X-CHIP: an integrated platform for high-throughput protein crystallization and on-the-chip X-ray diffraction data collection

The X-CHIP (X-ray Crystallography High-throughput Integrated Platform) is a novel microchip that has been developed to combine multiple steps of the crystallographic pipeline from crystallization to diffraction data collection on a single device to streamline the entire process

Spiral cracks in drying precipitates

We investigate the formation of spiral crack patterns during the desiccation of thin layers of precipitates in contact with a substrate. This symmetry-breaking fracturing mode is found to arise naturally not from torsion forces, but from a propagating stress front induced by the fold-up of the fragments. We model their formation mechanism using a coarse-grain model for fragmentation and successfully reproduce the spiral cracks. Fittings of experimental and simulation data show that the spirals are logarithmic, corresponding to constant deviation from a circular crack path. Theoretical aspects of the logarithmic spirals are discussed. In particular we show that this occurs generally when the crack speed is proportional to the propagating speed of stress front.Comment: 4 pages, 5 figures, RevTe

Diffusion-weighted MRI to determine response and long-term clinical outcomes in muscle-invasive bladder cancer following neoadjuvant chemotherapy.

OBJECTIVE: This study aims to determine local treatment response and long-term survival outcomes in patients with localised muscle-invasive bladder cancer (MIBC) patients receiving neoadjuvant chemotherapy (NAC) using diffusion-weighted MRI (DWI) and apparent diffusion coefficient (ADC) analysis. METHODS: Patients with T2-T4aN0-3M0 bladder cancer suitable for NAC were recruited prospectively. DWI was performed prior to NAC and was repeated following NAC completion. Conventional response assessment was performed with cystoscopy and tumour site biopsy. Response was dichotomised into response (15.5% was associated with significant improvement in OS (HR, 0.40; 95% CI, 0.19-0.86; p=0.0179), bCSS (HR, 0.26; 95% CI, 0.08-0.82; p=0.0214), PFS (HR, 0.16; 95% CI, 0.05-0.48; p=0.0012), and time to cystectomy (HR, 0.19; 95% CI, 0.07-0.47; p=0.0004). CONCLUSIONS: Quantitative ADC analysis can successfully identify NAC response and improved long-term clinical outcomes. Multi-centre validation to assess reproducibility and repeatability is required before testing within clinical trials to inform MIBC treatment decision making. ADVANCES IN KNOWLEDGE: We successfully demonstrated that measured change in DWI can successfully identify NAC response and improved long-term survival outcomes

Morphological Instabilities in a growing Yeast Colony: Experiment and Theory

We study the growth of colonies of the yeast Pichia membranaefaciens on agarose film. The growth conditions are controlled in a setup where nutrients are supplied through an agarose film suspended over a solution of nutrients. As the thickness of the agarose film is varied, the morphology of the front of the colony changes. The growth of the front is modeled by coupling it to a diffusive field of inhibitory metabolites. Qualitative agreement with experiments suggests that such a coupling is responsible for the observed instability of the front.Comment: RevTex, 4 pages and 3 figure

The Viscous Nonlinear Dynamics of Twist and Writhe

Exploiting the "natural" frame of space curves, we formulate an intrinsic dynamics of twisted elastic filaments in viscous fluids. A pair of coupled nonlinear equations describing the temporal evolution of the filament's complex curvature and twist density embodies the dynamic interplay of twist and writhe. These are used to illustrate a novel nonlinear phenomenon: ``geometric untwisting" of open filaments, whereby twisting strains relax through a transient writhing instability without performing axial rotation. This may explain certain experimentally observed motions of fibers of the bacterium B. subtilis [N.H. Mendelson, et al., J. Bacteriol. 177, 7060 (1995)].Comment: 9 pages, 4 figure

Dermcidin expression is associated with disease progression and survival among breast cancer patients

Improved diagnostic screening has led to earlier detection of many tumors, but screening may still miss many aggressive tumor types. Proteomic and genomic profiling studies of breast cancer samples have identified tumor markers that may help improve screening for more aggressive, rapidly growing breast cancers. To identify potential blood-based biomarkers for the early detection of breast cancer, we assayed serum samples via matrix-assisted laser desorption ionization–time of flight mass spectrometry from a rat model of mammary carcinogenesis. We found elevated levels of a fragment of the protein dermcidin (DCD) to be associated with early progression of N-methylnitrosourea-induced breast cancer, demonstrating significance at weeks 4 (p = 0.045) and 5 (p = 0.004), a time period during which mammary pathologies rapidly progress from ductal hyperplasia to adenocarcinoma. The highest serum concentrations were observed in rats bearing palpable mammary carcinomas. Increased DCD was also detected with immunoblotting methods in 102 serum samples taken from women just prior to breast cancer diagnosis. To validate these findings in a larger population, we applied a 32-gene in vitro DCD response signature to a dataset of 295 breast tumors and assessed correlation with intrinsic breast cancer subtypes and overall survival. The DCD-derived gene signature was significantly associated with subtype (p < 0.001) and poorer overall survival [HR (95 % CI) = 1.60 (1.01–2.51), p = 0.044]. In conclusion, these results present novel evidence that DCD levels may increase in early carcinogenesis, particularly among more aggressive forms of breast cancer

The Idea of Social Life

This paper reclaims the idea that human society is a form of life, an idea once vibrant in the work of Toennies, Durkheim, Simmel, Le Bon, Kroeber, Freud, Bion, and Follett but moribund today. Despite current disparagements, this idea remains the only and best answer to our primary experience of society as vital feeling. The main obstacle to conceiving society as a life is linguistic; the logical form of life is incommensurate with the logical form of language. However, it is possible to extend our conceptual reach by appealing to alternative symbolisms more congenial to living form such as, and especially, art.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68336/2/10.1177_004839319502500201.pd

On the origin of spaces: morphometric foundations of urban form evolution

The modern discipline of urban morphology gives us a ground for the comparative analysis of cities, which increasingly includes specific quantitative elements. In this paper, we make a further step forward towards the definition of a general method for the classification of urban form. We draw from morphometrics and taxonomy in life sciences to propose such method, which we name ‘urban morphometrics’. We then test it on a unit of the urban landscape named ‘Sanctuary Area’ (SA), explored in 45 cities whose origins span four historic time periods: Historic (medieval), Industrial (19th century), New Towns (post-WWII, high-rise) and Sprawl (post-WWII, low-rise). We describe each SA through 207 physical dimensions and then use these to discover features that discriminate them among the four temporal groups. Nine dimensions emerge as sufficient to correctly classify 90% of the urban settings by their historic origins. These nine attributes largely identify an area's ‘visible identity’ as reflected by three characteristics: (1) block perimeterness, or the way buildings define the street-edge; (2) building coverage, or the way buildings cover the land and (3) regular plot coverage, or the extent to which blocks are made of plots that have main access from a street. Hierarchical cluster analysis utilising only the nine key variables nearly perfectly clusters each SA according to its historic origin; moreover, the resulting dendrogram shows, just after WWII, the first ‘bifurcation’ of urban history, with the emergence of the modern city as a new ‘species’ of urban form. With ‘urban morphometrics’ we hope to extend urban morphological research and contribute to understanding the way cities evolve