Rapid compensatory evolution promotes the survival of conjugative plasmids

Conjugative plasmids play a vital role in bacterial adaptation through horizontal gene transfer. Explaining how plasmids persist in host populations however is difficult, given the high costs often associated with plasmid carriage. Compensatory evolution to ameliorate this cost can rescue plasmids from extinction. In a recently published study we showed that compensatory evolution repeatedly targeted the same bacterial regulatory system, GacA/GacS, in populations of plasmid-carrying bacteria evolving across a range of selective environments. Mutations in these genes arose rapidly and completely eliminated the cost of plasmid carriage. Here we extend our analysis using an individual based model to explore the dynamics of compensatory evolution in this system. We show that mutations which ameliorate the cost of plasmid carriage can prevent both the loss of plasmids from the population and the fixation of accessory traits on the bacterial chromosome. We discuss how dependent the outcome of compensatory evolution is on the strength and availability of such mutations and the rate at which beneficial accessory traits integrate on the host chromosome.

Learning Unions of Rectangles with Queries

We investigate the efficient learnability of unions of k rectangles in the discrete plane (1,...,n)[2] with equivalence and membership queries. We exhibit a learning algorithm that learns any union of k rectangles with O(k^3log n) queries, while the time complexity of this algorithm is bounded by O(k^5log n). We design our learning algorithm by finding "corners" and "edges" for rectangles contained in the target concept and then constructing the target concept from those "corners" and "edges". Our result provides a first approach to on-line learning of nontrivial subclasses of unions of intersections of halfspaces with equivalence and membership queries.

On the Performance of Polynomial-time CLIQUE Approximation Algorithms on Very Large Graphs

The performance of a randomized version of the subgraph-exclusion algorithm (called Ramsey) for CLIQUE by Boppana and Halldorsson is studied on very large graphs. We compare the performance of this algorithm with the performance of two common heuristic algorithms, the greedy heuristic and a version of simulated annealing. These algorithms are tested on graphs with up to 10,000 vertices on a workstation and graphs as large as 70,000 vertices on a Connection Machine. Our implementations establish the ability to run clique approximation algorithms on very large graphs. We test our implementations on a variety of different graphs. Our conclusions indicate that on randomly generated graphs minor changes to the distribution can cause dramatic changes in the performance of the heuristic algorithms. The Ramsey algorithm, while not as good as the others for the most common distributions, seems more robust and provides a more even overall performance. In general, and especially on deterministically generated graphs, a combination of simulated annealing with either the Ramsey algorithm or the greedy heuristic seems to perform best. This combined algorithm works particularly well on large Keller and Hamming graphs and has a competitive overall performance on the DIMACS benchmark graphs.

A Short History of Computational Complexity

National Science Foundation (CCR-998310); Army Research Office (DAAD19-02-1-0058)

Universal Quantum Circuits

We define and construct efficient depth universal and almost size universal quantum circuits. Such circuits can be viewed as general purpose simulators for central classes of quantum circuits and can be used to capture the computational power of the circuit class being simulated. For depth we construct universal circuits whose depth is the same order as the circuits being simulated. For size, there is a log factor blow-up in the universal circuits constructed here. We prove that this construction is nearly optimal. Our results apply to a number of well-studied quantum circuit classes.

On Finding Sensitivity of Quantum and Classical Gates

We consider a fault model of Boolean gates, both classical and quantum, where some of the inputs may not be connected to the actual gate hardware. This model is somewhat similar to the stuck-at model which is a very popular model in testing Boolean circuits. We consider the problem of detecting such faults; the detection algorithm can query the faulty gate and its complexity is the number of such queries. This problem is related to determining the sensitivity of Boolean functions. We show how quantum parallelism can be used to detect such faults. Specifically, we show that a quantum algorithm can detect such faults more efficiently than a classical algorithm for a Parity gate and an AND gate. We give explicit constructions of quantum detector algorithms and show lower bounds for classical algorithms. We show that the model for detecting such faults is similar to algebraic decision trees and extend some known results from quantum query complexity to prove some of our results.

A Recurrent Cooperative/Competitive Field for Segmentation of Magnetic Resonance Brain Imagery

The Grey-White Decision Network is introduced as an application of an on-center, off-surround recurrent cooperative/competitive network for segmentation of magnetic resonance imaging (MRI) brain images. The three layer dynamical system relaxes into a solution where each pixel is labeled as either grey matter, white matter, or "other" matter by considering raw input intensity, edge information, and neighbor interactions. This network is presented as an example of applying a recurrent cooperative/competitive field (RCCF) to a problem with multiple conflicting constraints. Simulations of the network and its phase plane analysis are presented.

Peanut Allergen Threshold Study (PATS): validation of eliciting doses using a novel single-dose challenge protocol

Background: The eliciting dose (ED) for a peanut allergic reaction in 5% of the peanut allergic population, the ED05, is 1.5 mg of peanut protein. This ED05 was derived from oral food challenges (OFC) that use graded, incremental doses administered at fixed time intervals. Individual patients’ threshold doses were used to generate population dose-distribution curves using probability distributions from which the ED05 was then determined. It is important to clinically validate that this dose is predictive of the allergenic response in a further unselected group of peanut-allergic individuals. Methods/Aims: This is a multi-centre study involving three national level referral and teaching centres. (Cork University Hospital, Ireland, Royal Children’s Hospital Melbourne, Australia and Massachusetts General Hospital, Boston, U.S.A.) The study is now in process and will continue to run until all centres have recruited 125 participates in each respective centre. A total of 375 participants, aged 1–18 years will be recruited during routine Allergy appointments in the centres. The aim is to assess the precision of the predicted ED05 using a single dose (6 mg peanut = 1.5 mg of peanut protein) in the form of a cookie. Validated Food Allergy related Quality of Life Questionnaires-(FAQLQ) will be self-administered prior to OFC and 1 month after challenge to assess the impact of a single dose OFC on FAQL. Serological and cell based in vitro studies will be performed. Conclusion: The validation of the ED05 threshold for allergic reactions in peanut allergic subjects has potential value for public health measures. The single dose OFC, based upon the statistical dose-distribution analysis of past challenge trials, promises an efficient approach to identify the most highly sensitive patients within any given food-allergic population.

Composition portfolio and commentaries

In an attempt to provide an analytical entry point into my compositional practice, I have identified eight themes which are significantly recurrent: reduction – the selection of a small number of elements; imperfection – a damaged or warped characteristic of sound; hierarchy – a concern with the roles of instruments with regard to their relative prominence; motion – apparently static sound masses consist of fine internal movement; listener perception – expectations for change influence the experience of affect; translation – the transitioning of electronic sounds to the acoustic realm, and vice versa; immersion – the creation of an accommodating soundscape; blurring – smearing and overlapping sounds or genres. Each of these eight factors is associated with relevant precedents in the history and theory of music that have been influential on my work. These include the minimalist compositions of Steve Reich and Arvo Pärt; the lo-fi aesthetic of Boards of Canada and My Bloody Valentine; concerns with political hierarchy in the work of Louis Andriessen; the variations of dynamics and microtonal shifts of Giacinto Scelsi; Leonard B. Meyer's account of expectation in music; cross-fertilisation of the acoustic and electronic in pieces by Gérard Grisey and Gyorgy Ligeti; the immersive technique of Brian Eno's ambient music; and the overlapping sounds of Aphex Twin. These eight factors are variously applicable to the eleven submitted pieces, which are individually analysed with reference to the most significant of the categories. Together they form a musical language that sustains the interaction of a variety of techniques, concepts and genres.

Figer: A Quadraphonic Electroacoustic Composition

Figer (to congeal, to solidify) is a quadraphonic electroacoustic composition. It was completed in the fall of 2003. Several software programs were used in creating and assembling the piece (C-Sound, Grain Mill, AL/Erwin (grain generator), Sound Forge and Acid Music). The sounds used in the piece are of two general types: synthesized and sampled, both of which were subjected to various processing techniques. The most important of these techniques, and one that formally defines large portions of the piece, is granular synthesis. Form The notion of time perception is of great importance in this piece. Figer addresses this question in several ways. In one sense, the form of Figer is simple. There are three layers of activity (see diagram). Layer 1 is continuous and non-sectional and supplies a backdrop (not necessarily a background) for the other two. The second and third layers overlap and interrupt one another. Each consists of two blocks of sound. The layers, and blocks within, relate to each other in various ways. Layer 1 is formally continuous. Layer 2 consists of well-defined columns of sound that evolve from soft and mild to loud and abrasive. The layer is, in reality, a whole that is simply cut into two parts (block 1 and block 2). In contrast, the blocks of layer 3 do not constitute a whole. Each is a complete unit and has its own self-contained evolutionary path. Those paths, however, do cross the paths of other units (layers, blocks), influencing them and absorbing some of their essence. At the heart of Figer lies a constant process of presenting materials or ideas and immediately, or, at times, simultaneously, commenting, reflecting on, or reinterpreting that material. All of the layers of this piece deal, both at local and global levels, with the problem of time and its perception relative to the materials, sonic or otherwise, that occupy it and the manner in which they unfold and relate to each other.

A navigation and object location device for the blind

Gemstone Team Vision

Affective and Experiential Influences on English Skills of Heritage Spanish Speakers

Gemstone Team GABS (Grammar Acquisition in Bilingual Students)

THE LESSER-KNOWN PIANO CHAMBER MUSIC OF CAMILLE SAINT-SAENS: A RECORDING PROJECT

Throughout his long and industrious lifetime, Camille Saint-Saens (1835-1921) devoted himself unconditionally to music both as a composer and a performer. Saint-Saens was a self-described traditionalist and musical purist, yet his works are distinctly expressive and imaginative, and they reflect the composer's own unique musical language which incorporates recognizably modem traits such as chromaticism and frequent modulation. As a performer, Saint-Saens preferred to premiere his own works and often included his chamber music in his concert programs. Regarded primarily as a symphonic composer in the present day, however, his extensive and varied collection of chamber music works is sadly neglected. Six varied small-ensemble works with piano from his chamber music repertoire have been selected for study and recording for this project: Piano Trio No. 1 in F Major, Op. 18 (1864); Sonata for Cello and Piano No. 1 inC Minor, Op. 32 (1872); two pieces for two pianos, Le Rouet d'Omphale (The Spinning Wheel ofOmphale), Op. 31 (1871) and Phaeton, Op. 39 (1874); piano duet Konig Harald Haifagar (King Harald Haarfager), Op. 59 (1880); and a wind quartet, Caprice sur des airs Danois et Russes (Caprice on Danish and Russian Airs) for Flute, Oboe, Clarinet and Piano, Op. 79 (1887). Analyses of the forms and harmonic structures of these compositions will be included in this dissertation paper as well as studies from the viewpoint of Saint-Saens' compositional style, ensemble characteristics, and writing for the piano. The recordings for this project were made in four sessions in LeFrak Concert Hall at Queens College, the City University of New York. On September 24, 2003, Op. 31, Op. 39 and Op. 59 were recorded with Professor Morey Ritt, piano. On March 2, 2004, Op. 18 was recorded with Elena Rojas, violin, and Clare Liu, cello, and on March 15, 2004, Op. 32 was recorded, also with Ms. Liu. The Caprice, Op. 79 was recorded on June 27, 2008 with Laura Conwesser, flute; Randall Wolfgang, oboe; and Steve Hartman, clarinet. The recordings may be found on file in the library at the University of Maryland, College Park.

Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study.

Duchenne muscular dystrophy is caused by dystrophin deficiency and muscle deterioration and preferentially affects boys. Antisense-oligonucleotide-induced exon skipping allows synthesis of partially functional dystrophin. We investigated the efficacy and safety of drisapersen, a 2'-O-methyl-phosphorothioate antisense oligonucleotide, given for 48 weeks.

A scalable strategy for the parallelization of multiphysics unstructured mesh-iterative codes on distributed-memory systems

Realizing scalable performance on high performance computing systems is not straightforward for single-phenomenon codes (such as computational fluid dynamics [CFD]). This task is magnified considerably when the target software involves the interactions of a range of phenomena that have distinctive solution procedures involving different discretization methods. The problems of addressing the key issues of retaining data integrity and the ordering of the calculation procedures are significant. A strategy for parallelizing this multiphysics family of codes is described for software exploiting finite-volume discretization methods on unstructured meshes using iterative solution procedures. A mesh partitioning-based SPMD approach is used. However, since different variables use distinct discretization schemes, this means that distinct partitions are required; techniques for addressing this issue are described using the mesh-partitioning tool, JOSTLE. In this contribution, the strategy is tested for a variety of test cases under a wide range of conditions (e.g., problem size, number of processors, asynchronous / synchronous communications, etc.) using a variety of strategies for mapping the mesh partition onto the processor topology.