Evolution Equation of Phenotype Distribution: General Formulation and Application to Error Catastrophe

An equation describing the evolution of phenotypic distribution is derived using methods developed in statistical physics. The equation is solved by using the singular perturbation method, and assuming that the number of bases in the genetic sequence is large. Applying the equation to the mutation-selection model by Eigen provides the critical mutation rate for the error catastrophe. Phenotypic fluctuation of clones (individuals sharing the same gene) is introduced into this evolution equation. With this formalism, it is found that the critical mutation rate is sometimes increased by the phenotypic fluctuations, i.e., noise can enhance robustness of a fitted state to mutation. Our formalism is systematic and general, while approximations to derive more tractable evolution equations are also discussed.Comment: 22 pages, 2 figure

A General Tool for Engineering the NAD/NADP Cofactor Preference of Oxidoreductases

The ability to control enzymatic nicotinamide cofactor utilization is critical for engineering efficient metabolic pathways. However, the complex interactions that determine cofactor-binding preference render this engineering particularly challenging. Physics-based models have been insufficiently accurate and blind directed evolution methods too inefficient to be widely adopted. Building on a comprehensive survey of previous studies and our own prior engineering successes, we present a structure-guided, semirational strategy for reversing enzymatic nicotinamide cofactor specificity. This heuristic-based approach leverages the diversity and sensitivity of catalytically productive cofactor binding geometries to limit the problem to an experimentally tractable scale. We demonstrate the efficacy of this strategy by inverting the cofactor specificity of four structurally diverse NADP-dependent enzymes: glyoxylate reductase, cinnamyl alcohol dehydrogenase, xylose reductase, and iron-containing alcohol dehydrogenase. The analytical components of this approach have been fully automated and are available in the form of an easy-to-use web tool: Cofactor Specificity Reversal–Structural Analysis and Library Design (CSR-SALAD)

The influence of distributed leadership on teachers' organizational commitment: a multilevel approach

In the present study the effects of a cooperative leadership team, distributed leadership, participative decision-making, and context variables on teachers' organizational commitment are investigated. Multilevel analyses on data from 1522 teachers indicated that 9% of the variance in teachers' organizational commitment is attributable to differences between schools. The analyses revealed that especially the presence of a cooperative leadership team and the amount of leadership support played a significantly positive key role in predicting teachers' organizational commitment. Also, participative decision-making and distribution of the supportive leadership function had a significant positive impact on teachers' organizational commitment. In contrast, distribution of the supervisory leadership function and teachers' job experience had a significant negative impact

Psychological interventions for adults with bipolar disorder: a systematic review and meta-analysis

Background Psychological interventions may be beneficial for bipolar disorder. Aims Efficacy evaluation of psychological interventions for adults with bipolar disorder. Methods A systematic review of randomised controlled trials.. Outcomes were meta-analysed using RevMan and confidence assessed using the GRADE-method. Results We included 55 trials with 6010 participants. Moderate quality evidence associated individual psychological interventions with reduced relapses at post-treatment and follow-up, and collaborative care with a reduction in hospitalisations. . Low quality evidence associated group interventions with fewer depression relapses at post-treatment and follow-up, and family psycho-education with reduced symptoms of depression and mania at post-treatment. Conclusions There is evidence that psychological interventions are effective for people with bipolar disorder. Limits were the very low quality of much of the evidence and therefore inconclusive. Further research should identify the most (cost)-effective interventions for each phase of this disorder

Caveat emptor: The combined effects of multiplicity and selective reporting

Clinical trials and systematic reviews of clinical trials inform healthcare decisions. There is growing concern, however, about results from clinical trials that cannot be reproduced. Reasons for nonreproducibility include that outcomes are defined in multiple ways, results can be obtained using multiple methods of analysis, and trial findings are reported in multiple sources ("multiplicity"). Multiplicity combined with selective reporting can influence dissemination of trial findings and decision-making. In particular, users of evidence might be misled by exposure to selected sources and overly optimistic representations of intervention effects. In this commentary, drawing from our experience in the Multiple Data Sources in Systematic Reviews (MUDS) study and evidence from previous research, we offer practical recommendations to enhance the reproducibility of clinical trials and systematic reviews

VerdictDB: Universalizing Approximate Query Processing

Despite 25 years of research in academia, approximate query processing (AQP) has had little industrial adoption. One of the major causes of this slow adoption is the reluctance of traditional vendors to make radical changes to their legacy codebases, and the preoccupation of newer vendors (e.g., SQL-on-Hadoop products) with implementing standard features. Additionally, the few AQP engines that are available are each tied to a specific platform and require users to completely abandon their existing databases---an unrealistic expectation given the infancy of the AQP technology. Therefore, we argue that a universal solution is needed: a database-agnostic approximation engine that will widen the reach of this emerging technology across various platforms. Our proposal, called VerdictDB, uses a middleware architecture that requires no changes to the backend database, and thus, can work with all off-the-shelf engines. Operating at the driver-level, VerdictDB intercepts analytical queries issued to the database and rewrites them into another query that, if executed by any standard relational engine, will yield sufficient information for computing an approximate answer. VerdictDB uses the returned result set to compute an approximate answer and error estimates, which are then passed on to the user or application. However, lack of access to the query execution layer introduces significant challenges in terms of generality, correctness, and efficiency. This paper shows how VerdictDB overcomes these challenges and delivers up to 171$\times$ speedup (18.45$\times$ on average) for a variety of existing engines, such as Impala, Spark SQL, and Amazon Redshift, while incurring less than 2.6% relative error. VerdictDB is open-sourced under Apache License.Comment: Extended technical report of the paper that appeared in Proceedings of the 2018 International Conference on Management of Data, pp. 1461-1476. ACM, 201

Complete genome sequence of the encephalomyelitic Burkholderia pseudomallei strain MSHR305

We describe the complete genome sequence of Burkholderia pseudomallei MSHR305, a clinical isolate taken from a fatal encephalomyelitis case, a rare form of melioidosis. This sequence will be used for comparisons to identify the genes that are involved in neurological cases

Complete genome sequence of the encephalomyelitic Burkholderia pseudomallei strain MSHR305

We describe the complete genome sequence of Burkholderia pseudomallei MSHR305, a clinical isolate taken from a fatal encephalomyelitis case, a rare form of melioidosis. This sequence will be used for comparisons to identify the genes that are involved in neurological cases