Neonatal lupus is a novel cause of positive newborn screening for X-linked adrenoleukodystrophy.

We report three unrelated individuals, each exposed to maternal autoantibodies during gestation and found to have elevated very long-chain fatty acids (VLCFAs) in the newborn period after screening positive by California newborn screening (NBS) for X-linked adrenoleukodystrophy (ALD). Two probands presented with clinical and laboratory features of neonatal lupus erythematosus (NLE); the third had features suggestive of NLE and a known maternal history of Sjogren's syndrome and rheumatoid arthritis. In all three individuals, subsequent biochemical and molecular evaluation for primary and secondary peroxisomal disorders was nondiagnostic with normalization of VLCFAs by 15 months of age. These cases add to the expanding differential diagnosis to consider in newborns who screen positive for ALD via elevated C26:0-lysophosphatidylcholine. Though the pathophysiology of how transplacental maternal anti-Ro antibodies damage fetal tissue is not well-understood, we postulate that the VLCFA elevations reflect a systemic inflammatory response and secondary peroxisomal dysfunction that improves once maternal autoantibodies wane after birth. Additional evaluation of this phenomenon is warranted to better understand the intricate biochemical, clinical, and possible therapeutic overlap between autoimmunity, inflammation, peroxisomal dysfunction, and human disease.

MT-ATP6 mitochondrial disease identified by newborn screening reveals a distinct biochemical phenotype.

Although decreased citrulline is used as a newborn screening (NBS) marker to identify proximal urea cycle disorders (UCDs), it is also a feature of some mitochondrial diseases, including MT-ATP6 mitochondrial disease. Here we describe biochemical and clinical features of 11 children born to eight mothers from seven separate families who were identified with low citrulline by NBS (range 3-5 µM; screening cutoff >5) and ultimately diagnosed with MT-ATP6 mitochondrial disease. Follow-up testing revealed a pattern of hypocitrullinemia together with elevated propionyl-(C3) and 3-hydroxyisovaleryl-(C5-OH) acylcarnitines, and a homoplasmic pathogenic variant in MT-ATP6 in all cases. Single and multivariate analysis of NBS data from the 11 cases using Collaborative Laboratory Integrated Reports (CLIR; https://clir.mayo.edu) demonstrated citrulline <1st percentile, C3 > 50th percentile, and C5-OH >90th percentile when compared with reference data, as well as unequivocal separation from proximal UCD cases and false-positive low citrulline cases using dual scatter plots. Five of the eight mothers were symptomatic at the time of their child(ren)'s diagnosis, and all mothers and maternal grandmothers evaluated molecularly and biochemically had a homoplasmic pathogenic variant in MT-ATP6, low citrulline, elevated C3, and/or elevated C5-OH. All molecularly confirmed individuals (n = 17) with either no symptoms (n = 12), migraines (n = 1), or a neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) phenotype (n = 3) were found to have an A or U mitochondrial haplogroup, while one child with infantile-lethal Leigh syndrome had a B haplogroup.

Profound neonatal lactic acidosis and renal tubulopathy in a patient with glycogen storage disease type IXɑ2 secondary to a de novo pathogenic variant in PHKA2.

The phenotype of individuals with glycogen storage disease (GSD) IX appears to be highly variable, even within subtypes. Features include short stature, fasting hypoglycemia with ketosis, hepatomegaly, and transaminitis. GSD IXɑ2 is caused by hemizygous pathogenic variants in PHKA2, and results in deficiency of the phosphorylase kinase enzyme, particularly in the liver. Like other GSDs, GSD IXɑ2 can present with hypoglycemia and post-prandial lactic acidosis, but has never been reported in a newborn, nor with lactic acidosis as the presenting feature. Here we describe the clinical presentation and course of a newborn boy with profound neonatal lactic and metabolic acidosis, renal tubulopathy, and sensorineural hearing loss (SNHL) diagnosed with GSD IXɑ2 through exome sequencing. Review of the literature suggests this case represents an atypical and severe presentation of GSD IXɑ2 and proposes expansion of the phenotype to include neonatal lactic acidosis and renal tubulopathy.

Aicardi-Goutières syndrome may present with positive newborn screen for X-linked adrenoleukodystrophy.

We report three unrelated probands, two male and one female, diagnosed with Aicardi-Goutières syndrome (AGS) after screening positive on California newborn screening (CA NBS) for X-linked adrenoleukodystrophy (X-ALD) due to elevated C26:0 lysophosphatidylcholine (C26:0-LPC). Follow-up evaluation was notable for elevated C26:0, C26:1, and C26:0/C22:0 ratio, and normal red blood cell plasmalogens levels in all three probands. Diagnoses were confirmed by molecular sequencing prior to 12 months of age after clinical evaluation was inconsistent with X-ALD or suggestive of AGS. For at least one proband, the early diagnosis of AGS enabled candidacy for enrollment into a therapeutic clinical trial. This report demonstrates the importance of including AGS on the differential diagnosis for individuals who screen positive for X-ALD, particularly infants with abnormal neurological features, as this age of onset would be highly unusual for X-ALD. While AGS is not included on the Recommended Universal Screening Panel, affected individuals can be identified early through state NBS programs so long as providers are aware of a broader differential that includes AGS. This report is timely, as state NBS algorithms for X-ALD are actively being established, implemented, and refined.

Tailoring the Composition of Eu3+-Doped Y3NbO7 Niobate: Structural Features and Luminescent Properties Induced by Spark Plasma Sintering.

The defective fluorite-related Y3NbO7 host lattice was doped with Eu3+ ions to understand the influence of spark plasma sintering (SPS) process on this host lattice. The intrinsic disorder due to the occurrence of oxygen vacancies results in amorphous-type responses of the luminescent cations, and the spectral distribution varies as a function of the niobium content. Two spectral fingerprints of europium emissions were clearly enhanced. The correlation between luminescence, X-ray diffraction, and electron diffraction characterizations shows the existence of local inhomogeneity. Indeed, the particular nonequilibrium sintering conditions allowed pointing out a lack of miscibility within the Y3NbO7 solid solution domain. Thus, the SPS pellet is a composite of two extreme compositions. This phase demixing is mainly induced by the pressure coupled with a current effect that makes possible ionic migration in this Y3NbO7 ionic conductive matrix.

Comparison of mouse and human ankles and establishment of mouse ankle osteoarthritis models by surgically-induced instability.

OBJECTIVE: Prevalence of ankle osteoarthritis (OA) is lower than that of knee OA, however, the molecular mechanisms underlying the difference remain unrevealed. In the present study, we developed mouse ankle OA models for use as tools to investigate pathophysiology of ankle OA and molecular characteristics of ankle cartilage. DESIGN: We anatomically and histologically examined ankle and knee joints of C57BL/6 mice, and compared them with human samples. We examined joints of 8-week-old and 25-month-old mice. For experimental models, we developed three different ankle OA models: a medial model, a lateral model, and a bilateral model, by resection of respective structures. OA severity was evaluated 8 weeks after the surgery by safranin O staining, and cartilage degradation in the medial model was sequentially examined. RESULTS: Anatomical and histological features of human and mouse ankle joints were comparable. Additionally, the mouse ankle joint was more resistant to cartilage degeneration with aging than the mouse knee joint. In the medial model, the tibiotalar joint was markedly affected while the subtalar joint was less degenerated. In the lateral model, the subtalar joint was mainly affected while the tibiotalar joint was less altered. In the bilateral model, both joints were markedly degenerated. In the time course of the medial model, TdT-mediated dUTP nick end labeling (TUNEL) staining and Adamts5 expression were enhanced at early and middle stages, while Mmp13 expression was gradually increased during the OA development. CONCLUSION: Since human and mouse ankles are comparable, the present models will contribute to ankle OA pathophysiology and general cartilage research in future.

Near-field probing of Mie resonances in single TiO2 microspheres at terahertz frequencies.

We show experimentally that poly-crystalline TiO2 spheres, 20-30 µm in diameter, exhibit a magnetic dipole Mie resonance in the terahertz (THz) frequency band (1.0-1.6 THz) with a narrow line-width (<40 GHz). We detect and investigate the magnetic dipole and electric dipole resonances in single high-permittivity TiO2 microspheres, using a near-field probe with a sub-wavelength (~λ/50) size aperture and THz time-domain spectroscopy technique. The Mie resonance signatures are observed in the electric field amplitude and phase spectra, as well as in the electric field distribution near the microspheres. The narrow line-width and the sub-wavelength size (λ/10) make the TiO2 microspheres excellent candidates for realizing low-loss THz metamaterials.

Flutter-driven triboelectrification for harvesting wind energy.

Technologies to harvest electrical energy from wind have vast potentials because wind is one of the cleanest and most sustainable energy sources that nature provides. Here we propose a flutter-driven triboelectric generator that uses contact electrification caused by the self-sustained oscillation of flags. We study the coupled interaction between a fluttering flexible flag and a rigid plate. In doing so, we find three distinct contact modes: single, double and chaotic. The flutter-driven triboelectric generator having small dimensions of 7.5 × 5 cm at wind speed of 15 ms(-1) exhibits high-electrical performances: an instantaneous output voltage of 200 V and a current of 60 µA with a high frequency of 158 Hz, giving an average power density of approximately 0.86 mW. The flutter-driven triboelectric generation is a promising technology to drive electric devices in the outdoor environments in a sustainable manner.

Origin of high photoconductive gain in fully transparent heterojunction nanocrystalline oxide image sensors and interconnects.

A technique for invisible image capture using a photosensor array based on transparent conducting oxide semiconductor thin-film transistors and transparent interconnection technologies is presented. A transparent conducting layer is employed for the sensor electrodes as well as interconnection in the array, providing about 80% transmittance at visible-light wavelengths. The phototransistor is a Hf-In-Zn-O/In-Zn-O heterostructure yielding a high quantum-efficiency in the visible range.

Novel multi-layered 1-D nanostructure exhibiting the theoretical capacity of silicon for a super-enhanced lithium-ion battery.

Silicon/carbon (Si/C) nanocomposites have recently received much attention as Li-ion battery negative electrodes due to their mutual synergetic effects in capacity and mechanical integrity. The contribution of Si to the total capacity of the Si/C nanocomposites determines their structural efficiency. Herein, we report on a multi-layered, one-dimensional nanostructure that exhibits the theoretical specific capacity of Si in the nanocomposite. Concentrically tri-layered, compartmentalized, C-core/Si-medium/C-shell nanofibers were fabricated by triple coaxial electrospinning. The pulverization of Si was accommodated inside the C-shell, whereas the conductive pathway of the Li-ions and electrons was provided by the C-core, which was proven by ex situ Raman spectroscopy. The compartmentalized Si in between the C-core and C-shell led to excellent specific capacity at a high current rate (>820 mA h g(-1) at 12000 mA g(-1)) and the realization of the theoretical specific capacity of the Li15Si4 phase of Si nanoparticles (3627 mA h g(-1)). The electrochemical characterization and inductively coupled plasma-atomic emission spectrometry provided direct evidence of full participation of Si in the electrochemical reactions.

Highly stretchable resistive pressure sensors using a conductive elastomeric composite on a micropyramid array.

A stretchable resistive pressure sensor is achieved by coating a compressible substrate with a highly stretchable electrode. The substrate contains an array of microscale pyramidal features, and the electrode comprises a polymer composite. When the pressure-induced geometrical change experienced by the electrode is maximized at 40% elongation, a sensitivity of 10.3 kPa(-1) is achieved.

Effects of substrate on piezoelectricity of electrospun poly(vinylidene fluoride)-nanofiber-based energy generators.

We report the effects of various substrates and substrate thicknesses on electrospun poly(vinylidene fluoride) (PVDF)-nanofiber-based energy harvesters. The electrospun PVDF nanofibers showed an average diameter of 84.6 ± 23.5 nm. A high relative ß-phase fraction (85.2%) was achieved by applying high voltage during electrospinning. The prepared PVDF nanofibers thus generated considerable piezoelectric potential in accordance with the sound-driven mechanical vibrations of the substrates. Slide glass, poly(ethylene terephthalate), poly(ethylene naphthalate), and paper substrates were used to investigate the effects of the intrinsic and extrinsic substrate properties on the piezoelectricity of the energy harvesters. The thinnest paper substrate (66 µm) with a moderate Young's modulus showed the highest voltage output (0.4885 V). We used high-performance 76, 66, and 33 µm thick papers to determine the effect of paper thickness on the output voltage. The thinnest paper substrate resulted in the highest voltage output (0.7781 V), and the numerical analyses of the sound-driven mechanical deformation strongly support the hypothesis that substrate thickness has a considerable effect on piezoelectric performance.

A plasma-treated chalcogenide switch device for stackable scalable 3D nanoscale memory.

Stackable select devices such as the oxide p-n junction diode and the Schottky diode (one-way switch) have been proposed for non-volatile unipolar resistive switching devices; however, bidirectional select devices (or two-way switch) need to be developed for bipolar resistive switching devices. Here we report on a fully stackable switching device that solves several problems including current density, temperature stability, cycling endurance and cycle distribution. We demonstrate that the threshold switching device based on As-Ge-Te-Si material significantly improves cycling endurance performance by reactive nitrogen deposition and nitrogen plasma hardening. Formation of the thin Si3N4 glass layer by the plasma treatment retards tellurium diffusion during cycling. Scalability of threshold switching devices is measured down to 30 nm scale with extremely fast switching speed of ~2 ns.

High-performance nanowire oxide photo-thin film transistor.

A gate-modulated nanowire oxide photosensor is fabricated by electron-beam lithography and conventional dry etch processing.. The device characteristics are good, including endurance of up to 10(6) test cycles, and gate-pulse excitation is used to remove persistent photoconductivity. The viability of nanowire oxide phototransistors for high speed and high resolution applications is demonstrated, thus potentially expanding the scope of exploitation of touch-free interactive displays.

In situ observation of filamentary conducting channels in an asymmetric Ta2O5-x/TaO2-x bilayer structure.

Electrically induced resistive switching in metal insulator-metal structures is a subject of increasing scientific interest because it is one of the alternatives that satisfies current requirements for universal non-volatile memories. However, the origin of the switching mechanism is still controversial. Here we report the fabrication of a resistive switching device inside a transmission electron microscope, made from a Pt/SiO2/a-Ta2O5-x/a-TaO2-x/Pt structure, which clearly shows reversible bipolar resistive switching behaviour. The current-voltage measurements simultaneously confirm each of the resistance states (set, reset and breakdown). In situ scanning transmission electron microscope experiments verify, at the atomic scale, that the switching effects occur by the formation and annihilation of conducting channels between a top Pt electrode and a TaO2-x base layer, which consist of nanoscale TaO1-x filaments. Information on the structure and dimensions of conductive channels observed in situ offers great potential for designing resistive switching devices with the high endurance and large scalability.

Resolution enhancement of holographic printer using a hogel overlapping method.

We propose a hogel overlapping method for the holographic printer to enhance the lateral resolution of holographic stereograms. The hogel size is directly related to the lateral resolution of the holographic stereogram. Our analysis by computer simulation shows that there is a limit to decreasing the hogel size while printing holographic stereograms. Instead of reducing the size of hogel, the lateral resolution of holographic stereograms can be enhanced by printing overlapped hogels, which makes it possible to take advantage of multiplexing property of the volume hologram. We built a holographic printer, and recorded two holographic stereograms using the conventional and proposed overlapping methods. The images and movies of the holographic stereograms experimentally captured were compared between the conventional and proposed methods. The experimental results confirm that the proposed hogel overlapping method improves the lateral resolution of holographic stereograms compared to the conventional holographic printing method.

Physical electro-thermal model of resistive switching in bi-layered resistance-change memory.

Tantalum-oxide-based bi-layered resistance-change memories (RRAMs) have recently improved greatly with regard to their memory performances. The formation and rupture of conductive filaments is generally known to be the mechanism that underlies resistive switching. The nature of the filament has been studied intensively and several phenomenological models have consistently predicted the resistance-change behavior. However, a physics-based model that describes a complete bi-layered RRAM structure has not yet been demonstrated. Here, a complete electro-thermal resistive switching model based on the finite element method is proposed. The migration of oxygen vacancies is simulated by the local temperature and electric field derived from carrier continuity and heat equations fully coupled in a 3-D geometry, which considers a complete bi-layered structure that includes the top and bottom electrodes. The proposed model accurately accounts for the set/reset characteristics, which provides an in-depth understanding of the nature of resistive switching.

Parental perceived benefits of OROS-methylphenidate treatment for the child with attention-deficit/hyperactivity disorder and for parents themselves.

Given the shortage of studies on parental perceived benefits of OROS-methylphenidate treatment in Asian populations, we assessed parental response to OROS-methylphenidate treatment of Korean children with attention-deficit/hyperactivity disorder (ADHD), in relation to children's academic performance and behavioral symptoms as well as parental rearing stress and depressive symptoms.We enrolled 132 medication-naïve children with ADHD into a multicenter, open-label, 12-week trial of OROS-MPH. The outcome measures were the ADHD rating scale-IV (ADHD-RS), the comprehensive attention test and academic performance rating scale, and the clinical global impression (CGI)-severity/improvement instrument (for the children) and Beck depression inventory and parenting stress index (for their parents).We found parent-perceived improvements in children's ADHD-related behavioral symptoms and academic function and their parents' depressive symptoms and parenting stress. Investigator-rated ADHD symptoms and subjects' neuropsychological function were also improved (p<0.001).Parents of Korean children with ADHD perceive that OROS-methylphenidate treatment improves their children's academic function and behavior as well as their own child-rearing stress and emotional state. These findings must be interpreted with caution, due to a non-comparative open-label trial.