Rotational spectroscopy of methyl tert-butyl ether with a new Ka band chirped-pulse Fourier transform microwave spectrometer.

Chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy is a powerful tool for performing broadband gas-phase rotational spectroscopy, and its applications include discovery of new molecules, complex mixture analysis, and exploration of fundamental molecular physics. Here we report the development of a new Ka band (26.5-40 GHz) CP-FTMW spectrometer that is equipped with a pulsed supersonic expansion source and a heated reservoir for low-volatility samples. The spectrometer is built around a 150 W traveling wave tube amplifier and has an instantaneous bandwidth that covers the entire Ka band spectral range. To test the performance of the spectrometer, the rotational spectrum of methyl tert-butyl ether (MTBE), a former gasoline additive and environmental pollutant, has been measured for the first time in this spectral range. Over 1000 spectroscopic transitions have been measured and assigned to the vibrational ground state and a newly-identified torsionally excited state; all transitions were fit using the XIAM program to a root-mean-square deviation of 22 kHz. The spectrum displays internal rotation splitting, nominally forbidden transitions, and an intriguing axis-switching effect between the ground and torsionally excited state that is a consequence of MTBE's extreme near-prolate nature. Finally, the sensitivity of the spectrometer enabled detection of all singly-substituted 13C and 18O isotopologues in natural abundance. This set of isotopic spectra allowed for a partial r0 structure involving the heavy atoms to be derived, resolving a structural discrepancy in the literature between previous microwave and electron diffraction measurements.

Automated Reaction Kinetics of Gas-Phase Organic Species over Multiwell Potential Energy Surfaces.

Automation of rate-coefficient calculations for gas-phase organic species became possible in recent years and has transformed how we explore these complicated systems computationally. Kinetics workflow tools bring rigor and speed and eliminate a large fraction of manual labor and related error sources. In this paper we give an overview of this quickly evolving field and illustrate, through five detailed examples, the capabilities of our own automated tool, KinBot. We bring examples from combustion and atmospheric chemistry of C-, H-, O-, and N-atom-containing species that are relevant to molecular weight growth and autoxidation processes. The examples shed light on the capabilities of automation and also highlight particular challenges associated with the various chemical systems that need to be addressed in future work.

Modulation of Beta Oscillations in the Pallidum During Externally Cued Gait.

Freezing of gait (FOG) is a particularly debilitating symptom of Parkinson's disease (PD) and is often refractory to treatment. A striking feature of FOG is that external sensory cues can be used to overcome freezing and improve gait. Local field potentials (LFPs) recorded from the subthalamic nucleus (STN) and globus pallidus (GP) show that beta-band power modulates with gait phase. In the STN, beta-band oscillations are modulated by external cues, but it is unknown if this relationship holds in the globus pallidus (GP). Here we report LFP data recorded from the left GP, using a Medtronic PC + S device, in a 68-year-old man with PD and FOG during treadmill walking. A "stepping stone" task was used during which stepping was cued using visual targets of constant color or targets that unpredictably changed color, requiring a step length adjustment. Gait performance was quantified using measures of treadmill ground reaction forces and center of pressure and body kinematics from video monitoring. Beta-band power (12-30 Hz) and number of freezing episodes were measured. Cues which unpredictably changed color improved FOG more than conventional cues and were associated with greater modulation of beta-band power in phase with gait. This preliminary finding suggests that cueing-induced improvement of FOG may relate to beta-band modulation.

Rotational and Vibrational Spectra of the Pyridyl Radicals: A Coupled-Cluster Study.

Pyridyl is a prototypical nitrogen-containing aromatic radical that may be a key intermediate in the formation of nitrogen-containing aromatic molecules under astrophysical conditions. On meteorites, a variety of complex molecules with nitrogen-containing rings have been detected with nonterrestrial isotopic abundances, and larger nitrogen-containing polycyclic aromatic hydrocarbons (PANHs) have been proposed to be responsible for certain unidentified infrared emission bands in the interstellar medium. In this work, the three isomers of pyridyl (2-, 3-, and 4-pyridyl) have been investigated with coupled cluster methods. For each species, structures were optimized at the CCSD(T)/cc-pwCVTZ level of theory and force fields were calculated at the CCSD(T)/ANO0 level of theory. Second-order vibrational perturbation theory (VPT2) was used to derive anharmonic vibrational frequencies and vibrationally corrected rotational constants, and resonances among vibrational states below 3500 cm-1 were treated variationally with the VPT2+K method. The results yield a complete set of spectroscopic parameters needed to simulate the pure rotational spectrum of each isomer, including electron-spin, spin-spin, and nuclear hyperfine interactions, and the calculated hyperfine parameters agree well with the limited available data from electron paramagnetic resonance spectroscopy. For the handful of experimentally measured vibrational frequencies determined from photoelectron spectroscopy and matrix isolation spectroscopy, the typical agreement is comparable to experimental uncertainty. The predicted parameters for rotational spectroscopy reported here can guide new experimental investigations into the yet-unobserved rotational spectra of these radicals.

REM Sleep Without Atonia and Gait Impairment in People with Mild-to-Moderate Parkinson's Disease.

BACKGROUND: Subtle gait deficits can be seen in people with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), a prodromal stage of Parkinson's disease (PD) and related alpha-synucleinopathies. It is unknown if the presence and level of REM sleep without atonia (RSWA, the electromyographic hallmark of RBD) is related to the severity of gait disturbances in people with PD. OBJECTIVE: We hypothesized that gait disturbances in people with mild-to-moderate PD would be greater in participants with RSWA compared to those without RSWA and matched controls, and that gait impairment would correlate with measures of RSWA. METHODS: Spatiotemporal characteristics of gait were obtained from 41 people with PD and 21 age-matched controls. Overnight sleep studies were used to quantify muscle activity during REM sleep and group participants with PD into those with RSWA (PD-RSWA+, n = 22) and normal REM sleep muscle tone (PD-RSWA-, n = 19). Gait characteristics were compared between groups and correlated to RSWA. RESULTS: The PD-RSWA+ group demonstrated significantly reduced gait speed and step lengths and increased stance and double support times compared to controls, and decreased speed and cadence and increased stride velocity variability compared to PD-RSWA- group. Larger RSWA scores were correlated with worse gait impairment in the PD group. CONCLUSION: The presence and level of muscle tone during REM sleep is associated with the severity of gait disturbances in PD. Pathophysiological processes contributing to disordered gait may occur earlier and/or progress more rapidly in people with PD and RBD.

Coupled Cluster Characterization of 1-, 2-, and 3-Pyrrolyl: Parameters for Vibrational and Rotational Spectroscopy.

Pyrrolyl (C4H4N) is a nitrogen-containing aromatic radical that is a derivative of pyrrole (C4H5N) and is an important intermediate in the combustion of biomass. It is also relevant for chemistry in Titan's atmosphere and may be present in the interstellar medium. The lowest-energy isomer, 1-pyrrolyl, has been involved in many experimental and theoretical studies of the N-H photodissociation of pyrrole, yet it has only been directly spectroscopically detected via electron paramagnetic resonance and through the photoelectron spectrum of the pyrrolide anion, yielding three vibrational frequencies. No direct measurements of 2- or 3-pyrrolyl have been made, and little information is known from theoretical calculations beyond their relative energies. Here, we present an ab initio quantum chemical characterization of the three pyrrolyl isomers at the CCSD(T) level of theory in their ground electronic states, with an emphasis on spectroscopic parameters relevant for vibrational and rotational spectroscopy. Equilibrium geometries were optimized at the CCSD(T)/cc-pwCVTZ level of theory, and the quadratic, cubic, and partial quartic force constants were evaluated at CCSD(T)/ANO0 for analysis using second-order vibrational perturbation theory to obtain harmonic and anharmonic vibrational frequencies. In addition, zero-point-corrected rotational constants, electronic spin-rotation tensors, and nuclear hyperfine tensors are calculated for rotational spectroscopy. Our computed structures and energies agree well with earlier density functional theory calculations, and spectroscopic parameters for 1-pyrrolyl are compared with the limited existing experimental data. Finally, we discuss strategies for detecting these radicals using rotational and vibrational spectroscopy on the basis of the calculated spectroscopic constants.

An acute, ulcerative, sarcoidal tattoo reaction following SARS-CoV-2 mRNA-1273 vaccination.

Two weeks after her first dose of the SARS-CoV-2 mRNA-1273 (Moderna) vaccine, a 38-year-old woman developed acute-onset pain and ulceration within a tattoo on the distal left leg. Progressive ulceration was noted approximately one week following her second dose of the vaccine. A biopsy revealed sarcoidal granulomas and a dense neutrophilic infiltrate. Ultimately, the final diagnosis of what we have termed a "sarcoidal reaction with a Sweet-like phenomenon" was made; the patient experienced a reduction in pain and re-epithelialization of the ulcers with two weeks of the use of topical clobetasol 0.05% cream twice daily.

Comparison of forward and backward postural perturbations in mild-to-moderate Parkinson's disease.

BACKGROUND: Assessing postural stability in Parkinson's disease (PD) often relies on measuring the stepping response to an imposed postural perturbation. The standard clinical technique relies on a brisk backwards pull at the shoulders by the examiner and judgement by a trained rater. In research settings, various quantitative measures and perturbation directions have been tested, but it is unclear which metrics and perturbation direction differ most between people with PD and controls. OBJECTIVES: (1) Use standardized forward vs. backward perturbations of a support surface to evaluate reactive stepping performance between PD and control participants. (2) Evaluate the utility of using principal components analysis to capture the dynamics of the reactive response and differences between groups. METHODS: Sixty-two individuals participated (40 mild-to-moderate PD, off medication). Standardized rapid translations of the support surface were applied, requiring at least one step, backward or forward, to restore balance. The number of steps taken and the projection of the first principal component (PC1) of the center of pressure (COP) time series were entered in linear repeated-measures mixed effect models. RESULTS: Forward falls required significantly fewer steps to recover than backward falls. PC1 captured more than half of the variance in the COP trajectory. Analysis of the PC1 projection revealed a significant interaction effect of group (PD vs. controls) by direction, such that there was a group difference in forward stepping, but not backward. SIGNIFICANCE: Forward reactive stepping in PD differed from controls more than backward-stepping. PC1 projections of the COP trajectory capture the dynamics of the postural response and differ between PD and controls.

REM sleep without atonia is associated with increased rigidity in patients with mild to moderate Parkinson's disease.

OBJECTIVE: Increased muscle activity during rapid eye movement (REM) sleep (i.e. REM sleep without atonia) is common in people with Parkinson's disease (PD). This study tested the hypotheses that people with PD and REM sleep without atonia (RSWA) would present with more severe and symmetric rigidity compared to individuals with PD without RSWA and age-matched controls. METHODS: Sixty-one individuals participated in this study (41 PD, 20 controls). An overnight sleep study was used to classify participants with PD as having either elevated (PD-RSWA+) or normal muscle activity (PD-RSWA-) during REM sleep. Quantitative measures of rigidity were obtained using a robotic manipulandum that passively pronated and supinated the forearm. RESULTS: Quantitative measures of forearm rigidity were significantly higher in the PD-RSWA+ group compared to the control group. Rigidity was significantly more asymmetric between limbs in the PD-RSWA- group compared with controls, while there was no significant difference in symmetry between the control and PD-RSWA+ groups. CONCLUSION: In people with mild to moderate PD, RSWA is associated with an increased and more symmetric presentation of upper limb rigidity. SIGNIFICANCE: Dysfunction of brainstem systems that control muscle tone during REM sleep may contribute to increased rigidity during wakefulness in people with PD.

VPA/PLGA microfibers produced by coaxial electrospinning for the treatment of central nervous system injury.

The central nervous system shows limited regenerative capacity after injury. Spinal cord injury (SCI) is a devastating traumatic injury resulting in loss of sensory, motor, and autonomic function distal from the level of injury. An appropriate combination of biomaterials and bioactive substances is currently thought to be a promising approach to treat this condition. Systemic administration of valproic acid (VPA) has been previously shown to promote functional recovery in animal models of SCI. In this study, VPA was encapsulated in poly(lactic-co-glycolic acid) (PLGA) microfibers by the coaxial electrospinning technique. Fibers showed continuous and cylindrical morphology, randomly oriented fibers, and compatible morphological and mechanical characteristics for application in SCI. Drug-release analysis indicated a rapid release of VPA during the first day of the in vitro test. The coaxial fibers containing VPA supported adhesion, viability, and proliferation of PC12 cells. In addition, the VPA/PLGA microfibers induced the reduction of PC12 cell viability, as has already been described in the literature. The biomaterials were implanted in rats after SCI. The groups that received the implants did not show increased functional recovery or tissue regeneration compared to the control. These results indicated the cytocompatibility of the VPA/PLGA core-shell microfibers and that it may be a promising approach to treat SCI when combined with other strategies.

The Transition from Standing to Walking Is Affected in People with Parkinson's Disease and Freezing of Gait.

BACKGROUND: It has been hypothesized that freezing of gait (FOG) in people with Parkinson's disease (PD) is due to abnormal coupling between posture and gait. OBJECTIVE: In this study, we examined the relationship between anticipatory postural adjustments (APAs) preceding gait initiation and the kinematics of the first two steps between people with FOG and without FOG. METHODS: The kinetics and kinematics of self-initiated gait were recorded in 25 people with PD (11 with FOG, 14 without FOG). Outcome variables included the amplitude and timing of the ground reaction forces (GRFs), center of pressure (CoP) shifts and the spatial and temporal characteristics of the first and second steps. RESULTS: The magnitude and timing of the APA phase of gait initiation were not significantly different between participants with and without FOG, yet the first step in the FOG group was distinguished by a significantly wider and less variable first step width, followed by a subsequent wider and shortened second step with reduced toe clearance. Multiple linear regression showed that the relationship between the initial conditions (stance width), APAs (posterior shift of the CoP) and the kinematics of the first step were different between groups with a significantly increased slope in the FOG group. CONCLUSION: These findings demonstrate that the transition from standing to walking is different between those with and without FOG and that alterations in the initial conditions or APAs are more likely to impact the execution of the two steps in people with FOG.

VPA/PLGA microfibers produced by coaxial electrospinning for the treatment of central nervous system injury

The central nervous system shows limited regenerative capacity after injury. Spinal cord injury (SCI) is a devastating traumatic injury resulting in loss of sensory, motor, and autonomic function distal from the level of injury. An appropriate combination of biomaterials and bioactive substances is currently thought to be a promising approach to treat this condition. Systemic administration of valproic acid (VPA) has been previously shown to promote functional recovery in animal models of SCI. In this study, VPA was encapsulated in poly(lactic-co-glycolic acid) (PLGA) microfibers by the coaxial electrospinning technique. Fibers showed continuous and cylindrical morphology, randomly oriented fibers, and compatible morphological and mechanical characteristics for application in SCI. Drug-release analysis indicated a rapid release of VPA during the first day of the in vitro test. The coaxial fibers containing VPA supported adhesion, viability, and proliferation of PC12 cells. In addition, the VPA/PLGA microfibers induced the reduction of PC12 cell viability, as has already been described in the literature. The biomaterials were implanted in rats after SCI. The groups that received the implants did not show increased functional recovery or tissue regeneration compared to the control. These results indicated the cytocompatibility of the VPA/PLGA core-shell microfibers and that it may be a promising approach to treat SCI when combined with other strategies.

Rotational Spectrum of the ß-Cyanovinyl Radical: A Possible Astrophysical N-Heterocycle Precursor.

A fundamental question in the field of astrochemistry is whether the molecules essential to life originated in the interstellar medium (ISM), and, if so, how they were formed. Nitrogen-containing heterocycles are of particular interest because of their role in biology; however, to date, no N-heterocycle has been detected in the ISM, and it is unclear how and where such species might form. Recently, the ß-cyanovinyl radical (HCCHCN) was implicated in the low-temperature gas-phase formation of pyridine. While neutral vinyl cyanide (H2CCHCN) has been rotationally characterized and detected in the ISM, HCCHCN has not. Here, we present the first theoretical study of all three cyanovinyl isomers at the CCSD(T)/ANO1 level of theory and the experimental rotational spectra of cis- and trans-HCCHCN, as well as those of their 15N isotopologues, from 5 to 75 GHz. The observed spectra are in good agreement with calculations and provide a basis for further laboratory and astronomical investigations of these radicals.

EMG-Based Control in a Test Platform for Exoskeleton with One Degree of Freedom.

There are several efforts to use the electrical signals generated by the human muscles to control virtual or even physical devices. It is expected that, the development of this method will provide a natural way to control these devices, requiring little user training, depending on the task complexity. With respect to the control of exoskeletons from the electric signals generated by the muscles, it is desirable that the exoskeleton acts in synergy with the user using surface electromyography (sEMG) signals to detect user intentions. One of the challenges of this approach is the variability of the sEMG signals due to factors such as electrode positioning and conditions of the volunteer at the time of acquisition. In previous work, a procedure based on an Autoregressive with Exogenous Input (ARX) linear model was developed to translate sEMG from biceps, triceps and brachioradialis muscles to elbow joint angle. In this work, we developed a method based on a Genetic Algorithm (GA) to update the ARX model coefficients online to minimize the training periods and we have used the EMG signals to control a one-degree of freedom exoskeleton.vThe GA was able to obtain ARX model coefficients that generate the joint angle reference from the EMG signals. In addition, the joint angle references generated from the offline sEMG from three muscles via an ARX model were used to control a device. At this point we are carrying out tests with the exoskeleton using real-time signals from sEMG.

Elbow Joint Angle Estimation with Surface Electromyography Using Autoregressive Models.

This paper presents a method to estimate the elbow joint angle from surface electromyography (sEMG) measurements of biceps, triceps and brachioradialis. This estimation is of major importance for the design of human robot interfaces based on sEMG. It is also relevant to model the muscular system and to design biomimetic mechanisms. However, the processing and interpretation of electromyographic signals is challenging due to nonlinearities, unmodeled muscle dynamics, noise and interferences. In order to determine an estimation model and a calibration procedure for the model parameters, a set of experiments were carried out with six subjects. The experiments consisted of series of continuous (cyclical) and discrete elbow flexo-extensions with three different loads (i.e. 0 kg, 1.5kg and 3 kg). The sEMG data from the biceps brachii, triceps brachii and brachioradialis and the joint angle were recorded. Four different modeling techniques were evaluated: State Space (SS), Autoregressive with Exogenous Input (ARX), Autoregressive Moving-Average with Exogenous Input (ARMAX), Autoregressive Integrated Moving-Average with Exogenous Input (ARIMAX). After the model was selected, a second experiment was performed in order to validate the estimation procedure. The results show a procedure to estimate the EMG-to-angle relation with high correlation and low meansquare- root errors with respect to the measured angle data.

The affinity of MhuD for heme is consistent with a heme degrading function in vivo.

MhuD is a protein found in mycobacteria that can bind up to two heme molecules per protein monomer and catalyze the degradation of heme to mycobilin in vitro. Here the Kd1 for heme dissociation from heme-bound MhuD was determined to be 7.6 ± 0.8 nM and the Kd2 for heme dissocation from diheme-bound MhuD was determined to be 3.3 ± 1.1 µM. These data strongly suggest that MhuD is a competent heme oxygenase in vivo.

Muscle Synergies Obtained from Comprehensive Mapping of the Cortical Forelimb Representation Using Stimulus Triggered Averaging of EMG Activity.

Neuromuscular control of voluntary movement may be simplified using muscle synergies similar to those found using non-negative matrix factorization. We recently identified synergies in electromyography (EMG) recordings associated with both voluntary movement and movement evoked by high-frequency long-duration intracortical microstimulation applied to the forelimb representation of the primary motor cortex (M1). The goal of this study was to use stimulus-triggered averaging (StTA) of EMG activity to investigate the synergy profiles and weighting coefficients associated with poststimulus facilitation, as synergies may be hard-wired into elemental cortical output modules and revealed by StTA. We applied StTA at low (LOW, ∼15 µA) and high intensities (HIGH, ∼110 µA) to 247 cortical locations of the M1 forelimb region in two male rhesus macaques while recording the EMG of 24 forelimb muscles. Our results show that 10-11 synergies accounted for 90% of the variation in poststimulus EMG facilitation peaks from the LOW-intensity StTA dataset while only 4-5 synergies were needed for the HIGH-intensity dataset. Synergies were similar across monkeys and current intensities. Most synergy profiles strongly activated only one or two muscles; all joints were represented and most, but not all, joint directions of motion were represented. Cortical maps of the synergy weighting coefficients suggest only a weak organization. StTA of M1 resulted in highly diverse muscle activations, suggestive of the limiting condition of requiring a synergy for each muscle to account for the patterns observed.SIGNIFICANCE STATEMENT Coordination of muscle activity and the neural origin of potential muscle synergies remains a fundamental question of neuroscience. We previously demonstrated that high-frequency long-duration intracortical microstimulation-evoked synergies were unrelated to voluntary movement synergies and were not clearly organized in the cortex. Here we present stimulus-triggered averaging facilitation-related muscle synergies, suggesting that when fundamental cortical output modules are activated, synergies approach the limit of single-muscle control. Thus, we conclude that if the CNS controls movement via linear synergies, those synergies are unlikely to be called from M1. This information is critical for understanding neural control of movement and the development of brain-machine interfaces.