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

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Characterization of Si(100) homoepitaxy grown in the STM at low temperatures

We explore the growth of low-temperature bulk-like Si(100) homoepitaxy with regard to microscopic surface roughness and defects We characterize films grown at different temperatures up to 500K in-situ by means of an effusion cell added to our UHVSTM. The development of novel architectures for future generation computers calls for high-quality homoepitaxial (WOO) grown at low temperature. Even though Si(100) can be grown crystalline up to a limited thickness: the microstructure reveals significant small-scale surface roughness and defects specific to low-temperature growth. Both can he detrimental to fabrication and operation of small-scale electronic devices

Importance of in Situ Monitors in the Preparation of Layered Oxide Heterostructures by Reactive MBE.

Using a variety of in situ monitors and when possible adsorption-controlled growth conditions, layered oxide heterostructures including new compounds and metastable superlattices have been grown by reactive molecular beam epitaxy (MBE). The heteroepitaxial layers grown include Bi{sub 4}Ti{sub 3}O{sub 12}-SrTiO{sub 3} and Bi{sub 4}Ti{sub 3}O{sub 12}-PbTiO{sub 3} Aurivillius phases, Sr{sub n+1}Ti{sub n}O{sub 3n+1} Ruddlesden-Popper phases, and metastable PbTiO{sub 3}/SrTiO{sub 3} and BaTiO{sub 3}/SrTiO{sub 3} superlattices. Accurate composition control is key to the controlled growth of such structures, and to this end combinations of reflection high-energy electron diffraction (RHEED), atomic absorption spectroscopy (AA), a quartz crystal microbalance (QCM), and adsorption-controlled growth conditions were employed during growth. The structural perfection of the films has been investigated using in situ RHEED, four-circle x-ray diffraction, atomic force microscopy (AFM), and high-resolution transmission electron microscopy (TEM)

Characterizing transport current defects in 1-cm-wide YBa[sub 2]Cu[sub 3]O[sub 7-delta] coated conductors.

We have used a low temperature magnetic imaging system to determine current pathways in 5 cm long 'good' and 'bad' regions of a 1-cm-wide YBa2Cu3O7-{delta} coated conductor. The good and bad regions were identified with 4 point probe measurements taken at 1 cm intervals along the tape length. The current density map from the good region showed the expected edge peaked structure, similar to that seen in previous work on high quality test samples grown on single crystal substrates. The structure was also consistent with theoretical understanding of thin film superconductors where demagnetizing effects are strong. The maps from the bad region showed that the current was primarily confined to the right half of the sample. The left half carried only a small current that reached saturation quickly. Effectively halving the sample width quantitatively explains the critical current measured in that section. Spatially resolved xray analysis with 1 mm resolution was used to further characterize the bad section and suggested an abnormally large amount of a-axis YBCO present. This may be the result of non-uniform heating leading to a low deposition temperature in that area

Nanoscale phosphorus atom arrays created using STM for the fabrication of a silicon based quantum computer.

Quantum computers offer the promise of formidable computational power for certain tasks. Of the various possible physical implementations of such a device, silicon based architectures are attractive for their scalability and ease of integration with existing silicon technology. These designs use either the electron or nuclear spin state of single donor atoms to store quantum information. Here we describe a strategy to fabricate an array of single phosphorus atoms in silicon for the construction of such a silicon based quantum computer. We demonstrate the controlled placement of single phosphorus bearing molecules on a silicon surface. This has been achieved by patterning a hydrogen mono-layer 'resist' with a scanning tunneling microscope (STM) tip and exposing the patterned surface to phosphine (PH3) molecules. We also describe preliminary studies into a process to incorporate these surface phosphorus atoms into the silicon crystal at the array sites. Keywords: Quantum computing, nanotechriology scanning turincling microscopy, hydrogen lithograph

A Polynesian-specific missense CETP variant alters the lipid profile

Summary: Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at CETP associate with serum lipid profiles and cardiovascular disease. Here, sequencing of CETP identified a missense variant rs1597000001 (p.Pro177Leu) specific to Māori and Pacific people that associates with higher HDL-C and lower LDL-C levels. Each copy of the minor allele associated with higher HDL-C by 0.236 mmol/L and lower LDL-C by 0.133 mmol/L. The rs1597000001 effect on HDL-C is comparable with CETP Mendelian loss-of-function mutations that result in CETP deficiency, consistent with our data, which shows that rs1597000001 lowers CETP activity by 27.9%. This study highlights the potential of population-specific genetic analyses for improving equity in genomics and health outcomes for population groups underrepresented in genomic studies

Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction