Calibration of the AKARI Far-Infrared Imaging Fourier Transform Spectrometer

The Far-Infrared Surveyor (FIS) onboard the AKARI satellite has a spectroscopic capability provided by a Fourier transform spectrometer (FIS-FTS). FIS-FTS is the first space-borne imaging FTS dedicated to far-infrared astronomical observations. We describe the calibration process of the FIS-FTS and discuss its accuracy and reliability. The calibration is based on the observational data of bright astronomical sources as well as two instrumental sources. We have compared the FIS-FTS spectra with the spectra obtained from the Long Wavelength Spectrometer (LWS) of the Infrared Space Observatory (ISO) having a similar spectral coverage. The present calibration method accurately reproduces the spectra of several solar system objects having a reliable spectral model. Under this condition the relative uncertainty of the calibration of the continuum is estimated to be $\pm$ 15% for SW, $\pm$ 10% for 70-85 cm^(-1) of LW, and $\pm$ 20% for 60-70 cm^(-1) of LW; and the absolute uncertainty is estimated to be +35/-55% for SW, +35/-55% for 70-85 cm^(-1) of LW, and +40/-60% for 60-70 cm^(-1) of LW. These values are confirmed by comparison with theoretical models and previous observations by the ISO/LWS.Comment: 22 pages, 10 figure

Pancreatic insulin release in vitamin C-deficient senescence marker protein-30/gluconolactonase knockout mice

We recently identified senescence marker protein-30 as the lactone-hydrolyzing enzyme gluconolactonase, which is involved in vitamin C biosynthesis. In this study, we investigated the effects of vitamin C on insulin secretion from pancreatic β-cells using senescence marker protein-30/gluconolactonase knockout mice. In intraperitoneal glucose tolerance tests, vitamin C-deficient senescence marker protein-30/gluconolactonase knockout mice demonstrated impaired glucose tolerance with significantly lower blood insulin levels at 30 and 120 min post-challenge than in wild type mice (p<0.01–0.05). In contrast, vitamin C-sufficient senescence marker protein-30/gluconolactonase knockout mice demonstrated significantly higher blood glucose and lower insulin only at the 30 min post-challenge time point (p<0.05). Senescence marker protein-30/gluconolactonase knockout mice showed enhanced insulin sensitivity regardless of vitamin C status. Static incubation of islets revealed that 20 mM glucose-stimulated insulin secretion and islet ATP production were significantly decreased at 60 min only in vitamin C-deficient SMP30/GNL knockout mice relative to wild type mice (p<0.05). These results indicate that the site of vitamin C action lies between glycolysis and mitochondrial oxidative phosphorylation, while SMP30 deficiency itself impairs the distal portion of insulin secretion pathway

Functional Interplay between P5 and PDI/ERp72 to Drive Protein Folding

The physiological functions of proteins are destined by their unique three-dimensional structures. Almost all biological kingdoms share conserved disulfide-catalysts and chaperone networks that assist in correct protein folding and prevent aggregation. Disruption of these networks is implicated in pathogenesis, including neurodegenerative disease. In the mammalian endoplasmic reticulum (ER), more than 20 members of the protein disulfide isomerase family (PDIs) are believed to cooperate in the client folding pathway, but it remains unclear whether complex formation among PDIs via non-covalent interaction is involved in regulating their enzymatic and chaperone functions. Herein, we report novel functional hetero complexes between PDIs that promote oxidative folding and inhibit aggregation along client folding. The findings provide insight into the physiological significance of disulfide-catalyst and chaperone networks and clues for understanding pathogenesis associated with disruption of the networks.P5 is one of protein disulfide isomerase family proteins (PDIs) involved in endoplasmic reticulum (ER) protein quality control that assists oxidative folding, inhibits protein aggregation, and regulates the unfolded protein response. P5 reportedly interacts with other PDIs via intermolecular disulfide bonds in cultured cells, but it remains unclear whether complex formation between P5 and other PDIs is involved in regulating enzymatic and chaperone functions. Herein, we established the far-western blot method to detect non-covalent interactions between P5 and other PDIs and found that PDI and ERp72 are partner proteins of P5. The enzymatic activity of P5-mediated oxidative folding is up-regulated by PDI, while the chaperone activity of P5 is stimulated by ERp72. These findings shed light on the mechanism by which the complex formations among PDIs drive to synergistically accelerate protein folding and prevents aggregation. This knowledge has implications for understanding misfolding-related pathology

Build-up functionalization of anti-EGFR × anti-CD3 bispecific diabodies by integrating high-affinity mutants and functional molecular formats

Designing non-natural antibody formats is a practical method for developing highly functional next-generation antibody drugs, particularly for improving the therapeutic efficacy of cancer treatments. One approach is constructing bispecific antibodies (bsAbs). We previously reported a functional humanized bispecific diabody (bsDb) that targeted epidermal growth factor receptor and CD3 (hEx3-Db). We enhanced its cytotoxicity by constructing an Fc fusion protein and rearranging order of the V domain. In this study, we created an additional functional bsAb, by integrating the molecular formats of bsAb and high-affinity mutants previously isolated by phage display in the form of Fv. Introducing the high-affinity mutations into bsDbs successfully increased their affinities and enhanced their cytotoxicity in vitro and in vivo. However, there were some limitations to affinity maturation of bsDb by integrating high-affinity Fv mutants, particularly in Fc-fused bsDb with intrinsic high affinity, because of their bivalency. The tetramers fractionated from the bsDb mutant exhibited the highest in vitro growth inhibition among the small bsAbs and was comparable to the in vivo anti-tumor effects of Fc-fused bsDbs. This molecule shows cost-efficient bacterial production and high therapeutic potential

Spatial correlation of aftershock locations and on-fault main shock properties

[1] We quantify the correlation between spatial patterns of aftershock hypocenter locations and the distribution of coseismic slip and stress drop on a main shock fault plane using two nonstandard statistical tests. Test T1 evaluates if aftershock hypocenters are located in low‐slip regions (hypothesis H1), test T2 evaluates if aftershock hypocenters occur in regions of increased shear stress (hypothesis H2). In the tests, we seek to reject the null hypotheses H0: Aftershock hypocenters are not correlated with (1) low‐slip regions or (2) regions of increased shear stress, respectively. We tested the hypotheses on four strike‐slip events for which multiple earthquake catalogs and multiple finite fault source models of varying accuracy exist. Because we want to retain earthquake clustering as the fundamental feature of aftershock seismicity, we generate slip distributions using a random spatial field model and derive the stress drop distributions instead of generating seismicity catalogs. We account for uncertainties in the aftershock locations by simulating them within their location error bounds. Our findings imply that aftershocks are preferentially located in regions of low‐slip (u ≤ equation imageu max) and of increased shear stress (Δσ < 0). In particular, the correlation is more significant for relocated than for general network aftershock catalogs. However, the results show that stress drop patterns provide less information content on aftershock locations. This implies that static shear stress change of the main shock may not be the governing process for aftershock genesis.ISSN:2169-9313ISSN:0148-0227ISSN:2169-935

Development of fully automated and ultrasensitive assays for urinary adiponectin and their application as novel biomarkers for diabetic kidney disease

Glomerular filtration rate (GFR) and urinary albumin excretion rate (UAER) are used to diagnose and classify the severity of chronic kidney disease. Total adiponectin (T-AN) and high molecular weight adiponectin (H-AN) assays were developed using the fully automated immunoassay system, HI-1000 and their significance over conventional biomarkers were investigated. The T-AN and H-AN assays had high reproducibility, good linearity, and sufficient sensitivity to detect trace amounts of adiponectin in the urine. Urine samples after gel filtration were analyzed for the presence of different molecular isoforms. Low molecular weight (LMW) forms and monomers were the major components (93%) of adiponectin in the urine from a diabetic patient with normoalbuminuria. Urine from a microalbuminuria patient contained both high molecular weight (HMW) (11%) and middle molecular weight (MMW) (28%) adiponectin, although the LMW level was still high (52%). The amount of HMW (32%) and MMW (42%) were more abundant than that of LMW (24%) in a diabetic patient with macroalbuminuria. T-AN (r = − 0.43) and H-AN (r = − 0.38) levels showed higher correlation with estimated GFR (eGFR) than UAER (r = − 0.23). Urinary levels of both T-AN and H-AN negatively correlated with renal function in diabetic patients and they may serve as new biomarkers for diabetic kidney disease

Performance of the Imaging Fourier Transform Spectrometer with Photoconductive Detector Arrays: An Application for the AKARI Far-Infrared Instrument

We have developed an imaging Fourier transform spectrometer (FTS) for space-based far-infrared astronomical observations. The FTS employs a newly developed photoconductive detector arrays with a capacitive trans-impedance amplifier, which makes the FTS a completely unique instrument. The FTS was installed as a function of the far-infrared instrument (FIS: Far-Infrared Surveyor) on the Japanese astronomical satellite, AKARI, which was launched on February 21, 2006 (UT) from the Uchinoura Space Center. The FIS-FTS had been operated for more than one year before liquid helium ran out on August 26, 2007. The FIS-FTS was operated nearly six hundreds times, which corresponds to more than one hundred hours of astronomical observations and almost the same amount of time for calibrations. As expected from laboratory measurements, the FIS-FTS performed well and has produced a large set of astronomical data for valuable objects. Meanwhile, it becomes clear that the detector transient effect is a considerable factor for FTSs with photoconductive detectors. In this paper, the instrumentation of the FIS-FTS and interesting phenomena related to FTS using photoconductive detectors are described, and future applications of this kind of FTS system are discussed.Comment: 10 pages, 6 figures, 2 tables, accepted for publication in PASJ AKARI special issu

Physics of Transport and Traffic Phenomena in Biology: from molecular motors and cells to organisms

Traffic-like collective movements are observed at almost all levels of biological systems. Molecular motor proteins like, for example, kinesin and dynein, which are the vehicles of almost all intra-cellular transport in eukayotic cells, sometimes encounter traffic jam that manifests as a disease of the organism. Similarly, traffic jam of collagenase MMP-1, which moves on the collagen fibrils of the extracellular matrix of vertebrates, has also been observed in recent experiments. Traffic-like movements of social insects like ants and termites on trails are, perhaps, more familiar in our everyday life. Experimental, theoretical and computational investigations in the last few years have led to a deeper understanding of the generic or common physical principles involved in these phenomena. In particular, some of the methods of non-equilibrium statistical mechanics, pioneered almost a hundred years ago by Einstein, Langevin and others, turned out to be powerful theoretical tools for quantitaive analysis of models of these traffic-like collective phenomena as these systems are intrinsically far from equilibrium. In this review we critically examine the current status of our understanding, expose the limitations of the existing methods, mention open challenging questions and speculate on the possible future directions of research in this interdisciplinary area where physics meets not only chemistry and biology but also (nano-)technology.Comment: 33 page Review article, REVTEX text, 29 EPS and PS figure

The Far-Infrared Surveyor (FIS) for AKARI

The Far-Infrared Surveyor (FIS) is one of two focal plane instruments on the AKARI satellite. FIS has four photometric bands at 65, 90, 140, and 160 um, and uses two kinds of array detectors. The FIS arrays and optics are designed to sweep the sky with high spatial resolution and redundancy. The actual scan width is more than eight arcmin, and the pixel pitch is matches the diffraction limit of the telescope. Derived point spread functions (PSFs) from observations of asteroids are similar to the optical model. Significant excesses, however, are clearly seen around tails of the PSFs, whose contributions are about 30% of the total power. All FIS functions are operating well in orbit, and its performance meets the laboratory characterizations, except for the two longer wavelength bands, which are not performing as well as characterized. Furthermore, the FIS has a spectroscopic capability using a Fourier transform spectrometer (FTS). Because the FTS takes advantage of the optics and detectors of the photometer, it can simultaneously make a spectral map. This paper summarizes the in-flight technical and operational performance of the FIS.Comment: 23 pages, 10 figures, and 2 tables. Accepted for publication in the AKARI special issue of the Publications of the Astronomical Society of Japa