rating System Results

This paper analyzes the impact of a change in the thermal insulating material on both the energy and environmental performance of a building, evaluated through two different green building assessment methods: Leadership in Energy and Environmental Design (LEED) and Istituto per l'innovazione e Trasparenza degli Appalti e la Compatibilità Ambientale (ITACA). LEED is one of the most qualified rating systems at an international level; it assesses building sustainability thanks to a point-based system where credits are divided into six different categories. One of these is fully related to building materials. The ITACA procedure derives from the international evaluation system Sustainable Building Tool (SBTool), modified according to the Italian context. In the region of Umbria, ITACA certification is composed of 20 technical sheets, which are classified into five macro-areas. The analysis was developed on a residential building located in the central Italy. It was built taking into account the principles of sustainability as far as both structural and technical solutions are concerned. In order to evaluate the influence of thermal insulating material, different configurations of the envelope were considered, replacing the original material (glass wool) with a synthetic one (expanded polystyrene, EPS) and two natural materials (wood fiber and kenaf). The study aims to highlight how the materials characteristics can affect building energy and environmental performance and to point out the different approaches of the analyzed protocols.

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Vaccines, Vol. 4, Pages 30: T-Regulatory Cells and Vaccination “Pay Attention and Do Not Neglect Them”: Lessons from HIV and Cancer Vaccine Trials

Efficient vaccines are characterized by the establishment of long-lived memory T cells, including T-helper (effectors and follicular) and T-regulatory cells (Tregs). While the former induces cytotoxic or antibody responses, the latter regulates immune responses by maintaining homeostasis. The role of Tregs in inflammatory conditions is ambiguous and their systematic monitoring in vaccination along with effector T-cells is not instinctive. Recent studies from the cancer field clearly showed that Tregs suppress vaccine-induced immune responses and correlate with poor clinical benefit. In HIV infection, Tregs are needed during acute infection to preserve tissue integrity from an overwhelmed activation, but are not beneficial in chronic infection as they suppress anti-HIV responses. Current assays used to evaluate vaccine-induced specific responses are limited as they do not take into account antigen-specific Tregs. However, new assays, such as the OX40 assay, which allow for the simultaneous detection of a full range of Th-responses including antigen-specific Tregs responses, can overcome these issues. In this review article we will revise the role of Tregs in vaccination and review the recent work performed in the field, including the available tools to monitor them, from novel assays to humanized mouse models.

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Micromachines, Vol. 7, Pages 158: Energy Dissipation in Graphene Mechanical Resonators with and without Free Edges

Graphene-based nanoelectromechanical systems (NEMS) have high future potential to realize sensitive mass and force sensors owing to graphene's low mass density and exceptional mechanical properties. One of the important remaining issues in this field is how to achieve mechanical resonators with a high quality factor (Q). Energy dissipation in resonators decreases Q, and suppressing it is the key to realizing sensitive sensors. In this article, we review our recent work on energy dissipation in doubly-clamped and circular drumhead graphene resonators. We examined the temperature (T) dependence of the inverse of a quality factor ( Q - 1 ) to reveal what the dominant dissipation mechanism is. Our doubly-clamped trilayer resonators show a characteristic Q - 1 -T curve similar to that observed in monolayer resonators: Q - 1 ∝ T 2 above ∼100 K and ∝ T 0.3 below ∼100 K. By comparing our results with previous experimental and theoretical results, we determine that the T 2 and T 0.3 dependences can be attributed to tensile strain induced by clamping metals and vibrations at the free edges in doubly-clamped resonators, respectively. The Q - 1 -T curve in our circular drumhead resonators indicates that removing free edges and clamping metal suppresses energy dissipation in the resonators, resulting in a linear T dependence of Q - 1 in a wide temperature range.

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The Effect of Advanced Motherhood on Newborn Offspring’s Hippocampal Neural Stem Cell Proliferation

Objective. To investigate the effect of advanced motherhood on rat hippocampal neural stem cell proliferation. Methods. Female parents were subdivided into control and old mother group by age, and neural stem cells were cultured from hippocampal tissues for 24 h newborn offspring. The diameter and numbers of neurospheres were examined by microscopy, and differences in proliferation were examined by EdU immunofluorescence, CCK-8 assay, and cell cycle analysis. Results. The number of neurospheres in the old mother group after culture was lower than the control group. Additionally, neurospheres' diameter was smaller than that of the control group (). The EdU positive rate of the old mother group was lower than that of the control group (). CCK-8 assay results showed that the absorbance values for the old mother group were lower than that of the control group at 48 h and 72 h (). The proportions of cells in the S and G2/M phases of the cell cycle for the older mother group were less than that found for the control group (). Conclusion. The proliferation rates of hippocampal NSCs seen in the older mother group were lower than that seen in the control group.

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Safety of Bronchoscopy in Patients with Echocardiographic Evidence of Pulmonary Hypertension

Background: Bronchoscopy with transbronchial and endobronchial biopsy and transbronchial needle aspiration is an important diagnostic tool in the pulmonologist's armamentarium. Safety in patients with pulmonary hypertension is controversial and many bronchoscopists consider this as a contraindication for the procedure. Objectives: To evaluate safety of bronchoscopy in patients with echocardiographic pulmonary hypertension and to compare with patients without it. Methods: Retrospective analysis of patients who underwent bronchoscopic transbronchial biopsy, endobronchial biopsy and/or endobronchial ultrasound-guided transbronchial needle aspiration. Patients were divided into two groups based on echocardiographic results: control group with systolic pulmonary artery pressure Results: One-hundred and ninety patients met the study criteria. Patients in the control group were younger with a lower incidence of chronic kidney disease. There was no difference in prevalence of congestive heart failure, obstructive airway disease, malignancy, liver disease, coagulopathy, use of antiplatelet agent or anticoagulant drugs. Incidence of minor bleeding due to bronchoscopic biopsies was 4.8% in both groups (p = 1.00). Incidence of major bleeding was similar in the groups (one patient in each group). In the control group, one patient had pneumothorax and another required prolonged mechanical ventilation (>4 h). In the eSPAP group, two patients required prolonged mechanical ventilation. There was no procedure-related mortality or sedation complications in the cohort. Conclusion: Our study provides additional support that in patients with echocardiographic evidence of pulmonary hypertension, transbronchial and endobronchial biopsies and endobronchial ultrasound-guided transbronchial needle aspiration are safe procedures.
Respiration

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Sedation for Bronchoscopy and Complications in Obese Patients

Background: Bronchoscopy is a safe and minimally invasive diagnostic tool, but no studies have reported prospectively on sedation and outcomes in patients with objectively defined obesity. Objectives: The purpose of the study is to determine if obese patients require more sedation or had more procedural complications during bronchoscopy under moderate sedation than non-obese patients. Methods: We evaluated complications and sedation requirements in non-obese versus obese patients, defined by multiple criteria including body mass index (BMI), neck circumference, abdominal height, and Mallampati scores. Results: Data were collected prospectively in 258 patients undergoing bronchoscopy under moderate sedation. By varying criteria, there were the following proportions of obese patients: 30% by BMI >30, 39% by neck circumference >40 cm, and 35% by abdominal height >22 cm in males and >20 cm in females. Sedative and analgesic dosing was not clinically significantly higher in obese patients than in non-obese patients. There was no difference in complications or procedural success based on obesity criteria. Hemoglobin oxygen desaturations occurred more often during bronchoscopy in patients with increasing Mallampati scores (p = 0.04), but this had no effect on bronchoscopy time or successful completion of the procedure. A subset of patients with previous polysomnogram-proven obstructive sleep apnea were more likely to have earlier termination of their procedure (15.8%) than patients with no diagnosed sleep apnea (2.3%; p = 0.002). Conclusion: In this prospective assessment of patients with obesity, we found neither clinically significant differences in sedation needs nor increases in complications in obese versus non-obese patients using a variety of indices of obesity.
Respiration

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High Diagnostic Value of a New Real-Time Pneumocystis PCR from Bronchoalveolar Lavage in a Real-Life Clinical Setting

Background: To diagnose Pneumocystis jirovecii pneumonia (PCP), PCR testing in bronchoalveolar lavage (BAL) fluid has recently become an alternative to immunofluorescence testing (IFT); however, its diagnostic accuracy is less clear. Objective: To analyze the diagnostic value of a new semiquantitative real-time PCR (RT-PCR) in BAL in a real-life clinical setting. Methods: Retrospective analysis of all RT-PCR results [semiquantitative: negative, weakly positive, and strongly positive; measured in cycle thresholds (Ct)] in BAL in the period between 2010 and 2014. The diagnosis of PCP was defined by clinical, radiological, and laboratory signs and by treatment initiation. Any positive PCR was compared with subsequent IFT. Results: Of 128 patient samples, 32 had PCP. There is a relevant correlation of high significance between positive PCR Ct and IFT (r = -0.7781, p Conclusion: A negative RT-PCR (Ct >45) rules out PCP. A strongly positive PCR (Ct Respiration

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Increased CD69 Expression on Peripheral Eosinophils from Patients with Food Protein-Induced Enterocolitis Syndrome

Background: Food protein-induced enterocolitis syndrome (FPIES) is an uncommon, non-IgE-mediated food allergy. We recently described a significant increase in fecal eosinophil-derived neurotoxin (EDN) after ingestion of the causative food. However, little is known about the activation status of circulating eosinophils in patients with an acute FPIES reaction. Methods: Surface CD69 expression was assessed by flow cytometry on peripheral eosinophils from 5 patients with FPIES before and after ingestion of the causative food. Fecal EDN was measured by enzyme-linked immunosorbent assay. Results: No eosinophil activation was observed before ingestion; however, a significant increase in CD69 expression on eosinophils after an acute FIPES reaction was demonstrated in all of the patients. There was no significant change in absolute eosinophil counts in the peripheral blood. The levels of fecal EDN increased on the day after ingestion of the causative food in all patients. Conclusion: These results suggest that circulating eosinophils as well as eosinophils in the intestinal mucosal tissue are activated in acute FPIES reactions and might be associated with systemic immune events in FPIES.
Int Arch Allergy Immunol 2016;170:201-205

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Cover Picture: A new fluorescent dye for cell tracing and mitochondrial imaging in vitro and in vivo (J. Biophotonics 9/2016)

Thumbnail image of graphical abstract

Mitochondria contribute to redox and calcium balance, and apoptosis thus regulating cellular fate. The described dye V07-07059 stains mitochondria effectively due to their membrane potential in vitro and in vivo. It further exhibits superior properties compared to currently used probes such as greater photostability and reduced cell toxicity. Therefore it is a novel tool for longitudinal and functional studies of mitochondria.

Further details can be found in the article by A. T. Press et al. on pp. 888–900.



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Contents: J. Biophotonics 9/2016



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Issue Information: J. Biophotonics 9/2016

No abstract is available for this article.



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Remote Sensing, Vol. 8, Pages 731: Integration of Ground and Multi-Resolution Satellite Data for Predicting the Water Balance of a Mediterranean Two-Layer Agro-Ecosystem

The estimation of site water budget is important in Mediterranean areas, where it represents a crucial factor affecting the quantity and quality of traditional crop production. This is particularly the case for spatially fragmented, multi-layer agricultural ecosystems such as olive groves, which are traditional cultivations of the Mediterranean basin. The current paper aims at demonstrating the effectiveness of spatialized meteorological data and remote sensing techniques to estimate the actual evapotranspiration (ETA) and the soil water content (SWC) of an olive orchard in Central Italy. The relatively small size of this orchard (about 0.1 ha) and its two-layer structure (i.e., olive trees and grasses) require the integration of remotely sensed data with different spatial and temporal resolutions (Terra-MODIS, Landsat 8-OLI and Ikonos). These data are used to drive a recently proposed water balance method (NDVI-Cws) and predict ETA and then site SWC, which are assessed through comparison with sap flow and soil wetness measurements taken in 2013. The results obtained indicate the importance of integrating satellite imageries having different spatio-temporal properties in order to properly characterize the examined olive orchard. More generally, the experimental evidences support the possibility of using widely available remotely sensed and ancillary datasets for the operational estimation of ETA and SWC in olive tree cultivation systems.

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Remote Sensing, Vol. 8, Pages 730: Deep-Learning-Based Classification for DTM Extraction from ALS Point Cloud

Airborne laser scanning (ALS) point cloud data are suitable for digital terrain model (DTM) extraction given its high accuracy in elevation. Existing filtering algorithms that eliminate non-ground points mostly depend on terrain feature assumptions or representations; these assumptions result in errors when the scene is complex. This paper proposes a new method for ground point extraction based on deep learning using deep convolutional neural networks (CNN). For every point with spatial context, the neighboring points within a window are extracted and transformed into an image. Then, the classification of a point can be treated as the classification of an image; the point-to-image transformation is carefully crafted by considering the height information in the neighborhood area. After being trained on approximately 17 million labeled ALS points, the deep CNN model can learn how a human operator recognizes a point as a ground point or not. The model performs better than typical existing algorithms in terms of error rate, indicating the significant potential of deep-learning-based methods in feature extraction from a point cloud.

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JMSE, Vol. 4, Pages 57: Erratum: Chen, C.Y.; Ward, D.M.; Williams, J.J.; Fisher, N.S. Metal Bioaccumulation by Estuarine Food Webs in New England, USA. J. Mar. Sci. Eng. 2016, 4, 41

The authors wish to correct the NIH grant number in this paper [1] as follows:[...]

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The Prognostic Role of Obstructive Sleep Apnea at the Onset of Amyotrophic Lateral Sclerosis

Background/Objective: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of central and peripheral motor neurons. Some studies have found discordant data in the presence of sleep apnea in ALS patients. An obstructive component also occurs with upper airways hypotonia and muscle weakness that may result in an excessive reduction of airway lumen, leading to obstructive sleep apnea (OSA). The aim of this study was to assess the role of obstructive apneic events at disease onset in the ALS prognosis. Methods: A longitudinal retrospective study was conducted on 42 clinically diagnosed ALS patients. The study population was divided into 2 groups according to their obstructive apnea/hypopnea index (AHIo): group 1 consisted of 20 patients with an AHIo ≥5 and group 2 consisted of 22 patients with an AHIo Results: The mean survival in ALS patients with an AHIo ≥5 was significantly shorter than in ALS without OSA (p = 0.0237). The sniff nasal inspiratory pressure test was significantly correlated with AHIo, time of oxyhemoglobin saturation below 90% and the oxyhemoglobin desaturation index (p Conclusions: Our study highlights the importance of an early diagnosis of OSA in ALS patients, allowing the identification of ALS patients with an OSA phenotype (AHIo ≥5), who are characterized by a worse prognosis.
Neurodegener Dis 2017;17:14-21

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Preparation of Thermosensitive Gel for Controlled Release of Levofloxacin and Their Application in the Treatment of Multidrug-Resistant Bacteria

Levofloxacin is a synthetic broad-spectrum antibacterial agent for oral or intravenous administration. Chemically, levofloxacin is the levorotatory isomer (L-isomer) of racemate ofloxacin, a fluoroquinolone antibacterial agent. Quinolone derivatives rapidly and specifically inhibit the synthesis of bacterial DNA. Levofloxacin has in vitro activity against a broad range of aerobic and anaerobic Gram-positive and Gram-negative bacteria. However, formulation of combined poloxamers thermoregulated (as Pluronic® F127) and levofloxacin for use in multiresistant bacterial treatment were poorly described in the current literature. Thus, the aim of the present work is to characterize poloxamers for levofloxacin controlled release and their use in the treatment of multidrug bacterial resistance. Micelles were produced in colloidal dispersions, with a diameter between 5 and 100 nm, which form spontaneously from amphiphilic molecules under certain conditions as concentration and temperature. Encapsulation of levofloxacin into nanospheres showed efficiency and enhancement of antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae when compared with only levofloxacin. Furthermore, all formulations were not cytotoxic for NIH/3T3 cell lineage. In conclusion, poloxamers combined with levofloxacin have shown promising results, better than alone, decreasing the minimal inhibitory concentration of the studied bacterial multiresistance strains. In the future, this new formulation will be used after being tested in animal models in patients with resistant bacterial strains.

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Key Challenges and Opportunities Associated with the Use of In Vitro Models to Detect Human DILI: Integrated Risk Assessment and Mitigation Plans

Drug-induced liver injury (DILI) is a major cause of late-stage clinical drug attrition, market withdrawal, black-box warnings, and acute liver failure. Consequently, it has been an area of focus for toxicologists and clinicians for several decades. In spite of considerable efforts, limited improvements in DILI prediction have been made and efforts to improve existing preclinical models or develop new test systems remain a high priority. While prediction of intrinsic DILI has improved, identifying compounds with a risk for idiosyncratic DILI (iDILI) remains extremely challenging because of the lack of a clear mechanistic understanding and the multifactorial pathogenesis of idiosyncratic drug reactions. Well-defined clinical diagnostic criteria and risk factors are also missing. This paper summarizes key data interpretation challenges, practical considerations, model limitations, and the need for an integrated risk assessment. As demonstrated through selected initiatives to address other types of toxicities, opportunities exist however for improvement, especially through better concerted efforts at harmonization of current, emerging and novel in vitro systems or through the establishment of strategies for implementation of preclinical DILI models across the pharmaceutical industry. Perspectives on the incorporation of newer technologies and the value of precompetitive consortia to identify useful practices are also discussed.

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Meta-Analysis of the Association between Vitiligo and Human Leukocyte Antigen-A

Objective. The objective of this study was to systematically evaluate the association between vitiligo and human leukocyte antigen- (HLA-) A. Methods. PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, and reference lists were searched for relevant original articles. Results. Nineteen case-control studies comprising 3042 patients and 5614 controls were included, in which 33 HLA-A alleles were reported. Overall, three alleles (HLA-02, 33, and A31) were significantly associated with increased risk of vitiligo, two (HLA-09 and A19) were associated with decreased risk, and the remaining 28 were unassociated. Twelve alleles, seven alleles, and 19 alleles were common to three ethnicities, both types of vitiligo, and both typing methods, respectively. In the subgroup analysis by ethnicity and typing methods, the association of six alleles and five alleles was inconsistent in three populations and both typing methods, respectively. In the subgroup analysis by clinical type, the association of all seven alleles was consistent in both types of vitiligo. Conclusion. The meta-analysis suggests that HLA-02, 33, and A31 are associated with increased risk of vitiligo, while HLA-09 and A19 are associated with decreased risk of vitiligo. The association of some alleles varies in terms of ethnicity and typing methods.

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Analyzing the miRNA-Gene Networks to Mine the Important miRNAs under Skin of Human and Mouse

Genetic networks provide new mechanistic insights into the diversity of species morphology. In this study, we have integrated the MGI, GEO, and miRNA database to analyze the genetic regulatory networks under morphology difference of integument of humans and mice. We found that the gene expression network in the skin is highly divergent between human and mouse. The GO term of secretion was highly enriched, and this category was specific in human compared to mouse. These secretion genes might be involved in eccrine system evolution in human. In addition, total 62,637 miRNA binding target sites were predicted in human integument genes (IGs), while 26,280 miRNA binding target sites were predicted in mouse IGs. The interactions between miRNAs and IGs in human are more complex than those in mouse. Furthermore, hsa-miR-548, mmu-miR-466, and mmu-miR-467 have an enormous number of targets on IGs, which both have the role of inhibition of host immunity response. The pattern of distribution on the chromosome of these three miRNAs families is very different. The interaction of miRNA/IGs has added the new dimension in traditional gene regulation networks of skin. Our results are generating new insights into the gene networks basis of skin difference between human and mouse.

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rLj-RGD3, a Novel Three-RGD-Motif-Containing Recombinant Protein from Lampetra japonica, Protects PC12 Cells from Injury Induced by Oxygen-Glucose Deprivation and Reperfusion

rLj-RGD3 is a 14.5 kDa recombinant protein with 3 RGD (Arg-Gly-Asp) motifs from the salivary gland secretions of Lampetra japonica, which is a histidine-rich and arginine-rich protein. Previous reports indicated that rLj-RGD3 has typical functions of RGD-toxin protein, such as platelet aggregation suppression tumour metastasis and angiogenesis inhibition. Because histidine and arginine have cerebral ischemia-reperfusion and neuroprotective functions, we investigated whether rLj-RGD3 has such activities and studied the mechanism. The effects of rLj-RGD3 on neuroprotection and antiapoptosis were determined. The expression level of focal adhesion kinase (FAK), p-FAK, Caspase-3, and Bcl-2 after oxygen-glucose deprivation and reperfusion (OGD-R) was examined. The viability of PC12 cells incubated with rLj-RGD3 at high concentrations (16 μmol/L) increased significantly due to its ability to protect the cells from apoptosis after OGD-R-induced injury. Furthermore, rLj-RGD3 attenuated the damage due to OGD-R. Most of the PC12 cells were apoptotic after OGD-R. In contrast, the number of apoptotic PC12 cells was significantly decreased in the group treated with a high-dose of rLj-RGD3. In addition, rLj-RGD3 activated FAK and p-FAK protein. rLj-RGD3 inhibited Caspase-3 and upregulated Bcl-2 protein expression in PC12 cells after OGD-R. The study provides the first evidence for neuroprotective effects of rLj-RGD3 in ischemic injury that may be partly mediated through inhibition of Caspase-3 and upregulation of Bcl-2, FAK, and p-FAK protein expression.

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Autoimmunity and the microbiome: T-cell receptor mimicry of “self” and microbial antigens mediates self tolerance in holobionts

I propose a T-cell receptor (TcR)-based mechanism by which immunity mediates both "genetic self" and "microbial self" thereby, connecting microbiome disease with autoimmunity. The hypothesis is based on simple principles. First, TcR are selected to avoid strong cross-reactivity with "self," resulting in selection for a TcR repertoire mimicking "genetic self." Second, evolution has selected for a "microbial self" that mimics "genetic self" so as to share tolerance. In consequence, our TcR repertoire also mimics microbiome antigenicity, providing a novel mechanism for modulating tolerance to it. Also, the microbiome mimics the TcR repertoire, acting as a secondary immune system. I call this TcR-microbiome mimicry "holoimmunity" to denote immune tolerance to the "holobiont self." Logically, microbiome-host mimicry means that autoimmunity directed at host antigens will also attack components of the microbiome, and conversely, an immunological attack on the microbiome may cross-react with host antigens producing "holoautoimmunity."

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T-cell receptors (TcR) and antibodies are selected to mimic "self" antigens. The microbiome avoids immunity by mimicking "self" antigens and TcR ("holoimmunity"). Pathogens, however, are complementary to "self," TcR, and the microbiome. A pathogen that also mimics "self" can trigger autoimmunity to the host, TcR, and microbiome simultaneously ("holoautoimmunity").



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Antibodies, Vol. 5, Pages 19: Antibody Aggregation: Insights from Sequence and Structure

Monoclonal antibodies (mAbs) are the fastest-growing biological therapeutics with important applications ranging from cancers, autoimmunity diseases and metabolic disorders to emerging infectious diseases. Aggregation of mAbs continues to be a major problem in their developability. Antibody aggregation could be triggered by partial unfolding of its domains, leading to monomer-monomer association followed by nucleation and growth. Although the aggregation propensities of antibodies and antibody-based proteins can be affected by the external experimental conditions, they are strongly dependent on the intrinsic antibody properties as determined by their sequences and structures. In this review, we describe how the unfolding and aggregation susceptibilities of IgG could be related to their cognate sequences and structures. The impact of antibody domain structures on thermostability and aggregation propensities, and effective strategies to reduce aggregation are discussed. Finally, the aggregation of antibody-drug conjugates (ADCs) as related to their sequence/structure, linker payload, conjugation chemistry and drug-antibody ratio (DAR) is reviewed.

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Separations, Vol. 3, Pages 27: Chromatographic Studies of Protein-Based Chiral Separations

The development of separation methods for the analysis and resolution of chiral drugs and solutes has been an area of ongoing interest in pharmaceutical research. The use of proteins as chiral binding agents in high-performance liquid chromatography (HPLC) has been an approach that has received particular attention in such work. This report provides an overview of proteins that have been used as binding agents to create chiral stationary phases (CSPs) and in the use of chromatographic methods to study these materials and protein-based chiral separations. The supports and methods that have been employed to prepare protein-based CSPs will also be discussed and compared. Specific types of CSPs that are considered include those that employ serum transport proteins (e.g., human serum albumin, bovine serum albumin, and alpha1-acid glycoprotein), enzymes (e.g., penicillin G acylase, cellobiohydrolases, and α-chymotrypsin) or other types of proteins (e.g., ovomucoid, antibodies, and avidin or streptavidin). The properties and applications for each type of protein and CSP will also be discussed in terms of their use in chromatography and chiral separations.

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Water, Vol. 8, Pages 379: Soil CO2 Uptake in Deserts and Its Implications to the Groundwater Environment

Recent studies of soil carbon cycle in arid and semi-arid ecosystems demonstrated that there exists an abiotic CO2 absorption by saline-alkali soils (Aa) at desert ecosystems and suggested potential contributions of CO2 dissolution beneath deserts to the terrestrial ecosystems carbon balance. However, the overall importance of such soil CO2 uptake is still undetermined and its implications to the groundwater environment remain unaddressed. In this manuscript, a simple method is proposed for the direct computation of Aa from the total soil CO2 flux (Fa) as well as for the evaluation of Aa importance to Fa. An artificial soil-groundwater system was employed to investigate the implications to groundwater environment and it was found that soil CO2 uptake in deserts can contribute a possible influence on the evolution of the groundwater environment, providing that the absorbed CO2 largely remained in the soil-groundwater system.

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Climate, Vol. 4, Pages 43: Polar Cyclone Identification from 4D Climate Data in a Knowledge-Driven Visualization System

Arctic cyclone activity has a significant association with Arctic warming and Arctic ice decline. Cyclones in the North Pole are more complex and less developed than those in tropical regions. Identifying polar cyclones proves to be a task of greater complexity. To tackle this challenge, a new method which utilizes pressure level data and velocity field is proposed to improve the identification accuracy. In addition, the dynamic, simulative cyclone visualized with a 4D (four-dimensional) wind field further validated the identification result. A knowledge-driven system is eventually constructed for visualizing and analyzing an atmospheric phenomenon (cyclone) in the North Pole. The cyclone is simulated with WebGL on in a web environment using particle tracing. To achieve interactive frame rates, the graphics processing unit (GPU) is used to accelerate the process of particle advection. It is concluded with the experimental results that: (1) the cyclone identification accuracy of the proposed method is 95.6% when compared with the NCEP/NCAR (National Centers for Environmental Prediction/National Center for Atmospheric Research) reanalysis data; (2) the integrated knowledge-driven visualization system allows for streaming and rendering of millions of particles with an interactive frame rate to support knowledge discovery in the complex climate system of the Arctic region.

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Remote Sensing, Vol. 8, Pages 732: Mapping Daily Air Temperature for Antarctica Based on MODIS LST

Spatial predictions of near-surface air temperature ( T a i r ) in Antarctica are required as baseline information for a variety of research disciplines. Since the network of weather stations in Antarctica is sparse, remote sensing methods have large potential due to their capabilities and accessibility. Based on the MODIS land surface temperature (LST) data, T a i r at the exact time of satellite overpass was modelled at a spatial resolution of 1 km using data from 32 weather stations. The performance of a simple linear regression model to predict T a i r from LST was compared to the performance of three machine learning algorithms: Random Forest (RF), generalized boosted regression models (GBM) and Cubist. In addition to LST, auxiliary predictor variables were tested in these models. Their relevance was evaluated by a Cubist-based forward feature selection in conjunction with leave-one-station-out cross-validation to reduce the impact of spatial overfitting. GBM performed best to predict T a i r using LST and the month of the year as predictor variables. Using the trained model, T a i r could be estimated with a leave-one-station-out cross-validated R 2 of 0.71 and a RMSE of 10.51 ∘ C. However, the machine learning approaches only slightly outperformed the simple linear estimation of T a i r from LST ( R 2 of 0.64, RMSE of 11.02 ∘ C). Using the trained model allowed creating time series of T a i r over Antarctica for 2013. Extending the training data by including more years will allow developing time series of T a i r from 2000 on.

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