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AST-001, a novel syrup formulation of L-serine, was developed for the treatment of autism spectrum disorders (ASD) in pediatric patients. This study aimed to establish a pharmacokinetic (PK)-pharmacodynamic (PD) model to elucidate the effect of AST-001 on adaptive behavior in children with ASD. Due to the absence of PK samples in pediatric patients, a previously published population PK model was used to link the PD model by applying an allometric scale to body weight. The time courses of Korean-Vineland Adaptive Behavior Scale-II Adaptive Behavior Composite (K-VABS-II-ABC) scores were best described by an effect compartment model with linear drug effects (Deff, 0.0022 L/μg) and linear progression, where an equilibration half-life to the effect compartment was approximately 15 weeks. Our findings indicated a positive correlation between the baseline K-VABS-II-ABC score (E0, 48.51) and the rate of natural progression (Kprog, 0.015 day -1 ), suggesting enhanced natural behavioral improvements in patients with better baseline adaptive behavior. Moreover, age was identified as a significant covariate for E0 and was incorporated into the model using a power function. Based on our model, the recommended dosing regimens for phase III trials are 2, 4, 6, 10, and 14 g, administered twice daily for weight ranges of 10-13, 14-20, 21-34, 35-49, and >50 kg, respectively. These doses are expected to significantly improve ASD symptoms. This study not only proposes an optimized dosing strategy for AST-001 but also provides valuable insights into the PK-PD relationship in pediatric ASD treatment., Competing Interests: Authors S-KH, J-SC, and HR were employed by Astrogen Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee, Hwang, Cho, Ryu and Chung.)

We used deep learning methods to develop an AI model capable of autonomously delineating cancerous regions in digital pathology images (H&E-stained images). By using a transgenic brain tumor model derived from the TS13-64 brain tumor cell line, we digitized a total of 187 H&E-stained images and annotated the cancerous regions in these images to compile a dataset. A deep learning approach was executed through DEEP:PHI, which abstracts Python coding complexities, thereby simplifying the execution of AI training protocols for users. By employing the Image Crop with Mask technique and patch generation method, we not only maintained an appropriate data class balance but also overcame the challenge of limited computing resources. This approach enabled us to successfully develop an AI training model that autonomously segments cancerous areas. This AI model enables the provision of guiding images for determining cancerous areas with minimal assistance from neuropathologists. In addition, the high-quality, large dataset curated for training using the proposed approach contributes to the development of novel terahertz imaging-based AI cancer diagnosis technologies and accelerates technological advancements., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Terahertz (THz) waves are electromagnetic waves in the 0.1 to 10 THz frequency range, and THz imaging is utilized in a range of applications, including security inspections, biomedical fields, and the non-destructive examination of materials. However, THz images have a low resolution due to the long wavelength of THz waves. Therefore, improving the resolution of THz images is a current hot research topic. We propose a novel network architecture called J-Net, which is an improved version of U-Net, to achieve THz image super-resolution. It employs simple baseline blocks which can extract low-resolution (LR) image features and learn the mapping of LR images to high-resolution (HR) images efficiently. All training was conducted using the DIV2K+Flickr2K dataset, and we employed the peak signal-to-noise ratio (PSNR) for quantitative comparison. In our comparisons with other THz image super-resolution methods, J-Net achieved a PSNR of 32.52 dB, surpassing other techniques by more than 1 dB. J-Net also demonstrates superior performance on real THz images compared to other methods. Experiments show that the proposed J-Net achieves a better PSNR and visual improvement compared with other THz image super-resolution methods.

Terahertz (THz) electromagnetic waves, known for their unique response to water, offer promising opportunities for next-generation biomedical diagnostics and novel cancer therapy technologies. This study investigated the impedance-matching effect, which enhances the efficiency of THz wave delivery into tissues and compensates for the signal distortion induced by the refractive index mismatch between the target and the sample substrate. Three candidate biocompatible materials, water, glycerol, and petroleum jelly were applied to a skin phantom and compared using THz two-dimensional imaging and time-of-flight imaging methods. Finally, we successfully demonstrated impedance-matching effect on mouse skin tissues., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2024 Optica Publishing Group.)

This study is the first to develop technology to evaluate the object recognition performance of camera sensors, which are increasingly important in autonomous vehicles owing to their relatively low price, and to verify the efficiency of camera recognition algorithms in obstruction situations. To this end, the concentration and color of the blockage and the type and color of the object were set as major factors, with their effects on camera recognition performance analyzed using a camera simulator based on a virtual test drive toolkit. The results show that the blockage concentration has the largest impact on object recognition, followed in order by the object type, blockage color, and object color. As for the blockage color, black exhibited better recognition performance than gray and yellow. In addition, changes in the blockage color affected the recognition of object types, resulting in different responses to each object. Through this study, we propose a blockage-based camera recognition performance evaluation method using simulation, and we establish an algorithm evaluation environment for various manufacturers through an interface with an actual camera. By suggesting the necessity and timing of future camera lens cleaning, we provide manufacturers with technical measures to improve the cleaning timing and camera safety.

The aim of this work is to investigate and analyze the operation mechanism and power control principle of a bolted Langevin type (BLT)-loaded phase-shifted control inverter and to find a safe power control method for a phase-shifted control inverter used to drive a high-power BLT by preventing the differential current (shock current) from occurring in the right branches of a phase-shifted full-bridge circuit. In this paper, by allowing the inverter operating frequency to operate under inductive loads that coincide with the zero points of voltage and current rather than the resonant frequency of the BLT, which results in the generation of a shock current in the right branch of the full-bridge circuit, the switches of the right-branch also enabled zero-voltage, zero-current switching on (ZVZCS turn-on). The proposed method can fundamentally eliminate the generation of shock current by realizing ZVZCS turn-on on the right-branch switch elements of the inverter. The phase-shift angle control limit for power control by this scheme is 90° and the power control range is 20%-100%., (© 2023 Acoustical Society of America.)

Autonomous driving includes recognition, judgment, and control technologies, and is implemented using sensors such as cameras, LiDAR, and radar. However, recognition sensors are exposed to the outside environment and their performance may deteriorate because of the presence of substances that interfere with vision, such as dust, bird droppings, and insects, during operation. Research on sensor cleaning technology to solve this performance degradation has been limited. This study used various types and concentrations of blockage and dryness to demonstrate approaches to the evaluation of cleaning rates for selected conditions that afford satisfactory results. To determine the effectiveness of washing, the study used the following criteria: washer, 0.5 bar/s and air, 2 bar/s, with 3.5 g being used three times to test the LiDAR window. The study found that blockage, concentration, and dryness are the most important factors, and in that order. Additionally, the study compared new forms of blockage, such as those caused by dust, bird droppings, and insects, with standard dust that was used as a control to evaluate the performance of the new blockage types. The results of this study can be used to conduct various sensor cleaning tests and ensure their reliability and economic feasibility.

11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) is a key enzyme that catalyzes the intracellular conversion of cortisone to physiologically active cortisol. Although 11βHSD1 has been implicated in numerous metabolic syndromes, such as obesity and diabetes, the functional roles of 11βHSD1 during progression of nonalcoholic steatohepatitis (NASH) and consequent fibrosis have not been fully elucidated. We found that pharmacological and genetic inhibition of 11βHSD1 resulted in reprogramming of hepatic stellate cell (HSC) activation via inhibition of p-SMAD3, α-SMA, Snail, and Col1A1 in a fibrotic environment and in multicellular hepatic spheroids (MCHSs). We also determined that 11βHSD1 contributes to the maintenance of NF-κB signaling through modulation of TNF, TLR7, ITGB3, and TWIST, as well as regulating PPARα signaling and extracellular matrix accumulation in activated HSCs during advanced fibrogenesis in MCHSs. Of great interest, the 11βHSD1 inhibitor J2H-1702 significantly attenuated hepatic lipid accumulation and ameliorated liver fibrosis in diet- and toxicity-induced NASH mouse models. Together, our data indicate that J2H-1702 is a promising new clinical candidate for the treatment of NASH., (© 2022. The Author(s).)

Osimertinib is an irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that was initially developed to overcome the EGFR T790M mutation and is used as a standard therapy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR-activating mutations. Despite the remarkable initial efficacy, osimertinib, like other EGFR-TKIs, is limited by the emergence of acquired resistance. As the EGFR mutation C797S has been identified as a key driver of acquired resistance to osimertinib, development of a drug that targets this clinically relevant mutation could help improve patient outcomes. Here, we report the discovery and preclinical efficacy of OBX02-011, a reversible fourth-generation EGFR TKI that overcomes the EGFR C797S mutation. Compared to approved EGFR TKIs, OBX02-011 showed potent anticancer effects and inhibited EGFR-related signaling in various models, including those harboring the EGFR C797S mutation. Additionally, in transgenic mouse models (EGFRL858R/T790M/C797S), OBX02-011 treatment effectively inhibited tumor growth and EGFR activity, leading to enhanced survival. Collectively, these results suggest that OBX02-011 may be a promising new EGFR TKI to overcome C797S-mediated resistance in NSCLC.

To develop unique small-molecule inhibitors of hepatitis C virus (HCV), thiophen urea (TU) derivatives were synthesised and screened for HCV entry inhibitory activities. Among them, seven TU compounds exhibited portent anti-viral activities against genotypes 1/2 (EC 50 < 30 nM) and subsequently, they were further investigated; based on the pharmacological, metabolic, pharmacokinetic, and safety profiles, J2H-1701 was selected as the optimised lead compound as an HCV entry inhibitor. J2H-1701 possesses effective multi-genotypic antiviral activity. The docking results suggested the potential interaction of J2H-1701 with the HCV E2 glycoprotein. These results suggest that J2H-1701 can be a potential candidate drug for the development of HCV entry inhibitors.

Hepatocellular carcinoma (HCC) is a highly malignant human cancer that has increasing mortality rates worldwide. Because CD133 + cells control tumor maintenance and progression, compounds that target CD133 + cancer cells could be effective in combating HCC. We found that the administration of chromenopyrimidinone (CPO) significantly decreased spheroid formation and the number of CD133 + cells in mixed HCC cell populations. CPO not only significantly inhibited cell proliferation in HCC cells exhibiting different CD133 expression levels, but also effectively induced apoptosis and increased the expression of LC3-II in HCC cells. CPO also exhibits in vivo therapeutic efficiency in HCC. Specifically, CPO suppressed the expression of CD133 by altering the subcellular localization of CD133 from the membrane to lysosomes in CD133 + HCC cells. Moreover, CPO treatment induced point mutations in the ADRB1, APOB, EGR2, and UBE2C genes and inhibited the expression of these proteins in HCC and the expression of UBE2C is particularly controlled by CD133 expression among those four proteins in HCC. Our results suggested that CPO may suppress stemness and malignancies in vivo and in vitro by decreasing CD133 and UBE2C expression in CD133 + HCC. Our study provides evidence that CPO could act as a novel therapeutic agent for the effective treatment of CD133 + HCC.

Research studies related to the polymorphs of l-Carnitine orotate (CO), a medication used for the treatment and prevention of liver diseases, are insignificant or almost nonexistent. Accordingly, in the present study, l-Carnitine orotate (CO) was prepared for investigating CO polymorphs. Here, a reactive crystallization was induced by reacting 1g of l-Carn (1 equivalent) and 0.97 g of OA (1 equivalent) in methanol (MeOH); as a result, CO form-I and CO form-II polymorphs were obtained after 1 h and 16 h of stirring, respectively. The characterization of CO polymorphs was carried out utilizing Powder X-ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA) and solid-state Nuclear Magnetic Resonance Spectroscopy (solid-state CP/MAS 13 C-NMR). The solution-mediated polymorphic transformation (SMPT) of CO polymorphs was investigated in MeOH at controlled temperature and fixed rotational speed. The results revealed that CO form-I is a metastable polymorph while CO form-II is a stable polymorph. From the same results, it was confirmed that CO form-I was converted to CO form-II during the polymorphic phase transformation process. Moreover, it was assessed that the increase in temperature and supersaturation level significantly promotes the rate of nucleation, as well as the rate of mass transfer of CO form-II. In addition, nucleation and mass transfer equations were employed for the quantitative determination of SMPT experimental results. Lastly, it was suggested that CO form-II was more thermodynamically stable than CO form-I and that both polymorphs belong to the monotropic system.

Introduction: Precise identification of botanical origin of plant species is crucial for the quality control of herbal medicine. In Korea, the root part of Cynanchum auriculatum has been misused for C. wilfordii in the herbal drug market due to their morphological similarities. Currently, DNA analysis using the polymerase chain reaction (PCR) method is employed to discriminate between these species., Objective: In order to develop a new analytical tool for the rapid discrimination of C. wilfordii and C. auriculatum, terahertz (THz) spectroscopy was employed., Methodology: Authentic samples of C. wilfordii and C. auriculatum were provided from the National Institute and standardized pellets for each species were prepared to get optimum results with terahertz time-domain spectroscopy (THz-TDS) in frequency range 0.2-1.20 THz., Results: The C. wilfordii pellet showed longer time delay compare to the sample of C. auriculatum and this was due to the difference in permittivity. The pellet samples of C. wilfordii and C. auriculatum showed a permittivity difference of about 0.08 at 0.2-1.20 THz., Conclusion: The experimental results indicated that THz-TDS analysis can be an effective and rapid method for the discrimination of C. wilfordii and C. auriculatum, and this application can be expanded for the discrimination of other similar herbal medicines., (Copyright © 2018 John Wiley & Sons, Ltd.)

2-Keto-3-deoxy-6-phosphogluconate (KDPG) aldolase, which catalyzes aldol cleavage and condensation reactions, has two distinct substrate-binding sites. The substrate-binding mode at the catalytic site and Schiff-base formation have been well studied. However, structural information on the phosphate-binding loop (P-loop) is limited. Zymomonas mobilis KDPG aldolase is one of the aldolases with a wide substrate spectrum. Its structure in complex with the substrate-mimicking 3-phosphoglycerate (3PG) shows that the phosphate moiety of 3PG interacts with the P-loop and a nearby conserved serine residue. 3PG-binding to the P-loop replaces water molecules aligned from the P-loop to the catalytic site, as observed in the apo-structure. The extra electron density near the P-loop and comparison with other aldolases suggest the diversity and flexibility of the serine-containing loop among KDPG aldolases. These structural data may help to understand the substrate-binding mode and the broad substrate specificity of the Zymomonas KDPG aldolase.

In this paper, we propose an asymmetric split-loop resonator with an outer square loop (ASLR-OSL) based on vanadium dioxide (VO 2 ) which can actively control the transmission characteristics of a terahertz wave while maintaining a high quality factor of the asymmetric split-loop resonator (ASLR) by adding an outer square loop. The proposed ASLR-OSL demonstrated transmission characteristics similar to those of ASLR, and the transmission characteristics of ASLR-OSL were successfully controlled by directly applying a bias voltage. These results show a simple method for imposing active properties on a common metamaterial having a high quality factor by adding a loop structure.

Background: Despite remarkable activity in epidermal growth factor receptor (EGFR)-mutant lung cancer patients, the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) is limited by the emergence of acquired resistance, which is mostly caused by a secondary T790M mutation. Fortunately, newly developed, mutant-selective EGFR-TKIs against T790M have been proven as an effective therapeutic approach although only osimertinib has received the FDA approval until now., Objective: To determine the in vitro and in vivo efficacy of a new EGFR TKI, OBX1-012 in cells with mutant EGFR., Methods: Effects of OBX1-012 on cellular viability and EGFR-related signaling were determined in EGFR-mutant non-small cell lung cancer (NSCLC) cells, including cells harboring T790M mutations. In addition, in vivo efficacy of OBX1-012 was evaluated in xenograft models., Results: We report the discovery and preclinical assessment of another novel, mutant-selective EGFR-TKI, OBX1-012. Compared with other mutant-selective EGFR-TKIs such as olumitinib and osimertinib, it showed similar potency and selectivity for mutant EGFR. OBX1-012 treatment was highly effective against human EGFR-mutant lung cancer models with or without EGFR T790M, not only in vitro but also in vivo. However, OBX1-012 like other EGFR-TKIs failed to exhibit efficacy for the exon 20 insertion mutation or C797S mutation, which was generated by site-directed mutagenesis and stable transfection of Ba/F3 cells., Conclusions: These results identify OBX1-012 as a highly effective, mutant-selective EGFR-TKI for the treatment of T790M-mediated resistance in NSCLC.

Tenofovir disoproxil (TD), an anti-virus drug, is currently marketed under its most stable form, Form-I of Tenofovir disoproxil fumarate (TDF). However, studies regarding the properties of TD free base crystal as a promising drug as well as its crystal structure have not yet been reported. This assumption was made because TD free base is not directly produced in a solid form during the manufacturing process. TD free base is first obtained in an oil form, and is then synthesized into TDF crystal. In this regard, the present study was conducted to investigate both the potentiality of TD free base to be an active pharmaceutical ingredient (API) and its crystal structure. Here, TD free base solid was produced by means of drowning-out crystallization. Next, single crystal X-ray diffraction (SXD) was employed to determine the crystal structure. Powder X-ray diffraction (PXRD) and a differential scanning calorimetry (DSC) analysis were performed to evaluate the crystal's properties. Furthermore, experiments were carried out at 15%, 35%, 55%, 75%, and 95% relative humidity (RH) for 12 h using a hygroscopic tester to determine and to compare the hygroscopicity and stability of TD free base with TDF crystal. Additionally, experiments were conducted under accelerated (40 °C, RH 75%) and stress storage (60 °C, RH 75%) conditions for 30 days to investigate the changes in purity and the formation of dimer. In this work, we report that TD free base possesses lower hygroscopicity, and thus does not generate dimer impurity from hydrolysis. Primarily, this is attributed to the fact that TD free base is not an easily ionized salt but comprises neutral hydrophobic molecules. According to the structural properties, the improved hygroscopic property of the TD free base crystal was due to the decrease of crystal polarity owing to the intermolecular H-bonds present in TD free base rings. In addition, the solubility investigation study carried out in aqueous solution and at gastrointestinal pH revealed a similarity in TDF and TD free base solubility under the mentioned conditions. Accordingly, we could confirm the potentiality of TD free base as an active pharmaceutical ingredient., Competing Interests: The authors declare no conflict of interest.

An electrically controllable square-loop metamaterial based on vanadium dioxide (VO2) thin film was proposed in the terahertz frequency regime. The square-loop shaped metamaterial was adopted to perform roles not only as a resonator but also as a micro-heater for the electrical control of the VO2. A dual-resonant square-loop structure was designed to realize band-pass characteristics in the desired frequency band. The measured Q-factors of the basic and scaled-down metamaterials fabricated on VO2 thin films were 2.22 and 1.61 at the center frequencies of 0.44 and 1.14 THz in the passbands, respectively. The transmittances of the proposed metamaterial were successfully controlled by applying a bias voltage without an external heater. The measured transmittance on-off ratios of the metamaterials were over 40 at the center frequencies in the passbands. In the future, electrically controllable terahertz metamaterial based on VO2 metamaterial could be employed as high-performance active filters or sensors.

Ionic liquids (ILs) are defined as salts with a melting point below 100 °C. ILs have received increasing attention as new alternative to organic solvents because of their unique physicochemical properties. Therefore, this study was conducted in the purpose to present the efficacy of ILs as new solvents capable to control the Polymorphic transformation phenomenon. Here, the polymorphic transformation phenomenon of adefovir dipivoxil, an efficient antiviral active pharmaceutical ingredient on human immunodeficiency virus, was investigated. The phase transformation phenomenon from the metastable polymorph, new form (NF) to the stable polymorph, Form-X in 1-allyl-3-ethylimidazolium tetrafluoroborate (AEImBF4) and 1-butyl-2,3-dimethylimidazolium tetrafluoroborate (BDMImBF4) ILs solutions was observed utilizing the solvent-mediated phase transformation method The thermodynamic factors, AEImBF4/BDMImBF4 solvent composition ratio of 3:7-6:4 and the temperature in range of 25-100 °C, as well as the dynamic factor, the rational speed in range of 300-1000 rpm were parameters studied in this experiment. The thermodynamic and dynamic equations involving nucleation and mass transfer were applied for the quantitative analysis. The result of the present study confirmed the use of ILs as substitute solvent for volatile organic solvents, and demonstrated the efficacy of ILs as potential solvent-media to control the polymorphic transformation.

A Ta/TaOx/Pt stacked capacitor-like device for resistive switching was fabricated and examined. The tested device demonstrated stable resistive switching characteristics including uniform distribution of resistive switching operational parameters, highly promising endurance, and retention properties. To reveal the resistive switching mechanism of the device, micro structure analysis using high-resolution transmission electron microscope (HR-TEM) was performed. From the observation results, two different phases of Ta-metal clusters of cubic α-Ta and tetragonal β-Ta were founded in the amorphous TaOx mother-matrix after the device was switched from high resistance state (HRS) to low resistance state (LRS) by externally applied voltage bias. The observed Ta metal clusters unveiled the origin of the electric conduction paths in the TaOx thin film at the LRS.

Background/aims: Only a small part of visible gas tric mucosal lesion can be removed by endoscopic resection. This study is aimed to identify incidence rate and associated risk factors of multiple and missed gastric lesions, and proper timing of follow-up en doscopy., Methodology: Endoscopic surveillance was performed on 1 week, and 1, 6, 12 months af ter endoscopic resection. All multiple gastric lesions were divided into main and accessory lesions. The accessory lesions were subdivided into detected and missed lesions., Results: Totally, 250 lesions of 215 patients were analyzed. There were 81 early gastric cancers, 50 high grade dysplasias and 119 low grade dysplasias. Thirty patients (14%) had multiple gastric neoplastic lesions, either adenoma or cancer, within 1 year follow-up after endoscopic resection. Old age, male gender and severe intestinal metaplasia were independent risk factors of multiple gastric lesions. Small size (≤ 1 cm) and flat morphology were major risk factors of missed lesion. Among 10 missed lesions, 9 (90%) could be detected within 6 month after resection., Conclusions: Old age, male gender, severe intestinal metaplasia were risk factors for multiple gastric lesions after endoscopic resection. Follow-up endoscopy is needed at least one time within six months after resection, with careful inspection of entire stomach.

We report a high-speed (~2 kHz) dynamic multiplexed fiber Bragg grating (FBG) sensor interrogation using a wavelength-swept laser (WSL) with a polygon-scanner-based wavelength filter. The scanning frequency of the WSL is 18 kHz, and the 10 dB scanning bandwidth is more than 90 nm around a center wavelength of 1,540 nm. The output from the WSL is coupled into the multiplexed FBG array, which consists of five FBGs. The reflected Bragg wavelengths of the FBGs are 1,532.02 nm, 1,537.84 nm, 1,543.48 nm, 1,547.98 nm, and 1,553.06 nm, respectively. A dynamic periodic strain ranging from 500 Hz to 2 kHz is applied to one of the multiplexed FBGs, which is fixed on the stage of the piezoelectric transducer stack. Good dynamic performance of the FBGs and recording of their fast Fourier transform spectra have been successfully achieved with a measuring speed of 18 kHz. The signal-to-noise ratio and the bandwidth over the whole frequency span are determined to be more than 30 dB and around 10 Hz, respectively. We successfully obtained a real-time measurement of the abrupt change of the periodic strain. The dynamic FBG sensor interrogation system can be read out with a WSL for high-speed and high-sensitivity real-time measurement.

A simple thickness measurement method based on the coherent homodyne CW THz system was demonstrated; it does not require precise control of the frequencies of the beat source, and only accurate scanning of the optical delay line is needed. Three beat frequencies are sufficient for measuring the thickness of a sample without considering the modulo 2π ambiguity. A novel compact 1.55 μm λ/4 phase-shifted dual-mode laser (DML) was developed as an optical beat source for the CW THz system. The thickness of a sample was accurately estimated from the measurements using the proposed method. Our results clearly show the possibility of a compact, simple, and cost-effective CW THz system for practical applications.

A widely tunable dual mode laser diode with a single cavity structure is demonstrated. This novel device consists of a distributed feedback (DFB) laser diode and distributed Bragg reflector (DBR). Micro-heaters are integrated on the top of each section for continuous and independent wavelength tuning of each mode. By using a single gain medium in the DFB section, an effective common optical cavity and common modes are realized. The laser diode shows a wide tunability of the optical beat frequency, from 0.48 THz to over 2.36 THz. Continuous wave THz radiation is also successfully generated with low-temperature grown InGaAs photomixers from 0.48 GHz to 1.5 THz.

We propose a compact fiber-pigtailed InGaAs photoconductive antenna (FPP) module having an effective heat-dissipation solution as well as a module volume of less than 0.7 cc. The heat-dissipation of the FPP modules when using a heat-conductive printed circuit board (PCB) and an aluminium nitride (AlN) submount, without any cooling systems, improve by 40% and 85%, respectively, when compared with a photoconductive antenna chip on a conventional PCB. The AlN submount is superior to those previously reported as a heat-dissipation solution. Terahertz time-domain spectroscopy (THz-TDS) using the FPP module perfectly detects the absorption lines of water vapor in free space and an α-lactose sample.

12(S)-Hydroxyheptadeca-5Z,8E,10E-trienoic acid (12- HHT) is an enzymatic product of prostaglandin H(2) (PGH(2)) derived from cyclooxygenase (COX)-mediated arachidonic acid metabolism. Despite the high level of 12-HHT present in tissues and bodily fluids, its precise function remains largely unknown. In this study, we found that 12-HHT treatment in HaCaT cells remarkably down-regulated the ultraviolet B (UVB) irradiation-induced synthesis of interleukin-6 (IL-6), a pro-inflammatory cytokine associated with cutaneous inflammation. In an approach to identify the down-stream signaling mechanism by which 12-HHT down-regulates UVB-induced IL-6 synthesis in keratinocytes, we observed that 12-HHT inhibits the UVB-stimulated activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB). In addition, we found that 12-HHT markedly up-regulates MAPK phosphatase-1 (MKP-1), a critical negative regulator of p38 MAPK. When MKP-1 was suppressed by siRNA knock-down, the 12-HHT-mediated inhibitory effects on the UVB-stimulated activation of p38 MAPK and NF-κB, as well as the production of IL-6, were attenuated in HaCaT cells. Taken together, our results suggest that 12-HHT exerts anti-inflammatory effect via up-regulation of MKP-1, which negatively regulates p38 MAPK and NF-κB, thus attenuating IL-6 production in UVB-irradiated HaCaT cells. Considering the critical role of IL-6 in cutaneous inflammation, our findings provide the basis for the application of 12-HHT as a potential anti-inflammatory therapeutic agent in UV-induced skin diseases.

We propose a rapidly frequency-swept optical beat source for continuous wave (CW) THz generation using a wavelength swept laser and a fixed distributed feedback (DFB) laser. The range of the sweeping bandwidth is about 17.3 nm (2.16 THz), 1541.42-1558.72 nm. The achieved side mode suppression ratio for both wavelengths within the full sweeping range is more than 45 dB. We observe CW THz signals for tunable optical beat sources using a fiber coupled CW THz measurement system to confirm the feasibility of using our frequency swept optical beat source as a CW THz radiation source. The THz output signal falls to the thermal noise level of the low-temperature grown (LTG) InGaAs photomixer beyond 1.0 THz. The rapidly frequency-swept optical beat source will be useful for generating high-speed tunable CW THz radiation.

The successful demonstration of an optical fiber-coupled terahertz time-domain spectroscopy (THz-TDS) system is described in this study. The terahertz output power of the emitter with two optical band rejection filters was 132 nW, which is an improvement of 70% over the output power without any filters. This improvement is due to the suppression of an optical modulated signal that is reverse-generated when an alternating current bias exceeding a certain threshold is applied to the emitter. Under the optimal alignment conditions, the terahertz detector in a fiber-coupled THz-TDS system clearly measured water vapor dips in the free space., (© 2011 Optical Society of America)

We demonstrate a tunable continuous-wave (CW) terahertz (THz) homodyne system with a novel detuned dual-mode laser diode (DML) and low-temperature-grown (LTG) InGaAs photomixers. The optical beat source with the detuned DML showed a beat frequency tuning range of 0.26 to over 1.07 THz. Log-spiral antenna integrated LTG InGaAs photomixers are used as THz wave generators and detectors. The CW THz radiation frequency was continuously tuned to over 1 THz. Our results clearly show the feasibility of a compact and fast scanning CW THz spectrometer consisting of a fiber-coupled detuned DML and photomixers operating in the 1.55-μm range.

Skin exposure to low-dose ultraviolet B (UVB) light up-regulates the expression of matrix metalloproteinase-1 (MMP-1), thus contributing to premature skin aging (photo-aging). Although cyclooxygenase-2 (COX- 2) and its product, prostaglandin E(2) (PGE((2))), have been associated with UVB-induced signaling to MMP expression, very little are known about the roles of lipoxygenases and their products, especially leukotriene B((4)) (LTB((4))) and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), in MMP-1 expression in skin keratinocytes. In the present study, we demonstrate that BLT2, a cell surface receptor for LTB((4)) and 12(S)-HETE, plays a critical role in UVB-mediated MMP-1 upregulation in human HaCaT keratinocytes. Moreover, our results demonstrated that BLT2-mediated MMP-1 upregulation occurs through a signaling pathway dependent on reactive oxygen species (ROS) production and the subsequent stimulation of ERK. Blockage of BLT2 via siRNA knockdown or with the BLT2-antagonist LY255283 completely abolished the up-regulated expression of MMP-1 induced by low-dose UVB irradiation. Finally, when HaCaT cells were transiently transfected with a BLT2 expression plasmid, MMP-1 expression was significantly enhanced, along with ERK phosphorylation, suggesting that BLT2 overexpression alone is sufficient for MMP-1 up-regulation. Together, our results suggest that the BLT2-ROS- ERK-linked cascade is a novel signaling mechanism for MMP-1 upregulation in low-dose UVB- irradiated keratinocytes and thus potentially contributes to photo-aging.

The role of reactive oxygen species (ROS) in UVB-induced apoptosis has been established, but the molecular mechanisms of their production in response to UVB irradiation in keratinocytes are not well understood. In this study, we demonstrate that levels of BLT2, a low-affinity leukotriene B(4) receptor, and its ligands (LTB(4) and 12(S)-HETE) are greatly increased by UVB irradiation and are responsible for the UVB-induced ROS generation in human keratinocytes. Blockade of BLT2 with a BLT2-specific antagonist, LY255283, or with siBLT2 attenuated ROS production and apoptotic cell death detected by a number of criteria. Moreover, we found that the NADPH oxidase family protein Nox1 lies downstream of BLT2 and mediates UVB-induced ROS production and apoptosis. Topical treatment of mouse epidermal skin with LY255283 gave significant protection against UVB-induced sunburn-associated apoptotic damage. Finally, when BLT2-overexpressing transgenic mice were irradiated with UVB, we observed more extensive skin apoptosis. Taken together, our results demonstrate that a "BLT2-Nox1"-linked pathway has a crucial role in UVB-induced ROS generation and mediates apoptosis in human keratinocytes.

Recent studies have suggested that mast cells have critical roles in angiogenesis. However, the detailed mechanism by which mast cells contribute to angiogenesis is not yet clearly understood, especially in response to proinflammatory cytokines. In this study, we showed that the proinflammatory cytokine IL-1beta induces the synthesis of IL-8, a potent angiogenic factor, in human mast cells via the leukotriene B(4) receptor (BLT)2. We also characterized the BLT2 downstream signaling pathway and determined that BLT2-mediated IL-8 synthesis involves the upregulation of Nox1, a member of the NADPH oxidase family, Nox1-dependent reactive oxygen species generation and the subsequent activation of the redox-sensitive transcription factor NF-kappaB. For instance, knockdown of BLT2 and Nox1 with specific small interfering RNA, treatment with a specific BLT2 antagonist, LY255283, or treatment with a potential Nox inhibitor, diphenylene iodonium, suppressed IL-1beta-induced IL-8 synthesis. We found that the conditioned media collected from IL-1beta-treated human mast cell line HMC-1 had significantly enhanced angiogenic activity that could be dramatically attenuated by either small interfering RNA knockdown of BLT2 or treatment with neutralizing Ab to IL-8. Finally, the experiments were repeated using human primary cord blood-derived mast cells, and the results were clearly reproduced. Taken together, our results suggest that BLT2-Nox1-reactive oxygen species-dependent pathway plays a role in promoting the secretion of IL-8 from human mast cells in response to the proinflammatory cytokine IL-1beta, thus contributing to angiogenesis.

Zymomonas mobilis ZM4 is an organism optimized for ethanol production which uses the Entner-Doudoroff (ED) pathway for the breakdown of glucose. The key enzyme in this process is 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase, which produces glyceraldehyde 3-phosphate and pyruvate. In order to provide a molecular background for the KDPG aldolase from this ethanologenic organism (zmKDPG aldolase), the ZMO0997 gene of Z. mobilis ZM4 coding for zmKDPG aldolase was cloned and expressed and the purified protein was crystallized from 25%(w/v) polyethylene glycol 3350 and 0.1 M bis-tris pH 5.5. Diffraction data were collected to 1.8 A resolution using synchrotron radiation. The crystal belonged to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 63.7, b = 83.0, c = 117.2 A. A trimeric zmKDPG aldolase molecule was present in the asymmetric unit, resulting in a crystal volume per unit protein weight of 2.40 A(3) Da(-1) and a solvent content of 48%.

Helicobacter pylori is one of the main causes of atrophic gastritis and gastric carcinogenesis. Gastritis can also occur in the absence of H. pylori as a result of bile reflux suggesting the eradication of H. pylori by bile acids. However, the bile salts are unable to eradicate H. pylori due to their low solubility and instability at acidic pH. This study examined the effect of a highly soluble and acid stable ursodeoxycholic acid (UDCA) formula on H. pylori-induced atrophic gastritis. The H. pylori infection decreased the body weight, mitochondrial membrane potential and ATP level in vivo. Surprisingly, H. pylori-induced expression of malate dehydrogenase (MDH), a key enzyme in the tricarboxylic acid cycle, at both the protein and mRNA levels. However, the UDCA formula repressed MDH expression and increased the membrane potential thereby increasing the ATP level and body weight in vivo. Moreover, UDCA scavenged the reactive oxygen species (ROS), increased the membrane potential, and inhibited apoptosis in AGS cells exposed to H(2)O(2) in vitro through the mitochondria-mediated pathway. Taken together, UDCA decreases the MDH and ROS levels, which can prevent apoptosis in H. pylori-induced gastritis.

Reactive oxygen species (ROS) are important regulatory molecules implicated in the signaling cascade triggered by tumor necrosis factor (TNF)alpha, although the events through which TNFalpha induces ROS generation are not well characterized. Here, we report that TNFalpha-induced ROS production was blocked by pretreatment with internalization inhibitor monodansyl cadaverine (MDC). Similarly, a transient expression of a GTP-binding and hydrolysis-defective dynamin mutant (dynamin(K44A)) that had been shown to be defective in internalization significantly attenuated the TNFalpha-induced intracellular ROS production. Importantly, the inhibition of receptor internalization suppressed TNFalpha signaling to mitogen-activated protein kinases (MAPKs) stimulation. Together, our results suggest that receptor internalization is somehow necessary for the TNFalpha-induced ROS generation and subsequent intracellular downstream signaling in non-phagocytes.

Single nucleotide polymorphisms (SNPs) in the MDR1 gene that are responsible for drug efflux can cause toxicity. Therefore, this study determined the SNPs of the Korean MDR1 gene, and analyzed the haplotypes and a linkage disequilibrium (LD) of the SNPs determined. The frequency of 9 SNPs from the MDR1 gene was determined by PCR-RFLP analyses of 100 to 500 healthy individuals. The frequcies of the SNPs were C3435T (47.7%), G2677T (37.6%), G2677A (4.4%), T1236C (21.7%), T129C (8%), A2956G (2.5%), T307C (1.5%), A41aG (9.2%), C145G (0%), and G4030C (0 %). Analyses of the haplotype structure and an estimation of the LD of the combined polymorphisms demonstrated that the frequency of the 1236T-2677G-3435T haplotype is much higher in Koreans (14.1%) than in Chinese and western black Africans and the C3435T SNP in Koreans appears to have LD with T129C in Koreans for the first time. These results provide insight into the genetic variation of MDR1 in Koreans, and demonstrated the possibility of a new LD in this gene.