Dissipative Parametric Gain in a GaAs/AlGaAs Superlattice.

Parametric generation of oscillations and waves is a paradigm, which is known to be realized in various physical systems. Unique properties of quantum semiconductor superlattices allow us to investigate high-frequency phenomena induced by the Bragg reflections and negative differential velocity of the miniband electrons. Effects of parametric gain in the superlattices at different strengths of dissipation have been earlier discussed in a number of theoretical works, but their experimental demonstrations are so far absent. Here, we report on the first observation of the dissipative parametric generation in a subcritically doped GaAs/AlGaAs superlattice subjected to a dc bias and a microwave pump. We argue that the dissipative parametric mechanism originates from a periodic variation of the negative differential velocity. It enforces excitation of slow electrostatic waves in the superlattice that provide a significant enhancement of the gain coefficient. This work paves the way for a development of a miniature solid-state parametric generator of GHz-THz frequencies operating at room temperature.

Superconditioning TMS for examining upper motor neuron function in MND.

We used transcranial magnetic stimulation (TMS) of motor cortex, including a novel four-pulse superconditioning (TMSsc) paradigm, in repeated examinations of motor-evoked potentials (MEPs) in eight subjects with motor neuron disease (MND), including seven with amyotrophic lateral sclerosis (ALS). The goals were: (1) to look for evidence of cortical hyperexcitability, including a reduction in short-interval intracortical inhibition (SICI); and (2) to examine the utility of using TMSsc for quantifying upper motor neuron function during MND progression. Testing of abductor pollicis brevis (APB) and tibialis anterior (TA) muscles bilaterally was carried out every 3 months in MND subjects for up to 2 years; results were compared to those from a cohort of 15 control subjects. Measures of SICI were not significantly different between control and MND subjects for either APB or TA muscles. Other measures of cortical excitability, including TMS threshold and MEP amplitude, were consistent with lowered cortical excitability in MND subjects. Certain combinations of superconditioning TMS were capable of causing stronger inhibition or facilitation of MEPs compared to dual-pulse TMS, for both APB and TA target muscles. Moreover, there were multiple cases in which target muscles unresponsive to strong single-pulse TMS, whether at rest or when tested with an active contraction, showed an MEP in response to TMSsc optimized for facilitation. Our findings suggest that a multi-faceted neurophysiologic protocol for examining upper motor neuron function in MND subjects might benefit from inclusion of TMSsc testing.

Four-pulse transcranial magnetic stimulation using multiple conditioning inputs. Normative MEP responses.

A four-pulse pattern of transcranial magnetic stimulation (TMS) was compared to traditional dual-pulse TMS for its ability to modulate motor cortical excitability. This novel pattern consisted of a three-pulse train of subthreshold conditioning pulses followed by a suprathreshold test pulse (i.e., SC-T). The intervals between these superconditioning (SC) pulses (1, 3, or 6 ms) and the follow-on test pulse (1, 3, 10, or 25 ms) were varied, and the resultant MEPs were compared to those elicited by: (1) single-pulse TMS; and (2) dual-pulse conditioning-test (C-T) TMS with either short (3 ms) or long (10 ms) intervals to elicit short-interval intracortical inhibition (SICI) or intracortical facilitation (ICF), respectively. Testing included abductor pollicis brevis (APB) and tibialis anterior (TA) in 15 neurologically normal adults. For superconditioning inputs, 10 ms test intervals caused especially strong facilitation of the test MEP, while 1 ms test intervals were particularly effective at causing inhibition of the test response. For both muscles and across all subjects, the most effective of the 12 SC-T inputs tested for causing either facilitation or inhibition was-with rare exception-superior to the dual-pulse TMS input for causing facilitation (i.e., ICF) or inhibition (i.e., SICI), while the overall magnitude of effect was more pronounced in APB compared to TA. Nevertheless, after normalization, the impact of a superconditioning input train on the test MEP was similar in APB and TA muscles, suggesting similar mechanisms of action. Limited findings from a single subject with amyotrophic lateral sclerosis (ALS) are included to further illustrate the potential advantages of using a train of conditioning pulses preceding a TMS test pulse to selectively investigate abnormal motor cortical excitatory and inhibitory circuitry.

Coexistence of Bloch and Parametric Mechanisms of High-Frequency Gain in Doped Superlattices.

The detailed theoretical study of high-frequency signal gain, when a probe microwave signal is comparable to the AC pump electric field in a semiconductor superlattice, is presented. We identified conditions under which a doped superlattice biased by both DC and AC fields can generate or amplify high-frequency radiation composed of harmonics, half-harmonics, and fractional harmonics. Physical mechanisms behind the effects are discussed. It is revealed that in a general case, the amplification mechanism in superlattices is determined by the coexistence of both the phase-independent Bloch and phase-dependent parametric gain mechanisms. The interplay and contribution of these gain mechanisms can be adjusted by the sweeping AC pump strength and leveraging a proper phase between the pump and strong probe electric fields. Notably, a transition from the Bloch gain to the parametric gain, often naturally occurring as the amplitude of the amplified signal field grows, can facilitate an effective method of fractional harmonic generation in DC-AC-driven superlattices. The study also uncovers that the pure parametric generation of the fractional harmonics can be initiated via their ignition by switching the DC pump electric field. The findings open a promising avenue for the advancement of new miniature GHz-THz frequency generators, amplifiers, and dividers operating at room temperature.

Green Removal of DUV-Polarity-Modified PMMA for Wet Transfer of CVD Graphene.

To fabricate graphene-based high-frequency electronic and optoelectronic devices, there is a high demand for scalable low-contaminated graphene with high mobility. Graphene synthesized via chemical vapor deposition (CVD) on copper foil appears promising for this purpose, but residues from the polymethyl methacrylate (PMMA) layer, used for the wet transfer of CVD graphene, drastically affect the electrical properties of graphene. Here, we demonstrate a scalable and green PMMA removal technique that yields high-mobility graphene on the most common technologically relevant silicon (Si) substrate. As the first step, the polarity of the PMMA was modified under deep-UV irradiation at λ = 254 nm, due to the formation of ketones and aldehydes of higher polarity, which simplifies hydrogen bonding in the step of its dissolution. Modification of PMMA polarity was confirmed by UV and FTIR spectrometry and contact angle measurements. Consecutive dissolution of DUV-exposed PMMA in an environmentally friendly, binary, high-polarity mixture of isopropyl alcohol/water (more commonly alcohol/water) resulted in the rapid and complete removal of DUV-exposed polymers without the degradation of graphene properties, as low-energy exposure does not form free radicals, and thus the released graphene remained intact. The high quality of graphene after PMMA removal was confirmed by SEM, AFM, Raman spectrometry, and by contact and non-contact electrical conductivity measurements. The removal of PMMA from graphene was also performed via other common methods for comparison. The charge carrier mobility in graphene films was found to be up to 6900 cm2/(V·s), demonstrating a high potential of the proposed PMMA removal method in the scalable fabrication of high-performance electronic devices based on CVD graphene.

Terahertz structured light: nonparaxial Airy imaging using silicon diffractive optics.

Structured light - electromagnetic waves with a strong spatial inhomogeneity of amplitude, phase, and polarization - has occupied far-reaching positions in both optical research and applications. Terahertz (THz) waves, due to recent innovations in photonics and nanotechnology, became so robust that it was not only implemented in a wide variety of applications such as communications, spectroscopic analysis, and non-destructive imaging, but also served as a low-cost and easily implementable experimental platform for novel concept illustration. In this work, we show that structured nonparaxial THz light in the form of Airy, Bessel, and Gaussian beams can be generated in a compact way using exclusively silicon diffractive optics prepared by femtosecond laser ablation technology. The accelerating nature of the generated structured light is demonstrated via THz imaging of objects partially obscured by an opaque beam block. Unlike conventional paraxial approaches, when a combination of a lens and a cubic phase (or amplitude) mask creates a nondiffracting Airy beam, we demonstrate simultaneous lensless nonparaxial THz Airy beam generation and its application in imaging system. Images of single objects, imaging with a controllable placed obstacle, and imaging of stacked graphene layers are presented, revealing hence potential of the approach to inspect quality of 2D materials. Structured nonparaxial THz illumination is investigated both theoretically and experimentally with appropriate extensive benchmarks. The structured THz illumination consistently outperforms the conventional one in resolution and contrast, thus opening new frontiers of structured light applications in imaging and inverse scattering problems, as it enables sophisticated estimates of optical properties of the investigated structures.

Comparison of training methods to improve walking in persons with chronic spinal cord injury: a randomized clinical trial.

OBJECTIVE: To compare two forms of device-specific training - body-weight-supported (BWS) ambulation on a fixed track (TRK) and BWS ambulation on a treadmill (TM) - to comprehensive physical therapy (PT) for improving walking speed in persons with chronic, motor-incomplete spinal cord injury (SCI). METHODS: Thirty-five adult subjects with a history of chronic SCI (>1 year; AIS 'C' or 'D') participated in a 13-week (1 hour/day; 3 days per week) training program. Subjects were randomized into one of the three training groups. Subjects in the two BWS groups trained without the benefit of additional input from a physical therapist or gait expert. For each training session, performance values and heart rate were monitored. Pre- and post-training maximal 10-m walking speed, balance, muscle strength, fitness, and quality of life were assessed in each subject. RESULTS: All three training groups showed significant improvement in maximal walking speed, muscle strength, and psychological well-being. A significant improvement in balance was seen for PT and TRK groups but not for subjects in the TM group. In all groups, post-training measures of fitness, functional independence, and perceived health and vitality were unchanged. CONCLUSIONS: Our results demonstrate that persons with chronic, motor-incomplete SCI can improve walking ability and psychological well-being following a concentrated period of ambulation therapy, regardless of training method. Improvement in walking speed was associated with improved balance and muscle strength. In spite of the fact that we withheld any formal input of a physical therapist or gait expert from subjects in the device-specific training groups, these subjects did just as well as subjects receiving comprehensive PT for improving walking speed and strength. It is likely that further modest benefits would accrue to those subjects receiving a combination of device-specific training with input from a physical therapist or gait expert to guide that training.

Superconditioning TMS unmasks latent voluntary innervation in MND - A case report.

Motor neuron disease (MND) includes both ALS and Progressive Muscular Atrophy (PMA) as variants. Abnormalities in brain excitability and upper motor neuron (UMN) function are characteristic of ALS, but by definition are absent in PMA. Transcranial magnetic stimulation (TMS) may be useful in demonstrating UMN pathology, but loss of muscle responsiveness with disease progression limits its usefulness in later stages of MND. We have developed a novel form of TMS comprised of 4 stimulating pulses that can enhance MEPs in target muscles already responding to traditional TMS inputs, in some cases even restoring MEPs in target muscles rendered unresponsive by the disease. An example of restored MEPs in response to this superconditioning TMS pattern (TMSsc) in a person with PMA is described, along with an unexpected finding. Despite a prolonged (> 5 year) history of movement paralysis in his right tibialis anterior (TA), immediately after cessation of TMSsc delivery the subject could now easily contract and relax this muscle; the presence of a latent pathway for voluntary innervation of his right TA was revealed. This modulation of central motor functional connectivity in response to TMSsc suggests a further, clinically-significant benefit of this form of noninvasive brain stimulation beyond its ability to enhance MEPs to traditional TMS inputs.

Efficacy of QuadroPulse rTMS for improving motor function after spinal cord injury: Three case studies.

CONTEXT/OBJECTIVE: To examine the effects of repetitive QuadroPulse transcranial magnetic stimulation (rTMS(QP)) on hand/leg function after spinal cord injury (SCI). DESIGN: Interventional proof-of-concept study. SETTING: University laboratory. PARTICIPANTS: Three adult subjects with cervical SCI. Interventions Repeated trains of magnetic stimuli were applied to the motor cortical hand/leg area. Several exploratory single-day rTMS(QP) protocols were examined. Ultimately we settled on a protocol using three 5-day trials of (1) rTMS(QP) only; (2) exercise only (targeting hand or leg function); and (3) rTMS(QP) combined with exercise. OUTCOME MEASURES: Hand motor function was assessed by Purdue Pegboard and Complete Minnesota Dexterity tests. Walking function was based on treadmill walking and the Timed Up and Go test. Electromyographic recordings were used for neurophysiological testing of cortical (by single- and double-pulse TMS) and spinal (via tendon taps and electrical nerve stimulation) excitability. RESULTS: Single-day rTMS(QP) application had no clear effect in the 2 subjects whose hand function was targeted, but improved walking speed in the person targeted for walking, accompanied by increased cortical excitability and reduced spinal excitability. All 3 subjects showed functional improvement following the 5-day rTMS(QP) intervention, an effect being even more pronounced after the five-day combined rTMS(QP) + exercise sessions. There were no rTMS(QP)-associated adverse effects. CONCLUSION: Our findings suggest a functional benefit of motor cortical rTMS(QP) after SCI. The effect of rTMS(QP) appears to be augmented when stimulation is accompanied by targeted exercises, warranting expansion of this pilot study to a larger subject population.

Interlimb reflex activity after spinal cord injury in man: strengthening response patterns are consistent with ongoing synaptic plasticity.

OBJECTIVE: Previous reports from our laboratory have described short-latency contractions in muscles of the distal upper limb following stimulation of lower limb nerves or skin in persons with injury to the cervical spinal cord. It takes 6 or more months for interlimb reflexes (ILR) to appear following acute spinal cord injury (SCI), suggesting they might be due to new synaptic interconnections between lower limb sensory afferents and motoneurons in the cervical enlargement. In this study, we asked if once formed, the strength of these synaptic connections increased over time, a finding that would be consistent with the above hypothesis. METHODS: We studied persons with sub-acute and/or chronic cervical SCI. ILR were elicited by brief trains of electrical pulses applied to the skin overlying the tibial nerve at the back of the knee. Responses were quantified based on their presence or absence in different upper limb muscles. We also generated peri-stimulus time histograms for single motor unit response latency, probability, and peak duration. Comparisons of these parameters were made in subjects at sub-acute versus chronic stages post-injury. RESULTS: In persons with sub-acute SCI, the probability of seeing ILR in a given muscle of the forearm or hand was low at first, but increased substantially over the next 1-2 years. Motor unit responses at this sub-acute stage had a prolonged and variable latency, with a lower absolute response probability, compared to findings from subjects with chronic (i.e. stable) SCI. CONCLUSIONS: Our findings demonstrate that interlimb reflex activity, once established after SCI, shows signs of strengthening synaptic contacts between afferent and efferent components, consistent with ongoing synaptic plasticity. SIGNIFICANCE: Neurons within the adult human spinal cord caudal to a lesion site are not static, but appear to be capable of developing novel-yet highly efficacious-synaptic contacts following trauma-induced partial denervation. In this case, such contacts between ascending afferents and cervical motoneurons do not appear to provide any functional benefit to the subject. In fact their presence may limit the regenerative effort of supraspinal pathways which originally innervated these motoneurons, should effort in animal models to promote regeneration across the lesion epicenter be successfully translated to humans with chronic SCI.

Impact of tissue heterogeneity on noninvasive near-infrared glucose measurements in interstitial fluid of rat skin.

BACKGROUND: Movement of the optical interface used to collect noninvasive near-infrared spectra is known to dramatically increase prediction errors for glucose concentration measurements within the interstitial fluid of living rat skin. Prediction errors increase by more than 2.5-fold when the interface is moved before each non-invasive measurement compared to measurements where the interface position is constant throughout. Chemical heterogeneity of the skin matrix is examined as a possible mechanism for the strong sensitivity to the interface placement during noninvasive measurements conducted from transmission near-infrared absorption spectroscopy. METHOD: Microspectroscopy was performed over a region of the near-infrared spectrum (4000-5000 cm(-1)) to map the concentrations of water, collagen protein, fat, and keratin protein within the skin tissue matrix through which noninvasive spectra are collected. Maps were created for multiple samples of skin excised from male and female animals. Sets of near-infrared spectra were constructed to simulate noninvasive spectra in accord with the basic tissue composition found from the microspectroscopic maps with added information corresponding to a span of glucose concentrations ranging from 5 to 35 mM and Gaussian-distributed noise. RESULTS: Microspectroscopic maps of rat skin reveal similar patterns of heterogeneity for major chemical components of skin samples excised from both male and female animals. These maps demonstrate concentration domains with dimensions similar to the size of the fiber interface used to collect noninvasive spectra. Partial least squares calibration models generated from sets of simulated spectra demonstrate increases in prediction errors for glucose when the spectral matrix is changed in accord with the degree of chemical heterogeneity displayed in the skin maps. Prediction errors typically increase between 100 and 1000% when comparing errors generated from spectra that represent a single tissue composition versus spectra that represent a varied skin composition in accord with the distribution displayed in the skin maps. CONCLUSIONS: The distribution of the major components of skin is not uniform, but establishes domains within the skin matrix that strongly impact prediction errors for the noninvasive spectroscopic measurement of glucose within the interstitial fluid of rat dermis tissue. The observed increase in prediction error (>2.5-fold) determined from actual noninvasive measurements is within the lower range of prediction error increases demonstrated by this simulation study. These findings implicate that chemical heterogeneity within the tissue matrix is a major factor in the sensitivity of the location of the fiber interface used to collect noninvasive spectral data.

Near-infrared microspectroscopic analysis of rat skin tissue heterogeneity in relation to noninvasive glucose sensing.

BACKGROUND: Noninvasive glucose measurements are possible by analysis of transmitted near-infrared light over the 4000- to 5000-cm(-1) spectral range. Such measurements are highly sensitive to the exact position of the fiber-optic interface on the surface of the skin sample. A critical question is the degree of heterogeneity of the major chemical components of the skin matrix in relation to the size of the fiber-optic probed used to collect noninvasive spectra. Microscopic spectral mapping is used to map the chemical distribution for a set of excised sections of rat skin. METHOD: A Fourier transform near-infrared microspectrometer was used to collect transmission spectra from 16 tissue samples harvested from a set of four healthy Harlan-Sprague male rats. A reference point in the center of the tissue sample was probed regularly to track dehydration, changes in tissue composition, and changes in instrument performance. Amounts of the major skin constituents were determined by fitting microspectra to a set of six pure component absorbance spectra corresponding to water, type I collagen protein, keratin protein, fat, an offset term, and a slope term. RESULTS: Microspectroscopy provides spectra with root mean square noise levels on 100% lines between 418 and 1475 microabsorbance units, which is sufficient for measuring the main chemical components of skin. The estimated spatial resolution of the microscope is 220 microm. The amounts of each tissue matrix component were determined for each 480 x 360-microm(2) location of a 4.8 x 3.6-mm(2) rectangular block of skin tissue. These spectra were used to generate two-dimensional distribution maps for each of the principal skin components. CONCLUSIONS: Distribution of the chemical components of rat skin is significant relative to the dimensions of noninvasive glucose sensing. Chemical distribution maps reveal that variations in the chemical composition of the skin samples are on the same length scale as the fiber-optic probe used to collect noninvasive near-infrared spectra. Analysis of variance between tissue slices collected for one animal and analysis of variations between animals indicate that animal-to-animal variation for all four chemical components is significantly higher than variations between samples for a given animal. These findings justify the collection and interpretation of near-infrared microspectroscopic maps of human skin to establish chemical heterogeneity and its impact on noninvasive glucose sensing for the management of diabetes.

Terahertz Bloch oscillator with a modulated bias.

Electrons performing Bloch oscillations in an energy band of a dc-biased superlattice in the presence of weak dissipation can potentially generate THz fields at room temperature. The realization of such a Bloch oscillator is a long-standing problem due to the instability of a homogeneous electric field in conditions of negative differential conductivity. We establish the theoretical feasibility of stable THz gain in a long superlattice device in which the bias is quasistatically modulated by microwave fields. The modulation waveforms must have at least two harmonics in their spectra.