Radiation control by defects in dark-state resonant photonic lattices.

In this Letter, we present and explain novel radiation properties enabled by defects in resonant photonic lattices (PLs). Incorporating a defect breaks the lattice symmetry and generates radiation through the stimulation of leaky waveguide modes near the non-radiant bound (or dark) state spectral location. Analyzing a simple one-dimensional (1D) subwavelength membrane structure, we show that the defects produce local resonant modes that correspond to asymmetric guided-mode resonances (aGMRs) in spectra and near-field profiles. Without a defect, a symmetric lattice in the dark state is neutral, generating only background scattering. Incorporating a defect into the PL induces high reflection or transmission by robust local resonance radiation depending on the background radiation state at the bound state in the continuum (BIC) wavelengths. With the example of a lattice under normal incidence, we demonstrate defect-induced high reflection as well as high transmission. The methods and results reported here have significant potential to enable new modalities of radiation control in metamaterials and metasurfaces based on defects.

Quantifying bound and leaky states of resonant optical lattices by Rytov-equivalent homogeneous waveguides.

The properties of periodic optical lattices are generally investigated with rigorous numerical methods. For physical insight and understanding of the complex processes underlying observed spectra, simple analytical models are needed. Accordingly, we show that by applying full Rytov effective-medium formalisms, the bound and leaky states of resonant photonic lattices can be quantified with high precision. Thus, all key properties are embodied in Rytov-equivalent homogeneous waveguides. The symmetric effective-medium theory (EMT) model quantifies rigorously computed guided-mode resonance (GMR) reflectance loci defining the leaky states. The asymmetric EMT formula similarly quantifies the bound state in the continuum (BIC) loci. Even with the period and wavelength on similar scales, the analytical EMT refractive index solutions agree exactly with rigorous solutions. We apply the Rytov formulas to explain the resonant leaky band structure including appearance of GMR and BIC states as well as band transitions and band closure points. The wavenumbers of the equivalent waveguides represent the BIC embedded eigenvalues as quantified here.

Search for Boosted Dark Matter in COSINE-100.

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

Substrate-wave-induced antireflection in metasurfaces.

We address the antireflection (AR) properties of periodic surfaces, or metasurfaces, supporting substrate waves. The work is motivated by recent literature where AR bands formed by substrate-wave propagation are incorrectly attributed to Mie scattering. In contrast, as clearly shown here, substrate-wave generation with corresponding AR signatures is a diffractive effect due to a periodic lattice and is not due to particle scattering as in Mie resonance. Treating both 1D and 2D surfaces, we demonstrate a clear quantitative connection between major AR loci and corresponding total substrate transmittance loci via maps in period versus wavelength. As shown, this holds for fully dispersed, lossy surfaces as well. The results presented here serve to elucidate the physical properties of periodic metasurfaces placed on substrates admitting propagating diffraction orders and may inform the design and implementation of grating-based AR structures.

Micro-electromechanical-system-tuned resonant filters spanning the 8-12 µm band.

The spectral band covering ∼8-12µm is atmospherically transparent and therefore important for terrestrial imaging, day/night situational awareness systems, and spectroscopic applications. There is a dearth of tunable filters spanning the band. Here, we propose and demonstrate a new, to the best of our knowledge, tunable-filter method engaging the fundamental physics of the guided-mode resonance (GMR) effect realized with a non-periodic lattice. The polarization-dependent filter is fashioned with a one-dimensional Ge grating on a ZnSe substrate and interrogated with a ∼1.5mm Gaussian beam to show clear transmittance nulls. To expand the tuning range, the device parameters are optimized for sequential operation in TM and TE polarization states. The theoretical model exhibits a tunable range exceeding 4 µm, thus covering the band fully. In the experiment, a prototype device exhibits a spectral range of 8.6-10.0 µm in TM and 9.9-11.7 µm in TE polarization or >3µm total. With additional efforts in fabrication, we expect to achieve the full range.

First Detection of sub-PeV Diffuse Gamma Rays from the Galactic Disk: Evidence for Ubiquitous Galactic Cosmic Rays beyond PeV Energies.

We report, for the first time, the long-awaited detection of diffuse gamma rays with energies between 100 TeV and 1 PeV in the Galactic disk. Particularly, all gamma rays above 398 TeV are observed apart from known TeV gamma-ray sources and compatible with expectations from the hadronic emission scenario in which gamma rays originate from the decay of π^{0}'s produced through the interaction of protons with the interstellar medium in the Galaxy. This is strong evidence that cosmic rays are accelerated beyond PeV energies in our Galaxy and spread over the Galactic disk.

Investigation of the optimal medium and application strategy for foot-and-mouth disease vaccine antigen production.

AIMS: For the effective production of 146S particles, which determines foot-and-mouth disease (FMD) vaccine efficacy, we aimed to identify the optimal medium that is easy-to-use, productive and economically affordable for the large-scale production of FMD vaccine. METHODS AND RESULTS: Nine combinations of cell growth media and replacement media were tested for virus propagation. Apart from the replacement strategy, we tested a simple addition strategy involving the addition of 30% v/v of fresh medium to the total spent medium using the Cellvento BHK-200 (Vento). Unlike other tested media that produced poor yields of 146S particles when the spent media were not eliminated, Vento exhibited high productivity with the 30% addition strategy. CONCLUSIONS: Considering its lower price and media consumption compared to those of other media that require media replacement, the 30% addition strategy of Vento is highly effective. Furthermore, owing to its simple application strategy, it makes the scale-up process easy and helps in saving the time and labour involved in spent media removal. SIGNIFICANCE AND IMPACT OF THE STUDY: Through the first comparative assessment of commercial media for the 146S particle recovery, this study suggests the best practical medium for the industrial-scale production of FMD vaccines.

Modification of the RANKL-RANK-binding site for the immunotherapeutic treatment of osteoporosis.

Here, we proposed the use of mutated RANKL as an immunogen for active immunization and to induce anti-cytokine antibodies for osteoporosis treatment. INTRODUCTION: Osteoclasts are responsible for bone resorption in bone-related disorders. Anti-cytokine therapeutic antibodies such as denosumab are effective for the treatment of osteoporosis. However, problems with antibody manufacturing and the immunogenicity caused by multiple antibody doses have led to the use of auto-cytokines as immunogens to induce anti-cytokine antibodies. METHODS: RANKL was point-mutated based on the crystal structure of the complex of RANKL and its receptor RANK. RESULTS: As a proof of concept, immunization with RANKL produced high levels of specific antibodies and blocked osteoclast development in vitro and inhibited osteoporosis in RANKL-treated or ovariectomized mouse models. CONCLUSIONS: The results demonstrate the successful use of mutated RANKL as an immunogen for the induction of anti-RANKL immune response. This strategy is useful in general anti-cytokine immunotherapy to avoid toxic side effects of osteoporosis treatment.

Resonant filters with concurrently tuned central wavelengths and sidebands.

Tunable infrared filters are important for various optical and optoelectronic systems. Ideally, such filters should span wide spectral ranges while retaining constant performance. Here, as a fundamental approach, we theoretically treat tunable resonant filters and realize favorable spectral profiles. Implementing a chirped zero-contrast grating on wedged sublayers, we optimize the resonant tunable filter for operation in the ∼5-14µm band. To clarify the root causes of the physical processes enabling the observed performance, attendant resonance modal processes and background reflection behavior are analyzed in detail by equivalent models as well as by rigorous electromagnetic models. The key innovative contribution of this research is that it enables efficient filters with simultaneously tuned operational wavelengths and sidebands.

Unpolarized resonant notch filters for the 8-12 µm spectral region.

The long-wave infrared (LWIR) spectral region spanning ∼8-12µm is useful for many scientific and industrial applications. As traditional multilayer film components are not straightforwardly realized at these bands, we provide design, fabrication, and testing of polarization independent bandstop filters based on the guided-mode resonance (GMR) effect. Focusing on the zero-contrast grating architecture, we successfully fabricate prototype filters in the Ge-on-ZnSe materials system. Applying mask-based photolithography and dry etching, photoresist patterns form the desired Ge grating structures. The resulting devices exhibit clean transmittance nulls and acceptably high sidebands. Moreover, we verify polarization independent notch filtering by assembling two identical GMR filters with gratings oriented orthogonally. This approach to realize effective GMR elements will be useful for various fields including photonic and optoelectronic devices operating in the LWIR region.

[Paraneoplastic subacute degeneration of the cerebellum in non-small cell lung cancer and positive anti-Tr3 antibodies]. / Paraneoplastische subakute Degeneration des Kleinhirns bei nichtkleinzelligem Bronchialkarzinom und positiven Anti-Tr3-Antikörpern.

Neurological disorders can occur before the diagnosis of a malignoma is set. These disorders are induced by a misguided immune response with antibodies against intracellular or cell surface antigens. One of the most common paraneoplastic diseases is the subacute degeneration of the cerebellum. In most of the cases antibodies against Anti Hu, CRMP5/CV2, Amphiphysin and Ma/Ta are found and small cell bronchial carcinoma, breast cancer and lymphoma are diagnosed. We report about a 67 years old man with cerebellar symptoms and a weight loss of 10 kg who was treated in our clinic. After our diagnostic work up we found a non small cell cancer and diagnosed a subacute degeneration of the cerebellum as a paraneoplastic disorder. We found a high positive titer for Anti-Tr3 antibodies while the rest of the paraneoplastic antibodies described as typically associated with the subacute degeneration of the cerebellum were negative. The Anti-Tr3 antibodies are usually found in patients with Hodgkin and less often Non-Hodgkin disease. After initiation of a tumor specific therapy and intravenous immunoglobulin therapy the cerebellar symptoms decreased. In future follow up examinations we will see if the anti-Tr3 antibodies were associated with the non small cell bronchial carcinoma or if a lymphoma will occur in our patient.

Search for a Dark Matter-Induced Annual Modulation Signal in NaI(Tl) with the COSINE-100 Experiment.

We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.

First Direct Search for Inelastic Boosted Dark Matter with COSINE-100.

A search for inelastic boosted dark matter (IBDM) using the COSINE-100 detector with 59.5 days of data is presented. This relativistic dark matter is theorized to interact with the target material through inelastic scattering with electrons, creating a heavier state that subsequently produces standard model particles, such as an electron-positron pair. In this study, we search for this electron-positron pair in coincidence with the initially scattered electron as a signature for an IBDM interaction. No excess over the predicted background event rate is observed. Therefore, we present limits on IBDM interactions under various hypotheses, one of which allows us to explore an area of the dark photon parameter space that has not yet been covered by other experiments. This is the first experimental search for IBDM using a terrestrial detector.

Production of Handmade Open Pulled Straw (OPS) Using Digital Heating Gun for the Vitrification Process.

BACKGROUND: Vitrification is the most popular technique for the cryopreservation of oocytes and embryos, replacing slow freezing methods. MATERIALS AND METHODS: This study evaluated the efficient manufacturing methods of handmade open pulled straw (OPS) with a digital heating gun that could be proposed for vitrification. RESULTS: Production efficiency of OPS using 0.5 mL straw was detected at 0, 66.1, 90.5 and 85.7% for 1~2 s and 9.5, 33.3, 47.6 and 23.8% for 2~3 s of heating time at 250, 350, 400 and 450°C respectively. The production rate of OPS using 0.25 mL straw was perceived at 33.3, 76.2, 83.3, 95.2 and 57.6 % for 1.5~2.5 s time with the optimized heat setting at 330, 340, 350, 360 and 370°C respectively. The desired inner diameter (200~300 µm) of OPS could be varied according to the gamete size, embryo developmental stages or cell lines of different species. Based on our data, the production efficiency of OPS using 0.25-mL straw were increased beyond using a 0.5-mL straw. CONCLUSION: Handmade OPSs could be efficiently produced with a digital heating gun to generate a vitrification device for freezing gametes, embryos and cell lines.

Antrodia cinnamomea reduces obesity and modulates the gut microbiota in high-fat diet-fed mice.

BACKGROUND: Obesity is associated with gut microbiota dysbiosis, disrupted intestinal barrier and chronic inflammation. Given the high and increasing prevalence of obesity worldwide, anti-obesity treatments that are safe, effective and widely available would be beneficial. We examined whether the medicinal mushroom Antrodia cinnamomea may reduce obesity in mice fed with a high-fat diet (HFD). METHODS: Male C57BL/6J mice were fed a HFD for 8 weeks to induce obesity and chronic inflammation. The mice were treated with a water extract of A. cinnamomea (WEAC), and body weight, fat accumulation, inflammation markers, insulin sensitivity and the gut microbiota were monitored. RESULTS: After 8 weeks, the mean body weight of HFD-fed mice was 39.8±1.2 g compared with 35.8±1.3 g for the HFD+1% WEAC group, corresponding to a reduction of 4 g or 10% of body weight (P<0.0001). WEAC supplementation reduced fat accumulation and serum triglycerides in a statistically significant manner in HFD-fed mice. WEAC also reversed the effects of HFD on inflammation markers (interleukin-1ß, interleukin-6, tumor necrosis factor-α), insulin resistance and adipokine production (leptin and adiponectin). Notably, WEAC increased the expression of intestinal tight junctions (zonula occludens-1 and occludin) and antimicrobial proteins (Reg3g and lysozyme C) in the small intestine, leading to reduced blood endotoxemia. Finally, WEAC modulated the composition of the gut microbiota, reducing the Firmicutes/Bacteroidetes ratio and increasing the level of Akkermansia muciniphila and other bacterial species associated with anti-inflammatory properties. CONCLUSIONS: Supplementation with A. cinnamomea produces anti-obesogenic, anti-inflammatory and antidiabetic effects in HFD-fed mice by maintaining intestinal integrity and modulating the gut microbiota.

Inflammatory microglia are glycolytic and iron retentive and typify the microglia in APP/PS1 mice.

Microglia, like macrophages, can adopt inflammatory and anti-inflammatory phenotypes depending on the stimulus. In macrophages, the evidence indicates that these phenotypes have different metabolic profiles with lipopolysaccharide (LPS)- or interferon-γ (IFNγ)-stimulated inflammatory cells switching to glycolysis as their main source of ATP and interleukin-4 (IL-4)-stimulated cells utilizing oxidative phosphorylation. There is a paucity of information regarding the metabolic signatures of inflammatory and anti-inflammatory microglia. Here, we polarized primary microglia with IFNγ and show that the characteristic increases in tumor necrosis factor-α (TNFα) and nitric oxide synthase 2 (NOS2) were accompanied by increased glycolysis and an increase in the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)3, an enzyme that plays a significant role in driving glycolysis. These changes were associated with increased expression of ferritin and retention of iron in microglia. Significantly, retention of iron in microglia increased TNFα expression and also increased glycolysis suggesting that increased intracellular iron concentration may drive the metabolic and/or inflammatory changes. Analysis of microglia prepared from wildtype mice and from transgenic mice that overexpress amyloid precursor protein (APP) and presenilin 1 (PS1; APP/PS1) revealed genotype-related increases in glycolysis, accompanied by increased PFKFB3, and an increase in the expression of ferritin. The data indicate a distinct metabolic signature of inflammatory microglia from APP/PS1 mice that are also distinguishable by their iron handling profiles.

Cost-effectiveness of multidisciplinary collaborative care versus usual care in the management of high-risk patients with diabetes in Singapore: Short-term results from a randomized controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Economic evidence of multidisciplinary collaborative care on glycaemic improvement in uncontrolled diabetic patients is limited. Therefore, the primary objective of this study was to assess the cost-effectiveness of multidisciplinary collaborative care versus usual care and the secondary objective was to assess the cost-effectiveness of these two care approaches in relation to varying glycaemic control of patients. METHODS: An economic evaluation based on a six-month randomized controlled trial involving high-risk uncontrolled diabetic Asian patients with polypharmacy and multiple comorbidities was conducted from a healthcare institution perspective. The control arm received usual care, while the intervention arm received multidisciplinary care with regular clinical pharmacist follow-up in addition to usual care. The study outcomes included glycated haemoglobin (HbA1c) change and total direct outpatient medical costs for diabetes-related care. The cost-effectiveness analyses were conducted for both arms and those stratified according to baseline HbA1c (Group 1:HbA1c 7.1%-7.9%, Group 2:HbA1c ≥8.0%). The incremental cost per glycaemic improvement (HbA1c improvement of 0.1% and above) per patient was examined followed by uncertainty evaluation via probabilistic sensitivity analyses. A range of willingness-to-pay (WTP) thresholds (US$165.21 to US$5000.00 per glycaemic improvement) was used in analysis. RESULTS AND DISCUSSION: Overall, the intervention arm had greater improvement in HbA1c (I: mean -0.4% [95% CI -0.6 to -0.2] vs C: mean -0.1% [95% CI -0.2 to 0.1]; P = .014) and lower mean total direct outpatient medical costs per patient in comparison with the control arm (I: US$516.77 ± 222.10 vs C: US$607.78 ± 268.39; P < .001). The intervention arm was the dominant strategy across varying baseline HbA1c with higher probability of Group 2 being cost-effective at higher WTP threshold. WHAT IS NEW AND CONCLUSIONS: The multidisciplinary collaborative care arm was cost-effective in managing Asian patients with varying baseline HbA1c control. The multidisciplinary collaborative care also showed greater probability of being cost-effective among Asian patients with poorly uncontrolled glycaemia.

Beyond first-line non-anthracycline-based chemotherapy for extranodal NK/T-cell lymphoma: clinical outcome and current perspectives on salvage therapy for patients after first relapse and progression of disease.

BACKGROUND: Current standard treatment, including non-anthracycline-based chemotherapy and optimal combining of radiotherapy, has dramatically improved outcomes of patients with extranodal natural killer/T-cell lymphoma (ENKTL) during the last decade. This study was conducted to investigate the clinical outcome of ENKTL patients with relapsed or progressive disease after initial current standard therapy. PATIENTS AND METHODS: We retrospectively reviewed patients diagnosed with ENKTL at six centers in four countries (China, France, Singapore, and South Korea) from 1997 to 2015 and analyzed 179 patients who had relapsed or progressed after initial current standard therapy. RESULTS: After a median follow-up of 58.6 months (range 27.9-89.2), the median second progression-free survival (PFS) was 4.1 months [95% confidence interval (CI) 3.04-5.16] and overall survival (OS) was 6.4 months (95% CI 4.36-8.51). Multivariate Cox-regression analysis revealed that elevated lactate dehydrogenase, multiple extranodal sites (≥2), and presence of B symptoms were associated with inferior OS (P < 0.05). OS and PFS were significantly different according to both prognostic index of natural killer lymphoma (PINK) and PINK-E (Epstein-Barr virus) models. Salvage chemotherapy with l-asparaginase (l-Asp)-based regimens showed a significantly better clinical benefit to response rate and PFS, although it did not lead to OS improvement. First use of l-Asp in the salvage setting and l-Asp rechallenge at least 6 months after initial treatment were the best candidates for salvage l-Asp containing chemotherapy. CONCLUSIONS: Most patients with relapsed or refractory ENKTL had poor prognosis with short survival. Further studies are warranted to determine the optimal treatment of patients with relapsed or refractory ENKTL.

Sterile Neutrino Search at the NEOS Experiment.

An experiment to search for light sterile neutrinos is conducted at a reactor with a thermal power of 2.8 GW located at the Hanbit nuclear power complex. The search is done with a detector consisting of a ton of Gd-loaded liquid scintillator in a tendon gallery approximately 24 m from the reactor core. The measured antineutrino event rate is 1976 per day with a signal to background ratio of about 22. The shape of the antineutrino energy spectrum obtained from the eight-month data-taking period is compared with a hypothesis of oscillations due to active-sterile antineutrino mixing. No strong evidence of 3+1 neutrino oscillation is found. An excess around the 5 MeV prompt energy range is observed as seen in existing longer-baseline experiments. The mixing parameter sin^{2}2θ_{14} is limited up to less than 0.1 for Δm_{41}^{2} ranging from 0.2 to 2.3 eV^{2} with a 90% confidence level.

Enantioselective cytotoxicity of ZnS:Mn quantum dots in A549 cells.

Chirality strongly influences many biological properties of materials, such as cell accumulation, enzymatic activity, and toxicity. In the past decade, it has been shown that quantum dots (QDs), fluorescent semiconductor nanoparticles with unique optical properties, can demonstrate optical activity due to chiral ligands bound on their surface. Optically active QDs could find potential applications in biomedical research, therapy, and diagnostics. Consequently, it is very important to investigate the interaction of QDs capped with chiral ligands with living cells. The aim of our study was to investigate the influence of the induced chirality of Mn-doped ZnS QDs on the viability of A549 cells. These QDs were stabilized with D- and L-cysteine using a ligand exchange technique. The optical properties of QDs were studied using UV-Vis, photoluminescence (PL), and circular dichroism (CD) spectroscopy. The cytotoxicity of QDs was investigated by high content screening analysis. It was found that QDs stabilized by opposite ligand enantiomers, had identical PL and UV-Vis spectra and mirror-imaged CD spectra, but displayed different cytotoxicity: QDs capped with D-cysteine had greater cytotoxicity than L-cysteine capped QDs.