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OBJECTIVES/SPECIFIC AIMS: The aims of this study are (1) to develop and characterize a novel nonhuman primate model of pneumococcal pneumonia that mimics human disease; and (2) determine whether Streptococcus pneumoniae can: (a) translocate to the heart, (b) cause adverse cardiac events, (c) induce cardiomyocyte death, and (d) lead to scar formation during severe pneumonia in baboons. METHODS/STUDY POPULATION: Six adult baboons (Papio cynocephalus) were surgically tethered to a monitoring system to continuously assess their heart rate, temperature, and electrocardiogram (ECG). A baseline transthoracic echocardiogram, 12-lead ECG, serum troponin-I levels, brain natriuretic peptide, and heart-type fatty acid binding protein (HFABP) levels were obtained before infection and at the end of the experiment to determine cardiovascular damage during pneumococcal pneumonia. Animals were challenged with 108 colony-forming units of S. pneumoniae in the right middle lobe using flexible bronchoscopy. Three baboons were rescued with ampicillin therapy (80 mg/kg/d) after the development of pneumonia. Cardiac damage was confirmed by examination of tissue sections using immunohistochemistry as well as electron and fluorescence microscopy. Western-blots and tissue staining were used to determine the presence of necroptosis (RIP3 and pMLKL) and apoptosis (Caspase-3) in the cardiac tissue. Cytokine and chemokine levels in the heart tissue were determined using Luminex technology. RESULTS/ANTICIPATED RESULTS: Four males (57%) and three (43%) females were challenged. The median age of all baboons was 11 (IQR, 10-19) years old, which corresponds to a middle-aged human. Infected baboons consistently developed severe pneumonia. All animals developed systemic inflammatory response syndrome with tachycardia, tachypnea, fever, and leukocytosis. Infection was characterized by initial leukocytosis followed by severe leukopenia on day 3 postinoculation. Non-specific ischemic alterations by ECG (ST segment and T-wave flattering) and in the premortem echocardiogram were observed. The median (IQR) levels of troponin I and HFABP at the end of the experiment were 3550 ng/mL (1717–5383) and 916.9 ng/mL (520.8–1323), respectively. Severe cardiomyopathy was observed using TEM and H&E stains in animals with severe pneumonia. Necroptosis was detected in cardiomyocytes of infected animals by the presence of pMLKL and RIP3 in cardiac tissues. Signs of cardiac remodeling indicated by disorganized collagen deposition was present in rescued animals but not in the other animals. DISCUSSION/SIGNIFICANCE OF IMPACT: We confirmed that baboons experience cardiac injury during severe pneumococcal pneumonia that is characterized by myocardial invasion, activation of necroptosis, and tissue remodeling in animals rescued by antimicrobial therapy. Cardiac damage by invading pneumococci may explain why adverse cardiac events that occur during and after pneumococcal pneumonia in adult human patients.
Metal Organic Decomposition (MOD)-made BaTiO3 (BT) thin films were prepared for Resistive Random Access Memory (ReRAM) under various annealing conditions and investigated for improving the properties of bipolar-type resistive switching, focusing on the relation between oxygen vacancies and the behavior of resistive hysteresis. BT thin films with both pre- and final- annealing in nitrogen showed the resistive hysteresis of bipolar-type switching with current ON/OFF ratios of 2 orders of magnitude for both bias polarities. Finally they showed the endurance property with the 106 switching cycles. It was suggested that oxygen vacancies near the oxide surface (both interfaces at metal electrode/oxide and between layer-by-layered oxide layers) are increased by N2 annealing and enhanced the interface-type resistive switching. Pre-annealing in N2 was also found to be very effective to improve endurance properties, implying that not only the electrode/oxide interface but also the middle part of the film would contribute the interface-type mechanism.
Depression is one of the most prevalent mental illnesses worldwide and a leading cause of disability, especially in the setting of treatment resistance. In recent years, repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative strategy for treatment-resistant depression and its clinical efficacy has been investigated intensively across the world. However, the underlying neurobiological mechanisms of the antidepressant effect of rTMS are still not fully understood. This review aims to systematically synthesize the literature on the neurobiological mechanisms of treatment response to rTMS in patients with depression. Medline (1996–2014), Embase (1980–2014) and PsycINFO (1806–2014) were searched under set terms. Three authors reviewed each article and came to consensus on the inclusion and exclusion criteria. All eligible studies were reviewed, duplicates were removed, and data were extracted individually. Of 1647 articles identified, 66 studies met both inclusion and exclusion criteria. rTMS affects various biological factors that can be measured by current biological techniques. Although a number of studies have explored the neurobiological mechanisms of rTMS, a large variety of rTMS protocols and parameters limits the ability to synthesize these findings into a coherent understanding. However, a convergence of findings suggest that rTMS exerts its therapeutic effects by altering levels of various neurochemicals, electrophysiology as well as blood flow and activity in the brain in a frequency-dependent manner. More research is needed to delineate the neurobiological mechanisms of the antidepressant effect of rTMS. The incorporation of biological assessments into future rTMS clinical trials will help in this regard.
Good outcomes have been reported regarding the use of cochlear implants for mumps deafness. The mumps virus induces meningitis and/or encephalitis, which can cause central nervous system damage resulting in retrolabyrinthine hearing loss, for which a cochlear implant would be less effective.
We installed a cochlear implant in two patients with bilateral mumps deafness; one achieved a good result with the cochlear implant, but the other did not. We discuss two possible reasons for the different outcomes. Case 1 was a three-year-old girl with bilateral parotid swelling, vomiting and walking disorder. One year after cochlear implant insertion, speech perception did not develop despite of good pure tone thresholds. Case 2 was an eight-year-old girl with bilateral parotid swelling. A cochlear implant enabled her to improve hearing perception.
Although cochlear implants have been reported to be helpful for mumps deafness, cases that involve central nervous system damage may not achieve good results.
We examined 20 300 raw shell chicken eggs sold at retail stores in Japan for Salmonella outside and inside eggs. The eggs were purchased at 220 retail stores throughout Japan between August 2007 and January 2008. Of 2030 pooled egg samples (10 eggs/sample), Salmonella was isolated from five shell samples (0·25%), but not from any of egg-content samples. The serovars of the isolates were Salmonella Enteritidis (2), S. Derby, S. Livingstone and S. Cerro. The samples positive for Salmonella originated from five different egg grading and packaging (GP) centres. All the GP centres washed their egg shells according to government guidelines for hygienic practice in GP centres. Thus, practical control measures at GP centres need to be reviewed and implemented to diminish Salmonella prevalence of egg shells because Salmonella contamination on eggs is a potential hazard for foodborne salmonellosis in Japan.
The Microlensing Observations in Astrophysics (MOA) is a microlensing survey conducted at Mt. John Observatory in New Zealand. We searched transiting planet candidates from the MOA-I Galactic bulge data, which have been obtained with a 61cm B&C telescope from 2000 to 2005 for a microlensing search. Although this survey data were dedicated to microlensing, they are also quite useful for searching transiting objects because of the large number of stars monitored (~7 million) and the long span of the survey (~6 years). From our analysis, we found 58 transiting planet candidates. We are planning to follow up these candidates with high-precision spectroscopic and photometric observations for further selection, toward the detection of planets by radial velocity observations.
We have developed a new silicon nitride (SiNx) multilayer barrier film by a plasma-enhanced chemical vapor deposition (CVD) for a flexible organic light emitting diode (OLED), which consists of SiNx films in two different deposition conditions, that is, a transparent SiNx layer (tr-SiNx) deposited with NH3 gas and an ultra-thin SiNx layer (cap-SiNx) deposited without NH3 gas, which caps over the former layer. This barrier film is expected to exhibit high durability under high temperature and high humidity conditions even at high deposition rate over 100 nm / minute, because the transparent SiNx layer, that is easily oxidized under such conditions, is protected by the cap-SiNx layer and the interface between them, and also show good transparency, because the opaque cap-SiNx layer is enough thin to be almost transparent to visible light. Thus, the multi-layer SiNx barrier film indicates the specific features as a high barrier performance, high transparency, and high productivity, and makes it possible to apply flexible OLED displays to automobile use.
The initial growth of non-epitaxial thin films was studied and discussed using the concept that thermodynamics controls the unit-structure within the surface diffusion length of deposits, whereas kinetics controls the ensemble-structure on a large scale. Three basic topics, growth mode (island shape), crystalline (island inner) structure, time-dependent properties of island ensemble (island size, distance, and density), are summarized based on the investigation of thin film growth of metals on TiO2, Cu on SiO2 and Ti/SiO2. This study provides fundamental understanding of structural control during thin film growth, and further can be applied to various advanced devices for electronics, photonics, catalysis, and energy applications.
The light curves for three eclipsing binaries in the Magellanic Clouds have been obtained using CCD uVJIC photometry. One target in the LMC, MACHO*05:36:48.7−69:17:00, is an eccentric system, e = 0.20, with a period of 3.853534 ± 0.000005 d. Initial solutions indicate a primary component in the range Teff,1 = 20,000−35,000K and the secondary Teff,2 1000−2000K cooler than the primary, with inclinations ranging i = 84.2° − 86.0°. Two targets in the SMC, MOA J005018.4-723855 and MOA J005623.5−722123, have periods of 1.8399±0.0004 and 2.3199 ± 0.0003 days respectively. Both have circular orbits with the former being a semi-detached system.
More than 4000 stars observed in both MOA and DENIS projects showing periodic or quasi-periodic light curves are studied. Almost all Mira stars are located on the classical period-luminosity relation, and the multiplicity of the period-luminosity relation is confirmed for small-amplitude stars. The colour-magnitude diagrams based on the MOA red band, Rm, and Ks constructed for the sequences, form a single strip with small successive shifts.
Configurations of shock wave reflection in steady supersonic flows have been experimentally
investigated using a combination of two wedges. It has been experimentally
proved by a symmetric arrangement that both regular and Mach reflections are possible
in the dual-solution domain for various aspect ratio models. In the arrangement
for the purpose of clarifying the influence of the wedge three-dimensionality, the transition
from regular to Mach reflection can happen at any inlet aspect ratio, both when
the inlet aspect ratio is increased and when it is reduced. The inlet aspect ratio has no
effect on the transition provided it is high enough for the regular reflection point at
the spanwise centre to be free from information from wedge edges. Flow visualization
data produced using the vapour screen technique indicate that, in a region influenced
by information from wedge edges, the three-dimensionality of experimental models
promotes regular reflection rather than Mach reflection. To study the criteria for
the transition between regular and Mach reflections, an asymmetric arrangement of
two wedges has been used, and a hysteresis effect is clearly evident. The transition
from regular to Mach reflection, however, occurs significantly below the detachment
condition, and moreover, the repeatability of the transition angle is not satisfactorily
achieved. These experimental results imply that wind tunnel disturbances may dominate
the transition in the dual-solution domain. The stability of regular reflection
in the dual-solution domain is discussed, and effects of free-stream disturbances are
experimentally examined by producing water vapour in the free stream as an artificial
By means of a systematic study carried out on In0.5Ga0.5As/GaAs quantum dot electroluminescent devices grown by Metal Organic Chemical Vapor Deposition, we show that the combination of internal electric fields in such structures dramatically blue shifts the emission wavelength with respect the photoluminescence emission that occurs at the expected value of 1.3 νm at room temperature. By comparing photoluminescence (PL), electroluminescence (EL) and photocurrent (PC) measurements in In0.5Ga0.5As QD structures emitting between 1.28 νm and 1.4 νm (at 300 K), we demonstrate that the electric field associated to the built-in dipole in the dots, directed from the base of the dots to their apex, and the device junction field (when parallel to the dipole field) lead to the depletion of the ground state. As a consequence, structures grown on n-type GaAs substrates exhibit electroluminescence only from the excited states. Instead, by growing the same device structure on p-type GaAs substrates, i.e. by reversing the direction of the built-in electric field of the device, the effect of the permanent dipole is strongly reduced, thus allowing us to obtain EL emission at the designed wavelength of 1.3 νm at 300 K, coincident to the PL. The consequence on the achievement of efficient lasing in the spectral region of interest for optical transmission. are illustrate.
This paper describes the results of extensive performance and reliability characterization of a silicon-based surface micro-machined tunable optical filter. The device comprises a high-finesse Fabry-Perot etalon with one flat and one curved dielectric mirror. The curved mirror is mounted on an electrostatically actuated silicon nitride membrane tethered to the substrate using silicon nitride posts. A voltage applied to the membrane allows the device to be tuned by adjusting the length of the cavity. The device is coupled optically to an input and an output single mode fiber inside a hermetic package. Extensive performance characterization (over operating temperature range) was performed on the packaged device. Parameters characterized included tuning characteristics, insertion loss, filter line-width and side mode suppression ratio. Reliability testing was performed by subjecting the MEMS structure to a very large number of actuations at an elevated temperature both inside the package and on a test board. The MEMS structure was found to be extremely robust, running trillions of actuations without failures. Package level reliability testing conforming to Telcordia standards indicated that key device parameters including insertion loss, filter line-width and tuning characteristics did not change measurably over the duration of the test.
Optical properties of several heterostructures representing two-layer opaline photonic crystals have been examined. Two separate stop-bands have been observed both in transmission and emission spectra. The effect of the interface disorder on the optical spectra was not observed, probably, due to the insufficient degree of order of the opaline layers.
Three-dimensional (3D) photonic crystals with one to four layers of woodpile structures have been fabricated by stacking two-dimensional (2D) photonic plates by micromanipulation. First, air-bridge photonic plates were fabricated as unit structures using conventional IC processing techniques. Then, the 2D photonic plates were stacked using a micromanipulation system. To obtain lattices with precise periodicity, microspheres were inserted into the round openings which were prepared in the frame of the plates. Since neighboring plates have pore openings at the same position, plates were laminated at the proper position automatically. Consequently, positioning error was kept within 50 nm. Optical characteristics of the crystals were evaluated by their reflectance and transmittance at wavenumber between 700 and 7000 cm-1. The formed photonic crystals were expected to have a photonic band gap at around 3030 cm-1. As the number of layers was increased, the reflectance at around 3030 cm-1 increased to 60 %, and the transmittance at the same wavelength region decreased to 30 %.
We have explored the growth of GaN on porous SiC substrates by plasma-assisted molecular beam epitaxy. The porous 4H- and 6H-SiC(0001) substrates used in this study contain 10 to 100-nm sized pores and a thin skin layer at the surface. This skin layer was partially removed prior to the growth by H-etching. Transmission electron microscopy (TEM) observations indicate that the epitaxial GaN growth initiates from the surface areas between pores, and the exposed surface pores tend to extend into GaN as open tubes and trap Ga droplets. Plan-view TEM observations indicate that the GaN layers grown on porous substrates contain fewer dislocations than layers grown on non-porous substrates by roughly a factor of two. The GaN layers grown on a porous SiC substrate were also found to be mechanically more relaxed than those grown on non-porous substrates; electron diffraction patterns indicate that the former are free of misfit strain or are even in tension after cooling to room temperature.
Structures and electrical properties of newly synthesized vinylidene fluoride (VDF) oligomer [CF3(CH2CF2)17I] films evaporated onto various substrates around liquid nitrogen temperature were investigated. As a result, the VDF oligomer films were mainly formed with ferroelectric phase (form I) crystals and the molecular chains were oriented parallel to the substrate surfaces regardless of both the kind of the substrates and the thickness of the VDF oligomer films. In addition to these properties, the VDF oligomer films showed polarization reversal due to 180° rotation of the polar VDF oligomer molecules according to the applied voltages. This ferroelectric behavior was verified by local poling and piezoresponse measurements with an atomic force microscope, and by measurements of D-E hysteresis curves.
We have investigated a novel approach for improving GaN crystal quality by utilizing a stack of quantum dots (QDs) in GaN grown on sapphire substrates by molecular beam epitaxy. The GaN films were grown on GaN/AlN buffer layers containing multiple QDs and characterized using x-ray diffraction, photoluminescence, atomic force microscopy, and transmission electron microscopy. The density of the dislocations in the films was determined by defect delineation wet chemical etching and atomic force microscopy. It was found that the insertion of a set of multiple GaN QD layers in the buffer layer effectively reduced the density of the dislocations in the epitaxial layers. As compared to a density of ∼1010 cm-2 in typical GaN films grown on AlN buffer layers, a density of ∼3×107 cm-2 was demonstrated in GaN films grown with the QD layers. Transmission electron microscopy observations confirmed termination of threading dislocations by the QD layers.
Luminescence on Si-epitaxial layers grown on Si-implated Al2O3 ( 1102) with 30 keV Si+ to a dose of 5×1015/cm2 has been investigated. To active the implanted Si+ ions in Al2O3, the post annealing was performed at 1100°C in Ar ambiant. Also, cathodoluminescence (CL) and photoluminescence (PL) have been used to study struc Al2O3tural and optical properties of nc-Si in the Si+-implanted (1102) Al2O3 substrates. In the PL and CL spectra for Si+-implanted samples, peaks to be responsible for nanocrystalline-Si (nc-Si) appear at 316 nm (3.92 eV) and 574 nm (2.16 eV), respectively. The crystallinity of nc-Si imbeded in Al2O3 has been about 5nm in size and the dislocation aligned parallel to the (0001) planes of (1102) Al2O3, confirmed by transmission electron microscopy (TEM).
We have developed a thermally stimulated narrow-band infrared source for sensing, spectroscopy and thermophotovoltaic applications by combining the unique advantages of two different structures: a photonic crystal that consists of an array of holes etched into a dielectric substrate and a periodically perforated metallic thin film. The dielectric photonic crystal structure is passive and exhibits a strong absorption at resonance. This acts as a radiation reservoir for the conductive array, which plays an active role through plasmon interactions and is opaque at all wavelengths except those at which coupling occurs. We have fabricated the arrays on silicon, silicon dioxide and silicon nitride substrates using MEMS-based processing methods. Infrared spectroscopic studies were used to characterize reflection, absorption and emission in the 2 to 14 micron range showing narrow band resonance. Spectral tuning was accomplished by controlling symmetry and lattice spacing of the arrays. The effects of the etch depth, metal and dielectric properties have been studied experimentally and theoretically. These structures have been used as an emitter/detector sensor chip to selectively detect industrial pollutants like carbon dioxide.