Estimating the degree of saturation in mutant screens

Large-scale screens for loss-of-function mutants have played a significant role in recent advances in developmental biology and other fields. In such mutant screens, it is desirable to estimate the degree of saturation of the screen (i.e., what fraction of the possible target genes has been identified). We applied Bayesian and maximum-likelihood methods for estimating the number of loci remaining undetected in large-scale screens and produced credibility intervals to assess the uncertainty of these estimates. Since different loci may mutate to alleles with detectable phenotypes at different rates, we also incorporated variation in the degree of mutability among genes, using either gamma-distributed mutation rates or multiple discrete mutation rate classes. We examined eight published data sets from large-scale mutant screens and found that credibility intervals are much broader than implied by previous assumptions about the degree of saturation of screens. The likelihood methods presented here are a significantly better fit to data from published experiments than estimates based on the Poisson distribution, which implicitly assumes a single mutation rate for all loci. The results are reasonably robust to different models of variation in the mutability of genes. We tested our methods against mutant allele data from a region of the Drosophila melanogaster genome for which there is an independent genomics-based estimate of the number of undetected loci and found that the number of such loci falls within the predicted credibility interval for our models. The methods we have developed may also be useful for estimating the degree of saturation in other types of genetic screens in addition to classical screens for simple loss-of-function mutants, including genetic modifier screens and screens for protein-protein interactions using the yeast two-hybrid method

Enhancing the charging power of quantum batteries

Can collective quantum effects make a difference in a meaningful thermodynamic operation? Focusing on energy storage and batteries, we demonstrate that quantum mechanics can lead to an enhancement in the amount of work deposited per unit time, i.e., the charging power, when $N$ batteries are charged collectively. We first derive analytic upper bounds for the collective \emph{quantum advantage} in charging power for two choices of constraints on the charging Hamiltonian. We then highlight the importance of entanglement by proving that the quantum advantage vanishes when the collective state of the batteries is restricted to be in the separable ball. Finally, we provide an upper bound to the achievable quantum advantage when the interaction order is restricted, i.e., at most $k$ batteries are interacting. Our result is a fundamental limit on the advantage offered by quantum technologies over their classical counterparts as far as energy deposition is concerned.Comment: In this new updated version Theorem 1 has been changed with Proposition 1. The paper has been published on PRL, and DOI included accordingl

System and method for attitude determination based on optical imaging

A method and apparatus is provide for receiving a first set of optical data from a first field of view and receiving a second set of optical data from a second field of view. A portion of the first set of optical data is communicated and a portion of the second set of optical data is reflected, both toward an optical combiner. The optical combiner then focuses the portions onto the image plane such that information at the image plane that is associated with the first and second fields of view is received by an optical detector and used to determine an attitude characteristic

Arabidopsis \u3ci\u3eGLABROUS1\u3c/i\u3e Gene Requires Downstream Sequences for Function

The Arabidopsis GLABROUSl (GL1) gene is a myb gene homolog required for the initiation of trichome development. In situ hybridiration revealed that the highest levels of GL1 transcripts were present in developing trichomes. In contrast, previous work had shown that putative promoter sequences from the 5‘ noncoding region of the GL1 gene directed the expression of a β-glucuronidase (GUS) reporter gene only in stipules. Deletion analysis of the 3’ noncoding region of GL1 has identified an enhancer that is essential for GL1 function. Sequences fmm the region containing the enhancer, in conjunction with GL1 upstream sequences, direct the expression of a GUS reporter gene in leaf primordia and developing trichomes in addition to stipules, indicating that the downstream enhancer is required for the normal expression pattern of GL1

Physiological Responses to Counterweighted Single-Leg Cycling in Older Males

International Journal of Exercise Science 13(2): 1487-1500, 2020. Single-leg cycling (SLC) allows for a greater muscle specific exercise capacity and therefore provides a greater stimulus for metabolic and vascular adaptations compared to double-leg cycling (DLC). The purpose of this investigation was to compare the cardiovascular, peripheral, and metabolic responses of counterweighted (10kg) SLC to DLC in a healthy older male population. Eleven males (56-86 years) performed two cycling modalities consisting of DLC and SLC. For each modality, participants performed 4-minute cycling trials (60rpm) at three work rates (25, 50, 75W). Repeated measures ANOVAs and paired samples T-test (α=0.05) were used to assess differences in physiological and perceptual responses. Heart rate (100±21 vs. 103±20bpm), oxygen uptake (12.1±3.6 vs. 11.7±2.8mL*kg-1*min-1) and mean arterial pressure (104±13 vs. 108±12mmHg) were not different between DLC and SLC, respectively. Femoral blood flow was greater during SLC at 50W (741.4±290.3 vs. 509.0±230.8mL/min) and 75W (993.8±236.2 vs. 680.6±278.0mL/min) (p≤0.01). Furthermore, carbohydrate oxidation during SLC was 30-40% greater than DLC across work rates (p≤0.011). Whole body rating of perceived exertion (RPE) at 25 and 50W were not different (p=0.065), however, whole body RPE at 75W and leg RPE were higher for SLC at all intensities (p≤0.018). Liking scores were not different between cycling modalities (p=0.060). At low and moderate intensities, SLC provides a greater peripheral stress with no difference in cardiovascular responses compared to DLC in a healthy older adult male population. Thus, SLC may be a feasible exercise modality to maximize peripheral adaptations for healthy and diseased (i.e. peripheral vascular disease/cardiovascular disease) older population

Cross-National Coverage of Cross-Border Transit Migration: A Community Structure Approach

A community structure analysis (exploring variations in community/national demographics linked to differences in reporting on critical issues) compared cross-national coverage of cross-border transit migration through Mediterranean and Central European countries in leading newspapers, one per country, in 16 countries, analyzing all articles of 250 words or more from 10/01/14 to 11/01/15. The resulting 238 total articles were coded for “prominence” and “direction” (“government responsibility,” “society responsibility” — including foreign aid, or “balanced/neutral” coverage) and combined into composite “media vector” scores for each newspaper (range 0.1132 to -0.2785, a total range of .3917). A majority of 12 of 16 (75%) of media vectors reflected societal responsibility of transit migration, with the minority (4 of 16, or 25%) registering government responsibility. Pearson correlations revealed the strength of three significant national demographic indicators, two of the three associated with coverage emphasizing government responsibility for transit migration. Crop production index (r= .423, p= .051), a measure of agricultural/economic vulnerability, was linked to coverage emphasizing government responsibility for transit migration. In contrast, another vulnerability measure, global peace index, was associated with more media emphasis on societal responsibility for transit migration (r= -.466, r =.050). One measure of privilege, females in the workforce (r= .426, p= .05), was also linked to government responsibility for transit migration. A regression analysis revealed the strength of a nation’s crop production index (21.2% of the variance), females in the workforce (22.2%) and corruption score (9.8%) all connected to coverage emphasizing government responsibility, collectively accounting for 53.1% of the variance. Contrary to conventional assumptions that media typically act as “guard dogs” reinforcing the interests of political and economic elites, systematic research on demographically linked variations in transit migration coverage reveal that media can “mirror” the interests of a society’s most “vulnerable” inhabitants

Process Compensated Resonance Testing Modeling for Damage Evolution and Uncertainty Quantification

Process Compensated Resonance Testing (PCRT) is a nondestructive evaluation method that measures and analyzes the resonance frequencies of a component for material state characterization, defect detection and process monitoring. PCRT inspections of gas turbine engine components have demonstrated the sensitivity of resonance frequencies to manufacturing defects and in-service thermal and mechanical damage. Prior work on PCRT modeling has developed forward modeling and model inversion techniques that simulate the effects of geometry variation, material property variation, and damage on Mar-M-247 nickel-based superalloy samples. Finite element method (FEM) forward model simulations predicted the effects of variation in geometry, material properties and damage on resonance frequencies. Model inversion used measured resonance frequencies to characterize the material state of components. Parallel work developed a process for uncertainty quantification (UQ) in PCRT models and measurements. The UQ process evaluated the propagation of uncertainty from various sources, identified the most significant uncertainty sources, and enabled uncertainty mitigation to improve model and measurement accuracy. Current efforts have expanded on those developments in several areas. One-factor-at-a-time (OFAT) forward model simulations were conducted on cylindrical dog bone coupons made from Mar-M-247. The simulations predicted the resonance frequency response to variation in geometry, elastic properties, crystallographic orientation, creep strain and cracking. The OFAT studies were followed by forward model Monte Carlo simulations that predicted the effects of multiple, concurrent sources of variation and damage on resonance frequencies, allowing characterization of virtual populations and quantification of uncertainty propagation. The Monte Carlo simulation design points were used to demonstrate the generation of a virtual database of components for training PCRT inspection applications, or “sorting modules.” Virtual database training sets can potentially overcome the limitations imposed by the availability of components and material states for training sets based on physical examples. Forward modeling tools and techniques were applied to titanium to simulate the effects of material variation, damage, and crystallographic texture. Forward modeling was also applied to more complex geometries, including a notional turbine blade, to demonstrate the application of modeling tools to shapes representative of gas turbine engine components. Model inversion tools and techniques have also advanced under the current effort. Prior inversion methods relied on iterative fitting to polynomial expressions for simple geometries and bulk material properties. Current efforts have demonstrated FEM-based model inversion which allows characterization of complex shapes and material states. FEM-based design spaces were generated, model inversion was carried out for surrogate modeled resonance spectra, and inversion performance was evaluated. Analysis of PCRT modeling results led to the development of automated resonance mode matching tools based on the calculation of modal assurance criteria (MAC) values, mode shape displacement metrics and Hungarian Algorithm sorting methods