Exponential Time Constant Research Articles

Abstract Mo105: End Systolic Pressure and Ejection Timing Correlate with Impaired Relaxation

Impaired relaxation is a common feature in most cases of diastolic dysfunction, including heart failure with preserved ejection fraction. Isovolumetric relaxation is typically characterized by τ, an exponential time constant, but may be broken into relaxation and stiffness-like parameters (µ and Ek). Recent in vitro work suggests that strain during late systole (protodiastolic period) modifies relaxation. We hypothesize that late systolic pressure and time indexes correlate with myocardial relaxation. Thirty-four (34) simultaneous aortic and left ventricular micromanometric (Millar) pressure traces were obtained from a comprehensive database of clinical cardiac catheterization patients. These patients underwent coronary artery disease screening and presented but did not have arterial blockages. Pressure and time parameters were calculated over a five-minute interval. Relaxation rate (1/τ), and stiffness (Ek) correlated to end systolic parameters in an orthogonal pattern to relaxation (µ). 1/τ showed strong correlations with time from peak pressure to aortic valve divided by ejection time (t54/t52, r = .675, p < .01) and moderate correlation to the pressure decline after peak pressure to aortic valve pressure divided by the pulse pressure (P45/P42, r = .577, p < .01). In parallel Ek showed moderate correlation with t54/t52 (r = .592, p < .01), and a moderate correlation with P45/P42 (r = .470, p < .01), the pressure at aortic valve closure (r = -.420, p < .05), and aortic augmentation index (AIx, r = -.360, p < .05). Finally, µ presented a moderate correlation to P45/P42 (r = .501, p < .05), the pressure at aortic valve closure (r = .404, p < .05), and AIx (r = -.357, p < .05). As predicted, ventricular relaxation in patients correlates with late systolic hemodynamics. Parameters or combinations of parameters may predict relaxation rates or correlate to in vivo late systolic strain. Prospective studies evaluating end systolic strain and relaxation merit consideration. Overall, these observations are consistent with in vitro studies that suggest that impaired cessation of contraction is a regulator of relaxation.

Inverter PQ Control With Trajectory Tracking Capability for Microgrids Based on Physics-Informed Reinforcement Learning

The increasing penetration of inverter-based resources (IBRs) calls for an advanced active and reactive power (PQ) control strategy in microgrids. To enhance the controllability and flexibility of the IBRs, this paper proposed an adaptive PQ control method with trajectory tracking capability, combining model-based analysis, physics-informed reinforcement learning (RL), and power hardware-in-the-loop (HIL) experiments. First, model-based analysis proves that there exists an adaptive proportional-integral controller with time-varying gains that can ensure any exponential PQ output trajectory of IBRs. These gains consist of a constant factor and an exponentially decaying factor, which are then obtained using a model-free deep reinforcement learning approach known as the twin delayed deeper deterministic policy gradient. With the model-based derivation, the learning space of the RL agent is narrowed down from a function space to a real space, which reduces the training complexity significantly. Finally, the proposed method is verified through numerical simulation in MATLAB-Simulink and power HIL experiments in the CURENT center.With the physics-informed learning method, exponential response time constants can be freely assigned to IBRs, and they can follow any predefined trajectory without complicated gain tuning.

Exponential history integration with diverse temporal scales in retrosplenial cortex supports hyperbolic behavior.

Animals use past experience to guide future choices. The integration of experiences typically follows a hyperbolic, rather than exponential, decay pattern with a heavy tail for distant history. Hyperbolic integration affords sensitivity to both recent environmental dynamics and long-term trends. However, it is unknown how the brain implements hyperbolic integration. We found that mouse behavior in a foraging task showed hyperbolic decay of past experience, but the activity of cortical neurons showed exponential decay. We resolved this apparent mismatch by observing that cortical neurons encode history information with heterogeneous exponential time constants that vary across neurons. A model combining these diverse timescales recreated the heavy-tailed, hyperbolic history integration observed in behavior. In particular, the time constants of retrosplenial cortex (RSC) neurons best matched the behavior, and optogenetic inactivation of RSC uniquely reduced behavioral history dependence. These results indicate that behavior-relevant history information is maintained across multiple timescales in parallel and that RSC is a critical reservoir of information guiding decision-making.

A high time-resolution analysis of the Ground-Level Enhancement (GLE) of 23 February 1956 in terms of the CSHKP standard flare model

The original real-time analog heritage data from the Huancayo recording ionization chamber is differentiated to yield 15–60 s resolution of the first 15 min of the cosmic ray Ground-Level Event (GLE) of 23 February 1956. The initial High-Energy Impulsive (HEI) event of >12.5–20 GeV solar cosmic rays has a rise time of 2 min 15 s with an exponential rise time constant of 49 s, a fluctuating peak pulse of duration 5–7 min, followed by an abrupt decrease of <1 min duration to ∼33% of the peak flux. Detailed analysis of these data shows close consistency with the Carmichael-Sturrock-Hirayama-Kopp-Pneuman (CSHKP) standard flare model. The <49-second acceleration time to >12.5 GeV is explicable in terms of any one of three separate mechanisms: super-Dreier electric acceleration, statistical (Fermi first order), and shock acceleration deep in the corona. The fluctuating solar cosmic ray flux, the abrupt cessation, and the strong cosmic ray anisotropy on arrival at Earth are consistent with the acceleration event consisting of a sequence of short-lived reconnection events within the parent active center. In addition, the HEI event had a duration and time domain profile similar to the gyro-synchrotron emission from electrons associated with the initial acceleration event in the CSHKP model, and the observation of a white light flare towards the end of the microwave pulse. The properties of the GLE-5 HEI event are similar to those accompanying ten other previously studied large GLEs to the west of 240 West on the solar disk. We conclude that the historic high-resolution data from the GLE on 23 February 1956 demonstrate previously unknown properties of the HEI event that are all consistent with cosmic ray acceleration to 25 GeV by the CSHKP and similar flare magnetic reconnection models. A slowly varying and smaller increase commenced 6 min after the commencement of the HEI event and rose steadily to a maximum ∼40 min later. This is consistent with several models of acceleration in association with the coronal mass ejection generated by the flare.

A-luminescence in CsI:Tl crystal excited by pulsed electron beam

The amplitude-time parameters of the A-luminescence at 3.12 eV are studied for CsI:Tl irradiated by a pulsed electron beam at temperatures 77–295 K. It has been established that the 3.12 eV band kinetics varies differently with temperature in two temperature ranges of 77–170 K and 170–295 K. The increase in temperature from 77 K to 170 K causes the decrease in the exponential decay time constant, while at temperatures above 170 K, there appeared the post-radiation rise stage followed by the slow exponential decay stage. The temperature behavior of the A-luminescence kinetics is interpreted in term of the model, according to which (i) the A band is due to the allowed electron transition 61P1 → 61S0 of Tl+ ions and (ii) the main excitation mechanism across the entire cathodoluminescence spectrum of CsI:Tl at temperatures near room temperature is the spontaneous disintegration of donor–acceptor dipoles [Tl0Vk].

Efficient SABRE-SHEATH Hyperpolarization of Potent Branched-Chain-Amino-Acid Metabolic Probe [1-13C]ketoisocaproate.

Efficient 13C hyperpolarization of ketoisocaproate is demonstrated in natural isotopic abundance and [1-13C]enriched forms via SABRE-SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei). Parahydrogen, as the source of nuclear spin order, and ketoisocaproate undergo simultaneous chemical exchange with an Ir-IMes-based hexacoordinate complex in CD3OD. SABRE-SHEATH enables spontaneous polarization transfer from parahydrogen-derived hydrides to the 13C nucleus of transiently bound ketoisocaproate. 13C polarization values of up to 18% are achieved at the 1-13C site in 1 min in the liquid state at 30 mM substrate concentration. The efficient polarization build-up becomes possible due to favorable relaxation dynamics. Specifically, the exponential build-up time constant (14.3 ± 0.6 s) is substantially lower than the corresponding polarization decay time constant (22.8 ± 1.2 s) at the optimum polarization transfer field (0.4 microtesla) and temperature (10 °C). The experiments with natural abundance ketoisocaproate revealed polarization level on the 13C-2 site of less than 1%-i.e., one order of magnitude lower than that of the 1-13C site-which is only partially due to more-efficient relaxation dynamics in sub-microtesla fields. We rationalize the overall much lower 13C-2 polarization efficiency in part by less favorable catalyst-binding dynamics of the C-2 site. Pilot SABRE experiments at pH 4.0 (acidified sample) versus pH 6.1 (unaltered sodium [1-13C]ketoisocaproate) reveal substantial modulation of SABRE-SHEATH processes by pH, warranting future systematic pH titration studies of ketoisocaproate, as well as other structurally similar ketocarboxylate motifs including pyruvate and alpha-ketoglutarate, with the overarching goal of maximizing 13C polarization levels in these potent molecular probes. Finally, we also report on the pilot post-mortem use of HP [1-13C]ketoisocaproate in a euthanized mouse, demonstrating that SABRE-hyperpolarized 13C contrast agents hold promise for future metabolic studies.

The Development of Electroretinographic Oscillatory Potentials in Healthy Young Children.

Purpose: This study aimed to summarize the electroretinographic oscillatory potential (OP) responses in healthy young children recorded by RETeval. Methods: By using the RETeval system, we recorded the implicit times and amplitudes of the OPs (OP1-5), in 132 healthy children aged from 0 to 11 years old. The age, gender, and data of implicit time and amplitude of each child were recorded and analyzed. Correlation analysis was performed between age and implicit time/amplitude. Results: No correlation was shown between the implicit times and amplitudes with gender. The implicit times and amplitudes of OP1-5 matured over 10 years of age, with exponential time constants of 1.9, 2.2, 1.8, 1.7, and 1.6 years and 2.1, 2.9, 2.8, 3.0, and 3.2 years, respectively. The majority of the trend occurred within the first 4.6 years. Conclusions: In order to diagnose and evaluate vision-related disorders, the OP response is commonly used. The percentiles and age dependence of OP responses calculated and shown in this study could be regarded as reference data in age-matched pediatric patients.

Transient analysis of MTR research reactor during fast and slow loss of flow accident

Abstract The main objective for reactor safety is to keep the fuel in a safe condition with adequate safety margins during all operational modes (normal-abnormal and accidental states). To achieve this purpose an accident analysis of different design base accidents (DBAs), one of them is the loss of flow accident (LOFA), is required for assessing reactor safety. In this research, the safety aspects of 22 MW MTR research reactor under steady state and during loss of flow accident is studied. The flow transients considered include fast loss of flow accident (FLOFA) and slow loss of flow accident (SLOFA) modeled with exponential flow decay and time constants of 1 and 25 s, respectively. The analysis is done using PARET, a neutronics-hydrodynamics-heat transfer code. The transients were initiated from a full power with a flow trip point at 85% nominal. The calculated parameters are the temperatures of different components (fuel, clad and coolant) as a function of time for the hot channel. The results indicate that in both accidents the calculated maximum cladding surface temperature for the hottest channel of the reactor core does not exceed the allowable safety limit and the fuel integrity is maintained.

(Invited, Digital Presentation) Development of Multiplex Electrode Array Sensors for Proteases Activity Profiling Toward Cancer Diagnosis

Proteases are a large family of enzymes involved in many important biological processes. Quantitative detection of the activity profile of specific target proteases is in high demand for the diagnosis and treatment monitoring of diseases such as cancers. The overexpression and enhanced activity of proteases were found to correlate well with cancer development. Protease inhibitors are also a class of major anti-cancer drug candidates. However, due to the presence of a large number (over 600) of proteases in human body, their complex interactions with each other, and large influence by the surrounding factors (such as buffer composition, pH value and temperature), it is challenging to accurately detect the activity of specific proteases in complex media. It is even more difficult to measure the activity profiles of a large set of proteases that are relevant to cancers. Here we summarize our studies on the development of a multiplex electrode array biosensor platform toward cancer diagnosis based on rapid profiling of multiple protease activities. Both nano- and micro-electrode arrays have been demonstrated for electrochemical detection of protease activities. The individually addressed 3x3 gold thin-film microelectrode array is particularly attractive for rapid profiling of multiple protease activities.The general sensor scheme involves attaching short peptides with specific sequences of 4 to 8 amino acids on the electrode surface of the electrochemical sensor chip, which serve as the substrates for selective proteolysis by the cognate proteases. The far end is covalently attached with a ferrocene (Fc) group as the redox tag for electrochemical measurements. The quantity of the intact peptides on the electrode surface is measured with an AC voltammetry (ACV) method, which is proportional to the peak current at the specific electrode potential when Fc oxidation is oxidized into ferrocenium (Fc+). As the peptide is cleaved by the cognate protease, the peak current decreases continuously in the continuously repeated ACV curves. The recorded kinetic proteolytic curve can be quantitatively described by the heterogeneous Michaelis-Menten model following an exponential decay. The inverse of exponential decay time constant, i.e., 1/τ, is found to represent the protease activity which equals to [E](kcat /KM), where [E] is the protease concentration and kcat /KM is the specificity constant defined by the kinetic proteolytic reaction constant kcat and the Michaelis equilibrium constant KM. The kcat /KM values have been investigated versus the substrate peptide sequence and length, temperature, and buffer composition to optimize the detection for activity of cathepsin B, a potential cancer biomarker. The limit of detection (LOD) for activated cathepsin B can reach down to 0.57 pM, sufficient to directly detect cathepsin B in diluted human serum.This electrochemical method has been compared and validated with the commonly used affinity assay, i.e., enzyme-linked immunosorbent assay (ELISA). The ELISA measurements were found to be more sensitive to the concentration of proenzyme (zymogen), while the electrochemical method detects the activity of the proteases which reflects the intrinsic biological function. This provides more critical information than the concentration derived from ELISA.Currently, two sets of peptides have been synthesized which are selective for detection of cathepsin B and ADAM-17, respectively. They are functionalized to the 3x3 gold thin-film microelectrode array and used to simultaneously detect these two types of proteases in serum samples from breast cancer patients at different stages. The activity profiles will be correlated to the cancer development. Figure 1

Quantitative analysis of heat-source estimation of high-intensity focused ultrasound using thermal strain imaging

For the clinical application of high-intensity focused ultrasound (HIFU), improvement in monitoring and guidance methods is necessary to enhance the treatment accuracy. Among the ultrasonic imaging techniques, thermal strain imaging has a potential to estimate temperature change based on the linear relationship between the thermally induced strain and temperature change via a tissue-dependent coefficient. In this study, the coefficient was experimentally measured and the temperature rise induced by the HIFU irradiation was estimated based on the measured coefficient in a tissue mimicking material phantom. The temperature rise estimated using the measured coefficient and that simulated based on a bioheat transfer equation showed a good agreement when the spatial averaged effect in the elevational direction was considered. The exponential decay time constants also agreed well within the range of measurement.

Ultrafast dynamics of adenine following XUV ionization

The dynamics of biologically relevant molecules exposed to ionizing radiation contains many facets and spans several orders of magnitude in time and energy. In the extreme ultraviolet (XUV) spectral range, multi-electronic phenomena and bands of correlated states with inner-valence holes must be accounted for in addition to a plethora of vibrational modes and available dissociation channels. The ability to track changes in charge density and bond length during ultrafast reactions is an important endeavor toward more general abilities to simulate and control photochemical processes, possibly inspired by those that have evolved biologically. By using attosecond XUV pulses extending up to 35 eV and few-femtosecond near-infrared pulses, we have previously time-resolved correlated electronic dynamics and charge migration occurring in the biologically relevant molecule adenine after XUV-induced sudden ionization. Here, using additional experimental data, we comprehensively report on both electronic and vibrational dynamics of this nucleobase in an energy range little explored to date with high temporal resolution. The time-dependent yields of parent and fragment ions in the mass spectra are analyzed to extract exponential time constants and oscillation periods. Together with time-dependent density functional theory and ab-initio Green’s function methods, we identify different vibrational and electronic processes. Beyond providing further insights into the XUV-induced dynamics of an important nucleobase, our work demonstrates that yields of specific dissociation outcomes can be influenced by sufficiently well-timed ultrashort pulses, therefore providing a new route for the control of the multi-electronic and dissociative dynamics of a DNA building block.

Mydriasis-Free Flicker Electroretinograms in 204 Healthy Children Aged 0-18 Years: Reference Data From Two Cohorts.

PurposeThe purpose of this study was to summarize the flicker electroretinogram responses (ERGs) in healthy children using RETeval, a small handheld mydriasis-free full-field flicker ERG system.MethodsFlicker ERGs were recorded with the use of the RETeval system in 204 healthy children (aged 18 years and below) from 2 countries, China and the United States. The effects on ERG measurements of the subject's demographics and location were analyzed.ResultsThe implicit times have no correlation with the population (China cohort and US cohort), sex, and refractive error. In contrast, the amplitudes were dependent on demographics. The amplitude differences were small compared to the 95% reference interval; therefore, a single (age-corrected) reference interval can be used in both locations and both sexes. The implicit times and amplitudes mature over the first decade of life with exponential time constants of 2.5 years and 4.1 years, respectively, whereas most of the trend is within the first 6 years (implicit times) and 9 years (amplitudes).ConclusionsThe age dependence and percentiles obtained in this study could serve as reference data against which the ERG responses from pediatric patients can be compared.Translational RelevanceThe flicker ERG is one of the standard methods for the assessment and diagnosis of vision-related disorders. This study provides reference data in pediatric subjects, which can then be used to aid in the interpretation of flicker ERG results.

An optimized pulse coupled neural network image de-noising method for a field-programmable gate array based polarization camera.

The quality of polarization images is easy to be affected by the noise in the image acquired by a polarization camera. Consequently, a de-noising method optimized with a Pulse Coupled Neural Network (PCNN) for polarization images is proposed for a Field-Programmable Gate Array (FPGA)-based polarization camera in this paper, in which the polarization image de-noising is implemented using an adaptive PCNN improved by Gray Wolf Optimization (GWO) and Bi-Dimensional Empirical Mode Decomposition (BEMD). Unlike other artificial neural networks, PCNN does not need to be trained, but the parameters of PCNN such as the exponential decay time constant, the synaptic junction strength factor, and the inherent voltage constant play a critical influence on its de-noising performance. GWO is able to start optimization by generating a set of random solutions as the first population and saves the optimized solutions of PCNN. In addition, BEMD can decompose a complicated image into different Bi-Dimensional Intrinsic Mode Functions with local stabilized characteristics according to the input source image, and the decomposition result is able to lower the complexity of heavy noise image analysis. Moreover, the circuit in the polarization camera is accomplished by FPGA so as to obtain the polarization image with higher quality synchronously. These two schemes are combined to attenuate different types of noises and improve the quality of the polarization image significantly. Compared with the state-of-the-art image de-noising algorithms, the noise in the polarization image is suppressed effectively by the proposed optimized image de-noising method according to the indices of peak signal-to-noise ratio, standard deviation, mutual information, structural similarity, and root mean square error.

Hydrolytic Degradation of 3D-Printed Poly (Lactic Acid) Structures

Hydrolytic degradation of commercially available 3D printing filament, i.e. poly (lactic acid) with broad molecular weight distribution was induced by incubating 3D-printed parts in deionized water at 3 temperatures. Small changes in orthogonal dimensions occurred due to relaxation of printing stresses, but no mass or volume loss were detected over the time-frame of the experiments. Molecular weight decreased while polydispersity remained constant. The most sensitive measure of degradation was found to be nondestructive, small-amplitude oscillatory tensile measurements. A rapid decay of tensile storage modulus was found with an exponential decay time constant of about an hour. This work demonstrates that practical monitoring of commercially available PLA degradation can be achieve with linear viscoelastic measurements of modulus.

(Invited) Toward Rapid Profiling of Proteases Activities for Cancer Diagnosis Based on Multiplex Microelectrode Array Sensors

We report the development of an electrochemical biosensor platform based on multiplex micro-/nano- electrode arrays toward cancer diagnosis based on rapid profiling of protease activities. Proteases are a large family of enzymes involved in many important biological processes. Quantitative detection of the activity profile of specific target proteases is in high demand for the diagnosis and treatment monitoring of diseases such as cancers. This study demonstrates the fabrication and characterization of a nanoelectrode array platform based on embedded vertically aligned carbon nanofibers for electrochemical detection of protease activities and further development into an individually addressed 3x3 gold thin-film microelectrode array for rapid profiling of multiple protease activities.Peptides with specific sequences of 4 to 8 amino acids are designed and synthesized as the substrates for selective proteolysis by the cognate proteases, which are attached to the electrode surface as the specific probes. The far end is covalently attached with a ferrocene (Fc) group as the redox moiety for electrochemical measurements. The quantity of the intact peptides on the electrode surface can be sensitively detected with an AC voltammetry method and presents as the peak current at the specific potential for Fc oxidation into ferrocenium (Fc+). As the peptide is cleaved by the cognate protease, the peak current decreases exponentially in the continuously repeated AC voltammetry measurements. The recorded kinetic proteolytic curve can be quantitatively described by a surface-based heterogeneous Michaelis-Menten model. The inverse of exponential decay time constant, 1/t, is found to represent the protease activity which equals to [E](kcat /KM), where [E] is the protease concentration and kcat /KM is the specificity constant defined by the kinetic proteolytic reaction constant kcat and the Michaelis equilibrium constant KM. We have systematically investigated the factors that affect the value of kcat /KM, including the peptide sequence, peptide length, temperature and buffer composition, and optimized the conditions for highly sensitive detection of protease activity of cathepsin B, a potential cancer biomarker.Toward rapid profiling of multiple proteases, we have developed a multiplex electrochemical sensor chip based on a 3x3 gold microelectrode array. The nine individual gold microelectrodes are partially buried underneath the surrounding SiO2 thin film, which show highly consistent cyclic voltammetric signals in gold surface cleaning experiments and detecting benchmark redox species in solution. Upon selectively functionalizing the individual gold microelectrodes with the specific ferrocene-labeled peptide probes, simultaneous detection of the proteolytic curves of the target proteases can be obtained over 9 channels by monitoring the decay of the AC voltammetry signal of the ferrocene-labeled peptide molecules. So far, the algorithm for fitting the kinetic proteolytic curves to accurately derive the activity of cathepsin B has been established. Simultaneous detection of the proteolysis of cathepsin B on the microelectrode array functionalized with three different hexapeptides has been demonstrated, showing the potential of this sensor platform for rapid detection of the activity profiles of multiple proteases.Interestingly, the above-discussed electrochemical method detects the activity of the proteases, which reflects the true biological function and is fundamentally different from the concentration derived from commonly used affinity biosensors or assays such as enzyme-linked immunosorbent assay (ELISA). The direct comparison has shown that ELISA measurements will give the same results no matter the original proenzyme form (zymogen) in the sample is activated or not, while the electrochemically measured activity shows dramatic increase after being chemically activated. In addition, in the current practice, each protease is measured separately in its optimal buffer with the pH value varying from 5 to 9. It is not possible to measure them in a common buffer simultaneously. We have demonstrated that the electrochemical method can be applied for protease activity profiling in a buffer at pH = 7.4 that is compatible to the physiology conditions. This enables measuring the activity of multiple proteases in human serum, which is a critical step toward protease activity for cancer diagnosis.The figure shows the optical images of (a) the whole 3x3 Au microelectrode array chip and (b) the active electrode area, and the schematic illustration of (c) the mechanism of proteolysis of the peptide probes, (d) the change of the AC voltammetry signal before and after proteolysis and (e) the kinetic proteolytic curves, i.e. the exponential peak current decay over time, at different protease concentration [E]. Figure 1

Quantitative Detection of Cathepsin B Activity in Neutral pH Buffers Using Gold Microelectrode Arrays: Toward Direct Multiplex Analyses of Extracellular Proteases in Human Serum.

Proteases are critical signaling molecules and prognostic biomarkers for many diseases including cancer. There is a strong demand for multiplex bioanalytical techniques that can rapidly detect the activity of extracellular proteases with high sensitivity and specificity. This study demonstrates an activity-based electrochemical biosensor of a 3 × 3 gold microelectrode array for the detection of cathepsin B activity in human serum diluted in a neutral buffer. Proteolysis of ferrocene-labeled peptide substrates functionalized on 200 × 200 μm microelectrodes is measured simultaneously over the nine channels by AC voltammetry. The protease activity is represented by the inverse of the exponential decay time constant (1/τ), which equals to (kcat/KM)[CB] based on the Michaelis-Menten model. An enhanced activity of the recombinant human cathepsin B (rhCB) is observed in a low-ionic-strength phosphate buffer at pH = 7.4, giving a very low limit of detection of 8.49 × 10-4 s-1 for activity and 57.1 pM for the active rhCB concentration that is comparable to affinity-based enzyme-linked immunosorbent assay (ELISA). The cathepsin B presented in the human serum sample is validated by ELISA, which mainly detects the inactive proenzyme, while the electrochemical biosensor specifically measures the active cathepsin B and shows significantly higher decay rates when rhCB and human serum are activated. Analyses of the kinetic electrochemical measurements with spiked active cathepsin B in human serum provide further assessment of the protease activity in the complex sample. This study lays the foundation to develop the gold microelectrode array into a multiplex biosensor for rapid detection of the activity of extracellular proteases toward cancer diagnosis and treatment assessment.

Acid-base equilibria of axial ligand and peripheral pyridyl group with stepwise formation of nine species of aluminum (III) tera(4-pyridyl) porphyrin

As one of the promising molecular catalysts for the two-electron water oxidation initiated through one-electron oxidation of the catalyst, trans-diaqua-coordinated 5, 10, 15, 20-tetra(4-pyridyl)porphyrinatealuminum (III) (AlTPyP(OH2)2) was studied on the protolytic behavior of the axial ligating water molecules and the redox properties in aqueous methanol solution. The reversible stepwise protolytic reactions of the two axially ligated water molecules, as well as four peripheral pyridyl groups at the meso-position of AlTPyP, were characterized using UV–vis absorption spectroscopy, 1H NMR, fluorescence lifetime measurements, and cyclic voltammetry. The result showed that four-step protolytic equilibrium reactions of the axial ligands proceeded under the basic pH condition and those of meso-substituted pyridyl groups did also under the acidic pH condition. All the nine species are in equilibria in the ground states as characterized with each pKa value. On the other hand, they exist as individual species in the excited states having each single exponential decay time constant. Here we will report the first detailed study on the formation of nine species from a single molecule of AlTPyP through protolytic reactions in the pH range between 0.54 and 12.3.

Ultrafast intraband Auger process in self-doped colloidal quantum dots

Summary Investigating the separate dynamics of electrons and holes has been challenging, although it is critical for the fundamental understanding of semiconducting nanomaterials. n-Type self-doped colloidal quantum dots (CQDs) with excess electrons occupying the low-lying state in the conduction band (CB) have attracted a great deal of attention because of not only their potential applications to infrared optoelectronics but also their intrinsic system that offers a platform for investigating electron dynamics without elusive contributions from holes in the valence band. Here, we show an unprecedented ultrafast intraband Auger process, electron relaxation between spin-orbit coupling states, and exciton-to-ligand vibrational energy transfer process that all occur exclusively in the CB of the self-doped β-HgS CQDs. The electron dynamics obtained by femtosecond mid-infrared spectroscopy will pave the way for further understanding of the blinking phenomenon, disproportionate charging in light-emitting diodes, and hot electron dynamics in higher quantum states coupled to surface states of CQDs.

A non-linear elastic approach to study the effect of ambient humidity on sandstone

We demonstrate that strong elastic pump wave pulses soften sandstone more in humidified conditions than they do in dry conditions and that this effect is repeatable and reversible. We assess these changes via the non-linear interactions of a strong pump wave with a weaker probe wave. We find that there is an exponential time constant (τ≈13days) associated with this process that is independent of the amplitudes of the pump and the probe, the phase delay between the two waves (the time between transmission of the pump and probe waves), the sampling rate, and whether the sample is being dried or humidified. We demonstrate that the humidity-dependent differences in the amount of softening are induced by only a very small amount of absorbed water vapor and argue that this water is intercalated within clay particles. We also show that our pump–probe experiments detect these humidity-dependent differences in the amount of softening easily and repeatably using an experimental design that does not rely on resonance conditions. This means that, in principle, our experiments could be more easily generalized to other experimental geometries to investigate non-linear elastic properties in complex or irregular sample geometries. Our method and findings have potential relevance in oil and gas exploration, civil engineering, and understanding of the mechanism of earthquakes.

Unusual Vestibulo-Ocular Reflex Responses in Patients With Peripheral Vestibular Disorders Detected by the Caloric Step Stimulus Test.

The caloric step stimulus test consists of the changes in head position from the sitting to supine positions and continuous caloric irrigation. This test can provide a single labyrinth with a stimulus similar to constant head acceleration in rotational testing and, therefore, can evaluate vestibulo-ocular reflex (VOR) dynamics more precisely than can conventional methods. To assess the clinical utility of the test in the assessment of the VOR dynamics of diseases, we performed the test in patients with peripheral vestibular disorders, including sudden idiopathic hearing loss, vestibular neuritis, Meniere disease, vestibular Meniere disease, or chronic unilateral idiopathic vestibulopathy and normal controls. Slow-phase eye velocity (SPV) was measured with videonystagmography. We fitted the time course of SPV across 2 min to a mathematical model containing two exponential components and time constants: the caloric step VOR time constant (T1) and caloric step VOR adaptation time constant (T2). All responses of normal controls (n = 15 ears) were fit to the model. Several responses of the 101 ears of the patients differed from the time courses predicted by the model. We divided the data of 116 ears into four patterns based on SPV, T1, and T2. The thresholds for the classification were determined according to the lower limits of the capability of curve fitting for SPV and the upper limits of normal controls for T1 and T2. Seventy-eight ears followed pattern A (normal T1 and T2): the SPV trajectory formed a rapid rise with subsequent decay. Nineteen followed pattern B (normal T1 and prolonged T2): the SPV trajectory formed a rapid rise without decay. Six followed pattern C (prolonged T1 and T2): the SPV trajectory formed a slow rise. Thirteen ears followed pattern D: a low VOR response. There were no significant differences in time constants between the affected and healthy ears in patients with each disease. However, prolonged T1 and T2 were significantly more frequent in the affected ears than the healthy ears. In conclusion, the caloric step stimulus test can be potentially useful in detecting unusual VOR responses and thus reflect some pathological changes in the vestibular system.