Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance

Abstract Background Non-coding regulatory elements (NCREs), such as enhancers, play a crucial role in gene regulation, and genetic aberrations in NCREs can lead to human disease, including brain disorders. The human brain is a complex organ that is susceptible to numerous disorders; many of these are caused by genetic changes, but a multitude remain currently unexplained. Understanding NCREs acting during brain development has the potential to shed light on previously unrecognized genetic causes of human brain disease. Despite immense community-wide efforts to understand the role of the non-coding genome and NCREs, annotating functional NCREs remains challenging. Methods Here we performed an integrative computational analysis of virtually all currently available epigenome data sets related to human fetal brain. Results Our in-depth analysis unravels 39,709 differentially active enhancers (DAEs) that show dynamic epigenomic rearrangement during early stages of human brain development, indicating likely biological function. Many of these DAEs are linked to clinically relevant genes, and functional validation of selected DAEs in cell models and zebrafish confirms their role in gene regulation. Compared to enhancers without dynamic epigenomic rearrangement, DAEs are subjected to higher sequence constraints in humans, have distinct sequence characteristics and are bound by a distinct transcription factor landscape. DAEs are enriched for GWAS loci for brain-related traits and for genetic variation found in individuals with neurodevelopmental disorders, including autism. Conclusion This compendium of high-confidence enhancers will assist in deciphering the mechanism behind developmental genetics of human brain and will be relevant to uncover missing heritability in human genetic brain disorders

A look to the Electricity Generation from Non-Conventional Renewable Energy Sources in Colombia

This study discusses the potentialities and current situation of the electricity generation from non-conventional renewable energy sources (NCRES) in Colombia. In particular, three scenarios considering the increment of NCRES electricity based generation installed capacity are discussed. The three scenarios are compared to the 2020 forecast of the Energy and Mining Planning Unit ((UPME). Overall, it id shown that Colombia has a significant unused NCRES potential, which makes possible to realize the 6% target for NCRE based electricity generation capacity installed by 2020. In particular, the photovoltaic energy is foresee to account for over half of the NCRE mix. Even though the law 1715 is a progress towards integrating NCRE to the National Electric System, more policies and developments are required, to further the NCRE based installed generation capacities

An analysis of electricity generation with renewable resources in Germany

Germany has an experience of renewable energy policies that encourages their usage, achieving technological migration and the redesign of its power generation matrix, achieving 112 GW of renewable resources at 2017. The research presents an analysis between the energy policies and the electricity statistics, the results forecast a date in which they will reach the goal of 50% of annual generation of total electric power by renewable sources, a goal set in 2012

Solar energy in Latin America: A review of the of the four leading markets

One method countries around the world are employing to transition away from fossil fuels is through increasing the share of renewable energy in electricity generation. Wind and solar energy projects are the least expensive option for electricity generation in many parts of the world due to costs falling significantly over the past several years. Solar energy is especially cost effective in places with high solar radiation such as Latin America. These lower costs have led to solar energy being an attractive option for satisfying the growing electricity demand in the region. Capacity in photovoltaic solar plants therefore grew significantly over the past five years specifically in Brazil, Mexico Chile and Argentina. This growth can be partially attributed to the government support through various regulatory policies and other mechanisms such as renewable energy auctions. This work seeks to provide an overview of the solar industry in Latin America, focusing on the four largest markets listed above, looking at their electricity sectors, the current state of the industry, evaluating the most effective support mechanisms used to help establish the market, and discussing common barriers. The report will end with a comparative analysis of the four markets, elaborating on why Brazil and Chile have been relatively more successful in developing the solar industry, the reasons for the slow progress witnessed in Argentina, and the issues Mexico is facing due to the current administration.Um método que os países de todo o mundo estão a utilizar para fugir aos combustíveis fósseis é através do aumento da quota de energias renováveis na produção de eletricidade. Investir em projetos de energia eólica e solar é a opção menos dispendiosa para a produção de eletricidade em muitas partes do mundo, devido à queda significativa dos custos nos últimos anos. A energia solar é especialmente rentável em locais com grande radiação solar, como a América Latina. Estes custos mais baixos levaram a que a energia solar fosse uma opção atraente para geração de eletricidade na região. Assim, a capacidade dos painéis solares fotovoltaicos cresceu significativamente nos últimos cinco anos especificamente no Brasil, México, Chile e Argentina. Este crescimento pode ser atribuído ao apoio dos governos através de várias políticas regulatórios e outros mecanismos, como os leilões de energias renováveis. Este trabalho procura fornecer uma visão geral da indústria solar na América Latina, focando-se nos quatro maiores mercados acima listados. Analisará os sectores de eletricidade, o estado atual da indústria, avaliará os mecanismos de apoio utilizados para ajudar a estabelecer o mercado e discute barreiras e obstáculos comuns. A dissertação terminará com uma análise comparativa dos quatro mercados elaborando as razões pelas quais o Brasil e o Chile têm tido relativamente mais sucesso no desenvolvimento da indústria solar, as razões dos lentos progressos verificados na Argentina e as questões que o México enfrenta devido à atual administração

Revisiting T2KK and T2KO physics potential and νμ\nu_\mu - νˉμ\bar{\nu}_\mu beam ratio

We revisit the sensitivity study of the Tokai-to-Kamioka-and-Korea (T2KK) and Tokai-to-Kamioka-and-Oki (T2KO) proposals where a water Cerenkov detector with the 100 kton fiducial volume is placed in Korea ($L = 1000$ km) and Oki island ($L = 653$ km) in Japan, respectively, in addition to the Super-Kamiokande for determination of the neutrino mass hierarchy and leptonic CP phase ($\delta_{CP}$). We systematically study the running ratio of the $\nu_\mu$ and $\bar{\nu}_\mu$ focusing beams with dedicated background estimation for the $\nu_e$ appearance and $\nu_\mu$ disappearance signals, especially improving treatment of the neutral current $\pi^0$ backgrounds. Using a $\nu_\mu$ - $\bar{\nu}_\mu$ beam ratio between 3 : 2 and 2.5 : 2.5 (in unit of $10^{21}$POT with the proton energy of 40 GeV), the mass hierarchy determination with the median sensitivity of 3 - 5 $\sigma$ by the T2KK and 1 - 4 $\sigma$ by the T2KO experiment are expected when $\sin^2\theta_{23} = 0.5$, depending on the mass hierarchy pattern and CP phase. These sensitivities are enhanced (reduced) by $30\%$ - $40\%$ in $\Delta \chi^2$ when $\sin^2\theta_{23} = 0.6\, (0.4)$. The CP phase is measured with the uncertainty of $20^\circ$ - $50^\circ$ by the T2KK and T2KO using the $\nu_\mu$ - $\bar{\nu}_\mu$ focusing beam ratio between 3.5 : 1.5 and 1.5 : 3.5. These findings indicate that inclusion of the $\bar{\nu}_\mu$ focusing beam improves the sensitivities of the T2KK and T2KO experiments to both the mass hierarchy determination and leptonic CP phase measurement simultaneously with the preferred beam ratio being between 3 : 2 - 2.5 : 2.5 ($\times 10^{21}$POT).Comment: 33 pages, 16 figures, 5 table

Socorro Chieftain, 10-05-1901

https://digitalrepository.unm.edu/socorro_c_news/1195/thumbnail.jp

Exploring missing heritability in neurodevelopmental disorders:Learning from regulatory elements

In this thesis, I aimed to solve part of the missing heritability in neurodevelopmental disorders, using computational approaches. Next to the investigations of a novel epilepsy syndrome and investigations aiming to elucidate the regulation of the gene involved, I investigated and prioritized genomic sequences that have implications in gene regulation during the developmental stages of human brain, with the goal to create an atlas of high confidence non-coding regulatory elements that future studies can assess for genetic variants in genetically unexplained individuals suffering from neurodevelopmental disorders that are of suspected genetic origin