Therapeutic potential of α7 nicotinic receptor agonists to regulate neuroinflammation in neurodegenerative diseases

Neurodegenerative diseases, such as Alzheimer＇s, Parkinson＇s and Huntington＇s diseases, are all character- ized by a component of innate immunity called neuroinflammation. Neuronal loss and neuroinflammation are two phenomena closely linked. Hence, the neuroinflammation is a relevant target for the management of the neurodegenerative diseases given that, to date, there is no treatment to stop neuronal loss. Several studies have investigated the potential effects of activators of alpha 7 nicotinic acetylcholine receptors in animal models of neurodegenerative diseases. These receptors are widely distributed in the central nervous system. After activation, they seem to mediate the cholinergic anti-inflammatory pathway in the brain. This anti-inflammatory pathway, first described in periphery, regulates activation of microglial cells considered as the resident macrophage population of the central nervous system. In this article, we shortly review the agonists of the alpha 7 nicotinic acetylcholine receptors that have been evaluated in vivo and we focused on the selective positive allosteric modulators of these receptors. These compounds represent a key element to enhance receptor activity only in the presence of the endogenous agonist.

A NEW MODULATION SCHEME FOR IR-UWB COMMUNICATION SYSTEMS

Since the poor performance of orthogonal binary Pulse Position Modulation (PPM) compared with binary Pulse Amplitude Modulation (PAM), this paper presents a new modulation scheme named Pulse Width Modulation (PWM) for Impulse Radio Ultra-WideBand (IR-UWB) communication systems. This modulation scheme uses pulses with equal amplitude and different widths to carry different information. The receiver employs differences between similarity coefficients among these pulses to distinguish different information. Both theoretical analysis and simulation results verify that this novel scheme has a Signal to Noise Ratio (SNR) gain of about 1.75 dB compared with or- thogonal binary PPM, and has an SNR loss of about 1.4 dB compared with binary PAM. Although both the theoretical analysis and simulations are based on time-hopping multiple access, this modulation scheme can also be applied to other accessing techniques of UWB communication systems.

Chaotic pulse position modulation ultra-wideband system based on particle filtering

Traditional chaotic pulse position modulation(CPPM)system has many drawbacks.It introduces delay into the feedback loop,which will lead to divergence of chaotic map easily.The wrong decision of data will cause error propagation.Mismatch of parameters and synchronization error between the receiver and transmitter will arouse high bit error rate.To solve these problems,a demodulation algorithm of CPPM based on particle filtering is proposed.According to the mathematical model of the system,it tracks the real signal by online separation in demodulation.Simulation results show that the proposed method can track the true signal better than the traditional CPPM scheme.What's more,it has good synchronization robustness,reduced error propagation by wrong decision and low bit error rate.

Ultra-low power anti-crosstalk collision avoidance light detection and ranging using chaotic pulse position modulation approach

A novel concept of collision avoidance single-photon light detection and ranging（LIDAR） for vehicles has been demonstrated, in which chaotic pulse position modulation is applied on the transmitted laser pulses for robust anti-crosstalk purposes. Besides, single-photon detectors（SPD） and time correlated single photon counting techniques are adapted, to sense the ultra-low power used for the consideration of compact structure and eye safety. Parameters including pulse rate, discrimination threshold, and number of accumulated pulses have been thoroughly analyzed based on the detection requirements, resulting in specified receiver operating characteristics curves. Both simulation and indoor experiments were performed to verify the excellent anti-crosstalk capability of the presented collision avoidance LIDAR despite ultra-low transmitting power.

Optimal design of basic pulse waveforms for THSS UWB radio systems

Ultrawide bandwidth (UWB) radio, a very promising technique carrying information in very short basic pulses, has properties that make it a viable candidate for short-range wireless communications. In this paper, several short-pulse waveforms based on Gaussian genetic monocycle as well as Gaussian pulse waveform, as candidates of basic UWB pulse waveforms, are firstly proposed and investigated. Their spectrum characteristics, bit transmission rate (BTR), and bit error rate (BER) performance in AWGN channel using time hopping spread spectrum (THSS) and pulse position modulation (PPM) are simulated and evaluated. The numerical results are compared and show that the basic pulse waveforms determine the spectrum characteristics of UWB signals and have much effect on the performance of UWB radio system. The performance of UWB radio system achieved by the proposed basic pulse waveforms is much better than that of UWB radio system realized by other used basic pulse waveforms under the uniform conditions. Also, the polarity of these short basic pulses does not affect the performance of UWB radio system.

The current agonists and positive allosteric modulators ofα7 nAChR for CNS indications in clinical trials

The alpha-7 nicotinic acetylcholine receptor(α7 nAChR), consisting of homomeric α7 subunits, is a ligand-gated Ca^(2+)-permeable ion channel implicated in cognition and neuropsychiatric disorders. Enhancement of α7 nAChR function is considered to be a potential therapeutic strategy aiming at ameliorating cognitive deficits of neuropsychiatric disorders such as Alzheimer's disease(AD) and schizophrenia. Currently, a number of α7 nAChR modulators have been reported and several of them have advanced into clinical trials. In this brief review, we outline recent progress made in understanding the role of the α7 nAChR in multiple neuropsychiatric disorders and the pharmacological effects of α7 nAChR modulators used in clinical trials.

THESEUS1 positively modulates plant defense responses against Botrytis cinerea through GUANINE EXCHANGE FACTOR4 signaling

The plant cell wall is an important interface for sensing pathogen attack and activating signaling pathways that promote plant immune responses.THESEUS1(THE1) acts as a sensor of cell wall integrity that controls cell elongation during plant growth.However, no specific role for THE1 in plant defense responses has been reported. Here, we found that THE1 interacts with GUANINE EXCHANGE FACTOR4(GEF4)and that both proteins play regulatory roles in plant resistance to the necrotrophic fungus Botrytis cinerea.Genetic analysis showed that THE1 and GEF4 function in the same genetic pathway to mediate plant defense responses. In addition, using transcriptome analysis, we identified various genes(such as defense-related,secondary metabolite-related, and transcription factor genes) that are likely downstream targets in the THE1-GEF4 signaling pathway. Our results suggest that THE1 functions as an upstream regulator of GEF4 signaling to positively regulate defense responses against B. cinerea in Arabidopsis.

Location-adaptive transmission for indoor visible light communication

A location-adaptive transmission scheme for indoor visible light communication(VLC) system is proposed in this paper.In this scheme,the symbol error rate(SER) of less than 10-3 should be guaranteed.And the scheme is realized by the variable multilevel pulse-position modulation(MPPM),where the transmitters adaptively adjust the number of time slots n in the MPPM symbol according to the position of the receiver.The purpose of our scheme is to achieve the best data rate in the indoor different locations.The results show that the location-adaptive transmission scheme based on the variable MPPM is superior in the indoor VLC system.

Label swapping and packet transmission of DPSK-labeled PPM signal in optical label switching

A label swapping scheme of an optical labeled signal with differential phase shift keying （DPSK） for label at 2.5 Gb/s and pulse position modulation （PPM） for payload at 40 Gb/s is demonstrated by simulation. Power penalties of -1.8 and -0.8 dB are achieved for both the payload and label over 80-kin single mode fiber （SMF） transmission. This labeling scheme allows the use of four-wave mixing （FWM） in semiconductor optical amplifier （SOA） to perform label erasure, with advantages of transparence for bit rate, high processing rate, simple architecture, and low cost. Label swapping is demonstrated with appropriate penalties of -3.5 and 0.8 dB for PPM payload and new DPSK label, respectively. To further prove the effectiveness of the proposed scheme, label swapping in the case of using 10-Gb/s DPSK label is also investigated with the nnwer penaltios af tq n.nd P dR fnr PPM paylnnrl and new dPRIC lnhol

The design, synthesis and α7 nicotinic acetylcholine receptors positive allosteric modulative evaluation of 3H-quinazolin-4-one derivatives

A series of new 6-substituted 3 H-quinazolin-4-ones（3 a-3 d） were designed, synthesized and evaluated as the type I positive allosteric modulators（PAMs） of human α7 n ACh R expressed in Xenopus ooctyes by two-electrode voltage clamp. However, no compound showed a better efficacious PAM than lead compound 2 in the presence of acetylcholine（100 μM）. The structure-activity relationship（SAR） analysis suggested that thiazolo[4,5-d]pyrimidin-7（6 H）-one was the key biological skeleton.

An approach for parameter estimation of combined CPPM and LFM radar signal

In this paper, the problem of parameter estimation of the combined radar signal adopting chaotic pulse position modulation （CPPM） and linear frequency modulation （LFM）, which can be widely used in electronic countermeasures, is addressed. An approach is proposed to estimate the initial frequency and chirp rate of the combined signal by exploiting the second-order cyclostationarity of the intra-pulse signal. In addition, under the condition of the equal pulse width, the pulse repetition interval （PRI） of the combined signal is predicted using the low-order Volterra adaptive filter. Simulations demonstrate that the proposed cyclic autocorrelation Hough transform （CHT） algorithm is theoretically tolerant to additive white Gaussian noise. When the value of signal noise to ratio （SNR） is less than 4 dB, it can still estimate the intra-pulse parameters well. When SNR = 3 dB, a good prediction of the PRI sequence can be achieved by the Volterra adaptive filter algorithm, even only 100 training samples.

A position sensor based on grating projection with spatial filtering and polarization modulation

A position sensor based on grating projection with spatial filtering and polarization modulation is presented. A grating is projected onto the object to be measured through a 4f optical system with a spatial filter. After reflected by the object, the grating projection is imaged on a detection grating through another 4f optical system to form moiré fringes, The polarization modulated moiré signal is detected to obtain the position information of the object. In the position sensor, the moiré signal varies sinusoidally with the position of object. The measurement is independent of the incident intensity on the projection grating and the reflectivity of the object to be measured, In experiments, the effectiveness of the position sensor is proved, and the root mean square （RMS） error at each measurement position is less than 13 nm.

Performance analysis of a low-complexity nonorthogonal multiple access scheme in visible light communication downlinks using pulse modulations

Although Successive Interference Cancellation(SIC)decoding is widely adopted in Nonorthogonal Multiple Access(NOMA)schemes for the recovery of user data at acceptable complexity,the imperfect SIC would cause Error Propagation(EP),which can severely degrade system performance.In this work,we propose an SIC-free NOMA scheme in pulse modulation based Visible Light Communication(VLC)downlinks,including two types of users with different data rate requirements.Low bit-rate users adopt on-off keying,whereas high bit-rate ones use Multiple Pulse Position Modulation(MPPM).The soft decision decoding scheme is exploited by high bit-rate users to decode MPPM signals,which could fundamentally eliminate the detrimental effect of EP;the scheme is also easier and faster to execute compared with the conventional SIC decoding scheme.Expressions of the symbol error rate and achievable data rate for two types of users are derived.Results of the Monte Carlo simulation are provided to confirm the correctness of theoretical results.

A novel repetition space-time coding scheme for mobile FSO systems

Considering the influence of more random atmospheric turbulence, worse pointing errors and highly dynamic link on the transmission performance of mobile multiple-input multiple-output （MIMO） free space optics （FSO） communica- tion systems, this paper establishes a channel model for the mobile platform. Based on the combination of Alamouti space-time code and time hopping ultra-wide band （TH-UWB） communications, a novel repetition space-time coding （RSTC） method for mobile 2x2 free-space optical communications with pulse position modulation （PPM） is devel- oped. In particular, two decoding methods of equal gain combining （EGC） maximum likelihood detection （MLD） and correlation matrix detection （CMD） are derived. When a quasi-static fading and weak turbulence channel model are considered, simulation results show that whether the channel state information （CSI） is known or not, the coding sys- tem demonstrates more significant performance of the symbol error rate （SER） than the uncoding. In other words, transmitting diversity can be achieved while conveying the information only through the time delays of the modulated signals transmitted from different antennas. CMD has almost the same effect of signal combining with maximal ratio combining （MRC）. However, when the channel correlation increases, SER performance of the coding 2×2 system de- grades significantly.

Sonogashira coupling reaction in the synthesis of novel positive allosteric modulators ofα7 nicotinic acetylcholine receptors

A series of 2-arylamino-1,3,5-triazine derivatives(4a–4g),which were designed and synthesized via Sonogashira coupling reaction,were evaluated using two-electrode voltage clamp(TEVC)recordings of humanα7 nAChR expressed in Xenopus ooctyes.Compound 4g as a positive allosteric modulator(PAM)showed better efficacy than lead compound 3(HZZ-A-11)with an EC50 value of 1.23±0.41μM.Further pharmacological evaluation of compound 4g might lead to the developmental potential for therapy of cognitive deficits commonly shared by neuropsychiatric disorders,such as schizophrenia and Alzheimer’s disease.

Modulation of the effective work function of TiN metal gate for PMOS application

It is important to find a way to modulate the work function of TiN metal gate towards the valence band edge of Si,which can meet the lower threshold voltage requirement of p-type metal-oxide-semiconductor（MOS） transistor.In this work,effects of TiN thickness,post-deposition annealing（PDA）,oxygen incorporation and N concentration variation on the work function of TiN metal gate in MOS structures are systematically investigated. It can be found that the work function positively shifts at the initial stage as the thickness of the TiN layer increases and stabilizes at such a thickness.PDA at N_2 ambience with a trace of O_2 can also cause a positive shift in the work function of TiN metal gate.The same tendency can be observed when oxygen is incorporated into TiN.Finally, increasing the N concentration in TiN can also positively shift the work function.All these measures are effective in modulating the TiN metal gate so that it is more suitable for PMOS application.