Serverification of Molecular Modeling Applications: the Rosetta Online Server that Includes Everyone (ROSIE)

The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction and high-resolution design of proteins, nucleic acids, and a growing number of non-natural polymers. Despite its free availability to academic users and improving documentation, use of Rosetta has largely remained confined to developers and their immediate collaborators due to the code's difficulty of use, the requirement for large computational resources, and the unavailability of servers for most of the Rosetta applications. Here, we present a unified web framework for Rosetta applications called ROSIE (Rosetta Online Server that Includes Everyone). ROSIE provides (a) a common user interface for Rosetta protocols, (b) a stable application programming interface for developers to add additional protocols, (c) a flexible back-end to allow leveraging of computer cluster resources shared by RosettaCommons member institutions, and (d) centralized administration by the RosettaCommons to ensure continuous maintenance. This paper describes the ROSIE server infrastructure, a step-by-step 'serverification' protocol for use by Rosetta developers, and the deployment of the first nine ROSIE applications by six separate developer teams: Docking, RNA de novo, ERRASER, Antibody, Sequence Tolerance, Supercharge, Beta peptide design, NCBB design, and VIP redesign. As illustrated by the number and diversity of these applications, ROSIE offers a general and speedy paradigm for serverification of Rosetta applications that incurs negligible cost to developers and lowers barriers to Rosetta use for the broader biological community. ROSIE is available at http://rosie.rosettacommons.org

Doctor of Philosophy

dissertationThe metabolic scaling theory identifies network architecture as a major predictor of whole plant metabolism via hydraulic conductance of the xylem and the shared stomatal pathway for water loss and carbon gain. To predict hydraulic properties, this theory utilizes the West, Brown, Enquist (WBE) architectural model, which is based on principles of space-filling, biomechanical stability, and optimality of hydraulic transport and it is meant to be generally representative of plants. However, plants are highly diverse in their network architecture. Does this diversity matter or does it represent different ways of accomplishing the same task? This dissertation addresses that question by extending WBE to include architectural variation and by testing model predictions and assumptions. The model predicts the scaling exponent between hydraulic conductance and plant size. This exponent depends on the ""bottleneck"" effect, where greater hydraulic resistance in leaves and twigs steepens the exponent. The bottleneck effect was greater when xylem conduits were much larger or more abundant in the trunk than in the twigs. Observed diversity in xylem properties predicted that different functional groups had substantial overlap in hydraulic transport and its scaling. Branching architecture did not influence the bottleneck effect. However, deviating from WBE increased hydraulic conductance and biomechanical stability while requiring less tissue but reducing light interception. Branching could alter hydraulic scaling if architecture changed ontogenetically, which data suggested. MST assumes direct proportionality between sap flow and growth. This was supported in five of six tested species. However, tree species grew more per water use than shrubs, likely reflecting differential allocation. Differences between species were partially attributable to xylem anatomy and plant size. Among this variation in xylem anatomy, branching architecture, and plant stature, the dimensions of leaves and twigs also vary with thicker twigs curiously tending to support few large leaves instead of many small leaves (Corner's rule). Why do plants coordinate leaf and twig size? Corner's rule was recast as the prediction that larger twig leaf areas are composed of larger leaves. Species supported this prediction and had highly convergent scaling. A model predicted that Corner's rule exists to optimize the return on investment in leaves

Charles M. Breder, Jr.: Bahamas and Florida

Dr. Charles M. Breder, a well known ichthyologist, kept meticulous field diaries throughout his career. This publication is a transcription of field notes recorded during the Bacon Andros Expeditions, and trips to Florida, Ohio and Illinois during the 1930s. Breder's work in Andros included exploration of a "blue hole", inland ecosystems, and collection of marine and terrestrial specimens. Anecdotes include descriptions of camping on the beach, the "filly-mingoes" (flamingos) of Andros Island, the Marine Studios of Jacksonville, FL, a trip to Havana, and the birth of seahorses. This publication is part of a series of transcriptions of Dr. Breder's diaries. (PDF contains 55 pages

Selective vascular isolation of the liver as part of initial damage control for grade 5 liver injuries: Shouldn’t we use it more frequently?

AbstractBackgroundSevere liver trauma (grade 4 and 5) carries mortality greater than 40%. It represents a major surgical challenge in patients with hemodynamic instability who require an immediate exploratory laparotomy. Perihepatic packing and damage control can sometimes work, but for severe liver injuries, adjunct maneuvers might be needed (such as early embolization or hepatic artery ligation). During a patient’s first operation for severe liver trauma, anatomic resection is rarely tolerated.Materials and methodsWe managed a 31 year-old male with a blunt grade 5 right-lobe liver injury in severe hypovolemic shock.ResultsAs part of the initial damage control operation, concurrently with intermittent Pringle maneuver, he underwent intra- and perihepatic packing; selective isolation and ligation of the right portal vein, right hepatic artery, and right hepatic vein; and repair of the retrohepatic inferior vena cava. Then, 36h later, the patient underwent a right hepatectomy.ConclusionFor patients with severe liver injuries, selective vascular isolation and ligation may be considered as part of damage control (in addition to intermittent Pringle maneuver) and might enable anatomic resection at a later stage

Master of Science

thesisThe curious pattern of metabolic rate scaling with mass to the ¾ power has been observed across organisms and has eluded biologists for nearly a century. Metabolic scaling in trees has recently attracted attention as scientists try to model ecosystem dynamics of the hydrologic cycle and the carbon cycle. In this study, we attempt to gain greater understanding about the mechanical and hydraulic principles that govern vascular networks, how water transport through these networks scale with tree size, and how water use relates to growth rates in functionally diverse ring-porous Quercus gambelii and diffuse-porous Acer grandidentatum. We parameterized a numeric network model with species-specific vascular and structural characters to predict water use and growth rate scaling with tree size. The network model currently is confined to optimal water supply. To better understand water use and growth rate patterns during variable season conditions, we measured whole-tree sapflow, conductance and growth rates over one growing season in these two species. The numeric network model did exceptionally well at predicting species-specific scaling of water use and growth rates with tree size. In addition, it accurately predicted relative water use per species. Comparison of these two sympatric species over the growing season suggested that ring-porous Q. gambelii has relatively stable (isohydric) water use patterns and similar growth rates to diffuse-porous A. grandidentatum which has more flexible water use strategy leading to variable growth rates. These two species are able to be co-dominant in this region due to unique water use niches and vasculature. The accuracy of the numeric model predictions tested here suggest that scaling models such as these could be valuable in making ecohydrological predictions enabling the prediction of water use and growth rates with tree size and scaling this up to the stand and ecosystem level. We hope this work infusing hydraulic and mechanical constraints driving water use and growth rates of individuals within and between species contributes to better understanding of processes that effect predictions of ecosystem challenges under global change

goSLP: Globally Optimized Superword Level Parallelism Framework

Modern microprocessors are equipped with single instruction multiple data (SIMD) or vector instruction sets which allow compilers to exploit superword level parallelism (SLP), a type of fine-grained parallelism. Current SLP auto-vectorization techniques use heuristics to discover vectorization opportunities in high-level language code. These heuristics are fragile, local and typically only present one vectorization strategy that is either accepted or rejected by a cost model. We present goSLP, a novel SLP auto-vectorization framework which solves the statement packing problem in a pairwise optimal manner. Using an integer linear programming (ILP) solver, goSLP searches the entire space of statement packing opportunities for a whole function at a time, while limiting total compilation time to a few minutes. Furthermore, goSLP optimally solves the vector permutation selection problem using dynamic programming. We implemented goSLP in the LLVM compiler infrastructure, achieving a geometric mean speedup of 7.58% on SPEC2017fp, 2.42% on SPEC2006fp and 4.07% on NAS benchmarks compared to LLVM's existing SLP auto-vectorizer.Comment: Published at OOPSLA 201

Development and Integration of Geometric and Optimization Algorithms for Packing and Layout Design

The research work presented in this dissertation focuses on the development and application of optimization and geometric algorithms to packing and layout optimization problems. As part of this research work, a compact packing algorithm, a physically-based shape morphing algorithm, and a general purpose constrained multi-objective optimization algorithm are proposed. The compact packing algorithm is designed to pack three-dimensional free-form objects with full rotational freedom inside an arbitrary enclosure such that the packing efficiency is maximized. The proposed compact packing algorithm can handle objects with holes or cavities and its performance does not degrade significantly with the increase in the complexity of the enclosure or the objects. It outputs the location and orientation of all the objects, the packing sequence, and the packed configuration at the end of the packing operation. An improved layout algorithm that works with arbitrary enclosure geometry is also proposed. Different layout algorithms for the SAE and ISO luggage are proposed that exploit the unique characteristics of the problem under consideration. Several heuristics to improve the performance of the packing algorithm are also proposed. The proposed compact packing algorithm is benchmarked on a wide variety of synthetic and hypothetical problems and is shown to outperform other similar approaches. The physically-based shape morphing algorithm proposed in this dissertation is specifically designed for packing and layout applications, and thus it augments the compact packing algorithm. The proposed shape morphing algorithm is based on a modified mass-spring system which is used to model the morphable object. The shape morphing algorithm mimics a quasi-physical process similar to the inflation/deflation of a balloon filled with air. The morphing algorithm starts with an initial manifold geometry and morphs it to obtain a desired volume such that the obtained geometry does not interfere with the objects surrounding it. Several modifications to the original mass-spring system and to the underlying physics that governs it are proposed to significantly speed-up the shape morphing process. Since the geometry of a morphable object continuously changes during the morphing process, most collision detection algorithms that assume the colliding objects to be rigid cannot be used efficiently. And therefore, a general-purpose surface collision detection algorithm is also proposed that works with deformable objects and does not require any preprocessing. Many industrial design problems such as packing and layout optimization are computationally expensive, and a faster optimization algorithm can reduce the number of iterations (function evaluations) required to find the satisfycing solutions. A new multi-objective optimization algorithm namely Archive-based Micro Genetic Algorithm (AMGA2) is presented in this dissertation. Improved formulation for various operators used by the AMGA2 such as diversity preservation techniques, genetic variation operators, and the selection mechanism are also proposed. The AMGA2 also borrows several concepts from mathematical sciences to improve its performance and benefits from the existing literature in evolutionary optimization. A comprehensive benchmarking and comparison of AMGA2 with other state-of-the-art optimization algorithms on a wide variety of mathematical problems gleaned from literature demonstrates the superior performance of AMGA2. Thus, the research work presented in this dissertation makes contributions to the development and application of optimization and geometric algorithms