JAK3 as an emerging target for topical treatment of inflammatory skin diseases

The recent interest and elucidation of the JAK/STAT signaling pathway created new targets for the treatment of inflammatory skin diseases (ISDs). JAK inhibitors in oral and topical formulations have shown beneficial results in psoriasis and alopecia areata. Patients suffering from other ISDs might also benefit from JAK inhibition. Given the development of specific JAK inhibitors, the expression patterns of JAKs in different ISDs needs to be clarified. We aimed to analyze the expression of JAK/STAT family members in a set of prevalent ISDs: psoriasis, lichen planus (LP), cutaneous lupus erythematosus (CLE), atopic dermatitis (AD), pyoderma gangrenosum (PG) and alopecia areata (AA) versus healthy controls for (p) JAK1, (p) JAK2, (p) JAK3, (p) TYK2, pSTAT1, pSTAT2 and pSTAT3. The epidermis carried in all ISDs, except for CLE, a strong JAK3 signature. The dermal infiltrate showed a more diverse expression pattern. JAK1, JAK2 and JAK3 were significantly overexpressed in PG and AD suggesting the need for pan-JAK inhibitors. In contrast, psoriasis and LP showed only JAK1 and JAK3 upregulation, while AA and CLE were characterized by a single dermal JAK signal (pJAK3 and pJAK1, respectively). This indicates that the latter diseases may benefit from more targeted JAK inhibitors. Our in vitro keratinocyte psoriasis model displayed reversal of the psoriatic JAK profile following tofacitinib treatment. This direct interaction with keratinocytes may decrease the need for deep skin penetration of topical JAK inhibitors in order to exert its effects on dermal immune cells. In conclusion, these results point to the important contribution of the JAK/STAT pathway in several ISDs. Considering the epidermal JAK3 expression levels, great interest should go to the investigation of topical JAK3 inhibitors as therapeutic option of ISDs

Pyrolysis-catalysis of waste plastic using a nickel-stainless steel mesh catalyst for high value carbon products.

A stainless steel mesh loaded with nickel catalyst was produced and used for the pyrolysis-catalysis of waste high density polyethylene with the aim of producing high value carbon products, including carbon nanotubes. The catalysis temperature and plastic to catalyst ratio were investigated to determine the influence on the formation of different types of carbon deposited on the nickel-stainless steel mesh catalyst. Increasing temperature from 700 to 900 °C resulted in an increase in the carbon deposited on the nickel loaded stainless steel mesh catalyst from 32.5 wt.% to 38.0 wt.%. The increase of sample to catalyst ratio reduced the amount of carbon deposited on the mesh catalyst in terms of g carbon g(-1) plastic. The carbons were found to be largely composed of filamentous carbons, with negligible disordered (amorphous) carbons. Transmission electron microscopy analysis of the filamentous carbons revealed them to be composed of a large proportion (estimated at ∼40%) multi-walled carbon nanotubes. The optimum process conditions for carbon nanotube production, in terms of yield and graphitic nature, determined by Raman spectroscopy, was catalysis temperature of 800 °C and plastic to catalyst ratio of 1:2 where a mass of 334 mg of filamentous/multi-walled carbon nanotubes g(-1) plastic was produced

Preval?ncia do consumo de tabaco entre estudantes rec?m-ingressantes em uma universidade p?blica da regi?o Sudeste do Brasil.

Programa de P?s-Gradua??o em Sa?de e Nutri??o. Escola de Nutri??o, Universidade Federal de Ouro Preto.Introdu??o: o uso do tabaco ? um crescente problema de sa?de p?blica entre os estudantes universit?rios, grupo de vulnerabilidade ao uso de drogas l?citas e il?citas. Objetivo: Avaliar a preval?ncia do uso de tabaco em estudantes rec?m ingressantes de uma Universidade P?blica do Sudeste do Brasil. Metodologia: Estudo transversal realizado com amostra aleat?ria de universit?rios que ingressaram no primeiro semestre de 2010 (n=252). Foram coletados dados s?cio-demogr?ficos, de atividade f?sica e informa??es sobre o grau de depend?ncia de tabaco (Teste de Fagerstrom). Para comparar propor??es foram utilizados os Testes Qui-quadrado e Exato de Fisher. Resultados: Foram inclu?dos 252 alunos, 52% do sexo feminino. A mediana de idade foi 19,7 anos, sendo que aproximadamente 94% da amostra tinha idade superior a 18 anos. Cinquenta e seis por cento dos estudantes avaliados foram classificados como sedent?rios em rela??o ? pr?tica de atividade f?sica. A maior parte da amostra foi composta por estudantes de ci?ncias sociais aplicadas. A preval?ncia de tabagismo foi de 13,9%, com idade m?dia de in?cio do consumo de cigarros de 16,63?1,59 anos. A maior parte dos tabagistas (62,9%) come?aram fumar com idade inferior a 18 anos. Entre os tabagistas (35), a maioria era do sexo masculino (62,86%), sem diferen?a significativa (p=0,06). Pela classifica??o do question?rio de Fagerstrom, 90,9% dos alunos apresenta??o grau de depend?ncia de nicotina muito baixo, com consumo inferior a 11 cigarros/dia. Al?m disso, 48,6% relataram terem come?ado fumar em festas e 22,9% com os amigos. Aproximadamente 46% dos fumantes relataram j? terem tentado abandonar o v?cio, sendo o nervosismo o motivo mais relatado para abandono da abstin?ncia (37,1%). Entre os tabagistas o h?bito de consumir bebidas alco?licas foi significativamente maior em rela??o aos n?o tabagistas ( 97,1% versus 73,2%; p=0,002). Al?m disso, em rela??o ao IMC, os alunos tabagistas aparentemente tiveram maior frequ?ncia de sobrepeso e obesidade (34,3% versus 24,9%); e menor frequ?ncia de eutr?ficos (60% versus 70,9%), em rela??o aos n?o tabagistas, por?m sem signific?ncia estat?stica. Conclus?o: Foi encontrada baixa preval?ncia de tabagismo entre os universit?rios rec?m ingressantes e muito baixo grau de depend?ncia de nicotina entre os tabagistas.Introduction: Tobacco use is a growing public health problem among college students, vulnerable group to drug use. Objective: Evaluate the prevalence of tobacco use in new freshmen students of a public university in the Southeast of Brazil. Methods: Cross-sectional study with a random sample of students who entered the first half of 2010 (n = 252). We collected socio-demographic data, physical activity and information on the degree of tobacco dependence (Fagerstrom test). To compare the proportions tests chi-square and Fisher exact tests were used. Results: We included 252 students, 52% female. The median age was 19.7 years, with approximately 94% under the age 18. Fifty-six percent of students assessed were classified as sedentary in relation to physical activity. Most of the sample consisted of students of applied social sciences. The prevalence of smoking was 13.9%, with an average age of onset of smoking of 16.63 ? 1.59 years. Most smokers (62.9%) started smoking under the age of 18. Among the smokers (35), most were male (62.86%), with no significant difference (p = 0.06). According to the Fagerstrom?s questionnaire, 90.9% of students show very low degree of nicotine dependence, with consumption of less than 11 cigarettes / day. In addition, 48.6% reported having started smoking at parties and 22.9% with friends. Approximately 46% of smokers reported having tried to quit, and the nervousness was the most reported reason for withdrawal of abandonment (37.1%). Among smokers the habit of consuming alcoholic drinks was significantly higher compared to non-smokers (97.1% versus 73.2%; p = 0.002). Furthermore, in relation to BMI, smokers students apparently had a higher frequency of overweight and obesity (34.3% versus 24.9%); and lower frequency of normal weight (60% versus 70.9%), compared to nonsmokers, but without statistical significance. Conclusion: We found low prevalence of smoking among college freshmen and new very low degree of nicotine dependence among smokers

SATURN - uma nova ferramenta de corre??o de dados U-Pb para LA-ICP-MS.

Programa de P?s-Gradua??o em Evolu??o Crustal e Recursos Naturais. Departamento de Geologia, Escola de Minas, Universidade Federal de Ouro Preto.Na geocronologia, s?o tratados e reduzidos dados que permitem calcular raz?es isot?picas e incertezas de amostras analisadas em espectr?metros de massas. Dentre as t?cnicas existentes para aquisi??o de dados, este trabalho utilizou como enfoque LA-ICP-MS (Laser Ablation-Inductively Coupled-Mass Spectrometry) para o m?todo geocronol?gico U-Th-Pb. A aquisi??o de dados, seja ela pelo sistema Multi-collector (MC), Setor Magn?tico (SF) ou Quadrupole (Q), necessita de tratamento e redu??es. Os dados adquiridos passam por corre??es (ex.: interfer?ncias isob?ricas e fracionamento induzido pelo laser) e redu??es, as quais consistem no c?lculo das raz?es isot?picas, e incertezas. As incertezas totais resultam da propaga??o das incertezas calculadas, quanto menos os dados necessitam serem reduzidos (corrigidos) menores ser?o as incertezas. Para este tratamento de dados, existem softwares dispon?veis (ex.: Glitter, Iolite) que mesmo que possuam uma interface gr?fica de f?cil utiliza??o e possibilitem a redu??o de dados on-line, n?o realizam corre??es de Pb comum ou o controle de dead-time dos contadores de ?ons. Como alternativa para estes softwares, existe a possibilidade de um tratamento de dados off-line utilizando de planilhas de Excel? e macros VBA. Neste ?ltimo caso, ? poss?vel a aplica??o das corre??es necess?rias, por?m o resultado final n?o ? obtido de modo pr?tico e din?mico. Na busca por preencher essas lacunas, quanto ao tratamento de dados na geocronologia, o atual trabalho buscou o aperfei?oamento de um software de redu??o de dados. Este software, desenvolvido no Departamento de Geologia da Universidade Federal de Ouro Preto, originalmente fez uso da linguagem computacional MatLAB?. A escolha por esta linguagem de programa??o se deve ao ambiente de f?cil utiliza??o para desenvolvimento dos algoritmos e interface gr?fica, al?m de ferramentas nativas, fun??es inbuilt para processamento matem?tico-estat?stico e ambiente din?mico para depura??o dos dados. Com o objetivo de aprimorar essa ferramenta, foram extra?dos da literatura as equa??es para c?lculo de concentra??es, raz?es, idades, esquemas de corre??o de diversas interfer?ncias e propaga??o de incertezas, sempre considerando as devidas adapta??es para dados origin?rios tanto do Neptune ICP-MS-MC quanto do Element II ICP-MS. Com uma avalia??o acerca dos m?todos e equa??es aplicadas no processo, componentes de corre??es foram eliminados ou modificados, resultando na obten??o de melhores incertezas. Os dados analisados anteriormente, e previamente cedidos, em projetos realizados por pesquisadores do Departamento de Geologia da Universidade Federal de Ouro Preto, foram comparados quanto ? sua redu??o no SATURN e por outros m?todos utilizados atualmente pelo departamento. Atrav?s da compara??o, com resultados preliminares, foram observadas menores incertezas aliadas a um processo mais eficiente e ?gil.In geochronology, data are analyzed and reduced to calculate isotope ratios and uncertainties of samples analyzed in mass spectrometers. Among the existing techniques for data acquisition, this work used as LA-ICP-MS (Laser Ablation-Inductively Coupled-Mass Spectrometry) approach for the U-ThPb geochronological method. Data acquisition, whether through the Multi-collector (MC), Sector Field (SF) or Quadrupole (Q), requires treatment and reductions. The acquired data undergoes corrections (eg isobaric interferences and laser induced fractionation) and reductions, which are the calculation of the isotope ratios, and uncertainties. The total uncertainties result from the propagation of the calculated uncertainties, the less the data need to be reduced (corrected) the lower the uncertainties. For this data processing, there are software available (eg, Glitter, Iolite) that even if they have a friendly graphical interface and make it possible to reduce data online, do not perform common Pb corrections or deadtime control of counters of ions. As an alternative to these software, there is the possibility of off-line data processing using Excel? spreadsheets and VBA macros. In the latter case, it is possible to apply the necessary corrections, but the final result is not obtained in a practical and dynamic way. In the search to fill these gaps, regarding the treatment of data in geochronology, the present work sought the improvement of data reduction software. This software, developed in the Department of Geology of the Federal University of Ouro Preto, originally made use of MatLAB? computational language. The choice for this programming language is due to the friendly environment for development of algorithms and graphical interface, in addition to native tools, inbuilt functions for mathematical-statistical processing and dynamic environment for data debugging. In order to improve this tool, was extracted from the literature the equations for calculating concentrations, ratios, ages, schemes for correction of various interferences and propagation of uncertainties, considering the appropriate adaptations for data from both Neptune ICP-MS-MC and Element II ICP-MS-SF. With an evaluation of the methods and equations applied in the process, components of corrections were eliminated or modified, resulting in better uncertainties. The previously analyzed data, previously assigned, in projects carried out by researchers of the Department of Geology of the Federal University of Ouro Preto, were compared in terms of their reduction in SATURN and other methods currently used by the department. Through the comparison, with preliminary results, smaller uncertainties were observed together with a more efficient and agile process

Structural changes in intestinal enteroendocrine cells after ileal interposition in normal rats

INTRODUCTION: No therapeutic approach has significantly impacted the progression of diabetes. As early improvement of glicaemic control is observed after bariatric surgeries, there is currently a search for surgical procedures that can promote euglycemia also in non-obese patients. Glicaemic control can be achieved by increasing the blood concentration of GLP-1, a hormone produced by L cells that are more densely concentrated in the terminal ileum. The interposition of ileal segment to a more anterior region (proximal jejunum) can promote a greater stimulation of the L cells by poorly digested food, increasing the production of GLP-1 and reflecting on glicaemic control.
AIMS: To investigate long-term histological modifications of intestinal mucosa of rats submitted to interposition of ileum segment to a proximal region (jejunum).
METHODS: Forty 8-week old male Wistar-EPM1 rats (Rattus norvegicus albinus) were randomly distributed into 3 groups: the Interposition Group (IG) was subjected to ileal interposition, the Sham Group (SG) was subjected to sham operations, and the Control Group (CG) was not subjected to surgery. All animals were followed until the 60th postoperative day (8 postoperative week) when they were euthanized. Segments of jejunum and ileum from all groups were collected and analyzed by optical microscopy and immunohistochemistry.
RESULTS: No structural nor histological changes in intestinal L cells in the interposed intestinal segment and other intestinal segments were noted after ileal interposition surgery. 
CONCLUSION: As L cells endocrine characteristics were likely maintained, the use of metabolic surgical techniques for the treatment of metabolic diseases, especially diabetes, seems to be justified

Towards Scaling Blockchain Systems via Sharding

Existing blockchain systems scale poorly because of their distributed consensus protocols. Current attempts at improving blockchain scalability are limited to cryptocurrency. Scaling blockchain systems under general workloads (i.e., non-cryptocurrency applications) remains an open question. In this work, we take a principled approach to apply sharding, which is a well-studied and proven technique to scale out databases, to blockchain systems in order to improve their transaction throughput at scale. This is challenging, however, due to the fundamental difference in failure models between databases and blockchain. To achieve our goal, we first enhance the performance of Byzantine consensus protocols, by doing so we improve individual shards' throughput. Next, we design an efficient shard formation protocol that leverages a trusted random beacon to securely assign nodes into shards. We rely on trusted hardware, namely Intel SGX, to achieve high performance for both consensus and shard formation protocol. Third, we design a general distributed transaction protocol that ensures safety and liveness even when transaction coordinators are malicious. Finally, we conduct an extensive evaluation of our design both on a local cluster and on Google Cloud Platform. The results show that our consensus and shard formation protocols outperform state-of-the-art solutions at scale. More importantly, our sharded blockchain reaches a high throughput that can handle Visa-level workloads, and is the largest ever reported in a realistic environment.Comment: This is an updated version of the Chain of Trust: Can Trusted Hardware Help Scaling Blockchains? paper. This version is to be appeared in SIGMOD 201

Perspectivas futuras postas ao Sistema ?nico de Sa?de ? SUS enquanto pol?tica p?blica

O presente trabalho pretendeu analisar os avan?os e desafios enfrentados pelo Sistema ?nico de Sa?de ? SUS. A quest?o se concentra nas pol?ticas p?blicas para a sa?de no Brasil, alinhando-se ? problem?tica da descontinuidade de planejamento entre as gest?es, que sustente a efic?cia de um sistema idealizado para servir aos que dependem desse servi?o. Tal esfor?o justifica-se pela possibilidade de os fatos compilados e as an?lises apresentadas, serem poss?veis de retroalimentar as Pol?ticas vigentes, com base no que historicamente j? se tem comprovado. Metodologicamente, procedeu-se um levantamento bibliogr?fico e an?lises documentais com base em legisla??es que regulamentam o SUS, a Lei Org?nica de Sa?de, Lei 8.080/90 e a Lei 8.142/90. Numa abordagem de an?lise qualitativa, de cunho descritivo e explorat?rio, tem-se uma estrutura te?rica e anal?tica, sem pretens?o de esgotar os fatos e a literatura. Buscou-se identificar os avan?os e desafios ocorridos e tamb?m investigar os rebatimentos que a Ementa Constitucional 55 traz para o SUS. Como resultados, foram apontadas as possibilidades de fortalecimento do SUS, via contribui??es te?ricas e anal?ticas, ? luz da problem?tica proposta; bem como apontada a exist?ncia de possibilidades de fortalecimento do SUS, atrav?s de solu??es, que possam ser vi?veis para a melhoria da pol?tica de sa?de no Brasil

Code2know ? um prot?tipo de sistema de ensino de programa??o baseado em juiz online

O presente trabalho prop?e o desenvolvimento de prot?tipo de um sistema baseado em juiz online com foco no ensino de programa??o. Com o objetivo de aperfei?oar os aspectos desses sistemas, como usabilidade, escalabilidade e um feedback claro aos alunos. O trabalho busca preencher lacunas existentes nos sistemas atuais, que muitas vezes s?o h?bridos entre competi??o e ensino. O sistema proposto visa melhorar o ambiente de aprendizado, permitindo que os alunos resolvam exerc?cios com casos de teste p?blicos e recebam o feedback personalizado de acordo com a exce??o obtida no processo de submiss?o. Como resultado foi obtido uma prova de conceito do sistema, com as funcionalidades b?sicas para ser implantado em sala de aula

Deployment of a smart and predictive maintenance system in an industrial case study

Industrial manufacturing environments are often characterized as being stochastic, dynamic and chaotic, being crucial the implementation of proper maintenance strategies to ensure the production efficiency, since the machines? breakdown leads to a degradation of the system performance, causing the loss of productivity and business opportunities. In this context, the use of emergent ICT technologies, such as Internet of Things (IoT), machine learning and augmented reality, allows to develop smart and predictive maintenance systems, contributing for the reduction of unplanned machines? downtime by predicting possible failures and recovering faster when they occur. This paper describes the deployment of a smart and predictive maintenance system in an industrial case study, that considers IoT and machine learning technologies to support the online and real-time data collection and analysis for the earlier detection of machine failures, allowing the visualization, monitoring and schedule of maintenance interventions to mitigate the occurrence of such failures. The deployed system also integrates machine learning and augmented reality technologies to support the technicians during the execution of maintenance interventions.2411-78B2-7CDB | Pedro Miguel MoreiraN/

The implementation of a structured specialized consultation for psoriasis management

Objectives: Psoriasis is a chronic skin disease requiring a multidimensional approach, given its varying appearance, presence of comorbidities and complex treatment regimens. Psoriasis care is however often performed fragmented and, in case of flares, reactive with little integrated information on and for the patient. Literature suggests a multileveled approach of psoriasis, but the effects of its implementation have not yet been validated. The aim of this study is to analyze the impact of a multileveled psoriasis consultation format, named PsoPlus, which has been implemented since 2012 in the Department of Dermatology at Ghent University Hospital in Belgium. Methods: The patient population was divided into two groups: one following the regular consultation and one following the PsoPlus format. Demographic data, clinical outcome and treatment approach of psoriasis patients were compared. Results: Patients who opted for the specialized PsoPlus consultation were younger and had longer disease duration. Decision parameters such as disease severity and quality of life were reported more often in the PsoPlus group. In the latter, a higher rate of patients were started on systemic therapy compared to the regular consultation group, and reporting on adverse events was done more frequently. Conclusion: The implementation of a specialized consultation with comprehensive guidance facilitates documentation on disease-relevant parameters such as disease severity and quality of life. This format can be seen as a guidance for capturing data in a structured manner, with evidence showing that it significantly impacts treatment decision, treating not only psoriasis but the patient as a whole