Scalable production of all-electronic DNA biosensors with high sensitivity and selectivity is a critical enabling step for research and applications associated with detection of DNA hybridization. We ...have developed a scalable and very reproducible (>90% yield) fabrication process for label-free DNA biosensors based upon graphene field effect transistors (GFETs) functionalized with single-stranded probe DNA. The shift of the GFET sensor Dirac point voltage varied systematically with the concentration of target DNA. The biosensors demonstrated a broad analytical range and limit of detection of 1 fM for 60-mer DNA oligonucleotide. In control experiments with mismatched DNA oligomers, the impact of the mismatch position on the DNA hybridization strength was confirmed. This class of highly sensitive DNA biosensors offers the prospect of detection of DNA hybridization and sequencing in a rapid, inexpensive, and accurate way.
The plant genus Oenothera has played an important role in the study of plant evolution of genomes and plant defense and reproduction. Here, we build on the 1kp transcriptomic dataset by creating 44 ...new transcriptomes and analyzing a total of 63 transcriptomes to present a large-scale comparative study across 29 Oenothera species. Our dataset included 30.4 million reads per individual and 2.3 million transcripts on average. We used this transcriptome resource to examine genome-wide evolutionary patterns and functional diversification by searching for orthologous genes and performed gene family evolution analysis. We found wide heterogeneity in gene family evolution across the genus, with section Oenothera exhibiting the most pronounced evolutionary changes. Overall, more significant gene family expansions occurred than contractions. We also analyzed the molecular evolution of phenolic metabolism by retrieving proteins annotated for phenolic enzymatic complexes. We identified 1,568 phenolic genes arranged into 83 multigene families that varied widely across the genus. All taxa experienced rapid phenolic evolution (fast rate of genomic turnover) involving 33 gene families, which exhibited large expansions, gaining about 2-fold more genes than they lost. Upstream enzymes phenylalanine ammonia-lyase (PAL) and 4-coumaroyl: CoA ligase (4CL) accounted for most of the significant expansions and contractions. Our results suggest that adaptive and neutral evolutionary processes have contributed to Oenothera diversification and rapid gene family evolution.
Abstract
Gravitational lensing by clusters of galaxies offers a powerful probe of their structure and mass distribution. Several research groups have developed techniques independently to achieve ...this goal. While these methods have all provided remarkably high-precision mass maps, particularly with exquisite imaging data from the Hubble Space Telescope (HST), the reconstructions themselves have never been directly compared. In this paper, we present for the first time a detailed comparison of methodologies for fidelity, accuracy and precision. For this collaborative exercise, the lens modelling community was provided simulated cluster images that mimic the depth and resolution of the ongoing HST Frontier Fields. The results of the submitted reconstructions with the un-blinded true mass profile of these two clusters are presented here. Parametric, free-form and hybrid techniques have been deployed by the participating groups and we detail the strengths and trade-offs in accuracy and systematics that arise for each methodology. We note in conclusion that several properties of the lensing clusters are recovered equally well by most of the lensing techniques compared in this study. For example, the reconstruction of azimuthally averaged density and mass profiles by both parametric and free-form methods matches the input models at the level of ∼10 per cent. Parametric techniques are generally better at recovering the 2D maps of the convergence and of the magnification. For the best-performing algorithms, the accuracy in the magnification estimate is ∼10 per cent at μtrue = 3 and it degrades to ∼30 per cent at μtrue ∼ 10.
When growing populations of bacteria are confronted with bactericidal antibiotics, the vast majority of cells are killed, but subpopulations of genetically susceptible but phenotypically resistant ...bacteria survive. In accord with the prevailing view, these "persisters" are non- or slowly dividing cells randomly generated from the dominant population. Antibiotics enrich populations for pre-existing persisters but play no role in their generation. The results of recent studies with Escherichia coli suggest that at least one antibiotic, ciprofloxacin, can contribute to the generation of persisters. To more generally elucidate the role of antibiotics in the generation of and selection for persisters and the nature of persistence in general, we use mathematical models and experiments with Staphylococcus aureus (Newman) and the antibiotics ciprofloxacin, gentamicin, vancomycin, and oxacillin. Our results indicate that the level of persistence varies among these drugs and their concentrations, and there is considerable variation in this level among independent cultures and mixtures of independent cultures. A model that assumes that the rate of production of persisters is low and persisters grow slowly in the presence of antibiotics can account for these observations. As predicted by this model, pre-treatment with sub-MIC concentrations of antibiotics substantially increases the level of persistence to drugs other than those with which the population is pre-treated. Collectively, the results of this jointly theoretical and experimental study along with other observations support the hypothesis that persistence is the product of many different kinds of errors in cell replication that result in transient periods of non-replication and/or slowed metabolism by individual cells in growing populations. This Persistence as Stuff Happens (PaSH) hypothesis can account for the ubiquity of this phenomenon. Like mutation, persistence is inevitable rather than an evolved character. What evolved and have been identified are genes and processes that affect the frequency of persisters.
The efficacy of antiretroviral therapy depends on patient adherence to a daily medication regimen, yet many patients fail to adhere at high enough rates to maintain health and reduce the risk of ...transmitting HIV. Given the explosive global growth of cellular-mobile phone use, text-messaging interventions to promote adherence are especially appropriate. This meta-analysis synthesized available text messaging interventions to promote antiretroviral therapy adherence in people living with HIV.
We performed Boolean searches of electronic databases, hand searches of recent year conference abstracts and reverse searches. Included studies (1) targeted antiretroviral therapy adherence in a sample of people living with HIV, (2) used a randomized-controlled trial design to examine a text messaging intervention, and (3) reported at least one adherence measurement or clinical outcome.
Eight studies, including 9 interventions, met inclusion criteria. Text-messaging interventions yielded significantly higher adherence than control conditions (OR = 1.39; 95% CI = 1.18, 1.64). Sensitivity analyses of intervention characteristics suggested that studies had larger effects when interventions (1) were sent less frequently than daily, (2) supported bidirectional communication, (3) included personalized message content, and (4) were matched to participants' antiretroviral therapy dosing schedule. Interventions were also associated with improved viral load and/or CD4+ count (k = 3; OR = 1.56; 95% CI = 1.11, 2.20).
Text-messaging can support antiretroviral therapy adherence. Researchers should consider the adoption of less frequent messaging interventions with content and timing that is individually tailored and designed to evoke a reply from the recipient. Future research is needed in order to determine how best to optimize efficacy.
Accelerating rates of species extinctions and disease emergence underscore the importance of understanding how changes in biodiversity affect disease outcomes. Over the past decade, a growing number ...of studies have reported negative correlations between host biodiversity and disease risk, prompting suggestions that biodiversity conservation could promote human and wildlife health. Yet the generality of the diversity-disease linkage remains conjectural, in part because empirical evidence of a relationship between host competence (the ability to maintain and transmit infections) and the order in which communities assemble has proven elusive. Here we integrate high-resolution field data with multi-scale experiments to show that host diversity inhibits transmission of the virulent pathogen Ribeiroia ondatrae and reduces amphibian disease as a result of consistent linkages among species richness, host composition and community competence. Surveys of 345 wetlands indicated that community composition changed nonrandomly with species richness, such that highly competent hosts dominated in species-poor assemblages whereas more resistant species became progressively more common in diverse assemblages. As a result, amphibian species richness strongly moderated pathogen transmission and disease pathology among 24,215 examined hosts, with a 78.4% decline in realized transmission in richer assemblages. Laboratory and mesocosm manipulations revealed an approximately 50% decrease in pathogen transmission and host pathology across a realistic diversity gradient while controlling for host density, helping to establish mechanisms underlying the diversity-disease relationship and their consequences for host fitness. By revealing a consistent link between species richness and community competence, these findings highlight the influence of biodiversity on infection risk and emphasize the benefit of a community-based approach to understanding infectious diseases.
Interlayer rotational alignment in van der Waals (vdW) structures of two-dimensional (2D) materials couples strongly to electronic properties and, therefore, has significant technological ...implications. Nevertheless, controlling the rotation of an arbitrary 2D material flake remains a challenge in the development of rotation-tunable electronics, for the emerging field of twistronics. In this article, we reveal a general moiré-driven mechanism that governs the interlayer rotation. Controlling the moiré can therefore hold promise for controlling the interlayer rotation. We further demonstrate mismatch strain engineering as a useful tool to design the interlayer rotation via changing the energy landscape of moiré within a finite-sized region. The robustness and programmable nature of our approach arise from moiré symmetry, energetics, and mechanics. Our approach provides another possibility to the on-demand design of rotation-tunable electronics.
Hemiparesis, defined as unilateral muscle weakness, often occurs in people post-stroke or people with cerebral palsy, however it is difficult to understand how this hemiparesis affects movement ...patterns as it often presents alongside a variety of other neuromuscular impairments. Predictive musculoskeletal modeling presents an opportunity to investigate how impairments affect gait performance assuming a particular cost function. Here, we use predictive simulation to quantify the spatiotemporal asymmetries and changes to metabolic cost that emerge when muscle strength is unilaterally reduced and how reducing spatiotemporal symmetry affects metabolic cost. We modified a 2-D musculoskeletal model by uniformly reducing the peak isometric muscle force unilaterally. We then solved optimal control simulations of walking across a range of speeds by minimizing the sum of the cubed muscle excitations. Lastly, we ran additional optimizations to test if reducing spatiotemporal asymmetry would result in an increase in metabolic cost. Our results showed that the magnitude and direction of effort-optimal spatiotemporal asymmetries depends on both the gait speed and level of weakness. Also, the optimal speed was 1.25 m/s for the symmetrical and 20% weakness models but slower (1.00 m/s) for the 40% and 60% weakness models, suggesting that hemiparesis can account for a portion of the slower gait speed seen in people with hemiparesis. Modifying the cost function to minimize spatiotemporal asymmetry resulted in small increases (~4%) in metabolic cost. Overall, our results indicate that spatiotemporal asymmetry may be optimal for people with hemiparesis. Additionally, the effect of speed and the level of weakness on spatiotemporal asymmetry may help explain the well-known heterogenous distribution of spatiotemporal asymmetries observed in the clinic. Future work could extend our results by testing the effects of other neuromuscular impairments on optimal gait strategies, and therefore build a more comprehensive understanding of the gait patterns observed in clinical populations.
From the earliest days of non-Native settlement of Montana, when
Chinese immigrants made up more than 10 percent of the territory's
population, Chinese pioneers played a key role in the region's
...development. But this population, so crucial to Montana's history,
remains underrepresented in historical accounts, and popular
attention to the Chinese in Montana tends to focus on sensational
elements-exoticizing Chinese Montanans and distancing their lived
experiences from our modern understanding. The Middle Kingdom
under the Big Sky seeks to recover the stories of Montana's
Chinese population in their own words and deepen understanding of
Chinese experiences in Montana by using a global lens. Mark T.
Johnson has mined several large collections of primary documents
left by Chinese pioneers, translated into English here for the
first time. These collections, spanning the 1880s through the
1950s, provide insight into the pressures the Chinese community
faced-from family members back in China and from non-Chinese
Montanans-as economic and cultural disturbances complicated
acceptance of Chinese residents in the state. Through their own
voices Johnson reveals the agency of Chinese Montanans in the
history of the American West and China.
Emphasizing the developmental need for positive peer relationships, in this study the authors tested a social-contextual view of the mechanisms and processes by which early adolescents' achievement ...and peer relationships may be promoted simultaneously. Meta-analysis was used to review 148 independent studies comparing the relative effectiveness of cooperative, competitive, and individualistic goal structures in promoting early adolescents' achievement and positive peer relationships. These studies represented over 8 decades of research on over 17,000 early adolescents from 11 countries and 4 multinational samples. As predicted by social interdependence theory, results indicate that higher achievement and more positive peer relationships were associated with cooperative rather than competitive or individualistic goal structures. Also as predicted, results show that cooperative goal structures were associated with a positive relation between achievement and positive peer relationships. Implications for theory and application are discussed.
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