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Background Nonsteroidal antiinflammatory drugs (NSAIDs) may exacerbate coronavirus disease 2019 (COVID-19) and worsen associated outcomes by upregulating the enzyme that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to in order to enter cells. Methods We conducted a cohort study using South Korea’s nationwide healthcare database, which contains data for all individuals who received a COVID-19 test (n = 69 793) as of 8 April 2020. We identified adults hospitalized with COVID-19, where cohort entry was the date of hospitalization. NSAID users were those prescribed NSAIDs in the 7 days before and including cohort entry, and nonusers were those not prescribed NSAIDs during this period. Our primary outcome was a composite of in-hospital death, intensive care unit admission, mechanical ventilation use, and sepsis; our secondary outcomes were cardiovascular complications and acute renal failure. We conducted logistic regression analysis to estimate odds ratio (OR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting to minimize confounding. Results Of 1824 adults hospitalized with COVID-19 (mean age, 49.0 years; female, 59%), 354 were NSAID users and 1470 were nonusers. Compared with nonuse, NSAID use was associated with increased risks of the primary composite outcome (OR, 1.54; 95% CI, 1.13–2.11) but insignificantly associated with cardiovascular complications (OR, 1.54; 95% CI, 0.96–2.48) or acute renal failure (OR, 1.45; 95% CI, 0.49–4.14). Conclusions While awaiting the results of confirmatory studies, we suggest NSAIDs be used with caution for COVID-19 patients as the harms associated with their use may outweigh their benefits.

Spatial resolution defines the physical limit of microscopes for probing biomolecular localization and interactions in cells. Whereas synchrotron-based X-ray microscopy (XRM) represents a unique approach for imaging a whole cell with nanoscale resolution due to its intrinsic nanoscale resolution and great penetration ability, existing approaches to label biomolecules rely on the use of exogenous tags that are multi-step and error-prone. Here, we repurpose engineered peroxidases as genetically encoded X-ray-sensitive tags (GXET) for site-specific labeling of protein-of-interest in mammalian cells. We find that 3,3′-diaminobenzidine (DAB) polymers that are in-situ catalytically formed by fusion-expressed peroxidases are visible under XRM. Using this new tag, we imaged the protein location associated with the alteration of a DNA-methylation pathway with an ultra-high resolution of 30 nanometers. Importantly, the excellent energy resolution of XRM enables multicolor imaging using different peroxidase tags. The development of GXET enlightens the way to nanoscopic imaging for biological studies., We report the development of genetcially-encoded tags for X-ray microscopic (XRM) imaging, which allows nanoscale localization of proteins in cells.

SummaryPurposeThere is uncertainty of the effect of immunosuppression, including corticosteroids, before COVID-19 infection on COVID-19 outcomes. The aim of this study was to investigate the relationship between prehospitalization immunosuppressants use (exposure), and COVID-19 patient outcomes.MethodsWe conducted a population-based retrospective cohort study using a nationwide healthcare claims database of South Korea as of May 15, 2020. Confirmed COVID-19 infection in hospitalized individuals aged 40 years or older were included for analysis. We defined exposure variable by using inpatient and outpatient prescription records of immunosuppressants from the database. Our primary outcome was a composite endpoint of all-cause death, intensive care unit (ICU) admission, and mechanical ventilation use. Inverse probability of treatment weighting (IPTW)-adjusted logistic regression analyses were used, to estimate odds ratio (OR) and 95% confidence intervals, comparing immunosuppressants users and non-users.ResultsWe identified 4,349 patients, for which 1,356 were immunosuppressants users and 2,903 were non-users. Patients who used immunosuppressants were at increased odds of the primary outcome of all-cause death, ICU admission and mechanical ventilation use (IPTW OR 1.32; 95% CI: 1.06 – 1.63). Patients who used corticosteroids were at increased odds of the primary outcome (IPTW OR 1.33; 95% CI: 1.07 – 1.64).ConclusionWe support the latest guidelines from the CDC, that people on immunosuppressants are at high risk of severe COVID-19 and immunocompromised people may need booster COVID-19 vaccinations.FundingYGC’s work was partially supported by 2020R1G1A1A01006229 awarded by the National Research Foundation of Korea.

We investigated the thermal annealing behavior of Ag-coated Cu nanoparticles in an epoxy matrix by using synchrotron X-ray transmission microscopy, coherent X-ray diffraction imaging, and scanning transmission X-ray microscopy (STXM). We observed thermal-annealing-induced void formation around the metal particles as well as shape changes in the metal particles because of the volume changes in the epoxy matrix. In addition, the density distribution of the metal particles was changed by thermal annealing. Based on the optical density measurements from the X-ray transmittance analysis, we could distinguish between the Cu-dominant region and the Ag-dominant region from the STXM images.

Frictional energy dissipation at the interfaces of two-dimensional (2D) materials through the excitation and transfer processes of kinetic energy into the bulk can be easily influenced by an intercalated water film. An enhancement of friction on water-intercalated graphene has been observed. Is this frictional enhancement by confined water a general phenomenon? We address this issue by investigating the frictional behavior of confined water layers intercalated between single-layer molybdenum disulfide (MoS2), synthesized using chemical vapor deposition, and a silica substrate. The icelike water was intercalated by exposure to high-humidity air. We found that the intercalated water molecules morphologically deform the 2D MoS2 sheet, forming distinct subdomains after the exposure to high humidity. We found that the adsorption of the icelike water layer between the MoS2 and the silica leads to friction enhancement, compared with a pristine MoS2/silica sample, which is associated with additional phononic fric...

IntroductionFamotidine is a competitive histamine H2-receptor antagonist most commonly used for gastric acid suppression but thought to have potential efficacy in treating patients with COVID-19. The aims of this systematic review and meta-analysis are to summarize the current literature and report clinical outcomes on the use of famotidine for treatment of hospitalized patients with COVID-19.MethodsFive databases were searched through February 12, 2021 to identify observational studies that reported on associations of famotidine use with outcomes in COVID-19. Meta-analysis was conducted for composite primary clinical outcome (e.g. rate of death, intubation, or intensive care unit admissions) and death separately, where either aggregate odds ratio (OR) or hazard ratio (HR) was calculated.ResultsFour studies, reporting on 46,435 total patients and 3,110 patients treated with famotidine, were included in this meta-analysis. There was no significant association between famotidine use and composite outcomes in patients with COVID-19: HR 0.63 (95% CI: 0.35, 1.16). Across the three studies that reported mortality separated from other endpoints, there was no association between famotidine use during hospitalization and risk of death - HR 0.67 (95% CI: 0.26, 1.73) and OR 0.79 (95% CI: 0.19, 3.34). Heterogeneity ranged from 83.69% to 88.07%.ConclusionBased on the existing observational studies, famotidine use is not associated with a reduced risk of mortality or combined outcome of mortality, intubation, and/or intensive care services in hospitalized individuals with COVID-19, though heterogeneity was high, and point estimates suggested a possible protective effect for the composite outcome that may not have been observed due to lack of power. Further RCTs may help determine the efficacy and safety of famotidine as a treatment for COVID-19 patients in various care settings of the disease.

IntroductionColchicine may inhibit inflammasome signaling and reduce proinflammatory cytokines, a purported mechanism of COVID-19 pneumonia. The aim of this systematic review and meta-analysis is to report on the state of the current literature on the use of colchicine in COVID-19 and to investigate the reported clinical outcomes in COVID-19 patients by colchicine usage.MethodsThe literature was searched from January 2019 through January 28, 2021. References were screened to identify studies that reported the effect of colchicine usage on COVID-19 outcomes including mortality, intensive care unit (ICU) admissions, or mechanical ventilation. Studies were meta-analyzed for mortality by the subgroup of trial design (RCT vs observational) and ICU status. Studies reporting an risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were analyzed separately.ResultsEight studies, reporting on 16,248 patients, were included in this review. The Recovery trial reported equivalent mortality between colchicine and non-colchicine users. Across the other studies, patients who received colchicine had a lower risk of mortality - HR of 0.25 (95% CI: 0.09, 0.66) and OR of 0.22 (95% CI: 0.09, 0.57). There was no statistical difference in risk of ICU admissions between patients with COVID-19 who received colchicine and those who did not – OR of 0.26 (95% CI: 0.06, 1.09).ConclusionColchicine may reduce the risk of mortality in individuals with COVID-19. Further prospective investigation may further determine the efficacy of colchicine as treatment in COVID-19 patients in various care settings of the disease, including post-hospitalization and long-term care.

Resonant elastic X-ray scattering has been widely employed for exploring complex electronic ordering phenomena, like charge, spin, and orbital order, in particular in strongly correlated electronic systems. In addition, recent developments of pump-probe X-ray scattering allow us to expand the investigation of the temporal dynamics of such orders. Here, we introduce a new time-resolved Resonant Soft X-ray Scattering (tr-RSXS) endstation developed at the Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL). This endstation has an optical laser (wavelength of 800 nm plus harmonics) as the pump source. Based on the commissioning results, the tr-RSXS at PAL-XFEL can deliver a soft X-ray probe (400-1300 eV) with a time resolution about ~100 fs without jitter correction. As an example, the temporal dynamics of a charge density wave on a high-temperature cuprate superconductor is demonstrated., 7 figures, 2 tables

There is ongoing debate as to whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) use is associated with poor prognosis of coronavirus disease-2019 (COVID-19). We sought to investigate the association between ACEI/ARB use and risk of poor clinical outcomes from COVID-19. We identified 1,290 patients with hypertension, of which 682 had recorded ACEI/ARB use and 608 without the use during 30 days preceding the date of COVID-19 diagnosis in completely enumerated COVID-19 cohort in South Korea. Our primary endpoint was the clinical outcomes comprised of all-cause mortality, use of mechanical ventilation, intensive care unit (ICU) admission, and sepsis. We used inverse probability of treatment weighting (IPTW) to mitigate selection bias, and Poisson regression model to estimate the relative risks (RR) and 95% confidence intervals (CI) to compare outcomes in ACEI/ARB users with non-users. Compared to non-use, ACEI/ARB use was associated with lower clinical outcomes (IPTW adjusted RR, 0.60; 95% CI, 0.42-0.85; p=0.0046). When assessed by individual outcomes, ACEI/ARB use was not associated with all-cause mortality (IPTW adjusted RR, 0.62; 95% CI, 0.35-1.09; p=0.0973) and respiratory events (IPTW adjusted RR, 0.99; 95% CI, 0.84-1.17; p=0.9043). Subgroup analysis showed a trend toward protective role of ACEIs and ARBs against overall outcomes in men (IPTW adjusted RR, 0.84; 95% CI, 0.69-1.03; p-for-interaction=0.008) and with pre-existing respiratory disease (IPTW adjusted RR, 0.74; 95% CI, 0.60-0.92; p-for-interaction=0.0023). We present clinical evidence to support continuing ACE/ARB use in completely enumerated hypertensive COVID-19 cohort in South Korea.

SUMMARYBACKGROUNDNon-steroidal anti-inflammatory drugs (NSAIDs) may exacerbate COVID-19 and worsen associated outcomes by upregulating the enzyme that SARS-CoV-2 binds to enter cells. However, to our knowledge, no study has examined the association between NSAID use and the risk of COVID-19-related outcomes among hospitalised patients.METHODSWe conducted a population-based cohort study using South Korea’s nationwide healthcare database, which contains data of all subjects who received a test for COVID-19 (n=69,793) as of April 8, 2020. We identified a cohort of adults hospitalised with COVID-19, where cohort entry was the date of hospitalisation. NSAIDs users were those prescribed NSAIDs in the 7 days before and including the date of cohort entry and non-users were those not prescribed NSAIDs during this period. Our primary outcome was a composite of in-hospital death, intensive care unit admission, mechanical ventilation use, and sepsis; our secondary outcome was cardiovascular or renal complications. We conducted logistic regression analysis to estimate odds ratio (OR) with 95% confidence intervals (CI) using inverse probability of treatment weighting to minimize potential confounding.FINDINGSOf 1,824 adults hospitalised with COVID-19 (mean age 490 years, standard deviation 19 0 years; female 59%), 354 were NSAIDs users and 1,470 were non-users. Compared with non-use, NSAIDs use was associated with increased risks of the primary composite outcome (OR 1 65, 95% CI 1-21-2-24) and of cardiovascular or renal complications (OR 187, 95% CI 1-25-2-80). Our main findings remained consistent when we extended the exposure ascertainment window to include the first three days of hospitalisation (OR 187, 95% CI 1 06-3 29).INTERPRETATIONUse of NSAIDs, compared with non-use, is associated with worse outcomes among hospitalised COVID-19 patients. While awaiting the results of confirmatory studies, we suggest NSAIDs be used with caution among patients with COVID-19 as the harms associated with their use may outweigh their benefits in this population.FUNDINGGovernment-wide R&D Fund for Infectious Disease Research (HG18C0068).

We have experimentally demonstrated circular polarization generation from linear polarized soft X-ray at synchrotron by adopting a thin magnetic film polarizer. Polarizer is composed of Co/Pt multilayer with a perpendicular magnetic anisotropy, which allows us to easily accommodate without needing any tilting angle into the measurement setup since the circular polarization is generated for the X-ray with normal incidence and transmission. Generated circular polarization is examined by observing magnetic domain features based on the X-ray magnetic circular dichroism, where ∼11% of circular component is estimated compared to the case of full circular polarization.

Correlation between the structural/electronic structure properties and bio-activity of graphene-based materials need to be thoroughly evaluated before their commercial implementation in the health and environment precincts. To better investigate the local hybridization of sp2/sp3 orbitals of the functional groups of graphene-oxide (GO) and their execution in the antimicrobial mechanism, we exemplify the antibacterial activity of GO sheets towards the Escherichia coli bacteria (E. coli) by applying the field-emission scanning electron microscopy (FESEM), near edge X-ray absorption fine structure (NEXAFS) and scanning transmission X-ray microscope (STXM) techniques. C K-edge and O K-edge NEXAFS spectra have revealed lesser sp2 carbon atoms in the aromatic ring and attachment of functional oxygen groups at GO sheets. Entrapment of E. coli bacteria by GO sheets is evidenced by FESEM investigations and has also been corroborated by nano-scale imaging of bacteria using the STXM. Spectroscopy evidence of functional oxygen moieties with GO sheets and physiochemical entrapment of E. coli bacteria have assisted us to elaborate the mechanism of cellular oxidative stress-induced disruption of bacterial membrane.

Introduction Famotidine is a competitive histamine H2-receptor antagonist most commonly used for gastric acid suppression but thought to have potential efficacy in treating patients with Coronavirus disease 2019 (COVID-19). The aims of this systematic review and meta-analysis are to summarize the current literature and report clinical outcomes on the use of famotidine for treatment of hospitalized patients with COVID-19. Methods Five databases were searched through February 12, 2021 to identify observational studies that reported on associations of famotidine use with outcomes in COVID-19. Meta-analysis was conducted for composite primary clinical outcome (e.g. rate of death, intubation, or intensive care unit admissions) and death separately, where either aggregate odds ratio (OR) or hazard ratio (HR) was calculated. Results Four studies, reporting on 46,435 total patients and 3,110 patients treated with famotidine, were included in this meta-analysis. There was no significant association between famotidine use and composite outcomes in patients with COVID-19: HR 0.63 (95% CI: 0.35, 1.16). Across the three studies that reported mortality separated from other endpoints, there was no association between famotidine use during hospitalization and risk of death—HR 0.67 (95% CI: 0.26, 1.73) and OR 0.79 (95% CI: 0.19, 3.34). Heterogeneity ranged from 83.69% to 88.07%. Conclusion Based on the existing observational studies, famotidine use is not associated with a reduced risk of mortality or combined outcome of mortality, intubation, and/or intensive care services in hospitalized individuals with COVID-19, though heterogeneity was high, and point estimates suggested a possible protective effect for the composite outcome that may not have been observed due to lack of power. Further randomized controlled trials (RCTs) may help determine the efficacy and safety of famotidine as a treatment for COVID-19 patients in various care settings of the disease.

High-density coherent fiber bundles, mainly used for high-resolution fiberscopes, consist of non-circular cores and have various optical noises such as auto-fluorescence, crosstalk, and honeycomb artifacts that may require excessive image processing. Binarization was applied to post-image processing to eliminate a calibration used as pre-image processing for traditional fiberscope image reconstruction. It was able to significantly reduce the complexity of implementing core peak detection and effectively reduce the overall processing time. For binarization, the global thresholding suggested by Otsu and the local thresholdings suggested by Bernsen, Niblack, and White and Rohrer were used. By applying a dynamic method to our method, we can further simplify the process and apply it to image sequencing. When evaluating the results comprehensively, the local thresholding proposed by Bernsen was best suited for interpolating our fiberscope images. By introducing binarization combined with local thresholding in post-image processing, we were able to successfully eliminate the preliminary calibration process and reduce the burden of overall image processing for image reconstruction in a high-resolution fiberscope.

We present all-optical imaging system for studying cerebral blood flow regulation. To investigate changes in blood flow in the brain, it is necessary to visualize the vascular microstructure between neurons, astrocytes, and vascular cells and monitor changes in vessel diameter and blood flow velocity. Optogenetics is an excellent technology that can be applied to cerebral blood flow regulation studies that require superior spatial and temporal resolution and individual control of cellular activity. The developed optical system is a new integrated optical imaging system that can apply all of the techniques mentioned above for cerebral blood flow regulation research. The optical system includes a dual-color fluorescence imaging system and a laser stimulation system. The system successfully performed dual-color fluorescence imaging with a 50 μm grid pattern in the two wavelength ranges of 515-545 nm and 608-631 nm. It also performed laser stimulation with a minimum output laser pattern size of 2 × 2 μm2 and a maximum intensity of up to 120 mW/mm2. In addition, the optical system measured the fast flow velocity of fluorescent microbeads up to 1.9 μm/ms. Experimental results show that the system can be a promising tool for cerebral blood flow regulation studies that require optogenetic stimulation and dual-fluorescence imaging while measuring blood flow velocity. In the future, the all-optical imaging system will be applied to fiber bundle-based endoscopic systems developed to study cerebral blood flow regulation using optogenetics in living animal brains.

Solution-based direct patterning on an elastomer substrate with meniscus-dragging deposition (MDD) enables fabrication of very thin carbon nanotube (CNT) layers in the nanometer scale (80&ndash, 330 nm). To fabricate the CNT pattern with CNT solution, contact angle, electrical variation, mechanical stress, and surface cracks of elastomer substrate were analyzed to identify the optimal conditions of O2 treatment (treatment for 30 s with RF power of 50 W in O2 atmosphere of 50 sccm) and mixture ratio between Ecoflex and polydimethylsiloxane (PDMS) (Ecoflex:PDMS = 5:1). The type of mask for patterning of the CNT layer was determined through quantitative analysis for sharpness and uniformity of the fabricated CNT pattern. Through these optimization processes, the CNT pattern was produced on the elastomer substrate with selected mask (30 &mu, m thick oriented polypropylene). The thickness of CNT pattern was also controlled to have hundreds nanometer and 500 &mu, m wide rectangular and circular shapes were demonstrated. Furthermore, the change in the current and resistance of the CNT layer according to the applied strain on the elastomer substrate was analyzed. Our results demonstrated the potential of the MDD method for direct CNT patterning with high uniformity and the possibility to fabricate a stretchable sensor.

The Pohang Accelerator Laboratory X-ray Free Electron Laser project, a new worldwide-user facility to deliver ultrashort, laser-like x-ray photon pulses, will begin user operation in 2017 after one year of commissioning. Initially, it will provide two beamlines for hard and soft x-rays, respectively, and two experimental end-stations for the hard x-ray beamline will be constructed by the end of 2015. This article introduces one of the two hard x-ray end-stations, which is for hard x-ray pump-probe experiments, and primarily outlines the overall design of this end-station and its critical components. The content of this article will provide useful guidelines for the planning of experiments conducted at the new facility.

We investigated the subdomain structures of single-layer graphene oxide (GO) by characterizing local friction and conductance using conductive atomic force microscopy. Friction and conductance mapping showed that a single-layer GO flake has subdomains several tens to a few hundreds of nanometers in lateral size. The GO subdomains exhibited low friction (high conductance) in the sp(2)-rich phase and high friction (low conductance) in the sp(3)-rich phase. Current-voltage spectroscopy revealed that the local current flow in single-layer GO depends on the quantity of hydroxyl and carboxyl groups, and epoxy bridges within the 2-dimensional carbon layer. The presence of subdomains with different sp(2)/sp(3) carbon ratios on a GO flake was also confirmed by chemical mapping using scanning transmission X-ray microscopy. These results suggest that spatial mapping of the friction and conductance can be used to rapidly identify the composition of heterogeneous single-layer GO at nanometer scale, which is essential for understanding charge transport in nanoelectronic devices.

Graphene-based spintronics has attracted much attention owing to the weak spin–orbit interaction and long spin relaxation length in graphene. For implementation of practical and high-density graphene-based spintronic devices, we need to define nanoscale areas with room-temperature ferromagnetism on graphene. Here we report the room-temperature ferromagnetism observed in nanoscale functionalized (oxidized and hydrogenated) graphene using atomic force microscope lithography without involving potential surface contamination and chemical agents. By performing magnetic force microscope (MFM) measurements, we can clearly distinguish the local ferromagnetic signal of selectively functionalized graphene from that of surrounding non-magnetic pristine graphene. The nanoscale functionalized graphene shows experimental evidence of room-temperature ferromagnetism: (1) larger MFM signal than that of graphene; (2) repulsive and attractive interaction with an MFM tip the magnetization of which points into and out of the graphene, respectively; and (3) MFM signal reversal after applying a high magnetic field at an elevated temperature of 400 K. Our first-principles calculations reveal that unpaired spins are present at non-passivated dangling bonds of vacancies on functionalized graphene and the stable ferromagnetic exchange interactions between them are favored. Therefore, nanoscale functionalized graphene is a good candidate for use as the spin injector or detector of high-density graphene-based spintronic devices.

A scanning transmission X-ray microscope is operational at the 10A beamline at the Pohang Light Source. The 10A beamline provides soft X-rays in the photon energy range 100–2000 eV using an elliptically polarized undulator. The practically usable photon energy range of the scanning transmission X-ray microscopy (STXM) setup is from ∼150 to ∼1600 eV. With a zone plate of 25 nm outermost zone width, the diffraction-limited space resolution, ∼30 nm, is achieved in the photon energy range up to ∼850 eV. In transmission mode for thin samples, STXM provides the element, chemical state and magnetic moment specific distributions, based on absorption spectroscopy. A soft X-ray fluorescence measurement setup has been implemented in order to provide the elemental distribution of thicker samples as well as chemical state information with a space resolution of ∼50 nm. A ptychography setup has been implemented in order to improve the space resolution down to 10 nm. Hardware setups and application activities of the STXM are presented.

We report our investigation on the magnetic-domain structure of a Co/Pt multilayer with perpendicular magnetic anisotropy under a horizontal in-plane field by using a high-resolution scanning transmission X-ray microscope (STXM) developed at Pohang Accelerator Laboratory. The ruggedshaped striped magnetic-domain structure that was initially formed under a field cycle along the out-of-the plane magnetic easy axis was found to be stretched and elongated along the direction of the horizontal in-plane field. As the in-plane field was strengthened, the striped pattern exhibited an anisotropic domain growth with further stretching and aligning, as well as with a modification of the magnetic-domain’s width.

Graphene has been used as an electrode and channel material in electronic devices because of its superior physical properties. Recently, electronic devices have changed from a planar to a complicated three-dimensional (3D) geometry to overcome the limitations of planar devices. The evolution of electronic devices requires that graphene be adaptable to a 3D substrate. Here, we demonstrate that chemical-vapor-deposited single-layer graphene can be transferred onto a silicon dioxide substrate with a 3D geometry, such as a concave-convex architecture. A variety of silicon dioxide concave-convex architectures were uniformly and seamlessly laminated with graphene using a thermal treatment. The planar graphene was stretched to cover the concave-convex architecture, and the resulting strain on the curved graphene was spatially resolved by confocal Raman spectroscopy; molecular dynamic simulations were also conducted and supported the observations. Changes in electrical resistivity caused by the spatially varying strain induced as the graphene-silicon dioxide laminate varies dimensionally from 2D to 3D were measured by using a four-point probe. The resistivity measurements suggest that the electrical resistivity can be systematically controlled by the 3D geometry of the graphene-silicon dioxide laminate. This 3D graphene-insulator laminate will broaden the range of graphene applications beyond planar structures to 3D materials.

On-the-spot visualization of biochemical responses of intact live cells is vital for a clear understanding of cell biology. The main obstacles for instant visualization of biochemical responses of living cells arise from the lack of a sophisticated detecting technique which can simultaneously provide chemical analysis tools and the biocompatible wet conditions. Here we introduce scanning transmission X-ray microscopy (STXM) combined with a liquid-enclosing graphene system (LGS), offering biocompatible conditions and improved X-ray absorption spectra to probe the chemical responses of live cells under wet conditions. This set-up enables us to probe a subtle change in absorption spectra depending on the oxidation state of a miniscule amount of oxygen in the functional groups present in each cell and its surroundings containing a minimal amount of liquid water. As an example of in situ biochemical responses of wet cells, chemical responses of a single Colo 205 cell are visualized and analyzed using X-ray absorption near the oxygen K-edge. This spectromicroscopic method using LGS can be applied to diverse biological samples under wet conditions for the analysis of their biochemical responses.

The exciplex forming co-host with phosphorescent dopant system has potential to realize highly efficient phosphorescent organic light emitting didoes (PhOLEDs). However, the exciplex forming co-host for blue phosphorescent OLEDs has been rarely introduced because of higher triplet level of the blue dopant than green and red dopants. In this work, a novel exciplex forming co-host with high triplet energy level is developed by mixing a phosphine oxide based electron transporting material, PO-T2T, and a hole transporting material, N,N′-dicarbazolyl-3,5-benzene (mCP). Photo-physical analysis shows that the exciplexes are formed efficiently in the host and the energy transfer from the exciplex to blue phosphorescent dopant (iridium(III)bis[(4,6-difluorophenyl)-pyridinato-N,C2′]picolinate; FIrpic) is also efficient, enabling the triplet harvest without energy loss. As a result, an unprecedented high performance blue PhOLED with the exciplex forming co-host is demonstrated, showing a maximum external quantum efficiency (EQE) of 30.3%, a maximum power efficiency of 66 lm W−1, and low driving voltage of 2.75 at 100 cd m−2, 3.29 V at 1000 cd m−2, and 4.65 V at 10 000 cd m−2, respectively. The importance of the exciton confinement in the exciplex forming co-host is further investigated which is directly related to the performance of PhOLEDs.

We report the design and fabrication of an integrated Mach–Zehnder interferometric (MZI) biochip based on silicon oxynitride layers deposited with a plasma-enhanced chemical vapor deposition (PECVD) process. A rib waveguide for an integrated MZI sensor has been designed to have a high surface sensitivity and a single-mode behavior by using an effective index method. The integrated MZI chip operating at 637 nm is fabricated via conventional photolithography and reactive ion etching. As a biosensor application, the real-time and label-free detection of the covalent immobilization and hybridization of DNA strands is performed and verified with this device.

Almost 100% internal quantum efficiency (IQE) is achieved with a green fluorescent organic light-emitting diode (OLED) exhibiting 30% external quantum efficiency (EQE). The OLED comprises an exciplex-forming co-host system doped with a fluorescent dye that has a strong delayed fluorescence as a result of reverse intersystem crossing (RISC); the exciplex-forming co-hosts stimulate energy transfer and charge balance in the system. The orientation of the transition dipole moment of the fluorescent dye is shown to have an influence on the EQE of the device.

We report catalytic decomposition of few-layer graphene on an Au/SiOx/Si surface wherein oxygen is supplied by dissociation of the native SiOx layer at a relatively low temperature of 400 °C. The detailed chemical evolution of the graphene covered SiOx/Si surface with and without gold during the catalytic process is investigated using a spatially resolved photoelectron emission method. The oxygen atoms from the native SiOx layer activate the gold-mediated catalytic decomposition of the entire graphene layer, resulting in the formation of direct contact between the Au and the Si substrate. The notably low contact resistivity found in this system suggests that the catalytic depletion of a SiOx layer could realize a new way to micromanufacture high-quality electrical contact.

In the present study, we applied a sonication based method to achieve graphene oxide (GO) and reduced graphene oxide (r-GO) nano-structures. X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), Transmission electron microscopy (TEM) and x-ray absorption near edge structure (XANES) spectroscopy measurements were applied to characterize the samples. XRD, TEM and Raman results demonstrate significant crystalline nature of GO nano sheets. On the other hand, the r-GO sample shows poor crystallinity with a large number of lattice defects. The FTIR spectrum conveys the attachment of significant oxygen-containing functional groups in GO sample. The detachment of oxygen function groups from the r-GO sample, under the reduction process, is also confirmed by the FTIR spectra. Local electronic structure investigations, from the C K-edge XANES of GO and r-GO nano sheets, convey the lowering of 1s → π* and 1s → σ* transitions and lesser sp2 character of the carbon ring. The O K-edge XANES spectra have shown the accumulation of C = O σ*, C–O σ* and O–H σ* states at the basal plane of GO and elimination of such functional groups in the r-GO samples and convey controlled tailoring of the functionalities of GO and r-GO nano sheets.

We report that high-quality single-layer graphene (SLG) has been successfully synthesized directly on various dielectric substrates including amorphous SiO2/Si by a Cu-vapor-assisted chemical vapor deposition (CVD) process. The Cu vapors produced by the sublimation of Cu foil that is suspended above target substrates without physical contact catalyze the pyrolysis of methane gas and assist nucleation of graphene on the substrates. Raman spectra and mapping images reveal that the graphene formed on a SiO2/Si substrate is almost defect-free and homogeneous single layer. The overall quality of graphene grown by Cu-vapor-assisted CVD is comparable to that of the graphene grown by regular metal-catalyzed CVD on a Cu foil. While Cu vapor induces the nucleation and growth of SLG on an amorphous substrate, the resulting SLG is confirmed to be Cu-free by synchrotron X-ray photoelectron spectroscopy. The SLG grown by Cu-vapor-assisted CVD is fabricated into field effect transistor devices without transfer steps that are generally required when SLG is grown by regular CVD process on metal catalyst substrates. This method has overcome two important hurdles previously present when the catalyst-free CVD process is used for the growth of SLG on fused quartz and hexagonal boron nitride substrates, that is, high degree of structural defects and limited size of resulting graphene, respectively.

High efficiency OLEDs based on phosphorescent, thermally activated delayed fluorescent (TADF) and fluorescent emitters will be presented. We will show that EQEs over 60% is achievable if OLEDs are fabricated using organic semiconductors with the refractive indices of 1.5 and fully horizontal emitting dipoles without any extra light extracting structure. We will also show that reverse intersystem crossing RISC rate plays an important role to reduce the efficiency roll-off in efficient TADF and fluorescent OLEDs and a couple to methods will be presented to increase the RISC rate in the devices.

For the structural characterization of the polystyrene (PS)-based photonic crystals (PCs), fast and direct imaging capabilities of full field transmission X-ray microscopy (TXM) were demonstrated at soft X-ray energy. PS-based PCs were prepared on an O2-plasma treated Si3N4 window and their local structures and defects were investigated using this label-free TXM technique with an image acquisition speed of ~10 sec/frame and marginal radiation damage. Micro-domains of face-centered cubic (FCC (111)) and hexagonal close-packed (HCP (0001)) structures were dominantly found in PS-based PCs, while point and line defects, FCC (100), and 12-fold symmetry structures were also identified as minor components. Additionally, in situ observation capability for hydrated samples and 3D tomographic reconstruction of TXM images were also demonstrated. This soft X-ray full field TXM technique with faster image acquisition speed, in situ observation, and 3D tomography capability can be complementally used with the other X-ray microscopic techniques (i.e., scanning transmission X-ray microscopy, STXM) as well as conventional characterization methods (e.g., electron microscopic and optical/fluorescence microscopic techniques) for clearer structure identification of self-assembled PCs and better understanding of the relationship between their structures and resultant optical properties.

In synchrotron facilities, imaging techniques are on high demand from the scientific community. Those related to X-ray microscopy are among the most prominent ones. Such techniques include scanning transmission x-ray microscopy (STXM), full-field transmission x-ray microscopy (TXM), and coherent diffraction imaging (CDI) which have a wide spectrum of applications ranging from clinical and biomedical sciences to nanotechnology and cultural heritage. Their advancement is achieved through specialisation and focused studies, often requiring dedicated beamline end-stations. On the other hand, scientific applications benefit from the combination of techniques in a complementary manner. Beamlines suitably designed to offer multiple techniques, instead of a single one, can host efficiently such combinatorial studies. In this paper, we present the diverse Soft X-ray microscopy techniques in use at the TwinMic beamline at Elettra Sincrotrone Trieste, namely, STXM combined with XRF spectroscopy, full-field TXM and Ptychography. We demonstrate the capabilities by examining two specific biological samples: U87MG cells exposed to CoFe2O4 nanoparticles and a stem section of a Solanum lycopersicum (tomato) plant. These specimens are representatives of a large sample class used in a wide range of scientific studies. The results show the potential that can be achieved in terms of imaging by accessing X-ray microscopy techniques during a single beamtime access in TwinMic.

An integrated Mach-Zehnder interferometric chip operating at 632.8 nm was designed and fabricated using planar rib waveguide technology for optical sensor applications. A rib waveguide with a silicon-oxynitride core layer and silicon-oxide clad layers was geometrically designed to have a singlemode operation and a high surface sensitivity by using an effective index method. A chromium mask layer was employed as an etch stop to protect the core layer of the rib waveguide and was patterned using an image reversal process with a photo mask applied to the sensor zone. The image reversal process was modified in order to obtain a longer chromium mask layer against the sensor zone. We have, therefore, established a fabrication method for an integrated Mach-Zehnder interferometric sensor without the addition of a new photo mask. The optical measurement with this device for a mixture of deionized water (DIW) and phosphate buffer solution (PBS) finally showed a sensitivity of about π/(6.25 × 10−4).

Alignment and operation of a zone-plate (ZP)-based transmission soft X-ray microscope (TXM) is difficult and time consuming, especially when the TXM has no dedicated X-ray source. We introduce here an efficient TXM alignment scheme. The TXM employed is a simple in-situ-experiment-capable setup. It includes ultrahigh-vacuum (UHV)-compatible conflat flanges and is mountable in tandem with any soft X-ray synchrotron radiation beamlines. Obtaining zeroth- and first-order diffracted (condenser-zone-plate [CZP]-focused) beams simultaneously by means of the objective zone plate (OZP) is the most essential step in the alignment scheme. We were able to acquire, in one hour at a radiation wavelength of 2.49 nm, an image of 50 nm spatial resolution.

The site-dependent and spontaneous functionalization of 4-bromobenzene diazonium tetrafluoroborate (4-BBDT) and its doping effect on a mechanically exfoliated graphene (MEG) were investigated. The spatially resolved Raman spectra obtained from both edge and basal region of MEG revealed that 4-BBDT molecules were noncovalently functionalized on the basal region of MEG, while they were covalently bonded to the edge of MEG. The chemical doping effect induced by noncovalently functionalized 4-BBDT molecules on a basal plane region of MEG was successfully explicated by Raman spectroscopy. The position of Fermi level of MEG and the type of doping charge carrier induced by the noncovalently adsorbed 4-BBDT molecules were determined from systematic G band and 2D band changes. The successful spectroscopic elucidation of the different bonding characters of 4-BBDT depending on the site of graphene is beneficial for the fundamental studies about the charge transfer phenomena of graphene as well as for the potential applications, such as electronic devices, hybridized composite structures, etc.

Label-free and real-time detections of mismatched dsDNAs are demonstrated using MutS-protein-immobilized, single-walled carbon nanotube field effect transistor (SWNT-FET) devices. The E. coli MutS proteins specifically recognizing mismatched dsDNAs are immobilized on SWNT-FET devices that have been fabricated for high sensitivity using a shadow mask lithographic technique to obtain a thin and wide Schottky contact region. The MutS-immobilized SWNT-FETs have successfully detected 40 base pair dsDNAs having single G-T mismatches at the 20th base pair positions by displaying significant electrical conductance drops at as low as 100 pM concentration. Systematic control experiments have revealed that the signal changes indeed originated from specific recognitions of mismatched DNAs by the immobilized MutS proteins.

This paper presents development of a scheduling methodology for module processing in thin film transistor liquid crystal display (TFT-LCD) manufacturing. The problem is a parallel machine scheduling problem with rework probabilities, sequence-dependent setup times and due dates. It is assumed that rework probability for each job on a machine can be given through historical data acquisition. The dispatching algorithm named GRPD (greedy rework probability with due-dates) is proposed in this paper focusing on the rework processes. The performance of GRPD is measured by the six diagnostic indicators. A large number of test problems are randomly generated to evaluate the performance of the proposed algorithm. Computational results show that the proposed algorithm is significantly superior to existing dispatching algorithms for the test problems.

The chemical states of GeTe thin film are investigated using high-resolution X-ray photoelectron spectroscopy (HRXPS) with synchrotron radiation, during amorphous to crystalline structural phase transition. As the temperature increases from 250 to 400 °C, we observe the rock-salt crystalline structure and phase with X-ray diffraction (XRD) and transmission electron microscopy (TEM). Spin-orbit splitting of the Ge 3d core-level spectrum clearly appears after annealing at 400 °C for 5 min. However, the binding energy of the Ge 3d 5/2 core-level peak of 29.8 eV does not change in the amorphous to crystalline structural phase transition. In the case of the Te 4d core-level, change in binding energy and peak shapes is also negligible. We assume that the Te atom is fixed at a site between the amorphous and crystalline phases. Although the structural environment of the Ge atoms changes during the structural phase transition, the chemical environment does not.

As predicted by Moore’s Law, [1] the feature size of semiconductor devices reached the 90 nm node in 2004. [2] Presently, research is focused on reaching 32 nm. [3] Unfortunately, standard UV lithography cannot be used at this scale. [3] Thus, several next-generation lithographic techniques have been proposed. [4–7] Work combining scanning probe lithography and self-assembly [8] has demonstrated that a hybridization of topdown and bottom-up techniques may be effective. [9] As photolithography using shorter-wavelength light, such as extreme UV or soft X-rays, is considered to be a leading next-generation lithography technology, a hybrid approach combining extreme UV lithography (EUVL) with bottom-up assembly could be used in the industrial production of microelectronic devices. Polymers have typically been used as templates for this type of hybrid patterning, [10,11] but thinner layers are required to continue to reduce feature sizes via EUVL. Nanolayers of small molecules on silicon consist of only a few atomic layers. As these systems are structurally simple and well ordered, a number of surface science studies have been performed to probe the behavior of these materials during the last several decades. [12] Therefore, they are well understood and are an excellent choice for studying EUV-induced surface modification at the atomic scale. EUV is normally used in the identification of chemical structures or the analysis of chemical environments, but an EUV-induced surface modification is clearly observed for a molecular nanolayer of Cl2 in this work. We report that EUV-induced surface modification can be used to pattern surfaces, resulting in a variety of possible functionalities. As surface modification originates from secondary electrons produced by EUV, it can also occur from primary electrons or photons with shorter wavelengths, suggesting that our concept could be extended to electron-beam (e-beam) and proximity X-ray lithographies.

The detection of biomarkers in the liquid phase using mechanical sensors is difficult because of noise caused by the liquid. To reduce and verify the side effects of liquid loading, we performed calculations and experiments to determine the shift in resonant frequency according to the loading conditions. A 2-μm-thick piezoelectric rectangular micro-diaphragm with a 500 × 500 μm membrane was used. These dimensions were determined such that there would be an analogous resonant frequency shift ratio in both (1, 1) and (2, 2) modes. By calculating and measuring the resonant frequency, we verified that the resonant frequency of the sensor would change only through contact with the liquid, even the resonant frequency change by only liquid much higher than the changes caused by the nanoparticles. The real signal constituted only 0.017% of the initial resonant frequency. To enhance the sensitivity by reducing the unexpected surface stress in the liquid, the liquid was dropped onto the surface of the micro-diaphragm. This resulted in an improvement of more than 10 times the sensitivity in both modes. In addition, by controlling the position in the micro-diaphragm resonating sensor, more sensitive positions with large displacements were determined according to each mode.

Changes in the structural and electrical properties of a Ge2Sb2Te5 alloy thin film induced by phase transition were investigated using various analytical techniques. X-ray diffraction and scanning photoelectron microscopy showed that the phase separation occurred in a local area of the film during a phase transition when the amorphous structure was being transformed into crystalline structures. It was found that the heterogeneous distribution of Sb atoms that diffused during the phase transition accompanied the phase separation. Atomic force microscopy was used to examine the changes in surface morphology and roughness. The electrical conductance of the film was dramatically improved after the phase transition from an amorphous structure to crystalline structures as evidenced by the sheet resistance measurements. The sheet resistance changed from ∼109to∼102Ω∕sq. during the phase transition. Differential scanning calorimetry was used to determine the exact phase transition temperature (160–170°C) and the e...

Double-walled carbon nanotubes (DWCNTs) were synthesized by using thermal chemical vapor deposition on MgO-supported Fe–Mo catalysts, in the temperature range 800–1000 °C. Outer diameters were 1.5–2 nm at all growth temperatures. As growth temperature was increased, C1s peaks of X-ray photoelectron spectroscopy became broader and valence band intensity increased due to stronger van der Waals interaction between DWCNTs induced by higher crystallinities. Field emission from the as-grown DWCNTs exhibited a large current density enhancement with increasing growth temperature.

In this paper, the development of compact transmission soft x-ray microscopy (XM) with sub-50 nm spatial resolution for biomedical applications is described. The compact transmission soft x-ray microscope operates at lambda = 2.88 nm (430 eV) and is based on a tabletop regenerative x-ray source in combination with a tandem ellipsoidal condenser mirror for sample illumination, an objective micro zone plate and a thinned back-illuminated charge coupled device to record an x-ray image. The new, compact x-ray microscope system requires the fabrication of proper x-ray optical devices in order to obtain high-quality images. For an application-oriented microscope, the alignment procedure is fully automated via computer control through a graphic user interface. In imaging studies using our compact XM system, a gold mesh image was obtained with 45 nm resolution at x580 magnification and 1 min exposure. Images of a biological sample (Coscinodiscus oculoides) were recorded.

Total electron yield (TEY) measurement was applied to the scanning photoelectron microscopy (SPEM). The resultant image showed the thickness variation of a zinc overlayer deposited on an iron substrate with 18 nm nominal thickness. The contrast and signal-to-noise ratio of the image were much higher than those of the images obtained by the conventional SPEM. When the order-sorting aperture (OSA) located between the Fresnel zone plate and the sample was biased to +80 V relative to the sample, the contrast of the image was further improved. It also made it possible to perform microscopic X-ray absorption spectroscopy in TEY mode by preventing the unwanted photoelectrons emitted from the OSA, which can cause false TEY, from reaching the sample. Oxidized areas of the iron substrate under the thick zinc overlayer were clearly identified.

A surface micromachining uncooled infrared detector with an optimized vanadium alloy oxide layer is fabricated, based on low temperature annealing of V–W alloy oxide layer. Vanadium oxide is a promising material for an uncooled bolometer, due to its high temperature coefficient of resistance at room temperature. An infrared active layer is needed to be with the reflective layer to enhance its IR absorption. Test bolometers are successfully fabricated and then are radiated by an IR laser source at various power levels with a chopper in a frequency range of 1–500 Hz. The responsivity and the noise of the test bolometer are measured and the detectivity is calculated. From the results, the calculated detectivity is 1.1 × 107 cm Hz1/2 W−1. Bolometer detectivity can be increased further if the noise in the device is reduced.

This paper describes polidimethylsiloxane(PDMS) based bonding for assembly of microstructure device, an UV lithography applications for fabricating a 3-dimensional (3D) feed-horn-shaped structure mold array, and obtaining parallel light by using a mirror-reflected parallel-beam illuminator (MRPBI) system. A 3D feed-horn-shaped micro-electro-mechanical systems (MEMS) antenna has some attractive features for array applications, which can be used to improve microbolometer performance and to enhance the optical efficiency for thin film transistor-liquid crystal display (TFT-LCD) and other display devices but currently, MEMS technology has faced many difficulties in the fabrication of a 3D feed-horn-shaped MEMS antenna array itself. The purpose of this paper is to propose a new fabrication method to realize a 3D feed-horn-shaped MEMS antenna array by using a mirror-reflected parallel-beam illuminator (MRPBI) System with a very slowly rotated, inclined x-y-z stage. With a conventional UV lithography apparatus, it is very difficult to fabricate high-aspect-ratio structures (HARS) because a typical UV lithography apparatus cannot produce perfectly parallel light. From a theoretical analysis, a columnar illuminator over 6 m in height is required to achieve parallel light, but generally a laboratory height is not 6 m. Also, a novel method of lithography was tried to make a 3D structure array by exposing a planar wafer to the generated parallel light and rotating an inclined x-y-z stage at an ultra-slow rate. An optimization of the 3D structure array can be achieved by simulating a 3D feed-horn MEMS antenna. The feasibility of fabricating both a 3D feed horn MEMS antenna and assembly of detector with 3D feed-horn MEMS antenna was demonstrated. As a result, it seems possible to use a 3D feed-horn-shaped MEMS antenna to improve microbolometer performance and to fabricate several optical microstructure applications.