Scanwave: A New Approach to Enhancing Spectral Data on a Tandem Quadrupole Mass Spectrometer

A new type of mass analyzer is described, which allows low-resolution axial ion ejection to be obtained from a traveling wave based, stacked ring collision cell. Linking this ejection temporally with the scanning of the second quadrupole of a tandem quadrupole mass spectrometer provides an improvement in sampling duty cycle, which results in significant signal intensity improvements for scanning acquisitions such as product ion spectra. A near 100% storage efficiency is enabled by a split cell design, which allows ion fragmentation and accumulation to be performed in one section of the collision cell whilst previously accumulated ions are simultaneously ejected from the rear of the cell. These characteristics combine to give an m/z-dependent signal gain of 7–20× over a conventional scanning quadrupole for a 1000 Th scan. The ability to swap very rapidly from a non-enhanced mode of operation to an enhanced mode whilst retaining the existing sensitivity, speed, and functionality of a conventional tandem quadrupole mass spectrometer is also described

ShapeCoder: Discovering Abstractions for Visual Programs from Unstructured Primitives

We introduce ShapeCoder, the first system capable of taking a dataset of shapes, represented with unstructured primitives, and jointly discovering (i) useful abstraction functions and (ii) programs that use these abstractions to explain the input shapes. The discovered abstractions capture common patterns (both structural and parametric) across a dataset, so that programs rewritten with these abstractions are more compact, and suppress spurious degrees of freedom. ShapeCoder improves upon previous abstraction discovery methods, finding better abstractions, for more complex inputs, under less stringent input assumptions. This is principally made possible by two methodological advancements: (a) a shape-to-program recognition network that learns to solve sub-problems and (b) the use of e-graphs, augmented with a conditional rewrite scheme, to determine when abstractions with complex parametric expressions can be applied, in a tractable manner. We evaluate ShapeCoder on multiple datasets of 3D shapes, where primitive decompositions are either parsed from manual annotations or produced by an unsupervised cuboid abstraction method. In all domains, ShapeCoder discovers a library of abstractions that captures high-level relationships, removes extraneous degrees of freedom, and achieves better dataset compression compared with alternative approaches. Finally, we investigate how programs rewritten to use discovered abstractions prove useful for downstream tasks

Hepatitis C quasispecies adaptation in the setting of a variable fidelity polymerase

Hepatitis C (HCV) is a virus characterized by an RNA-dependent RNA polymerase that lacks a proofreading mechanism and, as a result, generates a quasispecies. There is emerging evidence that this RNA-dependent RNA polymerase may in fact have variable fidelity. Here, we review the relevant concepts, including fitness landscapes, clonal interference, robustness, selection, adaptation, mutation rates, and their optimization, and provide a unique interpretation of a number of relevant theoretical models, evolving the theory of replicative homeostasis in light of their findings. We suggest that a variable fidelity polymerase can find its own optimal mutation rate, which is governed by the sequence itself and certain population dynamics. We propose that this concept can explain features of viral kinetics and clearance, both spontaneously and following treatment of chronic HCV. We point to evidence that supports this theory and explain how it refines replicative homeostasis and conclude by discussing particular areas of potential research that might augment our understanding of viral host interactions at an individual cellular level

Transcriptomic Analysis of Shiga-Toxigenic Bacteriophage Carriage Reveals a Profound Regulatory Effect on Acid Resistance in Escherichia coli

Shiga-toxigenic bacteriophages are converting lambdoid phages that impart the ability to produce Shiga toxin to their hosts. Little is known about the function of most of the genes carried by these phages or the impact that lysogeny has on the Escherichia coli host. Here we use next-generation sequencing to compare the transcriptomes of E. coli strains infected with an Stx phage, before and after triggering of the bacterial SOS response that initiates the lytic cycle of the phage. We were able to discriminate between bacteriophage genes expressed in the lysogenic and lytic cycles, and we describe transcriptional changes that occur in the bacterial host as a consequence of Stx phage carriage. Having identified upregulation of the glutamic acid decarboxylase (GAD) operon, confirmed by reverse transcription-quantitative PCR (RT-qPCR), we used phenotypic assays to establish the ability of the Stx prophage to confer a greater acid resistance phenotype on the E. coli host. Known phage regulators were overexpressed in E. coli, and the acid resistance of the recombinant strains was tested. The phage-encoded transcriptional regulator CII was identified as the controller of the acid response in the lysogen. Infection of an E. coli O157 strain, from which integrated Stx prophages were previously removed, showed increased acid resistance following infection with a nontoxigenic phage, ϕ24B. In addition to demonstrating this link between Stx phage carriage and E. coli acid resistance, with its implications for survival postingestion, the data set provides a number of other potential insights into the impact of lambdoid phage carriage on the biology of E. coli

Uncertainty Analysis via Failure Domain Characterization: Polynomial Requirement Functions

This paper proposes an uncertainty analysis framework based on the characterization of the uncertain parameter space. This characterization enables the identification of worst-case uncertainty combinations and the approximation of the failure and safe domains with a high level of accuracy. Because these approximations are comprised of subsets of readily computable probability, they enable the calculation of arbitrarily tight upper and lower bounds to the failure probability. A Bernstein expansion approach is used to size hyper-rectangular subsets while a sum of squares programming approach is used to size quasi-ellipsoidal subsets. These methods are applicable to requirement functions whose functional dependency on the uncertainty is a known polynomial. Some of the most prominent features of the methodology are the substantial desensitization of the calculations from the uncertainty model assumed (i.e., the probability distribution describing the uncertainty) as well as the accommodation for changes in such a model with a practically insignificant amount of computational effort

Swedish Farm SafetyPracticeand E.U. Influences

End of project reportAn All Island Farm Safety Conference took place on Wednesday, 18 June 2008 at the Hillgrove Hotel, Old Armagh Road, Monaghan. The presentations from this conference will be of interest to farmers, agricultural contractors, and anyone with an interest in safety and health in agriculture. The presentations from this conference will be of interest to farmers, agricultural contractors, and anyone with an interest in safety and health in agriculture. Each of the talk titles below is a link to the Microsoft PowerPoint presentation in PDF forma

Experimental observations and numerical modeling of lipid-shell microbubbles with calcium-adhering moieties for minimally-invasive treatment of urinary stones

A novel treatment modality incorporating calcium-adhering microbubbles has recently entered human clinical trials as a new minimally-invasive approach to treat urinary stones. In this treatment method, lipid-shell gas-core microbubbles can be introduced into the urinary tract through a catheter. Lipid moities with calcium-adherance properties incorporated into the lipid shell facilitate binding to stones. The microbubbles can be excited by an extracorporeal source of quasi-collimated ultrasound. Alternatively, the microbubbles can be excited by an intraluminal source, such as a fiber-optic laser. With either excitation technique, calcium-adhering microbubbles can significantly increase rates of erosion, pitting, and fragmentation of stones. We report here on new experiments using high-speed photography to characterize microbubble expansion and collapse. The bubble geometry observed in the experiments was used as one of the initial shapes for the numerical modeling. The modeling showed that the bubble dynamics strongly depends on bubble shape and stand-off distance. For the experimentally observed shape of microbubbles, the numerical modeling showed that the collapse of the microbubbles was associated with pressure increases of some two-to-three orders of magnitude compared to the excitation source pressures. This in-vitro study provides key insights into the use of microbubbles with calcium-adhering moieties in treatment of urinary stones

WormBase: a multi-species resource for nematode biology and genomics

WormBase (http://www.wormbase.org/) is the central data repository for information about Caenorhabditis elegans and related nematodes. As a model organism database, WormBase extends beyond the genomic sequence, integrating experimental results with extensively annotated views of the genome. The WormBase Consortium continues to expand the biological scope and utility of WormBase with the inclusion of large-scale genomic analyses, through active data and literature curation, through new analysis and visualization tools, and through refinement of the user interface. Over the past year, the nearly complete genomic sequence and comparative analyses of the closely related species Caenorhabditis briggsae have been integrated into WormBase, including gene predictions, ortholog assignments and a new synteny viewer to display the relationships between the two species. Extensive site-wide refinement of the user interface now provides quick access to the most frequently accessed resources and a consistent browsing experience across the site. Unified single-page views now provide complete summaries of commonly accessed entries like genes. These advances continue to increase the utility of WormBase for C.elegans researchers, as well as for those researchers exploring problems in functional and comparative genomics in the context of a powerful genetic system