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Affine frequency division multiplexing (AFDM), tailored as a novel multicarrier technique utilizing chirp signals for high-mobility communications, exhibits marked advantages compared to traditional orthogonal frequency division multiplexing (OFDM). AFDM is based on the discrete affine Fourier transform (DAFT) with two modifiable parameters of the chirp signals, termed as the pre-chirp parameter and post-chirp parameter, respectively. These parameters can be fine-tuned to avoid overlapping channel paths with different delays or Doppler shifts, leading to performance enhancement especially for doubly dispersive channel. In this paper, we propose a novel AFDM structure with the pre-chirp index modulation (PIM) philosophy (AFDM-PIM), which can embed additional information bits into the pre-chirp parameter design for both spectral and energy efficiency enhancement. Specifically, we first demonstrate that the application of distinct pre-chirp parameters to various subcarriers in the AFDM modulation process maintains the orthogonality among these subcarriers. Then, different pre-chirp parameters are flexibly assigned to each AFDM subcarrier according to the incoming bits. By such arrangement, aside from classical phase/amplitude modulation, extra binary bits can be implicitly conveyed by the indices of selected pre-chirping parameters realizations without additional energy consumption. At the receiver, both a maximum likelihood (ML) detector and a reduced-complexity ML-minimum mean square error (ML-MMSE) detector are employed to recover the information bits. It has been shown via simulations that the proposed AFDM-PIM exhibits superior bit error rate (BER) performance compared to classical AFDM, OFDM and IM-aided OFDM algorithms.

Affine frequency division multiplexing (AFDM) and orthogonal AFDM access (O-AFDMA) are promising techniques based on chirp signals, which are able to suppress the performance deterioration caused by Doppler shifts in high-mobility scenarios. However, the high peak-to-average power ratio (PAPR) in AFDM or O-AFDMA is still a crucial problem, which severely limits their practical applications. In this paper, we propose a discrete affine Fourier transform (DAFT)-spread AFDMA scheme based on the properties of the AFDM systems, named DAFT-s-AFDMA to significantly reduce the PAPR by resorting to the DAFT. We formulate the transmitted time-domain signals of the proposed DAFT-s-AFDMA schemes with localized and interleaved chirp subcarrier allocation strategies. Accordingly, we derive the guidelines for setting the DAFT parameters, revealing the insights of PAPR reduction. Finally, simulation results of PAPR comparison in terms of the complementary cumulative distribution function (CCDF) show that the proposed DAFT-s-AFDMA schemes with localized and interleaved strategies can both attain better PAPR performances than the conventional O-AFDMA scheme.

With the emergence of communication services with stringent requirements such as autonomous driving or on-flight Internet, the sixth-generation (6G) wireless network is envisaged to become an enabling technology for future transportation systems. In this paper, two ways of interactions between 6G networks and transportation are extensively investigated. On one hand, the new usage scenarios and capabilities of 6G over existing cellular networks are firstly highlighted. Then, its potential in seamless and ubiquitous connectivity across the heterogeneous space-air-ground transportation systems is demonstrated, where railways, airplanes, high-altitude platforms and satellites are investigated. On the other hand, we reveal that the introduction of 6G guarantees a more intelligent, efficient and secure transportation system. Specifically, technical analysis on how 6G can empower future transportation is provided, based on the latest research and standardization progresses in localization, integrated sensing and communications, and security. The technical challenges and insights for a road ahead are also summarized for possible inspirations on 6G enabled advanced transportation., Comment: Submitted to IEEE Transactions on Intelligent Transportation Systems (T-ITS)

This article presents a comprehensive study on the emerging near-space communications (NS-COM) within the context of space-air-ground-sea integrated network (SAGSIN). Specifically, we firstly explore the recent technical developments of NS-COM, followed by the discussions about motivations behind integrating NS-COM into SAGSIN. To further demonstrate the necessity of NS-COM, a comparative analysis between the NS-COM network and other counterparts in SAGSIN is conducted, covering aspects of deployment, coverage, channel characteristics and unique problems of NS-COM network. Afterwards, the technical aspects of NS-COM, including channel modeling, random access, channel estimation, array-based beam management and joint network optimization, are examined in detail. Furthermore, we explore the potential applications of NS-COM, such as structural expansion in SAGSIN communication, civil aviation communication, remote and urgent communication, weather monitoring and carbon neutrality. Finally, some promising research avenues are identified, including stratospheric satellite (StratoSat) -to-ground direct links for mobile terminals, reconfigurable multiple-input multiple-output (MIMO) and holographic MIMO, federated learning in NS-COM networks, maritime communication, electromagnetic spectrum sensing and adversarial game, integrated sensing and communications, StratoSat-based radar detection and imaging, NS-COM assisted enhanced global navigation system, NS-COM assisted intelligent unmanned system and free space optical (FSO) communication. Overall, this paper highlights that the NS-COM plays an indispensable role in the SAGSIN puzzle, providing substantial performance and coverage enhancement to the traditional SAGSIN architecture., Comment: 28 pages, 8 figures, 2 tables

The FK506-binding protein 51 (FKBP51) plays an important role in steroid hormone receptors (SHRs) regulation and is related to many pathologic states and diseases such as stress-related disorder, cancer, metabolic syndrome, and chronic pain. FKBP51 acts on several cellular pathways likely through protein-protein interactions via its multifunctional domains. However, the functional basis of FKBP51 in signalling remains obscure due to the poor characterization of its biochemical properties. Importantly, the current FKBP51 inhibitors are not able to inactivate FKBP51 completely based on the occupancy-driven pharmacology. In this thesis, I synthesized a series of small molecules which aim to degrade FK506 binding proteins (FKBPs) via the recently developed proteolysis targeting chimera (PROTAC) strategy. A PROTAC is a heterobifunctional molecule consisting of a ligand for the target protein and a ligand for an E3 ligase, which induces the proteasomal degradation of the target protein. Unlike classical small molecule drugs, PROTACs intend to eliminate the aberrantly functioning protein rather than to inhibit it. By utilizing a selective FKBP51 ligand and non-selective FKBPs ligands developed by our group, two series of PROTACs were designed and synthesized. All of the selective SAFit-PROTACs showed affinities in the nanomolar range for FKBP51, while retaining high selectivity over the close homologue FKBP52. The degradation of cellular FKBP51 was observed upon treatment with the PROTAC MTQ202. In turn, I explored rigidified linkers based on MTQ202 to afford more potent PROTACs. The bicyclic ligand-based PROTACs exhibited outstanding affinities for all of the tested FKBPs in the low nanomolar range to subnanomolar range. The most potent compound, MTQ509, showed the highest binding affinity for FKBP51 so far reported (Ki = 0.92 nM).

The FK506-binding protein 51 (FKBP51) plays an important role in steroid hormone receptors (SHRs) regulation and is related to many pathologic states and diseases such as stress-related disorder, cancer, metabolic syndrome, and chronic pain. FKBP51 acts on several cellular pathways likely through protein-protein interactions via its multifunctional domains. However, the functional basis of FKBP51 in signalling remains obscure due to the poor characterization of its biochemical properties. Importantly, the current FKBP51 inhibitors are not able to inactivate FKBP51 completely based on the occupancy-driven pharmacology. In this thesis, I synthesized a series of small molecules which aim to degrade FK506 binding proteins (FKBPs) via the recently developed proteolysis targeting chimera (PROTAC) strategy. A PROTAC is a heterobifunctional molecule consisting of a ligand for the target protein and a ligand for an E3 ligase, which induces the proteasomal degradation of the target protein. Unlike classical small molecule drugs, PROTACs intend to eliminate the aberrantly functioning protein rather than to inhibit it. By utilizing a selective FKBP51 ligand and non-selective FKBPs ligands developed by our group, two series of PROTACs were designed and synthesized. All of the selective SAFit-PROTACs showed affinities in the nanomolar range for FKBP51, while retaining high selectivity over the close homologue FKBP52. The degradation of cellular FKBP51 was observed upon treatment with the PROTAC MTQ202. In turn, I explored rigidified linkers based on MTQ202 to afford more potent PROTACs. The bicyclic ligand-based PROTACs exhibited outstanding affinities for all of the tested FKBPs in the low nanomolar range to subnanomolar range. The most potent compound, MTQ509, showed the highest binding affinity for FKBP51 so far reported (Ki = 0.92 nM).

The FK506-binding protein 51 (FKBP51) plays an important role in steroid hormone receptors (SHRs) regulation and is related to many pathologic states and diseases such as stress-related disorder, cancer, metabolic syndrome, and chronic pain. FKBP51 acts on several cellular pathways likely through protein-protein interactions via its multifunctional domains. However, the functional basis of FKBP51 in signalling remains obscure due to the poor characterization of its biochemical properties. Importantly, the current FKBP51 inhibitors are not able to inactivate FKBP51 completely based on the occupancy-driven pharmacology. In this thesis, I synthesized a series of small molecules which aim to degrade FK506 binding proteins (FKBPs) via the recently developed proteolysis targeting chimera (PROTAC) strategy. A PROTAC is a heterobifunctional molecule consisting of a ligand for the target protein and a ligand for an E3 ligase, which induces the proteasomal degradation of the target protein. Unlike classical small molecule drugs, PROTACs intend to eliminate the aberrantly functioning protein rather than to inhibit it. By utilizing a selective FKBP51 ligand and non-selective FKBPs ligands developed by our group, two series of PROTACs were designed and synthesized. All of the selective SAFit-PROTACs showed affinities in the nanomolar range for FKBP51, while retaining high selectivity over the close homologue FKBP52. The degradation of cellular FKBP51 was observed upon treatment with the PROTAC MTQ202. In turn, I explored rigidified linkers based on MTQ202 to afford more potent PROTACs. The bicyclic ligand-based PROTACs exhibited outstanding affinities for all of the tested FKBPs in the low nanomolar range to subnanomolar range. The most potent compound, MTQ509, showed the highest binding affinity for FKBP51 so far reported (Ki = 0.92 nM).

The FK506-binding protein 51 (FKBP51) plays an important role in steroid hormone receptors (SHRs) regulation and is related to many pathologic states and diseases such as stress-related disorder, cancer, metabolic syndrome, and chronic pain. FKBP51 acts on several cellular pathways likely through protein-protein interactions via its multifunctional domains. However, the functional basis of FKBP51 in signalling remains obscure due to the poor characterization of its biochemical properties. Importantly, the current FKBP51 inhibitors are not able to inactivate FKBP51 completely based on the occupancy-driven pharmacology. In this thesis, I synthesized a series of small molecules which aim to degrade FK506 binding proteins (FKBPs) via the recently developed proteolysis targeting chimera (PROTAC) strategy. A PROTAC is a heterobifunctional molecule consisting of a ligand for the target protein and a ligand for an E3 ligase, which induces the proteasomal degradation of the target protein. Unlike classical small molecule drugs, PROTACs intend to eliminate the aberrantly functioning protein rather than to inhibit it. By utilizing a selective FKBP51 ligand and non-selective FKBPs ligands developed by our group, two series of PROTACs were designed and synthesized. All of the selective SAFit-PROTACs showed affinities in the nanomolar range for FKBP51, while retaining high selectivity over the close homologue FKBP52. The degradation of cellular FKBP51 was observed upon treatment with the PROTAC MTQ202. In turn, I explored rigidified linkers based on MTQ202 to afford more potent PROTACs. The bicyclic ligand-based PROTACs exhibited outstanding affinities for all of the tested FKBPs in the low nanomolar range to subnanomolar range. The most potent compound, MTQ509, showed the highest binding affinity for FKBP51 so far reported (Ki = 0.92 nM).

The FK506-binding protein 51 (FKBP51) plays an important role in steroid hormone receptors (SHRs) regulation and is related to many pathologic states and diseases such as stress-related disorder, cancer, metabolic syndrome, and chronic pain. FKBP51 acts on several cellular pathways likely through protein-protein interactions via its multifunctional domains. However, the functional basis of FKBP51 in signalling remains obscure due to the poor characterization of its biochemical properties. Importantly, the current FKBP51 inhibitors are not able to inactivate FKBP51 completely based on the occupancy-driven pharmacology. In this thesis, I synthesized a series of small molecules which aim to degrade FK506 binding proteins (FKBPs) via the recently developed proteolysis targeting chimera (PROTAC) strategy. A PROTAC is a heterobifunctional molecule consisting of a ligand for the target protein and a ligand for an E3 ligase, which induces the proteasomal degradation of the target protein. Unlike classical small molecule drugs, PROTACs intend to eliminate the aberrantly functioning protein rather than to inhibit it. By utilizing a selective FKBP51 ligand and non-selective FKBPs ligands developed by our group, two series of PROTACs were designed and synthesized. All of the selective SAFit-PROTACs showed affinities in the nanomolar range for FKBP51, while retaining high selectivity over the close homologue FKBP52. The degradation of cellular FKBP51 was observed upon treatment with the PROTAC MTQ202. In turn, I explored rigidified linkers based on MTQ202 to afford more potent PROTACs. The bicyclic ligand-based PROTACs exhibited outstanding affinities for all of the tested FKBPs in the low nanomolar range to subnanomolar range. The most potent compound, MTQ509, showed the highest binding affinity for FKBP51 so far reported (Ki = 0.92 nM).