doublet stimulation protocol: Topics by Science.gov

Sample records for doublet stimulation protocol

History dependence of human muscle-fiber conduction velocity during voluntary isometric contractions.

PubMed

McGill, Kevin C; Lateva, Zoia C

2011-09-01

The conduction velocity (CV) of a muscle fiber is affected by the fiber's discharge history going back ∼1 s. We investigated this dependence by measuring CV fluctuations during voluntary isometric contractions of the human brachioradialis muscle. We recorded electromyogram (EMG) signals simultaneously from multiple intramuscular electrodes, identified potentials belonging to the same motor unit using EMG decomposition, and estimated the CV of each discharge from the interpotential interval. In 12 of 14 subjects, CV increased by ∼10% during the first second after recruitment and then fluctuated by about ±2% in a way that mirrored the fluctuations in the instantaneous firing rate. The CV profile could be precisely described in terms of the discharge history by a simple mathematical model. In the other two subjects, and one subject retested after cooling the arm, the CV fluctuations were inversely correlated with instantaneous firing rate. In all subjects, CV was additionally affected by very short interdischarge intervals (<25 ms): it was increased in doublets at recruitment, but decreased in doublets during continuous firing and after short interdischarge intervals in doubly innervated fibers. CV also exhibited a slow trend of about -0.05%/s that did not depend on the immediate discharge history. We suggest that measurements of CV fluctuations during voluntary contractions, or during stimulation protocols that involve longer and more complex stimulation patterns than are currently being used, may provide a sensitive approach for estimating the dynamic characteristics of ion channels in the human muscle-fiber membrane.
History dependence of human muscle-fiber conduction velocity during voluntary isometric contractions

PubMed Central

Lateva, Zoia C.

2011-01-01

The conduction velocity (CV) of a muscle fiber is affected by the fiber's discharge history going back ∼1 s. We investigated this dependence by measuring CV fluctuations during voluntary isometric contractions of the human brachioradialis muscle. We recorded electromyogram (EMG) signals simultaneously from multiple intramuscular electrodes, identified potentials belonging to the same motor unit using EMG decomposition, and estimated the CV of each discharge from the interpotential interval. In 12 of 14 subjects, CV increased by ∼10% during the first second after recruitment and then fluctuated by about ±2% in a way that mirrored the fluctuations in the instantaneous firing rate. The CV profile could be precisely described in terms of the discharge history by a simple mathematical model. In the other two subjects, and one subject retested after cooling the arm, the CV fluctuations were inversely correlated with instantaneous firing rate. In all subjects, CV was additionally affected by very short interdischarge intervals (<25 ms): it was increased in doublets at recruitment, but decreased in doublets during continuous firing and after short interdischarge intervals in doubly innervated fibers. CV also exhibited a slow trend of about −0.05%/s that did not depend on the immediate discharge history. We suggest that measurements of CV fluctuations during voluntary contractions, or during stimulation protocols that involve longer and more complex stimulation patterns than are currently being used, may provide a sensitive approach for estimating the dynamic characteristics of ion channels in the human muscle-fiber membrane. PMID:21565985
A microcontroller system for investigating the catch effect: functional electrical stimulation of the common peroneal nerve.

PubMed

Hart, D J; Taylor, P N; Chappell, P H; Wood, D E

2006-06-01

Correction of drop foot in hemiplegic gait is achieved by electrical stimulation of the common peroneal nerve with a series of pulses at a fixed frequency. However, during normal gait, the electromyographic signals from the tibialis anterior muscle indicate that muscle force is not constant but varies during the swing phase. The application of double pulses for the correction of drop foot may enhance the gait by generating greater torque at the ankle and thereby increase the efficiency of the stimulation with reduced fatigue. A flexible controller has been designed around the Odstock Drop Foot Stimulator to deliver different profiles of pulses implementing doublets and optimum series. A peripheral interface controller (PIC) microcontroller with some external circuits has been designed and tested to accommodate six profiles. Preliminary results of the measurements from a normal subject seated in a multi-moment chair (an isometric torque measurement device) indicate that profiles containing doublets and optimum spaced pulses look favourable for clinical use.
Augmenting Plasticity Induction in Human Motor Cortex by Disinhibition Stimulation.

PubMed

Cash, Robin F H; Murakami, Takenobu; Chen, Robert; Thickbroom, Gary W; Ziemann, Ulf

2016-01-01

Cellular studies showed that disinhibition, evoked pharmacologically or by a suitably timed priming stimulus, can augment long-term plasticity (LTP) induction. We demonstrated previously that transcranial magnetic stimulation evokes a period of presumably GABA(B)ergic late cortical disinhibition (LCD) in human primary motor cortex (M1). Here, we hypothesized that, in keeping with cellular studies, LCD can augment LTP-like plasticity in humans. In Experiment 1, patterned repetitive TMS was applied to left M1, consisting of 6 trains (intertrain interval, 8 s) of 4 doublets (interpulse interval equal to individual peak I-wave facilitation, 1.3-1.5 ms) spaced by the individual peak LCD (interdoublet interval (IDI), 200-250 ms). This intervention (total of 48 pulses applied over ∼45 s) increased motor-evoked potential amplitude, a marker of corticospinal excitability, in a right hand muscle by 147% ± 4%. Control experiments showed that IDIs shorter or longer than LCD did not result in LTP-like plasticity. Experiment 2 indicated topographic specificity to the M1 hand region stimulated by TMS and duration of the LTP-like plasticity of 60 min. In conclusion, GABA(B)ergic LCD offers a powerful new approach for augmenting LTP-like plasticity induction in human cortex. We refer to this protocol as disinhibition stimulation (DIS). © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Experimental testing of scattering polarization models

NASA Astrophysics Data System (ADS)

Li, Wenxian; Casini, Roberto; Tomczyk, Steven; Landi Degl'Innocenti, Egidio; Marsell, Brandan

2018-06-01

We realized a laboratory experiment to study the polarization of the Na I doublet at 589.3 nm, in the presence of a magnetic field. The purpose of the experiment is to test the theory of scattering polarization for illumination conditions typical of astrophysical plasmas. This work was stimulated by solar observations of the Na I doublet that have proven particularly challenging to reproduce with current models of polarized line formation, even casting doubts on our very understanding of the physics of scattering polarization on the Sun. The experiment has confirmed the fundamental correctness of the current theory, and demonstrated that the "enigmatic'' polarization of those observations is exclusively of solar origin.
Effect of tendon vibration during wide-pulse neuromuscular electrical stimulation (NMES) on muscle force production in people with spinal cord injury (SCI).

PubMed

Bochkezanian, Vanesa; Newton, Robert U; Trajano, Gabriel S; Vieira, Amilton; Pulverenti, Timothy S; Blazevich, Anthony J

2018-02-13

Neuromuscular electrical stimulation (NMES) is commonly used in skeletal muscles in people with spinal cord injury (SCI) with the aim of increasing muscle recruitment and thus muscle force production. NMES has been conventionally used in clinical practice as functional electrical stimulation (FES), using low levels of evoked force that cannot optimally stimulate muscular strength and mass improvements, and thus trigger musculoskeletal changes in paralysed muscles. The use of high intensity intermittent NMES training using wide-pulse width and moderate-intensity as a strength training tool could be a promising method to increase muscle force production in people with SCI. However, this type of protocol has not been clinically adopted because it may generate rapid muscle fatigue and thus prevent the performance of repeated high-intensity muscular contractions in paralysed muscles. Moreover, superimposing patellar tendon vibration onto the wide-pulse width NMES has been shown to elicit further increases in impulse or, at least, reduce the rate of fatigue in repeated contractions in able-bodied populations, but there is a lack of evidence to support this argument in people with SCI. Nine people with SCI received two NMES protocols with and without superimposing patellar tendon vibration on different days (i.e. STIM and STIM+vib), which consisted of repeated 30 Hz trains of 58 wide-pulse width (1000 μs) symmetric biphasic pulses (0.033-s inter-pulse interval; 2 s stimulation train; 2-s inter-train interval) being delivered to the dominant quadriceps femoris. Starting torque was 20% of maximal doublet-twitch torque and stimulations continued until torque declined to 50% of the starting torque. Total knee extensor impulse was calculated as the primary outcome variable. Total knee extensor impulse increased in four subjects when patellar tendon vibration was imposed (59.2 ± 15.8%) but decreased in five subjects (- 31.3 ± 25.7%). However, there were no statistically significant differences between these sub-groups or between conditions when the data were pooled. Based on the present results there is insufficient evidence to conclude that patellar tendon vibration provides a clear benefit to muscle force production or delays muscle fatigue during wide-pulse width, moderate-intensity NMES in people with SCI. ACTRN12618000022268 . Date: 11/01/2018. Retrospectively registered.
On the efficiency of FES cycling: a framework and systematic review.

PubMed

Hunt, K J; Fang, J; Saengsuwan, J; Grob, M; Laubacher, M

2012-01-01

Research and development in the art of cycling using functional electrical stimulation (FES) of the paralysed leg muscles has been going on for around thirty years. A range of physiological benefits has been observed in clinical studies but an outstanding problem with FES-cycling is that efficiency and power output are very low. The present work had the following aims: (i) to provide a tutorial introduction to a novel framework and methods of estimation of metabolic efficiency using example data sets, and to propose benchmark measures for evaluating FES-cycling performance; (ii) to systematically review the literature pertaining specifically to the metabolic efficiency of FES-cycling, to analyse the observations and possible explanations for the low efficiency, and to pose hypotheses for future studies which aim to improve performance. We recommend the following as benchmark measures for assessment of the performance of FES-cycling: (i) total work efficiency, delta efficiency and stimulation cost; (ii) we recommend, further, that these benchmark measures be complemented by mechanical measures of maximum power output, sustainable steady-state power output and endurance. Performance assessments should be carried out at a well-defined operating point, i.e. under conditions of well controlled work rate and cadence, because these variables have a strong effect on energy expenditure. Future work should focus on the two main factors which affect FES-cycling performance, namely: (i) unfavourable biomechanics, i.e. crude recruitment of muscle groups, non-optimal timing of muscle activation, and lack of synergistic and antagonistic joint control; (ii) non-physiological recruitment of muscle fibres, i.e. mixed recruitment of fibres of different type and deterministic constant-frequency stimulation. We hypothesise that the following areas may bring better FES-cycling performance: (i) study of alternative stimulation strategies for muscle activation including irregular stimulation patterns (e.g. doublets, triplets, stochastic patterns) and variable frequency stimulation trains, where it appears that increasing frequency over time may be profitable; (ii) study of better timing parameters for the stimulated muscle groups, and addition of more muscle groups: this path may be approached using EMG studies and constrained numerical optimisation employing dynamic models; (iii) development of optimal stimulation protocols for muscle reconditioning and FES-cycle training.
Counter-regulation by insulin and isoprenaline of a prominent fat-associated phosphoprotein doublet in rat adipocytes.

PubMed

Mooney, R A; Bordwell, K L

1991-03-01

1. In the adipocyte, phosphorylation/dephosphorylation of regulatory proteins is a common mechanism of metabolic regulation. We have observed a very prominent phosphoprotein doublet of 61 kDa and 63 kDa in rat adipocytes that is markedly responsive to hormones. The 63 kDa band was the predominant phosphoprotein in the cell in response to 0.1 microM-isoprenaline, whereas the 61 kDa band was nearly absent. Insulin alone did not alter 32P incorporation into the doublet, but partially counteracted the effects of isoprenaline, decreasing label in the 63 kDa band by as much as 50% and resulting in the reappearance of the 61 kDa band. 2. Subcellular fractionation demonstrated that both phosphoprotein bands were fat-associated. Neither insulin nor isoprenaline altered this localization. Peptide maps (one-dimensional) of the 61/63 kDa bands demonstrated close sequence similarity. Amino acid analysis revealed the presence of phosphoserine and phosphothreonine. The latter was more prominent in the 61 kDa band. Isoprenaline caused an absolute increase in both phosphoamino acids. 3. Permeabilization of 32P-labelled isoprenaline-treated cells with digitonin initiated rapid dephosphorylation of the 63 kDa band, with reappearance of the 61 kDa band. Insulin increased the rate of dephosphorylation by 2-3-fold when present with isoprenaline before permeabilization. 4. In permeabilized adipocytes, cyclic AMP (1 microM-1 mM) increased phosphorylation of the 61/63 kDa doublet by 4-10-fold in the presence of [gamma-32P]ATP, but insulin had no effect. 5. We conclude that this prominent phosphoprotein, migrating as a 61/63 kDa doublet, is coupled to the cyclic AMP-dependent protein kinase and is associated with an insulin-stimulated phosphoprotein phosphatase activity. This fat-associated phosphoprotein, which is under counter-regulatory hormonal control, may play a role in hormone-dependent lipid metabolism.
Triplet firing origin in human motor units: emerging hypotheses.

PubMed

Kudina, Lydia P; Andreeva, Regina E

2016-03-01

A specific feature of motor unit (MU) firing behaviour is rhythmic trains of single discharges at low rate resulting from the prolonged motoneuronal afterhyperpolarization. However, some MUs exhibit occasional doublets with uniquely short interspike intervals (2.5-20.0 ms). Motoneuronal delayed depolarization is commonly accepted to be doublet underlying mechanism. Apart from doublets, much scarcer MU triple discharges were described, but their mechanisms are disputable. The aim of the present study was to analyse MU triplet firing origin in healthy humans. MU triple discharges occasionally arising during gentle voluntary muscle contractions were compared with those arising in axons during motor nerve stimulation. Firing pattern was analysed in 109 MUs of four muscles: the tibialis anterior, the flexor carpi ulnaris, the abductor pollicis brevis, and the abductor digiti minimi. Our findings present evidence that during voluntary contractions two kinds of MU triplet firing can be occasionally observed: "true" motoneuronal triplets (interspike intervals of 3.6-17.3 ms) with the delayed depolarization as the possible underlying mechanism and axonal triple discharges including the M-response and F-wave. The findings can be useful not only for understanding mechanisms of the very rare motoneuronal firing in healthy humans but also for estimation of pathological triplet firing origin.
Palladium-based Mass-Tag Cell Barcoding with a Doublet-Filtering Scheme and Single Cell Deconvolution Algorithm

PubMed Central

Zunder, Eli R.; Finck, Rachel; Behbehani, Gregory K.; Amir, El-ad D.; Krishnaswamy, Smita; Gonzalez, Veronica D.; Lorang, Cynthia G.; Bjornson, Zach; Spitzer, Matthew H.; Bodenmiller, Bernd; Fantl, Wendy J.; Pe’er, Dana; Nolan, Garry P.

2015-01-01

SUMMARY Mass-tag cell barcoding (MCB) labels individual cell samples with unique combinatorial barcodes, after which they are pooled for processing and measurement as a single multiplexed sample. The MCB method eliminates variability between samples in antibody staining and instrument sensitivity, reduces antibody consumption, and shortens instrument measurement time. Here, we present an optimized MCB protocol with several improvements over previously described methods. The use of palladium-based labeling reagents expands the number of measurement channels available for mass cytometry and reduces interference with lanthanide-based antibody measurement. An error-detecting combinatorial barcoding scheme allows cell doublets to be identified and removed from the analysis. A debarcoding algorithm that is single cell-based rather than population-based improves the accuracy and efficiency of sample deconvolution. This debarcoding algorithm has been packaged into software that allows rapid and unbiased sample deconvolution. The MCB procedure takes 3–4 h, not including sample acquisition time of ~1 h per million cells. PMID:25612231
Comparison of results of cycles treated with modified mild protocol and short protocol for ovarian stimulation.

PubMed

Coelho, F; Aguiar, L F; Cunha, G S P; Cardinot, N; Lucena, E

2014-01-01

The ovarian stimulation has been applied in order to increase the number of oocytes to compensate for the poor results of in vitro fertilization, allowing the selection of one or more embryos to be transferred. Our aim is to compare the results obtained in IVF/ICSI cycles using the short protocol for controlled ovarian stimulation to the results from the modified mild protocol used in our department. A total of 240 cycles were conducted from January 2010 to December 2011. When comparing both protocols, it could be observed that there was a significant difference in the quantity of gonadotropins doses in the mild protocol and in the short protocol. No significant difference was observed regarding pregnancy rates per cycle, 22% and 26.2%, in short and mild protocols, respectively. The protocols of controlled ovarian stimulation are often associated with high risk of complications such as ovarian hyperstimulation syndrome, excessive emotional stress, high rates of treatment dropouts, and abdominal discomfort. With the data obtained in this study, one can conclude that there are less risks and complications for the patient when using the mild stimulation protocol. It was also observed that in this group there was a slightly higher rate.
Counter-regulation by insulin and isoprenaline of a prominent fat-associated phosphoprotein doublet in rat adipocytes.

PubMed Central

Mooney, R A; Bordwell, K L

1991-01-01

1. In the adipocyte, phosphorylation/dephosphorylation of regulatory proteins is a common mechanism of metabolic regulation. We have observed a very prominent phosphoprotein doublet of 61 kDa and 63 kDa in rat adipocytes that is markedly responsive to hormones. The 63 kDa band was the predominant phosphoprotein in the cell in response to 0.1 microM-isoprenaline, whereas the 61 kDa band was nearly absent. Insulin alone did not alter 32P incorporation into the doublet, but partially counteracted the effects of isoprenaline, decreasing label in the 63 kDa band by as much as 50% and resulting in the reappearance of the 61 kDa band. 2. Subcellular fractionation demonstrated that both phosphoprotein bands were fat-associated. Neither insulin nor isoprenaline altered this localization. Peptide maps (one-dimensional) of the 61/63 kDa bands demonstrated close sequence similarity. Amino acid analysis revealed the presence of phosphoserine and phosphothreonine. The latter was more prominent in the 61 kDa band. Isoprenaline caused an absolute increase in both phosphoamino acids. 3. Permeabilization of 32P-labelled isoprenaline-treated cells with digitonin initiated rapid dephosphorylation of the 63 kDa band, with reappearance of the 61 kDa band. Insulin increased the rate of dephosphorylation by 2-3-fold when present with isoprenaline before permeabilization. 4. In permeabilized adipocytes, cyclic AMP (1 microM-1 mM) increased phosphorylation of the 61/63 kDa doublet by 4-10-fold in the presence of [gamma-32P]ATP, but insulin had no effect. 5. We conclude that this prominent phosphoprotein, migrating as a 61/63 kDa doublet, is coupled to the cyclic AMP-dependent protein kinase and is associated with an insulin-stimulated phosphoprotein phosphatase activity. This fat-associated phosphoprotein, which is under counter-regulatory hormonal control, may play a role in hormone-dependent lipid metabolism. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:1848760
Characteristics and significance of doublets on needle EMG.

PubMed

Lamb, Christopher J; Rubin, Devon I

2017-04-01

Voluntary doublets are electrophysiological phenomena thought to be associated with metabolic derangements or neuromuscular conditions. We prospectively studied 232 consecutive patients examined by a single examiner during routine electromyography (EMG) to determine the frequency of doublets in individual patients, specific muscles, neuromuscular conditions, electrolyte levels, and doublet characteristics. Of 232 patients, 25 (10.7%) exhibited doublets. The mean age was 59 (52% men). Only 32 of 1,303 (2.5%) muscles exhibited doublets. Lower extremity and paraspinal groups represented 91% of muscles with doublets. Doublet frequency grouped by EMG diagnoses was: ALS (3 of 11; 27.1%), myopathy (3 of 10; 30.0%), axonal polyneuropathy (7 of 29; 24.1%), and no disease (7 of 109; 6.4%). There were no differences in serum electrolytes between doublet and matched subjects. Doublets occur in approximately 10% of patients, more commonly in lower extremity and paraspinal muscles, and are not correlated with a specific metabolic abnormality or neuromuscular condition. Muscle Nerve 55: 598-600, 2017. © 2016 Wiley Periodicals, Inc.
Matching initial torque with different stimulation parameters influences skeletal muscle fatigue.

PubMed

Bickel, C Scott; Gregory, Chris M; Azuero, Andres

2012-01-01

A fundamental barrier to using electrical stimulation in the clinical setting is an inability to maintain torque production secondary to muscle fatigue. Electrical stimulation parameters are manipulated to influence muscle torque production, and they may also influence fatigability during repetitive stimulation. Our purpose was to determine the response of the quadriceps femoris to three different fatigue protocols using the same initial torque obtained by altering stimulator parameter settings. Participants underwent fatigue protocols in which either pulse frequency (lowHz), pulse duration (lowPD), or voltage (lowV) was manipulated to obtain an initial torque that equaled 25% of maximum voluntary isometric contraction. Muscle soreness was reported on a visual analog scale 48 h after each fatigue test. The lowHz protocol resulted in the least fatigue (25% +/- 14%); the lowPD (50% +/- 13%) and lowV (48% +/- 14%) protocols had similar levels of fatigue. The lowHz protocol resulted in significantly less muscle soreness than the higher frequency protocols. Stimulation protocols that use a lower frequency coupled with long pulse durations and high voltages result in lesser amounts of muscle fatigue and perceived soreness. The identification of optimal stimulation patterns to maximize muscle performance will reduce the effect of muscle fatigue and potentially improve clinical efficacy.
Stimulation of the ovaries in women with breast cancer undergoing fertility preservation: Alternative versus standard stimulation protocols; the study protocol of the STIM-trial.

PubMed

Dahhan, T; Balkenende, E M E; Beerendonk, C C M; Fleischer, K; Stoop, D; Bos, A M E; Lambalk, C B; Schats, R; van Golde, R J T; Schipper, I; Louwé, L A; Cantineau, A E P; Smeenk, J M J; de Bruin, J P; Reddy, N; Kopeika, Y; van der Veen, F; van Wely, M; Linn, S C; Goddijn, M

2017-10-01

Chemotherapy for breast cancer may have a negative impact on reproductive function due to gonadotoxicity. Fertility preservation via banking of oocytes or embryos after ovarian stimulation with FSH can increase the likelihood of a future live birth. It has been hypothesized that elevated serum estrogen levels during ovarian stimulation may induce breast tumour growth. This has led to the use of alternative stimulation protocols with addition of tamoxifen or letrozole. The effectiveness of these stimulation protocols in terms of oocyte yield is unknown. Randomized open-label trial comparing ovarian stimulation plus tamoxifen and ovarian stimulation plus letrozole with standard ovarian stimulation in the course of fertility preservation. The study population consists of women with breast cancer who opt for banking of oocytes or embryos, aged 18-43years at randomisation. Primary outcome is the number of oocytes retrieved at follicle aspiration. Secondary outcomes are number of mature oocytes retrieved, number of oocytes or embryos banked and peak E2 levels during ovarian stimulation. Concerning the lack of evidence on which stimulation protocol should be used in women with breast cancer and the growing demand for fertility preservation, there is an urgent need to undertake this study. By performing this study, we will be able to closely monitor the effects of various stimulation protocols in women with breast cancer and pave the way for long term follow up on the safety of this procedure in terms of breast cancer prognosis. NTR4108. Copyright © 2017 Elsevier Inc. All rights reserved.
Comparison of Results of Cycles Treated with Modified Mild Protocol and Short Protocol for Ovarian Stimulation

PubMed Central

Aguiar, L. F.; Cunha, G. S. P.; Cardinot, N.; Lucena, E.

2014-01-01

The ovarian stimulation has been applied in order to increase the number of oocytes to compensate for the poor results of in vitro fertilization, allowing the selection of one or more embryos to be transferred. Our aim is to compare the results obtained in IVF/ICSI cycles using the short protocol for controlled ovarian stimulation to the results from the modified mild protocol used in our department. A total of 240 cycles were conducted from January 2010 to December 2011. When comparing both protocols, it could be observed that there was a significant difference in the quantity of gonadotropins doses in the mild protocol and in the short protocol. No significant difference was observed regarding pregnancy rates per cycle, 22% and 26.2%, in short and mild protocols, respectively. The protocols of controlled ovarian stimulation are often associated with high risk of complications such as ovarian hyperstimulation syndrome, excessive emotional stress, high rates of treatment dropouts, and abdominal discomfort. With the data obtained in this study, one can conclude that there are less risks and complications for the patient when using the mild stimulation protocol. It was also observed that in this group there was a slightly higher rate. PMID:25763398
Electrical Stimulation of Coleopteran Muscle for Initiating Flight.

PubMed

Choo, Hao Yu; Li, Yao; Cao, Feng; Sato, Hirotaka

2016-01-01

Some researchers have long been interested in reconstructing natural insects into steerable robots or vehicles. However, until recently, these so-called cyborg insects, biobots, or living machines existed only in science fiction. Owing to recent advances in nano/micro manufacturing, data processing, and anatomical and physiological biology, we can now stimulate living insects to induce user-desired motor actions and behaviors. To improve the practicality and applicability of airborne cyborg insects, a reliable and controllable flight initiation protocol is required. This study demonstrates an electrical stimulation protocol that initiates flight in a beetle (Mecynorrhina torquata, Coleoptera). A reliable stimulation protocol was determined by analyzing a pair of dorsal longitudinal muscles (DLMs), flight muscles that oscillate the wings. DLM stimulation has achieved with a high success rate (> 90%), rapid response time (< 1.0 s), and small variation (< 0.33 s; indicating little habituation). Notably, the stimulation of DLMs caused no crucial damage to the free flight ability. In contrast, stimulation of optic lobes, which was earlier demonstrated as a successful flight initiation protocol, destabilized the beetle in flight. Thus, DLM stimulation is a promising secure protocol for inducing flight in cyborg insects or biobots.
Electrical Stimulation of Coleopteran Muscle for Initiating Flight

PubMed Central

Choo, Hao Yu; Li, Yao; Cao, Feng; Sato, Hirotaka

2016-01-01

Some researchers have long been interested in reconstructing natural insects into steerable robots or vehicles. However, until recently, these so-called cyborg insects, biobots, or living machines existed only in science fiction. Owing to recent advances in nano/micro manufacturing, data processing, and anatomical and physiological biology, we can now stimulate living insects to induce user-desired motor actions and behaviors. To improve the practicality and applicability of airborne cyborg insects, a reliable and controllable flight initiation protocol is required. This study demonstrates an electrical stimulation protocol that initiates flight in a beetle (Mecynorrhina torquata, Coleoptera). A reliable stimulation protocol was determined by analyzing a pair of dorsal longitudinal muscles (DLMs), flight muscles that oscillate the wings. DLM stimulation has achieved with a high success rate (> 90%), rapid response time (< 1.0 s), and small variation (< 0.33 s; indicating little habituation). Notably, the stimulation of DLMs caused no crucial damage to the free flight ability. In contrast, stimulation of optic lobes, which was earlier demonstrated as a successful flight initiation protocol, destabilized the beetle in flight. Thus, DLM stimulation is a promising secure protocol for inducing flight in cyborg insects or biobots. PMID:27050093
Timing of pulsed electromagnetic field stimulation does not affect the promotion of bone cell development.

PubMed

Hannay, Gwynne; Leavesley, David; Pearcy, Mark

2005-12-01

Pulsed electromagnetic field (PEMF) devices have been used clinically to promote the healing of surgically resistant fractures in vivo. However, there is a sparsity of data on how the timing of an applied PEMF effects the osteogenic cells that would be present within the fracture gap. The purpose of this study was to examine the response of osteoblast-like cells to a PEMF stimulus, mimicking that of a clinically available device, using four protocols for the timing of the stimulus. The PEMF signal consisted of a 5 ms pulse burst (containing 20 pulses) repeated at 15 Hz. Cultures of a human osteosarcoma cell line, SaOS-2, were exposed to the four timing protocols, each conducted over 3 days. Protocol one stimulated the cells for 8 h each day, protocol two stimulated the cells for 24 h on the first day, protocol three stimulated the cells for 24 h on the second day, and protocol four stimulated the cells for 24 h on the third day. Cells were seeded with either 25,000 or 50,000 cells/well (24-well cell culture plates). All assays showed reduced proliferation and increased differentiation (alkaline phosphatase activity) in the PEMF stimulated cultures compared with the control cultures, except for protocol four alkaline phosphatase measurements. No clear trend was observed between the four protocols; however this may be due to cell density. The results indicated that an osteoblast-like cell line is responsive to a 15 Hz PEMF stimulus, which will stimulate the cell line to into an increasing state of maturity. Bioelectromagnetics (c) 2005 Wiley-Liss, Inc
Evaluation of results obtained with corifollitropin alfa after poor ovarian response in previous cycle using recombinant follicular stimulating hormone in the long-term protocol.

PubMed

Salgueiro, Lister L; Rolim, Juliana R; Moura, Bernardo R L; Machado, Suelen P P; Haddad, Carolina

2016-08-01

This study evaluated the use of Corifollitropin alfa in patients with previous poor response to recombinant follicle stimulating hormone in long-term protocols using gonadotropin-releasing hormone. Twenty-seven poor responders to previous treatment with the long term protocol using the recombinant follicle stimulating hormone (Group 1) were selected and then submitted to a second attempt using the same long term protocol with Corifollitropin alfa instead of the recombinant follicle stimulating hormone (Group 2).Ovarian down-regulation was achieved using subcutaneous administration of Leuprolide Acetate. Ovarian stimulation was performed with recombinant follicle stimulating hormone until the administration of human chorionic gonadotropin, followed by follicular aspiration (Group 1). Group 2 was submitted to this same protocol using Corifollitropin alfa instead of recombinant follicle stimulating hormone. There were significant differences in the number of aspirated oocytes, percentage of mature oocytes, amount of injected oocytes and transferred embryos - with all of these parameters being increased in the Corifollitropin alfa group. In addition, the rates of pregnancy and ongoing pregnancy were also significantly higher in the Corifollitropin alfa group. The present study demonstrated that the use of Corifollitropin alfa in the long-term protocol could be a highly effective alternative for patients with poor ovarian response, who were unsuccessful in a previous treatment with In Vitro Fertilization - Intracytoplasmic Sperm Injection.

A fast stimulability screening protocol for neuronal cultures on microelectrode arrays.

PubMed

Kapucu, Fikret E; Tanskanen, Jarno M A; Yuan, Yuting; Hyttinen, Jari A K

2015-01-01

Microelectrode arrays (MEAs) are used to study the electrical activity in brain slices and neuronal cultures. MEA experiments for the analysis of electrical stimulation responses require the tissue or culture to be prone to stimulation. For brain slices, potential stimulation sites may be directly visible in microscope, in which case the determination of stimulability at those locations is sufficient. In unstructured neuronal cultures, potential stimulation sites may not be known a priori, and spatial stimulability screening should be performed. Considering, e.g., 59 microelectrode sites, each to be stimulated several times, may result in long screening times, unacceptable with a MEA system without an integrated CO2 incubator, or in high stimulation effects on the networks. Here, we describe an implementation of a fast stimulation protocol employing pseudorandom stimulation site switching aiming at alleviating the network effects of the stimulability screening. In this paper, we show the usability of the proposed protocol by first detecting stimulable locations and subsequently apply repeated stimulation on the identified potentially stimulable locations to observe an exemplary neuronal pathway.
Impact of uncertain head tissue conductivity in the optimization of transcranial direct current stimulation for an auditory target

NASA Astrophysics Data System (ADS)

Schmidt, Christian; Wagner, Sven; Burger, Martin; van Rienen, Ursula; Wolters, Carsten H.

2015-08-01

Objective. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique to modify neural excitability. Using multi-array tDCS, we investigate the influence of inter-individually varying head tissue conductivity profiles on optimal electrode configurations for an auditory cortex stimulation. Approach. In order to quantify the uncertainty of the optimal electrode configurations, multi-variate generalized polynomial chaos expansions of the model solutions are used based on uncertain conductivity profiles of the compartments skin, skull, gray matter, and white matter. Stochastic measures, probability density functions, and sensitivity of the quantities of interest are investigated for each electrode and the current density at the target with the resulting stimulation protocols visualized on the head surface. Main results. We demonstrate that the optimized stimulation protocols are only comprised of a few active electrodes, with tolerable deviations in the stimulation amplitude of the anode. However, large deviations in the order of the uncertainty in the conductivity profiles could be noted in the stimulation protocol of the compensating cathodes. Regarding these main stimulation electrodes, the stimulation protocol was most sensitive to uncertainty in skull conductivity. Finally, the probability that the current density amplitude in the auditory cortex target region is supra-threshold was below 50%. Significance. The results suggest that an uncertain conductivity profile in computational models of tDCS can have a substantial influence on the prediction of optimal stimulation protocols for stimulation of the auditory cortex. The investigations carried out in this study present a possibility to predict the probability of providing a therapeutic effect with an optimized electrode system for future auditory clinical and experimental procedures of tDCS applications.
Comparison of mild and microdose GnRH agonist flare protocols on IVF outcome in poor responders.

PubMed

Karimzadeh, Mohammad Ali; Mashayekhy, Mehri; Mohammadian, Farnaz; Moghaddam, Fatemeh Mansoori

2011-05-01

To compare the IVF outcome of clomiphene citrate/gonadotropin/antagonist (mild protocol) and microdose GnRH agonist flare protocols for poor responders undergoing in vitro fertilization. 159 poor responder patients were randomized and ovarian stimulation was performed with clomiphene citrate, gonadotropin and antagonist (group I) or microdose GnRH agonist flare (group II) protocols. Main outcome was clinical pregnancy rate and secondary outcomes were doses of gonadotropin administration and duration of stimulation. There were no significant differences in age, causes of infertility, basal FSH, BMI, duration of infertility, E(2) level on the day of hCG injection in both groups. Although the cancellation, fertilization, and clinical pregnancy rates were similar in both groups, the endometrial thickness, number of retrieved oocytes, mature oocytes and implantation rate were significantly higher in mild protocol. The doses of gonadotropin administration and duration of stimulation were significantly lower in mild protocol. We recommend mild protocol in assisted reproductive technology cycles for poor responders based on our results regarding less doses of used gonadotropin and a shorter duration of stimulation.
Renormalization-group constraints on Yukawa alignment in multi-Higgs-doublet models

NASA Astrophysics Data System (ADS)

Ferreira, P. M.; Lavoura, L.; Silva, João P.

2010-05-01

We write down the renormalization-group equations for the Yukawa-coupling matrices in a general multi-Higgs-doublet model. We then assume that the matrices of the Yukawa couplings of the various Higgs doublets to right-handed fermions of fixed quantum numbers are all proportional to each other. We demonstrate that, in the case of the two-Higgs-doublet model, this proportionality is preserved by the renormalization-group running only in the cases of the standard type-I, II, X, and Y models. We furthermore show that a similar result holds even when there are more than two Higgs doublets: the Yukawa-coupling matrices to fermions of a given electric charge remain proportional under the renormalization-group running if and only if there is a basis for the Higgs doublets in which all the fermions of a given electric charge couple to only one Higgs doublet.
Synthesis of C13- and N15-Labeled DNAN

DTIC Science & Technology

2014-07-24

Multiplicities are described as singlet (s), doublet (d), triplet (t), quartet (q), doublet of doublets (dd), doublet of doublet of doublets ( ddd ), multiplet...dd, 4.8Hz, 2.6Hz, 1H), 8.40 ( ddd , 8.8Hz, 2.6Hz, 1.8Hz, 1H), and 7.81 (d, 8.8Hz, 1H) ppm. 13C NMR (CDCl3): δ 147.8 (dd, 18Hz, 3Hz), 146.3 (dd, 17Hz...Dinitroanisole mp: 86-88 °C 1H NMR (CDCl3): δ 8.77 (m, 4.8Hz, 2.6Hz, 1H), 8.46 ( ddd , 9.2Hz, 2.6Hz, 1.8Hz, 1H), 7.23 (d, 9.2Hz, 1H), and 4.10 (s, 3H
Anaemia management protocols in the care of haemodialysis patients: examining patient outcomes.

PubMed

Saunders, Sushila; MacLeod, Martha L P; Salyers, Vince; MacMillan, Peter D; Ogborn, Malcolm R

2013-08-01

To determine whether the use of a nurse-driven protocol in the haemodialysis setting is as safe and effective as traditional physician-driven approaches to anaemia management. The role of haemodialysis nurses in renal anaemia management has evolved through the implementation of nurse-driven protocols, addressing the trend of exceeding haemoglobin targets and rising costs of erythropoietin-stimulating agents. Retrospective, non-equivalent case control group design. The sample was from three haemodialysis units in a control group (n = 64) and three haemodialysis units in a protocol group (n = 43). The protocol group used a nurse-driven renal anaemia management protocol, while the control group used a traditional physician-driven approach to renal anaemia management. All retrospective data were obtained from a provincial renal database. Data were analysed using chi-square tests and t-tests. Patient outcomes examined were haemoglobin levels, transferrin saturation levels, erythropoietin-stimulating agents use and intravenous iron use. Cost comparisons were determined using average use of erythropoietin-stimulating agents and intravenous iron. Control and protocol groups reached haemoglobin target levels. In the protocol group, 75% reached transferrin saturation target levels in comparison with 25% of the control group. Use and costs for iron was higher in the control group, while use and costs for erythropoietin was higher in the protocol group. The higher usage of erythropoietin-stimulating agents was potentially related to comorbid conditions amongst the protocol group. A nurse-driven protocol approach to renal anaemia management was as effective as the physician-driven approach in reaching haemoglobin and transferrin saturation levels. Further examination of the use and dosing of erythropoietin-stimulating agents and intravenous iron, their impact on haemoglobin levels related to patient comorbidities and subsequent cost effectiveness of protocols is required. Using a nurse-driven protocol in practice supports the independent nursing role while contributing to safe patient outcomes. © 2013 Blackwell Publishing Ltd.
Dynamic aftereffects in supplementary motor network following inhibitory transcranial magnetic stimulation protocols.

PubMed

Ji, Gong-Jun; Yu, Fengqiong; Liao, Wei; Wang, Kai

2017-04-01

The supplementary motor area (SMA) is a key node of the motor network. Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the SMA can potentially improve movement disorders. However, the aftereffects of inhibitory rTMS on brain function remain largely unknown. Using a single-blind, crossover within-subject design, we investigated the role of aftereffects with two inhibitory rTMS protocols [1800 pulses of either 1-Hz repetitive stimulation or continuous theta burst stimulation (cTBS)] on the left SMA. A total of 19 healthy volunteers participated in the rTMS sessions on 2 separate days. Firstly, short-term aftereffects were estimated at three levels (functional connectivity, local activity, and network properties) by comparing the resting-state functional magnetic resonance imaging datasets (9min) acquired before and after each rTMS session. Local activity and network properties were not significantly altered by either protocol. Functional connectivity within the SMA network was increased (in the left paracentral gyrus) by 1-Hz stimulation and decreased (in the left inferior frontal gyrus and SMA/middle cingulate cortex) by cTBS. The subsequent three-way analysis of variance (site×time×protocol) did not show a significant interaction effect or "protocol" main effect, suggesting that the two protocols share an underlying mechanism. Secondly, sliding-window analysis was used to evaluate the dynamic features of aftereffects in the ~29min after the end of stimulation. Aftereffects were maintained for a maximum of 9.8 and 6.6min after the 1-Hz and cTBS protocols, respectively. In summary, this study revealed topographical and temporal aftereffects in the SMA network following inhibitory rTMS protocols, providing valuable information for their application in future neuroscience and clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.
Breakdown of doublet recirculation and direct line drives by far-field flow in reservoirs: implications for geothermal and hydrocarbon well placement

NASA Astrophysics Data System (ADS)

Weijermars, R.; van Harmelen, A.

2016-07-01

An important real world application of doublet flow occurs in well design of both geothermal and hydrocarbon reservoirs. A guiding principle for fluid management of injection and extraction wells is that mass balance is commonly assumed between the injected and produced fluid. Because the doublets are considered closed loops, the injection fluid is assumed to eventually reach the producer well and all the produced fluid ideally comes from stream tubes connected to the injector of the well pair making up the doublet. We show that when an aquifer background flow occurs, doublets will rarely retain closed loops of fluid recirculation. When the far-field flow rate increases relative to the doublet's strength, the area occupied by the doublet will diminish and eventually vanishes. Alternatively, rather than using a single injector (source) and single producer (sink), a linear array of multiple injectors separated by some distance from a parallel array of producers can be used in geothermal energy projects as well as in waterflooding of hydrocarbon reservoirs. Fluid flow in such an arrangement of parallel source-sink arrays is shown to be macroscopically equivalent to that of a line doublet. Again, any far-field flow that is strong enough will breach through the line doublet, which then splits into two vortices. Apart from fundamental insight into elementary flow dynamics, our new results provide practical clues that may contribute to improve the planning and design of doublets and direct line drives commonly used for flow management of groundwater, geothermal and hydrocarbon reservoirs.
Computer simulation of flagellar movement VIII: coordination of dynein by local curvature control can generate helical bending waves.

PubMed

Brokaw, Charles J

2002-10-01

Computer simulations have been carried out with a model flagellum that can bend in three dimensions. A pattern of dynein activation in which regions of dynein activity propagate along each doublet, with a phase shift of approximately 1/9 wavelength between adjacent doublets, will produce a helical bending wave. This pattern can be termed "doublet metachronism." The simulations show that doublet metachronism can arise spontaneously in a model axoneme in which activation of dyneins is controlled locally by the curvature of each outer doublet microtubule. In this model, dyneins operate both as sensors of curvature and as motors. Doublet metachronism and the chirality of the resulting helical bending pattern are regulated by the angular difference between the direction of the moment and sliding produced by dyneins on a doublet and the direction of the controlling curvature for that doublet. A flagellum that is generating a helical bending wave experiences twisting moments when it moves against external viscous resistance. At high viscosities, helical bending will be significantly modified by twist unless the twist resistance is greater than previously estimated. Spontaneous doublet metachronism must be modified or overridden in order for a flagellum to generate the planar bending waves that are required for efficient propulsion of spermatozoa. Planar bending can be achieved with the three-dimensional flagellar model by appropriate specification of the direction of the controlling curvature for each doublet. However, experimental observations indicate that this "hard-wired" solution is not appropriate for real flagella. Copyright 2002 Wiley-Liss, Inc.
The duration of gonadotropin stimulation does not alter the clinical pregnancy rate in IVF or ICSI cycles.

PubMed

Purandare, N; Emerson, G; Kirkham, C; Harrity, C; Walsh, D; Mocanu, E

2017-08-01

Ovarian stimulation is an essential part of assisted reproduction treatments. Research on whether the duration of stimulation alters the success in assisted reproduction has not been conclusive. The purpose of the study was to establish whether the duration of ovarian stimulation alters the success in assisted reproduction treatments. All fresh (non-donor) stimulation cycles performed in an academic tertiary referral ART centre over a period of 18 years, between 1st January 1997 and 31st December 2014, were identified. Data were prospectively and electronically collected. IVF and ICSI cycles were analysed independently. Each category was then subdivided into assisted reproduction cycles where the antagonist, long (down regulation) and flare protocol were used. Clinical pregnancy was the main outcome measured. A total of 10,478 stimulation cycles (6011 fresh IVF and 4467 fresh ICSI) reaching egg collection were included. We showed no significant difference in CP rates in IVF cycles for the long (p = 0.082), antagonist (p = 0.217) or flare (p = 0.741) protocol cycles or in ICSI cycles with the long (p = 0.223), antagonist (p = 0.766) or the flare (p = 0.690) protocol with regards the duration of stimulation. The duration of stimulation does not alter the CP rate in ICSI or IVF cycles using the long, antagonist or flare stimulation protocol.
Doublet Crater

NASA Image and Video Library

2010-12-22

This image from NASA Mars Odyssey is of a doublet crater located in Utopia Planitia, near the Elysium Volcanic region. Doublet craters are formed by simultaneous impact of a meteor that broke into two pieces prior to hitting the surface.
Analysis of grating doublets for achromatic beam-splitting

PubMed Central

Pacheco, Shaun; Milster, Tom; Liang, Rongguang

2015-01-01

Achromatic beam-splitting grating doublets are designed for both continuous phase and binary phase gratings. By analyzing the sensitivity to lateral shifts between the two grating layers, it is shown that continuous-profile grating doublets are extremely difficult to fabricate. Achromatic grating doublets that have profiles with a constant first spatial derivative are significantly more resistant to lateral shifts between grating layers, where one design case showed a 17 times improvement in performance. Therefore, binary phase, multi-level phase, and blazed grating doublets perform significantly better than continuous phase grating doublets in the presence of a lateral shift between two grating layers. By studying the sensitivity to fabrication errors in the height of both grating layers, one grating layer height can be adjusted to maintain excellent performance over a large wavelength range if the other grating layer is fabricated incorrectly. It is shown in one design case that the performance of an achromatic Dammann grating doublet can be improved by a factor of 215 if the heights of the grating layers are chosen to minimize the performance change in the presence of fabrication errors. PMID:26368261
Mechanical Stimulation Protocols of Human Derived Cells in Articular Cartilage Tissue Engineering - A Systematic Review.

PubMed

Khozoee, Baktash; Mafi, Pouya; Mafi, Reza; Khan, Wasim S

2017-01-01

Mechanical stimulation is a key factor in articular cartilage generation and maintenance. Bioreactor systems have been designed and built in order to deliver specific types of mechanical stimulation. The focus has been twofold, applying a type of preconditioning in order to stimulate cell differentiation, and to simulate in vivo conditions in order to gain further insight into how cells respond to different stimulatory patterns. Due to the complex forces at work within joints, it is difficult to simulate mechanical conditions using a bioreactor. The aim of this review is to gain a deeper understanding of the complexities of mechanical stimulation protocols by comparing those employed in bioreactors in the context of tissue engineering for articular cartilage, and to consider their effects on cultured cells. Allied and Complementary Medicine 1985 to 2016, Ovid MEDLINE[R] 1946 to 2016, and Embase 1974 to 2016 were searched using key terms. Results were subject to inclusion and exclusion criteria, key findings summarised into a table and subsequently discussed. Based on this review it is overwhelmingly clear that mechanical stimulation leads to increased chondrogenic properties in the context of bioreactor articular cartilage tissue engineering using human cells. However, given the variability and lack of controlled factors between research articles, results are difficult to compare, and a standardised method of evaluating stimulation protocols proved challenging. With improved standardisation in mechanical stimulation protocol reporting, bioreactor design and building processes, along with a better understanding of joint behaviours, we hope to perform a meta-analysis on stimulation protocols and methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Facilitatory non-invasive brain stimulation in older adults: the effect of stimulation type and duration on the induction of motor cortex plasticity.

PubMed

Puri, Rohan; Hinder, Mark R; Canty, Alison J; Summers, Jeffery J

2016-12-01

Despite holding significant promise for counteracting the deleterious effects of ageing on cognitive and motor function, little is known of the effects of facilitatory non-invasive brain stimulation (NBS) techniques on corticospinal excitability (CSE) in older adults. Thirty-three older adults (≥60 years) participated in four NBS sessions on separate days, receiving 10- and 20-min anodal transcranial direct current stimulation (atDCS), and 300 and 600 pulses of intermittent theta burst stimulation (iTBS) over the left M1. Motor-evoked potentials measured in the contralateral hand served as a measure of CSE before and for 30 min following each NBS intervention. At the group level, generalized post-stimulation CSE increases were observed (p < 0.001) with no significant differences between the two durations of each stimulation type (atDCS: p = 0.5; iTBS: p = 0.9). For individuals exhibiting overall facilitatory change to atDCS ('responders', n = 10), 20-min atDCS resulted in longer lasting CSE facilitation than 10 min. No such difference was observed between the two iTBS protocols. Considerable variability was observed inter-individually, where 52-58 % of the cohort exhibited the expected facilitation after each of the NBS protocols-as well as intra-individually, where 45-48 % of the cohort maintained consistent post-stimulation responses across the varying durations and types of stimulation. In conclusion, as shown previously in young adults, older adults demonstrate substantial variability in response to different facilitatory NBS protocols. Studies to assess the intra-individual reliability of these protocols are critical to progress towards translation of appropriate protocols (i.e. those that elicit the greatest response for each individual) into clinical practice.
Effects of breast stimulation for spontaneous onset of labor on salivary oxytocin levels in low-risk pregnant women: A feasibility study.

PubMed

Takahata, Kaori; Horiuchi, Shigeko; Tadokoro, Yuriko; Shuo, Takuya; Sawano, Erika; Shinohara, Kazuyuki

2018-01-01

This preliminary study aimed to 1) determine changes in the salivary oxytocin (OT) level during breast stimulation for promoting the spontaneous onset of labor in low-risk term pregnancies, and 2) clarify the feasibility of the breast stimulation intervention protocol in terms of practicality and acceptability. We used a single arm trial design. Sixteen low-risk pregnant women between 38 and 40 weeks of gestation with cephalic presentation participated. They performed breast stimulation for 3 days with an attendant midwife in a single maternity hospital. Each breast was stimulated for 15 minutes for a total of 1 hour per day. Saliva was collected 10 minutes before the intervention and 15, 30, 60, 75, and 90 minutes after the intervention, yielding 18 samples per woman. Among a total of 282 saliva samples from the 16 participants, OT level was measured in 142 samples (missing rate: 49.6%). The median OT level showed the highest values on day 3 of the breast stimulation, with a marked increase 30 min after the intervention. In the mixed models after multiple imputation for missing data, the OT level on the first day of intervention was significantly lower than that on the third day of intervention. Fatigue from breast stimulation decreased on subsequent days, and most of the women (75%) felt no discomfort with the protocol. Uterine hyperstimulation was not observed. Following a 3-day breast stimulation protocol for spontaneous onset of labor, the mean OT level showed the highest values on day 3. The breast stimulation intervention protocol showed good feasibility in terms of practicality and acceptability among the pregnant women. Additional large-scale studies are warranted to confirm the protocol's effectiveness.
The rate of high ovarian response in women identified at risk by a high serum AMH level is influenced by the type of gonadotropin.

PubMed

Arce, Joan-Carles; Klein, Bjarke M; La Marca, Antonio

2014-06-01

The aim was to compare ovarian response and clinical outcome of potential high-responders after stimulation with highly purified menotropin (HP-hMG) or recombinant follicle-stimulating hormone (rFSH) for in vitro fertilisation/intracytoplasmic sperm injection. Retrospective analysis was performed on data collected in two randomized controlled trials, one conducted following a long GnRH agonist protocol and the other with an antagonist protocol. Potential high-responders (n = 155 and n = 188 in the agonist and antagonist protocol, respectively) were defined as having an initial anti-Müllerian hormone (AMH) value >75th percentile (5.2 ng/ml). In both protocols, HP-hMG stimulation in women in the high AMH category was associated with a significantly lower occurrence of high response (≥15 oocytes retrieved) than rFSH stimulation; 33% versus 51% (p = 0.025) and 31% versus 49% (p = 0.015) in the long agonist and antagonist protocol, respectively. In the potential high-responder women, trends for improved live birth rate were observed with HP-hMG compared with rFSH (long agonist protocol: 33% versus 20%, p = 0.074; antagonist protocol: 34% versus 23%, p = 0.075; overall population: 34% versus 22%, p = 0.012). In conclusion, the type of gonadotropin used for ovarian stimulation influences high-response rates and potentially clinical outcome in women identified as potential high-responders.
Transcranial Electric Stimulation for Precision Medicine: A Spatiomechanistic Framework

PubMed Central

Yavari, Fatemeh; Nitsche, Michael A.; Ekhtiari, Hamed

2017-01-01

During recent years, non-invasive brain stimulation, including transcranial electrical stimulation (tES) in general, and transcranial direct current stimulation (tDCS) in particular, have created new hopes for treatment of neurological and psychiatric diseases. Despite promising primary results in some brain disorders, a more widespread application of tES is hindered by the unsolved question of determining optimum stimulation protocols to receive meaningful therapeutic effects. tES has a large parameter space including various montages and stimulation parameters. Moreover, inter- and intra-individual differences in responding to stimulation protocols have to be taken into account. These factors contribute to the complexity of selecting potentially effective protocols for each disorder, different clusters of each disorder, and even each single patient. Expanding knowledge in different dimensions of basic and clinical neuroscience could help researchers and clinicians to select potentially effective protocols based on tES modulatory mechanisms for future clinical studies. In this article, we propose a heuristic spatiomechanistic framework which contains nine levels to address tES effects on brain functions. Three levels refer to the spatial resolution (local, small-scale networks and large-scale networks) and three levels of tES modulatory effects based on its mechanisms of action (neurochemical, neuroelectrical and oscillatory modulations). At the group level, this framework could be helpful to enable an informed and systematic exploration of various possible protocols for targeting a brain disorder or its neuroscience-based clusters. Considering recent advances in exploration of neurodiversity at the individual level with different brain mapping technologies, the proposed framework might also be used in combination with personal data to design individualized protocols for tES in the context of precision medicine in the future. PMID:28450832
Origins of inert Higgs doublets

DOE PAGES

Kephart, Thomas W.; Yuan, Tzu -Chiang

2016-03-24

Here, we consider beyond the standard model embedding of inert Higgs doublet fields. We argue that inert Higgs doublets can arise naturally in grand unified theories where the necessary associated Z 2 symmetry can occur automatically. Several examples are discussed.
Doublet Pulse Coherent Laser Radar for Tracking of Resident Space Objects

DTIC Science & Technology

2014-09-01

based laser systems can be limited by the effects of tumbling, extremely accurate Doppler measurement is possible using a doublet coherent laser ...Doublet pulse coherent laser radar for tracking of resident space objects Narasimha S. Prasad *1 , Van Rudd 2 , Scott Shald 2 , Stephan...Doublet Pulse Coherent Laser Radar for Tracking of Resident Space Objects 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S
Oxaliplatin-Based Doublets Versus Cisplatin or Carboplatin-Based Doublets in the First-Line Treatment of Advanced Nonsmall Cell Lung Cancer.

PubMed

Yu, Jing; Xiao, Jing; Yang, Yifan; Cao, Bangwei

2015-07-01

The efficacy and toxicity of oxaliplatin-based versus carboplatin/cisplatin-based doublets in patients with previously untreated nonsmall cell lung cancer (NSCLC) have been compared.We searched published randomized controlled trials of oxaliplatin-based or carboplatin/cisplatin-based medications for NSCLC. A fixed effect model was used to analyze outcomes which were expressed as the hazard ratio for overall survival (OS) and time-to-progression (TTP), relative risk, overall response rate (ORR), disease control rate (DCR), 1-year survival, and the odds ratios for toxicity were pooled.Eight studies involving 1047 patients were included. ORR tended to favor carboplatin/cisplatin but the effect was not significantly different compared with oxaliplatin doublets (P = 0.05). The effects of OS, TTP, DCR, and 1-year survival between the 2 regimens were comparable. Oxaliplatin doublets caused less grade 3/4 leukocytopenia and neutropenia. Grades 3 to 4 nonhematological toxicities and grades 3 to 4 hematological toxicities showed little difference between oxaliplatin doublets and carboplatin/cisplatin doublets.Meta-analysis shows that the efficacy of oxaliplatin doublets is similar to that of other currently used platinum doublets. The lack of significant differences in the statistic analysis does not preclude genuine differences in clinical efficacy, because higher diversities between the studies covered differences between the 2 groups in each study. Oxaliplatin combined with a third-generation agent should be considered for use as alternative chemotherapy in patients who cannot tolerate conventional platinum-based regimens because the toxicity profile is much more favorable.

The splitting and oscillator strengths for the 2S/2/S-2p/2/P/0/ doublet in lithium-like sulfur. [during Skylab observed solar flares

NASA Technical Reports Server (NTRS)

Pegg, D. J.; Forester, J. P.; Elston, S. B.; Griffin, P. M.; Peterson, R. S.; Thoe, R. S.; Vane, C. R.; Sellin, I. A.; Groeneveld, K.-O.

1977-01-01

The beam-foil technique has been used to study the 2S(2)S-2p(2)P(0) doublet in S XIV. The results confirm the doublet splitting measured aboard Skylab during solar flare events. In addition, the oscillator strengths for the resonance transitions comprising this doublet have been measured and found to agree well with recent relativistic f-value calculations.
Disparities in reproductive outcomes according to the endometrial preparation protocol in frozen embryo transfer : The risk of early pregnancy loss in frozen embryo transfer cycles.

PubMed

Hatoum, I; Bellon, L; Swierkowski, N; Ouazana, M; Bouba, S; Fathallah, K; Paillusson, B; Bailly, M; Boitrelle, F; Alter, L; Bergère, M; Selva, J; Wainer, R

2018-03-01

The purpose of this study was to determine the effect of stimulated and artificial endometrial preparation protocols on reproductive outcomes in frozen embryo transfer (FET) cycles. We performed a retrospective study of 1926 FET cycles over a 3.5-year period in the Fertility Unit at a University Hospital. Stimulated and artificial protocols were used for endometrial preparation. The embryos for FET were obtained from either in vitro fertilization or intracytoplasmic sperm injection cycles. Live birth rate and early pregnancy loss rates were retrospectively compared. In artificial protocols, oral or vaginal administration of oestradiol 2 mg two or three times a day was followed by vaginal supplementation with progesterone 200 mg two or three times a day. In stimulated protocols, recombinant follicle-stimulating hormone was administered from day 4 onward. Vaginal ultrasound was used for endometrial and ovarian monitoring. A pregnancy test was performed 14 days after FET. If it was positive, oestradiol and progesterone were administered up until the 12th week of gestation in artificial cycles. We defined early pregnancy losses as biochemical pregnancies (preclinical losses) and miscarriages. Data on 865 artificial cycles (45% of the total) and 1061 stimulated cycles (55%) were collected. Early pregnancy loss rate was significantly lower for stimulated cycles (34.2%) than for artificial cycles (56.9%), and the live birth rate was significantly higher for stimulated cycles (59.7%) than for artificial cycles (29.1%). In frozen embryo transfer, artificial cycles were associated with more early pregnancy loss and lower live birth rate than stimulated cycles.
Comparing the force ripple during asynchronous and conventional stimulation.

PubMed

Downey, Ryan J; Tate, Mark; Kawai, Hiroyuki; Dixon, Warren E

2014-10-01

Asynchronous stimulation has been shown to reduce fatigue during electrical stimulation; however, it may also exhibit a force ripple. We quantified the ripple during asynchronous and conventional single-channel transcutaneous stimulation across a range of stimulation frequencies. The ripple was measured during 5 asynchronous stimulation protocols, 2 conventional stimulation protocols, and 3 volitional contractions in 12 healthy individuals. Conventional 40 Hz and asynchronous 16 Hz stimulation were found to induce contractions that were as smooth as volitional contractions. Asynchronous 8, 10, and 12 Hz stimulation induced contractions with significant ripple. Lower stimulation frequencies can reduce fatigue; however, they may also lead to increased ripple. Future efforts should study the relationship between force ripple and the smoothness of the evoked movements in addition to the relationship between stimulation frequency and NMES-induced fatigue to elucidate an optimal stimulation frequency for asynchronous stimulation. © 2014 Wiley Periodicals, Inc.
Brain lactate responses during visual stimulation in fasting and hyperglycemic subjects: a proton magnetic resonance spectroscopy study at 1.5 Tesla.

PubMed

Maddock, Richard J; Buonocore, Michael H; Lavoie, Shawn P; Copeland, Linda E; Kile, Shawn J; Richards, Anne L; Ryan, John M

2006-11-22

Proton magnetic resonance spectroscopy ((1)H-MRS) studies showing increased lactate during neural activation support a broader role for lactate in brain energy metabolism than was traditionally recognized. Proton MRS measures of brain lactate responses have been used to study regional brain metabolism in clinical populations. This study examined whether variations in blood glucose influence the lactate response to visual stimulation in the visual cortex. Six subjects were scanned twice, receiving either saline or 21% glucose intravenously. Using (1)H-MRS at 1.5 Tesla with a long echo time (TE=288 ms), the lactate doublet was visible at 1.32 ppm in the visual cortex of all subjects. Lactate increased significantly from resting to visual stimulation. Hyperglycemia had no effect on this increase. The order of the slice-selective gradients for defining the spectroscopy voxel had a pronounced effect on the extent of contamination by signal originating outside the voxel. The results of this preliminary study demonstrate a method for observing a consistent activity-stimulated increase in brain lactate at 1.5 T and show that variations in blood glucose across the normal range have little effect on this response.
The Northwest Geysers EGS Demonstration Project, California

DOE PAGES

Garcia, Julio; Hartline, Craig; Walters, Mark; ...

2015-09-04

Our project goal is to demonstrate the feasibility of stimulating a deep high-temperature reservoir (HTR) (up to 400 °C, 750 °F). There were two previously abandoned wells, Prati State 31 (PS-31) and Prati 32 (P-32), reopened and deepened to be used as an injection and production doublet to stimulate the HTR. The deepened portions of both wells have conductive temperature gradients of 10 °F/100 ft (182 °C/km), produce connate native fluids and magmatic gas, and the rocks were isotopically unexchanged by meteoric water. The ambient temperature meteoric water injected into these hot dry rocks has evidently created a permeability volume of several cubic kilometers asmore » determined by seismic monitoring. Preliminary isotopic analyses of the injected and produced water indicate that 50–75% of the steam from the created EGS reservoir is injection-derived.« less
Constraints on the Lee-Wick Higgs sector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carone, Christopher D.; Primulando, Reinard

2009-09-01

Lee-Wick partners to the standard model Higgs doublet may appear at a mass scale that is significantly lower than that of the remaining Lee-Wick partner states. The relevant effective theory is a two-Higgs doublet model in which one doublet has wrong-sign kinetic and mass terms. We determine bounds on this effective theory, including those from neutral B-meson mixing, b{yields}X{sub s}{gamma}, and Z{yields}bb. The results differ from those of conventional two-Higgs doublet models and lead to meaningful constraints on the Lee-Wick Higgs sector.
Doublet craters and the tidal disruption of binary asteroids

NASA Technical Reports Server (NTRS)

Melosh, H. J.; Stansberry, J. A.

1991-01-01

An evaluation is conducted of the possibility that the tidal disruption of a population of contact binary asteroids can account for terrestrial-impact 'doublet' craters. Detailed orbital integrations indicate that while such asteroids are often disrupted by tidal forces outside the Roche limit, the magnitude of the resulting separations is too small to account for the observed doublet craters. It is hypothesized that an initial population of km-scale earth-crossing objects encompassing 10-20 percent binaries must be responsible for doublet impacts, as may be verified by future observations of earth-approaching asteroids.
Photonic generation of ultra-wideband doublet pulse using a semiconductor-optical-amplifier based polarization-diversified loop.

PubMed

Luo, Bowen; Dong, Jianji; Yu, Yuan; Yang, Ting; Zhang, Xinliang

2012-06-15

We propose and demonstrate a novel scheme of ultra-wideband (UWB) doublet pulse generation using a semiconductor optical amplifier (SOA) based polarization-diversified loop (PDL) without any assistant light. In our scheme, the incoming gaussian pulse is split into two parts by the PDL, and each of them is intensity modulated by the other due to cross-gain modulation (XGM) in the SOA. Then, both parts are recombined with incoherent summation to form a UWB doublet pulse. Bi-polar UWB doublet pulse generation is demonstrated using an inverted gaussian pulse injection. Moreover, pulse amplitude modulation of UWB doublet is also experimentally demonstrated. Our scheme shows some advantages, such as simple implementation without assistant light and single optical carrier operation with good fiber dispersion tolerance.
Differential Effects of HRAS Mutation on LTP-Like Activity Induced by Different Protocols of Repetitive Transcranial Magnetic Stimulation.

PubMed

Dileone, Michele; Ranieri, Federico; Florio, Lucia; Capone, Fioravante; Musumeci, Gabriella; Leoni, Chiara; Mordillo-Mateos, Laura; Tartaglia, Marco; Zampino, Giuseppe; Di Lazzaro, Vincenzo

2016-01-01

Costello syndrome (CS) is a rare congenital disorder due to a G12S amino acid substitution in HRAS protoncogene. Previous studies have shown that Paired Associative Stimulation (PAS), a repetitive brain stimulation protocol inducing motor cortex plasticity by coupling peripheral nerve stimulation with brain stimulation, leads to an extremely pronounced motor cortex excitability increase in CS patients. Intermittent Theta Burst Stimulation (iTBS) represents a protocol able to induce motor cortex plasticity by trains of stimuli at 50 Hz. In healthy subjects PAS and iTBS produce similar after-effects in motor cortex excitability. Experimental models showed that HRAS-dependent signalling pathways differently affect LTP induced by different patterns of repetitive synaptic stimulation. We aimed to compare iTBS-induced after-effects on motor cortex excitability with those produced by PAS in CS patients and to observe whether HRAS mutation differentially affects two different forms of neuromodulation protocols. We evaluated in vivo after-effects induced by PAS and iTBS applied over the right motor cortex in 4 CS patients and in 21 healthy age-matched controls. Our findings confirmed HRAS-dependent extremely pronounced PAS-induced after-effects and showed for the first time that iTBS induces no change in MEP amplitude in CS patients whereas both protocols lead to an increase of about 50% in controls. CS patients are characterized by an impairment of iTBS-related LTP-like phenomena besides enhanced PAS-induced after-effects, suggesting that HRAS-dependent signalling pathways have a differential influence on PAS- and iTBS-induced plasticity in humans. Copyright © 2015 Elsevier Inc. All rights reserved.
Simple model for lambda-doublet propensities in bimolecular reactions

NASA Technical Reports Server (NTRS)

Bronikowski, Michael J.; Zare, Richard N.

1990-01-01

A simple geometric model is presented to account for lambda-doublet propensities in bimolecular reactions A + BC - AB + C. It applies to reactions in which AB is formed in a pi state, and in which the unpaired molecular orbital responsible for lambda-doubling arises from breaking the B-C bond. The lambda-doublet population ratio is predicted to be 2:1 provided that: (1) the motion of A in the transition state determines the plane of rotation of AB; (2) the unpaired pi orbital lying initially along the B-C bond may be resolved into a projection onto the AB plane of rotation and a projection perpendicular to this plane; (3) there is no preferred geometry for dissociation of ABC. The 2:1 lambda-doublet ratio is the 'unconstrained dynamics prior' lambda-doublet distribution for such reactions.
Inflation and dark matter in the inert doublet model

NASA Astrophysics Data System (ADS)

Choubey, Sandhya; Kumar, Abhass

2017-11-01

We discuss inflation and dark matter in the inert doublet model coupled non-minimally to gravity where the inert doublet is the inflaton and the neutral scalar part of the doublet is the dark matter candidate. We calculate the various inflationary parameters like n s , r and P s and then proceed to the reheating phase where the inflaton decays into the Higgs and other gauge bosons which are non-relativistic owing to high effective masses. These bosons further decay or annihilate to give relativistic fermions which are finally responsible for reheating the universe. At the end of the reheating phase, the inert doublet which was the inflaton enters into thermal equilibrium with the rest of the plasma and its neutral component later freezes out as cold dark matter with a mass of about 2 TeV.
The C IV doublet ratio intensity effect in symbiotic stars

NASA Technical Reports Server (NTRS)

Michalitsianos, A. G.; Fahey, M.; Kafatos, M.; Viotti, R.; Cassatella, A.

1988-01-01

High-resolution UV spectra in the 1200-2000 wavelength range of the symbiotic variable R Aqr and its nebular jet were obtained in July 1987 with the IUE. The line profile structure of the C IV 1548, 1550 doublet in the jet indicates multicomponent velocity structure from an optically thin emitting gas. The C IV doublet profiles in the compact H II region engulfing the Mira and hot companion binary also suggest multicomponent structure with radial velocities up to about -100 km/s. The value of the doublet intensity ratio in the R Aqr H II region has been observed in other similar symbiotic stars, such as RX Pup. It is suggested that the anomalous behavior of the C IV doublet intensities may be useful for studying the spatial structure and temporal nature of winds in symbiotic stars.
Quantifying the kinetics and morphological changes of the fusion of spheroid building blocks.

PubMed

Susienka, Michael J; Wilks, Benjamin T; Morgan, Jeffrey R

2016-10-10

Tissue fusion, whereby two or more spheroids coalesce, is a process that is fundamental to biofabrication. We have designed a quantitative, high-throughput platform to investigate the fusion of multicellular spheroids using agarose micro-molds. Spheroids of primary human chondrocytes (HCH) or human breast cancer cells (MCF-7) were self-assembled for 24 h and then brought together to form an array comprised of two spheroids (one doublet) per well. To quantify spheroid fusogenicity, we developed two assays: (1) an initial tack assay, defined as the minimum amount of time for two spheroids to form a mechanically stable tissue complex or doublet, and (2) a fusion assay, in which we defined and tracked key morphological parameters of the doublets as a function of time using wide-field fluorescence microscopy over a 24 h time-lapse. The initial tack of spheroid fusion was measured by inverting the micro-molds and centrifuging doublets at various time points to assess their connectedness. We found that the initial tack between two spheroids forms rapidly, with the majority of doublets remaining intact after centrifugation following just 30 min of fusion. Over the course of 24 h of fusion, several morphological changes occurred, which were quantified using a custom image analysis pipeline. End-to-end doublet lengths decreased over time, doublet widths decreased for chondrocytes and increased for MCF-7, contact lengths increased over time, and chondrocyte doublets exhibited higher intersphere angles at the end of fusion. We also assessed fusion by measuring the fluorescence intensity at the plane of fusion, which increased over time for both cell types. Interestingly, we observed that doublets moved and rotated in the micro-wells during fusion and this rotation was inhibited by ROCK inhibitor Y-27632 and myosin II inhibitor blebbistatin. Understanding and optimizing tissue fusion is essential for creating larger tissues, organs, or other structures using individual microtissues as building parts.
ANDRO-IVF: a novel protocol for poor responders to IVF controlled ovarian stimulation

PubMed Central

Bercaire, Ludmila; Nogueira, Sara MB; Lima, Priscila CM; Alves, Vanessa R; Donadio, Nilka; Dzik, Artur; Cavagna, Mario; Fanchin, Renato

2018-01-01

Objective This study aimed to assess a novel protocol designed to improve poor ovarian response through intra-ovarian androgenization. The endpoints were: number of oocytes and mature oocytes retrieved, fertilization, cancellation and pregnancy rates. Methods This prospective crossover study enrolled poor responders from previous ovarian stimulation cycles submitted to a novel protocol called ANDRO-IVF. The protocol included pretreatment with transdermal AndroGel(r) (Besins) 25 mg, oral letrozole 2.5 mg and subcutaneous hCG 2500 IU; cycle control was performed with estradiol valerate and micronized progesterone; ovarian stimulation was attained with gonadotropins FSH/LH 450 IU, GnRH antagonist and hCG 5000 IU. Results Fourteen poor responders were enrolled. One patient did not meet the inclusion criteria. Thirteen patients previously summited to the standard protocol were offered the ANDRO-IVF Protocol.-Standard Protocol: Mean age: 35.30 years; cancellation rate: 61.53%; mean number of MII oocytes retrieved per patient: 1.8; fertilization rate: 33.33%. Only two patients had embryo transfers, and none got pregnant.-ANDRO-IVF Protocol: Mean age: 35.83 years; cancellation rate: 7.69%; mean number of oocytes retrieved per patient: 5.58, MII oocytes: 3.91. ICSI was performed in 84.61% of the patients and a mean of 1.5 embryos were transferred per patient. Fertilization rate: 62.5%; cumulative pregnancy rate: 16.66%; mean duration of stimulation: 9.77 days. Conclusion ANDRO-IVF allows intra-ovarian androgenization by increasing serum and intra-follicular androgen levels and preventing androgen aromatization. This protocol apparently improved clinical outcomes of poor responders in parameters such as number of oocytes retrieved and clinical pregnancy rates. Further randomized controlled trials are needed to confirm these findings. PMID:29303236
Translational Neuromodulation: Approximating Human Transcranial Magnetic Stimulation Protocols In Rats

PubMed Central

Vahabzadeh-Hagh, Andrew M.; Muller, Paul A.; Gersner, Roman; Zangen, Abraham; Rotenberg, Alexander

2015-01-01

Objective Transcranial magnetic stimulation (TMS) is a well-established clinical protocol with numerous potential therapeutic and diagnostic applications. Yet, much work remains in the elucidation of TMS mechanisms, optimization of protocols, and in development of novel therapeutic applications. As with many technologies, the key to these issues lies in the proper experimentation and translation of TMS methods to animal models, among which rat models have proven popular. A significant increase in the number of rat TMS publications has necessitated analysis of their relevance to human work. We therefore review the essential principles necessary for the approximation of human TMS protocols in rats as well as specific methods that addressed these issues in published studies. Materials and Methods We performed an English language literature search combined with our own experience and data. We address issues that we see as important in the translation of human TMS methods to rat models and provide a summary of key accomplishments in these areas. Results An extensive literature review illustrated the growth of rodent TMS studies in recent years. Current advances in the translation of single, paired-pulse, and repetitive stimulation paradigms to rodent models are presented. The importance of TMS in the generation of data for preclinical trials is also highlighted. Conclusions Rat TMS has several limitations when considering parallels between animal and human stimulation. However, it has proven to be a useful tool in the field of translational brain stimulation and will likely continue to aid in the design and implementation of stimulation protocols for therapeutic and diagnostic applications. PMID:22780329
Effects of breast stimulation for spontaneous onset of labor on salivary oxytocin levels in low-risk pregnant women: A feasibility study

PubMed Central

Tadokoro, Yuriko; Shuo, Takuya; Sawano, Erika; Shinohara, Kazuyuki

2018-01-01

Objectives This preliminary study aimed to 1) determine changes in the salivary oxytocin (OT) level during breast stimulation for promoting the spontaneous onset of labor in low-risk term pregnancies, and 2) clarify the feasibility of the breast stimulation intervention protocol in terms of practicality and acceptability. Methods We used a single arm trial design. Sixteen low-risk pregnant women between 38 and 40 weeks of gestation with cephalic presentation participated. They performed breast stimulation for 3 days with an attendant midwife in a single maternity hospital. Each breast was stimulated for 15 minutes for a total of 1 hour per day. Saliva was collected 10 minutes before the intervention and 15, 30, 60, 75, and 90 minutes after the intervention, yielding 18 samples per woman. Results Among a total of 282 saliva samples from the 16 participants, OT level was measured in 142 samples (missing rate: 49.6%). The median OT level showed the highest values on day 3 of the breast stimulation, with a marked increase 30 min after the intervention. In the mixed models after multiple imputation for missing data, the OT level on the first day of intervention was significantly lower than that on the third day of intervention. Fatigue from breast stimulation decreased on subsequent days, and most of the women (75%) felt no discomfort with the protocol. Uterine hyperstimulation was not observed. Conclusion Following a 3-day breast stimulation protocol for spontaneous onset of labor, the mean OT level showed the highest values on day 3. The breast stimulation intervention protocol showed good feasibility in terms of practicality and acceptability among the pregnant women. Additional large-scale studies are warranted to confirm the protocol’s effectiveness. PMID:29447299
Transcranial magnetic stimulation with acepromazine or dexmedetomidine in combination with levomethadone/fenpipramide in healthy Beagle dogs.

PubMed

Amendt, H-L; Siedenburg, J S; Steffensen, N; Söbbeler, F J; Schütter, A; Tünsmeyer, J; Rohn, K; Kästner, S B R; Tipold, A; Stein, V M

2016-11-01

The aim of this study was to evaluate the influence of two sedation protocols on transcranial magnetic motor evoked potentials (TMMEPs) after transcranial magnetic stimulation in medium sized dogs. Onset latencies and peak-to-peak amplitudes, elicited in the extensor carpi radialis and cranial tibial muscles, were analysed in 10 healthy Beagles that received either acepromazine or dexmedetomidine in combination with levomethadone/fenpipramide, in a crossover design. Similar TMMEP recordings could be made using both sedation protocols at 80-90% stimulation intensity; however, there were significantly shorter onset latencies with the acepromazine-levomethadone/fenpipramide protocol at 100% stimulation intensity. Reference values were established and it was concluded that both drug combinations are feasible for measuring TMMEPs in medium sized dogs. Copyright © 2016 Elsevier Ltd. All rights reserved.
Pemetrexed Singlet Versus Nonpemetrexed-Based Platinum Doublet as Second-Line Chemotherapy after First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor Failure in Non-small Cell Lung Cancer Patients with EGFR Mutations.

PubMed

Park, Sehhoon; Keam, Bhumsuk; Kim, Se Hyun; Kim, Ki Hwan; Kim, Yu Jung; Kim, Jin-Soo; Kim, Tae Min; Lee, Se-Hoon; Kim, Dong-Wan; Lee, Jong Seok; Heo, Dae Seog

2015-10-01

Platinum-based doublet chemotherapy is the treatment of choice for patients with non-small cell lung cancer (NSCLC); however, the role of a platinum-based doublet as second-line therapy after failure of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for NSCLC patients has not yet been elucidated. The purpose of this study was to compare the clinical efficacy of pemetrexed versus a platinum-based doublet as second-line therapy after failure of EGFR TKI used as first-line therapy for NSCLC patients with EGFR mutations. We designed a multicenter retrospective cohort study of 314 NSCLC patients with EGFR mutations who received an EGFR TKI as first-line palliative chemotherapy. Our analysis included 83 patients who failed EGFR TKI therapy and received second-line cytotoxic chemotherapy. Forty-six patients were treated using a platinum-based doublet and 37 patients were treated using singlet pemetrexed. The overall response rates of patients receiving a platinum-based doublet and patients receiving pemetrexed were17.4% and 32.4%, respectively (p=0.111). The median progression-free survival (PFS) of patients receiving pemetrexed was significantly longer than that of patients receiving a platinum-based doublet (4.2 months vs. 2.7 months, respectively; p=0.008). The hazard ratio was 0.54 (95% confidence interval, 0.34 to 0.86; p=0.009). Our retrospective analysis found that second-line pemetrexed singlet therapy provided significantly prolonged PFS compared to second-line platinum-based doublet chemotherapy for NSCLC patients with EGFR mutations who failed first-line EGFR TKI. Conduct of prospective studies for confirmation of our results is warranted.
Separation of the 1+ /1- parity doublet in 20Ne

NASA Astrophysics Data System (ADS)

Beller, J.; Stumpf, C.; Scheck, M.; Pietralla, N.; Deleanu, D.; Filipescu, D. M.; Glodariu, T.; Haxton, W.; Idini, A.; Kelley, J. H.; Kwan, E.; Martinez-Pinedo, G.; Raut, R.; Romig, C.; Roth, R.; Rusev, G.; Savran, D.; Tonchev, A. P.; Tornow, W.; Wagner, J.; Weller, H. R.; Zamfir, N.-V.; Zweidinger, M.

2015-02-01

The (J , T) = (1 , 1) parity doublet in 20Ne at 11.26 MeV is a good candidate to study parity violation in nuclei. However, its energy splitting is known with insufficient accuracy for quantitative estimates of parity violating effects. To improve on this unsatisfactory situation, nuclear resonance fluorescence experiments using linearly and circularly polarized γ-ray beams were used to determine the energy difference of the parity doublet ΔE = E (1-) - E (1+) = - 3.2(± 0.7) stat(-1.2+0.6)sys keV and the ratio of their integrated cross sections Is,0(+) /Is,0(-) = 29(± 3) stat(-7+14)sys. Shell-model calculations predict a parity-violating matrix element having a value in the range 0.46-0.83 eV for the parity doublet. The small energy difference of the parity doublet makes 20Ne an excellent candidate to study parity violation in nuclear excitations.
Subnanometre-resolution structure of the doublet microtubule reveals new classes of microtubule-associated proteins

PubMed Central

Ichikawa, Muneyoshi; Liu, Dinan; Kastritis, Panagiotis L.; Basu, Kaustuv; Hsu, Tzu Chin; Yang, Shunkai; Bui, Khanh Huy

2017-01-01

Cilia are ubiquitous, hair-like appendages found in eukaryotic cells that carry out functions of cell motility and sensory reception. Cilia contain an intriguing cytoskeletal structure, termed the axoneme that consists of nine doublet microtubules radially interlinked and longitudinally organized in multiple specific repeat units. Little is known, however, about how the axoneme allows cilia to be both actively bendable and sturdy or how it is assembled. To answer these questions, we used cryo-electron microscopy to structurally analyse several of the repeating units of the doublet at sub-nanometre resolution. This structural detail enables us to unambiguously assign α- and β-tubulins in the doublet microtubule lattice. Our study demonstrates the existence of an inner sheath composed of different kinds of microtubule inner proteins inside the doublet that likely stabilizes the structure and facilitates the specific building of the B-tubule. PMID:28462916

A feasible repetitive transcranial magnetic stimulation clinical protocol in migraine prevention.

PubMed

Zardouz, Shawn; Shi, Lei; Leung, Albert

2016-01-01

This case series was conducted to determine the clinical feasibility of a repetitive transcranial magnetic stimulation protocol for the prevention of migraine (with and without aura). Five patients with migraines underwent five repetitive transcranial magnetic stimulation sessions separated in 1- to 2-week intervals for a period of 2 months at a single tertiary medical center. Repetitive transcranial magnetic stimulation was applied to the left motor cortex with 2000 pulses (20 trains with 1s inter-train interval) delivered per session, at a frequency of 10 Hz and 80% resting motor threshold. Pre- and post-treatment numerical rating pain scales were collected, and percent reductions in intensity, frequency, and duration were generated. An average decrease in 37.8%, 32.1%, and 31.2% were noted in the intensity, frequency, and duration of migraines post-repetitive transcranial magnetic stimulation, respectively. A mean decrease in 1.9±1.0 (numerical rating pain scale ± standard deviation; range: 0.4-2.8) in headache intensity scores was noted after the repetitive transcranial magnetic stimulation sessions. The tested repetitive transcranial magnetic stimulation protocol is a well-tolerated, safe, and effective method for migraine prevention.
Comparison of the ultrashort gonadotropin-releasing hormone agonist-antagonist protocol with microdose flare -up protocol in poor responders: a preliminary study.

PubMed

Berker, Bülent; Duvan, Candan İltemir; Kaya, Cemil; Aytaç, Ruşen; Satıroğlu, Hakan

2010-01-01

To determine the potential effect of the ultrashort gonadotropin-releasing hormone (GnRH) agonist/GnRH antagonist protocol versus the microdose GnRH agonist protocol in poor responders undergoing intracytoplasmic sperm injection (ICSI). The patients in the Agonist-Antagonist Group (n=41) were administered the ultrashort GnRH-agonist/ antagonist protocol, while the patients in the Microdose Group (n=41) were stimulated according to the microdose flare-up protocol. The mean number of mature oocytes retrieved was the primary outcome measure. Fertilization rate, implantation rate per embryo and clinical pregnancy rates were secondary outcome measures. There was no differenc between the mean number of mature oocytes retrieved in the two groups. There were also no statistical differences between the two groups in terms of peak serum E2 level, canceled cycles, endometrial thickness on hCG day, number of 2 pronucleus and number of embryos transferred. However, the total gonadotropin consumption and duration of stimulation were significantly higher with the Agonist-Antagonist Group compared with the Microdose Group. The implantation and clinical pregnancy rates were similar between the two groups. Despite the high dose of gonadotropin consumption and longer duration of stimulation with the ultrashort GnRH agonist/ antagonist protocol, it seems that the Agonist-Antagonist Protocol is not inferior to the microdose protocol in poor responders undergoing ICSI.
A new way of setting rFSH deposit: a case of severe injection error in IVF/ICSI cycle ending with live birth.

PubMed

Mayer, Richard Bernhard; Ebner, Thomas; Shebl, Omar; Tews, Gernot

2012-01-01

a 25- year old woman with secondary infertility caused by a male factor was enrolled in our IVF/ICSI-ET program. Stimulation was performed in a long- protocol and ovarian stimulation, using rFSH follitropin beta, starting on the third day of the menstrual cycle. The rFSH dose per day was 900 IU-0 IU-0 IU-0 IU. Due to normal ovarian response and follicle growth, stimulation was continued and there was no detriment in oocyte quality and no symptoms of OHSS. Following blastocyte transfer cesarean section was unpreventable at 37+5 weeks of gestation due to an impacted transverse lie. Different stimulation protocols are needed for appropriate treatment of various patients provided that the administration of treatment was done correctly. In the case of injection errors, continuing stimulation protocol seems to be achievable in certain cases considering hormone levels and the process of follicle growth.
A new way of setting rFSH deposit: a case of severe injection error in IVF/ICSI cycle ending with live birth

PubMed Central

Mayer, Richard Bernhard; Ebner, Thomas; Shebl, Omar; Tews, Gernot

2012-01-01

We present a case with a severe injection error: a 25- year old woman with secondary infertility caused by a male factor was enrolled in our IVF/ICSI-ET program. Stimulation was performed in a long- protocol and ovarian stimulation, using rFSH follitropin beta, starting on the third day of the menstrual cycle. The rFSH dose per day was 900 IU-0 IU-0 IU-0 IU. Due to normal ovarian response and follicle growth, stimulation was continued and there was no detriment in oocyte quality and no symptoms of OHSS. Following blastocyte transfer cesarean section was unpreventable at 37+5 weeks of gestation due to an impacted transverse lie. Different stimulation protocols are needed for appropriate treatment of various patients provided that the administration of treatment was done correctly. In the case of injection errors, continuing stimulation protocol seems to be achievable in certain cases considering hormone levels and the process of follicle growth. PMID:24592042
Doublet Production in the Development of Medieval and Modern Spanish: New Approaches to Phonolexical Duplication

ERIC Educational Resources Information Center

Haney, Darren W.

2011-01-01

This dissertation offers new approaches to an old and well-known problem in the study of the development of Romance varieties: duplicate lexis or doublets. Traditional analyses of duplication are narrow in scope both in what qualifies as a doublet (the popular/learned opposition has dominated, to the exclusion of other pairs) and in channels of…
Correlated Mutation in the Evolution of Catalysis in Uracil DNA Glycosylase Superfamily

NASA Astrophysics Data System (ADS)

Xia, Bo; Liu, Yinling; Guevara, Jose; Li, Jing; Jilich, Celeste; Yang, Ye; Wang, Liangjiang; Dominy, Brian N.; Cao, Weiguo

2017-04-01

Enzymes in Uracil DNA glycosylase (UDG) superfamily are essential for the removal of uracil. Family 4 UDGa is a robust uracil DNA glycosylase that only acts on double-stranded and single-stranded uracil-containing DNA. Based on mutational, kinetic and modeling analyses, a catalytic mechanism involving leaving group stabilization by H155 in motif 2 and water coordination by N89 in motif 3 is proposed. Mutual Information analysis identifies a complexed correlated mutation network including a strong correlation in the EG doublet in motif 1 of family 4 UDGa and in the QD doublet in motif 1 of family 1 UNG. Conversion of EG doublet in family 4 Thermus thermophilus UDGa to QD doublet increases the catalytic efficiency by over one hundred-fold and seventeen-fold over the E41Q and G42D single mutation, respectively, rectifying the strong correlation in the doublet. Molecular dynamics simulations suggest that the correlated mutations in the doublet in motif 1 position the catalytic H155 in motif 2 to stabilize the leaving uracilate anion. The integrated approach has important implications in studying enzyme evolution and protein structure and function.
Dynamics of neutrophil aggregation in couette flow revealed by videomicroscopy: effect of shear rate on two-body collision efficiency and doublet lifetime.

PubMed Central

Goldsmith, H L; Quinn, T A; Drury, G; Spanos, C; McIntosh, F A; Simon, S I

2001-01-01

During inflammation, neutrophil capture by vascular endothelial cells is dependent on L-selectin and beta(2)-integrin adhesion receptors. One of us (S.I.S.) previously demonstrated that homotypic neutrophil aggregation is analogous to this process in that it is also mediated by these receptors, thus providing a model for studying the dynamics of neutrophil adhesion. In the present work, we set out to confirm the hypothesis that cell-cell adhesion via selectins serves to increase the lifetimes of neutrophil doublets formed through shear-induced two-body collisions. In turn, this would facilitate the engagement of more stable beta(2)-integrin bonds and thus increase the two-body collision efficiency (fraction of collisions resulting in the formation of nonseparating doublets). To this end, suspensions of unstimulated neutrophils were subjected to a uniform shear field in a transparent counter-rotating cone and plate rheoscope, and the formation of doublets and growth of aggregates recorded using high-speed videomicroscopy. The dependence of neutrophil doublet lifetime and two-body collision-capture efficiency on shear rate, G, from 14 to 220 s(-1) was investigated. Bond formation during a two-body collision was indicated by doublets rotating well past the orientation predicted for break-up of doublets of inert spheres. A striking dependence of doublet lifetime on shear rate was observed. At low shear (G = 14 s(-1)), no collision capture occurred, and doublet lifetimes were no different from those of neutrophils pretreated with a blocking antibody to L-selectin, or in Ca(++)-depleted EDTA buffers. At G > or = 66 s(-1), doublet lifetimes increased, with increasing G reaching values twice those for the L-selectin-blocked controls. This correlated with capture efficiencies in excess of 20%, and, at G > or = 110 s(-1), led to the rapid formation of large aggregates, and this in the absence of exogenous chemotactic stimuli. Moreover, the aggregates almost completely broke up when the shear rate was reduced below 66 s(-1). Partial inhibition of aggregate formation was achieved by blocking beta(2)-integrin receptors with antibody. By direct observation of the shear-induced interactions between neutrophils, these data reveal that steady application of a threshold level of shear rate is sufficient to support homotypic neutrophil aggregation. PMID:11566775
Adaptive enhancement of learning protocol in hippocampal cultured networks grown on multielectrode arrays

PubMed Central

Pimashkin, Alexey; Gladkov, Arseniy; Mukhina, Irina; Kazantsev, Victor

2013-01-01

Learning in neuronal networks can be investigated using dissociated cultures on multielectrode arrays supplied with appropriate closed-loop stimulation. It was shown in previous studies that weakly respondent neurons on the electrodes can be trained to increase their evoked spiking rate within a predefined time window after the stimulus. Such neurons can be associated with weak synaptic connections in nearby culture network. The stimulation leads to the increase in the connectivity and in the response. However, it was not possible to perform the learning protocol for the neurons on electrodes with relatively strong synaptic inputs and responding at higher rates. We proposed an adaptive closed-loop stimulation protocol capable to achieve learning even for the highly respondent electrodes. It means that the culture network can reorganize appropriately its synaptic connectivity to generate a desired response. We introduced an adaptive reinforcement condition accounting for the response variability in control stimulation. It significantly enhanced the learning protocol to a large number of responding electrodes independently on its base response level. We also found that learning effect preserved after 4–6 h after training. PMID:23745105
[Prospective randomised study of long versus short agonist protocol with poor responder patients during in vitro fertilization].

PubMed

Chatillon-Boissier, K; Genod, A; Denis-Belicard, E; Felloni, B; Chene, G; Seffert, P; Chauleur, C

2012-11-01

Different ovarian stimulation protocols are used for in vitro fertilization (IVF) in "poor responder" patients. Our work aims at comparing two ovarian stimulation protocols (long agonist half-dose protocol versus short agonist protocol without pretreatment) in this population of women. This prospective, randomized study was realized at the University Hospital of Saint-Étienne and concerns "poor responder" patients (age between 38 and 42 years and FSH at day 3 more than 9.5 IU/L; and/or antral follicles count less or equal to 6; and/or failure of previous stimulation). The primary endpoint is based on the number of oocytes retrieved at the end of an IVF cycle. Out of the 44 patients randomized, 39 cycles were taken into account (20 in the long protocol, 19 in the short one). At the end of the stimulation (FSH-r 300 to 450 UI/d), the number of follicles recruited appears higher in the long protocol but the difference is not significant (diameter between 14 and 18 mm: 3.0±2.31 vs. 1.88±1.89 and diameter greater than 18 mm: 3.9±2 85 vs. 3.06±2.77). The same tendency is observed for all the following criteria: the number of retrieved oocytes (6.74±2.73 vs. 6.38±4.26), the total number of embryos (3.16±2.03 vs. 2.25±2.11), the pregnancy rate per retrieval (21% vs. 19%) and per cycle (20% vs. 16%), and the number of children born alive. The study did not reveal any difference between the two protocols but the long half-dose seems to be better. Copyright © 2011 Elsevier Masson SAS. All rights reserved.
A new rapid kindling variant for induction of cortical epileptogenesis in freely moving rats

PubMed Central

Morales, Juan Carlos; Álvarez-Ferradas, Carla; Roncagliolo, Manuel; Fuenzalida, Marco; Wellmann, Mario; Nualart, Francisco Javier; Bonansco, Christian

2014-01-01

Kindling, one of the most used models of experimental epilepsy is based on daily electrical stimulation in several brain structures. Unlike the classic or slow kindling protocols (SK), the rapid kindling types (RK) described until now require continuous stimulation at suprathreshold intensities applied directly to the same brain structure used for subsequent electrophysiological and immunohistochemical studies, usually the hippocampus. However, the cellular changes observed in these rapid protocols, such as astrogliosis and neuronal loss, could be due to experimental manipulation more than to epileptogenesis-related alterations. Here, we developed a new RK protocol in order to generate an improved model of temporal lobe epilepsy (TLE) which allows gradual progression of the epilepsy as well as obtaining an epileptic hippocampus, thus avoiding direct surgical manipulation and electric stimulation over this structure. This new protocol consists of basolateral amygdala (BLA) stimulation with 10 trains of biphasic pulses (10 s; 50 Hz) per day with 20 min-intervals, during 3 consecutive days, using a subconvulsive and subthreshold intensity, which guarantees tissue integrity. The progression of epileptic activity was evaluated in freely moving rats through electroencephalographic (EEG) recordings from cortex and amygdala, accompanied with synchronized video recordings. Moreover, we assessed the effectiveness of RK protocol and the establishment of epilepsy by evaluating cellular alterations of hippocampal slices from kindled rats. RK protocol induced convulsive states similar to SK protocols but in 3 days, with persistently lowered threshold to seizure induction and epileptogenic-dependent cellular changes in amygdala projection areas. We concluded that this novel RK protocol introduces a new variant of the chronic epileptogenesis models in freely moving rats, which is faster, highly reproducible and causes minimum cell damage with respect to that observed in other experimental models of epilepsy. PMID:25100948
A new rapid kindling variant for induction of cortical epileptogenesis in freely moving rats.

PubMed

Morales, Juan Carlos; Alvarez-Ferradas, Carla; Roncagliolo, Manuel; Fuenzalida, Marco; Wellmann, Mario; Nualart, Francisco Javier; Bonansco, Christian

2014-01-01

Kindling, one of the most used models of experimental epilepsy is based on daily electrical stimulation in several brain structures. Unlike the classic or slow kindling protocols (SK), the rapid kindling types (RK) described until now require continuous stimulation at suprathreshold intensities applied directly to the same brain structure used for subsequent electrophysiological and immunohistochemical studies, usually the hippocampus. However, the cellular changes observed in these rapid protocols, such as astrogliosis and neuronal loss, could be due to experimental manipulation more than to epileptogenesis-related alterations. Here, we developed a new RK protocol in order to generate an improved model of temporal lobe epilepsy (TLE) which allows gradual progression of the epilepsy as well as obtaining an epileptic hippocampus, thus avoiding direct surgical manipulation and electric stimulation over this structure. This new protocol consists of basolateral amygdala (BLA) stimulation with 10 trains of biphasic pulses (10 s; 50 Hz) per day with 20 min-intervals, during 3 consecutive days, using a subconvulsive and subthreshold intensity, which guarantees tissue integrity. The progression of epileptic activity was evaluated in freely moving rats through electroencephalographic (EEG) recordings from cortex and amygdala, accompanied with synchronized video recordings. Moreover, we assessed the effectiveness of RK protocol and the establishment of epilepsy by evaluating cellular alterations of hippocampal slices from kindled rats. RK protocol induced convulsive states similar to SK protocols but in 3 days, with persistently lowered threshold to seizure induction and epileptogenic-dependent cellular changes in amygdala projection areas. We concluded that this novel RK protocol introduces a new variant of the chronic epileptogenesis models in freely moving rats, which is faster, highly reproducible and causes minimum cell damage with respect to that observed in other experimental models of epilepsy.
Comparison of luteal estradiol patch and gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation versus microdose gonadotropin-releasing hormone agonist protocol for patients with a history of poor in vitro fertilization outcomes.

PubMed

Weitzman, Vanessa N; Engmann, Lawrence; DiLuigi, Andrea; Maier, Donald; Nulsen, John; Benadiva, Claudio

2009-07-01

To compare IVF outcomes in poor-responder patients undergoing stimulation after luteal phase E(2) patch/GnRH antagonist (LPG) protocol versus microdose GnRH agonist protocol. Retrospective analysis. University-based IVF center. Forty-five women undergoing ovarian stimulation for IVF using the LPG protocol were compared with 76 women stimulated with the microdose GnRH agonist protocol from May 2005 to April 2006. Cancellation rate, number of oocytes retrieved, and clinical pregnancy rates. The mean number of oocytes (9.1 +/- 4.1 vs. 8.9 +/- 4.3) and mature oocytes (6.7 +/- 3.5 vs. 6.8 +/- 3.1) retrieved were similar, as were the fertilization rates (70.0% +/- 24.2% vs. 69.9% +/- 21.5%) and the number of embryos transferred (2.5 +/- 1.1 vs. 2.7 +/- 1.3). The cancellation rate was not significantly different between the groups (13/45, 28.9% vs. 23/76, 30.3%). Likewise, there were no significant differences among the implantation rate (15.0% vs. 12.5%), clinical pregnancy rate (43.3% vs. 45.1%), and ongoing pregnancy rate per transfer (33.3% vs. 26.0%) between both groups. This study demonstrates that the use of an E(2) patch and a GnRH antagonist during the preceding luteal phase in patients with a history of failed cycles can provide similar IVF outcomes when compared with the microdose GnRH agonist protocol.
The added value of auditory cortex transcranial random noise stimulation (tRNS) after bifrontal transcranial direct current stimulation (tDCS) for tinnitus.

PubMed

To, Wing Ting; Ost, Jan; Hart, John; De Ridder, Dirk; Vanneste, Sven

2017-01-01

Tinnitus is the perception of a sound in the absence of a corresponding external sound source. Research has suggested that functional abnormalities in tinnitus patients involve auditory as well as non-auditory brain areas. Transcranial electrical stimulation (tES), such as transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex and transcranial random noise stimulation (tRNS) to the auditory cortex, has demonstrated modulation of brain activity to transiently suppress tinnitus symptoms. Targeting two core regions of the tinnitus network by tES might establish a promising strategy to enhance treatment effects. This proof-of-concept study aims to investigate the effect of a multisite tES treatment protocol on tinnitus intensity and distress. A total of 40 tinnitus patients were enrolled in this study and received either bifrontal tDCS or the multisite treatment of bifrontal tDCS before bilateral auditory cortex tRNS. Both groups were treated on eight sessions (two times a week for 4 weeks). Our results show that a multisite treatment protocol resulted in more pronounced effects when compared with the bifrontal tDCS protocol or the waiting list group, suggesting an added value of auditory cortex tRNS to the bifrontal tDCS protocol for tinnitus patients. These findings support the involvement of the auditory as well as non-auditory brain areas in the pathophysiology of tinnitus and demonstrate the idea of the efficacy of network stimulation in the treatment of neurological disorders. This multisite tES treatment protocol proved to be save and feasible for clinical routine in tinnitus patients.
Minimal stimulation protocol using letrozole versus microdose flare up GnRH agonist protocol in women with poor ovarian response undergoing ICSI.

PubMed

Mohsen, Iman Abdel; El Din, Rasha Ezz

2013-02-01

To compare the IVF outcomes of letrozole/antagonist and microdose GnRH agonist flare up protocols in poor ovarian responders undergoing intracytoplasmic sperm injection. A randomized controlled trial was performed in patients with one or more previous failed IVF cycles in which four or less oocytes were retrieved when the gonadotrophin starting dose was at least 300 IU/day. Sixty patients were randomized by computer-generated list to receive either letrozole/antagonist (mild stimulation) n = 30 or GnRH-a protocol (microdose flare) n = 30. Both groups were similar with respect to background and hormonal characteristics (age, duration of infertility, BMI, FSH, LH and E2). The clinical pregnancy rate per cycle was similar in both groups (13.3 vs. 16.6%; OR = 0.769; 95% CI = 0.185, 3.198). The doses of used gonadotropins and the number of stimulation days were significantly lower in the letrozole/antagonist protocol. The peak E2 level on the day of hCG, the endometrial thickness, the retrieved oocytes, the number of fertilized oocytes, the number of transferred embryos and the cancellation rate were statistically similar in both groups. The letrozole/antagonist protocol is a cost-effective and patient-friendly protocol that may be used in poor ovarian responders for IVF/ICSI.
Structural insights into microtubule doublet interactions inaxonemes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Downing, Kenneth H.; Sui, Haixin

2007-06-06

Coordinated sliding of microtubule doublets, driven by dynein motors, produces periodic beating of the axoneme. Recent structural studies of the axoneme have used cryo-electron tomography to reveal new details of the interactions among some of the multitude of proteins that form the axoneme and regulate its movement. Connections among the several sets of dyneins, in particular, suggest ways in which their actions may be coordinated. Study of the molecular architecture of isolated doublets has provided a structural basis for understanding the doublet's mechanical properties that are related to the bending of the axoneme, and has also offered insight into itsmore » potential role in the mechanism of dynein activity regulation.« less
Comparison of the ultrashort gonadotropin-releasing hormone agonist-antagonist protocol with microdose flare -up protocol in poor responders: a preliminary study

PubMed Central

Berker, Bülent; Duvan, Candan İltemir; Kaya, Cemil; Aytaç, Ruşen; Şatıroğlu, Hakan

2010-01-01

Objective To determine the potential effect of the ultrashort gonadotropin-releasing hormone (GnRH) agonist/GnRH antagonist protocol versus the microdose GnRH agonist protocol in poor responders undergoing intracytoplasmic sperm injection (ICSI). Material and Methods The patients in the Agonist-Antagonist Group (n=41) were administered the ultrashort GnRH-agonist/ antagonist protocol, while the patients in the Microdose Group (n=41) were stimulated according to the microdose flare-up protocol. The mean number of mature oocytes retrieved was the primary outcome measure. Fertilization rate, implantation rate per embryo and clinical pregnancy rates were secondary outcome measures. Results There was no differenc between the mean number of mature oocytes retrieved in the two groups. There were also no statistical differences between the two groups in terms of peak serum E2 level, canceled cycles, endometrial thickness on hCG day, number of 2 pronucleus and number of embryos transferred. However, the total gonadotropin consumption and duration of stimulation were significantly higher with the Agonist-Antagonist Group compared with the Microdose Group. The implantation and clinical pregnancy rates were similar between the two groups. Conclusion Despite the high dose of gonadotropin consumption and longer duration of stimulation with the ultrashort GnRH agonist/ antagonist protocol, it seems that the Agonist-Antagonist Protocol is not inferior to the microdose protocol in poor responders undergoing ICSI. PMID:24591934
Anti-Mullerian hormone-tailored stimulation protocols improve outcomes whilst reducing adverse effects and costs of IVF.

PubMed

Yates, A P; Rustamov, O; Roberts, S A; Lim, H Y N; Pemberton, P W; Smith, A; Nardo, L G

2011-09-01

Anti-Müllerian hormone (AMH) is increasingly used to quantify ovarian reserve, but it has not yet realized its full clinical potential in assisted reproduction technology. We investigated the possible benefits of using novel, stratified ovarian hyperstimulation protocols, tailored to individual AMH levels, compared with conventional stimulation. Retrospective data were collected from 769 women (first cycle of IVF, using fresh embryos), in a UK tertiary care unit: 346 women using conventional stimulation protocols; 423 women treated under new AMH-tailored protocols. Embryo transfer rates increased significantly (79-87%: P= 0.002) after the introduction of AMH-tailored stimulation protocols. Pregnancy rate per cycle started and live birth rate also increased significantly compared with conventionally treated women (17.9-27.7%, P= 0.002 and 15.9-23.9%, P = 0.007, respectively). Moreover, in the AMH group, the incidence of the ovarian hyperstimulation syndrome (OHSS) fell significantly (6.9-2.3%, P = 0.002) and failed fertilization fell from 7.8 to 4.5%. The cost of fertility drug treatment fell by 29% per patient and the overall cost of clinical management of OHSS fell by 43% in the AMH group. GnRH antagonist protocols, introduced as part of AMH-tailored treatment, may have contributed to the observed improvements: however, within the AMH-tailored group, the live birth rate was not significantly different between agonist and antagonist-treated groups. Although large, prospective, multicentre studies are indicated, we have clearly demonstrated that individualized, AMH-guided, controlled ovarian hyperstimulation protocols significantly improved positive clinical outcomes, reduced the incidence of complications and reduced the financial burden associated with assisted reproduction.
Semialigned two Higgs doublet model

NASA Astrophysics Data System (ADS)

Haba, Naoyuki; Umeeda, Hiroyuki; Yamada, Toshifumi

2018-02-01

In the left-right symmetric model based on S U (2 )L×S U (2 )R×U (1 )B -L gauge symmetry, there appear heavy neutral scalar particles mediating quark flavor changing neutral currents (FCNCs) at tree level. We consider a situation where such FCNCs give the only sign of the left-right model while WR gauge boson is decoupled, and name it "semialigned two Higgs doublet model" because the model resembles a two Higgs doublet model with mildly aligned Yukawa couplings to quarks. We predict a correlation among processes induced by quark FCNCs in the model, and argue that future precise calculation of meson-antimeson mixings and C P violation therein may hint at the semialigned two Higgs doublet model and the left-right model behind it.
Method to Reduce Muscle Fatigue During Transcutaneous Neuromuscular Electrical Stimulation in Major Knee and Ankle Muscle Groups.

PubMed

Sayenko, Dimitry G; Nguyen, Robert; Hirabayashi, Tomoyo; Popovic, Milos R; Masani, Kei

2015-09-01

A critical limitation with transcutaneous neuromuscular electrical stimulation as a rehabilitative approach is the rapid onset of muscle fatigue during repeated contractions. We have developed a method called spatially distributed sequential stimulation (SDSS) to reduce muscle fatigue by distributing the center of electrical field over a wide area within a single stimulation site, using an array of surface electrodes. To extend the previous findings and to prove feasibility of the method by exploring the fatigue-reducing ability of SDSS for lower limb muscle groups in the able-bodied population, as well as in individuals with spinal cord injury (SCI). SDSS was delivered through 4 active electrodes applied to the knee extensors and flexors, plantarflexors, and dorsiflexors, sending a stimulation pulse to each electrode one after another with 90° phase shift between successive electrodes. Isometric ankle torque was measured during fatiguing stimulations using SDSS and conventional single active electrode stimulation lasting 2 minutes. We demonstrated greater fatigue-reducing ability of SDSS compared with the conventional protocol, as revealed by larger values of fatigue index and/or torque peak mean in all muscles except knee flexors of able-bodied individuals, and in all muscles tested in individuals with SCI. Our study has revealed improvements in fatigue tolerance during transcutaneous neuromuscular electrical stimulation using SDSS, a stimulation strategy that alternates activation of subcompartments of muscles. The SDSS protocol can provide greater stimulation times with less decrement in mechanical output compared with the conventional protocol. © The Author(s) 2014.
[The application of high-frequency and iTBS transcranial magnetic stimulation for the treatment of spasticity in the patients presenting with secondary progressive multiple sclerosis].

PubMed

Korzhova, J E; Chervyakov, A V; Poydasheva, A G; Kochergin, I A; Peresedova, A V; Zakharova, M N; Suponeva, N A; Chernikova, L A; Piradov, M A

Spasticity is considered to be a common manifestation of multiple sclerosis. Muscle relaxants are not sufficiently effective; more than that, some of them often cause a variety of adverse reactions. Transcranial magnetic stimulation (TMS) can be a promising new tool for the treatment of spasticity. The objective of the present study was to compare the effectiveness of the two TMS protocols: rhythmic (high-frequency) TMS (rTMS) and stimulation with the theta bursts (iTBS) in terms of their ability to reduce spasticity in the patients presenting with multiple sclerosis. Twenty two patients with secondary-progressive multiple sclerosis were pseudo-randomized into two groups: those in the first (high-frequency) group received the treatment with the use of rTMS therapy at a frequency of 10 Hz; the patients of the second group, underwent stimulation with the theta bursts (iTBS). All the patients received 10 sessions of either stimulation applied to the primary motor area (M1) of both legs. The effectiveness of TMS protocols was evaluated before therapy and after 10 sessions of stimulation based on the Modified Ashworth scale (MAS), the expanded disability status scale (EDSS), and the Kurtzke functional scale (Kfs). In addition, the patients were interviewed before treatment, after 10 rTMS sessions, immediately after and within 2 and 12 weeks after the completion of the treatment using questionnaires for the evaluation of spasticity (SESS) , fatigue, and dysfunction of the pelvic organs (severity of defecation and urination disorders), fatigue. The study has demonstrated a significant reduction in spasticity in the patients of both groups at the end of the TMS protocol based on the MAS scale. There was no significant difference between the outcomes of the two protocols. Both had positive effect on the concomitant «non-motor» symptoms (fatigue, dysfunction of the pelvic organs). High-frequency transcranial magnetic stimulation (10 sessions of rTMS therapy at a frequency of 10 Hz) and stimulation with the theta-bursts applied to the M1 area in both legs can be an effective alternative treatment of spasticity in the patients with secondary-progressive multiple sclerosis. Further research is needed to detect more accurately the differences between the outcomes of the two stimulation protocols and the development of indications for their application on an individual basis.

Monitoring of Beachsaver Reef with Filter Blanket and Double-T Sill at Cape May Point, New Jersey, Section 227 Demonstration Site; First Year Monitoring - 2002-2003

DTIC Science & Technology

2005-07-01

evaluate the functional, structural, and economic performance of the patented Beachsaver Reef prefabricated concrete submerged breakwater and the less...expensive prefabricated concrete structure called a Double-T sill. This demonstration project was developed through a cooperative effort of the U.S...patented Beachsaver Reef prefabricated concrete submerged breakwater and a less expensive, prefabricated concrete structure called a Double-T sill. Data
Critical evaluation of measured line positions of 14N16O in X2П state

NASA Astrophysics Data System (ADS)

Sulakshina, O. N.; Borkov, Yu. G.

2018-04-01

All available line positions for unresolved and resolved Λ-doublets of the 14N16O molecule in the X2 П state were collected from the literature and tested using the RITZ computer code. These data have been critically analysed and used to obtain the most complete set of 1789 experimental energy levels of unresolved Λ-doublets covering the 0-35,866 cm-1 interval. A set of 425 experimental energy levels of resolved Λ-doublets covering the 0-5957 cm-1 interval for two states 2П1/2 and 2П3/2 also have been obtained. These levels together with calculated correlation matrix can be used to generate the precise list of transitions with confidence intervals. Comparisons with the HITRAN as well as with Amiot calculations are discussed. The systematic shift between experimental energy levels of unresolved Λ-doublets and those calculated by Amiot for 2П3/2 state was found. The same systematic shift for transitions frequencies of unresolved Λ-doublets in forbidden subbands 2П1/2↔2П3/2 is also established in the HITRAN database. Comparison of the RITZ energy levels with calculated energy levels by Wong at al. was also done. It was found, that experimental RITZ energy levels for resolved Λ-doublets of 14N16O coincide with those calculated by Wong at al. within experimental uncertainties.
Product lambda-doublet ratios as an imprint of chemical reaction mechanism

PubMed Central

Jambrina, P. G.; Zanchet, A.; Aldegunde, J.; Brouard, M.; Aoiz, F. J.

2016-01-01

In the last decade, the development of theoretical methods has allowed chemists to reproduce and explain almost all of the experimental data associated with elementary atom plus diatom collisions. However, there are still a few examples where theory cannot account yet for experimental results. This is the case for the preferential population of one of the Λ-doublet states produced by chemical reactions. In particular, recent measurements of the OD(2Π) product of the O(3P)+D2 reaction have shown a clear preference for the Π(A′) Λ-doublet states, in apparent contradiction with ab initio calculations, which predict a larger reactivity on the A′′ potential energy surface. Here we present a method to calculate the Λ-doublet ratio when concurrent potential energy surfaces participate in the reaction. It accounts for the experimental Λ-doublet populations via explicit consideration of the stereodynamics of the process. Furthermore, our results demonstrate that the propensity of the Π(A′) state is a consequence of the different mechanisms of the reaction on the two concurrent potential energy surfaces PMID:27834381
Some recent experimental results related to nuclear chirality

NASA Astrophysics Data System (ADS)

Timár, J.; Kuti, I.; Sohler, D.; Starosta, K.; Koike, T.; Paul, E. S.

2014-09-01

Detailed band structures of three chiral-candidate nuclei, 134Pr, 132La and 103Rh have been studied. The aim of the study was twofold. First, to try to explore the reasons behind the contradiction between the theoretically predicted chirality in these nuclei and the recently observed fingerprints that suggest non-chiral interpretation for the previous chiral candidate band doublets. Second, to search for multiple chiral bands of different types in these nuclei. In 134Pr a new πh11/2vh11/2 band has been observed besides the previously known chiral-candidate πh11/2vh11/2 doublet. This new band and the yrare πh11/2vh11/2 band show the expected features of a chiral doublet structure. This fact combined with the observed similarity between the band structures of 134Pr and 132La suggests that chirality might exist in these nuclei. The detailed study of the 103Rh band structure resulted in the observation of two new chiral-doublet looking structures besides the previously known one. This is indicative of possible existence of multiple chiral doublet structure in this nucleus.
Practices and Attitudes Regarding Women Undergoing Fertility Preservation: A Survey of the National Physicians Cooperative.

PubMed

Bortoletto, Pietro; Confino, Rafael; Smith, Brigid M; Woodruff, Teresa K; Pavone, Mary Ellen

2017-09-01

To describe physician attitudes and variations in oncofertility treatment strategies. An exploratory online survey administered between December 1, 2014 and January 27, 2015 to 185 members of the National Physicians Cooperative (NPC). Twenty-eight percent (52 of 185) of NPC members responded to the online survey. Fifty percent of respondents were obstetrician-gynecologists working largely in academic medical centers. Thirty-eight percent stated that 14 was the youngest age they felt comfortable performing oocyte retrievals with 35% stating that any age was acceptable as long as they were postpubertal. Short stimulation protocols, utilizing a gonadotropin-releasing hormone (GnRH) antagonist (86%), were more common than long stimulation or microdose Lupron flare protocols (23% and 18%), respectively, which utilize a GnRH agonist. Random start protocols were used by 77% and over 90% perform luteal phase starts. When using random start protocols, 64% use gonadotropins only and 32% start GnRH antagonists alone for several days before starting gonadotropins. Fifty-five percent of physicians were comfortable stimulating ovarian cancer patients only after clearance from an oncologist. Aromatase inhibitors (77%) were significantly more common than tamoxifen (24%) for stimulation in breast cancer patients (p = 0.0006). When considering ovarian stimulation after chemotherapy, 24% expressed comfort only if blood counts are normal, 38% tend to wait 3 months. Regarding experimental treatment, 83% report discussing the use of GnRH agonists alone and 64% of clinics offer ovarian tissue cryopreservation. This study underlines the wide variation that exists in stimulation and phase start techniques, patient selection, comfort levels, and cancer type-specific decision making.
Theory of feedback controlled brain stimulations for Parkinson's disease

NASA Astrophysics Data System (ADS)

Sanzeni, A.; Celani, A.; Tiana, G.; Vergassola, M.

2016-01-01

Limb tremor and other debilitating symptoms caused by the neurodegenerative Parkinson's disease are currently treated by administering drugs and by fixed-frequency deep brain stimulation. The latter interferes directly with the brain dynamics by delivering electrical impulses to neurons in the subthalamic nucleus. While deep brain stimulation has shown therapeutic benefits in many instances, its mechanism is still unclear. Since its understanding could lead to improved protocols of stimulation and feedback control, we have studied a mathematical model of the many-body neural network dynamics controlling the dynamics of the basal ganglia. On the basis of the results obtained from the model, we propose a new procedure of active stimulation, that depends on the feedback of the network and that respects the constraints imposed by existing technology. We show by numerical simulations that the new protocol outperforms the standard ones for deep brain stimulation and we suggest future experiments that could further improve the feedback procedure.
Energy Consumption of Actively Beating Flagella

NASA Astrophysics Data System (ADS)

Chen, Daniel; Nicastro, Daniela; Dogic, Zvonimir

2012-02-01

Motile cilia and flagella are important for propelling cells or driving fluid over tissues. The microtubule-based core in these organelles, the axoneme, has a nearly universal ``9+2'' arrangement of 9 outer doublet microtubules assembled around two singlet microtubules in the center. Thousands of molecular motor proteins are attached to the doublets and walk on neighboring outer doublets. The motors convert the chemical energy of ATP hydrolysis into sliding motion between adjacent doublet microtubules, resulting in precisely regulated oscillatory beating. Using demembranated sea urchin sperm flagella as an experimental platform, we simultaneously monitor the axoneme's consumption of ATP and its beating dynamics while key parameters, such as solution viscosity and ATP concentration, are varied. Insights into motor cooperativity during beating and energetic consequences of hydrodynamic interactions will be presented.
N-acetylcysteine inhibits muscle fatigue in humans.

PubMed Central

Reid, M B; Stokić, D S; Koch, S M; Khawli, F A; Leis, A A

1994-01-01

N-acetylcysteine (NAC) is a nonspecific antioxidant that selectively inhibits acute fatigue of rodent skeletal muscle stimulated at low (but not high) tetanic frequencies and that decreases contractile function of unfatigued muscle in a dose-dependent manner. The present experiments test the hypothesis that NAC pretreatment can inhibit acute muscular fatigue in humans. Healthy volunteers were studied on two occasions each. Subjects were pretreated with NAC 150 mg/kg or 5% dextrose in water by intravenous infusion. The subject then sat in a chair with surface electrodes positioned over the motor point of tibialis anterior, an ankle dorsiflexor of mixed-fiber composition. The muscle was stimulated to contract electrically (40-55 mA, 0.2-ms pulses) and force production was measured. Function of the unfatigued muscle was assessed by measuring the forces produced during maximal voluntary contractions (MVC) of ankle dorsiflexor muscle groups and during electrical stimulation of tibialis anterior at 1, 10, 20, 40, 80, and 120 Hz (protocol 1). Fatigue was produced using repetitive tetanic stimulations at 10 Hz (protocol 1) or 40 Hz (protocol 2); intermittent stimulations subsequently were used to monitor recovery from fatigue. The contralateral leg then was studied using the same protocol. Pretreatment with NAC did not alter the function of unfatigued muscle; MVC performance and the force-frequency relationship of tibialis anterior were unchanged. During fatiguing contractions stimulated at 10 Hz, NAC increased force output by approximately 15% (P < 0.0001), an effect that was evident after 3 min of repetitive contraction (P < 0.0125) and persisted throughout the 30-min protocol. NAC had no effect on fatigue induced using 40 Hz stimuli or on recovery from fatigue. N-acetylcysteine pretreatment can improve performance of human limb muscle during fatiguing exercise, suggesting that oxidative stress plays a causal role in the fatigue process and identifying antioxidant therapy as a novel intervention that may be useful clinically. PMID:7989604
Longitudinal vector form factors in weak decays of nuclei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Šimkovic, F.; Department of Nuclear Physics and Biophysics, Comenius University, Mlynská dolina F1 SK–842 48 Bratislava; Kovalenko, S.

2015-10-28

The longitudinal form factors of the weak vector current of particles with spin J = 1/2 and isospin I = 1/2 are determined by the mass difference and the charge radii of members of the isotopic doublets. The most promising reactions to measure these form factors are the reactions with large momentum transfers involving the spin-1/2 isotopic doublets with a maximum mass splitting. Numerical estimates of longitudinal form factors are given for nucleons and eight nuclear spin-1/2 isotopic doublets.
Random Start Ovarian Stimulation for Oocyte or Embryo Cryopreservation in Women Desiring Fertility Preservation Prior to Gonadotoxic Cancer Therapy.

PubMed

Danis, Rachel B; Pereira, Nigel; Elias, Rony T

2017-11-10

Women of reproductive age diagnosed with cancer are often interested in preserving gametes or reproductive tissue that would allow for future genetic parenthood. Preservation of fertility is often accomplished in young cancer patients via ovarian stimulation followed by oocyte or embryo cryopreservation. Conventional stimulation protocols, however, require 2-4 weeks to complete ovarian stimulation, oocyte retrieval and possible fertilization. Such a strategy may not be feasible in patients requiring urgent cancer treatment. Recent studies have highlighted that random start ovarian stimulation can be initiated irrespective of the phase of the menstrual cycle and is an attractive alternative to conventional ovarian stimulation. The primary aim of the current review is to discuss the feasibility and success of random start ovarian stimulation for oocyte or embryo cryopreservation in women desiring fertility preservation prior to gonadotoxic cancer therapy. We performed a systematic review of medical literature published between January 2000 to June 2017 reporting the utility of random start ovarian stimulation for fertility preservation. Search terms included "fertility preservation," "cancer," "ovarian stimulation," "random-start ovarian stimulation," "embryo cryopreservation, and" "oocyte cryopreservation." Publications were included in this review only if patients underwent random start ovarian stimulation prior to cancer therapy. Nineteen publications were identified and perused by the authors. Most publications described the utility of random start ovarian stimulation in the setting of breast cancer. Radom-start stimulation was associated with a reduced time interval between ovarian stimulation initiation and oocyte or embryo cryopreservation. The yield of mature oocytes and their developmental potential into embryos was comparable between conventional and random-start protocols, albeit with higher gonadotropin doses in the latter. The current review suggests that random start ovarian stimulation can shorten the interval between ovarian stimulation and oocyte retrieval, with the yield of oocytes and embryos being comparable to conventional stimulation protocols. Thus, random start ovarian stimulation may serve as a better option for fertility preservation in patients requiring urgent cancer treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Low-Frequency Repetitive Transcranial Magnetic Stimulation and Intensive Occupational Therapy for Poststroke Patients with Upper Limb Hemiparesis: Preliminary Study of a 15-Day Protocol

ERIC Educational Resources Information Center

Kakuda, Wataru; Abo, Masahiro; Kobayashi, Kazushige; Momosaki, Ryo; Yokoi, Aki; Fukuda, Akiko; Ishikawa, Atsushi; Ito, Hiroshi; Tominaga, Ayumi

2010-01-01

The purpose of the study was to determine the safety and feasibility of a 15-day protocol of low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with intensive occupational therapy (OT) on motor function and spasticity in hemiparetic upper limbs in poststroke patients. Fifteen poststroke patients (age at study entry 55 [plus…
Experimental parameter identification of a multi-scale musculoskeletal model controlled by electrical stimulation: application to patients with spinal cord injury.

PubMed

Benoussaad, Mourad; Poignet, Philippe; Hayashibe, Mitsuhiro; Azevedo-Coste, Christine; Fattal, Charles; Guiraud, David

2013-06-01

We investigated the parameter identification of a multi-scale physiological model of skeletal muscle, based on Huxley's formulation. We focused particularly on the knee joint controlled by quadriceps muscles under electrical stimulation (ES) in subjects with a complete spinal cord injury. A noninvasive and in vivo identification protocol was thus applied through surface stimulation in nine subjects and through neural stimulation in one ES-implanted subject. The identification protocol included initial identification steps, which are adaptations of existing identification techniques to estimate most of the parameters of our model. Then we applied an original and safer identification protocol in dynamic conditions, which required resolution of a nonlinear programming (NLP) problem to identify the serial element stiffness of quadriceps. Each identification step and cross validation of the estimated model in dynamic condition were evaluated through a quadratic error criterion. The results highlighted good accuracy, the efficiency of the identification protocol and the ability of the estimated model to predict the subject-specific behavior of the musculoskeletal system. From the comparison of parameter values between subjects, we discussed and explored the inter-subject variability of parameters in order to select parameters that have to be identified in each patient.
Dark matter and electroweak phase transition in the mixed scalar dark matter model

NASA Astrophysics Data System (ADS)

Liu, Xuewen; Bian, Ligong

2018-03-01

We study the electroweak phase transition in the framework of the scalar singlet-doublet mixed dark matter model, in which the particle dark matter candidate is the lightest neutral Higgs that comprises the C P -even component of the inert doublet and a singlet scalar. The dark matter can be dominated by the inert doublet or singlet scalar depending on the mixing. We present several benchmark models to investigate the two situations after imposing several theoretical and experimental constraints. An additional singlet scalar and the inert doublet drive the electroweak phase transition to be strongly first order. A strong first-order electroweak phase transition and a viable dark matter candidate can be accomplished in two benchmark models simultaneously, for which a proper mass splitting among the neutral and charged Higgs masses is needed.
Metaplasticity in human primary somatosensory cortex: effects on physiology and tactile perception

PubMed Central

Jones, Christina B.; Lulic, Tea; Bailey, Aaron Z.; Mackenzie, Tanner N.; Mi, Yi Qun; Tommerdahl, Mark

2016-01-01

Theta-burst stimulation (TBS) over human primary motor cortex evokes plasticity and metaplasticity, the latter contributing to the homeostatic balance of excitation and inhibition. Our knowledge of TBS-induced effects on primary somatosensory cortex (SI) is limited, and it is unknown whether TBS induces metaplasticity within human SI. Sixteen right-handed participants (6 females, mean age 23 yr) received two TBS protocols [continuous TBS (cTBS) and intermittent TBS (iTBS)] delivered in six different combinations over SI in separate sessions. TBS protocols were delivered at 30 Hz and were as follows: a single cTBS protocol, a single iTBS protocol, cTBS followed by cTBS, iTBS followed by iTBS, cTBS followed by iTBS, and iTBS followed by cTBS. Measures included the amplitudes of the first and second somatosensory evoked potentials (SEPs) via median nerve stimulation, their paired-pulse ratio (PPR), and temporal order judgment (TOJ). Dependent measures were obtained before TBS and at 5, 25, 50, and 90 min following stimulation. Results indicate similar effects following cTBS and iTBS; increased amplitudes of the second SEP and PPR without amplitude changes to SEP 1, and impairments in TOJ. Metaplasticity was observed such that TOJ impairments following a single cTBS protocol were abolished following consecutive cTBS protocols. Additionally, consecutive iTBS protocols altered the time course of effects when compared with a single iTBS protocol. In conclusion, 30-Hz cTBS and iTBS protocols delivered in isolation induce effects consistent with a TBS-induced reduction in intracortical inhibition within SI. Furthermore, cTBS- and iTBS-induced metaplasticity appear to follow homeostatic and nonhomeostatic rules, respectively. PMID:26984422
Metaplasticity in human primary somatosensory cortex: effects on physiology and tactile perception.

PubMed

Jones, Christina B; Lulic, Tea; Bailey, Aaron Z; Mackenzie, Tanner N; Mi, Yi Qun; Tommerdahl, Mark; Nelson, Aimee J

2016-05-01

Theta-burst stimulation (TBS) over human primary motor cortex evokes plasticity and metaplasticity, the latter contributing to the homeostatic balance of excitation and inhibition. Our knowledge of TBS-induced effects on primary somatosensory cortex (SI) is limited, and it is unknown whether TBS induces metaplasticity within human SI. Sixteen right-handed participants (6 females, mean age 23 yr) received two TBS protocols [continuous TBS (cTBS) and intermittent TBS (iTBS)] delivered in six different combinations over SI in separate sessions. TBS protocols were delivered at 30 Hz and were as follows: a single cTBS protocol, a single iTBS protocol, cTBS followed by cTBS, iTBS followed by iTBS, cTBS followed by iTBS, and iTBS followed by cTBS. Measures included the amplitudes of the first and second somatosensory evoked potentials (SEPs) via median nerve stimulation, their paired-pulse ratio (PPR), and temporal order judgment (TOJ). Dependent measures were obtained before TBS and at 5, 25, 50, and 90 min following stimulation. Results indicate similar effects following cTBS and iTBS; increased amplitudes of the second SEP and PPR without amplitude changes to SEP 1, and impairments in TOJ. Metaplasticity was observed such that TOJ impairments following a single cTBS protocol were abolished following consecutive cTBS protocols. Additionally, consecutive iTBS protocols altered the time course of effects when compared with a single iTBS protocol. In conclusion, 30-Hz cTBS and iTBS protocols delivered in isolation induce effects consistent with a TBS-induced reduction in intracortical inhibition within SI. Furthermore, cTBS- and iTBS-induced metaplasticity appear to follow homeostatic and nonhomeostatic rules, respectively. Copyright © 2016 the American Physiological Society.
Comparison of Ovulation Induction Protocols After Endometrioma Resection

PubMed Central

Yasa, Cenk; Dural, Ozlem; Mutlu, Mehmet Firat; Celik, Cem; Ugurlucan, Funda Gungor; Buyru, Faruk

2014-01-01

Background and Objectives: The aim of this study was to compare the in vitro fertilization (IVF) outcomes of long gonadotropin-releasing hormone agonist (GnRH-a) and GnRH-antagonist (GnRH-ant) protocols in endometriosis patients who have undergone laparoscopic endometrioma resection surgery. To our knowledge, there is no study in the current literature that compares the effectiveness of long GnRH-a and GnRH-ant protocols in management of IVF cycles in endometriosis patients who underwent laparoscopic endometrioma resection surgery. Methods: Eighty-six patients with stage III to IV endometriosis who had undergone laparoscopic resection surgery for endometrioma were divided into 2 groups: those who had ovarian stimulation with a long GnRH-a protocol (n = 44), and those who had ovarian stimulation with a GnRH-ant protocol (n = 42). Results: The number of follicles on human chorionic gonadotropin injection day, duration of hyperstimulation, number of retrieved metaphase II oocytes, and total number of grade 1 embryos were statically significantly higher in the long GnRH-a protocol. There were no significant differences in positive β-human chorionic gonadotropin pregnancy rates (25% vs 21.4%; P = .269) and ongoing pregnancy rates per patient (20.5% vs 19.1%; P = .302) between the 2 protocols. Conclusions: Long GnRH-a and GnRH-ant protocols both present similar IVF outcomes in patients with endometriosis who have undergone laparoscopic endometrioma resection surgery. A long GnRH-a protocol may lead to a higher number of embryos that can be cryopreserved, providing the possibility of additional embryo transfers without having to go through the process of ovarian stimulation again. PMID:25392665
Photonic generation of ultra-wide-band doublet pulse through monolithic integration of tapered directional coupler and quantum well waveguide.

PubMed

Kuo, Yu-Zheng; Wu, Jui-Pin; Wu, Tsu-Hsiu; Chiu, Yi-Jen

2012-10-22

We proposed and demonstrated a novel scheme of photonic ultra-wide-band (UWB) doublet pulse based on monolithic integration of tapered optical-direction coupler (TODC) and multiple-quantum-well (MQW) waveguide. TODC is formed by a top tapered MQW waveguide vertically integrating with an underneath passive waveguide. Through simultaneous field-driven optical index- and absorption- change in MQW, the partial optical coupling in TODC can be used to get a valley-shaped of optical transmission against voltage. Therefore, doublet-enveloped optical pulse can be realized by high-speed and high-efficient conversion of input electrical pulse. By just adjusting bias through MQW, 1530 nm photonic UWB doublet optical pulse with 75-ps pulse width, below -41.3 dBm power, 125% fractional bandwidth, and 7.5 GHz of -10 dB bandwidth has been demonstrated, fitted into FCC requirement (3.1 GHz~10.6 GHz). Doublet-pulse data transmission generated in optical fiber is also performed for further characterization, exhibiting a successful 1.25 Gb/s error-free transmission. It suggests such optoelectronic integration template can be applied for photonic UWB generation in fiber-based communications.
Scalable UWB photonic generator based on the combination of doublet pulses.

PubMed

Moreno, Vanessa; Rius, Manuel; Mora, José; Muriel, Miguel A; Capmany, José

2014-06-30

We propose and experimentally demonstrate a scalable and reconfigurable optical scheme to generate high order UWB pulses. Firstly, various ultra wideband doublets are created through a process of phase-to-intensity conversion by means of a phase modulation and a dispersive media. In a second stage, doublets are combined in an optical processing unit that allows the reconfiguration of UWB high order pulses. Experimental results both in time and frequency domains are presented showing good performance related to the fractional bandwidth and spectral efficiency parameters.
Method and system for calibrating acquired spectra for use in spectral analysis

DOEpatents

Reber, Edward L.; Rohde, Kenneth W.; Blackwood, Larry G.

2010-09-14

A method for calibrating acquired spectra for use in spectral analysis includes performing Gaussian peak fitting to spectra acquired by a plurality of NaI detectors to define peak regions. A Na and annihilation doublet may be located among the peak regions. A predetermined energy level may be applied to one of the peaks in the doublet and a location of a hydrogen peak may be predicted based on the location of at least one of the peaks of the doublet. Control systems for calibrating spectra are also disclosed.
A comparison between r-LH and urinary supplements containing LH activity in patients undergoing the microdose GnRH agonist flare protocol for in-vitro fertilization: a pilot study.

PubMed

Shavit, Tal; Agdi, Mohammed; Son, Weon Y; Hasson, Josseph; Dahan, Michael H

2016-08-01

The aim of this study was to compare pregnancy rates and stimulation parameters in patients with diminished ovarian reserve, who were treated with recombinant human luteinizing hormone (r-LH) or menopausal gonadotropins (hMG), as part of a microdose flare protocol. A retrospective cohort study was performed. Comparisons between the group that was stimulated with r-LH plus follicle stimulating hormone (FSH) to those treated with hMG and FSH, were performed. Measurements included: medication doses, number of oocyte collected, number of embryos obtained, pregnancy and clinical pregnancy rates. Patients in the r-LH group (N.=40) had significant higher clinical pregnancy rates (33% vs. 14%; P=0.04) and used lower dose of LH (1938 IU vs. 2807 IU; P=0.02) compared to patients that were stimulated with hMG (N.=39). r-LH may offer advantages for the treatment of diminished ovarian reserve when performing a microdose flare protocol when compared to hMG. Both larger and prospective studies should be carried out to confirm these findings.

Chapter 4- Fertility preservation in women with breast cancer

PubMed Central

Rodriguez-Wallberg, Kenny A.; Oktay, Kutluk

2010-01-01

Fertility preservation is an important issue for young women diagnosed with breast cancer. The most well-established options for fertility preservation in cancer patients, embryo and oocyte cryopreservation, have not been traditionally offered to breast cancer patients as estradiol rise during standard stimulation protocols may not be safe for those patients. Potentially safer stimulation protocols using tamoxifen and aromatase inhibitors induce lower levels of estradiol while similar results in terms of number of oocyte and embryo obtained to standard protocols. Cryopreservation of immature oocytes and ovarian cortical tissue, both still experimental methods, are also fertility preservation options for breast cancer patients. PMID:21048442
Discharge patterning in rat olfactory bulb mitral cells in vivo

PubMed Central

Leng, Gareth; Hashimoto, Hirofumi; Tsuji, Chiharu; Sabatier, Nancy; Ludwig, Mike

2014-01-01

Abstract Here we present a detailed statistical analysis of the discharge characteristics of mitral cells of the main olfactory bulb of urethane‐anesthetized rats. Neurons were recorded from the mitral cell layer, and antidromically identified by stimuli applied to the lateral olfactory tract. All mitral cells displayed repeated, prolonged bursts of action potentials typically lasting >100 sec and separated by similarly long intervals; about half were completely silent between bursts. No such bursting was observed in nonmitral cells recorded in close proximity to mitral cells. Bursts were asynchronous among even adjacent mitral cells. The intraburst activity of most mitral cells showed strong entrainment to the spontaneous respiratory rhythm; similar entrainment was seen in some, but not all nonmitral cells. All mitral cells displayed a peak of excitability at ~25 msec after spikes, as reflected by a peak in the interspike interval distribution and in the corresponding hazard function. About half also showed a peak at about 6 msec, reflecting the common occurrence of doublet spikes. Nonmitral cells showed no such doublet spikes. Bursts typically increased in intensity over the first 20–30 sec of a burst, during which time doublets were rare or absent. After 20–30 sec (in cells that exhibited doublets), doublets occurred frequently for as long as the burst persisted, in trains of up to 10 doublets. The last doublet was followed by an extended relative refractory period the duration of which was independent of train length. In cells that were excited by application of a particular odor, responsiveness was apparently greater during silent periods between bursts than during bursts. Conversely in cells that were inhibited by a particular odor, responsiveness was only apparent when cells were active. Extensive raw (event timing) data from the cells, together with details of those analyses, are provided as supplementary material, freely available for secondary use by others. PMID:25281614
Interaction forces between red cells agglutinated by antibody. II. Measurement of hydrodynamic force of breakup.

PubMed Central

Tha, S P; Shuster, J; Goldsmith, H L

1986-01-01

The expressions derived in the previous paper for the respective normal, F3, and shear forces, Fshear, acting along and perpendicular to the axis of a doublet of rigid spheres, were used to determine the hydrodynamic forces required to separate two red cell spheres of antigenic type B crosslinked by the corresponding antibody. Cells were sphered and swollen in isotonic buffered glycerol containing 8 X 10(-5) M sodium dodecyl sulfate, fixed in 0.085% glutaraldehyde, and suspended in aqueous glycerol (viscosity: 15-34 mPa s), containing 0.15 M NaCl and anti-B antibody from human hyperimmune antiserum at concentrations from 0.73 to 3.56 vol%. After incubating and mixing for 12 h, doublets were observed through a microscope flowing in a 178-micron tube by gravity feed between two reservoirs. Using a traveling microtube apparatus, the doublets were tracked in a constantly accelerating flow and the translational and rotational motions were recorded on videotape until breakup occurred. From a frame by frame replay of the tape, the radial position, velocity and orientation of the doublet were obtained and the normal and shear forces of separation at breakup computed. Both forces increased significantly with increasing antiserum concentration, the mean values of F3 increasing from 0.060 to 0.197 nN, and Fshear from 0.023 to 0.072 nN. There was no significant effect of glycerol viscosity on the forces of separation. It was not possible to determine whether the shear or normal force was responsible for doublet separation. Measurements of the mean dimensionless period of rotation, TG, of doublets in suspensions containing 0.73 and 2.40% antiserum undergoing steady flow were also made to test whether the spheres were rigidly linked or capable of some independent rotation. A fairly narrow distribution in TG about the value 15.64, predicted for rigidly-linked doublets, was obtained at both antiserum concentrations. Images FIGURE 1 PMID:3801572
Partial purification and functional properties of an endoprotease from bovine neurosecretory granules cleaving proocytocin/neurophysin peptides at the basic amino acid doublet.

PubMed

Clamagirand, C; Creminon, C; Fahy, C; Boussetta, H; Cohen, P

1987-09-22

An enriched preparation of neurosecretory granules from bovine pituitary neural lobes was used as a source of processing enzymes possibly involved in the cleavage of the proocytocin/neurophysin precursor. A synthetic eicosapeptide reproducing the entire (1-20) sequence of the NH2-terminal domain of the bovine ocytocin/neurophysin precursor was used as a substrate to monitor an endoprotease activity cleaving at the Lys11-Arg12 doublet. The 58-kDa endoprotease detected in the lysate of neurohypophyseal granules produced a single cleavage, after the doublet, at the Arg12-Ala13 peptide bond. This endoprotease with pHi 6.9 and 7.2 exhibits maximal activity at pH around neutrality (7.0) and was strongly inhibited by divalent cation chelating agents [ethylenediaminetetraacetic acid and ethylene glycol bis(beta-aminoethyl ether)-N,N,N',-N'-tetraacetic acid] and to some extent by p-(chloromercuri)benzoate and p-(chloromercuri)benzenesulfonic acid, while phenylmethanesulfonyl fluoride and pepstatin were not active. This endoprotease action was sensitive to any modification of the substrate at either basic amino acid of the doublet since replacement of either L-Lys11 or L-Arg12 by D-Lys or D-Arg and by L-Nle abolished the cleavage reaction. In contrast, reversal of the polarity of the doublet in [Arg11,Lys12]proocytocin/neurophysin(1-20) had no effect on the mode of endoproteolytic cleavage as well as modifications of Gly10 (replaced by Ala10). It is concluded that the selectivity of this endoprotease, which may be involved in the primary event occurring in proocytocin/neurophysin processing, is strictly dependent upon the integrity of the basic doublet but that other parameters determined by the amino acid sequence around this doublet may play an important role.
Sizable NSI from the SU(2) L scalar doublet-singlet mixing and the implications in DUNE

DOE PAGES

Forero, David V.; Huang, Wei -Chih

2017-03-03

Here, we propose a novel and simple mechanism where sizable effects of non-standard interactions (NSI) in neutrino propagation are induced from the mixing between an electrophilic second Higgs doublet and a charged singlet. The mixing arises from a dimensionful coupling of the scalar doublet and singlet to the standard model Higgs boson. In light of the small mass, the light mass eigenstate from the doublet-singlet mixing can generate much larger NSI than those induced by the heavy eigenstate. We show that a sizable NSI ε eτ (~0.3) can be attained without being excluded by a variety of experimental constraints. Furthermore,more » we demonstrate that NSI can mimic effects of the Dirac CP phase in the neutrino mixing matrix but they can potentially be disentangled by future long-baseline neutrino experiments, such as the Deep Underground Neutrino Experiment (DUNE).« less
Determination of carrier concentration by Fano interference of Raman scattering in heavily doped n-type 4H-SiC

NASA Astrophysics Data System (ADS)

Mitani, Takeshi; Nakashima, Shin-ichi; Kojima, Kazutoshi; Kato, Tomohisa; Okumura, Hajime

2012-08-01

For n-type 4H-SiC crystals with carrier concentrations between 2 × 1017 and 2.5 × 1020 cm-3, Fano interference of the folded transverse acoustic (FTA) doublet modes was observed. The Fano line-shape parameters were shown to vary with carrier concentration. It is proposed that the peak shifts in the FTA modes resulting from interference with an electronic continuum state can be used to measure carrier concentration for n-type 4H-SiC up to 1020 cm-3. In addition, the relative intensity of the FTA doublet modes varies markedly with carrier concentrations above 5 × 1018 cm-3. This suggests that mode coupling occurs between the FTA doublet components. The variation in the intensity ratio is attributed to the intensity transfer between the FTA doublet components. This mode coupling arises from a phonon-phonon interaction via electronic continuum state-phonon interactions.
Two Higgs doublets with fourth-generation fermions: Models for TeV-scale compositeness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soni A.; Bar-Shalom, S.; Nandi, S.

2011-09-21

We construct a class of two Higgs doublets models with a 4th sequential generation of fermions that may effectively accommodate the low-energy characteristics and phenomenology of a dynamical electroweak symmetry breaking scenario which is triggered by the condensates of the 4th family fermions. In particular, we single out the heavy quarks by coupling the heavier Higgs doublet ({Phi}{sub h}) which possesses a much larger VEV only to them while the lighter doublet ({Phi}{sub {ell}) couples only to the light fermions. We study the constraints on these models from precision electroweak data as well as from flavor data. We also discussmore » some distinct new features that have direct consequences on the production and decays of the 4th family quarks and leptons in high-energy colliders; in particular, the conventional search strategies for t{prime} and b{prime} may need to be significantly revised.« less
Sizable NSI from the SU(2) L scalar doublet-singlet mixing and the implications in DUNE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forero, David V.; Huang, Wei -Chih

Here, we propose a novel and simple mechanism where sizable effects of non-standard interactions (NSI) in neutrino propagation are induced from the mixing between an electrophilic second Higgs doublet and a charged singlet. The mixing arises from a dimensionful coupling of the scalar doublet and singlet to the standard model Higgs boson. In light of the small mass, the light mass eigenstate from the doublet-singlet mixing can generate much larger NSI than those induced by the heavy eigenstate. We show that a sizable NSI ε eτ (~0.3) can be attained without being excluded by a variety of experimental constraints. Furthermore,more » we demonstrate that NSI can mimic effects of the Dirac CP phase in the neutrino mixing matrix but they can potentially be disentangled by future long-baseline neutrino experiments, such as the Deep Underground Neutrino Experiment (DUNE).« less
Pulsatile desynchronizing delayed feedback for closed-loop deep brain stimulation

PubMed Central

Lysyansky, Borys; Rosenblum, Michael; Pikovsky, Arkady; Tass, Peter A.

2017-01-01

High-frequency (HF) deep brain stimulation (DBS) is the gold standard for the treatment of medically refractory movement disorders like Parkinson’s disease, essential tremor, and dystonia, with a significant potential for application to other neurological diseases. The standard setup of HF DBS utilizes an open-loop stimulation protocol, where a permanent HF electrical pulse train is administered to the brain target areas irrespectively of the ongoing neuronal dynamics. Recent experimental and clinical studies demonstrate that a closed-loop, adaptive DBS might be superior to the open-loop setup. We here combine the notion of the adaptive high-frequency stimulation approach, that aims at delivering stimulation adapted to the extent of appropriately detected biomarkers, with specifically desynchronizing stimulation protocols. To this end, we extend the delayed feedback stimulation methods, which are intrinsically closed-loop techniques and specifically designed to desynchronize abnormal neuronal synchronization, to pulsatile electrical brain stimulation. We show that permanent pulsatile high-frequency stimulation subjected to an amplitude modulation by linear or nonlinear delayed feedback methods can effectively and robustly desynchronize a STN-GPe network of model neurons and suggest this approach for desynchronizing closed-loop DBS. PMID:28273176
Changes in long luteal protocol affects the number of days of stimulation: evolution of an assisted reproductive technology practice.

PubMed

Palmer, C Benjamin; Forstein, David A; Higdon, H Lee; Boone, William R

2011-01-01

To determine if the types of drugs used in controlled ovarian hyperstimulation influence the number of days of stimulation. This retrospective study of couples presenting at an assisted reproductive technology (ART) facility January 1997 through December 2007 included patients who were < 40 years of age, had a body mass index (BMI) of 20-35, used fresh sperm or oocytes, had > or = 3 embryos available on day 3, never had previous ART, and did not use a gestational carrier. Data analysis was limited to patients treated with long luteal stimulation. Data were separated into two groups: patients stimulated with urinary drugs and those stimulated with recombinant drugs. The groups were not different in age and day 3 follicle-stimulating hormone values, but were different in BMI, diagnoses, and fertilization methods. There were a significantly greater number of days of stimulation, total number of follicles produced, and peak estradiol level in the recombinant group. The recombinant group had less drug given per day, less endometrial thickness, and fewer embryos transferred. A change in our long luteal stimulation protocol appears to have lengthened the days of stimulation for our patients without altering pregnancy rate.
The ISMAAR proposal on terminology for ovarian stimulation for IVF.

PubMed

Nargund, G; Fauser, B C J M; Macklon, N S; Ombelet, W; Nygren, K; Frydman, R

2007-11-01

IVF is performed with oocytes collected in natural and stimulated cycles. Different approaches to ovarian stimulation have been employed worldwide. Following the introduction of GnRH antagonists and strategies to reduce multiple births such as single embryo transfer, there is a genuine scientific interest in the revival of natural cycle and mild approaches to ovarian stimulation in IVF. Recent evidence suggests that application of natural and mild IVF is patient-centred, aimed at reducing the cost of treatment, patient discomfort and multiple pregnancies. However, there seems to be no consistency in the terminology used for definitions and protocols for ovarian stimulation in IVF cycles. Following the recent International Society for Mild Approaches in Assisted Reproduction (ISMAAR) meeting and communication with interested international experts, this article has recommended revised definitions and terminology for natural cycle IVF and different protocols used in ovarian stimulation for IVF. It is proposed that these terms are adopted internationally in order to achieve a consistency in clinical practice, research publications and communication with patients.
Technical aspects of neurostimulation: Focus on equipment, electric field modeling, and stimulation protocols.

PubMed

Klooster, D C W; de Louw, A J A; Aldenkamp, A P; Besseling, R M H; Mestrom, R M C; Carrette, S; Zinger, S; Bergmans, J W M; Mess, W H; Vonck, K; Carrette, E; Breuer, L E M; Bernas, A; Tijhuis, A G; Boon, P

2016-06-01

Neuromodulation is a field of science, medicine, and bioengineering that encompasses implantable and non-implantable technologies for the purpose of improving quality of life and functioning of humans. Brain neuromodulation involves different neurostimulation techniques: transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS), which are being used both to study their effects on cognitive brain functions and to treat neuropsychiatric disorders. The mechanisms of action of neurostimulation remain incompletely understood. Insight into the technical basis of neurostimulation might be a first step towards a more profound understanding of these mechanisms, which might lead to improved clinical outcome and therapeutic potential. This review provides an overview of the technical basis of neurostimulation focusing on the equipment, the present understanding of induced electric fields, and the stimulation protocols. The review is written from a technical perspective aimed at supporting the use of neurostimulation in clinical practice. Copyright © 2016 Elsevier Ltd. All rights reserved.
Deficiency of water molecules in the crystallographic structure of vauxite

NASA Astrophysics Data System (ADS)

Van Alboom, A.; da Costa, G. M.; De Grave, E.

2017-07-01

A vauxite mineral sample from Huanuni, Bolivia, was studied by XRD, TGA and Mössbauer spectroscopy. The XRD revealed the sample as having the typical triclinic structure of vauxite. The chemical formula was determined as (Fe0.88Mn0.01)Al1.99(PO4)2(OH)1.75(H2O)5.31, implying some Fe2+, OH- and H2O deficiencies. The TGA curve showed ca. 27% loss of weight over a temperature range from 80 to 400 °C, supposedly due to the loss of water and hydroxyl groups. For the first time, Mössbauer spectra for vauxite were collected over a wide temperature range between 9 and 310 K. No magnetic ordering was detected. The spectra could be successfully and consistently analyzed by a superposition of four doublet subspectra. On the basis of the relation between the center shift and the mean Fe-ligand distance on the one hand and the center shift values for the various doublets on the other hand, one doublet was assigned to Fe(2). For the other doublets, it is proposed that, as a result of the H2O deficiency in the structure of the present vauxite sample, vacancies are present in the second coordination spheres of some Fe(1) and that these vacancies affect the quadrupole splitting of the corresponding Fe(1) cations, thus causing three Fe(1) doublet components in the Mössbauer spectra. The temperature variations of center shift and quadrupole splitting of the various doublet contributions are presented and discussed.
Multi-Higgs doublet models: physical parametrization, sum rules and unitarity bounds

NASA Astrophysics Data System (ADS)

Bento, Miguel P.; Haber, Howard E.; Romão, J. C.; Silva, João P.

2017-11-01

If the scalar sector of the Standard Model is non-minimal, one might expect multiple generations of the hypercharge-1/2 scalar doublet analogous to the generational structure of the fermions. In this work, we examine the structure of a Higgs sector consisting of N Higgs doublets (where N ≥ 2). It is particularly convenient to work in the so-called charged Higgs basis, in which the neutral Higgs vacuum expectation value resides entirely in the first Higgs doublet, and the charged components of remaining N - 1 Higgs doublets are mass-eigenstate fields. We elucidate the interactions of the gauge bosons with the physical Higgs scalars and the Goldstone bosons and show that they are determined by an N × 2 N matrix. This matrix depends on ( N - 1)(2 N - 1) real parameters that are associated with the mixing of the neutral Higgs fields in the charged Higgs basis. Among these parameters, N - 1 are unphysical (and can be removed by rephasing the physical charged Higgs fields), and the remaining 2( N - 1)2 parameters are physical. We also demonstrate a particularly simple form for the cubic interaction and some of the quartic interactions of the Goldstone bosons with the physical Higgs scalars. These results are applied in the derivation of Higgs coupling sum rules and tree-level unitarity bounds that restrict the size of the quartic scalar couplings. In particular, new applications to three Higgs doublet models with an order-4 CP symmetry and with a Z_3 symmetry, respectively, are presented.
Transcranial Direct Current Stimulation for Treating Depression in a Patient With Right Hemispheric Dominance: A Case Study.

PubMed

Shiozawa, Pedro; da Silva, Mailu Enokibara; Cordeiro, Quirino

2015-09-01

We report the case of a 66-year-old male patient with major depressive disorder for the last 6 months. The patient had been diagnosed with dyslexia during childhood and was left-handed. The intervention protocol consisted in 10 consecutive daily transcranial direct current stimulation sessions. However, after 5 days of stimulation, the patient presented with intensification of depressive symptoms and panic attacks. It was hypothetized that the intensification of symptoms may have been due to stimulation protocol itself. Considering the patient was left-handed and presented comorbidity with dyslexia, there was a plausible hypothesis of right hemispheric dominance. This was corroborated by the Edinburgh Handedness Scale. In fact, dyslexic patients present right hemisphere dominance more frequently. The patient also presented a single photon emission computed tomography with a hypoperfusion area over the left posterior parietal lobe. After the patients agreement, a 10-day experimental repetitive transcranial magnetic stimulation low-frequency protocol over the left dorsolateral prefrontal cortex was started to inhibit the area, which was hypothetically hyperactivated following the rationale of right dominance. The patient presented amelioration of depressive and anxious symptoms. Given the hemispheric reversal we show in the present case study, however, it seems that therapies that are beneficial to right-handers could be detrimental to left-handers.
Programming for Stimulation-Induced Transient Nonmotor Psychiatric Symptoms after Bilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease

PubMed Central

Wu, Xi; Qiu, Yiqing; Simfukwe, Keith; Wang, Jiali; Chen, Jianchun

2017-01-01

Background Stimulation-induced transient nonmotor psychiatric symptoms (STPSs) are side effects following bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients. We designed algorithms which (1) determine the electrode contacts that induce STPSs and (2) provide a programming protocol to eliminate STPS and maintain the optimal motor functions. Our objective is to test the effectiveness of these algorithms. Materials and Methods 454 PD patients who underwent programming sessions after STN-DBS implantations were retrospectively analyzed. Only STPS patients were enrolled. In these patients, the contacts inducing STPS were found and the programming protocol algorithms used. Results Eleven patients were diagnosed with STPS. Of these patients, two had four episodes of crying, and two had four episodes of mirthful laughter. In one patient, two episodes of abnormal sense of spatial orientation were observed. Hallucination episodes were observed twice in one patient, while five patients recorded eight episodes of hypomania. There were no statistical differences between the UPDRS-III under the final stimulation parameter (without STPS) and previous optimum UPDRS-III under the STPSs (p = 1.000). Conclusion The flow diagram used for determining electrode contacts that induce STPS and the programming protocol employed in the treatment of these symptoms are effective. PMID:28894620
Thermally stimulated luminescence properties of BaY2F8 : Ce crystals

NASA Astrophysics Data System (ADS)

Vedda, A.; Martini, M.; di Martino, D.; Sani, E.; Toncelli, A.; Tonelli, M.

Wavelength resolved thermally stimulated luminescence (TSL) measurements were performed on BaY2 F-8 :1.8 mol% Ce crystals after X-ray irradiation at 10 K and at 300 K, in order to obtain preliminary information about both trap levels and recombination centres. After irradiation at 10 K, the TSL glow curve shows the presence of a strong peak at 50 K, together with additional structures at approximately 20 and 170 K. The TSL spectrum is dominated by the characteristic doublet emission due to transitions from the lowest energy level of the 5d configuration to the spin-orbit split F-2 ground state of Ce3+ . Above RT, the glow curve exhibits a peak at 60 degreesC, whose spectrum is again dominated by Ce3+ emission. The TSL emission is in accordance with radio-luminescence (RL) spectra performed in the 10-300 K region. Moreover, RL spectra at temperatures lower than 200 K display an additional weak high energy band at around 4.5 eV assigned to host lattice transitions.
Compressing the Inert Doublet Model

DOE PAGES

Blinov, Nikita; Kozaczuk, Jonathan; Morrissey, David E.; ...

2016-02-16

The Inert Doublet Model relies on a discrete symmetry to prevent couplings of the new scalars to Standard Model fermions. We found that this stabilizes the lightest inert state, which can then contribute to the observed dark matter density. In the presence of additional approximate symmetries, the resulting spectrum of exotic scalars can be compressed. Here, we study the phenomenological and cosmological implications of this scenario. In conclusion, we derive new limits on the compressed Inert Doublet Model from LEP, and outline the prospects for exclusion and discovery of this model at dark matter experiments, the LHC, and future colliders.
New approach to flavor symmetry and an extended naturalness principle

NASA Astrophysics Data System (ADS)

Barr, S. M.

2010-09-01

A class of nonsupersymmetric extensions of the standard model is proposed in which there is a multiplicity of light scalar doublets in a multiplet of a nonabelian family group with the standard model Higgs doublet. Anthropic tuning makes the latter light, and consequently the other scalar doublets remain light because of the family symmetry. The family symmetry greatly constrains the pattern of flavor-changing neutral-current interactions (FCNC) and p decay operators coming from scalar-exchange. Such models show that useful constraints on model-building can come from an extended naturalness principle when the electroweak scale is anthropically tuned.
The Use of Source-Sink and Doublet Distributions Extended to the Solution of Boundary-Value Problems in Supersonic Flow

NASA Technical Reports Server (NTRS)

Heaslet, Max A; Lomax, Harvard

1948-01-01

A direct analogy is established between the use of source-sink and doublet distributions in the solution of specific boundary-value problems in subsonic wing theory and the corresponding problems in supersonic theory. The correct concept of the "finite part" of an integral is introduced and used in the calculation of the improper integrals associated with supersonic doublet distributions. The general equations developed are shown to include several previously published results and particular examples are given for the loading on rolling and pitching triangular wings with supersonic leading edges.

Weekly Time Course of Neuro-Muscular Adaptation to Intensive Strength Training.

PubMed

Brown, Niklas; Bubeck, Dieter; Haeufle, Daniel F B; Weickenmeier, Johannes; Kuhl, Ellen; Alt, Wilfried; Schmitt, Syn

2017-01-01

Detailed description of the time course of muscular adaptation is rarely found in literature. Thus, models of muscular adaptation are difficult to validate since no detailed data of adaptation are available. In this article, as an initial step toward a detailed description and analysis of muscular adaptation, we provide a case report of 8 weeks of intense strength training with two active, male participants. Muscular adaptations were analyzed on a morphological level with MRI scans of the right quadriceps muscle and the calculation of muscle volume, on a voluntary strength level by isometric voluntary contractions with doublet stimulation (interpolated twitch technique) and on a non-voluntary level by resting twitch torques. Further, training volume and isokinetic power were closely monitored during the training phase. Data were analyzed weekly for 1 week prior to training, pre-training, 8 weeks of training and 2 weeks of detraining (no strength training). Results show a very individual adaptation to the intense strength training protocol. While training volume and isokinetic power increased linearly during the training phase, resting twitch parameters decreased for both participants after the first week of training and stayed below baseline until de-training. Voluntary activation level showed an increase in the first 4 weeks of training, while maximum voluntary contraction showed only little increase compared to baseline. Muscle volume increased for both subjects. Especially training status seemed to influence the acute reaction to intense strength training. Fatigue had a major influence on performance and could only be overcome by one participant. The results give a first detailed insight into muscular adaptation to intense strength training on various levels, providing a basis of data for a validation of muscle fatigue and adaptation models.
Compression Garments, Muscle Contractile Function, and Economy in Trail Runners.

PubMed

Vercruyssen, Fabrice; Gruet, Mathieu; Colson, Serge S; Ehrstrom, Sabine; Brisswalter, Jeanick

2017-01-01

Physiological mechanisms behind the use of compression garments (CGs) during off-road running are unknown. To investigate the influence of wearing CGs vs conventional running clothing (CON) on muscle contractile function and running economy before and after short-distance trail running. Knee-extensor neuromuscular function and running economy assessed from two 5-min treadmill runs (11 and 14 km/h) were evaluated before and after an 18.6-km short-distance trail run in 12 trained athletes wearing either CGs (stocking + short-tight) or CON. Quadriceps neuromuscular function was assessed from mechanical and EMG recording after maximal percutaneous electrical femoral-nerve stimulations (single-twitch doublets at 10 [Db 10 ] and 100 Hz [Db 100 ] delivered at rest and during maximal quadriceps voluntary contraction [MVC]). Running economy (in mL O 2 · km -1 · kg -1 ) increased after trail running independent of the clothing condition and treadmill speeds (P < .001). Similarly, MVC decreased after CON and CGs conditions (-11% and -13%, respectively, P < .001). For both clothing conditions, a significant decrease in quadriceps voluntary activation, Db 10 , Db 100 , and the low-to-high frequency doublet ratio were observed after trail running (time effect, all P < .01), without any changes in rectus femoris maximal M-wave. Wearing CGs does not reduce physiological alterations induced during short-distance trail running. Further studies should determine whether higher intensity of compression pressure during exercises of longer duration may be effective to induce any physiological benefits in experienced trail runners.
Experimental comparative study of doublet and triplet impinging atomization of gelled fuel based on PIV

NASA Astrophysics Data System (ADS)

Yang, Jian-lu; Li, Ning; Weng, Chun-sheng

2016-10-01

Gelled propellant is promising for future aerospace application because of its combination of the advantages of solid propellants and liquid propellants. An effort was made to reveal the atomization properties of gelled fuel by particle image velocimetry (PIV) system. The gelled fuel which was formed by gasoline and Nano-silica was atomized using a like-doublet impingement injector and an axisymmetric like-triplet impingement injector. The orifice diameter and length of the nozzle used in this work were of 0.8mm, 4.8mm, respectively. In the impinging spray process, the impingement angles were set at 90° and 120°, and the injection pressures were of 0.50MPa and 1.00MPa. The distance from the exit of the orifice to the impingement point was fixed at 9.6mm. In this study, high-speed visualization and temporal resolution particle image velocimetry techniques were employed to investigate the impingement atomization characteristics. The experimental investigation demonstrated that a long narrow high speed droplets belt formed around the axis of symmetry in the like-doublet impinging atomization area. However, there was no obvious high-speed belt with impingement angle 2θ = 90° and two high-speed belts appeared with impingement angle 2θ = 120° in the like-doublet impingement spray field. The high droplet velocity zone of the like-doublet impingement atomization symmetrically distributed around the central axis, and that of the like-triplet impingement spray deflected to the left of the central axis - opposite of injector. Although the droplets velocity distribution was asymmetry of like-triplet impingement atomization, the injectors were arranged like axisymmetric conical shape, and the cross section of spray area was similar to a circle rather than a narrow rectangle like the like-doublet impingement atomization.
Temporal changes of the inner core from waveform doublets

NASA Astrophysics Data System (ADS)

Yang, Y.; Song, X.

2017-12-01

Temporal changes of the Earth's inner core have been detected from earthquake waveform doublets (repeating sources with similar waveforms at the same station). Using doublets from events up to the present in the South Sandwich Island (SSI) region recorded by the station COLA (Alaska), we confirmed systematic temporal variations in the travel time of the inner-core-refracted phase (PKIKP, the DF branch). The DF phase arrives increasingly earlier than outer core phases (BC and AB) by rate of approximately 0.07 s per decade since 1970s. If we assume that the temporal change is caused by a shift of the lateral gradient from the inner core rotation as in previous studies, we estimate the rotation rate of 0.2-0.4 degree per year. We also analyzed the topography of the inner core boundary (ICB) using SSI waveform doublets recorded by seismic stations in Eurasia and North America with reflected phase (PKiKP) and refracted phases. There are clear temporal changes in the waveforms of doublets for PKiKP under Africa and Central America. In addition, for doublets recorded by three nearby stations (AAK, AML, and UCH), we observed systematic change in the relative travel time of PKiKP and PKIKP. The temporal change of the (PKiKP - PKIKP) differential time is always negative for the event pairs if both events are before 2007, while it fluctuates to positive if the later event occurs after 2007. The rapid temporal changes in space and time may indicate localized processes (e.g., freezing and melting) of the ICB in the recent decades under Africa. We are exploring 4D models consistent with the temporal changes.
Do Studies on Cortical Plasticity Provide a Rationale for Using Non-Invasive Brain Stimulation as a Treatment for Parkinson’s Disease Patients?

PubMed Central

Koch, Giacomo

2013-01-01

Animal models of Parkinson’s disease (PD) have shown that key mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD) can be impaired by the PD pathology. In humans protocols of non-invasive brain stimulation, such as paired associative stimulation (PAS) and theta-burst stimulation (TBS), can be used to investigate cortical plasticity of the primary motor cortex. Through the amplitude of the motor evoked potential these transcranial magnetic stimulation methods allow to measure both LTP-like and LTD-like mechanisms of cortical plasticity. So far these protocols have reported some controversial findings when tested in PD patients. While various studies described evidence for reduced LTP- and LTD-like plasticity, others showed different results, demonstrating increased LTP-like and normal LTD-like plasticity. Recent evidence provided support to the hypothesis that these different patterns of cortical plasticity likely depend on the stage of the disease and on the concomitant administration of l-DOPA. However, it is still unclear how and if these altered mechanisms of cortical plasticity can be taken as a reliable model to build appropriate protocols aimed at treating PD symptoms by applying repetitive sessions of repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS). The current article will provide an up-to-date overview of these issues together with some reflections on future studies in the field. PMID:24223573
Time-dependent Increase in the Network Response to the Stimulation of Neuronal Cell Cultures on Micro-electrode Arrays.

PubMed

Gertz, Monica L; Baker, Zachary; Jose, Sharon; Peixoto, Nathalia

2017-05-29

Micro-electrode arrays (MEAs) can be used to investigate drug toxicity, design paradigms for next-generation personalized medicine, and study network dynamics in neuronal cultures. In contrast with more traditional methods, such as patch-clamping, which can only record activity from a single cell, MEAs can record simultaneously from multiple sites in a network, without requiring the arduous task of placing each electrode individually. Moreover, numerous control and stimulation configurations can be easily applied within the same experimental setup, allowing for a broad range of dynamics to be explored. One of the key dynamics of interest in these in vitro studies has been the extent to which cultured networks display properties indicative of learning. Mouse neuronal cells cultured on MEAs display an increase in response following training induced by electrical stimulation. This protocol demonstrates how to culture neuronal cells on MEAs; successfully record from over 95% of the plated dishes; establish a protocol to train the networks to respond to patterns of stimulation; and sort, plot, and interpret the results from such experiments. The use of a proprietary system for stimulating and recording neuronal cultures is demonstrated. Software packages are also used to sort neuronal units. A custom-designed graphical user interface is used to visualize post-stimulus time histograms, inter-burst intervals, and burst duration, as well as to compare the cellular response to stimulation before and after a training protocol. Finally, representative results and future directions of this research effort are discussed.
Is the flexible GnRH antagonist protocol better suited for fresh eSET cycles?

PubMed

Dahdouh, Elias M; Gomes, Francisco L A F; Granger, Louis; Carranza-Mamane, Belina; Faruqi, Faez; Kattygnarath, Tiao-Virirak; St-Michel, Pierre

2014-10-01

This study was performed to evaluate the efficacy of the flexible GnRH antagonist protocol in comparison with the long GnRH agonist protocol in elective single embryo transfer (eSET) practice. It was conducted in a publicly funded in vitro fertilization program. We performed a prospective cohort analysis of data from a private infertility clinic from August 2010 to August 2011. Three hundred fourteen women with normal ovarian reserve and undergoing fresh eSET cycles were included. Sixty-four women underwent follicular stimulation using a flexible GnRH antagonist protocol, and 250 underwent stimulation with a standard long mid-luteal GnRH agonist protocol. Implantation rates (35.9% in the GnRH antagonist group and 29.6% in the GnRH agonist group, P = 0.5) and ongoing pregnancy rates (32.8% in the GnRH antagonist group and 28.8% in the GnRH agonist group, P = 0.5) were equivalent in both groups. The duration of stimulation (9.8 ± 2 days vs. 10.7 ± 1.8 days, P < 0.001) and total FSH dose required (2044 vs. 2775 IU, P < 0.001) were lower in the GnRH antagonist group than in the GnRH agonist group. The number of mature oocytes (6.0 vs. 10.0, P < 0. 001) and number of embryos (5.0 vs. 7.0, P < 0.001) were also lower in GnRH antagonist group. However, the number of embryos cryopreserved was similar in both groups (median 2.0, P = 0.3). In women undergoing in vitro fertilization, the flexible GnRH antagonist protocol yields implantation and ongoing pregnancy rates that are similar to the long GnRH agonist protocol, and requires lower doses of gonadotropins and a shorter duration of treatment. The flexible GnRH antagonist protocol appears to be the protocol of choice for an eSET IVF program.
The inert doublet model in the light of Fermi-LAT gamma-ray data: a global fit analysis

NASA Astrophysics Data System (ADS)

Eiteneuer, Benedikt; Goudelis, Andreas; Heisig, Jan

2017-09-01

We perform a global fit within the inert doublet model taking into account experimental observables from colliders, direct and indirect dark matter searches and theoretical constraints. In particular, we consider recent results from searches for dark matter annihilation-induced gamma-rays in dwarf spheroidal galaxies and relax the assumption that the inert doublet model should account for the entire dark matter in the Universe. We, moreover, study in how far the model is compatible with a possible dark matter explanation of the so-called Galactic center excess. We find two distinct parameter space regions that are consistent with existing constraints and can simultaneously explain the excess: One with dark matter masses near the Higgs resonance and one around 72 GeV where dark matter annihilates predominantly into pairs of virtual electroweak gauge bosons via the four-vertex arising from the inert doublet's kinetic term. We briefly discuss future prospects to probe these scenarios.
Doublet-spacing enhancement caused by {Lambda}N-{Sigma}N coupling in {sub {Lambda}L}i hypernuclear isotopes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Umeya, Atsushi; Harada, Toru; Research Center for Physics and Mathematics, Osaka Electro-Communication University, Neyagawa, Osaka 572-8530

2011-03-15

We theoretically investigate energy spacings of doublets in {sub {Lambda}L}i hypernuclear isotopes with A=7-10 in shell-model calculations with a {Lambda}N-{Sigma}N coupling effect. The calculated results show that the energy shifts are {Delta}{epsilon}=0.09-0.28 MeV and the {Sigma}-mixing probabilities are P{sub {Sigma}}=0.10%-0.34% in {Lambda} ground states for the isotopes because of the {Lambda}N-{Sigma}N coupling in the first-order perturbation. It is found that the energy spacing of the doublet is enhanced as a neutron number N increases; the contribution of the {Lambda}N-{Sigma}N coupling interaction is comparable to that of the {Lambda}N interaction in the neutron-rich {Lambda} hypernuclei. The coherent mechanism of this doublet-spacingmore » enhancement is also discussed in terms of Fermi-type and Gamow-Teller-type {Lambda}N-{Sigma}N couplings.« less
Spin-Rotation Hyperfine Splittings at Moderate to High J Values in Methanol

NASA Astrophysics Data System (ADS)

Xu, Li-Hong; Hougen, Jon T.; Belov, Sergey; Golubiatnikov, G. Yu; Lapinov, Alexander; Ilyushin, V.; Alekseev, E. A.; Mescheryakov, A. A.

2015-06-01

In this talk we present a possible explanation, based on torsionally mediated proton-spin-overall-rotation interaction operators, for the surprising observation in Nizhny Novgorod several years ago of doublets in some Lamb-dip sub-millimeter-wave transitions between torsion-rotation states of E symmetry in methanol. These observed doublet splittings, some as large as 70 kHz, were later confirmed by independent Lamb-dip measurements in Kharkov. In this talk we first show the observed J-dependence of the doublet splittings for two b-type Q branches (one from each laboratory), and then focus on our theoretical explanation. The latter involves three topics: (i) group theoretically allowed terms in the spin-rotation Hamiltonian, (ii) matrix elements of these terms between the degenerate components of torsion-rotation E states, calculated using wavefunctions from an earlier global fit of torsion-rotation transitions of methanol in the vt = 0, 1, and 2 states, and (iii) least-squares fits of coefficients of these terms to about 35 experimentally resolved doublet splittings in the quantum number ranges of K = -2 to +2, J = 13 to 34, and vt = 0. Rather pleasing residuals are obtained for these doublet splittings, and a number of narrow transitions, in which no doublet splitting could be detected, are also in agreement with predictions from the theory. Some remaining disagreements between experiment and the present theoretical explanation will be mentioned. G. Yu. Golubiatnikov, S. P. Belov, A. V. Lapinov, "CH_3OH Sub-Doppler Spectroscopy," (Paper MF04) and S.P. Belov, A.V. Burenin, G.Yu. Golubiatnikov, A.V. Lapinov, "What is the Nature of the Doublets in the E-Methanol Lamb-dip Spectra?" (Paper FB07), 68th International Symposium on Molecular Spectroscopy, Columbus, Ohio, June 2013. Li-Hong Xu, J. Fisher, R.M. Lees, H.Y. Shi, J.T. Hougen, J.C. Pearson, B.J. Drouin, G.A. Blake, R. Braakman, "Torsion-Rotation Global Analysis of the First Three Torsional States (vt = 0, 1, 2) and Terahertz Database for Methanol," J. Mol. Spectrosc., 251, 305-313, (2008).
Assessing viability of extracorporeal preserved muscle transplants using external field stimulation: a novel tool to improve methods prolonging bridge-to-transplantation time

PubMed Central

Taeger, Christian D.; Friedrich, Oliver; Dragu, Adrian; Weigand, Annika; Hobe, Frieder; Drechsler, Caroline; Geppert, Carol I.; Arkudas, Andreas; Münch, Frank; Buchholz, Rainer; Pollmann, Charlotte; Schramm, Axel; Birkholz, Torsten; Horch, Raymund E.; Präbst, Konstantin

2015-01-01

Preventing ischemia-related cell damage is a priority when preserving tissue for transplantation. Perfusion protocols have been established for a variety of applications and proven to be superior to procedures used in clinical routine. Extracorporeal perfusion of muscle tissue though cumbersome is highly desirable since it is highly susceptible to ischemia-related damage. To show the efficacy of different perfusion protocols external field stimulation can be used to immediately visualize improvement or deterioration of the tissue during active and running perfusion protocols. This method has been used to show the superiority of extracorporeal perfusion using porcine rectus abdominis muscles perfused with heparinized saline solution. Perfused muscles showed statistically significant higher ability to exert force compared to nonperfused ones. These findings can be confirmed using Annexin V as marker for cell damage, perfusion of muscle tissue limits damage significantly compared to nonperfused tissue. The combination of extracorporeal perfusion and external field stimulation may improve organ conservation research. PMID:26145230
Cardiac autonomic responses induced by mental tasks and the influence of musical auditory stimulation.

PubMed

Barbosa, Juliana Cristina; Guida, Heraldo L; Fontes, Anne M G; Antonio, Ana M S; de Abreu, Luiz Carlos; Barnabé, Viviani; Marcomini, Renata S; Vanderlei, Luiz Carlos M; da Silva, Meire L; Valenti, Vitor E

2014-08-01

We investigated the acute effects of musical auditory stimulation on cardiac autonomic responses to a mental task in 28 healthy men (18-22 years old). In the control protocol (no music), the volunteers remained at seated rest for 10 min and the test was applied for five minutes. After the end of test the subjects remained seated for five more minutes. In the music protocol, the volunteers remained at seated rest for 10 min, then were exposed to music for 10 min; the test was then applied over five minutes, and the subjects remained seated for five more minutes after the test. In the control and music protocols the time domain and frequency domain indices of heart rate variability remained unchanged before, during and after the test. We found that musical auditory stimulation with baroque music did not influence cardiac autonomic responses to the mental task. Copyright © 2014 Elsevier Ltd. All rights reserved.
Corifollitropin alfa compared to daily rFSH or HP-HMG in GnRH antagonist controlled ovarian stimulation protocol for patients undergoing assisted reproduction.

PubMed

Souza, Priscila Morais Galvão; Carvalho, Bruno Ramalho de; Nakagawa, Hitomi Miura; Rassi, Thalita Reis Esselin; Barbosa, Antônio César Paes; Silva, Adelino Amaral

2017-06-01

This study aimed to compare the outcomes of controlled ovarian stimulation (COS) with corifollitropin alfa versus daily recombinant follicle-stimulating hormone (rRFSH) or highly purified human menopausal gonadotropin (HP-HMG) in patients undergoing in vitro fertilization (IVF) cycles based on gonadotropin-releasing hormone (GnRH) antagonist protocols. The primary endpoints were total number of oocytes and mature oocytes. This retrospective study looked into 132 controlled ovarian stimulation cycles from IVF or oocyte cryopreservation performed in a private human reproduction center between January 1 and December 31, 2014. Enrollment criteria: women aged < 40 years submitted to COS with corifollitropin alfa 100µg or 150µg (n = 26) and rFSH or HP-HMG in the first seven days of treatment with daily doses of 150-225 IU (n = 106); all subjects were on GnRH antagonist protocols. The groups had similar mean ages and duration of stimulation. The mean number ± standard deviation of total aspirated oocytes and MII oocytes was 11.9±10 and 10.3±7.9 in the corifollitropin alfa group, and 10.9±7.2 and 8.6±5.7 in the group on rFSH or HMG (p>0.05). There were no significant differences in fertilization (76.9% vs. 76.8%, p=1.0), biochemical pregnancy (66.7% vs. 47.2%, p=0.1561) or embryo implantation rates (68.7% vs. 50%, p=0.2588) between the groups using corifollitropin alfa and rFSH or HMG, respectively. Corifollitropin alfa seems to be as effective as rFSH or HP-HMG when used in the first seven days of ovulation induction for patients undergoing assisted reproduction in GnRH antagonist protocols.
Method and system for detecting an explosive

DOEpatents

Reber, Edward L.; Rohde, Kenneth W.; Blackwood, Larry G.

2010-12-07

A method and system for detecting at least one explosive in a vehicle using a neutron generator and a plurality of NaI detectors. Spectra read from the detectors is calibrated by performing Gaussian peak fitting to define peak regions, locating a Na peak and an annihilation peak doublet, assigning a predetermined energy level to one peak in the doublet, and predicting a hydrogen peak location based on a location of at least one peak of the doublet. The spectra are gain shifted to a common calibration, summed for respective groups of NaI detectors, and nitrogen detection analysis performed on the summed spectra for each group.
Development of a neuromuscular electrical stimulation protocol for sprint training.

PubMed

Russ, David W; Clark, Brian C; Krause, Jodi; Hagerman, Fredrick C

2012-09-01

Sprint training is associated with several beneficial adaptations in skeletal muscle, including an enhancement of sarcoplasmic reticulum (SR) Ca(2+) release. Unfortunately, several patient populations (e.g., the elderly, those with cardiac dysfunction) that might derive great benefit from sprint exercise are unlikely to tolerate it. The purpose of this report was to describe the development of a tolerable neuromuscular electrical stimulation (NMES) protocol that induces skeletal muscle adaptations similar to those observed with sprint training. Our NMES protocol was modeled after a published sprint exercise protocol and used a novel electrode configuration and stimulation sequence to provide adequate training stimulus while maintaining subject tolerance. Nine young, healthy subjects (four men) began and completed the training protocol of the knee extensor muscles. All subjects completed the protocol, with ratings of discomfort far less than those reported in studies of traditional NMES. Training induced significant increases in SR Ca(2+) release and citrate synthase activity (~16% and 32%, respectively), but SR Ca(2+) uptake did not change. The percentage of myosin heavy chain IIx isoform was decreased significantly after training. At the whole muscle level, neither central activation nor maximum voluntary isometric contraction force were significantly altered, although isometric force did exhibit a trend toward an increase (~3%, P = 0.055). Surprisingly, the NMES training produced a significant increase in muscle cross-sectional area (~3%, P = 0.04). It seems that an appropriately designed NMES protocol can mimic many of the benefits of sprint exercise training, with a low overall time commitment and training volume. These findings suggest that NMES has the potential to bring the benefits of sprint exercise to individuals who are unable to tolerate traditional sprint training.
Creating experimental color harmony map

NASA Astrophysics Data System (ADS)

Chamaret, Christel; Urban, Fabrice; Lepinel, Josselin

2014-02-01

Starting in the 17th century with Newton, color harmony is a topic that did not reach a consensus on definition, representation or modeling so far. Previous work highlighted specific characteristics for color harmony on com- bination of color doublets or triplets by means of a human rating on a harmony scale. However, there were no investigation involving complex stimuli or pointing out how harmony is spatially located within a picture. The modeling of such concept as well as a reliable ground-truth would be of high value for the community, since the applications are wide and concern several communities: from psychology to computer graphics. We propose a protocol for creating color harmony maps from a controlled experiment. Through an eye-tracking protocol, we focus on the identification of disharmonious colors in pictures. The experiment was composed of a free viewing pass in order to let the observer be familiar with the content before a second pass where we asked "to search for the most disharmonious areas in the picture". Twenty-seven observers participated to the experiments that was composed of a total of 30 different stimuli. The high inter-observer agreement as well as a cross-validation confirm the validity of the proposed ground-truth.
How to personalize ovarian stimulation in clinical practice.

PubMed

Sighinolfi, Giovanna; Grisendi, Valentina; La Marca, Antonio

2017-09-01

Controlled ovarian stimulation (COS) in in vitro fertilization (IVF) cycles is the starting point from which couple's prognosis depends. Individualization in follicle-stimulating hormone (FSH) starting dose and protocol used is based on ovarian response prediction, which depends on ovarian reserve. Anti-Müllerian hormone levels and the antral follicle count are considered the most accurate and reliable markers of ovarian reserve. A literature search was performed for studies that addressed the ability of ovarian reserve markers to predict poor and high ovarian response in assisted reproductive technology cycles. According to the predicted response to ovarian stimulation (poor- normal- or high- response), it is possible to counsel couples before treatment about the prognosis, and also to individualize ovarian stimulation protocols, choosing among GnRH-agonists or antagonists for endogenous FSH suppression, and the FSH starting dose in order to decrease the risk of cycle cancellation and ovarian hyperstimulation syndrome. In this review we discuss how to choose the best COS therapy, based on ovarian reserve markers, in order to enhance chances in IVF.
Can a single pulse transcranial magnetic stimulation targeted to the motor cortex interrupt pain processing?

PubMed Central

Kisler, Lee-Bareket; Gurion, Ilan; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone

2018-01-01

The modulatory role of the primary motor cortex (M1), reflected by an inhibitory effect of M1-stimulation on clinical pain, motivated us to deepen our understanding of M1’s role in pain modulation. We used Transcranial Magnetic Stimulation (TMS)-induced virtual lesion (VL) to interrupt with M1 activity during noxious heat pain. We hypothesized that TMS-VL will effect experimental pain ratings. Three VL protocols were applied consisting of single-pulse TMS to transiently interfere with right M1 activity: (1) VLM1- TMS applied to 11 subjects, 20 msec before the individual’s first pain-related M1 peak activation, as determined by source analysis (sLORETA), (2) VL-50 (N = 16; TMS applied 50 ms prior to noxious stimulus onset), and (3) VL+150 (N = 16; TMS applied 150 ms after noxious stimulus onset). Each protocol included 3 conditions ('pain-alone', ' TMS-VL', and ‘SHAM-VL’), each consisted of 30 noxious heat stimuli. Pain ratings were compared, in each protocol, for TMS-VL vs. SHAM-VL and vs. pain-alone conditions. Repeated measures analysis of variance, corrected for multiple comparisons revealed no significant differences in the pain ratings between the different conditions within each protocol. Therefore, our results from this exploratory study suggest that a single pulse TMS-induced VL that is targeted to M1 failed to interrupt experimental pain processing in the specific three stimulation timing examined here. PMID:29630681
Can a single pulse transcranial magnetic stimulation targeted to the motor cortex interrupt pain processing?

PubMed

Kisler, Lee-Bareket; Gurion, Ilan; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone; Weissman-Fogel, Irit

2018-01-01

The modulatory role of the primary motor cortex (M1), reflected by an inhibitory effect of M1-stimulation on clinical pain, motivated us to deepen our understanding of M1's role in pain modulation. We used Transcranial Magnetic Stimulation (TMS)-induced virtual lesion (VL) to interrupt with M1 activity during noxious heat pain. We hypothesized that TMS-VL will effect experimental pain ratings. Three VL protocols were applied consisting of single-pulse TMS to transiently interfere with right M1 activity: (1) VLM1- TMS applied to 11 subjects, 20 msec before the individual's first pain-related M1 peak activation, as determined by source analysis (sLORETA), (2) VL-50 (N = 16; TMS applied 50 ms prior to noxious stimulus onset), and (3) VL+150 (N = 16; TMS applied 150 ms after noxious stimulus onset). Each protocol included 3 conditions ('pain-alone', ' TMS-VL', and 'SHAM-VL'), each consisted of 30 noxious heat stimuli. Pain ratings were compared, in each protocol, for TMS-VL vs. SHAM-VL and vs. pain-alone conditions. Repeated measures analysis of variance, corrected for multiple comparisons revealed no significant differences in the pain ratings between the different conditions within each protocol. Therefore, our results from this exploratory study suggest that a single pulse TMS-induced VL that is targeted to M1 failed to interrupt experimental pain processing in the specific three stimulation timing examined here.
Darbepoetin alfa therapeutic interchange protocol for anemia in dialysis.

PubMed

Brophy, Donald F; Ripley, Elizabeth Bd; Kockler, Denise R; Lee, Seina; Proeschel, Lori A

2005-11-01

Erythropoiesis-stimulating proteins, such as erythropoietin alfa and darbepoetin alfa, have positively impacted anemia management. These medications improve patient outcomes and quality of life. Their costs, however, remain a major barrier for health systems. To evaluate the development, implementation, and cost-effectiveness of an inpatient therapeutic interchange protocol for erythropoiesis-stimulating proteins at a large, tertiary care, university-affiliated health system. Virginia Commonwealth University Health System (VCUHS) developed and implemented a therapeutic interchange program to convert therapy for all inpatients undergoing dialysis from erythropoietin alfa to darbepoetin alfa for treatment of chronic kidney disease-related anemia. An evaluation of the economic impact of this program on drug expenditures over a fiscal quarter (2003) was conducted using historical comparator data (2002). Preliminary evaluation of the program demonstrated cost-savings and reduced drug utilization of erythropoiesis-stimulating proteins in hospitalized dialysis patients. For the first quarter of 2003 compared with the first quarter of 2002, VCUHS realized a cost-savings of nearly 10,000 US dollars, which was related to the program's aggressive screening procedure. When these data were normalized for equal numbers of patients in each group receiving one of the drugs, the actual cost-savings was over 2000 US dollars. These cost-savings are largely due to reduced utilization of these expensive biotechnology products with implementation of a dosing protocol. VCUHS has successfully developed and implemented a darbepoetin alfa therapeutic interchange protocol for hospitalized dialysis patients. This has translated into reduced use of erythropoiesis-stimulating proteins, resulting in cost-savings for the health system.

Cross-coupling effects in circuit-QED stimulated Raman adiabatic passage

NASA Astrophysics Data System (ADS)

Vepsäläinen, A.; Paraoanu, G. S.

2018-03-01

Stimulated Raman adiabatic passage is a quantum protocol that can be used for robust state preparation in a three-level system. It has been commonly employed in quantum optics, but recently this technique has drawn attention also in circuit quantum electrodynamics. The protocol relies on two slowly varying drive pulses that couple the initial and the target state via an intermediate state, which remains unpopulated. Here we study the detrimental effect of the parasitic couplings of the drives into transitions other than those required by the protocol. The effect is most prominent in systems with almost harmonic energy level structure, such as the transmon. We show that under these conditions in the presence of decoherence there exists an optimal STIRAP amplitude for population transfer.
Long-Term Functional Side-Effects of Stimulants and Sedatives in Drosophila melanogaster

PubMed Central

Matsagas, Kennedy; Lim, David B.; Horwitz, Marc; Rizza, Cristina L.; Mueller, Laurence D.; Villeponteau, Bryant; Rose, Michael R.

2009-01-01

Background Small invertebrate animals, such as nematodes and fruit flies, are increasingly being used to test candidate drugs both for specific therapeutic purposes and for long-term health effects. Some of the protocols used in these experiments feature such experimental design features as lifelong virginity and very low densities. By contrast, the ability of both fruit flies and nematodes to resist stress is frequently correlated with their longevity and other functional measures, suggesting that low-stress assays are not necessarily the only useful protocol for testing the long-term effects of drugs. Methodology/Principal Findings Here we report an alternative protocol for fruit fly drug-testing that maximizes reproductive opportunities and other types of interaction, with moderately high population densities. We validate this protocol using two types of experimental tests: 1. We show that this protocol detects previously well-established genetic differences between outbred fruit fly populations. 2. We show that this protocol is able to distinguish among the long-term effects of similar types of drugs within two broad categories, stimulants and tranquilizers. Conclusions Large-scale fly drug testing can be conducted using mixed-sex high-density cage assays. We find that the commonly-used stimulants caffeine and theobromine differ dramatically in their chronic functional effects, theobromine being more benign. Likewise, we find that two generic pharmaceutical tranquilizers, lithium carbonate and valproic acid, differ dramatically in their chronic effects, lithium being more benign. However, these findings do not necessarily apply to human subjects, and we thus do not recommend the use of any one substance over any other. PMID:19668379
Can Bronchoscopic Airway Anatomy Be an Indicator of Autism?

ERIC Educational Resources Information Center

Stewart, Barbara A.; Klar, Amar J. S.

2013-01-01

Bronchoscopic evaluations revealed that some children have double branching of bronchi (designated "doublets") in the lower lungs airways, rather than normal, single branching. Retrospective analyses revealed only one commonality in them: all subjects with doublets also had autism or autism spectrum disorder (ASD). That is, 49 subjects exhibited…
Adaptive change in electrically stimulated muscle: a framework for the design of clinical protocols.

PubMed

Salmons, Stanley

2009-12-01

Adult mammalian skeletal muscles have a remarkable capacity for adapting to increased use. Although this behavior is familiar from the changes brought about by endurance exercise, it is seen to a much greater extent in the response to long-term neuromuscular stimulation. The associated phenomena include a markedly increased resistance to fatigue, and this is the key to several clinical applications. However, a more rational basis is needed for designing regimes of stimulation that are conducive to an optimal outcome. In this review I examine relevant factors, such as the amount, frequency, and duty cycle of stimulation, the influence of force generation, and the animal model. From these considerations a framework emerges for the design of protocols that yield an overall functional profile appropriate to the application. Three contrasting examples illustrate the issues that need to be addressed clinically.
High frequency repetitive sensory stimulation improves temporal discrimination in healthy subjects.

PubMed

Erro, Roberto; Rocchi, Lorenzo; Antelmi, Elena; Palladino, Raffaele; Tinazzi, Michele; Rothwell, John; Bhatia, Kailash P

2016-01-01

High frequency electrical stimulation of an area of skin on a finger improves two-point spatial discrimination in the stimulated area, likely depending on plastic changes in the somatosensory cortex. However, it is unknown whether improvement also applies to temporal discrimination. Twelve young and ten elderly volunteers underwent the stimulation protocol onto the palmar skin of the right index finger. Somatosensory temporal discrimination threshold (STDT) was evaluated before and immediately after stimulation as well as 2.5h and 24h later. There was a significant reduction in somatosensory temporal threshold only on the stimulated finger. The effect was reversible, with STDT returning to the baseline values within 24h, and was smaller in the elderly than in the young participants. High frequency stimulation of the skin focally improves temporal discrimination in the area of stimulation. Given previous suggestions that the perceptual effects rely on plastic changes in the somatosensory cortex, our results are consistent with the idea that the timing of sensory stimuli is, at least partially, encoded in the primary somatosensory cortex. Such a protocol could potentially be used as a therapeutic intervention to ameliorate physiological decline in the elderly or in other disorders of sensorimotor integration. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Real-time intraoperative monitoring of brainstem auditory evoked potentials during microvascular decompression for hemifacial spasm.

PubMed

Joo, Byung-Euk; Park, Sang-Ku; Cho, Kyung-Rae; Kong, Doo-Sik; Seo, Dae-Won; Park, Kwan

2016-11-01

OBJECTIVE The aim of this study was to define a new protocol for intraoperative monitoring (IOM) of brainstem auditory evoked potentials (BAEPs) during microvascular decompression (MVD) surgery to treat hemifacial spasm (HFS) and to evaluate the usefulness of this new protocol to prevent hearing impairment. METHODS To define the optimal stimulation rate, estimate the number of trials to be averaged, and identify useful warning criteria in IOM of BAEPs, the authors performed a preliminary study of 13 patients with HFS in 2010. They increased the stimulation rate from 10.1 Hz/sec to 100.1 Hz/sec by 10-Hz increments, and they elevated the average time from 100 times to 1000 times by 100-unit increments at a fixed stimulus rate of 43.9 Hz. After defining the optimal stimulation rate and the number of trials that needed to be averaged for IOM of BAEPs, they also identified the useful warning criteria for this protocol for MVD surgery. From January to December 2013, 254 patients with HFS underwent MVD surgery following the new IOM of BAEPs protocol. Pure-tone audiometry and speech discrimination scoring were performed before surgery and 1 week after surgery. To evaluate the usefulness of the new protocol, the authors compared the incidence of postoperative hearing impairment with the results from the group that underwent MVD surgery prior to the new protocol. RESULTS Through a preliminary study, the authors confirmed that it was possible to obtain a reliable wave when using a stimulation rate of 43.9 Hz/sec and averaging 400 trials. Only a Wave V amplitude loss > 50% was useful as a warning criterion when using the new protocol. A reliable BAEP could be obtained in approximately 9.1 seconds. When the new protocol was used, 2 patients (0.8%) showed no recovery of Wave V amplitude loss > 50%, and only 1 of those 2 patients (0.39%) ultimately had postoperative hearing impairment. When compared with the outcomes in the pre-protocol group, hearing impairment incidence decreased significantly among patients who underwent surgery with the new protocol (0.39% vs 4.02%, p = 0.002). There were no significant differences between the 2 surgery groups regarding other complications, including facial palsy, sixth cranial nerve palsy, and vocal cord palsy. CONCLUSIONS There was a significant decrease in postoperative hearing impairment after MVD for HFS when the new protocol for IOM of BAEPs was used. Real-time IOM of BAEPs, which can obtain a reliable BAEP in less than 10 seconds, is a successful new procedure for preventing hearing impairment during MVD surgery for HFS.
Neutral sphingomyelinase-3 mediates TNF-stimulated oxidant activity in skeletal muscle.

PubMed

Moylan, Jennifer S; Smith, Jeffrey D; Wolf Horrell, Erin M; McLean, Julie B; Deevska, Gergana M; Bonnell, Mark R; Nikolova-Karakashian, Mariana N; Reid, Michael B

2014-01-01

Sphingolipid and oxidant signaling affect glucose uptake, atrophy, and force production of skeletal muscle similarly and both are stimulated by tumor necrosis factor (TNF), suggesting a connection between systems. Sphingolipid signaling is initiated by neutral sphingomyelinase (nSMase), a family of agonist-activated effector enzymes. Northern blot analyses suggest that nSMase3 may be a striated muscle-specific nSMase. The present study tested the hypothesis that nSMase3 protein is expressed in skeletal muscle and functions to regulate TNF-stimulated oxidant production. We demonstrate constitutive nSMase activity in skeletal muscles of healthy mice and humans and in differentiated C2C12 myotubes. nSMase3 (Smpd4 gene) mRNA is highly expressed in muscle. An nSMase3 protein doublet (88 and 85 kD) is derived from alternative mRNA splicing of exon 11. The proteins partition differently. The full-length 88 kD isoform (nSMase3a) fractionates with membrane proteins that are resistant to detergent extraction; the 85 kD isoform lacking exon 11 (nSMase3b) is more readily extracted and fractionates with detergent soluble membrane proteins; neither variant is detected in the cytosol. By immunofluorescence microscopy, nSMase3 resides in both internal and sarcolemmal membranes. Finally, myotube nSMase activity and cytosolic oxidant activity are stimulated by TNF. Both if these responses are inhibited by nSMase3 knockdown. These findings identify nSMase3 as an intermediate that links TNF receptor activation, sphingolipid signaling, and skeletal muscle oxidant production. Our data show that nSMase3 acts as a signaling nSMase in skeletal muscle that is essential for TNF-stimulated oxidant activity.
Stimulated Raman signals at conical intersections: Ab initio surface hopping simulation protocol with direct propagation of the nuclear wave function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kowalewski, Markus, E-mail: mkowalew@uci.edu; Mukamel, Shaul, E-mail: smukamel@uci.edu

2015-07-28

Femtosecond Stimulated Raman Spectroscopy (FSRS) signals that monitor the excited state conical intersections dynamics of acrolein are simulated. An effective time dependent Hamiltonian for two C—H vibrational marker bands is constructed on the fly using a local mode expansion combined with a semi-classical surface hopping simulation protocol. The signals are obtained by a direct forward and backward propagation of the vibrational wave function on a numerical grid. Earlier work is extended to fully incorporate the anharmonicities and intermode couplings.
Effects of transcranial direct current stimulation for treating depression: A modeling study.

PubMed

Csifcsák, Gábor; Boayue, Nya Mehnwolo; Puonti, Oula; Thielscher, Axel; Mittner, Matthias

2018-07-01

Transcranial direct current stimulation (tDCS) above the left dorsolateral prefrontal cortex (lDLPFC) has been widely used to improve symptoms of major depressive disorder (MDD). However, the effects of different stimulation protocols in the entire frontal lobe have not been investigated in a large sample including patient data. We used 38 head models created from structural magnetic resonance imaging data of 19 healthy adults and 19 MDD patients and applied computational modeling to simulate the spatial distribution of tDCS-induced electric fields (EFs) in 20 frontal regions. We evaluated effects of seven bipolar and two multi-electrode 4 × 1 tDCS protocols. For bipolar montages, EFs were of comparable strength in the lDLPFC and in the medial prefrontal cortex (MPFC). Depending on stimulation parameters, EF cortical maps varied to a considerable degree, but were found to be similar in controls and patients. 4 × 1 montages produced more localized, albeit weaker effects. White matter anisotropy was not modeled. The relationship between EF strength and clinical response to tDCS could not be evaluated. In addition to lDLPFC stimulation, excitability changes in the MPFC should also be considered as a potential mechanism underlying clinical efficacy of bipolar montages. MDD-associated anatomical variations are not likely to substantially influence current flow. Individual modeling of tDCS protocols can substantially improve cortical targeting. We make recommendations for future research to explicitly test the contribution of lDLPFC vs. MPFC stimulation to therapeutic outcomes of tDCS in this disorder. Copyright © 2018 Elsevier B.V. All rights reserved.
Effects of Maternal Stimulant Medication on Observed Parenting in Mother-Child Dyads with Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Chronis-Tuscano, Andrea; Rooney, Mary; Seymour, Karen E.; Lavin, Heather Jones; Pian, Jessica; Robb, Adelaide; Efron, Lisa; Conlon, Charles; Stein, Mark A.

2010-01-01

This pilot study of 23 mothers with attention-deficit/hyperactivity disorder (ADHD) and their offspring with ADHD examined the effects of maternal stimulant medication on observed interactions. Parent-child interactions were observed using a structured protocol before and after mothers underwent a 5-week, double-blind stimulant titration. Despite…
Modeling of heat extraction from variably fractured porous media in Enhanced Geothermal Systems

DOE PAGES

Hadgu, Teklu; Kalinina, Elena Arkadievna; Lowry, Thomas Stephen

2016-01-30

Modeling of heat extraction in Enhanced Geothermal Systems is presented. The study builds on recent studies on the use of directional wells to improve heat transfer between doublet injection and production wells. The current study focuses on the influence of fracture orientation on production temperature in deep low permeability geothermal systems, and the effects of directional drilling and separation distance between boreholes on heat extraction. The modeling results indicate that fracture orientation with respect to the well-pair plane has significant influence on reservoir thermal drawdown. As a result, the vertical well doublet is impacted significantly more than the horizontal wellmore » doublet« less
Exchange interactions in two-state systems: rare earth pyrochlores.

PubMed

Curnoe, S H

2018-06-13

The general form of the nearest neighbour exchange interaction for rare earth pyrochlores is derived based on symmetry. Generally, the rare earth angular momentum degeneracy is lifted by the crystal electric field (CEF) into singlets and doublets. When the CEF ground state is a doublet that is well-separated from the first excited state the CEF ground state doublet can be treated as a pseudo-spin of some kind. The general form of the nearest neighbour exchange interaction for pseudo-spins on the pyrochlore lattice is derived for three different types of pseudo-spins. The methodology presented in this paper can be applied to other two-state spin systems with a high space group symmetry.
Exchange interactions in two-state systems: rare earth pyrochlores

NASA Astrophysics Data System (ADS)

Curnoe, S. H.

2018-06-01

The general form of the nearest neighbour exchange interaction for rare earth pyrochlores is derived based on symmetry. Generally, the rare earth angular momentum degeneracy is lifted by the crystal electric field (CEF) into singlets and doublets. When the CEF ground state is a doublet that is well-separated from the first excited state the CEF ground state doublet can be treated as a pseudo-spin of some kind. The general form of the nearest neighbour exchange interaction for pseudo-spins on the pyrochlore lattice is derived for three different types of pseudo-spins. The methodology presented in this paper can be applied to other two-state spin systems with a high space group symmetry.
Modulation of Total Sleep Time by Transcranial Direct Current Stimulation (tDCS).

PubMed

Frase, Lukas; Piosczyk, Hannah; Zittel, Sulamith; Jahn, Friederike; Selhausen, Peter; Krone, Lukas; Feige, Bernd; Mainberger, Florian; Maier, Jonathan G; Kuhn, Marion; Klöppel, Stefan; Normann, Claus; Sterr, Annette; Spiegelhalder, Kai; Riemann, Dieter; Nitsche, Michael A; Nissen, Christoph

2016-09-01

Arousal and sleep are fundamental physiological processes, and their modulation is of high clinical significance. This study tested the hypothesis that total sleep time (TST) in humans can be modulated by the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS) targeting a 'top-down' cortico-thalamic pathway of sleep-wake regulation. Nineteen healthy participants underwent a within-subject, repeated-measures protocol across five nights in the sleep laboratory with polysomnographic monitoring (adaptation, baseline, three experimental nights). tDCS was delivered via bi-frontal target electrodes and bi-parietal return electrodes before sleep (anodal 'activation', cathodal 'deactivation', and sham stimulation). Bi-frontal anodal stimulation significantly decreased TST, compared with cathodal and sham stimulation. This effect was location specific. Bi-frontal cathodal stimulation did not significantly increase TST, potentially due to ceiling effects in good sleepers. Exploratory resting-state EEG analyses before and after the tDCS protocols were consistent with the notion of increased cortical arousal after anodal stimulation and decreased cortical arousal after cathodal stimulation. The study provides proof-of-concept that TST can be decreased by non-invasive bi-frontal anodal tDCS in healthy humans. Further elucidating the 'top-down' pathway of sleep-wake regulation is expected to increase knowledge on the fundamentals of sleep-wake regulation and to contribute to the development of novel treatments for clinical conditions of disturbed arousal and sleep.
Modulation of Total Sleep Time by Transcranial Direct Current Stimulation (tDCS)

PubMed Central

Frase, Lukas; Piosczyk, Hannah; Zittel, Sulamith; Jahn, Friederike; Selhausen, Peter; Krone, Lukas; Feige, Bernd; Mainberger, Florian; Maier, Jonathan G; Kuhn, Marion; Klöppel, Stefan; Normann, Claus; Sterr, Annette; Spiegelhalder, Kai; Riemann, Dieter; Nitsche, Michael A; Nissen, Christoph

2016-01-01

Arousal and sleep are fundamental physiological processes, and their modulation is of high clinical significance. This study tested the hypothesis that total sleep time (TST) in humans can be modulated by the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS) targeting a ‘top-down' cortico-thalamic pathway of sleep-wake regulation. Nineteen healthy participants underwent a within-subject, repeated-measures protocol across five nights in the sleep laboratory with polysomnographic monitoring (adaptation, baseline, three experimental nights). tDCS was delivered via bi-frontal target electrodes and bi-parietal return electrodes before sleep (anodal ‘activation', cathodal ‘deactivation', and sham stimulation). Bi-frontal anodal stimulation significantly decreased TST, compared with cathodal and sham stimulation. This effect was location specific. Bi-frontal cathodal stimulation did not significantly increase TST, potentially due to ceiling effects in good sleepers. Exploratory resting-state EEG analyses before and after the tDCS protocols were consistent with the notion of increased cortical arousal after anodal stimulation and decreased cortical arousal after cathodal stimulation. The study provides proof-of-concept that TST can be decreased by non-invasive bi-frontal anodal tDCS in healthy humans. Further elucidating the ‘top-down' pathway of sleep-wake regulation is expected to increase knowledge on the fundamentals of sleep-wake regulation and to contribute to the development of novel treatments for clinical conditions of disturbed arousal and sleep. PMID:27143601
Automatized set-up procedure for transcranial magnetic stimulation protocols.

PubMed

Harquel, S; Diard, J; Raffin, E; Passera, B; Dall'Igna, G; Marendaz, C; David, O; Chauvin, A

2017-06-01

Transcranial Magnetic Stimulation (TMS) established itself as a powerful technique for probing and treating the human brain. Major technological evolutions, such as neuronavigation and robotized systems, have continuously increased the spatial reliability and reproducibility of TMS, by minimizing the influence of human and experimental factors. However, there is still a lack of efficient set-up procedure, which prevents the automation of TMS protocols. For example, the set-up procedure for defining the stimulation intensity specific to each subject is classically done manually by experienced practitioners, by assessing the motor cortical excitability level over the motor hotspot (HS) of a targeted muscle. This is time-consuming and introduces experimental variability. Therefore, we developed a probabilistic Bayesian model (AutoHS) that automatically identifies the HS position. Using virtual and real experiments, we compared the efficacy of the manual and automated procedures. AutoHS appeared to be more reproducible, faster, and at least as reliable as classical manual procedures. By combining AutoHS with robotized TMS and automated motor threshold estimation methods, our approach constitutes the first fully automated set-up procedure for TMS protocols. The use of this procedure decreases inter-experimenter variability while facilitating the handling of TMS protocols used for research and clinical routine. Copyright © 2017 Elsevier Inc. All rights reserved.
Spectral features of the tunneling-induced transparency and the Autler-Townes doublet and triplet in a triple quantum dot.

PubMed

Luo, Xiao-Qing; Li, Zeng-Zhao; Jing, Jun; Xiong, Wei; Li, Tie-Fu; Yu, Ting

2018-02-15

We theoretically investigate the spectral features of tunneling-induced transparency (TIT) and Autler-Townes (AT) doublet and triplet in a triple-quantum-dot system. By analyzing the eigenenergy spectrum of the system Hamiltonian, we can discriminate TIT and double TIT from AT doublet and triplet, respectively. For the resonant case, the presence of the TIT does not exhibit distinguishable anticrossing in the eigenenergy spectrum in the weak-tunneling regime, while the occurrence of double anticrossings in the strong-tunneling regime shows that the TIT evolves to the AT doublet. For the off-resonance case, the appearance of a new detuning-dependent dip in the absorption spectrum leads to double TIT behavior in the weak-tunneling regime due to no distinguished anticrossing occurring in the eigenenergy spectrum. However, in the strong-tunneling regime, a new detuning-dependent dip in the absorption spectrum results in AT triplet owing to the presence of triple anticrossings in the eigenenergy spectrum. Our results can be applied to quantum measurement and quantum-optics devices in solid systems.
A Protocol for the Use of Remotely-Supervised Transcranial Direct Current Stimulation (tDCS) in Multiple Sclerosis (MS).

PubMed

Kasschau, Margaret; Sherman, Kathleen; Haider, Lamia; Frontario, Ariana; Shaw, Michael; Datta, Abhishek; Bikson, Marom; Charvet, Leigh

2015-12-26

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low amplitude direct currents to alter cortical excitability. With well-established safety and tolerability, tDCS has been found to have the potential to ameliorate symptoms such as depression and pain in a range of conditions as well as to enhance outcomes of cognitive and physical training. However, effects are cumulative, requiring treatments that can span weeks or months and frequent, repeated visits to the clinic. The cost in terms of time and travel is often prohibitive for many participants, and ultimately limits real-world access. Following guidelines for remote tDCS application, we propose a protocol that would allow remote (in-home) participation that uses specially-designed devices for supervised use with materials modified for patient use, and real-time monitoring through a telemedicine video conferencing platform. We have developed structured training procedures and clear, detailed instructional materials to allow for self- or proxy-administration while supervised remotely in real-time. The protocol is designed to have a series of checkpoints, addressing attendance and tolerability of the session, to be met in order to continue to the next step. The feasibility of this protocol was then piloted for clinical use in an open label study of remotely-supervised tDCS in multiple sclerosis (MS). This protocol can be widely used for clinical study of tDCS.
Previous exposure to musical auditory stimulation immediately influences the cardiac autonomic responses to the postural change maneuver in women.

PubMed

de Castro, Bianca Cr; Guida, Heraldo L; Roque, Adriano L; de Abreu, Luiz Carlos; Ferreira, Lucas L; Raimundo, Rodrigo D; Monteiro, Carlos Bm; Goulart, Flávia C; Ferreira, Celso; Marcomini, Renata S; Ribeiro, Vivian F; Ré, Alessandro Hn; Vanderlei, Luiz Carlos M; Valenti, Vitor E

2013-08-14

Chronic exposure to musical auditory stimulation has been reported to improve cardiac autonomic regulation. However, it is not clear if music acutely influences it in response to autonomic tests. We evaluated the acute effects of music on heart rate variability (HRV) responses to the postural change maneuver (PCM) in women. We evaluated 12 healthy women between 18 and 28 years old and HRV was analyzed in the time (SDNN, RMSSD, NN50 and pNN50) and frequency (LF, HF and LF/HF ratio) domains. In the control protocol, the women remained at seated rest for 10 minutes and quickly stood up within three seconds and remained standing still for 15 minutes. In the music protocol, the women remained at seated rest for 10 minutes, were exposed to music for 10 minutes and quickly stood up within three seconds and remained standing still for 15 minutes. HRV was recorded at the following time: rest, music (music protocol) 0-5, 5-10 and 10-15 min during standing. In the control protocol the SDNN, RMSSD and pNN50 indexes were reduced at 10-15 minutes after the volunteers stood up, while the LF (nu) index was increased at the same moment compared to seated rest. In the protocol with music, the indexes were not different from control but the RMSSD, pNN50 and LF (nu) were different from the music period. Musical auditory stimulation attenuates the cardiac autonomic responses to the PCM.
Reinstatement of contextual conditioned anxiety in virtual reality and the effects of transcutaneous vagus nerve stimulation in humans.

PubMed

Genheimer, Hannah; Andreatta, Marta; Asan, Esther; Pauli, Paul

2017-12-20

Since exposure therapy for anxiety disorders incorporates extinction of contextual anxiety, relapses may be due to reinstatement processes. Animal research demonstrated more stable extinction memory and less anxiety relapse due to vagus nerve stimulation (VNS). We report a valid human three-day context conditioning, extinction and return of anxiety protocol, which we used to examine effects of transcutaneous VNS (tVNS). Seventy-five healthy participants received electric stimuli (unconditioned stimuli, US) during acquisition (Day1) when guided through one virtual office (anxiety context, CTX+) but never in another (safety context, CTX-). During extinction (Day2), participants received tVNS, sham, or no stimulation and revisited both contexts without US delivery. On Day3, participants received three USs for reinstatement followed by a test phase. Successful acquisition, i.e. startle potentiation, lower valence, higher arousal, anxiety and contingency ratings in CTX+ versus CTX-, the disappearance of these effects during extinction, and successful reinstatement indicate validity of this paradigm. Interestingly, we found generalized reinstatement in startle responses and differential reinstatement in valence ratings. Altogether, our protocol serves as valid conditioning paradigm. Reinstatement effects indicate different anxiety networks underlying physiological versus verbal responses. However, tVNS did neither affect extinction nor reinstatement, which asks for validation and improvement of the stimulation protocol.

Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial.

PubMed

Desmyter, Stefanie; Duprat, Romain; Baeken, Chris; Van Autreve, Sara; Audenaert, Kurt; van Heeringen, Kees

2016-01-01

Objectives: We aimed to examine the effects and safety of accelerated intermittent Theta Burst Stimulation (iTBS) on suicide risk in a group of treatment-resistant unipolar depressed patients, using an extensive suicide assessment scale. Methods: In 50 therapy-resistant, antidepressant-free depressed patients, an intensive protocol of accelerated iTBS was applied over the left dorsolateral prefrontal cortex (DLPFC) in a randomized, sham-controlled crossover design. Patients received 20 iTBS sessions over 4 days. Suicide risk was assessed using the Beck Scale of Suicide ideation (BSI). Results: The iTBS protocol was safe and well tolerated. We observed a significant decrease of the BSI score over time, unrelated to active or sham stimulation and unrelated to depression-response. No worsening of suicidal ideation was observed. The effects of accelerated iTBS on mood and depression severity are reported in Duprat et al. (2016). The decrease in suicide risk lasted up to 1 month after baseline, even in depression non-responders. Conclusions: This accelerated iTBS protocol was safe. The observed significant decrease in suicide risk was unrelated to active or sham stimulation and unrelated to depression response. Further sham-controlled research in suicidal depressed patients is necessary. (Clinicaltrials.gov identifier: NCT01832805).
Auditory evoked potentials in the auditory system of a beluga whale Delphinapterus leucas to prolonged sound stimuli.

PubMed

Popov, Vladimir V; Sysueva, Evgenia V; Nechaev, Dmitry I; Rozhnov, Vyatcheslav V; Supin, Alexander Ya

2016-03-01

The effects of prolonged (up to 1500 s) sound stimuli (tone pip trains) on evoked potentials (the rate following response, RFR) were investigated in a beluga whale. The stimuli (rhythmic tone pips) were of frequencies of 45, 64, and 90 kHz at levels from 20 to 60 dB above threshold. Two experimental protocols were used: short- and long-duration. For the short-duration protocol, the stimuli were 500-ms-long pip trains that repeated at a rate of 0.4 trains/s. For the long-duration protocol, the stimuli were continuous pip successions lasting up to 1500 s. The RFR amplitude gradually decreased by three to seven times from 10 ms to 1500 s of stimulation. Decrease of response amplitude during stimulation was approximately proportional to initial (at the start of stimulation) response amplitude. Therefore, even for low stimulus level (down to 20 dB above the baseline threshold) the response was never suppressed completely. The RFR amplitude decay that occurred during stimulation could be satisfactorily approximated by a combination of two exponents with time constants of 30-80 ms and 3.1-17.6 s. The role of adaptation in the described effects and the impact of noise on the acoustic orientation of odontocetes are discussed.
Gauss-Legendre quadrature method used to evaluate the spatio-temporal intensity of ultrashort pulses in the focal region of lenses.

PubMed

García-Martínez, L; Rosete-Aguilar, M; Garduño-Mejia, J

2012-01-20

We analyze the spatio-temporal intensity of sub-20 femtosecond pulses with a carrier wavelength of 810 nm along the optical axis of low numerical aperture achromatic and apochromatic doublets designed in the IR region by using the scalar diffraction theory. The diffraction integral is solved by expanding the wave number around the carrier frequency of the pulse in a Taylor series up to third order, and then the integral over the frequencies is solved by using the Gauss-Legendre quadrature method. The numerical errors in this method are negligible by taking 96 nodes and the computational time is reduced by 95% compared to the integration method by rectangles. We will show that the third-order group velocity dispersion (GVD) is not negligible for 10 fs pulses at 810 nm propagating through the low numerical aperture doublets, and its effect is more important than the propagation time difference (PTD). This last effect, however, is also significant. For sub-20 femtosecond pulses, these two effects make the use of a pulse shaper necessary to correct for second and higher-order GVD terms and also the use of apochromatic optics to correct the PTD effect. The design of an apochromatic doublet is presented in this paper and the spatio-temporal intensity of the pulse at the focal region of this doublet is compared to that given by the achromatic doublet. © 2012 Optical Society of America
Inert two-Higgs-doublet model strongly coupled to a non-Abelian vector resonance

NASA Astrophysics Data System (ADS)

Rojas-Abatte, Felipe; Mora, Maria Luisa; Urbina, Jose; Zerwekh, Alfonso R.

2017-11-01

We study the possibility of a dark matter candidate having its origin in an extended Higgs sector which, at least partially, is related to a new strongly interacting sector. More concretely, we consider an i2HDM (i.e., a Type-I two Higgs doublet model supplemented with a Z2 under which the nonstandard scalar doublet is odd) based on the gauge group S U (2 )1×S U (2 )2×U (1 )Y . We assume that one of the scalar doublets and the standard fermion transform nontrivially under S U (2 )1 while the second doublet transforms under S U (2 )2. Our main hypothesis is that standard sector is weakly coupled while the gauge interactions associated to the second group is characterized by a large coupling constant. We explore the consequences of this construction for the phenomenology of the dark matter candidate and we show that the presence of the new vector resonance reduces the relic density saturation region, compared to the usual i2DHM, in the high dark matter mass range. In the collider side, we argue that the mono-Z production is the channel which offers the best chances to manifest the presence of the new vector field. We study the departures from the usual i2HDM predictions and show that the discovery of the heavy vector at the LHC is challenging even in the mono-Z channel since the typical cross sections are of the order of 10-2 fb .
Discovery and Characterization of Cadherin Domains in Saccharophagus degradans 2-40▿ †

PubMed Central

Fraiberg, Milana; Borovok, Ilya; Weiner, Ronald M.; Lamed, Raphael

2010-01-01

Saccharophagus degradans strain 2-40 is a prominent member of newly discovered group of marine and estuarine bacteria that recycle complex polysaccharides. The S. degradans 2-40 genome codes for 15 extraordinary long polypeptides, ranging from 274 to 1,600 kDa. Five of these contain at least 52 cadherin (CA) and cadherin-like (CADG) domains, the types of which were reported to bind calcium ions and mediate protein/protein interactions in metazoan systems. In order to evaluate adhesive features of these domains, recombinant CA doublet domains (two neighboring domains) from CabC (Sde_3323) and recombinant CADG doublet domains from CabD (Sde_0798) were examined qualitatively and quantitatively for homophilic and heterophilic interactions. In addition, CA and CADG doublet domains were tested for adhesion to the surface of S. degradans 2-40. Results showed obvious homophilic and heterophilic, calcium ion-dependent interactions between CA and CADG doublet domains. Likewise, CA and CADG doublet domains adhered to the S. degradans 2-40 surface of cells that were grown on xylan from birch wood or pectin, respectively, as a sole carbon source. This research shows for the first time that bacterial cadherin homophilic and heterophilic interactions may be similar in their nature to cadherin domains from metazoan lineages. We hypothesize that S. degradans 2-40 cadherin and cadherin-like multiple domains contribute to protein-protein interactions that may mediate cell-cell contact in the marine environment. PMID:20023015
THE MECHANISM OF ACTION OF COLCHICINE

PubMed Central

Wilson, Leslie; Meza, Isaura

1973-01-01

The thermal depolymerization procedure of Stephens (1970. J. Mol. Biol. 47:353) has been employed for solubilization of Strongylocentrotus purpuratus sperm tail outer doublet microtubules with the use of a buffer during solubilization which is of optimal pH and ionic strength for the preservation of colchicine binding activity of chick embryo brain tubulin. Colchicine binding values were corrected for first-order decay during heat solubilization at 50°C (t½ = 5.4 min) and incubation with colchicine at 37°C in the presence of vinblastine sulfate (t½ = 485 min). The colchicine binding properties of heat-solubilized outer doublet tubulin were qualitatively identical with those of other soluble forms of tubulin. The solubilized tubulin (mol wt, 115,000) bound 0.9 ± 0.2 mol of colchicine per mol of tubulin, with a binding constant of 6.3 x 105 liters/mol at 37°C. The colchicine binding reaction was both time and temperature dependent, and the binding of colchicine was prevented in a competitive manner by podophyllotoxin (Ki = 1.3 x 10-6 M). The first-order decay of colchicine binding activity was substantially decreased by the addition of the vinca alkaloids, vinblastine sulfate or vincristine sulfate, thus demonstrating the presence of a vinca alkaloid binding site(s) on the outer doublet tubulin. Tubulin contained within the assembled microtubules did not decay. Intact outer doublet microtubules bound less than 0.001 mol of colchicine per mol of tubulin contained in the microtubules, under conditions where soluble tubulin would have bound 1 mol of colchicine per mol of tubulin (saturating concentration of colchicine, no decay of colchicine binding activity). The presence of colchicine had no effect on the rate of solubilization of outer doublet microtubules during incubation at 37°C. Therefore, the colchicine binding site on tubulin is blocked (not available to bind colchicine) when the tubulin is in the assembled outer doublet microtubules. PMID:4747924
Differential effects of tactile high- and low-frequency stimulation on tactile discrimination in human subjects.

PubMed

Ragert, Patrick; Kalisch, Tobias; Bliem, Barbara; Franzkowiak, Stephanie; Dinse, Hubert R

2008-01-23

Long-term potentiation (LTP) and long-term depression (LTD) play important roles in mediating activity-dependent changes in synaptic transmission and are believed to be crucial mechanisms underlying learning and cortical plasticity. In human subjects, however, the lack of adequate input stimuli for the induction of LTP and LTD makes it difficult to study directly the impact of such protocols on behavior. Using tactile high- and low-frequency stimulation protocols in humans, we explored the potential of such protocols for the induction of perceptual changes. We delivered tactile high-frequency and low-frequency stimuli (t-HFS, t-LFS) to skin sites of approximately 50 mm2 on the tip of the index finger. As assessed by 2-point discrimination, we demonstrate that 20 minutes of t-HFS improved tactile discrimination, while t-LFS impaired performance. T-HFS-effects were stable for at least 24 hours whereas t-LFS-induced changes recovered faster. While t-HFS changes were spatially very specific with no changes on the neighboring fingers, impaired tactile performance after t-LFS was also observed on the right middle-finger. A central finding was that for both t-LFS and t-HFS perceptual changes were dependent on the size of the stimulated skin area. No changes were observed when the stimulated area was very small (< 1 mm2) indicating special requirements for spatial summation. Our results demonstrate differential effects of such protocols in a frequency specific manner that might be related to LTP- and LTD-like changes in human subjects.
Time and force dependence of the rupture of glycoprotein IIb-IIIa-fibrinogen bonds between latex spheres.

PubMed Central

Goldsmith, H L; McIntosh, F A; Shahin, J; Frojmovic, M M

2000-01-01

We studied the shear-induced breakup of doublets of aldehyde/sulfate (A/S) latex spheres covalently linked with purified platelet GPIIb-IIIa receptor, and cross-linked by fibrinogen. Flow cytometry with fluorescein isothiocyanate-fibrinogen showed than an average of 22,500 molecules of active GPIIb-IIIa were captured per sphere, with a mean K(d) = 56 nM for fibrinogen binding. The spheres, suspended in buffered 19% Ficoll 400 containing 120 or 240 pM fibrinogen, were subjected to Couette flow in a counter-rotating cone-plate rheoscope. Doublets, formed by two-body collisions at low shear rate (G = 8 s(-1)) for < or =15 min, were subjected to shear stress from 0.6 to 2.9 Nm(-2), their rotations recorded until they broke up or were lost to view. Although breakup was time dependent, occurring mostly in the first 2 rotations after the onset of shear, the percentage of doublets broken up after 10 rotations were almost independent of normal hydrodynamic force, F(n): at 240 pN, 15.6, 16.0, and 17.0% broke up in the force range 70-150 pN, 150-230 pN, and 230-310 pN. Unexpectedly, at both [fibrinogen], the initial rate of breakup was highest in the lowest force range, and computer simulation using a stochastic model of breakup was unable to simulate the time course of breakup. When pre-sheared at low G for >15 min, no doublets broke up within 10 rotations at 70 < F(n) < 310 pN; it required >3 min shear (>1110 rotations) at F(n) = 210 pN for significant breakup to occur. Other published work has shown that binding of fibrinogen to GPIIb-IIIa immobilized on plane surfaces exhibits an initial fast reversible process with relative low affinity succeeded by transformation of GPIIb-IIIa to a stable high-affinity complex. We postulate that most doublet breakups observed within 10 rotations were from a population of young doublets having low numbers of bonds, by dissociation of the initial receptor complex relatively unresponsive to force. The remaining, older doublets with GPIIb-IIIa in the high-affinity complex were not broken up in the time or range of forces studied. PMID:10692309
Second-line single-agent versus doublet chemotherapy as salvage therapy for metastatic urothelial cancer: a systematic review and meta-analysis.

PubMed

Raggi, D; Miceli, R; Sonpavde, G; Giannatempo, P; Mariani, L; Galsky, M D; Bellmunt, J; Necchi, A

2016-01-01

The efficacy and safety of a combination of chemotherapeutic agent compared with single-agent chemotherapy in the second-line setting of advanced urothelial carcinoma (UC) are unclear. We aimed to study the survival impact of single-agent compared with doublet chemotherapy as second-line chemotherapy of advanced UC. Literature was searched for studies including single-agent or doublet chemotherapy in the second-line setting after platinum-based chemotherapy. Random-effects models were used to pool trial-level data according to treatment arm, including median progression-free survival (PFS), overall survival (OS), objective response rate (ORR) probability, and grade 3-4 toxicity. Univariable and multivariable analyses, including sensitivity analyses, were carried out, adjusting for the percent of patients with ECOG performance status ≥1 and hepatic metastases. Forty-six arms of trials including 1910 patients were selected: 22 arms with single agent (n = 1202) and 24 arms with doublets (n = 708). The pooled ORR with single agents was 14.2% [95% confidence interval (CI) 11.1-17.9] versus 31.9% [95% CI 27.3-36.9] with doublet chemotherapy. Pooled median PFS was 2.69 and 4.05 months, respectively. The pooled median OS was 6.98 and 8.50 months, respectively. Multivariably, the odds ratio for ORR and the pooled median difference of PFS were statistically significant (P < 0.001 and P = 0.002) whereas the median difference in OS was not (P = 0.284). When including single-agent vinflunine or taxanes only, differences were significant only for ORR (P < 0.001) favoring doublet chemotherapy. No statistically significant differences in grade 3-4 toxicity were seen between the two groups. Despite significant improvements in ORR and PFS, doublet regimens did not extend OS compared with single agents for the second-line chemotherapy of UC. Prospective trials are necessary to elucidate the role of combination chemotherapy, with or without targeted agents, in the salvage setting. Currently, improvements in this field should be pursued considering single-agent chemotherapy as the foundation for new more active combinations. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Predicting human chronically paralyzed muscle force: a comparison of three mathematical models.

PubMed

Frey Law, Laura A; Shields, Richard K

2006-03-01

Chronic spinal cord injury (SCI) induces detrimental musculoskeletal adaptations that adversely affect health status, ranging from muscle paralysis and skin ulcerations to osteoporosis. SCI rehabilitative efforts may increasingly focus on preserving the integrity of paralyzed extremities to maximize health quality using electrical stimulation for isometric training and/or functional activities. Subject-specific mathematical muscle models could prove valuable for predicting the forces necessary to achieve therapeutic loading conditions in individuals with paralyzed limbs. Although numerous muscle models are available, three modeling approaches were chosen that can accommodate a variety of stimulation input patterns. To our knowledge, no direct comparisons between models using paralyzed muscle have been reported. The three models include 1) a simple second-order linear model with three parameters and 2) two six-parameter nonlinear models (a second-order nonlinear model and a Hill-derived nonlinear model). Soleus muscle forces from four individuals with complete, chronic SCI were used to optimize each model's parameters (using an increasing and decreasing frequency ramp) and to assess the models' predictive accuracies for constant and variable (doublet) stimulation trains at 5, 10, and 20 Hz in each individual. Despite the large differences in modeling approaches, the mean predicted force errors differed only moderately (8-15% error; P=0.0042), suggesting physiological force can be adequately represented by multiple mathematical constructs. The two nonlinear models predicted specific force characteristics better than the linear model in nearly all stimulation conditions, with minimal differences between the two nonlinear models. Either nonlinear mathematical model can provide reasonable force estimates; individual application needs may dictate the preferred modeling strategy.
Neuromuscular Fatigue during Prolonged Exercise in Hypoxia.

PubMed

Jubeau, Marc; Rupp, Thomas; Temesi, John; Perrey, Stéphane; Wuyam, Bernard; Millet, Guillaume Y; Verges, Samuel

2017-03-01

Prolonged cycling exercise performance in normoxia is limited because of both peripheral and central neuromuscular impairments. It has been reported that cerebral perturbations are greater during short-duration exercise in hypoxia compared with normoxia. The purpose of this study was to test the hypothesis that central deficits are accentuated in hypoxia compared with normoxia during prolonged (three bouts of 80 min separated by 25 min) whole-body exercise at the same relative intensity. Ten subjects performed two sessions consisting of three 80-min cycling bouts at 45% of their relative maximal aerobic power in normoxia and hypoxia (FiO2 = 0.12). Before exercise and after each bout, maximal voluntary force, voluntary activation assessed with nerve stimulation and transcranial magnetic stimulation, corticospinal excitability (motor evoked potential), intracortical inhibition (cortical silent period), and electrical (M-wave) and contractile (twitch and doublet peak forces) properties of the knee extensors were measured. Prefrontal and motor cortical oxygenation was also recorded during each cycling bout in both conditions. A significant but similar force reduction (≈-22%) was observed at the end of exercise in normoxia and hypoxia. The modifications of voluntary activation assessed with transcranial magnetic stimulation and nerve stimulation, motor evoked potential, cortical silent period, and M-wave were also similar in both conditions. However, cerebral oxygenation was reduced in hypoxia compared with normoxia. These findings show that when performed at the same relative low intensity, prolonged exercise does not induce greater supraspinal fatigue in hypoxia compared with normoxia. Despite lower absolute exercise intensities in hypoxia, reduced brain O2 availability might contribute to similar amounts of central fatigue compared with normoxia.
Neuromuscular Impairment Following Backpack Load Carriage

PubMed Central

Blacker, Sam D.; Fallowfield, Joanne L.; Bilzon, James L.J.; Willems, Mark E.T.

Load Carriage using backpacks is an occupational task and can be a recreational pursuit. The aim of this study was to investigate the mechanisms responsible for changes in neuromuscular function of the m. quadriceps femoris following load carriage. The physiological responses of 10 male participants to voluntary and electrically stimulated isometric contractions were measured before and immediately after two hours of treadmill walking at 6.5 km•h −1 during level walking with no load [LW], and level walking with load carriage (25 kg backpack) [LC]. Maximal voluntary contraction force decreased by 15 ± 11 % following LC (p=0.006), with no change following LW (p=0.292). Voluntary activation decreased after LW and LC (p=0.033) with no difference between conditions (p=0.405). Doublet contraction time decreased after both LW and LC (p=0.002), with no difference between conditions (p=0.232). There were no other changes in electrically invoked doublet parameters in either condition. The 20:50 Hz ratio did not change following LW (p=0.864) but decreased from 0.88 ± 0.04 to 0.84 ± 0.04 after LC (p=0.011) indicating reduced Ca2+ release from the sarcoplasmic reticulum during excitation contraction coupling. In conclusion, two hours of load carriage carrying a 25 kg back pack caused neuromuscular impairment through a decrease in voluntary activation (i.e. central drive) and fatigue or damage to the peripheral muscle, including impairment of the excitation contraction coupling process. This may reduce physical performance and increase the risk of musculoskeletal injury. PMID:24146709
Continuing the Original Stanford Sleep Surgery Protocol From Upper Airway Reconstruction to Upper Airway Stimulation: Our First Successful Case.

PubMed

Liu, Stanley Yung; Riley, Robert Wayne

2017-07-01

In 1993, a surgical protocol for dynamic upper airway reconstruction in patients with obstructive sleep apnea (OSA) was published, and it became commonly known as the Stanford phase 1 and 2 sleep surgery protocol. It served as a platform on which research and clinical studies have continued to perfect the surgical care of patients with OSA. However, relapse is inevitable in a chronic condition such as OSA, and a subset of previously cured surgical patients return with complaints of excessive daytime sleepiness. This report describes a patient who was successfully treated with phase 1 and 2 operations more than a decade previously. He returned at 65 years of age with relapse of moderate OSA, and after workup with polysomnography and drug-induced sleep endoscopy, he underwent upper airway stimulation of the hypoglossal nerve that resulted in a cure of OSA. This case shows why upper airway stimulation is an appropriate option for patients with OSA relapse, after previously successful maxillomandibular advancement. Copyright © 2017. Published by Elsevier Inc.
The combined effects of transcutaneous electrical nerve stimulation (TENS) and stretching on muscle hardness and pressure pain threshold.

PubMed

Karasuno, Hiroshi; Ogihara, Hisayoshi; Morishita, Katsuyuki; Yokoi, Yuka; Fujiwara, Takayuki; Ogoma, Yoshiro; Abe, Koji

2016-04-01

[Purpose] This study aimed to clarify the immediate effects of a combined transcutaneous electrical nerve stimulation and stretching protocol. [Subjects] Fifteen healthy young males volunteered to participate in this study. The inclusion criterion was a straight leg raising range of motion of less than 70 degrees. [Methods] Subjects performed two protocols: 1) stretching (S group) of the medial hamstrings, and 2) tanscutaneous electrical nerve stimulation (100 Hz) with stretching (TS group). The TS group included a 20-minute electrical stimulation period followed by 10 minutes of stretching. The S group performed 10 minutes of stretching. Muscle hardness, pressure pain threshold, and straight leg raising range of motion were analyzed to evaluate the effects. The data were collected before transcutaneous electrical nerve stimulation (T1), before stretching (T2), immediately after stretching (T3), and 10 minutes after stretching (T4). [Results] Combined transcutaneous electrical nerve stimulation and stretching had significantly beneficial effects on muscle hardness, pressure pain threshold, and straight leg raising range of motion at T2, T3, and T4 compared with T1. [Conclusion] These results support the belief that transcutaneous electrical nerve stimulation combined with stretching is effective in reducing pain and decreasing muscle hardness, thus increasing range of motion.
Maximal Voluntary Activation of the Elbow Flexors Is under Predicted by Transcranial Magnetic Stimulation Compared to Motor Point Stimulation Prior to and Following Muscle Fatigue

PubMed Central

Cadigan, Edward W. J.; Collins, Brandon W.; Philpott, Devin T. G.; Kippenhuck, Garreth; Brenton, Mitchell; Button, Duane C.

2017-01-01

Transcranial magnetic (TMS) and motor point stimulation have been used to determine voluntary activation (VA). However, very few studies have directly compared the two stimulation techniques for assessing VA of the elbow flexors. The purpose of this study was to compare TMS and motor point stimulation for assessing VA in non-fatigued and fatigued elbow flexors. Participants performed a fatigue protocol that included twelve, 15 s isometric elbow flexor contractions. Participants completed a set of isometric elbow flexion contractions at 100, 75, 50, and 25% of maximum voluntary contraction (MVC) prior to and following fatigue contractions 3, 6, 9, and 12 and 5 and 10 min post-fatigue. Force and EMG of the bicep and triceps brachii were measured for each contraction. Force responses to TMS and motor point stimulation and EMG responses to TMS (motor evoked potentials, MEPs) and Erb's point stimulation (maximal M-waves, Mmax) were also recorded. VA was estimated using the equation: VA% = (1−SITforce/PTforce) × 100. The resting twitch was measured directly for motor point stimulation and estimated for both motor point stimulation and TMS by extrapolation of the linear regression between the superimposed twitch force and voluntary force. MVC force, potentiated twitch force and VA significantly (p < 0.05) decreased throughout the elbow flexor fatigue protocol and partially recovered 10 min post fatigue. VA was significantly (p < 0.05) underestimated when using TMS compared to motor point stimulation in non-fatigued and fatigued elbow flexors. Motor point stimulation compared to TMS superimposed twitch forces were significantly (p < 0.05) higher at 50% MVC but similar at 75 and 100% MVC. The linear relationship between TMS superimposed twitch force and voluntary force significantly (p < 0.05) decreased with fatigue. There was no change in triceps/biceps electromyography, biceps/triceps MEP amplitudes, or bicep MEP amplitudes throughout the fatigue protocol at 100% MVC. In conclusion, motor point stimulation as opposed to TMS led to a higher estimation of VA in non-fatigued and fatigued elbow flexors. The decreased linear relationship between TMS superimposed twitch force and voluntary force led to an underestimation of the estimated resting twitch force and thus, a reduced VA. PMID:28979211
Maximal Voluntary Activation of the Elbow Flexors Is under Predicted by Transcranial Magnetic Stimulation Compared to Motor Point Stimulation Prior to and Following Muscle Fatigue.

PubMed

Cadigan, Edward W J; Collins, Brandon W; Philpott, Devin T G; Kippenhuck, Garreth; Brenton, Mitchell; Button, Duane C

2017-01-01

Transcranial magnetic (TMS) and motor point stimulation have been used to determine voluntary activation (VA). However, very few studies have directly compared the two stimulation techniques for assessing VA of the elbow flexors. The purpose of this study was to compare TMS and motor point stimulation for assessing VA in non-fatigued and fatigued elbow flexors. Participants performed a fatigue protocol that included twelve, 15 s isometric elbow flexor contractions. Participants completed a set of isometric elbow flexion contractions at 100, 75, 50, and 25% of maximum voluntary contraction (MVC) prior to and following fatigue contractions 3, 6, 9, and 12 and 5 and 10 min post-fatigue. Force and EMG of the bicep and triceps brachii were measured for each contraction. Force responses to TMS and motor point stimulation and EMG responses to TMS (motor evoked potentials, MEPs) and Erb's point stimulation (maximal M-waves, M max ) were also recorded. VA was estimated using the equation: VA% = (1- SITforce / PTforce ) × 100. The resting twitch was measured directly for motor point stimulation and estimated for both motor point stimulation and TMS by extrapolation of the linear regression between the superimposed twitch force and voluntary force. MVC force, potentiated twitch force and VA significantly ( p < 0.05) decreased throughout the elbow flexor fatigue protocol and partially recovered 10 min post fatigue. VA was significantly ( p < 0.05) underestimated when using TMS compared to motor point stimulation in non-fatigued and fatigued elbow flexors. Motor point stimulation compared to TMS superimposed twitch forces were significantly ( p < 0.05) higher at 50% MVC but similar at 75 and 100% MVC. The linear relationship between TMS superimposed twitch force and voluntary force significantly ( p < 0.05) decreased with fatigue. There was no change in triceps/biceps electromyography, biceps/triceps MEP amplitudes, or bicep MEP amplitudes throughout the fatigue protocol at 100% MVC. In conclusion, motor point stimulation as opposed to TMS led to a higher estimation of VA in non-fatigued and fatigued elbow flexors. The decreased linear relationship between TMS superimposed twitch force and voluntary force led to an underestimation of the estimated resting twitch force and thus, a reduced VA.
Feasibility and first results of a group program to increase the frequency of cognitively stimulating leisure activities in people with mild cognitive impairment (AKTIVA-MCI)

PubMed Central

Tesky, Valentina A; Köbe, Theresa; Witte, A Veronica; Flöel, Agnes; Schuchardt, Jan Philipp; Hahn, Andreas; Pantel, Johannes

2017-01-01

AKTIVA-MCI is a program for patients with mild cognitive impairment (MCI) that aims to enhance participation in cognitively stimulating leisure activities. Participation in cognitively stimulating activities seems to be a potential strategy for people with MCI delaying cognitive decline for a while. In total, 35 MCI patients were enrolled in the pilot study of whom 29 completed the whole program (16 female, 71.1±7.5 years; Mini Mental Status Examination score: 28±2.2). Daily activity protocols were used to measure the frequency of participation in cognitively stimulating activities during the program (12 sessions). Additional standardized psychometric tests and questionnaires were used to assess cognition, mood, and subjective memory decline. Analyses of the daily activity protocols showed that during the intervention participants increased the frequency of several cognitively stimulating leisure activities. Comparison of pre-post data indicates no changes in cognitive status, mood, and subjective memory decline. These findings indicate that the program is suitable for patients with MCI. PMID:28979108
Photographic Combustion Characterization of LOX/Hydrocarbon Type Propellants

NASA Technical Reports Server (NTRS)

Judd, D. C.

1980-01-01

The advantages and limitations of using high speed photography to identify potential combustion anomalies (pops, fuel freezing, reactive stream separation (RSS), carbon formation) were demonstrated. Combustion evaluation criteria were developed for evaluating, characterizing, and screening promising low cost propellant combination(s) and injector element(s) for long life, reusable engine systems. Carbon formation and RSS mechanisms and trends were identified by using high speed color photography at speeds up to 6000 frames/sec. Single element injectors were tested with LOX/RP-1, LOX/Propane, LOX/Methane and LOX/Ammonia propellants. Tests were conducted using seven separate injector elements. Five different conventionally machined elements were tested: OFO Triplet; Rectangular Unlike Doublet (RUD); Unlike Doublet (UD); Like on Lke Doublet (LOL-EDM); and Slit Triplet.
Search for Higgs bosons predicted in two-Higgs-doublet models via decays to tau lepton pairs in 1.96 TeV pp collisions.

PubMed

Aaltonen, T; Adelman, J; Akimoto, T; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Barria, P; Bartos, P; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Beecher, D; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Beringer, J; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burke, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Calancha, C; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; 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Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mathis, M; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzione, A; Merkel, P; Mesropian, C; Miao, T; Miladinovic, N; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moggi, N; Mondragon, M N; Moon, C S; Moore, R; Morello, M J; Morlock, J; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Nett, J; Neu, C; Neubauer, M S; Neubauer, S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Osterberg, K; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Peiffer, T; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Pueschel, E; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Renton, P; Renz, M; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Rutherford, B; Saarikko, H; Safonov, A; Sakumoto, W K; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sforza, F; Sfyrla, A; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shiraishi, S; Shochet, M; Shon, Y; Shreyber, I; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soha, A; Somalwar, S; Sorin, V; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Suh, J S; Sukhanov, A; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Ttito-Guzmán, P; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Tourneur, S; Trovato, M; Tsai, S-Y; Tu, Y; Turini, N; Ukegawa, F; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Wagner, P; Wagner, R G; Wagner, R L; Wagner, W; Wagner-Kuhr, J; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Weinelt, J; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Würthwein, F; Xie, S; Yagil, A; Yamamoto, K; Yamaoka, J; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yi, K; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zhang, X; Zheng, Y; Zucchelli, S

2009-11-13

We present the results of a search for Higgs bosons predicted in two-Higgs-doublet models, in the case where the Higgs bosons decay to tau lepton pairs, using 1.8 fb(-1) of integrated luminosity of pp collisions recorded by the CDF II experiment at the Fermilab Tevatron. Studying the mass distribution in events where one or both tau leptons decay leptonically, no evidence for a Higgs boson signal is observed. The result is used to infer exclusion limits in the two-dimensional space of tanbeta versus m(A) (the ratio of the vacuum expectation values of the two Higgs doublets and the mass of the pseudoscalar boson, respectively).
Performance comparison of four kinds of flat nonimaging Fresnel lenses made of polycarbonates and polymethyl methacrylate for concentrated photovoltaics.

PubMed

Languy, Fabian; Habraken, Serge

2011-07-15

Solar concentrators made of a single refractive primary optics are limited to a concentration ratio of about 1000× [Opt. Express 19, A280 (2011)], due only to longitudinal chromatic aberration, while mirrors are limited to ∼46,000× by the angular size of the Sun. To reduce the chromatic aberration while keeping cost-effective systems for concentrated photovoltaics, a study of four different kinds of flat Fresnel doublets made of polycarbonates and polymethyl methacrylate is presented. It reveals that Fresnel doublets may have fewer optical losses than non-Fresnel doublets, with a lower lateral chromatic split allowing for even higher concentration ratio. © 2011 Optical Society of America

Scalar dark matter in leptophilic two-Higgs-doublet model

NASA Astrophysics Data System (ADS)

Bandyopadhyay, Priyotosh; Chun, Eung Jin; Mandal, Rusa

2018-04-01

Two-Higgs-Doublet Model of Type-X in the large tan ⁡ β limit becomes leptophilic to allow a light pseudo-scalar A and thus provides an explanation of the muon g - 2 anomaly. Introducing a singlet scalar dark matter S in this context, one finds that two important dark matter properties, nucleonic scattering and self-annihilation, are featured separately by individual couplings of dark matter to the two Higgs doublets. While one of the two couplings is strongly constrained by direct detection experiments, the other remains free to be adjusted for the relic density mainly through the process SS → AA. This leads to the 4τ final states which can be probed by galactic gamma ray detections.
Radiative neutrino mass and Majorana dark matter within an inert Higgs doublet model

NASA Astrophysics Data System (ADS)

Ahriche, Amine; Jueid, Adil; Nasri, Salah

2018-05-01

We consider an extension of the standard model (SM) with an inert Higgs doublet and three Majorana singlet fermions to address both origin and the smallness of neutrino masses and dark matter (DM) problems. In this setup, the lightest Majorana singlet fermion plays the role of DM candidate and the model parameter space can be accommodated to avoid different experimental constraints such as lepton flavor violating processes and electroweak precision tests. The neutrino mass is generated at one-loop level a la Scotogenic model and its smallness is ensured by the degeneracy between the C P -odd and C P -even scalar members of the inert doublet. Interesting signatures at both leptonic and hadronic colliders are discussed.
Transcranial direct current stimulation improves neurorehabilitation of task-specific dystonia: a pilot study.

PubMed

Rosset-Llobet, Jaume; Fàbregas-Molas, Sílvia; Pascual-Leone, Alvaro

2014-03-01

Sensory-motor returning (SMR) can help the symptoms of task-specific focal hand dystonia. However, effects vary across patients and take many sessions. Here, we present proof of principle evidence that transcranial direct current stimulation (tDCS) can enhance these effects. We compared the effects of a combined tDCS-SMR protocol (n=4 patients) with the efficacy of SMR alone (n=30 patients). All 4 patients treated with the combined protocol showed greater improvement than those undergoing SMR alone. Results encourage a larger, parallel-group clinical trial with sham tDCS control.
Differences in Motor Evoked Potentials Induced in Rats by Transcranial Magnetic Stimulation under Two Separate Anesthetics: Implications for Plasticity Studies.

PubMed

Sykes, Matthew; Matheson, Natalie A; Brownjohn, Philip W; Tang, Alexander D; Rodger, Jennifer; Shemmell, Jonathan B H; Reynolds, John N J

2016-01-01

Repetitive transcranial magnetic stimulation (rTMS) is primarily used in humans to change the state of corticospinal excitability. To assess the efficacy of different rTMS stimulation protocols, motor evoked potentials (MEPs) are used as a readout due to their non-invasive nature. Stimulation of the motor cortex produces a response in a targeted muscle, and the amplitude of this twitch provides an indirect measure of the current state of the cortex. When applied to the motor cortex, rTMS can alter MEP amplitude, however, results are variable between participants and across studies. In addition, the mechanisms underlying any change and its locus are poorly understood. In order to better understand these effects, MEPs have been investigated in vivo in animal models, primarily in rats. One major difference in protocols between rats and humans is the use of general anesthesia in animal experiments. Anesthetics are known to affect plasticity-like mechanisms and so may contaminate the effects of an rTMS protocol. In the present study, we explored the effect of anesthetic on MEP amplitude, recorded before and after intermittent theta burst stimulation (iTBS), a patterned rTMS protocol with reported facilitatory effects. MEPs were assessed in the brachioradialis muscle of the upper forelimb under two anesthetics: a xylazine/zoletil combination and urethane. We found MEPs could be induced under both anesthetics, with no differences in the resting motor threshold or the average baseline amplitudes. However, MEPs were highly variable between animals under both anesthetics, with the xylazine/zoletil combination showing higher variability and most prominently a rise in amplitude across the baseline recording period. Interestingly, application of iTBS did not facilitate MEP amplitude under either anesthetic condition. Although it is important to underpin human application of TMS with mechanistic examination of effects in animals, caution must be taken when selecting an anesthetic and in interpreting results during prolonged TMS recording.
Maintained benefits and improved survival of dynamic cardiomyoplasty by activity-rest stimulation: 5-year results of the Italian trial on "demand" dynamic cardiomyoplasty.

PubMed

Rigatelli, Gianluca; Barbiero, Mario; Rigatelli, Giorgio; Riccardi, Roberto; Cobelli, Franco; Cotogni, Angelo; Bandello, Attilio; Carraro, Ugo

2003-01-01

Latissimus dorsi (LD) muscular degeneration caused by continuous electrical stimulation has been the main cause of the poor results of dynamic cardiomyoplasty (DCMP) and its exclusion from the recent international guidelines on heart failure. To avoid full transformation of the LD and to improve results, a new stimulation protocol was developed; fewer impulses per day are delivered, providing the LD wrap with daily periods of rest ("demand" stimulation), based on a heart rate cut-off. The aim of this work is to report the results at 5 years of follow-up of the Italian Trial of Demand Dynamic Cardiomyoplasty and to discuss their impact on the destiny of this type of cardiac assistance. Twelve patients with dilated myocardiopathy (M/F=11/1, mean age 58.2+/-5.8 years, sinus rhythm/atrial fibrillation=11/1) were submitted during the period 1993-1996 to DCMP and at different intervals to demand protocol. Clinical, echocardiographic, mechanographic and cardiac invasive assessments were scheduled before initiating the demand protocol and during the follow-up at 0, 6 and every 12 months. The mean duration of follow-up was 40.2+/-13.8 months (range 18-64). There were no perioperative deaths. The demand stimulation protocol showed a decrease in 5 years in New York Health Association (NYHA) class (3.17+/-0.38-1.67+/-0.77, P=0.0001), an improvement of left ventricular ejection fraction (22.6+/-4.38-32.0+/-7.0, P<0.001), a 5-year actuarial survival of 83.3% (one patient was switched to heart transplantation programme due to clinical worsening and another one died of massive pulmonary embolism). Demand DCMP maintains over time LD muscular properties, enhances clinical benefits and improves survival of DCMP, thus reopening the debate whether this type of treatment should be considered in patients with end-stage heart failure.
Differences in Motor Evoked Potentials Induced in Rats by Transcranial Magnetic Stimulation under Two Separate Anesthetics: Implications for Plasticity Studies

PubMed Central

Sykes, Matthew; Matheson, Natalie A.; Brownjohn, Philip W.; Tang, Alexander D.; Rodger, Jennifer; Shemmell, Jonathan B. H.; Reynolds, John N. J.

2016-01-01

Repetitive transcranial magnetic stimulation (rTMS) is primarily used in humans to change the state of corticospinal excitability. To assess the efficacy of different rTMS stimulation protocols, motor evoked potentials (MEPs) are used as a readout due to their non-invasive nature. Stimulation of the motor cortex produces a response in a targeted muscle, and the amplitude of this twitch provides an indirect measure of the current state of the cortex. When applied to the motor cortex, rTMS can alter MEP amplitude, however, results are variable between participants and across studies. In addition, the mechanisms underlying any change and its locus are poorly understood. In order to better understand these effects, MEPs have been investigated in vivo in animal models, primarily in rats. One major difference in protocols between rats and humans is the use of general anesthesia in animal experiments. Anesthetics are known to affect plasticity-like mechanisms and so may contaminate the effects of an rTMS protocol. In the present study, we explored the effect of anesthetic on MEP amplitude, recorded before and after intermittent theta burst stimulation (iTBS), a patterned rTMS protocol with reported facilitatory effects. MEPs were assessed in the brachioradialis muscle of the upper forelimb under two anesthetics: a xylazine/zoletil combination and urethane. We found MEPs could be induced under both anesthetics, with no differences in the resting motor threshold or the average baseline amplitudes. However, MEPs were highly variable between animals under both anesthetics, with the xylazine/zoletil combination showing higher variability and most prominently a rise in amplitude across the baseline recording period. Interestingly, application of iTBS did not facilitate MEP amplitude under either anesthetic condition. Although it is important to underpin human application of TMS with mechanistic examination of effects in animals, caution must be taken when selecting an anesthetic and in interpreting results during prolonged TMS recording. PMID:27766073
Electrical stimulation (ES) in the management of sexual pain disorders.

PubMed

Nappi, Rossella E; Ferdeghini, Francesea; Abbiati, Ileana; Vercesi, Claudia; Farina, Claudio; Polatti, Franco

2003-01-01

We performed an open study to investigate the use of electrical stimulation (ES) on the vestibular area and vaginal introitus in women with sexual pain disorders. We recruited 29 women (age range 20-45 years) from among the patients at our Reproductive Psychobiology Unit to participate in the present study. They each experienced vestibular pain, inducing dyspareunia and vaginism. We performed ES with an ECL43400 apparatus (Elite, EssediEsse srl, Milan, Italy) once a week for 10 weeks. To evaluate the muscular activity of the perineal floor and sexual function, we employed the same apparatus with a vaginal probe for recording myoelectrical activity (muV), we employed a VAS scale for evaluating pain, and we administered the Female Sexual Function Index (FSFI; Rosen et al., 2000) before and after the study protocol. We analyzed data by parametric and nonparametric comparisons and correlations, as appropriate. Our major findings were as follows: (a) the contractile ability of pelvic floor muscles (p < 0.001), as well as the resting ability (p < 0.001), significantly improved following ES; (b) the current intensity tolerated significantly increased (p < 0.001) throughout the study, from 41.3 +/- 7.4 mA at the start of the study to 50 +/- 7.4 mA at the end of the stimulation protocol; (c) the Visual Analogic Scale (VAS) for pain significantly declined (p < 0.001), whereas FSFI pain scores (p < 0.001) and full scale scores (p < 0.001) significantly improved following ES, and 4 out of 9 women with vaginism went back to coital activity; (d) FSFI pain score and the current intensity tolerated, both before (R = .59; p < 0.006) and at the end (R = .53; p < 0.02) of the stimulation protocol, positively correlated. ES may be effective in the management of sexual pain disorders. Further controlled studies are necessary to standardize stimulation protocols according to the severity of pain and to better clarify the long-term clinical effects of ES.
Exchange and Inelastic OH(+) + H Collisions on the Doublet and Quartet Electronic States.

PubMed

Bulut, Niyazi; Lique, François; Roncero, Octavio

2015-12-17

The exchange and inelastic state-to-state cross sections for the OH(+) + H collisions are computed from wave packet calculations using the doublet and quartet ground electronic potential energy surface (PES) correlating to the open shell reactants, for collision energies in the range of 1 meV to 0.7 eV. The doublet PES presents a deep insertion well, of ≈6 eV, but the exchange reaction has a rather low probability, showing that the mechanism is not statistical. This well is also responsible of a rather high rotational energy transfer, which makes the rigid-rotor approach overestimate the cross section for low Δj transitions and for high collisonal energies. The quartet PES, with a much shallower well, also presents a low exchange reaction cross section, but the inelastic state-to-state cross sections are very well reproduced by rigid-rotor calculations. When the electronic partition is used to obtain the total state-to-state cross section, the contribution of the doublet state becomes small, and the resulting total cross sections become close to those obtained for the quartet state. Thus, the total (quartet and doublet) cross sections for this open shell system can be reproduced rather satisfactorily by those obtained with the rigid-rotor approximation on the quartet state. Finally, we compare the new OH(+)-H cross sections with OH(+)-He ones recently computed. We found significant differences, especially for transitions with large Δj showing that specific OH(+)-H calculations had to be performed to accurately analyze the OH(+) emission from interstellar molecular clouds.
Electrical stimulation systems for cardiac tissue engineering

PubMed Central

Tandon, Nina; Cannizzaro, Christopher; Chao, Pen-Hsiu Grace; Maidhof, Robert; Marsano, Anna; Au, Hoi Ting Heidi; Radisic, Milica; Vunjak-Novakovic, Gordana

2009-01-01

We describe a protocol for tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cells with the application of pulsatile electrical fields designed to mimic those present in the native heart. Tissue culture is conducted in a customized chamber built to allow for cultivation of (i) engineered three-dimensional (3D) cardiac tissue constructs, (ii) cell monolayers on flat substrates or (iii) cells on patterned substrates. This also allows for analysis of the individual and interactive effects of pulsatile electrical field stimulation and substrate topography on cell differentiation and assembly. The protocol is designed to allow for delivery of predictable electrical field stimuli to cells, monitoring environmental parameters, and assessment of cell and tissue responses. The duration of the protocol is 5 d for two-dimensional cultures and 10 d for 3D cultures. PMID:19180087
New viable region of an inert Higgs doublet dark matter model with scotogenic extension

NASA Astrophysics Data System (ADS)

Borah, Debasish; Gupta, Aritra

2017-12-01

We explore the intermediate dark matter mass regime of the inert Higgs doublet model, approximately between 400 and 550 GeV, which is allowed by latest constraints from direct and indirect detection experiments, but the thermal relic abundance remains suppressed. We extend the model by three copies of right-handed neutrinos, odd under the built-in Z2 symmetry of the model. This discrete Z2 symmetry of the model allows these right-handed neutrinos to couple to the usual lepton doublets through the inert Higgs doublet allowing the possibility of radiative neutrino mass in the scotogenic fashion. Apart from generating nonzero neutrino mass, such an extension can also revive the intermediate dark matter mass regime. The late decay of the lightest right-handed neutrino to dark matter makes it possible for the usual thermally underabundant dark matter in this intermediate mass regime to satisfy the correct relic abundance limit. The revival of this wide intermediate mass range can have relevance not only for direct and indirect search experiments but also for neutrino experiments as the long lifetime of the lightest right-handed neutrino also results in almost vanishing lightest neutrino mass.
ARL2BP, a protein linked to Retinitis Pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure.

PubMed

Moye, Abigail R; Singh, Ratnesh; Kimler, Victoria A; Dilan, Tanya L; Munezero, Daniella; Saravanan, Thamaraiselvi; Goldberg, Andrew F X; Ramamurthy, Visvanathan

2018-05-02

The outer segment (OS) of photoreceptor cells is an elaboration of a primary cilium with organized stacks of membranous discs that contain the proteins needed for phototransduction and vision. Though cilia formation and function has been well characterized, little is known about the role of cilia in the development of photoreceptor OS. Nevertheless, progress has been made by studying mutations in ciliary proteins which often result in malformed outer segments and lead to blinding diseases. To investigate how ciliary proteins contribute to outer segment formation, we generated a knockout mouse model for ARL2BP, a ciliary protein linked to Retinitis Pigmentosa. The knockout mice display an early and progressive reduction in visual response. Prior to photoreceptor degeneration we observed disorganization of the photoreceptor OS, with vertically aligned discs and shortened axonemes. Interestingly, ciliary doublet microtubule structure was also impaired, displaying open B-tubule doublets, paired with loss of singlet microtubules. Based on results from this study, we conclude that ARL2BP is necessary for photoreceptor cilia doublet formation and axoneme elongation, which is required for outer segment morphogenesis and vision.
Vapor deposition on doublet airfoil substrates: Control of coating thickness and microstructure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodgers, Theron M.; Zhao, Hengbei; Wadley, Haydn N. G., E-mail: haydn@virginia.edu

Gas jet assisted vapor deposition processes for depositing coatings are conducted at higher pressures than conventional physical vapor deposition methods, and have shown promise for coating complex shaped substrates including those with non-line-of-sight (NLS) regions on their surface. These regions typically receive vapor atoms at a lower rate and with a wider incident angular distribution than substrate regions in line-of-sight (LS) of the vapor source. To investigate the coating of such substrates, the thickness and microstructure variation along the inner (curved) surfaces of a model doublet airfoil containing both LS and NLS regions has been investigated. Results from atomistic simulationsmore » and experiments confirm that the coating's thickness is thinner in flux-shadowed regions than in other regions for all the coating processes investigated. They also indicated that the coatings columnar microstructure and pore volume fraction vary with surface location through the LS to NLS transition zone. A substrate rotation strategy for optimizing the thickness over the entire doublet airfoil surface was investigated, and led to the identification of a process that resulted in only small variation of coating thickness, columnar growth angle, and pore volume fraction on all doublet airfoil surfaces.« less
Treatment strategies in colorectal cancer patients with initially unresectable liver-only metastases, a study protocol of the randomised phase 3 CAIRO5 study of the Dutch Colorectal Cancer Group (DCCG).

PubMed

Huiskens, Joost; van Gulik, Thomas M; van Lienden, Krijn P; Engelbrecht, Marc R W; Meijer, Gerrit A; van Grieken, Nicole C T; Schriek, Jonne; Keijser, Astrid; Mol, Linda; Molenaar, I Quintus; Verhoef, Cornelis; de Jong, Koert P; Dejong, Kees H C; Kazemier, Geert; Ruers, Theo M; de Wilt, Johanus H W; van Tinteren, Harm; Punt, Cornelis J A

2015-05-06

Colorectal cancer patients with unresectable liver-only metastases may be cured after downsizing of metastases by neoadjuvant systemic therapy. However, the optimal neoadjuvant induction regimen has not been defined, and the lack of consensus on criteria for (un)resectability complicates the interpretation of published results. CAIRO5 is a multicentre, randomised, phase 3 clinical study. Colorectal cancer patients with initially unresectable liver-only metastases are eligible, and will not be selected for potential resectability. The (un)resectability status is prospectively assessed by a central panel consisting of at least one radiologist and three liver surgeons, according to predefined criteria. Tumours of included patients will be tested for RAS mutation status. Patients with RAS wild type tumours will be treated with doublet chemotherapy (FOLFOX or FOLFIRI) and randomised between the addition of either bevacizumab or panitumumab, and patients with RAS mutant tumours will be randomised between doublet chemotherapy (FOLFOX or FOLFIRI) plus bevacizumab or triple chemotherapy (FOLFOXIRI) plus bevacizumab. Radiological evaluation to assess conversion to resectability will be performed by the central panel, at an interval of two months. The primary study endpoint is median progression-free survival. Secondary endpoints are the R0/1 resection rate, median overall survival, response rate, toxicity, pathological response of resected lesions, postoperative morbidity, and correlation of baseline and follow-up evaluation with respect to outcomes by the central panel. CAIRO5 is a prospective multicentre trial that investigates the optimal systemic induction therapy for patients with initially unresectable, liver-only colorectal cancer metastases. CAIRO 5 is registered at European Clinical Trials Database (EudraCT) (2013-005435-24). CAIRO 5 is registered at ClinicalTrials.gov: NCT02162563 , June 10, 2014.
The Effectiveness of Transcranial Brain Stimulation in Improving Clinical Signs of Hyperkinetic Movement Disorders.

PubMed

Obeso, Ignacio; Cerasa, Antonio; Quattrone, Aldo

2015-01-01

Repetitive transcranial magnetic stimulation (rTMS) is a safe and painless method for stimulating cortical neurons. In neurological realm, rTMS has prevalently been applied to understand pathophysiological mechanisms underlying movement disorders. However, this tool has also the potential to be translated into a clinically applicable therapeutic use. Several available studies supported this hypothesis, but differences in protocols, clinical enrollment, and variability of rTMS effects across individuals complicate better understanding of efficient clinical protocols. The aim of this present review is to discuss to what extent the evidence provided by the therapeutic use of rTMS may be generalized. In particular, we attempted to define optimal cortical regions and stimulation protocols that have been demonstrated to maximize the effectiveness seen in the actual literature for the three most prevalent hyperkinetic movement disorders: Parkinson's disease (PD) with levodopa-induced dyskinesias (LIDs), essential tremor (ET) and dystonia. A total of 28 rTMS studies met our search criteria. Despite clinical and methodological differences, overall these studies demonstrated that therapeutic applications of rTMS to "normalize" pathologically decreased or increased levels of cortical activity have given moderate progress in patient's quality of life. Moreover, the present literature suggests that altered pathophysiology in hyperkinetic movement disorders establishes motor, premotor or cerebellar structures as candidate regions to reset cortico-subcortical pathways back to normal. Although rTMS has the potential to become a powerful tool for ameliorating the clinical outcome of hyperkinetic neurological patients, until now there is not a clear consensus on optimal protocols for these motor disorders. Well-controlled multicenter randomized clinical trials with high numbers of patients are urgently required.
Outcomes from a university-based low-cost in vitro fertilization program providing access to care for a low-resource socioculturally diverse urban community.

PubMed

Herndon, Christopher N; Anaya, Yanett; Noel, Martha; Cakmak, Hakan; Cedars, Marcelle I

2017-10-01

To report on outcomes from a university-based low-cost and low-complexity IVF program using mild stimulation approaches and simplified protocols to provide basic access to ART to a socioculturally diverse low-income urban population. Retrospective cohort study. Academic infertility center. Sixty-five infertile couples were enrolled from a county hospital serving a low-resource largely immigrant population. Patients were nonrandomly allocated to one of four mild stimulation protocols: clomiphene/letrozole alone, two clomiphene/letrozole-based protocols involving sequential or flare addition of low-dose gonadotropins, and low-dose gonadotropins alone. Clinical fellows managed all aspects of cycle preparation, monitoring, oocyte retrieval, and embryo transfer under an attending preceptor. Retrieval was undertaken without administration of deep anesthesia, and laboratory interventions were minimized. All embryo transfers were performed at the cleavage stage. Sociomedical demographics, treatment response, and pregnancy outcomes were recorded. From August 2010 to June 2016, 65 patients initiated 161 stimulation IVF cycles, which resulted in 107 retrievals, 91 fresh embryo transfers, and 40 frozen embryo transfer cycles. The mean age of patients was 33.3 years, and mean reported duration of infertility was 5.3 years; 33.5% (54/161) of cycles were cancelled before oocyte retrieval, with 13% due to premature ovulation. Overall, cumulative live birth rates per retrieval including subsequent use of frozen embryos was 29.0%; 44.6% (29/65) of patients enrolled in the program achieved pregnancy. Use of mild stimulation protocols, simplified monitoring, and minimized laboratory handling procedures enabled access to care in a low-resource socioculturally diverse infertile population. Copyright © 2017. Published by Elsevier Inc.
Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: guidelines for technology and protocols.

PubMed

Charvet, Leigh E; Kasschau, Margaret; Datta, Abhishek; Knotkova, Helena; Stevens, Michael C; Alonzo, Angelo; Loo, Colleen; Krull, Kevin R; Bikson, Marom

2015-01-01

The effect of transcranial direct current stimulation (tDCS) is cumulative. Treatment protocols typically require multiple consecutive sessions spanning weeks or months. However, traveling to clinic for a tDCS session can present an obstacle to subjects and their caregivers. With modified devices and headgear, tDCS treatment can be administered remotely under clinical supervision, potentially enhancing recruitment, throughput, and convenience. Here we propose standards and protocols for clinical trials utilizing remotely-supervised tDCS with the goal of providing safe, reproducible and well-tolerated stimulation therapy outside of the clinic. The recommendations include: (1) training of staff in tDCS treatment and supervision; (2) assessment of the user's capability to participate in tDCS remotely; (3) ongoing training procedures and materials including assessments of the user and/or caregiver; (4) simple and fail-safe electrode preparation techniques and tDCS headgear; (5) strict dose control for each session; (6) ongoing monitoring to quantify compliance (device preparation, electrode saturation/placement, stimulation protocol), with corresponding corrective steps as required; (7) monitoring for treatment-emergent adverse effects; (8) guidelines for discontinuation of a session and/or study participation including emergency failsafe procedures tailored to the treatment population's level of need. These guidelines are intended to provide a minimal level of methodological rigor for clinical trials seeking to apply tDCS outside a specialized treatment center. We outline indication-specific applications (Attention Deficit Hyperactivity Disorder, Depression, Multiple Sclerosis, Palliative Care) following these recommendations that support a standardized framework for evaluating the tolerability and reproducibility of remote-supervised tDCS that, once established, will allow for translation of tDCS clinical trials to a greater size and range of patient populations.
Neuromuscular electrical stimulation improves exercise tolerance in patients with advanced heart failure on continuous intravenous inotropic support use-randomized controlled trial.

PubMed

Forestieri, Patrícia; Bolzan, Douglas W; Santos, Vinícius B; Moreira, Rita Simone Lopes; de Almeida, Dirceu Rodrigues; Trimer, Renata; de Souza Brito, Flávio; Borghi-Silva, Audrey; de Camargo Carvalho, Antonio Carlos; Arena, Ross; Gomes, Walter J; Guizilini, Solange

2018-01-01

To evaluate the impact of a short-term neuromuscular electrical stimulation program on exercise tolerance in hospitalized patients with advanced heart failure who have suffered an acute decompensation and are under continuous intravenous inotropic support. A randomized controlled study. Initially, 195 patients hospitalized for decompensated heart failure were recruited, but 70 were randomized. Patients were randomized into two groups: control group subject to the usual care ( n = 35); neuromuscular electrical stimulation group ( n = 35) received daily training sessions to both lower extremities for around two weeks. The baseline 6-minute walk test to determine functional capacity was performed 24 hours after hospital admission, and intravenous inotropic support dose was daily checked in all patients. The outcomes were measured in two weeks or at the discharge if the patients were sent back home earlier than two weeks. After losses of follow-up, a total of 49 patients were included and considered for final analysis (control group, n = 25 and neuromuscular electrical stimulation group, n = 24). The neuromuscular electrical stimulation group presented with a higher 6-minute walk test distance compared to the control group after the study protocol (293 ± 34.78 m vs. 265.8 ± 48.53 m, P < 0.001, respectively). Neuromuscular electrical stimulation group also demonstrated a significantly higher dose reduction of dobutamine compared to control group after the study protocol (2.72 ± 1.72 µg/kg/min vs. 3.86 ± 1.61 µg/kg/min, P = 0.001, respectively). A short-term inpatient neuromuscular electrical stimulation rehabilitation protocol improved exercise tolerance and reduced intravenous inotropic support necessity in patients with advanced heart failure suffering a decompensation episode.
Ovarian Stimulation in Patients With Cancer: Impact of Letrozole and BRCA Mutations on Fertility Preservation Cycle Outcomes.

PubMed

Turan, Volkan; Bedoschi, Giuliano; Emirdar, Volkan; Moy, Fred; Oktay, Kutluk

2018-01-01

Aromatase inhibitors (AI) have been introduced to reduce estrogen exposure in women with estrogen-sensitive cancer undergoing ovarian stimulation for oocyte/embryo cryopreservation. There have been questions regarding whether the addition of AI and the presence of BRCA mutations affect cycle outcomes. We sought to determine the impact of letrozole and BRCA mutations on fertility preservation (FP) cycle outcomes of patients undergoing ovarian stimulation with an antagonist protocol. The data were generated by the secondary analysis of a prospective database of all females diagnosed with cancer who underwent embryo or oocyte cryopreservation for FP. The final analysis included 145 patients stimulated with an antagonist protocol either using letrozole combined with recombinant follicle-stimulating hormone (rFSH; LF, n = 118) or rFSH alone (FA, n = 24). The mean number of total (15.6 [7.9] vs 10.2 [7.8]; P = .004) and mature oocytes (10.4 [5.1] vs 7.8 [3.5]; P = .044) and embryos frozen (7.7 [5.3] vs 5.3 [2.7]; P = .043) were significantly higher after LF stimulation versus FA. In the LF group, women with BRCA mutations produced significantly fewer oocytes (11.0 [8.0] vs 16.4 [7.7], P = .015) and embryos (5.1 [4.4] vs 8.2 [4.7], P = .013), compared to those who were mutation negative. After adjusting for age, body mass index, baseline FSH level, and BRCA status, LF protocol still resulted in higher number of total oocytes (95% confidence interval [CI]: 1.9 to 3.6; P = .002) mature oocyte (95% CI: 0.3 to 1.4; P = .028), and embryo yield (95% CI: 0.7 to 1.4; P = .015). In women with cancer undergoing FP, letrozole appears to enhance response to ovarian stimulation while the presence of BRCA mutations is associated with lower oocyte and embryo yield.
Generation of ultra-wideband triplet pulses based on four-wave mixing and phase-to-intensity modulation conversion.

PubMed

Li, Wei; Wang, Li Xian; Hofmann, Werner; Zhu, Ning Hua; Bimberg, Dieter

2012-08-27

We propose and demonstrate a novel scheme to generate ultra-wideband (UWB) triplet pulses based on four-wave mixing and phase-to-intensity modulation conversion. First a phase-modulated Gaussian doublet pulse is generated by four-wave mixing in a highly nonlinear fiber. Then an UWB triplet pulse is generated by generating the first-order derivative of the phase-modulated Gaussian doublet pulse using an optical filter serving as a frequency discriminator. By locating the optical signal at the linear slope of the optical filter, the phase modulated Gaussian doublet pulse is converted to an intensity-modulated UWB triplet pulse which well satisfies the Federal Communications Commission spectral mask requirements, even in the extremely power-restricted global positioning system band.
Comparison of analytical and experimental steadyand unsteady-pressure distributions at Mach number 0.78 for a high-aspect-ratio supercritical wing model with oscillating control surfaces

NASA Technical Reports Server (NTRS)

Mccain, W. E.

1984-01-01

The unsteady aerodynamic lifting surface theory, the Doublet Lattice method, with experimental steady and unsteady pressure measurements of a high aspect ratio supercritical wing model at a Mach number of 0.78 were compared. The steady pressure data comparisons were made for incremental changes in angle of attack and control surface deflection. The unsteady pressure data comparisons were made at set angle of attack positions with oscillating control surface deflections. Significant viscous and transonic effects in the experimental aerodynamics which cannot be predicted by the Doublet Lattice method are shown. This study should assist development of empirical correction methods that may be applied to improve Doublet Lattice calculations of lifting surface aerodynamics.

Simultaneous impact and lunar craters

NASA Technical Reports Server (NTRS)

Oberbeck, V. R.

1972-01-01

The existence of large terrestrial impact crater doublets and crater doublets that have been inferred to be impact craters on Mars suggests that simultaneous impact of two or more bodies can occur at nearly the same point on planetary surfaces. An experimental study of simultaneous impact of two projectiles near one another shows that doublet craters with ridges perpendicular to the bilateral axis of symmetry result when separation between impact points relative to individual crater diameter is large. When separation is progressively less, elliptical craters with central ridges and peaks, and circular craters with deep round bottoms are produced. These craters are similar in structure to many of the large lunar craters. Results suggest that the simultaneous impact of meteoroids near one another may be an important mechanism for the production of central peaks in large lunar craters.
Combined noninvasive language mapping by navigated transcranial magnetic stimulation and functional MRI and its comparison with direct cortical stimulation.

PubMed

Ille, Sebastian; Sollmann, Nico; Hauck, Theresa; Maurer, Stefanie; Tanigawa, Noriko; Obermueller, Thomas; Negwer, Chiara; Droese, Doris; Zimmer, Claus; Meyer, Bernhard; Ringel, Florian; Krieg, Sandro M

2015-07-01

Repetitive navigated transcranial magnetic stimulation (rTMS) is now increasingly used for preoperative language mapping in patients with lesions in language-related areas of the brain. Yet its correlation with intraoperative direct cortical stimulation (DCS) has to be improved. To increase rTMS's specificity and positive predictive value, the authors aim to provide thresholds for rTMS's positive language areas. Moreover, they propose a protocol for combining rTMS with functional MRI (fMRI) to combine the strength of both methods. The authors performed multimodal language mapping in 35 patients with left-sided perisylvian lesions by using rTMS, fMRI, and DCS. The rTMS mappings were conducted with a picture-to-trigger interval (PTI, time between stimulus presentation and stimulation onset) of either 0 or 300 msec. The error rates (ERs; that is, the number of errors per number of stimulations) were calculated for each region of the cortical parcellation system (CPS). Subsequently, the rTMS mappings were analyzed through different error rate thresholds (ERT; that is, the ER at which a CPS region was defined as language positive in terms of rTMS), and the 2-out-of-3 rule (a stimulation site was defined as language positive in terms of rTMS if at least 2 out of 3 stimulations caused an error). As a second step, the authors combined the results of fMRI and rTMS in a predefined protocol of combined noninvasive mapping. To validate this noninvasive protocol, they correlated its results to DCS during awake surgery. The analysis by different rTMS ERTs obtained the highest correlation regarding sensitivity and a low rate of false positives for the ERTs of 15%, 20%, 25%, and the 2-out-of-3 rule. However, when comparing the combined fMRI and rTMS results with DCS, the authors observed an overall specificity of 83%, a positive predictive value of 51%, a sensitivity of 98%, and a negative predictive value of 95%. In comparison with fMRI, rTMS is a more sensitive but less specific tool for preoperative language mapping than DCS. Moreover, rTMS is most reliable when using ERTs of 15%, 20%, 25%, or the 2-out-of-3 rule and a PTI of 0 msec. Furthermore, the combination of fMRI and rTMS leads to a higher correlation to DCS than both techniques alone, and the presented protocols for combined noninvasive language mapping might play a supportive role in the language-mapping assessment prior to the gold-standard intraoperative DCS.
Recruitment of Additional Corticospinal Pathways in the Human Brain with State-Dependent Paired Associative Stimulation.

PubMed

Kraus, Dominic; Naros, Georgios; Guggenberger, Robert; Leão, Maria Teresa; Ziemann, Ulf; Gharabaghi, Alireza

2018-02-07

Standard brain stimulation protocols modify human motor cortex excitability by modulating the gain of the activated corticospinal pathways. However, the restoration of motor function following lesions of the corticospinal tract requires also the recruitment of additional neurons to increase the net corticospinal output. For this purpose, we investigated a novel protocol based on brain state-dependent paired associative stimulation.Motor imagery (MI)-related electroencephalography was recorded in healthy males and females for brain state-dependent control of both cortical and peripheral stimulation in a brain-machine interface environment. State-dependency was investigated with concurrent, delayed, and independent stimulation relative to the MI task. Specifically, sensorimotor event-related desynchronization (ERD) in the β-band (16-22 Hz) triggered peripheral stimulation through passive hand opening by a robotic orthosis and transcranial magnetic stimulation to the respective cortical motor representation, either synchronously or subsequently. These MI-related paradigms were compared with paired cortical and peripheral input applied independent of the brain state. Cortical stimulation resulted in a significant increase in corticospinal excitability only when applied brain state-dependently and synchronously to peripheral input. These gains were resistant to a depotentiation task, revealed a nonlinear evolution of plasticity, and were mediated via the recruitment of additional corticospinal neurons rather than via synchronization of neuronal firing. Recruitment of additional corticospinal pathways may be achieved when cortical and peripheral inputs are applied concurrently, and during β-ERD. These findings resemble a gating mechanism and are potentially important for developing closed-loop brain stimulation for the treatment of hand paralysis following lesions of the corticospinal tract. SIGNIFICANCE STATEMENT The activity state of the motor system influences the excitability of corticospinal pathways to external input. State-dependent interventions harness this property to increase the connectivity between motor cortex and muscles. These stimulation protocols modulate the gain of the activated pathways, but not the overall corticospinal recruitment. In this study, a brain-machine interface paired peripheral stimulation through passive hand opening with transcranial magnetic stimulation to the respective cortical motor representation during volitional β-band desynchronization. Cortical stimulation resulted in the recruitment of additional corticospinal pathways, but only when applied brain state-dependently and synchronously to peripheral input. These effects resemble a gating mechanism and may be important for the restoration of motor function following lesions of the corticospinal tract. Copyright © 2018 the authors 0270-6474/18/381397-12$15.00/0.
[Evolution of ovarian stimulation in in vitro fertilization].

PubMed

Delbaere, A; Devreker, F; Hannes, M; Koenig, I; Holoye, A; Englert, Y

1999-10-01

This paper reviews the different treatments of ovarian stimulation for in vitro fertilization (IVF). It emphasizes the recent development of new molecules, including recombinant gonadotrophins and GnRH antagonists. Because of their higher purity, recombinant gonadotrophins are theoretically less immunogenic than the urinary forms. Their preparation mode ensures a better batch to batch consistency. Their clinical use in IVF seems to be associated with a higher number of developing follicules and retrieved oocytes, but pregnancy rates are comparable to those obtained after ovarian stimulation with urinary gonadotrophins. The GnRH antagonists induce a direct inhibition of the pituitary gonadotrophin secretion. In association with an ovarian stimulation with gonadotrophins, they efficiently prevent premature LH surges when administered during the end of the follicular phase. The GnRH antagonists are still in clinical evaluation phase and the optimal protocol and dose still to be defined. They should become available in the coming year. The risks related to the controlled hyperstimulation together with the reduction of the number of transferred embryos has recently led "soft stimulation" to a reevaluation of the stimulation protocols towards a simplified procedure. However, the validity of this attitude could be in opposition with the wish to limit the number of transferred embryos since embryo quality seems to be directly related to the total number of embryos.
Non-invasive electric current stimulation for restoration of vision after unilateral occipital stroke.

PubMed

Gall, Carolin; Silvennoinen, Katri; Granata, Giuseppe; de Rossi, Francesca; Vecchio, Fabrizio; Brösel, Doreen; Bola, Michał; Sailer, Michael; Waleszczyk, Wioletta J; Rossini, Paolo M; Tatlisumak, Turgut; Sabel, Bernhard A

2015-07-01

Occipital stroke often leads to visual field loss, for which no effective treatment exists. Little is known about the potential of non-invasive electric current stimulation to ameliorate visual functions in patients suffering from unilateral occipital stroke. One reason is the traditional thinking that visual field loss after brain lesions is permanent. Since evidence is available documenting vision restoration by means of vision training or non-invasive electric current stimulation future studies should also consider investigating recovery processes after visual cortical strokes. Here, protocols of repetitive transorbital alternating current stimulation (rtACS) and transcranial direct current stimulation (tDCS) are presented and the European consortium for restoration of vision (REVIS) is introduced. Within the consortium different stimulation approaches will be applied to patients with unilateral occipital strokes resulting in homonymous hemianopic visual field defects. The aim of the study is to evaluate effects of current stimulation of the brain on vision parameters, vision-related quality of life, and physiological parameters that allow concluding about the mechanisms of vision restoration. These include EEG-spectra and coherence measures, and visual evoked potentials. The design of stimulation protocols involves an appropriate sham-stimulation condition and sufficient follow-up periods to test whether the effects are stable. This is the first application of non-invasive current stimulation for vision rehabilitation in stroke-related visual field deficits. Positive results of the trials could have far-reaching implications for clinical practice. The ability of non-invasive electrical current brain stimulation to modulate the activity of neuronal networks may have implications for stroke rehabilitation also in the visual domain. Copyright © 2015 Elsevier Inc. All rights reserved.
Treatment for Stimulant Use Disorders. Treatment Improvement Protocol (TIP) Series 33.

ERIC Educational Resources Information Center

Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Center for Substance Abuse Treatment.

This TIP on the best practice guidelines for treatment of substance abuse provides basic knowledge for practitioners, educators, and paraprofessionals about the nature and treatment of stimulant use disorders. More specifically, it reviews what is currently known about treating the medical, psychiatric, and substance abuse/dependence problems…
Postfatigue potentiation of the paralyzed soleus muscle: evidence for adaptation with long-term electrical stimulation training

PubMed Central

Shields, Richard K.; Dudley-Javoroski, Shauna; Littmann, Andrew E.

2012-01-01

Understanding the torque output behavior of paralyzed muscle has important implications for the use of functional neuromuscular electrical stimulation systems. Postfatigue potentiation is an augmentation of peak muscle torque during repetitive activation after a fatigue protocol. The purposes of this study were 1) to quantify postfatigue potentiation in the acutely and chronically paralyzed soleus and 2) to determine the effect of long-term soleus electrical stimulation training on the potentiation characteristics of recently paralyzed soleus muscle. Five subjects with chronic paralysis (>2 yr) demonstrated significant postfatigue potentiation during a repetitive soleus activation protocol that induced low-frequency fatigue. Ten subjects with acute paralysis (<6 mo) demonstrated no torque potentiation in response to repetitive stimulation. Seven of these acute subjects completed 2 yr of home-based isometric soleus electrical stimulation training of one limb (compliance = 83%; 8,300 contractions/wk). With the early implementation of electrically stimulated training, potentiation characteristics of trained soleus muscles were preserved as in the acute postinjury state. In contrast, untrained limbs showed marked postfatigue potentiation at 2 yr after spinal cord injury (SCI). A single acute SCI subject who was followed longitudinally developed potentiation characteristics very similar to the untrained limbs of the training subjects. The results of the present investigation support that postfatigue potentiation is a characteristic of fast-fatigable muscle and can be prevented by timely neuromuscular electrical stimulation training. Potentiation is an important consideration in the design of functional electrical stimulation control systems for people with SCI. PMID:16575026
Postfatigue potentiation of the paralyzed soleus muscle: evidence for adaptation with long-term electrical stimulation training.

PubMed

Shields, Richard K; Dudley-Javoroski, Shauna; Littmann, Andrew E

2006-08-01

Understanding the torque output behavior of paralyzed muscle has important implications for the use of functional neuromuscular electrical stimulation systems. Postfatigue potentiation is an augmentation of peak muscle torque during repetitive activation after a fatigue protocol. The purposes of this study were 1) to quantify postfatigue potentiation in the acutely and chronically paralyzed soleus and 2) to determine the effect of long-term soleus electrical stimulation training on the potentiation characteristics of recently paralyzed soleus muscle. Five subjects with chronic paralysis (>2 yr) demonstrated significant postfatigue potentiation during a repetitive soleus activation protocol that induced low-frequency fatigue. Ten subjects with acute paralysis (<6 mo) demonstrated no torque potentiation in response to repetitive stimulation. Seven of these acute subjects completed 2 yr of home-based isometric soleus electrical stimulation training of one limb (compliance = 83%; 8,300 contractions/wk). With the early implementation of electrically stimulated training, potentiation characteristics of trained soleus muscles were preserved as in the acute postinjury state. In contrast, untrained limbs showed marked postfatigue potentiation at 2 yr after spinal cord injury (SCI). A single acute SCI subject who was followed longitudinally developed potentiation characteristics very similar to the untrained limbs of the training subjects. The results of the present investigation support that postfatigue potentiation is a characteristic of fast-fatigable muscle and can be prevented by timely neuromuscular electrical stimulation training. Potentiation is an important consideration in the design of functional electrical stimulation control systems for people with SCI.
Dual ovarian stimulation and random start in assisted reproductive technologies: from ovarian biology to clinical application.

PubMed

Vaiarelli, Alberto; Venturella, Roberta; Vizziello, Damiano; Bulletti, Francesco; Ubaldi, Filippo M

2017-06-01

The opportunity to use gonadotropins to stimulate the growth of antral follicles coming from different follicular waves available in different moment of the menstrual cycle allowed the implementation of innovative protocols in assisted reproductive technologies. The purpose of this review is to explore the possible advantages related to these new controlled ovarian stimulation (COS) strategies. Women exhibit major and minor wave patterns of ovarian follicular development during the menstrual cycle, as it is in animal species. These observations led to the introduction of two new strategies for COS: the random start and the double ovarian stimulation within a single menstrual cycle. The use of gonadotropin-releasing hormone antagonist COS protocols, started randomly at any day of the menstrual cycle, is today a standard procedure in those cases where obtaining oocytes is an urgent task, such as in case of fertility preservation for malignant diseases or other medical indications.On the other hand, in poor prognosis patients, double ovarian stimulation has been suggested with the aim of maximizing the number of oocytes retrieved within a single menstrual cycle and, in turn increasing the chance to obtain a reproductively competent embryo. Randomized control trials are necessary to confirm these preliminary findings.
Impact of gonadotropin type on progesterone elevation during ovarian stimulation in GnRH antagonist cycles.

PubMed

Lawrenz, B; Beligotti, F; Engelmann, N; Gates, D; Fatemi, H M

2016-11-01

Does hormonal stimulation with corifollitropin alpha (CFA) only, mimicking a step down protocol, result in lower incidence of progesterone elevation on the day of hCGtrigger as compared to sustained stimulation with recombinant FSH (rFSH)? The current findings support the concept that sustained FSH stimulus contributes to premature progesterone elevation in stimulated IVF cycles. Serum progesterone rise during the follicular phase of ovarian stimulation for IVF treatment seems to be related to a poorer reproductive outcome. However, the mechanism by which the rise in progesterone is caused is not yet fully understood. This study was a post hoc analysis of data from two multi-center, randomized, double-blind, double-dummy, active-controlled, non-inferiority trials, ENGAGE and PURSUE, conducted from June 2006 to January 2008 and from July 2010 to October 2012 respectively. In the ENGAGE-study, 1506 women, aged 18-36 years, were allocated to either a single injection of 150 mg CFA or daily injections of 200 IU rFSH in the first week of stimulation, using a standard GnRH antagonist protocol. In the PURSUE-study, a total of 1390 women, aged 35-42 years, were allocated to either a single injection of 150 mg of CFA or daily 300 IU of rFSH for the first week, again using a standard GnRH antagonist protocol. In both trials, daily rFSH was continued until three follicles reached >17 mm in size. All women had a body weight of between 50 and 90 kg, regular menstrual cycles and an indication for ovarian stimulation before IVF. The incidence of progesterone elevation on day of hCG-trigger in patients with CFA only or rFSH stimulation, and triggered on Day 8 of stimulation, was analyzed. Of patients with CFA only stimulation, 5.4% (13/239 patients) showed a progesterone elevation above 1.5 ng/ml on day of hCG-trigger, whereas patients with rFSH stimulation had a significant higher incidence of progesterone elevation (18.3%; 62/339 patients) (P < 0.001). Post hoc analysis of data from previously published trials could be considered as a reason for caution. Future studies should evaluate whether it would be possible to prevent a premature progesterone rise in cycles stimulated with daily FSH by using a step down protocol towards the end of the follicular phase. Financial/Material Support was provided by Merck & Co., Inc., Kenilworth, NJ, USA. Davis Gates is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and may own stock and/or hold stock options in the company. Fabiola Beligotti is an employee of MSD, Italy, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and may own stock and/or hold stock options in the company. Barbara Lawrenz, Nils Engelmann and Human M. Fatemi have no conflict of interest. ENGAGE study: ClinicalTrials.gov identifier NTC00696800. PURSUE-study: NCT01144416. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Structure of the nucleon's low-lying excitations

NASA Astrophysics Data System (ADS)

Chen, Chen; El-Bennich, Bruno; Roberts, Craig D.; Schmidt, Sebastian M.; Segovia, Jorge; Wan, Shaolong

2018-02-01

A continuum approach to the three valence-quark bound-state problem in quantum field theory is used to perform a comparative study of the four lightest (I =1 /2 ,JP=1 /2±) baryon isospin doublets in order to elucidate their structural similarities and differences. Such analyses predict the presence of nonpointlike, electromagnetically active quark-quark (diquark) correlations within all baryons; and in these doublets, isoscalar-scalar, isovector-pseudovector, isoscalar-pseudoscalar, and vector diquarks can all play a role. In the two lightest (1 /2 ,1 /2+) doublets, however, scalar and pseudovector diquarks are overwhelmingly dominant. The associated rest-frame wave functions are largely S -wave in nature; and the first excited state in this 1 /2+ channel has the appearance of a radial excitation of the ground state. The two lightest (1 /2 ,1 /2-) doublets fit a different picture: accurate estimates of their masses are obtained by retaining only pseudovector diquarks; in their rest frames, the amplitudes describing their dressed-quark cores contain roughly equal fractions of even- and odd-parity diquarks; and the associated wave functions are predominantly P -wave in nature, but possess measurable S -wave components. Moreover, the first excited state in each negative-parity channel has little of the appearance of a radial excitation. In quantum field theory, all differences between positive- and negative-parity channels must owe to chiral symmetry breaking, which is overwhelmingly dynamical in the light-quark sector. Consequently, experiments that can validate the contrasts drawn herein between the structure of the four lightest (1 /2 ,1 /2±) doublets will prove valuable in testing links between emergent mass generation and observable phenomena and, plausibly, thereby revealing dynamical features of confinement.
Transcranial direct current stimulation (tDCS) for treatment of major depression during pregnancy: study protocol for a pilot randomized controlled trial.

PubMed

Vigod, Simone; Dennis, Cindy-Lee; Daskalakis, Zafiris; Murphy, Kellie; Ray, Joel; Oberlander, Tim; Somerton, Sarah; Hussain-Shamsy, Neesha; Blumberger, Daniel

2014-09-18

Women with depression in pregnancy are faced with difficult treatment decisions. Untreated, antenatal depression has serious negative implications for mothers and children. While antidepressant drug treatment is likely to improve depressive symptoms, it crosses the placenta and may pose risks to the unborn child. Transcranial direct current stimulation is a focal brain stimulation treatment that improves depressive symptoms within 3 weeks of treatment by inducing changes to brain areas involved in depression, without impacting any other brain areas, and without inducing changes to heart rate, blood pressure or core body temperature. The localized nature of transcranial direct current stimulation makes it an ideal therapeutic approach for treating depression during pregnancy, although it has never previously been evaluated in this population. We describe a pilot randomized controlled trial of transcranial direct current stimulation among women with depression in pregnancy to assess the feasibility of a larger, multicentre efficacy study. Women over 18 years of age and between 14 and 32 weeks gestation can be enrolled in the study provided they meet diagnostic criteria for a major depressive episode of at least moderate severity and have been offered but refused antidepressant medication. Participants are randomized to receive active transcranial direct current stimulation or a sham condition that is administered in 15 30-minute treatments over three weeks. Women sit upright during treatment and receive obstetrical monitoring prior to, during and after each treatment session. Depressive symptoms, treatment acceptability, and pregnancy outcomes are assessed at baseline (prior to randomization), at the end of each treatment week, every four weeks post-treatment until delivery, and at 4 and 12 weeks postpartum. Transcranial direct current stimulation is a novel therapeutic option for treating depression during pregnancy. This protocol allows for assessment of the feasibility of, acceptability of and adherence with a clinical trial protocol to administer this treatment to pregnant women with moderate to severe depression. Results from this pilot study will guide the development of a larger multicentre trial to definitively test the efficacy and safety of transcranial direct current stimulation for pregnant women with depression. Clinical Trials Gov NCT02116127.
No significant effect of transcranial direct current stimulation (tDCS) found on simple motor reaction time comparing 15 different simulation protocols.

PubMed

Horvath, Jared Cooney; Carter, Olivia; Forte, Jason D

2016-10-01

Research exploring the behavioral impact of transcranial direct current stimulation (tDCS) over M1 has produced homogenous results. The most common explanations to address this homogeneity concerns the differential impact of varied tDCS parameters (such as stimulation intensity or electrode montage). To explore this, we systematically examined the effects of 15 different tDCS protocols on a well-elucidated neurobehavioral system: simple visual motor reaction time (smRT). For the initial phase of this study, 150 healthy participants were randomly assigned to one of 5 experimental groups (2mA anodal, 2mA cathodal, 1mA anodal, 1mA cathodal, or sham) across 3 different conditions (orbitofrontal, bilateral, or extracephalic reference electrode location). The active electrode was always placed over M1 and tDCS lasted for 20min. Starting ~5min prior to stimulation and running continuously for ~30min, participants were repeatedly presented with a visual cue centered on a computer monitor and asked to press a response button as quickly as possible at stimulus onset (stimuli number: 100 pre-, 400 during-, and 100-post stimulation - interstimulus interval: 1-3s). Ex-gaussian distribution curves, miss, and error rates were determined for each normalized batch of 100 RTs and compared using a two-way ANOVA. As the largest group differences were seen with 2mA anodal (compared to sham) stimulation using an orbitofrontal montage, an additional 60 healthy participants were recruited to further test for significance in this condition. No significant impact of tDCS was seen on any parameter of smRT distribution, error rate, or miss rate, regardless of polarity, stimulation intensity, electrode montage, or stimulation-to-task relationship. Our results suggest that tDCS over M1 might not have a predictable or reliable effect on short duration smRT. Our results raise interesting questions regarding the mechanisms by which tDCS might modulate more complex motor behaviors. Additional research utilizing multiple tDCS protocols as undertaken here will help address and clarify these concerns. Copyright © 2016 Elsevier Ltd. All rights reserved.
[Comparision of in vitro maturation applied in PCOS and non-PCOS patients undergo stimulated and unstimulated protocols].

PubMed

Wang, Peiyu; Zhao, Junzhao; Jin, Congcong; Yu, Rong; Lin, Jia; Zhu, Ruru; Wu, Yonggen

2014-12-01

To compare the laboratory and clinical results between unstimulated in vitro maturation (IVM) and IVM converted from in vitro fertilization (IVF) in polycystic ovarian syndrome (PCOS) and non-PCOS patients. We divided 591 IVM cycles in the First Affiliated Hospital of Wenzhou Medical Univesity from Jan. 2008 to Dec. 2013 into 4 groups: group A1B1, PCOS patients underwent unstimulated IVM protocol, 240 cycles; group A1B2, PCOS patients underwent IVM converted from conventional stimulated IVF protocol, 153 cycles; group A2B1, non-PCOS patients underwent unstimutlated IVM protocol, 103 cycles; group A2B2, non-PCOS patient underwent IVM converted from conventional stimulated IVF protocol, 95 cycles. Multiple linear regression method and binary logistic regression method were used to assess the influence of PCOS and protocols for IVM on laboratory and clinical outcomes. The mean number of oocytes retrieved was positively related with PCOS [partial regression coefficient (B) = 3.37, P < 0.01]. The maturation rate of oocytes was positively related with hCG-prime prior to oocyte aspiration (B = 0.05, P = 0.010). High-quality embryo rate was positively related with PCOS and IVM converted from IVF (B = 0.08, P = 0.010; B = 0.09, P = 0.001), as well as implantation rate related with them (B = 0.07, P = 0.010; B = 0.10, P < 0.01). PCOS and IVM converted from IVF improved hCG positive (hCG>10 U/L) rate (OR = 1.636, 95%CI: 1.113-2.204, P < 0.05; OR = 1.861, 95%CI: 1.307-2.649, P < 0.05) and the clinical pregnancy rate (OR = 1.507, 95%CI: 1.041-2.240, P < 0.05; OR = 1.881, 95%CI: 1.312-2.696, P < 0.05). IVM converted from IVF protocol decreased the spontaneous abortion rate (OR = 0.490, 95%CI: 0.245-0.978, P < 0.05). Multiple gestation rate and ectopic pregnancy rate were not affected by PCOS condition and protocol used (P > 0.05). PCOS and IVM converted from IVF protocol improved the high-quality embryo rate, implantation rate, hCG positive rate and clinical pregnancy rate. IVM converted from IVF protocol reduced the spontaneous abortion rate. PCOS patients may be more suitable for the IVM treatment. No matter PCOS or non-PCOS patients, IVM converted from IVF protocol had better pregnancy outcome than that of unstimulated cycle.
750 GeV diphoton excess at CERN LHC from a dark sector assisted scalar decay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharya, Subhaditya; Patra, Sudhanwa; Sahoo, Nirakar

2016-06-06

We present a simple extension of the Standard Model (SM) to explain the recent diphoton excess, reported by CMS and ATLAS at CERN LHC. The SM is extended by a dark sector including a vector-like lepton doublet and a singlet of zero electromagnetic charge, which are odd under a Z{sub 2} symmetry. The charged particle of the vector-like lepton doublet assist the additional scalar, different from SM Higgs, to decay to di-photons of invariant mass around 750 GeV and thus explaining the excess observed at LHC. The admixture of neutral component of the vector-like lepton doublet and singlet constitute themore » dark matter of the Universe. We show the relevant parameter space for correct relic density and direct detection of dark matter.« less
A higher order panel method for linearized supersonic flow

NASA Technical Reports Server (NTRS)

Ehlers, F. E.; Epton, M. A.; Johnson, F. T.; Magnus, A. E.; Rubbert, P. E.

1979-01-01

The basic integral equations of linearized supersonic theory for an advanced supersonic panel method are derived. Methods using only linear varying source strength over each panel or only quadratic doublet strength over each panel gave good agreement with analytic solutions over cones and zero thickness cambered wings. For three dimensional bodies and wings of general shape, combined source and doublet panels with interior boundary conditions to eliminate the internal perturbations lead to a stable method providing good agreement experiment. A panel system with all edges contiguous resulted from dividing the basic four point non-planar panel into eight triangular subpanels, and the doublet strength was made continuous at all edges by a quadratic distribution over each subpanel. Superinclined panels were developed and tested on s simple nacelle and on an airplane model having engine inlets, with excellent results.
The Higgs vacuum uplifted: revisiting the electroweak phase transition with a second Higgs doublet

NASA Astrophysics Data System (ADS)

Dorsch, G. C.; Huber, S. J.; Mimasu, K.; No, J. M.

2017-12-01

The existence of a second Higgs doublet in Nature could lead to a cosmological first order electroweak phase transition and explain the origin of the matter-antimatter asymmetry in the Universe. We explore the parameter space of such a two-Higgs-doublet-model and show that a first order electroweak phase transition strongly correlates with a significant uplifting of the Higgs vacuum w.r.t. its Standard Model value. We then obtain the spectrum and properties of the new scalars H 0, A 0 and H ± that signal such a phase transition, showing that the decay A 0 → H 0 Z at the LHC and a sizable deviation in the Higgs self-coupling λ hhh from its SM value are sensitive indicators of a strongly first order electroweak phase transition in the 2HDM.
Parity doublet structures in doubly-odd 216Fr

NASA Astrophysics Data System (ADS)

Pragati, Â.; Deo, A. Y.; Tandel, S. K.; Bhattacharjee, S. S.; Chakraborty, S.; Rai, S.; Wahid, S. G.; Kumar, S.; Muralithar, S.; Singh, R. P.; Bala, Indu; Garg, Ritika; Jain, A. K.

2018-04-01

Parity doublet structures are established in 216Fr, which lies at the lower boundary of enhanced octupole collectivity in the trans-lead region. The newly identified levels are established as the simplex partner of a previously reported band leading to parity doublets with small (˜55 keV) average energy splitting, a feature typical of nuclei with near-static octupole deformation. The observed levels do not follow a regular pattern of rotational bands, indicating low quadrupole collectivity. However, enhanced octupole correlations are evident from the small energy splitting and large B(E1)/B(E2) values. Staggering in E1 transition energies and B(E1)/B(E2) ratios is noted. The enhancement of octupole correlations in 216Fr is attributed to the availability of a neutron orbital with a K = 3/2 component.
Provision of Auricular Acupuncture and Acupressure in a University Setting

ERIC Educational Resources Information Center

Oyola-Santiago, Tamara; Knopf, Rachel; Robin, Tracy; Harvey, Kristen

2013-01-01

Auricular acupuncture using the National Acupuncture Detoxification Association (NADA) protocol stimulates 5 points in each ear--the Shen Men, sympathetic nervous system, liver, kidney, and lung. This protocol is also known as Acu Detox, and has been used for recovery in community-based settings and drug use treatment programs. It has also been…
Establishing an effective TMS protocol for craving in substance addiction: Is it possible?

PubMed

Enokibara, Mailu; Trevizol, Alisson; Shiozawa, Pedro; Cordeiro, Quirino

2016-01-01

Repetitive transcranial magnetic stimulation (TMS) is a non-invasive tool with known therapeutic efficacy in various neuropsychiatric disorders, such as depression, schizophrenia, mania, and anxiety disorders. We hereby, briefly present a brief review and meta-analysis on the use of TMS for craving in substance addiction. We present our brief review and meta-analysis following the recommendations of the Cochrane group. A total of eight randomized controlled trials fulfilled eligibility criteria and were selected. A total of 199 patients were studied. We found active stimulation to be superior than sham protocols only for trials focused on right DLPFC (with Hedge's g = 1.48; ES (95%CI: 0.126-2.834), p = 0.032. Main meta-analysis limitations include small number of studies, high heterogeneity among studies, and high publication bias. However challenging, our exploratory analysis underscored the amelioration of craving in substance addiction for trials using high frequency TMS protocols over the right DLPFC. We hereby, propose the use of this particular TMS protocol as a promising tool in clinical research. © American Academy of Addiction Psychiatry.

Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity

PubMed Central

Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R.; Baldelli, Pietro; Benfenati, Fabio

2013-01-01

Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows. PMID:23970852
Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity.

PubMed

Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R; Baldelli, Pietro; Benfenati, Fabio

2013-01-01

Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows.
Cycle-Triggered Cortical Stimulation during Slow Wave Sleep Facilitates Learning a BMI Task: A Case Report in a Non-Human Primate

PubMed Central

Rembado, Irene; Zanos, Stavros; Fetz, Eberhard E.

2017-01-01

Slow wave sleep (SWS) has been identified as the sleep stage involved in consolidating newly acquired information. A growing body of evidence has shown that delta (1–4 Hz) oscillatory activity, the characteristic electroencephalographic signature of SWS, is involved in coordinating interaction between the hippocampus and the neocortex and is thought to take a role in stabilizing memory traces related to a novel task. This case report describes a new protocol that uses neuroprosthetics training of a non-human primate to evaluate the effects of surface cortical electrical stimulation triggered from SWS cycles. The results suggest that stimulation phase-locked to SWS oscillatory activity promoted learning of the neuroprosthetic task. This protocol could be used to elucidate mechanisms of synaptic plasticity underlying off-line learning during sleep and offers new insights into the role of brain oscillations in information processing and memory consolidation. PMID:28450831
A pilot study of planar coil based magnetic stimulation using acute hippocampal slice in mice.

PubMed

Park, H J; Kang, H K; Wang, M; Jo, J; Chung, E; Kim, S

2017-07-01

Micromagnetic stimulation using small-sized implantable coils has recently been studied. The main advantage of this method is that it can provide sustainable stimulation performance even if a fibrotic encapsulation layer is formed around the implanted coil by inflammation response, because indirectly induced currents are used to induce neural responses. In previous research, we optimized the geometrical and control parameters used in implantable magnetic stimulation. Based on those results, we fabricated the planar coil and studied the LTP effect in the hippocampal slice by two different magnetic stimulation protocols using the quadripulse stimulation (QPS) pattern. We found that direct magnetic stimulation (DMS) induced insignificant LTP effect and priming magnetic stimulation (PMS) occluded LTP effect after tetanic stimulation, when QPS patterned magnetic stimulation with 1 A current pulse was applied to the planar coil.
New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF.

PubMed

Massin, Nathalie

2017-03-01

The advent of embryo and oocyte vitrification today gives reproductive specialists an opportunity to consider new strategies for improving the practice and results of IVF attempts. As the freezing of entire cohorts does not compromise, and may even improve, the results of IVF attempts, it is possible to break away from the standard sequence of stimulation-retrieval-transfer. The constraints associated with ovarian stimulation in relation to the potential harmful effects of the hormonal environment on endometrial receptivity can be avoided. This review will look at the new stimulation protocols where progesterone is used to block the LH surge. Thanks to 'freeze all' strategies, the increase in progesterone could actually be no longer a cause for concern. There are two ways of using progesterone, whether it be endogenous, as in luteal phase stimulation, or exogenous, as in the use of progesterone in the follicular phase i.e. progestin primed ovarian stimulation. A literature search was carried out (until September 2016) on MEDLINE. The following text words were utilized to generate the list of citations: progestin primed ovarian stimulation, luteal phase stimulation, luteal stimulation, duostim, double stimulation, random start. Articles and their references were then examined in order to identify other potential studies. All of the articles are reported in this review. The use of progesterone during ovarian stimulation is effective in blocking the LH surge, whether endogenous or exogenous, and it does not affect the number of oocytes collected or the quality of the embryos obtained. Its main constraint is that it requires total freezing and delayed transfer. A variety of stimulation protocols can be derived from these two methods, and their implications are discussed, from fertility preservation to ovarian response profiles to organization for the patients and clincs. These new regimens enable more flexibility and are of emerging interest in daily practice. However, their medical and economic significance remains to be demonstrated. The use of luteal phase or follicular phase protocols with progestins could rapidly develop in the context of oocyte donation and fertility preservation not related to oncology. Their place could develop even more in the general population of patients in IVF programs. The strategy of total freezing continues to develop, thanks to technical improvements, in particular vitrification and PGS on blastocysts, and thanks to studies showing improvements in embryo implantation when the transfer take place far removed from the hormonal changes caused by ovarian stimulation. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com
Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation.

PubMed

Monte-Silva, Katia; Kuo, Min-Fang; Hessenthaler, Silvia; Fresnoza, Shane; Liebetanz, David; Paulus, Walter; Nitsche, Michael A

2013-05-01

Non-invasive brain stimulation enables the induction of neuroplasticity in humans, however, with so far restricted duration of the respective cortical excitability modifications. Conventional anodal transcranial direct current stimulation (tDCS) protocols including one stimulation session induce NMDA receptor-dependent excitability enhancements lasting for about 1 h. We aimed to extend the duration of tDCS effects by periodic stimulation, consisting of two stimulation sessions, since periodic stimulation protocols are able to induce neuroplastic excitability alterations stable for days or weeks, termed late phase long term potentiation (l-LTP), in animal slice preparations. Since both, l-LTP and long term memory formation, require gene expression and protein synthesis, and glutamatergic receptor activity modifications, l-LTP might be a candidate mechanism for the formation of long term memory. The impact of two consecutive tDCS sessions on cortical excitability was probed in the motor cortex of healthy humans, and compared to that of a single tDCS session. The second stimulation was applied without an interval (temporally contiguous tDCS), during the after-effects of the first stimulation (during after-effects; 3, or 20 min interval), or after the after-effects of the first stimulation had vanished (post after-effects; 3 or 24 h interval). The during after-effects condition resulted in an initially reduced, but then relevantly prolonged excitability enhancement, which was blocked by an NMDA receptor antagonist. The other conditions resulted in an abolishment, or a calcium channel-dependent reversal of neuroplasticity. Repeated tDCS within a specific time window is able to induce l-LTP-like plasticity in the human motor cortex. Copyright © 2013 Elsevier Inc. All rights reserved.
Large Higgs-electron Yukawa coupling in 2HDM

NASA Astrophysics Data System (ADS)

Dery, Avital; Frugiuele, Claudia; Nir, Yosef

2018-04-01

The present upper bound on κ e , the ratio between the electron Yukawa coupling and its Standard Model value, is of O(600) . We ask what would be the implications in case that κ e is close to this upper bound. The simplest extension that allows for such enhancement is that of two Higgs doublet models (2HDM) without natural flavor conservation. In this framework, we find the following consequences: (i) Under certain conditions, measuring κ e and κ V would be enough to predict values of Yukawa couplings for other fermions and for the H and A scalars. (ii) In the case that the scalar potential has a softly broken Z 2 symmetry, the second Higgs doublet must be light, but if there is hard breaking of the symmetry, the second Higgs doublet can be much heavier than the electroweak scale and still allow the electron Yukawa coupling to be very different from its SM value. (iii) CP must not be violated at a level higher than O(0.01/{κ}_e) in both the scalar potential and the Yukawa sector. (iv) LHC searches for e + e - resonances constrain this scenario in a significant way. Finally, we study the implications for models where one of the scalar doublets couples only to the first generation, or only to the third generation.
Post-translational modification and stability of low molecular weight cyclin E.

PubMed

Mull, B B; Cox, J; Bui, T; Keyomarsi, K

2009-09-03

Our laboratory has previously described the presence of five tumor-specific low molecular weight isoforms of cyclin E in both tumor cell lines and breast cancer patient biopsies. We have also shown that one of these low forms arises from an alternate start site, whereas the other four appear as two sets of doublets following cleavage through an elastase-like enzyme. However, the origin of both sets of doublets was unknown. Here, we demonstrate that the larger isoform of each doublet is the result of phosphorylation at a key degradation site. Through site-directed mutagenesis of different phosphorylation sites within the cyclin E protein, we discovered that phosphorylation of threonine 395 is responsible for generating the larger isoform of each doublet. Because phosphorylation of threonine 395 has been linked to the proteasome-mediated degradation of full length cyclin E, we examined the stability of T395A phospho-mutants in both non-tumorigenic mammary epithelial cells and tumor cells. The results revealed that the low molecular weight isoforms appear to be stable in both a tumor cell line and a non-tumor forming cell line regardless of the presence of this critical phosphorylation site. The stability of low molecular weight cyclin E may have implications for both tumorigenesis and treatment of tumors expressing them.
Fe II fluorescence and anomalous C IV doublet intensities in symbiotic novae

NASA Technical Reports Server (NTRS)

Michalitsianos, A. G.; Kafatos, M.; Meier, S. R.

1992-01-01

The variation of absolute intensities of Bowen-excited Fe II emission in the symbiotic stars RR Tel, RX Pup, and AG Peg is examined. The C IV doublet intensity ratios in RR Tel were not anomalous between 1979 and 1989, and the ratio had typical values within the optically thin range. The intensity of individual Fe II Bowen-excited lines is correlated with the C IV 1548.2 A flux, suggesting the presence of a foreground Fe II region in which fluorescent-excited material responds to flux variations of C IV 1548.2 A. In RX Pup the combined fluxes of Fe II Bowen-pumped lines can account for an appreciable fraction of the flux deficit in the C IV 1548.2 A line when the C IV doublet ratio is less than the optically thick limit of unity. The Fe II Bowen lines in RX Pup exhibit a velocity range from 0 to 80 km/s, where several strong Fe II emission lines correspond to deep absorption structure in the C IV 1548.2 A line profile. In AG Peg and C IV 1548.2 A flux deficit cannot be explained by Fe II fluorescent absorption alone when the C IV doublet ratio anomaly is at an extreme.
Effect of ageing on the force development in tetanic contractions of motor units in rat medial gastrocnemius muscle.

PubMed

Łochyński, Dawid; Kaczmarek, Dominik; Krutki, Piotr; Celichowski, Jan

2010-09-01

The purpose of this study was to determine the effect of ageing on the rate of force generation of motor units, and the mechanical efficiency of contraction produced by a doublet discharge. The study was carried out on isolated motor units of rat medial gastrocnemius muscle of young (5-10 mo) and two groups of old (24-25 and 28-30 mo) Wistar rats. Motor units were classified into the fast fatigable (FF), fast resistant (FR) and slow (S) ones. The force output and rate of force development were determined for non-doublet unfused tetanic contractions evoked by a series of a constant-rate trains of pulses and corresponding doublet contractions starting with an initial brief interpulse interval of 5 ms, and for maximal tetanic contraction. In FF motor units the rate of force development and the force produced by the doublet discharge increased transiently at the age of 24-25 mo, while in S and FR motor units this increase was observed at the age of 28-30 mo. Age-related decrease in the rate of force development of skeletal muscle cannot be attributed to a decline in efficiency of force production by functioning motor units. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Highly efficient gene transfer using a retroviral vector into murine T cells for preclinical chimeric antigen receptor-expressing T cell therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kusabuka, Hotaka; Fujiwara, Kento; Tokunaga, Yusuke

Adoptive immunotherapy using chimeric antigen receptor-expressing T (CAR-T) cells has attracted attention as an efficacious strategy for cancer treatment. To prove the efficacy and safety of CAR-T cell therapy, the elucidation of immunological mechanisms underlying it in mice is required. Although a retroviral vector (Rv) is mainly used for the introduction of CAR to murine T cells, gene transduction efficiency is generally less than 50%. The low transduction efficiency causes poor precision in the functional analysis of CAR-T cells. We attempted to improve the Rv gene transduction protocol to more efficiently generate functional CAR-T cells by optimizing the period ofmore » pre-cultivation and antibody stimulation. In the improved protocol, gene transduction efficiency to murine T cells was more than 90%. In addition, almost all of the prepared murine T cells expressed CAR after puromycin selection. These CAR-T cells had antigen-specific cytotoxic activity and secreted multiple cytokines by antigen stimulation. We believe that our optimized gene transduction protocol for murine T cells contributes to the advancement of T cell biology and development of immunotherapy using genetically engineered T cells. - Highlights: • We established highly efficient gene transduction protocols for murine T cells. • CD8{sup +} CAR-T cells had antigen-specific cytotoxic activity. • CD4{sup +} CAR-T cells secreted multiple cytokines by antigen stimulation. • This finding can contribute to the development of T-cell biology and immunotherapy.« less
Effects of stimulation technique, anatomical region and time on human sweat lipid mediator profiles.

USDA-ARS?s Scientific Manuscript database

Few studies compare sampling protocol effect on sweat composition. Here we evaluate the impact of sweat stimulation mode and site of collection on lipid mediator composition. Sweat from healthy males (n = 7) was collected weekly for three weeks from the volar forearm following either pilocarpine ion...
A Short Term Therapy Approach to Processing Trauma: Art Therapy and Bilateral Stimulation

ERIC Educational Resources Information Center

Tripp, Tally

2007-01-01

This article describes a dynamic, short-term art therapy approach that has been developed for the treatment of trauma related disorders. Using a modified Eye Movement Desensitization and Reprocessing (EMDR) protocol with alternating tactile and auditory bilateral stimulation, associations are rapidly brought to conscious awareness and expressed in…
The role of the dorsolateral prefrontal cortex in early threat processing: a TMS study.

PubMed

Sagliano, Laura; D'Olimpio, Francesca; Panico, Francesco; Gagliardi, Serena; Trojano, Luigi

2016-12-01

Previous studies demonstrated that excitatory (high frequency) offline transcranial magnetic stimulation (TMS) over the left and right dorsolateral prefrontal cortex (DLPFC) modulates attention allocation on threatening stimuli in non-clinical samples. These studies only employed offline TMS protocol that did not allow investigating the effect of the stimulation on the early stage of threat processing. In this study, the role of the right and left dorsolateral prefrontal cortex in early threat processing was investigated in high and low anxious individuals by means of an inhibitory single-pulse online TMS protocol. Our results demonstrated the role of the left DLPFC in an early stage of threat processing and that this effect is modulated by individuals' anxiety level. The inhibitory stimulation of the left DLPFC determined a disengagement bias in high anxious individuals, while the same stimulation determined an attentional avoidance in low anxious individuals. The findings of the present study suggest that right and left DLPFC are differently involved in early threat processing of healthy individuals. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
Neuropeptide Y stimulation as primary target for preventive measures of maladaptative cardiovascular reactions in occupational chronic stress exposure.

PubMed

Ciumaşu-Rîmbu, Mălina; Popa, Livia; Vulpoi, Carmen

2012-01-01

Chronic stress may produce a decrease in central NPY expression and subjects exposed to it may prove hypersensitivity to a novel stressor with dysfunctions in the NPY system and cardiovascular maladaptation to stress, even hypertension. Upregulation of NPY expression may contribute to successful behavioral adaptation to stress by reducing cardiovascular tone and suppressing anxious behaviors. Adaptogens, a new class of metabolic regulators stimulate NPY expression and release. The aim of this study is to increase tolerance and adaptation to stress of hypersensitive to novel stressor, occupational chronic stress exposed subjects with cardiovascular maladaptation to mild new stressor using adaptogens as part of prevention protocol. 40 military personnel with known cardiostressor reactional mode and occupational chronic stress exposure were exposed to mild novel stressor: occupational medicine routine evaluation and clinically assessed for maladaptative cardiovascular response prior and before application of 30 day prevention protocol. Employees were randomly split in two groups, one receiving standard prevention protocol (lifestyle counseling) plus adaptogens in multiple dose administration, twice daily and the other receiving only standard prevention protocol. We found significant statistic differences in all cardiovascular parameters in adaptogen group and only in diastolic blood pressure in control group. Adaptogens could be an important factor in successful prevention protocols of chronic occupational stress dysfunctions involving NPY systems.
Auditory stimulation with music influences the geometric indices of heart rate variability in response to the postural change maneuver.

PubMed

de Castro, Bianca C R; Guida, Heraldo L; Roque, Adriano L; de Abreu, Luiz Carlos; Ferreira, Celso; Marcomini, Renata S; Monteiro, Carlos B M; Adami, Fernando; Ribeiro, Viviane F; Fonseca, Fernando L A; Santos, Vilma N S; Valenti, Vitor E

2014-01-01

It is poor in the literature the behavior of the geometric indices of heart rate variability (HRV) during the musical auditory stimulation. The objective is to investigate the acute effects of classic musical auditory stimulation on the geometric indexes of HRV in women in response to the postural change maneuver (PCM). We evaluated 11 healthy women between 18 and 25 years old. We analyzed the following indices: Triangular index, Triangular interpolation of RR intervals and Poincarι plot (standard deviation of the instantaneous variability of the beat-to beat heart rate [SD1], standard deviation of long-term continuous RR interval variability and Ratio between the short - and long-term variations of RR intervals [SD1/SD2] ratio). HRV was recorded at seated rest for 10 min. The women quickly stood up from a seated position in up to 3 s and remained standing still for 15 min. HRV was recorded at the following periods: Rest, 0-5 min, 5-10 min and 10-15 min during standing. In the second protocol, the subject was exposed to auditory musical stimulation (Pachelbel-Canon in D) for 10 min at seated position before standing position. Shapiro-Wilk to verify normality of data and ANOVA for repeated measures followed by the Bonferroni test for parametric variables and Friedman's followed by the Dunn's posttest for non-parametric distributions. In the first protocol, all indices were reduced at 10-15 min after the volunteers stood up. In the protocol musical auditory stimulation, the SD1 index was reduced at 5-10 min after the volunteers stood up compared with the music period. The SD1/SD2 ratio was decreased at control and music period compared with 5-10 min after the volunteers stood up. Musical auditory stimulation attenuates the cardiac autonomic responses to the PCM.
Growth Hormone Supplementation in the Luteal Phase Before Microdose GnRH Agonist Flare Protocol for In Vitro Fertilization.

PubMed

Dunne, Caitlin; Seethram, Ken; Roberts, Jeffrey

2015-09-01

Growth hormone (GH) acts in both early and late follicular development to stimulate the proliferation and differentiation of granulosa cells and to increase the production of estradiol in animal and human ovaries. Investigators have therefore explored GH supplementation to improve outcomes in women undergoing in vitro fertilization, with the greatest interest in women with diminished ovarian reserve. Recent meta-analyses indicate that GH supplementation can be beneficial for poor responders undergoing IVF. In most studies, GH has been given concomitantly with gonadotropins during the follicular phase; this may not be optimal, since follicular recruitment begins during the preceding luteal phase. We therefore wished to examine the effect of GH supplementation in the luteal phase before controlled ovarian stimulation (COH) with a microdose GnRH agonist flare (MDF) protocol in women undergoing in vitro fertilization. We performed a retrospective matched case-control study of patients undergoing treatment at a private IVF facility between June 2012 and July 2013. Patients identified as poor responders to COH were offered adjuvant GH treatment as part of their ovarian stimulation regimen. The patients in the experimental group chose to take GH, 3.33 mg daily by subcutaneous injection for 14 days, before starting COH. All patients had an MDF stimulation protocol using 450 IU of follicle stimulating hormone (FSH) daily. A total of 42 women were included in the study. There were 14 women in the experimental group (GH) and 28 controls (C) matched for age, BMI, and day 3 FSH level. There was no difference between the groups in clinical pregnancy rate (GH = 29%, C = 32%, P = 0.99), number of mature oocytes retrieved (GH = 2.5, C = 5.0, P = 0.13), cycle cancellation rate (GH = 21%, C = 14%, P = 0.88), duration of COH (GH = 10.1, C = 10.1, P = 0.93), or mean peak estradiol level (GH = 4174 pmol/L, C = 5105 pmol/L, P = 0.44). The administration of growth hormone during the luteal phase before a microdose GnRH agonist flare protocol for in vitro fertilization did not improve outcomes in "poor responder" patients.
Design and tolerance analysis of two null corrector designs for the Space Telescope fine guidance aspheric collimating mirror

NASA Technical Reports Server (NTRS)

Friedman, I.; Casas, R. E.

1982-01-01

The collimating mirror within the Fine Guidance Subsystem of the Space Telescope's Pointing Control System is aspherized in order to correct the pupil aberration. A null corrector is needed to test the collimating mirror in autocollimation. Triplet and doublet null corrector designs are subjected to tolerance sensitivity analyses, and the doublet design is chosen despite its more restricted tolerances because of its compactness and simplicity.
A search for close-mass lepton doublet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riles, J.K.

1989-04-01

Described is a search for a heavy charged lepton with an associated neutrino of nearly the same mass, together known as a close-mass lepton doublet. The search is conducted in e/sup +/e/sup/minus// annihilation data taken with the Mark II detector at a center-of-mass energy of 29 GeV. In order to suppress contamination from conventional two-photon reactions, the search applies a novel, radiative-tagging technique. Requiring the presence of an isolated, energetic photon allows exploration for lepton doublets with a mass splitting smaller than that previously accessible to experiment. No evidence for such a new lepton has been found, enabling limits tomore » be placed on allowed mass combinations. Mass differences as low as 250-300 MeV are excluded for charged lepton masses up to 10 GeV. 78 refs., 64 figs., 8 tabs.« less
Miniature optical planar camera based on a wide-angle metasurface doublet corrected for monochromatic aberrations

PubMed Central

Arbabi, Amir; Arbabi, Ehsan; Kamali, Seyedeh Mahsa; Horie, Yu; Han, Seunghoon; Faraon, Andrei

2016-01-01

Optical metasurfaces are two-dimensional arrays of nano-scatterers that modify optical wavefronts at subwavelength spatial resolution. They are poised to revolutionize optics by enabling complex low-cost systems where multiple metasurfaces are lithographically stacked and integrated with electronics. For imaging applications, metasurface stacks can perform sophisticated image corrections and can be directly integrated with image sensors. Here we demonstrate this concept with a miniature flat camera integrating a monolithic metasurface lens doublet corrected for monochromatic aberrations, and an image sensor. The doublet lens, which acts as a fisheye photographic objective, has a small f-number of 0.9, an angle-of-view larger than 60° × 60°, and operates at 850 nm wavelength with 70% focusing efficiency. The camera exhibits nearly diffraction-limited image quality, which indicates the potential of this technology in the development of optical systems for microscopy, photography, and computer vision. PMID:27892454

Collider signatures of flavorful Higgs bosons

DOE PAGES

Altmannshofer, Wolfgang; Eby, Joshua; Gori, Stefania; ...

2016-12-30

Motivated by our limited knowledge of the Higgs couplings to the first two generation fermions, we analyze the collider phenomenology of a class of two Higgs doublet models (2HDMs) with a nonstandard Yukawa sector. One Higgs doublet is mainly responsible for the masses of the weak gauge bosons and the third-generation fermions, while the second Higgs doublet provides mass for the lighter fermion generations. The characteristic collider signatures of this setup differ significantly from well-studied 2HDMs with natural flavor conservation, flavor alignment, or minimal flavor violation. New production mechanisms for the heavy scalar, pseudoscalar, and charged Higgs involving second-generation quarksmore » can become dominant. The most interesting decay modes include H/A → cc,tc,μμ,τμ and H ± → cb,cs,μν. As a result, searches for low-mass dimuon resonances are currently among the best probes of the heavy Higgs bosons in this setup.« less
Structural evolution across the insulator-metal transition in oxygen-deficient BaTiO 3-δ studied using neutron total scattering and Rietveld analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, I.-K.; Lee, Seunghun; Jeong, Se-Young

2011-08-29

Oxygen-deficient BaTiO 3-δ exhibits an insulator-metal transition with increasing δ. We performed neutron total scattering measurements to study structural evolution across an insulator-metal transition in BaTiO 3-δ. Despite its significant impact on resistivity, slight oxygen reduction (δ=0.09) caused only a small disturbance on the local doublet splitting of Ti-O bond. This finding implies that local polarization is well preserved under marginal electric conduction. In the highly oxygen-deficient metallic state (δ=0.25), however, doublet splitting of the Ti-O bond became smeared. The smearing of the local Ti-O doublet is complemented with long-range structural analysis and demonstrates that the metallic conduction in themore » highly oxygen-reduced BaTiO 3-δ is due to the appearance of nonferroelectric cubic lattice.« less
Miniature optical planar camera based on a wide-angle metasurface doublet corrected for monochromatic aberrations

NASA Astrophysics Data System (ADS)

Arbabi, Amir; Arbabi, Ehsan; Kamali, Seyedeh Mahsa; Horie, Yu; Han, Seunghoon; Faraon, Andrei

2016-11-01

Optical metasurfaces are two-dimensional arrays of nano-scatterers that modify optical wavefronts at subwavelength spatial resolution. They are poised to revolutionize optics by enabling complex low-cost systems where multiple metasurfaces are lithographically stacked and integrated with electronics. For imaging applications, metasurface stacks can perform sophisticated image corrections and can be directly integrated with image sensors. Here we demonstrate this concept with a miniature flat camera integrating a monolithic metasurface lens doublet corrected for monochromatic aberrations, and an image sensor. The doublet lens, which acts as a fisheye photographic objective, has a small f-number of 0.9, an angle-of-view larger than 60° × 60°, and operates at 850 nm wavelength with 70% focusing efficiency. The camera exhibits nearly diffraction-limited image quality, which indicates the potential of this technology in the development of optical systems for microscopy, photography, and computer vision.
Chiral U(1) flavor models and flavored Higgs doublets: the top FB asymmetry and the W jj

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ko, P.; Omura, Yuji; Yu, Chaehyun

2012-01-01

We present U(1) flavor models for leptophobic Z' with flavor dependent couplings to the right-handed up-type quarks in the Standard Model (SM), which can accommodate the recent data on the top forward-backward (FB) asymmetry and the dijet resonance associated with a W boson reported by CDF Collaboration. Such flavor-dependent leptophobic charge assignments generally require extra chiral fermions for anomaly cancellation. Also the chiral nature of U(1)' flavor symmetry calls for new U(1)'-charged Higgs doublets in order for the SM fermions to have realistic renormalizable Yukawa couplings. The stringent constraints from the top FB asymmetry at the Tevatron and the samemore » sign top pair production at the LHC can be evaded due to contributions of the extra Higgs doublets. We also show that the extension could realize cold dark matter candidates.« less
Modification of the Douglas Neumann program to improve the efficiency of predicting component interference and high lift characteristics

NASA Technical Reports Server (NTRS)

Bristow, D. R.; Grose, G. G.

1978-01-01

The Douglas Neumann method for low-speed potential flow on arbitrary three-dimensional lifting bodies was modified by substituting the combined source and doublet surface paneling based on Green's identity for the original source panels. Numerical studies show improved accuracy and stability for thin lifting surfaces, permitting reduced panel number for high-lift devices and supercritical airfoil sections. The accuracy of flow in concave corners is improved. A method of airfoil section design for a given pressure distribution, based on Green's identity, was demonstrated. The program uses panels on the body surface with constant source strength and parabolic distribution of doublet strength, and a doublet sheet on the wake. The program is written for the CDC CYBER 175 computer. Results of calculations are presented for isolated bodies, wings, wing-body combinations, and internal flow.
Fluctuations and All-In-All-Out Ordering in Dipole-Octupole Nd2Zr2O7

NASA Astrophysics Data System (ADS)

Lhotel, E.; Petit, S.; Guitteny, S.; Florea, O.; Ciomaga Hatnean, M.; Colin, C.; Ressouche, E.; Lees, M. R.; Balakrishnan, G.

2015-11-01

By means of neutron scattering and magnetization measurements down to 90 mK, we determine the magnetic ground state of the spin-ice candidate Nd2Zr2O7. We show that, despite ferromagnetic interactions, Nd2Zr2O7 undergoes a transition around 285 mK towards an all-in-all-out antiferromagnetic state, with a strongly reduced ordered magnetic moment. We establish the (H ,T ) phase diagram in the three directions of the applied field and reveal a metamagnetic transition around 0.1 T, associated with an unexpected shape of the magnetization curves. We propose that this behavior results from the peculiar nature of the Nd3 + doublet, a dipolar-octupolar doublet, different from the standard Kramers doublet studied to date, thus revealing the importance of multipolar correlations in the properties of pyrochlore oxides.
Insect-machine Hybrid System: Remote Radio Control of a Freely Flying Beetle (Mercynorrhina torquata).

PubMed

Vo Doan, T Thang; Sato, Hirotaka

2016-09-02

The rise of radio-enabled digital electronic devices has prompted the use of small wireless neuromuscular recorders and stimulators for studying in-flight insect behavior. This technology enables the development of an insect-machine hybrid system using a living insect platform described in this protocol. Moreover, this protocol presents the system configuration and free flight experimental procedures for evaluating the function of the flight muscles in an untethered insect. For demonstration, we targeted the third axillary sclerite (3Ax) muscle to control and achieve left or right turning of a flying beetle. A thin silver wire electrode was implanted on the 3Ax muscle on each side of the beetle. These were connected to the outputs of a wireless backpack (i.e., a neuromuscular electrical stimulator) mounted on the pronotum of the beetle. The muscle was stimulated in free flight by alternating the stimulation side (left or right) or varying the stimulation frequency. The beetle turned to the ipsilateral side when the muscle was stimulated and exhibited a graded response to an increasing frequency. The implantation process and volume calibration of the 3 dimensional motion capture camera system need to be carried out with care to avoid damaging the muscle and losing track of the marker, respectively. This method is highly beneficial to study insect flight, as it helps to reveal the functions of the flight muscle of interest in free flight.
Metalinguistic Knowledge in L2 Task Performance: A Verbal Protocol Analysis

ERIC Educational Resources Information Center

Roehr, Karen

2006-01-01

This paper reports a study employing stimulated recall protocols to investigate how L1 English-speaking learners of L2 German use their metalinguistic knowledge during the resolution of selected form-focused tasks. Verbal report data from 10 university level learners were analysed to gain insight into explicit knowledge in action during controlled…
A proposed draft protocol for the European Convention on Biomedicine relating to research on the human embryo and fetus.

PubMed

Byk, J C

1997-02-01

The objective of this paper is to stimulate academic debate on embryo and fetal research from the perspective of the drafting of a protocol to the European Convention on Biomedicine. The Steering Committee on Bioethics of the Council of Europe was mandated to draw up such a protocol and for this purpose organised an important symposium on reproductive technologies and embryo research, in Strasbourg from the 16th to the 18th of December 1996.
Sustained reduction in blood pressure from electrical activation of the baroreflex is mediated via the central pathway of unmyelinated baroreceptors.

PubMed

Turner, Michael J; Kawada, Toru; Shimizu, Shuji; Sugimachi, Masaru

2014-06-13

This study aims to identify the contribution of myelinated (A-fiber) and unmyelinated (C-fiber) baroreceptor central pathways to the baroreflex control of sympathetic nerve activity and arterial pressure. Two binary white noise stimulation protocols were used to electrically stimulate the aortic depressor nerve and activate reflex responses from either A-fiber (3 V, 20-100 Hz) or C-fiber (20 V, 0-10 Hz) baroreceptor in anesthetized Sprague-Dawley rats (n=10). Transfer function analysis was performed between stimulation and sympathetic nerve activity (central arc), sympathetic nerve activity and arterial pressure (peripheral arc), and stimulation and arterial pressure (Stim-AP arc). The central arc transfer function from nerve stimulation to splanchnic sympathetic nerve activity displayed derivative characteristics for both stimulation protocols. However, the modeled steady-state gain (0.28 ± 0.04 vs. 4.01 ± 0.2%·Hz(-1), P<0.001) and coherence at 0.01 Hz (0.44 ± 0.05 vs. 0.81 ± 0.03, P<0.05) were significantly lower for A-fiber stimulation compared with C-fiber stimulation. The slope of the dynamic gain was higher for A-fiber stimulation (14.82 ± 1.02 vs. 7.21 ± 0.79 dB·decade(-1), P<0.001). The steady-state gain of the Stim-AP arc was also significantly lower for A-fiber stimulation compared with C-fiber stimulation (0.23 ± 0.05 vs. 3.05 ± 0.31 mmHg·Hz(-1), P<0.001). These data indicate that the A-fiber central pathway contributes to high frequency arterial pressure regulation and the C-fiber central pathway provides more sustained changes in sympathetic nerve activity and arterial pressure. A sustained reduction in arterial pressure from electrical stimulation of arterial baroreceptor afferents is likely mediated through the C-fiber central pathway. Copyright © 2014 Elsevier Inc. All rights reserved.
Midbrain Raphe Stimulation Improves Behavioral and Anatomical Recovery from Fluid-Percussion Brain Injury

PubMed Central

Carballosa Gonzalez, Melissa M.; Blaya, Meghan O.; Alonso, Ofelia F.; Bramlett, Helen M.

2013-01-01

Abstract The midbrain median raphe (MR) and dorsal raphe (DR) nuclei were tested for their capacity to regulate recovery from traumatic brain injury (TBI). An implanted, wireless self-powered stimulator delivered intermittent 8-Hz pulse trains for 7 days to the rat's MR or DR, beginning 4–6 h after a moderate parasagittal (right) fluid-percussion injury. MR stimulation was also examined with a higher frequency (24 Hz) or a delayed start (7 days after injury). Controls had sham injuries, inactive stimulators, or both. The stimulation caused no apparent acute responses or adverse long-term changes. In water-maze trials conducted 5 weeks post-injury, early 8-Hz MR and DR stimulation restored the rate of acquisition of reference memory for a hidden platform of fixed location. Short-term spatial working memory, for a variably located hidden platform, was restored only by early 8-Hz MR stimulation. All stimulation protocols reversed injury-induced asymmetry of spontaneous forelimb reaching movements tested 6 weeks post-injury. Post-mortem histological measurement at 8 weeks post-injury revealed volume losses in parietal-occipital cortex and decussating white matter (corpus callosum plus external capsule), but not hippocampus. The cortical losses were significantly reversed by early 8-Hz MR and DR stimulation, the white matter losses by all forms of MR stimulation. The generally most effective protocol, 8-Hz MR stimulation, was tested 3 days post-injury for its acute effect on forebrain cyclic adenosine monophosphate (cAMP), a key trophic signaling molecule. This procedure reversed injury-induced declines of cAMP levels in both cortex and hippocampus. In conclusion, midbrain raphe nuclei can enduringly enhance recovery from early disseminated TBI, possibly in part through increased signaling by cAMP in efferent targets. A neurosurgical treatment for TBI using interim electrical stimulation in raphe repair centers is suggested. PMID:22963112
Impact of Prefrontal Theta Burst Stimulation on Clinical Neuropsychological Tasks.

PubMed

Viejo-Sobera, Raquel; Redolar-Ripoll, Diego; Boixadós, Mercè; Palaus, Marc; Valero-Cabré, Antoni; Marron, Elena M

2017-01-01

Theta burst stimulation (TBS) protocols hold high promise in neuropsychological rehabilitation. Nevertheless, their ability to either decrease (continuous, cTBS) or increase (intermittent, iTBS) cortical excitability in areas other than the primary motor cortex, and their consistency modulating human behaviors with clinically relevant tasks remain to be fully established. The behavioral effects of TBS over the dorsolateral prefrontal cortex (dlPFC) are particularly interesting given its involvement in working memory (WM) and executive functions (EF), often impaired following frontal brain damage. We aimed to explore the ability of cTBS and iTBS to modulate WM and EF in healthy individuals, assessed with clinical neuropsychological tests (Digits Backward, 3-back task, Stroop Test, and Tower of Hanoi). To this end, 36 participants were assessed using the four tests 1 week prior to stimulation and immediately following a single session of either cTBS, iTBS, or sham TBS, delivered to the left dlPFC. No significant differences were found across stimulation conditions in any of the clinical tasks. Nonetheless, in some of them, active stimulation induced significant pre/post performance modulations, which were not found for the sham condition. More specifically, sham stimulation yielded improvements in the 3-back task and the Color, Color-Word, and Interference Score of the Stroop Test, an effect likely caused by task practice. Both, iTBS and cTBS, produced improvements in Digits Backward and impairments in 3-back task accuracy. Moreover, iTBS increased Interference Score in the Stroop Test in spite of the improved word reading and impaired color naming, whereas cTBS decreased the time required to complete the Tower of Hanoi. Differing from TBS outcomes reported for cortico-spinal measures on the primary motor cortex, our analyses did not reveal any of the expected performance differences across stimulation protocols. However, if one considers independently pre/post differences for each individual outcome measure and task, either one or both of the active protocols appeared to modulate WM and EF. We critically discuss the value, potential explanations, and some plausible interpretations for this set of subtle impacts of left dlPFC TBS in humans.
Impact of Prefrontal Theta Burst Stimulation on Clinical Neuropsychological Tasks

PubMed Central

Viejo-Sobera, Raquel; Redolar-Ripoll, Diego; Boixadós, Mercè; Palaus, Marc; Valero-Cabré, Antoni; Marron, Elena M.

2017-01-01

Theta burst stimulation (TBS) protocols hold high promise in neuropsychological rehabilitation. Nevertheless, their ability to either decrease (continuous, cTBS) or increase (intermittent, iTBS) cortical excitability in areas other than the primary motor cortex, and their consistency modulating human behaviors with clinically relevant tasks remain to be fully established. The behavioral effects of TBS over the dorsolateral prefrontal cortex (dlPFC) are particularly interesting given its involvement in working memory (WM) and executive functions (EF), often impaired following frontal brain damage. We aimed to explore the ability of cTBS and iTBS to modulate WM and EF in healthy individuals, assessed with clinical neuropsychological tests (Digits Backward, 3-back task, Stroop Test, and Tower of Hanoi). To this end, 36 participants were assessed using the four tests 1 week prior to stimulation and immediately following a single session of either cTBS, iTBS, or sham TBS, delivered to the left dlPFC. No significant differences were found across stimulation conditions in any of the clinical tasks. Nonetheless, in some of them, active stimulation induced significant pre/post performance modulations, which were not found for the sham condition. More specifically, sham stimulation yielded improvements in the 3-back task and the Color, Color-Word, and Interference Score of the Stroop Test, an effect likely caused by task practice. Both, iTBS and cTBS, produced improvements in Digits Backward and impairments in 3-back task accuracy. Moreover, iTBS increased Interference Score in the Stroop Test in spite of the improved word reading and impaired color naming, whereas cTBS decreased the time required to complete the Tower of Hanoi. Differing from TBS outcomes reported for cortico-spinal measures on the primary motor cortex, our analyses did not reveal any of the expected performance differences across stimulation protocols. However, if one considers independently pre/post differences for each individual outcome measure and task, either one or both of the active protocols appeared to modulate WM and EF. We critically discuss the value, potential explanations, and some plausible interpretations for this set of subtle impacts of left dlPFC TBS in humans. PMID:28867993
Ovarian reserve and response to stimulation in women undergoing fertility preservation according to malignancy type.

PubMed

Lefebvre, Tiphaine; Mirallié, Sophie; Leperlier, Florence; Reignier, Arnaud; Barrière, Paul; Fréour, Thomas

2018-05-02

Does ovarian reserve and ovarian response to ovarian stimulation in women with cancer undergoing oocyte vitrification for fertility preservation vary according to the type of malignancy? Retrospective cohort study including 105 women aged between 18 and 40 years, who were referred for fertility preservation (oocyte vitrification) between 2013 and 2016. The women were divided into three groups: breast cancer, lymphoma or other cancer. All of them had been recently diagnosed with cancer, with gonadotoxic treatment scheduled, and had oocyte vitrification after ovarian stimulation with antagonist protocol. Baseline antral follicle count and anti-Müllerian hormone were no different between women with breast cancer, lymphoma or other cancer. The number of cancelled cycles for poor ovarian response was similar between the groups. The number of FSH units per mature oocyte, the number of mature oocytes (metaphase II) retrieved, and the oocyte maturity rate were not significantly different between the three groups. As the type of cancer does not seem to significantly affect ovarian reserve and ovarian response to ovarian stimulation, our results do not support the relevance of integrating this parameter when establishing ovarian stimulation protocol for oocyte vitrification cycle in women with cancer. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Academic Performance Enhancement: A Qualitative Study of the Perceptions and Habits of Prescription Stimulant-Using College Students

ERIC Educational Resources Information Center

Aikins, Ross D.

2011-01-01

This study explores the developmental implications of cognitive enhancement among college students. Data comes from interviews with a purposive sample of licit and illicit users of stimulant medications at a highly selective West Coast University. A semistructured protocol revolved around students' habits and perceptions relating to stimulant…
GnRH antagonist, cetrorelix, for pituitary suppression in modern, patient-friendly assisted reproductive technology.

PubMed

Tur-Kaspa, Ilan; Ezcurra, Diego

2009-10-01

Gonadotropin-releasing hormone (GnRH) analogues are used routinely to prevent a premature luteinizing hormone (LH) surge in women undergoing assisted reproductive technology (ART) treatments. In contrast to GnRH agonists, antagonists produce rapid and reversible suppression of LH with no initial flare effect. To review the role of cetrorelix, the first GnRH antagonist approved for the prevention of premature LH surges during controlled ovarian stimulation in modern ART. A review of published literature on cetrorelix. Both multiple- and single-dose cetrorelix protocols were shown to be at least as effective as long GnRH agonist regimens for pituitary suppression in Phase II/III clinical trials. Furthermore, cetrorelix co-treatment resulted in similar live birth rates but a shorter duration of gonadotropin stimulation, a lower total gonadotropin dose requirement and lower incidence of ovarian hyperstimulation syndrome compared with long agonist regimens. A single-dose cetrorelix protocol further decreased the number of injections required. Preliminary studies have also produced promising data on the use of cetrorelix in modified ART protocols, such as frozen embryo transfer and donor oocyte recipient cycles. Cetrorelix offers a potential therapeutic alternative to GnRH agonists during controlled ovarian stimulation and has become an integral part of modern, patient-friendly reproductive medicine.
Lipidomic Components Alterations of Human Follicular Fluid Reveal the Relevance of Improving Clinical Outcomes in Women Using Progestin-Primed Ovarian Stimulation Compared to Short-Term Protocol.

PubMed

Wen, Xiaowei; Kuang, Yanping; Zhou, Lixia; Yu, Baofeng; Chen, Qiuju; Fu, Yonglun; Yan, Zheng; Guo, Haiyan; Lyu, Qifeng; Xie, Jun; Chai, Weiran

2018-05-21

BACKGROUND Increasing the success rate of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is a duty of clinicians that has made many seek a variety of protocols. This study was undertaken to use a liquid chromatography-mass spectrometry (LC-MS) to define the alterations of follicular fluid (FF) lipid metabolites in patients undergoing progestin-primed ovarian stimulation (PPOS) compared with short-term protocol, revealing potential correlations between the differentially expressed lipids and ameliorative clinical outcomes. MATERIAL AND METHODS Ninety-three infertile women undergoing IVF/ICSI treatment with PPOS (n=62) or a short-term protocol (n=31) were prospectively enrolled in a randomized controlled trial. FF samples were obtained from dominant follicles at the time of oocyte retrieval. Lipid metabolism profiles were analyzed using LC-MS. RESULTS Twelve lipids were found to be higher in patients treated with the PPOS protocol than in those receiving the short-term protocol, including triacylglycerols (TAG-34: 1+NH4, TAG-58: 0+NH4, TAG-64: 3+NH4, and TAG-64: 8+NH4), diacylglycerol DAG-38: 6+NH4, phosphatidylglycerols (PG-26: 0, PG-30: 2, and PG-40: 5), phosphatidylethanolamine PE-32: 2, lysophosphatidylethanolamine LPE-14: 1, lysophosphatidylinositol LPI-12: 0, and lysophosphatidylcholine LPC-16: 0. CONCLUSIONS Our data demonstrate that the PPOS protocol increases the levels of 12 lipids in FF, which reveals a strong association between the differentially elevated lipids and better IVF/ICSI outcomes.
Long-lasting desynchronization in rat hippocampal slice induced by coordinated reset stimulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tass, P. A.; Barnikol, U. B.; Department of Stereotaxic and Functional Neurosurgery, University of Cologne, D-50931 Cologne

2009-07-15

In computational models it has been shown that appropriate stimulation protocols may reshape the connectivity pattern of neural or oscillator networks with synaptic plasticity in a way that the network learns or unlearns strong synchronization. The underlying mechanism is that a network is shifted from one attractor to another, so that long-lasting stimulation effects are caused which persist after the cessation of stimulation. Here we study long-lasting effects of multisite electrical stimulation in a rat hippocampal slice rendered epileptic by magnesium withdrawal. We show that desynchronizing coordinated reset stimulation causes a long-lasting desynchronization between hippocampal neuronal populations together with amore » widespread decrease in the amplitude of the epileptiform activity. In contrast, periodic stimulation induces a long-lasting increase in both synchronization and amplitude.« less
A microcontroller-based implantable nerve stimulator used for rats.

PubMed

Sha, Hong; Zheng, Zheng; Wang, Yan; Ren, Chaoshi

2005-01-01

A microcontroller-based stimulator that can be flexible programmed after it has been implanted into a rat was studied. Programmability enables implanted stimulators to generate customized, complex protocols for experiments. After implantation, a coded light pulse train that contains information of specific identification will unlock a certain stimulator. If a command that changing the parameters is received, the microcontroller will update its flash memory after it affirms the commands. The whole size of it is only 1.6 cubic centimeters, and it can work for a month. The devices have been successfully used in animal behavior experiments, especially on rats.
Physiologic parameters associated with sexual arousal in women with incomplete spinal cord injuries.

PubMed

Sipski, M L; Alexander, C J; Rosen, R C

1997-03-01

To compare the physiologic sexual responses of women with incomplete spinal cord injuries (SCIs) with and without preservation of the ability to perceive T11-L2 pinprick sensation. Controlled laboratory-based analysis of responses to varying combinations of audiovisual erotic stimulation, manual genital stimulation, and performance of a distracting task coupled with manual genital stimulation. The sexual physiology laboratory at our freestanding rehabilitation hospital. A volunteer sample of 17 women with incomplete SCIs. Two 78-minute protocols using 6-minute baselines alternating with 12-minute testing conditions. One protocol was designed to study the effects of psychogenic and psychogenic combined with manual sexual stimulation, while the other was designed to examine the effects of genital sexual stimulation performed in conjunction with a distracting task. Vaginal pulse amplitude, subjective arousal, heart rate, respiratory rate, and blood pressure. Subjective arousal increased in both groups of subjects with isolated audiovisual erotic stimulation; however, only those subjects with the ability to perceive T11-L2 pinprick sensation had concomitant increases in vaginal pulse amplitude. In contrast, when manual genital stimulation was added to the audiovisual erotic stimulation, both groups of subjects developed increases in vaginal pulse amplitude, whereas only those subjects with the ability to perceive T11-L2 demonstrated a further increase in their level of subjective arousal. Performance of manual genital stimulation in conjunction with a distracting task resulted in significantly increased vaginal pulse amplitude and arousal level only in those subjects with preservation of the ability to perceive T11-L2 pinprick sensation. With the changeover to masturbation, neither group of subjects developed significant increases in vaginal pulse amplitude. During masturbation, both groups of subjects had increases in their level of sexual arousal; however, only those subjects with T11-L2 pinprick preservation had a significant increase. Women with preservation of the ability to perceive T11-L2 pinprick sensation tended to maintain the ability for psychogenic genital vasocongestion. Psychogenic protocol results showed that all subjects appeared to develop reflex genital vasocongestion when manual stimulation was added to audiovisual erotic stimulation. Manual genital stimulation in conjunction with the performance of a distracting task only resulted in increased vaginal pulse amplitudes in those subjects with preservation of T11-L2 pinprick sensation. We believe that this was due to increased subjective sexual arousal and that the reason all subjects did not develop increased genital vasocongestion under these conditions was due to poor hand function. Further research examining women with lower levels of SCI is necessary to understand the neurophysiology of female sexual response after SCI.

Alpha decay hindrance factors and reflection asymmetry in nuclei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheline, R.K.; Bossinga, B.B.

1991-07-01

All available hindrance factors of alpha transitions to low-lying negative-parity states in doubly even nuclei, to odd-{ital A} parity doublets and to doubly odd parity doublet bands, are used to study the systematics of reflection asymmetry in the {ital A}{similar to}218--230 region. Special attention is given to the polarization effect of the odd particle in increasing reflection asymmetry and therefore decreasing hindrance factors to the opposite parity states of octupole bands.
Bsrightarrowtau+tau- decay in the general two Higgs doublet

NASA Astrophysics Data System (ADS)

Iltan, Erhan Onur; Turan, Gursevil

2002-11-01

We study the exclusive decay Bsrightarrowtau+tau- in the general two Higgs doublet model. We analyse the dependencies of the branching ratio on the model parameters, including the leading order QCD corrections. We found that there is an enhancement in the branching ratio, especially for rtb = bar xiN,ttU/bar xiN,bbD > 1 case. Further, the neutral Higgs effects are detectable for large values of the parameter bar xiN,tautauD.
Dynamical relaxation in 2HDM models

NASA Astrophysics Data System (ADS)

Lalak, Zygmunt; Markiewicz, Adam

2018-03-01

Dynamical relaxation provides an interesting solution to the hierarchy problem in face of the missing signatures of any new physics in recent experiments. Through a dynamical process taking place in the inflationary phase of the Universe it manages to achieve a small electroweak scale without introducing new states observable in current experiments. Appropriate approximation makes it possible to derive an explicit formula for the final vevs in the double-scanning scenario extended to a model with two Higgs doublets (2HDM). Analysis of the relaxation in the 2HDM confirms that in a general case it is impossible to keep vevs of both scalars small, unless fine-tuning is present or additional symmetries are cast upon the Lagrangian. Within the slightly constrained variant of the 2HDM, where odd powers of the fields’ expectation values are not present (which can be easily enforced by requiring that the doublets have different gauge transformations or by imposing a global symmetry) it is shown that the difference between the vevs of two scalars tends to be proportional to the cutoff. The analysis of the relaxation in 2HDM indicates that in a general case the relaxation would be stopped by the first doublet that gains a vev, with the other one remaining vevless with a mass of the order of the cutoff. This happens to conform with the inert doublet model.
Design of a dee vacuum vessel for Doublet III

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davis, L.G.

1983-04-01

The Doublet III tokamak is to be modified wherein the original 'doublet' plasma containment vacuum vessel will be exchanged with one of a large dee-shaped cross section. The basic dimensions of the dee vessel will allow plasmas of 1.7-m major radius, 0.7-m minor radius, and a vertical elongation of 1.8. Installation of a large dee vessel in Doublet III is made possible by the demountable toroidal field coils and the large, low-ripple volume they include. Ripple at the plasma edge will be less than one percent. The plasma parameters affecting the design of the vessel will be reviewed including plasmamore » current, power, disruption time, allowable error field, impurity control techniques, pulse length, and limiter schemes. A driving requirement for the design of the vessel is to maximize the access to the plasma for auxiliary heating (both neutral beam injection and radio frequency heating), diagnostics, developmental component and material testing, and pumping. The dee vessel is structurally designed along the same lines as the present vessel: an Inconel 625, all-welded, continuous chamber in a corrugated sandwich construction. An overview of the vessel design and its solutions to the design criteria will be presented. An overview will also be presented of the entire modification project which includes replacement of some coils, and addition of support structure, limiters and vessel armor, and power system components.« less
An Improved Red Spectrum of the Methane or T Dwarf SDSS 1624+0029: The Role of the Alkali Metals.

PubMed

Liebert; Reid; Burrows; Burgasser; Kirkpatrick; Gizis

2000-04-20

A Keck II low-resolution spectrum shortward of 1 µm is presented for SDSS 1624+0029, the first field methane or T dwarf discovered in the Sloan Digital Sky Survey. Significant flux is detected down to the spectrum's short-wavelength limit of 6200 Å. The spectrum exhibits a broad absorption feature centered at 7700 Å, which we interpret as the K i lambdalambda7665, 7699 resonance doublet. The observed flux declines shortward of 7000 Å, most likely owing to the red wing of the Na i doublet. Both Cs i doublet lines are detected more strongly than in an earlier red spectrum. Neither Li i absorption nor Halpha emission are detected. An exploratory model fit to the spectrum suggests that the shape of the red spectrum can be primarily accounted for by the broad wings of the K i and Na i doublets. This behavior is consistent with the argument proffered by Burrows, Marley, & Sharp that strong alkali absorption is principally responsible for depressing T dwarf spectra shortward of 1 µm. In particular, there seems no compelling reason at this time to introduce dust or an additional opacity source in the atmosphere of the Sloan object. The width of the K i and strengths of the Cs i lines also indicate that the Sloan object is warmer than Gl 229B.
Surface-distributed low-frequency asynchronous stimulation delays fatigue of stimulated muscles.

PubMed

Maneski, Lana Z Popović; Malešević, Nebojša M; Savić, Andrej M; Keller, Thierry; Popović, Dejan B

2013-12-01

One important reason why functional electrical stimulation (FES) has not gained widespread clinical use is the limitation imposed by rapid muscle fatigue due to non-physiological activation of the stimulated muscles. We aimed to show that asynchronous low-pulse-rate (LPR) electrical stimulation applied by multipad surface electrodes greatly postpones the occurrence of muscle fatigue compared with conventional stimulation (high pulse rate, HPR). We compared the produced force vs. time of the forearm muscles responsible for finger flexion in 2 stimulation protocols, LPR (fL = 10 Hz) and HPR (fH = 40 Hz). Surface-distributed low-frequency asynchronous stimulation (sDLFAS) doubles the time interval before the onset of fatigue (104 ± 80%) compared with conventional synchronous stimulation. Combining the performance of multipad electrodes (increased selectivity and facilitated positioning) with sDLFAS (decreased fatigue) can improve many FES applications in both the lower and upper extremities. Copyright © 2013 Wiley Periodicals, Inc.
Does prolonged pituitary down-regulation with gonadotropin-releasing hormone agonist improve the live-birth rate in in vitro fertilization treatment?

PubMed

Ren, Jianzhi; Sha, Aiguo; Han, Dongmei; Li, Ping; Geng, Jie; Ma, Chaihui

2014-07-01

To evaluate the effects of a prolonged duration of gonadotropin-releasing hormone agonist (GnRH-a) in pituitary down-regulation for controlled ovarian hyperstimulation (COH) on the live-birth rate in nonendometriotic women undergoing in vitro fertilization and embryo transfer (IVF-ET). Retrospective cohort study. University-affiliated hospital. Normogonadotropic women undergoing IVF. Three hundred seventy-eight patients receiving a prolonged pituitary down-regulation with GnRH-a before ovarian stimulation and 422 patients receiving a GnRH-a long protocol. Live-birth rate per fresh ET. In comparison with the long protocol, the prolonged down-regulation protocol required a higher total dose of gonadotropins. A lower serum luteinizing hormone (LH) level on the starting day of gonadotropin and the day of human chorionic gonadotropin (hCG) and a fewer number of oocytes and embryos were observed in the prolonged down-regulation protocol. However, the duration of stimulation and number of high-quality embryos were comparable between the two groups. A statistically significantly higher implantation rate (50.27% vs. 39.69%), clinical pregnancy rate (64.02% vs. 56.87%) and live-birth rate per fresh transfer cycle (55.56% vs. 45.73%) were observed in the prolonged protocol. Prolonged down-regulation in a GnRH-a protocol might increase the live-birth rates in normogonadotropic women. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Effects of electrical stimulation-induced gluteal versus gluteal and hamstring muscles activation on sitting pressure distribution in persons with a spinal cord injury.

PubMed

Smit, C A J; Haverkamp, G L G; de Groot, S; Stolwijk-Swuste, J M; Janssen, T W J

2012-08-01

Ten participants underwent two electrical stimulation (ES) protocols applied using a custom-made electrode garment with built-in electrodes. Interface pressure was measured using a force-sensitive area. In one protocol, both the gluteal and hamstring (g+h) muscles were activated, in the other gluteal (g) muscles only. To study and compare the effects of electrically induced activation of g+h muscles versus g muscles only on sitting pressure distribution in individuals with a spinal cord injury (SCI). Ischial tuberosities interface pressure (ITs pressure) and pressure gradient. In all participants, both protocols of g and g+h ES-induced activation caused a significant decrease in IT pressure. IT pressure after g+h muscles activation was reduced significantly by 34.5% compared with rest pressure, whereas a significant reduction of 10.2% after activation of g muscles only was found. Pressure gradient reduced significantly only after stimulation of g+h muscles (49.3%). g+h muscles activation showed a decrease in pressure relief (Δ IT) over time compared with g muscles only. Both protocols of surface ES-induced of g and g+h activation gave pressure relief from the ITs. Activation of both g+h muscles in SCI resulted in better IT pressure reduction in sitting individuals with a SCI than activation of g muscles only. ES might be a promising method in preventing pressure ulcers (PUs) on the ITs in people with SCI. Further research needs to show which pressure reduction is sufficient in preventing PUs.
Role of adrenal vein sampling in primary aldosteronism: the Monash Health experience.

PubMed

Teng, J; Hutchinson, M E; Doery, J C G; Choy, K W; Chong, W; Fuller, P J; Yang, J

2015-11-01

Adrenal vein sampling (AVS) is useful for distinguishing unilateral versus bilateral hypersecretion in primary aldosteronism (PA), but is technically challenging. Furthermore, the use of adrenocorticotropic hormone (ACTH)-stimulation in AVS is controversial. We implemented a Monash Health-specific AVS protocol in 2010. The audit aimed to: (i) examine the impact of a dedicated protocol on success rates of AVS at a tertiary referral centre; (ii) evaluate the impact of AVS on sub-typing of PA; and (iii) assess the utility of ACTH stimulation in AVS. AVS was performed on patients with PA confirmed by positive saline suppression testing (aldosterone level >140 pmol/L post-saline infusion), with sequential sampling of adrenal and peripheral veins, pre- and post-ACTH infusion. Patients with unilateral aldosterone-producing adenoma diagnosed on successful AVS were referred for adrenalectomy. Between 2010 and 2014 inclusive, a total of 28 AVS procedures was performed, with complete pre- and post-ACTH data for 19 procedures. Bilateral successful cannulation rates improved post-implementation of our protocol (61% vs 41%). Of the patients, 32% had discordant imaging and AVS results: four patients with unilateral adenomas did not lateralise on AVS and were managed medically; four patients with bilateral or no adenomas on imaging, lateralised on AVS and had surgery. Overall, use of ACTH did not increase successful cannulation and tended to mask lateralisation. AVS is crucial in subtype classification of PA and should be performed by a dedicated radiologist with a standardised protocol. AVS outcomes were not improved with the use of ACTH stimulation. © 2015 Royal Australasian College of Physicians.
Studying frequency processing of the brain to enhance long-term memory and develop a human brain protocol.

PubMed

Friedrich, Wernher; Du, Shengzhi; Balt, Karlien

2015-01-01

The temporal lobe in conjunction with the hippocampus is responsible for memory processing. The gamma wave is involved with this process. To develop a human brain protocol, a better understanding of the relationship between gamma and long-term memory is vital. A more comprehensive understanding of the human brain and specific analogue waves it uses will support the development of a human brain protocol. Fifty-eight participants aged between 6 and 60 years participated in long-term memory experiments. It is envisaged that the brain could be stimulated through binaural beats (sound frequency) at 40 Hz (gamma) to enhance long-term memory capacity. EEG recordings have been transformed to sound and then to an information standard, namely ASCII. Statistical analysis showed a proportional relationship between long-term memory and gamma activity. Results from EEG recordings indicate a pattern. The pattern was obtained through the de-codification of an EEG recording to sound and then to ASCII. Stimulation of gamma should enhance long term memory capacity. More research is required to unlock the human brains' protocol key. This key will enable the processing of information directly to and from human memory via gamma, the hippocampus and the temporal lobe.
Deep brain stimulation of the basolateral amygdala for treatment-refractory combat post-traumatic stress disorder (PTSD): study protocol for a pilot randomized controlled trial with blinded, staggered onset of stimulation.

PubMed

Koek, Ralph J; Langevin, Jean-Philippe; Krahl, Scott E; Kosoyan, Hovsep J; Schwartz, Holly N; Chen, James W Y; Melrose, Rebecca; Mandelkern, Mark J; Sultzer, David

2014-09-10

Combat post-traumatic stress disorder (PTSD) involves significant suffering, impairments in social and occupational functioning, substance use and medical comorbidity, and increased mortality from suicide and other causes. Many veterans continue to suffer despite current treatments. Deep brain stimulation (DBS) has shown promise in refractory movement disorders, depression and obsessive-compulsive disorder, with deep brain targets chosen by integration of clinical and neuroimaging literature. The basolateral amygdala (BLn) is an optimal target for high-frequency DBS in PTSD based on neurocircuitry findings from a variety of perspectives. DBS of the BLn was validated in a rat model of PTSD by our group, and limited data from humans support the potential safety and effectiveness of BLn DBS. We describe the protocol design for a first-ever Phase I pilot study of bilateral BLn high-frequency DBS for six severely ill, functionally impaired combat veterans with PTSD refractory to conventional treatments. After implantation, patients are monitored for a month with stimulators off. An electroencephalographic (EEG) telemetry session will test safety of stimulation before randomization to staggered-onset, double-blind sham versus active stimulation for two months. Thereafter, patients will undergo an open-label stimulation for a total of 24 months. Primary efficacy outcome is a 30% decrease in the Clinician Administered PTSD Scale (CAPS) total score. Safety outcomes include extensive assessments of psychiatric and neurologic symptoms, psychosocial function, amygdala-specific and general neuropsychological functions, and EEG changes. The protocol requires the veteran to have a cohabiting significant other who is willing to assist in monitoring safety and effect on social functioning. At baseline and after approximately one year of stimulation, trauma script-provoked 18FDG PET metabolic changes in limbic circuitry will also be evaluated. While the rationale for studying DBS for PTSD is ethically and scientifically justified, the importance of the amygdaloid complex and its connections for a myriad of emotional, perceptual, behavioral, and vegetative functions requires a complex trial design in terms of outcome measures. Knowledge generated from this pilot trial can be used to design future studies to determine the potential of DBS to benefit both veterans and nonveterans suffering from treatment-refractory PTSD. PCC121657, 19 March 2014.
Effectiveness outcomes and health related quality of life impact of disease progression in patients with advanced nonsquamous NSCLC treated in real-world community oncology settings: results from a prospective medical record registry study.

PubMed

Walker, Mark S; Wong, William; Ravelo, Arliene; Miller, Paul J E; Schwartzberg, Lee S

2017-08-14

Treatment options for advanced nonsquamous non-small cell lung cancer (NSCLC) in the first line include platinum-based doublet therapy with or without bevacizumab. This study examined efficacy outcomes and patient reported outcomes (PROs) in a community oncology patient sample. Advanced nonsquamous NSCLC patients from 34 U.S. community oncology practices treated in first line with bevacizumab regimens (A platinum doublet; gemcitabine doublet; pemetrexed with platinum) or non-bevacizumab regimens (B platinum doublet; gemcitabine doublet; C pemetrexed with platinum) were recruited for this prospective study. Patient characteristics and clinical outcomes were accessed from routine care records. Three validated and widely used PRO measures of health related quality of life (HRQOL) and symptom burden were collected prospectively at each visit and up to one-year follow-up. Effectiveness outcomes were progression free survival (PFS) and overall survival (OS) assessed by Kaplan-Meier and Cox regression methods. PROs were analyzed with linear mixed model regression to examine changes over time, and the effect of disease progression. Of 147 patients in the study, 145 provided PRO data. Patients in treatment groups were: A (n = 66, 44.9%); B (n = 25, 17.0%); C (n = 56, 38.1%). A was associated with significantly longer OS than B (HR = 0.341, p = 0.0012), and significantly longer than C (HR = 0.602, p = 0.0354). PFS results were similar. Irrespective of regimen group and on 12/32 measures, patients showed significant and clinically meaningful worsening of symptoms and HRQOL at disease progression. After disease progression, the pattern of symptom and HRQOL change showed continued worsening. Bevacizumab-containing regimens were associated with longer PFS and OS compared with non-bevacizumab regimens. PRO measures show disease progression is associated with worsening HRQOL. Delaying disease progression can sustain better HRQL and reduce symptom burden.
Wafer-level fabrication of arrays of glass lens doublets

NASA Astrophysics Data System (ADS)

Passilly, Nicolas; Perrin, Stéphane; Albero, Jorge; Krauter, Johann; Gaiffe, Olivier; Gauthier-Manuel, Ludovic; Froehly, Luc; Lullin, Justine; Bargiel, Sylwester; Osten, Wolfgang; Gorecki, Christophe

2016-04-01

Systems for imaging require to employ high quality optical components in order to dispose of optical aberrations and thus reach sufficient resolution. However, well-known methods to get rid of optical aberrations, such as aspherical profiles or diffractive corrections are not easy to apply to micro-optics. In particular, some of these methods rely on polymers which cannot be associated when such lenses are to be used in integrated devices requiring high temperature process for their further assembly and separation. Among the different approaches, the most common is the lens splitting that consists in dividing the focusing power between two or more optical components. In here, we propose to take advantage of a wafer-level technique, devoted to the generation of glass lenses, which involves thermal reflow in silicon cavities to generate lens doublets. After the convex lens sides are generated, grinding and polishing of both stack sides allow, on the first hand, to form the planar lens backside and, on the other hand, to open the silicon cavity. Nevertheless, silicon frames are then kept and thinned down to form well-controlled and auto-aligned spacers between the lenses. Subsequent accurate vertical assembly of the glass lens arrays is performed by anodic bonding. The latter ensures a high level of alignment both laterally and axially since no additional material is required. Thanks to polishing, the generated lens doublets are then as thin as several hundreds of microns and compatible with micro-opto-electro-systems (MOEMS) technologies since they are only made of glass and silicon. The generated optical module is then robust and provide improved optical performances. Indeed, theoretically, two stacked lenses with similar features and spherical profiles can be almost diffraction limited whereas a single lens characterized by the same numerical aperture than the doublet presents five times higher wavefront error. To demonstrate such assumption, we fabricated glass lens doublets and compared them to single lenses of equivalent focusing power. For similar illumination, the optical aberrations are significantly reduced.
Anthracycline-based triplets do not improve the efficacy of platinum-fluoropyrimidine doublets in first-line treatment of advanced gastric cancer: real-world data from the AGAMEMON National Cancer Registry.

PubMed

Carmona-Bayonas, A; Jiménez-Fonseca, P; Custodio, A; Sánchez Cánovas, M; Hernández, R; Pericay, C; Echavarria, I; Lacalle, A; Visa, L; Rodríguez Palomo, A; Mangas, M; Cano, J M; Buxo, E; Álvarez-Manceñido, F; García, T; Lorenzo, J E; Ferrer-Cardona, M; Viudez, A; Azkarate, A; Ramchandani, A; Arias, D; Longo, F; López, C; Sánchez Bayona, R; Limón, M L; Díaz-Serrano, A; Fernández Montes, A; Sala, P; Cerdá, P; Rivera, F; Gallego, J

2018-01-01

Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry. Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression. A total of 1002 patients were included (doublets, n = 653; anthracycline-based triplets, n = 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), and (log-rank test, p = 0.226). Response rates (42.1 vs. 33.1%, p = 0.12) and PFS (HR 0.95, CI 95%, 0.80-1.13, log-rank test, p = 0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3-4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision. Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.
A new look at the International Duration Evaluation of Adjuvant therapy (IDEA) classification-Defining novel predictive and prognostic markers in stage III colon cancer.

PubMed

Margalit, Ofer; Mamtani, Ronac; Yang, Yu-Xiao; Reiss, Kim A; Golan, Talia; Halpern, Naama; Aderka, Dan; Giantonio, Bruce; Shacham-Shmueli, Einat; Boursi, Ben

2018-04-23

The International Duration Evaluation of Adjuvant therapy (IDEA) pooled analysis compared 3 to 6 months of adjuvant chemotherapy for stage III colon cancer. The overarching goal was to reduce chemotherapy-related toxicity, mainly oxaliplatin-induced neuropathy. Patients were classified into low-risk and high-risk groups, suggesting that low-risk patients may be offered only 3 months of treatment. We aimed to evaluate the benefit of monotherapy versus doublet chemotherapy in low and high IDEA risk groups. Using the National Cancer Database (2004-2014), we identified 56,728 low-risk and 47,557 high-risk individuals with stage III colon cancer, according to the IDEA classification. We used multivariate Cox regression to evaluate the magnitude of survival differences between IDEA risk groups, according to treatment intensity (doublet versus monotherapy). In a secondary analysis, we examined the prognostic and predictive value of subgroups of age, tumour sidedness and lymph node ratio (LNR). Low and high IDEA risk groups derived similar benefit from doublet adjuvant chemotherapy as compared with monotherapy, with hazard ratios (HRs) of 0.83 (95% confidence interval [CI] 0.79-0.86) and 0.80 (95% CI 0.78-0.83), respectively. The only subpopulations that did not benefit from doublet chemotherapy were low-risk patients older than 72 years (HR = 0.95, 95% CI 0.90-1.01) and high-risk patients older than 85 years (HR = 0.90, 95% CI 0.77-1.05). LNR and tumour sidedness were shown as additional prognostic, but not predictive, factors within the IDEA risk groups. IDEA risk classification per se does not predict for treatment benefit from doublet chemotherapy in stage III colon cancer. However, omission of oxaliplatin can be considered in IDEA low-risk patients older than 72 years. Copyright © 2018 Elsevier Ltd. All rights reserved.
Assessing Mitochondrial Bioenergetics in Isolated Mitochondria from Various Mouse Tissues Using Seahorse XF96 Analyzer.

PubMed

Iuso, Arcangela; Repp, Birgit; Biagosch, Caroline; Terrile, Caterina; Prokisch, Holger

2017-01-01

Working with isolated mitochondria is the gold standard approach to investigate the function of the electron transport chain in tissues, free from the influence of other cellular factors. In this chapter, we outline a detailed protocol to measure the rate of oxygen consumption (OCR) with the high-throughput analyzer Seahorse XF96. More importantly, this protocol wants to provide practical tips for handling many different samples at once, and take a real advantage of using a high-throughput system. As a proof of concept, we have isolated mitochondria from brain, heart, liver, muscle, kidney, and lung of a wild-type mouse, and measured basal respiration (State II), ADP-stimulated respiration (State III), non-ADP-stimulated respiration (State IV o ), and FCCP-stimulated respiration (State III u ) using respiratory substrates specific to the respiratory chain complex I (RCCI) and complex II (RCCII). Mitochondrial purification and Seahorse runs were performed in less than eight working hours.
Maintaining ocular safety with light exposure, focusing on devices for optogenetic stimulation

PubMed Central

Yan, Boyuan; Vakulenko, Maksim; Min, Seok-Hong; Hauswirth, William W.; Nirenberg, Sheila

2016-01-01

Optogenetics methods are rapidly being developed as therapeutic tools for treating neurological diseases, in particular, retinal degenerative diseases. A critical component of the development is testing the safety of the light stimulation used to activate the optogenetic proteins. While the stimulation needs to be sufficient to produce neural responses in the targeted retinal cell class, it also needs to be below photochemical and photothermal limits known to cause ocular damage. The maximal permissible exposure is determined by a variety of factors, including wavelength, exposure duration, visual angle, pupil size, pulse width, pulse pattern, and repetition frequency. In this paper, we develop utilities to systematically and efficiently assess the contributions of these parameters in relation to the limits, following directly from the 2014 American National Standards Institute (ANSI). We also provide an array of stimulus protocols that fall within the bounds of both safety and effectiveness. Additional verification of safety is provided with a case study in rats using one of these protocols. PMID:26882975
Sodium bicarbonate supplementation delays neuromuscular fatigue without changes in performance outcomes during a basketball match simulation protocol.

PubMed

Ansdell, Paul; Dekerle, Jeanne

2017-10-10

To investigate the development of neuromuscular fatigue during a basketball game simulation and ascertain whether sodium bicarbonate (NaHCO3) supplementation attenuates any neuromuscular fatigue that persists. Ten participants ingested 0.2 g.kg of NaHCO3 (or an equimolar placebo dosage of sodium chloride [NaCl]) 90 and 60 minutes prior to commencing a basketball game simulation (ALK-T vs PLA-T). Isometric maximal voluntary contractions of the knee extensors (MVIC) and potentiated high (100 Hz) and low (10 Hz) frequency doublet twitches were recorded before and after each match quarter for both trials. In addition, 15 m sprint times and layup completion (%) were recorded during each quarter. MVIC, 100 and 10 Hz twitch forces declined progressively in both trials (P<0.05) with a less pronounced decrease in MVIC during ALK-T (P<0.01). Both 100 and 10 Hz twitch forces were also significantly greater in ALK-T (P<0.05). 15 m sprint time increased over the course of both trials (∼2%, P<0.01); however, no significant condition or time effect was found for layup completion (P>0.05). A basketball simulation protocol induces a substantial amount of neuromuscular (reduction in knee extensor MVICs) and peripheral fatigue with a concomitant increase in 15 m sprint time over the protocol. NaHCO3 supplementation attenuated the rate of fatigue development by protecting contractile elements of the muscle fibres. This study provides coaches with information about the magnitude of fatigue induced by a simulated basketball game, and provides evidence of the efficacy of NaHCO3 in attenuating fatigue.
Chemokine receptor binding and signal transduction in native cells of the central nervous system.

PubMed

Davis, Christopher N; Chen, Shuzhen; Boehme, Stefen A; Bacon, Kevin B; Harrison, Jeffrey K

2003-04-01

Chemokine receptors belong to the superfamily of seven-transmembrane-spanning, G-protein-coupled receptors, and their expression by central nervous system cells is clearly documented. As this gene family has become the target of novel therapeutic development, the analysis of these receptors requires radioligand binding techniques as well as methods that entail assessing receptor stimulation of signal transduction pathways. Herein, we describe specific protocols for measuring radiolabeled chemokine binding to their cognate receptors on cultured glial cells as well as to receptors expressed in heterologous cell systems. Multiple downstream signaling pathways, including intracellular calcium influx and receptor-dependent kinase activation, are associated with chemokine receptor stimulation. Protocols for measuring these signaling events in chemokine-receptor-expressing cells are also presented.
Minimalism in inflation model building

NASA Astrophysics Data System (ADS)

Dvali, Gia; Riotto, Antonio

1998-01-01

In this paper we demand that a successful inflationary scenario should follow from a model entirely motivated by particle physics considerations. We show that such a connection is indeed possible within the framework of concrete supersymmetric Grand Unified Theories where the doublet-triplet splitting problem is naturally solved. The Fayet-Iliopoulos D-term of a gauge U(1)ξ symmetry, which plays a crucial role in the solution of the doublet-triplet splitting problem, simultaneously provides a built-in inflationary slope protected from dangerous supergravity corrections.

Energy anisotropy as a function of the direction of spin magnetization for a doublet system

NASA Astrophysics Data System (ADS)

Cherry, Peter J.; Malkin, Vladimir G.; Malkina, Olga L.; Asher, James R.

2016-11-01

This manuscript describes new phenomena that currently are not taken into account in both experimental EPR spectra interpretations and quantum chemical calculations of EPR parameters. This article presents an argument, with evidence, against the common belief that in the absence of an external magnetic field the total energy of a doublet system is independent of the spin orientation. Consequences of this phenomenon for interpretation of EPR experimental studies as well as for quantum chemical calculations of EPR parameters are discussed.
Computation of Incompressible Potential Flow over an Airfoil Using a High Order Aerodynamic Panel Method Based on Circular Arc Panels.

DTIC Science & Technology

1982-08-01

Vortex Sheet Figure 4 - Properties of Singularity Sheets they may be used to model different types of flow. Transfer of boundary... Vortex Sheet Equivalence Singularity Behavior Using Green’s theorem it is clear that the problem of potential flow over a body can be modeled using ...that source, doublet, or vortex singularities can be used to model potential flow problems, and that the doublet and vortex singularities are
Radiative model of neutrino mass with neutrino interacting MeV dark matter

DOE PAGES

Arhrib, Abdesslam; Bohm, Celine; Ma, Ernest; ...

2016-04-26

We consider the radiative generation of neutrino mass through the interactions of neutrinos with MeV dark matter. We construct a realistic renormalizable model with one scalar doublet (in additional to the standard model doublet) and one complex singlet together with three light singlet Majorana fermions, all transforming under a dark U(1)(D) symmetry which breaks softly to Z(2). We study in detail the scalar sector which supports this specific scenario and its rich phenomenology.
Controlled ovarian hyperstimulation with sequential letrozole co-treatment in normo/high responders.

PubMed

Ecemis, Tolga; Tasci, Yasemin; Caglar, Gamze Sinem

2016-01-01

To investigate the effect of co-administration of letrozole in an ovarian stimulation protocol using recombinant FSH and GnRH antagonists for ICSI in normo/high responders. Computerized data of 320 antagonist ICSI/ET cycles with or without letrozole were retrospectively analyzed. In 105 cases, letrozole (5 mg/day) was started at the second day of the cycle continued for 5 days. At the second day of letrozole, gonadotropins were added. The remaining 215 cases were stimulated with recombinant FSH only. In all cases on day 6, GnRH antagonist was started. Ovarian stimulation protocols with or without letrozole were compared for cycle outcome parameters. In cycles with letrozole, significantly lower gonadotropin consumption and lower peak estradiol levels were found. In cycles with letrozole, mean number of metaphase II and fertilized oocytes retrieved were significantly higher compared to cycles without letrozole. The pregnancy and clinical pregnancy rates were similar. Should the number of oocytes retrieved being higher in letrozole group might indicate that letrozole might contribute to successful ovarian stimulation with a lower dosage of gonadotropins. Despite the lower peak estradiol levels, pregnancy rates being similar to other group also support the idea that letrozole can contribute to normal potential of implantation.
Hyperventilation and photic stimulation are useful additions to a placebo-based suggestive seizure induction protocol in patients with psychogenic nonepileptic seizures.

PubMed

Popkirov, Stoyan; Grönheit, Wenke; Wellmer, Jörg

2015-05-01

The early and definitive diagnosis of psychogenic nonepileptic seizures is a common challenge in epileptology practice. Suggestive seizure induction is a valuable tool to aid the differentiation between epileptic and psychogenic nonepileptic seizures, especially when long-term video-EEG monitoring is inconclusive or unavailable. In this retrospective analysis, we compared the diagnostic yield of a classical, placebo-based induction protocol with that of an extended protocol that includes hyperventilation and photic stimulation as means of suggestion while also implementing more open, standardized patient information. We investigated whether the diversification of suggestive seizure induction has an effect on diagnostic yield and whether it preempts the administration of placebo. Data from 52 patients with confirmed psychogenic nonepileptic seizures were analyzed. While suggestive seizure induction using only placebo-based suggestion provoked a typical event in 13 of 20 patients (65%), the extended protocol was positive in 27 of 34 cases (84%); this improvement was not significant (p=0.11). Noninvasive suggestion techniques accounted for 78% of inductions, avoiding placebo administration in a majority of patients. Still, placebo remains an important part of suggestive seizure induction, responsible for 22% (6 out of 27) of successful inductions using our extended protocol. Our study demonstrates that the diversification of suggestive seizure induction is feasible and beneficial for both patients and diagnosticians. Copyright © 2015 Elsevier Inc. All rights reserved.
Transcranial direct current stimulation for depression in Alzheimer's disease: study protocol for a randomized controlled trial.

PubMed

Narita, Zui; Yokoi, Yuma

2017-06-19

Patients with Alzheimer's disease frequently elicit neuropsychiatric symptoms as well as cognitive deficits. Above all, depression is one of the most common neuropsychiatric symptoms in Alzheimer's disease but antidepressant drugs have not shown significant beneficial effects on it. Moreover, electroconvulsive therapy has not ensured its safety for potential severe adverse events although it does show beneficial clinical effect. Transcranial direct current stimulation can be the safe alternative of neuromodulation, which applies weak direct electrical current to the brain. Although transcranial direct current stimulation has plausible evidence for its effect on depression in young adult patients, no study has explored it in older subjects with depression in Alzheimer's disease. Therefore, we present a study protocol designed to evaluate the safety and clinical effect of transcranial direct current stimulation on depression in Alzheimer's disease in subjects aged over 65 years. This is a two-arm, parallel-design, randomized controlled trial, in which patients and assessors will be blinded. Subjects will be randomized to either an active or a sham transcranial direct current stimulation group. Participants in both groups will be evaluated at baseline, immediately, and 2 weeks after the intervention. This study investigates the safety and effect of transcranial direct current stimulation that may bring a significant impact on both depression and cognition in patients with Alzheimer's disease, and may be useful to enhance their quality of life. ClinicalTrials.gov, NCT02351388 . Registered on 27 January 2015. Last updated on 30 May 2016.
Auditory beat stimulation and its effects on cognition and mood States.

PubMed

Chaieb, Leila; Wilpert, Elke Caroline; Reber, Thomas P; Fell, Juergen

2015-01-01

Auditory beat stimulation may be a promising new tool for the manipulation of cognitive processes and the modulation of mood states. Here, we aim to review the literature examining the most current applications of auditory beat stimulation and its targets. We give a brief overview of research on auditory steady-state responses and its relationship to auditory beat stimulation (ABS). We have summarized relevant studies investigating the neurophysiological changes related to ABS and how they impact upon the design of appropriate stimulation protocols. Focusing on binaural-beat stimulation, we then discuss the role of monaural- and binaural-beat frequencies in cognition and mood states, in addition to their efficacy in targeting disease symptoms. We aim to highlight important points concerning stimulation parameters and try to address why there are often contradictory findings with regard to the outcomes of ABS.
A proposed draft protocol for the European Convention on Biomedicine relating to research on the human embryo and fetus.

PubMed Central

Byk, J C

1997-01-01

The objective of this paper is to stimulate academic debate on embryo and fetal research from the perspective of the drafting of a protocol to the European Convention on Biomedicine. The Steering Committee on Bioethics of the Council of Europe was mandated to draw up such a protocol and for this purpose organised an important symposium on reproductive technologies and embryo research, in Strasbourg from the 16th to the 18th of December 1996. PMID:9055160
Transcranial Alternating Current Stimulation Attenuates Neuronal Adaptation.

PubMed

Kar, Kohitij; Duijnhouwer, Jacob; Krekelberg, Bart

2017-03-01

We previously showed that brief application of 2 mA (peak-to-peak) transcranial currents alternating at 10 Hz significantly reduces motion adaptation in humans. This is but one of many behavioral studies showing that weak currents applied to the scalp modulate neural processing. Transcranial stimulation has been shown to improve perception, learning, and a range of clinical symptoms. Few studies, however, have measured the neural consequences of transcranial current stimulation. We capitalized on the strong link between motion perception and neural activity in the middle temporal (MT) area of the macaque monkey to study the neural mechanisms that underlie the behavioral consequences of transcranial alternating current stimulation. First, we observed that 2 mA currents generated substantial intracranial fields, which were much stronger in the stimulated hemisphere (0.12 V/m) than on the opposite side of the brain (0.03 V/m). Second, we found that brief application of transcranial alternating current stimulation at 10 Hz reduced spike-frequency adaptation of MT neurons and led to a broadband increase in the power spectrum of local field potentials. Together, these findings provide a direct demonstration that weak electric fields applied to the scalp significantly affect neural processing in the primate brain and that this includes a hitherto unknown mechanism that attenuates sensory adaptation. SIGNIFICANCE STATEMENT Transcranial stimulation has been claimed to improve perception, learning, and a range of clinical symptoms. Little is known, however, how transcranial current stimulation generates such effects, and the search for better stimulation protocols proceeds largely by trial and error. We investigated, for the first time, the neural consequences of stimulation in the monkey brain. We found that even brief application of alternating current stimulation reduced the effects of adaptation on single-neuron firing rates and local field potentials; this mechanistic insight explains previous behavioral findings and suggests a novel way to modulate neural information processing using transcranial currents. In addition, by developing an animal model to help understand transcranial stimulation, this study will aid the rational design of stimulation protocols for the treatment of mental illnesses, and the improvement of perception and learning. Copyright © 2017 the authors 0270-6474/17/372325-11$15.00/0.
Optimal timing of pulse onset for language mapping with navigated repetitive transcranial magnetic stimulation.

PubMed

Krieg, Sandro M; Tarapore, Phiroz E; Picht, Thomas; Tanigawa, Noriko; Houde, John; Sollmann, Nico; Meyer, Bernhard; Vajkoczy, Peter; Berger, Mitchel S; Ringel, Florian; Nagarajan, Srikantan

2014-10-15

Within the primary motor cortex, navigated transcranial magnetic stimulation (nTMS) has been shown to yield maps strongly correlated with those generated by direct cortical stimulation (DCS). However, the stimulation parameters for repetitive nTMS (rTMS)-based language mapping are still being refined. For this purpose, the present study compares two rTMS protocols, which differ in the timing of pulse train onset relative to picture presentation onset during object naming. Results were the correlated with DCS language mapping during awake surgery. Thirty-two patients with left-sided perisylvian tumors were examined by rTMS prior to awake surgery. Twenty patients underwent rTMS pulse trains starting at 300 ms after picture presentation onset (delayed TMS), whereas another 12 patients received rTMS pulse trains starting at the picture presentation onset (ONSET TMS). These rTMS results were then evaluated for correlation with intraoperative DCS results as gold standard in terms of differential consistencies in receiver operating characteristics (ROC) statistics. Logistic regression analysis by protocols and brain regions were conducted. Within and around Broca's area, there was no difference in sensitivity (onset TMS: 100%, delayed TMS: 100%), negative predictive value (NPV) (onset TMS: 100%, delayed TMS: 100%), and positive predictive value (PPV) (onset TMS: 55%, delayed TMS: 54%) between the two protocols compared to DCS. However, specificity differed significantly (onset TMS: 67%, delayed TMS: 28%). In contrast, for posterior language regions, such as supramarginal gyrus, angular gyrus, and posterior superior temporal gyrus, early pulse train onset stimulation showed greater specificity (onset TMS: 92%, delayed TMS: 20%), NPV (onset TMS: 92%, delayed TMS: 57%) and PPV (onset TMS: 75%, delayed TMS: 30%) with comparable sensitivity (onset TMS: 75%, delayed TMS: 70%). Logistic regression analysis also confirmed the greater fit of the predictions by rTMS that had the pulse train onset coincident with the picture presentation onset when compared to the delayed stimulation. Analyses of differential disruption patterns of mapped cortical regions were further able to distinguish clusters of cortical regions standardly associated with semantic and pre-vocalization phonological networks proposed in various models of word production. Repetitive nTMS predictions by both protocols correlate well with DCS outcomes especially in Broca's region, particularly with regard to TMS negative predictions. With this study, we have demonstrated that rTMS stimulation onset coincident with picture presentation onset improves the accuracy of preoperative language maps, particularly within posterior language areas. Moreover, immediate and delayed pulse train onsets may have complementary disruption patterns that could differentially capture cortical regions causally necessary for semantic and pre-vocalization phonological networks. Published by Elsevier Inc.
Undiscovered role of endogenous thromboxane A2 in activation of cardiac sympathetic afferents during ischaemia

PubMed Central

Fu, Liang-Wu; Guo, Zhi-Ling; Longhurst, John C

2008-01-01

Myocardial ischaemia activates blood platelets, which in turn stimulate cardiac sympathetic afferents, leading to chest pain and sympathoexcitatory reflex cardiovascular responses. Previous studies have shown that activated platelets stimulate ischaemically sensitive cardiac sympathetic afferents, and that thromboxane A2 (TxA2) is one of the mediators released from activated platelets during myocardial ischaemia. The present study tested the hypothesis that endogenous TxA2 stimulates cardiac afferents during ischaemia through direct activation of TxA2 (TP) receptors coupled with the phospholipase C–protein kinase C (PLC–PKC) cellular pathway. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicantes (T2–T5) in anaesthetized cats. Single fields of 39 afferents (conduction velocity = 0.27–3.65 m s−1) were identified in the left or right ventricle initially with mechanical stimulation and confirmed with a stimulating electrode. Five minutes of myocardial ischaemia stimulated all 39 cardiac afferents (8 Aδ-, 31 C-fibres) and the responses of these 39 afferents to chemical stimuli were further studied in the following four protocols. In the first protocol, 2.5, 5 and 10 μg of the TxA2 mimetic, U46619, injected into the left atrium (LA), stimulated seven ischaemically sensitive cardiac afferents in a dose-dependent manner. Second, BM13,177, a selective TxA2 receptor antagonist, abolished the responses of six afferents to 5 μg of U46619 injected into the left atrium and attenuated the ischaemia-related increase in activity of seven other afferents by 44%. In contrast, cardiac afferents, in the absence of TP receptor blockade responded consistently to repeated administration of U46619 (n = 6) and to recurrent myocardial ischaemia (n = 7). In the fourth protocol, administration of PKC-(19–36), a selective PKC inhibitor, attenuated the responses of six other cardiac afferents to U46619 by 38%. Finally, using an immunohistochemical staining approach, we observed that TP receptors were expressed in cardiac sensory neurons in thoracic dorsal root ganglia. Taken together, these data indicate that endogenous TxA2 contributes to the activation of cardiac afferents during myocardial ischaemia through direct stimulation of TP receptors probably located in the cardiac sensory nervous system and that the stimulating effect of TxA2 on cardiac afferents is dependent, at least in part, upon the PLC–PKC cellular pathway. PMID:18483073
Reynolds-number-dependent dynamical transitions on hydrodynamic synchronization modes of externally driven colloids

NASA Astrophysics Data System (ADS)

Oyama, Norihiro; Teshigawara, Kosuke; Molina, John Jairo; Yamamoto, Ryoichi; Taniguchi, Takashi

2018-03-01

The collective dynamics of externally driven Np-colloidal systems (1 ≤Np≤4 ) in a confined viscous fluid have been investigated using three-dimensional direct numerical simulations with fully resolved hydrodynamics. The dynamical modes of collective particle motion are studied by changing the particle Reynolds number as determined by the strength of the external driving force and the confining wall distance. For a system with Np=3 , we found that at a critical Reynolds number a dynamical mode transition occurs from the doublet-singlet mode to the triplet mode, which has not been reported experimentally. The dynamical mode transition was analyzed in detail from the following two viewpoints: (1) spectrum analysis of the time evolution of a tagged particle velocity and (2) the relative acceleration of the doublet cluster with respect to the singlet particle. For a system with Np=4 , we found similar dynamical mode transitions from the doublet-singlet-singlet mode to the triplet-singlet mode and further to the quartet mode.
Reynolds-number-dependent dynamical transitions on hydrodynamic synchronization modes of externally driven colloids.

PubMed

Oyama, Norihiro; Teshigawara, Kosuke; Molina, John Jairo; Yamamoto, Ryoichi; Taniguchi, Takashi

2018-03-01

The collective dynamics of externally driven N_{p}-colloidal systems (1≤N_{p}≤4) in a confined viscous fluid have been investigated using three-dimensional direct numerical simulations with fully resolved hydrodynamics. The dynamical modes of collective particle motion are studied by changing the particle Reynolds number as determined by the strength of the external driving force and the confining wall distance. For a system with N_{p}=3, we found that at a critical Reynolds number a dynamical mode transition occurs from the doublet-singlet mode to the triplet mode, which has not been reported experimentally. The dynamical mode transition was analyzed in detail from the following two viewpoints: (1) spectrum analysis of the time evolution of a tagged particle velocity and (2) the relative acceleration of the doublet cluster with respect to the singlet particle. For a system with N_{p}=4, we found similar dynamical mode transitions from the doublet-singlet-singlet mode to the triplet-singlet mode and further to the quartet mode.
Miniature optical planar camera based on a wide-angle metasurface doublet corrected for monochromatic aberrations

DOE PAGES

Arbabi, Amir; Arbabi, Ehsan; Kamali, Seyedeh Mahsa; ...

2016-11-28

Optical metasurfaces are two-dimensional arrays of nano-scatterers that modify optical wavefronts at subwavelength spatial resolution. They are poised to revolutionize optics by enabling complex low-cost systems where multiple metasurfaces are lithographically stacked and integrated with electronics. For imaging applications, metasurface stacks can perform sophisticated image corrections and can be directly integrated with image sensors. Here we demonstrate this concept with a miniature flat camera integrating a monolithic metasurface lens doublet corrected for monochromatic aberrations, and an image sensor. The doublet lens, which acts as a fisheye photographic objective, has a small f-number of 0.9, an angle-of-view larger than 60° ×more » 60°, and operates at 850 nm wavelength with 70% focusing efficiency. The camera exhibits nearly diffraction-limited image quality, which indicates the potential of this technology in the development of optical systems for microscopy, photography, and computer vision.« less
The flavor-locked flavorful two Higgs doublet model

NASA Astrophysics Data System (ADS)

Altmannshofer, Wolfgang; Gori, Stefania; Robinson, Dean J.; Tuckler, Douglas

2018-03-01

We propose a new framework to generate the Standard Model (SM) quark flavor hierarchies in the context of two Higgs doublet models (2HDM). The `flavorful' 2HDM couples the SM-like Higgs doublet exclusively to the third quark generation, while the first two generations couple exclusively to an additional source of electroweak symmetry breaking, potentially generating striking collider signatures. We synthesize the flavorful 2HDM with the `flavor-locking' mechanism, that dynamically generates large quark mass hierarchies through a flavor-blind portal to distinct flavon and hierarchon sectors: dynamical alignment of the flavons allows a unique hierarchon to control the respective quark masses. We further develop the theoretical construction of this mechanism, and show that in the context of a flavorful 2HDM-type setup, it can automatically achieve realistic flavor structures: the CKM matrix is automatically hierarchical with | V cb | and | V ub | generically of the observed size. Exotic contributions to meson oscillation observables may also be generated, that may accommodate current data mildly better than the SM itself.
Chiral geometry in multiple chiral doublet bands

NASA Astrophysics Data System (ADS)

Zhang, Hao; Chen, Qibo

2016-02-01

The chiral geometry of multiple chiral doublet bands with identical configuration is discussed for different triaxial deformation parameters γ in the particle rotor model with . The energy spectra, electromagnetic transition probabilities B(M1) and B(E2), angular momenta, and K-distributions are studied. It is demonstrated that the chirality still remains not only in the yrast and yrare bands, but also in the two higher excited bands when γ deviates from 30°. The chiral geometry relies significantly on γ, and the chiral geometry of the two higher excited partner bands is not as good as that of the yrast and yrare doublet bands. Supported by Plan Project of Beijing College Students’ Scientific Research and Entrepreneurial Action, Major State 973 Program of China (2013CB834400), National Natural Science Foundation of China (11175002, 11335002, 11375015, 11461141002), National Fund for Fostering Talents of Basic Science (NFFTBS) (J1103206), Research Fund for Doctoral Program of Higher Education (20110001110087) and China Postdoctoral Science Foundation (2015M580007)
Solar wind diagnostics from Doppler-enhanced scattering

NASA Technical Reports Server (NTRS)

Noci, Giancarlo; Kohl, John L.; Withbroe, George L.

1987-01-01

Solar wind ions can attain sufficient outflow speed, w, to cause line excitation by chromospheric or transition region radiation in a nearby line. It is shown that this extends the diagnostic possibilities of a coronal EUV line to much larger values of w than would be possible if pumping were limited to radiation from the same spectral line. For the 1037.6 A coronal line of O VI, the pumping effect of the chromospheric C II 1037.0 A line is efficient for w between 100 and 250 km/s. An approximate expression for the line ratio for a doublet of the Li or Na isoelectronic sequences is derived, and the diagnostic capabilities of doublet line ratios, either by themselves or combined with the observation of other quantities, are discussed. In particular, that the determination of doublet line ratios at several heights can be sufficient to yield the solar wind velocity at those heights together with a constraint on other coronal parameters.
Next-to-minimal two Higgs Doublet Model

DOE PAGES

Chen, Chien -Yi; Freid, Michael; Sher, Marc

2014-04-07

The simplest extension of the Two Higgs Doublet Model is the addition of a real scalar singlet, S. The effects of mixing between the singlet and the doublets can be manifested in two ways. It can modify the couplings of the 126 GeV Higgs boson, h, and it can lead to direct detection of the heavy Higgs at the LHC. In this paper, we show that in the type-I Model, for heavy Higgs masses in the 200-600 GeV range, the latter effect will be detected earlier than the former for most of parameter space. Should no such Higgs be discoveredmore » in this mass range, then the upper limit on the mixing will be sufficiently strong such that there will be no significant effects on the couplings of the h for most of parameter space. Thus, the reverse is true in the type-II model, the limits from measurements of the couplings of the h will dominate over the limits from non-observation of the heavy Higgs.« less
Investigation of iron(III) complex with crown-porphyrin

NASA Astrophysics Data System (ADS)

Pankratov, Denis A.; Dolzhenko, Vladimir D.; Stukan, Reonald A.; Al Ansari, Yana F.; Savinkina, Elena V.; Kiselev, Yury M.

2013-08-01

Iron complex of 5-(4-(((4'-hydroxy-benzo-15-crown-5)-5'-yl)diazo)phenyl)-10,15,20-triphenylporphyrin was investigated by 57Fe Mössbauer spectroscopy and EPR. Two Fe sites were identified; they give two differing signals, doublet and wide absorption in a large velocity interval. EPR spectra of solutions of the complex in chloroform at room temperature also show two signals with g = 2.064, AFe = 0.032 cm - 1; g = 2.015, AFe = 0.0034 cm - 1. The doublet asymmetry is studied vs. temperature and normal angle to the sample plane and gamma-beam. The isomer shift δ in the doublet varies from 0.25 to 0.41 mm/s in the 360-5 K temperature range, whereas quadruple splitting value is constant, Δ ˜ 0.65 mm/s. The relax absorption may be described as a wide singlet ( δ = 0.30- 0.44 mm/s and Γ = 2.83-3.38 mm/s); its relative area strongly depends on temperature. According to δ, both signals are assigned to Fe(III).
Identification of two structurally related proteins involved in proteolytic processing of precursors targeted to the chloroplast.

PubMed Central

Oblong, J E; Lamppa, G K

1992-01-01

Two proteins of 145 and 143 kDa were identified in pea which co-purify with a chloroplast processing activity that cleaves the precursor for the major light-harvesting chlorophyll binding protein (preLHCP). Antiserum generated against the 145/143 kDa doublet recognizes only these two polypeptides in a chloroplast soluble extract. In immunodepletion experiments the antiserum removed the doublet, and there was a concomitant loss of cleavage of preLHCP as well as of precursors for the small subunit of Rubisco and the acyl carrier protein. The 145 and 143 kDa proteins co-eluted in parallel with the peak of processing activity during all fractionation procedures, but they were not detectable as a homo- or heterodimeric complex. The 145 and 143 kDa proteins were used separately to affinity purify immunoglobulins; each preparation recognized both polypeptides, indicating that they are antigenically related. Wheat chloroplasts contain a soluble species similar in size to the 145/143 kDa doublet. Images PMID:1385116

The deep Peru 2015 doublet earthquakes

NASA Astrophysics Data System (ADS)

Ruiz, S.; Tavera, H.; Poli, P.; Herrera, C.; Flores, C.; Rivera, E.; Madariaga, R.

2017-11-01

On 24 November 2015 two events of magnitude Mw 7.5 and Mw 7.6 occurred at 600 km depth under the Peru-Brazil boundary. These two events were separated in time by 300 s. Deep event doublets occur often under South America. The characteristics that control these events and the dynamic interaction between them are an unresolved problem. We used teleseismic and regional data, situated above the doublet, to perform source inversion in order to characterize their ruptures. The overall resemblance between these two events suggests that they share similar rupture process. They are not identical but occur on the same fault surface dipping westward. Using a P-wave stripping and stretching method we determine rupture speed of 2.25 km/s. From regional body wave inversion we find that stress drop is similar for both events, they differ by a factor of two. The similarity in geometry, rupture velocity, stress drop and radiated energy, suggests that these two events looked like simple elliptical ruptures that propagated like classical sub-shear brittle cracks.
The comparison of microdose flare-up and multiple dose antagonist protocols based on hCG day estradiol (E2), progesterone (P) and P/E2 ratio among poor responder patients in ICSI-ET cycles.

PubMed

Cicek, M N; Kahyaoglu, I; Kahyaoglu, S

2015-02-01

Elevated progesterone levels surpassing exact treshold values impede endometrial receptivity and decrease clinical pregnancy rates in different responder patients during assisted reproductive techniques. A progesterone (P): estradiol (E2) ratio of > 1 on the day of hCG administration has also been suggested to be a manifestation of low ovarian reserve. The clinical significance of P/E2 ratio on the day of hCG administration was investigated among poor responder patients. Based on the ESHRE Bologna consensus criteria related to poor ovarian response diagnosis, 48 poor responder patients were treated with the microdose flare-up regimen and 34 patients were treated with the multiple-dose GnRH antagonist protocol. All patients were destined to perform a ICSI-ET procedure at the end of the stimulation protocols. Progesterone levels and P/E2 ratios have been detected during controlled ovarian hyperstimulation. In the microdose flare-up group; the duration of stimulation, total gonadotropin dose used and hCG day E2 levels were significantly higher than the multiple dose antagonist group. However, the mean hCG day P/E2 rate in the microdose flare-up group was less than that in the multiple-dose antagonist group. The clinical pregnancy rates were non significantly higher in the multiple dose antagonist protocol group than in microdose flare-up group. Impaired endometrial receptivity caused by elevated P levels results with lower pregnancy rates. Regardless of the selected stimulation protocol, poor responder patients are not prone to exhibit high P and E2 secretion. Increased P/E2 ratio of > 1 on hCG day has limited value to predict cycle outcomes in poor responder patients because of ovarian follicle depletion.
Design of Interrogation Protocols for Radiation Dose Measurements Using Optically-Stimulated Luminescent Dosimeters.

PubMed

Abraham, Sara A; Kearfott, Kimberlee J; Jawad, Ali H; Boria, Andrew J; Buth, Tobias J; Dawson, Alexander S; Eng, Sheldon C; Frank, Samuel J; Green, Crystal A; Jacobs, Mitchell L; Liu, Kevin; Miklos, Joseph A; Nguyen, Hien; Rafique, Muhammad; Rucinski, Blake D; Smith, Travis; Tan, Yanliang

2017-03-01

Optically-stimulated luminescent dosimeters are capable of being interrogated multiple times post-irradiation. Each interrogation removes a fraction of the signal stored within the optically-stimulated luminescent dosimeter. This signal loss must be corrected to avoid systematic errors in estimating the average signal of a series of optically-stimulated luminescent dosimeter interrogations and requires a minimum number of consecutive readings to determine an average signal that is within a desired accuracy of the true signal with a desired statistical confidence. This paper establishes a technical basis for determining the required number of readings for a particular application of these dosimeters when using certain OSL dosimetry systems.
Centrioles to basal bodies in the spermiogenesis of Mastotermes darwiniensis (Insecta, Isoptera).

PubMed

Riparbelli, Maria Giovanna; Callaini, Giuliano; Mercati, David; Hertel, Horst; Dallai, Romano

2009-05-01

In addition to their role in centrosome organization, the centrioles have another distinct function as basal bodies for the formation of cilia and flagella. Centriole duplication has been reported to require two alternate assembly pathways: template or de novo. Since spermiogenesis in the termite Mastotermes darwiniensis lead to the formation of multiflagellate sperm, this process represents a useful model system in which to follow basal body formation and flagella assembly. We present evidence of a possible de novo pathway for basal body formation in the differentiating germ cell. This cell also contains typical centrosomal proteins, such as centrosomin, pericentrin-like protein, gamma-tubulin, that undergo redistribution as spermatid differentiation proceeds. The spermatid centrioles are long structures formed by nine doublet rather than triplet microtubules provided with short projections extending towards the surrounding cytoplasm and with links between doublets. The sperm basal bodies are aligned in parallel beneath the nucleus. They consist of long regions close to the nucleus showing nine doublets in a cartwheel array devoid of any projections; on the contrary, the short region close to the plasma membrane, where the sperm flagella emerge, is characterized by projections similar to those observed in the centrioles linking the basal body to the plasma membrane. It is hypothesized that this appearance is in connection with the centriole elongation and further with the flagellar axonemal organization. Microtubule doublets of sperm flagellar axonemes are provided with outer dynein arms, while inner arms are rarely visible. (c) 2009 Wiley-Liss, Inc.
Higgs couplings and new signals from Flavon-Higgs mixing effects within multi-scalar models

NASA Astrophysics Data System (ADS)

Diaz-Cruz, J. Lorenzo; Saldaña-Salazar, Ulises J.

2016-12-01

Testing the properties of the Higgs particle discovered at the LHC and searching for new physics signals, are some of the most important tasks of Particle Physics today. Current measurements of the Higgs couplings to fermions and gauge bosons, seem consistent with the Standard Model, and when taken as a function of the particle mass, should lay on a single line. However, in models with an extended Higgs sector the diagonal Higgs couplings to up-quarks, down-quarks and charged leptons, could lay on different lines, while non-diagonal flavor-violating Higgs couplings could appear too. We describe these possibilities within the context of multi-Higgs doublet models that employ the Froggatt-Nielsen (FN) mechanism to generate the Yukawa hierarchies. Furthermore, one of the doublets can be chosen to be of the inert type, which provides a viable dark matter candidate. The mixing of the Higgs doublets with the flavon field, can provide plenty of interesting signals, including: i) small corrections to the couplings of the SM-like Higgs, ii) exotic signals from the flavon fields, iii) new signatures from the heavy Higgs bosons. These aspects are studied within a specific model with 3 + 1 Higgs doublets and a singlet FN field. Constraints on the model are derived from the study of K and D mixing and the Higgs search at the LHC. For last, the implications from the latter aforementioned constraints to the FCNC top decay t → ch are presented too.
Spatiotemporal analysis of turbulent jets enabled by 100-kHz, 100-ms burst-mode particle image velocimetry

NASA Astrophysics Data System (ADS)

Miller, Joseph D.; Jiang, Naibo; Slipchenko, Mikhail N.; Mance, Jason G.; Meyer, Terrence R.; Roy, Sukesh; Gord, James R.

2016-12-01

100-kHz particle image velocimetry (PIV) is demonstrated using a double-pulsed, burst-mode laser with a burst duration up to 100 ms. This enables up to 10,000 time-sequential vector fields for capturing a temporal dynamic range spanning over three orders of magnitude in high-speed turbulent flows. Pulse doublets with inter-pulse spacing of 2 µs and repetition rate of 100 kHz are generated using a fiber-based oscillator and amplified through an all-diode-pumped, burst-mode amplifier. A physics-based model of pulse doublet amplification in the burst-mode amplifier is developed and used to accurately predict oscillator pulse width and pulse intensity inputs required to generate equal-energy pulse doublets at 532 nm for velocity measurements. The effect of PIV particle response and high-speed-detector limitations on the spatial and temporal resolution are estimated in subsonic turbulent jets. An effective spatial resolution of 266-275 µm and temporal resolution of 10 µs are estimated from the 8 × 8 pixel correlation window and inter-doublet time spacing, respectively. This spatiotemporal resolution is sufficient for quantitative assessment of integral time and length scales in highly turbulent jets with Reynolds numbers in the range 15,000-50,000. The temporal dynamic range of the burst-mode PIV measurement is 1200, limited by the 85-ms high-energy portion of the burst and 30-kHz high-frequency noise limit.
PEMF as treatment for delayed healing of foot and ankle arthrodesis.

PubMed

Saltzman, Charles; Lightfoot, Andrew; Amendola, Annunziato

2004-11-01

Arthrodesis is the most common surgical treatment for foot and ankle arthritis. In adults, these procedures are associated with a 5% to 10% rate of nonunion. Pulsed electromagnetic field (PEMF) stimulation was approved by the Federal Drug Administration (FDA) for treatment of delayed unions after long-bone fractures and joint arthrodesis. The purpose of this study was to examine the results of PEMF treatment for delayed healing after foot and ankle arthrodesis. Three hundred and thirty-four foot and ankle arthrodeses were done. Nineteen resulted in delayed unions that were treated with a protocol of immobilization, limited weightbearing, and PEMF stimulation for a median of 7 (range 5 to 27) months. All patients were followed clinically and radiographically. The use of PEMF, immobilization, and limited weightbearing to treat delayed union after foot and ankle arthrodesis was successful in 5 of 19 (26%) patients. Of the other 14 patients with nonunions, nine had revision surgery with autogenous grafting, continued immobilization, and PEMF stimulation. Seven of these eventually healed at a median of 5.5 (range 2 to 26) months and two did not heal. One patient had a below-knee amputation, and four refused further treatment. The protocol of PEMF, immobilization, and limited weightbearing had a relatively low success rate in this group of patients. We no longer use this protocol alone to treat delayed union after foot and ankle arthrodesis.
Non-invasive vagus nerve stimulation acutely improves spontaneous cardiac baroreflex sensitivity in healthy young men: A randomized placebo-controlled trial.

PubMed

Antonino, Diego; Teixeira, André L; Maia-Lopes, Paulo M; Souza, Mayara C; Sabino-Carvalho, Jeann L; Murray, Aaron R; Deuchars, Jim; Vianna, Lauro C

Despite positive outcomes of transcutaneous vagus nerve stimulation (tVNS) via the auricular branch of the vagus nerve (ABVN), the mechanisms underlying these outcomes remain unclear. Additionally, previous studies have not been controlled the possible placebo effects of tVNS. To test the hypothesis that tVNS acutely improves spontaneous cardiac baroreflex sensitivity (cBRS) and autonomic modulation, and that these effects are specific to stimulation of ABVN. Thirteen healthy men (23±1yrs) were randomized across three experimental visits. In active tVNS, electrodes were placed on the tragus of the ear and electrical current was applied by using a Transcutaneous Electrical Nerve Stimulation device. A time-control visit was performed with the electrodes placed on tragus, but no current was applied (sham-T). Additionally, to avoid a placebo effect, another sham protocol was performed with same electrical current of the active visit, but the electrodes were placed on the ear lobe (an area without cutaneous nerve endings from the vagus - tLS). Beat-to-beat heart rate (HR) and blood pressure (BP) were monitored at rest, during stimulation (active, sham-T and tLS) and recovery. cBRS was measured via sequence technique. Both HR (HRV) and BP variability (BPV) were also measured. Arterial BP and BPV were not affected by any active or sham protocols (P > 0.05). Resting HR and LF/HF ratio of HRV decreased (Δ-3.4 ± 1% and Δ-15 ± 12%, P < 0.05, respectively) and cBRS increased (Δ24 ± 8%, P < 0.05) during active tVNS, but were unchanged during both sham protocols. tVNS acutely improves cBRS and autonomic modulation in healthy young men. Copyright © 2017 Elsevier Inc. All rights reserved.
The effects of physical therapy with neuromuscular electrical stimulation in patients with septic shock: Study protocol for a randomized cross-over design.

PubMed

Lago, Alessandra Fabiane; de Oliveira, Anamaria Siriani; de Souza, Hugo Celso Dutra; da Silva, João Santana; Basile-Filho, Anibal; Gastaldi, Ada Clarice

2018-02-01

Septic shock is a potentially fatal organ dysfunction caused by an imbalance of the host response to infection. The changes in microcirculation during sepsis can be explained by the alterations in the endothelial barrier function. Endothelial progenitor cells (EPCs) are a potential recovery index of endothelial function and it an increase in response to neuromuscular electrical stimulation (NMES) was demonstrated. Therefore, the objective of this study is to investigate the effects of NMES in patients with septic shock. It is a study protocol for a randomized cross-over design in an intensive care unit of a tertiary University hospital. Thirty-one patients aged 18 to 65 years. The study will be divided in 2 phases: the phase one will be held in the first 72 hours of septic shock and the phase two after 3 days of first assessment. Patients will be randomly selected to the intervention protocol (decubitus position with the limbs raised and NMES) and control protocol (decubitus position with the limbs raised without NMES). After this procedure, the patients will be allocated in group 1 (intervention and control protocol) or group 2 (control and intervention protocol) with a wash-out period of 4 to 6 hours between them. The main outcome is mobilization of EPCs. The secondary outcome is metabolic and hemodynamic data. A linear mixed model will be used for analysis of dependent variables and estimated values of the mean of the differences of each effect.
Optimal number of stimulation contacts for coordinated reset neuromodulation

PubMed Central

Lysyansky, Borys; Popovych, Oleksandr V.; Tass, Peter A.

2013-01-01

In this computational study we investigate coordinated reset (CR) neuromodulation designed for an effective control of synchronization by multi-site stimulation of neuronal target populations. This method was suggested to effectively counteract pathological neuronal synchrony characteristic for several neurological disorders. We study how many stimulation sites are required for optimal CR-induced desynchronization. We found that a moderate increase of the number of stimulation sites may significantly prolong the post-stimulation desynchronized transient after the stimulation is completely switched off. This can, in turn, reduce the amount of the administered stimulation current for the intermittent ON–OFF CR stimulation protocol, where time intervals with stimulation ON are recurrently followed by time intervals with stimulation OFF. In addition, we found that the optimal number of stimulation sites essentially depends on how strongly the administered current decays within the neuronal tissue with increasing distance from the stimulation site. In particular, for a broad spatial stimulation profile, i.e., for a weak spatial decay rate of the stimulation current, CR stimulation can optimally be delivered via a small number of stimulation sites. Our findings may contribute to an optimization of therapeutic applications of CR neuromodulation. PMID:23885239
The simultaneous ex vivo detection of low-frequency antigen-specific CD4+ and CD8+ T-cell responses using overlapping peptide pools.

PubMed

Singh, Satwinder Kaur; Meyering, Maaike; Ramwadhdoebe, Tamara H; Stynenbosch, Linda F M; Redeker, Anke; Kuppen, Peter J K; Melief, Cornelis J M; Welters, Marij J P; van der Burg, Sjoerd H

2012-11-01

The ability to measure antigen-specific T cells at the single-cell level by intracellular cytokine staining (ICS) is a promising immunomonitoring tool and is extensively applied in the evaluation of immunotherapy of cancer. The protocols used to detect antigen-specific CD8+ T-cell responses generally work for the detection of antigen-specific T cells in samples that have undergone at least one round of in vitro pre-stimulation. Application of a common protocol but now using long peptides as antigens was not suitable to simultaneously detect antigen-specific CD8+ and CD4+ T cells directly ex vivo in cryopreserved samples. CD8 T-cell reactivity to monocytes pulsed with long peptides as antigens ranged between 5 and 25 % of that observed against monocytes pulsed with a direct HLA class I fitting minimal CTL peptide epitope. Therefore, we adapted our ICS protocol and show that the use of tenfold higher concentration of long peptides to load APC, the use of IFN-α and poly(I:C) to promote antigen processing and improve T-cell stimulation, does allow for the ex vivo detection of low-frequency antigen-specific CD8+ and CD4+ T cells in an HLA-independent setting. While most of the improvements were related to increasing the ability to measure CD8+ T-cell reactivity following stimulation with long peptides to at least 50 % of the response detected when using a minimal peptide epitope, the final analysis of blood samples from vaccinated patients successfully showed that the adapted ICS protocol also increases the ability to ex vivo detect low-frequency p53-specific CD4+ T-cell responses in cryopreserved PBMC samples.
Optogenetically inspired deep brain stimulation: linking basic with clinical research.

PubMed

Lüscher, Christian; Pollak, Pierre

2016-01-01

In the last decade, optogenetics has revolutionised the neurosciences. The technique, which allows for cell-type specific excitation and inhibition of neurons in the brain of freely moving rodents, has been used to tighten the links of causality between neural activity and behaviour. Optogenetics is also enabling an unprecedented characterisation of circuits and their dysfunction in a number of brain diseases, above all those conditions that are not caused by neurodegeneration. Notable progress has been made in addiction, depression and obsessive-compulsive disorders, as well as other anxiety disorders. By extension, the technique has also been used to propose blueprints for innovative rational treatment of these diseases. The goal is to design manipulations that disrupt pathological circuit function or restore normal activity. This can be achieved by targeting specific projections in order to apply specific stimulation protocols validated by ex-vivo analysis of the mechanisms underlying the dysfunction. In a number of cases, specific forms of pathological synaptic plasticity have been implicated. For example, addictive drugs via strong increase of dopamine trigger a myriad of alterations of glutamate and γ-aminobutyric acid transmission, also called drug-evoked synaptic plasticity. This opens the way to the design of optogenetic reversal protocols, which might restore normal transmission with the hope to abolish the pathological behaviour. Several proof of principle studies for this approach have recently been published. However, for many reasons, optogenetics will not be translatable to human applications in the near future. Here, we argue that an intermediate step is novel deep brain stimulation (DBS) protocols that emulate successful optogenetic approaches in animal models. We provide a roadmap for a translational path to rational, optogenetically inspired DBS protocols to refine existing approaches and expand to novel indications.
Microdose flare protocol with interrupted follicle stimulating hormone and added androgen for poor responders--an observational pilot study.

PubMed

Mitri, Frederic; Behan, Lucy Ann; Murphy, Courtney A; Hershko-Klement, Anat; Casper, Robert F; Bentov, Yaakov

2016-01-01

To investigate whether temporarily withholding FSH and adding androgen could improve follicular response during a microdose flare protocol in women with slow follicular growth or asynchronous follicular development. Observational pilot study. University-affiliated private fertility center. Twenty-six women aged 34-47 years with poor response to stimulation or a previous cancelled IVF cycle and with slow or asynchronous follicular growth during a microdose flare cycle. For 13 women, after initiation of ovarian stimulation using the microdose flare protocol, gonadotropin administration was interrupted and transdermal testosterone gel was added for several days (4.4 ± 1.2 d) starting after cycle day 7 (mean cycle day 10 ± 2.6). FSH, E2, follicular growth, and total number of mature oocytes retrieved were determined for all of the patients. Cycle cancellation rate as well as pregnancy rate following embryo transfer were also documented when applicable. FSH levels declined (25.2 ± 6.5 to 6.8 ± 3.2 IU/L), E2 levels increased (896 ± 687 to 2,163 ± 1,667 pmol/L), and follicular growth improved significantly during gonadotropin interruption and were tracked for 2 days during this time frame. The average number of oocytes retrieved was 5.3 ± 2.6, and the ratio of mature to total oocytes was 4:5. Four of the 13 women in the interruption group conceived following frozen embryo transfer, whereas none in the control group did. The androgen-interrupted FSH protocol may improve follicular response to gonadotropins in cycles that might otherwise be cancelled. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Lasting improvements in left spatial neglect following a protocol combining neck-muscle vibration and voluntary arm movements: a case-study.

PubMed

Ceyte, Hadrien; Beis, Jean-Marie; Simon, Mathilde; Rémy, Ariane; Anxionnat, René; Paysant, Jean; Caudron, Sébastien

2018-01-22

Beyond promising experimental results of sensory passive stimulations in spatial cognition disorders, some questions still remain regarding interests of these stimulations during the daily activities in neglect. The aim of this case-study was to evaluate the effects of a protocol combining left neck-muscle vibration with daily simple movements, like arm pointing movements, on perceptivo-locomotor deficits in a left spatial neglect patient. Two neuropsychological tests, one subjective straight-ahead pointing (SSA) test and one wheelchair navigation test were carried out before the combination protocol, immediately after, 1 h later, and 24 h later. The results showed a reduction of neglect spatial bias following the protocol lasted at least 24 h in all the tests (except for the SSA test due to the unavailability of the pointing device). The range of improvements in the symptoms of spatial neglect suggests that this therapeutic intervention based on the combining neck-muscle vibration to voluntary arm movements could be a useful treatment for this condition. One of future investigation axes should be the development of a vibratory tool in order to facilitate the combining this proprioceptive stimulation to daily activities. Implications for rehabilitation Spatial neglect is a perplexing neuropsychological syndrome, affecting different domains of spatial cognition and impacting also the functional domain. The treatments based on neck-muscle vibration are simple to use, non-invasive and requires none active participation of patient. A therapeutic intervention based on the combining left neck-muscle vibration and voluntary arm movements in a left-spatial-neglect show a lasting reduction of symptoms especially in daily activities. The combination of treatments based on the Bottom-Up approach opens innovative perspectives in rehabilitation.
Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses

PubMed Central

Mishra, Asht M.; Pal, Ajay; Gupta, Disha

2017-01-01

Key points Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord.The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone.Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal.Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Abstract Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. PMID:28752624
Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses.

PubMed

Mishra, Asht M; Pal, Ajay; Gupta, Disha; Carmel, Jason B

2017-11-15

Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord. The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone. Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal. Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.
Neuromuscular adaptations associated with knee joint angle-specific force change.

PubMed

Noorkõiv, Marika; Nosaka, Kazunori; Blazevich, Anthony J

2014-08-01

Neuromuscular adaptations to joint angle-specific force increases after isometric training have not yet been fully elucidated. This study examined angle-specific neuromuscular adaptations in response to isometric knee extension training at short (SL, joint angle 38.1° ± 3.7°) versus long (LL, 87.5° ± 6.0°) muscle lengths. Sixteen men trained three times a week for 6 wk either at SL (n = 8) or LL (n = 8). Voluntary maximal isometric knee extensor (MVC) force, doublet twitch force, EMG amplitudes (EMG/Mmax), and voluntary activation during MVC force (VA%) were measured at eight knee joint angles (30°-100°) at weeks 0, 3, and 6. Muscle volume and cross-sectional area (CSA) were measured from magnetic resonance imaging scans, and fascicle length (Lf) was assessed using ultrasonography before and after training. Clear joint angle specificity of force increase was seen in SL but not in LL. The 13.4% ± 9.7% (P = 0.01) force increase around the training angle in SL was related to changes in vastus lateralis and vastus medialis EMG/Mmax around the training angle (r = 0.84-0.88, P < 0.05), without changes in the doublet twitch force-angle relation or muscle size. In LL, muscle volume and CSA increased and the changes in CSA at specific muscle regions were correlated with changes in MVC force. A 5.4% ± 4.9% (P = 0.001) increase in Lf found in both groups was not associated with angle-specific force changes. There were no angle-specific changes in VA%. The EMG/Mmax, although not VA%, results suggest that neural adaptations underpinned training-related changes at short quadriceps lengths, but hypertrophic changes predominated after training at long lengths. The findings of this study should contribute to the development of more effective and evidence-based rehabilitation and strength training protocols.
In Silico Oncology: Quantification of the In Vivo Antitumor Efficacy of Cisplatin-Based Doublet Therapy in Non-Small Cell Lung Cancer (NSCLC) through a Multiscale Mechanistic Model

PubMed Central

Kolokotroni, Eleni; Dionysiou, Dimitra; Veith, Christian; Kim, Yoo-Jin; Franz, Astrid; Grgic, Aleksandar; Bohle, Rainer M.; Stamatakos, Georgios

2016-01-01

The 5-year survival of non-small cell lung cancer patients can be as low as 1% in advanced stages. For patients with resectable disease, the successful choice of preoperative chemotherapy is critical to eliminate micrometastasis and improve operability. In silico experimentations can suggest the optimal treatment protocol for each patient based on their own multiscale data. A determinant for reliable predictions is the a priori estimation of the drugs’ cytotoxic efficacy on cancer cells for a given treatment. In the present work a mechanistic model of cancer response to treatment is applied for the estimation of a plausible value range of the cell killing efficacy of various cisplatin-based doublet regimens. Among others, the model incorporates the cancer related mechanism of uncontrolled proliferation, population heterogeneity, hypoxia and treatment resistance. The methodology is based on the provision of tumor volumetric data at two time points, before and after or during treatment. It takes into account the effect of tumor microenvironment and cell repopulation on treatment outcome. A thorough sensitivity analysis based on one-factor-at-a-time and latin hypercube sampling/partial rank correlation coefficient approaches has established the volume growth rate and the growth fraction at diagnosis as key features for more accurate estimates. The methodology is applied on the retrospective data of thirteen patients with non-small cell lung cancer who received cisplatin in combination with gemcitabine, vinorelbine or docetaxel in the neoadjuvant context. The selection of model input values has been guided by a comprehensive literature survey on cancer-specific proliferation kinetics. The latin hypercube sampling has been recruited to compensate for patient-specific uncertainties. Concluding, the present work provides a quantitative framework for the estimation of the in-vivo cell-killing ability of various chemotherapies. Correlation studies of such estimates with the molecular profile of patients could serve as a basis for reliable personalized predictions. PMID:27657742
Spatial factors and muscle spindle input influence the generation of neuromuscular responses to stimulation of the human foot

NASA Astrophysics Data System (ADS)

Layne, Charles S.; Forth, Katharine E.; Abercromby, Andrew F. J.

2005-05-01

Removal of the mechanical pressure gradient on the soles leads to physiological adaptations that ultimately result in neuromotor degradation during spaceflight. We propose that mechanical stimulation of the soles serves to partially restore the afference associated with bipedal loading and assists in attenuating the negative neuromotor consequences of spaceflight. A dynamic foot stimulus device was used to stimulate the soles in a variety of conditions with different stimulation locations, stimulation patterns and muscle spindle input. Surface electromyography revealed the lateral side of the sole elicited the greatest neuromuscular response in ankle musculature, followed by the medial side, then the heel. These responses were modified by preceding stimulation. Neuromuscular responses were also influenced by the level of muscle spindle input. These results provide important information that can be used to guide the development of a "passive" countermeasure that relies on sole stimulation and can supplement existing exercise protocols during spaceflight.
Auditory Beat Stimulation and its Effects on Cognition and Mood States

PubMed Central

Chaieb, Leila; Wilpert, Elke Caroline; Reber, Thomas P.; Fell, Juergen

2015-01-01

Auditory beat stimulation may be a promising new tool for the manipulation of cognitive processes and the modulation of mood states. Here, we aim to review the literature examining the most current applications of auditory beat stimulation and its targets. We give a brief overview of research on auditory steady-state responses and its relationship to auditory beat stimulation (ABS). We have summarized relevant studies investigating the neurophysiological changes related to ABS and how they impact upon the design of appropriate stimulation protocols. Focusing on binaural-beat stimulation, we then discuss the role of monaural- and binaural-beat frequencies in cognition and mood states, in addition to their efficacy in targeting disease symptoms. We aim to highlight important points concerning stimulation parameters and try to address why there are often contradictory findings with regard to the outcomes of ABS. PMID:26029120

Stimulation-Based Control of Dynamic Brain Networks

PubMed Central

Pasqualetti, Fabio; Gu, Shi; Cieslak, Matthew

2016-01-01

The ability to modulate brain states using targeted stimulation is increasingly being employed to treat neurological disorders and to enhance human performance. Despite the growing interest in brain stimulation as a form of neuromodulation, much remains unknown about the network-level impact of these focal perturbations. To study the system wide impact of regional stimulation, we employ a data-driven computational model of nonlinear brain dynamics to systematically explore the effects of targeted stimulation. Validating predictions from network control theory, we uncover the relationship between regional controllability and the focal versus global impact of stimulation, and we relate these findings to differences in the underlying network architecture. Finally, by mapping brain regions to cognitive systems, we observe that the default mode system imparts large global change despite being highly constrained by structural connectivity. This work forms an important step towards the development of personalized stimulation protocols for medical treatment or performance enhancement. PMID:27611328
Freezing oocytes or embryos after controlled ovarian hyperstimulation in cancer patients: the state of the art.

PubMed

Bénard, Julie; Duros, Solène; El Hachem, Hady; Sonigo, Charlotte; Sifer, Christophe; Grynberg, Michaël

2016-07-01

Quality of life of young cancer survivors has become a major issue. However, anticancer therapies can have a detrimental impact on fertility. It is now well-established that all patients should receive information about the fertility risks associated with their cancer treatment and the fertility preservation options available. Currently, oocyte or embryo banking after controlled ovarian hyperstimulation represents the most effective method for preserving female fertility. Over the past years innovative protocols of ovarian stimulation have been developed to enable cancer patients to undergo oocyte or embryo cryopreservation irrespective of the phase of the cycle or without exogenous follicle-stimulating hormone-related increase in serum estradiol levels. The present article reviews the different protocols of ovarian hyperstimulation for cancer patients, candidates for fertility preservation.
Repetitive transcranial magnetic stimulation induces oscillatory power changes in chronic tinnitus

PubMed Central

Schecklmann, Martin; Lehner, Astrid; Gollmitzer, Judith; Schmidt, Eldrid; Schlee, Winfried; Langguth, Berthold

2015-01-01

Chronic tinnitus is associated with neuroplastic changes in auditory and non-auditory cortical areas. About 10 years ago, repetitive transcranial magnetic stimulation (rTMS) of auditory and prefrontal cortex was introduced as potential treatment for tinnitus. The resulting changes in tinnitus loudness are interpreted in the context of rTMS induced activity changes (neuroplasticity). Here, we investigate the effect of single rTMS sessions on oscillatory power to probe the capacity of rTMS to interfere with tinnitus-specific cortical plasticity. We measured 20 patients with bilateral chronic tinnitus and 20 healthy controls comparable for age, sex, handedness, and hearing level with a 63-channel electroencephalography (EEG) system. Educational level, intelligence, depressivity and hyperacusis were controlled for by analysis of covariance. Different rTMS protocols were tested: Left and right temporal and left and right prefrontal cortices were each stimulated with 200 pulses at 1 Hz and with an intensity of 60% stimulator output. Stimulation of central parietal cortex with 6-fold reduced intensity (inverted passive-cooled coil) served as sham condition. Before and after each rTMS protocol 5 min of resting state EEG were recorded. The order of rTMS protocols was randomized over two sessions with 1 week interval in between. Analyses on electrode level showed that people with and without tinnitus differed in their response to left temporal and right frontal stimulation. In tinnitus patients left temporal rTMS decreased frontal theta and delta and increased beta2 power, whereas right frontal rTMS decreased right temporal beta3 and gamma power. No changes or increases were observed in the control group. Only non-systematic changes in tinnitus loudness were induced by single sessions of rTMS. This is the first study to show tinnitus-related alterations of neuroplasticity that were specific to stimulation site and oscillatory frequency. The observed effects can be interpreted within the thalamocortical dysrhythmia model assuming that slow waves represent processes of deafferentiation and that high frequencies might be indicators for tinnitus loudness. Moreover our findings confirm the role of the left temporal and the right frontal areas as relevant hubs in tinnitus related neuronal network. Our results underscore the value of combined TMS-EEG measurements for investigating disease related changes in neuroplasticity. PMID:26557055
Subthalamic nucleus deep brain stimulation for Parkinson's disease: evidence for effectiveness and limitations from 12 years' experience.

PubMed

Chan, Anne Y Y; Yeung, Jonas H M; Mok, Vincent C T; Ip, Vincent H L; Wong, Adrian; Kuo, S H; Chan, Danny T M; Zhu, X L; Wong, Edith; Lau, Claire K Y; Wong, Rosanna K M; Tang, Venus; Lau, Christine; Poon, W S

2014-12-01

To present the result and experience of subthalamic nucleus deep brain stimulation for Parkinson's disease. Case series. Prince of Wales Hospital, Hong Kong. A cohort of patients with Parkinson's disease received subthalamic nucleus deep brain stimulation from September 1998 to January 2010. Patient assessment data before and after the operation were collected prospectively. Forty-one patients (21 male and 20 female) with Parkinson's disease underwent bilateral subthalamic nucleus deep brain stimulation and were followed up for a median interval of 12 months. For the whole group, the mean improvements of Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III were 32.5% and 31.5%, respectively (P<0.001). Throughout the years, a multidisciplinary team was gradually built. The deep brain stimulation protocol evolved and was substantiated by updated patient selection criteria and outcome assessment, integrated imaging and neurophysiological targeting, refinement of surgical technique as well as the accumulation of experience in deep brain stimulation programming. Most of the structural improvement occurred before mid-2005. Patients receiving the operation before June 2005 (19 cases) and after (22 cases) were compared; the improvements in UPDRS part III were 13.2% and 55.2%, respectively (P<0.001). There were three operative complications (one lead migration, one cerebral haematoma, and one infection) in the group operated on before 2005. There was no operative mortality. The functional state of Parkinson's disease patients with motor disabilities refractory to best medical treatment improved significantly after subthalamic nucleus deep brain stimulation. A dedicated multidisciplinary team building, refined protocol for patient selection and assessment, improvement of targeting methods, meticulous surgical technique, and experience in programming are the key factors contributing to the improved outcome.
Engineered biomaterial and biophysical stimulation as combinatorial strategies to address prosthetic infection by pathogenic bacteria.

PubMed

Boda, Sunil Kumar; Basu, Bikramjit

2017-10-01

A plethora of antimicrobial strategies are being developed to address prosthetic infection. The currently available methods for implant infection treatment include the use of antibiotics and revision surgery. Among the bacterial strains, Staphylococcus species pose significant challenges particularly, with regard to hospital acquired infections. In order to combat such life threatening infectious diseases, researchers have developed implantable biomaterials incorporating nanoparticles, antimicrobial reinforcements, surface coatings, slippery/non-adhesive and contact killing surfaces. This review discusses a few of the biomaterial and biophysical antimicrobial strategies, which are in the developmental stage and actively being pursued by several research groups. The clinical efficacy of biophysical stimulation methods such as ultrasound, electric and magnetic field treatments against prosthetic infection depends critically on the stimulation protocol and parameters of the treatment modality. A common thread among the three biophysical stimulation methods is the mechanism of bactericidal action, which is centered on biophysical rupture of bacterial membranes, the generation of reactive oxygen species (ROS) and bacterial membrane depolarization evoked by the interference of essential ion-transport. Although the extent of antimicrobial effect, normally achieved through biophysical stimulation protocol is insufficient to warrant therapeutic application, a combination of antibiotic/ROS inducing agents and biophysical stimulation methods can elicit a clinically relevant reduction in viable bacterial numbers. In this review, we present a detailed account of both the biomaterial and biophysical approaches for achieving maximum bacterial inactivation. Summarizing, the biophysical stimulation methods in a combinatorial manner with material based strategies can be a more potent solution to control bacterial infections. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2174-2190, 2017. © 2016 Wiley Periodicals, Inc.
A second Higgs doublet in the early universe: baryogenesis and gravitational waves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dorsch, G.C.; Konstandin, T.; Huber, S.J.

We show that simple Two Higgs Doublet models might still provide a viable explanation for the matter-antimatter asymmetry of the Universe via electroweak baryogenesis, even after taking into account the recent order-of-magnitude improvement on the electron-EDM experimental bound by the ACME Collaboration. Moreover we show that, in the region of parameter space where baryogenesis may be possible, the gravitational wave spectrum generated at the end of the electroweak phase transition is within the sensitivity reach of the future space-based interferometer LISA.
Neutrinophilic two Higgs doublet model with dark matter under an alternative U(1)_{B-L} gauge symmetry

NASA Astrophysics Data System (ADS)

Nomura, Takaaki; Okada, Hiroshi

2018-03-01

We propose a Dirac type active neutrino with rank two mass matrix and a Majorana fermion dark matter candidate with an alternative local U(1)_{B-L} extension of neutrinophilic two Higgs doublet model. Our dark matter candidate can be stabilized due to charge assignment under the gauge symmetry without imposing extra discrete Z_2 symmetry and the relic density is obtained from an Z' boson exchanging process. Taking into account collider constraints on the Z' boson mass and coupling, we estimate the relic density.
New decay modes of heavy Higgs bosons in a two Higgs doublet model with vectorlike leptons

DOE PAGES

Dermíšek, Radovan; Lunghi, Enrico; Shin, Seodong

2016-05-25

In models with extended Higgs sector and additional matter fields, the decay modes of heavy Higgs bosons can be dominated by cascade decays through the new fermions rendering present search strategies ineffective. Here, we investigate new decay topologies of heavy neutral Higgses in two Higgs doublet model with vectorlike leptons. We also discus constraints from existing searches and discovery prospects. Among the most interesting signatures are monojet, mono Z, mono Higgs, and Z and Higgs bosons produced with a pair of charged leptons.
Vector boson fusion in the inert doublet model

NASA Astrophysics Data System (ADS)

Dutta, Bhaskar; Palacio, Guillermo; Restrepo, Diego; Ruiz-Álvarez, José D.

2018-03-01

In this paper we probe the inert Higgs doublet model at the LHC using vector boson fusion (VBF) search strategy. We optimize the selection cuts and investigate the parameter space of the model and we show that the VBF search has a better reach when compared with the monojet searches. We also investigate the Drell-Yan type cuts and show that they can be important for smaller charged Higgs masses. We determine the 3 σ reach for the parameter space using these optimized cuts for a luminosity of 3000 fb-1 .
Color correction strategies in optical design

NASA Astrophysics Data System (ADS)

Pfisterer, Richard N.; Vorndran, Shelby D.

2014-12-01

An overview of color correction strategies is presented. Starting with basic first-order aberration theory, we identify known color corrected solutions for doublets and triplets. Reviewing the modern approaches of Robb-Mercado, Rayces-Aguilar, and C. de Albuquerque et al, we find that they confirm the existence of glass combinations for doublets and triplets that yield color corrected solutions that we already know exist. Finally we explore the use of the y, ӯ diagram in conjunction with aberration theory to identify the solution space of glasses capable of leading to color corrected solutions in arbitrary optical systems.
Elastic anomalies associated with two successive transitions of PrV2Al20 probed by ultrasound measurements

NASA Astrophysics Data System (ADS)

Nakanishi, Y.; Taniguchi, M.; Nakamura, M. M.; Hasegawa, J.; Ohyama, R.; Nakamura, M.; Yoshizawa, M.; Tsujimoto, M.; Nakatsuji, S.

2018-05-01

We have performed the ultrasound measurement on the non-Kramers doublet system PrV2Al20 in order to figure out the low-temperature multi-quadrupolar phase appearing at low temperatures. Elastic anomalies and their systematic magnetic field evolution were clearly observed in the temperature dependence of the elastic constant C44(T). We discuss the possible origin and implications of the rich variety of phases emerging from the simple ground state: the well-isolated non-Kramers doublet Γ3 subspace.
Re-derived overclosure bound for the inert doublet model

NASA Astrophysics Data System (ADS)

Biondini, S.; Laine, M.

2017-08-01

We apply a formalism accounting for thermal effects (such as modified Sommerfeld effect; Salpeter correction; decohering scatterings; dissociation of bound states), to one of the simplest WIMP-like dark matter models, associated with an "inert" Higgs doublet. A broad temperature range T ˜ M/20 . . . M/104 is considered, stressing the importance and less-understood nature of late annihilation stages. Even though only weak interactions play a role, we find that resummed real and virtual corrections increase the tree-level overclosure bound by 1 . . . 18%, depending on quartic couplings and mass splittings.
Encapsulation of a [Dy(OH2)8](3+) cation: magneto-optical and theoretical studies of a caged, emissive SMM.

PubMed

Al Hareri, M; Gavey, E L; Regier, J; Ras Ali, Z; Carlos, L D; Ferreira, R A S; Pilkington, M

2016-10-15

The first supramolecular cage formed by three benzo-15-crown-5 macrocycles encapsulating a [Dy(OH2)8](3+) guest cation is reported, with the Dy(iii) centre exhibiting local pseudo square antiprismatic D4d symmetry. The anisotropy barrier extracted from ac susceptibility studies, emission spectroscopy and ab initio calculations reveals that the second excited state Kramers doublet plays a key role in the magnetization dynamics due to the Ising character and near coparallel nature of the ground and first excited Kramers doublets.
Microdose GnRH Agonist Flare-Up versus Ultrashort GnRH Agonist Combined with Fixed GnRH Antagonist in Poor Responders of Assisted Reproductive Techniques Cycles.

PubMed

Eftekhar, Maryam; Mohammadian, Farnaz; Yousefnejad, Fariba; Khani, Parisa

2013-01-01

This study compares the microdose flare-up protocol to the ultrashort gonadotropinreleasing hormone (GnRH) agonist flare combined with the fixed multidose GnRH antagonist protocol in poor responders undergoing ovarian stimulation. In this randomized clinical trial, 120 women who were candidates for assisted reproductive techniques (ART) and had histories of one or more failed in vitro fertilization (IVF) cycles with three or fewer retrieved oocytes were prospectively randomized into two groups. Group I (60 patients) received the microdose flare-up regimen and group II (60 patients) received the ultrashort GnRH agonist combined with fixed GnRH antagonist. There were no significant differences between the groups in the number of used gonadotropin ampoules (p=0.591), duration of stimulation (p=0.610), number of retrieved oocytes (p=0.802), fertilization rate (p=0.456), and the number of transferred embryos (p=0.954). The clinical pregnancy rates were statistically similar in group I (10%) compared with group II (13.3%, p=0.389). According to our results, there is no significant difference between these protocols for improving the ART outcome in poor responders. Additional prospective, randomized studies with more patients is necessary to determine the best protocol (Registration Number: IRCT201105096420N1).
Follicular synchronization using transdermal estradiol patch and GnRH antagonists in the luteal phase; does it increase oocyte yield in poor responders to gonadotropin stimulation for in vitro fertilization (IVF)? A comparative study with microdose flare-up protocol.

PubMed

Ata, Baris; Zeng, Xing; Son, Weon Y; Holzer, Hananel; Tan, Seang L

2011-11-01

The aim of this retrospective study was to compare the oocyte yield with the luteal estradiol patch (LPA) - GnRH antagonist and microdose (MD) flare-up protocols in anticipated poor responders. Fifty-seven women who underwent IVF treatment following stimulation with LPA or MD protocols at McGill Reproductive Centre were matched for age and markers of ovarian reserve. Numbers of oocytes collected (6 vs 7), mature oocytes collected (5 vs 5), and oocyte maturation rates (72% vs 74%) were similar. The numbers of good quality embryos available (2 vs 1) and embryos transferred (3 vs 3) were likewise similar. Embryo implantation rate of 16.7% and clinical pregnancy rate of 38.9% achieved in the LPA group were almost 50% higher than the corresponding figures at 10.3% and 22.2% in the MD group; however, the differences were not statistically significant (p > 0.05 for all comparisons). Although the results do not suggest an increased oocyte yield or follicular synchronization with the LPA protocol, the observed trend toward higher embryo implantation and clinical pregnancy rates requires further research.
The effects of physical therapy with neuromuscular electrical stimulation in patients with septic shock

PubMed Central

Lago, Alessandra Fabiane; de Oliveira, Anamaria Siriani; de Souza, Hugo Celso Dutra; da Silva, João Santana; Basile-Filho, Anibal; Gastaldi, Ada Clarice

2018-01-01

Abstract Introduction: Septic shock is a potentially fatal organ dysfunction caused by an imbalance of the host response to infection. The changes in microcirculation during sepsis can be explained by the alterations in the endothelial barrier function. Endothelial progenitor cells (EPCs) are a potential recovery index of endothelial function and it an increase in response to neuromuscular electrical stimulation (NMES) was demonstrated. Therefore, the objective of this study is to investigate the effects of NMES in patients with septic shock. Methods and analysis: It is a study protocol for a randomized cross-over design in an intensive care unit of a tertiary University hospital. Thirty-one patients aged 18 to 65 years. The study will be divided in 2 phases: the phase one will be held in the first 72 hours of septic shock and the phase two after 3 days of first assessment. Patients will be randomly selected to the intervention protocol (decubitus position with the limbs raised and NMES) and control protocol (decubitus position with the limbs raised without NMES). After this procedure, the patients will be allocated in group 1 (intervention and control protocol) or group 2 (control and intervention protocol) with a wash-out period of 4 to 6 hours between them. The main outcome is mobilization of EPCs. The secondary outcome is metabolic and hemodynamic data. A linear mixed model will be used for analysis of dependent variables and estimated values of the mean of the differences of each effect. PMID:29419665
Comparison of microdose flare-up and antagonist multiple-dose protocols for poor-responder patients: a randomized study.

PubMed

Demirol, Aygul; Gurgan, Timur

2009-08-01

To compare the efficacy of the microdose flare-up and multiple-dose antagonist protocols for poor-responder patients in intracytoplasmic sperm injection-ET cycles. A randomized, prospective study. Center for assisted reproductive technology in Turkey. Ninety patients with poor ovarian response in a minimum of two previous IVF cycles. All women were prospectively randomized into two groups by computer-assisted randomization. The patients in group 1 were stimulated according to the microdose flare-up protocol (n = 45), while the patients in group 2 were stimulated according to antagonist multiple-dose protocol (n = 45). The mean number of mature oocytes retrieved was the primary outcome measure, and fertilization rate, implantation rate per embryo, and clinical pregnancy rates were secondary outcome measures. The mean age of the women, the mean duration of infertility, basal FSH level, and the number of previous IVF cycles were similar in both groups. The total gonadotropin dose used was significantly higher in group 2, while the number of oocytes retrieved was significantly greater in group 1. Although the fertilization and clinical pregnancy rates were nonsignificantly higher in group 1 compared with group 2, the implantation rate was significantly higher in the microdose flare-up group than in the multiple-dose antagonist group (22% vs. 11%). The microdose flare-up protocol seems to have a better outcome in poor-responder patients, with a significantly higher mean number of mature oocytes retrieved and higher implantation rate.
The effect of angiotensin-converting enzyme inhibition throughout a superovulation protocol in ewes.

PubMed

Pereira, Alécio Matos; de Souza Júnior, Antônio; Machado, Fernanda Brandão; Gonçalves, Gleisy Kelly Neves; Feitosa, Lauro César Soares; Reis, Adelina Martha; Santos, Robson Augusto Souza; Honorato-Sampaio, Kinulpe; Costa, Amilton Raposo

2015-12-01

Many studies identified new components of the renin–angiotensin system (RAS), such as Angiotensin-(1-7) [Ang-(1–7)] and Angiotensin-converting enzyme type 2 (ACE2), in mammalian ovaries.We previously showed Angiotensin-Converting Enzyme (ACE) inhibition, which increases the level of Ang-(1–7), stimulated ovarian estradiol output in ewe after estrous synchronization. Considering that Ang-(1–7) stimulates ovarian function and elevated estradiol before ovulation is associated with increased chance of achieving pregnancy, the present study investigated whether ACE inhibition throughout a superovulation protocol in ewe might improve ovulation outcome. At first, immunohistochemistry in ovaries of nonpregnant ewes revealed localization of Angiotensin II (Ang II), Ang-(1–7) and ACE2 in theca cells of antral follicles and in corpus luteum. Ang II and Ang-(1–7)were also detected in follicular fluid (FF) by Radioimmunoassay (RIA). Enalapril treatment throughout the superovulation protocol decreased 17β-estradiol (E2) output and raised progesterone:estradiol (P4:E2) ratio without a direct influence on ovulation and quality of embryos.
High-resolution Modeling Assisted Design of Customized and Individualized Transcranial Direct Current Stimulation Protocols

PubMed Central

Bikson, Marom; Rahman, Asif; Datta, Abhishek; Fregni, Felipe; Merabet, Lotfi

2012-01-01

Objectives Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity currents facilitating or inhibiting spontaneous neuronal activity. tDCS is attractive since dose is readily adjustable by simply changing electrode number, position, size, shape, and current. In the recent past, computational models have been developed with increased precision with the goal to help customize tDCS dose. The aim of this review is to discuss the incorporation of high-resolution patient-specific computer modeling to guide and optimize tDCS. Methods In this review, we discuss the following topics: (i) The clinical motivation and rationale for models of transcranial stimulation is considered pivotal in order to leverage the flexibility of neuromodulation; (ii) The protocols and the workflow for developing high-resolution models; (iii) The technical challenges and limitations of interpreting modeling predictions, and (iv) Real cases merging modeling and clinical data illustrating the impact of computational models on the rational design of rehabilitative electrotherapy. Conclusions Though modeling for non-invasive brain stimulation is still in its development phase, it is predicted that with increased validation, dissemination, simplification and democratization of modeling tools, computational forward models of neuromodulation will become useful tools to guide the optimization of clinical electrotherapy. PMID:22780230
Monitoring muscle metabolic indexes by time-domain near-infrared spectroscopy during knee flex-extension induced by functional electrical stimulation.

PubMed

Ferrante, Simona; Contini, Davide; Spinelli, Lorenzo; Pedrocchi, Alessandra; Torricelli, Alessandro; Molteni, Franco; Ferrigno, Giancarlo; Cubeddu, Rinaldo

2009-01-01

A noninvasive methodology, combining functional electrical stimulation and time-domain near-infrared spectroscopy (TD-NIRS), is developed to verify whether stroke-altered muscular metabolism on postacute patients. Seven healthy subjects and nine postacute stroke patients undergo a protocol of knee flex-extension induced by quadricep electrical stimulation. During the protocol, TD-NIRS measurements are performed on both rectus femoris to investigate whether significant differences arise between able-bodied and stroke subjects and between patients' paretic and healthy legs. During baseline, metabolic parameters do not show any significant differences among subjects. During stimulation, paretic limbs produce a knee angle significantly lower than healthy legs. During recovery, patients' healthy limbs show a metabolic behavior correlated to able-bodied subjects. Instead, the correlation between the metabolic behavior of the paretic and able-bodied legs allows the definition of two patients' subgroups: one highly correlated (R>0.87) and the other uncorrelated (R<0.08). This grouping reflects the patient functional condition. The results obtained on the most impaired patients suggest that stroke does not produce any systemic consequences at the muscle, but the metabolic dysfunction seems to be local and unilateral. It is crucial to enlarge the sample size of the two subgroups before making these preliminary results a general finding.

Monitoring muscle metabolic indexes by time-domain near-infrared spectroscopy during knee flex-extension induced by functional electrical stimulation

NASA Astrophysics Data System (ADS)

Ferrante, Simona; Contini, Davide; Spinelli, Lorenzo; Pedrocchi, Alessandra; Torricelli, Alessandro; Molteni, Franco; Ferrigno, Giancarlo; Cubeddu, Rinaldo

2009-07-01

A noninvasive methodology, combining functional electrical stimulation and time-domain near-infrared spectroscopy (TD-NIRS), is developed to verify whether stroke-altered muscular metabolism on postacute patients. Seven healthy subjects and nine postacute stroke patients undergo a protocol of knee flex-extension induced by quadricep electrical stimulation. During the protocol, TD-NIRS measurements are performed on both rectus femoris to investigate whether significant differences arise between able-bodied and stroke subjects and between patients' paretic and healthy legs. During baseline, metabolic parameters do not show any significant differences among subjects. During stimulation, paretic limbs produce a knee angle significantly lower than healthy legs. During recovery, patients' healthy limbs show a metabolic behavior correlated to able-bodied subjects. Instead, the correlation between the metabolic behavior of the paretic and able-bodied legs allows the definition of two patients' subgroups: one highly correlated (R>0.87) and the other uncorrelated (R<0.08). This grouping reflects the patient functional condition. The results obtained on the most impaired patients suggest that stroke does not produce any systemic consequences at the muscle, but the metabolic dysfunction seems to be local and unilateral. It is crucial to enlarge the sample size of the two subgroups before making these preliminary results a general finding.
Effects of intermittent theta burst stimulation on spasticity after spinal cord injury.

PubMed

Nardone, Raffaele; Langthaler, Patrick B; Orioli, Andrea; Höller, Peter; Höller, Yvonne; Frey, Vanessa N; Brigo, Francesco; Trinka, Eugen

2017-01-01

Spasticity is a common disorder in patients with spinal cord injury (SCI). The aim of this study was to investigate whether intermittent theta burst stimulation (iTBS), a safe, non-invasive and well-tolerated protocol of excitatory repetitive transcranial magnetic stimulation (rTMS), is effective in modulating spasticity in SCI patients. In this randomized, double-blind, crossover, sham-controlled study, ten subjects with incomplete cervical or thoracic SCI received 10 days of daily sessions of real or sham iTBS. The H/M amplitude ratio of the Soleus H reflex, the amplitude of the motor evoked potentials (MEPs) at rest and during background contraction, as well as Modified Ashworth Scale (MAS) and the Spinal Cord Injury Assessment Tool for Spasticity (SCAT) were compared before and after the stimulation protocols. Patients receiving real iTBS showed significant increased resting and active MEPs amplitude and a significant reduction of the H/M amplitude ratio. In these patients also the MAS and SCAT scores were significantly reduced after treatment. These changes persisted up to 1 week after the end of the iTBS treatment, and were not observed under the sham-TBS condition. These findings suggest that iTBS may be a promising therapeutic tool for the spasticity in SCI patients.
Oxygen consumption is a quality marker for human oocyte competence conditioned by ovarian stimulation regimens.

PubMed

Tejera, Aberto; Herrero, Javier; de Los Santos, M J; Garrido, Nicolás; Ramsing, Niels; Meseguer, Marcos

2011-09-01

To evaluate the effect of different ovarian stimulation protocols on oocyte respiration and to investigate the relationship between oocyte oxygen consumption and reproductive outcome. Prospective observational cohort study. Infertility clinic in a university hospital. A total of 349 oocytes from 56 IVF treatment cycles in our oocyte donation program. None. Average oocyte oxygen consumption rate in fmol/s. We correlated oxygen consumption values with ovarian stimulation features, fertilization, embryo quality on days 2 and 3, and implantation. Differences in the measured oxygen consumption rates were found depending on which type of gonadotropins were used in the stimulation protocol. Higher consumption rates were found for oocytes that underwent normal fertilization compared with rates from nonfertilized or abnormal oocytes (odds ratio = 1.340; 95% confidence intervals = 1.037-1.732). Furthermore, higher oxygen consumption was observed for those oocytes which generated embryos that implanted compared with those that did not implant (6.21 ± 0.849 fmol/s vs. 5.23 ± 0.345 fmol/s. Measurement of oxygen consumption rates for individual oocytes before fertilization provides a noninvasive marker of oocyte quality and hence a quantitative assessment of the reproductive potential for the oocyte. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Motor Cortex Stimulation in Patients Suffering from Chronic Neuropathic Pain: Summary of Expert Meeting and Premeeting Questionnaire, Combined with Literature Review.

PubMed

Kurt, Erkan; Henssen, Dylan J H A; Steegers, Monique; Staal, Michiel; Beese, Ulrich; Maarrawi, Joseph; Pirotte, Benoit; Garcia-Larrea, Luis; Rasche, Dirk; Vesper, Jan; Holsheimer, Jan; Duyvendak, Wim; Herregodts, Patrick; van Dongen, Robert; Moens, Maarten

2017-12-01

Motor cortex stimulation (MCS) was introduced in the early 1990s by Tsubokawa and his group for patients diagnosed with drug-resistant, central neuropathic pain. Inconsistencies concerning the details of this therapy and its outcomes and poor methodology of most clinical essays divide the neuromodulation society worldwide into "believers" and "nonbelievers." A European expert meeting was organized in Brussels, Belgium by the Benelux Neuromodulation Society in order to develop uniform MCS protocols in the preoperative, intraoperative, and postoperative courses. An expert meeting was organized, and a questionnaire was sent out to all the invited participants before this expert meeting. An extensive literature research was conducted in order to enrich the results. Topics that were addressed during the expert meeting were 1) inclusion and exclusion criteria, 2) targeting and methods of stimulation, 3) effects of MCS, and 4) results from the questionnaire. Substantial commonalities but also important methodologic divergencies emerged from the discussion of MCS experts from 7 European Centers. From this meeting and questionnaire, all participants concluded that there is a need for more homogenous standardized protocols for MCS regarding patient selection, implantation procedure, stimulation parameters, and follow-up-course. Copyright © 2017 Elsevier Inc. All rights reserved.
Geophysical and Geochemical Signatures Associated with Mantle Fluids Beneath an Active Shear Zone, Southwest Japan

NASA Astrophysics Data System (ADS)

Umeda, K.; Asamori, K.; Sueoka, S.; Tamura, H.; Shimizu, M.

2014-12-01

In 1997, the Kagoshima earthquake doublet, consisting of two closely associated Mw ~ 6 strike-slip events, five km and 48 days apart, has occurred in southwest Japan. The location is where an E-W trending discontinuity along 32°N latitude on southern Kyushu Island is clearly defined in GPS velocities, indicating the presence of a highly active left-lateral shear zone. However, there have not been any obvious indications of active faulting at the surface prior to the earthquake doublet, which could be associated with this shear zone. Three-dimensional inversion of magnetotelluric sounding data obtained in the source region of the earthquake doublet reveals a near-vertical conductive zone with a width of 20 km, extending down to the base of the crust and perhaps into the upper mantle toward the Okinawa trough. The prominent conductor corresponds to the western part of the active shear zone. Elevated 3He/4He ratios in groundwaters sampled from hot spring and drinking water wells suggest the emission of mantle-derived helium from the seismic source region. The geophysical and geochemical observations are significant indications that the invasion of mantle fluids into the crust, driven by upwelling asthenosphere from the Okinawa trough, triggers the notable left-lateral shearing in the zone in the present-day subduction system. In addition, the existence of aqueous fluids in and below the seismogenic layer could change the strength of the zones, and alter the local stress regime, resulting in the occurrence of the 1997 earthquake doublet.
A comparison of muscular activity during single and double mouse clicks.

PubMed

Thorn, Stefan; Forsman, Mikael; Hallbeck, Susan

2005-05-01

Work-related musculoskeletal disorders (WMSDs) in the neck/shoulder region and the upper extremities are a common problem among computer workers. Occurrences of motor unit (MU) double discharges with very short inter-firing intervals (doublets) have been hypothesised as a potential additional risk for overuse of already exhausted fibres during long-term stereotyped activity. Doublets are reported to be present during double-click mouse work tasks. A few comparative studies have been carried out on overall muscle activities for short-term tasks with single types of actions, but none on occurrences of doublets during double versus single clicks. The main purpose of this study was to compare muscle activity levels of single and double mouse clicks during a long-term combined mouse/keyboard work task. Four muscles were studied: left and right upper trapezius, right extensor digitorum communis (EDC) and right flexor carpi ulnaris. Additionally, MU activity was analysed through intramuscular electromyography in the EDC muscle for a selection of subjects. The results indicate that double clicking produces neither higher median or 90th percentile levels in the trapezius and EDC muscles, nor a higher disposition for MU doublets, than does single clicking. Especially for the 90th percentile levels, the indications are rather the opposite (in the EDC significantly higher during single clicks in 8 of 11 subjects, P < 0.05). Although it cannot be concluded from the present study that double clicks are harmless, there were no signs that double clicks during computer work generally constitute a larger risk factor for WMSDs than do single clicks.
An In Vitro Spectroscopic Analysis to Determine Whether para-Chloroaniline is Produced from Mixing Sodium Hypochlorite and Chlorhexidine

PubMed Central

Thomas, John E.; Sem, Daniel S.

2009-01-01

Introduction The purpose of this in vitro study was to determine whether para-chloroaniline (PCA) is formed through the reaction of mixing sodium hypochlorite (NaOCl) and chlorhexidine (CHX). Methods Initially commercially available samples of chlorhexidine acetate (CHXa) and PCA were analyzed with 1H NMR spectroscopy. Two solutions, NaOCl and CHXa, were warmed to 37°C and when mixed they produced a brown precipitate. This precipitate was separated in half and pure PCA was added to one of the samples for comparison before they were each analyzed with 1H NMR spectroscopy. Results The peaks in the 1H NMR spectra of CHXa and PCA were assigned to specific protons of the molecules, and the location of the aromatic peaks in the PCA spectrum defined the PCA doublet region. While the spectrum of the precipitate alone resulted in a complex combination of peaks, upon magnification there were no peaks in the PCA doublet region which were intense enough to be quantified. In the spectrum of the precipitate, to which PCA was added, two peaks do appear in the PCA doublet region. Comparing this spectrum to that of precipitate alone, the peaks in the PCA doublet region are not visible prior to the addition of PCA. Conclusions Based on this in vitro study, the reaction mixture of NaOCl and CHXa does not produce PCA at any measurable quantity and further investigation is needed to determine the chemical composition of the brown precipitate. PMID:20113799
Noise-Enhanced Measurement of Weak Doublet Spectra with a Fourier-Transform Spectrometer and a 1-Bit Analog-to-Digital Converter.

PubMed

Lim, M; Saloma, C

2001-04-10

We demonstrate an efficient noise dithering procedure for measuring the power spectrum of a weak spectral doublet with a Fourier-transform spectrometer in which the subthreshold interferogram is measured by a 1-bit analog-to-digital converter without oversampling. In the absence of noise, no information is obtained regarding the doublet spectrum because the modulation term s(x) of its interferogram is below the instrumental detection limit B, i.e., |s(x)| < B, for all path difference x values. Extensive numerical experiments are carried out concerning the recovery of the doublet power spectrum that is represented by s(x) = (s(0)/2)exp(-pi(2)x(2)/beta)[cos(2pif(1)x) + cos(2pif(2)x)], where s(0) is a constant, beta is the linewidth factor, and ?f? = (f(1) + f(2))/2. Different values of ?f?, s(0), and beta are considered to evaluate thoroughly the accuracy of the procedure to determine the unknown values of f(1) and f(2), the spectral linewidth, and the peak values of the spectral profiles. Our experiments show that, even for short observation times, the resonant frequencies of s(x) could be located with high accuracy over a wide range of ?f? and beta values. Signal-to-noise ratios as high as 50 are also gained for the recovered power spectra. The performance of the procedure is also analyzed with respect to another method that recovers the amplitude values of s(x) directly.
Electronic design of a multichannel programmable implant for neuromuscular electrical stimulation.

PubMed

Arabi, K; Sawan, M A

1999-06-01

An advanced stimulator for neuromuscular stimulation of spinal cord injured patients has been developed. The stimulator is externally controlled and powered by a single encoded radio frequency carrier and has four independently controlled bipolar stimulation channels. It offers a wide range of reprogrammability and flexibility, and can be used in many neuromuscular electrical stimulation applications. The implant system is adaptable to patient's needs and to future developments in stimulation algorithms by reprogramming the stimulator. The stimulator is capable of generating a wide range of stimulation waveforms and stimulation patterns and therefore is very suitable for selective nerve stimulation techniques. The reliability of the implant has been increased by using a forward error detection and correction communication protocol and by designing the chip for structural testability based on scan test approach. Implemented testability scheme makes it possible to verify the complete functionality of the implant before and after implantation. The stimulators architecture is designed to be modular and therefore its different blocks can be reused as standard building blocks in the design and implementation of other neuromuscular prostheses. Design for low-power techniques have also been employed to reduce power consumption of the electronic circuitry.
Promoting communication with older adults: protocols for resolving interpersonal conflicts and for enhancing interactions with doctors.

PubMed

Weitzman, Patricia Flynn; Weitzman, Eben A

2003-07-01

In this paper, we review the importance of effective communication in older adulthood, and ideas for promoting it. We focus on theoretical and applied work in two communicative encounters that have particular relevance for older adult health, i.e., interpersonal conflict and visits with a healthcare provider. Little applied work has aimed to adapt training protocols for older adults in these two areas. We will present training protocols we have developed in constructive conflict resolution for older adults, and on enhancing doctor-patient communication. We present these protocols to stimulate ideas on the part of the reader on how to further develop and refine training efforts for older adults in effective communication.
Efficacy of intermittent Theta Burst Stimulation (iTBS) and 10-Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant unipolar depression: study protocol for a randomised controlled trial.

PubMed

Bulteau, Samuel; Sébille, Veronique; Fayet, Guillemette; Thomas-Ollivier, Veronique; Deschamps, Thibault; Bonnin-Rivalland, Annabelle; Laforgue, Edouard; Pichot, Anne; Valrivière, Pierre; Auffray-Calvier, Elisabeth; Fortin, June; Péréon, Yann; Vanelle, Jean-Marie; Sauvaget, Anne

2017-01-13

The treatment of depression remains a challenge since at least 40% of patients do not respond to initial antidepressant therapy and 20% present chronic symptoms (more than 2 years despite standard treatment administered correctly). Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy but still not ideal. Intermittent Theta Burst Stimulation (iTBS), which has only been used recently in clinical practice, could have a faster and more intense effect compared to conventional protocols, including 10-Hz high-frequency rTMS (HF-rTMS). However, no controlled study has so far highlighted the superiority of iTBS in resistant unipolar depression. This paper focuses on the design of a randomised, controlled, double-blind, single-centre study with two parallel arms, carried out in France, in an attempt to assess the efficacy of an iTBS protocol versus a standard HF- rTMS protocol. Sixty patients aged between 18 and 75 years of age will be enrolled. They must be diagnosed with major depressive disorder persisting despite treatment with two antidepressants at an effective dose over a period of 6 weeks during the current episode. The study will consist of two phases: a treatment phase comprising 20 sessions of rTMS to the left dorsolateral prefrontal cortex, localised via a neuronavigation system and a 6-month longitudinal follow-up. The primary endpoint will be the number of responders per group, defined by a decrease of at least 50% in the initial score on the Montgomery and Asberg Rating Scale (MADRS) at the end of rTMS sessions. The secondary endpoints will be: response rate 1 month after rTMS sessions; number of remissions defined by a MADRS score of <8 at the endpoint and 1 month after; the number of responses and remissions maintained over the next 6 months; quality of life; and the presence of predictive markers of the therapeutic response: clinical (dimensional scales), neuropsychological (evaluation of cognitive functions), motor (objective motor testing) and neurophysiological (cortical excitability measurements). The purpose of our study is to check the assumption of iTBS superiority in the management of unipolar depression and we will discuss its effect over time. In case of a significant increase in the number of therapeutic responses with a prolonged effect, the iTBS protocol could be considered a first-line protocol in resistant unipolar depression. ClinicalTrials.gov, Identifier NCT02376491 . Registered on 17 February 2015 at http://clinicaltrials.gov .
Multiplexed droplet single-cell RNA-sequencing using natural genetic variation.

PubMed

Kang, Hyun Min; Subramaniam, Meena; Targ, Sasha; Nguyen, Michelle; Maliskova, Lenka; McCarthy, Elizabeth; Wan, Eunice; Wong, Simon; Byrnes, Lauren; Lanata, Cristina M; Gate, Rachel E; Mostafavi, Sara; Marson, Alexander; Zaitlen, Noah; Criswell, Lindsey A; Ye, Chun Jimmie

2018-01-01

Droplet single-cell RNA-sequencing (dscRNA-seq) has enabled rapid, massively parallel profiling of transcriptomes. However, assessing differential expression across multiple individuals has been hampered by inefficient sample processing and technical batch effects. Here we describe a computational tool, demuxlet, that harnesses natural genetic variation to determine the sample identity of each droplet containing a single cell (singlet) and detect droplets containing two cells (doublets). These capabilities enable multiplexed dscRNA-seq experiments in which cells from unrelated individuals are pooled and captured at higher throughput than in standard workflows. Using simulated data, we show that 50 single-nucleotide polymorphisms (SNPs) per cell are sufficient to assign 97% of singlets and identify 92% of doublets in pools of up to 64 individuals. Given genotyping data for each of eight pooled samples, demuxlet correctly recovers the sample identity of >99% of singlets and identifies doublets at rates consistent with previous estimates. We apply demuxlet to assess cell-type-specific changes in gene expression in 8 pooled lupus patient samples treated with interferon (IFN)-β and perform eQTL analysis on 23 pooled samples.
A 400 Gbps/100 m free-space optical link

NASA Astrophysics Data System (ADS)

Lin, Chun-Yu; Lu, Hai-Han; Ho, Chun-Ming; Cheng, Ming-Te; Huang, Sheng-Jhe; Wang, Yun-Chieh; Chi, Jing-Kai

2017-02-01

A 400 Gbps/100 m free-space optical (FSO) link with dense-wavelength-division-multiplexing (DWDM)/space-division-multiplexing (SDM) techniques and a doublet lens scheme is proposed. To the best of our knowledge, this is the first time that a link adopting DWDM and SDM techniques and a doublet lens scheme has demonstrated a 400 Gbps/100 m FSO link. The experimental results show that the free-space transmission rate is significantly enhanced by the DWDM and SDM techniques, and the free-space transmission distance is greatly increased by the doublet lens scheme. A 16-channel FSO link with a total transmission rate of 400 Gbps (25 Gbps/λ × 16 λ = 400 Gbps) over a 100 m free-space link is successfully demonstrated. Such a 400 Gbps/100 m DWDM/SDM FSO link provides the advantages of optical wireless communications for high transmission rates and long transmission distances, which is very useful for high-speed and long-haul light-based WiFi (LiFi) applications.
Economical Unsteady High-Fidelity Aerodynamics for Structural Optimization with a Flutter Constraint

NASA Technical Reports Server (NTRS)

Bartels, Robert E.; Stanford, Bret K.

2017-01-01

Structural optimization with a flutter constraint for a vehicle designed to fly in the transonic regime is a particularly difficult task. In this speed range, the flutter boundary is very sensitive to aerodynamic nonlinearities, typically requiring high-fidelity Navier-Stokes simulations. However, the repeated application of unsteady computational fluid dynamics to guide an aeroelastic optimization process is very computationally expensive. This expense has motivated the development of methods that incorporate aspects of the aerodynamic nonlinearity, classical tools of flutter analysis, and more recent methods of optimization. While it is possible to use doublet lattice method aerodynamics, this paper focuses on the use of an unsteady high-fidelity aerodynamic reduced order model combined with successive transformations that allows for an economical way of utilizing high-fidelity aerodynamics in the optimization process. This approach is applied to the common research model wing structural design. As might be expected, the high-fidelity aerodynamics produces a heavier wing than that optimized with doublet lattice aerodynamics. It is found that the optimized lower skin of the wing using high-fidelity aerodynamics differs significantly from that using doublet lattice aerodynamics.
From high-scale leptogenesis to low-scale one-loop neutrino mass generation

NASA Astrophysics Data System (ADS)

Zhou, Hang; Gu, Pei-Hong

2018-02-01

We show that a high-scale leptogenesis can be consistent with a low-scale one-loop neutrino mass generation. Our models are based on the SU(3)c × SU(2)L × U(1)Y × U(1) B - L gauge groups. Except a complex singlet scalar for the U(1) B - L symmetry breaking, the other new scalars and fermions (one scalar doublet, two or more real scalar singlets/triplets and three right-handed neutrinos) are odd under an unbroken Z2 discrete symmetry. The real scalar decays can produce an asymmetry stored in the new scalar doublet which subsequently decays into the standard model lepton doublets and the right-handed neutrinos. The lepton asymmetry in the standard model leptons then can be partially converted to a baryon asymmetry by the sphaleron processes. By integrating out the heavy scalar singlets/triplets, we can realize an effective theory to radiatively generate the small neutrino masses at the TeV scale. Furthermore, the lightest right-handed neutrino can serve as a dark matter candidate.
What can platinum offer yet in the treatment of PS2 NSCLC patients? A systematic review and meta-analysis.

PubMed

Bronte, Giuseppe; Rolfo, Christian; Passiglia, Francesco; Rizzo, Sergio; Gil-Bazo, Ignacio; Fiorentino, Eugenio; Cajozzo, Massimo; Van Meerbeeck, Jan P; Lequaglie, Cosimo; Santini, Daniele; Pauwels, Patrick; Russo, Antonio

2015-09-01

Randomized phase III trials showed interesting, but conflicting results, regarding the treatment of NSCLC, PS2 population. This meta-analysis aims to review all randomized trials comparing platinum-based doublets and single-agents in NSCLC PS2 patients. Data from all published randomized trials, comparing efficacy and safety of platinum-based doublets to single agents in untreated NSCLC, PS2 patients, were collected. Pooled ORs were calculated for the 1-year Survival-Rate (1y-SR), Overall Response Rate (ORR), and grade 3-4 (G3-4) hematologic toxicities. Six eligible trials (741 patients) were selected. Pooled analysis showed a significant improvement in ORR (OR: 3.243; 95% CI: 1.883-5.583) and 1y-SR (OR: 1.743; 95% CI: 1.203-2.525) in favor of platinum-based doublets. G3-4 hematological toxicities were also more frequent in this group. This meta-analysis suggests that platinum-combination regimens are superior to singleagent both in terms of ORR and survival-rate with increase of severe hematological toxicities. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Alignment telescope for Antares

NASA Astrophysics Data System (ADS)

Appert, Q. D.; Swann, T. A.; Ward, J. H.; Hardesty, C.; Wright, L.

The Antares Automatic Alignment System employs a specially designed telescope for alignment of its laser beamlines. There are two telescopes in the system, and since each telescope is a primary alignment reference, stringent boresight accuracy and stability over the focus range were required. Optical and mechanical designs, which meet this requirements as well as that of image quality over a wide wavelength band, are described. Special test techniques for initial assembly and alignment of the telescope are also presented. The telescope, which has a 180-mm aperture FK51-KZF2 type glass doublet objective, requires a boresight accuracy of 2.8 (SIGMA)rad at two focal lengths, and object distances between 11 meters and infinity. Travel of a smaller secondary doublet provides focus from 11 m to infinity with approximately 7.8 m effective focal length. By flipping in a third doublet, the effective focal length is reduced to 2.5 m. Telescope alignment was accomplished by using a rotary air bearing to establish an axis in front of the system and placing the focus of a Laser Unequal Path Interferometer (LUPI) at the image plane.
Alignment Telescope For Antares

NASA Astrophysics Data System (ADS)

Appert, Q. D.; Swann, T. A.; Ward, J. H.; Hardesty, C.; Wrignt, L.

1983-11-01

The Antares Automatic Alignment System employs a specially designed telescope for alignment of its laser beamlines. There are two telescopes in the system, and since eacn telescope is a primary alignment reference, stringent boresight accuracy and stability over the focus range were required. Optical and mechanical designs, which meet this requirement as well as that of image quality over a wide wavelength band, are described. Special test techniques for initial assembly and alignment of the telescope are also presented. The telescope, which has a 180-mm aperture FK51-KZF2 type glass doublet objective, requires a boresight accuracy of 2.8 prad at two focal lengths, and object distances between 11 meters and infinity. Travel of a smaller secondary doublet provides focus from 11 m to infinity with approximately 7.8 m effective focal length. By flipping in a third doublet, the effective focal length is reduced to 2.5 m. Telescope alignment was accomplished by using a rotary air bearing to establish an axis in front of the system and placing the focus of a Laser Unequal Path Interferometer (LUPI) at the image plane.
Design, performance, and analysis of an aquifer thermal-energy-storage experiment using the doublet-well configuration

NASA Astrophysics Data System (ADS)

Molz, F. J.; Melville, J. G.; Gueven, O.; Parr, A. D.

1983-09-01

In March 1980 Auburn University began a series of aquifer thermal energy storage (ATES) experiments using the doublet well configuration. The test site was in Mobile, Alabama. The objectives of the three experimental cycles were to demonstrate the technical feasibility of the ATES concept, to identify and resolve operational problems, and to acquire a data base for developing and testing mathematical models. Pre-injection tests were performed and analyses of hydraulic, geochemical, and thermodynamic data were completed. Three injection-storage-recovery cycles had injection volumes of 25,402 m(3), 58,010 m(3), and 58,680 m(3) and average injection temperatures of 58.50C, 81.00C. and 79.00C, respectively. The first cycle injection began in February 1981 and the third cycle recovery was completed in November 1982. Attributable to the doublet well configuration no clogging of injection wells occurred. Energy recovery percentages based on recovery volumes equal to the injection volumes were 56, 45, and 42%. Thermal convection effects were observed. Aquifer nonhomogeneity, not detectable using standard aquifer testing procedures, was shown to reduce recovery efficiency.
Multivariate analysis in provenance studies: Cerrillos obsidians case, Peru

NASA Astrophysics Data System (ADS)

Bustamante, A.; Delgado, M.; Latini, R. M.; Bellido, A. V. B.

2007-02-01

We present the preliminary results of a provenance study of obsidians samples from Cerrillos (ca. 800 100 b.c.) using Mössbauer Spectroscopy. The Cerrillos archaeological site, located in the Upper Ica Valley, Peru, is the only Paracas ceremonial center excavated so far. The archaeological data collected suggest the existence of a complex social and economic organization on the south coast of Peru. Provenance research of obsidian provides valuable information about the selection of lithic resources by our ancestors and eventually about the existence of communication routes and exchange networks. We characterized 18 obsidian artifacts samples by Mössbauer spectroscopy from Cerrillos. The spectra, recorded at room temperature using different velocities, are mainly composed of broad asymmetric doublets due to the superposition of at least two quadrupole doublets corresponding to Fe2+ in two different sites (species A and B), one weak Fe3+ doublet (specie C) and magnetic components associated to the presence of small particles of magnetite. Multivariate statistical analysis of the Mössbauer data (hyperfine parameters) allows to defined two main groups of obsidians, reflecting different geographical origins.

APIC: Absolute Position Interfero Coronagraph for direct exoplanet detection: first laboratory results

NASA Astrophysics Data System (ADS)

Allouche, Fatmé; Glindemann, Andreas; Aristidi, Eric; Vakili, Farrokh

2010-07-01

For the detection and direct imaging of exoplanets, when the intensity ratio between a star and its orbiting planet can largely exceed 106, coronagraphic methods are mandatory. In 1996, a concept of achromatic interferocoronagraph (AIC) was presented by J. Gay and Y. Rabbia for the detection of very faint stellar companions, such as exoplanets. In an earlier paper, we presented a modified version of the AIC permitting to determine the relative position of these faint companions with respect to the parent star, a problem unsolved in the original design of the AIC. Our modification lied in the use of cylindrical lens doublets as field rotator. By placing two of them in one arm of the interferometric set-up of AIC, we destroyed the axis of symmetry induced by the AIC's original design. Our theoretical study, along with the numerical computations, presented then, and the preliminary test bench results aiming at validating the cylindrical lens doublet field rotation capability, presented in this paper, show that the axis of symmetry is destroyed when one of the cylindrical doublets is rotated around the optic axis.
Self-consistent Dark Matter simplified models with an s-channel scalar mediator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bell, Nicole F.; Busoni, Giorgio; Sanderson, Isaac W., E-mail: n.bell@unimelb.edu.au, E-mail: giorgio.busoni@unimelb.edu.au, E-mail: isanderson@student.unimelb.edu.au

We examine Simplified Models in which fermionic DM interacts with Standard Model (SM) fermions via the exchange of an s -channel scalar mediator. The single-mediator version of this model is not gauge invariant, and instead we must consider models with two scalar mediators which mix and interfere. The minimal gauge invariant scenario involves the mixing of a new singlet scalar with the Standard Model Higgs boson, and is tightly constrained. We construct two Higgs doublet model (2HDM) extensions of this scenario, where the singlet mixes with the 2nd Higgs doublet. Compared with the one doublet model, this provides greater freedommore » for the masses and mixing angle of the scalar mediators, and their coupling to SM fermions. We outline constraints on these models, and discuss Yukawa structures that allow enhanced couplings, yet keep potentially dangerous flavour violating processes under control. We examine the direct detection phenomenology of these models, accounting for interference of the scalar mediators, and interference of different quarks in the nucleus. Regions of parameter space consistent with direct detection measurements are determined.« less
Analysis of volcanic tephra as a material of environment

NASA Astrophysics Data System (ADS)

Sitek, J.; Dekan, J.; Fang, X.; Xiaoli, P.; Chmielewská, E.

2012-10-01

Tephra is a fragmental material produced by volcanic eruption. Here, volcanic tephra deposit from the northeast of China was used for our study. Samples of unaltered tephra are usually composed of feldspar, glass, pyroxene, and olivine. Moreover, these volcanic alteration products also contain Fe oxides, phylosilicates, sulfates, and amorphous Al-Si-bearing material. Six different samples of tephra obtained were analyzed by Mössbauer spectroscopy. A typical Mössbauer spectrum of tephra consists of magnetic and non-magnetic components (magnetic component represents about 11% and non-magnetic component about 89% of spectral area). According to the structural composition, it may be supposed that the magnetic component can be assigned to titanomagnetite. Non-magnetic components contain two quadrupole doublets (Fe2+ species) and one doublet containing Fe3+. According to the measured values of Mössbauer spectra, the first two doublets are very similar with pyroxene, olivine and the third to phylosilicate, aluminosilicate or iron oxide of FeO type. Recently, volcanic tephra was applied as an ecological substance. Special solution was proposed for tephra utilization, especially for phosphate removal from contaminated water.
Quantum spin ices and magnetic states from dipolar-octupolar doublets on the pyrochlore lattice

NASA Astrophysics Data System (ADS)

Chen, Gang

We consider a class of electron systems in which dipolar-octupolar Kramers doublets arise on the pyrochlore lattice. In the localized limit, the Kramers doublets are described by the effective spin 1/2 pseudospins. The most general nearest-neighbor exchange model between these pseudospins is the XYZ model. In additional to dipolar ordered and octupolar ordered magnetic states, we show that this XYZ model exhibits two distinct quantum spin ice (QSI) phases, that we dub dipolar QSI and octupolar QSI. These two QSIs are distinct symmetry enriched U(1) quantum spin liquids, enriched by the lattice symmetry. Moreover, the XYZ model is absent from the notorious sign problem for a quantum Monte Carlo simulation in a large parameter space. We discuss the potential relevance to real material systems such as Dy2Ti2O7, Nd2Zr2O7, Nd2Hf2O7, Nd2Ir2O7, Nd2Sn2O7 and Ce2Sn2O7. chggst@gmail.com, Refs: Y-P Huang, G Chen, M Hermele, Phys. Rev. Lett. 112, 167203 (2014).
Characterizing Rat PNS Electrophysiological Response to Electrical Stimulation Using in vitro Chip-Based Human Investigational Platform (iCHIP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khani, Joshua; Prescod, Lindsay; Enright, Heather

Ex vivo systems and organ-on-a-chip technology offer an unprecedented approach to modeling the inner workings of the human body. The ultimate goal of LLNL’s in vitro Chip-based Human Investigational Platform (iCHIP) is to integrate multiple organ tissue cultures using microfluidic channels, multi-electrode arrays (MEA), and other biosensors in order to effectively simulate and study the responses and interactions of the major organs to chemical and physical stimulation. In this study, we focused on the peripheral nervous system (PNS) component of the iCHIP system. Specifically we sought to expound on prior research investigating the electrophysiological response of rat dorsal root ganglionmore » cells (rDRGs) to chemical exposures, such as capsaicin. Our aim was to establish a protocol for electrical stimulation using the iCHIP device that would reliably elicit a characteristic response in rDRGs. By varying the parameters for both the stimulation properties – amplitude, phase width, phase shape, and stimulation/ return configuration – and the culture conditions – day in vitro and neural cell types - we were able to make several key observations and uncover a potential convention with a minimal number of devices tested. Future work will seek to establish a standard protocol for human DRGs in the iCHIP which will afford a portable, rapid method for determining the effects of toxins and novel therapeutics on the PNS.« less
Myocardial Scaffold-based Cardiac Tissue Engineering: Application of Coordinated Mechanical and Electrical Stimulations

PubMed Central

Wang, Bo; Wang, Guangjun; To, Filip; Butler, J. Ryan; Claude, Andrew; McLaughlin, Ronald M.; Williams, Lakiesha N.; de Jongh Curry, Amy L.; Liao, Jun

2013-01-01

Recently, we have developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserved natural extracellular matrix structure, mechanical anisotropy, and vasculature templates, and also showed good cell recellularization and differentiation potential. In this study, a multi-stimulation bioreactor was built to provide coordinated mechanical and electrical stimulations for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (106 cells/ml) by needle injection and subjected to 5-azacytidine treatment (3 μmol/L, 24 h) and various bioreactor conditioning protocols. We found that, after 2-day culture with mechanical (20% strain) and electrical stimulation (5 V, 1 Hz), high cell density and good cell viability were observed in the reseeded scaffold. Immunofluorescence staining demonstrated that the differentiated cells showed cardiomyocyte-like phenotype, by expressing sarcomeric α-actinin, myosin heavy chain, cardiac troponin T, connexin-43, and N-cadherin. Biaxial mechanical testing demonstrated that positive tissue remodeling took place after 2-day bioreactor conditioning (20% strain + 5 V, 1 Hz); passive mechanical properties of the 2-day and 4-day tissue constructs were comparable to the tissue constructs produced by stirring reseeding followed by 2-week static culture, implying the effectiveness and efficiency of the coordinated simulations in promoting tissue remodeling. In short, the synergistic stimulations might be beneficial not only for the quality of cardiac construct development, but also for patients by reducing the waiting time in future clinical scenarios. PMID:23923967
Bone stimulation for fracture healing: What's all the fuss?

PubMed Central

Victoria, Galkowski; Petrisor, Brad; Drew, Brian; Dick, David

2009-01-01

Approximately 10% of the 7.9 million annual fracture patients in the United States experience nonunion and/or delayed unions, which have a substantial economic and quality of life impact. A variety of devices are being marketed under the name of “bone growth stimulators.” This article provides an overview of electrical and electromagnetic stimulation, ultrasound, and extracorporeal shock waves. More research is needed for knowledge of appropriate device configurations, advancement in the field, and encouragement in the initiation of new trials, particularly large multicenter trials and randomized control trials that have standardized device and protocol methods. PMID:19838359
Adjuvant Docetaxel and Cyclophosphamide (DC) with Prophylactic Granulocyte Colony-Stimulating Factor (G-CSF) on Days 8 &12 in Breast Cancer Patients: A Retrospective Analysis

PubMed Central

Yerushalmi, Rinat; Goldvaser, Hadar; Sulkes, Aaron; Ben-Aharon, Irit; Hendler, Daniel; Neiman, Victoria; Ciuraru, Noa Beatrice; Bonilla, Luisa; Amit, Limor; Zer, Alona; Granot, Tal; Rizel, Shulamith; Stemmer, Salomon M.

2014-01-01

Purpose Four cycles of docetaxel/cyclophosphamide (DC) resulted in superior survival than doxorubicin/cyclophosphamide in the treatment of early breast cancer. The original study reported a 5% incidence of febrile neutropenia (FN) recommending prophylactic antibiotics with no granulocyte colony-stimulating factor (G-CSF) support. The worldwide adoption of this protocol yielded several reports on substantially higher rates of FN events. We explored the use of growth factor (GF) support on days 8 and 12 of the cycle with the original DC protocol. Methods Our study included all consecutive patients with stages I–II breast cancer who were treated with the DC protocol at the Institute of Oncology, Davidoff Center (Rabin Medical Center, Petah Tikva, Israel) from April, 2007 to March, 2012. Patient, tumor characteristics, and toxicity were reported. Results: In total, 123 patients received the DC regimen. Median age was 60 years, (range, 25–81 years). Thirty-three patients (26.8%) were aged 65 years and older. Most of the women (87%) adhered to the planned G-CSF protocol (days 8 &12). 96% of the patients completed the 4 planned cycles of chemotherapy. Six patients (5%) had dose reductions, 6 (5%) had treatment delays due to non-medical reasons. Thirteen patients (10.6%) experienced at least one event of FN (3 patients had 2 events), all requiring hospitalization. Eight patients (6.5%) required additional support with G-CSF after the first chemotherapy cycle, 7 because of FN and one due to neutropenia and diarrhea. In Conclusion Primary prophylactic G-CSF support on days 8 and 12 of the cycle provides a tolerable option to deliver the DC protocol. Our results are in line with other retrospective protocols using longer schedules of GF support. PMID:25330205
Adjuvant Docetaxel and Cyclophosphamide (DC) with prophylactic granulocyte colony-stimulating factor (G-CSF) on days 8 &12 in breast cancer patients: a retrospective analysis.

PubMed

Yerushalmi, Rinat; Goldvaser, Hadar; Sulkes, Aaron; Ben-Aharon, Irit; Hendler, Daniel; Neiman, Victoria; Ciuraru, Noa Beatrice; Bonilla, Luisa; Amit, Limor; Zer, Alona; Granot, Tal; Rizel, Shulamith; Stemmer, Salomon M

2014-01-01

Four cycles of docetaxel/cyclophosphamide (DC) resulted in superior survival than doxorubicin/cyclophosphamide in the treatment of early breast cancer. The original study reported a 5% incidence of febrile neutropenia (FN) recommending prophylactic antibiotics with no granulocyte colony-stimulating factor (G-CSF) support. The worldwide adoption of this protocol yielded several reports on substantially higher rates of FN events. We explored the use of growth factor (GF) support on days 8 and 12 of the cycle with the original DC protocol. Our study included all consecutive patients with stages I-II breast cancer who were treated with the DC protocol at the Institute of Oncology, Davidoff Center (Rabin Medical Center, Petah Tikva, Israel) from April, 2007 to March, 2012. Patient, tumor characteristics, and toxicity were reported. In total, 123 patients received the DC regimen. Median age was 60 years, (range, 25-81 years). Thirty-three patients (26.8%) were aged 65 years and older. Most of the women (87%) adhered to the planned G-CSF protocol (days 8 &12). 96% of the patients completed the 4 planned cycles of chemotherapy. Six patients (5%) had dose reductions, 6 (5%) had treatment delays due to non-medical reasons. Thirteen patients (10.6%) experienced at least one event of FN (3 patients had 2 events), all requiring hospitalization. Eight patients (6.5%) required additional support with G-CSF after the first chemotherapy cycle, 7 because of FN and one due to neutropenia and diarrhea. Primary prophylactic G-CSF support on days 8 and 12 of the cycle provides a tolerable option to deliver the DC protocol. Our results are in line with other retrospective protocols using longer schedules of GF support.
Simultaneous transcranial magnetic stimulation and single neuron recording in alert non-human primates

PubMed Central

Mueller, Jerel K.; Grigsby, Erinn M.; Prevosto, Vincent; Petraglia, Frank W.; Rao, Hrishikesh; Deng, Zhi-De; Peterchev, Angel V.; Sommer, Marc A.; Egner, Tobias; Platt, Michael L.; Grill, Warren M.

2014-01-01

Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report novel methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally perturbed by stimulation artifact in intact, awake monkeys (Macaca mulatta). We recorded action potentials within ~1 ms after 0.4 ms TMS pulses and observed changes in activity that differed significantly for active stimulation as compared to sham stimulation. The methodology is compatible with standard equipment in primate laboratories, allowing for easy implementation. Application of these new tools will facilitate the refinement of next generation TMS devices, experiments, and treatment protocols. PMID:24974797
Transcranial direct current stimulation for motor recovery of upper limb function after stroke.

PubMed

Lüdemann-Podubecká, Jitka; Bösl, Kathrin; Rothhardt, Sandra; Verheyden, Geert; Nowak, Dennis Alexander

2014-11-01

Changes in neural processing after stroke have been postulated to impede recovery from stroke. Transcranial direct current stimulation has the potential to alter cortico-spinal excitability and thereby might be beneficial in stroke recovery. We review the pertinent literature prior to 30/09/2013 on transcranial direct current stimulation in promoting motor recovery of the affected upper limb after stroke. We found overall 23 trials (they included 523 participants). All stimulation protocols pride on interhemispheric imbalance model. In a comparative approach, methodology and effectiveness of (a) facilitation of the affected hemisphere, (b) inhibition of the unaffected hemisphere and (c) combined application of transcranial direct current stimulation over the affected and unaffected hemispheres to treat impaired hand function after stroke are presented. Transcranial direct current stimulation is associated with improvement of the affected upper limb after stroke, but current evidence does not support its routine use. Copyright © 2014 Elsevier Ltd. All rights reserved.
Bio-heat transfer model of deep brain stimulation-induced temperature changes

NASA Astrophysics Data System (ADS)

Elwassif, Maged M.; Kong, Qingjun; Vazquez, Maribel; Bikson, Marom

2006-12-01

There is a growing interest in the use of chronic deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. Fundamental questions remain about the physiologic effects of DBS. Previous basic research studies have focused on the direct polarization of neuronal membranes by electrical stimulation. The goal of this paper is to provide information on the thermal effects of DBS using finite element models to investigate the magnitude and spatial distribution of DBS-induced temperature changes. The parameters investigated include stimulation waveform, lead selection, brain tissue electrical and thermal conductivities, blood perfusion, metabolic heat generation during the stimulation and lead thermal conductivity/heat dissipation through the electrode. Our results show that clinical DBS protocols will increase the temperature of surrounding tissue by up to 0.8 °C depending on stimulation/tissue parameters.
Toward rational design of electrical stimulation strategies for epilepsy control

PubMed Central

Sunderam, Sridhar; Gluckman, Bruce; Reato, Davide; Bikson, Marom

2009-01-01

Electrical stimulation is emerging as a viable alternative for epilepsy patients whose seizures are not alleviated by drugs or surgery. Its attractions are temporal and spatial specificity of action, flexibility of waveform parameters and timing, and the perception that its effects are reversible unlike resective surgery. However, despite significant advances in our understanding of mechanisms of neural electrical stimulation, clinical electrotherapy for seizures relies heavily on empirical tuning of parameters and protocols. We highlight concurrent treatment goals with potentially conflicting design constraints that must be resolved when formulating rational strategies for epilepsy electrotherapy: namely seizure reduction versus cognitive impairment, stimulation efficacy versus tissue safety, and mechanistic insight versus clinical pragmatism. First, treatment markers, objectives, and metrics relevant to electrical stimulation for epilepsy are discussed from a clinical perspective. Then the experimental perspective is presented, with the biophysical mechanisms and modalities of open-loop electrical stimulation, and the potential benefits of closed-loop control for epilepsy. PMID:19926525
Efficacy of transcranial direct-current stimulation (tDCS) in women with provoked vestibulodynia: study protocol for a randomized controlled trial.

PubMed

Morin, Annie; Léonard, Guillaume; Gougeon, Véronique; Waddell, Guy; Bureau, Yves-André; Girard, Isabelle; Morin, Mélanie

2016-05-14

Provoked vestibulodynia is the most common form of vulvodynia. Despite its high prevalence and deleterious sexual, conjugal, and psychological repercussions, effective evidence-based interventions for provoked vestibulodynia remain limited. For a high proportion of women, significant pain persists despite the currently available treatments. Growing evidence suggests that the central nervous system (CNS) could play a key role in provoked vestibulodynia; thus, treatment targeting the CNS, rather than localized dysfunctions, may be beneficial for women suffering from provoked vestibulodynia. In this study, we aim to build on the promising results of a previous case report and evaluate whether transcranial direct-current stimulation, a non-invasive brain stimulation technique targeting the CNS, could be an effective treatment option for women with provoked vestibulodynia. This single-center, triple-blind, parallel group, randomized, controlled trial aims to compare the efficacy of transcranial direct-current stimulation with sham transcranial direct-current stimulation in women with provoked vestibulodynia. Forty women diagnosed with provoked vestibulodynia by a gynecologist, following a standardized treatment protocol, are randomized to either active transcranial direct-current stimulation treatment for ten sessions of 20 minutes at an intensity of 2 mA or sham transcranial direct-current stimulation over a 2-week period. Outcome measures are collected at baseline, 2 weeks after treatment and at 3-month follow-up. The primary outcome is pain during intercourse, assessed with a numerical rating scale. Secondary measurements focus on the sexual function, vestibular pain sensitivity, psychological distress, treatment satisfaction, and the patient's global impression of change. To our knowledge, this study is the first randomized controlled trial to examine the efficacy of transcranial direct-current stimulation in women with provoked vestibulodynia. Findings from this trial are expected to provide significant information about a promising intervention targeting the centralization of pain in women with provoked vestibulodynia. Clinicaltrials.gov, NCT02543593 . Registered on September 4, 2015.
Compassionate Use Protocol for the Treatment of Autoinflammatory Syndromes

ClinicalTrials.gov

2018-04-17

Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature (CANDLE); Juvenile Dermatomyositis (JDM); Stimulator of Interferon Genes (STING)-Associated Vasculopathy With Onset During Infancy (SAVI); Aicardi-Goutières Syndrome (AGS)
Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury.

PubMed

Song, Weiguo; Amer, Alzahraa; Ryan, Daniel; Martin, John H

2016-03-01

An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. M1 was activated epidurally using an electrical analog of intermittent theta burst stimulation (iTBS). The cervical spinal cord was co-activated by trans-spinal direct current stimulation (tsDCS) that was targeted to the cervical enlargement, simulated from finite element method. In intact rats, forelimb motor evoked potentials (MEPs) were strongly facilitated during iTBS and for 10 min after cessation of stimulation. Cathodal, not anodal, tsDCS alone facilitated MEPs and also produced a facilitatory aftereffect that peaked at 10 min. Combined iTBS and cathodal tsDCS (c-tsDCS) produced further MEP enhancement during stimulation, but without further aftereffect enhancement. Correlations between forelimb M1 local field potentials and forelimb electromyogram (EMG) during locomotion increased after electrical iTBS alone and further increased with combined stimulation (iTBS+c-tsDCS). This optimized combined stimulation was then used to promote function after PTX because it enhanced functional connections between M1 and spinal circuits and greater M1 engagement in muscle contraction than either stimulation alone. Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 min/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor recovery and substantial CST outgrowth with only 27 min of daily stimulation compared with 6h, as in our prior study, making it a potential therapy for humans with spinal cord injury. Copyright © 2015 Elsevier Inc. All rights reserved.
Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury

PubMed Central

Song, Weiguo; Amer, Alzahraa; Ryan, Daniel; Martin, John H.

2016-01-01

An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. M1 was activated epidurally using an electrical analog of intermittent theta burst stimulation (iTBS). The cervical spinal cord was co-activated by trans-spinal direct current stimulation (tsDCS) that was targeted to the cervical enlargement, simulated from finite element method. In intact rats, forelimb motor evoked potentials (MEPs) were strongly facilitated during iTBS and for 10 minutes after cessation of stimulation. Cathodal, not anodal, tsDCS alone facilitated MEPs and also produced a facilitatory aftereffect that peaked at 10 minutes. Combined iTBS and cathodal tsDCS (c-tsDCS) produced further MEP enhancement during stimulation, but without further aftereffect enhancement. Correlations between forelimb M1 local field potentials and forelimb electromyogram (EMG) during locomotion increased after electrical iTBS alone and further increased with combined stimulation (iTBS + c-tsDCS). This optimized combined stimulation was then used to promote function after PTX because it enhanced functional connections between M1 and spinal circuits and greater M1 engagement in muscle contraction than either stimulation alone. Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 minutes/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor recovery and substantial CST outgrowth with only 27 minutes of daily stimulation compared with 6 hours, as in our prior study, making it a potential therapy for humans with spinal cord injury. PMID:26708732
Acute effects and after-effects of acoustic coordinated reset neuromodulation in patients with chronic subjective tinnitus.

PubMed

Adamchic, Ilya; Toth, Timea; Hauptmann, Christian; Walger, Martin; Langguth, Berthold; Klingmann, Ingrid; Tass, Peter Alexander

2017-01-01

Chronic subjective tinnitus is an auditory phantom phenomenon characterized by abnormal neuronal synchrony in the central auditory system. As shown computationally, acoustic coordinated reset (CR) neuromodulation causes a long-lasting desynchronization of pathological synchrony by downregulating abnormal synaptic connectivity. In a previous proof of concept study acoustic CR neuromodulation, employing stimulation tone patterns tailored to the dominant tinnitus frequency, was compared to noisy CR-like stimulation, a CR version significantly detuned by sparing the tinnitus-related pitch range and including substantial random variability of the tone spacing on the frequency axis. Both stimulation protocols caused an acute relief as measured with visual analogue scale scores for tinnitus loudness (VAS-L) and annoyance (VAS-A) in the stimulation-ON condition (i.e. 15 min after stimulation onset), but only acoustic CR neuromodulation had sustained long-lasting therapeutic effects after 12 weeks of treatment as assessed with VAS-L, VAS-A scores and a tinnitus questionnaire (TQ) in the stimulation-OFF condition (i.e. with patients being off stimulation for at least 2.5 h). To understand the source of the long-lasting therapeutic effects, we here study whether acoustic CR neuromodulation has different electrophysiological effects on oscillatory brain activity as compared to noisy CR-like stimulation under stimulation-ON conditions and immediately after cessation of stimulation. To this end, we used a single-blind, single application, cross over design in 18 patients with chronic tonal subjective tinnitus and administered three different 16-minute stimulation protocols: acoustic CR neuromodulation, noisy CR-like stimulation and low frequency range (LFR) stimulation, a CR type stimulation with deliberately detuned pitch and repetition rate of stimulation tones, as control stimulation. We measured VAS-L and VAS-A scores together with spontaneous EEG activity pre-, during- and post-stimulation. Under stimulation-ON conditions acoustic CR neuromodulation and noisy CR-like stimulation had similar effects: a reduction of VAS-L and VAS-A scores together with a decrease of auditory delta power and an increase of auditory alpha and gamma power, without significant differences. In contrast, LFR stimulation had significantly weaker EEG effects and no significant clinical effects under stimulation-ON conditions. The distinguishing feature between acoustic CR neuromodulation and noisy CR-like stimulation were the electrophysiological after-effects. Acoustic CR neuromodulation caused the longest significant reduction of delta and gamma and increase of alpha power in the auditory cortex region. Noisy CR-like stimulation had weaker and LFR stimulation hardly any electrophysiological after-effects. This qualitative difference further supports the assertion that long-term effects of acoustic CR neuromodulation on tinnitus are mediated by a specific disruption of synchronous neural activity. Furthermore, our results indicate that acute electrophysiological after-effects might serve as a marker to further improve desynchronizing sound stimulation.
Broadening and collisional interference of lines in the IR spectra of ammonia. Theory

NASA Astrophysics Data System (ADS)

Cherkasov, M. R.

2016-06-01

The general theory of relaxation spectral shape parameters in the impact approximation (M. R. Cherkasov, J. Quant. Spectrosc. Radiat. Transfer 141, 73 (2014)) is adapted to the case of line broadening of infrared spectra of ammonia. Specific features of line broadening of parallel and perpendicular bands are discussed. It is shown that in both cases the spectrum consists of independently broadened singlets and doublets; however, the components of doublets can be affected by collisional interference. The paper is the first part of a cycle of studies devoted to the problems of spectral line broadening of ammonia.
Silicon technology compatible photonic molecules for compact optical signal processing

NASA Astrophysics Data System (ADS)

Barea, Luis A. M.; Vallini, Felipe; Jarschel, Paulo F.; Frateschi, Newton C.

2013-11-01

Photonic molecules (PMs) based on multiple inner coupled microring resonators allow to surpass the fundamental constraint between the total quality factor (QT), free spectral range (FSR), and resonator size. In this work, we use a PM that presents doublets and triplets resonance splitting, all with high QT. We demonstrate the use of the doublet splitting for 34.2 GHz signal extraction by filtering the sidebands of a modulated optical signal. We also demonstrate that very compact optical modulators operating 2.75 times beyond its resonator linewidth limit may be obtained using the PM triplet splitting, with separation of ˜55 GHz.

The Influence of Ballistic Damage on the Aeroelastic Characteristics of Lifting Surfaces.

DTIC Science & Technology

1979-07-01

the pressure distribution. The finite-element method, often referred to as a vortex- lattice or doublet- lattice method, divides the lifting surface into...finite-element modeling, such as doublet- lattice , would provide a better understanding of the near-field effects of a damage hole and allow a data base...0.17 0.33 0.50 6.67 0.833 1.00 Figure 42 125 CASE 5 and CASE 5D 0 Ye=.57 = UNDAMAGED M = DAMAGED 0 C3/ C22 CD QCD 6.330,4 0/ Fiue4 02 CASE 5 and CASE
Photonic-chip-based all-optical ultra-wideband pulse generation via XPM and birefringence in a chalcogenide waveguide.

PubMed

Tan, Kang; Marpaung, David; Pant, Ravi; Gao, Feng; Li, Enbang; Wang, Jian; Choi, Duk-Yong; Madden, Steve; Luther-Davies, Barry; Sun, Junqiang; Eggleton, Benjamin J

2013-01-28

We report a photonic-chip-based scheme for all-optical ultra-wideband (UWB) pulse generation using a novel all-optical differentiator that exploits cross-phase modulation and birefringence in an As₂S₃ chalcogenide rib waveguide. Polarity-switchable UWB monocycles and doublets were simultaneously obtained with single optical carrier operation. Moreover, transmission over 40-km fiber of the generated UWB doublets is demonstrated with good dispersion tolerance. These results indicate that the proposed approach has potential applications in multi-shape, multi-modulation and long-distance UWB-over-fiber communication systems.
A survey of interstellar neutral potassium. I - Abundances and physical conditions in clouds toward 188 early-type stars

NASA Technical Reports Server (NTRS)

Chaffee, F. H., Jr.; White, R. E.

1982-01-01

Observations of interstellar absorption in the resonance doublet 7664, 7698 A of neutral potassium toward 188 early-type stars at a spectral resolution of 8 km/s are reported. The 7664 A line is successfully separated from nearly coincident telluric O2 absorption for all but a few of the 165 stars for which K I absorption is detected, making possible an abundance analysis by the doublet ratio method. The relationships between the potassium abundances and other atomic abundances, the abundance of molecular hydrogen, and interstellar reddening are investigated.
Standard model anatomy of WIMP dark matter direct detection. I. Weak-scale matching

NASA Astrophysics Data System (ADS)

Hill, Richard J.; Solon, Mikhail P.

2015-02-01

We present formalism necessary to determine weak-scale matching coefficients in the computation of scattering cross sections for putative dark matter candidates interacting with the Standard Model. We pay particular attention to the heavy-particle limit. A consistent renormalization scheme in the presence of nontrivial residual masses is implemented. Two-loop diagrams appearing in the matching to gluon operators are evaluated. Details are given for the computation of matching coefficients in the universal limit of WIMP-nucleon scattering for pure states of arbitrary quantum numbers, and for singlet-doublet and doublet-triplet mixed states.
Discovery of Charm

DOE R&D Accomplishments Database

Goldhaber, G.

1984-11-01

In my talk I will cover the period 1973 to 1976 which saw the discoveries of the J/psi and psi' resonances and most of the Psion spectroscopy, the tau lepton and the D0030099,D0015599 charmed meson doublet. Occasionally I will refer briefly to more recent results. Since this conference is on the history of the weak-interactions I will deal primarily with the properties of naked charm and in particular the weakly decaying doublet of charmed mesons. Most of the discoveries I will mention were made with the SLAC-LBL Magnetic Detector or MARK I which we operated at SPEAR from 1973 to 1976.
Enhanced Soft Tissue Attachment and Fixation Using a Mechanically-Stimulated Cytoselective Tissue-Specific ECM Coating

DTIC Science & Technology

2012-08-01

currently used for surgical reinforcement for tendon rotator cuff repair . All scaffolds in this study were seeded using this protocol. PLA fabric...extracellular matrix scaffolds for rotator cuff tendon repair . Biomechanical, biochemical, and cellular properties. J Bone Joint Surg Am 2006;88(12):2665-72...mechanical stimulation of a co-cultured biomaterial scaffold can improve/expedite healing of a tendon-to-bone interface for soft tissue repair . There
Preparation of acellular myocardial scaffolds with well-preserved cardiomyocyte lacunae, and method for applying mechanical and electrical simulation to tissue construct.

PubMed

Wang, Bo; Williams, Lakiesha N; de Jongh Curry, Amy L; Liao, Jun

2014-01-01

Cardiac tissue engineering/regeneration using decellularized myocardium has attracted great research attention due to its potential benefit for myocardial infarction (MI) treatment. Here we describe an optimal decellularization protocol to generate 3D porcine myocardial scaffolds with well-preserved cardiomyocyte lacunae and a multi-stimulation bioreactor that is able to provide coordinated mechanical and electrical stimulation for facilitating cardiac construct development.
Testosterone Combined with Electrical Stimulation and Standing: Effect on Muscle and Bone

DTIC Science & Technology

2015-10-01

JJPVAMC). During year 1 of the study, the Study Team (Drs. Forrest, Bauman, and Harkema) established a new partnership with a pharmaceutical company...AbbVie) to supply Drug and Placebo for all potential study participants. Each of the study sites submitted to the pharmaceutical company all requested...stimulation, dynamic standing protocol, muscle volume, MRI , bone mineral density, DXA, QCT scans, blood markers, urine markers, 60 sessions of training
Combination therapy for radiation-induced bone marrow aplasia in nonhuman primates using synthokine SC-55494 and recombinant human granulocyte colony-stimulating factor.

PubMed

MacVittie, T J; Farese, A M; Herodin, F; Grab, L B; Baum, C M; McKearn, J P

1996-05-15

Combination cytokine therapy continues to be evaluated in an effort to stimulate multilineage hematopoietic reconstitution after bone marrow myelosuppression. This study evaluated the efficacy of combination therapy with the synthetic interleukin-3 receptor agonist, Synthokine-SC55494, and recombinant methionyl human granulocyte colony-stimulating factor (rhG-CSF) on platelet and neutrophil recovery in nonhuman primates exposed to total body 700 cGy 60Co gamma radiation. After irradiation on day (d) 0, cohorts of animals subcutaneously received single-agent protocols of either human serum albumin (HSA; every day [QD], 15 micrograms/kg/d, n = 10), Synthokine (twice daily [BID], 100, micrograms/kg/d, n = 15), rhG-CSF (QD, 10 micrograms/kg/d, n = 5), or a combination of Synthokine and rhG-CSF (BID, 100 and 10 micrograms/kg/d, respectively, n = 5) for 23 days beginning on d1. Complete blood counts were monitored for 60 days postirradiation and the durations of neutropenia (absolute neutrophil count < 500/microL) and thrombocytopenia (platelet count < 20,000/microL) were assessed. Animals were provided clinical support in the form of antibiotics, fresh irradiated whole blood, and fluids. All cytokine protocols significantly (P < .05) reduced the duration thrombocytopenia versus the HSA-treated animals. Only the combination protocol of Synthokine + rhG-CSF and rhG-CSF alone significantly shortened the period neutropenia (P < .05). The combined Synthokine/rhG-CSF protocol significantly improved platelet nadir versus Synthokine alone and HSA controls and neutrophil nadir versus rhG-CSF alone and HSA controls. All cytokine protocols decreased the time to recovery to preirradiation neutrophil and platelet values. The Synthokine/rhG-CSF protocol also reduced the transfusion requirements per treatment group to 0 among 5 animals as compared with 2 among 5 animals for Synthokine alone, 8 among 5 animals for rhG-CSF, and 17 among 10 animals for HSA. These data showed that the combination of Synthokine, SC-55494, and rhG-CSF further decreased the cytopenic periods and nadirs for both platelets and neutrophils relative to Synthokine and rhG-CSF monotherapy and suggest that this combination therapy would be effective against both neutropenia and thrombocytopenia consequent to drug- or radiation- induced myelosuppression.
Monocyte-derived dendritic cells from patients with cervical intraepithelial lesions

PubMed Central

Lopes, Angela Maria Moed; Michelin, Márcia Antoniazi; Murta, Eddie Fernando Cândido

2017-01-01

Immunotherapy with dendritic cells (DCs) is a great promise for the treatment of neoplasms. However, the obtainment and protocol of differentiation of these cells may depend on extrinsic factors such as the tumor itself. The aim of the present study was to verify the influence of cervical neoplasia on different protocols of differentiation of monocyte-derived DCs resulting in an increased maturation phenotype. A total of 83 women were included in the study. The patients were grouped in low-grade squamous intraepithelial lesion (LSIL) (n=30), high-grade squamous intraepithelial lesion (HSIL) (n=22), cervical cancer (n=10) and healthy patients (n=21) groups. The mononuclear cells of patients were subjected to three differentiation protocols. In protocol I (pI), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and tumor necrosis factor (TNF)-α were used for the differentiation of mature DCs (pIDCs). In protocol II (pII), monocytes were stimulated with GM-CSF, IL-4, TNF-α and activated lymphocytes in the absence of non-adherent cells (pIIDCs). In protocol III (pIII), monocytes were stimulated with GM-CSF, IL-4, TNF-α and activated lymphocytes in the presence of non-adherent cells (pIIIDCs). These cells were evaluated by flow cytometry for the expression of maturation markers such as cluster of differentiation (CD)11c, CD86 and human leukocyte antigen-antigen D related (HLA-DR). The main cytokines secreted (IL-4, IL-12 and transforming growth factor-β) were measured by ELISA. Our results indicate a significantly lower mature profile of pIIDCs and a significant increase in CD11c+ pIIIDCs able to produce IL-12 (P=0.0007). Furthermore, a significant reduction in cervical cancer HLA-DR+ pIDCs (P=0.0113) was also observed. HSIL patients exhibited a higher percentage of HLA-DR+ pIIDCs (P=0.0113), while LSIL patients had a lower percentage of CD11c+ pIIIDCs (P=0.0411). These findings suggest that the extent of cervical lesions affects the process of differentiation of DCs. Furthermore, activated lymphocytes may induce a better maturation of monocyte-derived DCs, and the presence of mononuclear cells appears to contribute to the DC differentiation process. PMID:28454277
Monocyte-derived dendritic cells from patients with cervical intraepithelial lesions.

PubMed

Lopes, Angela Maria Moed; Michelin, Márcia Antoniazi; Murta, Eddie Fernando Cândido

2017-03-01

Immunotherapy with dendritic cells (DCs) is a great promise for the treatment of neoplasms. However, the obtainment and protocol of differentiation of these cells may depend on extrinsic factors such as the tumor itself. The aim of the present study was to verify the influence of cervical neoplasia on different protocols of differentiation of monocyte-derived DCs resulting in an increased maturation phenotype. A total of 83 women were included in the study. The patients were grouped in low-grade squamous intraepithelial lesion (LSIL) (n=30), high-grade squamous intraepithelial lesion (HSIL) (n=22), cervical cancer (n=10) and healthy patients (n=21) groups. The mononuclear cells of patients were subjected to three differentiation protocols. In protocol I (pI), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and tumor necrosis factor (TNF)-α were used for the differentiation of mature DCs (pIDCs). In protocol II (pII), monocytes were stimulated with GM-CSF, IL-4, TNF-α and activated lymphocytes in the absence of non-adherent cells (pIIDCs). In protocol III (pIII), monocytes were stimulated with GM-CSF, IL-4, TNF-α and activated lymphocytes in the presence of non-adherent cells (pIIIDCs). These cells were evaluated by flow cytometry for the expression of maturation markers such as cluster of differentiation (CD)11c, CD86 and human leukocyte antigen-antigen D related (HLA-DR). The main cytokines secreted (IL-4, IL-12 and transforming growth factor-β) were measured by ELISA. Our results indicate a significantly lower mature profile of pIIDCs and a significant increase in CD11c + pIIIDCs able to produce IL-12 (P=0.0007). Furthermore, a significant reduction in cervical cancer HLA-DR + pIDCs (P=0.0113) was also observed. HSIL patients exhibited a higher percentage of HLA-DR + pIIDCs (P=0.0113), while LSIL patients had a lower percentage of CD11c + pIIIDCs (P=0.0411). These findings suggest that the extent of cervical lesions affects the process of differentiation of DCs. Furthermore, activated lymphocytes may induce a better maturation of monocyte-derived DCs, and the presence of mononuclear cells appears to contribute to the DC differentiation process.
Repetitive Transcranial Magnetic Stimulation of the Primary Somatosensory Cortex Modulates Perception of the Tendon Vibration Illusion.

PubMed

Huh, D C; Lee, J M; Oh, S M; Lee, J-H; Van Donkelaar, P; Lee, D H

2016-10-01

The effect of repetitive transcranial magnetic stimulation on kinesthetic perception, when applied to the somatosensory cortex, was examined. Further, the facilitatory and inhibitory effects of repetitive transcranial magnetic stimulation using different stimulation frequencies were tested. Six female (M age = 32.0 years, SD = 6.7) and nine male (M age = 32.9 years, SD = 6.6) participants were asked to perceive the tendon vibration illusion of the left wrist joint and to replicate the illusion with their right hand. When comparing changes in the corresponding movement amplitude and velocity after three different repetitive transcranial magnetic stimulation protocols (sham, 1 Hz inhibitory, and 5 Hz facilitatory repetitive transcranial magnetic stimulation), the movement amplitude was found to decrease with the inhibitory repetitive transcranial magnetic stimulation, while the movement velocity respectively increased and decreased with the facilitatory and inhibitory repetitive transcranial magnetic stimulation. These results confirmed the modulating effects of repetitive transcranial magnetic stimulation on kinesthetic perception in a single experimental paradigm. © The Author(s) 2016.
Boosting Cognition: Effects of Multiple-Session Transcranial Direct Current Stimulation on Working Memory.

PubMed

Talsma, Lotte J; Kroese, Henryk A; Slagter, Heleen A

2017-04-01

Transcranial direct current stimulation (tDCS) is a promising tool for neurocognitive enhancement. Several studies have shown that just a single session of tDCS over the left dorsolateral pFC (lDLPFC) can improve the core cognitive function of working memory (WM) in healthy adults. Yet, recent studies combining multiple sessions of anodal tDCS over lDLPFC with verbal WM training did not observe additional benefits of tDCS in subsequent stimulation sessions nor transfer of benefits to novel WM tasks posttraining. Using an enhanced stimulation protocol as well as a design that included a baseline measure each day, the current study aimed to further investigate the effects of multiple sessions of tDCS on WM. Specifically, we investigated the effects of three subsequent days of stimulation with anodal (20 min, 1 mA) versus sham tDCS (1 min, 1 mA) over lDLPFC (with a right supraorbital reference) paired with a challenging verbal WM task. WM performance was measured with a verbal WM updating task (the letter n-back) in the stimulation sessions and several WM transfer tasks (different letter set n-back, spatial n-back, operation span) before and 2 days after stimulation. Anodal tDCS over lDLPFC enhanced WM performance in the first stimulation session, an effect that remained visible 24 hr later. However, no further gains of anodal tDCS were observed in the second and third stimulation sessions, nor did benefits transfer to other WM tasks at the group level. Yet, interestingly, post hoc individual difference analyses revealed that in the anodal stimulation group the extent of change in WM performance on the first day of stimulation predicted pre to post changes on both the verbal and the spatial transfer task. Notably, this relationship was not observed in the sham group. Performance of two individuals worsened during anodal stimulation and on the transfer tasks. Together, these findings suggest that repeated anodal tDCS over lDLPFC combined with a challenging WM task may be an effective method to enhance domain-independent WM functioning in some individuals, but not others, or can even impair WM. They thus call for a thorough investigation into individual differences in tDCS respondence as well as further research into the design of multisession tDCS protocols that may be optimal for boosting cognition across a wide range of individuals.
Brain stimulation-induced neuroplasticity underlying therapeutic response in phantom sounds.

PubMed

Poeppl, Timm B; Langguth, Berthold; Lehner, Astrid; Frodl, Thomas; Rupprecht, Rainer; Kreuzer, Peter M; Landgrebe, Michael; Schecklmann, Martin

2018-01-01

Noninvasive brain stimulation can modify phantom sounds for longer periods by modulating neural activity and putatively inducing regional neuroplastic changes. However, treatment response is limited and there are no good demographic or clinical predictors for treatment outcome. We used state-of-the-art voxel-based morphometry (VBM) to investigate whether transcranial magnetic stimulation-induced neuroplasticity determines therapeutic outcome. Sixty subjects chronically experiencing phantom sounds (i.e., tinnitus) received repetitive transcranial magnetic stimulation (rTMS) of left dorsolateral prefrontal and temporal cortex according to a protocol that has been shown to yield a significantly higher number of treatment responders than sham stimulation and previous stimulation protocols. Structural magnetic resonance imaging was performed before and after rTMS. In VBM whole-brain analyses (P < 0.05, FWE corrected), we assessed longitudinal gray matter changes as well as structural connectivity between the ensuing regions. We observed longitudinal mesoscopic gray matter changes of left dorsolateral prefontal (DLPFC), left operculo-insular, and right inferior temporal cortex (ITC) in responders (N = 22) but not nonresponders (N = 38), as indicated by a group × time interaction and post-hoc tests. These results were neither influenced by age, sex, hearing loss nor by tinnitus laterality, duration, and severity at baseline. Furthermore, we found robust DLPFC-insula and insula-ITC connectivity in responders, while only relatively weak DLPFC-insula connectivity and no insula-ITC connectivity could be demonstrated in nonresponders. Our results reinforce the implication of nonauditory brain regions in phantom sounds and suggest the dependence of therapeutic response on their neuroplastic capabilities. The latter in turn may depend on (differences in) their individual structural connectivity. Hum Brain Mapp 39:554-562, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Electrical stimulation of cardiac adipose tissue-derived progenitor cells modulates cell phenotype and genetic machinery.

PubMed

Llucià-Valldeperas, A; Sanchez, B; Soler-Botija, C; Gálvez-Montón, C; Prat-Vidal, C; Roura, S; Rosell-Ferrer, J; Bragos, R; Bayes-Genis, A

2015-11-01

A major challenge of cardiac tissue engineering is directing cells to establish the physiological structure and function of the myocardium being replaced. Our aim was to examine the effect of electrical stimulation on the cardiodifferentiation potential of cardiac adipose tissue-derived progenitor cells (cardiac ATDPCs). Three different electrical stimulation protocols were tested; the selected protocol consisted of 2 ms monophasic square-wave pulses of 50 mV/cm at 1 Hz over 14 days. Cardiac and subcutaneous ATDPCs were grown on biocompatible patterned surfaces. Cardiomyogenic differentiation was examined by real-time PCR and immunocytofluorescence. In cardiac ATDPCs, MEF2A and GATA-4 were significantly upregulated at day 14 after stimulation, while subcutaneous ATDPCs only exhibited increased Cx43 expression. In response to electrical stimulation, cardiac ATDPCs elongated, and both cardiac and subcutaneous ATDPCs became aligned following the linear surface pattern of the construct. Cardiac ATDPC length increased by 11.3%, while subcutaneous ATDPC length diminished by 11.2% (p = 0.013 and p = 0.030 vs unstimulated controls, respectively). Compared to controls, electrostimulated cells became aligned better to the patterned surfaces when the pattern was perpendicular to the electric field (89.71 ± 28.47º for cardiac ATDPCs and 92.15 ± 15.21º for subcutaneous ATDPCs). Electrical stimulation of cardiac ATDPCs caused changes in cell phenotype and genetic machinery, making them more suitable for cardiac regeneration approaches. Thus, it seems advisable to use electrical cell training before delivery as a cell suspension or within engineered tissue. Copyright © 2013 John Wiley & Sons, Ltd.
Modulatory Effect of Association of Brain Stimulation by Light and Binaural Beats in Specific Brain Waves

PubMed Central

Calomeni, Mauricio Rocha; Furtado da Silva, Vernon; Velasques, Bruna Brandão; Feijó, Olavo Guimarães; Bittencourt, Juliana Marques; Ribeiro de Souza e Silva, Alair Pedro

2017-01-01

Introduction: One of the positive effects of brain stimulation is interhemispheric modulation as shown in some scientific studies. This study examined if a type of noninvasive stimulation using binaural beats with led-lights and sound would show different modulatory effects upon Alfa and SMR brain waves of elderlies and children with some disease types. Subjects: The sample included 75 individuals of both genders, being, randomly, divided in 6 groups. Groups were named elderly without dementia diagnosis (EWD), n=15, 76±8 years, elderly diagnosed with Parkinson’s disease (EDP), n=15, 72±7 years, elderly diagnosed with Alzheimer’s disease (EDA), n=15, 81±6 years. The other groups were named children with Autism (CA), n=10, 11±4 years, children with Intellectual Impairment (CII), n=10, 12 ±5 years and children with normal cognitive development (CND), n=10, 11±4 years. Instruments and procedure: Instruments were the Mini Mental State Examination Test (MMSE), EEG-Neurocomputer instrument for brain waves registration, brain stimulator, Digit Span Test and a Protocol for working memory training. Data collection followed a pre and post-conjugated stimulation version. Results: The results of the inferential statistics showed that the stimulation protocol had different effects on Alpha and SMR brain waves of the patients. Also, indicated gains in memory functions, for both, children and elderlies as related to gains in brain waves modulation. Conclusion: The results may receive and provide support to a range of studies examining brain modulation and synaptic plasticity. Also, it was emphasized in the results discussion that there was the possibility of the technique serving as an accessory instrument to alternative brain therapies. PMID:29238390
Modulatory Effect of Association of Brain Stimulation by Light and Binaural Beats in Specific Brain Waves.

PubMed

Calomeni, Mauricio Rocha; Furtado da Silva, Vernon; Velasques, Bruna Brandão; Feijó, Olavo Guimarães; Bittencourt, Juliana Marques; Ribeiro de Souza E Silva, Alair Pedro

2017-01-01

One of the positive effects of brain stimulation is interhemispheric modulation as shown in some scientific studies. This study examined if a type of noninvasive stimulation using binaural beats with led-lights and sound would show different modulatory effects upon Alfa and SMR brain waves of elderlies and children with some disease types. The sample included 75 individuals of both genders, being, randomly, divided in 6 groups. Groups were named elderly without dementia diagnosis (EWD), n=15, 76±8 years, elderly diagnosed with Parkinson's disease (EDP), n=15, 72±7 years, elderly diagnosed with Alzheimer's disease (EDA), n=15, 81±6 years. The other groups were named children with Autism (CA), n=10, 11±4 years, children with Intellectual Impairment (CII), n=10, 12 ±5 years and children with normal cognitive development (CND), n=10, 11±4 years. Instruments were the Mini Mental State Examination Test (MMSE), EEG-Neurocomputer instrument for brain waves registration, brain stimulator, Digit Span Test and a Protocol for working memory training. Data collection followed a pre and post-conjugated stimulation version. The results of the inferential statistics showed that the stimulation protocol had different effects on Alpha and SMR brain waves of the patients. Also, indicated gains in memory functions, for both, children and elderlies as related to gains in brain waves modulation. The results may receive and provide support to a range of studies examining brain modulation and synaptic plasticity. Also, it was emphasized in the results discussion that there was the possibility of the technique serving as an accessory instrument to alternative brain therapies.
Inter-individual variability in cortical excitability and motor network connectivity following multiple blocks of rTMS

PubMed Central

Nettekoven, Charlotte; Volz, Lukas J.; Leimbach, Martha; Pool, Eva-Maria; Rehme, Anne K.; Eickhoff, Simon B.; Fink, Gereon R.; Grefkes, Christian

2016-01-01

The responsiveness to non-invasive neuromodulation protocols shows high inter-individual variability, the reasons of which remain poorly understood. We here tested whether the response to intermittent theta-burst stimulation (iTBS) – an effective repetitive transcranial magnetic stimulation (rTMS) protocol for increasing cortical excitability – depends on network properties of the cortical motor system. We furthermore investigated whether the responsiveness to iTBS is dose-dependent. To this end, we used a sham-stimulation controlled, single-blinded within-subject design testing for the relationship between iTBS aftereffects and (i) motor-evoked potentials (MEPs) as well as (ii) resting-state functional connectivity (rsFC) in 16 healthy subjects. In each session, three blocks of iTBS were applied, separated by 15 min. We found that non-responders (subjects not showing an MEP increase of ≥10% after one iTBS block) featured stronger rsFC between the stimulated primary motor cortex (M1) and premotor areas before stimulation compared to responders. However, only the group of responders showed increases in rsFC and MEPs, while most non-responders remained close to baseline levels after all three blocks of iTBS. Importantly, there was still a large amount of variability in both groups. Our data suggest that responsiveness to iTBS at the local level (i.e., M1 excitability) depends upon the pre-interventional network connectivity of the stimulated region. Of note, increasing iTBS dose did not turn non-responders into responders. The finding that higher levels of pre-interventional connectivity precluded a response to iTBS could reflect a ceiling effect underlying non-responsiveness to iTBS at the systems level. PMID:26052083
Inter-individual variability in cortical excitability and motor network connectivity following multiple blocks of rTMS.

PubMed

Nettekoven, Charlotte; Volz, Lukas J; Leimbach, Martha; Pool, Eva-Maria; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

2015-09-01

The responsiveness to non-invasive neuromodulation protocols shows high inter-individual variability, the reasons of which remain poorly understood. We here tested whether the response to intermittent theta-burst stimulation (iTBS) - an effective repetitive transcranial magnetic stimulation (rTMS) protocol for increasing cortical excitability - depends on network properties of the cortical motor system. We furthermore investigated whether the responsiveness to iTBS is dose-dependent. To this end, we used a sham-stimulation controlled, single-blinded within-subject design testing for the relationship between iTBS aftereffects and (i) motor-evoked potentials (MEPs) as well as (ii) resting-state functional connectivity (rsFC) in 16 healthy subjects. In each session, three blocks of iTBS were applied, separated by 15min. We found that non-responders (subjects not showing an MEP increase of ≥10% after one iTBS block) featured stronger rsFC between the stimulated primary motor cortex (M1) and premotor areas before stimulation compared to responders. However, only the group of responders showed increases in rsFC and MEPs, while most non-responders remained close to baseline levels after all three blocks of iTBS. Importantly, there was still a large amount of variability in both groups. Our data suggest that responsiveness to iTBS at the local level (i.e., M1 excitability) depends upon the pre-interventional network connectivity of the stimulated region. Of note, increasing iTBS dose did not turn non-responders into responders. The finding that higher levels of pre-interventional connectivity precluded a response to iTBS could reflect a ceiling effect underlying non-responsiveness to iTBS at the systems level. Copyright © 2015 Elsevier Inc. All rights reserved.
Feasibility Study of Sequentially Alternating EGFR-TKIs and Chemotherapy for Patients with Non-small Cell Lung Cancer.

PubMed

Takemura, Yoshizumi; Chihara, Yusuke; Morimoto, Yoshie; Tanimura, Keiko; Imabayashi, Tatsuya; Seko, Yurie; Kaneko, Yoshiko; Date, Koji; Ueda, Mikio; Arimoto, Taichiro; Iwasaki, Yoshinobu; Takayama, Koichi

2018-04-01

The purpose of this trial was to evaluate the feasibility and efficacy of alternating platinum-based doublet chemotherapy with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant non-small cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced NSCLC harboring an EGFR mutation were enrolled. All patients underwent induction chemotherapy by sequentially alternating pemetrexed/cisplatin/bevacizumab and EGFR-TKIs followed by maintenance therapy with pemetrexed/bevacizumab and EGFR-TKIs. The primary outcome was the completion rate of the induction therapy. Eighteen eligible patients were enrolled between May 2011 and March 2016. The completion rate of induction therapy was 72.2% (13/18). Unfortunately, one patient developed grade 4 acute renal injury, but no other serious complications concerning this protocol were observed. Furthermore, diarrhea, rashes, and hematological adverse effects were mild. The completion rate of induction therapy was promising. Alternating chemotherapy and EGFR-TKIs should be further investigated regarding feasibility and efficacy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Surmounting retraining limits in musicians' dystonia by transcranial stimulation.

PubMed

Furuya, Shinichi; Nitsche, Michael A; Paulus, Walter; Altenmüller, Eckart

2014-05-01

Abnormal cortical excitability is evident in various movement disorders that compromise fine motor control. Here we tested whether skilled finger movements can be restored in musicians with focal hand dystonia through behavioral training assisted by transcranial direct current stimulation to the motor cortex of both hemispheres. The bilateral motor cortices of 20 pianists (10 with focal dystonia, 10 healthy controls) were electrically stimulated noninvasively during bimanual mirrored finger movements. We found improvement in the rhythmic accuracy of sequential finger movements with the affected hand during and after cathodal stimulation over the affected cortex and simultaneous anodal stimulation over the unaffected cortex. The improvement was retained 4 days after intervention. Neither a stimulation with the reversed montage of electrodes nor sham stimulation yielded any improvement. Furthermore, the amount of improvement was positively correlated with the severity of the symptoms. Bihemispheric stimulation without concurrent motor training failed to improve fine motor control, underlining the importance of combined retraining and stimulation for restoring the dystonic symptoms. For the healthy pianists, none of the stimulation protocols enhanced movement accuracy. These results suggest a therapeutic potential of behavioral training assisted by bihemispheric, noninvasive brain stimulation in restoring fine motor control in focal dystonia. © 2014 American Neurological Association.
The Effect of Paired Muscle Stimulation on Preparation for Movement.

PubMed

Brownjohn, Philip W; Blakemore, Rebekah L; Fox, Jonathan A; Shemmell, Jonathan

2018-06-07

Paired muscle stimulation is used clinically to facilitate the performance of motor tasks for individuals with motor dysfunction. However, the optimal temporal relationship between stimuli for enhancing movement remains unknown. We hypothesized that synchronous, muscle stimulation would increase the extent to which stimulated muscles are concurrently prepared for movement. We validated a measure of muscle-specific changes in corticomotor excitability prior to movement. We used this measure to examine the preparation of the first dorsal interosseous (FDI), abductor digiti minimi (ADM), abductor pollicis brevis (APB) muscles prior to voluntary muscle contractions before and after paired muscle stimulation at four interstimulus intervals (0, 5, 10, and 75 ms). Paired muscle stimulation increased premovement excitability in the stimulated FDI, but not in the ADM muscle. Interstimulus interval was not a significant factor in determining efficacy of the protocol. Paired stimulation, therefore, did not result in a functional association being formed between the stimulated muscles. Somatosensory potentials evoked by the muscle stimuli were small compared to those commonly elicited by stimulation of peripheral nerves, suggesting that the lack of functional association formation between muscles may be due to the small magnitude of afferent volleys from the stimulated muscles, particularly the ADM, reaching the cortex.
Microdose GnRH Agonist Flare-Up versus Ultrashort GnRH Agonist Combined with Fixed GnRH Antagonist in Poor Responders of Assisted Reproductive Techniques Cycles

PubMed Central

Eftekhar, Maryam; Mohammadian, Farnaz; Yousefnejad, Fariba; Khani, Parisa

2013-01-01

Background: This study compares the microdose flare-up protocol to the ultrashort gonadotropinreleasing hormone (GnRH) agonist flare combined with the fixed multidose GnRH antagonist protocol in poor responders undergoing ovarian stimulation. Materials and Methods: In this randomized clinical trial, 120 women who were candidates for assisted reproductive techniques (ART) and had histories of one or more failed in vitro fertilization (IVF) cycles with three or fewer retrieved oocytes were prospectively randomized into two groups. Group I (60 patients) received the microdose flare-up regimen and group II (60 patients) received the ultrashort GnRH agonist combined with fixed GnRH antagonist. Results: There were no significant differences between the groups in the number of used gonadotropin ampoules (p=0.591), duration of stimulation (p=0.610), number of retrieved oocytes (p=0.802), fertilization rate (p=0.456), and the number of transferred embryos (p=0.954). The clinical pregnancy rates were statistically similar in group I (10%) compared with group II (13.3%, p=0.389). Conclusion: According to our results, there is no significant difference between these protocols for improving the ART outcome in poor responders. Additional prospective, randomized studies with more patients is necessary to determine the best protocol (Registration Number: IRCT201105096420N1). PMID:24520450
Comparison of basophil activation tests using CD63 or CD203c expression in patients with insect venom allergy.

PubMed

Eberlein-König, B; Varga, R; Mempel, M; Darsow, U; Behrendt, H; Ring, J

2006-09-01

Flow cytometric basophil activation tests have been developed as cellular tests for in vitro diagnosis of IgE-mediated reactions. Different activation markers (CD63 or CD203c) with distinct ways of regulation have been used after stimulation with various allergens. It was the aim of the present study to compare basophil activation tests by measuring both CD63 and CD203c upregulation in patients with insect venom allergy. 43 patients with a history of insect venom anaphylaxis were examined. A careful allergy history was taken, and skin tests and determination of specific IgE-antibodies were performed. Basophil activation tests (BAT) using CD63 or CD203c expression were done after stimulation with different concentrations of bee and wasp venom extracts. 25 healthy subjects with negative history of insect venom allergy were studied as controls. The CD203c protocol showed a slightly higher sensitivity than the CD63 protocol (97% vs. 89%) with regard to patients' history. The magnitude of basophil response was higher with CD203c in comparison to CD63 for both insect venoms. Specificity was 100% for the CD63 protocol and 89% for the CD203c protocol with regard to controls with negative history and negative RAST. These results support the reliability of basophil activation tests using either CD63 or CD203c as cellular tests in the in vitro diagnosis of patients with bee or wasp venom allergy with a slightly higher sensitivity for the CD203c protocol.
FISH-Flow, a protocol for the concurrent detection of mRNA and protein in single cells using fluorescence in situ hybridization and flow cytometry

PubMed Central

Arrigucci, Riccardo; Bushkin, Yuri; Radford, Felix; Lakehal, Karim; Vir, Pooja; Pine, Richard; Martin, December; Sugarman, Jeffrey; Zhao, Yanlin; Yap, George S; Lardizabal, Alfred A; Tyagi, Sanjay; Gennaro, Maria Laura

2017-01-01

We describe a flow-cytometry-based protocol for intracellular mRNA measurements in nonadherent mammalian cells using fluorescence in situ hybridization (FISH) probes. The method, which we call FISH-Flow, allows for high-throughput multiparametric measurements of gene expression, a task that was not feasible with earlier, microscopy-based approaches. The FISH-Flow protocol involves cell fixation, permeabilization and hybridization with a set of fluorescently labeled oligonucleotide probes. In this protocol, surface and intracellular protein markers can also be stained with fluorescently labeled antibodies for simultaneous protein and mRNA measurement. Moreover, a semiautomated, single-tube version of the protocol can be performed with a commercially available cell-wash device that reduces cell loss, operator time and interoperator variability. It takes ~30 h to perform this protocol. An example of FISH-Flow measurements of cytokine mRNA induction by ex vivo stimulation of primed T cells with specific antigens is described. PMID:28518171
Relationships of the internodal distance of biological tissue with its sound velocity and attenuation at high frequency in doublet mechanics

NASA Astrophysics Data System (ADS)

Cheng, Kai-Xuan; Wu, Rong-Rong; Liu, Xiao-Zhou; Liu, Jie-Hui; Gong, Xiu-Fen; Wu, Jun-Ru

2015-04-01

In view of the discrete characteristics of biological tissue, doublet mechanics has demonstrated its advantages in the mathematic description of tissue in terms of high frequency (> 10 MHz) ultrasound. In this paper, we take human breast biopsies as an example to study the influence of the internodal distance, a microscope parameter in biological tissue in doublet mechanics, on the sound velocity and attenuation by numerical simulation. The internodal distance causes the sound velocity and attenuation in biological tissue to change with the increase of frequency. The magnitude of such a change in pathological tissue is distinctly different from that in normal tissue, which can be used to differentiate pathological tissue from normal tissue and can depict the diseased tissue structure by obtaining the sound and attenuation distribution in the sample at high ultrasound frequency. A comparison of sensitivity between the doublet model and conventional continuum model is made, indicating that this is a new method of characterizing ultrasound tissue and diagnosing diseases. Project supported by the National Basic Research Program of China (Grant Nos. 2012CB921504 and 2011CB707902), the National Natural Science Foundation of China (Grant No. 11274166), the Fundamental Research Funds for the Central Universities, China (Grant Nos. 1113020403 and 1101020402), the State Key Laboratory of Acoustics, Chinese Academy of Sciences (Grant No. SKLA201401), the China Postdoctoral Science Foundation (Grant No. 2013M531313), the Priority Academic Program Development of Jiangsu Provincial Higher Education Institutions and Scientific Research Foundation for Returned Overseas Chinese Scholars, State Education Ministry, and the Project of Interdisciplinary Center of Nanjing University, China (Grant No. NJUDC2012004).
A Vrancea doublet of earthquakes on September 23 and December 27, 2016: comparative analysis of effects

NASA Astrophysics Data System (ADS)

Rogozea, Maria; Radulian, Mircea; Placinta, Anica; Toma-Danila, Dragos

2017-04-01

A pair of moderate earthquakes of similar magnitude (Mw = 5.6) occurred in the Vrancea seismic source, a well-defined seismicity nest located in the mantle, beneath the South-Eastern Carpathians Arc in Romania. The two events are separated in time by two months (September 23, 2016 at 23:11:20 GMT and December 27, 2016 at 23:20:55 GMT). They are located close each other (45.7140N, 26.6180E, h = 92 km, and 45.7090N, 26.6030E, h = 99 km, respectively) and could be considered as belonging to an earthquake doublet. Similar doublets generated in the same depth range were recorded in 01 August 1985 (Mw = 5.2 and 5.8) and in 30-31 May 1990 (Mw = 6.9 and 6.4). The main purpose of this paper is to investigate comparatively the macroseismic effects associated to the earthquake doublet of 2016 and to analyze possible correlations with source characteristics, acceleration distribution and focal mechanism. Macroseismic information is collected using the on-line questionnaires from the website of the National Institute for Earth Physics (NIEP) and of the European Mediterranean Seismological Center (EMSC). The two earthquakes were felt over an extended area covering most of the Romania, north of Bulgaria, Republic of Moldova and south of Ukraine. We estimate the maximum observed intensity at V (MSK-64 scale). Although the two events have similar locations, time of occurrence and focal mechanism, significant differences were reported in the way that they were felt: on September 2017 the effects were stronger toward NE (Moldova) and SE (Dobrogea), while on December 2017 they were stronger toward NW (Transylvania) and SW (Romanian Plain). Possible source effects (complexity, rupture size) are investigated in this respect.
Infinite-range Heisenberg model and high-temperature superconductivity

NASA Astrophysics Data System (ADS)

Tahir-Kheli, Jamil; Goddard, William A., III

1993-11-01

A strongly coupled variational wave function, the doublet spin-projected Néel state (DSPN), is proposed for oxygen holes in three-band models of high-temperature superconductors. This wave function has the three-spin system of the oxygen hole plus the two neighboring copper atoms coupled in a spin-1/2 doublet. The copper spins in the neighborhood of a hole are in an eigenstate of the infinite-range Heisenberg antiferromagnet (SPN state). The doublet three-spin magnetic polaron or hopping polaron (HP) is stabilized by the hopping terms tσ and tτ, rather than by the copper-oxygen antiferromagnetic coupling Jpd. Although, the HP has a large projection onto the Emery (Dg) polaron, a non-negligible amount of doublet-u (Du) character is required for optimal hopping stabilization. This is due to Jdd, the copper-copper antiferromagnetic coupling. For the copper spins near an oxygen hole, the copper-copper antiferromagnetic coupling can be considered to be almost infinite ranged, since the copper-spin-correlation length in the superconducting phase (0.06-0.25 holes per in-plane copper) is approximately equal to the mean separation of the holes (between 2 and 4 lattice spacings). The general DSPN wave function is constructed for the motion of a single quasiparticle in an antiferromagnetic background. The SPN state allows simple calculations of various couplings of the oxygen hole with the copper spins. The energy minimum is found at symmetry (π/2,π/2) and the bandwidth scales with Jdd. These results are in agreement with exact computations on a lattice. The coupling of the quasiparticles leads to an attraction of holes and its magnitude is estimated.
Cryo-EM reconstruction of AlfA from Bacillus subtilis reveals the structure of a simplified actin-like filament at 3.4-Å resolution.

PubMed

Szewczak-Harris, Andrzej; Löwe, Jan

2018-03-27

Low copy-number plasmid pLS32 of Bacillus subtilis subsp. natto contains a partitioning system that ensures segregation of plasmid copies during cell division. The partitioning locus comprises actin-like protein AlfA, adaptor protein AlfB, and the centromeric sequence parN Similar to the ParMRC partitioning system from Escherichia coli plasmid R1, AlfA filaments form actin-like double helical filaments that arrange into an antiparallel bipolar spindle, which attaches its growing ends to sister plasmids through interactions with AlfB and parN Because, compared with ParM and other actin-like proteins, AlfA is highly diverged in sequence, we determined the atomic structure of nonbundling AlfA filaments to 3.4-Å resolution by cryo-EM. The structure reveals how the deletion of subdomain IIB of the canonical actin fold has been accommodated by unique longitudinal and lateral contacts, while still enabling formation of left-handed, double helical, polar and staggered filaments that are architecturally similar to ParM. Through cryo-EM reconstruction of bundling AlfA filaments, we obtained a pseudoatomic model of AlfA doublets: the assembly of two filaments. The filaments are antiparallel, as required by the segregation mechanism, and exactly antiphasic with near eightfold helical symmetry, to enable efficient doublet formation. The structure of AlfA filaments and doublets shows, in atomic detail, how deletion of an entire domain of the actin fold is compensated by changes to all interfaces so that the required properties of polymerization, nucleotide hydrolysis, and antiparallel doublet formation are retained to fulfill the system's biological raison d'être.
Sequential segmental neuromuscular stimulation: an effective approach to enhance fatigue resistance.

PubMed

Zonnevijlle, E D; Somia, N N; Stremel, R W; Maldonado, C J; Werker, P M; Kon, M; Barker, J H

2000-02-01

Electrical stimulation of skeletal muscle flaps is used clinically in applications that require contraction of muscle and force generation at the recipient site, for example, to assist a failing myocardium (cardiomyoplasty) or to reestablish urinary or fecal continence as a neo-sphincter (dynamic graciloplasty). A major problem in these applications (muscle fatigue) results from the nonphysiologic manner in which most of the fibers within the muscle are recruited in a single burst-like contraction. To circumvent this problem, current protocols call for the muscle to be put through a rigorous training regimen to transform it from a fatigue-prone to a fatigue-resistant state. This process takes several weeks during which, aside from becoming fatigue-resistant, the muscle loses power and contraction speed. This study tested the feasibility of electrically stimulating a muscle flap in a more physiologic way; namely, by stimulating different anatomical parts of the muscle sequentially rather than the entire muscle all at once. Sequential segmental neuromuscular stimulation (SSNS) allows parts of the muscle to rest while other parts are contracting. In a paired designed study in dogs (n = 7), the effects of SSNS on muscle fatigability and muscle blood perfusion in gracilis muscles were compared with conventional stimulation: SSNS on one side and whole muscle stimulation on the other. In SSNS, electrodes were implanted in the muscles in such a way that four separate segments of each muscle could be stimulated separately. Then, each segment was stimulated so that part of the muscle was always contracted while part was always resting. This type of stimulation permitted sequential yet continuous force generation. Muscles in both groups maintained an equal amount of continuous force. In SSNS muscles, separate segments were stimulated so that the duty cycle for any one segment was 25, 50, 75, or 100 percent, thus varying the amount of work and rest that any segment experienced at any one time. With duty cycles of 25, 50, and 75 percent, SSNS produced significantly (p < 0.01) enhanced resistance to fatigue. In addition, muscle perfusion was significantly (p < 0.01) increased in these sequentially stimulated muscles compared with the controls receiving whole muscle stimulation. It was concluded that SSNS reduces muscle fatigue and enhances muscle blood flow during stimulation. These findings suggest that using SSNS in clinical myoplasty procedures could obviate the need for prolonged training protocols and minimize problems associated with muscle training.
Activity-rest stimulation protocol improves cardiac assistance in dynamic cardiomyoplasty.

PubMed

Rigatelli, Gianluca; Carraro, Ugo; Barbiero, Mario; Zanchetta, Mario; Dimopoulos, Konstantinos; Cobelli, Franco; Riccardi, Riccardo; Rigatelli, Giorgio

2002-03-01

No data have ever been published regarding cardiac assistance in demand dynamic cardiomyoplasty (DDCMP). We tested the efficacy of the Doppler flow wire in measuring beat-to-beat aortic flow velocity and evaluating cardiac assistance in demand cardiomyoplasty patients. The technique was tested in seven patients (M/F=6/1; age=57.1+/-6.2 years; atrial fibrillation/sinus rhythm=1/6; NYHA=1.4+/-0.5). Measurements were done using a 0.018inch peripheral Doppler flow wire advanced through a 5F arterial femoral sheath. Three 1-min periods with the stimulator off and three 1-min periods with clinical stimulation were recorded. We measured peak aortic flow velocity in all beats. Latissimus dorsi (LD) mechanogram was simultaneously recorded. Comparison between pre-operative and follow-up data showed significantly higher values of tetanic fusion frequency (TFF) and ejection fraction at follow-up, whereas mean NYHA class was significantly lower. Statistical analysis showed an increase in aortic flow velocity not only in assisted versus rest period, but also in assisted versus unassisted beats (8.42+/-6.98% and 7.55+/-3.07%). A linear correlation was found between the increase in flow velocity and LD wrap TFF (r(2)=0.53). In DDCMP, systolic assistance is significant and correlated to LD speed of contraction; demand stimulation protocol maintains muscle properties and increases muscle performance.
Muscle contractile characteristics: relationship to high-intensity exercise.

PubMed

Morris, Martyn G; Dawes, Helen; Howells, Ken; Scott, Oona M; Cramp, Mary; Izadi, Hooshang

2010-09-01

We investigated the relationship between muscle contractile characteristics, collected using percutaneous electrical stimulation, and high-intensity exercise performance. Seventeen participants performed a muscle performance test for the calculation of rate of torque development (RTD), rate of relaxation (RR(1/2)), rate of fatigue and fatigue resistance. On a second visit the participants completed a Wingate cycle ergometer test with peak power, mean power, fatigue index and fatigue rate calculated. The muscle fatigue index related significantly to the WAnT fatigue index and fatigue rate (p < 0.01). The change in rate of torque development (%DeltaRTD) was also related significantly to the fatigue rate (W/s) during the WAnT. Subjects displaying the greatest reduction in RTD had the greatest fatigue rate during the WAnT and greater fatigue during the electrical stimulation protocol. There were no significant relationships between peak (r 0.36; p > 0.01) or mean power (r -0.11, p > 0.01) with any of the muscle performance measures. These findings demonstrate that muscle contractile characteristics, elicited during standardised in vivo electrical stimulation, relate to performance during a Wingate anaerobic test. They suggest that muscle contraction characteristics play an important role in high-intensity exercise performance and indicate that electrical stimulation protocols can be a useful additional tool to explore muscle contraction characteristics in relation to exercise performance and trainability.
Measurement of Basal and Forskolin-stimulated Lipolysis in Inguinal Adipose Fat Pads.

PubMed

Baskaran, Padmamalini; Thyagarajan, Baskaran

2017-07-21

Lipolysis is a process by which the lipid stored as triglycerides in adipose tissues are hydrolyzed into glycerol and fatty acids. This article describes the method for the measurement of basal and forskolin (FSK)-stimulated lipolysis in the inguinal fat pads isolated from wild type mice fed either normal chow diet (NCD), high fat diet (HFD) or a high fat diet containing 0.01% of capsaicin (CAP; transient receptor potential vanilloid subfamily 1 (TRPV1) agonist) for 32 weeks. The method described here for performing ex vivo lipolysis is adopted from Schweiger et al. 1 We present a detailed protocol for measuring glycerol levels by UV-Visible (UV/VIS) spectrophotometry. The method described here can be used to successfully isolate inguinal fat pads for lipolysis measurements to obtain consistent results. The protocol described for inguinal fat pads can readily be extended to measure lipolysis in other tissues.
Transcranial Alternating Current Stimulation (tACS) Mechanisms and Protocols

PubMed Central

Tavakoli, Amir V.; Yun, Kyongsik

2017-01-01

Perception, cognition and consciousness can be modulated as a function of oscillating neural activity, while ongoing neuronal dynamics are influenced by synaptic activity and membrane potential. Consequently, transcranial alternating current stimulation (tACS) may be used for neurological intervention. The advantageous features of tACS include the biphasic and sinusoidal tACS currents, the ability to entrain large neuronal populations, and subtle control over somatic effects. Through neuromodulation of phasic, neural activity, tACS is a powerful tool to investigate the neural correlates of cognition. The rapid development in this area requires clarity about best practices. Here we briefly introduce tACS and review the most compelling findings in the literature to provide a starting point for using tACS. We suggest that tACS protocols be based on functional brain mechanisms and appropriate control experiments, including active sham and condition blinding. PMID:28928634
Sequential segmental neuromuscular stimulation reduces fatigue and improves perfusion in dynamic graciloplasty.

PubMed

Zonnevijlle, E D; Somia, N N; Abadia, G P; Stremel, R W; Maldonado, C J; Werker, P M; Kon, M; Barker, J H

2000-09-01

Dynamic graciloplasty is used as a treatment modality for total urinary incontinence caused by a paralyzed sphincter. A problem with this application is undesirable fatigue of the muscle caused by continuous electrical stimulation. Therefore, the neosphincter must be trained via a rigorous regimen to transform it from a fatigue-prone state to a fatigue-resistant state. To avoid or shorten this training period, the application of sequential segmental neuromuscular stimulation (SSNS) was examined. This form of stimulation proved previously to be highly effective in acutely reducing fatigue caused by electrical stimulation. The contractile function and perfusion of gracilis muscles employed as neosphincters were compared between conventional, single-channel, continuous stimulation, and multichannel sequential stimulation in 8 dogs. The sequentially stimulated neosphincter proved to have an endurance 2.9 times longer (as measured by halftime to fatigue) than continuous stimulation and a better blood perfusion during stimulation (both of which were significant changes, p < 0.05). Clinically, this will not antiquate training of the muscle, but SSNS could reduce the need for long and rigorous training protocols, making dynamic graciloplasty more attractive as a method of treating urinary or fecal incontinence.
Chronology of desert margin in western India using improved luminescence dating protocols

NASA Astrophysics Data System (ADS)

Chauhan, Naveen; Morthekai, P.

2017-12-01

The present study provides improved chronology for the desert margin fluvial sediments of semi-arid region located in the Mahi river basin, western India. The sequence has preserved a near-continuous record of climate change since the Last Interglacial. An earlier attempt of dating based on feldspar IRSL chronology shows a combined effect of anomalous fading and unbleached components resulting in age inversions. The present work tries to explore the possibility of using blue light stimulated luminescence (BLSL) of quartz, infra-red stimulated luminescence (IRSL) of feldspar and the newly developed methodologies, like natural correction factor based single aliquot regeneration (NCF-SAR) protocol and decision making schemes based on distribution of doses and beta heterogeneity concept for luminescence dating of sediments. Observations suggest that quartz suffered from significant sensitivity changes during natural signal measurement and partial bleaching. A combination of NCF-SAR protocol and sample specific equivalent dose computation helped in arriving at better age estimate for present samples. The study also compares the criteria for the selection of different age models that are used at present. The age of the alluvial sequence is now bracketed between 10 ka (upper aeolian unit) and 75 ka (lowermost fluvial unit).
Shifting paradigms in diminished ovarian reserve and advanced reproductive age in assisted reproduction: customization instead of conformity.

PubMed

Reed, Beverly G; Babayev, Samir N; Bukulmez, Orhan

2015-05-01

As women are increasingly delaying childbearing into their 30s and beyond, diminished ovarian reserve (DOR) and advanced reproductive age (ARA) patients are bound to become a large proportion of all assisted reproductive technology practices. Traditional controlled ovarian stimulation (COS) protocols for DOR and/or ARA have had some limited success, but pregnancy rates are lower and cycle cancellation rates are higher than their younger counterparts with normal ovarian reserve. Though many physicians have a selection of favorite standard protocols that they use, patients with DOR may require closer monitoring and customization of the treatment cycle to address the common problems that come with low ovarian reserve. Frequent issues that surface in women with DOR and/or ARA include poor follicular response, premature luteinizing hormone surge, and poor embryo quality. Limited published evidence exists to guide treatment for DOR. However, use of minimal or mild doses of gonadotropins, avoidance of severe pituitary suppression, and consideration for luteal phase stimulation and a "freeze all" approach are possible customized treatment options that can be considered for such patients who have failed more traditional COS protocols. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
The effect of optokinetic stimulation on daytime sleepiness

NASA Technical Reports Server (NTRS)

Leslie, K. R.; Stickgold, R.; Dizio, P.; Lackner, J. R.; Hobson, J. A.

1997-01-01

This study examined the effect of optokinetic stimulation on objective sleepiness, as measured by the Multiple Sleep Latency Test (MSLT). The Nightcap, a portable sleep monitor, was used in a novel way to perform MSLTs, as well as record sleep in the home. Subjects wore the Nightcap for seven consecutive nights. On days 3 and 5 of the protocol, subjects came into the lab for an MSLT. On the experimental day, subjects underwent 10 minutes optokinetic stimulation (OKS), resulting in moderate motion sickness prior to each MSLT trial. Although subjects in the OKS condition reported significantly more drowsiness than controls, this did not result in significantly reduced sleep latencies.
Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation

NASA Technical Reports Server (NTRS)

Andrews, Russell J.

2003-01-01

Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.
Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation.

PubMed

Andrews, Russell J

2003-05-01

Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.

Rhythmic Haptic Stimuli Improve Short-Term Attention.

PubMed

Zhang, Shusheng; Wang, Dangxiao; Afzal, Naqash; Zhang, Yuru; Wu, Ruilin

2016-01-01

Brainwave entrainment using rhythmic visual and/or auditory stimulation has shown its efficacy in modulating neural activities and cognitive ability. In the presented study, we aim to investigate whether rhythmic haptic stimulation could enhance short-term attention. An experiment with sensorimotor rhythm (SMR) increasing protocol was performed in which participants were presented sinusoidal vibrotactile stimulus of 15 Hz on their palm. Test of Variables of Attention (T.O.V.A.) was performed before and after the stimulating session. Electroencephalograph (EEG) was recorded across the stimulating session and the two attention test sessions. SMR band power manifested a significant increase after stimulation. Results of T.O.V.A. tests indicated an improvement in the attention of participants who had received the stimulation compared to the control group who had not received the stimulation. The D prime score of T.O.V.A. reveals that participants performed better in perceptual sensitivity and sustaining attention level compared to their baseline performance before the stimulating session. These findings highlight the potential value of using haptics-based brainwave entrainment for cognitive training.
Effects of triploidy incidence on clinical outcomes for IVF-ET cycles in different ovarian stimulation protocols.

PubMed

Li, Mingzhao; Xue, Xia; Zhang, Silin; Li, Wei; Zhao, Xiaoli; Ren, Wenjuan; Shi, Juanzi

2015-10-01

To discuss the relationship between triploidy incidence and clinical outcomes of embryos derived from normally fertilized oocytes from the same cohort for in vitro fertilization-embryo transfer (IVF-ET) cycles in different ovarian stimulation protocol. This study included 2070 in vitro fertilization (IVF) cycles with long-term protocol, 802 IVF cycles with ultra short-term protocol and 508 IVF-D (in vitro fertilization by donor semen) cycles with long-term protocol from January 2013 to September 2014. According to the different 3PN rate, patients were divided into three groups as follows: Group 1 included patients with 0% 3PN zygotes, Group 2 included patients with 1-25% 3PN zygotes and Group 3 included patients with >25% 3PN zygotes. female age, no. of retrieved oocytes, normal fertilization rate, day-3 grade I + II embryos rate, day-3 grade I + II + III embryos rate, implantation rate, pregnancy rate and early abortion rate. Triploidy cycle incidence rate in IVF and IVF-D cycles with long-term protocol were significantly higher than in IVF cycles with ultra short-term protocol (p < 0.001). Triploidy fertilization rate found no significant difference between the three groups (p > 0.05). In three protocols, normal fertilization rate in 3PN = 0% and 3PN = 1-25% groups were significantly higher compared to 3PN > 25% group (p < 0.001). In IVF cycles with long-term protocol, the day-3 grade I + II embryos, implantation and pregnancy rate in 3PN > 25% group were significantly lower than other two groups (p < 0.05). The day-3 grade I + II + III embryos and early abortion rate found no significant difference between the three groups (p > 0.05). In IVF cycles with ultra short-term protocol, there were no significant differences found in day-3 grade I + II embryos, day-3 grade I + II + III embryos, implantation, pregnancy and early abortion rate (p > 0.05). In IVF-D cycles with long-term protocol, the day-3 grade I + II embryos, day-3 grade I + II + III embryos and implantation rate in 3PN > 25% group were significantly lower than other two groups (p < 0.05). The pregnancy and early abortion rates found no significant difference in the three groups (p > 0.05). We observed that high proportion of triploid zygotes made a negative effect on clinical outcomes for IVF-ET cycles with long-term protocol.
Age-dependent effects of topiramate on the acquisition and the retention of rapid kindling.

PubMed

Mazarati, Andréy; Shin, Don; Auvin, Stéphane; Sankar, Raman

2007-04-01

To examine antiepileptogenic, disease modifying, and anticonvulsant effects of topiramate under conditions of rapid kindling at different stages of development. Afterdischarge threshold (ADT) and duration (ADD) were examined in 2-, 3-, and 5-week-old Wistar rats before and after administration of topiramate (200 mg/kg). Animals underwent a rapid kindling protocol (sixty 10-s trains, bipolar 20 Hz square wave pulses delivered every 5 min). The progression of behavioral and electrographic seizures, and responses to test stimulations 24 h after the protocol were compared between topiramate and vehicle-treated control rats. In addition, rats that were previously given vehicle only prior to kindling, were then given topiramate to examine the effect on established kindled seizures. In 2-week-old animals, topiramate affected neither the baseline afterdischarge, nor the progression of kindled seizures. In 3-week-old rats, topiramate did not modify the baseline afterdischarge, but significantly delayed the occurrence of full motor seizures in response to repeated stimulations. Topiramate treatment of 5-week-old rats increased baseline ADT, shortened ADD, and delayed the progression of kindled seizures. Twenty-four h after the last kindling stimulation, animals of all ages exhibited a decreased ADT, an increase ADD, and developed behavioral seizures in response to threshold stimulation. Vehicle-treated kindled rats that were then given topiramate displayed significantly attenuated behavioral seizures induced by the threshold stimulation. Topiramate exhibited age-dependent disease-modifying effects under conditions of rapid kindling, but failed to block epileptogenesis. Topiramate also inhibited kindled seizures with equal efficacy across the three ages.
Age-Dependent Effects of Topiramate on the Acquisition and the Retention of Rapid Kindling

PubMed Central

Mazarati, Andréy; Shin, Don; Auvin, Stéphane; Sankar, Raman

2008-01-01

Summary Purpose To examine antiepileptogenic, disease-modifying, and anticonvulsant effects of topiramate under conditions of rapid kindling at different stages of development. Methods Afterdischarge threshold (ADT) and duration (ADD) were examined in two-, three-, and five-week old Wistar rats before and after administration of topiramate (200 mg/kg). Animals underwent a rapid kindling protocol (sixty 10 second trains, bipolar 20 Hz square wave pulses delivered every five minutes). The progression of behavioral and electrographic seizures, and responses to test stimulations 24 hours after the protocol were compared between topiramate and vehicle treated control rats. In addition, rats that were previously given vehicle only prior to kindling, were then given topiramate to examine the effect on established kindled seizures. Results In two-week old animals, topiramate affected neither the baseline afterdischarge, nor the progression of kindled seizures. In three-week old rats, topiramate did not modify the baseline afterdischarge, but significantly delayed the occurrence of full motor seizures in response to repeated stimulations. Topiramate treatment of five-week old rats increased baseline ADT, shortened ADD, and delayed the progression of kindled seizures. Twenty four hours after the last kindling stimulation, animals of all ages exhibited a decreased ADT, an increase ADD, and developed behavioral seizures in response to threshold stimulation. Vehicle treated kindled rats that were then given topiramate displayed significantly attenuated behavioral seizures induced by the threshold stimulation. Conclusions Topiramate exhibited age-dependent disease-modifying effects under conditions of rapid kindling, but failed to block epileptogenesis. Topiramate also inhibited kindled seizures with equal efficacy across the three ages. PMID:17319916
Stress inversion using borehole images and geometry evolution of the fractures in the Rittershoffen EGS project (Alsace, France).

NASA Astrophysics Data System (ADS)

Azzola, Jérôme; Valley, Benoît; Schmittbuhl, Jean; Genter, Albert; Hehn, Régis

2017-04-01

In the Upper Rhine Graben, several deep geothermal projects based on the Enhanced Geothermal System (EGS) exploit local geothermal reservoirs. The principle underlying this technology consists of increasing the hydraulic performances of the reservoir by stimulating natural fractures using different methods, in order to extract hot water with commercially flow rates. In this domain, the knowledge of the in-situ stress state is of central importance to predict the response of the rock mass to stimulations. Here we characterized the stress tensor from Ultrasonic Borehole Imager (UBI) in the open hole section of the EGS doublet located in Rittershoffen, France (in the Upper Rhine Graben). Interestingly extensive logging programs were leaded at different key moments of the development of the injection well using hydraulic, thermal and chemical stimulation (Baujard et al., 2017)1. The time lapse UBI dataset consists of images of the injection well before, shortly and lastly after the stimulation. The geometry of the induced fractures in compression (breakouts) picked on the UBI images are used to determine the orientation of the in-situ stress tensor. The magnitude of the principal stresses is deduced from the drilling data. The magnitude of the maximum horizontal principal stress is evaluated using an inversion method with three failure criteria (Mohr-Coulomb, Mogi-Coulomb and modified Hoek-Brown criterion) and under the assumption of a vertical or a deviated well. Moreover, the characteristic of the dataset enables the analysis of the evolution of the borehole fracturing, as the deepening or widening of the induced fractures. The correlation of the UBI image allows firstly to determine the tool trajectory and to adapt the post and pre-stimulation images. It secondly leads to the estimation of a complete displacement field which characterizes the deformation induced by the stimulations. Even if the variable image quality deeply conditions the comparison, the considered dataset enabled a consistent evaluation of the in-situ stress field taking place in the underground of the EGS plant, as showed by the comparison to results obtained in the vicinity. Moreover, the study of the evolution of fracturing shows the influence of the stimulation process on the fractures geometry. 1(Baujard, C., Genter, A., Dalmais, E., Maurer, V., Hehn, R., Rosillette, R., Vidal, J., Schmittbuhl, J., 2017). Hydrothermal Characterization of wells GRT-1 and GRT-2 in Rittershoffen, France: Implications on the understanding of natural flow systems in the Rhine Graben, Geothermics, 65, 255-268.
rTMS of the dorsomedial prefrontal cortex for major depression: safety, tolerability, effectiveness, and outcome predictors for 10 Hz versus intermittent theta-burst stimulation.

PubMed

Bakker, Nathan; Shahab, Saba; Giacobbe, Peter; Blumberger, Daniel M; Daskalakis, Zafiris J; Kennedy, Sidney H; Downar, Jonathan

2015-01-01

Conventional rTMS protocols for major depression commonly employ stimulation sessions lasting >30 min. However, recent studies have sought to improve costs, capacities, and outcomes by employing briefer protocols such as theta burst stimulation (iTBS). To compare safety, effectiveness, and outcome predictors for DMPFC-rTMS with 10 Hz (30 min) versus iTBS (6 min) protocols, in a large, naturalistic, retrospective case series. A chart review identified 185 patients with a medication-resistant major depressive episode who underwent 20-30 sessions of DMPFC-rTMS (10 Hz, n = 98; iTBS, n = 87) at a single Canadian clinic from 2011 to 2014. Clinical characteristics of 10 Hz and iTBS patients did not differ prior to treatment, aside from significantly higher age in iTBS patients. A total 7912 runs of DMPFC-rTMS (10 Hz, 4274; iTBS, 3638) were administered, without any seizures or other serious adverse events, and no significant differences in rates of premature discontinuation between groups. Dichotomous outcomes did not differ significantly between groups (Response/remission rates: Beck Depression Inventory-II: 10 Hz, 40.6%/29.2%; iTBS, 43.0%/31.0%. 17-item Hamilton Rating Scale for Depression: 10 Hz, 50.6%/38.5%; iTBS, 48.5%/27.9%). On continuous outcomes, there was no significant difference between groups in pre-treatment or post-treatment scores, or percent improvement on either measure. Mixed-effects modeling revealed no significant group-by-time interaction on either measure. Both 10 Hz and iTBS DMPFC-rTMS appear safe and tolerable at 120% resting motor threshold. The effectiveness of 6 min iTBS and 30 min 10 Hz protocols appears comparable. Randomized trials comparing 10 Hz to iTBS may be warranted. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Effects of a common transcranial direct current stimulation (tDCS) protocol on motor evoked potentials found to be highly variable within individuals over 9 testing sessions.

PubMed

Horvath, Jared Cooney; Vogrin, Simon J; Carter, Olivia; Cook, Mark J; Forte, Jason D

2016-09-01

Transcranial direct current stimulation (tDCS) uses a weak electric current to modulate neuronal activity. A neurophysiologic outcome measure to demonstrate reliable tDCS modulation at the group level is transcranial magnetic stimulation engendered motor evoked potentials (MEPs). Here, we conduct a study testing the reliability of individual MEP response patterns following a common tDCS protocol. Fourteen participants (7m/7f) each underwent nine randomized sessions of 1 mA, 10 min tDCS (3 anode; 3 cathode; 3 sham) delivered using an M1/orbito-frontal electrode montage (sessions separated by an average of ~5.5 days). Fifteen MEPs were obtained prior to, immediately following and in 5 min intervals for 30 min following tDCS. TMS was delivered at 130 % resting motor threshold using neuronavigation to ensure consistent coil localization. A number of non-experimental variables were collected during each session. At the individual level, considerable variability was seen among different testing sessions. No participant demonstrated an excitatory response ≥20 % to all three anodal sessions, and no participant demonstrated an inhibitory response ≥20 % to all three cathodal sessions. Intra-class correlation revealed poor anodal and cathodal test-retest reliability [anode: ICC(2,1) = 0.062; cathode: ICC(2,1) = 0.055] and moderate sham test-retest reliability [ICC(2,1) = 0.433]. Results also revealed no significant effect of tDCS at the group level. Using this common protocol, we found the effects of tDCS on MEP amplitudes to be highly variable at the individual level. In addition, no significant effects of tDCS on MEP amplitude were found at the group level. Future studies should consider utilizing a more strict experimental protocol to potentially account for intra-individual response variations.
Response profiles of murine spiral ganglion neurons on multi-electrode arrays

NASA Astrophysics Data System (ADS)

Hahnewald, Stefan; Tscherter, Anne; Marconi, Emanuele; Streit, Jürg; Widmer, Hans Rudolf; Garnham, Carolyn; Benav, Heval; Mueller, Marcus; Löwenheim, Hubert; Roccio, Marta; Senn, Pascal

2016-02-01

Objective. Cochlear implants (CIs) have become the gold standard treatment for deafness. These neuroprosthetic devices feature a linear electrode array, surgically inserted into the cochlea, and function by directly stimulating the auditory neurons located within the spiral ganglion, bypassing lost or not-functioning hair cells. Despite their success, some limitations still remain, including poor frequency resolution and high-energy consumption. In both cases, the anatomical gap between the electrode array and the spiral ganglion neurons (SGNs) is believed to be an important limiting factor. The final goal of the study is to characterize response profiles of SGNs growing in intimate contact with an electrode array, in view of designing novel CI devices and stimulation protocols, featuring a gapless interface with auditory neurons. Approach. We have characterized SGN responses to extracellular stimulation using multi-electrode arrays (MEAs). This setup allows, in our view, to optimize in vitro many of the limiting interface aspects between CIs and SGNs. Main results. Early postnatal mouse SGN explants were analyzed after 6-18 days in culture. Different stimulation protocols were compared with the aim to lower the stimulation threshold and the energy needed to elicit a response. In the best case, a four-fold reduction of the energy was obtained by lengthening the biphasic stimulus from 40 μs to 160 μs. Similarly, quasi monophasic pulses were more effective than biphasic pulses and the insertion of an interphase gap moderately improved efficiency. Finally, the stimulation with an external electrode mounted on a micromanipulator showed that the energy needed to elicit a response could be reduced by a factor of five with decreasing its distance from 40 μm to 0 μm from the auditory neurons. Significance. This study is the first to show electrical activity of SGNs on MEAs. Our findings may help to improve stimulation by and to reduce energy consumption of CIs and thereby contribute to the development of fully implantable devices with better auditory resolution in the future.
Evaluation of Interactive Visualization on Mobile Computing Platforms for Selection of Deep Brain Stimulation Parameters

PubMed Central

Butson, Christopher R.; Tamm, Georg; Jain, Sanket; Fogal, Thomas; Krüger, Jens

2012-01-01

In recent years there has been significant growth in the use of patient-specific models to predict the effects of neuromodulation therapies such as deep brain stimulation (DBS). However, translating these models from a research environment to the everyday clinical workflow has been a challenge, primarily due to the complexity of the models and the expertise required in specialized visualization software. In this paper, we deploy the interactive visualization system ImageVis3D Mobile, which has been designed for mobile computing devices such as the iPhone or iPad, in an evaluation environment to visualize models of Parkinson’s disease patients who received DBS therapy. Selection of DBS settings is a significant clinical challenge that requires repeated revisions to achieve optimal therapeutic response, and is often performed without any visual representation of the stimulation system in the patient. We used ImageVis3D Mobile to provide models to movement disorders clinicians and asked them to use the software to determine: 1) which of the four DBS electrode contacts they would select for therapy; and 2) what stimulation settings they would choose. We compared the stimulation protocol chosen from the software versus the stimulation protocol that was chosen via clinical practice (independently of the study). Lastly, we compared the amount of time required to reach these settings using the software versus the time required through standard practice. We found that the stimulation settings chosen using ImageVis3D Mobile were similar to those used in standard of care, but were selected in drastically less time. We show how our visualization system, available directly at the point of care on a device familiar to the clinician, can be used to guide clinical decision making for selection of DBS settings. In our view, the positive impact of the system could also translate to areas other than DBS. PMID:22450824
Equivalent brain SPECT perfusion changes underlying therapeutic efficiency in pharmacoresistant depression using either high-frequency left or low-frequency right prefrontal rTMS.

PubMed

Richieri, Raphaëlle; Boyer, Laurent; Padovani, Romain; Adida, Marc; Colavolpe, Cécile; Mundler, Olivier; Lançon, Christophe; Guedj, Eric

2012-12-03

Functional neuroimaging studies have suggested similar mechanisms underlying antidepressant effects of distinct therapeutics. This study aimed to determine and compare functional brain patterns underlying the antidepressant response of 2 distinct protocols of repetitive transcranial magnetic stimulation (rTMS). 99mTc-ECD SPECT was performed before and after rTMS of dorsolateral prefrontal cortex in 61 drug-resistant right-handed patients with major depression, using high frequency (10Hz) left-side stimulation in 33 patients, and low frequency (1Hz) right-side stimulation in 28 patients. Efficiency of rTMS response was defined as at least 50% reduction of the baseline Beck Depression Inventory score. We compared the whole-brain voxel-based brain SPECT changes in perfusion after rTMS, between responders and non-responders in the whole sample (p<0.005, uncorrected), and separately in the subgroup of patients with left- and right-stimulation. Before rTMS, the left- and right-prefrontal stimulation groups did not differ from clinical data and brain SPECT perfusion. rTMS efficiency (evaluated on % of responders) was statistically equivalent in the two groups of patients. In the whole-group of responder patients, a perfusion decrease was found after rTMS, in comparison to non-responders, within the left perirhinal cortex (BA35, BA36). This result was secondarily confirmed separately in the two subgroups, i.e. after either left stimulation (p=0.017) or right stimulation (p<0.001), without significant perfusion differences between these two subgroups. These data show that distinct successful rTMS protocols induce equivalent brain functional changes associated to antidepressive efficiency, consisting to a remote brain limbic activity decrease within the left perirhinal cortex. However, these results will have to be confirmed in a double-blind randomized trial using a sham control group. Copyright © 2012 Elsevier Inc. All rights reserved.
Measuring Feedforward Inhibition and Its Impact on Local Circuit Function.

PubMed

Hull, Court

2017-05-01

This protocol describes a series of approaches to measure feedforward inhibition in acute brain slices from the cerebellar cortex. Using whole-cell voltage and current clamp recordings from Purkinje cells in conjunction with electrical stimulation of the parallel fibers, these methods demonstrate how to measure the relationship between excitation and inhibition in a feedforward circuit. This protocol also describes how to measure the impact of feedforward inhibition on Purkinje cell excitability, with an emphasis on spike timing. © 2017 Cold Spring Harbor Laboratory Press.
Hidden U (1 ) gauge symmetry realizing a neutrinophilic two-Higgs-doublet model with dark matter

NASA Astrophysics Data System (ADS)

Nomura, Takaaki; Okada, Hiroshi

2018-04-01

We propose a neutrinophilic two-Higgs-doublet model with hidden local U (1 ) symmetry, where active neutrinos are Dirac type, and a fermionic dark matter (DM) candidate is naturally induced as a result of remnant symmetry even after the spontaneous symmetry breaking. In addition, a physical Goldstone boson arises as a consequence of two types of gauge singlet bosons and contributes to the DM phenomenologies as well as an additional neutral gauge boson. Then, we analyze the relic density of DM within the safe range of direct detection searches and show the allowed region of dark matter mass.
57Fe Mössbauer study of the asbestiform silicates balangeroite and carlosturanite

NASA Astrophysics Data System (ADS)

Deriu, Antonio; Ferraris, Giovanni; Belluso, Elena

1994-08-01

57FeMössbauer spectra of the two silicate minerals balangeroite (BAL) and carlosturanite (CST) have been collected at 80 and 295 K under normal and magic angle geometry. For both minerals the spectra have been fitted with two ferrous and two ferric doublets; Fe2+ accounts for 80 and 62% of Fetot in Bal and CST, respectively. The number of doublets used to fit the spectra supports the hypotheses that: (i) in the serpentine-like structure of CST iron occupies only octahedra which lie between the tetrahedral silicate strips; (ii) the octahedral framework of BAL (actually monoclinic) is satisfactorily described with an orthorhombic sub-cell.
Measuring the separation of the sodium D-doublet with a Michelson interferometer

NASA Astrophysics Data System (ADS)

D'Anna, M.; Corridoni, T.

2018-01-01

Revisiting a method proposed by Fizeau in 1862, in this paper we measure the separation of the Na-doublet (the wavelength difference {{Δ }}λ between the two emission D-lines of the sodium spectrum) with a didactical Michelson interferometer. We describe the setup, how the measurements have been done and develop a mathematical model in order to explain the principal features of the collected data. Discussing the limits of this model, we suggest further experimental and theoretical extensions of the experience, also focusing on the didactical aspects to show how this experiment could bring advanced modern physics topics into high schools.
Higgs boson from the metastable supersymmetric breaking sector

NASA Astrophysics Data System (ADS)

Bai, Yang; Fan, Jiji; Han, Zhenyu

2007-09-01

We construct a calculable model of electroweak symmetry breaking in which the Higgs doublet emerges from the metastable SUSY breaking sector as a pseudo Nambu-Goldstone boson. The Higgs boson mass is further protected by the little Higgs mechanism, and naturally suppressed by a two-loop factor from the SUSY breaking scale of 10 TeV. Gaugino and sfermion masses arise from standard gauge mediation, but the Higgsino obtains a tree-level mass at the SUSY breaking scale. At 1 TeV, aside from new gauge bosons and fermions similar to other little Higgs models and their superpartners, our model predicts additional electroweak triplets and doublets from the SUSY breaking sector.
Neutrino-two-Higgs-doublet model with the inverse seesaw mechanisms

NASA Astrophysics Data System (ADS)

Tang, Yi-Lei; Zhu, Shou-hua

2017-09-01

In this paper, we combine the ν -two-Higgs-doublet-model with the inverse seesaw mechanisms. In this model, the Yukawa couplings involving the sterile neutrinos and the exotic Higgs bosons can be of order 1 in the case of a large tan β . We calculated the corrections to the Z -resonance parameters Rli,Al i, and Nν, together with the l1→l2γ branching ratios and the muon anomalous g -2 . Compared with the current bounds and plans for the future colliders, we find that the corrections to the electroweak parameters can be constrained or discovered in much of the parameter space.
Relativistic Confinement Resonances

NASA Astrophysics Data System (ADS)

Keating, David; Manson, Steven; Deshmukh, Pranawa

2017-04-01

Photoionization of confined atoms in a C60 fullerene have been under intense investigation in the recent years, in particular the confinement induced resonances, termed confinement resonances. The effects of the C60 potential are modeled by a static spherical well, with (in atomic units) inner radius r0 = 5.8, width Δ = 1.9, and depth U0 = -0.302, which is reasonable in the energy region well above the C60 plasmons. At very high Z, relativistic interactions become important contributors to even the qualitative nature of atomic properties; this is true for confined atomic properties as well. To explore the extent of these interactions, a theoretical study of several heavy atoms has been performed using the relativistic random phase approximation (RRPA) methodology. In order to determine which features in the photoionization cross section are due to relativity, calculations using the (nonrelativistic) random phase approximation with exchange method (RPAE) are performed for comparison. The existence of the second subshell of the spin-orbit-split doublets can induce new confinement resonances in the total cross section, which is the sum of the spin-orbit-split doublets, due to the shift in the doublet's threshold. Several examples for confined high-Z atoms are presented. Work supported by DOE and NSF.
DYF-1 Is Required for Assembly of the Axoneme in Tetrahymena thermophila▿ †

PubMed Central

Dave, Drashti; Wloga, Dorota; Sharma, Neeraj; Gaertig, Jacek

2009-01-01

In most cilia, the axoneme can be subdivided into three segments: proximal (the transition zone), middle (with outer doublet microtubules), and distal (with singlet extensions of outer doublet microtubules). How the functionally distinct segments of the axoneme are assembled and maintained is not well understood. DYF-1 is a highly conserved ciliary protein containing tetratricopeptide repeats. In Caenorhabditis elegans, DYF-1 is specifically needed for assembly of the distal segment (G. Ou, O. E. Blacque, J. J. Snow, M. R. Leroux, and J. M. Scholey. Nature. 436:583-587, 2005). We show that Tetrahymena cells lacking an ortholog of DYF-1, Dyf1p, can assemble only extremely short axoneme remnants that have structural defects of diverse natures, including the absence of central pair and outer doublet microtubules and incomplete or absent B tubules on the outer microtubules. Thus, in Tetrahymena, DYF-1 is needed for either assembly or stability of the entire axoneme. Our observations support the conserved function for DYF-1 in axoneme assembly or stability but also show that the consequences of loss of DYF-1 for axoneme segments are organism specific. PMID:19581442
Tubulin Glutamylation Regulates Ciliary Motility by Altering Inner Dynein Arm Activity

PubMed Central

Suryavanshi, Swati; Eddé, Bernard; Fox, Laura A.; Guerrero, Stella; Hard, Robert; Hennessey, Todd; Kabi, Amrita; Malison, David; Pennock, David; Sale, Winfield S.; Wloga, Dorota; Gaertig, Jacek

2010-01-01

SUMMMARY How microtubule-associated motor proteins are regulated is not well understood. A potential mechanism for spatial regulation of motor proteins is provided by post-translational modifications of tubulin subunits that form patterns on microtubules. Glutamylation is a conserved tubulin modification [1] that is enriched in axonemes. The enzymes responsible for this PTM, glutamic acid ligases (E-ligases), belong to a family of proteins with a tubulin tyrosine ligase (TTL) homology domain (TTL-like or TTLL proteins) [2]. We show that in cilia of Tetrahymena, TTLL6 E-ligases generate glutamylation mainly on the B-tubule of outer doublet microtubules, the site of force production by ciliary dynein. Deletion of two TTLL6 paralogs caused severe deficiency in ciliary motility associated with abnormal waveform and reduced beat frequency. In isolated axonemes with a normal dynein arm composition, TTLL6 deficiency did not affect the rate of ATP-induced doublet microtubule sliding. Unexpectedly, the same TTLL6 deficiency increased the velocity of microtubule sliding in axonemes that also lack outer dynein arms, in which forces are generated by inner dynein arms. We conclude that tubulin glutamylation on the B-tubule inhibits the net force imposed on sliding doublet microtubules by inner dynein arms. PMID:20189389
Fin whale song variability in southern California and the Gulf of California.

PubMed

Širović, Ana; Oleson, Erin M; Buccowich, Jasmine; Rice, Ally; Bayless, Alexandra R

2017-08-31

Songs are distinct, patterned sounds produced by a variety of animals including baleen whales. Fin whale songs, which consist of short pulses repeated at regular interpulse intervals (IPIs), have been suggested as a tool to distinguish populations. Fin whale songs were analyzed from data collected from 2000-2012 in Southern California and from 2004-2010 in the Gulf of California using autonomous acoustic recorders. IPIs were measured for each identifiable song sequence during two random days of each month with recordings. Four distinct song types were identified: long doublet, short doublet, long triplet, and short triplet. Long and short doublets were the dominant songs in Southern California, while long and short triplets were dominant in the Gulf of California. An abrupt change in song type occurred in both areas during the monitoring period. We argue that each song type is unique to a population and these changes represent a shift in the primary population in the monitoring area. Occasional temporal and spatial song overlap indicated some exchange or visitation among populations. Fin whales appear to synchronize and gradually modify song rhythm over long time scales. A better understanding of the evolutionary and ecological importance of songs to fin whale populations is needed.

Photoelectron Spectroscopy Study of Quinonimides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, Ekram; Deng, Shihu M.; Gozem, Samer

Structures and energetics of o-, m- and p-quinonimide anions (OC6H4N) and quinoniminyl radicals have been investigated by using negative ion photoelectron spectroscopy. Modeling of the photoelectron spectrum of the ortho isomer shows that the ground state of the anion is a triplet, while the quinoniminyl radical has a doublet ground state with a doublet-quartet splitting of 35.5 kcal/mol. The para radical has doublet ground state, but a band for a quartet state is missing from the photoelectron spectrum indicating that the anion has a singlet ground state, in contrast to previously reported calculations. The theoretical modeling is revisited here, andmore » it is shown that accurate predictions for the electronic structure of the para quinonimide anion require both an accurate account of electron correlation and a sufficiently diffuse basis set. Electron affinities of o- and p-quinoniminyl radicals are measured to be 1.715 ± 0.010 and 1.675 ± 0.010 eV, respectively. The photoelectron spectrum of the m-quinonimide anion shows that the ion undergoes several different rearrangements, including a rearrangement to the energetically favorable para isomer. Such rearrangements preclude a meaningful analysis of the experimental spectrum.« less
Flavor from the electroweak scale

DOE PAGES

Bauer, Martin; Carena, Marcela; Gemmler, Katrin

2015-11-04

We discuss the possibility that flavor hierarchies arise from the electroweak scale in a two Higgs doublet model, in which the two Higgs doublets jointly act as the flavon. Quark masses and mixing angles are explained by effective Yukawa couplings, generated by higher dimensional operators involving quarks and Higgs doublets. Modified Higgs couplings yield important effects on the production cross sections and decay rates of the light Standard Model like Higgs. In addition, flavor changing neutral currents arise at tree-level and lead to strong constraints from meson-antimeson mixing. Remarkably, flavor constraints turn out to prefer a region in parameter spacemore » that is in excellent agreement with the one preferred by recent Higgs precision measurements at the Large Hadron Collider (LHC). Direct searches for extra scalars at the LHC lead to further constraints. Precise predictions for the production and decay modes of the additional Higgs bosons are derived, and we present benchmark scenarios for searches at the LHC Run II. As a result, flavor breaking at the electroweak scale as well as strong coupling effects demand a UV completion at the scale of a few TeV, possibly within the reach of the LHC.« less
H2-broadening, shifting and mixing coefficients of the doublets in the ν2 and ν4 bands of PH3 at room temperature

NASA Astrophysics Data System (ADS)

Salem, Jamel; Blanquet, Ghislain; Lepère, Muriel; Younes, Rached ben

2018-05-01

The broadening, shifting and mixing coefficients of the doublet spectral lines in the ν2 and ν4 bands of PH3 perturbed by H2 have been determined at room temperature. Indeed, the collisional spectroscopic parameters: intensities, line widths, line shifts and line mixing parameters, are all grouped together in the collisional relaxation matrix. To analyse the collisional process and physical effects on spectra of phosphine (PH3), we have used the measurements carried out using a tunable diode-laser spectrometer in the ν2 and ν4 bands of PH3 perturbed by hydrogen (H2) at room temperature. The recorded spectra are fitted by the Voigt profile and the speed-dependent uncorrelated hard collision model of Rautian and Sobelman. These profiles are developed in the studies of isolated lines and are modified to account for the line mixing effects in the overlapping lines. The line widths, line shifts and line mixing parameters are given for six A1 and A2 doublet lines with quantum numbers K = 3n, (n = 1, 2, …) and overlapped by collisional broadening at pressures of less than 50 mbar.
Comparative analysis of the heme iron electronic structure and stereochemistry in tetrameric rabbit hemoglobin and monomeric soybean leghemoglobin a using Mössbauer spectroscopy with a high velocity resolution

NASA Astrophysics Data System (ADS)

Alenkina, I. V.; Kumar, A.; Berkovsky, A. L.; Oshtrakh, M. I.

2018-02-01

A comparative study of tetrameric rabbit hemoglobin and monomeric soybean leghemoglobin a in the oxy- and deoxy-forms was carried out using 57Fe Mössbauer spectroscopy with a high velocity resolution in order to analyze the heme iron electronic structure and stereochemistry in relation to the Mössbauer hyperfine parameters. The Mössbauer spectra of tetrameric rabbit hemoglobin in both forms were fitted using two quadrupole doublets related to the 57Fe in ɑ- and β-subunits. In contrast, the Mössbauer spectra of monomeric soybean leghemoglobin a were fitted using: (i) two quadrupole doublets for the oxy-form related to two conformational states of the distal His E7 imidazole ring and different hydrogen bonding of oxygen molecule in the oxy-form and (ii) using three quadrupole doublets for deoxy-form related to three conformational states of the proximal His F8 imidazole ring. Small variations of Mössbauer hyperfine parameters related to small differences in the heme iron electronic structure and stereochemistry in tetrameric rabbit hemoglobin and monomeric soybean leghemoglobin a are discussed.
Higgs naturalness and dark matter stability by scale invariance

NASA Astrophysics Data System (ADS)

Guo, Jun; Kang, Zhaofeng

2015-09-01

Extending the spacetime symmetries of standard model (SM) by scale invariance (SI) may address the Higgs naturalness problem. In this article we attempt to embed accidental dark matter (DM) into SISM, requiring that the symmetry protecting DM stability is accidental due to the model structure rather than imposed by hand. In this framework, if the light SM-like Higgs boson is the pseudo Goldstone boson of SI spontaneously breaking, we can even pine down the model, two-Higgs-doublets plus a real singlet: The singlet is the DM candidate and the extra Higgs doublet triggers electroweak symmetry breaking via the Coleman-Weinberg mechanism; Moreover, it dominates DM dynamics. We study spontaneously breaking of SI using the Gillard-Weinberg approach and find that the second doublet should acquire vacuum expectation value near the weak scale. Moreover, its components should acquire masses around 380 GeV except for a light CP-odd Higgs boson. Based on these features, we explore viable ways to achieve the correct relic density of DM, facing stringent constraints from direct detections of DM. For instance, DM annihilates into b b bar near the SM-like Higgs boson pole, or into a pair of CP-odd Higgs boson with mass above that pole.
57Fe CEMS study on dilute metal ions codoped SnO2 thin films prepared by spray pyrolysis

NASA Astrophysics Data System (ADS)

Nomura, Kiyoshi; Koike, Yuya; Nakanishi, Akio

2017-11-01

Dilute Mn-Fe, Co-Fe and V-Fe codoped tin oxide films prepared by spray pyrolysis were characterized by 57Fe conversion electron Mössbauer spectrometry (CEMS) at room temperature (RT) and at 20 K. Two kinds of paramagnetic Fe3+ species were detected at RT; one doublet 1 (D1) with IS = 0.36-0.37 mm/s, QS = 0.69-0.75 mm/s and LW = 0.32-0.40 mm/s, and another doublet 2 (D2) with IS = 0.31-0.35 mm/s QS = 1.16-1.25 mm/s and LW = 0.46-0.52 mm/s. CEMS at 20 K provided more distinguished doublets than at RT. It is found that especially D2 with relatively small IS and large QS values are influenced by other metal ions codoped in SnO2 matrix, whereas D1 with relatively large IS and small QS has the parameters close to the models of Fe-VO1 and Fe-2VO1-Fe models (Nomura et al. Phys. Rev. B 75, 184411 2007; Mudarra Navarro et al. J. Phys. Chem. C 119, 5596-5603 2015).
Signal-to-solar clutter calculations of AK-47 muzzle flash at various spectral bandpasses near the potassium D1/D2 doublet

NASA Astrophysics Data System (ADS)

Klett, Karl K., Jr.

2010-04-01

An analysis was performed, using MODTRAN, to determine the best filters to use for detecting the muzzle flash of an AK-47 in daylight conditions in the desert. Filters with bandwidths of 0.05, 0.1, 0.5, 1.0, 3.0, and 5.0 nanometers (nm) were analyzed to understand how the optical bandwidth affects the signal-to-solar clutter ratio. These filters were evaluated near the potassium D1 and D2 doublet emission lines that occur at 769.89 and 766.49 nm respectively that are observed where projectile propellants are used. The maximum spectral radiance, from the AK-47 muzzle flash, is 1.88 x 10-2 W/cm2 str micron, and is approximately equal to the daytime atmospheric spectral radiance. The increased emission, due to the potassium doublet lines, and decreased atmospheric transmission, due to oxygen absorption, combine to create a condition where the signal-to-solar clutter ratio is greater than 1. The 3 nm filter, has a signal-to-solar clutter ratio of 2.09 when centered at 765.37 nm and provides the best combination of both cost and signal sensitivity.
[Photographic documentation during safe laparoscopic cholecystectomy].

PubMed

Bolívar-Rodríguez, Martín A; Pamanes-Lozano, Adrián; Matus-Rojas, Jaime; Cázarez-Aguilar, Marcel A; Fierro-López, Rodolfo

2018-01-01

Laparoscopic cholecystectomy is the most frequent procedure for the general surgeon. Biliary injury is a concern that must be addressed with the purpose of lowering the rate. The critical view of safety (CVS) is a target of dissection that impulses safety during the procedure. Determine by an ambispective analysis the safety during dissection of laparoscopic cholecystectomy in Hospital Civil de Culiacán (México). Descriptive, ambispective, observational, cross-sectional. Patients admitted to the operating room for a laparoscopic cholecystectomy were scored with Doublet photography rating criteria from January 1 st 2015 to January 31, 2017. 321 patients were evaluated, 77.9% were female and 22.1% male. The mean age was 45.57 ± 16.17 years. 65.4% had admission diagnosis of cholelithiasis, 24.3% acute cholecystitis, 5.9% chronic cholecystitis, 3.7% hydrocolecist and 0.6% pyocolecist. Surgeries were scored with Doublet photography. The CVS was obtained in 41.4% of the procedures with a statistical significance between a HPB surgeon and a general surgery resident (p ≤ 0.05). Recording Doublet photography provides a reliable CVS dissection criterion. It can be easily reproduced during laparoscopic cholecystectomy. The identification of cystic structures adds to the culture of safety during laparoscopic cholecystectomy. Copyright: © 2018 Permanyer.
Adjusted Indirect Comparison Using Propensity Score Matching of Osimertinib to Platinum-Based Doublet Chemotherapy in Patients with EGFRm T790M NSCLC Who Have Progressed after EGFR-TKI.

PubMed

Mann, Helen; Andersohn, Frank; Bodnar, Carolyn; Mitsudomi, Tetsuya; Mok, Tony S K; Yang, James Chih-Hsin; Hoyle, Christopher

2018-04-01

An adjusted indirect comparison was conducted to assess efficacy outcomes, particularly overall survival (OS), of osimertinib versus platinum-based doublet chemotherapy in patients with epidermal growth factor receptor-mutated (EGFRm) T790M mutation-positive non-small-cell lung cancer (NSCLC) who had progressed following an EGFR tyrosine kinase inhibitor (TKI). Analysis of treatment effect from two separate trials had the potential to more accurately estimate the magnitude of OS benefit due to absence of confounding due to treatment switching from the control arm to the osimertinib arm of the ongoing randomized control trial, AURA3. Two non-randomized individual datasets were compared: pooled patients from the AURA extension and AURA2 trials (osimertinib 80 mg, n = 405, with a confirmed T790M mutation using tissue samples), and patients from the control arm of the IMPRESS study (platinum-based doublet chemotherapy, n = 61, with a confirmed T790M mutation using plasma circulating tumour DNA [ctDNA]). A propensity score-based approach was used to account for differences in baseline demographics and disease characteristics. After adjustment for baseline differences between the two groups, osimertinib demonstrated a statistically significant improvement in progression-free survival (PFS) versus platinum-based doublet chemotherapy (hazard ratio [HR] = 0.278, 95% confidence interval [CI] 0.188-0.409, p < 0.0001; median PFS 10.9 vs. 5.3 months). Improvements were also observed for objective response rate (ORR) and disease control rate (DCR) (ORR: 64.3 vs. 33.3%; odds ratio [OR] = 5.31, 95% CI 2.47-11.40, p < 0.001; DCR: 92.1 vs. 75.0%; OR = 4.72, 95% CI 1.92-11.58, p < 0.001). Similar results were obtained for patients who received osimertinib as second-line treatment only. A statistically significant improvement in OS was observed for the osimertinib group (HR = 0.412, 95% CI 0.273-0.622, p < 0.0001). Median OS for osimertinib was not reached. In this indirect comparison, osimertinib showed a statistically significant improvement in efficacy outcomes versus platinum-based doublet chemotherapy in patients with EGFRm T790M NSCLC who had progressed after EGFR-TKI therapy.
Serotonin modulates substance P-induced plasma extravasation and vasodilatation in rat skin by an action through capsaicin-sensitive primary afferent nerves.

PubMed

Khalil, Z; Helme, R D

1990-09-17

Using a blister model of inflammation in the rat hind footpad, the present study was undertaken to examine the ability of serotonin (5-HT) to modulate an inflammatory reaction manifested as plasma extravasation and vasodilatation induced by the neuropeptide substance P (SP). In addition, the role of primary afferent sensory nerve fibres in these modulatory effects was studied in capsaicin pretreated rats. Using a protocol of simultaneous perfusion of amine and peptide over the blister base, no major modulatory effect was observed. On the other hand, using a protocol of sequential perfusion, 5-HT was found to extend the plasma extravasation and vasodilatation responses to SP. 5-HT maintained the plasma extravasation response to SP after cessation of stimulation (during the post-stimulation period). On the other hand, it extended the vasodilatation response to SP during the actual stimulation period by preventing the occurrence of tachyphylaxis. These modulatory effects were absent in capsacin-pretreated rats. The present study provides evidence for the first time in vivo to suggest that serotonin can modulate an inflammatory response to SP via a mechanism that involves capsaicin-sensitive sensory fibres.
Influence of gravitational sympathetic stimulation on the Surgical Plethysmographic Index.

PubMed

Colombo, R; Marchi, A; Borghi, B; Fossali, T; Tobaldini, E; Guzzetti, S; Raimondi, F

2015-01-01

Surgical Plethysmographic Index (SPI), calculated from pulse photo-plethysmographic amplitude oscillations, has been proposed as a tool to measure nociception anti-nociception balance during general anesthesia, but it is affected by several confounding factor that alter the autonomic nervous system (ANS) modulation. We hypothesized that SPI may be mainly affected by sympathetic stimulation independently from nociception. We studied the effects of two sympathetic stimuli on SPI, delivered through passive head-up tilt at 45 and 90 degrees angles, in nine awake healthy adults. The sympathetic modulation was assessed by means of heart rate variability (HRV) analysis. Mean (SD) SPI significantly increased from baseline to 45 degrees [from 38.6 (13.7) to 60.8 (7.6), p<0.001)] and to 90 degrees angle tilt [82.3 (5.4), p<0.001]. The electrocardiographic mean R-to-R interval significantly shortened during both passive tilts, whereas systolic arterial pressure did not change during the study protocol. HRV changed significantly during the study protocol towards a predominance of sympathetic modulation during passive tilt. Gravitational sympathetic stimulation at two increasing angles, in absence of any painful stimuli, affects SPI in awake healthy volunteers. SPI seems to reflect the sympathetic outflow directed to peripheral vessels.
Measurement of the local muscular metabolism by time-domain near infrared spectroscopy during knee flex-extension induced by functional electrical stimulation

NASA Astrophysics Data System (ADS)

Contini, D.; Spinelli, L.; Torricelli, A.; Ferrante, S.; Pedrocchi, A.; Molteni, F.; Ferrigno, G.; Cubeddu, R.

2009-02-01

We present a preliminary study that combines functional electrical stimulation and time-domain near infrared spectroscopy for a quantitative measurement of the local muscular metabolism during rehabilitation of post-acute stroke patients. Seven healthy subjects and nine post-acute stroke patients underwent a protocol of knee flex-extension of the quadriceps induced by functional electrical stimulation. During the protocol time-domain near infrared spectroscopy measurement were performed on both left and right muscle. Hemodynamic parameters (concentration of oxy- and deoxy-genated hemoglobin) during baseline did not show any significant differences between healthy subject and patients, while functional performances (knee angle amplitude) were distinctly different. Nevertheless, even if their clinical histories were noticeably different, there was no differentiation among functional performances of patients. On the basis of the hemodynamic parameters measured during the recovery phase, instead, it was possible to identify two classes of patients showing a metabolic trend similar or very different to the one obtained by healthy subjects. The presented results suggest that the combination of functional and metabolic information can give an additional tool to the clinicians in the evaluation of the rehabilitation in post-acute stroke patients.
Modulation of Electrophysiology by Transcranial Direct Current Stimulation in Psychiatric Disorders: A Systematic Review.

PubMed

Kim, Minah; Kwak, Yoo Bin; Lee, Tae Young; Kwon, Jun Soo

2018-04-27

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique increasingly used to relieve symptoms of psychiatric disorders. Electrophysiologic markers, such as electroencephalography (EEG) and event-related potentials (ERP), have high temporal resolution sensitive to detect plastic changes of the brain associated with symptomatic improvement following tDCS application. We performed systematic review to identify electrophysiological markers that reflect tDCS effects on plastic brain changes in psychiatric disorders. A total of 638 studies were identified by searching PubMed, Embase, psychINFPO. Of these, 21 full-text articles were assessed eligible and included in the review. Although the reviewed studies were heterogeneous in their choices of tDCS protocols, targeted electrophysiological markers, and disease entities, their results strongly support EEG/ERPs to sensitively reflect plastic brain changes and the associated symptomatic improvement following tDCS. EEG/ERPs may serve a potent tool in revealing the mechanisms underlying psychiatric symptoms, as well as in localizing the brain area targeted for stimulation. Future studies in each disease entities employing consistent tDCS protocols and electrophysiological markers would be necessary in order to substantiate and further elaborate the findings of studies included in the present systematic review.
Abnormal Cortical Plasticity in Youth with Autism Spectrum Disorder: A Transcranial Magnetic Stimulation Case-Control Pilot Study.

PubMed

Pedapati, Ernest V; Gilbert, Donald L; Erickson, Craig A; Horn, Paul S; Shaffer, Rebecca C; Wink, Logan K; Laue, Cameron S; Wu, Steve W

2016-09-01

This case-control study investigated the use of a low-intensity repetitive transcranial magnetic stimulation (rTMS) protocol to measure motor cortex (M1) plasticity in youth with autism spectrum disorder (ASD) compared with typically developing children (TDC). We hypothesized that impairments in long-term potentiation-like properties represent a neurophysiological biomarker of abnormal cortical function in ASD. We studied youth with ASD aged 11-18 years and matched controls (TDC). Intermittent theta burst stimulation (iTBS) was delivered to the dominant M1 at an intensity of 70% of resting motor threshold. Suprathreshold single-pulse TMS was performed to compare amplitudes of motor-evoked potentials (MEP) measured from surface electromyography electrodes on a target muscle before (20 pulses) and after (10 pulses/time point) iTBS at predefined timepoints (up to 30 minutes) to measure any potentiation effects. A linear mixed model was used to examine group differences in MEP amplitudes over time following iTBS. Nine youth with ASD (mean age 15.6; 7 males; 6 right-hand dominant) and 9 TDC (mean age 14.5; 5 males; 9 right-hand dominant) participated. All subjects tolerated the procedure well. Both groups had a mean increase in excitability after iTBS for 30 minutes; however, the time course of excitability changes differed (F9,144 = 2.05; p = 0.038). Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons. In this study, we demonstrate early evidence for a potential physiological biomarker of cortical plasticity in youth with ASD using a rapid low-intensity rTMS protocol with a discriminate measure at 20 minutes following stimulation. The procedure was well tolerated by all 18 participants. Future work will include modification of the protocol to improve the ability to distinguish subtypes of ASD based on behavioral and cognitive testing.
Efficacy of corifollitropin alfa followed by recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist protocol for Korean women undergoing assisted reproduction.

PubMed

Park, Hyo Young; Lee, Min Young; Jeong, Hyo Young; Rho, Yong Sook; Song, Sang Jin; Choi, Bum-Chae

2015-06-01

To evaluate the effect of a gonadotropin-releasing hormone (GnRH) antagonist protocol using corifollitropin alfa in women undergoing assisted reproduction. Six hundred and eighty-six in vitro fertilization-embryo transfer (IVF)/intracytoplasmic sperm injection (ICSI) cycles were analyzed. In 113 cycles, folliculogenesis was induced with corifollitropin alfa and recombinant follicle stimulating hormone (rFSH), and premature luteinizing hormone (LH) surges were prevented with a GnRH antagonist. In the control group (573 cycles), premature LH surges were prevented with GnRH agonist injection from the midluteal phase of the preceding cycle, and ovarian stimulation was started with rFSH. The treatment duration, quality of oocytes and embryos, number of embryo transfer (ET) cancelled cycles, risk of ovarian hyperstimulation syndrome (OHSS), and the chemical pregnancy rate were evaluated in the two ovarian stimulation protocols. There were no significant differences in age and infertility factors between treatment groups. The treatment duration was shorter in the corifollitropin alfa group than in the control group. Although not statistically significant, the mean numbers of matured (86.8% vs. 85.1%) and fertilized oocytes (84.2% vs. 83.1%), good embryos (62.4% vs. 60.3%), and chemical pregnancy rates (47.2% vs. 46.8%) were slightly higher in the corifollitropin alfa group than in the control group. In contrast, rates of ET cancelled cycles and the OHSS risk were slightly lower in the corifollitropin alfa group (6.2% and 2.7%) than in the control group (8.2% and 3.5%), although these differences were also not statistically significant. Although no significant differences were observed, the use of corifollitropin alfa seems to offer some advantages to patients because of its short treatment duration, safety, lower ET cancellation rate and reduced risk of OHSS.
Implementation fidelity of self-administered transcutaneous electrical nerve stimulation (TENS) in patients with chronic back pain: an observational study.

PubMed

Pallett, Edward J; Rentowl, Patricia; Johnson, Mark I; Watson, Paul J

2014-03-01

The efficacy of transcutaneous electrical nerve stimulation (TENS) for pain relief has not been reliably established. Inconclusive findings could be due to inadequate TENS delivery and inappropriate outcome assessment. Electronic monitoring devices were used to determine patient compliance with a TENS intervention and outcome assessment protocol, to record pain scores before, during, and after TENS, and measure electrical output settings. Patients with chronic back pain consented to use TENS daily for 2 weeks and to report pain scores before, during, and after 1-hour treatments. A ≥ 30% reduction in pain scores was used to classify participants as TENS responders. Electronic monitoring devices "TLOG" and "TSCORE" recorded time and duration of TENS use, electrical settings, and pain scores. Forty-two patients consented to participate. One of 35 (3%) patients adhered completely to the TENS use and pain score reporting protocol. Fourteen of 33 (42%) were TENS responders according to electronic pain score data. Analgesia onset occurred within 30 to 60 minutes for 13/14 (93%) responders. It was not possible to correlate TENS amplitude, frequency, or pulse width measurements with therapeutic response. Findings from TENS research studies depend on the timing of outcome assessment; pain should be recorded during stimulation. TENS device sophistication might be an issue and parameter restriction should be considered. Careful protocol design is required to improve adherence and monitoring is necessary to evaluate the validity of findings. This observational study provides objective evidence to support concerns about poor implementation fidelity in TENS research.
Dopaminergic Modulation of Cortical Plasticity in Alzheimer's Disease Patients

PubMed Central

Koch, Giacomo; Di Lorenzo, Francesco; Bonnì, Sonia; Giacobbe, Viola; Bozzali, Marco; Caltagirone, Carlo; Martorana, Alessandro

2014-01-01

In animal models of Alzheimer's disease (AD), mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD) are impaired. In AD patients, LTP-like cortical plasticity is abolished, whereas LTD seems to be preserved. Dopaminergic transmission has been hypothesized as a new player in ruling mechanisms of cortical plasticity in AD. We aimed at investigating whether administration of the dopamine agonist rotigotine (RTG) could modulate cortical plasticity in AD patients, as measured by theta burst stimulation (TBS) protocols of repetitive transcranial stimulation applied over the primary motor cortex. Thirty mild AD patients were tested in three different groups before and after 4 weeks of treatment with RTG, rivastigmine (RVT), or placebo (PLC). Each patient was evaluated for plasticity induction of LTP/LTD-like effects using respectively intermittent TBS (iTBS) or continuous TBS protocols. Short-latency afferent inhibition (SAI) protocol was performed to indirectly assess central cholinergic activity. A group of age-matched healthy controls was recruited for baseline comparisons. Results showed that at baseline, AD patients were characterized by impaired LTP-like cortical plasticity, as assessed by iTBS. These reduced levels of LTP-like cortical plasticity were increased and normalized after RTG administration. No effect was induced by RVT or PLC on LTP. LTD-like cortical plasticity was not modulated in any condition. Cholinergic activity was increased by both RTG and RVT. Our findings reveal that dopamine agonists may restore the altered mechanisms of LTP-like cortical plasticity in AD patients, thus providing novel implications for therapies based on dopaminergic stimulation. PMID:24859851
Engineering the next generation of clinical deep brain stimulation technology.

PubMed

McIntyre, Cameron C; Chaturvedi, Ashutosh; Shamir, Reuben R; Lempka, Scott F

2015-01-01

Deep brain stimulation (DBS) has evolved into a powerful clinical therapy for a range of neurological disorders, but even with impressive clinical growth, DBS technology has been relatively stagnant over its history. However, enhanced collaborations between neural engineers, neuroscientists, physicists, neurologists, and neurosurgeons are beginning to address some of the limitations of current DBS technology. These interactions have helped to develop novel ideas for the next generation of clinical DBS systems. This review attempts collate some of that progress with two goals in mind. First, provide a general description of current clinical DBS practices, geared toward educating biomedical engineers and computer scientists on a field that needs their expertise and attention. Second, describe some of the technological developments that are currently underway in surgical targeting, stimulation parameter selection, stimulation protocols, and stimulation hardware that are being directly evaluated for near term clinical application. Copyright © 2015 Elsevier Inc. All rights reserved.
Rational modulation of neuronal processing with applied electric fields.

PubMed

Bikson, Marom; Radman, Thomas; Datta, Abhishek

2006-01-01

Traditional approaches to electrical stimulation, using trains of supra-threshold pulses to trigger action potentials, may be replaced or augmented by using 'rational' sub-threshold stimulation protocols that incorporate knowledge of single neuron geometry, inhomogeneous tissue properties, and nervous system information coding. Sub-threshold stimulation, at intensities (well) below those sufficient to trigger action potentials, may none-the-less exert a profound effect on brain function through modulation of concomitant neuronal activity. For example, small DC fields may coherently polarize a network of neurons and thus modulate the simultaneous processing of afferent synaptic input as well as resulting changes in synaptic plasticity. Through 'activity-dependent plasticity', sub-threshold fields may allow specific targeting of pathological networks and are thus particularly suitable to overcome the poor anatomical focus of noninvasive (transcranial) electrical stimulation. Additional approaches to improve targeting in transcranial stimulation using novel electrode configurations are also introduced.
Development and positioning reliability of a TMS coil holder for headache research.

PubMed

Chronicle, Edward P; Pearson, A Jane; Matthews, Cheryl

2005-01-01

Accurate and reproducible coil positioning is important for headache research using transcranial magnetic stimulation protocols. We aimed to design a transcranial magnetic stimulation coil holder and demonstrate reliability of test-retest coil positioning. A coil holder was developed and manufactured according to three principles of stability, durability, and three-dimensional positional accuracy. Reliability of coil positioning was assessed by stimulating over the motor cortex of four neurologically normal subjects and recording finger muscle responses, both at a test phase and a retest phase several hours later. In all four subjects, repositioning of the transcranial magnetic stimulation coil solely on the basis of coil holder coordinates was accurate to within 2 mm. The coil holder demonstrated good test-retest reliability of coil positioning, and is thus a promising tool for transcranial magnetic stimulation-based headache research, particularly studies of prophylactic drug effect where several laboratory visits with identical coil positioning are necessary.

Salvage immunotherapy of malignant glioma.

PubMed

Ingram, M; Jacques, S; Freshwater, D B; Techy, G B; Shelden, C H; Helsper, J T

1987-12-01

We present the preliminary results of a phase I trial of adoptive immunotherapy for recurrent or residual malignant glioma. The protocol is based on surgical debulking followed by implantation into the tumor bed of autologous lymphocytes that have been stimulated with phytohemagglutinin-P and then cultured in vitro in the presence of interleukin 2. Fifty-five patients with a mean Karnofsky rating of 64 were treated between February 1985 and March 1987. No significant toxicity was associated with the immunotherapy. Fifty patients had a positive initial response to therapy, nine patients had early recurrence (two to four months after treatment), and 22 patients died. We comment on major differences between the protocol described and other immunotherapy protocols.
Fundamentals of Transcranial Electric and Magnetic Stimulation Dose: Definition, Selection, and Reporting Practices

PubMed Central

Peterchev, Angel V.; Wagner, Timothy A.; Miranda, Pedro C.; Nitsche, Michael A.; Paulus, Walter; Lisanby, Sarah H.; Pascual-Leone, Alvaro; Bikson, Marom

2011-01-01

The growing use of transcranial electric and magnetic (EM) brain stimulation in basic research and in clinical applications necessitates a clear understanding of what constitutes the dose of EM stimulation and how it should be reported. The biological effects of EM stimulation are mediated through an electromagnetic field injected (via electric stimulation) or induced (via magnetic stimulation) in the body. Therefore, transcranial EM stimulation dose ought to be defined by all parameters of the stimulation device that affect the electromagnetic field generated in the body, including the stimulation electrode or coil configuration parameters: shape, size, position, and electrical properties, as well as the electrode or coil current (or voltage) waveform parameters: pulse shape, amplitude, width, polarity, and repetition frequency; duration of and interval between bursts or trains of pulses; total number of pulses; and interval between stimulation sessions and total number of sessions. Knowledge of the electromagnetic field generated in the body may not be sufficient but is necessary to understand the biological effects of EM stimulation. We believe that reporting of EM stimulation dose should be guided by the principle of reproducibility: sufficient information about the stimulation parameters should be provided so that the dose can be replicated. This paper provides fundamental definition and principles for reporting of dose that encompass any transcranial EM brain stimulation protocol. PMID:22305345
Fundamentals of transcranial electric and magnetic stimulation dose: definition, selection, and reporting practices.

PubMed

Peterchev, Angel V; Wagner, Timothy A; Miranda, Pedro C; Nitsche, Michael A; Paulus, Walter; Lisanby, Sarah H; Pascual-Leone, Alvaro; Bikson, Marom

2012-10-01

The growing use of transcranial electric and magnetic (EM) brain stimulation in basic research and in clinical applications necessitates a clear understanding of what constitutes the dose of EM stimulation and how it should be reported. This paper provides fundamental definitions and principles for reporting of dose that encompass any transcranial EM brain stimulation protocol. The biologic effects of EM stimulation are mediated through an electromagnetic field injected (via electric stimulation) or induced (via magnetic stimulation) in the body. Therefore, transcranial EM stimulation dose ought to be defined by all parameters of the stimulation device that affect the electromagnetic field generated in the body, including the stimulation electrode or coil configuration parameters: shape, size, position, and electrical properties, as well as the electrode or coil current (or voltage) waveform parameters: pulse shape, amplitude, width, polarity, and repetition frequency; duration of and interval between bursts or trains of pulses; total number of pulses; and interval between stimulation sessions and total number of sessions. Knowledge of the electromagnetic field generated in the body may not be sufficient but is necessary to understand the biologic effects of EM stimulation. We believe that reporting of EM stimulation dose should be guided by the principle of reproducibility: sufficient information about the stimulation parameters should be provided so that the dose can be replicated. Copyright © 2012 Elsevier Inc. All rights reserved.
Spatial Disorientation in Military Vehicles: Causes, Consequences and Cures (Desorientation spaiale dans les vehicules militaires: causes, consequences et remedes)

DTIC Science & Technology

2003-02-01

servcice warfighters (Training devices and protocols, Onboard equipment, Cognitive and sensorimotor aids, Visual and auditory symbology, Peripheral visual...vestibular stimulation causing a decrease in cerebral blood pressure with the consequent reduction in G-tolerance and increased likelihood of ALOC or GLOC...tactile stimulators (e.g. one providing a sensation of movement) or of displays with a more complex coding (e.g. by increase in the number of tactors, or
OSL properties of three commonly available salt brands in India for its use in accident dosimetry

NASA Astrophysics Data System (ADS)

Singh, A. K.; Menon, S. N.; Kadam, S. Y.; Koul, D. K.; Datta, D.

2018-03-01

Thermally stimulated luminescence (TL) and Optically Stimulated Luminescence (OSL) characterization of three commonly available salt brands in India were undertaken for their application in accident dosimetry. The investigations showed that the luminescence properties differed to some extent with that reported in literature. Dosimetric properties of these salt samples showed that these can be useful in accident dosimetry. Based on the sensitization and fading behaviour of the samples a Single Aliquot Regenerative (SAR) protocol has been proposed for dose estimation.
Fidelity of an optical memory based on stimulated photon echoes.

PubMed

Staudt, M U; Hastings-Simon, S R; Nilsson, M; Afzelius, M; Scarani, V; Ricken, R; Suche, H; Sohler, W; Tittel, W; Gisin, N

2007-03-16

We investigated the preservation of information encoded into the relative phase and amplitudes of optical pulses during storage and retrieval in an optical memory based on stimulated photon echo. By interfering photon echoes produced in a single-mode Ti:Er:LiNbO(3) waveguide, we found that decoherence in the medium translates only as loss and not as degradation of information. We measured a visibility for interfering echoes close to 100%. These results may have important implications for future long-distance quantum communication protocols.
Temporal Code-Driven Stimulation: Definition and Application to Electric Fish Signaling

PubMed Central

Lareo, Angel; Forlim, Caroline G.; Pinto, Reynaldo D.; Varona, Pablo; Rodriguez, Francisco de Borja

2016-01-01

Closed-loop activity-dependent stimulation is a powerful methodology to assess information processing in biological systems. In this context, the development of novel protocols, their implementation in bioinformatics toolboxes and their application to different description levels open up a wide range of possibilities in the study of biological systems. We developed a methodology for studying biological signals representing them as temporal sequences of binary events. A specific sequence of these events (code) is chosen to deliver a predefined stimulation in a closed-loop manner. The response to this code-driven stimulation can be used to characterize the system. This methodology was implemented in a real time toolbox and tested in the context of electric fish signaling. We show that while there are codes that evoke a response that cannot be distinguished from a control recording without stimulation, other codes evoke a characteristic distinct response. We also compare the code-driven response to open-loop stimulation. The discussed experiments validate the proposed methodology and the software toolbox. PMID:27766078
Differential Modulation of Excitatory and Inhibitory Neurons during Periodic Stimulation

PubMed Central

Mahmud, Mufti; Vassanelli, Stefano

2016-01-01

Non-invasive transcranial neuronal stimulation, in addition to deep brain stimulation, is seen as a promising therapeutic and diagnostic approach for an increasing number of neurological diseases such as epilepsy, cluster headaches, depression, specific type of blindness, and other central nervous system disfunctions. Improving its effectiveness and widening its range of use may strongly rely on development of proper stimulation protocols that are tailored to specific brain circuits and that are based on a deep knowledge of different neuron types response to stimulation. To this aim, we have performed a simulation study on the behavior of excitatory and inhibitory neurons subject to sinusoidal stimulation. Due to the intrinsic difference in membrane conductance properties of excitatory and inhibitory neurons, we show that their firing is differentially modulated by the wave parameters. We analyzed the behavior of the two neuronal types for a broad range of stimulus frequency and amplitude and demonstrated that, within a small-world network prototype, parameters tuning allow for a selective enhancement or suppression of the excitation/inhibition ratio. PMID:26941602
Temporal Code-Driven Stimulation: Definition and Application to Electric Fish Signaling.

PubMed

Lareo, Angel; Forlim, Caroline G; Pinto, Reynaldo D; Varona, Pablo; Rodriguez, Francisco de Borja

2016-01-01

Closed-loop activity-dependent stimulation is a powerful methodology to assess information processing in biological systems. In this context, the development of novel protocols, their implementation in bioinformatics toolboxes and their application to different description levels open up a wide range of possibilities in the study of biological systems. We developed a methodology for studying biological signals representing them as temporal sequences of binary events. A specific sequence of these events (code) is chosen to deliver a predefined stimulation in a closed-loop manner. The response to this code-driven stimulation can be used to characterize the system. This methodology was implemented in a real time toolbox and tested in the context of electric fish signaling. We show that while there are codes that evoke a response that cannot be distinguished from a control recording without stimulation, other codes evoke a characteristic distinct response. We also compare the code-driven response to open-loop stimulation. The discussed experiments validate the proposed methodology and the software toolbox.
Stimulation of thyroid hormone secretion by thyrotropin in beluga whales, Delphinapterus leucas.

PubMed Central

St Aubin, D J

1987-01-01

Bovine thyroid stimulating hormone administered to three beluga whales, Delphinapterus leucas, was effective in producing an increase in circulating levels of triiodothyronine and thyroxine. A single dose of 10 I.U. of thyroid stimulating hormone resulted in a 145% increase in triiodothyronine and a 35% increase in thyroxine after nine hours in a whale tested within two hours after capture. The response was less pronounced in an animal tested with the same does on two occasions after four and eight weeks in captivity. In the third whale, 10 I.U. of thyroid stimulating hormone given on each of three consecutive days produced a marked increase in triiodothyronine and thyroxine. The elevation of thyroxine concentration persisted for at least two days after the last injection of thyroid stimulating hormone. A subsequent decrease in thyroxine to levels below baseline signalled the suppression of endogenous thyroid stimulating hormone. This preliminary study helps to establish a protocol for testing thyroid function in cetaceans. PMID:3651900
No effects of transcranial DLPFC stimulation on implicit task sequence learning and consolidation.

PubMed

Savic, Branislav; Cazzoli, Dario; Müri, René; Meier, Beat

2017-08-29

Neurostimulation of the dorsolateral prefrontal cortex (DLPFC) can modulate performance in cognitive tasks. In a recent study, however, transcranial direct current stimulation (tDCS) of the DLPFC did not affect implicit task sequence learning and consolidation in a paradigm that involved bimanual responses. Because bimanual performance increases the coupling between homologous cortical areas of the hemispheres and left and right DLPFC were stimulated separately the null findings may have been due to the bimanual setup. The aim of the present study was to test the effect of neuro-stimulation on sequence learning in a uni-manual setup. For this purpose two experiments were conducted. In Experiment 1, the DLPFC was stimulated with tDCS. In Experiment 2 the DLPFC was stimulated with transcranial magnetic stimulation (TMS). In both experiments, consolidation was measured 24 hours later. The results showed that sequence learning was present in all conditions and sessions, but it was not influenced by stimulation. Likewise, consolidation of sequence learning was robust across sessions, but it was not influenced by stimulation. These results replicate and extend previous findings. They indicate that established tDCS and TMS protocols on the DLPFC do not influence implicit task sequence learning and consolidation.
Further insights into cortactin conformational regulation

PubMed Central

Evans, Jason V; Kelley, Laura C; Hayes, Karen E; Ammer, Amanda Gatesman; Martin, Karen H

2011-01-01

The actin regulatory protein cortactin is involved in multiple signaling pathways impinging on the cortical actin cytoskeleton. Cortactin is phosphorylated by ERK1/2 and Src family tyrosine kinases, resulting in neuronal Wiskott Aldrich Syndrome protein (N-WASp) activation and enhanced actin related protein (Arp)2/3-mediated actin nucleation. Cortactin migrates as an 80/85 kDa doublet when analyzed by SDS-PAGE. Phosphorylation by ERK1/2 is associated with conversion of the 80 kDa to the 85 kDa form, postulated to occur by inducing a conformational alteration that releases the carboxyl-terminal SH3 domain from autoinhibition. Our recent analysis of the 80–85 kDa cortactin “shift” in tumor cells indicates that while ERK1/2 phosphorylation is associated with the 85 kDa shift, this phosphorylation event is not required for the shift to occur, nor does ERK1/2 phosphorylation appreciably alter global cortactin confirmation. These data indicate that additional factors besides ERK1/2 phosphorylation contribute to generating and/or maintaining the activated 85 kDa cortactin form in stimulated cells. PMID:21866257
Cost-effectiveness comparison between pituitary down-regulation with a gonadotropin-releasing hormone agonist short regimen on alternate days and an antagonist protocol for assisted fertilization treatments.

PubMed

Maldonado, Luiz Guilherme Louzada; Franco, José Gonçalves; Setti, Amanda Souza; Iaconelli, Assumpto; Borges, Edson

2013-05-01

To compare cost-effectiveness between pituitary down-regulation with a GnRH agonist (GnRHa) short regimen on alternate days and GnRH antagonist (GnRHant) multidose protocol on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcome. Prospective, randomized. A private center. Patients were randomized into GnRHa (n = 48) and GnRHant (n = 48) groups. GnRHa stimulation protocol: administration of triptorelin on alternate days starting on the first day of the cycle, recombinant FSH (rFSH), and recombinant hCG (rhCG) microdose. GnRHant protocol: administration of a daily dose of rFSH, cetrorelix, and rhCG microdose. ICSI outcomes and treatment costs. A significantly lower number of patients underwent embryo transfer in the GnRHa group. Clinical pregnancy rate was significantly lower and miscarriage rate was significantly higher in the GnRHa group. It was observed a significant lower cost per cycle in the GnRHa group compared with the GnRHant group ($5,327.80 ± 387.30 vs. $5,900.40 ± 472.50). However, mean cost per pregnancy in the GnRHa was higher than in the GnRHant group ($19,671.80 ± 1,430.00 vs. $11,328.70 ± 907.20). Although the short controlled ovarian stimulation protocol with GnRHa on alternate days, rFSH, and rhCG microdose may lower the cost of an individual IVF cycle, it requires more cycles to achieve pregnancy. NCT01468441. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Characterizing Deep Brain Stimulation effects in computationally efficient neural network models.

PubMed

Latteri, Alberta; Arena, Paolo; Mazzone, Paolo

2011-04-15

Recent studies on the medical treatment of Parkinson's disease (PD) led to the introduction of the so called Deep Brain Stimulation (DBS) technique. This particular therapy allows to contrast actively the pathological activity of various Deep Brain structures, responsible for the well known PD symptoms. This technique, frequently joined to dopaminergic drugs administration, replaces the surgical interventions implemented to contrast the activity of specific brain nuclei, called Basal Ganglia (BG). This clinical protocol gave the possibility to analyse and inspect signals measured from the electrodes implanted into the deep brain regions. The analysis of these signals led to the possibility to study the PD as a specific case of dynamical synchronization in biological neural networks, with the advantage to apply the theoretical analysis developed in such scientific field to find efficient treatments to face with this important disease. Experimental results in fact show that the PD neurological diseases are characterized by a pathological signal synchronization in BG. Parkinsonian tremor, for example, is ascribed to be caused by neuron populations of the Thalamic and Striatal structures that undergo an abnormal synchronization. On the contrary, in normal conditions, the activity of the same neuron populations do not appear to be correlated and synchronized. To study in details the effect of the stimulation signal on a pathological neural medium, efficient models of these neural structures were built, which are able to show, without any external input, the intrinsic properties of a pathological neural tissue, mimicking the BG synchronized dynamics.We start considering a model already introduced in the literature to investigate the effects of electrical stimulation on pathologically synchronized clusters of neurons. This model used Morris Lecar type neurons. This neuron model, although having a high level of biological plausibility, requires a large computational effort to simulate large scale networks. For this reason we considered a reduced order model, the Izhikevich one, which is computationally much lighter. The comparison between neural lattices built using both neuron models provided comparable results, both without traditional stimulation and in presence of all the stimulation protocols. This was a first result toward the study and simulation of the large scale neural networks involved in pathological dynamics.Using the reduced order model an inspection on the activity of two neural lattices was also carried out at the aim to analyze how the stimulation in one area could affect the dynamics in another area, like the usual medical treatment protocols require.The study of population dynamics that was carried out allowed us to investigate, through simulations, the positive effects of the stimulation signals in terms of desynchronization of the neural dynamics. The results obtained constitute a significant added value to the analysis of synchronization and desynchronization effects due to neural stimulation. This work gives the opportunity to more efficiently study the effect of stimulation in large scale yet computationally efficient neural networks. Results were compared both with the other mathematical models, using Morris Lecar and Izhikevich neurons, and with simulated Local Field Potentials (LFP).
The comparision of effect of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients.

PubMed

Ozcan Cenksoy, Pinar; Ficicioglu, Cem; Kizilkale, Ozge; Suhha Bostanci, Mehmet; Bakacak, Murat; Yesiladali, Mert; Kaspar, Cigdem

2014-07-01

To compare the effects of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients. Of 225 patients, 83 patients were in microdose flare-up group (Group 1), 70 patients were in GnRH antagonist/letrozole group (Group 2) and 72 patients were in GnRH antagonist/clomiphene citrate group (Group 3). Demographic and endocrine characteristics, the total number of oocytes retrieved, cancellation rate and clinical pregnancy rate were collected Results: Total dosage of gonadotropins (p=0.002) and serum E2 levels on the day of hCG administration (p=0.010) were significantly higher and duration of stimulations (p=0.03) was significantly longer in group 1. The number of oocytes retrieved was significantly greater in group 1 and 2 when compare to those of group 3 (p=0,000). There was a trend towards increasing cycle cancellation rates with GnRH antagonist/clomiphene citrate and GnRH antagonist/letrozole. Our finding suggest that the results of microdose flare-up protocol are better than other two used treatment protocols, in terms of maximum estradiol levels, number of mature oocytes retrieved, and cancellation rate and it still seems to be superior the ovarian stimulation regime for the poor responder patients.
Chronic idiopathic anal pain. Results of a diagnostic-therapeutic protocol in a colorectal referral unit.

PubMed

Armañanzas, Laura; Arroyo, Antonio; Ruiz-Tovar, Jaime; López, Alberto; Santos, Jair; Moya, Pedro; Gómez, María Amparo; Candela, Fernando; Calpena, Rafael

2015-01-01

Chronic idiopathic anal pain (CIAP) remains a diagnosis of exclusion. Its study and management still lack a standardized protocol. The aim of this study is to evaluate the results obtained with the diagnostic-therapeutic protocol established in our service. We performed a retrospective study of patients diagnosed with CIAP at the Colorectal Unit of the General University Hospital of Elche, between 2005 and 2011. We evaluated 57 patients with a diagnosis of chronic anal pain for functional anorectal disease (FAD). After the application of our diagnostic protocol, final diagnosis of chronic anal pain (CAP) was achieved in 43 cases (75%), including 22 cases of descending perineum syndrome, 12 of proctalgia fugax, 2 of pudendal neuritis and 7 of coccydynia. In 14 patients exclusion diagnosis of CIAP was established. Among the therapies used on patients with CIAP, biofeedback combined with conservative measures improved symptoms in 43% of the cases. Sacral nerve stimulation was assessed in patients who did not respond to other treatments. Through proper anamnesis, physical examination and complementary tests, a specific diagnosis of the cause of CAP by FAD can be achieved, reducing exclusion diagnosis of CIAP to 25% of cases. Conservative measures combined with biofeedback achieved an improvement in pain in more than 40% of the cases of CIAP in our study. Sacral nerve stimulation can be considered as a treatment option in refractory cases. Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.
Effects of patterned peripheral nerve stimulation on soleus spinal motor neuron excitability

PubMed Central

Dileone, Michele; Campolo, Michela; Carrasco-Lopez, Carmen; Moitinho-Ferreira, Fabricia; Gallego-Izquierdo, Tomas; Siebner, Hartwig R.; Valls-Solé, Josep; Aguilar, Juan

2018-01-01

Spinal plasticity is thought to contribute to sensorimotor recovery of limb function in several neurological disorders and can be experimentally induced in animals and humans using different stimulation protocols. In healthy individuals, electrical continuous Theta Burst Stimulation (TBS) of the median nerve has been shown to change spinal motoneuron excitability in the cervical spinal cord as indexed by a change in mean H-reflex amplitude in the flexor carpi radialis muscle. It is unknown whether continuous TBS of a peripheral nerve can also shift motoneuron excitability in the lower limb. In 26 healthy subjects, we examined the effects of electrical TBS given to the tibial nerve in the popliteal fossa on the excitability of lumbar spinal motoneurons as measured by H-reflex amplitude of the soleus muscle evoked by tibial nerve stimulation. Continuous TBS was given at 110% of H-reflex threshold intensity and compared to non-patterned regular electrical stimulation at 15 Hz. To disclose any pain-induced effects, we also tested the effects of TBS at individual sensory threshold. Moreover, in a subgroup of subjects we evaluated paired-pulse inhibition of H-reflex. Continuous TBS at 110% of H-reflex threshold intensity induced a short-term reduction of H-reflex amplitude. The other stimulation conditions produced no after effects. Paired-pulse H-reflex inhibition was not modulated by continuous TBS or non-patterned repetitive stimulation at 15 Hz. An effect of pain on the results obtained was discarded, since non-patterned 15 Hz stimulation at 110% HT led to pain scores similar to those induced by EcTBS at 110% HT, but was not able to induce any modulation of the H reflex amplitude. Together, the results provide first time evidence that peripheral continuous TBS induces a short-lasting change in the excitability of spinal motoneurons in lower limb circuitries. Future studies need to investigate how the TBS protocol can be optimized to produce a larger and longer effect on spinal cord physiology and whether this might be a useful intervention in patients with excessive excitability of the spinal motorneurons. PMID:29451889
[Passive tactile stimulation and its clinical and neurophysiological repercussions (P300) in blind children with symptoms of attention deficit disorder].

PubMed

Serrano-Marugán, Isabel; Herrera, Begoña; Romero, Sara; Nogales, Ramón; Poch-Broto, Joaquín; Quintero, Javier; Ortiz, Tomás

2014-02-24

Tactile stimulation is key for the posterior brain re-organization activity and attention processes, however the impact of tactile stimulation on attention deficit disorder (ADD) in blind children remains unexplored. We carried out a study with children having or not ADD (four per group). The subjects have been exposed during six months to tactile stimulation protocol consisting in two daily sessions (morning and afternoon sessions) of 30 minutes each. We have measured the ability to detect an infrequent tactile stimulus, reaction time, latency of P300, sources of brain activity, and ADD clinical symptoms, before and after tactile training. Passive tactile stimulation significantly improves ADD clinical symptoms, particularly attention, behavior and self-control of involuntary movements and tics. In addition, tactile stimulation changes the pattern of brain activity in ADD blind children inducing activity in frontal and occipital areas, which could be associated to a compensation of the attention deficit. Passive tactile stimulation training may improve ADD clinical symptoms and can reorganize the pattern of brain activity in blind ADD children.
Oral contraceptive pretreatment does not improve outcome in microdose gonadotrophin-releasing hormone agonist protocol among poor responder intracytoplasmic sperm injection patients.

PubMed

Duvan, Candan Iltemir; Berker, Bulent; Turhan, Nilgun Ozturk; Satiroglu, Hakan

2008-01-01

To compare oral contraceptive (OC) pretreatment plus microdose GnRH-a in flare-up protocol and non-OC microdose GnRH-a in flare-up protocol among poor responder ICSI patients. A retrospective analysis of poor responder ICSI patients. Patients were divided into two groups according to used microdose protocol. Precycle treatment with OC followed by follicular phase administration of 40 microg s.c. leuprolide acetate (LA) every 12 h beginning on after 2 day pill-free period and rFSH administration was begun on the third day of LA administration (OC-Group, n=26). Alternatively on day 2 after menses, patients were administered similar stimulation regime (non-OC Group, n=27). There were no significant differences between groups in the number of oocytes, peak estradiol levels, endometrial thickness, fertilization rates and embryo quality. Implantations and pregnancy rates per embryo transfer were similar. OC pretreatment plus microdose GnRHa in flare-up protocol does not offer advantages over non-OC microdose GnRHa in flare-up protocol among poor responder ICSI patients.
Measuring bioenergetics in T cells using a Seahorse Extracellular Flux Analyzer

PubMed Central

van der Windt, Gerritje J.W.; Chang, Chih-Hao; Pearce, Erika L.

2016-01-01

This unit contains several protocols to determine the energy utilization of T cells in real-time using a Seahorse Extracellular Flux Analyzer (www.seahorsebio.com). The advantages to using this machine over traditional metabolic assays include the simultaneous measurement of glycolysis and mitochondrial respiration, in real-time, on relatively small numbers of cells, without any radioactivity. The Basic Protocol describes a standard mitochondrial stress test on the XFe96, which yields information about oxidative phosphorylation and glycolysis, two energy-generating pathways. The alternate protocols provide examples of adaptations to the Basic Protocol, including adjustments for the use of the XFe24. A protocol for real-time bioenergetic responses to T cell activation allows for the analysis of immediate metabolic changes after T cell receptor stimulation. Specific substrate utilization can be determined by the use of differential assay media, or the injection of drugs that specifically affect certain metabolic processes. Accurate cell numbers, purity, and viability are critical to obtain reliable results. PMID:27038461

Measuring Bioenergetics in T Cells Using a Seahorse Extracellular Flux Analyzer.

PubMed

van der Windt, Gerritje J W; Chang, Chih-Hao; Pearce, Erika L

2016-04-01

This unit contains several protocols to determine the energy utilization of T cells in real-time using a Seahorse Extracellular Flux Analyzer (http://www.seahorsebio.com). The advantages to using this machine over traditional metabolic assays include the simultaneous measurement of glycolysis and mitochondrial respiration, in real-time, on relatively small numbers of cells, without any radioactivity. The Basic Protocol describes a standard mitochondrial stress test on the XF(e) 96, which yields information about oxidative phosphorylation and glycolysis, two energy-generating pathways. The alternate protocols provide examples of adaptations to the Basic Protocol, including adjustments for the use of the XF(e) 24. A protocol for real-time bioenergetic responses to T cell activation allows for the analysis of immediate metabolic changes after T cell receptor stimulation. Specific substrate utilization can be determined by the use of differential assay media, or the injection of drugs that specifically affect certain metabolic processes. Accurate cell numbers, purity, and viability are critical to obtain reliable results. Copyright © 2016 John Wiley & Sons, Inc.
The Sommerfeld enhancement in the scotogenic model with large electroweak scalar multiplets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chowdhury, Talal Ahmed; Nasri, Salah, E-mail: talal@du.ac.bd, E-mail: snasri@uaeu.ac.ae

2017-01-01

We investigate the Sommerfeld enhancement (SE) in the generalized scotogenic model with large electroweak multiplets. We focus on scalar dark matter (DM) candidate of the model and compare DM annihilation cross sections to WW , ZZ , γγ and γ Z at present day in the galactic halo for scalar doublet and its immediate generalization, the quartet in their respective viable regions of parameter space. We find that larger multiplet has sizable Sommerfeld enhanced annihilation cross section compared to the doublet and because of that it is more likely to be constrained by the current H.E.S.S. results and future CTAmore » sensitivity limits.« less
An advanced panel method for analysis of arbitrary configurations in unsteady subsonic flow

NASA Technical Reports Server (NTRS)

Dusto, A. R.; Epton, M. A.

1980-01-01

An advanced method is presented for solving the linear integral equations for subsonic unsteady flow in three dimensions. The method is applicable to flows about arbitrary, nonplanar boundary surfaces undergoing small amplitude harmonic oscillations about their steady mean locations. The problem is formulated with a wake model wherein unsteady vorticity can be convected by the steady mean component of flow. The geometric location of the unsteady source and doublet distributions can be located on the actual surfaces of thick bodies in their steady mean locations. The method is an outgrowth of a recently developed steady flow panel method and employs the linear source and quadratic doublet splines of that method.
Superluminal propagation in a poly-chromatically driven gain assisted four-level N-type atomic system

NASA Astrophysics Data System (ADS)

Amin Bacha, Bakht; Ahmad, Iftikhar; Ullah, Arif; Ali, Hazrat

2013-10-01

We investigate the behavior of light propagation in an N-type four-level gain assisted model (Agarwal and Dasgupta 2004 Phys. Rev. A 70 023802) under poly-chromatic pump fields. The system exhibits interesting results of multiple controllable pairs of the gain doublet profile with changes in the intensity of the control field. We observe multiple anomalous dispersive regions for superluminal propagation in the medium. A negative group velocity of -37.50 m s-1 with a negative time delay of -8 ms is observed between each gain doublet in anomalous dispersive regions. This generalized model and its predictions can be tested with existing experimental setups.
The nuclear structure of 223Fr

NASA Astrophysics Data System (ADS)

Kurcewicz, W.; Løvhøiden, G.; Thorsteinsen, T. F.; Borge, M. J. G.; Burke, D. G.; Cronqvist, M.; Gabelmann, H.; Gietz, H.; Hill, P.; Kaffrell, N.; Naumann, R. A.; Nybø, K.; Nyman, G.; Rogowski, J.; Isolde Collaboration

1992-03-01

The γ-rays following the β- decay of 223Rn have been investigated by means of γ-ray singles including multispectrum analysis, and γγ-coincidence measurements using Ge detectors. Multipolarities of 38 transitions in 223Fr have been established by measuring conversion electrons with a mini-orange electron spectrometer. Most of the observed transitions could be placed in a level scheme comprising 53 excited states of 223Fr. The level structure is interpreted in terms of K π = {3}/{2}± and {1}/{2}± parity doublet bands, and a second K π = {3}/{2}± higher-lying parity doublet. The experimental data are compared with the theoretical predictions of the reflection-asymmetric rotor model.
Measurements of multipolarities in 225Ra

NASA Astrophysics Data System (ADS)

Andersen, E.; Borge, M. J. G.; Burke, D. G.; Gietz, H.; Hill, P.; Kaffrell, N.; Kurcewicz, W.; Løvhøiden, G.; Mattsson, S.; Naumann, R. A.; Nybø, K.; Nyman, G.; Thorsteinsen, T. F.; Isolde Collaboration

1989-01-01

Multipolarities of 45 transitions in 225Ra have been established by investigating the radiations associated with the β - decay of 225Fr. The study includes β -, e - and γ-singles spectra, e -γ- and γγ-coincidence measurements. The conversion electrons were measured with a mini-orange electron spectrometer, and the γ-spectra with Ge detectors. The multipolarities obtained from the measured conversion coefficients support the assignments of spin-parity doublets thus giving evidence for a stable octupole deformation of this nucleus. The negative parity of the 394.2 keV level established in the present work indicates that this level is a candidate for the parity-doublet partner of the {5}/{2}+ state at 236.3 keV.
Does a 5/2 sup + -5/2 sup minus ground-state parity doublet exist in sup 229 Pa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grafen, V.; Ackermann, B.; Baltzer, H.

1991-11-01

The 1/2(530) decoupled band in {sup 229}Pa has been identified up to the 19/2{sup {minus}} level in ({ital p},{ital t}) and ({ital p},2{ital n}{gamma}) experiments. It is found that the 3/2{sup {minus}} band head has an excitation energy of 19(10) keV, and can thus not be identified with a 123 keV level observed in the {sup 229}U electron capture decay. This removes the evidence presented earlier for a spin-parity assignment of 5/2{sup +-}5/2{sup {minus}} to a proposed nearly degenerate ground-state doublet in {sup 229}Pa.
Strong Electron Correlation in Photoionization of Spin-Orbit Doublets

NASA Astrophysics Data System (ADS)

Amusia, M. Ya.; Chernsheva, L. V.; Mnason, S. T.; Msezane, A. Z.; Radojevic, V.

2002-05-01

A new and explicitly many-body aspect of the "leveraging" of the spin-orbit interaction is demonstrated, spin-orbit activated interchannel coupling, which can significantly alter the photoionization cross section of a spin-orbit doublet. As an example, using a modified version of the Spin-Polarized Random-Phase-Approximation with Exchange methodology, a recently observed structure in the photoionization of Xe 3d(A. Kivimaki et al, Phys. Rev. A 63), 012716 (2000) has been explained both qualitatively and quantitatively. The structure is entirely due to this new spin-orbit activated interchannel coupling effect, which should be a general feature of inner-shell photoionization. This work was supported by NSF, NASA, DOE and ISTC.
Reopen parameter regions in two-Higgs doublet models

NASA Astrophysics Data System (ADS)

Staub, Florian

2018-01-01

The stability of the electroweak potential is a very important constraint for models of new physics. At the moment, it is standard for Two-Higgs doublet models (THDM), singlet or triplet extensions of the standard model to perform these checks at tree-level. However, these models are often studied in the presence of very large couplings. Therefore, it can be expected that radiative corrections to the potential are important. We study these effects at the example of the THDM type-II and find that loop corrections can revive more than 50% of the phenomenological viable points which are ruled out by the tree-level vacuum stability checks. Similar effects are expected for other extension of the standard model.
Myocardial scaffold-based cardiac tissue engineering: application of coordinated mechanical and electrical stimulations.

PubMed

Wang, Bo; Wang, Guangjun; To, Filip; Butler, J Ryan; Claude, Andrew; McLaughlin, Ronald M; Williams, Lakiesha N; de Jongh Curry, Amy L; Liao, Jun

2013-09-03

Recently, we developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserve the natural extracellular matrix structure, mechanical anisotropy, and vasculature templates and also show good cell recellularization and differentiation potential. In this study, a multistimulation bioreactor was built to provide coordinated mechanical and electrical stimulation for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (10(6) cells/mL) by needle injection and subjected to 5-azacytidine treatment (3 μmol/L, 24 h) and various bioreactor conditioning protocols. We found that after 2 days of culturing with mechanical (20% strain) and electrical stimulation (5 V, 1 Hz), high cell density and good cell viability were observed in the reseeded scaffold. Immunofluorescence staining demonstrated that the differentiated cells showed a cardiomyocyte-like phenotype by expressing sarcomeric α-actinin, myosin heavy chain, cardiac troponin T, connexin-43, and N-cadherin. Biaxial mechanical testing demonstrated that positive tissue remodeling took place after 2 days of bioreactor conditioning (20% strain + 5 V, 1 Hz); passive mechanical properties of the 2 day and 4 day tissue constructs were comparable to those of the tissue constructs produced by stirring reseeding followed by 2 weeks of static culturing, implying the effectiveness and efficiency of the coordinated simulations in promoting tissue remodeling. In short, the synergistic stimulations might be beneficial not only for the quality of cardiac construct development but also for patients by reducing the waiting time in future clinical scenarios.
Effects of tDCS on Bimanual Motor Skills: A Brief Review

PubMed Central

Pixa, Nils H.; Pollok, Bettina

2018-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that allows the modulation of cortical excitability as well as neuroplastic reorganization using a weak constant current applied through the skull on the cerebral cortex. TDCS has been found to improve motor performance in general and motor learning in particular. However, these effects have been reported almost exclusively for unimanual motor tasks such as serial reaction time tasks, adaptation tasks, or visuo-motor tracking. Despite the importance of bimanual actions in most activities of daily living, only few studies have investigated the effects of tDCS on bimanual motor skills. The objectives of this review article are: (i) to provide a concise overview of the few existing studies in this area; and (ii) to discuss the effects of tDCS on bimanual motor skills in healthy volunteers and patients suffering from neurological diseases. Despite considerable variations in stimulation protocols, the bimanual tasks employed, and study designs, the data suggest that tDCS has the potential to enhance bimanual motor skills. The findings imply that the effects of tDCS vary with task demands, such as complexity and the level of expertise of the participating volunteers. Nevertheless, optimized stimulation protocols tailored to bimanual tasks and individual performance considering the underlying neural substrates of task execution are required in order to probe the effectiveness of tDCS in greater detail, thus creating an opportunity to support motor recovery in neuro-rehabilitation. PMID:29670514
Muscle Fatigue Affects the Interpolated Twitch Technique When Assessed Using Electrically-Induced Contractions in Human and Rat Muscles.

PubMed

Neyroud, Daria; Cheng, Arthur J; Bourdillon, Nicolas; Kayser, Bengt; Place, Nicolas; Westerblad, Håkan

2016-01-01

The interpolated twitch technique (ITT) is the gold standard to assess voluntary activation and central fatigue. Yet, its validity has been questioned. Here we studied how peripheral fatigue can affect the ITT. Repeated contractions at submaximal frequencies were produced by supramaximal electrical stimulations of the human adductor pollicis muscle in vivo and of isolated rat soleus fiber bundles; an extra stimulation pulse was given during contractions to induce a superimposed twitch. Human muscles fatigued by repeated 30-Hz stimulation trains (3 s on-1 s off) showed an ~80% reduction in the superimposed twitch force accompanied by a severely reduced EMG response (M-wave amplitude), which implies action potential failure. Subsequent experiments combined a less intense stimulation protocol (1.5 s on-3 s off) with ischemia to cause muscle fatigue, but which preserved M-wave amplitude. However, the superimposed twitch force still decreased markedly more than the potentiated twitch force; with ITT this would reflect increased "voluntary activation." In contrast, the superimposed twitch force was relatively spared when a similar protocol was performed in rat soleus bundles. Force relaxation was slowed by >150% in fatigued human muscles, whereas it was unchanged in rat soleus bundles. Accordingly, results similar to those in the human muscle were obtained when relaxation was slowed by cooling the rat soleus muscles. In conclusion, our data demonstrate that muscle fatigue can confound the quantification of central fatigue using the ITT.
Microvascularization of corpus luteum of bovine treated with equine chorionic gonadotropin.

PubMed

Moura, Carlos Eduardo Bezerra; Rigoglio, Nathia Nathaly; Braz, Janine Karla França S; Machado, Marcello; Baruselli, Pietro S; Papa, Paula De Carvalho

2015-09-01

This study aimed to evaluate the morphological changes in microvascular density and corpus luteum (CL) vascularization in cows treated with eCG during stimulatory and superovulatory protocols. Sixteen cows were synchronized and divided into three groups: control (n = 6), stimulated (n = 4) and superovulated (n =6), one was submitted to estrous synchronization (ES) and received no eCG (control), and those that were submitted to ES and received eCG before or after follicular deviation (superovulation and stimulation of the dominant follicle, respectively). Ovulation was synchronized using a progesterone device-based protocol. After six days of ovulation, the cows were slaughtered and the ovaries and CL were collected. The CLs were processed and photomicrographs were taken under light microscopy to assess the vascular volume density (Vv) by stereology, and scanning electron microscopy (SEM) was used to perform ultrastructural analysis of the microvasculature. The Vv in stimulated and superovulated cows significantly increased (P ≤ 0.0001) when compared to control, indicating that the eCG is able to induce angiogenic activity in bovine CL. However, no significant differences were observed between stimulated and superovulated cows. The SEM demonstrated ratings indicative of angiogenesis, marked by several button-shaped projections in the capillaries, and the presence of more dilated capillaries in CL treated with eCG. These morphological findings are evidence of an angiogenic effect of the eCG treatment in CL of cows. © 2015 Wiley Periodicals, Inc.
Electrical Stimulation of Artificial Heart Muscle: A Look Into the Electrophysiologic and Genetic Implications.

PubMed

Mohamed, Mohamed A; Islas, Jose F; Schwartz, Robert J; Birla, Ravi K

Development of tissue-engineered hearts for treatment of myocardial infarction or biologic pacemakers has been hindered by the production of mostly arrhythmic or in-synergistic constructs. Electrical stimulation (ES) of these constructs has been shown to produce tissues with greater twitch force and better adrenergic response. To further our understanding of the mechanisms underlying the effect of ES, we fabricated a bioreactor capable of delivering continuous or intermittent waveforms of various types to multiple constructs simultaneously. In this study, we examined the effect of an intermittent biphasic square wave on our artificial heart muscle (AHM) composed of neonatal rat cardiac cells and fibrin gel. Twitch forces, spontaneous contraction rates, biopotentials, gene expression profiles, and histologic observations were examined for the ES protocol over a 12 day culture period. We demonstrate improved consistency between samples for twitch force and contraction rate, and higher normalized twitch force amplitudes for electrically stimulated AHMs. Improvements in electrophysiology within the AHM were noted by higher conduction velocities and lower latency in electrical response for electrically stimulated AHMs. Genes expressing key electrophysiologic and structural markers peaked at days 6 and 8 of culture, only a few days after the initiation of ES. These results may be used for optimization strategies to establish protocols for producing AHMs capable of replacing damaged heart tissue in either a contractile or electrophysiologic capacity. Optimized AHMs can lead to alternative treatments to heart failure and alleviate the limited donor supply crisis.
Electrical Stimulation of Artificial Heart Muscle: a look into the electrophysiological and genetic implications

PubMed Central

Mohamed, Mohamed A; Islas, Jose F; Schwartz, Robert J; Birla, Ravi K

2016-01-01

Development of tissue-engineered hearts for treatment of myocardial infarction or biological pacemakers has been hindered by the production of mostly arrhythmic or in-synergistic constructs. Electrical stimulation (ES) of these constructs has been shown to produce tissues with greater twitch force and better adrenergic response. In order to further our understanding of the mechanisms underlying the effect of ES, we fabricated a bioreactor capable of delivering continuous or intermittent waveforms of various types to multiple constructs simultaneously. In this study, we examined the effect of an intermittent biphasic square wave on our artificial heart muscle (AHM) composed of neonatal rat cardiac cells and fibrin gel. Twitch forces, spontaneous contraction rates, biopotentials, gene expression profiles, and histological observations were examined for the ES protocol over a 12 day culture period. We demonstrate improved consistency between samples for twitch force and contraction rate, and higher normalized twitch force amplitudes for electrically stimulated AHM. Improvements in electrophysiology within the AHM was noted by higher conduction velocities and lower latency in electrical response for electrically stimulated AHM. Genes expressing key electrophysiological and structural markers peaked at days 6 and 8 of culture, only a few days after the initiation of ES. These results may be used for optimization strategies to establish protocols for producing AHM capable of replacing damaged heart tissue in either a contractile or electrophysiological capacity. Optimized AHM can lead to alternative treatments to heart failure and alleviate the limited donor supply crisis. PMID:28459744
Safety of repetitive transcranial magnetic stimulation in patients with implanted cortical electrodes. An ex-vivo study and report of a case.

PubMed

Phielipp, Nicolás M; Saha, Utpal; Sankar, Tejas; Yugeta, Akihiro; Chen, Robert

2017-06-01

To evaluate the safety of repetitive transcranial magnetic stimulation (rTMS) in patients with implanted subdural cortical electrodes. We performed ex-vivo experiments to test the temperature, displacement and current induced in the electrodes with single pulse transcranial magnetic stimulation (TMS) from 10 to 100% of stimulator output and tested a typical rTMS protocol used in a clinical setting. We then used rTMS to the motor cortex to treat a patient with refractory post-herpetic neuralgia who had previously been implanted with a subdural motor cortical electrode for pain management. The rTMS protocol consisted of ten sessions of 2000 stimuli at 20Hz and 90% of resting motor threshold. The ex-vivo study showed an increase in the coil temperature of 2°C, a maximum induced charge density of 30.4μC/cm 2 /phase, and no electrode displacement with TMS. There was no serious adverse effect associated with rTMS treatment of the patient. Cortical tremor was observed in the intervals between trains of stimuli during one treatment session. TMS was safe in a patient with implanted Medtronic Resume II electrode (model 3587A) subdural cortical electrode. TMS may be used as a therapeutic, diagnostic or research tool in patients this type of with implanted cortical electrodes. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.
Effects of tDCS on Bimanual Motor Skills: A Brief Review.

PubMed

Pixa, Nils H; Pollok, Bettina

2018-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that allows the modulation of cortical excitability as well as neuroplastic reorganization using a weak constant current applied through the skull on the cerebral cortex. TDCS has been found to improve motor performance in general and motor learning in particular. However, these effects have been reported almost exclusively for unimanual motor tasks such as serial reaction time tasks, adaptation tasks, or visuo-motor tracking. Despite the importance of bimanual actions in most activities of daily living, only few studies have investigated the effects of tDCS on bimanual motor skills. The objectives of this review article are: (i) to provide a concise overview of the few existing studies in this area; and (ii) to discuss the effects of tDCS on bimanual motor skills in healthy volunteers and patients suffering from neurological diseases. Despite considerable variations in stimulation protocols, the bimanual tasks employed, and study designs, the data suggest that tDCS has the potential to enhance bimanual motor skills. The findings imply that the effects of tDCS vary with task demands, such as complexity and the level of expertise of the participating volunteers. Nevertheless, optimized stimulation protocols tailored to bimanual tasks and individual performance considering the underlying neural substrates of task execution are required in order to probe the effectiveness of tDCS in greater detail, thus creating an opportunity to support motor recovery in neuro-rehabilitation.
Intrasulcal Electrocorticography in Macaque Monkeys with Minimally Invasive Neurosurgical Protocols

PubMed Central

Matsuo, Takeshi; Kawasaki, Keisuke; Osada, Takahiro; Sawahata, Hirohito; Suzuki, Takafumi; Shibata, Masahiro; Miyakawa, Naohisa; Nakahara, Kiyoshi; Iijima, Atsuhiko; Sato, Noboru; Kawai, Kensuke; Saito, Nobuhito; Hasegawa, Isao

2011-01-01

Electrocorticography (ECoG), multichannel brain-surface recording and stimulation with probe electrode arrays, has become a potent methodology not only for clinical neurosurgery but also for basic neuroscience using animal models. The highly evolved primate's brain has deep cerebral sulci, and both gyral and intrasulcal cortical regions have been implicated in important functional processes. However, direct experimental access is typically limited to gyral regions, since placing probes into sulci is difficult without damaging the surrounding tissues. Here we describe a novel methodology for intrasulcal ECoG in macaque monkeys. We designed and fabricated ultra-thin flexible probes for macaques with micro-electro-mechanical systems technology. We developed minimally invasive operative protocols to implant the probes by introducing cutting-edge devices for human neurosurgery. To evaluate the feasibility of intrasulcal ECoG, we conducted electrophysiological recording and stimulation experiments. First, we inserted parts of the Parylene-C-based probe into the superior temporal sulcus to compare visually evoked ECoG responses from the ventral bank of the sulcus with those from the surface of the inferior temporal cortex. Analyses of power spectral density and signal-to-noise ratio revealed that the quality of the ECoG signal was comparable inside and outside of the sulcus. Histological examination revealed no obvious physical damage in the implanted areas. Second, we placed a modified silicone ECoG probe into the central sulcus and also on the surface of the precentral gyrus for stimulation. Thresholds for muscle twitching were significantly lower during intrasulcal stimulation compared to gyral stimulation. These results demonstrate the feasibility of intrasulcal ECoG in macaques. The novel methodology proposed here opens up a new frontier in neuroscience research, enabling the direct measurement and manipulation of electrical activity in the whole brain. PMID:21647392
Relationship Between Non-invasive Brain Stimulation-induced Plasticity and Capacity for Motor Learning.

PubMed

López-Alonso, Virginia; Cheeran, Binith; Fernández-del-Olmo, Miguel

2015-01-01

Cortical plasticity plays a key role in motor learning (ML). Non-invasive brain stimulation (NIBS) paradigms have been used to modulate plasticity in the human motor cortex in order to facilitate ML. However, little is known about the relationship between NIBS-induced plasticity over M1 and ML capacity. NIBS-induced MEP changes are related to ML capacity. 56 subjects participated in three NIBS (paired associative stimulation, anodal transcranial direct current stimulation and intermittent theta-burst stimulation), and in three lab-based ML task (serial reaction time, visuomotor adaptation and sequential visual isometric pinch task) sessions. After clustering the patterns of response to the different NIBS protocols, we compared the ML variables between the different patterns found. We used regression analysis to explore further the relationship between ML capacity and summary measures of the MEPs change. We ran correlations with the "responders" group only. We found no differences in ML variables between clusters. Greater response to NIBS protocols may be predictive of poor performance within certain blocks of the VAT. "Responders" to AtDCS and to iTBS showed significantly faster reaction times than "non-responders." However, the physiological significance of these results is uncertain. MEP changes induced in M1 by PAS, AtDCS and iTBS appear to have little, if any, association with the ML capacity tested with the SRTT, the VAT and the SVIPT. However, cortical excitability changes induced in M1 by AtDCS and iTBS may be related to reaction time and retention of newly acquired skills in certain motor learning tasks. Copyright © 2015 Elsevier Inc. All rights reserved.
Clinically Effective Treatment of Fibromyalgia Pain With High-Definition Transcranial Direct Current Stimulation: Phase II Open-Label Dose Optimization.

PubMed

Castillo-Saavedra, Laura; Gebodh, Nigel; Bikson, Marom; Diaz-Cruz, Camilo; Brandao, Rivail; Coutinho, Livia; Truong, Dennis; Datta, Abhishek; Shani-Hershkovich, Revital; Weiss, Michal; Laufer, Ilan; Reches, Amit; Peremen, Ziv; Geva, Amir; Parra, Lucas C; Fregni, Felipe

2016-01-01

Despite promising preliminary results in treating fibromyalgia (FM) pain, no neuromodulation technique has been adopted in clinical practice because of limited efficacy, low response rate, or poor tolerability. This phase II open-label trial aims to define a methodology for a clinically effective treatment of pain in FM by establishing treatment protocols and screening procedures to maximize efficacy and response rate. High-definition transcranial direct current stimulation (HD-tDCS) provides targeted subthreshold brain stimulation, combining tolerability with specificity. We aimed to establish the number of HD-tDCS sessions required to achieve a 50% FM pain reduction, and to characterize the biometrics of the response, including brain network activation pain scores of contact heat-evoked potentials. We report a clinically significant benefit of a 50% pain reduction in half (n = 7) of the patients (N = 14), with responders and nonresponders alike benefiting from a cumulative effect of treatment, reflected in significant pain reduction (P = .035) as well as improved quality of life (P = .001) over time. We also report an aggregate 6-week response rate of 50% of patients and estimate 15 as the median number of HD-tDCS sessions to reach clinically meaningful outcomes. The methodology for a pivotal FM neuromodulation clinical trial with individualized treatment is thus supported. Registered in Clinicaltrials.gov under registry number NCT01842009. In this article, an optimized protocol for the treatment of fibromyalgia pain with targeted subthreshold brain stimulation using high-definition transcranial direct current stimulation is outlined. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

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