Modulation Of Oscillations Research Articles

Mitotic kinase oscillation governs the latching of cell cycle switches

In 1996, Kim Nasmyth1 proposed that the eukaryotic cell cycle is an alternating sequence of transitions from G1 to S-G2-M and back again. These two phases correlate to high activity of cyclin-dependent kinases (CDKs) that trigger S-G2-M events and CDK antagonists that stabilize G1 phase. We associated these "alternative phases" with the coexistence of two stable steady states of the biochemical reactions among CDKs and their antagonists.2,3 Transitions between these steady states (G1-to-S and M-to-G1) are driven by "helper" proteins. The fact that the transitions are irreversible is guaranteed by a "latching" property of the molecular switches, as we have argued in previous publications.4,5 Here, we show that if the latch is broken, then the biochemical reactions can swing back-and-forth across the transitions; either G1-S-G1-S … (periodic DNA replication without mitosis or cell division) or M-(G1)-M-(G1) … (periodic Cdc14 release, without fully exiting mitosis). Using mathematical modeling of the molecular control circuit in budding yeast, we provide a fresh account of aberrant cell cycles in mutant strains: endoreplication in the clb1-5Δ strain6 and periodic release and resequestration of Cdc14 (an "exit" phosphatase) in the CLB2kdΔ strain.7,8 In our opinion, these "endocycles" are not autonomous oscillatory modules that must be entrained by the CDK oscillator6,7 but rather inadvertent and deleterious oscillations that are normally suppressed by the CDK latching-gate mechanism.8.

Sleep Deficits, Repetitive Behaviors, and Increased Slow Gamma Power in an Ank3 Mouse Model of Epilepsy‐Mood Disorder Comorbidity

The ANK3 gene is a leading bipolar disorder candidate gene in humans. Previous studies showed that a bipolar disorder (BD)‐associated variant of ANK3 (ANK3‐1b) leads to increased firing threshold and diminished action potential dynamic range of parvalbumin (PV) interneurons and absence epilepsy in mice, thus providing a potential mechanistic link between epilepsy and BD. To better understand the impact of PV interneurons on network activity and behavior in these mice, we examined spectral correlates of behaviors seen in Ank3‐1b knockout (KO) mice during overnight home‐cage activity using paired video‐EEG recordings. PV interneuron dysfunction and aberrant gamma rhythms have been implicated in BD. Also, the fast‐spiking properties of PV interneurons make them important for generating and modulating high frequency gamma oscillations. Thus, we anticipated changes in the power of EEG signals in the gamma frequency range (> 25 Hz) during behaviors related to BD symptoms seen in human patients such as changes in sleep and activity levels. Ank3‐1b KO mice exhibited an overall increase in slow gamma (~25‐45 Hz) power compared to controls, and slow gamma power correlated with seizure phenotype severity across behaviors. Notably, during sleep, increased slow gamma power co‐occurred with decreases in time spent in the rapid eye movement (REM) phase. We also identified a repetitive behaviors phenotype in Ank3‐1b KO mice that co‐occurred with increased slow gamma power. These results further support the association of Ank3‐1b with BD and suggest modulation of gamma oscillations as a potential therapeutic target.

A reconfigurable wireless superheterodyne receiver for multi-standard communication systems

ABSTRACT The rapid growth of the communication frequency band leads to the diversity of receiving frequency bands of smart devices. This paper proposes a reconfigurable wireless superheterodyne receiver for multi-standard communication systems. The receiver is designed through architecture design, chip selection, layout drawing, and physical measurement. The designed receiver consists of receiving module, local oscillator module, and control module. Unlike previous receivers, the proposed receiver selects the frequency channel, local oscillator frequency, and link gain through the control module in the current scene. The control module consists of a single-chip microcomputer and computer. The receiver can work in application scenarios including 2.4–2.5 GHz, 3.3–3.6 GHz, and 4.8–6.0 GHz. This paper discusses the design process of the proposed reconfigurable receiver in detail. Compared with the traditional receiver, the proposed receiver can change its working mode by software and has the characteristics of flexible reconfiguration. In addition, it has the advantages of a large link gain range and good demodulation performance. Moreover, the receiver is low in design cost and easy to manufacture. Therefore, it can be widely used in receiving modules of WLAN and 5G communication systems.

Altered alpha and theta oscillations correlate with sequential working memory in Parkinson's disease.

Daily activities such as preparing a meal rely on the ability to arrange thoughts and actions in the right order. Patients with Parkinson’s disease have difficulties in sequencing tasks. Their deficits in sequential working memory have been associated with basal ganglia dysfunction. Here we demonstrate that altered parietal alpha and theta oscillations correlate with sequential working memory in Parkinson’s disease. We included 15 patients with Parkinson’s disease (6 women, mean age: 66.0 years), 24 healthy young (14 women, mean age: 24.1 years), and 16 older participants (7 women, mean age: 68.6 years). All participants completed a picture ordering task with scalp electroencephalogram (EEG) recording, where they arranged five pictures in a specific order and memorized them over a delay. When encoding and maintaining picture sequences, patients with Parkinson’s disease showed a lower baseline alpha peak frequency with higher alpha power than healthy young and older participants. Patients with a higher baseline alpha power responded more slowly for ordered trials. When manipulating picture sequences, patients with Parkinson’s disease showed a lower frequency of maximal power change for random versus ordered trials than healthy young and older participants. Healthy older participants showed a higher frequency of maximal power change than healthy young participants. Compared with patients with frequency of maximal power change in the alpha band (8–15 Hz), patients with frequency of maximal power change in the theta band (4–7 Hz) showed a higher ordering-related accuracy cost (random versus ordered) in the main task and tended to respond more slowly and less accurately in an independent working memory test. In conclusion, altered baseline alpha oscillations and task-dependent modulation of alpha and theta oscillations may be neural markers of poor sequential working memory in Parkinson’s disease.

Frequency‐dependent modulation of neural oscillations across the gait cycle

Balance and walking are fundamental to support common daily activities. Relatively accurate characterizations of normal and impaired gait features were attained at the kinematic and muscular levels. Conversely, the neural processes underlying gait dynamics still need to be elucidated. To shed light on gait‐related modulations of neural activity, we collected high‐density electroencephalography (hdEEG) signals and ankle acceleration data in young healthy participants during treadmill walking. We used the ankle acceleration data to segment each gait cycle in four phases: initial double support, right leg swing, final double support, left leg swing. Then, we processed hdEEG signals to extract neural oscillations in alpha, beta, and gamma bands, and examined event‐related desynchronization/synchronization (ERD/ERS) across gait phases. Our results showed that ERD/ERS modulations for alpha, beta, and gamma bands were strongest in the primary sensorimotor cortex (M1), but were also found in premotor cortex, thalamus and cerebellum. We observed a modulation of neural oscillations across gait phases in M1 and cerebellum, and an interaction between frequency band and gait phase in premotor cortex and thalamus. Furthermore, an ERD/ERS lateralization effect was present in M1 for the alpha and beta bands, and in the cerebellum for the beta and gamma bands. Overall, our findings demonstrate that an electrophysiological source imaging approach based on hdEEG can be used to investigate dynamic neural processes of gait control. Future work on the development of mobile hdEEG‐based brain–body imaging platforms may enable overground walking investigations, with potential applications in the study of gait disorders.

Effect of long-term paired associative stimulation on the modulation of cortical sensorimotor oscillations after spinal cord injury

Study designA prospective interventional case series.ObjectivesTo explore changes in the modulation of cortical sensorimotor oscillations after long-term paired associative stimulation (PAS) in participants with spinal cord injury (SCI).SettingBioMag Laboratory, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.MethodsFive patients with chronic incomplete SCI received unilateral spinal PAS to upper limb for 16–22 days. Changes in the modulation of sensorimotor oscillations in response to tactile stimulus and active and imaginary hand movements were assessed with magnetoencephalography recorded before and after the intervention.ResultsPAS restored the modulation of sensorimotor oscillations in response to active hand movement in four patients, whereas the modulation following tactile stimulation remained unaltered. The observed change was larger in the hemisphere that received PAS and preceded the clinical effect of the intervention.ConclusionsLong-term spinal PAS treatment, which enhances the motor functions of SCI patients, also restores the modulation of cortical sensorimotor oscillations.

Neural markers of improved auditory selective attention following neurofeedback training

We designed a neurofeedback training paradigm to enhance the attentional modulation of cortical auditory evoked responses. Two concurrent speech streams—a female voice repeating “Up” five times and a male voice repeating “Down” four times in three secondsi—were played from left and right loudspeakers, respectively. Subjects were instructed to attend one of those streams by a pre-stimulus visual cue (e.g., “Target: Up”). Attention was decoded from single-trial EEG signals. Subjects received neurofeedback (i.e., a visual object on the computer screen moves upward if the EEG decoder determines the “up” stream was attended; or vice versa). Subjects repeated this training for four sessions across four weeks. During the last session, compared to the first, subjects exhibited strengthened alpha oscillation in the right parietal cortex while they attended right and ignored left, indicating that spatial inhibitory processing to suppress sounds left was enhanced. The temporal cortex exhibited greater attentional modulation of beta oscillation after the four weeks of training, indicating enhanced neural activity to predict the target. The strength of attentional modulation on cortical evoked responses to sounds was also improved. These results prove that neurofeedback training effectively enhances the cortical processing for auditory selective attention.

Design of a 0.5–18 GHz Wideband Frequency Down-Converter Module with a Local Circuit for an Electronic Support Measurement System

In this paper, we describe the design and fabrication of a wideband frequency down converter module that has a local circuit with high gain, low spurious, high IP3 (3rd intercept point) characteristics, and reliability; this is accomplished by applying a chip-and-wire process using a bare type monolithic microwave integrated circuit (MMIC) device. To compensate for the mismatch among many sub-modules, an input module, filter bank module, output module, and local oscillator (LO) module suitable for sub-band frequency characteristics were designed and applied to the down converter. Th e frequency down converter module had three paths: 0.5−2 GHz (direct), 2−6 GHz (direct), and 6−18 GHz (converter). Amplitude-matched radio frequency (RF) semi-rigid cables of different lengths were used to connect to the internal sub-modules of the frequency down converter. The main RF line was a dielectric substrate, RT/duroid 5880, with a relative dielectric constant of 2.2 and a dielectric thickness of 0.127 mm. In the wideband frequency down converter module, the gain was 22.7 dB at low band (input frequency, 0.5−2 GHz) with a flatness of about 3.4 dB. Th e gain was 22.6 dB at mid band (input frequency, 2−6 GHz) having flatness about 2.0 dB. The gain was from 30 dB at edge frequency of high band (input frequency, 14−18 GHz) with a flatness of about 4.2 dB. The measured value of IP3 at LB was +23.52 dBm, +25.66 dBm and +23.44 dBm as the maximum value. The measured value of spurious (LO-2IF) at the converter path was 34.97 dBc as the maximum value.

An improved local oscillator modulation of modulated sampling scheme for multiple mono-pulse radar signals reconstruction

The modulated sampling scheme can intercept noncooperative signals distributed in a wide frequency band by using a single receiving channel, which is an efficient architecture in many radar and communication applications. The modulated sampling scheme employs a non-uniform sample pulse train to fold the intercepted signal prior to quantization/digitization by using a local oscillator (LO) that contains a certain modulation type. Since the mono-pulse radar signals are widely used in many radar systems, the modulated sampling scheme will receive the multiple mono-pulse radar signals simultaneously in dense signal environment, and the folded outputs of the modulated sampling scheme may meet frequency aliasing. Thus, it is necessary to investigate the reconstruction of the multiple mono-pulse signals intercepted by the modulated sampling scheme in the frequency aliasing situation. In this paper, based on the orthogonal matching pursuit algorithm, the LO modulation type of the modulated sampling scheme is analyzed to achieve a better reconstruction performance of the multiple mono-pulse signals. The drawback of the typical LO using sinusoidal frequency modulation to reconstruct multiple mono-pulse signals is investigated firstly. Then, an improved LO using periodic linear frequency modulation is proposed, and its effectiveness to reconstruct multiple mono-pulse signals is analyzed. Furthermore, the parameter setting criterion of the improved LO modulation is given, and the comparison using other modulation types is discussed. Finally, several simulations are conducted to prove our analysis and the improved LO modulation can reconstruct multiple mono-pulse signals under the frequency aliasing condition.

Neural dynamics driving audio-visual integration in autism.

Audio-visual (AV) integration plays a crucial role in supporting social functions and communication in autism spectrum disorder (ASD). However, behavioral findings remain mixed and, importantly, little is known about the underlying neurophysiological bases. Studies in neurotypical adults indicate that oscillatory brain activity in different frequencies subserves AV integration, pointing to a central role of (i) individual alpha frequency (IAF), which would determine the width of the cross-modal binding window; (ii) pre-/peri-stimulus theta oscillations, which would reflect the expectation of AV co-occurrence; (iii) post-stimulus oscillatory phase reset, which would temporally align the different unisensory signals. Here, we investigate the neural correlates of AV integration in children with ASD and typically developing (TD) peers, measuring electroencephalography during resting state and in an AV integration paradigm. As for neurotypical adults, AV integration dynamics in TD children could be predicted by the IAF measured at rest and by a modulation of anticipatory theta oscillations at single-trial level. Conversely, in ASD participants, AV integration/segregation was driven exclusively by the neural processing of the auditory stimulus and the consequent auditory-induced phase reset in visual regions, suggesting that a disproportionate elaboration of the auditory input could be the main factor characterizing atypical AV integration in autism.

Modulation of Brain Rhythm Oscillations by Xingnao Kaiqiao Acupuncture Correlates with Stroke Recovery: A Randomized Control Trial.

Objectives: In China, Xingnao Kaiqiao (XNKQ) acupuncture has been widely used for stroke treatment. However, its electrophysiological mechanism remains unclear. Hence, this study aims to study how XNKQ acupuncture modulates brain rhythm oscillations of stroke patients, and investigate its correlation with stroke recovery. Design: Randomized control trial. Subjects: Twenty (sub)acute ischemic stroke patients were enrolled and randomly assigned to two groups (an acupuncture group [AG] [n = 10] and a control group [CG] [n = 10]), and four patients (two patients in each group) dropped out of the study. Interventions: All patients received conventional treatments, and the patients in AG received additional XNKQ acupuncture treatment once a day for 10 consecutive days. Outcome measures: Before treatment, 14 days after, and 30 days after treatment onset, their movement impairments and neurologic deficits were measured using the National Institute of Health Stroke Scale (NIHSS), the Fugl-Meyer (FM) Scale, the Modified Rankin Scale (mRS), and the Modified Barthel Index (MBI), and their electroencephalogram data were recorded. Results: Compared with the CG, the AG showed more improvement in FM scores (p = 0.02), as well as decreased relative delta power and increased relative alpha power after 2 weeks' treatment. The decrease of the relative delta power and the increase of the relative alpha power in the ipsilesional frontal area were significantly correlated with the FM improvement (F5, F7, FC1, and Fz electrodes, all |r| > 0.517, p < 0.040). Conclusions: The curative effect of XNKQ acupuncture related to its electrophysiological modulation. This study was registered at the Chinese Clinical Trial Registry (ChiCTR2000038560).

Modulation of Gamma Spectral Amplitude and Connectivity During Reaching Predicts Peak Velocity and Movement Duration

Modulation of gamma oscillations recorded from the human motor cortex and basal ganglia appears to play a key role in movement execution. However, there are still major questions to be answered about the specific role of cortical gamma activity in both the planning and execution of movement features such as the scaling of peak velocity and movement time. In this study, we characterized movement-related gamma oscillatory dynamics and its relationship with kinematic parameters based on 256-channels EEG recordings in 64 healthy subjects while performing fast and uncorrected reaching movements to targets located at three distances. In keeping with previous studies, we found that movement-related gamma synchronization occurred during movement execution. As a new finding, we showed that gamma synchronization occurred also before movement onset, with planning and execution phases involving different gamma peak frequencies and topographies. Importantly, the amplitude of gamma synchronization in both planning and execution increased with target distance and predicted peak velocity and movement time. Additional analysis of phase coherence revealed a gamma-coordinated long-range network involving occipital, frontal and central regions during movement execution that was positively related to kinematic features. This is the first evidence in humans supporting the notion that gamma synchronization amplitude and phase coherence pattern can reliably predict peak velocity amplitude and movement time. Therefore, these findings suggest that cortical gamma oscillations have a crucial role for the selection, implementation and control of the appropriate kinematic parameters of goal-directed reaching movements.

Modulation of cortical oscillations by periodic electrical stimulation is frequency-dependent

The brain oscillations play a pivotal role in transmitting and processing the information. Periodic electrical stimulation has been proposed to shape the oscillations. However, how the periodic electrical stimulation modulates the oscillatory activities remains poorly understood. To address this question, a modified cortical network by adding the brain state information (eye–open and eye–closed states) and synaptic plasticity is employed. Constraining on eye–open state and without considering the synaptic plasticity, the numerical simulation results have shown that the network responses are strong frequency–dependent and the underlying mechanism of the network oscillations has been recognized as three typical neural phenomena, that is resonance, entrainment, and nonlinear oscillation, induced by periodic stimulation with different frequencies and amplitudes. We further prove the frequency dependency of network responses through theoretical analysis. Moreover, the impacts of the brain state have been explored. It is shown that the brain state has little impact on the network oscillatory response during stimulus and generates only a very short–lasting effect. However, the introduce of the plasticity in the cortical network makes the periodic stimulation generate obvious post—stimulus effects. Even though the stimulation is removed, the cortical network can still maintain the resonance, entrainment, and nonlinear oscillatory activities. The frequency–dependent network response mechanism provides a profound understanding of neural information communication theory induced by the periodic stimulus.

Conditioned up and down modulations of short latency gamma band oscillations in visual cortex during fear learning in humans

Over the course of evolution, the human brain has been shaped to prioritize cues that signal potential danger. Thereby, the brain does not only favor species-specific prepared stimulus sets such as snakes or spiders but can learn associations between new cues and aversive outcomes. One important mechanism to achieve this is associated with learning induced plasticity changes in sensory cortex that optimizes the representation of motivationally relevant sensory stimuli. Animal studies have shown that the modulation of gamma band oscillations predicts plasticity changes in sensory cortices by shifting neurons’ responses to fear relevant features as acquired by Pavlovian fear conditioning. Here, we report conditioned gamma band modulations in humans during fear conditioning of orthogonally oriented sine gratings representing fear relevant and irrelevant conditioned cues. Thereby, pairing of a sine grating with an aversive loud noise not only increased short latency (during the first 180 ms) evoked visual gamma band responses, but was also accompanied by strong gamma power reductions for the fear irrelevant control grating. The current findings will be discussed in the light of recent neurobiological models of plasticity changes in sensory cortices and classic learning models such as the Rescorla–Wagner framework.

Dorsal-to-ventral imbalance in the superior longitudinal fasciculus mediates methylphenidate's effect on beta oscillations in ADHD.

While pharmacological treatment with methylphenidate (MPH) is a first line intervention for ADHD, its mechanisms of action have yet to be elucidated. We here seek to identify the white matter tracts that mediate MPH’s effect on beta oscillations. We implemented a double‐blind placebo‐controlled crossover design, where boys diagnosed with ADHD underwent behavioral and MEG measurements during a spatial attention task while on and off MPH. The results were compared with an age/IQ‐matched control group. Estimates of white matter tracts were obtained using diffusion tensor imaging (DTI). Via a stepwise model selection strategy, we identified the fiber tracts (regressors) significantly predicting values of the dependent variables of interest (i.e., oscillatory power, behavioral performance, and clinical symptoms): the anterior thalamic radiation (ATR), the superior longitudinal fasciculus (“parietal endings”) (SLFp), and superior longitudinal fasciculus (“temporal endings”) (SLFt). ADHD symptoms severity was associated with lower fractional anisotropy (FA) within the ATR. In addition, individuals with relatively higher FA in SLFp compared to SLFt, led to stronger behavioral effects of MPH in the form of faster and more accurate responses. Furthermore, the same parietotemporal FA gradient explained the effects of MPH on beta modulation: subjects with ADHD exhibiting higher FA in SLFp compared to SLFt also displayed greater effects of MPH on beta power during response preparation. Our data suggest that the behavioral deficits and aberrant oscillatory modulations observed in ADHD depend on a possibly detrimental structural connectivity imbalance within the SLF, caused by a diffusivity gradient in favor of parietal rather than temporal, fiber tracts.

Tensor decomposition of human narrowband oscillatory brain activity in frequency, space and time

Many brain processes in health and disease are associated with modulation of narrowband brain oscillations (NBOs) in the scalp-recorded EEG, which exhibit specific frequency spectra and scalp topography. Isolating and tracking NBOs over time using algorithms is useful in domains such as brain-computer interfaces or when measuring the EEG effects of experimental manipulations. Previously, we successfully applied modified tensor methods for identifying and tracking NBO activity over time or conditions. We introduced frequency and spatial constraints that greatly improved their physiological plausibility. In this paper we rigorously demonstrate the power and precision of tensor methods to separate, isolate and track NBOs using sources simulated with an anatomical forward model. This allows us to control the attributes of NBOs and validate tensor solutions. We find that tensor methods can accurately identify, separate and track NBOs over time, using realistic sources either alone or in combination, and compare favorably to well-known spatio-spectral decomposition methods for NBO estimation.

Frequency-dependent genetic modulation of neuronal oscillations: a combined transcriptome and resting-state functional MRI study.

Neuronal oscillations within certain frequency bands are assumed to associate with specific neural processes and cognitive functions. To examine this hypothesis, transcriptome-neuroimaging spatial correlation analysis was applied to resting-state functional magnetic resonance imaging data from 793 healthy individuals and gene expression data from the Allen Human Brain Atlas. We found that expression measures of 336 genes were correlated with fractional amplitude of low-frequency fluctuations (fALFF) in the slow-4 band (0.027-0.073Hz), whereas there were no expression-fALFF correlations for the other frequency bands. Furthermore, functional enrichment analyses showed that these slow-4 fALFF-related genes were mainly enriched for ion channel, synaptic function, and neuronal system as well as many neuropsychiatric disorders. Specific expression analyses demonstrated that these genes were specifically expressed in brain tissue, in neurons, and during the late stage of cortical development. Concurrently, the fALFF-related genes were linked to multiple behavioral domains, including dementia, attention, and emotion. In addition, these genes could construct a protein-protein interaction network supported by 30 hub genes. Our findings of a frequency-dependent genetic modulation of spontaneous neuronal activity may support the concept that neuronal oscillations within different frequency bands capture distinct neurobiological processes from the perspective of underlying molecular mechanisms.

The Madden–Julian Oscillation in the Energy Exascale Earth System Model Version 1

AbstractThe present study examines the characteristics of the Madden–Julian Oscillation (MJO) events represented in the Energy Exascale Earth System Model version 1 (E3SMv1), DOE’s new Earth system model. The coupled E3SMv1 realistically simulates the eastward propagation of precipitation and moist static energy (MSE) anomalies associated with the MJO. As in observations, horizontal moisture advection and longwave radiative feedback are found to be the dominant processes in E3SMv1 that lead to the eastward movement and maintenance of the MJO MSE anomalies, respectively. Modulation of the diurnal cycle of precipitation in the Maritime Continent region by the MJO is also well represented in the model despite systematic biases in the magnitude and phase of the precipitation diurnal cycle. On the MJO impact over the midlatitude, E3SMv1 reasonably captures the pattern of the MJO teleconnections across the North Pacific and North America, with improvement in the performance in a high‐resolution version, despite the magnitude being a bit weaker than the observed. Regarding the interannual variability of the MJO, the El Niño‐Southern Oscillation (ENSO) modulation of the zonal extent of MJO’s eastward propagation, as well as associated changes in the mean state moisture gradient in the tropical west Pacific, are well reproduced in the model. However, MJO in E3SMv1 exhibits no sensitivity to the Quasi‐Biennial Oscillation (QBO), with the MJO propagation characteristics being almost identical between easterly QBO and westerly QBO years. Processes that have been suggested as critical to MJO simulation are also examined by utilizing recently developed process‐oriented diagnostics.

Targeted Discovery of Amantamide B, an Ion Channel Modulating Nonapeptide from a South China Sea Oscillatoria Cyanobacterium.

Amantamide B (1) is a new linear nonapeptide analogue of the cyanobacterial natural product amantamide A (2), and both have methyl ester and butanamide termini. These compounds were discovered in this study from the organic extract of a tropical marine filamentous cyanobacterium, Oscillatoria sp., collected around the Paracel Islands in the South China Sea. The use of LC-MS/MS molecular networking for sample prioritization and as an analytical dereplication tool facilitated the targeted isolation of 1 and 2. These molecules were characterized by spectroscopy and spectrometry, and configurational assignments were determined using chemical degradation and chiral-phase HPLC analysis. Compounds 1 and 2 modulated spontaneous calcium oscillations without notable cytotoxicity at 10 μM in short duration in vitro testing on primary cultured neocortical neurons, a model system that evaluates neuronal excitability and/or the potential activity on Ca2+ signaling. Both molecules were also found to be moderately cytotoxic in longer duration bioassays, with in vitro IC50 values of 1-10 μM against CCRF-CEM human T lymphoblastoid cells and U937 human histiocytic lymphoma cells. These formerly undiscovered bioactivities of known compound 2 expand upon its previously reported function as a selective CXCR7 agonist among 168 GPCR targets.

Design and Development of an Android App (HanDex) to Enhance Hand Dexterity in Children With Poor Handwriting

According to the oscillation theory of handwriting, letters are formed by the coupled modulation of horizontal and vertical oscillation of our hands. This modulation-oscillation scheme requires human motor control. Hence one of the reasons for poor handwriting is lack of fine motor skills. The main objective of this study is to design, develop and evaluate a hand therapeutic-application (HanDex) for children with writing difficulties, to enhance their hand dexterity. Hence this paper describes the design, development and evaluation of the HanDex app. It has mainly five activities for improving tripod grip, hand-eye coordination, spatial organization, letter formation and fine motor skills. The main principle behind the design of all these activities is the oscillation theory of handwriting. A set of user interface (UI) guidelines have been followed in the UI design for simplicity, user-motivation, easy navigation, etc. User evaluation of the prototype was conducted by ten participants in five iterations and the final product was built by considering their feedback. After that, we have conducted case studies in two primary school children with poor handwriting to test the effectiveness of the application. The study used a single subject pretest-posttest design to observe and measure the efficacy of the HanDex application. The post test results showed a positive impact on letter formation, size of letters, spacing of letters and words, placement, speed and legibility in these children. Hence the HanDex app is promising and warrants further investigation on more children with different levels of handwriting difficulty.