Dilute Alloys Based on Au, Ag, or Cu for Efficient Catalysis: From Synthesis to Active Sites.

The development of new catalyst materials for energy-efficient chemical synthesis is critical as over 80% of industrial processes rely on catalysts, with many of the most energy-intensive processes specifically using heterogeneous catalysis. Catalytic performance is a complex interplay of phenomena involving temperature, pressure, gas composition, surface composition, and structure over multiple length and time scales. In response to this complexity, the integrated approach to heterogeneous dilute alloy catalysis reviewed here brings together materials synthesis, mechanistic surface chemistry, reaction kinetics, in situ and operando characterization, and theoretical calculations in a coordinated effort to develop design principles to predict and improve catalytic selectivity. Dilute alloy catalysts─in which isolated atoms or small ensembles of the minority metal on the host metal lead to enhanced reactivity while retaining selectivity─are particularly promising as selective catalysts. Several dilute alloy materials using Au, Ag, and Cu as the majority host element, including more recently introduced support-free nanoporous metals and oxide-supported nanoparticle "raspberry colloid templated (RCT)" materials, are reviewed for selective oxidation and hydrogenation reactions. Progress in understanding how such dilute alloy catalysts can be used to enhance selectivity of key synthetic reactions is reviewed, including quantitative scaling from model studies to catalytic conditions. The dynamic evolution of catalyst structure and composition studied in surface science and catalytic conditions and their relationship to catalytic function are also discussed, followed by advanced characterization and theoretical modeling that have been developed to determine the distribution of minority metal atoms at or near the surface. The integrated approach demonstrates the success of bridging the divide between fundamental knowledge and design of catalytic processes in complex catalytic systems, which can accelerate the development of new and efficient catalytic processes.

Nanostructured silicon via metal assisted catalyzed etch (MACE): chemistry fundamentals and pattern engineering.

There are a range of different methods to generate a nanostructured surface on silicon (Si) but the most cost effective and optically interesting is the metal assisted wet chemical etching (MACE) (Koynov et al 2006 Appl. Phys. Lett. 88 203107). MACE of Si is a controllable, room-temperature wet-chemical technique that uses a thin layer of metal to etch the surface of Si, leaving behind various nano- and micro-scale surface features or 'black silicon'. MACE-fabricated nanowires (NWs) provide improved antireflection and light trapping functionality (Toor et al 2016 Nanoscale 8 15448-66) compared with the traditional 'iso-texturing' (Campbell and Green 1987 J. Appl. Phys. 62 243-9). The resulting lower reflection and improved light trapping can lead to higher short circuit currents in NW solar cells (Toor et al 2011 Appl. Phys. Lett. 99 103501). In addition, NW cells can have higher fill factors and voltages than traditionally processed cells, thus leading to increased solar cell efficiencies (Cabrera et al 2013 IEEE J. Photovolt. 3 102-7). MACE NW processing also has synergy with next generation Si solar cell designs, such as thin epitaxial-Si and passivated emitter rear contact (Toor et al 2016 Nanoscale 8 15448-66). While several companies have begun manufacturing black Si, and many more are researching these techniques, much of the work has not been published in traditional journals and is publicly available only through conference proceedings and patent publications, which makes learning the field challenging. There have been three specialized review articles published recently on certain aspects of MACE or black Si, but do not present a full review that would benefit the industry (Liu et al 2014 Energy Environ. Sci. 7 3223-63; Yusufoglu et al 2015 IEEE J. Photovolt. 5 320-8; Huang et al 2011 Adv. Mater. 23 285-308). In this feature article, we review the chemistry of MACE and explore how changing parameters in the wet etch process effects the resulting texture on the Si surface. Then we review efforts to increase the uniformity and reproducibility of the MACE process, which is critical for commercializing the black Si technology.

Facioscapulohumeral muscular dystrophy family studies of DUX4 expression: evidence for disease modifiers and a quantitative model of pathogenesis.

Facioscapulohumeral muscular dystrophy (FSHD), the most prevalent myopathy afflicting both children and adults, is predominantly associated with contractions in the 4q35-localized macrosatellite D4Z4 repeat array. Recent studies have proposed that FSHD pathology is caused by the misexpression of the DUX4 (double homeobox 4) gene resulting in production of a pathogenic protein, DUX4-FL, which has been detected in FSHD, but not in unaffected control myogenic cells and muscle tissue. Here, we report the analysis of DUX4 mRNA and protein expression in a much larger collection of myogenic cells and muscle biopsies derived from biceps and deltoid muscles of FSHD affected subjects and their unaffected first-degree relatives. We confirmed that stable DUX4-fl mRNA and protein were expressed in myogenic cells and muscle tissues derived from FSHD affected subjects, including several genetically diagnosed adult FSHD subjects yet to show clinical manifestations of the disease in the assayed muscles. In addition, we report DUX4-fl mRNA and protein expression in muscle biopsies and myogenic cells from genetically unaffected relatives of the FSHD subjects, although at a significantly lower frequency. These results establish that DUX4-fl expression per se is not sufficient for FSHD muscle pathology and indicate that quantitative modifiers of DUX4-fl expression and/or function and family genetic background are determinants of FSHD muscle disease progression.

The role of apoptosis in neuromuscular diseases and prospects for anti-apoptosis therapy.

Although genetic mutations that are responsible for most of the inherited neuromuscular diseases have been identified, the molecular and cellular mechanisms that cause muscle and nerve depletion are not well understood and therapies are lacking. Histological studies of many neuromuscular diseases indicated that loss of motor-nerve and/or skeletal-muscle function might be due to excessive cell death by apoptosis. Recent studies have confirmed this possibility by showing that pathology in mouse models of amyotrophic lateral sclerosis, congenital muscular dystrophy, oculopharyngeal muscular dystrophy and collagen-VI deficiency, but not Duchenne muscular dystrophy, is significantly ameliorated by genetic or pharmacological interventions that have been designed to inhibit apoptosis. Thus, apoptosis greatly contributes to pathology in mouse models of several neuromuscular diseases, and appropriate anti-apoptosis therapy might therefore be beneficial for the corresponding human diseases.

Metal assisted catalyzed etched (MACE) black Si: optics and device physics.

Metal-assisted catalyzed etching (MACE) of silicon (Si) is a controllable, room-temperature wet-chemical technique that uses a thin layer of metal to etch the surface of Si, leaving behind various nano- and micro-scale surface features, including nanowires (NWs), that can be tuned to achieve various useful engineering goals, in particular with respect to Si solar cells. In this review, we introduce the science and technology of MACE from the literature, and provide an in-depth analysis of MACE to enhance Si solar cells, including the outlook for commercial applications of this technology.

Individual epigenetic status of the pathogenic D4Z4 macrosatellite correlates with disease in facioscapulohumeral muscular dystrophy.

BACKGROUND: Both forms of facioscapulohumeral muscular dystrophy (FSHD) are associated with aberrant epigenetic regulation of the chromosome 4q35 D4Z4 macrosatellite. Chromatin changes due to large deletions of heterochromatin (FSHD1) or mutations in chromatin regulatory proteins (FSHD2) lead to relaxation of epigenetic repression and increased expression of the deleterious double homeobox 4 (DUX4) gene encoded within the distal D4Z4 repeat. However, many individuals with the genetic requirements for FSHD remain asymptomatic throughout their lives. Here we investigated family cohorts of FSHD1 individuals who were either affected (manifesting) or without any discernible weakness (nonmanifesting/asymptomatic) and their unaffected family members to determine if individual epigenetic status and stability of repression at the contracted 4q35 D4Z4 array in myocytes correlates with FSHD disease. RESULTS: Family cohorts were analyzed for DNA methylation on the distal pathogenic 4q35 D4Z4 repeat on permissive A-type subtelomeres. We found DNA hypomethylation in FSHD1-affected subjects, hypermethylation in healthy controls, and distinctly intermediate levels of methylation in nonmanifesting subjects. We next tested if these differences in DNA methylation had functional relevance by assaying DUX4-fl expression and the stability of epigenetic repression of DUX4-fl in myogenic cells. Treatment with drugs that alter epigenetic status revealed that healthy cells were refractory to treatment, maintaining stable repression of DUX4, while FSHD1-affected cells were highly responsive to treatment and thus epigenetically poised to express DUX4. Myocytes from nonmanifesting subjects had significantly higher levels of DNA methylation and were more resistant to DUX4 activation in response to epigenetic drug treatment than cells from FSHD1-affected first-degree relatives containing the same contraction, indicating that the epigenetic status of the contracted D4Z4 array is reflective of disease. CONCLUSIONS: The epigenetic status of the distal 4qA D4Z4 repeat correlates with FSHD disease; FSHD-affected subjects have hypomethylation, healthy unaffected subjects have hypermethylation, and nonmanifesting subjects have characteristically intermediate methylation. Thus, analysis of DNA methylation at the distal D4Z4 repeat could be used as a diagnostic indicator of developing clinical FSHD. In addition, the stability of epigenetic repression upstream of DUX4 expression is a key regulator of disease and a viable therapeutic target.

Myogenic enhancers regulate expression of the facioscapulohumeral muscular dystrophy-associated DUX4 gene.

Facioscapulohumeral muscular dystrophy (FSHD) is linked to epigenetic dysregulation of the chromosome 4q35 D4Z4 macrosatellite. However, this does not account for the tissue specificity of FSHD pathology, which requires stable expression of an alternative full-length mRNA splice form of DUX4 (DUX4-fl) from the D4Z4 array in skeletal muscle. Here, we describe the identification of two enhancers, DUX4 myogenic enhancer 1 (DME1) and DME2 which activate DUX4-fl expression in skeletal myocytes but not fibroblasts. Analysis of the chromatin revealed histone modifications and RNA polymerase II occupancy consistent with DME1 and DME2 being functional enhancers. Chromosome conformation capture analysis confirmed association of DME1 and DME2 with the DUX4 promoter in vivo. The strong interaction between DME2 and the DUX4 promoter in both FSHD and unaffected primary myocytes was greatly reduced in fibroblasts, suggesting a muscle-specific interaction. Nucleosome occupancy and methylome sequencing analysis indicated that in most FSHD myocytes, both enhancers are associated with nucleosomes but have hypomethylated DNA, consistent with a permissive transcriptional state, sporadic occupancy, and the observed DUX4 expression in rare myonuclei. Our data support a model in which these myogenic enhancers associate with the DUX4 promoter in skeletal myocytes and activate transcription when epigenetically derepressed in FSHD, resulting in the pathological misexpression of DUX4-fl.

Muscle-specific BCL2 expression ameliorates muscle disease in laminin {alpha}2-deficient, but not in dystrophin-deficient, mice.

To examine the role of apoptosis in neuromuscular disease progression, we have determined whether pathogenesis in dystrophin-deficient (mdx) and laminin alpha2-deficient (Lama2-null) mice is ameliorated by overexpression of the anti-apoptosis protein BCL2 in diseased muscles. The mdx mice are a model for the human disease, Duchenne muscular dystrophy (DMD), and the Lama2-null mice are a model for human congenital muscular dystrophy type 1A (MDC1A). For these studies, we generated transgenic mice that overexpressed human BCL2 under control of muscle-specific MyoD or MRF4 promoter fragments. We then used cross-breeding to introduce the transgenes into diseased mdx or Lama2-null mice. In mdx mice, we found that overexpression of BCL2 failed to produce any significant differences in muscle pathology. In contrast, in the Lama2-null mice, we found that muscle-specific expression of BCL2 led to a several-fold increase in lifespan and an increased growth rate. Thus, BCL2-mediated apoptosis appears to play a significant role in pathogenesis of laminin alpha2 deficiency, but not of dystrophin deficiency, suggesting that therapies designed to ameliorate disease by inhibition of apoptosis are more likely to succeed in MDC1A than in DMD.