Wake-sleep cycles are severely disrupted by diseases affecting cytoplasmic homeostasis.

The circadian clock is based on a transcriptional feedback loop with an essential time delay before feedback inhibition. Previous work has shown that PERIOD (PER) proteins generate circadian time cues through rhythmic nuclear accumulation of the inhibitor complex and subsequent interaction with the activator complex in the feedback loop. Although this temporal manifestation of the feedback inhibition is the direct consequence of PER's cytoplasmic trafficking before nuclear entry, how this spatial regulation of the pacemaker affects circadian timing has been largely unexplored. Here we show that circadian rhythms, including wake-sleep cycles, are lengthened and severely unstable if the cytoplasmic trafficking of PER is disrupted by any disease condition that leads to increased congestion in the cytoplasm. Furthermore, we found that the time delay and robustness in the circadian clock are seamlessly generated by delayed and collective phosphorylation of PER molecules, followed by synchronous nuclear entry. These results provide clear mechanistic insight into why circadian and sleep disorders arise in such clinical conditions as metabolic and neurodegenerative diseases and aging, in which the cytoplasm is congested.

Impact of Obesity on the IL-6 Immune Marker and Th17 Immune Cells in C57BL/6 Mice Models with Imiquimod-Induced Psoriasis.

Obese psoriatic patients experience higher disease severity and exhibit poorer treatment responses and clinical outcomes. It has been proposed that proinflammatory cytokines produced by adipose tissue exacerbate psoriasis; however, the role of obesity in psoriasis remains unclear. This study aimed to elucidate the role of obesity in the pathogenesis of psoriasis, focusing on immunological changes. To induce obesity, mice were fed a high-fat diet for 20 weeks. We then applied imiquimod to the skin on a mouse's back for seven consecutive days to induce psoriasis and scored lesion severity every day for seven days. Cytokine levels in serum and the Th17 cell population in the spleen and draining lymph nodes were studied to identify immunological differences. The clinical severity was more remarkable, and histologically the epidermis was also significantly thicker in the obese group. Increased levels of IL-6 and TNF-α were observed in serum after psoriasis. They were elevated to a greater degree, with greater expansion of the functional Th17 cell population in the obese group. It is concluded that obesity could exacerbate psoriasis through mechanisms that involve elevated proinflammatory cytokine secretion and an expanded Th17 cell population.

RISE: robust iterative surface extension for sub-nanometer X-ray mirror fabrication.

Precision optics have been widely required in many advanced technological applications. X-ray mirrors, as an example, serve as the key optical components at synchrotron radiation and free electron laser facilities. They are rectangular silicon or glass substrates where a rectangular Clear Aperture (CA) needs to be polished to sub-nanometer Root Mean Squared (RMS) to keep the imaging capability of the incoming X-ray wavefront at the diffraction limit. The convolutional polishing model requires a CA to be extended with extra data, from which the dwell time is calculated via deconvolution. However, since deconvolution is very sensitive to boundary errors and noise, the existing surface extension methods can hardly fulfill the sub-nanometer requirement. On one hand, the figure errors in a CA were improperly modeled during the extension, leading to continuity issues along the boundary. On the other hand, uncorrectable high-frequency errors and noise were also extended. In this study, we propose a novel Robust Iterative Surface Extension (RISE) method that resolves these problems with a data fitting strategy. RISE models the figure errors in a CA with orthogonal polynomials and ensures that only correctable errors are fit and extended. Combined with boundary conditions, an iterative refinement of dwell time is then proposed to compensate the errors brought by the extension and deconvolution, which drastically reduces the estimated figure error residuals in a CA while the increase of total dwell time is negligible. To our best knowledge, RISE is the first data fitting-based surface extension method and is the first to optimize dwell time based on iterative extension. An experimental verification of RISE is given by fabricating two elliptic cylinders (10 mm × 80 mm CAs) starting from a sphere with a radius of curvature around 173 m using ion beam figuring. The figure errors in the two CAs greatly improved from 204.96 nm RMS and 190.28 nm RMS to 0.62 nm RMS and 0.71 nm RMS, respectively, which proves that RISE is an effective method for sub-nanometer level X-ray mirror fabrication.

Biomonitoring the effects of urban-stream waters on the health status of pale chub (Zacco platypus): A comparative analysis of biological indexes and biomarker levels.

The objective of this study was to biomonitor the effects of potential environmental pollutants in urban-stream waters, on fish health. Pale chub (Zacco platypus), a dominant species in the Korea urban stream waters, was chosen and biomonitoring indicators for the different spatial characteristics were tailored in an urban watershed. Biological responses including biotic-somatic index as well as gonadal development phase and plasma steroids levels, and the biochemical responses, ethoxyresorufin-o-deethylase (EROD) and acetylcholinesterase (AChE) activities, were measured. No significant difference was observed in the length-weight relationship between the up-stream waters and the down-stream waters. However, changes in the gonad-somatic index (GSI) levels, plasma 17ß-estradiol (E2) levels, and mature oocyte frequencies in the female fish collected during the spawning season were observed in the down-stream waters at each monitoring site. Moreover, intersex condition (testis-ova) in the male fish in down-stream waters was recorded, even if it was just one fish. Although no significant difference was observed in the EROD and AChE activities between the up-stream waters and the down-stream waters, changes in the reproductive biomarker levels, including the GSI levels, plasma E2 levels, and gonadal maturation, lead to variable biomonitoring endpoints between the spatial different sites. These results imply that exposure to the down-stream waters can cause reproductive impairment in wild Z. platypus, individual variability in the biological responses further indicate the reproductive health was affected more by the down-stream waters than the up-stream waters. The finding from this study can provide the biomonitoring endpoint on the wild fish health in urban watershed that is crucial to the early risk assessment of its biological impacts. More multi-biomarkers studies reflecting the variation in the biological organization of wild fish and, therefore, the effects of urban-stream waters in the fish health are warranted.

Effect of Viscosity on the Formation of Porous Polydimethylsiloxane for Wearable Device Applications.

Medical devices, which enhance the quality of life, have experienced a gradual increase in demand. Various research groups have attempted to incorporate soft materials such as skin into wearable devices. We developed a stretchable substrate with high elasticity by forming a porous structure on polydimethylsiloxane (PDMS). To optimize the porous structure, we propose a manufacturing process that utilizes a high-pressure steam with different viscosities (400, 800, 2100, and 3000 cP) of an uncured PDMS solution. The proposed method simplifies the manufacturing of porous structures and is cost-effective compared to other technologies. Porous structures of various viscosities were formed, and their electrical and mechanical properties evaluated. Porous PDMS (3000 cP) was formed in a sponge-like three-dimensional porous structure, compared to PDMS formed by other viscosities. The elongation of porous PDMS (3000 cP) was increased by up to 30%, and the relative resistance changed to less than 1000 times with the maximum strain test. The relative resistance increased the initial resistance (R0) by approximately 10 times during the 1500-times repeated cycling tests with 30% strain. As a result, patch-type wearable devices based on soft materials can provide an innovative platform that can connect with the human skin for robotics applications and for continuous health monitoring.

Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy.

In mammals, the master circadian clock synchronizes daily rhythms of physiology and behavior with the day-night cycle. Failure of synchrony, which increases the risk for numerous chronic diseases, can be treated by phase adjustment of the circadian clock pharmacologically, for example, with melatonin, or a CK1δ/ε inhibitor. Here, using in silico experiments with a systems pharmacology model describing molecular interactions, and pharmacokinetic and behavioral experiments in cynomolgus monkeys, we find that the circadian phase delay caused by CK1δ/ε inhibition is more strongly attenuated by light in diurnal monkeys and humans than in nocturnal mice, which are common preclinical models. Furthermore, the effect of CK1δ/ε inhibition strongly depends on endogenous PER2 protein levels, which differs depending on both the molecular cause of the circadian disruption and the patient's lighting environment. To circumvent such large interindividual variations, we developed an adaptive chronotherapeutics to identify precise dosing regimens that could restore normal circadian phase under different conditions. Our results reveal the importance of photosensitivity in the clinical efficacy of clock-modulating drugs, and enable precision medicine for circadian disruption.

Parametric removal rate survey study and numerical modeling for deterministic optics manufacturing.

Surface errors directly affect the performance of optical systems in terms of contrast and resolution. Surface figure errors at different surface scales are deterministically removed using controlled material removal rate (MRR) during a precision optics fabrication process. We systematically sectioned the wide range of MRR space with systematic parameters and experimentally evaluated and mapped the MRR values using a flexible membrane-polishing tool. We performed numerical analysis with a tool influence function model using a distributed MRR-based Preston's constant evaluation approach. The analysis procedure was applied to a series of experimental data along with the tool influence function models to evaluate removal rates. In order to provide referenceable survey data without entangled information, we designed the experiments using Taguchi's L27 orthogonal array involving five control parameters and statistically analyzed a large number of programmatic experiments. The analysis of variance showed that the most significant parameters for achieving a higher MRR are the spot size and active diameter.

Dual-tool multiplexing model of parallel computer controlled optical surfacing.

Fabrication of large optics is a time-consuming process and requires a vast investment in manpower and financial resources. Increasing the material removal rate of polishing tools and minimizing dwell time are two common ways of reducing the processing time. Indeed, the polishing efficiency can be further improved if multiple tools are used at the same time. In this Letter, we propose a dual-tool deterministic polishing model, which multiplexes the dwell time and optimizes the run parameters of two polishing tools simultaneously. The run velocities of the two tools are coordinated by boundary conditions with a velocity adjustment algorithm, and the corresponding polishing paths are studied. We demonstrate this model with a simulation of polishing one segment of the Giant Magellan Telescope, where, with the proposed dual-tool multiplexing, the processing time of an ø8.4 m mirror has been reduced by 50.54% compared with that using two tools in a sequential schedule.

Interference of two diverging beams reflected from a plane parallel plate: stationary fringes with characteristic stable period.

We investigated interference fringes due to superposition of diverging light waves reflected from the two sides of a plane parallel plate. A non-localized fringe pattern of high contrast was obtained as a function of incident angle when we used a coherent diverging beam. We found that the fringe density increased to a certain angle and then decreased thereafter, against the common belief that the fringe density increases monotonically with the angle of incidence. Because the fringe density is maximum at this angle and does not change rapidly in the vicinity, we could employ Fourier analysis to estimate interferometric parameters, such as thickness, refractive index, and wavelength, that determine the characteristic stationary fringe density.

Five-channel fiber-based laser Doppler vibrometer for underwater acoustic field measurement.

In this paper, a 1550 nm five-channel all-fiber homodyne laser Doppler vibrometer with high sensitivity and good signal probing probability is presented. Under the anechoic tank, standing on an airborne platform above the water surface 3 m away, the calibration experiments of the designed system are conducted. The minimum detectable sound pressure level is up to 101.73 dB re 1 µPa at 10 kHz under the hydrostatic water surface condition, and the time distribution of the final outputs are consistent with that of the underwater sound transducer. For the hydrodynamic detection capability, with the help of a 1064 nm high-pulse-energy laser whose pulse energy is 6J, pulse duration is about 8 ns, and repetition rate is 1 Hz, the system performance is tested in Qiandao Lake. And the signal probing probability of the whole sensing system is up to 59.77%.

Flight model characterization of the wide-field off-axis telescope for the MATS satellite.

We present optical characterization, calibration, and performance tests of the Mesospheric Airglow/Aerosol Tomography Spectroscopy (MATS) satellite, which for the first time, to the best of our knowledge, for a satellite, applies a linear-astigmatism-free confocal off-axis reflective optical design. Mechanical tolerances of the telescope were investigated using Monte Carlo methods and single-element perturbations. The sensitivity analysis results indicate that tilt errors of the tertiary mirror and a surface RMS error of the secondary mirror mainly degrade optical performance. From the Monte Carlo simulation, the tolerance limits were calculated to ±0.5mm, ±1mm, and ±0.15∘ for decenter, despace, and tilt, respectively. We performed characterization measurements and optical tests with the flight model of the satellite. Multi-channel relative pointing, total optical system throughput, and distortion of each channel were characterized for end-users. Optical performance was evaluated by measuring the modulation transfer function (MTF) and point spread function (PSF). The final MTF performance was 0.25 MTF at 20 lp/mm for the ultraviolet channel (304.5 nm), and 0.25-0.54 MTF at 10 lp/mm for infrared channels. The salient fact of the PSF measurement of this system is that there is no noticeable linear astigmatism detected over a wide field of view (5.67∘×0.91∘). All things considered, the design method showed great advantages in wide field of view observations with satellite-level optical performance.

Development of a position-velocity-time-modulated two-dimensional ion beam figuring system for synchrotron x-ray mirror fabrication.

With the rapid evolution of synchrotron x-ray sources, the demand for high-quality precision x-ray mirrors has greatly increased. Single nanometer shape accuracy is required to keep imaging capabilities at the diffraction limit. Ion beam figuring (IBF) has been used frequently for ultra-precision finishing of mirrors, but achieving the ultimate accuracy depends on three important points: careful alignment, accurate dwell time calculation and implementation, and accurate optical metrology. The Optical Metrology Group at National Synchrotron Light Source II has designed and built a position-velocity-time-modulated two-dimensional IBF system (PVT-IBF) with three novel characteristics: (1) a beam footprint on the mirror was used as a reference to align the coordinate systems between the metrology and the IBF hardware; (2) the robust iterative Fourier transform-based dwell time algorithm proposed by our group was applied to obtain an accurate dwell time map; and (3) the dwell time was then transformed to velocities and implemented with the PVT motion scheme. In this study, the technical aspects of the PVT-IBF systems are described in detail, followed by an experimental demonstration of the figuring results. In our first experiment, the 2D RMS in a $ 50\;{\rm mm} \times 5\;{\rm mm} $50mm×5mm clear aperture was reduced from 3.4 to 1.1 nm after one IBF run. In our second experiment, due to a 5 mm pinhole installed in front of the source, the 2D RMS in a $ 50\;{\rm mm} \times 5\;{\rm mm} $50mm×5mm clear aperture was reduced from 39.1 to 1.9 nm after three IBF runs, demonstrating that our PVT-IBF solution is an effective and deterministic figuring process.

Conversion of Glycosylated Platycoside E to Deapiose-Xylosylated Platycodin D by Cytolase PCL5.

Platycosides, the saponins abundant in Platycodi radix (the root of Platycodon grandiflorum), have diverse pharmacological activities and have been used as food supplements. Since deglycosylated saponins exhibit higher biological activity than glycosylated saponins, efforts are on to enzymatically convert glycosylated platycosides to deglycosylated platycosides; however, the lack of diversity and specificities of these enzymes has limited the kinds of platycosides that can be deglycosylated. In the present study, we examined the enzymatic conversion of platycosides and showed that Cytolase PCL5 completely converted platycoside E and polygalacin D3 into deapiose-xylosylated platycodin D and deapiose-xylosylated polygalacin D, respectively, which were identified by LC-MS analysis. The platycoside substrates were hydrolyzed through the following novel hydrolytic pathways: platycoside E → platycodin D3 → platycodin D → deapiosylated platycodin D → deapiose-xylosylated platycodin D; and polygalacin D3 → polygalacin D → deapiosylated polygalacin D → deapiose-xylosylated polygalacin D. Our results show that cytolast PCL5 may have a potential role in the development of biologically active platycosides that may be used for their diverse pharmacological activities.

Freeform surface selection based on parametric fitness function using modal wavefront fitting.

We present an analytic methodology to guide the selection of a surface within an optical design to apply freeform optimization. The methodology is discussed in the context of other means currently available, such as human intuition, aberration theory, and other direct surface construction methods. We describe the selection criteria for our proposed method and provide the form of the parametric fitness function used to combine the criterion. Finally, a case study comparing a design optimization procedure guided by the proposed methodology to human intuition is presented based on a real instrument designed for a millimeter-wave astronomy application. The methodology is shown to be effective even in the case of an optical system with a large number of freeform/optical surfaces. The proposed approach provides an objective and scalable solution to guide freeform optical system design by aiding a human's design intuition.

High contrast thermal deflectometry using long-wave infrared time modulated integrating cavity source.

We introduce a scalable temporally modulated long-wave infrared source design. The design makes use of an array of resistive blackbody heating elements which radiate into a custom aluminum integrating cavity. The output of the box is a rectangular slit, built to match the traditional tungsten ribbon profile for an infrared deflectometry source. Temporal modulation allows for signal isolation and improved resilience to background fluctuations in an infrared deflectometry source. Infrared deflectometry measurements using the new source design and a traditional tungsten ribbon, both with similar radiant flux, were compared for a ground glass surface, an aluminum blank, and an aluminum blank under thermal load (150 °C). Signal-to-noise ratio was ∼4 times higher for the new design and demonstrated improved source temporal stability and geometry. Further, the new design successfully measured the previously untestable hot aluminum flat. The new design improves infrared deflectometry and allows for high contrast thermal deflectometry measurements of optics under thermal load.

Multi-field merit-function-based regression method for Wide Field Infrared Survey Telescope grism system alignment.

The grating prism (grism), slitless spectrometer aboard the Wide Field Infrared Survey Telescope enables a survey of emission-line galaxies. To facilitate its opto-mechanical alignment, a six-degree-of-freedom element was fabricated using alignment fiducials and integral flats and used to measure a wavefront by using an infrared interferometer placed at various field points over a 20×14 deg field of view in the grism coordinate frame. Modeling identified E2 to be the most sensitive element to the grism wavefront error and was used to efficiently align the system. The merit function regression method for a wide field of view was further used to verify the higher efficiency and accuracy of the proposed alignment technique compared with the conventional sensitivity table method.

Production of 8S- and 10S-hydroxy polyunsaturated fatty acids by recombinant Escherichia coli cells expressing mouse arachidonate 8S-lipoxygenase.

OBJECTIVE: To quantitatively hydroxylate 8S- and 10S-positions on polyunsaturated fatty acids by recombinant Escherichia coli cells expressing mouse arachidonate 8S-lipoxygenase (8S-LOX). RESULTS: Hydroxylated products gained from the conversion of arachidonic acid (20:4Δ5Z,8Z,11Z,14Z, AA), eicosapentanoic acid (20:5Δ5Z,8Z,11Z,14Z,17Z, EPA), and (22:6Δ4Z,7Z,10Z,13Z,16Z,19Z, DHA) by recombinant E. coli cells containing 8S-LOX from mouse were identified as 8S-hydroxy-5,9,11,14(Z,E,Z,Z)-eicosatetranoic acid (8S-HETE), 8S-hydroxy-5,9,11,14,17(Z,E,Z,Z,Z)-eicosapentanoic acid (8S-HEPE), and 10S-hydroxy-4,8,12,14,16,19(Z,E,Z,Z,Z,Z)-docosahexaenoic acid (10S-HDoHE), respectively. Under the optimal hydroxylation conditions of pH 7.5, 30 °C, 5% (v/v) ethanol, 15 g cells l-1, and 5 mM substrate, AA, EPA, and DHA were hydroxylated into 4.37 mM 8S-HETE, 3.77 mM 8S-HEPE, and 3.13 mM 10S-HDoHE for 60, 90, and 60 min, with 87, 75, and 63% molar conversions, respectively. CONCLUSION: To the best of our knowledge, this is the first quantitatively biotechnological production of 8S-HETE, 8S-HEPE, and 10S-HDoHE.

Cloning and characterization of α-L-rhamnosidase from Chloroflexus aurantiacus and its application in the production of isoquercitrin from rutin.

OBJECTIVE: This study was conducted to characterize recombinant α-L-rhamnosidase from Chloroflexus aurantiacus and apply the enzyme in the production of isoquercitrin from rutin. RESULTS: The α-L-rhamnosidase from C. aurantiacus was cloned and expressed in Escherichia coli BL21 and purified as a soluble enzyme. α-L-rhamnosidase purified from C. aurantiacus has a molecular mass of approximately 105 kDa and is predicted to exist as a homodimer with a native enzyme of 200 kDa. The purified enzyme exhibited the highest specific activity for rutin among the reported isoquercitrin producing α-L-rhamnosidases and was applied in the production of isoquercitrin from rutin. Under the optimised conditions of pH 6.0, 50 °C, 0.6 U mL-1 α-L-rhamnosidase, and 30 mM rutin, α-L-rhamnosidase from C. aurantiacus produced 30 mM isoquercitrin after 2 h with a 100% conversion yield and productivity of 15 mM h-1. CONCLUSIONS: We achieved a high productivity of isoquercitrin from rutin. Moreover, these results suggest that α-L-rhamnosidase from C. aurantiacus is an effective isoquercitrin producer.

Adaptive Shack-Hartmann wavefront sensor accommodating large wavefront variations.

Shack-Hartmann wavefront sensors (SHWFSs) usually have fixed subaperture areas on the detector, in order to fix the minimum and maximum amounts of wavefront departure, or the dynamic range of measurement. We introduce an active approach, named Adaptive Shack Hartmann Wavefront Sensor (A-SHWFS). A-SHWFS is used to reconfigure detection subaperture areas by either blocking or unblocking desired lenslets by using an electronically modulated mask. This mask either increases or decreases the measurable aberration magnitude by placing a liquid crystal display (LCD) panel in front of the lenslet array. Depending on which control signal that is sent to the LCD, the variable, application-dependent blocking pattern (horizontal, vertical, diagonal, uneven) makes this an adaptive and efficient sensor with a variable dynamic range of measurement. This scheme is also useful for regional blocking, which occurs when the wavefront is severely aberrated in a limited region.

Model-free deflectometry for freeform optics measurement using an iterative reconstruction technique.

We present a novel model-free iterative data-processing approach that improves surface reconstruction accuracy for deflectometry tests of unknown surfaces. This new processing method iteratively reconstructs the surface, leading to reduced error in the final reconstructed surface. The method was implemented in a deflectometry system, and a freeform surface was tested and compared to interferometric test results. The reconstructed departure from interferometric results was reduced from 15.80 µm RMS with model-based deflectometry down to 5.20 µm RMS with the iterative technique reported here.