Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Evaluation of accuracy and precision in polymer gel dosimetry

PURPOSE: To assess the overall reproducibility and accuracy of an X-ray computed tomography (CT) polymer gel dosimetry (PGD) system and investigate what effects the use of generic, interbatch, and intrabatch gel calibration have on dosimetric and spatial accuracy.METHODS: A N-isopropylacrylamide (NIPAM)-based gel formulation optimized for X-ray CT gel dosimetry was used, and the results over four different batches of gels were analyzed. All gels were irradiated with three 6 MV beams in a calibration pattern at both the bottom and top of the dosimeter. Postirradiation CT images of the gels were processed using background subtraction, image averaging, adaptive mean filtering, and remnant artifact removal. The gel dose distributions were calibrated using a Monte Carlo (Vancouver Island Monte Carlo system) calculated dose distribution of the calibration pattern. Using the calibration results from all gels, an average or "generic" calibration curve was calculated and this generic calibration curve was used to calibrate each of the gels within the sample. For each of the gels, the irradiation pattern at the bottom of the dosimeter was also calibrated using the irradiation pattern at the top of the dosimeter to evaluate intragel calibration.RESULTS: Comparison of gel measurements with Monte Carlo dose calculations found excellent dosimetric accuracy when using an average (or generic) calibration with a mean dose discrepancy of 1.8% in the low-dose gradient region which compared to a "best-case scenario" self-calibration method with a mean dose discrepancy of 1.6%. The intragel calibration method investigated produced large dose discrepancies due to differences in dose response at the top and bottom of the dosimeter, but the use of a dose-dependent correction reduced these dose errors. Spatial accuracy was found to be excellent for the average calibration method with a mean distance-to-agreement (DTA) of 0.63 mm and 99.6% of points with a DTA < 2 mm in high-dose gradient regions. This compares favorably to the self-calibration method which produced a mean DTA of 0.61 mm and 99.8% of points with a DTA < 2 mm. Gamma analysis using a 3%/3 mm criterion also found good agreement between the gel measurement and Monte Carlo dose calculation when using either the average calibration or self-calibration methods (96.8% and 98.2%, respectively).CONCLUSIONS: An X-ray CT PGD system was evaluated and found to have excellent dosimeteric and spatial accuracy when compared to Monte Carlo dose calculations and the use of generic and interbatch calibration methods were found to be effective. The establishment of the accuracy and reproducibility of this system provides important information for clinical implementation

High-throughput genotyping of intermediate-size structural variation

The contribution of large-scale and intermediate-size structural variation (ISV) to human genetic disease and disease susceptibility is only beginning to be understood. The development of high-throughput genotyping technologies is one of the most critical aspects for future studies of linkage disequilibrium (LD) and disease association. Using a simple PCR-based method designed to assay the junctions of the breakpoints, we gen-otyped seven simple insertion and deletion polymorphisms ranging in size from 6.3 to 24.7 kb among 90 CEPH individuals. We then extended this analysis to a larger collection of samples (n 5 460) by application of an oligonucleotide extension–ligation genotyping assay. The analysis showed a high level of concor-dance (99%) when compared with PCR/sequence-validated genotypes. Using the available HapMap data, we observed significant LD (r 2 5 0.74–0.95) between each ISV and flanking single nucleotide polymorph-isms, but this observation is likely to hold only for similar simple insertion/deletion events. The approach we describe may be used to characterize a large number of individuals in a cost-effective manner once the sequence organization of ISVs is known

Ultrafast Au(III)-Mediated Arylation of Cysteine

Through mechanistic work and rational design, we have developed the fastest organometallic abiotic Cys bioconjugation. As a result, the developed organometallic Au(III) bioconjugation reagents enable selective labeling of Cys moieties down to picomolar concentrations and allow for the rapid construction of complex heterostructures from peptides, proteins, and oligonucleotides. This work showcases how organometallic chemistry can be interfaced with biomolecules and lead to a range of reactivities that are largely unmatched by classical organic chemistry tools

Progress on the BL2 beam measurement of the neutron lifetime

A precise value of the neutron lifetime is important in several areas of physics, including determinations of the quark-mixing matrix element |Vud|, related tests of the Standard Model, and predictions of light element abundances in Big Bang Nucleosynthesis models. We report the progress on a new measurement of the neutron lifetime utilizing the cold neutron beam technique. Several experimental improvements in both neutron and proton counting that have been developed over the last decade are presented. This new effort should yield a final uncertainty on the lifetime of 1 s with an improved understanding of the systematic effects

Global relationships in tree functional traits

Due to massive energetic investments in woody support structures, trees are subject to unique physiological, mechanical, and ecological pressures not experienced by herbaceous plants. Despite a wealth of studies exploring trait relationships across the entire plant kingdom, the dominant traits underpinning these unique aspects of tree form and function remain unclear. Here, by considering 18 functional traits, encompassing leaf, seed, bark, wood, crown, and root characteristics, we quantify the multidimensional relationships in tree trait expression. We find that nearly half of trait variation is captured by two axes: one reflecting leaf economics, the other reflecting tree size and competition for light. Yet these orthogonal axes reveal strong environmental convergence, exhibiting correlated responses to temperature, moisture, and elevation. By subsequently exploring multidimensional trait relationships, we show that the full dimensionality of trait space is captured by eight distinct clusters, each reflecting a unique aspect of tree form and function. Collectively, this work identifies a core set of traits needed to quantify global patterns in functional biodiversity, and it contributes to our fundamental understanding of the functioning of forests worldwide.Understanding patterns in woody plant trait relationships and trade-offs is challenging. Here, by applying machine learning and data imputation methods to a global database of georeferenced trait measurements, the authors unravel key relationships in tree functional traits at the global scale