A Novel Method for Quantifying the Inhaled Dose of Air Pollutants Based on Heart Rate,Breathing Rate and Forced Vital Capacity

To better understand the interaction of physical activity and air pollution exposure, it is important to quantify the change in ventilation rate incurred by activity. In this paper, we describe a method for estimating ventilation using easily-measured variables such as heart rate (HR), breathing rate (f_B), and forced vital capacity (FVC). We recruited healthy adolescents to use a treadmill while we continuously measured HR, f_B, and the tidal volume (V_T) of each breath. Participants began at rest then walked and ran at increasing speed until HR was 160–180 beats per minute followed by a cool down period. The novel feature of this method is that minute ventilation (V˙E) was normalized by FVC. We used general linear mixed models with a random effect for subject and identified nine potential predictor variables that influence either V˙E or FVC. We assessed predictive performance with a five-fold cross-validation procedure. We used a brute force selection process to identify the best performing models based on cross-validation percent error, the Akaike Information Criterion and the p-value of parameter estimates. We found a two-predictor model including HR and f_B to have the best predictive performance (V˙E/FVC = -4.247+0.0595HR+0.226f_B, mean percent error = 8.1±29%); however, given the ubiquity of HR measurements, a one-predictor model including HR may also be useful (V˙E/FVC = -3.859+0.101HR, mean percent error = 11.3±36%).     

Higher ventilatory responses during and after passive walking-like leg movement in older individuals

Background

Minute ventilation (V·E) during walking has been shown to be higher in older individuals than in young individuals, but the mechanisms underlying the higher ventilatory response is unclear. Central command and peripheral neural reflex are important neural control mechanisms underlying ventilatory response during exercise. Passive leg movement has been used to exclude the influence of central command due to the lack of voluntary activation of muscles. The aim of the present study was to compare the ventilatory response during and after passive walking-like leg movement (PWM) in young and older individuals.

Methods

Eight young subjects (20 ± 2 years) and seven older subjects (70 ± 1 years) participated in this study. Subjects spent 7 minutes in a quiet standing (QS) position. Thereafter, they performed 14-minute rhythmic PWM at 1 Hz and this was followed by 7 minutes of QS.

Results

V·E values during pre-PWM QS were calculated as 1-minute averages using data obtained between 5 and 6 minutes. V·E values at pre-PWM QS in the young and older groups were 8.4 ± 2.1 and 7.5 ± 1.2 l/minute, respectively. V·E values increased significantly at the first minute of PWM to 11.4 ± 2.2 and 10.4 ± 2.5 l/minute in the young and older groups, respectively (P <0.001). In the young group, V·E at the last minute of PWM (9.2 ± 2.0 l/minute) was not significantly different from that at pre-PWM QS due to a decline in V·E, whereas V·E at the last minute of PWM in the older group (9.4 ± 2.2 l/minute) was still significantly higher (P <0.01). On the other hand, V·E at the first minute of post-PWM QS (7.2 ± 1.8 l/minute) was significantly lower than that during pre-PWM QS in the young group (P <0.05) but not in the older group.

Conclusions

Ventilatory response during and after PWM is higher in older individuals than in young individuals. This may be associated with a mechanism(s) other than central command. Our findings may explain part of the higher V·E response while walking in older individuals.     

Preload-Based Starling-Like Control for Rotary Blood Pumps: Numerical Comparison with Pulsatility Control and Constant Speed Operation

In this study, we evaluate a preload-based Starling-like controller for implantable rotary blood pumps (IRBPs) using left ventricular end-diastolic pressure (PLVED) as the feedback variable. Simulations are conducted using a validated mathematical model. The controller emulates the response of the natural left ventricle (LV) to changes in PLVED. We report the performance of the preload-based Starling-like controller in comparison with our recently designed pulsatility controller and constant speed operation. In handling the transition from a baseline state to test states, which include vigorous exercise, blood loss and a major reduction in the LV contractility (LVC), the preload controller outperformed pulsatility control and constant speed operation in all three test scenarios. In exercise, preload-control achieved an increase of 54% in mean pump flow (QP-) with minimum loading on the LV, while pulsatility control achieved only a 5% increase in flow and a decrease in mean pump speed. In a hemorrhage scenario, the preload control maintained the greatest safety margin against LV suction. PLVED for the preload controller was 4.9 mmHg, compared with 0.4 mmHg for the pulsatility controller and 0.2 mmHg for the constant speed mode. This was associated with an adequate mean arterial pressure (MAP) of 84 mmHg. In transition to low LVC, QP- for preload control remained constant at 5.22 L/min with a PLVED of 8.0 mmHg. With regards to pulsatility control, QP- fell to the nonviable level of 2.4 L/min with an associated PLVED of 16 mmHg and a MAP of 55 mmHg. Consequently, pulsatility control was deemed inferior to constant speed mode with a PLVED of 11 mmHg and a QP- of 5.13 L/min in low LVC scenario. We conclude that pulsatility control imposes a danger to the patient in the severely reduced LVC scenario, which can be overcome by using a preload-based Starling-like control approach.     

Effect of Ocean Acidification and pH Fluctuations on the Growth and Development of Coralline Algal Recruits,and an Associated Benthic Algal Assemblage

Coralline algae are susceptible to the changes in the seawater carbonate system associated with ocean acidification (OA). However, the coastal environments in which corallines grow are subject to large daily pH fluctuations which may affect their responses to OA. Here, we followed the growth and development of the juvenile coralline alga Arthrocardia corymbosa, which had recruited into experimental conditions during a prior experiment, using a novel OA laboratory culture system to simulate the pH fluctuations observed within a kelp forest. Microscopic life history stages are considered more susceptible to environmental stress than adult stages; we compared the responses of newly recruited A. corymbosa to static and fluctuating seawater pH with those of their field-collected parents. Recruits were cultivated for 16 weeks under static pH 8.05 and 7.65, representing ambient and 4× preindustrial pCO₂ concentrations, respectively, and two fluctuating pH treatments of daily x~ = 8.05 (daytime pH = 8.45, night-time pH = 7.65) and daily x~ = 7.65 (daytime pH = 8.05, night-time pH = 7.25). Positive growth rates of new recruits were recorded in all treatments, and were highest under static pH 8.05 and lowest under fluctuating pH 7.65. This pattern was similar to the adults’ response, except that adults had zero growth under fluctuating pH 7.65. The % dry weight of MgCO₃ in calcite of the juveniles was reduced from 10% at pH 8.05 to 8% at pH 7.65, but there was no effect of pH fluctuation. A wide range of fleshy macroalgae and at least 6 species of benthic diatoms recruited across all experimental treatments, from cryptic spores associated with the adult A. corymbosa. There was no effect of experimental treatment on the growth of the benthic diatoms. On the community level, pH-sensitive species may survive lower pH in the presence of diatoms and fleshy macroalgae, whose high metabolic activity may raise the pH of the local microhabitat.     

Patch utilization and flower visitations by wild bees in a honey bee‐dominated,grassland landscape

Understanding habitat needs and patch utilization of wild and managed bees has been identified as a national research priority in the United States. We used occupancy models to investigate patterns of bee use across 1030 transects spanning a gradient of floral resource abundance and richness and distance from apiaries in the Prairie Pothole Region (PPR) of the United States. Estimates of transect use by honey bees were nearly 1.0 during our 3.5‐month sampling period, suggesting honey bees were nearly ubiquitous across transects. Wild bees more frequently used transects with higher flower richness and more abundant flowers; however, the effect size of the native flower abundance covariate (β^native = 3.90 ± 0.65 [1SE]) was four times greater than the non‐native flower covariate (β^non‐native = 0.99 ± 0.17). We found some evidence that wild bee use was lower at transects near commercial apiaries, but the effect size was imprecise (β^distance = 1.4 ± 0.81). Honey bees were more frequently detected during sampling events with more non‐native flowers and higher species richness but showed an uncertain relationship with native flower abundance. Of the 4039 honey bee and flower interactions, 85% occurred on non‐native flowers, while only 43% of the 738 wild bee observations occurred on non‐native flowers. Our study suggests wild bees and honey bees routinely use the same resource patches in the PPR but often visit different flowering plants. The greatest potential for resource overlap between honey bees and wild bees appears to be for non‐native flowers in the PPR. Our results are valuable to natural resource managers tasked with supporting habitat for managed and wild pollinators in agroecosystems.     

DNA,Flexibly Flexible

Investigators have constructed dsDNA molecules with several different base modifications and have characterized their bending and twisting flexibilities using atomic force microscopy, DNA ring closure, and single-molecule force spectroscopy with optical tweezers. The three methods provide persistence length measurements that agree semiquantitatively, and they show that the persistence length is surprisingly similar for all of the modified DNAs. The circular dichroism spectra of modified DNAs differ substantially. Simple explanations based on base stacking strength, polymer charge, or groove occupancy by functional groups cannot explain the results, which will guide further high-resolution theory and experiments.Real double-stranded DNA molecules differ from the idealized zero-Kelvin A, B, and Z forms. They can adopt deformed average conformations, as in bent A-tract DNA or protein-DNA complexes. The path of the DNA helix axis also varies due to thermal energy, so at very long lengths DNA behaves as a random coil. The term “long lengths” is relative to the persistence length P of the wormlike chain model. P is the average offset of the end of a chain along its initial direction, or alternatively the length over which the unit vectors μ1→ and μ2→ tangent to the helix axis lose colinearity according to〈μ1→⋅μ2→〉=〈cosθ〉=e−d12/P,where d₁₂ is the contour length from point 1 to point 2, as in Fig. 1. P can be measured by hydrodynamics (1), atomic force microscopy (AFM) (2), DNA ring closure (3) or protein-DNA looping (4), tethered particle microscopy (5), or single-molecule optical tweezers experiments (6). The long-range loss of memory of DNA direction grows out of local variations in the helix axis direction specified by roll, tilt, and twist angles that parameterize changes in the helix axis direction. For harmonic bending potentials, the bending persistence length is related to roll and tilt according toσroll2+σtilt2=2ℓ/P,where ℓ = 3.4 Å, so for P ∼ 50 nm (147 bp) the average standard deviations in the roll and tilt angles σ_roll and σ_tilt are ∼4.7°, although in real DNA, roll varies more than tilt. Similar relationships hold for twist flexibility (7).Open in a separate windowFigure 1The base modifications studied by Peters et al. (13,14) affect both Watson-Crick hydrogen bonding and groove occupancy. They used AFM, DNA ring closure, single-molecule force spectroscopy, and circular dichroism spectroscopy (not shown) to characterize the resulting changes in bending and twisting flexibility. DNA molecules are not shown to scale. To see this figure in color, go online.DNA flexibility can be studied at contour length scales from Ångstroms to microns. Flexibility at the atomic scale accessed by nuclear magnetic resonance, x-ray crystallography, cryo-electron microscopy, and molecular dynamics simulations (8) refers to many aspects of conformational variability. One active thread of research at this scale concerns interconversion among helical forms, base flipping, DNA kinking, changes in backbone torsion angles, and the sequence dependence of all of these local properties. Local fluctuations in the basepair roll, tilt, and twist angles do seem to predict the correct long-range behavior (9). A second thread asks whether the wormlike chain model holds at DNA lengths shorter than P (2,10); the active controversy concerning enhanced bendability at short lengths has recently been reviewed by Vologodskii and Frank-Kamenetskii (11). A third thread asks whether we can understand the underlying biophysical causes of long-range DNA flexibility. These presumably include base stacking, electrostatic repulsion along the backbone, changes in the counterion atmosphere (12), occupancy of the major and minor grooves by functional groups, conformational entropy, the strength of Watson-Crick hydrogen bonding, and water structure. Helical polymorphisms and the junctions between polymorphs presumably affect the sequence dependence of the persistence length.Peters et al. (13,14) have attempted to understand bending and twisting flexibility by characterizing a variety of modified nucleic acids using DNA ring closure, AFM, and optical tweezer methods, sketched in Fig. 1. In previous work (13), they used ring closure to show that major groove substituents that alter the charge on the polymer do not have substantial effects on the bending persistence length, and that the effects were not correlated in an obvious way to the stacking propensity of the modified bases. The work described in this issue of the Biophysical Journal (14) uses all three methods to demonstrate that DNA with 2-amino-adenosine (a.k.a., 2,6-diaminopurine) substituted for adenosine has an increased persistence length, whereas inosine substitution for guanosine reduces the persistence length, as would be expected if groove occupancy (or the number of Watson-Crick hydrogen bonds) affects flexibility. However, the authors did one experiment too many—when they measured the effects of the earlier major groove substituents (13) using AFM, the correlation with groove occupancy disappeared. This could be because changes in helical geometry, as evidenced by the circular dichroism spectroscopy also reported in the article, alter the grooves sufficiently to prevent a straightforward connection to flexibility.The magnitude of the effect of base modifications on P is the largest for the optical tweezers and the smallest for DNA ring closure, showing that no more than one of the experiments is perfect. The Supporting Material for both articles (13,14) offers valuable resources for the careful evaluation of experimental results and possible sources of error within and between experiments. For example, the DNA lengths and the ionic conditions required by the different methods differ. Ring closure results depend critically on the purity of the DNA and appropriate ligation conditions. Analysis of AFM results averaged several different statistical measures of decaying angular correlations and end-to-end distance, which did not individually always agree. In force spectroscopy there are variations in the bead attachment for each molecule, errors in the stretch modulus can affect the measured persistence length, force can induce DNA melting, and very few molecules can be observed. Rare kinking events proposed to explain enhanced bendability should affect the cyclization experiment most markedly; no evidence for enhanced flexibility was seen. Finally, Peters et al. (14) have observed that DNA twist and twisting flexibility seem to be more sensitive than the persistence length to base modifications.Taken as a whole, this extremely thorough series of experiments shows that we still do not understand the fundamental origins of the remarkable stiffness of double-stranded DNA. There may be compensating effects that make the dissection difficult. For example, changing the charge on the polymer may induce a corresponding adjustment in the counterion condensation atmosphere, leading to a relatively constant residual charge. Groove substituents that enhance basepair stability could enhance bendability for steric reasons. Stacking thermodynamics may not change very much for the very small bend angles at any individual basepair. Locally stiff regions may introduce nearby junctions that are flexible.The stiffness of DNA relative to other biopolymers inspired the development of DNA nanotechnology (although that field has adopted bridged synthetic constructs that are even more rigid). Further research on the biophysics, and specifically the long-range mechanical properties of DNA, will be essential as we build better models of DNA in the cell, which has evolved many proteins that act to increase apparent flexibility. The various aspects of DNA flexibility influence the protein-DNA complexes that mediate DNA’s informational role, the induction of and responses to supercoiling used for long-range communication among sites (15), and chromosome structure and genome organization.     

Enhancement of Chemotactic Cell Aggregation by Haptotactic Cell-To-Cell Interaction

The crawling of biological cell is a complex phenomenon involving various biochemical and mechanical processes. Some of these processes are intrinsic to individual cells, while others pertain to cell-to-cell interactions and to their responses to extrinsically imposed cues. Here, we report an interesting aggregation dynamics of mathematical model cells, when they perform chemotaxis in response to an externally imposed global chemical gradient while they influence each other through a haptotaxis-mediated social interaction, which confers intriguing trail patterns. In the absence of the cell-to-cell interaction, the equilibrium population density profile fits well to that of a simple Keller-Segal population dynamic model, in which a chemotactic current density J→chemo∼∇p competes with a normal diffusive current density J→diff∼∇ρ, where p and ρ refer to the concentration of chemoattractant and population density, respectively. We find that the cell-to-cell interaction confers a far more compact aggregation resulting in a much higher peak equilibrium cell density. The mathematical model system is applicable to many biological systems such as swarming microglia and neutrophils or accumulating ants towards a localized food source.     

A Variable Sampling Interval Synthetic Xbar Chart for the Process Mean

The usual practice of using a control chart to monitor a process is to take samples from the process with fixed sampling interval (FSI). In this paper, a synthetic X¯ control chart with the variable sampling interval (VSI) feature is proposed for monitoring changes in the process mean. The VSI synthetic X¯ chart integrates the VSI X¯ chart and the VSI conforming run length (CRL) chart. The proposed VSI synthetic X¯ chart is evaluated using the average time to signal (ATS) criterion. The optimal charting parameters of the proposed chart are obtained by minimizing the out-of-control ATS for a desired shift. Comparisons between the VSI synthetic X¯ chart and the existing X¯, synthetic X¯, VSI X¯ and EWMA X¯ charts, in terms of ATS, are made. The ATS results show that the VSI synthetic X¯ chart outperforms the other X¯ type charts for detecting moderate and large shifts. An illustrative example is also presented to explain the application of the VSI synthetic X¯ chart.