Quinoidal Azaacenes: 99 % Diradical Character

Quinoidal azaacenes with almost pure diradical character (y=0.95 to y=0.99) were synthesized. All compounds exhibit paramagnetic behavior investigated by EPR and NMR spectroscopy, and SQUID measurements, revealing thermally populated triplet states with an extremely low-energy gap ΔEST′ of 0.58 to 1.0 kcal mol−1. The species are persistent in solution (half-life≈14–21 h) and in the solid state they are stable for weeks

UM ESTUDO DE CASO: PALESTRA COMO FERRAMENTA DE CONSTRUÇÃO DO ENSINO E APRENDIZADO SOBRE “DESASTRES AMBIENTAIS” PARA REDUÇÃO DE RISCOS DE DESASTRES NA DISCIPLINA DE CIÊNCIAS

 O processo de desenvolvimento urbano sem planejamento, de parte considerável das cidades brasileiras, apresentam como consequência dois tipos de cidades. Uma cidade “formal” e uma cidade “informal”, oculta das estatísticas oficiais. A cidade informal se caracteriza por moradias irregulares, sem equipamentos urbanos básicos e situam-se em áreas que geralmente deveriam ser Áreas de Preservação Permanente (APP). Justamente estas áreas inapropriadas para ocupação, apresentam-se os maiores riscos de desastres ambientais, recorrentes no Vale do Itajaí. Neste sentido, a abordagem do conteúdo “Desastres Ambientais”, no ensino fundamental é de extrema importância como forma de educação para minimizar a suscetibilidade aos desastres futuros. O objetivo deste trabalho foi analisar o conhecimento construído pelos estudantes a partir de uma palestra ministrada pelo responsável da coordenação da Defesa Civil e aplicada aos estudantes de sexto ano do ensino fundamental. O conteúdo da palestra foi o tema Prevenção aos riscos Desastres Ambientais, com ênfase em deslizamento de solo. Essa prática docente ocorreu em uma escola da rede estadual do município de Brusque, em Santa Catarina. Após a palestra, os estudantes foram avaliados através de atividade de desenho, para representar duas situações: “casa em área de risco” e “casa fora da área de risco”. O resultado da análise indicou que praticamente todos os alunos apresentaram no desenho elementos relacionado à situação de risco. Os elementos identificados, em situação de risco foram moradias em encostas, aterros inadequados e a presença de chuva. Os elementos identificados em situação fora de risco foram residências em área planas, presença de vegetação e murros de proteção. Tendo visto a relevância do conteúdo “desastres ambientais” inserido no currículo do ensino fundamental, espera-se que práticas docentes tornem-se comuns nas escolas, visando a redução de riscos aos desastres

Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design

Parkinson's disease in GTP cyclohydrolase 1 mutation carriers.

"This is the peer reviewed version of the following article: Mencacci et al. 2014. Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers, which has been published in final form at Brain, Volume 137, Issue 9, 1 September 2014, Pages 2480–2492, https://doi.org/10.1093/brain/awu179. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions."GTP cyclohydrolase 1, encoded by the GCH1 gene, is an essential enzyme for dopamine production in nigrostriatal cells. Loss-of-function mutations in GCH1 result in severe reduction of dopamine synthesis in nigrostriatal cells and are the most common cause of DOPA-responsive dystonia, a rare disease that classically presents in childhood with generalized dystonia and a dramatic long-lasting response to levodopa. We describe clinical, genetic and nigrostriatal dopaminergic imaging ([(123)I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane single photon computed tomography) findings of four unrelated pedigrees with DOPA-responsive dystonia in which pathogenic GCH1 variants were identified in family members with adult-onset parkinsonism. Dopamine transporter imaging was abnormal in all parkinsonian patients, indicating Parkinson's disease-like nigrostriatal dopaminergic denervation. We subsequently explored the possibility that pathogenic GCH1 variants could contribute to the risk of developing Parkinson's disease, even in the absence of a family history for DOPA-responsive dystonia. The frequency of GCH1 variants was evaluated in whole-exome sequencing data of 1318 cases with Parkinson's disease and 5935 control subjects. Combining cases and controls, we identified a total of 11 different heterozygous GCH1 variants, all at low frequency. This list includes four pathogenic variants previously associated with DOPA-responsive dystonia (Q110X, V204I, K224R and M230I) and seven of undetermined clinical relevance (Q110E, T112A, A120S, D134G, I154V, R198Q and G217V). The frequency of GCH1 variants was significantly higher (Fisher's exact test P-value 0.0001) in cases (10/1318 = 0.75%) than in controls (6/5935 = 0.1%; odds ratio 7.5; 95% confidence interval 2.4-25.3). Our results show that rare GCH1 variants are associated with an increased risk for Parkinson's disease. These findings expand the clinical and biological relevance of GTP cycloydrolase 1 deficiency, suggesting that it not only leads to biochemical striatal dopamine depletion and DOPA-responsive dystonia, but also predisposes to nigrostriatal cell loss. Further insight into GCH1-associated pathogenetic mechanisms will shed light on the role of dopamine metabolism in nigral degeneration and Parkinson's disease.This study was supported by the Wellcome Trust/Medical Research Council (MRC) Joint Call in Neurodegeneration award (WT089698) to the UK Parkinson's Disease Consortium. This project was also supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre and the Grigioni Foundation for Parkinson Disease. This work was also supported in part by the Intramural Research Programs of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Aging (NIA), and the National Institute of Environmental Health Sciences both part of the National Institutes of Health, Department of Health and Human Services; project numbers Z01-AG000949-02 and Z01-ES101986. In addition this work was supported by the Department of Defense (award W81XWH-09-2-0128), and the Michael J Fox Foundation for Parkinson’s Disease Research. This work was supported by National Institutes of Health grants R01NS037167, R01CA141668, American Parkinson Disease Association (APDA); Barnes Jewish Hospital Foundation; Greater St Louis Chapter of the APDA; Hersenstichting Nederland; Neuroscience Campus Amsterdam; the Deutsche Forschungsgemeinschaft (SFB 936). This study was also funded by the German National Genome Network (NGFNplus number 01GS08134, German Ministry for Education and Research); by the German Federal Ministry of Education and Research (NGFN 01GR0468, PopGen); and 01EW0908 in the frame of ERA-NET NEURON and Helmholtz Alliance Mental Health in an Ageing Society (HA-215), which was funded by the Initiative and Networking Fund of the Helmholtz Association. Funding for the project was provided by the Wellcome Trust under award 076113, 085475 and 090355. The work was also funded in part by Parkinson's UK (Grants 8047 and J-1101) and the Medical Research Council UK (G0700943, G1100643) for H.R.M and S.J.L

UM ESTUDO DE CASO: PALESTRA COMO FERRAMENTA DE CONSTRUÇÃO DO ENSINO E APRENDIZADO SOBRE “DESASTRES AMBIENTAIS” PARA REDUÇÃO DE RISCOS DE DESASTRES NA DISCIPLINA DE CIÊNCIAS

 O processo de desenvolvimento urbano sem planejamento, de parte considerável das cidades brasileiras, apresentam como consequência dois tipos de cidades. Uma cidade “formal” e uma cidade “informal”, oculta das estatísticas oficiais. A cidade informal se caracteriza por moradias irregulares, sem equipamentos urbanos básicos e situam-se em áreas que geralmente deveriam ser Áreas de Preservação Permanente (APP). Justamente estas áreas inapropriadas para ocupação, apresentam-se os maiores riscos de desastres ambientais, recorrentes no Vale do Itajaí. Neste sentido, a abordagem do conteúdo “Desastres Ambientais”, no ensino fundamental é de extrema importância como forma de educação para minimizar a suscetibilidade aos desastres futuros. O objetivo deste trabalho foi analisar o conhecimento construído pelos estudantes a partir de uma palestra ministrada pelo responsável da coordenação da Defesa Civil e aplicada aos estudantes de sexto ano do ensino fundamental. O conteúdo da palestra foi o tema Prevenção aos riscos Desastres Ambientais, com ênfase em deslizamento de solo. Essa prática docente ocorreu em uma escola da rede estadual do município de Brusque, em Santa Catarina. Após a palestra, os estudantes foram avaliados através de atividade de desenho, para representar duas situações: “casa em área de risco” e “casa fora da área de risco”. O resultado da análise indicou que praticamente todos os alunos apresentaram no desenho elementos relacionado à situação de risco. Os elementos identificados, em situação de risco foram moradias em encostas, aterros inadequados e a presença de chuva. Os elementos identificados em situação fora de risco foram residências em área planas, presença de vegetação e murros de proteção. Tendo visto a relevância do conteúdo “desastres ambientais” inserido no currículo do ensino fundamental, espera-se que práticas docentes tornem-se comuns nas escolas, visando a redução de riscos aos desastres

Simulation of Vacuum UV Absorption and Electronic Circular Dichroism Spectra of Methyl Oxirane: The Role of Vibrational Effects

SFX Get it!(opens in a new window)|View at Publisher| Export | Download | Add to List | More... Journal of Chemical Theory and Computation Volume 12, Issue 6, 14 June 2016, Pages 2820-2833 Simulation of Vacuum UV Absorption and Electronic Circular Dichroism Spectra of Methyl Oxirane: The Role of Vibrational Effects (Article) Hodecker, M.ab, Biczysko, M.c , Dreuw, A.b, Barone, V.a a Scuola Normale Superiore, Piazza dei Cavalieri 7, Pisa, Italy b Interdisciplinary Center for Scientific Computing, Heidelberg University, Im Neuenheimer Feld 368, Heidelberg, Germany c International Centre for Quantum and Molecular Structures, College of Sciences, Shanghai University, 99 Shangda Road, Shanghai, China View additional affiliations View references (103) Abstract Vibrationally resolved one-photon absorption and electronic circular dichroism spectra of (R)-methyl oxirane were calculated with different electronic and vibronic models selecting, through an analysis of the convergence of the results, the best compromise between reliability and computational cost. Linear-response TD-DFT/CAM-B3LYP/SNST electronic computations in conjunction with the simple vertical gradient vibronic model were chosen and employed for systematic comparison with the available experimental data. Remarkable agreement between simulated and experimental spectra was achieved for both one-photon absorption and circular dichroism concerning peak positions, relative intensities, and general spectral shapes considering the computational efficiency of the chosen theoretical approach. The significant improvement of the results with respect to smearing of vertical electronic transitions by phenomenological Gaussian functions and the possible inclusion of solvent effects by polarizable continuum models at a negligible additional cost paves the route toward the simulation and analysis of spectral shapes of complex molecular systems in their natural environment. \ua9 2016 American Chemical Society

Influence of Individual Bracket Base Design on the Shear Bond Strength of In-Office 3D Printed Brackets—An In Vitro Study

(1) Background: Novel high-performance polymers for medical 3D printing enable in-office manufacturing of fully customized brackets. Previous studies have investigated clinically relevant parameters such as manufacturing precision, torque transmission, and fracture stability. The aim of this study is to evaluate different design options of the bracket base concerning the adhesive bond between the bracket and tooth, measured as the shear bond strength (SBS) and maximum force (Fmax) according to DIN 13990. (2) Methods: Three different designs for printed bracket bases were compared with a conventional metal bracket (C). The following configurations were chosen for the base design: Matching of the base to the anatomy of the tooth surface, size of the cross-sectional area corresponding to the control group (C), and a micro- (A) and macro- (B) retentive design of the base surface. In addition, a group with a micro-retentive base (D) matched to the tooth surface and an increased size was studied. The groups were analyzed for SBS, Fmax, and adhesive remnant index (ARI). The Kruskal–Wallis test with a post hoc test (Dunn–Bonferroni) and Mann–Whitney U test were used for statistical analysis (significance level: p max were highest in C (SBS: 12.0 ± 3.8 MPa; Fmax: 115.7 ± 36.6 N). For the printed brackets, there were significant differences between A and B (A: SBS 8.8 ± 2.3 MPa, Fmax 84.7 ± 21.8 N; B: SBS 12.0 ± 2.1 MPa, Fmax 106.5 ± 20.7 N). Fmax was significantly different for A and D (D: Fmax 118.5 ± 22.8 N). The ARI score was highest for A and lowest for C. (4) Conclusions: This study shows that conventional brackets form a more stable bond with the tooth than the 3D-printed brackets. However, for successful clinical use, the shear bond strength of the printed brackets can be increased with a macro-retentive design and/or enlargement of the base

mTOR target NDRG1 confers MGMT-dependent resistance to alkylating chemotherapy

A hypoxic microenvironment induces resistance to alkylating agents by activating targets in the mammalian target of rapamycin (mTOR) pathway. The molecular mechanisms involved in this mTOR-mediated hypoxia-induced chemoresistance, however, are unclear. Here we identify the mTOR target N-myc downstream regulated gene 1 (NDRG1) as a key determinant of resistance toward alkylating chemotherapy, driven by hypoxia but also by therapeutic measures such as irradiation, corticosteroids, and chronic exposure to alkylating agents via distinct molecular routes involving hypoxia-inducible factor (HIF)-1alpha, p53, and the mTOR complex 2 (mTORC2)/serum glucocorticoid-induced protein kinase 1 (SGK1) pathway. Resistance toward alkylating chemotherapy but not radiotherapy was dependent on NDRG1 expression and activity. In posttreatment tumor tissue of patients with malignant gliomas, NDRG1 was induced and predictive of poor response to alkylating chemotherapy. On a molecular level, NDRG1 bound and stabilized methyltransferases, chiefly O(6)-methylguanine-DNA methyltransferase (MGMT), a key enzyme for resistance to alkylating agents in glioblastoma patients. In patients with glioblastoma, MGMT promoter methylation in tumor tissue was not more predictive for response to alkylating chemotherapy in patients who received concomitant corticosteroids

Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers

GTP cyclohydrolase 1, encoded by the GCH1 gene, is an essential enzyme for dopamine production in nigrostriatal cells. Loss-of-function mutations in GCH1 result in severe reduction of dopamine synthesis in nigrostriatal cells and are the most common cause of DOPA-responsive dystonia, a rare disease that classically presents in childhood with generalized dystonia and a dramatic long-lasting response to levodopa. We describe clinical, genetic and nigrostriatal dopaminergic imaging ([(123)I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane single photon computed tomography) findings of four unrelated pedigrees with DOPA-responsive dystonia in which pathogenic GCH1 variants were identified in family members with adult-onset parkinsonism. Dopamine transporter imaging was abnormal in all parkinsonian patients, indicating Parkinson's disease-like nigrostriatal dopaminergic denervation. We subsequently explored the possibility that pathogenic GCH1 variants could contribute to the risk of developing Parkinson's disease, even in the absence of a family history for DOPA-responsive dystonia. The frequency of GCH1 variants was evaluated in whole-exome sequencing data of 1318 cases with Parkinson's disease and 5935 control subjects. Combining cases and controls, we identified a total of 11 different heterozygous GCH1 variants, all at low frequency. This list includes four pathogenic variants previously associated with DOPA-responsive dystonia (Q110X, V204I, K224R and M230I) and seven of undetermined clinical relevance (Q110E, T112A, A120S, D134G, I154V, R198Q and G217V). The frequency of GCH1 variants was significantly higher (Fisher's exact test P-value 0.0001) in cases (10/1318 = 0.75%) than in controls (6/5935 = 0.1%; odds ratio 7.5; 95% confidence interval 2.4-25.3). Our results show that rare GCH1 variants are associated with an increased risk for Parkinson's disease. These findings expand the clinical and biological relevance of GTP cycloydrolase 1 deficiency, suggesting that it not only leads to biochemical striatal dopamine depletion and DOPA-responsive dystonia, but also predisposes to nigrostriatal cell loss. Further insight into GCH1-associated pathogenetic mechanisms will shed light on the role of dopamine metabolism in nigral degeneration and Parkinson's disease