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1.
Proc Natl Acad Sci U S A ; 118(34)2021 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-34408019

RESUMEN

Understanding how populations' daily behaviors change during the COVID-19 pandemic is critical to evaluating and adapting public health interventions. Here, we use residential electricity-consumption data to unravel behavioral changes within peoples' homes in this period. Based on smart energy-meter data from 10,246 households in Singapore, we find strong positive correlations between the progression of the pandemic in the city-state and the residential electricity consumption. In particular, we find that the daily new COVID-19 cases constitute the most dominant influencing factor on the electricity demand in the early stages of the pandemic, before a lockdown. However, this influence wanes once the lockdown is implemented, signifying that residents have settled into their new lifestyles under lockdown. These observations point to a proactive response from Singaporean residents-who increasingly stayed in or performed more activities at home during the evenings, despite there being no government mandates-a finding that surprisingly extends across all demographics. Overall, our study enables policymakers to close the loop by utilizing residential electricity usage as a measure of community response during unprecedented and disruptive events, such as a pandemic.


Asunto(s)
COVID-19/epidemiología , COVID-19/prevención & control , Control de Enfermedades Transmisibles/métodos , Conducta Cooperativa , Equipos y Suministros Eléctricos/estadística & datos numéricos , Electricidad , Cuarentena , COVID-19/transmisión , Composición Familiar , Humanos , Salud Pública , SARS-CoV-2/aislamiento & purificación , Singapur/epidemiología
2.
Dev Dyn ; 247(4): 620-629, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28691197

RESUMEN

BACKGROUND: Humans with heterozygous mutations in the axon guidance receptor DCC display congenital mirror movements (MMs), which are involuntary movements of body parts, such as fingers, on one side of the body that mirror voluntary movement of the opposite side. In mice, the homozygous Dcckanga mutant allele causes synchronous MM-like hindlimb movements during locomotion, resulting in hopping. In both human and mice, the neuroanatomical defect responsible for the deficit in lateralized motor control remains to be elucidated. RESULTS: Using the HoxB8-Cre line to specifically remove Dcc from the spinal cord, we found misrouting of commissural axons during their migration toward the floor plate, resulting in fewer axons crossing the midline. These mice also have a hopping gait, indicating that spinal cord guidance defects alone are sufficient to cause hopping. CONCLUSIONS: Dcc plays a role in the development of local spinal networks to ensure proper lateralization of motor control during locomotion. Local spinal cord defects following loss of Dcc cause a hopping gait in mice and may contribute to MM in humans. Developmental Dynamics 247:620-629, 2018. © 2017 Wiley Periodicals, Inc.


Asunto(s)
Receptor DCC/genética , Médula Espinal/fisiopatología , Animales , Receptor DCC/deficiencia , Lateralidad Funcional , Marcha , Humanos , Locomoción , Ratones
3.
J Cell Sci ; 129(20): 3832-3844, 2016 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-27632999

RESUMEN

Sonic Hedgehog (Shh) is a secreted morphogen that is an essential regulator of patterning and growth. The Shh full-length protein undergoes autocleavage in the endoplasmic reticulum to generate the biologically active N-terminal fragment (ShhN), which is destined for secretion. We identified sortilin (Sort1), a member of the VPS10P-domain receptor family, as a new Shh trafficking receptor. We demonstrate that Sort-Shh interact by performing coimmunoprecipitation and proximity ligation assays in transfected cells and that they colocalize at the Golgi. Sort1 overexpression causes re-distribution of ShhN and, to a lesser extent, of full-length Shh to the Golgi and reduces Shh secretion. We show loss of Sort1 can partially rescue Hedgehog-associated patterning defects in a mouse model that is deficient in Shh processing, and we show that Sort1 levels negatively regulate anterograde Shh transport in axons in vitro and Hedgehog-dependent axon-glial interactions in vivo Taken together, we conclude that Shh and Sort1 can interact at the level of the Golgi and that Sort1 directs Shh away from the pathways that promote its secretion.


Asunto(s)
Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Proteínas Hedgehog/metabolismo , Animales , Astrocitos/citología , Axones/metabolismo , Células CHO , Células COS , Proliferación Celular , Chlorocebus aethiops , Cricetinae , Cricetulus , Técnicas de Inactivación de Genes , Aparato de Golgi/metabolismo , Mutación/genética , Nervio Óptico/metabolismo , Células PC12 , Unión Proteica , Procesamiento Proteico-Postraduccional , Transporte de Proteínas , Ratas , Células Ganglionares de la Retina/metabolismo , Vías Secretoras
4.
Nat Commun ; 13(1): 3213, 2022 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-35680877

RESUMEN

An adequate charging infrastructure is key to enabling high personal electric vehicle (EV) adoption rates. However, urban flooding-whose frequency and intensity are increasing due to climate change-may be an impediment. Here, we study how geographically-correlated outages due to floods impact public EV charging networks in Greater London. While we find no appreciable impact on the ability of battery EVs to serve typical urban driving behaviors, we observe disproportionate stresses on chargers both near, and surprisingly significantly farther from, the flooded regions. For instance, we find over 50% increase in charger utilization and 260% increase in the distance to the nearest available charger in parts of Greater London over 10 km away. Concerningly, the impact is most concentrated on already-stressed sections of the network, underscoring the infrastructure's vulnerability. Finally, we develop and evaluate four strategies for city planners to enhance the flood resilience of cities' public EV charging networks.


Asunto(s)
Cambio Climático , Inundaciones , Ciudades
5.
Sci Rep ; 12(1): 13714, 2022 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-35962019

RESUMEN

Increasing the inertia is widely considered to be the solution to resolving unstable interactions between coupled oscillators. In power grids, Virtual Synchronous Generators (VSGs) are proposed to compensate for reducing inertia as rotating fossil-fuel-based generators are being phased out. Yet, modeling how VSGs and rotating generators simultaneously contribute energy and inertia, we surprisingly find that instabilities of a small-signal nature could arise despite fairly high system inertia if the generators' controls are not coordinated at the system level. Importantly, we show there exist both an optimal and a maximum number of such VSGs that can be safely supported, a previously unknown result directly useful for power utilities in long-term planning and prosumer contracting. Meanwhile, to resolve instabilities in the short term until system-level coordination can be achieved, we argue that the new market should include another commodity that we call stability storage, whereby-analogous to energy storage buffering energy imbalances-VSGs act as decentralized stability buffers. While demonstrating the effectiveness of this concept for a wide range of energy futures, we provide policymakers and utilities with a roadmap towards achieving a 100% renewable grid.

6.
eNeuro ; 9(2)2022.
Artículo en Inglés | MEDLINE | ID: mdl-35115383

RESUMEN

Axon guidance receptors such as deleted in colorectal cancer (DCC) contribute to the normal formation of neural circuits, and their mutations can be associated with neural defects. In humans, heterozygous mutations in DCC have been linked to congenital mirror movements, which are involuntary movements on one side of the body that mirror voluntary movements of the opposite side. In mice, obvious hopping phenotypes have been reported for bi-allelic Dcc mutations, while heterozygous mutants have not been closely examined. We hypothesized that a detailed characterization of Dcc heterozygous mice may reveal impaired corticospinal and spinal functions. Anterograde tracing of the Dcc+/- motor cortex revealed a normally projecting corticospinal tract, intracortical microstimulation (ICMS) evoked normal contralateral motor responses, and behavioral tests showed normal skilled forelimb coordination. Gait analyses also showed a normal locomotor pattern and rhythm in adult Dcc+/- mice during treadmill locomotion, except for a decreased occurrence of out-of-phase walk and an increased duty cycle of the stance phase at slow walking speed. Neonatal isolated Dcc+/- spinal cords had normal left-right and flexor-extensor coupling, along with normal locomotor pattern and rhythm, except for an increase in the flexor-related motoneuronal output. Although Dcc+/- mice do not exhibit any obvious bilateral impairments like those in humans, they exhibit subtle motor deficits during neonatal and adult locomotion.


Asunto(s)
Locomoción , Tractos Piramidales , Animales , Receptor DCC/genética , Heterocigoto , Locomoción/genética , Ratones , Neuronas Motoras/fisiología , Fenotipo
7.
IEEE Trans Cybern ; 51(7): 3687-3698, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32452784

RESUMEN

This article investigates the impact of data integrity attacks (DIAs) on cooperative economic dispatch of distributed generators (DGs) in an ac microgrid. To establish resiliency against such attacks and ensure optimal operation, a localized event-driven attack-resilient scheme is proposed. Most of the existing works examine neighboring information to infer the presence of DIAs, where the detection is limited to events such as multiple link failures. Two kinds of DIAs are considered in this article-namely, fault and random attacks, which are segregated based on the final values of consensus updates. First, to improve the robustness of the detection theory, a localized resilient control update is designed by modeling each DG with a reference incremental cost. Second, event-driven control signal is generated for the local incremental cost and held upon the detection of attacks, to prevent malicious data from propagating to the neighboring nodes. The proposed strategy acts immediately upon the detection of DIA to ensure maximization in the economic profit. Furthermore, the proposed detection approach is theoretically verified and validated using simulation conditions.

8.
Sci Rep ; 11(1): 5329, 2021 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-33674635

RESUMEN

Disinformation continues to raise concerns due to its increasing threat to society. Nevertheless, a threat of a disinformation-based attack on critical infrastructure is often overlooked. Here, we consider urban traffic networks and focus on fake information that manipulates drivers' decisions to create congestion at a city scale. Specifically, we consider two complementary scenarios, one where drivers are persuaded to move towards a given location, and another where they are persuaded to move away from it. We study the optimization problem faced by the adversary when choosing which streets to target to maximize disruption. We prove that finding an optimal solution is computationally intractable, implying that the adversary has no choice but to settle for suboptimal heuristics. We analyze one such heuristic, and compare the cases when targets are spread across the city of Chicago vs. concentrated in its business district. Surprisingly, the latter results in more far-reaching disruption, with its impact felt as far as 2 km from the closest target. Our findings demonstrate that vulnerabilities in critical infrastructure may arise not only from hardware and software, but also from behavioral manipulation.

9.
PLoS One ; 15(8): e0236517, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32785250

RESUMEN

Social media has made it possible to manipulate the masses via disinformation and fake news at an unprecedented scale. This is particularly alarming from a security perspective, as humans have proven to be one of the weakest links when protecting critical infrastructure in general, and the power grid in particular. Here, we consider an attack in which an adversary attempts to manipulate the behavior of energy consumers by sending fake discount notifications encouraging them to shift their consumption into the peak-demand period. Using Greater London as a case study, we show that such disinformation can indeed lead to unwitting consumers synchronizing their energy-usage patterns, and result in blackouts on a city-scale if the grid is heavily loaded. We then conduct surveys to assess the propensity of people to follow-through on such notifications and forward them to their friends. This allows us to model how the disinformation may propagate through social networks, potentially amplifying the attack impact. These findings demonstrate that in an era when disinformation can be weaponized, system vulnerabilities arise not only from the hardware and software of critical infrastructure, but also from the behavior of the consumers.


Asunto(s)
Comunicación , Difusión de la Información , Medios de Comunicación Sociales , Red Social , Ciudades , Sistemas de Computación , Decepción , Humanos , Londres , Programas Informáticos , Encuestas y Cuestionarios
10.
Neuron ; 97(2): 326-340.e4, 2018 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-29346753

RESUMEN

At the optic chiasm choice point, ipsilateral retinal ganglion cells (RGCs) are repelled away from the midline by guidance cues, including Ephrin-B2 and Sonic Hedgehog (Shh). Although guidance cues are normally produced by cells residing at the choice point, the mRNA for Shh is not found at the optic chiasm. Here we show that Shh protein is instead produced by contralateral RGCs at the retina, transported anterogradely along the axon, and accumulates at the optic chiasm to repel ipsilateral RGCs. In vitro, contralateral RGC axons, which secrete Shh, repel ipsilateral RGCs in a Boc- and Smo-dependent manner. Finally, knockdown of Shh in the contralateral retina causes a decrease in the proportion of ipsilateral RGCs in a non-cell-autonomous manner. These findings reveal a role for axon-axon interactions in ipsilateral RGC guidance, and they establish that remotely produced cues can act at axon guidance midline choice points.


Asunto(s)
Transporte Axonal/fisiología , Axones/fisiología , Proteínas Hedgehog/metabolismo , Proteínas del Tejido Nervioso/fisiología , Quiasma Óptico/embriología , Células Ganglionares de la Retina/metabolismo , Animales , Inmunoglobulina G/fisiología , Ratones , Quiasma Óptico/metabolismo , Transporte de Proteínas , Receptores de Superficie Celular/fisiología , Receptor Smoothened/fisiología
11.
Science ; 351(6275): 849-54, 2016 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-26912893

RESUMEN

Astrocytes are specialized and heterogeneous cells that contribute to central nervous system function and homeostasis. However, the mechanisms that create and maintain differences among astrocytes and allow them to fulfill particular physiological roles remain poorly defined. We reveal that neurons actively determine the features of astrocytes in the healthy adult brain and define a role for neuron-derived sonic hedgehog (Shh) in regulating the molecular and functional profile of astrocytes. Thus, the molecular and physiological program of astrocytes is not hardwired during development but, rather, depends on cues from neurons that drive and sustain their specialized properties.


Asunto(s)
Astrocitos/metabolismo , Corteza Cerebelosa/citología , Proteínas Hedgehog/metabolismo , Neuronas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animales , Femenino , Eliminación de Gen , Proteínas Hedgehog/genética , Masculino , Ratones , Ratones Mutantes , Receptores Acoplados a Proteínas G/genética , Transducción de Señal , Receptor Smoothened
12.
Curr Opin Neurobiol ; 23(1): 109-18, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22989473

RESUMEN

Mirror movements (MM) are a peculiar motor defect in humans where the intended unilateral movement of a body part results in involuntary movement of the same body part on the opposite side. This loss in the lateralization of motor control can be caused by genetic mutations that result in an aberrant projection of the corticospinal tract. However, recent evidence suggests that the same genes controlling corticospinal tract development also play roles in the development of other circuits involved in motor control, including local spinal circuits and the corpus callosum. These recent studies in humans and mouse models of MM will be discussed to provide an overview of the basis of MM and the molecular mechanisms underlying the lateralization of motor control.


Asunto(s)
Lateralidad Funcional/genética , Trastornos del Movimiento/genética , Animales , Humanos , Corteza Motora/fisiología , Trastornos del Movimiento/fisiopatología , Tractos Piramidales/fisiología
13.
Dev Cell ; 17(4): 459-69, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19853560

RESUMEN

PTEN is one of the most commonly lost tumor suppressors in human cancer and is known to inhibit insulin signaling. Eph receptor tyrosine kinases (RTKs) have also been implicated in cancer formation and progression, and they have diverse functions, including nervous and vascular system development. We show that in C. elegans, the VAB-1 Eph kinase domain physically interacts with and phosphorylates PTEN (DAF-18), diminishing its protein levels and function. vab-1 mutants show increased longevity and sensitivity to dauer conditions, consistent with increased DAF-18/PTEN activity and decreased insulin-like signaling. Moreover, daf-18 mutations suppress vab-1 oocyte maturation phenotypes independent of PI3K signaling. We also present evidence that DAF-18 has protein phosphatase activity to antagonize VAB-1 action. Possible implications for human cancers are discussed, based on the idea that mutually inhibitory interactions between PTEN and Eph RTKs may be conserved.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ciclo Celular/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptores de la Familia Eph/metabolismo , Animales , Animales Modificados Genéticamente , Western Blotting , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Proteínas de Ciclo Celular/genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Técnicas para Inmunoenzimas , Insulina/metabolismo , Mutación/genética , Neuronas/citología , Neuronas/metabolismo , Oocitos/citología , Oocitos/metabolismo , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Tirosina Quinasas Receptoras/genética , Receptores de la Familia Eph/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Técnicas del Sistema de Dos Híbridos
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