We have developed a simple approach to high-performance, stretchable, and foldable integrated circuits. The systems integrate inorganic electronic materials, including aligned arrays of nanoribbons of single crystalline silicon, with ultrathin plastic and elastomeric substrates. The designs combine multilayer neutral mechanical plane layouts and "wavy" structural configurations in silicon complementary logic gates, ring oscillators, and differential amplifiers. We performed three-dimensional analytical and computational modeling of the mechanics and the electronic behaviors of these integrated circuits. Collectively, the results represent routes to devices, such as personal health monitors and other biomedical devices, that require extreme mechanical deformations during installation/use and electronic properties approaching those of conventional systems built on brittle semiconductor wafers.

Fear can be acquired vicariously through social observation of others suffering from aversive stimuli. We found that mice (observers) developed freezing behavior by observing other mice (demonstrators) receive repetitive foot shocks. Observers had higher fear responses when demonstrators were socially related to themselves, such as siblings or mating partners. Inactivation of anterior cingulate cortex (ACC) and parafascicular or mediodorsal thalamic nuclei, which comprise the medial pain system representing pain affection, substantially impaired this observational fear learning, whereas inactivation of sensory thalamic nuclei had no effect. The ACC neuronal activities were increased and synchronized with those of the lateral amygdala at theta rhythm frequency during this learning. Furthermore, an ACC-limited deletion of Ca v 1.2 Ca 2+ channels in mice impaired observational fear learning and reduced behavioral pain responses. These results demonstrate the functional involvement of the affective pain system and Ca v 1.2 channels of the ACC in observational social fear.Fear is a biological response to dangerous, threatening situations or stimuli. Fear can be acquired and expressed in a variety of ways 1 . First, fear can be learned from direct experience of an adverse situation (for example, an unconditioned stimulus in classical Pavlovian fear conditioning). In a classical conditioning experiment, pairing of a neutral, conditioned stimulus (for example, a tone) with an aversive, unconditioned stimulus (for example, a foot shock) causes an animal to express fear behaviors when the animal is later exposed to the conditioned Correspondence should be addressed to H.-S.S. (shin@kist.re.kr). 6 Present address: Department of Neurology, Seoul National University Hospital, Seoul, Korea.Note: Supplementary information is available on the Nature Neuroscience website. AUTHOR CONTRIBUTIONS COMPETING FINANCIAL INTERESTSThe authors declare no competing financial interests.Reprints and permissions information is available online at http://www.nature.com/reprintsandpermissions/. 1,[6][7][8][9][10][11][12] . Previous studies using a barpressing protocol found that rats seeing a distressed conspecific (by electric shocks) display fearful behavioral responses, such as crouching or motionlessness 13,14 . A recent study found that C57BL/6J mice that observed unfamiliar mice experiencing classical fear conditioning displayed freezing behaviors when they were later exposed to the conditioned stimulus alone 15 . These findings demonstrate social transfer of fear in rodents. Unlike classical fear conditioning, however, the neural substrate and mechanism underlying observational social fear has not been well defined. NIH Public AccessACC is known to receive sensory signals from the somatosensory cortices and other cortical areas, including the anterior insular cortex [16][17][18][19][20] . Brain-imaging studies in humans have shown that the neuronal activities of the ACC and the amygdala change during observation of others experi...

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Clever combinations of different types of functional nanostructured materials will enable the development of multifunctional nanomedical platforms for multimodal imaging or simultaneous diagnosis and therapy. Mesoporous silica nanoparticles (MSNs) possess unique structural features such as their large surface areas, tunable nanometer-scale pore sizes, and well-defined surface properties. Therefore, they are ideal platforms for constructing multifunctional materials that incorporate a variety of functional nanostructured materials. In this Account, we discuss recent progress by our group and other researchers in the design and fabrication of multifunctional nanocomposite nanoparticles based on mesoporous silica nanostructures for applications to simultaneous diagnosis and therapy. Versatile mesoporous silica-based nanocomposite nanoparticles were fabricated using various methods. Here, we highlight two synthetic approaches: the encapsulation of functional nanoparticles within a mesoporous silica shell and the assembly of nanoparticles on the surface of silica nanostructures. Various nanoparticles were encapsulated in MSNs using surfactants as both phase transfer agents and pore-generating templates. Using MSNs as a scaffold, functional components such as magnetic nanoparticles and fluorescent dyes have been integrated within these systems to generate multifunctional nanocomposite systems that maintain their individual functional characteristics. For example, uniform mesoporous dye-doped silica nanoparticles immobilized with multiple magnetite nanocrystals on their surfaces have been fabricated for their use as a vehicle capable of simultaneous magnetic resonance (MR) and fluorescence imaging and drug delivery. The resulting nanoparticle-incorporated MSNs were then tested in mice with tumors. These in vivo experiments revealed that these multifunctional nanocomposite nanoparticles were delivered to the tumor sites via passive targeting. These nanocomposite nanoparticles served as successful multimodal imaging probes and also delivered anticancer drugs to the tumor site. With innumerable combinations of imaging modalities and drug delivery available within these vehicles, multifunctional nanocomposite nanoparticles provide new opportunities for clinical diagnostics and therapeutics.

A major challenge for implantable medical systems is the inclusion or reliable delivery of electrical power. We use ultrasound to deliver mechanical energy through skin and liquids and demonstrate a thin implantable vibrating triboelectric generator able to effectively harvest it. The ultrasound can induce micrometer-scale displacement of a polymer thin membrane to generate electrical energy through contact electrification. We recharge a lithium-ion battery at a rate of 166 microcoulombs per second in water. The voltage and current generated ex vivo by ultrasound energy transfer reached 2.4 volts and 156 microamps under porcine tissue. These findings show that a capacitive triboelectric electret is the first technology able to compete with piezoelectricity to harvest ultrasound in vivo and to power medical implants.

Focal cortical dysplasia type II (FCDII) is a sporadic developmental malformation of the cerebral cortex characterized by dysmorphic neurons, dyslamination and medically refractory epilepsy. It has been hypothesized that FCD is caused by somatic mutations in affected regions. Here, we used deep whole-exome sequencing (read depth, 412-668×) validated by site-specific amplicon sequencing (100-347,499×) in paired brain-blood DNA from four subjects with FCDII and uncovered a de novo brain somatic mutation, mechanistic target of rapamycin (MTOR) c.7280T>C (p.Leu2427Pro) in two subjects. Deep sequencing of the MTOR gene in an additional 73 subjects with FCDII using hybrid capture and PCR amplicon sequencing identified eight different somatic missense mutations found in multiple brain tissue samples of ten subjects. The identified mutations accounted for 15.6% of all subjects with FCDII studied (12 of 77). The identified mutations induced the hyperactivation of mTOR kinase. Focal cortical expression of mutant MTOR by in utero electroporation in mice was sufficient to disrupt neuronal migration and cause spontaneous seizures and cytomegalic neurons. Inhibition of mTOR with rapamycin suppressed cytomegalic neurons and epileptic seizures. This study provides, to our knowledge, the first evidence that brain somatic activating mutations in MTOR cause FCD and identifies mTOR as a treatment target for intractable epilepsy in FCD.

We report a coaxial fiber supercapacitor, which consists of carbon microfiber bundles coated with multiwalled carbon nanotubes as a core electrode and carbon nanofiber paper as an outer electrode. The ratio of electrode volumes was determined by a half-cell test of each electrode. The capacitance reached 6.3 mF cm(-1) (86.8 mF cm(-2)) at a core electrode diameter of 230 μm and the measured energy density was 0.7 μWh cm(-1) (9.8 μWh cm(-2)) at a power density of 13.7 μW cm(-1) (189.4 μW cm(-2)), which were much higher than the previous reports. The change in the cyclic voltammetry characteristics was negligible at 180° bending, with excellent cycling performance. The high capacitance, high energy density, and power density of the coaxial fiber supercapacitor are attributed to not only high effective surface area due to its coaxial structure and bundle of the core electrode, but also all-carbon materials electrodes which have high conductivity. Our coaxial fiber supercapacitor can promote the development of textile electronics in near future.

Perfluorocarbon nanoemulsions can deliver lipophilic therapeutic agents to solid tumors and simultaneously provide for monitoring nanocarrier biodistribution via ultrasonography and/or 19F MRI. In the first generation of block copolymer stabilized perfluorocarbon nanoemulsions, perfluoropentane (PFP) was used as the droplet forming compound. Although manifesting excellent therapeutic and ultrasound imaging properties, PFP nanoemulsions were unstable at storage, difficult to handle, and underwent hard to control phenomenon of irreversible droplet-to-bubble transition upon injection. To solve the above problems, perfluoro-15-crown-5-ether (PFCE) was used as a core forming compound in the second generation of block copolymer stabilized perfluorocarbon nanoemulsions. PFCE nanodroplets manifest both ultrasound and fluorine (19F) MR contrast properties, which allows using multimodal imaging and 19F MR spectroscopy for monitoring nanodroplet pharmacokinetics and biodistribution. In the present paper, acoustic, imaging, and therapeutic properties of unloaded and paclitaxel (PTX) loaded PFCE nanoemulsions are reported. As manifested by the 19F MR spectroscopy, PFCE nanodroplets are long circulating, with about 50% of the injected dose remaining in circulation two hours after the systemic injection. Sonication with 1-MHz therapeutic ultrasound triggered reversible droplet-to-bubble transition in PFCE nanoemulsions. Microbubbles formed by acoustic vaporization of nanodroplets underwent stable cavitation. The nanodroplet size (200 nm to 350 nm depending on a type of the shell and conditions of emulsification) as well as long residence in circulation favored their passive accumulation in tumor tissue that was confirmed by ultrasonography. In the breast and pancreatic cancer animal models, ultrasound-mediated therapy with paclitaxel-loaded PFCE nanoemulsions showed excellent therapeutic properties characterized by tumor regression and suppression of metastasis. Anticipated mechanisms of the observed effects are discussed.