The information in the term structure: A non-parametric investigation

This paper proposes a non-linear term structure model that nests the discrete and continuous time models as special cases. I estimate the model non-parametrically using nearest-neighbours regression. In sample, the non-linear model matches the standard theories, but out of sample, it offers substantial improvement. Linear models fail to track future interest rates: a random walk dominates the forward rate as a predictor for 3-month Treasury bills. A non-linear forecast based on the spread is shown statistically to be the best forecast.     

THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia

Characterization of previously described intraflagellar transport (IFT) mouse mutants has led to the proposition that normal primary cilia are required for mammalian cells to respond to the sonic hedgehog (SHH) signal. Here we describe an N-ethyl-N-nitrosourea-induced mutant mouse, alien (aln), which has abnormal primary cilia and shows overactivation of the SHH pathway. The aln locus encodes a novel protein, THM1 (tetratricopeptide repeat-containing hedgehog modulator-1), which localizes to cilia. aln-mutant cilia have bulb-like structures at their tips in which IFT proteins (such as IFT88) are sequestered, characteristic of Chlamydomonas reinhardtii and Caenorhabditis elegans retrograde IFT mutants. RNA-interference knockdown of Ttc21b (which we call Thm1 and which encodes THM1) in mouse inner medullary collecting duct cells expressing an IFT88-enhanced yellow fluorescent protein fusion recapitulated the aln-mutant cilial phenotype, and live imaging of these cells revealed impaired retrograde IFT. In contrast to previously described IFT mutants, Smoothened and full-length glioblastoma (GLI) proteins localize to aln-mutant cilia. We hypothesize that the aln retrograde IFT defect causes sequestration of IFT proteins in aln-mutant cilia and leads to the overactivated SHH signaling phenotype. Specifically, the aln mutation uncouples the roles of anterograde and retrograde transport in SHH signaling, suggesting that anterograde IFT is required for GLI activation and that retrograde IFT modulates this event.     

The value of data

Data citation and the derivation of semantic constructs directly from datasets have now both found their place in scientific communication. The social challenge facing us is to maintain the value of traditional narrative publications and their relationship to the datasets they report upon while at the same time developing appropriate metrics for citation of data and data constructs.     

Genome partitioning of genetic variation for complex traits using common SNPs

We estimate and partition genetic variation for height, body mass index (BMI), von Willebrand factor and QT interval (QTi) using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that ～45%, ～17%, ～25% and ～21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further ～0.5-1% can be explained by X chromosome SNPs. We show that the variance explained by each chromosome is proportional to its length, and that SNPs in or near genes explain more variation than SNPs between genes. We propose a new approach to estimate variation due to cryptic relatedness and population stratification. Our results provide further evidence that a substantial proportion of heritability is captured by common SNPs, that height, BMI and QTi are highly polygenic traits, and that the additive variation explained by a part of the genome is approximately proportional to the total length of DNA contained within genes therein.     

Genome-wide association study identifies three new melanoma susceptibility loci

We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 × 10(-9)), an SNP in MX2 (rs45430, P = 2.9 × 10(-9)) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 × 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 × 10(-7) under a fixed-effects model and P = 1.2 × 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.     

Density and biomass of redband trout relative to stream shading and temperature in southwestern Idaho

Density and biomass of redband trout ( Oncorhynchus mykiss gairdneri ) relative to stream temperature were examined in headwater reaches of Big Jacks and Little Jacks Creeks in southwestern Idaho. Stream shading was greater (mean of 80% versus 46%) and solar insolation was lower (mean of 7.9 versus 15.1 mJ · m -2 · day -1 ) in Little Jacks Creek ( P P ≤ 0.07) but increased more rapidly and to higher levels (24° - 26° C) in Big Jacks Creek. Daily maximum water temperatures (23 km downstream of headwater springs) during July 1996 were lower in Little Jacks Creek (ranged from 18° to 22° C) than in Big Jacks Creek (20.2° to 26° C, P P -2 and 25.0 g · m -2 ) compared to Big Jacks Creek (0.3 fish · m -2 and 8.9 g · m -2 , P = 0.01). Trout density was negatively correlated with increases in water temperature ( P = 0.03) and solar insolation ( P = 0.09) in both streams. Trout biomass increased with stream shading and was negatively correlated with solar insolation ( P < 0.1). Warmer water temperatures in Big Jacks Creek were likely due to historical summerlong livestock grazing, which drastically reduced riparian shading.     

Alhazen,Leonardo, and late-medieval speculation on the inversion of images in the eye

No one before Platter and Kepler proposed retinal reception of an inverted visual image. The dominant tradition in visual theory, especially that of Alhazen and his Western followers, subordinated the intra-ocular geometry of visual rays to the requirement for an upright image and to preconceptions about the precise nature of the visual spirit and its part in vision. Henry of Langenstein and an anonymous glossator in the late Middle Ages proposed alternatives to Alhazen, including the suggestion of double inversion of the image. Leonardo da Vinci was aware of both Alhazen's theory and Henry's contradiction, but perhaps not of the anonymous hypothesis of double inversion. Leonardo's visual ‘theory’ has more the character of a critique than of a theoretical alternative, and he did not transcend the medieval concept of visual spirit.     

Proposition II (Book I) of Newton’s <Emphasis Type="Italic">Principia</Emphasis>

After preparing the way with comments on evanescent quantities and then Newton’s interpretation of his second law, this study of Proposition II (Book I)— Proposition II Every body that moves in some curved line described in a plane and, by a radius drawn to a point, either unmoving or moving uniformly forward with a rectilinear motion, describes areas around that point proportional to the times, is urged by a centripetal force tending toward that same point. —asks and answers the following questions: When does a version of Proposition II first appear in Newton’s work? What revisions bring that initial version to the final form in the 1726 Principia? What, exactly, does this proposition assert? In particular, what does Newton mean by the motion of a body “urged by a centripetal force”? Does it assert a true mathematical claim? If not, what revision makes it true? Does the demonstration of Proposition II persuade? Is it as convincing, for example, as the most convincing arguments of the Principia? If not, what revisions would make the demonstration more persuasive? What is the importance of Proposition II, to the physics of Book III and the mathematics of Book I?