Mechanical Systems with Symmetry, Variational Principles, and Integration Algorithms

This paper studies variational principles for mechanical systems with symmetry and their applications to integration algorithms. We recall some general features of how to reduce variational principles in the presence of a symmetry group along with general features of integration algorithms for mechanical systems. Then we describe some integration algorithms based directly on variational principles using a discretization technique of Veselov. The general idea for these variational integrators is to directly discretize Hamilton’s principle rather than the equations of motion in a way that preserves the original systems invariants, notably the symplectic form and, via a discrete version of Noether’s theorem, the momentum map. The resulting mechanical integrators are second-order accurate, implicit, symplectic-momentum algorithms. We apply these integrators to the rigid body and the double spherical pendulum to show that the techniques are competitive with existing integrators

Regulation of Spike Timing-Dependent Plasticity of Olfactory Inputs in Mitral Cells in the Rat Olfactory Bulb

The recent history of activity input onto granule cells (GCs) in the main olfactory bulb can affect the strength of lateral inhibition, which functions to generate contrast enhancement. However, at the plasticity level, it is unknown whether and how the prior modification of lateral inhibition modulates the subsequent induction of long-lasting changes of the excitatory olfactory nerve (ON) inputs to mitral cells (MCs). Here we found that the repetitive stimulation of two distinct excitatory inputs to the GCs induced a persistent modification of lateral inhibition in MCs in opposing directions. This bidirectional modification of inhibitory inputs differentially regulated the subsequent synaptic plasticity of the excitatory ON inputs to the MCs, which was induced by the repetitive pairing of excitatory postsynaptic potentials (EPSPs) with postsynaptic bursts. The regulation of spike timing-dependent plasticity (STDP) was achieved by the regulation of the inter-spike-interval (ISI) of the postsynaptic bursts. This novel form of inhibition-dependent regulation of plasticity may contribute to the encoding or processing of olfactory information in the olfactory bulb

Receptor-Mediated Enhancement of Beta Adrenergic Drug Activity by Ascorbate In Vitro and In Vivo

RATIONALE: Previous in vitro research demonstrated that ascorbate enhances potency and duration of activity of agonists binding to alpha 1 adrenergic and histamine receptors. OBJECTIVES: Extending this work to beta 2 adrenergic systems in vitro and in vivo. METHODS: Ultraviolet spectroscopy was used to study ascorbate binding to adrenergic receptor preparations and peptides. Force transduction studies on acetylcholine-contracted trachealis preparations from pigs and guinea pigs measured the effect of ascorbate on relaxation due to submaximal doses of beta adrenergic agonists. The effect of inhaled albuterol with and without ascorbate was tested on horses with heaves and sheep with carbachol-induced bronchoconstriction. MEASUREMENTS: Binding constants for ascorbate binding to beta adrenergic receptor were derived from concentration-dependent spectral shifts. Dose- dependence curves were obtained for the relaxation of pre-contracted trachealis preparations due to beta agonists in the presence and absence of varied ascorbate. Tachyphylaxis and fade were also measured. Dose response curves were determined for the effect of albuterol plus-and-minus ascorbate on airway resistance in horses and sheep. MAIN RESULTS: Ascorbate binds to the beta 2 adrenergic receptor at physiological concentrations. The receptor recycles dehydroascorbate. Physiological and supra-physiological concentrations of ascorbate enhance submaximal epinephrine and isoproterenol relaxation of trachealis, producing a 3-10-fold increase in sensitivity, preventing tachyphylaxis, and reversing fade. In vivo, ascorbate improves albuterol's effect on heaves and produces a 10-fold enhancement of albuterol activity in "asthmatic" sheep. CONCLUSIONS: Ascorbate enhances beta-adrenergic activity via a novel receptor-mediated mechanism; increases potency and duration of beta adrenergic agonists effective in asthma and COPD; prevents tachyphylaxis; and reverses fade. These novel effects are probably caused by a novel mechanism involving phosphorylation of aminergic receptors and have clinical and drug-development applications

Vitamin A, carotenoid and vitamin E plasma concentrations in children from Laos in relation to sex and growth failure

BACKGROUND: Deficiencies of vitamin A and its precursors, the carotenoids are common problems in developing countries. Plasma levels of these components are used as biomarkers of their availability. The study was conducted to evaluate whether blood plasma obtained from capillaries can be compared with plasma obtained from venous blood with regard to its levels of retinol, carotenoids and α-tocopherol and secondly to apply this technique to evaluate the levels of these components in children in a region with possible deficiencies. METHODS: The survey was conducted in a region of Laos in 81 children (age 35 to 59 months). Dietary intake was assessed by a questionnaire. Retinol, carotenoids and α-tocopherol were determined by HPLC. Blood plasma was obtained either from capillary blood collected into microcapillaries and for reasons of methodological comparison in 14 adults from venous blood. RESULTS: The comparison between capillary and venous blood revealed that all components except zeaxanthin were 9 – 23 % higher in plasma obtained from capillary blood. Results in Laotian children showed that all investigated components except retinol were significantly lower (P < 0.01) compared to European children of slightly older age. Contrary to children in Europe, most components were significantly lower in boys compared to girls. In children from Laos, lutein was the dominant carotenoid, while in children in Europe, β-carotene was dominant. Within the Laotian children only a few differences were observed between stunted and non-stunted children and between children from lowland areas and high land areas. CONCLUSIONS: Results show that in consideration of slightly lower levels than in venous blood, capillary blood can be used to evaluate retinol, carotenoids and α-tocopherol as biomarkers of intake or status and to evaluate the possible effect of diet on absolute and relative carotenoid composition in children from Europe and Laos. Observed sex related differences might not be related to diet and would need further investigation

Feasibility and initial experience of assessment of mechanical dyssynchrony using cardiovascular magnetic resonance and semi-automatic border detection

<p>Abstract</p> <p>Background</p> <p>The systolic dyssynchrony index (SDI) has been introduced as a measure of mechanical dyssynchrony using three-dimensional echocardiography to select patients who may benefit from cardiac resynchronization therapy (CRT). However, three-dimensional echocardiography may be inadequate in a number of patients with suboptimal acoustic window and no single echocardiographic measure of dyssynchrony has proven to be of value in selecting patients for CRT. Thus, the aim of this study was to determine the value of cardiovascular magnetic resonance (CMR) for the assessment of the SDI in patients with reduced LV function as well as in healthy controls using semi-automatic border tracking.</p> <p>Methods</p> <p>We investigated a total of 45 patients including 35 patients (65 ± 8 years) with reduced LV function (EF 30 ± 11%) and a wide QRS complex as well as 10 control subjects (42 ± 21 years, EF 70 ± 11%). For cine imaging a standard SSFP imaging sequence was used with a temporal resolution of 40 frames per RR-interval. Quantitative analysis was performed off-line using a software prototype for semi-automatic border detection. Global volumes, ejection fraction and the SDI were calculated in each subject. SDI was compared with standard echocardiographic parameters of dyssynchrony.</p> <p>Results</p> <p>The mean SDI differed significantly between patients (14 ± 5%) and controls (5 ± 2%, p < 0.001). An exponential correlation between the EF and the SDI was observed (r = -0.84; p < 0.001). In addition, a significant association between the SDI and the standard deviation of time to peak systolic motion of 12 LV segments (Ts-SD) determined by echocardiography was observed (r = 0.66, p = 0.002).</p> <p>Conclusion</p> <p>The results of this preliminary study suggest that CMR with semi-automatic border detection may be useful for the assessment of mechanical dyssynchrony in patients with reduced LV function.</p> <p>No trial registration due to recruitment period between October 2004 and November 2006</p

Adipose Tissue Serves as a Reservoir for Recrudescent Rickettsia prowazekii Infection in a Mouse Model

Brill-Zinsser disease, the relapsing form of epidemic typhus, typically occurs in a susceptible host years or decades after the primary infection; however, the mechanisms of reactivation and the cellular reservoir during latency are poorly understood. Herein we describe a murine model for Brill-Zinsser disease, and use PCR and cell culture to show transient rickettsemia in mice treated with dexamethasone >3 months after clinical recovery from the primary infection. Treatment of similarly infected mice with cyclosporine failed to produce recrudescent bacteremia. Therapy with doxycycline for the primary infection prevented recrudescent bacteremia in most of these mice following treatment with dexamethasone. Rickettsia prowazekii (the etiologic agent of epidemic typhus) was detected by PCR, cell culture, and immunostaining methods in murine adipose tissue, but not in liver, spleen, lung, or central nervous system tissues of mice 4 months after recovery from the primary infection. The lungs of dexamethasone-treated mice showed impaired expression of β-defensin transcripts that may be involved in the pathogenesis of pulmonary lesions. In vitro, R. prowazekii rickettsiae infected and replicated in the murine adipocyte cell line 3T3-L1. Collectively these data suggest a role for adipose tissue as a potential reservoir for dormant infections with R. prowazekii

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Reexamining age, race, site, and thermometer type as variables affecting temperature measurement in adults – A comparison study

BACKGROUND: As a result of the recent international vigilance regarding disease assessment, accurate measurement of body temperature has become increasingly important. Yet, trusted low-tech, portable mercury glass thermometers are no longer available. Thus, comparing accuracy of mercury-free thermometers with mercury devices is essential. Study purposes were 1) to examine age, race, site as variables affecting temperature measurement in adults, and 2) to compare clinical accuracy of low-tech Galinstan-in-glass device to mercury-in-glass at oral, axillary, groin, and rectal sites in adults. METHODS: Setting 176 bed accredited healthcare facility, rural northwest US Participants Convenience sample (N = 120) of hospitalized persons ≥ 18 years old. Instruments Temperatures (°F) measured at oral, skin (simultaneous), immediately followed by rectal sites with four each mercury-glass (BD) and Galinstan-glass (Geratherm) thermometers; 10 minute dwell times. RESULTS: Participants averaged 61.6 years (SD 17.9), 188 pounds (SD 55.3); 61% female; race: 85% White, 8.3% Native Am., 4.2% Hispanic, 1.7 % Asian, 0.8% Black. For both mercury and Galinstan-glass thermometers, within-subject temperature readings were highest rectally; followed by oral, then skin sites. Galinstan assessments demonstrated rectal sites 0.91°F > oral and ≅ 1.3°F > skin sites. Devices strongly correlated between and across sites. Site difference scores between devices showed greatest variability at skin sites; least at rectal site. 95% confidence intervals of difference scores by site (°F): oral (0.142 – 0.265), axilla (0.167 – 0.339), groin (0.037 – 0.321), and rectal (-0.111 – 0.111). Race correlated with age, temperature readings each site and device. CONCLUSION: Temperature readings varied by age, race. Mercury readings correlated with Galinstan thermometer readings at all sites. Site mean differences between devices were considered clinically insignificant. Still considered the gold standard, mercury-glass thermometers may no longer be available worldwide. Therefore, mercury-free, environmentally safe low-tech Galinstan-in-glass may be an appropriate replacement. This is especially important as we face new, internationally transmitted diseases