Статті в журналах з теми "Q modulator impairments"

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1

Anttila, Lauri, Peter Händel, Olli Mylläri, and Mikko Valkama. "Recursive learning-based joint digital predistorter for power amplifier and I/Q modulator impairments." International Journal of Microwave and Wireless Technologies 2, no. 2 (April 2010): 173–82. http://dx.doi.org/10.1017/s1759078710000280.

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The main implementation impairments degrading the performance of direct-conversion radio transmitters are in-phase/quadrature (I/Q) mismatch, local oscillator (LO) leakage, and power amplifier (PA) nonlinear distortion. In this article, we propose a recursive least-squares-based learning algorithm for joint digital predistortion (PD) of frequency-dependent PA and I/Q modulator impairments. The predistorter is composed of a parallel connection of two parallel Hammerstein (PH) predistorters and an LO leakage compensator, yielding a predistorter which as a whole is fully linear in the parameters. In the parameter estimation stage, proper feedback signal from the transmitter radio frequency (RF) stage back to the digital parts is deployed, combined with the indirect learning architecture and recursive least-squares training. The proposed structure is one of the first techniques to explicitly consider the joint estimation and mitigation of frequency-dependent PA and I/Q modulator impairments. Extensive simulation and measurement analysis is carried out to verify the operation and efficiency of the proposed PD technique. In general, the obtained results demonstrate linearization and I/Q modulator calibration performance clearly exceeding the performance of current state-of-the-art reference techniques.
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2

Anttila, Lauri, Peter Handel, and Mikko Valkama. "Joint Mitigation of Power Amplifier and I/Q Modulator Impairments in Broadband Direct-Conversion Transmitters." IEEE Transactions on Microwave Theory and Techniques 58, no. 4 (April 2010): 730–39. http://dx.doi.org/10.1109/tmtt.2010.2041579.

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3

Anastasijevic, Ana, Duska Coja, Natasa Neskovic, Aleksandar Neskovic, and Djuradj Budimir. "Joint power amplifier and I/Q modulator impairments modelling and compensation for LTE transmitters using artificial neural networks." AEU - International Journal of Electronics and Communications 69, no. 2 (February 2015): 529–38. http://dx.doi.org/10.1016/j.aeue.2014.11.005.

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4

Tyagi, Rishita. "Simulation and Performance Analysis of RoF System Using Fiber Impairments." International Journal for Research in Applied Science and Engineering Technology 10, no. 5 (May 31, 2022): 2055–61. http://dx.doi.org/10.22214/ijraset.2022.42759.

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Abstract: A Radio over Fiber (RoF) system has a unique feature of containing both a fiber optic link and a free space radio path. Fiber based wireless access facilitates high-capacity multimedia services in a real-time basis. In this research paper, the RoF system is simulated in the presence of fiber impairments, namely, Polarization Mode Dispersion (PMD) and Cross Phase Modulation (XPM) and Four-Wave Mixing (FWM) with the help of OptiSystem simulation tool. The variations in Quality factor (Q factor) and Bit Error Rate (BER) with respect to wavelength of 1552 nm and bit rates of 10 Gb/s of input signal is analyzed in the presence of the linear and non-linear impairments of the fiber. Keywords: Radio over Fiber (RoF), Polarization Mode Dispersion (PMD), Cross Phase Modulation (XPM), Four-Wave Mixing (FWM), OptiSystem, Bit Error Rate (BER), Q factor.
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5

Wu, Yibo, Ulf Gustavsson, Alexandre Graell I. Amat, and Henk Wymeersch. "Low Complexity Joint Impairment Mitigation of I/Q Modulator and PA Using Neural Networks." IEEE Journal on Selected Areas in Communications 40, no. 1 (January 2022): 54–64. http://dx.doi.org/10.1109/jsac.2021.3126024.

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6

Muhammad, Fazal, Farman Ali, Usman Habib, Muhammad Usman, Imran Khan, and Sunghwan Kim. "Time Domain Equalization and Digital Back-Propagation Method-Based Receiver for Fiber Optic Communication Systems." International Journal of Optics 2020 (February 12, 2020): 1–13. http://dx.doi.org/10.1155/2020/3146374.

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Анотація:
Fiber optic communication systems (FOCSs) have attained a lot of attention by revolutionizing the telecommunication industry and offering new possibilities with the technical advancements in state-of-the-art high speed digital electronics. Advanced modulation formats make use of the phase, amplitude, and polarization of the optical signals at the same time to provide high spectral efficiency as compared with 1 bit/s/Hz for the intensity modulation direct detection system (IMDD), but are highly prone to transmission impairments. Thus, the effects that add up to the optical fiber impairments such as optical fiber chromatic dispersion (OFCD), polarization model dispersion (PMD), and phase offset and noise (POaN) need to be addressed at the receiver side. The development of components and algorithms to minimize these effects in next generation FOCSs with 100 Gbps data rate and beyond with long-haul transmission is still a challenging issue. In this paper, digital signal processing- (DSP-) assisted dispersion and nonlinear compensation techniques are presented to compensate for physical layer impairments including OFCD, PMD, and POaN. The simulations are performed considering Dual Polarization- (DP-) QPSK modulation format to achieve two-fold data rate to achieve spectral efficiency of 3.28 bits/s/Hz by making use of the polarization diversity and system performance is investigated in terms of bit error rate (BER), constellation diagrams, and quality factor (Q-factor) for different values of optical signal-to-noise ratio (OSNR), launch power (PL), and fiber length.
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7

Trombley, Paul Q. "Selective Modulation of GABAA Receptors by Aluminum." Journal of Neurophysiology 80, no. 2 (August 1, 1998): 755–61. http://dx.doi.org/10.1152/jn.1998.80.2.755.

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Trombley, Paul Q. Selective modulation of GABAA receptors by aluminum. J. Neurophysiol. 80: 755–761, 1998. Aluminum has been implicated in several neurodegenerative conditions including Alzheimer's disease. Because the mammalian olfactory system has an unusual capacity for the uptake and transneuronal spread of inhaled substances such as aluminum, whole cell recording techniques were used to examine the actions of aluminum on basic membrane properties and amino acid receptors on rat olfactory bulb mitral/tufted (M/T) neurons in culture. Aluminum had little direct effects on M/T neurons. Aluminum (100 μM) did not evoke a membrane current or alter action-potential shape or duration. Aluminum also had no marked effects on the family of voltage-gated membrane currents evoked by a series of 10-mV, 50-ms depolarizing steps. However, aluminum dramatically potentiated the current evoked by 30 μM γ-aminobutyric acid (GABA) at concentrations <100 μM. Conversely, higher concentrations of aluminum blocked the GABA-evoked current. The effects of aluminum on GABA-evoked currents were not voltage dependent. Aluminum (100 μM) equally potentiated both inward currents at −30 mV and outward currents at + 30 mV. At 300 μM, aluminum blocked both inward and outward currents to a similar extent. In some neurons, aluminum only blocked the current and potentiation was not observed. The biphasic action of aluminum on GABA-evoked currents suggests separate binding sites: a high-affinity potentiating site and a low-affinity inhibiting site. Despite its effects on GABA-evoked currents, aluminum did not alter membrane currents evoked by glutamate, N-methyl-d-aspartate, kainate, or glycine. Aluminum also did not reduce spontaneous excitatory synaptic activity, suggesting little, if any, effect on glutamate release. Although a causal role for aluminum in Alzheimer's disease and other neuropathological conditions remains controversial, it is clear that elevated aluminum concentrations in the brain are associated with a variety of cognitive impairments. The present results indicate that aluminum can alter the function of GABAA receptors and may suggest that aluminum can contribute to cognitive impairment through disruption of inhibitory circuits.
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8

Hosseini-Sharifabad, Ali, Mohammad Reza Mofid, Majid Moradmand, and Mohammad Keimasi. "The Effect of Omega-lycotoxin on the Cognitive Impairment Induced by Kainic Acid in Rats." Iranian Journal of Toxicology 15, no. 1 (January 1, 2021): 49–56. http://dx.doi.org/10.32598/ijt.15.1.740.1.

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Background: Excitotoxicity is a common pathological process in neurodegenerative diseases associated with overactivity of N-methyl-D-aspartate (NMDA) and P/Q type voltage-gated calcium (Cav2.1) channels. Omega-lycotoxin-Gsp2671g is a therapeutic tool to modulate overactive Cav2.1 (P/Q type) channels. Omega-lycotoxin binds to Cav2.1 channels with high affinity and selectivity. This study aimed to investigate the effects of Omega-lycotoxin on the cognitive impairment induced by kainic acid in rats. Methods: The effect of pre-treatment and post-treatment trials of intra-hippocampal Cornu Ammonis-3 administration of omega-lycotoxin (0.5, 1 or 2µg) was studied on the cognitive impairment induced by kainic acid in rats. The rats’ learning and memory were assessed by the passive avoidance and a single-day testing version of the Morris water maze method. Results: Omega-lycotoxin caused a significant increase in the latency of the passive avoidance test and the duration of their presence in the target area of the Morris water maze test compared to the groups treated with kainic acid (P<0.0001). There were statistically significant differences for the effects of various doses of omega-lycotoxin. The post-treatment groups showed a greater improvement than those in the pretreatment groups. Conclusion: The findings demonstrated that a single dose of omega-lycotoxin can prevent or revert the memory impairment caused by kainic acid in rats.
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9

Mugridge, K. G., M. Perretti, P. Ghiara, C. L. Galeotti, M. Melli, and L. Parente. "Gastric antisecretory and anti-ulcer actions of IL-1 in rat involve different IL-1 receptor types." American Journal of Physiology-Gastrointestinal and Liver Physiology 269, no. 5 (November 1, 1995): G763—G769. http://dx.doi.org/10.1152/ajpgi.1995.269.5.g763.

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Limited knowledge exists concerning the interleukin-1 (IL-1) receptor type (IL-1RT) mediating the potent antisecretory and gastro-protective actions of IL-1. In the present study, the gastric actions of IL-1 beta and two related mutant proteins, yIL-1 beta delta 4, an analogue that preferentially binds to IL-1-RTII, and mutant yIL-1 beta N7/Q, an analogue that has equal affinity as IL-1 beta for IL-1RTI and IL-1RTII, have been compared. Modulation of IL-1 gastric actions were also investigated using monoclonal antibody (MAb) preparations raised against IL-1RTI or IL-1RTII. In the pylorus-ligated rat, yIL-1 beta delta 4, yIL-1 beta N7/Q, and IL-1 beta (all at 1 microgram/kg ip) reduced gastric acid secretion (50, 79, and 78%, respectively), indicating the importance of IL-1RTII binding for antisecretory activity. This was further substantiated in experiments using the MAb preparations, which showed that IL-1 beta (1 microgram/kg ip) antisecretory activity was reversed by MAb IL-1RTII (10-50 micrograms/kg sc) but not by MAb IL-1RTI (50 micrograms/kg sc). In contrast, at dosages 10-fold higher (10 micrograms/kg ip) than that used in the study to inhibit acid secretion, IL-1 beta and yIL-1N7/Q equally reduced (approximately 80%) indomethacin-induced gastric damage, but yIL-1 beta delta 4 was ineffective. The results using yIL-1 beta delta 4 indicated that impairment of IL-1RTI binding capacity appeared to be paralleled by a decreased gastroprotective effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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10

Giacomucci, Giulia, Salvatore Mazzeo, Sonia Padiglioni, Silvia Bagnoli, Laura Belloni, Camilla Ferrari, Laura Bracco, Benedetta Nacmias, Sandro Sorbi, and Valentina Bessi. "Gender differences in cognitive reserve: implication for subjective cognitive decline in women." Neurological Sciences 43, no. 4 (October 8, 2021): 2499–508. http://dx.doi.org/10.1007/s10072-021-05644-x.

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Abstract Background Subjective Cognitive Decline (SCD) is a self-experienced decline in cognitive capacity with normal performance on standardized cognitive tests, showing to increase risk of Alzheimer’s Disease (AD). Cognitive reserve seems to influence the progression from SCD to Mild Cognitive Impairment (MCI) and to AD. The aim of our study was to investigate gender differences in cognitive reserve evaluating how sex might modulate the role of cognitive reserve on SCD. Methods We included 381 SCD patients who underwent clinical evaluation, neuropsychological assessment, evaluation of premorbid intelligence by the Test di Intelligenza Breve (TIB), cognitive complaints by the Memory Assessment Clinics Questionnaire (MAC-Q), and apolipoprotein E (APOE) genotyping. Results The proportion between women and men was significantly different (68.7% [95% CI 63.9–73.4 vs 31.4%, 95% CI 26.6–36.0]). Women were younger than men at onset of SCD and at the baseline visit (p = 0.021), had lower years of education (p = 0.007), lower TIB scores (p < 0.001), and higher MAC-Q scores (p = 0.012). TIB was directly associated with age at onset of SCD in both women and men, while years of education was inversely associated with age at onset only in women. Multivariate analysis showed that sex influences TIB independently from years of education. TIB was directly associated with MAC-Q in men. Conclusions Sex interacts with premorbid intelligence and education level in influencing the age at onset and the severity of SCD. As the effect of education was different between men and women, we speculated that education might act as a minor contributor of cognitive reserve in women.
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11

Mondéjar-Parreño, Gema, Bianca Barreira, María Callejo, Daniel Morales-Cano, Vincenzo Barrese, Sergio Esquivel-Ruiz, Miguel A. Olivencia, et al. "Uncovered Contribution of Kv7 Channels to Pulmonary Vascular Tone in Pulmonary Arterial Hypertension." Hypertension 76, no. 4 (October 2020): 1134–46. http://dx.doi.org/10.1161/hypertensionaha.120.15221.

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K + channels play a fundamental role regulating membrane potential of pulmonary artery (PA) smooth muscle cells and their impairment is a common feature in pulmonary arterial hypertension (PAH). K + voltage-gated channel subfamily Q ( KCNQ1-5 ) or Kv7 channels and their regulatory subunits subfamily E (KCNE) regulatory subunits are known to regulate vascular tone, but whether Kv7 channel function is impaired in PAH and how this can affect the rationale for targeting Kv7 channels in PAH remains unknown. Here, we have studied the role of Kv7/KCNE subunits in rat PA and their possible alteration in PAH. Using the patch-clamp technique, we found that the total K + current is reduced in PA smooth muscle cells from pulmonary hypertension animals (SU5416 plus hypoxia) and Kv7 currents made a higher contribution to the net K + current. Likewise, enhanced vascular responses to Kv7 channel modulators were found in pulmonary hypertension rats. Accordingly, KCNE4 subunit was highly upregulated in lungs from pulmonary hypertension animals and patients. Additionally, Kv7 channel activity was enhanced in the presence of Kv1.5 and TASK-1 channel inhibitors and this was associated with an increased KCNE4 membrane abundance. Compared with systemic arteries, PA showed a poor response to Kv7 channel modulators which was associated with reduced expression and membrane abundance of Kv7.4 and KCNE4. Our data indicate that Kv7 channel function is preserved and KCNE4 is upregulated in PAH. Therefore, compared with other downregulated channels, the contribution of Kv7 channels is increased in PAH resulting in an enhanced sensitivity to Kv7 channel modulators. This study provides insight into the potential usefulness of targeting Kv7 channels in PAH.
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12

El-Nahal, Fady. "Coherent 16 Quadrature Amplitude Modulation (16QAM) Optical Communication Systems." Photonics Letters of Poland 10, no. 2 (June 30, 2018): 57. http://dx.doi.org/10.4302/plp.v10i2.809.

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Анотація:
Coherent optical fiber communications for data rates of 100Gbit/s and beyond have recently been studied extensively primarily because high sensitivity of coherent receivers could extend the transmission distance. Spectrally efficient modulation techniques such as M-ary quadrature amplitude modulation (M-QAM) can be employed for coherent optical links. The integration of multi-level modulation formats based on coherent technologies with wavelength-division multiplexed (WDM) systems is key to meet the aggregate bandwidth demand. This paper reviews coherent 16 quadrature amplitude modulation (16QAM) systems to scale the network capacity and maximum reach of current optical communication systems to accommodate traffic growth. Full Text: PDF ReferencesK. Kikuchi, "Fundamentals of Coherent Optical Fiber Communications", J. Lightwave Technol., vol. 34, no. 1, pp. 157-179, 2016. CrossRef S. Tsukamoto, D.-S. Ly-Gagnon, K. Katoh, and K. Kikuchi, "Coherent Demodulation of 40-Gbit/s Polarization-Multiplexed QPSK Signals with16-GHz Spacing after 200-km Transmission", Proc. OFc, Paper PDP29, (2005). DirectLink K. Kikuchi, "Coherent Optical Communication Technology", Proc. OFC, Paper Th4F.4, (2015). CrossRef J. M. Kahn and K.-P. Ho, "Spectral efficiency limits and modulation/detection techniques for DWDM systems", IEEE J. Sel. Topics Quantum Electron., vol. 10, no. 2, pp. 259–272, (2004). CrossRef S. Tsukamoto, K. Katoh, and K. Kikuchi, "Coherent demodulation of optical multilevel phase-shift-keying signals using homodyne detection and digital signal processing", IEEE Photon. Technol. Lett., vol. 18, no. 10, pp. 1131–1133, (2006). CrossRef Y. Mori, C. Zhang, K. Igarashi, K. Katoh, and K. Kikuchi, "Unrepeated 200-km transmission of 40-Gbit/s 16-QAM signals using digital coherent receiver", Opt. Exp., vol. 17, no. 32, pp. 1435–1441, (2009). CrossRef H. Nakashima, Et al., "Digital Nonlinear Compensation Technologies in Coherent Optical Communication Systems", Proc. OFC, Paper W1G.5, (2017). CrossRef S. J. Savory, "Digital filters for coherent optical receivers", Opt. Exp., vol. 16, no. 2, pp. 804–817, (2008). CrossRef D. S. Millar, T. Koike-Akino, S. Ö. Arık, K. Kojima, K. Parsons, T. Yoshida, and T. Sugihara, "High-dimensional modulation for coherent optical communications systems", Opt. Express, vol. 22, no. 7, pp 8798-8812, (2014). CrossRef R. Griffin and A. Carter, "Optical differential quadrature phase-shift key (oDQPSK) for high capacity optical transmission", Proc. OFC, Paper WX6, (2002). DirectLink K. Kikuchi, "Digital coherent optical communication systems: fundamentals and future prospects", IEICE Electron. Exp., vol. 8, no. 20, pp. 1642–1662, (2011). CrossRef F. Derr, "Optical QPSK transmission system with novel digital receiver concept", Electron Lett., vol. 27, no. 23, pp. 2177–2179, (1991). CrossRef R. No’e, "Phase noise tolerant synchronous QPSK receiver concept with digital I&Q baseband processing", Proc. OECC, Paper 16C2-5, (2004). DirectLink D.-S. Ly-Gagnon, S. Tsukamoto, K. Katoh, and K. Kikuchi, "Coherent detection of optical quadrature phase-shift keying signals with carrier phase estimation", J. Lightw. Technol., vol. 24, no. 1, pp. 12–21, (2006). CrossRef M. Taylor, "Coherent detection method using DSP for demodulation of signal and subsequent equalization of propagation impairments", IEEE Photon. Technol. Lett., vol. 16, no. 2, pp. 674–676, (2004). CrossRef S. Tsukamoto, K. Katoh, and K. Kikuchi, "Unrepeated transmission of 20-Gb/s optical quadrature phase-shift-keying signal over 200-km standard single-mode fiber based on digital processing of homodyne-detected signal for Group-velocity dispersion compensation", IEEE Photon. Technol. Lett., vol. 18, no. 9, pp. 1016–1018, (2006). CrossRef S. Tsukamoto, Y. Ishikawa, and K. Kikuchi, "Optical Homodyne Receiver Comprising Phase and Polarization Diversities with Digital Signal Processing", Proc. ECOC, Paper Mo4.2.1, (2006). CrossRef K. Kikuchi and S. Tsukamoto, "Evaluation of Sensitivity of the Digital Coherent Receiver", J. Lightw. Technol., vol. 20, no. 13, pp. 1817–1822, (2008). CrossRef S. Ishimura and K. Kikuchi, "Multi-dimensional Permutation Modulation Aiming at Both High Spectral Efficiency and High Power Efficiency", Proc. OFC/NFOEC, Paper M3A.2, (2014). CrossRef F. I. El-Nahal and A. H. M. Husein, "Radio over fiber access network architecture employing RSOA with downstream OQPSK and upstream re-modulated OOK data", (Optik) Int. J. Light Electron Opt., vol. 123, no. 14, pp: 1301-1303, (2012). CrossRef T. Koike-Akino, D. S. Millar, K. Kojima, and K. Parsons, "Eight-Dimensional Modulation for Coherent Optical Communications", Proc. ECOC, Paper Tu.3.C.3, (2013). DirectLink B. Sklar, Digital communications: Fundamentals and Applications, Prentice-Hall, (2001).
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13

Sullivan, Jane M. "Mechanisms of Cannabinoid-Receptor–Mediated Inhibition of Synaptic Transmission in Cultured Hippocampal Pyramidal Neurons." Journal of Neurophysiology 82, no. 3 (September 1, 1999): 1286–94. http://dx.doi.org/10.1152/jn.1999.82.3.1286.

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Cannabinoids, such as marijuana, are known to impair learning and memory perhaps through their actions in the hippocampus where cannabinoid receptors are expressed at high density. Although cannabinoid receptor activation decreases glutamatergic synaptic transmission in cultured hippocampal neurons, the mechanisms of this action are not known. Cannabinoid receptor activation also inhibits calcium channels that support neurotransmitter release in these cells, making modulation of these channels a candidate for cannabinoid-receptor–mediated effects on synaptic transmission. Whole cell patch-clamp recordings of glutamatergic neurons cultured from the CA1 and CA3 regions of the hippocampus were used to identify the mechanisms of the effects of cannabinoids on synaptic transmission. Cannabinoid receptor activation reduced excitatory postsynaptic current (EPSC) size by ∼50% but had no effect on the amplitude of spontaneous miniature EPSCs (mEPSCs). This reduction in EPSC size was accompanied by an increase in paired-pulse facilitation measured in low (1 mM) extracellular calcium and by a decrease in paired-pulse depression measured in normal (2.5 mM) extracellular calcium. Together, these results strongly support the hypothesis that cannabinoid receptor activation decreases EPSC size by reducing release of neurotransmitter presynaptically while having no effect on postsynaptic sensitivity to glutamate. Further experiments were done to identify the molecular mechanisms underlying this cannabinoid-receptor–mediated decrease in neurotransmitter release. Cannabinoid receptor activation had no effect on the size of the presynaptic pool of readily releasable neurotransmitter-filled vesicles, eliminating reduction in pool size as a mechanism for cannabinoid-receptor–mediated effects. After blockade of Q- and N-type calcium channels with ω-agatoxin TK and ω-conotoxin GVIA; however, activation of cannabinoid receptors reduced EPSC size by only 14%. These results indicate that cannabinoid receptor activation reduces the probability that neurotransmitter will be released in response to an action potential via an inhibition of presynaptic Q- and N-type calcium channels. This molecular mechanism most likely contributes to the impairment of learning and memory produced by cannabinoids and may participate in the analgesic, antiemetic, and anticonvulsive effects of these drugs as well.
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14

Aldaya, Ivan, Elias Giacoumidis, Geraldo de Oliveira, Jinlong Wei, Julián Leonel Pita, Jorge Diego Marconi, Eric Alberto Mello Fagotto, Liam Barry, and Marcelo Luis Francisco Abbade. "Histogram Based Clustering for Nonlinear Compensation in Long Reach Coherent Passive Optical Networks." Applied Sciences 10, no. 1 (December 23, 2019): 152. http://dx.doi.org/10.3390/app10010152.

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Анотація:
In order to meet the increasing capacity requirements, network operators are extending their optical infrastructure closer to the end-user while making more efficient use of the resources. In this context, long reach passive optical networks (LR-PONs) are attracting increasing attention.Coherent LR-PONs based on high speed digital signal processors represent a high potential alternative because, alongside with the inherent mixing gain and the possibility of amplitude and phase diversity formats, they pave the way to compensate linear impairments in a more efficient way than in traditional direct detection systems. The performance of coherent LR-PONs is then limited by the combined effect of noise and nonlinear distortion. The noise is particularly critical in single channel systems where, in addition to the the elevated fibre loss, the splitting losses should be considered. In such systems, Kerr induced self-phase modulation emerges as the main limitation to the maximum capacity. In this work, we propose a novel clustering algorithm, denominated histogram based clustering (HBC), that employs the spatial density of the points of a 2D histogram to identify the borders of high density areas to classify nonlinearly distorted noisy constellations. Simulation results reveal that for a 100 km long LR-PON with a 1:64 splitting ratio, at optimum power levels, HBC presents a Q-factor 0.57 dB higher than maximum likelihood and 0.21 dB higher than k-means. In terms of nonlinear tolerance, at a BER of 2×10 − 3 , our method achieves a gain of ∼2.5 dB and ∼1.25 dB over maximum likelihood and k-means, respectively. Numerical results also show that the proposed method can operate over blocks as small as 2500 symbols.
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15

Bossi, P., D. Parolini, C. Bergamini, L. D. Locati, E. Orlandi, M. Franceschini, M. Palazzi, P. Olmi, P. Potepan, and L. Licitra. "TPF induction chemotherapy (CT) followed by concomitant cisplatin/radiotherapy (cCTRT) in locally advanced nasopharyngeal cancer (LANPC)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 6046. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.6046.

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6046 Background: Recent meta-analysis showed better event free survival in LANPC with induction CT. In head and neck cancer, docetaxel, cisplatin and 5 FU (TPF) induction chemotherapy led to survival gain over cisplatin and 5FU alone. We studied feasibility and activity of TPF induction CT followed by cCTRT in LANPC. Methods: From October 2004 to May 2008, 45 pts with LANPC were treated at our Institution with 2 to 4 cycles (median 3) of induction TPF (docetaxel 75 mg/sm and cisplatin 75 mg/sm on day 1, and 5-FU 750 mg/sm/day ci for 96 hrs. Prophylactic ciprofloxacin was administered for 10 days each cycle, while use of G-CSF was not allowed. Following CT, pts received full doses radiotherapy (RT) concurrent with cisplatin 100 mg/sm q 21 days. Intensity modulated radiotherapy (IMRT) was delivered to 34 pts (76%). All but two pts had non-keratinizing carcinoma. Stage IV pts were 60%, stage III 34%, and 6% stage II. T4 was present in 24% and N3 disease was diagnosed in 42% of the pts. Results: TPF was well tolerated, with main toxicity consisting in neutropenia (31% G3–4). Response rate was 87%. RT dose ranged from 64 Gy to 70 Gy (median 70 Gy). Main toxicities during cCTRT were: neutropenia (38% G3, 4% G4), febrile neutropenia (11% G3), thrombocytopenia (7% G3–4) and mucositis (40% G3, 4% G4). Nasogastric tube was placed in 33% of pts and maintained for a median of 40 days. During cCTRT, platinum compounds mean dose delivery was 75%, with 6 pts shifting to carboplatin for renal function impairment. Observed late toxicities were xerostomia (G3 in 38% of cases) and peripheral neurotoxicity (G1 in 27%, G2 in 7% and G3 in 2% of the pts). After treatment completion, complete and partial response were recorded in 78% and 20% of the pts respectively, while 1 pt showed stable disease. With a median follow up of 22 months (range 7 to 47), 9 pts showed recurrence or progressive disease (7 at local and/or regional level, 2 distant metastases and 1 at both sites), with a 2-years event free survival of 78% and an overall survival of 85%. Conclusions: TPF followed by cCTRT is feasible in LANPC. In this high-stage nonendemic population local-regional disease control still remains the main therapeutic goal. Supported in part by AIRC. [Table: see text]
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16

Belle, Ludovic, Erin Koester, Emily Hansen, Michael Lawlor, Cecilia Hillard, and William R. Drobyski. "Host Interleukin 6 and Indoleamine 2,3 Dioxygenase Regulate Inflammation in the Brain during Graft Versus Host Disease." Blood 128, no. 22 (December 2, 2016): 2145. http://dx.doi.org/10.1182/blood.v128.22.2145.2145.

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Abstract Graft versus host disease (GVHD) commonly induces pathological damage in peripheral target organs such as the skin, liver and gastrointestinal tract leading to well characterized organ-specific clinical manifestations. A number of studies, however, have shown that patients with GVHD can also have behavioral and mood alterations that can affect overall cognitive function and lead to significant impairments in quality of life. The extent to which GVHD contributes to cognitive dysfunction and induces inflammation within the central nervous system (CNS), however, has not been critically examined. To address this question, we conducted studies using two well-defined murine GVHD models [C57BL/6(H-2b)→Balb/c (H-2d) and B10.BR(H-2k)→B6 (H-2b)]. We observed that there was a significant increase in the number of donor-derived CD4+ and CD8+ T cells in the brains of GVHD recipients early (days 7 -14) and late (day 42) post transplantation compared to BM controls. Histological studies revealed activated microglial cells and CD3+ T cell infiltration in the periventricular regions of brains in GVHD recipients that were not present in BM animals. Real time q-PCR analysis also demonstrated significant increases in IFN-γ, TNF-α, and IL-6 mRNA expression indicative of a proinflammatory state. Notably, GVHD animals exhibited behavioral changes in the forced swim test and elevated plus maze which are validated assays of stress coping and anxiety, respectively. Since IL-6, in particular, plays a pivotal role in GVHD pathogenesis in murine models and humans, we examined whether blockade of IL-6 signaling altered neuroinflammation. Animals treated with an anti-IL-6R antibody had a significant reduction in the number of donor-derived CD4+ and CD8+T cells in the brain compared to isotype control-treated mice. Anti-IL-6R treatment of GVHD mice also resulted in significant reductions in IFN-γ, TNF-α, and IL-6 mRNA and normalized behavior in the forced swim test, indicative of a decreased inflammatory response. Since IL-6 is produced by a wide variety of cells, including microglial and T cells, both donor and recipient cells have the potential to modulate GVHD severity within the CNS. To define whether donor or host IL-6 production was most critical for inducing neuroinflammation, experiments were conducted employing IL-6-/- mice as either donors or recipients. Whereas the absence of IL-6 in donor-derived cells had no impact on the degree of inflammation within the CNS, recipient animals that lacked IL-6 had a significant decrease in the number of donor-derived T cells which accumulated in the brain as well as a marked reduction in inflammatory cytokines, indicating that host IL-6 production was critical. To define the downstream pathways of IL-6-mediated CNS inflammation, we examined the role of indoleamine 2,3-dioxygenase (IDO) since IL-6 has been shown to upregulate IDO-1 expression under inflammatory conditions. We observed that IDO-1 mRNA levels were significantly increased in the brains of GVHD animals, and that blockade of IL-6 signaling resulted in a marked decrease in IDO mRNA levels. Additionally, transplantation studies using IDO-/- mice revealed that host, but not donor, IDO production was required for maximal inflammatory effects. Serotoninergic projections to the prefrontal cortex (PFC), in particular, are sensitive to inflammation and contribute to stress coping behavior. Therefore, to further interrogate this pathway, we performed quantitative mass spectrometry of brain extracts from the PFC. We found that tryptophan and 5HT concentrations were not different between BM and GVHD groups. However, there was an increase in the IDO product, kynurenic acid, in GVHD recipients consistent with an increase in brain IDO expression. To provide additional support for the premise that IL-6 effects were mediated through the IDO pathway, recipient mice were treated with either 1-methyltryptophan (1-MT), a completive inhibitor of IDO, or a vehicle control. GVHD mice treated with 1-MT had decreased accumulation of T cells in the brain and normal behavior in the forced swim test, demonstrating that inhibition of IDO abrogated CNS inflammation and behavioral changes in the presence of intact IL-6 signaling. In summary, these studies demonstrate that host IL-6 and IDO regulate inflammation and adversely impact behavioral function within the brain during GVHD through the tryptophan metabolic pathway. Disclosures No relevant conflicts of interest to declare.
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17

Kumar, Anil, and Karamjit Kaur. "Impact of System Parameters of Optical Fiber Link on Four Wave Mixing." Recent Advances in Computer Science and Communications 13 (December 27, 2019). http://dx.doi.org/10.2174/2666255813666191227143529.

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Background: The invention of WDM technology in optical communication system has completely revolutionized the telecomm industry through its high data carrying capacity and efficiency of transmission. Advanced optical modulation formats with high spectral efficiency, advanced components like Reconfigurable Optical Add Drop Multiplexers (ROADMS), OXC, and large bandwidth requirements contributed significantly in existence of dynamic, flexible translucent and transparent networks. In these networks, it is common practice to increase the power levels as much as possible to overcome the power penalty effects and better transmission, but this introduces several non-linear impairments in the link and hence degrades the quality of signal flowing. These impairments arise when several high strength optical fields of different wavelengths interact with molecular vibrations and acoustic waves. The different non-linear impacts include Self Phase Modulation (SPM), Cross Phase Modulation (XPM), Four Wave Mixing (FWM) and scattering effects like Stimulated Raman Scattering (SRS), Stimulated Brillouin Scattering (SBS. The main cause of these impairments is variation in refractive index of fiber (also called Kerr effect) due to intensity of signal flowing through fiber. Due to the degradation impact posed by these impairments, it is crucial to analyze their cause, their influence on system performance and mitigation techniques so as to improve the overall quality of transmission. The monitoring of impairments is quite a challenging task due to their dependency on time, present state of network, signals flowing in adjoining channels and fibers. Objective: The present work aims to identify and describe the role of FWM in optical networks. The mathematical model of FWM is studied to know the parameters influencing the overall impact on system performance. The power of optical source, channel spacing, distance of transmission and presence of dispersion are considered as key factors influencing FWM power being developed. Their impact on FWM power and hence, FWM efficiency is calculated. In addition, the influence of FWM on Quality of transmission is quantified in terms of BER and Q-factor. Method: The analysis is done through a two-channel transmitter system with varied power, channel spacing, distance of transmission and presence of other degradation factors (dispersion) is taken into account. The corresponding optical spectrums are analysed. Result & Conclusion: In this paper, the non-linear impairment FWM posing degradation effect on the signal quality has been discussed. The basics involved are presented along with the mathematical model. It has been found that FWM results in power transfer from one channel to generation of new waves which may lead to power depletion and interference. The new waves generated depend on the number of wavelengths travelling in the fiber and channel spacing. The influence of FWM on system performance is presented in terms of BER and Q-value. It has been concluded that the increased power of transmission and decreased channel spacing are the crucial factors increasing the magnitude of FWM and need to be closely monitored. On the other hand, increased distance of propagation and presence of certain level of dispersion leads to decrease in FWM power. Therefore, if selected carefully, they may act as source of FWM mitigation without requiring any external compensating device
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18

Kumar, Vikram, and Santos Kumar Das. "Physical layer impairment-aware ant colony optimization approach in WDM network." Journal of Optical Communications, August 10, 2020. http://dx.doi.org/10.1515/joc-2019-0209.

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AbstractPhysical layer impairments (PLIs) is a matter of great concern in optical networks to achieve the optimum performance. In order to mitigate the PLI, a better routing and wavelength assignment (RWA) technique is required in optical wavelength division multiplexing (WDM) networks. In this paper, a dynamic ant colony routing algorithm with the consideration of various PLIs has been presented. This work also presents a Q-factor estimation model that includes impairments such as amplified spontaneous emission (ASE) noise, four-wave mixing (FWM), and cross phase modulation (XPM). The simulation results also prove that the proposed ant colony optimization (ACO) based algorithm significantly reduces the blocking probability as compared to dynamic load based shortest path algorithm (LB-SPA).
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19

Kaur, Karamjit, and Anil Kumar. "Role of Self Phase Modulation and Cross Phase Modulation on Quality of Signal in Optical Links." Recent Advances in Computer Science and Communications 13 (November 27, 2019). http://dx.doi.org/10.2174/2666255813666191127105440.

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Background: In WDM networks, there is a crucial need to monitor signal degradation factors in order to maintain the quality of transmission. This is more critical in dynamic optical networks as non-linear impairments are network state dependent. Moreover, PLIs are accumulative in nature, so the overall impact is increased tremendously as the length of signal path is increased. The interactions between different impairments along the path also influence their overall impact. Objective: Among the different impairments, the present work focus on phase modulations owing to intensities of signals themselves as well as the neighboring signals. It includes the influence of SPM, SPM and XPM, system parameters like signal power, wavelength and fiber parameters like attenuation coefficient, dispersion coefficient and their influence on Q-value and BER. Method: The analysis is done through a single and two-channel transmitter system with varied power, wavelengths and system parameters. The corresponding optical spectrums are analysed. Result & Conclusion: It has been found that SPM and XPM pose broadening effect on spectrum without any effect on temporal distributions. The magnitude of signal power is among the parameters significantly influencing the broadening of spectrum. Higher is the power, more is the magnitude of broadening. It has been found that in order to neglect the impact of input power; its magnitude must be kept below 20 mW. Also, the dispersion and attenuation value need to be carefully as they pose counteracting effect to SPM and XPM for certain values and hence can be used as compensation measure without any additional cost.
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20

Pagare, Rajendraprasad A., Santosh Kumar, and Abhilasha Mishra. "Design and investigation of N1-class next-generation passive optical network-2 (NG-PON2) coexistence architecture in the presence of Kerr effect and four-wave mixing (FWM) for fiber to the home (FTTX) access networks." Journal of Optical Communications, April 8, 2021. http://dx.doi.org/10.1515/joc-2020-0299.

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Abstract In this paper, we investigated N1-class Time and Wavelength Division Multiplexing (TWDM) Next-Generation Passive Optical Network-2 (NG-PON2) supporting symmetric and coexistence configuration in a worst-case scenario. The network is optimized in the presence of linear and nonlinear impairments such as chromatic dispersion (CD), self-phase modulation (SPM), cross-phase modulation (XPM), and four-wave mixing (FWM). On-off key (OOK) modulation technique incorporating hybrid optical distribution network (ODN) i.e., wavelength select (WS) and wavelength-routed (WR) ODN is used to connect downstream (D/S) and upstream (U/S) channels supporting symmetric 80 Gbps data rate operating at 2.5/2.5 and 10/10 Gbps, respectively. G.652 single-mode (SM) fiber channel is modeled for fiber launch power PTODN = 3 dBm and 4 dBm for D/S and U/S channels to implement N1-class network. The D/S and U/S receiver sensitivity (Rxs) demonstrated are −44.23/−37.46 dBm and −28.46/−35.32 dBm and inter-channel crosstalk (Cc) is −31.97/−31.39 dB accommodating 640 splitter configuration at 50 km in the presence of impairments at 10E-7 bit error rate (BER) and Quality (Q)-factor of 5 for 10 Gbps channel.
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21

Musa, Ahmed. "Impairments Computation for Routing Purposes in a Transparent-Access Optical Network Based on Optical CDMA and WDM." Journal of Optical Communications 37, no. 2 (January 1, 2016). http://dx.doi.org/10.1515/joc-2015-0039.

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AbstractOptical access networks are becoming more widespread and the use of multiple services might require a transparent optical network (TON). Multiplexing and privacy could benefit from the combination of wavelength division multiplexing (WDM) and optical coding (OC) and wavelength conversion in optical switches. The routing process needs to be cognizant of different resource types and characteristics such as fiber types, fiber linear impairments such as attenuation, dispersion, etc. as well as fiber nonlinear impairments such as four-wave mixing, cross-phase modulation, etc. Other types of impairments, generated by optical nodes or photonic switches, also affect the signal quality (Q) or the optical signal to noise ratio (OSNR), which is related to the bit error rate (BER). Therefore, both link and switch impairments must be addressed and somehow incorporated into the routing algorithm. However, it is not practical to fully integrate all photonic-specific attributes in the routing process. In this study, new routing parameters and constraints are defined that reflect the distinct characteristics of photonic networking. These constraints are applied to the design phase of TON and expressed as a cost or metric form that will be used in the network routing algorithm.
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22

Ravipudi, Jaya Lakshmi, and Maite Brandt-Pearce. "Impairment- and Fragmentation Aware Dynamic Routing, Modulation and Spectrum Allocation in C+L Band Elastic Optical Networks Using Q-Learning." SSRN Electronic Journal, 2022. http://dx.doi.org/10.2139/ssrn.4048954.

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23

Murari, Anjaneyulu, Naga S. V. Goparaju, Shauna-Kay Rhooms, Kaniz F. B. Hossain, Felix G. Liang, Christian J. Garcia, Cindy Osei, et al. "IDH2-mediated regulation of the biogenesis of the oxidative phosphorylation system." Science Advances 8, no. 19 (May 13, 2022). http://dx.doi.org/10.1126/sciadv.abl8716.

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Several subunits in the matrix domain of mitochondrial complex I (CI) have been posited to be redox sensors for CI, but how elevated levels of reactive oxygen species (ROS) impinge on CI assembly is unknown. We report that genetic disruption of the mitochondrial NADPH-generating enzyme, isocitrate dehydrogenase 2 (IDH2), in Drosophila flight muscles results in elevated ROS levels and impairment of assembly of the oxidative phosphorylation system (OXPHOS). Mechanistically, this begins with an inhibition of biosynthesis of the matrix domain of CI and progresses to involve multiple OXPHOS complexes. Despite activation of multiple compensatory mechanisms, including enhanced coenzyme Q biosynthesis and the mitochondrial unfolded protein response, ferroptotic cell death ensues. Disruption of enzymes that eliminate hydrogen peroxide, but not those that eliminate the superoxide radical, recapitulates the phenotype, thereby implicating hydrogen peroxide as the signaling molecule involved. Thus, IDH2 modulates the assembly of the matrix domain of CI and ultimately that of the entire OXPHOS.
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24

Mullegama, Sureni V., Steven D. Klein, Stephen R. Williams, Jeffrey W. Innis, Frank J. Probst, Chad Haldeman-Englert, Julian A. Martinez-Agosto, et al. "Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes." Scientific Reports 11, no. 1 (May 28, 2021). http://dx.doi.org/10.1038/s41598-021-90798-z.

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AbstractMBD5-associated neurodevelopmental disorder (MAND) is an autism spectrum disorder (ASD) characterized by intellectual disability, motor delay, speech impairment and behavioral problems; however, the biological role of methyl-CpG-binding domain 5, MBD5, in neurodevelopment and ASD remains largely undefined. Hence, we created neural progenitor cells (NPC) derived from individuals with chromosome 2q23.1 deletion and conducted RNA-seq to identify differentially expressed genes (DEGs) and the biological processes and pathways altered in MAND. Primary skin fibroblasts from three unrelated individuals with MAND and four unrelated controls were converted into induced pluripotent stem cell (iPSC) lines, followed by directed differentiation of iPSC to NPC. Transcriptome analysis of MAND NPC revealed 468 DEGs (q < 0.05), including 20 ASD-associated genes. Comparison of DEGs in MAND with SFARI syndromic autism genes revealed a striking significant overlap in biological processes commonly altered in neurodevelopmental phenotypes, with TGFβ, Hippo signaling, DNA replication, and cell cycle among the top enriched pathways. Overall, these transcriptome deviations provide potential connections to the overlapping neurocognitive and neuropsychiatric phenotypes associated with key high-risk ASD genes, including chromatin modifiers and epigenetic modulators, that play significant roles in these disease states.
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25

Li, Xuling, Tingting Zhao, Junling Gu, Zhe Wang, Jing Lin, Rushang Wang, Tingting Duan, et al. "Intake of flavonoids from Astragalus membranaceus ameliorated brain impairment in diabetic mice via modulating brain-gut axis." Chinese Medicine 17, no. 1 (February 12, 2022). http://dx.doi.org/10.1186/s13020-022-00578-8.

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Abstract Background Brain impairment is one of a major complication of diabetes. Dietary flavonoids have been recommended to prevent brain damage. Astragalus membranaceus is a herbal medicine commonly used to relieve the complications of diabetes. Flavonoids is one of the major ingredients of Astragalus membranaceus, but its function and mechanism on diabetic encepholopathy is still unknown. Methods Type 2 diabetes mellitus (T2DM) model was induced by high fat diet and STZ in C57BL/6J mice, and BEnd.3 and HT22 cell lines were applied in the in vitro study. Quality of flavonoids was evaluated by LC–MS/MS. Differential expressed proteins in the hippocampus were evaluated by proteomics; influence of the flavonoids on composition of gut microbiota was analyzed by metagenomics. Mechanism of the flavonoids on diabetic encepholopathy was analyzed by Q-PCR, Western Blot, and multi-immunological methods et al. Results We found that flavonoids from Astragalus membranaceus (TFA) significantly ameliorated brain damage by modulating gut-microbiota-brain axis: TFA oral administration decreased fasting blood glucose and food intake, repaired blood brain barrier, protected hippocampus synaptic function; improved hippocampus mitochondrial biosynthesis and energy metabolism; and enriched the intestinal microbiome in high fat diet/STZ-induced diabetic mice. In the in vitro study, we found TFA increased viability of HT22 cells and preserved gut barrier integrity in CaCO2 monocellular layer, and PGC1α/AMPK pathway participated in this process. Conclusion Our findings demonstrated that flavonoids from Astragalus membranaceus ameliorated brain impairment, and its modulation on gut-brain axis plays a pivotal role. Our present study provided an alternative solution on preventing and treating diabetic cognition impairment.
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26

Ranjan, Prabhat, Rajesh Kumari, Harish Pal, Prasanna Krishnamurthy, Gangjian Qin, Raj Kishore, and Suresh K. Verma. "Abstract 362: Role of Dysregulated Exosomal MiRNAs in Functional Impairment of Cardiac Endothelial Cells." Circulation Research 127, Suppl_1 (July 31, 2020). http://dx.doi.org/10.1161/res.127.suppl_1.362.

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Objective: Endothelial cells (ECs) play critical role to maintain the normal heart function. It is shown that fibroblast-derived exosomes have the ability to enhance cardiac myocytes hypertrophy in pressure-overloaded myocardium. However, their effect on endothelial cell function has not been studied. Others and we have previously shown that stress-induced chronic inflammation induces cardiac fibroblasts and mediates endothelial cells dysfunction. Here we hypothesized that activated cardiac fibroblasts-derived exosomes (FB-Exo) mediates cardiac ECs dysfunction and leads for cardiac pathology and restoring the altered FB-Exo contents will improve endothelial cells function and biology. Methods: We cultured mouse primary endothelial cells in EC growth media. Cells were treated with fibroblasts-derived-Exo. Exosomes were isolated from fibroblast condition media by ultracentrifugation and characterized by nanosight & electron microscopy. Results: Fibroblasts were significantly activated by TGFβ treatment as shown by qPCR and western blot (smad2/3, p-Smad2/3, p38, p-p38) data. Endothelial cells dysfunction as shown by Matrigel assay, real-time Q-PCR and western data (eNOS and Hif1α) data was observed in TGFβ-FB-Exo treatment endothelial cell. MTT, TUNEL and migration assay also followed the same trend as TGFβ-FB-Exo treatment significantly induced endothelial cell death and inhibits its proliferation and migration. Furthermore, microRNA array and PCR analysis revealed dysregulation of miR-132-3p, miR-2001-3p and miR-125b-5p in TGFβ-FB-Exo treated endothelial cells. Conclusions: Taken together, this study demonstrates that TGFβ treated fibroblasts-derived exosomes are enriched in pro-fibrotic factors and can lead to endothelial dysfunction and promotes cardiac fibrosis in PO myocardium. In future study, we will modulate the target miRs in fibroblasts to see whether it rescue reparative function of endothelial cell and inhibits cardiac fibrosis in failing heart.
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Janebodin, Kajohnkiart, Rakchanok Chavanachat, Aislinn Hays, and Morayma Reyes Gil. "Silencing VEGFR-2 Hampers Odontoblastic Differentiation of Dental Pulp Stem Cells." Frontiers in Cell and Developmental Biology 9 (June 25, 2021). http://dx.doi.org/10.3389/fcell.2021.665886.

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Dental pulp stem cells (DPSCs) are a source of postnatal stem cells essential for maintenance and regeneration of dentin and pulp tissues. Previous in vivo transplantation studies have shown that DPSCs are able to give rise to odontoblast-like cells, form dentin/pulp-like structures, and induce blood vessel formation. Importantly, dentin formation is closely associated to blood vessels. We have previously demonstrated that DPSC-induced angiogenesis is VEGFR-2-dependent. VEGFR-2 may play an important role in odontoblast differentiation of DPSCs, tooth formation and regeneration. Nevertheless, the role of VEGFR-2 signaling in odontoblast differentiation of DPSCs is still not well understood. Thus, in this study we aimed to determine the role of VEGFR-2 in odontoblast differentiation of DPSCs by knocking down the expression of VEGFR-2 in DPSCs and studying their odontoblast differentiation capacity in vitro and in vivo. Isolation and characterization of murine DPSCs was performed as previously described. DPSCs were induced by VEGFR-2 shRNA viral vectors transfection (MOI = 10:1) to silence the expression of VEGFR-2. The GFP+ expression in CopGFP DPSCs was used as a surrogate to measure the efficiency of transfection and verification that the viral vector does not affect the expression of VEGFR-2. The efficiency of viral transfection was shown by significant reduction in the levels of VEGFR-2 based on the Q-RT-PCR and immunofluorescence in VEGFR-2 knockdown DPSCs, compared to normal DPSCs. VEGFR-2 shRNA DPSCs expressed not only very low level of VEGFR-2, but also that of its ligand, VEGF-A, compared to CopGFP DPSCs in both transcriptional and translational levels. In vitro differentiation of DPSCs in osteo-odontogenic media supplemented with BMP-2 (100 ng/ml) for 21 days demonstrated that CopGFP DPSCs, but not VEGFR-2 shRNA DPSCs, were positive for alkaline phosphatase (ALP) staining and formed mineralized nodules demonstrated by positive Alizarin Red S staining. The expression levels of dentin matrix proteins, dentin matrix protein-1 (Dmp1), dentin sialoprotein (Dspp), and bone sialoprotein (Bsp), were also up-regulated in differentiated CopGFP DPSCs, compared to those in VEGFR-2 shRNA DPSCs, suggesting an impairment of odontoblast differentiation in VEGFR-2 shRNA DPSCs. In vivo subcutaneous transplantation of DPSCs with hydroxyapatite (HAp/TCP) for 5 weeks demonstrated that CopGFP DPSCs were able to differentiate into elongated and polarized odontoblast-like cells forming loose connective tissue resembling pulp-like structures with abundant blood vessels, as demonstrated by H&amp;E, Alizarin Red S, and dentin matrix staining. On the other hand, in VEGFR-2 shRNA DPSC transplants, odontoblast-like cells were not observed. Collagen fibers were seen in replacement of dentin/pulp-like structures. These results indicate that VEGFR-2 may play an important role in dentin regeneration and highlight the potential of VEGFR-2 modulation to enhance dentin regeneration and tissue engineering as a promising clinical application.
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