Gcap14 is a microtubule plus-end-tracking protein coordinating microtubule-actin crosstalk during neurodevelopment.

Regulation of microtubule dynamics is required to properly control various steps of neurodevelopment. In this study, we identified granule cell antiserum-positive 14 (Gcap14) as a microtubule plus-end-tracking protein and as a regulator of microtubule dynamics during neurodevelopment. Gcap14 knockout mice exhibited impaired cortical lamination. Gcap14 deficiency resulted in defective neuronal migration. Moreover, nuclear distribution element nudE-like 1 (Ndel1), an interacting partner of Gcap14, effectively corrected the downregulation of microtubule dynamics and the defects in neuronal migration caused by Gcap14 deficiency. Finally, we found that the Gcap14-Ndel1 complex participates in the functional link between microtubule and actin filament, thereby regulating their crosstalks in the growth cones of cortical neurons. Taken together, we propose that the Gcap14-Ndel1 complex is fundamental for cytoskeletal remodeling during neurodevelopmental processes such as neuronal processes elongation and neuronal migration.

High-Performance p-n Junction Transition Metal Dichalcogenide Photovoltaic Cells Enabled by MoOx Doping and Passivation.

Layered semiconducting transition metal dichalcogenides (TMDs) are promising materials for high-specific-power photovoltaics due to their excellent optoelectronic properties. However, in practice, contacts to TMDs have poor charge carrier selectivity, while imperfect surfaces cause recombination, leading to a low open-circuit voltage (VOC) and therefore limited power conversion efficiency (PCE) in TMD photovoltaics. Here, we simultaneously address these fundamental issues with a simple MoOx (x ≈ 3) surface charge-transfer doping and passivation method, applying it to multilayer tungsten disulfide (WS2) Schottky-junction solar cells with initially near-zero VOC. Doping and passivation turn these into lateral p-n junction photovoltaic cells with a record VOC of 681 mV under AM 1.5G illumination, the highest among all p-n junction TMD solar cells with a practical design. The enhanced VOC also leads to record PCE in ultrathin (<90 nm) WS2 photovoltaics. This easily scalable doping and passivation scheme is expected to enable further advances in TMD electronics and optoelectronics.

Disrupted-in-schizophrenia 1 (DISC1) regulates dysbindin function by enhancing its stability.

Dysbindin and DISC1 are schizophrenia susceptibility factors playing roles in neuronal development. Here we show that the physical interaction between dysbindin and DISC1 is critical for the stability of dysbindin and for the process of neurite outgrowth. We found that DISC1 forms a complex with dysbindin and increases its stability in association with a reduction in ubiquitylation. Furthermore, knockdown of DISC1 or expression of a deletion mutant, DISC1 lacking amino acid residues 403-504 of DISC1 (DISC1(Δ403-504)), effectively decreased levels of endogenous dysbindin. Finally, the neurite outgrowth defect induced by knockdown of DISC1 was partially reversed by coexpression of dysbindin. Taken together, these results indicate that dysbindin and DISC1 form a physiologically functional complex that is essential for normal neurite outgrowth.

Creation of matrix protein gene variants of two serotypes of vesicular stomatitis virus as prime-boost vaccine vectors.

UNLABELLED: To take advantage of live recombinant vesicular stomatitis viruses (rVSVs) as vaccine vectors for their high yield and for their induction of strong and long-lasting immune responses, it is necessary to make live vaccine vectors safe for use without losing their immunogenicity. We have generated safer and highly efficient recombinant VSV vaccine vectors by combining the M51R mutation in the M gene of serotype VSV-Indiana (VSVInd) with a temperature-sensitive mutation (tsO23) of the VSVInd Orsay strain. In addition, we have generated two new serotype VSV-New Jersey (VSVNJ) vaccine vectors by combining M48R and M51R mutations with G22E and L110F mutations in the M gene, rVSVNJ(G22E M48R M51R) [rVSVNJ(GMM)] and VSVNJ(G22E M48R M51R L110F) [rVSVNJ(GMML)]. The combined mutations G21E, M51R, and L111F in the M protein of VSVInd significantly reduced the burst size of the virus by up to 10,000-fold at 37°C without affecting the level of protein expression. BHK21 cells and SH-SY5Y human neuroblastoma cells infected with rVSVInd(GML), rVSVNJ(GMM), and rVSVNJ(GMML) showed significantly reduced cytopathic effects in vitro at 37°C, and mice injected with 1 million infectious virus particles of these mutants into the brain showed no neurological dysfunctions or any other adverse effects. In order to increase the stability of the temperature-sensitive mutant, we have replaced the phenylalanine with alanine. This will change all three nucleotides from UUG (leucine) to GCA (alanine). The resulting L111A mutant showed the temperature-sensitive phenotype of rVSVInd(GML) and increased stability. Twenty consecutive passages of rVSVInd(GML) with an L111A mutation did not convert back to leucine (UUG) at position 111 in the M protein gene. IMPORTANCE: Recombinant vesicular stomatitis viruses as live vaccine vectors are very effective in expressing foreign genes and inducing adaptive T cell and B cell immune responses. As with any other live viruses in humans or animals, the use of live rVSVs as vaccine vectors demands the utmost safety. Our strategy to attenuate rVSVInd by utilizing a temperature-sensitive assembly-defective mutation of L111A and combining it with an M51R mutation in the M protein of rVSVInd significantly reduced the pathogenicity of the virus while maintaining highly effective virus production. We believe our new temperature-sensitive M gene mutant of rVSVInd(GML) and M gene mutants of rVSVNJ(GMM) and rVSVNJ(GMML) add excellent vaccine vectors to the pool of live viral vectors.

High absorptivity nanotextured powders for additive manufacturing.

The widespread application of metal additive manufacturing (AM) is limited by the ability to control the complex interactions between the energy source and the feedstock material. Here, we develop a generalizable process to introduce nanoscale grooves to the surface of metal powders which increases the powder absorptivity by up to 70% during laser powder bed fusion. Absorptivity enhancements in copper, copper-silver, and tungsten enable energy-efficient manufacturing, with printing of pure copper at relative densities up to 92% using laser energy densities as low as 83 joules per cubic millimeter. Simulations show that the enhanced powder absorptivity results from plasmon-enabled light concentration in nanoscale grooves combined with multiple scattering events. The approach taken here demonstrates a general method to enhance the absorptivity and printability of reflective and refractory metal powders by changing the surface morphology of the feedstock without altering its composition.

Multi-Resonant Mie Resonator Arrays for Broadband Light Trapping in Ultrathin c-Si Solar Cells.

Effective photon management is critical to realize high power conversion efficiencies for thin crystalline silicon (c-Si) solar cells. Standard few-100-µm-thick bulk cells achieve light trapping with macroscopic surface textures covered by thin, continuous antireflection coatings. Such sizeable textures are challenging to implement on ultrathin cells. Here, it is illustrated how nanoscale Mie-resonator-arrays with a bimodal size distribution support multiple resonances that can work in concert to achieve simultaneous antireflection and light-trapping across the broad solar spectrum. The effectiveness of these light-trapping antireflection coatings is experimentally demonstrated on a 2.8 µm-thick c-Si solar cell. The measured short-circuit current and corresponding power conversion efficiency are notably improved, achieving efficiencies as high as 11.2%. Measurements of the saturation current density on completed cells indicate that thermal oxides can effectively limit surface recombination. The presented design principles are applicable to a wide range of solar cells.

A regression-based machine learning approach for pH and glucose detection with redox-sensitive colorimetric paper sensors.

Colorimetric paper sensors are used in various fields due to their convenience and intuitive manner. However, these sensors present low accuracy in practical use because it is difficult to distinguish color changes for a minute amount of analyte with the naked eye. Herein, we demonstrate that a machine learning (ML)-based paper sensor platform accurately determines the color changes. We fabricated a colorimetric paper sensor by adsorbing polyaniline nanoparticles (PAni-NPs), whose color changes from blue to green when the ambient pH decreases. Adding glucose oxidase (GOx) to the paper sensor enables colorimetric glucose detection. Target analytes (10 µL) were aliquoted onto the paper sensors, and their images were taken with a smartphone under the same conditions in a darkroom. The red-green-blue (RGB) data from the images were extracted and used to train and test three regression models: support vector regression (SVR), decision tree regression (DTR), and random forest regression (RFR). Of the three regression models, RFR performed the best at estimating pH levels (R2 = 0.957) ranging from pH 2 to 10 and glucose concentrations (R2 = 0.922) ranging from 0 to 10 mg mL-1.

High-specific-power flexible transition metal dichalcogenide solar cells.

Semiconducting transition metal dichalcogenides (TMDs) are promising for flexible high-specific-power photovoltaics due to their ultrahigh optical absorption coefficients, desirable band gaps and self-passivated surfaces. However, challenges such as Fermi-level pinning at the metal contact-TMD interface and the inapplicability of traditional doping schemes have prevented most TMD solar cells from exceeding 2% power conversion efficiency (PCE). In addition, fabrication on flexible substrates tends to contaminate or damage TMD interfaces, further reducing performance. Here, we address these fundamental issues by employing: (1) transparent graphene contacts to mitigate Fermi-level pinning, (2) MoOx capping for doping, passivation and anti-reflection, and (3) a clean, non-damaging direct transfer method to realize devices on lightweight flexible polyimide substrates. These lead to record PCE of 5.1% and record specific power of 4.4 W g-1 for flexible TMD (WSe2) solar cells, the latter on par with prevailing thin-film solar technologies cadmium telluride, copper indium gallium selenide, amorphous silicon and III-Vs. We further project that TMD solar cells could achieve specific power up to 46 W g-1, creating unprecedented opportunities in a broad range of industries from aerospace to wearable and implantable electronics.

Sequential phosphorylation of NDEL1 by the DYRK2-GSK3ß complex is critical for neuronal morphogenesis.

Neuronal morphogenesis requires multiple regulatory pathways to appropriately determine axonal and dendritic structures, thereby to enable the functional neural connectivity. Yet, however, the precise mechanisms and components that regulate neuronal morphogenesis are still largely unknown. Here, we newly identified the sequential phosphorylation of NDEL1 critical for neuronal morphogenesis through the human kinome screening and phospho-proteomics analysis of NDEL1 from mouse brain lysate. DYRK2 phosphorylates NDEL1 S336 to prime the phosphorylation of NDEL1 S332 by GSK3ß. TARA, an interaction partner of NDEL1, scaffolds DYRK2 and GSK3ß to form a tripartite complex and enhances NDEL1 S336/S332 phosphorylation. This dual phosphorylation increases the filamentous actin dynamics. Ultimately, the phosphorylation enhances both axonal and dendritic outgrowth and promotes their arborization. Together, our findings suggest the NDEL1 phosphorylation at S336/S332 by the TARA-DYRK2-GSK3ß complex as a novel regulatory mechanism underlying neuronal morphogenesis.

Treatment of multiple test readers in diagnostic accuracy systematic reviews-meta-analyses of imaging studies.

OBJECTIVE: To evaluate the handling of multiple readers in imaging diagnostic accuracy systematic reviews-meta-analyses. METHODS: Search was performed for imaging diagnostic accuracy systematic reviews that performed meta-analysis from 2005-2015. Handling of multiple readers was classified as: 1) averaged; 2) 'best' reader; 3) 'most experienced' reader; 4) each reader counted individually; 5) random; 6) other; 7) not specified. Incidence and reporting of multiple reader data was assessed in primary diagnostic accuracy studies that were included in a random sample of reviews. RESULTS: Only 28/296 (9.5%) meta-analyses specified how multiple readers were handled: 7/28 averaged results, 2/28 included the best reader, 14/28 treated each reader as a separate data set, 1/28 randomly selected a reader, 4/28 used other methods. Sample of 27/268 'not specified' reviews generated 442 primary studies. 270/442 (61%) primary studies had multiple readers: 164/442 (37%) reported consensus reading, 87/442 (20%) reported inter-observer variability, 9/442 (2%) reported independent datasets for each reader. 26/27 (96%) meta-analyses contained at least one primary study with multiple readers. CONCLUSIONS: Reporting how multiple readers were treated in imaging systematic reviews-meta-analyses is uncommon and method used varied widely. This may result from a lack of guidance, unavailability of appropriate statistical methods for handling multiple readers in meta-analysis, and sub-optimal primary study reporting.

DISC1 Modulates Neuronal Stress Responses by Gate-Keeping ER-Mitochondria Ca2+ Transfer through the MAM.

A wide range of Ca2+-mediated functions are enabled by the dynamic properties of Ca2+, all of which are dependent on the endoplasmic reticulum (ER) and mitochondria. Disrupted-in-schizophrenia 1 (DISC1) is a scaffold protein that is involved in the function of intracellular organelles and is linked to cognitive and emotional deficits. Here, we demonstrate that DISC1 localizes to the mitochondria-associated ER membrane (MAM). At the MAM, DISC1 interacts with IP3R1 and downregulates its ligand binding, modulating ER-mitochondria Ca2+ transfer through the MAM. The disrupted regulation of Ca2+ transfer caused by DISC1 dysfunction leads to abnormal Ca2+ accumulation in mitochondria following oxidative stress, which impairs mitochondrial functions. DISC1 dysfunction alters corticosterone-induced mitochondrial Ca2+ accumulation in an oxidative stress-dependent manner. Together, these findings link stress-associated neural stimuli with intracellular ER-mitochondria Ca2+ crosstalk via DISC1, providing mechanistic insight into how environmental risk factors can be interpreted by intracellular pathways under the control of genetic components in neurons.

Metadisorder for designer light in random systems.

Disorder plays a critical role in signal transport by controlling the correlation of a system, as demonstrated in various complex networks. In wave physics, disordered potentials suppress wave transport, because of their localized eigenstates, from the interference between multiple scattering paths. Although the variation of localization with tunable disorder has been intensively studied as a bridge between ordered and disordered media, the general trend of disorder-enhanced localization has remained unchanged, and the existence of complete delocalization in highly disordered potentials has not been explored. We propose the concept of "metadisorder": randomly coupled optical systems in which eigenstates can be engineered to achieve unusual localization. We demonstrate that one of the eigenstates in a randomly coupled system can always be arbitrarily molded, regardless of the degree of disorder, by adjusting the self-energy of each element. Ordered waves with the desired form are then achieved in randomly coupled systems, including plane waves and globally collective resonances. We also devise counterintuitive functionalities in disordered systems, such as "small-world-like" transport from non-Anderson-type localization, phase-conserving disorder, and phase-controlled beam steering.

Comparison of Solitaire thrombectomy and Penumbra suction thrombectomy in patients with acute ischemic stroke caused by basilar artery occlusion.

BACKGROUND AND PURPOSE: Acute ischemic stroke (AIS) caused by basilar artery occlusion (BAO) is a very severe neurological disease with a high mortality rate and poor clinical outcomes. In this study, we compared our experience of mechanical thrombectomy using the Solitaire stent (Solitaire thrombectomy) and manual aspiration thrombectomy using the Penumbra reperfusion catheter (Penumbra suction thrombectomy) in patients with AIS caused by BAO. MATERIALS AND METHODS: Between March 2011 and December 2011, 13 patients received Solitaire thrombectomy. In January 2012, the Korean Food and Drug Administration banned the use of the Solitaire stent as a thrombectomy device, and a further 18 patients received Penumbra suction thrombectomy until December 2013. We compared parameters between patients treated with each device. RESULTS: Successful recanalization rates (Thrombolysis in Cerebral Infarction (TICI) score ≥2b: 84.6% vs 100%, p=0.168) and clinical outcomes (judged by the modified Rankin Scale scores recorded at 3 months: 3.6±2.6 vs 3.2±2.6, p=0.726) were not significantly different between the two groups. However, complete recanalization rates (TICI score of 3: 23.1% vs 72.2%, p=0.015) and total procedure times (101.9±41.4 vs 62.3±34.8 min, p=0.044) were significantly higher, and shorter, respectively, in patients treated by Penumbra suction thrombectomy. CONCLUSIONS: The two thrombectomy devices were associated with similar recanalization rates and clinical outcomes in patients with AIS caused by BAO. However, Penumbra suction thrombectomy seemed to allow more rapid and complete recanalization than Solitaire thrombectomy.

Suppression of Radiative Damping and Enhancement of Second Harmonic Generation in Bull's Eye Nanoresonators.

We report a drastic increase of the damping time of plasmonic eigenmodes in resonant bull's eye (BE) nanoresonators to more than 35 fs. This is achieved by tailoring the groove depth of the resonator and by coupling the confined plasmonic field in the aperture to an extended resonator mode such that spatial coherence is preserved over distances of more than 10 µm. Experimentally, this is demonstrated by probing the plasmon dynamics at the field level using broadband spectral interferometry. The nanoresonator allows us to efficiently concentrate the incident field inside the central aperture of the BE and to tailor its local optical nonlinearity by varying the aperture geometry. By replacing the central circular hole with an annular ring structure, we obtain 50-times higher second harmonic generation efficiency, allowing us to demonstrate the efficient concentration of long-lived plasmonic modes inside nanoapertures by interferometric frequency-resolved autocorrelation. Such a light concentration in a nanoresonator with high quality factor has high potential for sensing and coherent control of light-matter interactions on the nanoscale.

Regulation of the actin cytoskeleton by the Ndel1-Tara complex is critical for cell migration.

Nuclear distribution element-like 1 (Ndel1) plays pivotal roles in diverse biological processes and is implicated in the pathogenesis of multiple neurodevelopmental disorders. Ndel1 function by regulating microtubules and intermediate filaments; however, its functional link with the actin cytoskeleton is largely unknown. Here, we show that Ndel1 interacts with TRIO-associated repeat on actin (Tara), an actin-bundling protein, to regulate cell movement. In vitro wound healing and Boyden chamber assays revealed that Ndel1- or Tara-deficient cells were defective in cell migration. Moreover, Tara overexpression induced the accumulation of Ndel1 at the cell periphery and resulted in prominent co-localization with F-actin. This redistribution of Ndel1 was abolished by deletion of the Ndel1-interacting domain of Tara, suggesting that the altered peripheral localization of Ndel1 requires a physical interaction with Tara. Furthermore, co-expression of Ndel1 and Tara in SH-SY5Y cells caused a synergistic increase in F-actin levels and filopodia formation, suggesting that Tara facilitates cell movement by sequestering Ndel1 at peripheral structures to regulate actin remodeling. Thus, we demonstrated that Ndel1 interacts with Tara to regulate cell movement. These findings reveal a novel role of the Ndel1-Tara complex in actin reorganization during cell movement.

Disrupted-in-schizophrenia 1 (DISC1) and Syntaphilin collaborate to modulate axonal mitochondrial anchoring.

In neuronal axons, the ratio of motile-to-stationary mitochondria is tightly regulated by neuronal activation, thereby meeting the need for local calcium buffering and maintaining the ATP supply. However, the molecular players and detailed regulatory mechanisms behind neuronal mitochondrial movement are not completely understood. Here, we found that neuronal activation-induced mitochondrial anchoring is regulated by Disrupted-in-schizophrenia 1 (DISC1), which is accomplished by functional association with Syntaphilin (SNPH). DISC1 deficiency resulted in reduced axonal mitochondrial movement, which was partially reversed by concomitant SNPH depletion. In addition, a SNPH deletion mutant lacking the sequence for interaction with DISC1 exhibited an enhanced mitochondrial anchoring effect than wild-type SNPH. Moreover, upon neuronal activation, mitochondrial movement was preserved by DISC1 overexpression, not showing immobilized response of mitochondria. Taken together, we propose that DISC1 in association with SNPH is a component of a modulatory complex that determines mitochondrial anchoring in response to neuronal activation.

Spectral separation of optical spin based on antisymmetric Fano resonances.

We propose a route to the spectral separation of optical spin angular momentum based on spin-dependent Fano resonances with antisymmetric spectral profiles. By developing a spin-form coupled mode theory for chiral materials, the origin of antisymmetric Fano spectra is clarified in terms of the opposite temporal phase shift for each spin, which is the result of counter-rotating spin eigenvectors. An analytical expression of a spin-density Fano parameter is derived to enable quantitative analysis of the Fano-induced spin separation in the spectral domain. As an application, we demonstrate optical spin switching utilizing the extreme spectral sensitivity of the spin-density reversal. Our result paves a path toward the conservative spectral separation of spins without any need of the magneto-optical effect or circular dichroism, achieving excellent purity in spin density superior to conventional approaches based on circular dichroism.

Bloch-like waves in random-walk potentials based on supersymmetry.

Bloch's theorem was a major milestone that established the principle of bandgaps in crystals. Although it was once believed that bandgaps could form only under conditions of periodicity and long-range correlations for Bloch's theorem, this restriction was disproven by the discoveries of amorphous media and quasicrystals. While network and liquid models have been suggested for the interpretation of Bloch-like waves in disordered media, these approaches based on searching for random networks with bandgaps have failed in the deterministic creation of bandgaps. Here we reveal a deterministic pathway to bandgaps in random-walk potentials by applying the notion of supersymmetry to the wave equation. Inspired by isospectrality, we follow a methodology in contrast to previous methods: we transform order into disorder while preserving bandgaps. Our approach enables the formation of bandgaps in extremely disordered potentials analogous to Brownian motion, and also allows the tuning of correlations while maintaining identical bandgaps, thereby creating a family of potentials with 'Bloch-like eigenstates'.

A Comprehensive Analysis of Authorship in Radiology Journals.

OBJECTIVES: The purpose of our study was to investigate authorship trends in radiology journals, and whether International Committee of Medical Journal Editors (ICMJE) recommendations have had an impact on these trends. A secondary objective was to explore other variables associated with authorship trends. METHODS: A retrospective, bibliometric analysis of 49 clinical radiology journals published from 1946-2013 was conducted. The following data was exported from MEDLINE (1946 to May 2014) for each article: authors' full name, year of publication, primary author institution information, language of publication and publication type. Microsoft Excel Visual Basics for Applications scripts were programmed to categorize extracted data. Statistical analysis was performed to determine the overall mean number of authors per article over time, impact of ICMJE guidelines, authorship frequency per journal, country of origin, article type and language of publication. RESULTS: 216,271 articles from 1946-2013 were included. A univariate analysis of the mean authorship frequency per year of all articles yielded a linear relationship between time and authorship frequency. The mean number of authors per article in 1946 (1.42) was found to have increased consistently by 0.07 authors/ article per year (R² = 0.9728, P<0.001) to 5.79 authors/article in 2013. ICMJE guideline dissemination did not have an impact on this rise in authorship frequency. There was considerable variability in mean authors per article and change over time between journals, country of origin, language of publication and article type. CONCLUSION: Overall authorship for 49 radiology journals across 68 years has increased markedly with no demonstrated impact from ICMJE guidelines. A higher number of authors per article was seen in articles from: higher impact journals, European and Asian countries, original research type, and those journals who explicitly endorse the ICMJE guidelines.