Increase In On-time Research Articles

Study of the temperature distribution in insulated gate bipolar transistor module under different test conditions

Following improvements in their operating voltage levels, insulated gate bipolar transistors (IGBTs) are largely packaged using parallel packaging processes. However, these processes introduce an uneven temperature distribution problem, regardless of whether pressed or welded packaging is used. In this paper, the temperature inhomogeneity of IGBT modules under various test conditions is studied using a thermography camera. The temperature uniformity is determined for each chip using the difference between its maximum and average temperatures. IGBT module temperature uniformity is evaluated using the difference between the highest temperature and the average temperature of three chips. Experimental results show that when the current level increases, the overall IGBT module temperature also increases. The temperatures of both the module and the chip become increasingly uneven. The temperature of the module shows a Gaussian mode distribution. The positional and discrete parameters of the Gaussian distribution increase with increasing current. As the ambient temperature increases, the temperature inhomogeneity in each IGBT chip increases, but this trend is not dramatic. When the current on-time increases, the temperature distributions of the three IGBT chips and the module gradually become nonuniform.

Amantadine ER (Gocovri®) Significantly Increases ON Time Without Any Dyskinesia: Pooled Analyses From Pivotal Trials in Parkinson's Disease.

Background: Clinical trials for antiparkinsonian drugs aimed at managing motor complications typically use patient diaries to divide levodopa-induced dyskinesias (LID) into “troublesome” and “non-troublesome” categories. Yet, given the choice, most patients would prefer to live without experiencing any dyskinesia. However, the concept of evaluating time spent ON without any dyskinesia as an outcome has never been tested. We conducted analyses of pooled Gocovri pivotal trial data in order to evaluate the extent to which Gocovri increased the time PD patients spent ON without dyskinesia (troublesome or non-troublesome), beyond its already identified improvement in reducing troublesome dyskinesia.Methods: Patients enrolled in phase 3 trials (EASE LID [NCT02136914] or EASE LID 3 [NCT02274766]) recorded time spent in the following PD diary states at baseline and Week 12 (endpoint): asleep, OFF, ON with troublesome dyskinesia, ON with non-troublesome dyskinesia, and ON without dyskinesia. Mixed model repeated measures analyses with estimated Cohen D effect sizes were performed on the modified intent to treat population to evaluate changes in time spent in these states.Results: Patients randomized to receive Gocovri showed an increase in ON time without dyskinesia and corresponding decreases in ON time with dyskinesia and OFF time vs. placebo. Treatment effects were statistically significant for Gocovri vs. placebo starting at Week 2 and were sustained until Week 12. On MMRM analysis at Week 12, patients in the Gocovri group showed an adjusted mean ± SE increase over placebo of 2.9 ± 0.6 h in ON time without dyskinesia (Cohen D effect size 0.79) and an adjusted mean ± SE decrease of −1.9 ± 0.6 h in ON time with dyskinesia (troublesome + non-troublesome) (Cohen D effect size 0.49), that included a −1.5 ± 0.4 h placebo-adjusted reduction in ON time with troublesome dyskinesia and a −0.6 ± 0.4 h reduction in ON time with non-troublesome dyskinesia. OFF time was reduced by −1.0 ± 0.3 h compared to placebo.Conclusions: Gocovri treatment more than doubled the daily time patients spent ON without dyskinesia. These results suggest that the Gocovri treatment effect was driven by a reduction in overall motor complications including ON time with both troublesome and non-troublesome dyskinesia as well as time spent OFF.

Optical Repumping of Resonantly Excited Quantum Emitters in Hexagonal Boron Nitride

Resonant excitation of solid-state quantum emitters enables coherent control of quantum states and generation of coherent single photons, which are required for scalable quantum photonics applications. However, these systems can often decay to one or more intermediate dark states or spectrally jump, resulting in the lack of photons on resonance. Here, we present an optical co-excitation scheme which uses a weak non-resonant laser to reduce transitions to a dark state and amplify the photoluminescence from quantum emitters in hexagonal boron nitride (hBN). Utilizing a two-laser repumping scheme, we achieve optically stable resonance fluorescence of hBN emitters and an overall increase of ON time by an order of magnitude compared to only resonant excitation. Our results are important for the deployment of atom-like defects in hBN as reliable building blocks for quantum photonic applications.

Infusion Therapies for Parkinson's Disease.

Advanced Parkinson's disease (APD) is marked by significant motor and non-motor complications affecting the patient's quality of life. Optimization of standard oral therapies (SOT) at some point fails to provide adequate relief. Among the available device-aided therapies, infusion therapies (IT) work on the rationale that continuous striatal dopaminergic stimulation can significantly reduce the motor fluctuations and smoothen the treatment response. This review serves to familiarize readers with available IT for APD with a focus on motor and non-motor effects, and safety. Several recent longitudinal studies have demonstrated a reduction in OFF and an equivalent increase in ON time with the use of levodopa-carbidopa intestinal gel infusion (LCIG). Additionally, the benefit is noted on dyskinesia and non-motor symptoms. Similarly, backed by long-term clinical experience and open-label studies, a recent double-blind trial validates the efficacy of continuous subcutaneous apomorphine infusion (CSAI). Both IT are accompanied by a high rate of mild to moderate adverse events (AE) that can influence patient selection and clinical utility. While device and procedure-related AE are common for LCIG, infusion site reactions dominate the CSAI AE. IT are a viable and superior alternative for APD over SOT. Both therapies provide meaningful improvement of the motor fluctuations with a positive impact on the quality of life.

Enhancing the Tool Die Steel P rofile C utting P erformance in WEDM P rocess

This work elaborates the experimental work on Material Removal Rate (MRR) and Surface Roughness (SR) output conditions of Wire-Electrical Discharge Machining (WEDM) and finding the optimal input conditions through Taguchi method coupled with Grey relational analysis for lower SR and higher MRR during profile cutting of high strength D3 tool steel, which is the need of the hour in industries. The machining factors considered for investigation which influences MRR and SR were: cutting speed, pulse on-time and off-time, input current, wire tension and feed and servo feed and voltage. A L18 orthogonal array was considered for mixed-level experimental design through Taguchi’s approach and for multi-criteria optimization Grey Relational Analysis was applied. Outcome shows that SR increases with the increase of pulse on-time and decreases with increase in pulse off-time and MRR increases as the pulse on-time increases due to longer spark duration. Both SR and MRR are well within the control limits and servo voltage is the most influential parameter contributing by 48.48%, followed by wire feed rate, input current and servo feed rate with an R2 value of 95.85%, identified through Analysis of Variance (ANOVA). With obtained optimum conditions, a validation experiment was conducted to authenticate the results, which indicates a worthy agreement with predicted output characteristics.

Pharmacokinetic drug evaluation of opicapone for the treatment of Parkinson’s disease

ABSTRACT Introduction: Opicapone (OPC) is a novel, potent, reversible, and purely peripheral third-generation COMT inhibitor, which provides an enhancement in levodopa (L-Dopa) availability. It represents adjunctive therapy for L-Dopa treated patients with PD and motor fluctuations. Areas covered: The purpose of this study was to evaluate pharmacokinetic of OPC for the treatment of PD. Expert commentary: Oral OPC exhibits linear, dose-dependent absorption. However, following concomitant ingestion of a high-fat, high-calorie meal, the maximum plasma concentration will be decreased. A once-daily bedtime administration of OPC 1 h after the last daily L-Dopa/AADCi, are considered to avoid any interaction during the L-Dopa absorption phase. There are no clinically relevant effects of age (in adults), renal impairment or race on the pharmacokinetics of OPC. OPC dose adjustment is not needed in patients with mild to moderate chronic hepatic impairment. Opicapone exhibits the lowest potential for cytotoxicity in comparison with other COMT inhibitors. It significantly decreases COMT activity, with half-life of COMT inhibition in human erythrocytes of 61.6 h and increases systemic exposure to L-Dopa. This provides an enhancement in L-Dopa availability that translates into clinical benefit for PD patients in terms of significant decrease of OFF periods and increase in ON-time without troublesome dyskinesia.

Optimization of Pulsed Electrochemical Micromachining in Stainless Steel

The machining of materials at micro and submicroscales is considered a key technology of the future and plays a role increasingly important in the miniaturization of complete machines, with important applications as bioengineering, MEMS, microsensors and microactuators. In this work the process of Pulsed Electrochemical Micromachining was studied. The experiments were carried out in a workpiece of Stainless Steel sunk in an electrochemical cell with an electrode of Tungsten with very small diameter (2-8μm). Pulses of voltage with very small width are introduced between the electrode and the part, so that the current is confined under the area of the tool tip. With this method microholes and microslots were obtained. It is observed that there is a minimum pulse-on time for each value of the voltage to make the current flow. Nevertheless, for values of voltage of 7V and higher there is always material removal for any value of pulse-on time. A maximum ratio between pulse-on time and period of 1/3 and an interelectrode gap in the order of micrometers are required to provide a localized material removal under the tip of the tool. In these conditions, the confinement will decrease when the pulse on-time increases. The main parameter that determines the material removal rate in the process is the current intensity. Surface roughness increases with pulse-on time, as well as the average current of the process and hence the material removal rate. Therefore, there is a compromise between surface finish and material removal rate.

Population pharmacokinetic and pharmacodynamic analyses of safinamide in subjects with Parkinson's disease.

Safinamide is an orally administered α‐aminoamide derivative with both dopaminergic and non‐dopaminergic properties. Nonlinear mixed effects models for population pharmacokinetic (PK) and pharmacokinetic–pharmacodynamic (PKPD) analyses were developed using records from, respectively, 623 and 668 patients belonging to two Phase 3, randomized, placebo‐controlled, double‐blind efficacy studies. The aim was to estimate safinamide population PK parameters in patients with Parkinson's disease (PD) on stable levodopa therapy, and to develop a model of safinamide effect on the PD phase of normal functioning (ON‐time). The final models were internally evaluated using visual predictive checks (VPCs), prediction corrected‐VPC, and nonparametric bootstrap analysis. Safinamide profiles were adequately described by a linear one‐compartmental model with first‐order absorption and elimination. CL/F, Vd/F, and KA (95% confidence interval [CI]) were 4.96 (4.73–5.21) L/h, 166 (158–174) L, and 0.582 (0.335–0.829) h−1, respectively. CL/F and Vd/F increased with body weight, while age, gender, renal function, and exposure to levodopa did not influence safinamide PK. The observed ON‐time values were adequately described by a linear model, with time in the study period as dependent variable, and rate of ON‐time change and baseline plus offset effect as slope and intercept parameters. Safinamide treatment resulted in an increase in ON‐time of 0.73 h (week 4), with further ON‐time increase with the same slope as placebo. The increase was not influenced by age, levodopa, or safinamide exposure. The population models adequately describe the population PK of safinamide and safinamide effect on ON‐time. No dose adjustments in elderly and mild to moderate renally impaired patients are requested.

Motor outcomes in patients with advanced Parkinson's disease treated with levodopa/carbidopa intestinal gel in Italy: an interim analysis from the GREENFIELD observational study.

Several levodopa/carbidopa intestinal gel (LCIG) studies showed a significant reduction of OFF time and a significant increase of ON time, as well as a reduction of dyskinesia, and improvement of non-motor symptoms and quality of life. However, few studies have been conducted in a large population for more than 3 years. Interim outcomes from GREENFIELD observational study on a large Italian cohort of advanced PD patients who started LCIG in routine care between 2007 and 2014, still on treatment at the enrollment, are presented. Comparison between baseline (before LCIG start) and visit 1 (at enrollment) is reported. Primary endpoint was Unified Parkinson’s Disease Rating Scale (UPDRS) IV Item 39; secondary endpoints were UPDRS I and II, as outcome of quality of life. Overall, 145 of 148 enrolled patients from 14 Movement Disorder Centers in Italy were evaluable with a mean LCIG treatment period of 1.38 ± 1.66 years at enrollment. Compared with baseline, the mean score regarding daily time spent in OFF (UPDRS IV Item 39) at visit 1 significantly decreased from 2.1 ± 0.8 to 0.9 ± 0.7 (57 % reduction vs baseline, P < 0.0001); UPDRS IV improved by 39 % (P < 0.0001); scores for dyskinesia duration and disability were reduced by 28 % (1.8 ± 1.0–1.3 ± 0.9; P < 0.0001) and 33 % (1.5 ± 1.1 to 1.0 ± 1.0; P < 0.0001), respectively; and the scores for painful dyskinesia and early morning dystonia were reduced by 56 % (0.9 ± 1.0–0.4 ± 0.7; P < 0.0001) and 25 % (0.4 ± 0.5–0.3 ± 0.5; P < 0.001), respectively. The preliminary results of this interim analysis support the efficacy of LCIG on motor complications and activities of daily living.

Preladenant: An Adenosine A 2A Receptor Antagonist For Parkinson‘s Disease

Preladenant (SCH 420814) is a potent selective antagonist at the adenosine A2A receptor that is being studied for treatment in early Parkinson’s disease (PD) as a monotherapy, and in moderate-to-severe PD as an add on to levodopa therapy. Unlike other drugs used for this disease, preladenant modulates adenosine action at the striatal level in order to block the inhibitory action of the basal ganglia output nuclei. Animal models of PD suggested that preladenant could be an effective treatment, which was further supported in a Phase II study of subjects with idiopathic PD who demonstrated a benefit in reducing off-time with an increase in on-time. In this article, we review current perspectives concerning pharmacological approaches to PD, the pharmacological properties of preladenant, its efficiency and safety, as well as the results reported for parkinsonian subjects treated with this drug.

Long‐term safety and efficacy of preladenant in subjects with fluctuating Parkinson's disease

Preladenant is a selective adenosine A₂A receptor antagonist under investigation for Parkinson's disease treatment. A phase 2 36-week open-label follow-up of a double-blind study using preladenant 5 mg twice a day as a levodopa adjunct in 140 subjects with fluctuating Parkinson's disease was conducted. The primary end point was adverse event (AE) assessment. Secondary (efficacy) analyses included hours/day spent in OFF and ON states and dyskinesia prevalence/severity. The 36-week open-label phase was completed by 106 of 140 subjects (76%). AE-related treatment discontinuations occurred in 19 subjects (14%). Treatment-emergent AEs, reported by ≥15% of subjects, were dyskinesia (33%) and constipation (19%). Preladenant 5 mg twice a day provided OFF time reductions (1.4-1.9 hours/day) and ON time increases (1.2-1.5 hours/day) throughout the 36-week treatment relative to the baseline of the double-blind study. Long-term preladenant treatment (5 mg twice a day) was generally well tolerated and provided sustained OFF time reductions and ON time increases.

Collective fluorescence enhancement in nanoparticle clusters

Many nanoscale systems are known to emit light intermittently under continuous illumination. In the fluorescence of single semiconductor nanoparticles, the distributions of bright and dark periods ('on' and 'off' times) follow Lévy statistics. Although fluorescence from single-quantum dots and from macroscopic quantum dot ensembles has been studied, there has been little study of fluorescence from small ensembles. Here we show that blinking nanorods (NRs) interact with each other in a cluster, and the interactions affect the blinking statistics. The on-times in the fluorescence of a NR cluster increase dramatically; in a cluster with N NRs, the maximum on-time increases by a factor of N or more compared with the combined signal from N well-separated NRs. Our study emphasizes the use of statistical properties in identifying the collective dynamics. The scaling of this interaction-induced increase of on-times with number of NRs reveals a novel collective effect at the nanoscale.

A 12-week, placebo-controlled study (6002-US-006) of istradefylline in Parkinson disease

The safety and efficacy of istradefylline, a selective adenosine A(2A) receptor antagonist, was evaluated in a 12-week, double-blind study in levodopa-treated Parkinson disease (PD) subjects with motor complications. Levodopa-treated PD subjects (n = 395) received istradefylline 20 mg/day (n = 163), istradefylline 60 mg/day (n = 155), or placebo (n = 77) at 40 sites. The primary efficacy variable was the change in the percentage of time per day spent in the OFF state. Secondary measurements assessed change in ON time, Unified Parkinson's Disease Rating Scale, and Clinical Global Impression. Safety monitoring included clinical laboratory, electrocardiograms, vital signs, physical/neurologic examinations, and adverse events (AEs). Changes from baseline to endpoint in the percentage OFF time in the active groups compared with placebo were -4.35% (95% CI -8.16 to -0.54; p = 0.026) for istradefylline 20 mg/day and -4.49% (95% CI -8.35 to -0.62; p = 0.024) for 60 mg/day; these changes were significant (analysis of covariance). For total hours, istradefylline demonstrated mean differences from placebo of -0.64 hours (95% CI -1.30 to 0.01) for 20 mg/day and -0.77 hours (95% CI -1.44 to -0.11) for 60 mg/day (p = 0.065; overall treatment effect). Clinical response occurred by the second week and was maintained throughout the study. Istradefylline was well tolerated. The common AEs were dyskinesia, nausea, dizziness, and hallucinations. Istradefylline demonstrated a significant reduction in the percentage of awake time per day spent in the OFF state, which resulted in a clinically meaningful reduction in OFF time, without an increase in ON time with troublesome dyskinesia, and was well tolerated as adjunctive treatment to levodopa in Parkinson disease.

Influence of pulse parameters on the microstructure and microhardness of nickel electrodeposits

Square-wave cathodic current modulation was used to electrodeposit fine-grained nickel from an additive-free and saccharin-containing Watts bath. The influence of pulse on-time, off-time, peak current density and saccharin on the grain size, surface morphology, crystal orientation, and microhardness was determined. The study showed that at constant off-time and peak current density, the crystal size of the deposits was found initially to decrease with pulse on-time before it started to increase with further increase in on-time. The crystal orientation progressively changed from a (111) texture at the on-time of 0.1 ms to a strong (200) texture at an on-time of 8 ms. An increase in the pulse off-time at constant on-time and peak current density resulted in a progressive increase in crystal size. However, the crystal orientation remained unaffected with increasing off-time. An increase in peak current density resulted in considerable refinement in crystal size of the deposits. The crystal orientation progressively changed from an almost random distribution at the lowest peak current density of 0.2 A/m 2 to a strong (200) texture at a peak current density of 2.0 A/m 2. The nanocrystalline nickel with grain size in the order of 30 nm can be produced from saccharin-containing Watts' baths. In contrast, when using an organic-free Watts' bath and similar pulse-plating conditions, the grain size can only be refined down to about 80–100 nm. The microhardness of deposits is related with grain size: when the grain size is large, the microhardness is consistent with Hall–Petch law (HPL); when the grain size is ultrafine, “nano-effect” would be generated, the microhardness is against HPL.

Effect of frequency and pulse width on the properties of ta:C films prepared by FCVA together with substrate pulse biasing

An investigation has been carried out to study the effect of frequency and pulse width on the deposition rate, intrinsic stress, morphological, micro-structural, mechanical and adhesive behaviour of tetrahedral amorphous carbon (ta:C) films prepared by a Filtered Cathodic Vacuum Arc (FCVA) system in conjunction with substrate pulse biasing. It is observed that the deposition rate increases with increasing frequency and pulse width in the lower ranges before it reaches to a more or less steady value of 25 nm/min at higher frequencies and pulse widths. The intrinsic stress in the film is reduced to a greater extent by the application of substrate pulse biasing. A stress reduction of approximately 85% can be easily obtained with an on-time (duty cycle) of 0.125%. The stress reduces further with increase in on-time, but at a slower rate. The morphological surface roughness increases with both frequency and pulse width. The micro-structural evaluation of the film using visible Raman spectroscopy shows that the intensity ratio of D-peak to G-peak ( I D/ I G) increases with increasing frequency. It is also observed that the G-peak width (FWHM) and the stress display a second order logarithmic correlation. The hardness shows a decrease in trend with increasing frequency. A noticeable increase in adhesion (critical load) with frequency is also observed in the lower ranges.

Quantitative texture analysis in pulse reverse current electroforming of nickel

The crystallographic texture of nickel deposits is known to be related to its magnetic and mechanical properties. However, up to now, most of the texture analyses of electrodeposited nickels have been semi-quantitative and still use a nickel sulphate bath, which is mainly for decorative industrial applications. In this paper, a quantitative texture analysis using ODF (orientation distribution function) has been carried out to study the effect of a pulse reverse current on the crystallographic texture of electroformed nickels, with the use of a nickel sulphamate bath, which is now commonly used for functional industrial applications and micro- or precise components. It was found that the [100] fibre texture with different orientation densities was formed at different on-times and off-times. With a constant off-time of 0.5 ms, an increase in on-time led to a gradual decrease in the orientation density of the [100] texture, whereas with a constant on-time of 5 ms, an increase in off-time has affected the change of the orientation density of the [100] texture in a more complicated manner. All of these phenomena are considered to be related to the change of the amount of inhibiting chemical species such as nickel hydroxide adsorbed on the cathode surface and the nickel deposition rate.

Microstructural evolution in pulse plated nickel electrodeposits

Square-wave cathodic current modulation was used to electrodeposit ultra-fine-grained nickel from an additive-free Watts bath. The influence of pulse parameters, namely, pulse on-time, off-time and peak current density on the grain size, surface morphology and crystal orientation was determined. The study showed that an increase in peak current density resulted in considerable refinement in crystal size of the deposit. The crystal orientation progressively changed from an almost random distribution at the lowest peak current density of 400 mA cm −2 to a strong (200) texture at a peak current density of 1600 mA cm −2. At constant peak current density and off-time, the crystal size of the deposit was found initially to decrease with pulse on-time before it started to increase with further increase in on-time. The crystal orientation progressively changed from an almost random distribution at the shortest on-time of 1 ms to a strong (200) fibre texture at an on-time of 8 ms. An increase in the pulse off-time at constant on-time and peak current density resulted in a progressive increase in crystal size. However, the crystal orientation remained unaffected with increasing off-time.

パルス電解法による亜鉛めっきの形態

In the pulsed current electrolysis of both zinc chloride and zinc sulphate baths, changes in the morphology of zinc deposits, cathodic overpotential and differential capacity were studied as a function of pulse current density, on-time and off-time. High pulse current density and long off-time electrolysis increased the cathodic overpotentials and thus produced fine grained deposits. Increase in on-time, however, gave no effect on the grain size of the deposits and overpotential values. These results suggest that the crystallization process of zinc in the pulsed current electrolysis is influenced by the cathodic overpotentials during on-time and the initial stage of off-time.