Quantitative gas pressure measurement by molecular spectroscopy using chip-based supercontinuum in the mid-infrared.

We demonstrate the quantitative pressure measurement of gas molecules in the mid-infrared using chip-based supercontinuum and cepstrum analysis without additional measurements for baseline normalization. A supercontinuum generated in an on-chip waveguide made of chalcogenide glass having high nonlinearity passes through CO gas and provides a transmission spectrum. The gas absorption information is deconvoluted from the original supercontinuum spectral information containing temporal fluctuation by cepstrum analysis and extracted simply by applying a bandpass filter in the temporal domain. The gas pressure estimated from the extracted absorption information is consistent with the value measured by a pressure gauge within a difference of 1.25%, despite spectral fluctuations in the supercontinuum baseline comparable to the spectral depth of the gas absorption lines.

MicroRNA 29a therapy for CEACAM6-expressing lung adenocarcinoma.

BACKGROUND: Non-coding microRNAs (miRNAs) play critical roles in tumor progression and hold great promise as therapeutic agents for multiple cancers. MicroRNA 29a (miR-29a) is a tumor suppressor miRNA that inhibits cancer cell growth and tumor progression in non-small cell lung cancer. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), which plays an important role in lung cancer progression, has been identified as a target of miR-29a. Here, we evaluated the therapeutic efficacy of a peptide vector capable of delivering miR-29a intracellularly using the acidic tumor microenvironment in a lung adenocarcinoma xenograft mouse model. METHODS: A miRNA delivery vector was constructed by tethering the peptide nucleic acid form of miR-29a to a peptide with a low pH-induced transmembrane structure (pHLIP) to enable transport of the miRNAs across the plasma membrane. Tumor suppressive effects of pHLIP-miR29a on lung adenocarcinoma development in vivo were assessed using a BALB/c xenograft model injected with A549 cells. RESULTS: Incubation of A549 cells with pHLIP-miR-29a at an acidic pH downregulated endogenous CEACAM6 expression and reduced cell viability. Intravenous injection of the mice with pHLIP-miR-29a inhibited tumor growth by up to 18.1%. Intraperitoneal injection of cisplatin reduced tumor volume by 29.9%. Combined pHLIP-miR-29a + cisplatin treatment had an additive effect, reducing tumor volume up to 39.7%. CONCLUSIONS: Delivery of miR-29a to lung adenocarcinoma cells using a pHLIP-mediated method has therapeutic potential as a unique cancer treatment approach.

Simulation-Based Cybersecurity Testing and Evaluation Method for Connected Car V2X Application Using Virtual Machine.

In a connected car, the vehicle's internal network is connected to the outside through communication technology. However, this can cause new security vulnerabilities. In particular, V2X communication, to provide the safety of connected cars, can directly threaten the lives of passengers if a security attack occurs. For V2X communication security, standards such as IEEE 1609.2 define the technical functions that digital signature and encryption to provide security of V2X messages. However, it is difficult to verify the security technology by applying it to the environment with real roads because it can be made up of other safety accidents. In addition, vehicle simulation R&D is steadily being carried out, but there is no simulation that evaluates security for the V2X application level. Therefore, in this paper, a virtual machine was used to implement a V2X communication simulation environment that satisfies the requirements for the security evaluation of connected cars. Then, we proposed scenarios for cybersecurity testing and evaluation, implemented and verified through CANoe Option.Car2X. Through this, it is possible to perform sufficient preliminary verification to minimize the variables before verifying security technology in a real road environment.

Association between focused cardiac ultrasound and time to furosemide administration in acute heart failure.

BACKGROUND: Heart failure (HF) is a global health burden, and its management in the emergency department (ED) is important. This study aimed to evaluate the association between focused cardiac ultrasound (FoCUS) and early administration of diuretics in patients with acute HF admitted to the ED. METHODS: This retrospective observational study was conducted at a tertiary academic hospital. Patients with acute HF patients who were admitted to the ED and receiving intravenous medication between January 2018 and December 2019 were enrolled. The main exposure was a FoCUS examination performed within 2 h of ED triage. The primary outcome was the time to furosemide administration. RESULTS: Of 1154 patients with acute HF, 787 were included in the study, with 116 of them having undergone FoCUS. The time to furosemide was significantly shorter in the FoCUS group (median time (q1-q3), 112 min; range, 65-163 min) compared to the non-FoCUS group (median time, 131 min; range, 71-229 min). In the multivariable logistic regression analysis adjusting for age, sex, chief complaint, mode of arrival, triage level, shock status, and desaturation at triage, early administration of furosemide within 2 h from triage was significantly higher in the FoCUS group (adjusted odds ratio, 1.63; 95% confidence intervals, 1.04-2.55) than in the non-FoCUS group. CONCLUSIONS: Early administration of intravenous furosemide was associated with FoCUS examination in patients with acute HF admitted to the ED. An early screening protocol could be useful for improving levels in clinical practice at EDs.

Supercontinuum generation in As2S3 waveguides fabricated without direct etching.

We report a supercontinuum generation (SCG) in a waveguide that spontaneously forms without an etching process during the deposition of a core material on a preformed ${\rm{Si}}{{\rm{O}}_2}$ substructure. The mechanism of dispersion control for this new, to the best of our knowledge, type of waveguide is analyzed by numerical simulation, which results in a design rule to achieve a target dispersion profile by adjusting the substructure geometry. SCG is experimentally demonstrated with a waveguide made of ${\rm{A}}{{\rm{s}}_2}{{\rm{S}}_3}$, chalcogenide glass, which has low material absorption over the mid-IR range. A dispersion-controlled waveguide with a length of 10 mm pumped with 77 pJ pulses at a telecommunication wavelength of 1560 nm resulted in a supercontinuum that extends by more than 1.5 octaves.

MST2 silencing induces apoptosis and inhibits tumor growth for estrogen receptor alpha-positive MCF-7 breast cancer.

Mammalian sterile 20-like kinase 1/2 (MST1/2) plays an important role in cell growth and apoptosis and functions as a tumor suppressor. Previously, we showed that MST2 overexpression activates Estrogen receptor alpha (ERα) in human breast cancer MCF-7 cells in the absence of a ligand. Here, we examined the role of MST2 in the growth of ER-positive MCF-7 cells. Cell cycle, apoptosis, and mammosphere formation assay method were implemented to detect the biological effects of MST2 ablation on the growth of MCF-7 cells in vitro. The effect of MST2-siRNA on MCF-7 cells tumor growth in vivo was studied in tumor-bearing mouse model. Kaplan-Meier plotter analysis was used to determine the effect of MST2 on overall survival in breast cancer patients. MST2 overexpression increased cell viability marginally. The ablation of MST2 using siRNA dramatically suppressed the viability of the MCF-7 cells, but not ER-negative MDA-MB-231 breast cancer cells. Furthermore, MST2 knockdown increased caspase-dependent apoptosis and led to decreased mammosphere formation. Treatment of MCF-7 tumor-bearing mice with MST2 siRNA significantly inhibited tumor growth. The tumor weight was reduced further when tamoxifen was added. Patients with ER-positive breast cancer with low MST2 expression had better overall survival than did those with high MST2 expression in Kaplan-Meier survival analyses using public datasets. Our results provide new insight into the role of MST2, a key component of the Hippo signaling pathway, in mediating breast cancer progression.

MST2 kinase regulates osteoblast differentiation by phosphorylating and inhibiting Runx2 in C2C12 cells.

The mammalian Ste20-like kinase (MST) pathway or Hippo pathway plays essential roles in cell proliferation, apoptosis, organ size control, and development. Runx2 is a key transcription factor in osteoblast differentiation. The objective of this study was to investigate whether the MST pathway could modulate Runx2 and osteoblast differentiation. First, we found that Runx2 interacted with MST2 and SAV1 via the WW domain of SAV1 and amino acid 292-445 of Runx2 containing a PY motif. Results of OSE luciferase reporter assay revealed that co-expression of MST2 and SAV1 inhibited the transcriptional activity of Runx2 whereas siRNA-mediated down-regulation of Mst1 and Mst2 increased its activity. MST2 and SAV1 significantly reduced mRNA levels of osteoblast differentiation marker genes such as alkaline phosphatase and osteocalcin in differentiating C2C12 cells. MST2 and SAV1 also hampered osteoblast differentiation of C2C12 cells induced by Runx2 as shown by alkaline phosphatase activity assay and Alizarin Red staining. Mass spectrometric analysis of immunoprecipitated Runx2 protein from HEK293 cells overexpressing MST2 and SAV1 revealed two novel phosphorylation sites at Ser-339 and Ser-370 residues of mouse Runx2 protein. Mutation of both serine residues to alanine interfered with the inhibitory effect of MST2 and SAV1 on the transcriptional activity of Runx2 and osteoblast differentiation induced by Runx2. Our results suggest that the MST kinase pathway can directly regulate osteoblast differentiation by modulating Runx2 activity through phosphorylation.

Mammalian Hippo kinase pathway is downregulated by BCL-2 via protein degradation.

Mammalian ste20-like kinase (MST) signaling pathway plays a significant part in control of cell death and cell cycle. It was originally found as Hippo pathway in Drosophila and composed of MST kinase and Salvador-1 (SAV1), a scaffold protein. In mammalian cells, MST pathway induces cell-cycle exit and apoptosis in response to various signals. BCL-2, an anti-apoptotic protein, inhibits cell death and plays an important part in tumorigenesis. In the present report, we present evidence showing that BCL-2 is a new regulator of MST pathway. First, protein levels of MST2 and SAV1 were reduced significantly by co-expression of BCL-2. Physical interaction of BCL-2 with SAV1 was correlated with proteasomal degradation of SAV1 and MST2 proteins. In SH-SY5Y neuroblastoma cell line expressing a high level of BCL-2 but low levels of MST2 and SAV1, siRNA-induced knockdown of BCL-2 restored the expression of MST2 and SAV1. Inhibition of BCL-2 with BAD or ABT-737, a BCL-2 inhibitor, reversed its effect on MST2 and SAV1 proteins. ABT737 increased HEK293 cell death significantly when both MST2 and SAV1 were co-expressed. These results suggest that cancer cells may avoid cell death through enhanced expression of BCL-2 which down-regulates the pro-apoptotic MST pathway.

Synthesis of Metal Boride Nanoparticles Using Triple Thermal Plasma Jet System.

Titanium, nickel, and tungsten boride nanoparticles were synthesized in the triple thermal plasma jet system. The coalesced high-enthalpy thermal plasma jet not only generates extensive high temperature regions but also allows the starting materials to penetrate into the center of high temperature regions effectively. The synthesis process of metal boride was investigated according to the nucleation temperature of three metals and boron. In the case of titanium and nickel borides synthesis, metals nucleation temperatures are lower than boron. The crystallinity of synthesized titanium boride nanoparticles was higher than nickel boride nanoparticles, since not only the nucleation temperature of titanium is higher than nickel but also the Gibbs free energy of all titanium boride was lower than whole nickel boride. However, the nucleation temperature of tungsten is higher than boron where nanoparticle synthesis process differed from former synthesis processes. It had influence on the crystal growth time in the high temperature regions where tungsten boride crystal structure was strongly prepared than nickel boride nanoparticles.

Synthesis of Tungsten Carbide Nanomaterials in Triple DC Thermal Plasma Jet System.

The tungsten carbide nanomaterials were synthesized in the triple DC thermal plasma jet system using refractory tungsten, and carbon sources such as multi wall carbon nanotube (MWCNT), amorphous carbon and methane. The starting materials were evaporated in the high temperature region of triple plasma jet, then condensed particles were prepared in nanoscale under 100 nm. The effect of carbon sources was investigated on a view of crystal phase structure and morphology. W2C crystal nanoparticles were mainly synthesized and WC and WC1-x phase nanoparticles were observed additionally with all carbon sources. From MWCNT starting material, tungsten carbide attached MWCNT composite were produced with spherical tungsten carbide nanoparticles. In case of amorphous carbon, spherical and rod-shaped tungsten carbide was synthesized. Only spherical tungsten carbide nanoparticles were synthesized by methane. In addition, it was revealed that the main crystal structure was changed from W2C to WC1-x by increasing W/CH4 composition ratio.

Associations between the HaeIII Single Nucleotide Polymorphism in the SLC2A1 Gene and Diabetic Nephropathy in Korean Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Diabetic nephropathy (DN) is the most serious microvascular complication of diabetes mellitus and is one of the leading causes of end stage renal failure. In previous studies, the contribution of genetic susceptibility to DN showed inconsistent results. In this study, we investigated the association between the solute carrier family 2 facilitated glucose transporter member 1 (SLC2A1) HaeIII polymorphism and DN in Korean patients with type 2 diabetes mellitus (T2DM) according to disease duration. METHODS: A total of 846 patients with T2DM (mean age, 61.3 ± 12.3 years; mean duration of T2DM, 10.3 ± 7.9 years; 55.3% men) who visited the Chungbuk National University Hospital were investigated. The HaeIII polymorphism of the SLC2A1 gene was determined by the real time polymerase chain reaction method. Genotyping results were presented as GG, AG, or AA. A subgroup analysis was performed according to duration of T2DM (≤ 10 years, > 10 years). RESULTS: The AG + AA genotype showed a significantly higher risk of DN compared with the GG genotype in patients with a type 2 DM duration less than 10 years (12.4% vs. 4.2%; P < 0.001). No significant differences were observed in terms of other diabetic complications, including retinopathy, peripheral neuropathy, cardiovascular disease, cerebrovascular disease or peripheral artery disease, according to the genotypes of the SLC2A1 HaeIII polymorphism. CONCLUSION: The SLC2A1 HaeIII polymorphism was associated with DN in Korean patients with T2DM, particularly in the group with a relatively short disease duration.

Estrogen Deficiency Potentiates Thioacetamide-Induced Hepatic Fibrosis in Sprague-Dawley Rats.

Hepatic fibrosis is characterized by persistent deposition of extracellular matrix proteins and occurs in chronic liver diseases. The aim of the present study is to investigate whether estrogen deficiency (ED) potentiates hepatic fibrosis in a thioacetamide (TAA)-treated rat model. Fibrosis was induced via intraperitoneal injection (i.p.) of TAA (150 mg/kg/day) for four weeks in ovariectomized (OVX) female, sham-operated female, or male rats. In TAA-treated OVX rats, the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) were significantly increased compared to those in TAA-treated sham-operated OVX rats or TAA-treated male rats. Furthermore, α-smooth muscle actin (α-SMA) expression was significantly increased compared to that in TAA-treated sham-operated rats. This was accompanied by the appearance of fibrosis biomarkers including vimentin, collagen-I, and hydroxyproline, in the liver of TAA-treated OVX rats. In addition, ED markedly reduced total glutathione (GSH) levels, as well as catalase (CAT) and superoxide dismutase (SOD) activity in TAA-treated OVX rats. In contrast, hepatic malondialdehyde (MDA) levels were elevated in TAA-treated OVX rats. Apoptosis significantly increased in TAA-treated OVX rats, as reflected by elevated p53, Bcl-2, and cleaved caspase 3 levels. Significant increases in interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations were exhibited in TAA-treated OVX rats, and this further aggravated fibrosis through the transforming growth factor-ß (TGF-ß)/Smad pathway. Our data suggest that ED potentiates TAA-induced oxidative damage in the liver, suggesting that ED may enhance the severity of hepatic fibrosis in menopausal women.

Monolithic integration of self-aligned nanoisland laser with shifted-air-hole waveguide.

We report a novel scheme for monolithic integration of a nanoisland laser with a shifted-air-hole waveguide by employing selective etching techniques. An active L3 laser cavity and passive shifted-air-hole waveguide are simultaneously formed through a single fabrication step. In the shifted-air-hole waveguide, the air-hole position is adjusted to be compatible with selective etching. The spectral overlap between the L3 laser resonance and guided mode is achieved by introducing small air holes at the nodes of the shifted-air-hole waveguide. Experiments show that >60% of the light is coupled from the nanoisland laser to the end of the 12-µm-long waveguide.

Evaluation of subchronic exposure to triclosan on hepatorenal and reproductive toxicities in prepubertal male rats.

Triclosan (TCS), a common antimicrobial ingredient, is present in many consumer products, including soaps, shampoos, and toothpaste. Owing to its widespread use, potential adverse effects on animals and humans may arise from lifetime exposure, but data on chronic prepubertal exposure of TCS are still lacking. The aim of the present study was to investigate the influence of subchronic TCS exposure (0.25, 25, 250, or 750 mg/kg) on target organ toxicity in prepubertal male rats. After daily administration of TCS to rats by oral gavage for 60 d, a significant reduction in body weight and relative weights of liver, kidneys, testes, and adrenal glands was observed in the 750-mg/kg (high dose) group. Serum alanine aminotransferase and aspartate aminotransferase activities as well as levels of blood urea nitrogen, and creatinine were significantly increased at 750 mg/kg TCS. Further, TCS (750 mg/kg) elevated the protein expressions of hepatic CYP2B1, RXR/PPAR, and levels of malondialdehyde. High-dose TCS exposure induced histological changes as evidenced by reduction of Bowman's space, occlusion of the tubular lumen, and degeneration of tubular epithelial cells in the kidney. Tubular necrosis was confirmed as evidenced by a rise in expression of high mobility group box 1 renal protein. Daily sperm production was significantly diminished by high doses of TCS with marked inhibition of androgen receptor protein expression. Our results indicated that subchronic exposure to excessively high concentrations of 750 mg/kg TCS induced hepatorenal and reproductive toxicities in prepubertal male rats; however, the biological relevance of these findings is questionable as these drug levels are not encountered in the environment.

Self-aligned deterministic coupling of single quantum emitter to nanofocused plasmonic modes.

The quantum plasmonics field has emerged and been growing increasingly, including study of single emitter-light coupling using plasmonic system and scalable quantum plasmonic circuit. This offers opportunity for the quantum control of light with compact device footprint. However, coupling of a single emitter to highly localized plasmonic mode with nanoscale precision remains an important challenge. Today, the spatial overlap between metallic structure and single emitter mostly relies either on chance or on advanced nanopositioning control. Here, we demonstrate deterministic coupling between three-dimensionally nanofocused plasmonic modes and single quantum dots (QDs) without any positioning for single QDs. By depositing a thin silver layer on a site-controlled pyramid QD wafer, three-dimensional plasmonic nanofocusing on each QD at the pyramid apex is geometrically achieved through the silver-coated pyramid facets. Enhancement of the QD spontaneous emission rate as high as 22 ± 16 is measured for all processed QDs emitting over ∼150-meV spectral range. This approach could apply to high fabrication yield on-chip devices for wide application fields, e.g., high-efficiency light-emitting devices and quantum information processing.

Self-aligned nanoislands nanobeam bandedge lasers.

We propose and demonstrate a novel one-dimensional nanobeam bandedge laser constituted by self-aligned nanoisland quantum-well (QW) structures. The formation of self-aligned InGaAsP nanoislands sandwiched between two InP claddings is the result of selective removal of QW through wet-etching processes. By controlling wet-etching time, we show a good spatial and spectral overlap between the dielectric mode and the self-aligned nanoisland structures leads to the realization of nanobeam bandedge lasers with low-threshold operations and high slope efficiencies. Optical characterization results indicate a strong correlation between the size of individual nanoisland and the threshold power of our nanobeam bandedge lasers. We obtain an approximately 81% reduction in the absorbed threshold power as we optimize the size of the nanoislands.

Salvage radiotherapy with or without concurrent chemotherapy for pelvic recurrence after hysterectomy alone for early-stage uterine cervical cancer.

PURPOSE: Treatment outcomes of patients with pelvic recurrence after hysterectomy alone for uterine cervical cancer who received salvage radiotherapy (RT) with or without concurrent chemotherapy were investigated. METHODS: Salvage RT for recurrent cervical cancer confined to the pelvic cavity after hysterectomy alone was received by 33 patients. The median interval between initial hysterectomy and recurrence was 26 months. Whole-pelvic irradiation was delivered to median dose of 45 Gy, followed by a boost with a median dose of 16 Gy to the gross tumor volume. Cisplatin-based concurrent chemotherapy was administered to 29 patients. RESULTS: The median follow-up period was 53 months for surviving patients. Most patients (97.0%) completed salvage RT of ≥45 Gy. Complete response (CR) was achieved in 23 patients (69.7%). Pelvic sidewall involvement and evaluation with positron-emission tomography-computed tomography were significantly associated with CR. The 5­year progression-free survival (PFS), local control (LC), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 62.7, 79.5, 72.5, and 60.1%, respectively. Initial International Federation of Gynecology and Obstetrics stage, pelvic sidewall involvement, and CR status were significant factors for PFS and OS rates in multivariate analysis. The incidence of severe acute and late toxicities (≥grade 3) was 12.1 and 3.0%, respectively. CONCLUSION: Aggressive salvage RT with or without concurrent chemotherapy for recurrent cervical cancer confined to the pelvic cavity was feasible, with promising treatment outcomes and acceptable toxicities. However, even more intensive novel treatment strategies should be investigated for patients with unfavorable prognostic factors.

A terahertz metamaterial with unnaturally high refractive index.

Controlling the electromagnetic properties of materials, going beyond the limit that is attainable with naturally existing substances, has become a reality with the advent of metamaterials. The range of various structured artificial 'atoms' has promised a vast variety of otherwise unexpected physical phenomena, among which the experimental realization of a negative refractive index has been one of the main foci thus far. Expanding the refractive index into a high positive regime will complete the spectrum of achievable refractive index and provide more design flexibility for transformation optics. Naturally existing transparent materials possess small positive indices of refraction, except for a few semiconductors and insulators, such as lead sulphide or strontium titanate, that exhibit a rather high peak refractive index at mid- and far-infrared frequencies. Previous approaches using metamaterials were not successful in realizing broadband high refractive indices. A broadband high-refractive-index metamaterial structure was theoretically investigated only recently, but the proposed structure does not lend itself to easy implementation. Here we demonstrate that a broadband, extremely high index of refraction can be realized from large-area, free-standing, flexible terahertz metamaterials composed of strongly coupled unit cells. By drastically increasing the effective permittivity through strong capacitive coupling and decreasing the diamagnetic response with a thin metallic structure in the unit cell, a peak refractive index of 38.6 along with a low-frequency quasi-static value of over 20 were experimentally realized for a single-layer terahertz metamaterial, while maintaining low losses. As a natural extension of these single-layer metamaterials, we fabricated quasi-three-dimensional high-refractive-index metamaterials, and obtained a maximum bulk refractive index of 33.2 along with a value of around 8 at the quasi-static limit.

Carotid artery reactivity during sympathetic activation following acute resistance exercise.

OBJECTIVE: Acute resistance exercise has been shown to reduce brachial endothelial function. Whether there are concomitant reductions in carotid endothelial function remains unexplored. METHODS: Cold pressor test-mediated vasodilation of the carotid artery was used to assess carotid endothelial function in 15 young and healthy participants (age 26 ± 1 years, body mass index 24 ± 1 kg/m2) after acute resistance exercise or an inactive time control condition. RESULTS: Acute resistance exercise had no effect on the cold pressor test-mediated vasodilation compared to time control (5.8 ± 0.8 vs 6.2 ± 0.9% dilation, p > 0.05). INTERPRETATION: Carotid endothelial function may not be compromised following acute resistance exercise in young healthy adults.