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Abstract Leg movements during sleep occur in patients with sleep pathology and healthy individuals. Some (but not all) leg movements during sleep are related to cortical arousals which occur without conscious awareness but have a significant effect of sleep fragmentation. Detecting leg movements during sleep that are associated with cortical arousals can provide unique insight into the nature and quality of sleep. In this study, a novel leg movement monitor that uses a unique capacitive displacement sensor and 6-axis inertial measurement unit, is used in conjunction with polysomnography to understand the relationship between leg movement and electroencephalogram (EEG) defined cortical arousals. In an approach that we call neuro-extremity analysis, directed connectivity metrics are used to interrogate causal linkages between EEG and leg movements measured by the leg movement sensors. The capacitive displacement measures were more closely related to EEG-defined cortical arousals than inertial measurements. Second, the neuro-extremity analysis reveals a temporally evolving connectivity pattern that is consistent with a model of cortical arousals in which brainstem dysfunction leads to near-instantaneous leg movements and a delayed, filtered signal to the cortex leading to the cortical arousal during sleep.

Substance use disorder (SUD) is a dangerous epidemic that develops out of recurrent use of alcohol and/or drugs and has the capability to severely damage one’s brain and behaviour. Stress is an established risk factor in SUD’s development of addiction and in reinstating drug seeking. Despite this expanding epidemic and the potential for its grave consequences, there are limited options available for management and treatment, as well as pharmacotherapies and psychosocial treatments. To this end, there is a need for new and improved devices dedicated to the detection, management, and treatment of SUD. In this paper, the negative effects of SUD-related stress were discussed, and based on that, a few significant biomarkers were selected from a set of eight features collected by a chest-worn device, RespiBAN Professional, on fifteen individuals. We used three machine learning classifiers on these optimal biomarkers to detect stress. Based on the accuracies, the best biomarkers to detect stress and those considered as features for classification were determined to be electrodermal activity (EDA), body temperature, and a chest-worn accelerometer. Additionally, the differences between mental stress and physical stress, as well as different administrations of meditation during the study, were identified and analysed. Challenges, implications, and applications were also discussed. In the near future, we aim to replicate the proposed methods in individuals with SUD.

The hypothesis that the central nervous system (CNS) makes use of synergies or movement primitives in achieving simple to complex movements has inspired the investigation of different types of synergies. Kinematic and muscle synergies have been extensively studied in the literature, but only a few studies have compared and combined both types of synergies during the control and coordination of the human hand. In this paper, synergies were extracted first independently (called kinematic and muscle synergies) and then combined through data fusion (called musculoskeletal synergies) from 26 activities of daily living in 22 individuals using principal component analysis (PCA) and independent component analysis (ICA). By a weighted linear combination of musculoskeletal synergies, the recorded kinematics and the recorded muscle activities were reconstructed. The performances of musculoskeletal synergies in reconstructing the movements were compared to the synergies reported previously in the literature by us and others. The results indicate that the musculoskeletal synergies performed better than the synergies extracted without fusion. We attribute this improvement in performance to the musculoskeletal synergies that were generated on the basis of the cross-information between muscle and kinematic activities. Moreover, the synergies extracted using ICA performed better than the synergies extracted using PCA. These musculoskeletal synergies can possibly improve the capabilities of the current methodologies used to control high dimensional prosthetics and exoskeletons.

Summary: Unfolding followed by fibrillation of insulin even in the presence of various excipients grappled with restricted clinical application. Thus, there is an unmet need for better thermostable, nontoxic molecules to preserve bioactive insulin under varying physiochemical perturbations. In search of cross-amyloid inhibitors, prion-derived tetrapeptide library screening reveals a consensus V(X)YR motif for potential inhibition of insulin fibrillation. A tetrapeptide VYYR, isosequential to the β2-strand of prion, effectively suppresses heat- and storage-induced insulin fibrillation and maintains insulin in a thermostable bioactive form conferring adequate glycemic control in mouse models of diabetes and impedes insulin amyloidoma formation. Besides elucidating the critical insulin-IS1 interaction (R4 of IS1 to the N24 insulin B-chain) by nuclear magnetic resonance spectroscopy, we further demonstrated non-canonical dimer-mediated conformational trapping mechanism for insulin stabilization. In this study, structural characterization and preclinical validation introduce a class of tetrapeptide toward developing thermostable therapeutically relevant insulin formulations.

Down-regulation or loss of MHC class I expression is a major mechanism used by cancer cells to evade immunosurveillance and increase their oncogenic potential. MHC I mediated antigen presentation is a complex regulatory process, controlled by antigen processing machinery (APM) dictating immune response. Transcriptional regulation of the APM that can modulate gene expression profile and their correlation to MHC I mediated antigen presentation in cancer cells remain enigmatic. Here, we reveal that Scaffold/Matrix-Associated Region 1- binding protein (SMAR1), positively regulates MHC I surface expression by down-regulating calnexin, an important component of antigen processing machinery (APM) in cancer cells. SMAR1, a bonafide MAR binding protein acts as a transcriptional repressor of several oncogenes. It is down-regulated in higher grades of cancers either through proteasomal degradation or through loss of heterozygosity (LOH) at the Chr.16q24.3 locus where the human homolog of SMAR1 (BANP) has been mapped. It binds to a short MAR region of the calnexin promoter forming a repressor complex in association with GATA2 and HDAC1. A reverse correlation between SMAR1 and calnexin was thus observed in SMAR1-LOH cells and also in tissues from breast cancer patients. To further extrapolate our findings, influenza A (H1N1) virus infection assay was performed. Upon viral infection, the levels of SMAR1 significantly increased resulting in reduced calnexin expression and increased MHC I presentation. Taken together, our observations establish that increased expression of SMAR1 in cancers can positively regulate MHC I surface expression thereby leading to higher chances of tumor regression and elimination of cancer cells.

Operation of superconducting radio frequency (SRF) cavities with high loaded quality factors is becoming increasingly preferred for applications which involve low beam loading including energy recovery linacs (ERL). Vibration induced microphonics detuning poses a major operational bottleneck in these low bandwidth systems, adversely affecting field stability. Besides passive measures of mitigating the vibration sources, modern SRF cavities are also attached to fast tuners incorporating piezoelectric actuators. We demonstrate the narrow band active noise control algorithm for realizing active resonance control and propose a modification based on the least mean square approach to adaptively tune the control parameters and study its stability and performance. We discuss our experience of using passive mitigation techniques while commissioning the main linac cryomodule of the Cornell-BNL ERL test accelerator and report a net reduction in peak detuning by more than a factor of 2 in its unstiffened cavities. Finally, we demonstrate stable performance of our resonance control system with consistent reduction of peak microphonics detuning by almost a factor of 2 on multiple cavities.