The Nikolaevskiy equation with dispersion

The Nikolaevskiy equation was originally proposed as a model for seismic waves and is also a model for a wide variety of systems incorporating a neutral, Goldstone mode, including electroconvection and reaction-diffusion systems. It is known to exhibit chaotic dynamics at the onset of pattern formation, at least when the dispersive terms in the equation are suppressed, as is commonly the practice in previous analyses. In this paper, the effects of reinstating the dispersive terms are examined. It is shown that such terms can stabilise some of the spatially periodic traveling waves; this allows us to study the loss of stability and transition to chaos of the waves. The secondary stability diagram (Busse balloon) for the traveling waves can be remarkably complicated.Comment: 24 pages; accepted for publication in Phys. Rev.

Successful unrelated donor cord blood transplantation for Glanzmann’s thrombasthenia

GT, a rare disorder of platelet function, can lead to life-threatening bleeding, particularly following the development of antiplatelet antibodies. Curative therapy includes HCT but previous reports are limited predominantly to matched siblings and have excluded CBT. Delayed or non-engraftment of platelets because of antiplatelet antibodies might be particularly concerning after CBT for GT. Here, we report two successful unrelated cord blood transplants for GT. Recurrent life-threatening bleeding was the primary indication for HCT, with one patient developing antiplatelet antibodies pre-HCT. Bleeding risks associated with delivery of the conditioning regimen and the toxicity that follows should be carefully considered, including tunneled central venous line catheter placement, inclusion of B cell-specific therapy to potentially decrease antiplatelet antibody production, and targeted busulfan dosing. This is the first report of successful unrelated cord blood HCT for GT and indicates that modifications to supportive care can improve the safety of this potentially curative therapy for patients with severe, life-threatening disease manifestations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78580/1/j.1399-3046.2009.01251.x.pd

Associations between multimorbidity and neuropathology in dementia: a case for considering functional cognitive disorders, psychiatric illness, and dementia mimics

Cognitive impairment in older people has a variety of underlying causes. In addition to neurodegenerative causes such as Alzheimer's disease, a dementia-like cognitive disorder may appear due to non-degenerative factors. Multimorbidity has been previously associated with clinical dementia risk, though whether this was due to greater risk of dementia-related neuropathology, or other factors that mimic dementia, was unclear. We provide evidence that physical multimorbidity is not associated with greater pathological changes at autopsy. Other factors related to multimorbidity and cognitive impairments may be important targets for investigation, such as functional cognitive disorders, primary psychiatric disorders (depression, anxiety, psychosis) and polypharmacy

The silicon trypanosome

African trypanosomes have emerged as promising unicellular model organisms for the next generation of systems biology. They offer unique advantages, due to their relative simplicity, the availability of all standard genomics techniques and a long history of quantitative research. Reproducible cultivation methods exist for morphologically and physiologically distinct life-cycle stages. The genome has been sequenced, and microarrays, RNA-interference and high-accuracy metabolomics are available. Furthermore, the availability of extensive kinetic data on all glycolytic enzymes has led to the early development of a complete, experiment-based dynamic model of an important biochemical pathway. Here we describe the achievements of trypanosome systems biology so far and outline the necessary steps towards the ambitious aim of creating a , a comprehensive, experiment-based, multi-scale mathematical model of trypanosome physiology. We expect that, in the long run, the quantitative modelling enabled by the Silicon Trypanosome will play a key role in selecting the most suitable targets for developing new anti-parasite drugs

The Signature of Primordial Grain Growth in the Polarized Light of the AU Mic Debris Disk

We have used the Hubble Space Telescope/ACS coronagraph to make polarization maps of the AU Mic debris disk. The fractional linear polarization rises monotonically from about 0.05 to 0.4 between 20 and 80 AU. The polarization is perpendicular to the disk, indicating that the scattered light originates from micron sized grains in an optically thin disk. Disk models, which simultaneously fit the surface brightness and polarization, show that the inner disk (< 40-50 AU) is depleted of micron-sized dust by a factor of more than 300, which means that the disk is collision dominated. The grains have high maximum linear polarization and strong forward scattering. Spherical grains composed of conventional materials cannot reproduce these optical properties. A Mie/Maxwell-Garnett analysis implicates highly porous (91-94%) particles. In the inner Solar System, porous particles form in cometary dust, where the sublimation of ices leaves a "bird's nest" of refractory organic and silicate material. In AU Mic, the grain porosity may be primordial, because the dust "birth ring" lies beyond the ice sublimation point. The observed porosities span the range of values implied by laboratory studies of particle coagulation by ballistic cluster-cluster aggregation. To avoid compactification, the upper size limit for the parent bodies is in the decimeter range, in agreement with theoretical predictions based on collisional lifetime arguments. Consequently, AU Mic may exhibit the signature of the primordial agglomeration process whereby interstellar grains first assembled to form macroscopic objects.Comment: 12 pages, 8 figures, ApJ, in pres

Using an external exposome framework to examine pregnancy-related morbidities and mortalities: Implications for health disparities research

© 2015 by the authors; licensee MDPI, Basel, Switzerland. Objective: We have conducted a study to assess the role of environment on the burden of maternal morbidities and mortalities among women using an external exposome approach for the purpose of developing targeted public health interventions to decrease disparities. Methods: We identified counties in the 48 contiguous USA where observed low birthweight (LBW) rates were higher than expected during a five-year study period. The identification was conducted using a retrospective space-time analysis scan for statistically significant clusters with high or low rates by a Discrete Poisson Model. Results: We observed statistically significant associations of LBW rate with a set of predictive variables. However, in one of the two spatiotemporal models we discovered LBW to be associated with five predictive variables (teen birth rate, adult obesity, uninsured adults, physically unhealthy days, and percent of adults who smoke) in two counties situated in Alabama after adjusting for location changes. Counties with higher than expected LBW rates were similarly associated with two environmental variables (ozone and fine particulate matter). Conclusions: The county-level predictive measures of LBW offer new insights into spatiotemporal patterns relative to key contributory factors. An external framework provides a promising place-based approach for identifying “hotspots” with implications for designing targeted interventions and control measures to reduce and eliminate health disparities

Comparative endurance testing of the Biomet Matthews Nail and the Dynamic Compression Screw, in simulated condylar and supracondylar femoral fractures

<p>Abstract</p> <p>Background</p> <p>The dynamic compression screw is a plate and screws implant used to treat fractures of the distal femur. The Biomet Matthews Nail is a new retrograde intramedullary nail designed as an alternative surgical option to treat these fractures. The objective of this study was to assess the comparative endurance of both devices.</p> <p>Method</p> <p>The dynamic compression screw (DCS) and Biomet Matthews Nail (BMN) were implanted into composite femurs, which were subsequently cyclically loaded using a materials testing machine. Simulated fractures were applied to each femur prior to the application of load. Either a Y type fracture or a transverse osteotomy was prepared on each composite femur using a jig to enable consistent positioning of cuts.</p> <p>Results</p> <p>The Biomet Matthews Nail demonstrated a greater endurance limit load over the dynamic compression screw in both fracture configurations.</p> <p>Conclusion</p> <p>The distal locking screws pass through the Biomet Matthews Nail in a unique "cruciate" orientation. This allows for greater purchase in the bone of the femoral condyle and potentially improves the stability of the fracture fixation. As these fractures are usually in weak osteoporotic bone, the Biomet Matthews Nail represents a favourable surgical option in these patients.</p

Testing Electrostatic Complementarity in Enzyme Catalysis: Hydrogen Bonding in the Ketosteroid Isomerase Oxyanion Hole

A longstanding proposal in enzymology is that enzymes are electrostatically and geometrically complementary to the transition states of the reactions they catalyze and that this complementarity contributes to catalysis. Experimental evaluation of this contribution, however, has been difficult. We have systematically dissected the potential contribution to catalysis from electrostatic complementarity in ketosteroid isomerase. Phenolates, analogs of the transition state and reaction intermediate, bind and accept two hydrogen bonds in an active site oxyanion hole. The binding of substituted phenolates of constant molecular shape but increasing p K (a) models the charge accumulation in the oxyanion hole during the enzymatic reaction. As charge localization increases, the NMR chemical shifts of protons involved in oxyanion hole hydrogen bonds increase by 0.50–0.76 ppm/p K (a) unit, suggesting a bond shortening of ˜0.02 Å/p K (a) unit. Nevertheless, there is little change in binding affinity across a series of substituted phenolates (ΔΔG = −0.2 kcal/mol/p K (a) unit). The small effect of increased charge localization on affinity occurs despite the shortening of the hydrogen bonds and a large favorable change in binding enthalpy (ΔΔH = −2.0 kcal/mol/p K (a) unit). This shallow dependence of binding affinity suggests that electrostatic complementarity in the oxyanion hole makes at most a modest contribution to catalysis of ˜300-fold. We propose that geometrical complementarity between the oxyanion hole hydrogen-bond donors and the transition state oxyanion provides a significant catalytic contribution, and suggest that KSI, like other enzymes, achieves its catalytic prowess through a combination of modest contributions from several mechanisms rather than from a single dominant contribution