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Purpose – Considering the relevance of innovative business models in the digitally transformed market and the lack of clarity on the internet of services (IoS) contribution for a business model deployment in current literature, this study aims to fill this gap by evaluating a business model that converges to an IoS adoption in a direct sale of free-range eggs from farmers to consumers. Design/methodology/approach – From the bibliographical research regarding the IoS and business model, the authors developed an IoS-based model framework. The framework has been evaluated in a real business scenario by using a single case study through an interview with the entrepreneur and documental analysis. Findings – As the main result, a framework with the attributes can be considered a tool for an IoS-based business model deployment. The case study concluded that the business is aligned with the IoS adoption, and the framework presents adherence to it. Research limitations/implications – The case study was limited to only one company owing to the IoS’s novelty and the lack of correlated business models. Although the case study limits to the agriculture field, the proposed framework may be broadly applied. Originality/value – Considering that the lack of a comprehensive business model causes new businesses to face challenges, it is relevant bringing up the present case study of the IoS-based business model, which correlates these two subjects, still poorly explored in the scientific literature: IoS and business models.

In this study, we utilized an in vitro model consisting of human malignant melanoma as well as non-tumorigenic immortalized keratinocyte cells with the aim of characterizing the therapeutic effectiveness of the clinical epigenetic drug Tazemetostat alone or in combination with various isothiocyanates. In doing so, we assessed markers of cell viability, apoptotic induction, and expression levels of key proteins capable of mediating the therapeutic response. Our data indicated, for the first time, that Tazemetostat caused a significant decrease in viability levels of malignant melanoma cells in a dose- and time-dependent manner via the induction of apoptosis, while non-malignant keratinocytes were more resistant. Moreover, combinatorial treatment protocols caused a further decrease in cell viability, together with higher apoptotic rates. In addition, a significant reduction in the Polycomb Repressive Complex 2 (PRC2) members [e.g., Enhancer of Zeste Homologue 2 (EZH2), Embryonic Ectoderm Development (EED), and suppressor of zeste 12 (SUZ12)] and tri-methylating lysine 27 at Histone 3 (H3K27me3) protein expression levels was observed, at least partially, under specific combinatorial exposure conditions. Reactivation of major apoptotic gene targets was determined at much higher levels in combinatorial treatment protocols than Tazemetostat alone, known to be involved in the induction of intrinsic and extrinsic apoptosis. Overall, we developed an optimized experimental therapeutic platform aiming to ensure the therapeutic effectiveness of Tazemetostat in malignant melanoma while at the same time minimizing toxicity against neighboring non-tumorigenic keratinocyte cells.

Phenethyl isothiocyanate (PEITC) is a secondary metabolic product yielded upon the hydrolysis of gluconasturtiin and it is highly accumulated in the flowers of watercress. The aim of the current study was to assess the role of a naturally derived PEITC-enriched extract in the induction of oxidative stress and to evaluate its anti-melanoma potency through the regulation of its metabolism with the concurrent production of the N-acetyl cysteine conjugated by-product. For this purpose, an in vitro melanoma model was utilized consisting of human primary (A375) cells as well as metastatic (COLO-679) malignant melanoma cells together with non-tumorigenic immortalized keratinocytes (HaCaT). Cytotoxicity was assessed via the Alamar Blue assay whereas the antioxidant/prooxidant activity of PEITC was determined via spectrophotometric assays. Finally, kinetic characterization of the end-product of PEITC metabolism was monitored via UPLC coupled to a tandem mass spectrometry (MS/MS). Our results indicate that although PhEF showed very minor antioxidant activity in a cell-free system, in a cell-based system, it can modulate the activity of key enzyme(s) involved in cellular antioxidant defense mechanism(s). In addition, we have shown that PhEF induces lipid and protein oxidation in a concentration-dependent manner, while its cytotoxicity is not only dependent on PEITC itself but also on its N-acetylated cysteine conjugated form.

The aim of the current study was to (i) extract isolated fractions of watercress flowers enriched in polyphenols, phenethyl isothiocyanate and glucosinolates and (ii) characterize the anticancer mode of action of non-lethal, sub-lethal and lethal concentrations of the most potent extract fraction in primary (A375) and metastatic (COLO-679) melanoma cells as well as non-tumorigenic immortalized keratinocyte (HaCaT) cells. Cytotoxicity was assessed via the Alamar Blue assay, whereas ultrastructural alterations in mitochondria and the endoplasmic reticulum were determined via transmission electron microscopy. Mitochondrial membrane depolarization was determined using Mito-MP dye, whereas apoptosis was evaluated through the activation of caspases-3, -8 and -9. Among all extract fractions, the phenethyl isothiocyanate-enriched one (PhEF) possessed significant cytotoxicity against A375 and COLO-679 cells, while HaCaT cells remained relatively resistant at sub-lethal and lethal concentrations. Additionally, ultrastructural subcellular alterations associated with apoptosis were observed by means of increased mitochondrial area and perimeter, decreased cristae density and a shorter distance of the endoplasmic reticulum to the mitochondria, all taking place during “early” time points (2–4 h) of exposure. Moreover, PhEF induced mitochondrial membrane depolarization associated with “late” time points (24 h) of exposure, thereby leading to the activation of intrinsic apoptosis. Finally, the inhibition of cytosolic Ca2+ efflux reduced levels of caspases-9 and -3 activity, suggesting the involvement of Ca2+ efflux in modulating the activation of intrinsic apoptosis. To conclude, our data demonstrate an association of “early” ultrastructural alterations in mitochondria and the endoplasmic reticulum with the “late” induction of intrinsic apoptosis via the modulation of Ca2+ efflux.

Broiler flock welfare is usually assessed through mortality, physiology, behavior, and walking ability. The possibility of assessing broiler chicken lameness using the bird walking ability was investigated using the machine learning approach for the first time. Data on broiler walking speed and acceleration, genetic strain, and sex were recorded and input in a dataset. Broilers were classified according to the 6-point gait score (GS0 is a sound bird, and GS5 is a severely lame bird). Decision trees were built initially using all datasets. The confusion matrix of each developed model was analyzed. The pruning technique was used, removing from the dataset the variables that did not infer in the classification results. We reorganized the dataset and re-arranged the data by grouping the intermediate target class of gait score using the Borda Count method. Re-processing data, we obtained a new set of decision trees. Using the 3-point gait score (GS0 is a sound bird, and GS2 is a lame bird), we obtained a new model with better accuracy (78%); however, the model had a lower accuracy for classifying lame broilers (GS2, 5%). The final decision tree was selected for classifying broilers, either sound or lame, according to their walking speed. The developed model presented good accuracy (91%), and it ordered properly sound (86%) and lame birds (92%). The novel model might be used to assess broiler lameness on-farm by registering the bird displacement velocity. Further developments using the model might allow flock lameness detection automatically.

Watercress (Nasturtium officinale) is a rich source of secondary metabolites with disease-preventing and/or health-promoting properties. Herein, we have utilized extraction procedures to isolate fractions of polyphenols, glucosinolates and isothiocyanates to determine their identification, and quantification. In doing so, we have utilized reproducible analytical methodologies based on liquid chromatography with tandem mass spectrometry by either positive or negative ion mode. Due to the instability and volatility of isothiocyanates, we followed an ammonia derivatization protocol which converts them into respective ionizable thiourea derivatives. The analytes’ content distribution map was created on watercress flowers, leaves and stems. We have demonstrated that watercress contains significantly higher levels of gluconasturtiin, phenethyl isothiocyanate, quercetin-3-O-rutinoside and isorhamnetin, among others, with their content decreasing from flowers (82.11 ± 0.63, 273.89 ± 0.88, 1459.30 ± 12.95 and 289.40 ± 1.37 ng/g of dry extract respectively) to leaves (32.25 ± 0.74, 125.02 ± 0.52, 1197.86 ± 4.24 and 196.47 ± 3.65 ng/g of det extract respectively) to stems (9.20 ± 0.11, 64.7 ± 0.9, 41.02 ± 0.18, 65.67 ± 0.84 ng/g of dry extract respectivbely). Pearson’s correlation analysis has shown that the content of isothiocyanates doesn’t depend only on the bioconversion of individual glucosinolates but also on other glucosinolates of the same group. Overall, we have provided comprehensive analytical data of the major watercress metabolites thereby providing an opportunity to exploit different parts of watercress for potential therapeutic applications.

Malignant melanoma is an aggressive type of skin cancer characterised by high metastatic capacity and mortality rate. On the other hand, Epilobium parviflorum is known for its medicinal properties, including its anticancer potency. In this context, we aimed to (i) isolate various extracts of E. parviflorum, (ii) characterize their phytochemical content, and (iii) determine their cytotoxic potential in an in vitro model of human malignant melanoma. To these ends, we utilized various spectrophotometric and chromatographic (UPLC-MS/MS) approaches to document the higher content of the methanolic extract in polyphenols, soluble sugars, proteins, condensed tannins, and chlorophylls -a and -b as opposed to those of dichloromethane and petroleum. In addition, the cytotoxicity profiling of all extracts was assessed through a colorimetric-based Alamar Blue assay in human malignant melanoma (A375 and COLO-679) as well as non-tumorigenic immortalized keratinocyte (HaCaT) cells. Overall, the methanolic extract was shown to exert significant cytotoxicity, in a time- and concentration-dependent manner, as opposed to the other extracts. The observed cytotoxicity was confined only to human malignant melanoma cells, whereas non-tumorigenic keratinocyte cells remained relatively unaffected. Finally, the expression levels of various apoptotic genes were assessed by qRT-PCR, indicating the activation of both intrinsic and extrinsic apoptotic cascades.

The severe consequences of the Zika virus (ZIKV) infections resulting in congenital Zika syndrome in infants and the autoimmune Guillain–Barre syndrome in adults warrant the development of safe and efficacious vaccines and therapeutics. Currently, there are no approved treatment options for ZIKV infection. Herein, we describe the development of a bacterial ferritin-based nanoparticle vaccine candidate for ZIKV. The viral envelope (E) protein domain III (DIII) was fused in-frame at the amino-terminus of ferritin. The resulting nanoparticle displaying the DIII was examined for its ability to induce immune responses and protect vaccinated animals upon lethal virus challenge. Our results show that immunization of mice with a single dose of the nanoparticle vaccine candidate (zDIII-F) resulted in the robust induction of neutralizing antibody responses that protected the animals from the lethal ZIKV challenge. The antibodies neutralized infectivity of other ZIKV lineages indicating that the zDIII-F can confer heterologous protection. The vaccine candidate also induced a significantly higher frequency of interferon (IFN)-γ positive CD4 T cells and CD8 T cells suggesting that both humoral and cell-mediated immune responses were induced by the vaccine candidate. Although our studies showed that a soluble DIII vaccine candidate could also induce humoral and cell-mediated immunity and protect from lethal ZIKV challenge, the immune responses and protection conferred by the nanoparticle vaccine candidate were superior. Further, passive transfer of neutralizing antibodies from the vaccinated animals to naïve animals protected against lethal ZIKV challenge. Since previous studies have shown that antibodies directed at the DIII region of the E protein do not to induce antibody-dependent enhancement (ADE) of ZIKV or other related flavivirus infections, our studies support the use of the zDIII-F nanoparticle vaccine candidate for safe and enhanced immunological responses against ZIKV.

Abstract Sex-related differences in the occurrence of autoimmune diseases is well documented, with females showing a greater propensity to develop these diseases than their male counterparts. Sex hormones, namely dihydrotestosterone and estrogens, have been shown to ameliorate the severity of inflammatory diseases. Immunologically, the beneficial effects of sex hormones have been ascribed to the suppression of effector lymphocyte responses accompanied by immune deviation from pro-inflammatory to anti-inflammatory cytokine production. In this review, we present our view of the mechanisms of sex hormones that contribute to their ability to suppress autoimmune responses with an emphasis on the pathogenesis of experimental autoimmune encephalomyelitis.

Abstract Background Elderly people have high rates of functional decline, which compromises independence, self-confidence, and quality of life (QoL). Physical exercise leads to significant improvements in strength, balance, functional mobility, and QoL, but there is still reduced access to this therapeutic strategy due to difficulties in locomotion to training centers or lack of adaptation to the exercise environment. Methods/design The purpose of this clinical trial will be to verify the effect of a progressive and semi-supervised, home-based exercise program on the functional mobility, and in the QoL of sedentary elderly people. This is a protocol of a consecutive, single-center, single-blind, and randomized controlled trial. The design, conduct, and report follows the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Sedentary elderly people will be enrolled, and randomly allocated into two groups. The intervention group will perform exercises in their own home and the control group will not perform exercises. The evaluations will occur at study enrollment and after 3 months of intervention, and will be performed using the functional mobility Timed Up & Go (TUG) test and sociodemographic and QoL questionnaires. In the statistical analysis, comparisons of mean and correlation analyses will be performed. The primary expected outcome is the improvement in functional mobility verified through the TUG test and the secondary outcome is the improvement in QoL verified by the WHOQOL-OLD. Discussion The lack of scientific evidence demonstrating the benefits of semi-supervised home exercise on functional mobility and QoL in elderly people represents an obstacle to the development of guidelines for clinical practice and for policy-makers. The World Health Organization highlighted the importance of musculoskeletal health programs for elderly people, and the exercise program described in this protocol was designed to be viable, easy to implement, and inexpensive, and could be performed at the home of elderly subjects after receiving only guidelines and follow-up via periodic visits. Based on these facts, we hope that this study will demonstrate that a well-structured, home-based exercise program can be effective in improving functional mobility and QoL of sedentary elderly people, even without constant supervision during exercise. Trial registration Registro Brasileiro de Ensaios Clínicos (ReBEC), Identifier: RBR-3cqzfy. Registered on 2 December 2016.

ABSTRACT: Benford Law (BL) states that the occurrence of significant digits in many natural and human phenomena data sets are not uniformly scattered, as one could naively expect, but follow a logarithmic-type distribution. Here, we present a method that consists of the use of BL analysis over first and first-two digits, three statistical conformity tests – Z-statistics, Mean Absolute Deviation (MAD) and Chi-square (χ2) as well as the summation test which looks for excessively large numbers, having fraud detection as one of its application. We developed the method for fraud detection in the case of the Brazilian Bolsa Familia welfare program. In this case, we submitted four periods of Brazilian welfare program payments to the method with a dataset of 13,442,529 records. We provide a practical implementation of the method based on open-source R library released on a public repository. Furthermore, code implementation of the algorithm as well as datasets are freely available. Advantages of the algorithm are listed below:• The method was developed based on open source libraries• The technique is simple, rapid and ease of use• Easily applicable to other social welfare program auditing

Isothiocyanates are biologically active secondary metabolites liberated via enzymatic hydrolysis of their sulfur enriched precursors, glucosinolates, upon tissue plant disruption. The importance of this class of compounds lies in their capacity to induce anti-cancer, anti-microbial, anti-inflammatory, neuroprotective, and other bioactive properties. As such, their isolation from natural sources is of utmost importance. In this review article, an extensive examination of the various parameters (hydrolysis, extraction, and quantification) affecting the isolation of isothiocyanates from naturally-derived sources is presented. Overall, the effective isolation/extraction and quantification of isothiocyanate is strongly associated with their chemical and physicochemical properties, such as polarity-solubility as well as thermal and acidic stability. Furthermore, the successful activation of myrosinase appears to be a major factor affecting the conversion of glucosinolates into active isothiocyanates.

Arsenic, a naturally occurring metalloid derived from the environment, has been studied worldwide for its causative effects in various cancers. However, the effects of arsenic toxicity on the development and progression of metabolic syndrome, including obesity and diabetes, has received less attention. Many studies suggest that metabolic dysfunction and autophagy dysregulation of adipose and muscle tissues are closely related to the development of metabolic disease. In the USA, arsenic contamination has been reported in some ground water, soil and grain samples in major agricultural regions, but the effects on adipose and muscle tissue metabolism and autophagy have not been investigated much. Here, we highlight arsenic toxicity according to the species, dose and exposure time and the effects on adipose and muscle tissue metabolism and autophagy. Historically, arsenic was used as both a poison and medicine, depending on the dose and treatment time. In the modern era, arsenic intoxication has significantly increased due to exposure from water, soil and food, which could be a contributing factor in the development and progression of metabolic disease. From this review, a better understanding of the pathogenic mechanisms by which arsenic alters metabolism and autophagy regulation could become a cornerstone leading to the development of therapeutic strategies against arsenic-induced toxicity and metabolic disease.

In the brain, mitochondrial metabolism has been largely associated with energy production, and its dysfunction is linked to neuronal cell loss. However, the functional role of mitochondria in glial cells has been poorly studied. Recent reports have demonstrated unequivocally that astrocytes do not require mitochondria to meet their bioenergetics demands. Then, the question remaining is, what is the functional role of mitochondria in astrocytes? In this work, we review current evidence demonstrating that mitochondrial central carbon metabolism in astrocytes regulates overall brain bioenergetics, neurotransmitter homeostasis and redox balance. Emphasis is placed in detailing carbon source utilization (glucose and fatty acids), anaplerotic inputs and cataplerotic outputs, as well as carbon shuttles to neurons, which highlight the metabolic specialization of astrocytic mitochondria and its relevance to brain function.

There is a well-established relation between the spatial asymmetry in the initial stage of a heavy-ion collision and the final momentum anisotropy, which allows for a separation of effects from initial conditions vs. later evolution and has proved exceptionally powerful. However, until recently it has only been studied in two dimensions — either through boost-invariant simulations or studying only quantities at mid-rapidity. We explore an extension to 3 dimensions, in order to determine whether a similar understanding can be obtained for the rapidity dependence of the collision system. In particular, we introduce rapidity-dependent eccentricities and investigate a trivial extension of the 2D eccentricity scaling of elliptic and triangular flow, as well as a way to systematically improve these initial-state estimators. We then explore the dependence of the resulting new response coefficients on shear viscosity and initial total energy.

Ambient air pollution is one of the leading five health risks worldwide. One of the most harmful air pollutants is particulate matter (PM), which has different physical characteristics (particle size and number, surface area and morphology) and a highly complex and variable chemical composition. Our goal was first to comparatively assess the effects of exposure to PM regarding cytotoxicity, release of pro-inflammatory mediators and gene expression in human bronchial epithelia (HBE) reflecting normal and compromised health status. Second, we aimed at evaluating the impact of various PM components from anthropogenic and biogenic sources on the cellular responses. Air-liquid interface (ALI) cultures of fully differentiated HBE derived from normal and cystic fibrosis (CF) donor lungs were exposed at the apical cell surface to water-soluble PM filter extracts for 4 h. The particle dose deposited on cells was 0.9–2.5 and 8.8–25.4 μg per cm2 of cell culture area for low and high PM doses, respectively. Both normal and CF HBE show a clear dose-response relationship with increasing cytotoxicity at higher PM concentrations. The concurrently enhanced release of pro-inflammatory mediators at higher PM exposure levels links cytotoxicity to inflammatory processes. Further, the PM exposure deregulates genes involved in oxidative stress and inflammatory pathways leading to an imbalance of the antioxidant system. Moreover, we identify compromised defense against PM in CF epithelia promoting exacerbation and aggravation of disease. We also demonstrate that the adverse health outcome induced by PM exposure in normal and particularly in susceptible bronchial epithelia is magnified by anthropogenic PM components. Thus, including health-relevant PM components in regulatory guidelines will result in substantial human health benefits and improve protection of the vulnerable population.

The relevance of the Internet of Services (IoS) comes from the global reach of the Internet into everyone’s home and daily activities and from the move from a manufacturing-based economy to a service-based economy. The IoS is seen as a new ecosystem where service providers and consumers explore their business networks for service provision and consumption. The scientific literature refers to IoS as an important cornerstone for Industry 4.0 and Future Internet; thus, it becomes relevant to study how IoS interacts with business models. Nevertheless, there is a lack of clarity on such an intersection. Moreover, a systematic review of IoS-based business models is still missing. This paper aims to make a systematic review of IoS-based business models and their application fields. We included studies from Scopus and Web of Science databases, we excluded duplicated papers and short conference versions of the later full paper journal publications. Twenty-three different studies are presented, categorized in the sub-areas of IoS, and then by the fields of applications. The main finding highlights the opportunities of IoS applications in different fields, offering directions for future research on this new arena.

Watercress is an enriched source of phenethyl isothiocyanate (PEITC), among other phytochemicals, with an antioxidant capacity. The aim of this study was to (i) chemically characterize and (ii) biologically evaluate the profile of the main health-promoting compounds contained in edible (i.e., mixture of leaves and lateral buds) and non-edible (i.e., stems) parts of watercress in an in vitro model of malignant melanoma consisting of human malignant melanoma (A375), non-melanoma (A431) and keratinocyte (HaCaT) cells. The extraction of the main constituents of watercress was performed by subjecting the freeze-dried edible and non-edible samples through different extraction protocols, whereas their concentration was obtained utilizing analytical methodologies. In addition, cell viability was evaluated by the Alamar Blue assay, whereas levels of oxidative stress and apoptosis were determined by commercially available kits. The edible watercress sample contained a higher amount of various nutrients and phytochemicals in the hexane fraction compared to the non-edible one, as evidenced by the presence of PEITC, phenolics, flavonoids, pigments, ascorbic acid, etc. The cytotoxicity potential of the edible watercress sample in the hexane fraction was considerably higher than the non-edible one in A375 cells, whereas A431 and HaCaT cells appeared to be either more resistant or minimally affected, respectively. Finally, levels of oxidative stress and apoptotic induction were increased in both watercress samples, but the magnitude of the induction was much higher in the edible than the non-edible watercress samples. Herein, we provide further evidence documenting the potential development of watercress extracts (including watercress waste by-products) as promising anti-cancer agent(s) against malignant melanoma cells.

Abstract Background The amino acid taurine (2-Aminoethanesulfonic acid) modulates inhibitory neurotransmitter receptors. This study aimed to determine if the dual action of taurine on GABAC-ρ1R relates to its structure. To address this, we tested the ability of the structurally related compounds homotaurine, hypotaurine, and isethionic acid to modulate GABAC-ρ1R. Results In Xenopus laevis oocytes, hypotaurine and homotaurine partially activate heterologously expressed GABAC-ρ1R, showing an increment in its deactivation time with no changes in channel permeability, whereas isethionic acid showed no effect. Competitive assays suggest that hypotaurine and homotaurine compete for the GABA-binding site. In addition, their effects were blocked by the ion-channel blockers picrotixin and Methyl(1,2,5,6-tetrahydropyridine-4-yl) phosphinic acid. In contrast to taurine, co-application of GABA with hypotaurine or homotaurine revealed that the dual effect is present separately for each compound: hypotaurine modulates positively the GABA current, while homotaurine shows a negative modulation, both in a dose-dependent manner. Interestingly, homotaurine diminished hypotaurine-induced currents. Thus, these results strongly suggest a competitive interaction between GABA and homotaurine or hypotaurine for the same binding site. “In silico” modeling confirms these observations, but it also shows a second binding site for homotaurine, which could explain the negative effect of this compound on the current generated by GABA or hypotaurine, during co-application protocols. Conclusions The sulfur-containing compounds structurally related to taurine are partial agonists of GABAC-ρ1R that occupy the agonist binding site. The dual effect is unique to taurine, whereas in the case of hypotaurine and homotaurine it presents separately; hypotaurine increases and homotaurine decreases the GABA current.

Malignant melanoma is one of the most aggressive types of skin cancer with an increasing incidence worldwide. Thus, the development of innovative therapeutic approaches is of great importance. Salvia fruticosa (SF) is known for its anticancer properties and in this context, we aimed to investigate its potential anti-melanoma activity in an in vitro model of human malignant melanoma. Cytotoxicity was assessed through a colorimetric-based sulforhodamine-B (SRB) assay in primary malignant melanoma (A375), non-malignant melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte neighbouring keratinocyte (HaCaT) cells. Among eight (8) different fractions of S. fruticosa extracts (SF1-SF8) tested, SF3 was found to possess significant cytotoxic activity against A375 cells, while A431 and HaCaT cells remained relatively resistant or exerted no cytotoxicity, respectively. In addition, the total phenolic (Folin–Ciocalteu assay) and total flavonoid content of SF extracts was estimated, whereas the antioxidant capacity was measured via the inhibition of tert-butyl hydroperoxide-induced lipid peroxidation and protein oxidation levels. Finally, apoptotic cell death was assessed by utilizing a commercially available kit for the activation of caspases - 3, - 8 and - 9. In conclusion, the anti-melanoma properties of SF3 involve the induction of both extrinsic and intrinsic apoptotic pathway(s), as evidenced by the increased activity levels of caspases - 8, and - 9, respectively.

In the last few years, two technological events emerged. First, the rising of Industry 4.0 concepts and technologies such as IoT allowed the direct link between machines on the shop floor, establishing a machine-to-machine communication (M2M). Second, blockchain enables transactions such payments and contracts without a formal reliable or accreditation institutions, such as banks or government. Goal: The goal of this paper is to explore the state-of-art of the blockchain technology applied to the manufacture sector. In this sense, the option of the M2M transaction being intermediated by blockchain on the shop floor is a hypothesis to be tested. Moreover, it could be questioned if these subjects are being appreciated by the academia. Design / Methodology / Approach: a systematic review of the literature was conducted, considering blockchain, the industrial context, and the Industry 4.0 related technologies. Results: As a result, only 12 papers that were classified according to their application fields and practice stages were obtained. Limitations of the investigation: this field of application is brand new; thus, the available literature is scarce; only 12 papers were obtained. Practical implications: As the main result, it was identified that the possibilities of blockchain applications to Industry have been poorly explored by literature. Originality / Value: The paper addresses the possibility of application of blockchain in M2M-based manufacture, and detaches the research gap in the academic literature related to it.

Malignant melanoma is one of the most deadly types of solid cancers, a property mainly attributed to its highly aggressive metastatic form. On the other hand, different classes of isothiocyanates, a class of phytochemicals, present in cruciferous vegetables have been characterized by considerable anti-cancer activity in both in vitro and in vivo experimental models. In the current study, we investigated the anti-cancer response of five isothiocyanates in an in vitro model of melanoma consisting of non-metastatic (A375, B16F-10) and metastatic (VMM1, Hs294T) malignant melanoma as well as non-melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte-neighboring keratinocyte (HaCaT) cells. Our aim was to compare different endpoints of cytotoxicity (e.g., reactive oxygen species, intracellular glutathione content, cell cycle growth arrest, apoptosis and necrosis) descriptive of an anti-cancer response between non-metastatic and metastatic melanoma as well as non-melanoma epidermoid carcinoma and non-tumorigenic cells. Our results showed that exposure to isothiocyanates induced an increase in intracellular reactive oxygen species and glutathione contents between non-metastatic and metastatic melanoma cells. The distribution of cell cycle phases followed a similar pattern in a manner where non-metastatic and metastatic melanoma cells appeared to be growth arrested at the G2/M phase while elevated levels of metastatic melanoma cells were shown to be at sub G1 phase, an indicator of necrotic cell death. Finally, metastatic melanoma cells were more sensitive apoptosis and/or necrosis as higher levels were observed compared to non-melanoma epidermoid carcinoma and non-tumorigenic cells. In general, non-melanoma epidermoid carcinoma and non-tumorigenic cells were more resistant under any experimental exposure condition. Overall, our study provides further evidence for the potential development of isothiocyanates as promising anti-cancer agents against non-metastatic and metastatic melanoma cells, a property specific for these cells and not shared by non-melanoma epidermoid carcinoma or non-tumorigenic melanocyte cells.

Introducción: El LaTeX es un programa para crear y documentos que requieren una salida de impresión de alta calidad de edición. Tiene características complejas que exigen la creación de plantillas para facilitar su uso. El propósito de este artículo fue la de crear un modelo de tesis y disertaciones en LaTeX, para el Programa de Estudios de Posgrado en Ingeniería de Producción de la Universidad Paulista con el fin de facilitar la inclusión students's y permitiendo la presentación de trabajos dentro de los estándares internacionales. Método: Se adoptó la metodología de Design Science Research (DSR), que contiene las directrices para la creación o adaptación y evaluación de artefactos, como el software, y otros instrumentos científicos. Como requisitos se utilizó el manual de normas académicas disponibles en el sitio web de la institución. La evaluación se llevó a cabo a través de simulaciones y presentación para los estudiantes y los profesores del programa, seguido de un cuestionario aplicado a 34 encuestados. Resultados: se encontró que casi el 40% respondió que conocía el programa aunque 60% no. Después de la presentación, alrededor del 32% de los encuestados indicó la plantilla como difícil de usar, el 50% consideró razonable, y el 18% respondió que era "fácil". Acerca de 76,5% de los grupos formados para el análisis señaló positivamente que se podría reemplazar los editores convencionales para LaTeX, aunque el 23,5%. tuvo una opinión diferente. Las variables más destacadas para la aceptación fueron: la calidad tipográfica y la concentración lógica del contenido y sus facilidades. Estudiantes de maestría tuvieron mayor homogeneidad en las respuestas. Conclusión: la plantilla propuesta fue aceptada con entusiasmo, a pesar de que se insistió que la dificultad de uso requiere un período de capacitación.

ABSTRACT: The present study aimed to evaluate the use of aqueous wheat extracts as an adjunct to antineoplastic therapy with carboplatin. In this study, 32 rats were used which were randomly distributed into 4 groups: G1 - negative control; G2 - control treated with physiological solution; G3 - animals treated with aqueous extract of wheat in the concentration of 100mg/kg; G4 - animals treated with aqueous wheat extract at the concentration of 400mg/kg; 300mg/m² of carboplatin was administered intraperitoneally at day 0 in animals from groups G2, G3, and G4, whereas 1ml of physiological solution was administered by the same route in animals from group G1. Animals were treated daily for 21 days by orogastric gavage according to their respective experimental group. Blood was collected from animals on days 3, 7 and 21 for complete blood count (CBC), biochemistry, and measurement of paraoxonase 1 (PON1) activity. On day 21, animals were euthanized and necropsied. Promising results were obtained regarding oxidative balance in groups G3 and G4. Both presented better PON1 activity in comparison with group G2 (P

Gene multiplications or point mutations in alpha (α)-synuclein are associated with familial and sporadic Parkinson's disease (PD). An increase in copper (Cu) levels has been reported in the cerebrospinal fluid and blood of PD patients, while occupational exposure to Cu has been suggested to augment the risk to develop PD. We aimed to elucidate the mechanisms by which α-synuclein and Cu regulate dopaminergic cell death. Short-term overexpression of wild type (WT) or mutant A53T α-synuclein had no toxic effect in human dopaminergic cells and primary midbrain cultures, but it exerted a synergistic effect on Cu-induced cell death. Cell death induced by Cu was potentiated by overexpression of the Cu transporter protein 1 (Ctr1) and depletion of intracellular glutathione (GSH) indicating that the toxic effects of Cu are linked to alterations in its intracellular homeostasis. Using the redox sensor roGFP, we demonstrated that Cu-induced oxidative stress was primarily localized in the cytosol and not in the mitochondria. However, α-synuclein overexpression had no effect on Cu-induced oxidative stress. WT or A53T α-synuclein overexpression exacerbated Cu toxicity in dopaminergic and yeast cells in the absence of α-synuclein aggregation. Cu increased autophagic flux and protein ubiquitination. Impairment of autophagy by overexpression of a dominant negative Atg5 form or inhibition of the ubiquitin/proteasome system (UPS) with MG132 enhanced Cu-induced cell death. However, only inhibition of the UPS stimulated the synergistic toxic effects of Cu and α-synuclein overexpression. Our results demonstrate that α-synuclein stimulates Cu toxicity in dopaminergic cells independent from its aggregation via modulation of protein degradation pathways.

Dentro da prática fisioterápica verifica-se a ampla utilização do ultrassom terapêutico para tratamento das diversas afecções musculoesqueléticas. O objetivo deste estudo foi avaliar o efeito da irradiação Ultrassônica de Baixa Intensidade, com diferentes regimes de pulsos e intensidade, em cultura celular de fibroblastos L929 (ATCC CCL-1 NCTC), de modo a verificar a viabilidade celular e definir parâmetros de dosimetria. Para isso, utilizou-se a aplicação de ultrassom pulsado, com frequência de 1Mhz, em cultura de células fibroblásticas, divididas em cinco grupos (controle e com intensidade instantâneas de 0,3W/cm2-10%; 0,3W/cm2 -20 %; 0,5W/cm2 -10% e US 0,5W/cm2 -20 % - 100Hz). A irradiação ocorreu com intervalos de 24, 48 e 72 horas, por dois minutos, e após 24 horas de cada irradiação foi realizado teste de MTT Brometo de [3-(4,5-dimetiltiazol)-2,5-difeniltetrazólio]. Os resultados revelaram que ao compararem-se os valores de células viáveis pelo método MTT nos cinco grupos, não foi possível encontrar diferença estatisticamente significativa em nenhum deles, nos três momentos avaliados (24, 48 e 72 horas); enquanto que, ao se realizar a análise de medida repetida nos diferentes grupos, encontrou-se diferença estatisticamente significativa apenas no grupo irradiado com ultrassom a 0,5W/ cm2com regime de pulso de 10% (p=0,003). Com base nesses resultados, conclui-se que a irradiação Ultrassônica de Baixa Intensidade em cultura celular de fibroblastos L929, somente no grupo com intensidade de 0,5W/cm2-10% obteve o crescimento numérico, com significância estatística em todos os períodos de avaliação.

Embora com menor benefício que na logística direta, os principais Sistemas de Informação dedicados ao apoio as atividades logísticas, contribuem de forma significativa no gerenciamento dos retornos. No entanto, a pesquisa (survey) realizada com um grupo profissionais envolvidos com o processo de retorno, provenientes de empresas de médio e grande porte da indústria e varejo do estado de SP que teve como objetivo identificar estas contribuições mostrou que ao invés destas soluções, mais de 90% das empresas que automatizam os seus processos, utilizam soluções paliativas provenientes dos seus Enterprise Resource Planning – ERPs, desenvolvidas internamente ou o próprio ERP. Embora este grupo tenha apresentado alguns benefícios no processo como: redução de custo e tempo, melhora operacional e competitividade, em geral 79% dos respondentes consideram que estas soluções atendem parcialmente suas necessidades. Conclui-se que a obtenção dos benefícios do SI no processo de retorno vai além das soluções de gestão, é necessária sua utilização na operação do processo para obtenção de melhores benefícios no gerenciamento das atividades de retorno.

Many studies have shown evidence in support of the beneficial effects of phytochemicals in preventing chronic diseases, including cancer. Among such phytochemicals, sulphur-containing compounds (e.g., isothiocyanates (ITCs)) have raised scientific interest by exerting unique chemo-preventive properties against cancer pathogenesis. ITCs are the major biologically active compounds capable of mediating the anticancer effect of cruciferous vegetables. Recently, many studies have shown that a higher intake of cruciferous vegetables is associated with reduced risk of developing various forms of cancers primarily due to a plurality of effects, including (i) metabolic activation and detoxification, (ii) inflammation, (iii) angiogenesis, (iv) metastasis and (v) regulation of the epigenetic machinery. In the context of human malignant melanoma, a number of studies suggest that ITCs can cause cell cycle growth arrest and also induce apoptosis in human malignant melanoma cells. On such basis, ITCs could serve as promising chemo-therapeutic agents that could be used in the clinical setting to potentiate the efficacy of existing therapies.

Skin cancer is among the most common cancer types accompanied by rapidly increasing incidence rates, thus making the development of more efficient therapeutic approaches a necessity. Recent studies have revealed the potential role of decosahexaenoic acid ester of phloridzin (PZDHA) in suppressing proliferation of liver, breast, and blood cancer cell lines. In the present study, we investigated the cytotoxic potential of PZDHA in an in vitro model of skin cancer consisting of melanoma (A375), epidermoid carcinoma (A431), and non-tumorigenic (HaCaT) cell lines. Decosahexaenoic acid ester of phloridzin led to increased cytotoxicity in all cell lines as revealed by cell viability assays. However, growth inhibition and induction of both apoptosis and necrosis was more evident in melanoma (A375) and epidermoid carcinoma (A431) cells, whereas non-tumorigenic keratinocytes (HaCaT) appeared to be more resistant as detected by flow cytometry. More specifically, PZDHA-induced cell cycle growth arrest at the G2/M phase in A375 and A431 cells in contrast to HaCaT cells, which were growth arrested at the G0/G1 phase. Elevated intracellular generation of reactive oxygen species ROS was detected in all cell lines. Overall, our findings support the potential of PZDHA as a novel therapeutic means against human skin cancer.

This study was conducted to map and model the business processes of the HEI (Higher Education Institutions). It aims to show the importance of business processes modelling as a precondition for information system design. It shows the concepts of Activity-Based Costing (ABC) and its update, the TDABC (Time-Driven Activity-Based Costing), to support the development of a costing system for public universities. For the modelling of business processes, it was used the BPMN (Business Process Management Notation). It can be conclude that public processes implemented in public services are both complex and bureaucratic, mainly due to regulations. A bidding procedure of acquisition materials or services demand eight sectors activities. The contribution of this study is to present how a business process modelling should be applied to public service for the optimization of resources. This research presents the normal flow of bids, but in practice there is some variation.

This study aims to propose a cost-effective technical solution in monitoring the distance of workers operating in hazardous areas or under strong external influences. A prototype was built to measure body temperature, relative air humidity and ambient temperature through of an applied research. Body temperature data is display in a graph, within a predetermined period, wherein the measurement range can be easily set. As a result, the system first tests were stable solution and for using open source tools, it was possible to develop a low cost prototype.

Resumen de la tesis Doctoral “Modelos urbanos y proceso de transformación territorial en la ciudad de Aguascalientes: de la ocupación periférica a la liquidación del centro tradicional”. Defendida por D. Rodrigo Franco Muñoz en el Instituto Universitario de Urbanística de la Universidad de Valladolid el 1 de octubre de 2010. Director: Dr. Alfonso Álvarez Mora. Tribunal: Dr. Juan Luis de Las Rivas Sanz, Dr. Xosé Lois Martínez Suárez, Dr. Francisco Valverde Díaz de León, Dra. María Castrillo Romón y Dr. Agustín Hernández Aja.

O uso intensivo de Sistemas de Informação é uma possível solução para a integração das atividades de projeto em AEC, permitindo que decisões sejam tomadas ainda na fase de projeto e, conseqüentemente, evitando-se retrabalhos em obra. Neste sentido, esforços têm sido realizados para padronizar conceitos e terminologias de AEC, permitindo a troca e armazenagem de informações, como a norma ISO 12006-2 e os padrões estabelecidos pelo IFC. Ambas são baseadas na linguagem EXPRESS, assim como é o padrão industrial STEP. Entretanto, as representações de informação usadas na indústria de produtos não são as mais adequadas para a Engenharia de Software, responsável pelo desenvolvimento de Sistemas de Informação, onde as representações semânticas envolvem não somente a representação estrutural da informação, mas também a representação comportamental. Este artigo contribui com uma visão de implementação em UML da informação de um projeto de AEC e tornam explícitas, sob a ótica do desenvolvimento de software, as relações semânticas existentes. Os resultados desta pesquisa foram obtidos através da realização de um estudo de caso de projeto de produção em CAD 3D dos subsistemas alvenaria e revestimento para um edifício residencial. A partir das observações do estudo de caso foi feita a modelagem em UML dos objetos pertinentes. O principal resultado obtido foi a representação explícita das interfaces entre objetos AEC.

Silibinin, extracted from milk thistle (Silybum marianum L.), has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways. Here we hypothesized that silibinin’s pleiotropic effects may reflect its interference with epigenetic mechanisms in human prostate cancer cells. More specifically, we have demonstrated that silibinin reduces gene expression levels of the Polycomb Repressive Complex 2 (PRC2) members Enhancer of Zeste Homolog 2 (EZH2), Suppressor of Zeste Homolog 12 (SUZ12), and Embryonic Ectoderm Development (EED) in DU145 and PC3 human prostate cancer cells, as evidenced by Real Time Polymerase Chain Reaction (RT-PCR). Furthermore immunoblot and immunofluorescence analysis revealed that silibinin-mediated reduction of EZH2 levels was accompanied by an increase in trimethylation of histone H3 on lysine (Κ)-27 residue (H3K27me3) levels and that such response was, in part, dependent on decreased expression levels of phosphorylated Akt (ser473) (pAkt) and phosphorylated EZH2 (ser21) (pEZH2). Additionally silibinin exerted other epigenetic effects involving an increase in total DNA methyltransferase (DNMT) activity while it decreased histone deacetylases 1-2 (HDACs1-2) expression levels. We conclude that silibinin induces epigenetic alterations in human prostate cancer cells, suggesting that subsequent disruptions of central processes in chromatin conformation may account for some of its diverse anticancer effects.