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The COVID-19 pandemic has had a significant impact on education, forcing schools to close and move to remote learning. Prospective math teachers are particularly challenged by technology integration. This is because mathematics is a subject that is often taught in a traditional, lecture-based format. It can be challenging for prospective math teachers to find effective ways to use technology online to demonstrate teaching and learning mathematics. In this study, the researchers investigated the perceived barriers to technology integration experienced by prospective math teachers during emergency remote learning. This study used a descriptive correlational survey design given to fifty-one (51) respondents enrolled at Surigao del Norte State University (SNSU). Data analysis was performed using SPSS. Moreover, the researchers utilized descriptive statistics such as frequency distributions and measures of central tendency, and non-parametric tests such as Fisher's exact tests to treat the data. The results showed that the respondents demonstrated moderately positive beliefs regarding the appropriateness of curriculum content for the technology used and the complementarity of technology and content in the course. Second, the respondents generally had a high level of commitment to attending synchronous online learning sessions. Third, gender, age, and income class do not play a significant role in determining respondents' perceived barriers to technology integration. Lastly, there was no significant relationship between respondents' perceived barriers to technology integration and their self-reported attendance (p = 0.099). However, the p-value was close to the conventional threshold for statistical significance (p < 0.05), suggesting that there may be a weak association between these two variables.

The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.

Motor stereotypies are frequently reported in individuals with autism spectrum disorder, but determinants of stereotypies remain poorly understood. In this study, a randomized sample of children with diagnosis of autism spectrum disorder was investigated to identify the prevalence and determinants of stereotypies. A total of 134 children who carried the diagnosis of autism spectrum disorder were included (aged 2.3-17.6 years; 79.1% male). Stereotypies were classified during a standardized protocol with video recording. The prevalence of stereotypies was 56.7%. Among 1198 captured stereotypies, hand/arm stereotypies were the most frequent. Thirty-five morphology patterns were identified, the most frequent being hand flapping, tapping, and jumping. In univariate analysis, an association was found between stereotypies and younger age (odds ratio = 0.74), developmental delay, or intellectual disability (odds ratio = 5.25), being nonverbal (odds ratio = 0.06), epilepsy (odds ratio = 3.89), Autism Diagnostic Interview--Revised-A score (odds ratio = 1.17), Autism Diagnostic Interview--Revised-C score (odds ratio = 1.25), and Autism Diagnostic Observation Schedule--2 score (odds ratio = 1.65). After multivariate analysis, only younger age, being nonverbal, and Autism Diagnostic Interview--Revised-A and Autism Diagnostic Observation Schedule--2 scores remained as determinants of stereotypies. The prevalence of stereotypies in autism spectrum disorder was close to the values obtained in a previous meta-analysis and seems to represent a valid value. The combination of younger age, being nonverbal, and autism severity seems to increase the odds of stereotypies.

Com o presente trabalho pretende-se investigar as diretrizes constitucionais e normativas acerca da competência e políticas públicas em matéria de meio ambiente com foco em um modelo sistêmico. Dessa forma, visa-se responder ao problema de pesquisa: quais as contribuições que uma teoria sistêmica das políticas públicas pode contribuir na concretização do direito fundamental ao meio ambiente? Para tanto utilizou-se do método de abordagem dedutivo, método de procedimento adotou-se o monográfico e, as técnicas de pesquisa resumem-se a consulta a livros, artigos, periódicos, teses, dissertações, dentre outros meios. Considerando que a pesquisa encontra-se em andamento, os resultados preliminares são no sentido de que é fundamental uma observação sistêmica das políticas públicas utilizando referenciais não apenas jurídicos, mas também sociais e políticos.

Background and purposeImage-guided adapted brachytherapy (IGABT) is superior to other radiotherapy techniques in the treatment of locally advanced cervical cancer (LACC). We aimed to investigate the benefit of interstitial needles (IN) for a combined intracavitary/interstitial (IC/IS) approach using IGABT over the intracavitary approach (IC) alone in patients with LACC after concomitant external beam radiotherapy (EBRT) and chemotherapy.Materials and methodsWe included consecutive patients with LACC who were treated with IC/IS IGABT after radiochemotherapy (RCT) in our retrospective, observational study. Dosimetric gain and sparing of organs at risk (OAR) were investigated by comparing the IC/IS IGABT plan with a simulated plan without needle use (IC IGABT plan) and the impact of other clinical factors on the benefit of IC/IS IGABT.ResultsNinety-nine patients were analyzed, with a mean EBRT dose of 45.5 ± 1.7 Gy; 97 patients received concurrent chemotherapy. A significant increase in median D90% High Risk Clinical target volume (HR-CTV) was found for IC/IS (82.8 Gy) vs IC (76.2 Gy) (p < 10-4). A significant decrease of the delivered dose for all OAR was found for IC/IS vs IC for median D2cc to the bladder (77.2 Gy), rectum (68 Gy), sigmoid (53.2 Gy), and small bowel (47 Gy) (all p < 10-4).ConclusionHR-CTV coverage was higher with IC/IS IGABT than with IC IGABT, with lower doses to the OAR in patients managed for LACC after RCT. Interstitial brachytherapy in the management of LACC after radiotherapy provides better coverage of the target volumes, this could contribute to better local control and improved survival of patients.

O presente trabalho tem como objetivo realizar um estudo sobre a necessidade de controle dos atos da administração pública no contexto do Estado Democrático de Direito. Com isso, tem-se o seguinte problema de pesquisa: qual a relevância dos mecanismos de controle da administração pública no contexto do Estado Democrático de Direito? Estruturalmente, a pesquisa será dividida em três tópicos, no primeiro serão abordados os aspectos do Estado Democrático de Direito, seguido de uma relação dos mecanismos de controle da administração pública com a sua importância democrática. Por fim, a análise terá como objetivo o estudo das modalidades de controle da administração pública com foco na realidade brasileira. Assim, visa-se demonstrar a importância de instituição dos mecanismos de controle tendo em conta que estes podem ser considerados como pressupostos basilares do Estado Democrático de Direito.

PurposeWe assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers.MethodsRetrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort.ResultsThe ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10-72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10-50). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10-22) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10-12) carriers. The associations in the prospective cohort were similar.ConclusionPopulation-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.

Estimates of aboveground biomass (AGB) in forests have been made in the context of climate change mitigation. There were limited studies about Falcata aboveground biomass and carbon stock estimation using the traditional method; however, that is time-intensive and expensive. Hence, this study was executed to utilize remote sensing and assess the potential of the synergistic use of Sentinel-1 and Sentinel-2 images in estimating the AGB and carbon stock of Falcata. The methodology consists of boundary demarcation of Falcata plantations in Butuan City, development of aboveground biomass models, and estimation and mapping of aboveground biomass and carbon stock. Among the developed models, the model which is the combination of Sentinel-1 and Sentinel-2 has the highest coefficient of determination (R2) of 0.632 and lowest Root Mean Square Error (RMSE) of 1.94 ton/pixel and was found to perform best in predicting the AGB and carbon stock of 4-year-old Falcata and performed poorly in 1-year-old Falcata. Nevertheless, its overall R2 and RMSE have proven that the model is moderately good and acceptable in predicting AGB of all stand ages of Falcata and, indirectly, the carbon stock. This study demonstrates that combining satellites generates a robust and more accurate AGB and Carbon Stock model than the models derived from the individual satellites.

Este estudo propõe uma análise dos programas governamentais em âmbito federal que compõem o conjunto da política pública educacional voltados à Educação Básica. Delimita-se este tema a partir das premissas da Constituição Federal de 1988, observando o compromisso da Educação em promover o preparo ao exercício da cidadania e sua qualificação para o trabalho, por meio da promoção de um ensino de qualidade. O problema que orienta essa pesquisa é buscar quais são os problemas políticos de ordem coletiva no âmbito da educação básica que os programas dentro da política pública educacional, criados em âmbito federal, visam solucionar? A hipótese repercute de diferentes formas já que são diversas as demandas no âmbito da educação a serem solucionadas. O trabalho utiliza-se do método dedutivo, apresentando os seguintes resultados: grande percentual dos programas constituidores da política pública educacional visa soluções para os grandes desafios sociais na educação, com foco na diminuição dos diferentes níveis de escolaridade, e as diferenças sociais dentro da sala de aula; lidam, portanto, com problemas de ordem coletiva trazidos ao plano político, considerando a conceituação de que uma política pública enfrenta um problema público, entendido como coletivamente relevante.

The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.

O objetivo geral deste trabalho é avaliar, de forma crítica, como os fundamentos teóricos da Democracia Radical, nomeadamente os expendidos por Chantal Mouffe e seus interlocutores, podem contribuir no aprofundamento da Democracia Deliberativa de acento habermasiano e seus fundamentos de participação política. O problema que pretendemos destacar diz com a possibilidade de equalizarmos as convergências e divergências entre os fundamentos da Democracia Radical e da Democracia Deliberativa, visando constituir o aprimoramento da participação política contemporânea. Em face desses problemas, nossa hipótese é a de que determinados aportes da Democracia Radical são adequados e sinérgicos à Democracia Deliberativa; todavia, outros não, e sobre estes pretendemos identificar insuficiências de sustentação.

Nestes tempos de pandemia causada pelo vírus da Covid-19, muitas ações governamentais da União Federal, Estados e Municípios, que reclamam urgência e são onerosas, estão e vão precisar se desenvolver superando determinados requisitos formais de procedimentos tradicionais, o que apresenta riscos de abusos de autoridade e desvio de poder/finalidades. Em face disto, pretendemos no presente texto avaliar alguns riscos e perigos destes cenários, colocando como problema a ser enfrentado o de sabermos se é possível e necessário existir controles preventivos e curativos, em tempo real, da gestão desta calamidade pública que configura a Covid-19, tendo como hipótese neural a de que é possível compatibilizar medidas de urgências em estados de emergências e calamidade pública com sistemas de controles internos e externos dos poderes instituídos. Enquanto objetivos específicos, vamos tratar de demarcar conceitualmente alguns dos elementos constitutivos da desordem social e administrativa que caracterizam a Sociedade de Riscos que vivemos, em especial os trazidos pela pandemia referida, identificando a importância de constituirmos limites de contenção as suas causas e consequências; por fim, queremos sustentar que desconsiderar o sistema jurídico brasileiro nestas situações, merece controle eficaz, evitação e reprimenda através de mecanismos normativos que já dispomos.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.

Abstract Background Diagnostic ionizing radiation is a risk factor for breast cancer (BC). BC risk increases with increased dose to the chest and decreases with increased age at exposure, with possible effect modification related to familial or genetic predisposition. While chest X-rays increase the BC risk of BRCA1/2 mutation carriers compared to non-carriers, little is known for women with a hereditary predisposition to BC but who tested negative for a BRCA1 or BRCA2 (BRCA1/2) mutation. Methods We evaluated the effect of chest X-rays from diagnostic medical procedures in a dataset composed of 1552 BC cases identified through French family cancer clinics and 1363 unrelated controls. Participants reported their history of X-ray exposures in a detailed questionnaire and were tested for 113 DNA repair genes. Logistic regression and multinomial logistic regression models were used to assess the association with BC. Results Chest X-ray exposure doubled BC risk. A 3% increased BC risk per additional exposure was observed. Being 20 years old or younger at first exposure or being exposed before first full-term pregnancy did not seem to modify this risk. Birth after 1960 or carrying a rare likely deleterious coding variant in a DNA repair gene other than BRCA1/2 modified the effect of chest X-ray exposure. Conclusion Ever/never chest X-ray exposure increases BC risk 2-fold regardless of age at first exposure and, by up to 5-fold when carrying 3 or more rare variants in a DNA repair gene. Further studies are needed to evaluate other DNA repair genes or variants to identify those which could modify radiation sensitivity. Identification of subpopulations that are more or less susceptible to ionizing radiation is important and potentially clinically relevant.

Efficient and accurate mapping of forest and other industrial tree plantations (ITPs) is essential to ensure better monitoring and sustainable management of these plantations. In Caraga Region, Mindanao, Philippines, ITPs planted with Falcata (Paraserianthes falcataria (L.) Nielsen) are widespread and has contributed to more than 50% of the nationwide log production. At present, there is limited information on the location and extent of existing plantations. This provides an opportunity to evaluate satellite remote sensing approaches for mapping these plantations from images, particularly those provided by the Sentinel-2 mission. The objective of this study is to evaluate machine learning classifiers for mapping Falcata plantations in Sentinel-2 image using a 9 × 9 km2 study area in Caraga Region. It also aims to find the best classifier that can provide acceptable levels of accuracy by utilizing only the four bands of the 10-m spatial resolution and the 9 bands of the 20-m spatial resolution Level 2A Sentinel-2 image, respectively. The following classifiers and their variants were evaluated: Linear Support Vector Machine (SVM), Polynomial SVM, Radial Basis Function (RBF) SVM, Artificial Neural Network (Neural Net), Random Forest (RF), and Maximum Likelihood (ML). One or more of these classifiers have been successfully used in in natural and plantation forest mapping, including tree species classification from remotely sensed images. However, their performance and accuracy in detecting and discriminating Falcata plantations is yet to be evaluated. Results of the evaluation showed that the ML classifier has the highest overall accuracy (OA) of 90.90% and has more consistent values for Producer’s Accuracy (PA), and User’s Accuracy (UA) for Falcata and Non-Falcata classes, and hence, provides better Falcata classification results than the other classifiers when the 10-m spatial resolution Sentinel-2 image was used. The accuracy assessment of the 20-m subset classification provides relative different results from that of the 10-m subset, perhaps due to the inclusion of more bands. The highest OA was obtained by the Linear and RBF SVM classifiers at 92.05% each. The SVM classifiers have consistent performance and produce more accurate classification results than the other classifiers (i.e., more than 90% OA, PA, and UA). From these results, it can be concluded that Maximum Likelihood classifier is best to use for Falcata mapping using the 10-m spatial resolution Sentinel-2 image. For the 20-m resolution image, any of the two SVMs (linear or RBF) is more appropriate to use. However, it should be noted that these results are based on classifications where default parameters were used. Improvement in the classification accuracy may be achieved if these parameters were optimized.

Abstract Reactive oxygen species (ROS) are implicated in triggering cell signalling events and pathways to promote and maintain tumorigenicity. Chemotherapy and radiation can induce ROS to elicit cell death allows for targeting ROS pathways for effective anti-cancer therapeutics. Coenzyme Q10 is a critical cofactor in the electron transport chain with complex biological functions that extend beyond mitochondrial respiration. This study demonstrates that delivery of oxidized Coenzyme Q10 (ubidecarenone) to increase mitochondrial Q-pool is associated with an increase in ROS generation, effectuating anti-cancer effects in a pancreatic cancer model. Consequent activation of cell death was observed in vitro in pancreatic cancer cells, and both human patient-derived organoids and tumour xenografts. The study is a first to demonstrate the effectiveness of oxidized ubidecarenone in targeting mitochondrial function resulting in an anti-cancer effect. Furthermore, these findings support the clinical development of proprietary formulation, BPM31510, for treatment of cancers with high ROS burden with potential sensitivity to ubidecarenone.

The present article seeks to analyze the legal situation of urban requirements for the regularity of a plot of urban land, considering the minimum conditions for a house to be considered worthy, and as a way of guiding public land regularization policies. In this way, it is questioned how the flexibilization of these requirements should take place, which was provided by law for the purpose of facilitating real estate legalization, without compromising the well-being of the inhabitants. Through the dialectical hermeneutic method, the objective is to clarify, without the intent of exhausting the topic, the scope of the forecasts used in the legislation in comparison with the dictates of housing. This brief research space concludes that the a priori list of urban improvements is not possible, leaving the urban inspection entities to instrumentalize techniques for the correct determination, in each social case, of the needs of the urban area that is being regularized.

Abstract Metabolic reprogramming in cancer cells, vs. non-cancer cells, elevates levels of reactive oxygen species (ROS) leading to higher oxidative stress. The elevated ROS levels suggest a vulnerability to excess prooxidant loads leading to selective cell death, a therapeutically exploitable difference. Co-enzyme Q10 (CoQ10) an endogenous mitochondrial resident molecule, plays an important role in mitochondrial redox homeostasis, membrane integrity, and energy production. BPM31510 is a lipid-drug conjugate nanodispersion specifically formulated for delivery of supraphysiological concentrations of ubidecarenone (oxidized CoQ10) to the cell and mitochondria, in both in vitro and in vivo model systems. In this study, we sought to investigate the therapeutic potential of ubidecarenone in the highly treatment-refractory glioblastoma. Rodent (C6) and human (U251) glioma cell lines, and non-tumor human astrocytes (HA) and rodent NIH3T3 fibroblast cell lines were utilized for experiments. Tumor cell lines exhibited a marked increase in sensitivity to ubidecarenone vs. non-tumor cell lines. Further, elevated mitochondrial superoxide production was noted in tumor cells vs. non-tumor cells hours before any changes in proliferation or the cell cycle could be detected. In vitro co-culture experiments show ubidecarenone differentially affecting tumor cells vs. non-tumor cells, resulting in an equilibrated culture. In vivo activity in a highly aggressive orthotopic C6 glioma model demonstrated a greater than 25% long-term survival rate. Based on these findings we conclude that high levels of ubidecarenone delivered using BPM31510 provide an effective therapeutic modality targeting cancer-specific modulation of redox mechanisms for anti-cancer effects.

Abstract Background The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. Methods A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. Results There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94–1.61) or BRCA2 (HR = 0.88; 95% CI 0.62–1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40–1.15) and 1.07 (95% CI 0.69–1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26–0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. Conclusion We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.

O presente trabalho tem como tema a transparência ativa e passiva como ferramenta ao exercício do controle social em um Estado Democrático de Direito à luz da cidadania participativa e da Lei de Acesso à informação. Como problema central o seguinte questionamento: Considerando-se a prerrogativa do Estado Democrático de Direito, a efetividade da Lei de Acesso à Informação tem fim em si mesmo para o exercício do controle social como forma de enfrentamento à corrupção? Propõe-se como objetivos demonstrar que a importância da cidadania participativa na concepção de um Estado Democrático de Direito; identificar se a Lei de Acesso à Informação é uma forma direta de exercício do controle social; e analisar os desafios e efetividade da Lei de Acesso à Informação após sua entrada em vigor em relação ao cumprimento das exigências dos parâmetros da transparência e de enfrentamento à corrupção. Para isso, usou-se como parâmetro os dados dos relatórios disponibilizados pelo Tribunal de Contas do Rio Grande do Sul, 2018 e 2019, em relação aos municípios do estado. A metodologia utilizada foi a bibliográfica, bem ainda se utilizou do processo de visitação no site do Tribunal de Contas do Rio Grande do Sul. Desse modo, conclui-se que a transparência ativa e passiva são ferramentas de meio para efetivar o controle social e, com efeito, formas de inibir a prática da corrupção na gestão pública.

AbstractThe spindle assembly checkpoint protects the integrity of the genome by ensuring that chromosomes are properly attached to the mitotic spindle before they are segregated during anaphase. Activation of the spindle checkpoint results in inhibition of the Anaphase-Promoting Complex (APC), an E3 ubiquitin ligase that triggers the metaphase–anaphase transition. Here, we show that levels of Ubc1, an E2 enzyme that functions in complex with the APC, modulate the response to spindle checkpoint activation in Saccharomyces cerevisiae

After publication of the original article [1], we were notified that columns in Table 2 were erroneously displayed.

As perspectivas que cientistas políticos e juristas vêm tendo sobre o futuro o Estado Democrático de Direito na Sociedade de Riscos tem sido mais pessimista do que otimistas, em especial quando o fenômeno da corrupção é levado em conta para os fins de pensarmos a própria Democracia. Em face disto é que o presente texto pretende discutir como tem se dado esta equação entre Estado, Democracia e Corrupção, quais seus pontos mais frágeis e o que podemos fazer para superar os aspectos negativos que ela apresenta. Para tanto, vamos buscar elementos teóricos e pragmáticos que proponham formas e instrumentos objetivos para tal escopo.

Devido à necessidade e urgência de defesa e de proteção ao meio ambiente, direito garantido pela ordem constitucional, instrumentos que possibilitam o controle e a participação social em matéria ambiental, recebem apreço. Nessa perspectiva, traz-se a importância da participação social na garantia do direito fundamental ao meio ambiente, para introduzir o estudo do instituto do amicus curiae, que vem contribuir de forma plena e eficaz nesse objetivo. Sendo assim, o presente trabalho traz a seguinte interrogação: o instituto do amicus curiae, que proporciona a participação social nos processos judiciais, trata-se de um instrumento que possibilita a defesa e a proteção ao meio ambiente? Para dar conta dessa tarefa, utilizar-se-á o método hipotético-dedutivo e a pesquisa bibliográfica e jurisprudencial. Verifica-se, ao final, que o amicus curiae configura-se em um mecanismo de democratização e de pluralização do processo, fazendo com que as decisões que envolvam as questões ambientais fiquem mais alinhadas às demandas da sociedade, permitindo a participação social nessas demandas, o que propicia a defesa e proteção a esse direito fundamental.

O presente trabalho tem como objetivo verificar em que medida o controle de integridade, pensado a partir de modelos como o compliance, pode aprimorar os sistemas de controle interno da Administração Pública brasileira. O problema de pesquisa visa responder quais medidas podem ser adotadas para melhorar estes sistemas de controle, a hipótese é de que se faz necessário a adoção dos mecanismos de integridade como forma de qualificar os instrumentos de controle interno. Para isso serão demarcados elementos conceituais da integridade na gestão, constituindo o compliance como espaço de qualificação do controle interno e da ação administrativa governativa.

Upper limb amputation severely affects the quality of life and the activities of daily living of a person. In the last decade, many robotic hand prostheses have been developed which are controlled by using various sensing technologies such as artificial vision and tactile and surface electromyography (sEMG). If controlled properly, these prostheses can significantly improve the daily life of hand amputees by providing them with more autonomy in physical activities. However, despite the advancements in sensing technologies, as well as excellent mechanical capabilities of the prosthetic devices, their control is often limited and usually requires a long time for training and adaptation of the users. The myoelectric prostheses use signals from residual stump muscles to restore the function of the lost limbs seamlessly. However, the use of the sEMG signals in robotic as a user control signal is very complicated due to the presence of noise, and the need for heavy computational power. In this article, we developed motion intention classifiers for transradial (TR) amputees based on EMG data by implementing various machine learning and deep learning models. We benchmarked the performance of these classifiers based on overall generalization across various classes and we presented a systematic study on the impact of time domain features and pre-processing parameters on the performance of the classification models. Our results showed that Ensemble learning and deep learning algorithms outperformed other classical machine learning algorithms. Investigating the trend of varying sliding window on feature-based and non-feature-based classification model revealed interesting correlation with the level of amputation. The study also covered the analysis of performance of classifiers on amputation conditions since the history of amputation and conditions are different to each amputee. These results are vital for understanding the development of machine learning-based classifiers for assistive robotic applications.

O presente trabalho tem como objetivo delimitar quais posturas podem ser adotadas para sanar os déficits no controle externo da administração pública. Com isso, diante das considerações doutrinárias e análise de jurisprudência quanto ao controle externo da administração pública brasileira, tem-se o seguinte problema de pesquisa: quais medidas podem ser adotadas para sanar os déficits encontrados no controle externo da administração pública? Para tanto se utilizou o método de abordagem dedutivo, método de procedimento monográfico e técnicas de pesquisa que se resumem à pesquisa bibliográfica em livros, revistas, periódicos, notícias, teses, dissertações, bem como decisões do Tribunal de Contas do Estado do Rio Grande do Sul. Os objetivos específicos são conceituar o controle da administração pública e suas formas; analisar o controle externo da administração pública a partir da atuação do Tribunal de Contas do Estado do Rio Grande do Sul no que se refere a irregularidades em contratos administrativos e; propor medidas que possam ser utilizadas para sanar os déficits encontrados. Desse modo, a conclusão é no sentido da necessidade de serem aprimorados os instrumentos de controle da administração pública, sobretudo no que tange a colaboração interinstitucional dos agentes colaboradores, bem como da adoção de políticas públicas.

Abstract Background Diabetes mellitus is associated with an increased risk in diabetic cardiomyopathy (DCM) that is distinctly not attributed to co-morbidities with other vasculature diseases. To date, while dysregulation of calcium handling is a key hallmark in cardiomyopathy, studies have been inconsistent in the types of alterations involved. In this study human cardiomyocytes were exposed to an environmental nutritional perturbation of high glucose, fatty acids, and l-carnitine to model DCM and iTRAQ-coupled LC–MS/MS proteomic analysis was used to capture proteins affected by the perturbation. The proteins captured were then compared to proteins currently annotated in the cardiovascular disease (CVD) gene ontology (GO) database to identify proteins not previously described as being related to CVD. Subsequently, GO analysis for calcium regulating proteins and endoplasmic/sarcoplasmic reticulum (ER/SR) associated proteins was carried out. Results Here, we identified CCDC47 (calumin) as a unique calcium regulating protein altered in our in vitro nutritional perturbation model. The cellular and functional role of CCDC47 was then assessed in rat cardiomyocytes. In rat H9C2 myocytes, overexpression of CCDC47 resulted in increase in ionomycin-induced calcium release and reuptake. Of interest, in a diet-induced obese (DIO) rat model of DCM, CCDC47 mRNA expression was increased in the atrium and ventricle of the heart, but CCDC47 protein expression was significantly increased only in the atrium of DIO rats compared to lean control rats. Notably, no changes in ANP, BNP, or β-MHC were observed between DIO rats and lean control rats. Conclusions Together, our in vitro and in vivo studies demonstrate that CCDC47 is a unique calcium regulating protein that is associated with early onset hypertrophic cardiomyopathy.

Abstract Background The ataxia telangiectasia mutated (ATM) gene is a moderate-risk breast cancer susceptibility gene; germline loss-of-function variants are found in up to 3% of hereditary breast and ovarian cancer (HBOC) families who undergo genetic testing. So far, no clear histopathological and molecular features of breast tumours occurring in ATM deleterious variant carriers have been described, but identification of an ATM-associated tumour signature may help in patient management. Methods To characterise hallmarks of ATM-associated tumours, we performed systematic pathology review of tumours from 21 participants from ataxia-telangiectasia families and 18 participants from HBOC families, as well as copy number profiling on a subset of 23 tumours. Morphology of ATM-associated tumours was compared with that of 599 patients with no BRCA1 and BRCA2 mutations from a hospital-based series, as well as with data from The Cancer Genome Atlas. Absolute copy number and loss of heterozygosity (LOH) profiles were obtained from the OncoScan SNP array. In addition, we performed whole-genome sequencing on four tumours from ATM loss-of-function variant carriers with available frozen material. Results We found that ATM-associated tumours belong mostly to the luminal B subtype, are tetraploid and show LOH at the ATM locus at 11q22–23. Unlike tumours in which BRCA1 or BRCA2 is inactivated, tumours arising in ATM deleterious variant carriers are not associated with increased large-scale genomic instability as measured by the large-scale state transitions signature. Losses at 13q14.11-q14.3, 17p13.2-p12, 21p11.2-p11.1 and 22q11.23 were observed. Somatic alterations at these loci may therefore represent biomarkers for ATM testing and harbour driver mutations in potentially ‘druggable’ genes that would allow patients to be directed towards tailored therapeutic strategies. Conclusions Although ATM is involved in the DNA damage response, ATM-associated tumours are distinct from BRCA1-associated tumours in terms of morphological characteristics and genomic alterations, and they are also distinguishable from sporadic breast tumours, thus opening up the possibility to identify ATM variant carriers outside the ataxia-telangiectasia disorder and direct them towards effective cancer risk management and therapeutic strategies.

Abstract Background Inhibition of Hsp90 has been shown to improve glucose tolerance and insulin sensitivity in mouse models of diabetes. In the present report, the specific isoform Hsp90ab1, was identified as playing a major role in regulating insulin signaling and glucose metabolism. Methods In a diet-induced obese (DIO) mouse model of diabetes, expression of various Hsp90 isoforms in skeletal tissue was examined. Subsequent experiments characterized the role of Hsp90ab1 isoform in glucose metabolism and insulin signaling in primary human skeletal muscle myoblasts (HSMM) and a DIO mouse model. Results In DIO mice Hsp90ab1 mRNA was upregulated in skeletal muscle compared to lean mice and knockdown using anti-sense oligonucleotide (ASO) resulted in reduced expression in skeletal muscle that was associated with improved glucose tolerance, reduced fed glucose and fed insulin levels compared to DIO mice that were treated with a negative control oligonucleotide. In addition, knockdown of HSP90ab1 in DIO mice was associated with reduced pyruvate dehydrogenase kinase-4 mRNA and phosphorylation of the muscle pyruvate dehydrogenase complex (at serine 232, 293 and 300), but increased phosphofructokinase 1, glycogen synthase 1 and long-chain specific acyl-CoA dehydrogenase mRNA. In HSMM, siRNA knockdown of Hsp90ab1 induced an increase in substrate metabolism, mitochondrial respiration capacity, and insulin sensitivity, providing further evidence for the role of Hsp90ab1 in metabolism. Conclusions The data support a novel role for Hsp90ab1 in arbitrating skeletal muscle plasticity via modulation of substrate utilization including glucose and fatty acids in normal and disease conditions. Hsp90ab1 represents a novel target for potential treatment of metabolic disease including diabetes.

Abstract Background Exosomes and other extracellular vesicles (EVs) have emerged as an important mechanism of cell-to-cell communication. However, previous studies either did not fully resolve what genetic materials were shuttled by exosomes or only focused on a specific set of miRNAs and mRNAs. A more systematic method is required to identify the genetic materials that are potentially transferred during cell-to-cell communication through EVs in an unbiased manner. Results In this work, we present a novel next generation of sequencing (NGS) based approach to identify EV mediated mRNA exchanges between co-cultured adipocyte and macrophage cells. We performed molecular and genomic profiling and jointly considered data from RNA sequencing (RNA-seq) and genotyping to track the “sequence varying mRNAs” transferred between cells. We identified 8 mRNAs being transferred from macrophages to adipocytes and 21 mRNAs being transferred in the opposite direction. These mRNAs represented biological functions including extracellular matrix, cell adhesion, glycoprotein, and signal peptides. Conclusions Our study sheds new light on EV mediated RNA communications between adipocyte and macrophage cells, which may play a significant role in developing insulin resistance in diabetic patients. This work establishes a new method that is applicable to examining genetic material exchanges in many cellular systems and has the potential to be extended to in vivo studies as well.

Este trabalho parte da premissa de que o enfrentamento da corrupção hoje já não é mais tarefa exclusiva dos poderes públicos instituídos, mas de toda a comunidade e do mercado também, haja vista que estes sofrem impactos violentos em termos de funcionamento e competitividade, assim como os Direitos Fundamentais Individuais e Sociais dos cidadãos são atingidos direta e indiretamente quando há omissões que retroalimentam as redes corruptivas global e localmente. Ocorre que até pouco tempo atrás segmentos importantes do mercado não eram considerados como fomentadores da corrupção, razão pela qual queremos demonstrar alguns efeitos que eles têm provocado neste sentido, em especial na Democracia, e sugerir formas de enfrentamento deste problema.

O presente artigo traz a definição do que é considerado corrupção, e a dificuldade de sua conceituação. Baseando-se em dados da Transparência Internacional, em 2016, nosso país está dentre os mais corruptos do mundo. A FIESP realizou uma pesquisa demonstrando os direitos sociais e fundamentais que o Brasil deixa de realizar devido à ocorrência da corrupção. Concluímos que são justamente as pessoas mais pobres as maiores vítimas, que acabam não tendo direitos sociais fundamentais atendidos. Palavras-chave: Corrupção. Direitos Sociais Fundamentais. Prejuízos Abstract: The present article brings the definition of what is considered corruption, and the difficulty of its conceptualization. Based on data from Transparency International in 2016, our country is among the most corrupt in the world. FIESP conducted a survey demonstrating the social and fundamental rights that Brazil fails to fulfill due to the occurrence of corruption. We conclude that it is precisely the poorest people who are the main victims, who end up not having fundamental social rights taken care of. Keywords: Corruption. Fundamental Social Rights. Losses

The emergence of COVID-19 progressed into a global pandemic that has functionally put the world at a standstill and catapulted major healthcare systems into an overburdened state. The dire need for therapeutic strategies to mitigate and successfully treat COVID-19 is now a public health crisis with national security implications for many countries. The current study employed Bayesian networks to a longitudinal proteomic dataset generated from Caco-2 cells transfected with SARS-CoV-2 (isolated from patients returning from Wuhan to Frankfurt). Two different approaches were employed to assess the Bayesian models, a titer-center topology analysis and a drug signature enrichment analysis. Topology analysis identified a set of proteins directly linked to the SAR-CoV2 titer, including ACE2, a SARS-CoV-2 binding receptor, MAOB and CHECK1. Aligning with the topology analysis, MAOB and CHECK1 were also identified within the enriched drug-signatures. Taken together, the data output from this network has identified nodal host proteins that may be connected to 18 chemical compounds, some already marketed, which provides an immediate opportunity to rapidly triage these assets for safety and efficacy against COVID-19.

No presente trabalho busca-se problematizar o tormentoso tema da responsabilidade penal das pessoas jurídicas por atos de corrupção, a partir de alguns fundamentos filosóficos e políticos que atualmente se colocam no debate nacional e internacional

This article aims to analyze the issue of the collision of fundamental principles and rights in the light of the theories of Robert Alexy and the theory of the double dimension of the human rights Narciso Leandro Xavier Baez. It proposes an analysis of the concepts developed by Robert Alexy on norms and principles and situations of conflicts between rights. Alexy proposes weighting rules as an alternative to resolving conflicts between principles, providing the prevalence of one over the other in this case by applying a formula. Baez presents the theory of the double dimension of human rights as an alternative to the solution of cases in which there is violation of human rights, serving as a tool for resolving apparent conflicts between rights in these situations. In the article, exposes the case of infanticide in northern villages of Brazil, where cultural aspects of those people are in conflict with the right to life of the murdered children. The application of Alexy and Baez theories lead to similar results, demonstrating effective use of both for the interpretation of cases of conflicts between fundamental principles and rights.

This article aims to analyze the phenomenon of corruption and money laundering and how they are being addressed this issue under the Convention on Combating Public Officials Corruption Foreigners in Transactions Organization of International Trade for Economic Cooperation and Development (OECD) and the formulation of public policies for Combating Corruption and Money Laundering, by the Brazilian State. The Money Laundering is a species of corrupting practices, so that this type of illicit undertakes the realization of fundamental rights, social rights, economic criminal law, the democratic rule of law affecting, directly, public policy tax as a result of the commission of unlawful acts and offenses linked to issues of an economic nature, such as bribery, fraud, tax evasion, bribery, money laundering, drug trafficking, arms linked indirectly, to organized crime. Whereas the article is a bibliographic nature, it will be used as the method of approach to be adopted in its deductive development, with general assumption arguments (major premise) for particular arguments (minor premise); while the procedure is analytical. Key words: Public Policy Tax, Money Laundering, Corruption of Foreign Public Officials, economic, illegalities. Money Laundering CRIME UNDER THE CONVENTION ON THE FIGHT AGAINST CORRUPTION OF FOREIGN public employee in the business operations of the International Organization for Economic Cooperation and Development (OECD) This article AIMS to analyze the phenomenon of corruption and money laundering and how it is addressing this issue under the Convention on Combating Bribery of Foreign Public Officials in International Business Transactions of the Organization for Economic Cooperation and Economic Development (OECD) and the formulation of public policies for the Fight against Corruption and Money Laundering, by the Brazilian government. Money laundering is a kind of corrupt practices, so this type of crime committed with the observance of fundamental rights, social rights, economic criminal law, the democratic rule of law Affecting directly the tax public policy because the commission of unlawful acts and related crimes to financial issues such as bribery, fraud, tax evasion, bribery, money laundering, drug trafficking, arms linked to the crime Indirectly organizado.Considerando que the article is a bibliographic character, will be used as a method of approach is ADOPTED in its deductive development , with arguments general assumption (major premise) for particular arguments (minor premise); while the procedure is analytic. Keywords: Public fiscal policy, money laundering, bribery of foreign public officals, economic, illegalities

O artigo aborda os impactos da corrução sobre o direito fundamental a uma prestação jurisdicional adequada baseando-se na administração da justiça, analisando os direitos das partes envolvidas, a eficiência dos procedimentos e sua efetividade, com base na ideia de processo justo, trazendo suas vertentes conceituais normativas e pragmáticas. Ademais, demonstra a partir da análise de caso as desfuncionalidades cartorárias que ocorrem em serventias judiciais e sua relação com a corrupção, diante dos problemas relativos com a eficiência do sistema de justiça, burocracia e gestão dos tribunais e seus órgãos, evidenciando a necessidade de se fazer o mapeamento dos riscos da corrupção no Poder Judiciário.