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1.
Angew Chem Int Ed Engl ; 61(26): e202202012, 2022 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-35393733

RESUMEN

The planar SnO2 electron transport layer (ETL) has contributed to the reported power conversion efficiency (PCE) record of perovskite solar cells (PSCs), while the high-temperature mesoporous SnO2 ETL (mp-SnO2 ) brings poor device performance. Herein, we report the application of mp-SnO2 for efficient printable PSCs via oxygen vacancy (OV) management by introducing magnesium (Mg) into the paste. We find that high-temperature annealing suppresses self-doping of SnO2 by reducing OVs. The introduced Mg occupies both the Sn site and interstitial site of SnO2 and promotes the formation of OVs. Lattice Mg tends to induce neutral OVs and interstitial Mg could promote the ionization of neutral OVs for self-doping. The synergy effect on OVs increases the carrier density and upshifts the Fermi level energy of mp-SnO2 , ensuring its capability as the well-performed ETL with trap-less charge transport and suppressed surface recombination for dramatic improved device PCE from 6.62 % to 17.25 %.

2.
Genet Med ; 23(6): 1028-1040, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33658631

RESUMEN

PURPOSE: We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. METHODS: We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. RESULTS: These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. CONCLUSION: These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Trastorno Autístico , Discapacidad Intelectual , Adulto , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno del Espectro Autista/genética , Trastorno Autístico/genética , Humanos , Discapacidad Intelectual/genética , Factores de Transcripción del Factor Regulador X , Factores de Transcripción/genética
3.
DNA Cell Biol ; 40(3): 441-456, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33600242

RESUMEN

IGT family genes function critically to regulate lateral organ orientation in plants. However, little information is available about this family of genes in Brassica napus. In this study, 27 BnIGT genes were identified on 16 chromosomes and divided into seven clades, namely LAZY1∼LAZY6 and TAC1 (Tiller Angle Control 1), based on their phylogenetic relationships. Duplication analysis revealed that 91.1% of the gene pairs were derived from whole-genome duplication. Most BnIGT genes had a similar structural pattern with one or two very short exons followed by a long and a shorter exon. Common and specific motifs were identified among the seven clades, and motif 1, containing the family-specific GφL(A/T)IGT sequence, was observed in all clades except LAZY5. Three types of cis-elements pertinent to transcription factor binding, light responses, and hormone signaling were detected in the BnIGT promoters. Intriguingly, more than half of the BnIGT genes exhibited no or very low expression in various tissues, and the LAZY1 and TAC1 clade members showed distinct tissue expression preferences. Coexpression analysis revealed that the LAZY1 members had strong associations with cell wall biosynthesis genes. This analysis provides a deeper understanding of the BnIGT gene family and will facilitate further deduction of their role in regulating plant architecture in B. napus.


Asunto(s)
Brassica napus , Regulación de la Expresión Génica de las Plantas/fisiología , Familia de Multigenes , Proteínas de Plantas , Tetraploidía , Brassica napus/genética , Brassica napus/metabolismo , Estudio de Asociación del Genoma Completo , Proteínas de Plantas/biosíntesis , Proteínas de Plantas/genética
4.
Bioorg Med Chem ; 18(1): 292-304, 2010 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-19962319

RESUMEN

B-Raf protein kinase, which is a key signaling molecule in the RAS-RAF-MEK-ERK signaling pathway, plays an important role in many cancers. The B-Raf V600E mutation represents the most frequent oncogenic kinase mutation known and is responsible for increased kinase activity in approximately 7% of all human cancers, establishing B-Raf as an important therapeutic target for inhibition. Through the use of an iterative program that utilized a chemocentric approach and a rational structure based design, we have developed novel, potent, and specific DFG-out allosteric inhibitors of B-Raf kinase. Here, we present efficient and versatile chemistry that utilizes a key one pot, [3+2] cycloaddition reaction to obtain highly substituted imidazoles and their application in the design of allosteric B-Raf inhibitors. Inhibitors based on this scaffold display subnanomolar potency and a favorable kinase profile.


Asunto(s)
Imidazoles/química , Imidazoles/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas Proto-Oncogénicas B-raf/metabolismo , Animales , Ciclización , Humanos , Imidazoles/síntesis química , Ratones , Modelos Moleculares , Unión Proteica , Proteínas Proto-Oncogénicas B-raf/química
5.
Ann N Y Acad Sci ; 1158: 302-13, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19348651

RESUMEN

This paper describes the technique designated best performer in the 2nd conference on Dialogue for Reverse Engineering Assessments and Methods (DREAM2) Challenge 5 (unsigned genome-scale network prediction from blinded microarray data). Existing algorithms use the pairwise correlations of the expression levels of genes, which provide valuable but insufficient information for the inference of regulatory interactions. Here we present a computational approach based on the recently developed context likelihood of related (CLR) algorithm, extracting additional complementary information using the information theoretic measure of synergy and assigning a score to each ordered pair of genes measuring the degree of confidence that the first gene regulates the second. When tested on a set of publicly available Escherichia coli gene-expression data with known assumed ground truth, the synergy augmented CLR (SA-CLR) algorithm had significantly improved prediction performance when compared to CLR. There is also enhanced potential for biological discovery as a result of the identification of the most likely synergistic partner genes involved in the interactions.


Asunto(s)
Algoritmos , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Escherichia coli/genética , Perfilación de la Expresión Génica , Modelos Genéticos , Análisis de Secuencia por Matrices de Oligonucleótidos , Reproducibilidad de los Resultados
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