Ward Bosses and Reformers: An Analysis of Boston’s Irish Political Machine, 1884-1914

This essay examines the rise and fall of Boston’s ward-based Irish political machine, from the 1880s to its demise in the 1914 municipal elections. The bosses who ran the machine, though initially successful, undermined themselves by limiting their outreach to the city’s Irish population. Meanwhile, the machine fractured at the turn of the century, with bosses fighting for power, weakening the machine. With waning support and the rise of factional bickering, the machine was weakened by the reformist 1909 city charter, then destroyed by the unforeseen dark horse victory of Irish politician James Michael Curley in the 1914 mayoral election

Effect of Nanofiber Morphology on PVDF Air Filter Performance

Poly(vinylidene fluoride) (PVDF) can be formed into small nanofibers by electrospinning that are useful for a variety of applications. Air filters produced with PVDF are known to capture ionic particles with high efficiency. Existing studies have focused on the effects of electrospinning conditions on nanofiber morphology. In this study fibers were generated with varying morphologies. Air filters were then made from each sample and then characterized by TSI. Air filters were found to have increased resistances relative to their capture efficiencies according to particle diameter. Capture efficiencies did not correlate strongly with particle diameter, and the presence of beads in fiber samples did not have an impact on filter performance. Subsequent studies should focus on the development of statically charged PVDF mats to compare performance with the data generated by this study

Integrating methods for determining length-at-age to improve growth estimates for two large scombrids

Fish growth is commonly estimated from length-at-age data obtained from otoliths. There are several techniques for estimating length-at-age from otoliths including 1) direct observed counts of annual increments; 2) age adjustment based on a categorization of otolith margins; 3) age adjustment based on known periods of spawning and annuli formation; 4) back-calculation to all annuli, and 5) back-calculation to the last annulus only. In this study we compared growth estimates (von Bertalanffy growth functions) obtained from the above five methods for estimating length-at-age from otoliths for two large scombrids: narrow-barred Spanish mackerel (Scomberomorus commerson) and broad-barred king mackerel (Scomberomorus semifasciatus). Likelihood ratio tests revealed that the largest differences in growth occurred between the back-calculation methods and the observed and adjusted methods for both species of mackerel. The pattern, however, was more pronounced for S. commerson than for S. semifasciatus, because of the pronounced effect of gear selectivity demonstrated for S. commerson. We propose a method of substituting length-at-age data from observed or adjusted methods with back-calculated length-at-age data to provide more appropriate estimates of population growth than those obtained with the individual methods alone, particularly when faster growing young fish are disproportionately selected for. Substitution of observed or adjusted length-at-age data with back-calculated length-at-age data provided more realistic estimates of length for younger ages than observed or adjusted methods as well as more realistic estimates of mean maximum length than those derived from backcalculation methods alone

High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.

Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo

Cold Atom Space Payload Atmospheric Drag Mission (CASPA-ADM)

To gain better understanding of the upper atmospheric dynamics requires more accurate determination of the mass density distribution in the thermosphere. Improved measurements of drag, by means of satellite accelerometery, can be used to more precisely determine this distribution. In addition, atmospheric drag in Low Earth Orbit (LEO) is particularly of interest for climate modelling, weather forecasting and satellite orbit prediction. RAL Space, Teledyne-e2v and the University of Birmingham are developing a Cold Atom Space Payload Atmospheric Drag Mission (CASPA-ADM). The aim of the project, supported by the UK Centre for Earth Observation Instrumentation (CEOI), is to develop a technology demonstrator based on Cold Atom Interferometry (CAI) to take sensitive measurements of atmospheric drag. The underlying CAI technology has been previously flown on the Chinese Space Station, the International Space Station, and in sounding rockets. However, it has not yet been used as the fundamental sensor technology in a free flight space mission. The team is producing a space-suitable accelerometer that can be embedded in small satellites such as 16U CubeSats and are addressing the engineering challenges associated with space qualification and miniaturisation, while keeping the performance level of systems with larger Size, Weight and Power (SWaP)

Enabling scientific workflow and gateways using the standards-based XSEDE architecture

The XSEDE project seeks to provide “a single virtual system that scientists can use to interactively share computing resources, data and experience.” The potential compute resources in XSEDE are diverse in many dimensions, node architectures, interconnects, memory, local queue management systems, and authentication policies to name a few. The diversity is particularly rich when one considers the NSF funded service providers and the many campuses that wish to participate via campus bridging activities. Resource diversity presents challenges to both application developers and application platform developers (e.g., developers of gateways, portals, and workflow engines). The XSEDE Execution Management Services (EMS) architecture is an instance of the Open Grid Services Architecture EMS and is used by higher level services such as gateways and workflow engines to provide end users with execution services that meet their needs. The contribution of this paper is to provide a concise explanation and concrete examples of how the EMS works, how it can be used to support scientific gateways and workflow engines, and how the XSEDE EMS and other OGSA EMS architectures can be used by applications developers to securely access heterogeneous distributed computing and data resources

Comparative genomics reveals high biological diversity and specific adaptations in the industrially and medically important fungal genus Aspergillus

Peer reviewe

A systems analysis of the chemosensitivity of breast cancer cells to the polyamine analogue PG-11047

<p>Abstract</p> <p>Background</p> <p>Polyamines regulate important cellular functions and polyamine dysregulation frequently occurs in cancer. The objective of this study was to use a systems approach to study the relative effects of PG-11047, a polyamine analogue, across breast cancer cells derived from different patients and to identify genetic markers associated with differential cytotoxicity.</p> <p>Methods</p> <p>A panel of 48 breast cell lines that mirror many transcriptional and genomic features present in primary human breast tumours were used to study the antiproliferative activity of PG-11047. Sensitive cell lines were further examined for cell cycle distribution and apoptotic response. Cell line responses, quantified by the GI₅₀(dose required for 50% relative growth inhibition) were correlated with the omic profiles of the cell lines to identify markers that predict response and cellular functions associated with drug sensitivity.</p> <p>Results</p> <p>The concentrations of PG-11047 needed to inhibit growth of members of the panel of breast cell lines varied over a wide range, with basal-like cell lines being inhibited at lower concentrations than the luminal cell lines. Sensitive cell lines showed a significant decrease in S phase fraction at doses that produced little apoptosis. Correlation of the GI₅₀values with the omic profiles of the cell lines identified genomic, transcriptional and proteomic variables associated with response.</p> <p>Conclusions</p> <p>A 13-gene transcriptional marker set was developed as a predictor of response to PG-11047 that warrants clinical evaluation. Analyses of the pathways, networks and genes associated with response to PG-11047 suggest that response may be influenced by interferon signalling and differential inhibition of aspects of motility and epithelial to mesenchymal transition.</p> <p>See the related commentary by Benes and Settleman: <url>http://www.biomedcentral.com/1741-7015/7/78</url></p

Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in Rag-dependent immunodeficiency

The contribution of B cells to the pathology of Omenn syndrome and leaky severe combined immunodeficiency (SCID) has not been previously investigated. We have studied a mut/mut mouse model of leaky SCID with a homozygous Rag1 S723C mutation that impairs, but does not abrogate, V(D)J recombination activity. In spite of a severe block at the pro–B cell stage and profound B cell lymphopenia, significant serum levels of immunoglobulin (Ig) G, IgM, IgA, and IgE and a high proportion of Ig-secreting cells were detected in mut/mut mice. Antibody responses to trinitrophenyl (TNP)-Ficoll and production of high-affinity antibodies to TNP–keyhole limpet hemocyanin were severely impaired, even after adoptive transfer of wild-type CD4+ T cells. Mut/mut mice produced high amounts of low-affinity self-reactive antibodies and showed significant lymphocytic infiltrates in peripheral tissues. Autoantibody production was associated with impaired receptor editing and increased serum B cell–activating factor (BAFF) concentrations. Autoantibodies and elevated BAFF levels were also identified in patients with Omenn syndrome and leaky SCID as a result of hypomorphic RAG mutations. These data indicate that the stochastic generation of an autoreactive B cell repertoire, which is associated with defects in central and peripheral checkpoints of B cell tolerance, is an important, previously unrecognized, aspect of immunodeficiencies associated with hypomorphic RAG mutations