The HTLV-I oncoprotein Tax inactivates the tumor suppressor FBXW7.

Human T-cell leukemia virus type 1 (HTLV-I) is the etiological agent of adult T-cell leukemia (ATL). Mutational analysis has demonstrated that the tumor suppressor, F-box and WD repeat domain containing 7 (FBXW7/FBW7/CDC4), is mutated in primary ATL patients. However, even in the absence of genetic mutations, FBXW7 substrates are stabilized in ATL cells, suggesting additional mechanisms can prevent FBXW7 functions. Here, we report that the viral oncoprotein Tax represses FBXW7 activity, resulting in the stabilization of activated Notch intracellular domain, c-MYC, Cyclin E, and myeloid cell leukemia sequence 1 (BCL2-related) (Mcl-1). Mechanistically, we demonstrate that Tax directly binds to FBXW7 in the nucleus, effectively outcompeting other targets for binding to FBXW7, resulting in decreased ubiquitination and degradation of FBXW7 substrates. In support of the nuclear role of Tax, a non-degradable form of the nuclear factor kappa B subunit 2 (NFκB2/p100) was found to delocalize Tax to the cytoplasm, thereby preventing Tax interactions with FBXW7 and Tax-mediated inhibition of FBXW7. Finally, we characterize a Tax mutant that is unable to interact with FBXW7, unable to block FBXW7 tumor suppressor functions, and unable to effectively transform fibroblasts. These results demonstrate that HTLV-I Tax can inhibit FBXW7 functions without genetic mutations to promote an oncogenic state. These results suggest that Tax-mediated inhibition of FBXW7 is likely critical during the early stages of the cellular transformation process. IMPORTANCE: F-box and WD repeat domain containing 7 (FBXW7), a critical tumor suppressor of human cancers, is frequently mutated or epigenetically suppressed. Loss of FBXW7 functions is associated with stabilization and increased expression of oncogenic factors such as Cyclin E, c-Myc, Mcl-1, mTOR, Jun, and Notch. In this study, we demonstrate that the human retrovirus human T-cell leukemia virus type 1 oncoprotein Tax directly interacts with FBXW7, effectively outcompeting other targets for binding to FBXW7, resulting in decreased ubiquitination and degradation of FBXW7 cellular substrates. We further demonstrate that a Tax mutant unable to interact with and inactivate FBXW7 loses its ability to transform primary fibroblasts. Collectively, our results describe a novel mechanism used by a human tumor virus to promote cellular transformation.

Unmanned-aerial-vehicle based optical camera communication system using light-diffusing fiber and rolling-shutter image-sensor.

We put forward and demonstrate a light-diffusing fiber equipped unmanned-aerial-vehicle (UAV) to provide a large field-of-view (FOV) optical camera communication (OCC) system. The light-diffusing fiber can act as a bendable, lightweight, extended and large FOV light source for the UAV-assisted optical wireless communication (OWC). During UAV flying, the light-diffusing fiber light source could be tilted or bended; hence, offering large FOV as well as supporting large receiver (Rx) tilting angle are particularly important for the UAV-assisted OWC systems. To improve the transmission capacity of the OCC system, one method based on the camera shutter mechanism, which is known as rolling-shuttering is utilized. The rolling-shuttering method makes use of the feature of complementary-metal-oxide-semiconductor (CMOS) image sensor to extract signal pixel-row by pixel-row. The data rate can be significantly increased since the capture start time for each pixel-row is different. As the light-diffusing fiber is thin and occupies only a few pixels in the CMOS image frame, Long-short-term-memory neural-network (LSTM-NN) is used to enhance the rolling-shutter decoding. Experimental results show that the light-diffusing fiber can satisfactorily act as an "omnidirectional optical antenna" providing wide FOVs and 3.6 kbit/s can be achieved, accomplishing the pre-forward error correction bit-error-rate (pre-FEC BER = 3.8 × 10-3).

A novel dynamic cardiorespiratory coupling quantification method reveals the effect of aging on the autonomic nervous system.

Traditional cardiopulmonary coupling (CPC) based on the Fourier transform shares an inherent trade-off between temporal and frequency resolutions with fixed window designs. Therefore, a cross-wavelet cardiorespiratory coupling (CRC) method was developed to highlight interwave cardiorespiratory dynamics and applied to evaluate the age effect on the autonomic regulation of cardiorespiratory function. The cross-wavelet CRC visualization successfully reflected dynamic alignments between R-wave interval signal (RR intervals) and respiration. Strong and continuous CRC was shown if there was perfect temporal coordination between consecutive R waves and respiration, while CRC becomes weaker and intermittent without such coordination. Using real data collected on electrocardiogram (ECG) and respiratory signals, the heart rate variability (HRV) and CRC were calculated. Subsequently, comparisons were conducted between young and elderly individuals. Young individuals had significantly higher partial time and frequency HRV indices than elderly individuals, indicating stronger control of parasympathetic regulation. The overall coupling strength of the CRC of young individuals was higher than that of elderly individuals, especially in high-frequency power, which was significantly lower in the elderly group than in the young group, achieving better results than the HRV indices in terms of statistical significance. Further analyses of the time-frequency dynamics of CRC indices revealed that the coupling strength was consistently higher in the high-frequency (HF) band (0.15-0.4 Hz) in young participants compared to elderly individuals. The dynamic CRC between respiration and HRV indices was accessible by integrating the cross-wavelet spectrum and coherence. Young participants had a significantly higher level of CRC in the HF band, indicating that aging reduces vagus nerve modulation.

Bi-Directional Free-Space Visible Light Communication Supporting Multiple Moveable Clients Using Light Diffusing Optical Fiber.

In this work, we put forward and demonstrate a bi-direction free-space visible light communication (VLC) system supporting multiple moveable receivers (Rxs) using a light-diffusing optical fiber (LDOF). The downlink (DL) signal is launched from a head-end or central office (CO) far away to the LDOF at the client side via a free-space transmission. When the DL signal is launched to the LDOF, which acts as an optical antenna to re-transmit the DL signal to different moveable Rxs. The uplink (UL) signal is sent via the LDOF towards the CO. In a proof-of-concept demonstration, the LDOF is 100 cm long, and the free space VLC transmission between the CO and the LDOF is 100 cm. 210 Mbit/s DL and 850 Mbit/s UL transmissions meet the pre-forward-error-correction bit error rate (pre-FEC BER = 3.8 × 10-3) threshold.

Flexible Data Rate Allocation Using Non-Orthogonal Multiple Access (NOMA) in a Mode Division Multiplexing (MDM) Optical Power Splitter for System-on-Chip Networks.

We put forward and demonstrate a silicon photonics (SiPh)-based mode division multiplexed (MDM) optical power splitter that supports transverse-electric (TE) single-mode, dual-mode, and triple-mode (i.e., TE0, TE1, and TE2). An optical power splitter is needed for optical signal distribution and routing in optical interconnects. However, a traditional optical splitter only divides the power of the input optical signal. This means the same data information is received at all the output ports of the optical splitter. The powers at different output ports may change depending on the splitting ratio of the optical splitter. The main contributions of our proposed optical splitter are: (i) Different data information is received at different output ports of the optical splitter via the utilization of NOMA. By adjusting the power ratios of different channels in the digital domain (i.e., via software control) at the Tx, different channel data information can be received at different output ports of the splitter. It can increase the flexibility of optical signal distribution and routing. (ii) Besides, the proposed optical splitter can support the fundamental TE0 mode and the higher modes TE1, TE2, etc. Supporting mode-division multiplexing and multi-mode operation are important for future optical interconnects since the number of port counts is limited by the chip size. This can significantly increase the capacity besides wavelength division multiplexing (WDM) and spatial division multiplexing (SDM). The integrated SiPh MDM optical power splitter consists of a mode up-conversion section implemented by asymmetric directional couplers (ADCs) and a Y-branch structure for MDM power distribution. Here, we also propose and discuss the use of the Genetic algorithm (GA) for the MDM optical power splitter parameter optimization. Finally, to provide adjustable data rates at different output ports after the MDM optical power splitter, non-orthogonal multiple access-orthogonal frequency division multiplexing (NOMA-OFDM) is also employed. Experimental results validate that, in three modes (TE0, TE1, and TE2), user-1 and user-2 achieve data rates of (user-1: greater than 22 Gbit/s; user-2: greater than 12 Gbit/s) and (user-1: greater than 12 Gbit/s; user-2: 24 Gbit/s), respectively, at power-ratio (PR) = 2.0 or 3.0. Each channel meets the hard-decision forward-error-correction (HD-FEC, i.e., BER = 3.8 × 10-3) threshold. The proposed method allows flexible data rate allocation for multiple users for optical interconnects and system-on-chip networks.

Wideband and Channel Switchable Mode Division Multiplexing (MDM) Optical Power Divider Supporting 7.682 Tbit/s for On-Chip Optical Interconnects.

Silicon photonics (SiPh) are considered a promising technology for increasing interconnect speed and capacity while decreasing power consumption. Mode division multiplexing (MDM) enables signals to be transmitted in different orthogonal modes in a single waveguide core. Wideband MDM components simultaneously supporting wavelength division multiplexing (WDM) and orthogonal frequency-division multiplexing (OFDM) can significantly increase the transmission capacity for optical interconnects. In this work, we propose, fabricate and demonstrate a wideband and channel switchable MDM optical power divider on an SOI platform, supporting single, dual and triple modes. The switchable MDM power divider consists of two parts. The first part is a cascaded Mach-Zehnder interferometer (MZI) for switching the data from their original TE0, TE1 and TE2 modes to different modes among themselves. After the target modes are identified, mode up-conversion and Y-branch are utilized in the second part for the MDM power division. Here, 48 WDM wavelength channels carrying OFDM data are successfully switched and power divided. An aggregated capacity of 7.682 Tbit/s is achieved, satisfying the pre-forward error correction (pre-FEC) threshold (bit-error-rate, BER = 3.8 × 10-3). Although up to three MDM modes are presented in the proof-of-concept demonstration here, the proposed scheme can be scaled to higher order modes operation.

Design Consideration, Numerical and Experimental Analyses of Mode-Division-Multiplexed (MDM) Silicon Photonics Integrated Circuit with Sharp Bends.

Due to the popularity of different high bandwidth applications, it is becoming increasingly difficult to satisfy the huge data capacity requirements, since the traditional electrical interconnects suffer significantly from limited bandwidth and huge power consumption. Silicon photonics (SiPh) is one of the important technologies for increasing interconnect capacity and decreasing power consumption. Mode-division multiplexing (MDM) allows signals to be transmitted simultaneously, at different modes, in a single waveguide. Wavelength-division multiplexing (WDM), non-orthogonal multiple access (NOMA) and orthogonal-frequency-division multiplexing (OFDM) can also be utilized to further increase the optical interconnect capacity. In SiPh integrated circuits, waveguide bends are usually inevitable. However, for an MDM system with a multimode bus waveguide, the modal fields will become asymmetric when the waveguide bend is sharp. This will introduce inter-mode coupling and inter-mode crosstalk. One simple approach to achieve sharp bends in multimode bus waveguide is to use a Euler curve. Although it has been reported in the literature that sharp bends based on a Euler curve allow high performance and low inter-mode crosstalk multimode transmissions, we discover, by simulation and experiment, that the transmission performance between two Euler bends is length dependent, particularly when the bends are sharp. We investigate the length dependency of the straight multimode bus waveguide between two Euler bends. High transmission performance can be achieved by a proper design of the waveguide length, width, and bend radius. By using the optimized MDM bus waveguide length with sharp Euler bends, proof-of-concept NOMA-OFDM experimental transmissions, supporting two MDM modes and two NOMA users, are performed.

Optical camera communication (OCC) using a laser-diode coupled optical-diffusing fiber (ODF) and rolling shutter image sensor.

We demonstrate an optical-camera-communication (OCC) system utilizing a laser-diode (LD) coupled optical-diffusing-fiber (ODF) transmitter (Tx) and rolling-shutter based image sensor receiver (Rx). The ODF is a glass optical fiber produced for decorative lighting or embedded into small areas where bulky optical sources cannot fit. Besides, decoding the high data rate rolling-shutter pattern from the thin ODF Tx is very challenging. Here, we propose and experimentally demonstrate the pixel-row-per-bit based neural-network (PPB-NN) to decode the rolling-shutter-pattern emitted by the thin ODF Tx. The proposed PPB-NN algorithm is discussed. The proposed PPB-NN method can satisfy the pre-forward error correction (FEC) BER at data rate of 3,300 bit/s at a transmission distance of 35 cm. Theoretical analysis of the maximum ODF Tx angle is also discussed; and our experimental values agree with our theoretical results.

2.805 Gbit/s high-bandwidth phosphor white light visible light communication utilizing an InGaN/GaN semipolar blue micro-LED.

We propose and implement a high-bandwidth white-light visible light communication (VLC) system accomplishing data rate of 2.805 Gbit/s utilizing a semipolar blue micro-LED. The system uses an InGaN/GaN semipolar (20-21) blue micro-LED to excite yellow phosphor film for high-speed VLC. The packaged 30 µm 2 × 4 blue micro-LED array has an electrical-to-optical (EO) bandwidth of 1042.5 MHz and a peak wavelength of 447 nm. The EO bandwidth of the white-light VLC system is 849 MHz. Bit error rate (BER) of 2.709 × 10-3 meeting the pre-forward error correction (FEC) threshold is accomplished by employing a bit and power loaded orthogonal frequency division multiplexing (OFDM) signal. The proposed white-light VLC system employs simple and inexpensive yellow phosphor film for white-light conversion, complex color conversion material is not needed. Besides, no optical blue filter is employed in the white-light VLC system. The fabrication of the InGaN/GaN semipolar (20-21) blue micro-LED is discussed, and its characteristics are also evaluated.

Using lighting design tool to simplify the visible light positioning plan and reduce the deep learning loading.

We put forward and transform the commercially available lighting design software into an indoor visible light positioning (VLP) design tool. The proposed scheme can work well with different deep learning methods for reducing the loading of training data set collection. The indoor VLP models under evaluation include second order regression, fully-connected neural-network (FC-NN), and convolutional neural-network (CNN). Experimental results show that the similar positioning accuracy can be obtained when the indoor VLP models are trained with experimentally acquired data set or trained with software obtained data set. Hence, the proposed method can reduce the training loading for the indoor VLP.

Recording of a holographic cylindrical vector beam converter with a truncated cone prism.

This Letter proposes a holographic cylindrical vector beam converter (HCVBC) design that incorporates a continuously polarization-selective volume hologram circular-grating. A specially designed truncated cone prism is adopted for recording, which is conducted with a single incident, expanded, radially polarized beam. A prototype of this HCVBC was recorded and tested successfully. This design has the advantages of high diffraction efficiency, a narrow band, compactness, and planar configuration; thus, it is especially suitable for low-cost mass production and has high potential for application in related fields.

3D Visible Light-Based Indoor Positioning System Using Two-Stage Neural Network (TSNN) and Received Intensity Selective Enhancement (RISE) to Alleviate Light Non-Overlap Zones.

The high precision three-dimensional (3D) visible light-based indoor positioning (VLIP) systems have gained much attention recently for people or robot navigation, access tracking, etc. In this work, we put forward and present the first demonstration, up to the authors' knowledge, of a 3D VLIP system utilizing a two-stage neural network (TSNN) model. The positioning performance would degrade when the distance between the light emitting diode (LED) plane and the receiver (Rx) plane increases; however, because of the finite LED field-of-view (FOV), light non-overlap zones are created. These light non-overlap zones will produce high positioning error particularly for the 3D VLIP systems. Here, we also propose and demonstrate the Received-Intensity-Selective-Enhancement scheme, known as RISE, to alleviate the light non-overlap zones in the VLIP system. In a practical test-room with dimensions of 200 × 150 × 300 cm3, the experimental results show that the mean errors in the training and testing data sets are reduced by 54.1% and 27.9% when using the TSNN model with RISE in the z-direction, and they are reduced by 39.1% and 37.8% in the xy-direction, respectively, when comparing that with using a one stage NN model only. At the cumulative distribution function (CDF) P90, the TSNN model with RISE can reduce the errors by 36.78% when compared with that in the one stage NN model.

Optical Beam Steerable Visible Light Communication (VLC) System Supporting Multiple Users Using RGB and Orthogonal Frequency Division Multiplexed (OFDM) Non-Orthogonal Multiple Access (NOMA).

In order to achieve high-capacity visible light communication (VLC), five dimensions in physics, including frequency, time, quadrature modulation, space, and polarization can be utilized. Orthogonality should be maintained in order to reduce the crosstalk among different dimensions. In this work, we illustrate a high-capacity 21.01 Gbit/s optical beam steerable VLC system with vibration mitigation based on orthogonal frequency division multiplexed (OFDM) non-orthogonal multiple access (NOMA) signals using red, green, and blue (RGB) laser-diodes (LDs). The OFDM-NOMA can increase the spectral efficiency of VLC signal by allowing high overlapping of different data channel spectra in the power domain to maximize the bandwidth utilization. In the NOMA scheme, different data channels are digitally multiplexed using different levels of power with superposition coding at the transmitter (Tx). Successive interference cancellation (SIC) is then utilized at the receiver (Rx) to retrieve different power multiplexed data channels. The total data rates (i.e., Data 1 and Data 2) achieved by the R/G/B OFDM-NOMA channels are 8.07, 6.62, and 6.32 Gbit/s, respectively, achieving an aggregated data rate of 21.01 Gbit/s. The corresponding average signal-to-noise ratios (SNRs) of Data 1 in the R, G, and B channels are 9.05, 9.18 and 8.94 dB, respectively, while that of Data 2 in the R, G, and B channels are 14.92, 14.29, and 13.80 dB, respectively.

High-bandwidth InGaN/GaN semipolar micro-LED acting as a fast photodetector for visible light communications.

We propose and demonstrate a green semipolar (20-21) micro-light emitting diode (LED) acting as a high speed visible light communication (VLC) photodiode (PD). The micro-LED PD has the optical-to-electrical (OE) response of 228 MHz. A record data rate of 540 Mbit/s in on-off-keying (OOK) format with free-space transmission distance of 1.1 m was achieved, fulfilling the pre-forward error correction (FEC) limit. Many transmitters (Txs) and receivers (Rxs) is required to support the high density pico/femto-cells in future wireless networks, as well as the Internet-of-Things (IOT) networks. The proposed work could allow the realization of a low-cost, small-footprint and a high level of integration of VLC Txs and Rxs on the same platform.

Hybrid Fiber-Optic Sensing Integrating Brillouin Optical Time-Domain Analysis and Fiber Bragg Grating for Long-Range Two-Parameter Measurement.

Distributed fiber sensing (DFS) can provide real-time signals and warnings. The entire length of fiber optic cable can act as a sensing element, but the accuracy is sometimes limited. On the other hand, point-to-point fiber sensing (PPFS) is usually implemented using one or more fiber Bragg gratings (FBGs) at specific positions along with the fiber for the monitoring of specific parameters (temperature, strain, pressure, and so on). However, the cost becomes expensive when the number of FBGs increases. A hybrid fiber sensing scheme is thus proposed, combining the advantages of DFS and PPFS. It is based on a Brillouin optical time-domain analysis (BOTDA) fiber system with additional FBGs embedded at certain positions where it is necessary to detect specific parameters. The hybrid fiber sensing system has the advantages of full sensing coverage at essential locations that need to be carefully monitored. In our work, the test results showed that the proposed system could achieve a sensing distance of 16 km with the single-mode fiber with a 2 m spatial resolution. For FBG parameter measurements, the temperature variation was 52 °C, from 25 °C to 77 °C, with a temperature sensitivity of 23 pm/°C, and the strain was from 0 to 400 µÎµ, with a strain sensitivity of 0.975 pm/µÎµ, respectively, using two FBGs.

Loss of FBXW7-mediated degradation of BRAF elicits resistance to BET inhibitors in adult T cell leukemia cells.

BACKGROUND: Human T cell leukemia virus type 1 (HTLV-1)-associated adult T cell leukemia (ATL) has a very poor prognosis with a median survival of 8 months and a 4-year overall survival of 11% for acute ATL. Present treatment options are limited and there is no curative therapy for ATL. Ubiquitin ligase FBXW7 is commonly mutated or functionally inactivated in human cancers. Consistent with the notion that FBXW7 controls the degradation of many oncoproteins, loss of FBXW7 has been linked to increased drug resistance or sensitivity in cancer cells. METHOD: In this study, we have characterized FBXW7 mutants previously identified in HTLV-I-infected ATL patient samples. TET-inducible ATL cells carrying wild type or mutated FBXW7 were analyzed for target degradation and for drug sensitivity. RESULTS: Our results demonstrate that mutations in FBXW7 can selectively disrupt ubiquitination and proteasome degradation of target proteins: c-MYC, cyclin E and MCL1. Both c-MYC and MYCN were highly expressed in uncultured ATL patient's samples and ATL-derived cell lines; and ATL cells demonstrated sensitivity to BET inhibitors in vitro and in vivo. High-throughput reverse phase protein array revealed BRAF as a novel target of FBXW7 and further experiments showed that mutations in FBXW7 preventing degradation of BRAF provided resistance to BET inhibitors. In contrast to R465, hot spot FBXW7 mutations at R505C retained degradation of BRAF but not NOTCH1, c-MYC, cyclin E, or MCL1. Finally, a combination therapy using BET inhibitors along with a BRAF or an ERK inhibitor prevented tumor cell resistance and growth. CONCLUSION: Our results suggest that FBXW7 status may play an important role in drug therapy resistance of cancer cells. Genetic characterization of FBXW7 may be one factor included in future personalized cancer treatment identification.

Multi-Gbit/s phosphor-based white-light and blue-filter-free visible light communication and lighting system with practical transmission distance.

High speed visible light communication (VLC) is a technology with great potential for future mobile and wireless communication. Here, we report and demonstrate a 2.705 Gbit/s white-light VLC and illumination system supporting indoor transmission distance of 1.5 m, corresponding a illumination of 545 lux. We also study the performance tolerance offset ranges in both x- and y-directions.

Visible light positioning (VLP) system using low-cost organic photovoltaic cell (OPVC) for low illumination environments.

We propose and demonstrate a received-signal-strength (RSS) based visible light positioning (VLP) system using a low-cost organic photovoltaic cell (OPVC) receiver (Rx). The OPVC is a passive device without the need of external power supply. It could detect VLC signal and harvest energy. Our developed OPVC has a high power conversion efficiency (PCE) of 9.8%. The VLP system can be operated at a low illumination of 130 lux. The regression machine learning (ML) algorithm is used to enhance the positioning accuracy.

Probing age-related changes in cardio-respiratory dynamics by multimodal coupling assessment.

Quantifying respiratory sinus arrhythmia (RSA) can provide an index of parasympathetic function. Fourier spectral analysis, the most widely used approach, estimates the power of the heart rate variability in the frequency band of breathing. However, it neglects the time-varying characteristics of the transitions as well as the nonlinear properties of the cardio-respiratory coupling. Here, we propose a novel approach based on Hilbert-Huang transform, called the multimodal coupling analysis (MMCA) method, to assess cardio-respiratory dynamics by examining the instantaneous nonlinear phase interactions between two interconnected signals (i.e., heart rate and respiration) and compare with the counterparts derived from the wavelet-based method. We used an online database. The corresponding RSA components of the 90-min ECG and respiratory signals of 20 young and 20 elderly healthy subjects were extracted and quantified. A cycle-based analysis and a synchro-squeezed wavelet transform were also introduced to assess the amplitude or phase changes of each respiratory cycle. Our results demonstrated that the diminished mean and standard deviation of the derived dynamical RSA activities can better discriminate between elderly and young subjects. Moreover, the degree of nonlinearity of the cycle-by-cycle RSA waveform derived from the differences between the instantaneous frequency and the mean frequency of each respiratory cycle was significantly decreased in the elderly subjects by the MMCA method. The MMCA method in combination with the cycle-based analysis can potentially be a useful tool to depict the aging changes of the parasympathetic function as well as the waveform nonlinearity of RSA compared to the Fourier-based high-frequency power and the wavelet-based method.

Alternating Modulation of Subthalamic Nucleus Beta Oscillations during Stepping.

Gait disturbances in Parkinson's disease are commonly refractory to current treatment options and majorly impair patient's quality of life. Auditory cues facilitate gait and prevent motor blocks. We investigated how neural dynamics in the human subthalamic nucleus of Parkinsons's disease patients (14 male, 2 female) vary during stepping and whether rhythmic auditory cues enhance the observed modulation. Oscillations in the beta band were suppressed after ipsilateral heel strikes, when the contralateral foot had to be raised, and reappeared after contralateral heel strikes, when the contralateral foot rested on the floor. The timing of this 20-30 Hz beta modulation was clearly distinct between the left and right subthalamic nucleus, and was alternating within each stepping cycle. This modulation was similar, whether stepping movements were made while sitting, standing, or during gait, confirming the utility of the stepping in place paradigm. During stepping in place, beta modulation increased with auditory cues that assisted patients in timing their steps more regularly. Our results suggest a link between the degree of power modulation within high beta frequency bands and stepping performance. These findings raise the possibility that alternating deep brain stimulation patterns may be superior to constant stimulation for improving parkinsonian gait.SIGNIFICANCE STATEMENT Gait disturbances in Parkinson's disease majorly reduce patients' quality of life and are often refractory to current treatment options. We investigated how neural activity in the subthalamic nucleus of patients who received deep brain stimulation surgery covaries with the stepping cycle. 20-30 Hz beta activity was modulated relative to each step, alternating between the left and right STN. The stepping performance of patients improved when auditory cues were provided, which went along with enhanced beta modulation. This raises the possibility that alternating stimulation patterns may also enhance beta modulation and may be more beneficial for gait control than continuous stimulation, which needs to be tested in future studies.