JSAN, Vol. 8, Pages 5: IoT-Based Solid Waste Management Solutions: A Survey

JSAN, Vol. 8, Pages 5: IoT-Based Solid Waste Management Solutions: A Survey

Journal of Sensor and Actuator Networks doi: 10.3390/jsan8010005

Authors: Kellow Pardini Joel J. P. C. Rodrigues Sergei A. Kozlov Neeraj Kumar Vasco Furtado

With the increase of population density and the rural exodus to cities, urbanization is assuming extreme proportions and presents a tremendous urban problem related to waste generation. The increase of waste generation has been considered a significant challenge to large urban centers worldwide and represents a critical issue for countries with accelerated population growth in cities. The Internet of Things (IoT) and cloud computing offer an automation possibility through cyberphysical systems that will change the way solid waste management is performed. Considering IoT requirements, a review analysis of waste management models available in the literature is performed in detail in this paper. Then, a deep review is undertaken of the related literature based on IoT infrastructure for efficient handling of waste generated in urban scenarios, focusing on the interaction among concessionaires and waste generators (citizens) from the perspective of a shorter collection time with reduced costs, as well as citizenship promotion. An IoT-based reference model is described, and a comparison analysis of the available solutions is presented, with the goal to highlight the most relevant approaches and identify open research issues on the topic.

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JSAN, Vol. 8, Pages 4: Impact of Multi-Sensor Technology for Enhancing Global Security in Closed Environments Using Cloud-Based Resources

JSAN, Vol. 8, Pages 4: Impact of Multi-Sensor Technology for Enhancing Global Security in Closed Environments Using Cloud-Based Resources

Journal of Sensor and Actuator Networks doi: 10.3390/jsan8010004

Authors: Saleh Altowaijri Mohamed Ayari Yamen El Touati

By nature, some jobs are always in closed environments and employees may stay for long periods. This is the case for many professional activities such as military watch tours of borders, civilian buildings and facilities that need efficient control processes. The role assigned to personnel in such environments is usually sensitive and of high importance, especially in terms of security and protection. With this in mind, we proposed in our research a novel approach using multi-sensor technology to monitor many safety and security parameters including the health status of indoor workers, such as those in watchtowers and at guard posts. In addition, the data gathered for those employees (heart rate, temperature, eye movement, human motion, etc.) combined with the room's sensor data (temperature, oxygen ratio, toxic gases, air quality, etc.) were saved by appropriate cloud services, which ensured easy access to the data without ignoring the privacy protection aspect of such critical material. This information can be used later by specialists to monitor the evolution of the worker's health status as well as its cost-effectiveness, which gives the possibility to improve productivity in the workplace and general employee health.

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2018 Rosetta Stones Roundup: A Very Hot Year for Geology

We take a look back at some of the hottest geology of 2018, and get a glimpse of what 2019 has to offer.

-- Read more on ScientificAmerican.com

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A novel fuzzy rule extraction approach using Gaussian kernel-based granular computing

Abstract

In this paper, we present a novel fuzzy rule extraction approach by employing the Gaussian kernels and fuzzy concept lattices. First we introduce the Gaussian kernel to interval type-2 fuzzy rough sets to model fuzzy similarity relations and introduce a few concepts and theorems to improve the classification performance with fewer attributes accordingly. Based on this idea, we propose a novel attribute reduction algorithm, which can achieve better classification performance of deducing reduction subset of fewer attributes, and this will be used in the subsequent decision rule extraction. Then we justify the necessary and sufficient conditions of our fuzzy rule extraction approach through three implicit rule theorems and present a novel fuzzy decision rule extraction algorithm using fuzzy concept lattices and introduce the concepts of frequent nodes and candidate 2-tuples to our pruning strategy. Also, comparative performance experiments are carried out on the UCI datasets, and the results of both reduction subset size and classification ability show the advantages of our algorithm.

http://bit.ly/2Qb8oLf

Robust Shrinkage Range Estimation Algorithms Based on Hampel and Skipped Filters

Herein, we present robust shrinkage range estimation algorithms for which received signal strength measurements are used to estimate the distance between emitter and sensor. The concepts of robustness for the Hampel filter and skipped filter are combined with shrinkage for the positive blind minimax and Bayes shrinkage estimation. It is demonstrated that the estimation accuracies of the proposed methods are higher than those of the existing median-based shrinkage methods through extensive simulations.

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Fixed Point Theory and Positive Solutions for a Ratio-Dependent Elliptic System

We consider a ratio-dependent predator-prey model under zero Dirichlet boundary condition. By using topological degree theory and fixed index theory, we study the necessary and sufficient conditions for the existence of positive solutions. Then we present the asymptotic behavior analysis of positive solutions, by bifurcation theory and energy estimates.

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A Destination Prediction Network Based on Spatiotemporal Data for Bike-Sharing

Bike-sharing is a new low-carbon and environment-friendly mode of public transport based on the "sharing economy". Since 2017, the bike-sharing market has boomed in China's major cities. Bikes equipped with GPS transmitters are docked along sidewalks that can be easily accessed through smartphone apps. However, this new form of transport has also led to problems, such as illegal parking, vandalism, and theft, each of which presents a major administrative challenge. Further, imbalances in user demand and bike availability need to be overcome to ensure a convenient, flexible service for customers. Hence, predicting a cyclist's destination could be of great importance to shared-bike operators. In this paper, we propose an innovative deep learning model to predict the most probable destination for each user. The model, called destination prediction network based on spatiotemporal data (DPNst), comprises three steps. First, the data is preprocessed and a pool of likely candidate destinations is generated based on frequent item mining. This candidate set is then used to build the DPNst model: a long short-term memory network learns the user's behavior; a convolutional neural network learns the spatial relationships between the origin and the candidate destinations; and a fully connected neural network learns the external features. In the final step, DPNst dynamically aggregates the output of the three neural networks based on the given data and generates the predictions. In a series of experiments on real-world stationless bike-sharing data, DPNst returned an F1 score of 42.71% and demonstrated better performance overall than the compared baselines.

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A Cloud Service Trust Evaluation Model Based on Combining Weights and Gray Correlation Analysis

Cloud services are cloud computing resources and applications deployed on the Internet or cloud computing platform, and users can access the required cloud services at any time. However, users face the diversity and complexity of quality of service (QoS) when evaluating and selecting cloud services. Therefore, it is important to study and establish an effective and objective trust model to improve user satisfaction and interaction success rate. In this paper, a model based on combining weights and gray correlation analysis is proposed. Firstly, direct trust, recommendation trust, and reputation together form a comprehensive trust, resulting in a more accurate overall trust. Second, rough set theory and analytic hierarchy process (AHP)-based method are used for the direct trust. Meanwhile, the degree of similarity recommendation trust is calculated by a gray relational analysis method. In order to ensure the accuracy of direct trust, this paper proposes a dynamic trust update mechanism. Finally, the simulation experiment is carried out to verify that the cloud services trust evaluation model (CSTEM) is more robust than the other three methods. It protects against malicious entities; at the same time, it can increase user satisfaction and interaction success rate.

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Corrigendum to “Total Intravenous Anaesthesia with High-Dose Remifentanil Does Not Aggravate Postoperative Nausea and Vomiting and Pain, Compared with Low-Dose Remifentanil: A Double-Blind and Randomized Trial”

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Spectral Collocation Method for Fractional Differential/Integral Equations with Generalized Fractional Operator

Generalized fractional operators are generalization of the Riemann-Liouville and Caputo fractional derivatives, which include Erdélyi-Kober and Hadamard operators as their special cases. Due to the complicated form of the kernel and weight function in the convolution, it is even harder to design high order numerical methods for differential equations with generalized fractional operators. In this paper, we first derive analytical formulas for order fractional derivative of Jacobi polynomials. Spectral approximation method is proposed for generalized fractional operators through a variable transform technique. Then, operational matrices for generalized fractional operators are derived and spectral collocation methods are proposed for differential and integral equations with different fractional operators. At last, the method is applied to generalized fractional ordinary differential equation and Hadamard-type integral equations, and exponential convergence of the method is confirmed. Further, based on the proposed method, a kind of generalized grey Brownian motion is simulated and properties of the model are analyzed.

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On the Alpha Power Transformed Power Lindley Distribution

In this paper, we introduce a new generalization of the power Lindley distribution referred to as the alpha power transformed power Lindley (APTPL). The APTPL model provides a better fit than the power Lindley distribution. It includes the alpha power transformed Lindley, power Lindley, Lindley, and gamma as special submodels. Various properties of the APTPL distribution including moments, incomplete moments, quantiles, entropy, and stochastic ordering are obtained. Maximum likelihood, maximum products of spacings, and ordinary and weighted least squares methods of estimation are utilized to obtain the estimators of the population parameters. Extensive numerical simulation is performed to examine and compare the performance of different estimates. Two important data sets are employed to show how the proposed model works in practice.

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Standalone Containment Analysis of Four Phébus Tests with the ASTEC and the MELCOR Codes

After the severe accident (SA) occurred at the Three-Miles Island Nuclear Power Plant (NPP), important efforts on the investigation of the different phenomena during this kind of accidents have been started. Several experimental campaigns investigating one phenomenon at time or the combination of two or more phenomena have been performed. Today, the Phébus experimental campaign is probably the most important activity on the evaluation of the coupling among different phenomena. Four out of five tests investigated the degradation of an intact Pressurized Water Reactor (PWR) fuel bundle and the subsequent transport of Fission Products (FP) and Structural Materials (SM) through the primary circuit and into the containment, while the fifth test was only the degradation of a bed of PWR fuel bundle debris. These tests were performed between 1990 and 2010 at the CEA Cadarache laboratories (France) in a 5000:1 scaled facility. The main four tests varied the employed control rod materials, the fuel burn-up, and the oxidizing conditions of the atmosphere (strongly or weakly). The outcomes of this experimental campaign created a solid base for the understanding of the involved phenomena and allowed the development of models and software codes capable of simulating the evolution of a SA in a real NPP. ASTEC and MELCOR were two of the main SA codes profiting from the results of this Phébus campaign. These two codes were further improved in the latest years to account for the findings obtained in more recent experimental campaigns. A continuous verification and validation work is then necessary to check how the newer code's versions reproduce the tests performed in these older experimental campaigns such as Phébus one. The present work is intended to be the final step of a series of publications covering the activities carried out at University of Pisa with the ASTEC and the MELCOR SA codes on the four Phébus tests employing an intact PWR fuel bundle. Because of the complexity and the extent of these tests, only the containment aspects were considered in the precedent works, i.e., only the thermal-hydraulics transient and its coupling with the FP and SM behavior. Then, general conclusions based on the outcomes of these precedent works are summarized in this work.

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Exclusive Breastfeeding Practice and Associated Factors among Mothers in Boditi Town, Wolaita Zone, Southern Ethiopia, 2018: A Community-Based Cross-Sectional Study

Background. Exclusive breastfeeding tops the table of life-saving interventions for newborns. A child who is exclusively breastfed is 14 times less likely to die in the first six months compared to its counterpart. Approximately 18,000 children globally still die every day and if current trend continues, some 60 million children under age 5 will die between 2017 and 2030, and half of them will be newborns. Five countries, including Ethiopia, accounted for half of all newborn deaths in the world. Objective. To assess the prevalence and associated factors of exclusive breastfeeding practice among mothers who have infants 6-12 months of age in Boditi Town, Wolaita Zone, Southern Ethiopia, 2018. Methods. Community-based cross-sectional study was conducted among 412 randomly selected mothers having 6 to 12 month infants from April 1 to 14, 2018. A pretested interviewer administered questionnaire was used for data collection. The data were entered using Epi Data version 3.1 and analyzed using SPSS version 20. Descriptive statistics was made. Bivariate and multivariate logistic regression was also carried out to see the effect of each independent variable on the dependent variable. Results. Of 412 mother-infant pairs sampled, 403 were participated, which made a response rate of 97.8%. Prevalence of EBF computed using since birth dietary recall method was 64.8% (95% C.I= 60.0, 69.0). From multivariable analysis, child birth attended by health care provider (AOR = 5.303, 95% C.I = 1.613, 17.436), postnatal care utilization (AOR = 1.91, C.I = 1.083, 3.370), and mothers who did not report any breast related problem for the first six months after child birth (AOR = 1.864, C.I = 1.090, 3.189) were factors positively associated with exclusive breastfeeding practice. Conclusion. Although the prevalence of exclusive breastfeeding practice in this study was relatively high, more effort to meet World Health Organization (WHO) recommendations is still necessary to benefit from its intervention. There is a need to promote child births to be attended by health care providers and postnatal care utilization. Further, women should be educated on what to do and where to seek care if breast problem occurs after child birth.

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JCM, Vol. 8, Pages 33: Polymorphisms in ERCC5 rs17655 and ERCC1 rs735482 Genes Associated with the Survival of Male Patients with Postoperative Oral Squamous Cell Carcinoma Treated with Adjuvant Concurrent Chemoradiotherapy

JCM, Vol. 8, Pages 33: Polymorphisms in ERCC5 rs17655 and ERCC1 rs735482 Genes Associated with the Survival of Male Patients with Postoperative Oral Squamous Cell Carcinoma Treated with Adjuvant Concurrent Chemoradiotherapy

Journal of Clinical Medicine doi: 10.3390/jcm8010033

Authors: Thomas Senghore Huei-Tzu Chien Wen-Chang Wang You-Xin Chen Chi-Kuang Young Shiang-Fu Huang Chih-Ching Yeh

The nucleotide excision repair (NER) pathway plays a major role in the repair of DNA damaged by exogenous agents, such as chemotherapeutic and radiotherapeutic agents. Thus, we investigated the association between key potentially functional single nucleotide polymorphisms (SNPs) in the NER pathway and clinical outcomes in oral squamous cell carcinoma (OSCC) patients treated with concurrent chemoradiotherapy (CCRT). Thirteen SNPs in five key NER genes were genotyped in 319 male OSCC patients using iPLEX MassARRAY. Cox proportional hazards models and Kaplan–Meier survival curves were used to estimate the risk of death or recurrence. Carriers of the XPC rs2228000 TT genotype showed a borderline significant increased risk of poor overall survival under the recessive model (hazard ratio (HR) = 1.81, 95% confidence interval (CI) = 0.99–3.29). The CC genotypes of ERCC5 rs17655 (HR = 1.54, 95% CI = 1.03–2.29) and ERCC1 rs735482 (HR = 1.65, 95% CI = 1.06–2.58) were associated with an increased risk of worse disease-free survival under the recessive model. In addition, participants carrying both the CC genotypes of ERCC5 rs17655 and ERCC1 rs735482 exhibited an enhanced susceptibility for recurrence (HR = 2.60, 95% CI = 1.11–6.09). However, no statistically significant interaction was observed between them. Our findings reveal that the ERCC5 rs17655 CC and ERCC1 rs735482 CC genotypes were associated with an increased risk of recurrence in male patients with OSCC treated with CCRT. Therefore, CCRT may not be beneficial, and alternative treatments are required for such patients.

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JCM, Vol. 8, Pages 34: Impact of Self-Rated Health on Progression to a Metabolically Unhealthy Phenotype in Metabolically Healthy Obese and Non-Obese Individuals

JCM, Vol. 8, Pages 34: Impact of Self-Rated Health on Progression to a Metabolically Unhealthy Phenotype in Metabolically Healthy Obese and Non-Obese Individuals

Journal of Clinical Medicine doi: 10.3390/jcm8010034

Authors: Mi-Hyun Kim Yoosoo Chang Hyun-Suk Jung Hocheol Shin Seungho Ryu

We examined the association between self-rated health (SRH), a subjective measure of an individual’s health status, and the incidence of metabolic abnormalities, as well as the effect of obesity on this association in metabolically healthy individuals. The cohort study included 85,377 metabolically healthy men and women who were followed annually or biennially for a median of 3.0 years (interquartile range, 1.9–4.1 years). A parametric proportional hazard model was used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between SRH and the incidence of metabolic abnormalities. During 258,689.03 person-years, 40,858 participants developed metabolic abnormalities. Poorer SRH was significantly associated with increased risk of developing any metabolic abnormality including hypertriglyceridemia, high homeostasis model assessment of insulin resistance (HOMA-IR), and fatty liver in a dose-dependent manner (p for trend <0.05). The association between SRH and progression to metabolically unhealthy status was much stronger in individuals with obesity than those without, especially in relation to any metabolic abnormality, fatty liver, and high C-reactive protein (all p for interaction by obesity <0.05). The multivariable-adjusted HR (95% CI) for any metabolic abnormality comparing the “poor or very poor” vs. the “very good” self-rated health category was 0.97 (0.90–1.05) among non-obese subjects, whereas the corresponding HR (95% CI) among obese subjects was 1.25 (1.02–1.52). Low SRH, as assessed by a single question, was independently associated with increased risk of progression to metabolically unhealthy status in metabolically healthy individuals, especially metabolically healthy individuals with obesity. SRH may help identify individuals at high risk for progression to metabolically unhealthy status.

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Pathogens, Vol. 8, Pages 2: Staphylococcus aureus Superantigen-Like Protein SSL1: A Toxic Protease

Pathogens, Vol. 8, Pages 2: Staphylococcus aureus Superantigen-Like Protein SSL1: A Toxic Protease

Pathogens doi: 10.3390/pathogens8010002

Authors: Aihua Tang Armando R. Caballero Michael A. Bierdeman Mary E. Marquart Timothy J. Foster Ian R. Monk Richard J. O'Callaghan

Staphylococcus aureus is a major cause of corneal infections that can cause reduced vision, even blindness. Secreted toxins cause tissue damage and inflammation resulting in scars that lead to vision loss. Identifying tissue damaging proteins is a prerequisite to limiting these harmful reactions. The present study characterized a previously unrecognized S. aureus toxin. This secreted toxin was purified from strain Newman ΔhlaΔhlg, the N-terminal sequence determined, the gene cloned, and the purified recombinant protein was tested in the rabbit cornea. The virulence of a toxin deletion mutant was compared to its parent and the mutant after gene restoration (rescue strain). The toxin (23 kDa) had an N-terminal sequence matching the Newman superantigen-like protein SSL1. An SSL1 homodimer (46 kDa) had proteolytic activity as demonstrated by zymography and cleavage of a synthetic substrate, collagens, and cytokines (IL-17A, IFN-γ, and IL-8); the protease was susceptible to serine protease inhibitors. As compared to the parent and rescue strains, the ssl1 mutant had significantly reduced virulence, but not reduced bacterial growth, in vivo. The ocular isolates tested had the ssl1 gene, with allele type 2 being the predominant type. SSL1 is a protease with corneal virulence and activity on host defense and structural proteins.

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Pore Network Investigation of Trapped Gas and Foam Generation Mechanisms

Abstract

The mobility of gas is greatly reduced when the injected gas is foamed. The reduction in gas mobility is attributed to the reduction in gas relative permeability and the increase in gas effective viscosity. The reduction in the gas relative permeability is a consequence of the larger amount of gas trapped when foam is present while the increase in gas effective viscosity is explicitly a function of foam texture. Therefore, understanding how foam is generated and subsequent trapped foam behavior is of paramount importance to modeling of gas mobility. In this paper, we push the envelope to enlighten our decisions of which descriptions are most physical to foam flow in porous media regarding both the flowing foam fraction and the rate of generation. We use a statistical pore network interwoven with the invasion percolation with memory algorithm to model foam flow as a drainage process and investigate the dependence of the flowing foam fraction on the pressure gradient and to shed light on foam generation mechanisms. A critical snap-off probability is required for strong foam to emerge in our network. The pressure gradient and, hence, the gas mobility reduction are very low below this critical snap-off probability. Above this snap-off probability threshold, we find that the steady-state flowing lamellae fraction scales as \((\nabla \tilde{p})^{0.19}\) in 2D lattices and as \((\nabla \tilde{p})^{0.32}\) in 3D lattices. Results obtained from our network were convolved with percolation network scaling ideas to compare the probabilities of snap-off and lamella division mechanisms in the network during the initial gas displacement at the leading edge of the gas front. At this front, during strong foam flow, lamella division is practically nonexistent in 2D lattices. In 3D lattices, lamella division occurs, but the probability of snap-off is always greater than the probability of lamella division.

http://bit.ly/2F2M58J

Potentiation of a neuronal nicotinic receptor via pseudo-agonist site

Abstract

Neuronal nicotinic receptors containing α4 and β2 subunits assemble in two pentameric stoichiometries, (α4)₃(β2)₂ and (α4)₂(β2)₃, each with distinct pharmacological signatures; (α4)₃(β2)₂ receptors are strongly potentiated by the drug NS9283, whereas (α4)₂(β2)₃ receptors are unaffected. Despite this stoichiometry-selective pharmacology, the molecular identity of the target for NS9283 remains elusive. Here, studying (α4)₃(β2)₂ receptors, we show that mutations at either the principal face of the β2 subunit or the complementary face of the α4 subunit prevent NS9283 potentiation of ACh-elicited single-channel currents, suggesting the drug targets the β2–α4 pseudo-agonist sites, the α4–α4 agonist site, or both sites. To distinguish among these possibilities, we generated concatemeric receptors with mutations at specified subunit interfaces, and monitored the ability of NS9283 to potentiate ACh-elicited single-channel currents. We find that a mutation at the principal face of the β2 subunit at either β2–α4 pseudo-agonist site suppresses potentiation, whereas mutation at the complementary face of the α4 subunit at the α4–α4 agonist site allows a significant potentiation. Thus, monitoring potentiation of single concatemeric receptor channels reveals that the β2–α4 pseudo-agonist sites are required for stoichiometry-selective drug action. Together with the recently determined structure of the (α4)₃(β2)₂ receptor, the findings have implications for structure-guided drug design.

http://bit.ly/2CIImvu

Mentor-spotting: recommending expert mentors to mentees for live trouble-shooting in Codementor

Abstract

Live mentoring services are recent novel social media, in which mentees can input expertise requests and wait for accepting some expert mentor who is willing to tackle the requests in a live and one-by-one manner. While mentee's satisfaction of being mentored is determined by the matched mentor, it is crucial to have an effective mentor–mentee matching. This paper aims at recommending mentors based on the requests in Codementor, which is one of the popular live mentoring services. An accurate mentor recommendation will support the mentees' decisions in finding suitable mentors, support the mentors' decisions in filtering out irrelevant requests, and support the mentoring services' decisions in assigning mentors to mentees. We divide the mentor recommendation problem into two tasks, Mentor Willingness Prediction (MWP) and Mentee Acceptance Prediction (MAP). MWP is to predict whether a mentor is willing to tackle a request, while MAP is to predict whether a mentee user will accept a recommended mentor. We propose to simultaneously deal with such two tasks by recommending a ranked list of mentors such that the recommended mentors who are really willing to tackle the request are as many as possible (MWP) and the final mentor who is accepted by the mentee can be ranked as high as possible (MAP). We develop four categories of features, availability, capability, activity, and proximity, to model the willingness of a mentor dealing with the request and the potential of a mentee to accept the recommended mentor. By applying various supervised learning methods, experimental results show the effectiveness of these features and provide extensive analyses to reveal more factors that can affect the quality of mentor recommendation. In addition, we also conduct a user study on Codementor platform to exhibit the practical performance of the proposed method. The innovation of this work includes the formulation of MWP and MAP problem in online mentoring services, feature engineering for mentoring prediction tasks, and data-driven experimental studies in prediction and a practical user study.

http://bit.ly/2LGAHAw

JSAN, Vol. 8, Pages 3: A Fleet of MEC UAVs to Extend a 5G Network Slice for Video Monitoring with Low-Latency Constraints

JSAN, Vol. 8, Pages 3: A Fleet of MEC UAVs to Extend a 5G Network Slice for Video Monitoring with Low-Latency Constraints

Journal of Sensor and Actuator Networks doi: 10.3390/jsan8010003

Authors: Christian Grasso Giovanni Schembra

In the last decade, video surveillance systems have become more and more popular. Thanks to a decrease in price of video camera devices and the diffusion of cheap small unmanned aerial vehicles (UAVs), video monitoring is today adopted in a wide range of application cases, from road traffic control to precision agriculture. This leads to capture a great amount of visual material to be monitored and screened for event detection. However, information that is gathered from a platform of video monitoring UAVs may produce high-volume data, whose processing is unfeasible to be done locally by the same UAVs that perform monitoring. Moreover, because of the limited bandwidth of wireless links connecting UAVs to computing infrastructures that are installed on ground, offloading these data to edge clouds renders these platforms infeasible for video analysis applications with low-latency requirements. The target of this paper is to extend a 5G network slice for video monitoring with a Flying Ad-hoc NETwork (FANET) constituted by UAVs with multi-access edge computing (MEC) facilities (MEC UAVs), flying very close to the layer of UAVs monitoring the area of interest. A policy for mutual help among MEC UAVS is defined in order to increase the performance of the whole aerial MEC platform, so further reducing end-to-end latency between sources and actuators, and increasing system reliability. A use case is considered for a numerical analysis of the proposed platform.

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Regeneration of Osteochondral Defects Using Developmentally Inspired Cartilaginous Templates

Tissue Engineering Part A, Ahead of Print.


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Mammalian class I odorant receptors exhibit a conserved vestibular-binding pocket

Abstract

Odorant receptors represent the largest family of mammalian G protein-coupled receptors. Phylogenetically, they are split into two classes (I and II). By analyzing the entire subclass I odorant receptors sequences, we identified two class I-specific and highly conserved motifs. These are predicted to face each other at the extra-cellular portion of the transmembrane domain, forming a vestibular site at the entrance to the orthosteric-binding cavity. Molecular dynamics simulation combined with site-directed mutagenesis and in vitro functional assays confirm the functional role of this vestibular site in ligand-driven activation. Mutations at this part of the receptor differentially affect the receptor response to four agonists. Since this vestibular site is involved in ligand recognition, it could serve ligand design that targets specifically this sub-genome of mammalian odorant receptors.

http://bit.ly/2QgvCj9

The dual face of glutamate: from a neurotoxin to a potential survival factor—metabolic implications in health and disease

Abstract

Glutamate is the major excitatory neurotransmitter in the central nervous system. Beyond this function, glutamate also plays a key role in intermediary metabolism in all organs and tissues, linking carbohydrate and amino acid metabolism via the tricarboxylic acid cycle. Under both physiological and pathological conditions, we have recently found that the ability of glutamate to fuel cell metabolism selectively relies on the activity of two main transporters: the sodium–calcium exchanger (NCX) and the sodium-dependent excitatory amino-acid transporters (EAATs). In ischemic settings, when glutamate is administered at the onset of the reoxygenation phase, the coordinate activity of EAAT and NCX allows glutamate to improve cell viability by stimulating ATP production. So far, this phenomenon has been observed in both cardiac and neuronal models. In this review, we focus on the most recent findings exploring the unusual activity of glutamate as a potential survival factor in different settings.

http://bit.ly/2VovWAe

Cellular senescence is associated with reorganization of the microtubule cytoskeleton

Abstract

Senescent cells undergo structural and functional changes that affect essentially every aspect of cell physiology. To date, the impact of senescence on the cytoskeleton is poorly understood. This study evaluated the cytoskeleton in two independent cellular models of kidney epithelium senescence. Our work identified multiple senescence-related alterations that impact microtubules and filamentous actin during interphase. Both filamentous systems reorganized profoundly when cells became senescent. As such, microtubule stability increased during senescence, making these filaments more resistant to disassembly in the cold or by nocodazole. Microtubule stabilization was accompanied by enhanced α-tubulin acetylation on lysine 40 and the depletion of HDAC6, the major deacetylase for α-tubulin lysine 40. Rho-associated kinase Rock1 is an upstream regulator that modulates key properties of the cytoplasmic cytoskeleton. Our research shows that Rock1 concentrations were reduced significantly in senescent cells, and we revealed a mechanistic link between microtubule stabilization and Rock1 depletion. Thus, Rock1 overexpression partially restored the cold sensitivity of microtubules in cells undergoing senescence. Additional components relevant to microtubules were affected by senescence. Specifically, we uncovered the senescence-related loss of the microtubule nucleating protein γ-tubulin and aberrant formation of γ-tubulin foci. Concomitant with the alterations of microtubule and actin filaments, senescent cells displayed functional changes. In particular, cell migration was impaired significantly in senescent cells. Taken together, our study identified new senescence-associated deficiencies of the microtubule and actin cytoskeleton, provided insights into the underlying molecular mechanisms and demonstrated functional consequences that are important to the physiology and function of renal epithelial cells.

http://bit.ly/2QcNUBH

Transcriptional repression of the ectodomain sheddase ADAM10 by TBX2 and potential implication for Alzheimer’s disease

Abstract

Background

The ADAM10-mediated cleavage of transmembrane proteins regulates cellular processes such as proliferation or migration. Substrate cleavage by ADAM10 has also been implicated in pathological situations such as cancer or Morbus Alzheimer. Therefore, identifying endogenous molecules, which modulate the amount and consequently the activity of ADAM10, might contribute to a deeper understanding of the enzyme's role in both, physiology and pathology.

Method

To elucidate the underlying cellular mechanism of the TBX2-mediated repression of ADAM10 gene expression, we performed overexpression, RNAi-mediated knockdown and pharmacological inhibition studies in the human neuroblastoma cell line SH-SY5Y. Expression analysis was conducted by e.g. real-time RT-PCR or western blot techniques. To identify the binding region of TBX2 within the ADAM10 promoter, we used luciferase reporter assay on deletion constructs and EMSA/WEMSA experiments. In addition, we analyzed a TBX2 loss-of-function Drosophila model regarding the expression of ADAM10 orthologs by qPCR. Furthermore, we quantified the mRNA level of TBX2 in post-mortem brain tissue of AD patients.

Results

Here, we report TBX2 as a transcriptional repressor of ADAM10 gene expression: both, the DNA-binding domain and the repression domain of TBX2 were necessary to effect transcriptional repression of ADAM10 in neuronal SH-SY5Y cells. This regulatory mechanism required HDAC1 as a co-factor of TBX2. Transcriptional repression was mediated by two functional TBX2 binding sites within the core promoter sequence (− 315 to − 286 bp). Analysis of a TBX2 loss-of-function Drosophila model revealed that kuzbanian and kuzbanian-like, orthologs of ADAM10, were derepressed compared to wild type. Vice versa, analysis of cortical brain samples of AD-patients, which showed reduced ADAM10 mRNA levels, revealed a 2.5-fold elevation of TBX2, while TBX3 and TBX21 levels were not affected.

Conclusion

Our results characterize TBX2 as a repressor of ADAM10 gene expression and suggest that this regulatory interaction is conserved across tissues and species.

http://bit.ly/2VmVrSo

Multiple endocannabinoid-mediated mechanisms in the regulation of energy homeostasis in brain and peripheral tissues

Abstract

The endocannabinoid (eCB) system is widely expressed in many central and peripheral tissues, and is involved in a plethora of physiological processes. Among these, activity of the eCB system promotes energy intake and storage, which, however, under pathophysiological conditions, can favour the development of obesity and obesity-related disorders. It is proposed that eCB signalling is evolutionary beneficial for survival under periods of scarce food resources. Remarkably, eCB signalling is increased both in hunger and in overnutrition conditions, such as obesity and type-2 diabetes. This apparent paradox suggests a role of the eCB system both at initiation and at clinical endpoint of obesity. This review will focus on recent findings about the role of the eCB system controlling whole-body metabolism in mice that are genetically modified selectively in different cell types. The current data in fact support the notion that eCB signalling is not only engaged in the development but also in the maintenance of obesity, whereby specific cell types in central and peripheral tissues are key sites in regulating the entire body's energy homeostasis.

http://bit.ly/2Qjcp0k

Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion

Abstract

Mutations in the gene encoding the CFTR chloride channel produce cystic fibrosis (CF). CF patients are more susceptible to bacterial infections in lungs. The most accepted hypothesis sustains that a reduction in the airway surface liquid (ASL) volume favor infections. Alternatively, it was postulated that a reduced HCO₃⁻ transport through CFTR leads to a decreased ASL pH, favoring bacterial colonization. The issue is controversial, since recent data from cultured primary cells and CF children showed normal pH values in the ASL. We have reported previously a decreased mitochondrial Complex I (mCx-I) activity in cultured cells with impaired CFTR activity. Thus, we hypothesized that the reduced mCx-I activity could lead to increased lactic acid production (Warburg-like effect) and reduced extracellular pH (pHe). In agreement with this idea, we report here that cells with impaired CFTR function (intestinal Caco-2/pRS26, transfected with an shRNA-CFTR, and lung IB3-1 CF cells) have a decreased pHe. These cells showed increased lactate dehydrogenase (LDH) activity, LDH-A expression, and lactate secretion. Similar effects were reproduced in control cells stimulated with recombinant IL-1β. The c-Src and JNK inhibitors PP2 and SP600125 were able to increase the pHe, although the differences between control and CFTR-impaired cells were not fully compensated. Noteworthy, the LDH inhibitor oxamate completely restored the pHe of the intestinal Caco-2/pRS26 cells and have a significant effect in lung IB3-1 cells; therefore, an increased lactic acid secretion seems to be the key factor that determine a reduced pHe in these epithelial cells.

http://bit.ly/2Vmxcna

Protein-Level Interactions as Mediators of Sexual Conflict in Ants [Research]

All social insects with obligate reproductive division of labour evolved from strictly monogamous ancestors, but multiple queen-mating (polyandry) arose de novo in several evolutionarily derived lineages. Polyandrous ant queens are inseminated soon after hatching and store sperm mixtures for a potential reproductive life of decades. However, they cannot re-mate later in life and are thus expected to control the loss of viable sperm because their life-time reproductive success is ultimately sperm-limited. In the leaf-cutting ant Atta colombica, the survival of newly inseminated sperm is known to be compromised by seminal fluid of rival males and to be protected by secretions of the queen sperm storage organ (spermatheca). Here we investigate the main protein-level interactions that appear to mediate sperm competition dynamics and sperm preservation. We conducted an artificial insemination experiment and DIGE-based proteomics to identify proteomic changes when seminal fluid is exposed to spermathecal fluid, and then a mass spectrometry analysis of both secretions that allowed us to identify the sex-specific origins of the proteins that had changed in abundance. We found that spermathecal fluid targets only seven (2%) of the identified seminal fluid proteins for degradation, including two proteolytic serine proteases, a SERPIN inhibitor, and a semen-liquefying acid phosphatase. In vitro and in vivo experiments provided further confirmation that these proteins are key molecules mediating sexual conflict over sperm competition and viability preservation during sperm storage. Exposure to spermathecal fluid reduced the capacity of seminal fluid to compromise survival of rival sperm in a matter of hours and biochemical inhibition of these seminal fluid proteins largely eliminated that adverse effect. Our findings indicate that A. colombica queens are in control of sperm competition and sperm storage, a capacity that has not been documented in other animals, but is predicted to have independently evolved in other polyandrous social insects.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2VkUWIA

Cost optimization based on influence and user preference

Abstract

The popularity of e-business and preference learning techniques have contributed a huge amount of product and user preference data. Analyzing the influence of an existing or new product among the users is critical to unlock the great scientific and social–economic value of these data. In this paper, we advocate the problem of influence-based cost optimization for the user preference and product data, which is fundamental in many real applications such as marketing and advertising. Generally, we aim to find a cost optimal position for a new product such that it can attract at least k or a particular percentage of users for the given user preference functions and competitors' products. Although we show the solution space of our problem can be reduced to a finite number of possible positions (points) by utilizing the classical k-level computation techniques, the computation cost is still very expensive due to the nature of the high combinatorial complexity of the k-level problem. To alleviate this issue, we develop efficient pruning and query processing techniques to significantly improve the performance. In particular, our traverse-based 2-dimensional algorithm is very efficient with time complexity O(n) where n is the number of user preference functions. For general multi-dimensional spaces, we develop space partition-based algorithm to significantly improve the performance by utilizing cost-based, influence-based and local dominance-based pruning techniques. Then, we show that the performance of the partition-based algorithm can be further enhanced by utilizing sampling approach, where the problem can be reduced to the classical half-space intersection problem. Based on the problem of influence-based cost optimization, two naturally extended problems are proposed, which are Batch-Query and the most cost-effective influence query. We demonstrate the efficiency of our techniques with extensive experiments over real and synthetic datasets.

http://bit.ly/2Vk0q69

Joint prediction of time series data in inventory management

Abstract

The problem of time series prediction has been well explored in the community of data mining. However, little research attention has been paid to the case of predicting the movement of a collection of related time series data. In this work, we study the problem of simultaneously predicting multiple time series data using joint predictive models. We observe that in real-world applications, strong relationships between different time-sensitive variables are often held, either explicitly predefined or implicitly covered in nature of the application. Such relationships indicate that the prediction on the trajectory of one given time series could be improved by incorporating the properties of other related time series data into predictive models. The key challenge is to capture the temporal dynamics of these relationships to jointly predict multiple time series. In this research, we propose a predictive model for multiple time series forecasting and apply it to the domain of inventory management. The relationships among multiple time series are modeled as a class of constraints, and in turn, refine the predictions on the corresponding time series. Experimental results on real-world data reveal that the proposed algorithms outperform well-established methods of time series forecasting.

http://bit.ly/2QgAqos

Investigations into Data Ecosystems: a systematic mapping study

Abstract

Data Ecosystems are socio-technical complex networks in which actors interact and collaborate with each other to find, archive, publish, consume, or reuse data as well as to foster innovation, create value, and support new businesses. While the Data Ecosystem field is thus arguably gaining in importance, research on this subject is still in its early stages of development. Up until now, not many academic papers related to Data Ecosystems have been published. Furthermore, to the best of our knowledge, there has been no systematic review of the literature on Data Ecosystems. In this study, we provide an overview of the current literature on Data Ecosystems by conducting a systematic mapping study. This study is intended to function as a snapshot of the research in the field and by doing so identifies the different definitions of Data Ecosystem and analyzes the evolution of Data Ecosystem research. The studies selected have been classified into categories related to the study method, contribution, research topic, and ecosystem domains. Finally, we analyze how Data Ecosystems are structured and organized, and what benefits can be expected from Data Ecosystems and what their limitations are.

http://bit.ly/2VtSwr8

IJMS, Vol. 20, Pages 131: CCAR2/DBC1 and Hsp60 Positively Regulate Expression of Survivin in Neuroblastoma Cells

IJMS, Vol. 20, Pages 131: CCAR2/DBC1 and Hsp60 Positively Regulate Expression of Survivin in Neuroblastoma Cells

International Journal of Molecular Sciences doi: 10.3390/ijms20010131

Authors: Wootae Kim Jaewook Ryu Ja-Eun Kim

CCAR2 (cell cycle and apoptosis regulator 2) controls a variety of cellular functions; however, its main function is to regulate cell survival and cell death in response to genotoxic and metabolic stresses. Recently, we reported that CCAR2 protects cells from apoptosis following mitochondrial stress, possibly by co-operating with Hsp60. However, it is not clear how CCAR2 and Hsp60 control cell survival and death. Here, we found that depleting CCAR2 and Hsp60 downregulated expression of survivin, a member of the inhibitor of apoptosis (IAP) family. Survivin expression in neuroblastoma tissues and human cancer cell lines correlated positively with expression of CCAR2 and Hsp60. Furthermore, high expression of CCAR2, Hsp60, and survivin was associated with poor survival of neuroblastoma patients. In summary, both CCAR2 and Hsp60 are required for expression of survivin, and both promote cancer cell survival, at least in part, by maintaining survivin expression. Therefore, CCAR2, Hsp60, and survivin are candidate tumor biomarkers and prognostic markers in neuroblastomas.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2VmAmr9

A ligand-induced structural change in fatty acid-binding protein 1 is associated with potentiation of peroxisome proliferator-activated receptor {alpha} agonists [Gene Regulation]

Peroxisome proliferator-activated receptor α (PPARα) is a transcriptional regulator of lipid metabolism. GW7647 is a potent PPARα agonist that must reach the nucleus to activate this receptor. In cells expressing human fatty acid–binding protein 1 (FABP1), GW7647 treatment increases FABP1's nuclear localization, and potentiates GW7647-mediated PPARα activation; GW7647 is less effective in cells that do not express FABP1. To elucidate the underlying mechanism, here we substituted residues in FABP1 known to dictate lipid signaling by other intracellular lipid-binding proteins. Substitutions of Lys-20 and Lys-31 to Ala in the FABP1 helical cap affected neither its nuclear localization nor PPARα activation. In contrast, Ala substitution of Lys-57, Glu-77, and Lys-96, located in the loops adjacent to the ligand-binding portal region, abolished both FABP1 nuclear localization and GW7647-induced PPARα activation, but had little effect on GW7647–FABP1 binding affinity. Using solution NMR spectroscopy, we determined the wildtype FABP1 structure and analyzed the dynamics in the apo and GW7647-bound structures of both the wildtype and the K57A/E77A/K96A triple mutant. We found that GW7647 binding causes little change in the FABP1 backbone, but solvent-exposes several residues in the loops around the portal region, including Lys-57, Glu-77, and Lys-96. These residues also become more solvent exposed upon binding of FABP1 with the endogenous PPARα agonist oleic acid. Together with previous observations, our findings suggest that GW7647 binding stabilizes a FABP1 conformation that promotes its interaction with PPARα. We conclude that full PPARα agonist activity of GW7647 requires FABP1-dependent transport and nuclear localization processes.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2EZKNLB

TGF-{beta}2 uses the concave surface of its extended finger region to bind betaglycan’s ZP domain via three residues specific to TGF-{beta} and Inhibin-{alpha} [Protein Structure and Folding]

Betaglycan (BG) is a membrane-bound co-receptor of the TGF-β family that selectively binds transforming growth factor-β (TGF-β) isoforms and inhibin A (InhA) to enable temporal-spatial patterns of signaling essential for their functions in vivo. Here, using NMR titrations of methyl-labeled TGF-β2 with BG's C-terminal binding domain, BGZP-C, and surface plasmon resonance binding measurements with TGF-β2 variants, we found that the BGZP-C binding site on TGF-β2 is located on the inner surface of its extended finger region. Included in this binding site are Ile92, Lys97, and Glu99, which are entirely or mostly specific to the TGF-β isoforms and the InhA α-subunit, but unconserved in other TGF-β family growth factors (GFs). In accord with the proposed specificity-determining role of these residues, BG bound bone morphogenetic protein 2 (BMP-2) weakly or not at all, and TGF-β2 variants with the corresponding residues from BMP-2 bound BGZP-C more weakly than corresponding alanine variants. The BGZP-C binding site on InhA previously was reported to be located on the outside of the extended finger region, yet at the same time, to include, Ser112 and Lys119, homologous to TGF-β2 Ile92 and Lys97, on the inside of the fingers. Therefore, it is likely that both TGF-β2 and InhA bind BGZP-C through a site on the inside of their extended finger regions. Overall, these results identify the BGZP-C–binding site on TGF-β2 and shed light on the specificity of BG for select TGF-β–type GFs and the mechanisms by which BG influences their signaling.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2EZLW6v

Ribosomal protein L6 (RPL6) is recruited to DNA damage sites in a poly (ADP-ribose) polymerase-dependent manner and regulates the DNA damage response [Signal Transduction]

Ribosomal proteins are the building blocks of ribosome biogenesis. Beyond their known participation in ribosome assembly, the ribosome-independent functions of ribosomal proteins are largely unknown. Here, using immunoprecipitation, subcellular fractionation, His-ubiquitin pull-down, and immunofluorescence microscopy assays along with siRNA-based knockdown approaches, we demonstrate that ribosomal protein L6 (RPL6) directly interacts with histone H2A and is involved in the DNA damage response (DDR). We found that in response to DNA damage, RPL6 is recruited to DNA damage sites in a poly-(ADP-ribose) polymerase (PARP)-dependent manner, promoting its interaction with H2A. We also observed that RPL6 depletion attenuates the interaction between mediator of DNA damage checkpoint 1 (MDC1) and H2A histone family member X (γH2AX), impairs the accumulation of MDC1 at DNA damage sites, and reduces both the recruitment of ring finger protein 168 (RNF168) and H2A Lys-15 ubiquitination (H2AK15ub). These RPL6 depletion–induced events subsequently inhibited the recruitment of the downstream repair proteins tumor protein P53 binding protein 1 (TP53BP1) and BRCA1, DNA repair–associated (BRCA1). Moreover, the RPL6 knockdown resulted in defects in the DNA damage–induced G2–M checkpoint, DNA damage repair, and cell survival. In conclusion, our study identifies RPL6 as a critical regulatory factor involved in the DDR. These findings expand our knowledge of the extra-ribosomal functions of ribosomal proteins in cell physiology and deepen our understanding of the molecular mechanisms underlying DDR regulation.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2EZJrR6

Membrane-associated epithelial cell adhesion molecule is slowly cleaved by {gamma}-secretase prior to efficient proteasomal degradation of its intracellular domain [Protein Synthesis and Degradation]

Regulated intramembrane proteolysis (RIP) is a key mechanism for activating transmembrane proteins such as epithelial cell adhesion molecule (EpCAM) for cellular signaling and degradation. EpCAM is highly expressed in carcinomas and progenitor and embryonic stem cells, and is involved in the regulation of cell adhesion, proliferation, and differentiation. Strictly sequential cleavage of EpCAM through RIP involves initial shedding of the extracellular domain by α-secretase (ADAM) and β-secretase (BACE) sheddases, generating a membrane-tethered C-terminal fragment EpCTF. Subsequently, the rate-limiting γ-secretase complex catalyzes intramembrane cleavage of EpCTF, generating an extracellular EpCAM-Aβ–like fragment and an intracellular EpICD fragment involved in nuclear signaling. Here, we have combined biochemical approaches with live cell imaging of fluorescent protein-tags to investigate the kinetics of γ-secretase–mediated intramembrane cleavage of EpCTF by. We demonstrate that γ-secretase–mediated proteolysis of exogenously and endogenously expressed EpCTF is a slow process with a 50% protein turnover in cells ranging from 45 minutes to 5.5 hours. The slow cleavage was dictated by γ-secretase activity and not by EpCTF species, as indicated by cross-species swapping experiments. Furthermore, both human and murine EpICDs generated from EpCTF by γ-secretase were degraded efficiently (94-99%) by the proteasome. Hence, proteolytic cleavage of EpCTF is a comparably slow process, and EpICD generation does not appear to be suited for rapidly transducing extracellular cues into nuclear signaling, but appears to provide steady signals that can be further controlled through efficient proteasomal degradation. Our approach provides an unbiased bioassay to investigate proteolytic processing of EpCTF in single living cells.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2F2tnP2

Depletion of dAKAP1-protein kinase A signaling islands from the outer mitochondrial membrane alters breast cancer cell metabolism and motility [Cell Biology]

Breast cancer screening and new precision therapies have improved patient outcomes. Yet, a positive prognosis is less certain when primary tumors metastasize. Metastasis requires a coordinated program of cellular changes that promote increased survival, migration, and energy consumption. These pathways converge on mitochondrial function, where distinct signaling networks of kinases, phosphatases, and metabolic enzymes regulate these processes. The A-kinase anchoring protein dAKAP1 compartmentalizes protein kinase A (PKA) and other signaling enzymes at the outer mitochondrial membrane and thereby controls mitochondrial function and dynamics. Modulation of these processes occurs in part through regulation of dynamin-related protein 1 (Drp1). Here, we report an inverse relationship between the expression of dAKAP1 and mesenchymal markers in breast cancer. Molecular, cellular, and in silico analyses of breast cancer cell lines confirmed that dAKAP1 depletion is associated with impaired mitochondrial function and dynamics, as well as with increased glycolytic potential and invasiveness. Furthermore, disruption of dAKAP1–PKA complexes affected cell motility and mitochondrial movement toward the leading edge in invasive breast cancer cells. We therefore propose that depletion of dAKAP1–PKA "signaling islands" from the outer mitochondrial membrane augments progression toward metastatic breast cancer.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2EYSHor

Glutaredoxin 1 up-regulates deglutathionylation of {alpha}4 integrin and thereby restricts neutrophil mobilization from bone marrow [Immunology]

α4 integrin plays a crucial role in retention and release of neutrophils from bone marrow. Although α4 integrin is known to be a potential target of reactive oxygen species (ROS)-induced cysteine glutathionylation, the physiological significance and underlying regulatory mechanism of this event remain elusive. Here, using in vitro and in vivo biochemical and cell biology approaches, we show that physiological, ROS-induced glutathionylation of α4 integrin in neutrophils increases the binding of neutrophil-associated α4 integrin to vascular cell adhesion molecule 1 (VCAM-1) on human endothelial cells. This enhanced binding was reversed by extracellular glutaredoxin 1 (Grx1), a thiol disulfide oxidoreductase promoting protein deglutathionylation. Furthermore, in a murine inflammation model, Grx1 disruption dramatically elevated α4 glutathionylation and subsequently enhanced neutrophil egress from the bone marrow. Corroborating this observation, intravenous injection of recombinant Grx1 into mice inhibited α4 glutathionylation and thereby suppressed inflammation-induced neutrophil mobilization from the bone marrow. Taken together, our results establish ROS-elicited glutathionylation and its modulation by Grx1 as pivotal regulatory mechanisms controlling α4 integrin affinity and neutrophil mobilization from the bone marrow in physiological conditions.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2EYMdXB

Blood-brain and blood-cerebrospinal fluid passage of BRICHOS domains from two molecular chaperones in mice [Protein Structure and Folding]

Targeting toxicity associated with amyloid-β (Aβ) misfolding and aggregation is a promising therapeutic strategy for preventing or managing Alzheimer's disease (AD). The BRICHOS domains from human prosurfactant protein C (proSP-C) and integral membrane protein 2B (Bri2) efficiently reduce neurotoxicity associated with Aβ42 fibril formation both in vitro and in vivo. In this study, we have evaluated the serum half-lives and permeability into the brain and the cerebrospinal fluid (CSF) of recombinant human (rh) proSP-C and Bri2 BRICHOS domains intravenously injected into wild type mice. We found that rh proSP-C BRICHOS has a longer blood serum half-life compared to rh Bri2 BRICHOS and passed into the CSF but not into the brain parenchyma. As judged by western blots, immunohistochemistry and ELISA assays, rh Bri2 BRICHOS passed into both CSF and brain. Intracellular immunostaining for rh Bri2 BRICHOS was observed in the choroid plexus epithelium as well as in the cerebral cortex. Our results indicate that intravenously administered rh proSP-C and Bri2 BRICHOS domains have different pharmacokinetic properties and blood-brain/blood-CSF permeabilities in mice. The finding that rh Bri2 BRICHOS can reach the brain parenchyma after peripheral administration may be harnessed in the search for new therapeutic strategies for managing AD.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2EYo6Y5

[ASAP] Orthogonal Lithography for Halide Perovskite Optoelectronic Nanodevices

ACS Nano

DOI: 10.1021/acsnano.8b05859

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2R1WZCz

Effect of Imatinib on Bone Marrow Morphology and Angiogenesis in Chronic Myeloid Leukemia

Background and Objectives. Chronic myeloid leukemia (CML) is characterized by hyperproliferation of myeloid precursors, increased fibrosis, and neoangiogenesis in the bone marrow. Imatinib inhibits BCR-ABL tyrosine kinase produced due to reciprocal translocation t(9;22) in neoplastic CML cells. It reduces hyperproliferation of myeloid precursors and has been found to affect bone marrow fibrosis and angiogenesis. This study was done to assess the effect of imatinib on bone marrow morphology and angiogenesis in CML. Methods. 31 newly diagnosed CML patients were evaluated before and after 3 months of imatinib therapy. A marrow morphological response (MMR) score was used to assess marrow cytological and histological features including grade of fibrosis. Mean microvessel density (MVD) was also assessed. Hematological parameters and BCR-ABL transcript levels were assessed in the peripheral blood. Results. 86.21% of patients showed decrease in marrow cellularity with normalization of M:E ratio. 72.42% of patients had decrease in grade of fibrosis and 17.24% showed no change while 10.34% of patients showed progression of fibrosis grade. Patients with MMR score ≥ 2 (n=4) and those with progression of fibrosis grade (n=3) showed suboptimal molecular response (BCR-ABL transcripts > 10%). Pretherapy mean MVD of patients (14.69 ± 5.28) was higher than that of controls (6.32 ± 1.64). A significant reduction of 66.51% was observed in posttherapy mean MVD (4.98 ± 2.77) of CML patients (p

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2BWPD94

Ginsenoside Re Improves Isoproterenol-Induced Myocardial Fibrosis and Heart Failure in Rats

Objective. Panax ginseng is used widely for treatment of cardiovascular disorders in China. Ginsenoside Re is the main chemical component of P. ginseng. We aimed to investigate the protective effect of ginsenoside Re on isoproterenol-induced myocardial fibrosis and heart failure in rats. Methods. A model of myocardial fibrosis and heart failure was established by once-daily subcutaneous injection of isoproterenol (5 mg/kg/day) to rats for 7 days. Simultaneously, rats were orally administrated ginsenoside Re (5 or 20 mg/kg) or vehicle daily for 4 weeks. Results. Isoproterenol enhanced the heart weight, myocardial fibrosis, and hydroxyproline content in rat hearts. Ginsenoside Re inhibited (at least in part) the isoproterenol-induced increase in heart weight, myocardial fibrosis, and hydroxyproline content. Compared with the isoproterenol group, treatment with ginsenoside Re ameliorated changes in left ventricular systolic pressure, left ventricular end diastolic pressure, and the positive and negative maximal values of the first derivative of left ventricular pressure. Ginsenoside Re administration also resulted in decreased expression of transforming growth factor (TGF)-β1 in serum and decreased expression of Smad3 and collagen I in heart tissue. Conclusion. Ginsenoside Re can improve isoproterenol-induced myocardial fibrosis and heart failure by regulation of the TGF-β1/Smad3 pathway.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2CGYc9M

Extraction/Preconcentration Procedures for Determination of Metal and Organometallic Species in Environmental, Biological, and Food Samples

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2Tn9vcO

Effect of Employees’ Values on Employee Satisfaction in Japanese Retail and Service Industries

The Japanese workforce has decreased rapidly over the past few decades, and this is expected to continue. Retail and service industries are already experiencing human-resource shortages. In these industries, nonregular employees feature prominently. For most companies, recruitment is difficult, and employees change jobs often, making securing staff an important business issue. Nonregular and regular employees are treated differently; the problem is thus partly social in nature. However, some nonregular employees are content, although their work conditions are not good. Here, text mining was used to explore differences between the values of regular and nonregular employees in the retail and service industries.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2BPN8Fx

Wear Inducing Phase Transformation of Plasma Transfer Arc Coated Tools during Friction Stir Welding with Al Alloy

The friction stir welding process (friction stir welding/processing, FSW/FSP) has wear problems related to stirring tools. In this study, the plasma transfer arc (PTA) method was used with stellite 1 powders (Co-based) to coat on the head of a SKD61 stirring tool (SKD61-ST1) in order to investigate the wear performance and phase transformation of SKD61-ST1 after FSW. Under the same experimental parameters, the wear data were compared with the high-speed steel SKH51 (tempering material SKH51-T and annealed material SKH51-A) and tungsten-carbide cobalt (TCC). Results showed the PTA coating was a γ-Co solidification matrix with M7C3 and M23C6 carbides. After FSW, the wear resistance of SKD61-ST1 was better than that of SKH51-A and SKH51-T and lower than that of TCC. The SKD61-ST1, SKH51-A, and SKH51-T stirring tools exhibited sliding wear after FSP, where the pin and shoulder of the stirring tool formed a phase transfer layer on the surface, and the peeling of the phase transfer layer caused wear weight loss. The main phase of the phase transfer layer of the SKD61-ST1 tool was Al9Co2. The affinity and adhesion energy of the Co-Al phase was lower than that of Fe-Al phase, and the phase transfer layer of the SKD61-ST1 tool was thinner and had lower coverage, thereby increasing the wear resistance of the SKD61-ST1 stirring tools during FSW.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2CIKQK8

How to Efficiently Produce Ultrapure Acids

Subboiling distillation has been used since two decades for the purification of analytical grade acids from inorganic contaminants and demonstrated an efficient method to obtain pure acids starting from reagent grade chemicals. Nevertheless, the effect of the subboiling parameters on the purity of the distilled acids has never been methodically investigated. Aim of the present research is a systematic evaluation of the subboiling distillation protocol for the production of pure hydrochloric and nitric acid. In particular, the effect of the subboiling temperature and the number of subsequent distillations was investigated as these parameters were recognised as the most important factors controlling acid purity, acid concentration, and distillation yield. The concentration of twenty elements in the purified acids was determined by Inductively Coupled Plasma-Mass Spectrometry. As a result, the subboiling temperature (up to 82°C) and the number of subsequent distillations (up to four) were demonstrated not to affect the purity of the distilled nitric and hydrochloric acids. Under normal laboratory conditions, the residual elemental concentrations were in most cases below 10 ng/L in both nitric (2.75% w/w) and hydrochloric (0.1 M) blanks. Ultrapure nitric and hydrochloric acids could accordingly be produced under the most favorable conditions, i.e., the highest temperature and one distillation process only.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2To2gRV

Review of Carbonation Resistance in Hydrated Cement Based Materials

Blended cements are preferred to Ordinary Portland Cement (OPC) in construction industry due to costs and technological and environmental benefits associated with them. Prevalence of significant quantities of carbon dioxide (CO2) in the atmosphere due to increased industrial emission is deleterious to hydrated cement materials due to carbonation. Recent research has shown that blended cements are more susceptible to degradation due to carbonation than OPC. The ingress of CO2 within the porous mortar matrix is a diffusion controlled process. Subsequent chemical reaction between CO2 and cement hydration products (mostly calcium hydroxide [CH] and calcium silicate hydrate [CSH]) results in degradation of cement based materials. CH offers the buffering capacity against carbonation in hydrated cements. Partial substitution of OPC with pozzolanic materials however decreases the amount of CH in hydrated blended cements. Therefore, low amounts of CH in hydrated blended cements make them more susceptible to degradation as a result of carbonation compared to OPC. The magnitude of carbonation affects the service life of cement based structures significantly. It is therefore apparent that sufficient attention is given to carbonation process in order to ensure resilient cementitious structures. In this paper, an indepth review of the recent advances on carbonation process, factors affecting carbonation resistance, and the effects of carbonation on hardened cement materials have been discussed. In conclusion, carbonation process is influenced by internal and external factors, and it has also been found to have both beneficial and deleterious effects on hardened cement matrix.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2CJ0ncX

Corrigendum to “Efficacy and Tolerability of Intravenous Ferric Carboxymaltose in Patients with Iron Deficiency at a Hospital Outpatient Clinic: A Retrospective Cohort Study of Real-World Clinical Practice”

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2TiRPyN

[ASAP] Core–Satellite Nanomedicines for Real-Time Monitoring of Enzyme-Activatable Drug Release by Fluorescence and Photoacoustic Dual-Modal Imaging

ACS Nano

DOI: 10.1021/acsnano.8b05136

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2Viv8wJ

[ASAP] Targeting 3D Bladder Cancer Spheroids with Urease-Powered Nanomotors

ACS Nano

DOI: 10.1021/acsnano.8b06610

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2Qgzxwa

[ASAP] Epitaxial Growth of Two-Dimensional Metal–Semiconductor Transition-Metal Dichalcogenide Vertical Stacks (VSe2/MX2) and Their Band Alignments

ACS Nano

DOI: 10.1021/acsnano.8b08677

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2VgcdTb

Prehistoric Shark May Have Caught a Dinner on the Wing

A fossil tooth hints at a startling interaction between an ancient shark and a flying reptile.

-- Read more on ScientificAmerican.com

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2CGYbTp

Protein-Level Interactions as Mediators of Sexual Conflict in Ants [Research]

All social insects with obligate reproductive division of labour evolved from strictly monogamous ancestors, but multiple queen-mating (polyandry) arose de novo in several evolutionarily derived lineages. Polyandrous ant queens are inseminated soon after hatching and store sperm mixtures for a potential reproductive life of decades. However, they cannot re-mate later in life and are thus expected to control the loss of viable sperm because their life-time reproductive success is ultimately sperm-limited. In the leaf-cutting ant Atta colombica, the survival of newly inseminated sperm is known to be compromised by seminal fluid of rival males and to be protected by secretions of the queen sperm storage organ (spermatheca). Here we investigate the main protein-level interactions that appear to mediate sperm competition dynamics and sperm preservation. We conducted an artificial insemination experiment and DIGE-based proteomics to identify proteomic changes when seminal fluid is exposed to spermathecal fluid, and then a mass spectrometry analysis of both secretions that allowed us to identify the sex-specific origins of the proteins that had changed in abundance. We found that spermathecal fluid targets only seven (2%) of the identified seminal fluid proteins for degradation, including two proteolytic serine proteases, a SERPIN inhibitor, and a semen-liquefying acid phosphatase. In vitro and in vivo experiments provided further confirmation that these proteins are key molecules mediating sexual conflict over sperm competition and viability preservation during sperm storage. Exposure to spermathecal fluid reduced the capacity of seminal fluid to compromise survival of rival sperm in a matter of hours and biochemical inhibition of these seminal fluid proteins largely eliminated that adverse effect. Our findings indicate that A. colombica queens are in control of sperm competition and sperm storage, a capacity that has not been documented in other animals, but is predicted to have independently evolved in other polyandrous social insects.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2H1fS4j

Deep Learning for Musculoskeletal Force Prediction

Abstract

Musculoskeletal models permit the determination of internal forces acting during dynamic movement, which is clinically useful, but traditional methods may suffer from slowness and a need for extensive input data. Recently, there has been interest in the use of supervised learning to build approximate models for computationally demanding processes, with benefits in speed and flexibility. Here, we use a deep neural network to learn the mapping from movement space to muscle space. Trained on a set of kinematic, kinetic and electromyographic measurements from 156 subjects during gait, the network's predictions of internal force magnitudes show good concordance with those derived by musculoskeletal modelling. In a separate set of experiments, training on data from the most widely known benchmarks of modelling performance, the international Grand Challenge competitions, generates predictions that better those of the winning submissions in four of the six competitions. Computational speedup facilitates incorporation into a lab-based system permitting real-time estimation of forces, and interrogation of the trained neural networks provides novel insights into population-level relationships between kinematic and kinetic factors.

http://bit.ly/2RpnIIK

Extinction and the Rise of the Dinosaurs

Paleontologists are still puzzling over why dinosaurs succeeded while crocodile cousins faded away.

-- Read more on ScientificAmerican.com

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2TfktAS

The Dinosaur Who Went Out to Sea

The skeleton of a new carnivorous dinosaur bears damage caused by seagoing invertebrates.

-- Read more on ScientificAmerican.com

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2CHs2uR

The ESCRT and autophagy machineries cooperate to repair ESX-1-dependent damage at the Mycobacterium-containing vacuole but have opposite impact on containing the infection

by Ana T. López-Jiménez, Elena Cardenal-Muñoz, Florence Leuba, Lilli Gerstenmaier, Caroline Barisch, Monica Hagedorn, Jason S. King, Thierry Soldati

Phagocytic cells capture and kill most invader microbes within the bactericidal phagosome, but some pathogens subvert killing by damaging the compartment and escaping to the cytosol. To prevent the leakage of pathogen virulence and host defence factors, as well as bacteria escape, host cells have to contain and repair the membrane damage, or finally eliminate the cytosolic bacteria. All eukaryotic cells engage various repair mechanisms to ensure plasma membrane integrity and proper compartmentalization of organelles, including the Endosomal Sorting Complex Required for Transport (ESCRT) and autophagy machineries. We show that during infection of Dictyostelium discoideum with Mycobacterium marinum, the ESCRT-I component Tsg101, the ESCRT-III protein Snf7/Chmp4/Vps32 and the AAA-ATPase Vps4 are recruited to sites of damage at the Mycobacterium-containing vacuole. Interestingly, damage separately recruits the ESCRT and the autophagy machineries. In addition, the recruitment of Vps32 and Vps4 to repair sterile membrane damage depends on Tsg101 but appears independent of Ca²⁺. Finally, in absence of Tsg101, M. marinum accesses prematurely the cytosol, where the autophagy machinery restricts its growth. We propose that ESCRT has an evolutionary conserved function to repair small membrane damage and to contain intracellular pathogens in intact compartments.

from Genes Mutations Carcinogenesis via alexandrossfakianakis on Inoreader http://bit.ly/2EWA98l

Diversification of DNA binding specificities enabled SREBP transcription regulators to expand the repertoire of cellular functions that they govern in fungi

by Valentina del Olmo Toledo, Robert Puccinelli, Polly M. Fordyce, J. Christian Pérez

The Sterol Regulatory Element Binding Proteins (SREBPs) are basic-helix-loop-helix transcription regulators that control the expression of sterol biosynthesis genes in higher eukaryotes and some fungi. Surprisingly, SREBPs do not regulate sterol biosynthesis in the ascomycete yeasts (Saccharomycotina) as this role was handed off to an unrelated transcription regulator in this clade. The SREBPs, nonetheless, expanded in fungi such as the ascomycete yeasts Candida spp., raising questions about their role and evolution in these organisms. Here we report that the fungal SREBPs diversified their DNA binding preferences concomitantly with an expansion in function. We establish that several branches of fungal SREBPs preferentially bind non-palindromic DNA sequences, in contrast to the palindromic DNA motifs recognized by most basic-helix-loop-helix proteins (including SREBPs) in higher eukaryotes. Reconstruction and biochemical characterization of the likely ancestor protein suggest that an intrinsic DNA binding promiscuity in the family was resolved by alternative mechanisms in different branches of fungal SREBPs. Furthermore, we show that two SREBPs in the human commensal yeast Candida albicans drive a transcriptional cascade that inhibits a morphological switch under anaerobic conditions. Preventing this morphological transition enhances C. albicans colonization of the mammalian intestine, the fungus' natural niche. Thus, our results illustrate how diversification in DNA binding preferences enabled the functional expansion of a family of eukaryotic transcription regulators.

from Genes Mutations Carcinogenesis via alexandrossfakianakis on Inoreader http://bit.ly/2QfqZWn

Bayesian multiple logistic regression for case-control GWAS

by Saikat Banerjee, Lingyao Zeng, Heribert Schunkert, Johannes Söding

Genetic variants in genome-wide association studies (GWAS) are tested for disease association mostly using simple regression, one variant at a time. Standard approaches to improve power in detecting disease-associated SNPs use multiple regression with Bayesian variable selection in which a sparsity-enforcing prior on effect sizes is used to avoid overtraining and all effect sizes are integrated out for posterior inference. For binary traits, the logistic model has not yielded clear improvements over the linear model. For multi-SNP analysis, the logistic model required costly and technically challenging MCMC sampling to perform the integration. Here, we introduce the quasi-Laplace approximation to solve the integral and avoid MCMC sampling. We expect the logistic model to perform much better than multiple linear regression except when predicted disease risks are spread closely around 0.5, because only close to its inflection point can the logistic function be well approximated by a linear function. Indeed, in extensive benchmarks with simulated phenotypes and real genotypes, our Bayesian multiple LOgistic REgression method (B-LORE) showed considerable improvements (1) when regressing on many variants in multiple loci at heritabilities ≥ 0.4 and (2) for unbalanced case-control ratios. B-LORE also enables meta-analysis by approximating the likelihood functions of individual studies by multivariate normal distributions, using their means and covariance matrices as summary statistics. Our work should make sparse multiple logistic regression attractive also for other applications with binary target variables. B-LORE is freely available from: http://bit.ly/2Qfr1gX.

from Genes Mutations Carcinogenesis via alexandrossfakianakis on Inoreader http://bit.ly/2Vp2hH9