Inhibition of CREB Binding and Function with a Dual-Targeting Ligand.

CBP/p300 is a master transcriptional coactivator that regulates gene activation by interacting with multiple transcriptional activators. Dysregulation of protein-protein interactions (PPIs) between the CBP/p300 KIX domain and its activators is implicated in a number of cancers, including breast, leukemia, and colorectal cancer. However, KIX is typically considered "undruggable" because of its shallow binding surfaces lacking both significant topology and promiscuous binding profiles. We previously reported a dual-targeting peptide (MybLL-tide) that inhibits the KIX-Myb interaction with excellent specificity and potency. Here, we demonstrate a branched, second-generation analogue, CREBLL-tide, that inhibits the KIX-CREB PPI with higher potency and selectivity. Additionally, the best of these CREBLL-tide analogues shows excellent and selective antiproliferation activity in breast cancer cells. These results indicate that CREBLL-tide is an effective tool for assessing the role of KIX-activator interactions in breast cancer and expanding the dual-targeting strategy for inhibiting KIX and other coactivators that contain multiple binding surfaces.

Turbulence-resistant free space optical communication via chaotic block-matching and 3D filtering.

In this paper, we propose a chaotic block-matching and three-dimensional (C-BM3D) filtering algorithm to remove the noise and enhance the security in the turbulent channel of free space optical (FSO) communication. We experimentally demonstrate the performance of C-BM3D by comparing it with chaotic non-local means filtering (C-NLM), chaotic Gaussian filtering and chaotic Median filtering based on Log-normal and Gamma-Gamma turbulence models. The results show that the peak signal-to-noise ratios (PSNRs) of C-BM3D in the weak turbulence under Log-normal and Gamma-Gamma models are up to 96.2956 and 93.2853, respectively. The C-BM3D also achieves superior image similarity in Log-normal turbulent channel, with its structural similarity index measures (SSIMs) nearly equal to 1. Additionally, the signal-to-noise ratio (SNR) of C-BM3D ranks the highest, and its bit error rate (BER) improves by at least 15 dB compared to that of the other three algorithms. The experimental results indicate that the C-BM3D can be a good candidate for the next generation of FSO communication in security and turbulence resistance.

Two-stage look-up-table-based 16QAM vector millimeter-wave signal generation and reception.

We propose a two-stage look-up table (LUT) scheme for a photonic 16 quadrature-amplitude-modulation (QAM) millimeter-wave (MMW) communication system. The first-stage LUT is used at the transmitter, which can eliminate complex computational processes and adaptively adjust the precoded amplitude values to achieve optimal performance without being affected by half-wave voltage variations. We have completed a signal transmission below the hard-decision forward error correction (HD-FEC) threshold of 3.8 × 10-3 at the baud rate of 2/4 GBaud for weak turbulence and 2 GBaud for medium turbulence free-space optics (FSO) channel transmission. The second-stage LUT is used for post-compensation at the receiver as a nonlinear scheme that records the average pattern-related distortion of the channel and mitigates transmission impairment through nonlinear post-compensation. With the help of the second-stage LUT, the sensitivity of the optical receiver is improved by 0.15 dB at a baud rate of 2 GBaud for medium turbulence FSO channel transmission. As the baud rate increases to 4 GBaud, the system's bit error ratio (BER) can reach the soft-decision forward error correction (SD-FEC) threshold of 4.2 × 10-2 only after applying the second-stage LUT.

Hybrid digital-analog FSO fronthaul system with channel-adaptive insertion of analog bandwidth.

With the arrival of the 5th generation mobile network, the number of user devices is increasing exponentially, and thus it is necessary to expand the capacity of transmission systems. In order to further improve the system spectral efficiency on the basis of existing mobile fronthaul devices, we propose a hybrid digital-analog fronthaul transmission system with adaptive insertion of analog bandwidth, which can dynamically change the position of inserted analog bandwidth based on the state information of free space optical (FSO) channel. We consider the effects of atmospheric attenuation and turbulence on the FSO channel and derive an analytical expression for the maximum analog signal bandwidth that can be inserted into the first null of the digital signal spectrum to meet BER requirement of 3.8 × 10-3. Through a comprehensive simulation, it is verified that the analog bandwidth is obtained by this expression can exactly represent the lower bound of the simulation results under weak turbulence condition. The obtained results show that the maximum insertable analog bandwidth beyond the spectral null of the digital signal can reach 10% of the digital signal bandwidth, even in the FSO link with a transmission distance of 0.5 km and attenuation factor of 8 dB/km.

Secure turbulence-resistant coherent free-space optical communications via chaotic region-optimized probabilistic constellation shaping.

We propose a chaotic region-optimized probabilistic constellation shaping (CRPCS) scheme to enhance the security and the resistance to turbulence for free-space optical (FSO) communications. For this approach, a four-dimensional hyperchaotic system generates a pseudorandom sequence to rotate and encrypt the constellation. Constellation distribution of short pseudorandom sequences behaves as the law of a non-uniform character. Grouping long pseudorandom sequences and counting the characteristics of constellation distribution can realize probabilistic constellation shaping with low and fixed redundant information. We demonstrate a 56 Gbyte/s coherent FSO communication system based on log-normal and Gamma-Gamma turbulence models with a key space of 1075. The results show that the optical receiver sensitivity is improved by 0.3-1.1 dB, and the transmission distance is also improved by 3.2%-7.0% in different shaping cases.

Independent dual-single-sideband QPSK signal detection based on a single photodetector.

The two sidebands of the independent dual-single-sideband (dual-SSB) signal can carry different information to achieve higher spectral efficiency. However, the two sidebands of the independent dual-SSB vector signal are received independently. Generally, the receiver divides the signal into two channels. For each channel, we use an optical bandpass filter (OBPF) to select the left sideband (LSB) or right sideband (RSB), respectively. Then a photodetector (PD) is used for photoelectric conversion, followed by subsequent digital signal processing (DSP). To reduce the complexity and cost of the receiver, we propose a new independent dual-SSB vector signal detection scheme based on a single PD combined with conventional DSP. An electric bandpass filter (EBPF) filters out high-frequency components after photoelectric conversion, and then the signal is quadrature demodulated and processed by the DSP algorithm. The LSB and RSB are quadrature phase-shift keying (QPSK) modulated with an initial phase difference of π/4. Simulation results show that the proposed scheme performs better bit error rate (BER). For back-to-back (BTB) transmission, the BER of 2-Gbaud independent dual-SSB vector signal (1-Gbuad RSB and 1-Gbaud LSB) can reach the hard-decision forward error correction (HD-FEC) threshold of 3.8 × 10-3 when the input optical power into PD is -20 dBm. For 1-km and 2-km weak turbulence free-space optical (FSO) channel transmission, the BER of 2-Gbaud independent dual-SSB vector signal can reach the HD-FEC threshold when the input optical power into PD is -18.8 and -17 dBm, respectively. For 1-km weak turbulence FSO channel transmission, the BER of 4-, 8-, and 16-Gbuad independent dual-SSB vector signal can reach the HD-FEC threshold when the input optical power into PD is -17.8, -16, and -15 dBm, respectively.

Full-duplex transmission without an uplink light source for a millimeter-wave radio over a free-space optical system.

The radio over free-space optical (RoFSO) system is a promising alternative technique for mobile fronthaul networks such as aerial base stations where fiber link is unavailable to deploy. However, the full-duplex transmission imposes challenges on the design of the RoFSO system due to the additional structural complexity when ease-of-installation is a mandatory request. The interplay between the uplink and downlink for a simplified structure has been less investigated in related works. In this paper, we propose a full-duplex RoFSO transmission system structure in which the uplink light source is physically saved. The optical center carrier of the double-sideband (DSB) modulated signal in the downlink is extracted as the light source for the uplink, and thus the system complexity is reduced. In order to mitigate the permanence degradation of uplink transmission due to the attenuated light source, channel estimation and power pre-compensation are implemented without additional training symbols by utilizing the characteristics of the channel correlation between uplink and downlink and the information independence of optical center carrier in the DSB. The proposed channel estimation algorithm is verified theoretically and experimentally. The results show that the difference between uplink and downlink channel attenuation is -0.7dB. In case of the excessive power compensation and the resulting effects, a power control mechanism is introduced to the power pre-compensation. By using the power pre-compensation mechanism, the bit error rate (BER) can reach 1.58×10-3 and 3.8×10-3, respectively, under the channel conditions of medium turbulence and weak turbulence. Owing to the power control mechanism, the power saving rates of downlink and uplink are up to 78% and 67%.

Norstictic Acid Is a Selective Allosteric Transcriptional Regulator.

Inhibitors of transcriptional protein-protein interactions (PPIs) have high value both as tools and for therapeutic applications. The PPI network mediated by the transcriptional coactivator Med25, for example, regulates stress-response and motility pathways, and dysregulation of the PPI networks contributes to oncogenesis and metastasis. The canonical transcription factor binding sites within Med25 are large (∼900 Å2) and have little topology, and thus, they do not present an array of attractive small-molecule binding sites for inhibitor discovery. Here we demonstrate that the depsidone natural product norstictic acid functions through an alternative binding site to block Med25-transcriptional activator PPIs in vitro and in cell culture. Norstictic acid targets a binding site comprising a highly dynamic loop flanking one canonical binding surface, and in doing so, it both orthosterically and allosterically alters Med25-driven transcription in a patient-derived model of triple-negative breast cancer. These results highlight the potential of Med25 as a therapeutic target as well as the inhibitor discovery opportunities presented by structurally dynamic loops within otherwise challenging proteins.

Channel prediction for intelligent FSO transmission system.

Free space optical (FSO) communication has attracted significant attention due to its high transmission rate and information security. Nevertheless, the FSO link is sensitive to various weather conditions which limit its application range. Thus, research on the FSO channel plays an important role for combatting channel fading. In the paper, we first establish a FSO transmission testbed to obtain received signal strength indication (RSSI) information of optical signal. Then we utilize an environmental chamber for indoor experiments to simulate weather changes in the real world. Finally, based on the true meteorological dataset from the official department and the RSSI dataset from the experiments, we employ expanded gated recurrent unit (GRU) neural networks to implement the FSO channel prediction. The results demonstrate that the proposed scheme can achieve the prediction of FSO channel fading with a high precision, where the absolute percentage error (APE) values lower than 6.9% account for up to ninety% of results.

Asymmetric constellation transmission for a coherent free-space optical system with spatial diversity.

Spatial diversity is widely recognized as an effective technique for free-space optical (FSO) communication to combat channel fading. Most existing works on spatial diversity in FSO systems focus on intensity modulation and direct detection, while fewer mention coherent optical detection, which excels in optical receiver responsivity. Spatial diversity enables the FSO coherent system to demodulate the signal components of in-phase (I) and quadrature (Q) separately and thus simplify the coherent detector. More importantly, due to the differential channel conditions between I and Q components, we are offered a chance to realize an asymmetric quadrature amplitude modulation (QAM) constellation that can utilize the channel capacity of both I and Q components more sufficiently. Performance results demonstrate that the simplified structure and improved spectrum efficiency can be realized in the asymmetric QAM transmission system with an acceptable bit-error-rate loss.