The Uses of Argument in Mathematics

Stephen Toulmin once observed that `it has never been customary for philosophers to pay much attention to the rhetoric of mathematical debate'. Might the application of Toulmin's layout of arguments to mathematics remedy this oversight? Toulmin's critics fault the layout as requiring so much abstraction as to permit incompatible reconstructions. Mathematical proofs may indeed be represented by fundamentally distinct layouts. However, cases of genuine conflict characteristically reflect an underlying disagreement about the nature of the proof in question.Comment: 10 pages, 5 figures. To be presented at the Ontario Society for the Study of Argumentation Conference, McMaster University, May 2005 and LOGICA 2005, Hejnice, Czech Republic, June 200

AlbaTraDIS:Comparative analysis of large datasets from parallel transposon mutagenesis experiments

Bacteria need to survive in a wide range of environments. Currently, there is an incomplete understanding of the genetic basis for mechanisms underpinning survival in stressful conditions, such as the presence of anti-microbials. Transposon directed insertion-site sequencing (TraDIS) is a powerful tool to identify genes and networks which are involved in survival and fitness under a given condition by simultaneously assaying the fitness of millions of mutants, thereby relating genotype to phenotype and contributing to an understanding of bacterial cell biology. A recent refinement of this approach allows the roles of essential genes in conditional stress survival to be inferred by altering their expression. These advancements combined with the rapidly falling costs of sequencing now allows comparisons between multiple experiments to identify commonalities in stress responses to different conditions. This capacity however poses a new challenge for analysis of multiple data sets in conjunction. To address this analysis need, we have developed 'AlbaTraDIS'; a software application for rapid large-scale comparative analysis of TraDIS experiments that predicts the impact of transposon insertions on nearby genes. AlbaTraDIS can identify genes which are up or down regulated, or inactivated, between multiple conditions, producing a filtered list of genes for further experimental validation as well as several accompanying data visualisations. We demonstrate the utility of our new approach by applying it to identify genes used by Escherichia coli to survive in a wide range of different concentrations of the biocide Triclosan. AlbaTraDIS identified all well characterised Triclosan resistance genes, including the primary target, fabI. A number of new loci were also implicated in Triclosan resistance and the predicted phenotypes for a selection of these were validated experimentally with results being consistent with predictions. AlbaTraDIS provides a simple and rapid method to analyse multiple transposon mutagenesis data sets allowing this technology to be used at large scale. To our knowledge this is the only tool currently available that can perform these tasks. AlbaTraDIS is written in Python 3 and is available under the open source licence GNU GPL 3 from https://github.com/quadram-institute-bioscience/albatradis

Examination of Fluconazole-Induced Alopecia in an Animal Model and Human Cohort.

Fluconazole-induced alopecia is a significant problem for patients receiving long-term therapy. We evaluated the hair cycle changes of fluconazole in a rat model and investigated potential molecular mechanisms. Plasma and tissue levels of retinoic acid were not found to be causal. Human patients with alopecia attributed to fluconazole also underwent detailed assessment and in both our murine model and human cohort fluconazole induced telogen effluvium. Future work further examining the mechanism of fluconazole-induced alopecia should be undertaken

First Science Observations with SOFIA/FORCAST: Properties of Intermediate-Luminosity Protostars and Circumstellar Disks in OMC-2

We examine eight young stellar objects in the OMC-2 star forming region based on observations from the SOFIA/FORCAST early science phase, the Spitzer Space Telescope, the Herschel Space Observatory, 2MASS, APEX, and other results in the literature. We show the spectral energy distributions of these objects from near-infrared to millimeter wavelengths, and compare the SEDs with those of sheet collapse models of protostars and circumstellar disks. Four of the objects can be modelled as protostars with infalling envelopes, two as young stars surrounded by disks, and the remaining two objects have double-peaked SEDs. We model the double-peaked sources as binaries containing a young star with a disk and a protostar. The six most luminous sources are found in a dense group within a 0.15 x 0.25 pc region; these sources have luminosities ranging from 300 L_sun to 20 L_sun. The most embedded source (OMC-2 FIR 4) can be fit by a class 0 protostar model having a luminosity of ~50 L_sun and mass infall rate of ~10^-4 solar masses per year.Comment: Accepted by ApJ Letter

Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation

The gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson’s disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing the ten currently available 16S microbiome datasets to investigate whether common alterations in the gut microbiota of PD patients exist across cohorts. We found significant alterations in the PD-associated microbiome, which are robust to study-specific technical heterogeneities, although differences in microbiome structure between PD and controls are small. Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations. This dysbiosis might result in a pro-inflammatory status which could be linked to the recurrent gastrointestinal symptoms affecting PD patients

A Departmental Focus on High Impact Undergraduate Research Experiences

Undergraduate research experiences have become an integral part of the Hamilton College chemistry experience. The major premise of the chemistry department’s curriculum is that research is a powerful teaching tool. Curricular offerings have been developed and implemented to better prepare students for the independence required for successful undergraduate research experiences offered during the academic year and the summer. Administrative support has played a critical role in our ability to initiate and sustain scholarly research programs for all faculty members in the department. The research-rich curriculum is built directly upon or derived from the scholarly research agendas of our faculty members. The combined strengths and synergies of our curriculum and summer research program have allowed us to pursue several programmatic initiatives

TraDIS-Xpress: a high-resolution whole-genome assay identifies novel mechanisms of triclosan action and resistance

Understanding the genetic basis for a phenotype is a central goal in biological research. Much has been learnt about bacterial genomes by creating large mutant libraries and looking for conditionally important genes. However, current genome-wide methods are largely unable to assay essential genes which are not amenable to disruption. To overcome this limitation, we developed a new version of “TraDIS” (transposon directed insertion-site sequencing) that we term “TraDIS-Xpress” that combines an inducible promoter into the transposon cassette. This allows controlled overexpression and repression of all genes owing to saturation of inserts adjacent to all open reading frames as well as conventional inactivation. We applied TraDIS-Xpress to identify responses to the biocide triclosan across a range of concentrations. Triclosan is endemic in modern life, but there is uncertainty about its mode of action with a concentration-dependent switch from bacteriostatic to bactericidal action unexplained. Our results show a concentration-dependent response to triclosan with different genes important in survival between static and cidal exposures. These genes include those previously reported to have a role in triclosan resistance as well as a new set of genes, including essential genes. Novel genes identified as being sensitive to triclosan exposure include those involved in barrier function, small molecule uptake, and integrity of transcription and translation. We anticipate the approach we show here, by allowing comparisons across multiple experimental conditions of TraDIS data, and including essential genes, will be a starting point for future work examining how different drug conditions impact bacterial survival mechanisms

Elongation factor Tu is a multifunctional and processed moonlighting protein

Many bacterial moonlighting proteins were originally described in medically, agriculturally, and commercially important members of the low G + C Firmicutes. We show Elongation factor Tu (Ef-Tu) moonlights on the surface of the human pathogens Staphylococcus aureus (SaEf-Tu) and Mycoplasma pneumoniae (MpnEf-Tu), and the porcine pathogen Mycoplasma hyopneumoniae (MhpEf-Tu). Ef-Tu is also a target of multiple processing events on the cell surface and these were characterised using an N-terminomics pipeline. Recombinant MpnEf-Tu bound strongly to a diverse range of host molecules, and when bound to plasminogen, was able to convert plasminogen to plasmin in the presence of plasminogen activators. Fragments of Ef-Tu retain binding capabilities to host proteins. Bioinformatics and structural modelling studies indicate that the accumulation of positively charged amino acids in short linear motifs (SLiMs), and protein processing promote multifunctional behaviour. Codon bias engendered by an A + T rich genome may influence how positively-charged residues accumulate in SLiMs

Design and development of MOSFIRE: the Multi-Object Spectrometer For Infra-Red Exploration at the Keck Observatory

MOSFIRE is a unique multi-object spectrometer and imager for the Cassegrain focus of the 10 m Keck 1 telescope. A refractive optical design provides near-IR (0.97 to 2.45 μm) multi-object spectroscopy over a 6.14' x 6.14' field of view with a resolving power of R~3,270 for a 0.7" slit width (2.9 pixels in the dispersion direction), or imaging over a field of view of 6.8' diameter with 0.18" per pixel sampling. A single diffraction grating can be set at two fixed angles, and order-sorting filters provide spectra that cover the K, H, J or Y bands by selecting 3rd, 4th, 5th or 6th order respectively. A folding flat following the field lens is equipped with piezo transducers to provide tip/tilt control for flexure compensation at the 0.1 pixel level. A special feature of MOSFIRE is that its multiplex advantage of up to 46 slits is achieved using a cryogenic Configurable Slit Unit or CSU developed in collaboration with the Swiss Centre for Electronics and Micro Technology (CSEM). The CSU is reconfigurable under remote control in less than 5 minutes without any thermal cycling of the instrument. Slits are formed by moving opposable bars from both sides of the focal plane. An individual slit has a length of 7.1" but bar positions can be aligned to make longer slits. When masking bars are removed to their full extent and the grating is changed to a mirror, MOSFIRE becomes a wide-field imager. Using a single, ASIC-driven, 2K x 2K H2-RG HgCdTe array from Teledyne Imaging Sensors with exceptionally low dark current and low noise, MOSFIRE will be extremely sensitive and ideal for a wide range of science applications. This paper describes the design and testing of the instrument prior to delivery later in 2010