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A new perspective on the brilliance of one of Western art's most celebrated visionaries through an esteemed collection of drawings. The works of Michelangelo (1475-1564) remain an enduring source of awe and fascination more than 500 years after his death. Michelangelo:Mind of the Master offers a new context for understanding the drawings of one of art's greatest visionaries. Through a group of drawings held since 1793 in the Teylers Museum and once in the eminent collection of Queen Christina of Sweden (1626-1689), this book sheds new light on Michelangelo's inventive preparations for his most important commissions in the realms of painting, sculpture, and architecture. Among other works, the volume features preliminary designs for some of the artist's best-known projects, including the Sistine Chapel ceiling and the Medici Chapel tombs. Essays in the volume further explore the history and fate of Michelangelo's drawings during his life, as well as the role of Queen Christina and her heirs in amassing a group of drawings that are among the best preserved by the master today. -- Publisher description.

Active in Florence for much of his career, the Veronese-born Jacopo Ligozzi (c. 1547-1627) has been studied in the literature as a designer for prints, but virtually nothing was previously known about his possible contributions to the art of cartography. The identification of the drawing and map that are the subject of this short note permits an introduction to this relatively obscure aspect of Ligozzi's oeuvre, which can be seen as part of the larger context of his activity as a leading artist and illustrator of natural specimens in the early modern age of scientific exploration. The map is bordered by the Alps on the north, by Etna in Sicily on the south, by Dalmatia on the east, and by the Duchy of Savoy and Provence on the west.

One of the most fascinating drawings in the J. Paul Getty Museum, Los Angeles, is by the Renaissance sculptor, painter, and architect Michelangelo Buonarroti (1475-1564) and is traditionally referred to by the subject of its recto, the Holy Family with the Infant St. John the Baptist (Fig. I).1 The opportunity to examine this sheet afresh arose with the exhibition Michelangelo: Mind of the Master, which was co-organized by the Cleveland Museum of Art (22 September 2019-5 January 2020) and the Getty Museum (25 February-13 March 2020). Regrettably, the exhibition due to have remained open at its Los Angeles venue until 7 June 2020-closed merely three weeks after opening to the public, owing to the COVID-19 pandemic.

Born and trained in Northern Italy, the artist Jacopo Ligozzi (1547–1627) arrived in Florence in 1577 and spent the rest of his life working in the grand ducal capital. During his career in Tuscany, he frequently changed his style to suit different audiences. In some instances, he adjusted his output to local traditions, while in others he distinguished himself from his Florentine colleagues by exaggerating the foreign characters of his work. While his heterogeneous style has posed a problem to scholarship, the present dissertation considers it the outcome of strategies employed by a migrant artist in his new environment. Accordingly, the dissertation carefully examines Ligozzi’s various strategies, focusing primarily on the period between 1590 and 1620 when the artist was operating outside the grand ducal court, taking commissions from a variety of patrons. In order to understand the Florentine attitude towards migrant artists and foreign styles, the dissertation also explores concepts of foreignness, including the interpretative frameworks of humor theories and geographical determinism that enabled people in the late sixteenth and early seventeenth centuries to understand alterity.

Dive deeply into the quantitative finance domain using R with 'Mastering R for Quantitative Finance.' Through this book, you'll explore advanced R programming techniques tailored to financial modeling, risk assessment, and trading strategy optimization. This comprehensive guide aims to equip you with the tools to build practical quantitative finance solutions. What this Book will help me do Analyze detailed financial data using R and quantitative techniques. Develop predictive models for time series and risk management. Implement advanced trading strategies tailored to current market conditions. Master simulation techniques for scenarios without analytical solutions. Evaluate portfolio risks and potential returns with advanced methods. Author(s) None Gabler is a seasoned expert in quantitative finance and R programming, bringing years of practical experience to this book. Her approach combines theoretical depth with practical examples to ensure readers can apply the learned concepts in real-world financial contexts. Her passion for teaching and clear writing style make complex topics accessible to both practitioners and learners. Who is it for? This book is for financial professionals and data scientists seeking to delve into quantitative finance using R. Ideal readers are familiar with the basics of economics and statistics and are looking to apply advanced analytics in finance. If you are aiming to refine your modeling skills or develop precise strategies, this book is tailored for you. It's perfect for those eager to bridge the gap between theory and practical application.

Gaucher disease is a lysosomal storage disorder caused by insufficient glucocerebrosidase activity. Its hallmark manifestations are attributed to infiltration and inflammation by macrophages. Current therapies for Gaucher disease include life−long intravenous administration of recombinant glucocerebrosidase and orally-available glucosylceramide synthase inhibitors. An alternative approach is to engineer the patient’s own hematopoietic system to restore glucocerebrosidase expression, thereby replacing the affected cells, and constituting a potential one-time therapy for this disease. Here, we report an efficient CRISPR/Cas9-based approach that targets glucocerebrosidase expression cassettes with a monocyte/macrophage-specific element to the CCR5 safe-harbor locus in human hematopoietic stem and progenitor cells. The targeted cells generate glucocerebrosidase-expressing macrophages and maintain long-term repopulation and multi-lineage differentiation potential with serial transplantation. The combination of a safe-harbor and a lineage-specific promoter establishes a universal correction strategy and circumvents potential toxicity of ectopic glucocerebrosidase in the stem cells. Furthermore, it constitutes an adaptable platform for other lysosomal enzyme deficiencies. Gaucher disease is a lysosomal storage disorder caused by insufficient glucocerebrosidase expression. Here, the authors describe a CRISPR/Cas9-based gene-editing approach to re-express this enzyme in human blood stem cells and show that they can engraft in NSG mice and differentiate into functional macrophages.

Weak hydrogen bonds, such as O-H···π and C-H···O, are thought to direct biochemical assembly, molecular recognition, and chemical selectivity but are seldom observed in solution. We have used neutron diffraction combined with H/D isotopic substitution to obtain a detailed spatial and orientational picture of the structure of benzene-methanol mixtures. Our analysis reveals that methanol fully solvates and surrounds each benzene molecule. The expected O-H···π interaction is highly localised and directional, with the methanol hydroxyl bond aligned normal to the aromatic plane and the hydrogen at a distance of 2.30 Å from the ring centroid. Simultaneously, the tendency of methanol to form chain and cyclic motifs in the bulk liquid is manifest in a highly templated solvation structure in the plane of the ring. The methanol molecules surround the benzene so that the O-H bonds are coplanar with the aromatic ring while the oxygens interact with C-H groups through simultaneous bifurcated hydrogen bonds. This demonstrates that weak hydrogen bonding can modulate existing stronger interactions to give rise to highly ordered cooperative structural motifs that persist in the liquid phase. Understanding liquid behavior is a challenge due to their disorder nature and rapid molecular rearrangements. Here, the authors show how weak interactions between OH groups and aromatic rings can participate in cooperative mechanisms that give rise to highly structured molecular arrangements in the liquid state.

Our objective was to investigate the mitochondrial dynamics following oxygen-glucose deprivation (OGD) in cultured rat cortical neurons. We documented changes in morphology, protein expression, and DNA levels in mitochondria following OGD and examined the roles of mitochondrial fission [dynamin-related protein 1 (Drp1), fission protein-1 (Fis1)] and fusion [mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and optic atrophy-1 protein (OPA1)] proteins on mitochondrial biogenesis and morphogenesis. We tested the effects of two Drp1 blockers [15-deoxy-Δ12,14-Prostaglandin J2 (PGJ2) and Mitochondrial Division Inhibitor (Mdivi-1)] on mitochondrial dynamics and cell survival. One hour of OGD had minimal effects on neuronal viability but mitochondria appeared condensed. Three hours of OGD caused a 60% decrease in neuronal viability accompanied by a transition from primarily normal/tubular and lesser number of rounded mitochondria during normoxia to either poorly labeled or small and large rounded mitochondria. The percentage of rounded mitochondria remained the same. The mitochondrial voltage-dependent anion channel, Complex V, and mitoDNA levels increased after OGD associated with a dramatic reduction in Drp1 expression, less reduction in Mfn2 expression, an increase in Mfn1 expression, with no changes in either OPA1 or Fis1. Although PGJ2 increased polymerization of Drp1, it did not reduce cell death or alter mitochondrial morphology following OGD and Mdivi-1 did not protect neurons against OGD. In summary, mitochondrial biogenesis and maintained fusion occurred in neurons along with mitochondrial fission following OGD; thus Mfn1 but not Drp1 may be a major regulator of these processes.

Farmland biodiversity is strongly declining in most of Western Europe, but still survives in traditional low intensity agricultural landscapes in Central and Eastern Europe. Accession to the EU however intensifies agriculture, which leads to the vanishing of traditional farming. Our aim was to describe the pollinator assemblages of the last remnants of these landscapes, thus set the baseline of sustainable farming for pollination, and to highlight potential measures of conservation. In these traditional farmlands in the Transylvanian Basin, Romania (EU accession in 2007), we studied the major pollinator groups-wild bees, hoverflies and butterflies. Landscape scale effects of semi-natural habitats, land cover diversity, the effects of heterogeneity and woody vegetation cover and on-site flower resources were tested on pollinator communities in traditionally managed arable fields and grasslands. Our results showed: (i) semi-natural habitats at the landscape scale have a positive effect on most pollinators, especially in the case of low heterogeneity of the direct vicinity of the studied sites; (ii) both arable fields and grasslands hold abundant flower resources, thus both land use types are important in sustaining pollinator communities; (iii) thus, pollinator conservation can rely even on arable fields under traditional management regime. This has an indirect message that the tiny flower margins around large intensive fields in west Europe can be insufficient conservation measures to restore pollinator communities at the landscape scale, as this is still far the baseline of necessary flower resources. This hypothesis needs further study, which includes more traditional landscapes providing baseline, and exploration of other factors behind the lower than baseline level biodiversity values of fields under agri-environmental schemes (AES).

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.