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Democracy's beginning : the Athenian story
\"The first democracy, established in ancient Greece more than 2,500 years ago, has served as the foundation for every democratic system of government instituted down the centuries. In this lively history, author Thomas N. Mitchell tells the full and remarkable story of how a radical new political order was born out of the revolutionary movements that swept through the Greek world in the seventh and sixth centuries B.C., how it took firm hold and evolved over the next two hundred years, and how it was eventually undone by the invading Macedonian conquerors, a superior military power. Mitchell's superb history addresses the most crucial issues surrounding this first paradigm of democratic governance, including what initially inspired the political beliefs underpinning it, the ways the system succeeded and failed, how it enabled both an empire and a cultural revolution that transformed the world of arts and philosophy, and the nature of the Achilles heel that hastened the demise of Athenian democracy\"-- Provided by publisher.
Book
The mutational landscape of human somatic and germline cells
Over the course of an individual’s lifetime, normal human cells accumulate mutations
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. Here we compare the mutational landscape in 29 cell types from the soma and germline using multiple samples from the same individuals. Two ubiquitous mutational signatures, SBS1 and SBS5/40, accounted for the majority of acquired mutations in most cell types, but their absolute and relative contributions varied substantially. SBS18, which potentially reflects oxidative damage
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, and several additional signatures attributed to exogenous and endogenous exposures contributed mutations to subsets of cell types. The rate of mutation was lowest in spermatogonia, the stem cells from which sperm are generated and from which most genetic variation in the human population is thought to originate. This was due to low rates of ubiquitous mutational processes and may be partially attributable to a low rate of cell division in basal spermatogonia. These results highlight similarities and differences in the maintenance of the germline and soma.
The authors report the mutational landscape of 29 cell types from microdissected biopsies from 19 organs and explore the mechanisms underlying mutation rates in normal tissues.
Journal Article
VMware vSphere for dummies
Provides information on using VMware technology to create a virtual system, covering installation, configuration, administration, and troubleshooting.
Book
Azure PowerShell Quick Start Guide
As an IT professional, it is important to keep up with cloud technologies and learn to manage those technologies. PowerShell is a critical tool that must be learned in order to effectively and more easily manage many Azure resources. This book is designed to teach you to leverage PowerShell to perform many day-to-day tasks in Microsoft Azure.
eBook
Timing the initiation of multiple myeloma
The evolution and progression of multiple myeloma and its precursors over time is poorly understood. Here, we investigate the landscape and timing of mutational processes shaping multiple myeloma evolution in a large cohort of 89 whole genomes and 973 exomes. We identify eight processes, including a mutational signature caused by exposure to melphalan. Reconstructing the chronological activity of each mutational signature, we estimate that the initial transformation of a germinal center B-cell usually occurred during the first 2
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-3
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decades of life. We define four main patterns of activation-induced deaminase (AID) and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) mutagenesis over time, including a subset of patients with evidence of prolonged AID activity during the pre-malignant phase, indicating antigen-responsiveness and germinal center reentry. Our findings provide a framework to study the etiology of multiple myeloma and explore strategies for prevention and early detection.
The initial mutational processes and how these lead to progression in multiple myeloma (MM) are unclear. Here, the authors identify mutational signatures that occur over time in a large cohort of MM patients and suggest features that may help in early diagnosis.
Journal Article
Mesoscopic Damage and Fracturing of Heterogeneous Brittle Rocks Based on Three-dimensional Polycrystalline Discrete Element Method
Rock heterogeneities often control microcracking on the grain scale and therefore the mechanical behavior of the rock on the macroscale. We therefore studied the fracture patterns, mechanical behavior and strength of granular rocks using the three-dimensional numerical modeling code 3DEC. The numerical rock specimens, built using software package Neper, comprised an assemblage of Voronoi polyhedra designed to resemble grains. Different grains, representing different rock-forming minerals, and the contacts between the grains were assigned different mechanical and physical properties, accounting for the grain scale heterogeneity observed in natural granular rocks. The model accurately captured the evolution of damage on the grain scale (tensile and shear microcracks) and the macroscopic mechanical behavior, strength, and failure patterns observed in laboratory experiments performed on sandstone. Based on this validation, we explored the influence of grain size and shape distribution on the mechanical behavior of granular rock. We show that rock specimens characterized by a wide grain size distribution were weaker than those with a narrow grain size distribution, but that grain sphericity distributions does not significantly influence strength. We also found that increasing the initial porosity reduced specimen strength, due to the concentration of stress around the voids, and that intergranular cracking was the dominant contact damage mechanism during uniaxial compression. Due to the ease of flexibility in varying grain scale parameters, we conclude that the model used herein is a powerful tool that can be used to study the mechanical behavior, strength, and failure patterns of rock.
Journal Article
The mutational landscape of normal human endometrial epithelium
All normal somatic cells are thought to acquire mutations, but understanding of the rates, patterns, causes and consequences of somatic mutations in normal cells is limited. The uterine endometrium adopts multiple physiological states over a lifetime and is lined by a gland-forming epithelium
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,
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. Here, using whole-genome sequencing, we show that normal human endometrial glands are clonal cell populations with total mutation burdens that increase at about 29 base substitutions per year and that are many-fold lower than those of endometrial cancers. Normal endometrial glands frequently carry ‘driver’ mutations in cancer genes, the burden of which increases with age and decreases with parity. Cell clones with drivers often originate during the first decades of life and subsequently progressively colonize the epithelial lining of the endometrium. Our results show that mutational landscapes differ markedly between normal tissues—perhaps shaped by differences in their structure and physiology—and indicate that the procession of neoplastic change that leads to endometrial cancer is initiated early in life.
Whole-genome sequencing of normal human endometrial glands shows that most are clonal cell populations and frequently carry cancer driver mutations that occur early in life, and that parity has a protective effect.
Journal Article