The Apparent Constant-Phase-Element Behavior of an Ideally Polarized Blocking Electrode

Two numerical methods were used to calculate the influence of geometry-induced current and potential distributions on the impedance response of an ideally polarized disk electrode. A coherent notation is proposed for local and global impedance which accounts for global, local, local interfacial, and both global and local ohmic impedances. The local and ohmic impedances are shown to provide insight into the frequency dispersion associated with the geometry of disk electrodes. The high-frequency global impedance response has the appearance of a constant-phase element CPE but can be considered to be only an apparent CPE because the CPE exponent is a function of frequency

The Apparent Constant-Phase-Element Behavior of a Disk Electrode with Faradaic Reactions

Geometry-induced current and potential distributions modify the global impedance response of a disk electrode subject to faradaic reactions. The problem was treated for both linear and Tafel kinetic regimes. The apparent capacity of a disk electrode embedded in an insulating plane was shown to vary considerably with frequency. At frequencies above the characteristic frequency for the faradaic reaction, the global impedance response has a quasi-constant-phase element (CPE) character, but with a CPE coefficient alpha that is a function of both dimensionless frequency K and dimensionless current density J. For small values of J, alpha approached unity, whereas, for larger values of J, alpha reached values near 0.78. The calculated values of alpha are typical of those obtained in impedance measurements on disk electrodes. For determining the interfacial capacitance, the influence of current and potential distributions on the impedance response cannot be neglected, even if the apparent CPE exponent alpha has values close to unity. Several methods taken from the literature were tested to determine their suitability for extracting interfacial capacitance values from impedance data on disk electrodes. The best results were obtained using a formula which accounted for both ohmic and charge-transfer resistances

Local electrochemical impedance spectroscopy: A review and some recent developments

Local electrochemical impedance spectroscopy (LEIS), which provides a powerful tool for exploration of electrode heterogeneity, has its roots in the development of electrochemical techniques employing scanning of microelectrodes. The historical development of local impedance spectroscopy measurements is reviewed, and guidelines are presented for implementation of LEIS. The factors which control the limiting spatial resolution of the technique are identified. The mathematical foundation for the technique is reviewed, including definitions of interfacial and local Ohmic impedances on both local and global scales. Experimental results for the reduction of ferricyanide show the correspondence between local and global impedances. Simulations for a single Faradaic reaction on a disk electrode embedded in an insulator are used to show that the Ohmic contribution, traditionally considered to be a real value, can have complex character in certain frequency ranges

Local electrochemical impedance spectroscopy: Considerations about the cell geometry

Local electrochemical impedance spectroscopy provides a powerful tool for the investigation of surface heterogeneities on electrode surfaces. However, measurements are greatly influenced by geometry-induced frequency dispersion. In order to account for this frequency dispersion, both simulations and experiments were performed to explore the influence of a recessed electrode on the local and global impedance response. The calculations presented here demonstrated that the depth of the recessed electrode required to achieve a uniform primary current distribution was twice the electrode radius. The calculations provide guidelines for design of LEIS measurements, and were in good agreement with results obtained for a stainless steel disk electrode in a Na2SO4 electrolyte

A Cell-Based β-Lactamase Reporter Gene Assay for the CREB Signaling Pathway

The Cyclic-AMP Response Element Binding (CREB) proteins comprise a family of transcription factors that stimulate or repress the expression of a wide variety of genes by binding to nucleotide sequences known as cAMP Response Elements. CREB-mediated transcription has been implicated in a wide variety of important physiological processes, including long-term memory, and enhancement of CREB signaling has been suggested as an attractive therapeutic strategy for human memory disorders. To identify small molecule compounds that enhance CREB pathway signaling, we have optimized and validated a cell-based β-lactamase reporter gene CREB pathway assay in 1536-well plate format. The LOPAC library of 1280 compounds was screened in triplicate in this assay on a quantitative high throughput screening (qHTS) platform. A variety of compounds which affect known members of the CREB pathway were identified as active, including twelve known phosphodiesterase (PDE) inhibitors, and forskolin, a known activator of adenylate cyclase, thus validating the assay’s performance. This qHTS platform assay will facilitate identification of novel small molecule CREB signaling enhancers, which will be useful for chemical genetic dissection of the CREB pathway and as starting points for potentially memory-enhancing therapeutics

Discovering medication patterns for high-complexity drug-using diseases through electronic medical records

An Electronic Medical Record (EMR) is a professional document that contains all data generated during the treatment process. The EMR can utilize various data formats, such as numerical data, text, and images. Mining the information and knowledge hidden in the huge amount of EMR data is an essential requirement for clinical decision support, such as clinical pathway formulation and evidence-based medical research. In this paper, we propose a machine-learning-based framework to mine the hidden medication patterns in EMR text. The framework systematically integrates the Jaccard similarity evaluation, spectral clustering, the modified Latent Dirichlet Allocation and cross-matching among multiple features to find the residuals that describe additional knowledge and clusters hidden in multiple perspectives of highly complex medication patterns. These methods work together, step by step to reveal the underlying medication pattern. We evaluated the method by using real data from EMR text (patients with cirrhotic ascites) from a large hospital in China. The proposed framework outperforms other approaches for medication pattern discovery, especially for this disease with subtle medication treatment variances. The results also revealed little overlap among the discovered patterns; thus, the distinct features of each pattern are well studied through the proposed framework

Novel Lipophilic Probe for Detecting Near-Membrane Reactive Oxygen Species Responses and Its Application for Studies of Pancreatic Acinar Cells: Effects of Pyocyanin and L-Ornithine

Aims: The aim of this study was to develop a fluorescent reactive oxygen species (ROS) probe, which is preferentially localized in cellular membranes and displays a strong change in fluorescence upon oxidation. We also aimed to test the performance of this probe for detecting pathophysiologically relevant ROS responses in isolated cells. Results: We introduced a novel lipophilic ROS probe dihydrorhodamine B octadecyl ester (H2RB-C18). We then applied the new probe to characterize the ROS changes triggered by inducers of acute pancreatitis in pancreatic acinar cells. We resolved ROS changes produced by L-ornithine, L-arginine, cholecystokinin-8, acetylcholine, taurolithocholic acid 3-sulfate, palmitoleic acid ethyl ester, and the bacterial toxin pyocyanin. Particularly prominent ROS responses were induced by pyocyanin and L-ornithine. These ROS responses were accompanied by changes in cytosolic Ca2+concentration ([Ca2+]i), mitochondrial membrane potential (ΔΨ), and NAD(P)H concentration. Innovation: The study describes a novel sensitive lipophilic ROS probe. The probe is particularly suitable for detecting ROS in near-membrane regions and therefore for reporting the ROS environment of plasma membrane channels and pumps. Conclusions: In our experimental conditions, the novel probe was more sensitive than 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein (CM-H2DCF) and dihydrorhodamine123 (H2R123) and allowed us to resolve ROS responses to secretagogues, pyocyanin, and L-ornithine. Changes in the fluorescence of the new probe were particularly prominent in the peripheral plasma membrane-associated regions. Our findings suggest that the new probe will be a useful tool in studies of the contribution of ROS to the pathophysiology of exocrine pancreas and other organs/tissues

Interocular Shift of Visual Attention Enhances Stereopsis and Visual Acuities of Anisometropic Amblyopes beyond the Critical Period of Visual Development: A Novel Approach

Aims. Increasing evidence shows that imbalanced suppressive drive prior to binocular combination may be the key factor in amblyopia. We described a novel binocular approach, interocular shift of visual attention (ISVA), for treatment of amblyopia in adult patients. Methods. Visual stimuli were presented anaglyphically on a computer screen. A square target resembling Landolt C had 2 openings, one in red and one in cyan color. Through blue-red goggles, each eye could only see one of the two openings. The patient was required to report the location of the opening presented to the amblyopic eye. It started at an opening size of 800 sec of arc, went up and down in 160 sec of arc step, and stopped when reaching the 5th reversals. Ten patients with anisometropic amblyopia older than age 14 (average age: 26.7) were recruited and received ISVA treatment for 6 weeks, with 2 training sessions per day. Results. Both Titmus stereopsis (z = −2.809, P = 0.005) and Random-dot stereopsis (z = −2.317, P = 0.018) were significantly improved. Average improvement in best corrected visual acuity (BCVA) was 0.74 line (t = 5.842, P < 0.001). Conclusions. The ISVA treatment may be effective in treating amblyopia and restoring stereoscopic function

The Association of Social Distancing, Population Density, and Temperature with the SARS-CoV-2 Instantaneous Reproduction Number in Counties Across the United States

AbstractImportanceThe Covid-19 pandemic has been marked by considerable heterogeneity in outbreaks across the United States. Local factors that may be associated with variation in SARS-CoV-2 transmission have not been well studied.ObjectiveTo examine the association of county-level factors with variation in the SARS-CoV-2 reproduction number over time.DesignObservational studySetting211 counties in 46 states and the District of Columbia between February 25, 2020 and April 23, 2020.ParticipantsResidents within the counties (55% of the US population)ExposuresSocial distancing as measured by percent change in visits to non-essential businesses, population density, lagged daily wet bulb temperatures.Main Outcomes and MeasuresThe instantaneous reproduction number (Rt) which is the estimated number of cases generated by one case at a given time during the pandemic.ResultsMedian case incidence was 1185 cases and fatality rate was 43.7 deaths per 100,000 people for the top decile of 21 counties, nearly ten times the incidence and fatality rate in the lowest density quartile. Average Rt in the first two weeks was 5.7 (SD 2.5) in the top decile, compared to 3.1 (SD 1.2) in the lowest quartile. In multivariable analysis, a 50% decrease in visits to non-essential businesses was associated with a 57% decrease in Rt (95% confidence interval, 56% to 58%). Cumulative temperature effects over 4 to 10 days prior to case incidence were nonlinear; relative Rt decreased as temperatures warmed above 32°F to 53°F, which was the point of minimum Rt, then increased between 53°F and 66°F, at which point Rt began to decrease. At 55°F, and with a 70% reduction in visits to non-essential business, 96% of counties were estimated to fall below a threshold Rt of 1.0, including 86% of counties among the top density decile and 98% of counties in the lowest density quartile.Conclusions and RelevanceSocial distancing, lower population density, and temperate weather change were associated with a decreased SARS-Co-V-2 Rt in counties across the United States. These relationships can inform selective public policy planning in communities during the SARS-CoV-2 pandemic.Key PointsQuestionHow is the instantaneous reproduction number (Rt) of SARS-CoV-2 influenced by local area effects of social distancing, wet bulb temperature, and population density in counties across the United States?FindingsSocial distancing, temperate weather, and lower population density were associated with a decrease in Rt. Of these county-specific factors, social distancing appeared to be the most significant in reducing SARS-CoV-2 transmission.MeaningRt varies significantly across counties. The relationship between Rt and county-specific factors can inform policies to reduce SARS-CoV-2 transmission in selective and heterogeneous communities.</jats:sec

A specific group of genes respond to cold dehydration stress in cut Alstroemeria flowers whereas ambient dehydration stress accelerates developmental senescence expression patterns

Petal development and senescence entails a normally irreversible process. It starts with petal expansion and pigment production, and ends with nutrient remobilization and ultimately cell death. In many species this is accompanied by petal abscission. Post-harvest stress is an important factor in limiting petal longevity in cut flowers and accelerates some of the processes of senescence such as petal wilting and abscission. However, some of the effects of moderate stress in young flowers are reversible with appropriate treatments. Transcriptomic studies have shown that distinct gene sets are expressed during petal development and senescence. Despite this, the overlap in gene expression between developmental and stress-induced senescence in petals has not been fully investigated in any species. Here a custom-made cDNA microarray from Alstroemeria petals was used to investigate the overlap in gene expression between developmental changes (bud to first sign of senescence) and typical post-harvest stress treatments. Young flowers were stressed by cold or ambient temperatures without water followed by a recovery and rehydration period. Stressed flowers were still at the bud stage after stress treatments. Microarray analysis showed that ambient dehydration stress accelerates many of the changes in gene expression patterns that would normally occur during developmental senescence. However, a higher proportion of gene expression changes in response to cold stress were specific to this stimulus and not senescence related. The expression of 21 transcription factors was characterized, showing that overlapping sets of regulatory genes are activated during developmental senescence and by different stresses