In animal cells, microtubule and actin tracks and their associated motors (dynein, kinesin, and myosin) are thought to regulate long- and short-range transport, respectively 1–8. Consistent with ...this, microtubules extend from the perinuclear centrosome to the plasma membrane and allow bidirectional cargo transport over long distances (>1 μm). In contrast, actin often comprises a complex network of short randomly oriented filaments, suggesting that myosin motors move cargo short distances. These observations underpin the “highways and local roads” model for transport along microtubule and actin tracks 2. The “cooperative capture” model exemplifies this view and suggests that melanosome distribution in melanocyte dendrites is maintained by long-range transport on microtubules followed by actin/myosin-Va-dependent tethering 5, 9. In this study, we used cell normalization technology to quantitatively examine the contribution of microtubules and actin/myosin-Va to organelle distribution in melanocytes. Surprisingly, our results indicate that microtubules are essential for centripetal, but not centrifugal, transport. Instead, we find that microtubules retard a centrifugal transport process that is dependent on myosin-Va and a population of dynamic F-actin. Functional analysis of mutant proteins indicates that myosin-Va works as a transporter dispersing melanosomes along actin tracks whose +/barbed ends are oriented toward the plasma membrane. Overall, our data highlight the role of myosin-Va and actin in transport, and not tethering, and suggest a new model in which organelle distribution is determined by the balance between microtubule-dependent centripetal and myosin-Va/actin-dependent centrifugal transport. These observations appear to be consistent with evidence coming from other systems showing that actin/myosin networks can drive long-distance organelle transport and positioning 10, 11.
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•Microtubules are essential for centripetal, but not centrifugal, melanosome transport•Myosin-Va and a dynamic actin pool drive long-range centrifugal melanosome transport•Myosin-Va is a processive plus-end-directed motor, and not a tether, in melanocytes•Opposing myosin-Va/actin and microtubule forces regulate melanosome distribution
In animal cells, microtubules and actin are thought to regulate long- and short-range transport, respectively. Here, Evans et al. test the contribution of these systems to organelle transport using melanocyte pigment granules as a model. Surprisingly, they find that myosin-Va and dynamic actin drive long-range transport to the membrane.
Goal: The aim of the study herein reported was to review mobile health (mHealth) technologies and explore their use to monitor and mitigate the effects of the COVID-19 pandemic. Methods: A Task Force ...was assembled by recruiting individuals with expertise in electronic Patient-Reported Outcomes (ePRO), wearable sensors, and digital contact tracing technologies. Its members collected and discussed available information and summarized it in a series of reports. Results: The Task Force identified technologies that could be deployed in response to the COVID-19 pandemic and would likely be suitable for future pandemics. Criteria for their evaluation were agreed upon and applied to these systems. Conclusions: mHealth technologies are viable options to monitor COVID-19 patients and be used to predict symptom escalation for earlier intervention. These technologies could also be utilized to monitor individuals who are presumed non-infected and enable prediction of exposure to SARS-CoV-2, thus facilitating the prioritization of diagnostic testing.
Background
Measuring free-living gait using wearable devices may offer higher granularity and temporal resolution than the current clinical assessments for patients with Parkinson disease (PD). ...However, increasing the number of devices worn on the body adds to the patient burden and impacts the compliance.
Objective
This study aimed to investigate the impact of reducing the number of wearable devices on the ability to assess gait impairments in patients with PD.
Methods
A total of 35 volunteers with PD and 60 healthy volunteers performed a gait task during 2 clinic visits. Participants with PD were assessed in the On and Off medication state using the Movement Disorder Society version of the Unified Parkinson Disease Rating Scale (MDS-UPDRS). Gait features derived from a single lumbar-mounted accelerometer were compared with those derived using 3 and 6 wearable devices for both participants with PD and healthy participants.
Results
A comparable performance was observed for predicting the MDS-UPDRS gait score using longitudinal mixed-effects model fit with gait features derived from a single (root mean square error RMSE=0.64; R2=0.53), 3 (RMSE=0.64; R2=0.54), and 6 devices (RMSE=0.54; R2=0.65). In addition, MDS-UPDRS gait scores predicted using all 3 models differed significantly between On and Off motor states (single device, P=.004; 3 devices, P=.004; 6 devices, P=.045).
Conclusions
We observed a marginal benefit in using multiple devices for assessing gait impairments in patients with PD when compared with gait features derived using a single lumbar-mounted accelerometer. The wearability burden associated with the use of multiple devices may offset gains in accuracy for monitoring gait under free-living conditions.
Desmoid type fibromatosis (DTF) is a rare benign tumor of connective tissue origin. While these tumors are typically not malignant, they can exhibit aggressive growth patterns causing mass effect on ...surrounding organs. These tumors typically present in the extremities and abdominal wall, rarely occurring in the mesentery, and abdominal organs. Due to the rarity of this tumor and the variable size and origin, it is difficult to provide exact prognosis, recurrence, and treatment efficacy regarding desmoid tumors arising from the ileocolic mesentery. We present a case of a young male with a sporadic 31 × 25 × 12 cm DTF arising from the ileocolic mesentery that was complicated by mass effect on bowel and intra-abdominal organs requiring surgical intervention. On presentation, the patient exhibited weight gain and abdominal pressure. Abdominal distension without tenderness on palpation was noted on physical examination. The tumor biopsy confirmed the diagnosis of DTF. No evidence of familial adenomatous polyposis or Gardner syndrome was identified. The tumor was surgically excised and intimately associated with the bowel requiring ileocolonic resection with primary anastomosis. At 3-months follow up, surveillance MRI showed no residual or recurrent lesion. A multi-disciplinary approach to this patient's diagnosis and treatment allowed for an accurate diagnosis, efficient treatment, and follow up plan.
Patients with atopic dermatitis experience increased nocturnal pruritus which leads to scratching and sleep disturbances that significantly contribute to poor quality of life. Objective measurements ...of nighttime scratching and sleep quantity can help assess the efficacy of an intervention. Wearable sensors can provide novel, objective measures of nighttime scratching and sleep; however, many current approaches were not designed for passive, unsupervised monitoring during daily life. In this work, we present the development and analytical validation of a method that sequentially processes epochs of sample-level accelerometer data from a wrist-worn device to provide continuous digital measures of nighttime scratching and sleep quantity. This approach uses heuristic and machine learning algorithms in a hierarchical paradigm by first determining when the patient intends to sleep, then detecting sleep-wake states along with scratching episodes, and lastly deriving objective measures of both sleep and scratch. Leveraging reference data collected in a sleep laboratory (NCT ID: NCT03490877), results show that sensor-derived measures of total sleep opportunity (TSO; time when patient intends to sleep) and total sleep time (TST) correlate well with reference polysomnography data (TSO: r = 0.72, p < 0.001; TST: r = 0.76, p < 0.001; N = 32). Log transformed sensor derived measures of total scratching duration achieve strong agreement with reference annotated video recordings (r = 0.82, p < 0.001; N = 25). These results support the use of wearable sensors for objective, continuous measurement of nighttime scratching and sleep during daily life.
Technological advances in multimodal wearable and connected devices have enabled the measurement of human movement and physiology in naturalistic settings. The ability to collect continuous activity ...monitoring data with digital devices in real-world environments has opened unprecedented opportunity to establish clinical digital phenotypes across diseases. Many traditional assessments of physical function utilized in clinical trials are limited because they are episodic, therefore, cannot capture the day-to-day temporal fluctuations and longitudinal changes in activity that individuals experience. In order to understand the sensitivity of gait speed as a potential endpoint for clinical trials, we investigated the use of digital devices during traditional clinical assessments and in real-world environments in a group of healthy younger (
= 33, 18-40 years) and older (
= 32, 65-85 years) adults. We observed good agreement between gait speed estimated using a lumbar-mounted accelerometer and gold standard system during the performance of traditional gait assessment task in-lab, and saw discrepancies between in-lab and at-home gait speed. We found that gait speed estimated in-lab, with or without digital devices, failed to differentiate between the age groups, whereas gait speed derived during at-home monitoring was able to distinguish the age groups. Furthermore, we found that only three days of at-home monitoring was sufficient to reliably estimate gait speed in our population, and still capture age-related group differences. Our results suggest that gait speed derived from activities during daily life using data from wearable devices may have the potential to transform clinical trials by non-invasively and unobtrusively providing a more objective and naturalistic measure of functional ability.
This article presents a novel ramp rate control and active power smoothing and shifting methodology for net-load profiles in large power distribution networks where high amount of photovoltaic (PV) ...penetration levels exist. The novelty is that the proposed methodology uses dynamic state-of-charge (SoC) management, energy storage optimal use of any given size and fast-Fourier transform-based reference curves that adequately fit energy storage system (ESS) active and reactive power capabilities. Then, a least square minimization-based optimization method is applied taking both ancillary applications into consideration and to maintain SoC within limits based on ESS capacity. The methodology is applied on a 8500 nodes US power grid model using CYMEDist simulation platform and applied on a real US power distribution system. Results show significant level of net-load ramp rate reduction as well as smoothing of fast fluctuations (up to 60%) due to both PV intermittency and load changes. The approach is also capable of breaking large systems into virtual local net-load locations where ESS's are installed to mitigate the severity of the anticipated shape of system net-loads.
This article proposes a distributed control architecture for distributed energy resources (DERs) that include photovoltaics (PVs) and battery energy storage systems (BESSs). The control architecture ...is based on the virtual clustering of DERs to provide power balance (minimizing the net load (generation load) in each cluster) in each cluster considering the state of charge of the BESS. First, the architecture designs a spectral clustering to develop optimal clusters based on the number of DERs that provide clusters with minimum power transfer between clusters. Then, an error-minimization-based optimal control architecture provides sufficient set points to the BESS intending to provide power balance. The novelty of the proposed clustering is that it provides a distributed dynamic model of the grid with measurements that are stable and scalable. The control approach not only provides an optimal set point for the BESS but also takes into account the state of charge and provides intercluster balance. This framework can also manage the local grid effectively as the distribution is dynamic considering the state of the BESS and the number of DERs. The distributed control objectives are efficient and scalable. The architecture is tested on the IEEE 123-bus system and the IEEE 8500-bus system and observed that the approach provides effective power balance and outperforms the existing methods.
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