The Newton letters (Vols. I and II)

The metaphysical commitment to the circle as the essential element in the analysis of celestial motion has long been recognized as the hallmark of classical astronomy. What has not always been clear, however, is that the circle continued to serve Kepler as a central element in his astronomy after the discovery of the elliptical orbit of Mars. Moreover, the circle also functioned for Kepler in geometry to select the basic polygons, in music to select the basic harmonies, and in astrology to select the basic aspects. His basic set of polygons consisted of those figures that could be constructed using only a compass and a rule; the set of fundamental harmonies consisted of the consonances of the just intonation; and the traditional set of astrological aspects were enlarged by Kepler to include three new aspects in order to make the astrological set consistent with geometry and music. And as the circle served to unify these three areas, so also did it serve to supply the fundamental answers to astronomical problems well after the discovery of his new astronomy—a topic to be discussed in Part II of this paper.     

Ruling engines and diffraction gratings before Rowland: the work of Lewis Rutherfurd and William Rogers

Diffraction gratings are famously associated with Henry Rowland of Johns Hopkins University but there were precursors. Although gratings were first made and used in Europe, reliable machines for ruling gratings were developed in the USA, and two men, Lewis Rutherfurd and William Rogers, tackled the problem before Rowland. Rutherfurd, a wealthy independent astronomer, designed and built the first screw-operated engine for ruling diffraction gratings, the fore-runner of almost all subsequent ruling engines. With it he and his assistant D. C. Chapman ruled many gratings which he generously distributed to practising scientists, thereby materially advancing the science of spectroscopy. Rogers was a Harvard astronomer who developed an interest in the ruling of fine lines on glass that led him to construct a ruling engine with which he investigated the causes of the errors in the rulings he had examined. He continued to seek improvements with a second engine designed for ruling diffraction gratings. He ceased developing this engine when Rowland’s excellent gratings began to be available, concentrating instead on related problems to which he could apply the knowledge and skills he had gained, but his investigations assisted Rowland and other later ruling engine builders. This paper brings together what is known about the ruling engines of Rutherfurd and Rogers, their development, the gratings they produced, their quality and the work that was done with them, and assesses and compares their achievements and the impacts of the work of these two men.     

Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.     

Population density, biomass, and age-class structure of an invasive clam Corbicula fluminea in rivers of the lower San Joaquin River watershed

Corbicula fluminea is well known as an invasive filter-feeding freshwater bivalve with a variety of effects on ecosystem processes. However, C. fluminea has been relatively unstudied in the rivers of the western United States. In June 2003, we sampled C. fluminea at 16 sites in the San Joaquin River watershed of California, which was invaded by C. fluminea in the 1940s. Corbicula fluminea was common in 2 tributaries to the San Joaquin River, reaching densities of 200 clams ? m –2 , but was rare in the San Joaquin River. Biomass followed a similar pattern. Clams of the same age were shorter in the San Joaquin River than in the tributaries. Distribution of clams was different in the 2 tributaries, but the causes of the difference are unknown. The low density and biomass of clams in the San Joaquin River was likely due to stressful habitat or to water quality, because food was abundant. The success of C. fluminea invasions and subsequent effects on trophic processes likely depends on multiple factors. As C. fluminea continues to expand its range around the world, questions regarding invasion success and effects on ecosystems will become important in a wide array of environmental settings.     

Mutations in the pre-replication complex cause Meier-Gorlin syndrome

Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears1?3. Both pre- and post-natal growth are impaired in this disorder, and although microcephaly is often evident, intellect is usually normal in this syndrome. We report here that individuals with this disorder show marked locus heterogeneity, and we identify mutations in five separate genes: ORC1, ORC4, ORC6, CDT1 and CDC6. All of these genes encode components of the pre-replication complex, implicating defects in replication licensing as the cause of a genetic syndrome with distinct developmental abnormalities.     

Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus

Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 × 10(-8), odds ratio = 1.70) and Korean (P = 8.33 × 10(-10), odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-κB subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.     

Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 × 10?? and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.     

Common variants in ZNF365 are associated with both mammographic density and breast cancer risk

High-percent mammographic density adjusted for age and body mass index is one of the strongest risk factors for breast cancer. We conducted a meta analysis of five genome-wide association studies of percent mammographic density and report an association with rs10995190 in ZNF365 (combined P = 9.6 × 10(-10)). Common variants in ZNF365 have also recently been associated with susceptibility to breast cancer.     

Multiple newly identified loci associated with prostate cancer susceptibility

Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at 相似文献