380 research outputs found

    As práticas regulatórias no setor de táxi : uma análise constitucional das barreiras de entrada

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    Monografia (graduação)—Universidade de Brasília, Faculdade de Direito, 2014.A barreira de entrada ou também denominada como controle de acesso ao setor é prática que existe no Brasil e no mundo desde inícios da regulação sobre o setor de táxi. Trata-se de estipulação de número máximo de agentes econômicos realizando a atividade em uma localidade e também de exigências mínimas para a participação nessa atividade. Mas, nas últimas décadas, ocorreram em diversas localidades pelo mundo alterações nas práticas regulatórias do setor que colocaram em xeque os fundamentos da barreira. No entanto, no Brasil, não se ensaia qualquer previsão de modificação do setor em consonância com a tendência global de desregulação. Ainda sim, resultados positivos nos locais desregulados produziram e deram destaque na literatura acadêmica a modelos e argumentos críticos à barreira de entrada e outras regulações estatais no setor. Desta forma, o objetivo do trabalho é analisar essa prática comum sob o aspecto paradigmático da Constituição Federal de 1988, analisando a viabilidade das barreiras de entrada e fixação tarifária. Tendo em vista o tratamento diferenciado na Constituição entre a exploração de serviços públicos e os demais serviços, além da dificuldade de estipulação em relação ao ato administrativo em espécie adequado para a outorga da exploração do serviço de táxi, foi necessário realizar uma pesquisa na doutrina jurídica em relação ao conceito de serviço público e das espécies de atos administrativos para assim poder consultar às fontes doutrinárias, legais e jurisprudências quanto a seu enquadramento, e só então chegar a uma opinião. Ainda, explorou-se a evolução da função econômica do Estado para chegar ao paradigma atual e diferenciá-lo das anteriores, bem como buscou dar significado constitucional ao princípio da livre concorrência, e então concluir as funções e motivações que fundamentam a regulação econômica do estado à luz da Constituição com a finalidade de verificar quais das regulações no setor seriam ou não compatíveis com as razões de intervenção estatal. Em seguida parte-se para uma análise específica do setor de táxi que demonstra tendência a forte controle de mercado pelos seus agentes através do poder regulador municipal, que limita o número de agentes, percebendo-se a existência de prejuízos aos consumidores e à sociedade, uma vez que são caracterizadas tendências de oligopólio no mercado. Ainda se assevera as consequências sociais, jurídicas, econômicas e políticas da desregulação do limite quantitativo de agentes no setor em diversos países. Por fim, são trazidos à tona os argumentos a favor da desregulação dos critérios quantitativos de barreira, e conclui-se pelo conflito direto desses instrumentos regulatórios com a função econômica do Estado visada pela Constituição Federal, conflito também com o princípio da livre concorrência e, ainda, com a finalidade específica da regulação econômica de trazer maiores benefícios aos indivíduos. Portanto, se depreende uma patente incompatibilidade dessas práticas com os preceitos fundamentais constitucionais aludidos

    Modulation of microRNA editing, expression and processing by ADAR2 deaminase in glioblastoma.

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    Background: ADAR enzymes convert adenosines to inosines within double-stranded RNAs, including microRNA (miRNA) precursors, with important consequences on miRNA retargeting and expression. ADAR2 activity is impaired in glioblastoma and its rescue has anti-tumoral effects. However, how ADAR2 activity may impact the miRNome and the progression of glioblastoma is not known. Results: By integrating deep-sequencing and array approaches with bioinformatics analyses and molecular studies, we show that ADAR2 is essential to edit a small number of mature miRNAs and to significantly modulate the expression of about 90 miRNAs in glioblastoma cells. Specifically, the rescue of ADAR2 activity in cancer cells recovers the edited miRNA population lost in glioblastoma cell lines and tissues, and rebalances expression of onco-miRNAs and tumor suppressor miRNAs to the levels observed in normal human brain. We report that the major effect of ADAR2 is to reduce the expression of a large number of miRNAs, most of which act as onco-miRNAs. ADAR2 can edit miR-222/221 and miR-21 precursors and decrease the expression of the corresponding mature onco-miRNAs in vivo and in vitro, with important effects on cell proliferation and migration. Conclusions: Our findings disclose an additional layer of complexity in miRNome regulation and provide information to better understand the impact of ADAR2 editing enzyme in glioblastoma. We propose that ADAR2 is a key factor for maintaining edited-miRNA population and balancing the expression of several essential miRNAs involved in cancer

    Combined NMDA Inhibitor Use in a Patient With Multisubstance-induced Psychotic Disorder

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    This document is an Accepted Manuscript reprinted from Journal of Addiction Medicine, Vol. 12 (3): 247-251, May 2018, with permission of Kluwer Law International. Under embargo until 1 May 2019. The Version of Record is available online at DOI: https://doi.org/10.1097/ADM.0000000000000390: Novel psychoactive substance use is a major social concern. Their use may elicit or uncover unpredictably as yet undescribed clinical pictures. We aimed to illustrate a multisubstance use case indistinguishable from paranoid schizophrenia, so to alert clinicians on possibly misdiagnosing substance-induced psychotic disorders. CASE REPORT: We describe a case of a 32-year-old man who started at 18 years with cannabinoids and ketamine, and is currently using N-methyl-D-aspartate (NMDA) antagonists. At age 23, he developed social withdrawal after being assaulted by a stranger, but did not consult psychiatrists until age 26; during this period, he was using internet-purchased methoxetamine and ketamine, and was persecutory, irritable, suspicious, and insomniac and discontinued all received medical prescriptions. He added dextromethorphan to his list of used substances. At age 31, while using phencyclidine, and, for the first time, methoxphenidine, he developed a religious delusion, involving God calling him to reach Him, and the near-death experiences ensured by NMDA antagonists backed his purpose. He received Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnosis of multisubstance-induced psychotic disorder and was hospitalized 8 times, 6 of which after visiting the emergency room due to the development of extreme anguish, verbal and physical aggression, and paranoia. He reportedly used methoxphenidine, methoxyphencyclidine, ethylnorketamine, norketamine, and deschlorketamine, to achieve near-death experiences, and eventually to reach God in heavens. CONCLUSIONS: This case points to the need for better control of drugs sold on the internet. It also illustrates that people using NMDA antagonists may present clinical pictures indistinguishable from those of major psychoses and are likely to be misdiagnosed.Peer reviewe

    Coexistence of multiple silicene phases in silicon grown on Ag(111)

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    Silicene, the silicon equivalent of graphene, is attracting increasing scientific and technological attention in view of the exploitation of its exotic electronic properties. This novel material has been theoretically predicted to exist as a free-standing layer in a low-buckled, stable form, and can be synthesized by the deposition of Si on appropriate crystalline substrates. By employing low-energy electron diffraction and microscopy, we have studied the growth of Si on Ag(111) and observed a rich variety of rotationally non-equivalent silicene structures. Our results highlight a very complex formation diagram, reflecting the coexistence of different and nearly degenerate silicene phases, whose relative abundance can be controlled by varying the Si coverage and growth temperature. At variance with other studies, we find that the formation of single-phase silicene monolayers cannot be achieved on Ag(111)

    Recurrent atypical meningiomas: combining surgery and radiosurgery in one effective multimodal treatment

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    OBJECTIVE: Owing to their rarity and proteiform pathologic features, the clinical behavior of atypical meningiomas is not yet well characterized. Though the extent of resection is believed to be a key determinant of prognosis, limited data exist regarding optimal management of patients with recurrent disease. METHODS: In this 20-year retrospective case series, we reviewed the medical records of 46 patients with recurrent atypical meningiomas (185 lesions, 89 of which were local, 78 marginal, and 18 distant recurrences); treatment was radiosurgery (n = 60), surgery (n = 56), or both (n = 8). The median follow-up period was 53 months. Outcome measures were length of overall survival and disease-free intervals and prognostic factors for survival. RESULTS: Overall, the median progression-free survival was 26 months at the first recurrence and 100 months thereafter (the sum of the later intervals). Multivariate analysis showed that no treatment-related factors influenced prognosis, whereas recurrence at the skull base was a significant tumor-related factor limiting further treatment. Irrespective of treatment type, the recurrence-free interval was increasingly shorter during the clinical course, with a higher occurrence of marginal and distant lesions migrating to the midline and to the skull base. In sporadic cases, disease-free intervals were longer after wide craniotomy, tumor and dural resection with tumor-free margin. CONCLUSIONS: The disease-free interval was substantially similar after surgery and radiosurgery for treating recurrent disease in patients with atypical meningiomas. Surgery is the mainstay for prolonging survival, while radiosurgery can be an adjuvant strategy to gain time for clinical observation and planning aggressive surgical treatment

    Development of Rhyzopertha dominica (F.) (Coleoptera Bostrichidae) on durum wheat kernels and semolina

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    he time necessary to larvae of Rhyzopertha dominica to drill kernels with or without dusts (semolina or debris from adults), and the possibility of development on semolina were evaluated. T ests were carried out on durum wheat kernels (Triticum durum Desfontaines), debris deriving from rearing, and semolina. Development was observed also on 0.5 and 6 mm of semolina and of debris. T hirty replicates were carried out for each test. The number of first instar larvae, that successfully drill sound kernels within 10 days, was higher by adding semolina or debris. When only kernels were provided, the time needed to larvae to drill increased. Development and the number of emerging adults were not significantly influenced by the addition of semolina to the kernels. Larvae couldn’t develop on 0.5 mm, while an equal number of individuals completed the development to adult in 6 mm of semolina as in the tests with kernels. When development was on debris, a lower number of emerged adults was observed

    The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity

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    Long noncoding RNAs (lncRNAs) are major regulators of physiological and disease-related gene expression, particularly in the central nervous system. Dysregulated lncRNA expression has been documented in several human cancers, and their tissue-specificity makes them attractive candidates as diagnostic/prognostic biomarkers and/or therapeutic agents. Here we show that linc-NeD125, which we previously characterized as a neuronal-induced lncRNA, is significantly overexpressed in Group 4 medulloblastomas (G4 MBs), the largest and least well characterized molecular MB subgroup. Mechanistically, linc-NeD125 is able to recruit the miRNA-induced silencing complex (miRISC) and to directly bind the microRNAs miR-19a-3p, miR-19b-3p and miR-106a-5p. Functionally, linc-NeD125 acts as a competing endogenous RNA (ceRNA) that, sequestering the three miRNAs, leads to de-repression of their targets CDK6, MYCN, SNCAIP, and KDM6A, which are major driver genes of G4 MB. Accordingly, linc-NeD125 downregulation reduces G4 cell proliferation. Moreover, we also provide evidence that linc-NeD125 ectopic expression in the aggressive Group 3 MB cells attenuates their proliferation, migration and invasion. This study unveils the first lncRNA-based ceRNA network in central nervous system tumours and provides a novel molecular circuit underlying the enigmatic Group 4 medulloblastoma

    β-arrestin1-mediated acetylation of Gli1 regulates Hedgehog/Gli signaling and modulates self-renewal of SHH medulloblastoma cancer stem cells

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    Background Aberrant Sonic Hedgehog/Gli (Hh/Gli) signaling pathway is a critical regulator of Sonic hedgehog medulloblastoma (SHH-MB). Cancer stem cells (CSCs), thought to be largely responsible for tumor initiation, maintenance, dissemination and relapse, have been identified in SHH-MB. Since we previously demonstrated that Hh/Gli signaling controls CSCs features in SHH-MB and that in these tumors miR-326 is down regulated, here we investigated whether there is a functional link between Hh/Gli signaling and miR-326. Methods We evaluated β-arrestin1 (Arrb1) and its intragenic miR-326 levels in CSCs derived from SHH-MB. Subsequently, we modulated the expression of Arrb1 and miR-326 in CSCs in order to gain insight into their biological role. We also analyzed the mechanism by which Arrb1 and miR-326 control Hh/Gli signaling and self-renewal, using luciferase and protein immunoprecipitation assays. Results Low levels of Arrb1 and miR-326 represent a feature of CSCs derived from SHH-MB. We observed that re-expression of Arrb1 and miR-326 inhibits Hh/Gli signaling pathway at multiple levels, which cause impaired proliferation and self-renewal, accompanied by down regulation of Nanog levels. In detail, miR-326 negatively regulates two components of the Hh/Gli pathway the receptor Smoothened (Smo) and the transcription factor Gli2, whereas Arrb1 suppresses the transcriptional activity of Gli1, by potentiating its p300-mediated acetylation. Conclusions Our results identify a new molecular mechanism involving miR-326 and Arrb1 as regulators of SHH-MB CSCs. Specifically, low levels of Arrb1 and miR-326 trigger and maintain Hh/Gli signaling and self-renewal
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