Mean Time Constant Research Articles

Application of advanced thermal analysis for characterization of crystalline and amorphous phases of carvedilol

The thermal behaviour of crystalline and amorphous carvedilol (CAR) phases was studied by advanced thermal analysis using Quantum Design Physical Property Measurement System and Differential Scanning Calorimetry. Theoretical functions describing crystalline carvedilol heat capacity at low temperatures and the Debye-Einstein function for high temperatures were obtained. Based on the experimental heat capacity values, solid and liquid baselines were established, and the state functions (H, S, G) for solid and liquid states were calculated. A comprehensive characterization of melting and glass transition processes was obtained. CAR is easily amorphizable by cooling the liquid. The residual entropy, which quantifies the extent of frozen-in disorder in the amorphous solid, for glassy CAR was estimated as 51 J·mol–1·K–1. The Kauzmann temperature (TK) was estimated based on enthalpy and entropy. Molecular motions in the amorphous phase were also studied. The activation energy for structural relaxation (Ea = 539 kJ·mol–1) and fragility parameter (m = 91) were obtained from the non-isothermal physical ageing. The isothermal physical ageing kinetics of amorphous CAR was studied by applying Kohlrausch-Williams-Watts (KWW) model. The mean molecular relaxation time constant (τKWW = 117 min) and relaxation constant (βKWW = 0.33) were obtained. CAR was classified as a fragile glass-former. Furthermore, τKWW constant for samples aged at 303.15 K is very low, thus, the physical ageing will occur during the short- and long-term storage of amorphous CAR, potentially changing its physicochemical properties during the ageing process. However, the results of molecular mobility studies (high molecular motions) show that the relationship between molecular motions in a glassy solid and its tendency to crystallization does not seem to follow an expected pattern, i.e., no crystallization occurred by thermal treatment of glassy, supercooled liquid and liquid phases of CAR as one would expect. Modern calorimetry and quantitative thermal analysis provided the fundamental kinetic and thermodynamic information about the crystalline and amorphous states of CAR.

Sestrin2 is an endogenous antioxidant that improves contractile function in the heart during exposure to ischemia and reperfusion stress

Sestrin2 (Sesn2) is a stress-inducible protein that plays a critical role in the response to ischemic stress. We recently recognized that Sesn2 may protect the heart against ischemic insults by reducing the generation of reactive oxygen species (ROS). After 45 min of ischemia followed by 24 h of reperfusion, myocardial infarcts were significantly larger in Sesn2 KO hearts than in wild-type hearts. Isolated cardiomyocytes from wild-type hearts treated with hypoxia and reoxygenation (H/R) stress showed significantly greater Sesn2 levels, compared with normoxic hearts (p < 0.05). Intriguingly, the administration of adeno-associated virus 9-Sesn2 into Sesn2 knockout (KO) hearts rescued Sesn2 protein levels and significantly improved the cardiac function of Sesn2 KO mice exposed to ischemia and reperfusion. The rescued levels of Sesn2 in Sesn2 KO hearts significantly ameliorated ROS generation and the activation of ROS-related stress signaling pathways during ischemia and reperfusion. Moreover, the rescued Sesn2 levels in Sesn2 KO cardiomyocytes improved the maximal velocity of cardiomyocyte shortening by H/R stress. Rescued Sesn2 levels also improved peak height, peak shortening amplitude, and maximal velocity of the re-lengthening of Sesn2 KO cardiomyocytes subjected to H/R. Finally, the rescued Sesn2 levels significantly augmented intracellular calcium levels and reduced the mean time constant of transient calcium decay in Sesn2 KO cardiomyocytes exposed to H/R. Overall, these findings indicated that Sesn2 can act as an endogenous antioxidant to maintain intracellular redox homeostasis under ischemic stress conditions.

Suite of methods for assessing inner retinal temporal dynamics across spatial and temporal scales in the living human eye.

.Significance: There are no label-free imaging descriptors related to physiological activity of inner retinal cells in the living human eye. A major reason is that inner retinal neurons are highly transparent and reflect little light, making them extremely difficult to visualize and quantify.Aim: To measure physiologically-induced optical changes of inner retinal cells despite their challenging optical properties.Approach: We developed an imaging method based on adaptive optics and optical coherence tomography (AO-OCT) and a suite of postprocessing algorithms, most notably a new temporal correlation method.Results: We captured the temporal dynamics of entire inner retinal layers, of specific tissue types, and of individual cells across three different timescales from fast (seconds) to extremely slow (one year). Time correlation analysis revealed significant differences in time constant (up to 0.4 s) between the principal layers of the inner retina with the ganglion cell layer (GCL) being the most dynamic. At the cellular level, significant differences were found between individual GCL somas. The mean time constant of the GCL somas () was smaller than that of nerve fiber bundles and inner plexiform layer synapses and processes. Across longer durations, temporal speckle contrast and time-lapse imaging revealed motion of macrophage-like cells (over minutes) and GCL neuron loss and remodeling (over one year).Conclusions: Physiological activity of inner retinal cells is now measurable in the living human eye.

Differences in Transient Thermal Response of Commercial Esophageal Temperature Probes: Insights From an Experimental Study.

The purpose of this study was to evaluate the differences in transient thermal response (TTR) among various types of commercial esophageal temperature probes (ETPs) in the United States in an experimental model. There is little information regarding the variation in TTR among various commercial ETPs that are approved for atrial fibrillation ablation. We compared various thermodynamic characteristics including, mean thermal time constant (τ), time to rise 1°C (T1°C), timetopeak temperature (Tpeak), and decay time among 22 different ETPs. Each probe was submerged in a constant-temperature water bath maintained at 37 ± 0.5°C and then quickly (<0.5 s) submerged into another water bathat 45 ± 0.5°C. The experiments were repeated 3 times with each probe. TTR properties were compared on the basis of probe size, design, and number of sensors. The τ was significantly higher with the larger 24- and 18-F ETPs compared with the smaller 9-F ETPs. Compared with the 18-F probe, T1°C (11.9s vs. 5 s), Tpeak (40.3s vs. 14.4 s), and Tdecay (92.4s vs. 32.4 s) was shorter with the 9-F ETPs. Solid-shaft ETPs had shorter τ (8.6s vs. 20.5 s), T1°C (4.4s vs. 10.1 s) and Tpeak (13.5s vs. 32.5 s) compared with acoustascopes. Multisensor ETPs had shorter τs (3.9s vs. 9.1 s), T1°C (2.3s vs. 5 s), and Tpeak (6.2s vs. 14.4 s) compared with single-sensor ETPs. There is a significant variation in TTR among the various commercially available ETPs. The use of certain ETPs might result in underestimation of luminal esophageal temperature, which can potentially lead to adverse events.

Pharmacological characterization of a homomeric nicotinic acetylcholine receptor formed by Ancylostoma caninum ACR-16.

Parasitic nematode infections are treated using anthelmintic drugs, some of which target nicotinic acetylcholine receptors (nAChRs) located in different parasite tissues. The limited arsenal of anthelmintic agents and the prevalence of drug resistance imply that future defense against parasitic infections will depend on the discovery of novel targets and therapeutics. Previous studies have suggested that Ascaris suum ACR-16 nAChRs are a suitable target for the development of antinematodal drugs. In this study, we characterized the pharmacology of the Ancylostoma caninum ACR-16 receptor using two-electrode voltage-clamp electrophysiology. This technique allowed us to study the effects of cholinergic agonists and antagonists on the nematode nAChRs expressed in Xenopus laevis oocytes. Aca-ACR-16 was not sensitive to many of the existing cholinomimetic anthelmintics (levamisole, oxantel, pyrantel, and tribendimidine). 3-Bromocytisine was the most potent agonist (> 130% of the control acetylcholine current) on the Aca-ACR-16 nAChR but, unlike Asu-ACR-16, oxantel did not activate the receptor. The mean time constants of desensitization for agonists on Aca-ACR-16 were longer than the rates observed in Asu-ACR-16. In contrast to Asu-ACR-16, the A. caninum receptor was completely inhibited by DHβE and moderately inhibited by α-BTX. In conclusion, we have successfully reconstituted a fully functional homomeric nAChR, ACR-16, from A. caninum, a model for human hookworm infections. The pharmacology of the receptor is distinct from levamisole-sensitive nematode receptors. The ACR-16 homologue also displayed some pharmacological differences from Asu-ACR-16. Hence, A. caninum ACR-16 may be a valid target site for the development of anthelmintics against hookworm infections.

Abdominal obesity linked to a longer cone-mediated dark-adaptation recovery time in healthy eyes

Obesity has been associated with abnormal lipid metabolism and with tissue hypoxia. Human Bruch's membrane (BrM) lipid deposits have been proposed to create a diffusion barrier to metabolic exchange between the choroid and photoreceptors, delaying the regeneration of photopigments. The speed of retinal dark adaptation (DA) is dependent on the regeneration of these photopigments. While the retina is extremely sensitive to hypoxia, the inner retina, which encodes visual contrast, is more affected by hypoxia than the outer retina. This study examines the association between adiposity measures and the time course of DA measured psychophysically through contrast detection to test the functionality of both the outer and inner retina. Cone-mediated DA recovery of contrast threshold (CT) was measured following near-total photopigment bleach for 6 min in 52 healthy eyes of 52 individuals (42.6 ± 18.3 years). Stimuli were sine-wave gratings of low-spatial frequency (1 cycle-per-degree (cpd)) and low luminance (1 cd/m2) generated at the centre of a CRT monitor. CT recovery functions were fitted to an exponential decay model to determine the time constant (τ, seconds) of cone sensitivity recovery, final cone CT (CTf) and CT elevation (CT0). Weight, height and waist circumference (WC) were measured and body mass index (BMI) and waist-to-height ratio (WHtR) calculated. Relationships were examined through Spearman correlation and through multiple linear regression using age, optical and adiposity measures as independent variables. The repeatability of cone time constant measurements was estimated by the Bland-Altman method and reported as the coefficient of repeatability (CoR). Mean ± SD of time constant and CTf were 57.3 ± 27.7 s and −1.78 ± 0.20 log10 units respectively. Cone time constant showed positive Spearman correlation with WC (p = 0.008) and WHtR (p = 0.023) but not with BMI (p = 0.058). Only WHtR emerged as an independent predictor of time constant (p = 0.001). CTf was not correlated with any adiposity measures. Mean cone time constant was 41 s slower in subjects (25%, n = 13) with abdominal obesity (WHtR≥0.5). Mean CTf was not significantly different in subjects with or without abdominal obesity. CoR for cone time constant was ±16 s. In adult subjects, greater abdominal obesity (WHtR) was related to a longer contrast recovery time for cone-mediated DA (time to dark-adapt) suggesting outer retinal dysfunction. Final contrast threshold, preferentially processed by inner retinal cells, was unaffected by abdominal obesity.

Non-invasive estimation of muscle oxygen uptake kinetics with pseudorandom binary sequence and step exercise responses.

The aim of the study was to test for significant differences in non-invasively estimated muscle oxygen uptake ([Formula: see text]) kinetics, assessed by a square-wave exercise protocol (STEP) as well as by a time series approach with pseudorandom binary sequence (PRBS) work rate (WR) changes. Seventeen healthy and active individuals (10 women, 7 men; 23 ± 2years old; height 175 ± 11cm; body mass 73 ± 14kg [mean ± SD]) completed five repetitions of WR transitions from 30 to 80W for the STEP approach and two sequences of pseudorandom binary WR changes between 30 and 80W for the PRBS approach. Pulmonary oxygen uptake ([Formula: see text]) was measured breath by breath. [Formula: see text] kinetics were estimated during phase II [Formula: see text] in the STEP approach and during the pseudorandom binary sequence WR changes in the PRBS approach. No significant differences were observed between different models of the STEP and the PRBS approach for estimation of [Formula: see text] kinetics (p > 0.05). In addition, a very high variability between the models was determined for [Formula: see text] kinetics [mean time constants (τ) difference: - 2.5 ± 11.4s]. A significant correlation for τ of [Formula: see text] between the STEP approach with experimentally determined phase I [Formula: see text] lengths and the PRBS approach was noticed (r = 0.536; p < 0.05). Both approaches (STEP and PRBS) are not significantly different for estimating the [Formula: see text] kinetics, but the very high variability impairs the predictability between the models. However, the determination of the length of phase I [Formula: see text] should be as appropriate as possible because predefined duration lengths can result in overestimations in [Formula: see text] kinetics.

Investigation on transient temperature of a reciprocating compressor based on a two-thermocouple probe

Measuring transient pressure and temperature simultaneously inside a compressor can lead to a thorough characterization of the thermodynamic process in the compressor. However, the rapid changes in airflow temperature make it difficult to measure these conditions precisely, partly due to large thermal inertia of common thermometers such as thermistors and thermocouples. Measurement of rapid temperature changes requires thermometers that have a time constant of a few microseconds or less. Therefore, in this study, two fine wire thermocouples 18 and 35 μm in diameter, respectively, were prepared in advance. A two-thermocouple probe consisting of these two fine wire thermocouples was then used to measure the transient temperature of airflow in the working chamber of a reciprocating compressor. The temperatures detected by the two-thermocouple probe were used to reconstruct the true temperatures. Mean and fluctuating time constants were both evaluated and used to compensate for the raw temperatures. The estimated mean time constants of the two thermocouples were 9.98 and 29.97 ms at 420 rpm, respectively. The maximum difference between the two reconstructed temperatures was 9.7 °C, with an average value of 2.4 °C. Cycle-by-cycle variations of the transient temperatures were also measured.

In vitro characterization of cell-level neurophysiological diversity in the rostral nucleus reuniens of adult mice.

The nucleus reuniens (Re), a nucleus of the midline thalamus, is part of a cognitive network including the hippocampus and the medial prefrontal cortex. To date, very few studies have examined the electrophysiological properties of Re neurons at a cellular level. The majority of Re neurons exhibit spontaneous action potential firing at rest. This is independent of classical amino-acid mediated synaptic transmission. When driven by various forms of depolarizing current stimulus, Re neurons display considerable diversity in their firing patterns. As a result of the presence of a low threshold Ca2+ channel, spike output functions are strongly modulated by the prestimulus membrane potential. Finally, we describe a novel form of activity-dependant intrinsic plasticity that eliminates the high-frequency burst firing present in many Re neurons. These results provide a comprehensive summary of the intrinsic electrophysiological properties of Re neurons allowing us to better consider the role of the Re in cognitive processes. The nucleus reuniens (Re) is the largest of the midline thalamic nuclei. We have performed a detailed neurophysiological characterization of neurons in the rostral Re of brain slices prepared from adult male mice. At resting potential (-63.7±0.6mV), ∼90% of Re neurons fired action potentials, typically continuously at ∼8Hz. Although Re neurons experience a significant spontaneous barrage of fast, amino-acid-mediate synaptic transmission, this was not predominantly responsible for spontaneous spiking because firing persisted in the presence of glutamate and GABA receptor antagonists. With resting potential preset to -80mV, -20pA current injections revealed a mean input resistance of 615MΩ and a mean time constant of 38ms. Following cessation of this stimulus, a significant rebound potential was seen that was sometimes sufficiently large to trigger a short burst of very high frequency (100-300Hz) firing. In most cells, short (2ms), strong (2nA) current injections elicited a single spike followed by a large afterdepolarizing potential which, when suprathreshold, generated high-frequency spiking. Similarly, in the majority of cells preset at -80mV, 500ms depolarizing current injections to cells led to a brief initial burst of very high-frequency firing, although this was lost when cells were preset at -72mV. Biophysical and pharmacological experiments indicate a prominent role for T-type Ca2+ channels in the high-frequency bursting of Re neurons. Finally, we describe a novel form of activity-dependent intrinsic plasticity that persistently eliminates the burst firing potential of Re neurons.

Nominal Carbonic Anhydrase Activity Mitigates Airway‐Surface Liquid pH Changes During the Respiratory Cycle

The airway‐surface liquid pH (pHASL) is slightly acidic relative to the plasma pH and becomes more acidic in airway disease (e.g., cystic fibrosis, asthma, and COPD). Pathological pHASL may dysregulate ASL viscosity, mucociliary transport, and bacterial killing. Under constant 5% CO2, porcine large airways are more acidic (~7.0) than small airways (~7.4). However, the small airways are exposed to a constant 5% CO2, whereas the large airways are exposed to wide swings in pCO2 during respiration. Therefore, pHASL in the large airway may oscillate and be more alkaline during respiration. In this study, we investigated how oscillating CO2 affects the large airway pHASL for differentiated porcine tracheal epithelia cultured at the airway‐liquid interface. The apical surface of epithelia was initially exposed to 5% CO2. Apical CO2 was then rapidly switched to 0.04% CO2, allowed to equilibrate, and was then returned to 5% CO2. The pH was monitored by SNARF‐1 dextran fluorescence. Relative to a breath (~4 s), the time constant for pH changes were unexpectedly slow (τ = 51.9 ± 5.8 s, n = 12). We hypothesize that this slow time constant might be due to low carbonic anhydrase activity, which catalyzes the carbonic buffering reaction. Consistent with this hypothesis, the carbonic anhydrase inhibitor acetazolamide did not appreciably change the time constant (τ = 64.1 ± 6.1 s, n = 10; p = 0.21 vs. non‐treated). In contrast, adding exogenous carbonic anhydrase strikingly decreased the mean time constant (τ = 17.3 ± 3.1 s, n = 16; p &lt; 0.01 vs. non‐treated). Curated mRNA microarray data indicated nominal expression for all extracellular and secreted carbonic anhydrase isoforms in large airway epithelia. To further understand how CO2 affects pHASL in the large airway, we modeled the pHASL during respiration using the pH‐dependent rates (dph/dt) obtained from our functional experiments. There were three major findings from our simulations. First, under physiological conditions (inspiratory:expiratory ratio = 1:2; respiration rate = 15 breathes per minute), the pHASL oscillations were small (peak‐to‐peak pHASL = 0.09 ± 0.02 pH units). In contrast, adding carbonic anhydrase increased the pHASL oscillations (peak‐to‐peak pHASL = 0.56 ± 0.16 pH units). Second, correcting the large airway steady‐state pHASL for the respiratory cycle still yields an acidic pHASL relative to the small airway (pHlarge 7.05 vs. pHsmall 7.45). Third, the inspiratory:expiratory ratio affected the average pHASL, whereas the respiration rate affected the magnitude of pHASL oscillations. Thus, minimal carbonic anhydrase activity in large airways prevents sizeable shifts in pHASL during respiration. Maintaining relatively constant pHASL may optimize airway host defense by antimicrobials and mucociliary transport.Support or Funding InformationNIH HL091842, NIH HL5167, CF Foundation LI1410

Body sway adaptation to addition but not withdrawal of stabilizing visual information is delayed by a concurrent cognitive task.

The aim of this study was to test the effects of a concurrent cognitive task on the promptness of the sensorimotor integration and reweighting processes following addition and withdrawal of vision. Fourteen subjects stood in tandem while vision was passively added and removed. Subjects performed a cognitive task, consisting of counting backward in steps of three, or were "mentally idle." We estimated the time intervals following addition and withdrawal of vision at which body sway began to change. We also estimated the time constant of the exponential change in body oscillation until the new level of sway was reached, consistent with the current visual state. Under the mentally idle condition, mean latency was 0.67 and 0.46 s and the mean time constant was 1.27 and 0.59 s for vision addition and withdrawal, respectively. Following addition of vision, counting backward delayed the latency by about 300 ms, without affecting the time constant. Following withdrawal, counting backward had no significant effect on either latency or time constant. The extension by counting backward of the time interval to stabilization onset on addition of vision suggests a competition for allocation of cortical resources. Conversely, the absence of cognitive task effect on the rapid onset of destabilization on vision withdrawal, and on the relevant reweighting time course, advocates the intervention of a subcortical process. Diverting attention from a challenging standing task discloses a cortical supervision on the process of sensorimotor integration of new balance-stabilizing information. A subcortical process would instead organize the response to removal of the stabilizing sensory input.NEW & NOTEWORTHY This study is the first to test the effect of an arithmetic task on the time course of balance readjustment following visual withdrawal or addition. Performing such a cognitive task increases the time delay following addition of vision but has no effect on withdrawal dynamics. This suggests that sensorimotor integration following addition of a stabilizing signal is performed at a cortical level, whereas the response to its withdrawal is "automatic" and accomplished at a subcortical level.

Competitive Excimer Formation and Energy Transfer in Zr-Based Heterolinker Metal-Organic Frameworks.

The spectroscopy and dynamics of a series of Zr-based MOFs in dichloromethane suspension are reported. These Zr-NADC MOFs were constructed by using different mixtures of 2,6-naphthalenedicarboxylate (NDC) and 4-amino-2,6-naphthalenedicarboxylate (NADC) as organic linkers. The fraction of NADC relative to NDC in these heterolinker MOFs ranges from 2 to 35 %. The results indicate two competitive photoprocesses: NDC excimer formation and an energy transfer (ET) from excited NDC linkers to NADC linkers. Increasing the fraction of NADC linkers in the Zr-NADC nanostructure decreases the mean time constant of NDC excimer formation, while the NADC emission intensity experiences a drop at the highest fraction of this linker in the MOF. The first observation is explained by an increase in the energy-transfer probability between the two linkers, and the second by emission quenching in the NADC linkers due to ultrafast charge transfer assisted by the amino group. Femtosecond time-resolved emission studies showed that the ET process (recorded as decaying and rising components) from excited NDC to NADC takes place in 1.2 ps. Direct excitation of the NADC linkers (at 410 nm) shows a decaying, but not rising, component of 250-480 fs, which could reflect the formation of a nonemissive charge-separation state. The results show that by using MOFs having heterolinkers it is possible to trigger and tune excimer formation and ET processes.

Expiratory Time Constant and Sleep Apnea Severity in the Overlap Syndrome.

Lung mechanics in the overlap of COPD and sleep apnea impact the severity of sleep apnea. Specifically, increased lung compliance with hyperinflation protects against sleep apnea, whereas increased airway resistance worsens sleep apnea. We sought to assess whether the expiratory time constant, which reflects lung mechanics, is associated with sleep apnea severity in such patients. Polysomnographies in 34 subjects with the overlap syndrome were reviewed. Three time constants were measured for each of up to 5 stages (wake, NREM stages, and REM). The time constants were derived by fitting time and pressure coordinates on the expiratory portion of a nasal pressure signal along an exponentially decaying equation, and solving for the time constant. Demographics, morphometrics, wake end-tidal CO2, right diaphragmatic arc on a chest radiograph, and the apnea-hypopnea index (AHI) were recorded. The time constant was not associated with age, gender, body mass index, right diaphragmatic arc, or wake end-tidal CO2, and was not significantly different between sleep stages. A mean time constant (TC) was therefore obtained. Subjects with a TC > 0.5 seconds had a greater AHI than those with a TC ≤ 0.5 seconds (median AHI 58 vs. 18, respectively, p = 0.003; Odds ratio of severe sleep apnea 10.6, 95% CI 3.9-51.1, p = 0.005). A larger time constant in the overlap syndrome is associated with increased odds of severe sleep apnea, suggesting a greater importance of airway resistance relative to lung compliance in sleep apnea causation in these subjects.

The Modulation of Cardiac Contractile Function by the Pharmacological and Toxicological Effects of Urocortin2.

Urocortin2 (Ucn2) has been revealed to enhance cardiac function in heart failure. However, the pharmacological and toxicological effects of Ucn2 on cardiomyocytes are incompletely understood. In this study, we investigated the possible mechanisms of Ucn2 on mediating the contractility of cardiomyocytes. Mechanical properties and intracellular Ca(2+) properties were measured in isolated cardiomyocytes from different treatment groups. The stress signaling was evaluated using Western blot. The results demonstrated that Ucn2 induced maximal velocity of shortening (+dL/dt), peak height, peak shortening (PS) amplitude, maximal velocity of relengthening (-dL/dt), accompanied by a significant rise in intracellular Ca(2+) level and a fall of the mean time constant of Ca(2+) transient decay (Tau) in WT cardiomyocytes. However, these effects were abolished by preincubation of type 2 CRF receptors (CRFR2) antagonist anti-sauvagine 30 (a-SVG-30). We also found that Ucn2 treatment activated the AMPK pathway in isolated cardiomyocytes via CRFR2. Furthermore, Ucn2 induced protein kinase A (PKA) and phospholamban (PLN) phosphorylation. Pretreatment of PKA inhibitor H89 reduced the inotropic and lusitropic effects of Ucn2 as well as decreased the intracellular Ca(2+) load and slowed down the Ca(2+) transient decay. We also showed that preincubation of Compound C, an inhibitor of AMPK, inhibited the phosphorylation of PKA and the intracellular Ca(2+) level in cardiomyocytes without affecting the contractile function and the Tau of cardiomyocytes. Taken together, it suggests that Ucn2 facilitate the contractility of cardiomyocytes via activating both AMPK and PKA.

The contribution of dynamic changes in photosynthesis to shade tolerance of two conifer species.

Generally 'shade tolerance' refers to the capacity of a plant to exist at low light levels but characteristics of shade can vary and must be taken into account in defining the term. We studied Abies amabilis Dougl. ex J.Forbes and Tsuga heterophylla (Raf.) Sarg. under a forest canopy in the northwest of the Olympic Peninsula, USA, which has low annual sunshine hours and frequent overcast days. Using BF3 sunshine sensors, we surveyed diffuse and total light received by saplings growing under a range of canopy openness up to 30%. We measured variation in photosynthetic capacity over the growing season and within days and estimated photosynthesis induction in relation to ambient light. Three components of shade tolerance are associated with variation in light climate: (i) Total light on the floor of an 88-year stand of naturally regenerated T. heterophylla was greater on overcast than clear days. Light on overcast days varied throughout the day sometimes with a cyclical pattern. (ii) Photosynthetic capacity, Amax, varied both through the growing season and within days. Amax was generally greater in the latter part of the growing season, being limited by temperature and stomatal conductance, gs, at times during the early part. Saplings in more shaded areas had lower Amax and in the latter part of the growing season Amax was found to decline from mid-afternoon. (iii) Two patterns of photosynthesis induction to increased light were found. In a mean ambient light of 139 μmol m(-2) s(-1), induction had a curvilinear response to a step increase in light with a mean time constant, τ, of 112.3 s. In a mean ambient light of 74 μmol m(-2) s(-1), induction had a two-part increase: one with τ1 of 11.3 s and the other with τ2 of 184.0 s. These are the smallest published values of τ to date. (iv) Both variation in photosynthetic capacity and induction are components of shade tolerance where light varies over time. Amax acclimates to seasonal and diurnal changes in light and varies between microenvironments. The rapid induction processes can cause a rapid response of photosynthesis to changes in diffuse or direct light.

Glucose Sensing in the Peritoneal Space Offers Faster Kinetics Than Sensing in the Subcutaneous Space

The paramount goal in the treatment of type 1 diabetes is the maintenance of normoglycemia. Continuous glucose monitoring (CGM) technologies enable frequent sensing of glucose to inform exogenous insulin delivery timing and dosages. The most commonly available CGMs are limited by the physiology of the subcutaneous space in which they reside. The very same advantages of this minimally invasive approach are disadvantages with respect to speed. Because subcutaneous blood flow is sensitive to local fluctuations (e.g., temperature, mechanical pressure), subcutaneous sensing can be slow and variable. We propose the use of a more central, physiologically stable body space for CGM: the intraperitoneal space. We compared the temporal response characteristics of simultaneously placed subcutaneous and intraperitoneal sensors during intravenous glucose tolerance tests in eight swine. Using compartmental modeling based on simultaneous intravenous sensing, blood draws, and intraarterial sensing, we found that intraperitoneal kinetics were more than twice as fast as subcutaneous kinetics (mean time constant of 5.6 min for intraperitoneal vs. 12.4 min for subcutaneous). Combined with the known faster kinetics of intraperitoneal insulin delivery over subcutaneous delivery, our findings suggest that artificial pancreas technologies may be optimized by sensing glucose and delivering insulin in the intraperitoneal space.

Measurement of cone dark adaptation: a comparison of four psychophysical methods

Dark adaptometry is an important clinical tool for the diagnosis of a range of conditions, including age-related macular degeneration. In order to identify the most robust, clinically applicable technique for the measurement of cone dark adaptation, the repeatability and agreement of four psychophysical methods were assessed. Data were obtained from 31 healthy adults on two occasions, using four psychophysical methods. Participants' pupils were dilated, and 96% of cone photopigment was bleached before threshold was monitored in the dark using one of the techniques, selected at random. This procedure was repeated for each of the remaining methods. An exponential recovery function was fitted to all threshold recovery data. The coefficient of repeatability (CoR) was calculated to assess the repeatability of the methods, and a repeated-measures analysis of variance was used to compare mean recovery parameters. All four methods demonstrated a similar level of intersession repeatability for measurement of cone recovery, yielding CoRs between 1.18 and 1.56min. There were no statistically significant differences in estimates of mean time constant of cone recovery (cone τ) between the four methods (p=0.488); however, significant differences between initial and final cone thresholds were reported (p<0.005). All of the techniques were capable of monitoring the rapid changes in visual threshold that occur during cone dark adaptation, and the repeatability of the techniques was similar. This indicates that despite the respective advantages and disadvantages of these psychophysical techniques, all four methods would be suitable for measuring cone dark adaptation in clinical practice.

Visual fatigue effects on vergence dynamics in asymptomatic individuals

To evaluate objectively changes in vergence dynamics following intentional visual fatiguing tasks using congruent (C) and non-congruent (NC) vergence stimulus demands. Pre- and post-task vergence dynamics to a 10.3° disparity stimulus were recorded objectively in 12 adult, asymptomatic individuals for both convergence and divergence. There were two fatigue-inducing tasks: Congruent or C-task: Subjects altered bifixation (50 cycles) between reduced Snellen charts at 2 m and at 20 cm every 3 s. Non-congruent or NC task: Subjects performed 50 cycles of vergence flipper (7Δ BO/BI), while bifixating a reduced Snellen chart at 40 cm. Pre- and post-task mean amplitude, time constant, peak velocity, and steady-state response variability were compared. There was a significant increase in mean post-task, steady-state response variability for both the C and NC tasks. However, there were no significant group differences for either convergence or divergence between the pre- and post-mean amplitude, time constant, and peak velocity parameters for both the C and NC tasks, although post-task peak velocity was consistently reduced. Steady-state vergence response variability was found to be the critical objective parameter to demonstrate significant fatigue effects in the group. Peak velocity was also consistently reduced to a small extent in the NC task. We speculate that these fatigue effects are of a central, and not of peripheral, origin.

Thermometry of Red Blood Cell Concentrate: Magnetic Resonance Decoding Warm Up Process

PurposeTemperature is a key measure in human red blood cell concentrate (RBC) quality control. A precise description of transient temperature distributions in RBC units removed from steady storage exposed to ambient temperature is at present unknown. Magnetic resonance thermometry was employed to visualize and analyse RBC warm up processes, to describe time courses of RBC mean, surface and core temperatures by an analytical model, and to determine and investigate corresponding model parameters.MethodsWarm-up processes of 47 RBC units stored at 1–6°C and exposed to 21.25°C ambient temperature were investigated by proton resonance frequency thermometry. Temperature distributions were visualized and analysed with dedicated software allowing derivation of RBC mean, surface and core temperature-time courses during warm up. Time-dependence of mean temperature was assumed to fulfil a lumped capacitive model of heat transfer. Time courses of relative surface and core temperature changes to ambient temperature were similarly assumed to follow shifted exponential decays characterized by a time constant and a relative time shift, respectively.ResultsThe lumped capacitive model of heat transfer and shifted exponential decays described time-dependence of mean, surface and core temperatures close to perfect (mean R2 were 0.999±0.001, 0.996±0.004 and 0.998±0.002, respectively). Mean time constants were τ mean = 55.3±3.7 min, τ surface = 41.4±2.9 min and τ core = 76.8±7.1 min, mean relative time shifts were Δsurface = 0.07±0.02 and Δcore = 0.04±0.01. None of the constants correlated significantly with temperature differences between ambient and storage temperature.ConclusionLumped capacitive model of heat transfer and shifted exponential decays represent simple analytical formulas to describe transient mean, surface and core temperatures of RBC during warm up, which might be a helpful tool in RBC temperature monitoring and quality control. Independence of constants on differences between ambient and storage temperature suggests validity of models for arbitrary storage and ambient temperatures.

Visual Fatigue and Accommodative Dynamics in Asymptomatic Individuals

To evaluate accommodative dynamics immediately before and after visual fatigue-inducing tasks with congruent (C) and noncongruent (NC) visual stimuli. Accommodative dynamics for a 2-diopter (D) step (2.5 ↔ 4.5 D) stimulus were assessed using the WAM-5500 open-field autorefractor in 10 visually normal, asymptomatic, young-adult subjects before and after C and NC tasks performed on different days in a counterbalanced manner. For the C task, subjects altered binocular fixation (50 cycles) between reduced Snellen charts at 50 and 20 cm every 3 seconds to the beat of a metronome. For the NC task, subjects performed 50 cycles of accommodative flipper (± 1.5 D) as rapidly as possible while binocularly fixating on a reduced Snellen chart at 40 cm. Mean steady-state (SS) response level reflecting its accuracy was significantly (p ≤ 0.05) reduced post-NC task for both increasing (4.5-D level) and decreasing (2.5-D) accommodation. Although the SS response variability was significantly (p ≤ 0.05) increased post-NC task at the 4.5-D stimulus level, it did not change significantly (p > 0.05) for the C task. There were no significant differences between the pretask and posttask group mean initial amplitude, time constant, and peak velocity for either the C or the NC task for both increasing and decreasing accommodation. The accommodative system exhibited consistent fatigue effects with respect to SS variability and response accuracy. There was no objective evidence of oculomotor learning for these specific tasks.