Nanopore sequencers can be used to selectively sequence certain DNA molecules in a pool by reversing the voltage across individual nanopores to reject specific sequences, enabling enrichment and depletion to address biological questions. Previously, we achieved this using dynamic time warping to map the signal to a reference genome, but the method required substantial computational resources and did not scale to gigabase-sized references. Here we overcome this limitation by using GPU base calling. We show enrichment of specific chromosomes from the human genome and of low-abundance organisms in mixed populations without a priori knowledge of sample composition. Finally, we enrich targeted panels comprising 25,600 exons from 10,000 human genes and 717 genes implicated in cancer, identifying PML-RARA fusions in the NB4 cell line in <15 hours sequencing. These methods can be used to efficiently screen any target panel of genes without specialised sample preparation using any computer and suitable GPU. Our toolkit, readfish, is available at https://www.github.com/looselab/readfish .

Recent reports suggest that historically typical sexual identity labels-"gay," "lesbian" and "bisexual"-have lost meaning and relevance for contemporary adolescents. Yet there is little empirical evidence that contemporary teenagers are "post-gay." In this brief study we investigate youths' sexual identity labels. The Preventing School Harassment survey included 2,560 California secondary school students administered over 3 years: 2003-2005. We examined adolescents' responses to a closed-ended survey question that asked for self-reports of sexual identity, including an option to write-in a response; we content analyzed the write-in responses. Results suggest that historically typical sexual identity labels are endorsed by the majority (71%) of non-heterosexual youth. Some non-heterosexual youth report that they are "questioning" (13%) their sexual identities or that they are "queer" (5%); a small proportion (9%) provided alternative labels that describe ambivalence or resistance to sexual identity labels, or fluidity in sexual identities. Our results show that lesbian, gay, and bisexual identities remain relevant for contemporary adolescents.

Abstract-This paper proposes a new framework for linear active circuits that can encompass both circuit analysis and synthesis. The framework is based on a definition of port equivalence for admittance matrices. This is extended to cover circuits with ideal active elements through the introduction of a special type of limit-variable called the infinity-variable ( -variable). A theorem is developed for matrices containing -variables that may be utilized in both circuit analysis and synthesis. The notation developed in this framework can describe nonideal elements as well as ideal elements and therefore the framework encompasses systematic circuit modeling.

Nanopore sequencers enable selective sequencing of single molecules in real time by individually reversing the voltage across specific nanopores. Thus DNA molecules can be rejected and replaced with new molecules enabling targeted sequencing to enrich, deplete or achieve specific coverage in a set of reads to address a biological question. We previously demonstrated this method worked using dynamic time warping mapping signal to reference, but required significant compute and did not scale to gigabase references. Using direct base calling with GPU we can now scale to gigabase references. We enrich for specific chromosomes mapping against the human genome and we develop pipelines enriching low abundance organisms from mixed populations without prior knowledge of sample composition. Finally, we enrich panels including 25,600 exon targets from 10,000 human genes and 717 genes implicated in cancer. Using this approach we identify PML-RARA fusions in the NB4 cell line in under 15 hours sequencing. These methods can be used to efficiently screen any target panel of genes without specialised sample preparation using a single computer and suitably powerful GPU.

Antagonism of αvβ6 is emerging as a potential treatment of idiopathic pulmonary fibrosis based on strong target validation. Starting from an αvβ3 antagonist lead and through simple variation in the nature and position of the aryl substituent, the discovery of compounds with improved αvβ6 activity is described. The compounds also have physicochemical properties commensurate with oral bioavailability and are high quality starting points for a drug discovery program. Compounds 33S and 43E1 are pan αv antagonists having ca. 100 nM potency against αvβ3, αvβ5, αvβ6, and αvβ8 in cell adhesion assays. Detailed structure activity relationships with these integrins are described which also reveal substituents providing partial selectivity (defined as at least a 0.7 log difference in pIC50 values between the integrins in question) for αvβ3 and αvβ5.

Searches for primordial gravitational waves have resulted in constraints in a large frequency range from a variety of sources. The standard Cosmic Microwave Background (CMB) technique is to parameterise the tensor power spectrum in terms of the tensor-to-scalar ratio, r, and spectral index, n t , and constrain these using measurements of the temperature and polarization power spectra. Another method, applicable to modes well inside the cosmological horizon at recombination, uses the shortwave approximation, under which gravitational waves behave as an effective neutrino species. In this paper we give model-independent CMB constraints on the energy density of gravitational waves, Ω gw h 2 , for the entire range of observable frequencies. On large scales, f 10 −16 Hz, we reconstruct the initial tensor power spectrum in logarithmic frequency bins, finding maximal sensitivity for scales close to the horizon size at recombination. On small scales, f 10 −15 Hz, we use the shortwave approximation, finding Ω gw h 2 < 1.7 × 10 −6 for adiabatic initial conditions and Ω gw h 2 < 2.9 × 10 −7 for homogeneous initial conditions (both 2σ upper limits). For scales close to the horizon size at recombination, we use second-order perturbation theory to calculate the back-reaction from gravitational waves, finding Ω gw h 2 < 8.4 × 10 −7 , in the absence of neutrino anisotropic stress and Ω gw h 2 < 8.6 × 10 −7 when including neutrino anisotropic stress. These constraints are valid for 10 −15 Hz f 3 × 10 −16 Hz.

Highlights HEALing Communities Study is a parallel-group cluster randomized controlled trial. Communities That HEAL intervention’s goal is to reduce opioid overdose deaths. Structured consensus decision-making strategy guided study measure development. More than 80 study measure specifications and a common data model were developed. The study will provide methodology and longitudinal community data for research.

Highlights National Institutes on Health launched Helping to End Addiction Long-term SM Initiative to address opioid crisis National Institute on Drug Abuse and Substance Abuse and Mental Health Services Organization partner to support the HEALing Communities Study HEALing Communities Study goal to reduce opioid overdose deaths by 40% in 3 years across highly impacted communities HEALing Communities Study intended to develop a community-based data-driven approach to implementing multiple evidence-based practices to reduce opioid overdose deaths across multiple systems: healthcare, behavioral health, justice, etc.