Immobilization of the Erupting Molar in the Syrian Hamster

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67148/2/10.1177_00220345650440061901.pd

Effect of tetragonal distortion on ferroelectric domain switching: A case study on La-doped BiFeO3-PbTiO3 ceramics

The ferroelectric and piezoelectric properties of (1-x)BiFeO3-xPbTiO(3) (BF-PT) ceramics were investigated as a function of tetragonal distortion. The latter was adjusted by employing La-doping (0-30 at %) while keeping the material near the morphotropic phase boundary by varying x between 0.35 and 0.46. This allows changing the c/a ratio of tetragonal BF-PT in the range from 1.10-1.01 and consequently alters the level of compatibility stresses. It was found that the c/a ratio has a significant influence on domain switching as inferred from electric field induced polarization, strain hysteresis, and Rayleigh measurements. Specifically, a threshold c/a ratio of about 1.045 was identified below which the electric field induced domain mobility increases sharply.open342

Outcome-related metabolomic patterns from 1H/31P NMR after mild hypothermia treatments of oxygen–glucose deprivation in a neonatal brain slice model of asphyxia

Human clinical trials using 72 hours of mild hypothermia (32°C–34°C) after neonatal asphyxia have found substantially improved neurologic outcomes. As temperature changes differently modulate numerous metabolite fluxes and concentrations, we hypothesized that 1H/31P nuclear magnetic resonance (NMR) spectroscopy of intracellular metabolites can distinguish different insults, treatments, and recovery stages. Three groups of superfused neonatal rat brain slices underwent 45 minutes oxygen–glucose deprivation (OGD) and then were: treated for 3 hours with mild hypothermia (32°C) that began with OGD, or similarly treated with hypothermia after a 15-minute delay, or not treated (normothermic control group, 37°C). Hypothermia was followed by 3 hours of normothermic recovery. Slices collected at different predetermined times were processed, respectively, for 14.1 Tesla NMR analysis, enzyme-linked immunosorbent assay (ELISA) cell-death quantification, and superoxide production. Forty-nine NMR-observable metabolites underwent a multivariate analysis. Separated clustering in scores plots was found for treatment and outcome groups. Final ATP (adenosine triphosphate) levels, severely decreased at normothermia, were restored equally by immediate and delayed hypothermia. Cell death was decreased by immediate hypothermia, but was equally substantially greater with normothermia and delayed hypothermia. Potentially important biomarkers in the 1H spectra included PCr-1H (phosphocreatine in the 1H spectrum), ATP-1H (adenosine triphosphate in the 1H spectrum), and ADP-1H (adenosine diphosphate in the 1H spectrum). The findings suggest a potential role for metabolomic monitoring during therapeutic hypothermia

Shear induced instabilities in layered liquids

Motivated by the experimentally observed shear-induced destabilization and reorientation of smectic A like systems, we consider an extended formulation of smectic A hydrodynamics. We include both, the smectic layering (via the layer displacement u and the layer normal p) and the director n of the underlying nematic order in our macroscopic hydrodynamic description and allow both directions to differ in non equilibrium situations. In an homeotropically aligned sample the nematic director does couple to an applied simple shear, whereas the smectic layering stays unchanged. This difference leads to a finite (but usually small) angle between n and p, which we find to be equivalent to an effective dilatation of the layers. This effective dilatation leads, above a certain threshold, to an undulation instability of the layers. We generalize our earlier approach [Rheol. Acta, vol.39(3), 15] and include the cross couplings with the velocity field and the order parameters for orientational and positional order and show how the order parameters interact with the undulation instability. We explore the influence of various material parameters on the instability. Comparing our results to recent experiments and molecular dynamic simulations, we find a good qualitative agreement.Comment: 15 pages, 12 figures, accepted for publication in PR

Modeling pathogenesis of emergent and pre-emergent human coronaviruses in mice

The emergence of highly pathogenic human coronaviruses (hCoVs) in the last two decades has illuminated their potential to cause high morbidity and mortality in human populations and disrupt global economies. Global pandemic concerns stem from their high mortality rates, capacity for human-to-human spread by respiratory transmission, and complete lack of approved therapeutic countermeasures. Limiting disease may require the development of virus-directed and host-directed therapeutic strategies due to the acute etiology of hCoV infections. Therefore, understanding how hCoV-host interactions cause pathogenic outcomes relies upon mammalian models that closely recapitulate the pathogenesis of hCoVs in humans. Pragmatism has largely been the driving force underpinning mice as highly effective mammalian models for elucidating hCoV-host interactions that govern pathogenesis. Notably, tractable mouse genetics combined with hCoV reverse genetic systems has afforded the concomitant manipulation of virus and host genetics to evaluate virus-host interaction networks in disease. In addition to assessing etiologies of known hCoVs, mouse models have clinically predictive value as tools to appraise potential disease phenotypes associated with pre-emergent CoVs. Knowledge of CoV pathogenic potential before it crosses the species barrier into the human population provides a highly desirable preclinical platform for addressing global pathogen preparedness, an overarching directive of the World Health Organization. Although we recognize that results obtained in robust mouse models require evaluation in non-human primates, we focus this review on the current state of hCoV mouse models, their use as tractable complex genetic organisms for untangling complex hCoV-host interactions, and as pathogenesis models for preclinical evaluation of novel therapeutic interventions

Increasing the translation of mouse models of MERS coronavirus pathogenesis through kinetic hematological analysis

Newly emerging viral pathogens pose a constant and unpredictable threat to human and animal health. Coronaviruses (CoVs) have a penchant for sudden emergence, as evidenced by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV) and most recently, swine acute diarrhea syndrome coronavirus (SADS-CoV). Small animal models of emerging viral pathogenesis are crucial to better understand the virus and host factors driving disease progression. However, rodent models are often criticized for their limited translatability to humans. The complete blood count is the most ordered clinical test in the United States serving as the cornerstone of clinical medicine and differential diagnosis. We recently generated a mouse model for MERS-CoV pathogenesis through the humanization of the orthologous entry receptor dipeptidyl peptidase 4 (DPP4). To increase the translatability of this model, we validated and established the use of an automated veterinary hematology analyzer (VetScan HM5) at biosafety level 3 for analysis of peripheral blood. MERS-CoV lung titer peaked 2 days post infection concurrent with lymphopenia and neutrophilia in peripheral blood, two phenomena also observed in MERS-CoV infection of humans. The fluctuations in leukocyte populations measured by Vetscan HM5 were corroborated by standard flow cytometry, thus confirming the utility of this approach. Comparing a sublethal and lethal dose of MERS-CoV in mice, analysis of daily blood draws demonstrates a dose dependent modulation of leukocytes. Major leukocyte populations were modulated before weight loss was observed. Importantly, neutrophil counts on 1dpi were predictive of disease severity with a lethal dose of MERS-CoV highlighting the predictive value of hematology in this model. Taken together, the inclusion of hematological measures in mouse models of emerging viral pathogenesis increases their translatability and should elevate the preclinical evaluation of MERS-CoV therapeutics and vaccines to better mirror the complexity of the human condition

Domain switching energies: Mechanical versus electrical loading in La-doped bismuth ferrite-lead titanate

The mechanical stress-induced domain switching and energy dissipation in morphotropic phase boundary (1 - x)(Bi(1-y)La(y))FeO(3)-xPbTiO(3) during uniaxial compressive loading have been investigated at three different temperatures. The strain obtained was found to decrease with increasing lanthanum content, although a sharp increase in strain was observed for compositions doped with 7.5 and 10 at. % La. Increased domain switching was found in compositions with decreased tetragonality. This is discussed in terms of the competing influences of the amount of domain switching and the spontaneous strain on the macroscopic behavior under external fields. Comparison of the mechanically and electrically dissipated energy showed significant differences, discussed in terms of the different microscopic interactions of electric field and stress.open10