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Hepatotoxicity is one of the most common toxicities observed in non-clinical safety studies of drug candidates, and it is important to understand the hepatotoxicity mechanism to assess the risk of drug-induced liver injury in humans. In this study, we investigated the mechanism of hepatotoxicity caused by 2-[2-Methyl-1-(oxan-4-yl)-1H-benzimidazol-5-yl]-1,3-benzoxazole (DSP-0640), a drug candidate that showed hepatotoxicity characterized by centrilobular hypertrophy and vacuolation of hepatocytes in a 4-week oral repeated-dose toxicity study in male rats. In the liver of rats treated with DSP-0640, the expression of aryl hydrocarbon receptor (AHR) target genes, including Cyp1a1, was upregulated. In in vitro reporter assays, however, DSP-0640 showed only minimal AHR-activating potency. Therefore, we investigated the possibility that DSP-0640 indirectly activated AHR by inhibiting the CYP1 enzyme-dependent clearance of endogenous AHR agonists. In in vitro assays, DSP-0640 showed inhibitory effects on both rat and human CYP1A1 and enhanced rat and human AHR-mediated reporter gene expression induced by 6-formylindolo[3,2-b]carbazole, a well-known endogenous AHR agonist. The possible involvement of CYP1A1 inhibition in AHR activation was also demonstrated with other hepatotoxic compounds tacrine and albendazole. These results suggest that CYP1A1 inhibition-mediated AHR activation is involved in the hepatotoxicity caused by DSP-0640 and that DSP-0640 might induce hepatotoxicity in humans as well. We propose that CYP1A1 inhibition-mediated AHR activation is a novel mechanism for drug-induced hepatotoxicity.

Microsampling (MS) has been increasingly used in toxicity studies reducing animal use for toxicokinetic analysis. However, especially for drugs with hematotoxic properties, the potential effects of MS on hematological parameters and subsequent toxicity assessment should be considered, while such properties are frequently unknown at the discovery stage. Here, we conducted a rat 2-week study of hematotoxic compounds and evaluated the effects of MS on toxicity assessment. Six-week-old female SD rats were orally dosed with vehicle, methylene blue trihydrate (MB: 300 mg/kg/day), or azathioprine (AZP: 12 and 24 mg/kg/day) for 2 weeks. Each treatment group was divided into non-MS and MS subgroups, and in the MS subgroups, 50 μL/time point of blood was collected from the jugular vein at 7 time points each on Days 1 and 13 of dosing. The test items included clinical signs, body weight, urinalysis, hematology, blood chemistry, necropsy, organ weight, and histopathology. In the MB non-MS subgroup, there were low values in red blood cell parameters, high values in reticulocytes and bilirubin, and increased extramedullary hematopoiesis, reflecting hemolytic anemia. In the AZP non-MS subgroup, there were low values of red and white blood cell parameters and decreased cellularity in the bone marrow, reflecting myelosuppression. The effects of MB and AZP were similarly observed in the MS subgroups, and the effects of MS on the toxicological endpoints were generally small. Based on these results, the effects of MS on toxicity assessment were considered to be small in rat toxicity studies even for hematotoxic compounds.

Background: Although clozapine-induced granulocytopenia (CIG) is less severe than clozapine-induced agranulocytosis (CIA), and some patients with CIG may not go on to develop serious complications, clozapine is discontinued in cases of both CIA and CIG. Understanding the pathogenic mechanisms of CIA/CIG could provide better management of clozapine therapy. Recently, as a mechanistic insight into adaptive immune systems, European groups reported clozapine-specific proliferative responses and clozapine-specific T cells using blood taken from patients with CIA and/or CIG. Aims: The aims of our study are to support this mechanistic evidence and to investigate the difference in the lymphocyte response to clozapine between patients with CIG and those with CIA. Methods: Lymphocyte stimulation tests (LSTs) were conducted using CD25-positive cell-depleted peripheral blood-derived mononuclear cells (PBMCs) isolated from blood of four Japanese patients with CIA, four patients with CIG, and nine clozapine-tolerant subjects. Results: Three of four patients with CIA and one of four patients with CIG showed proliferative responses to clozapine with a stimulation index of greater than 2. In contrast, none of the nine clozapine-tolerant subjects showed any response to clozapine. Olanzapine did not stimulate PBMCs of patients with CIA, patients with CIG, or clozapine-tolerant subjects. Conclusions: Clozapine- and CIA-specific lymphocyte reactions in a Japanese population provided supportive evidence that the pathogenesis of CIA is based on adaptive immune reactions. In addition, patients with CIG who show a positive response to an LST may at the very least not be chosen for clozapine-rechallenge and further prospective studies are desirable to verify this hypothesis.

Summary Background Agonists of 5‐hydroxytryptamine 4 receptor are potential agents for irritable bowel syndrome with predominant constipation (IBS‐C). However, only tegaserod has been approved for a very limited population in the US. Aim To evaluate the efficacy and safety of minesapride in patients with Rome IV defined IBS‐C. Methods A double‐blind, placebo‐controlled, dose‐finding study was performed. Overall, 411 patients were randomised to receive minesapride at 10, 20 or 40 mg/d, or placebo for 12 weeks. The primary endpoint was Food and Drug Administration (FDA) composite endpoint (responder: a patient who reported an increase in one or more complete spontaneous bowel movements from baseline and improvement of ≥30% from baseline in weekly average of worst abdominal pain score, both in the same week for ≥6/12 weeks). Results The FDA composite responder rate was 13.6% (14/103) in the placebo group, 13.6% (14/103) in the 10 mg group, 19.2% (20/104) in the 20 mg group and 14.9% (15/101) in the 40 mg group, and no dose‐response relationship was found. A greater percentage of minesapride 40 mg‐treated patients than placebo‐treated patients met both responder requirements for ≥9/12 weeks as the stricter composite evaluation (P

Small diameter-deep hole drilling is indispensable when several main parts of which airplane, automobile, machine tool and metal mould are manufactured. Especially, medical appliances, medical implants and surgical operation tools for brain and bone invariably need small diameter-deep hole drilling for hard-to-machine metals such as stainless steel and Ti6Al4V. The authors newly designed and manufactured a small diameter-deep hole drilling machine by applying technological developments which consist of a direct drive servo spindle motor controlled more precisely, removable steady rests to prevent for a slender fluted hollow shaft of gun drill to be deflected and a highly pressure circulation system of cutting fluid to prevent being clogged with chips. By using the small diameter-deep hole drilling machine and a special gun drill (specially made to order in BOTEK) a drilling of ϕ1.0×400 mm (L/D=400) for Ti6Al4V was carried out. As a result, it was ascertained that the drilled hole has high accuracy in the items of hole diameter, concentricity, roundness and inner surface roughness.

We studied the conditions under which c-waves of the electroretinogram (ERG), that represent retinal pigment epithelium (RPE) function, were detectable using an alternating current (AC) amplifier and whether the c-wave recorded using an AC amplifier was useful for evaluating RPE function.We recorded ERG responses in rats to 5 s stimuli under the conditions in which the low-cut frequency and the stimulus luminance were varied. In addition, changes in ERGs were studied after intravenous injection of sodium iodate (SI) to induce RPE degeneration.The c-wave was detected clearly when the frequency of the low-cut filter was set at 0.01 Hz and light stimulus luminances were ≥ - 1.0 log cd/mThe c-wave was easily detectable using an AC amplifier with the low-cut filter set at 0.01 Hz. Using the AC amplifier may allow easier c-wave recording, compared with the conventional use of a direct current (DC) amplifier, and could be useful for evaluating RPE function.

We present the development status of Type II superlattice infrared detector (T2SL) for future space applications in JAXA. Space-borne infrared detectors require higher sensitivity, higher resolution, and larger formats than ground-based infrared detectors. The Geostationary Earth observation satellite is one of mission candidates to adopt T2SL for infrared sensor. In order to meet more demanding for such mission requirements, JAXA has developed T2SL. T2SL has preferable characteristics in terms of operating temperature and spectral sensityivity in the range of near infrared to very long wavelength infrared region. In this presentation, we report the development history of T2SL focal plane array in JAXA.

Promising results of InGaAs/GaAsSb material systems suggest that it is an alternate for extended InGaAs and HgCdTe in the SWIR region. Understanding the dark current that is caused by the deep level will further improve device performance. In this work, photocapacitance under constant capacitance method was used to characterize the deep levels in the InGaAs/GaAsSb type-II quantum well photodiode for the first time. Deep levels are identified at 0.28 eV, 0.32–0.34 eV, 0.47 eV, and 0.65 eV from the photocapacitance results. Deep levels at 0.28 eV, 0.47 and 0.65 eV are from the InGaAs layers, possibly donor like defect. Deep levels at 0.32–0.34 eV are from the GaAsSb layer contribution, possibly acceptor like defect. Estimated deep level density of the type-II InGaAs/GaAsSb MQW sample is around 1 × 1014 cm−3.

We have successfully fabricated extended SWIR photodetectors with the cutoff wavelength of 2.5 μm by using InGaAs (-0.3 %)/GaAsSb(+0.3 %) strain compensated type-II quantum wells as an absorption layer. The 250-pair InGaAs/GaAsSb quantum wells were grown on an InP substrate by metal organic vapor phase epitaxy. The p-n junction was formed in the absorption layer by selective zinc diffusion. Dark current was low and showed diffusion current limited mode. Quantum efficiency in the wavelength region between 2.0 μm and 2.5 μm which corresponds to the type-II absorption became twice as high as that of the normal lattice-matched InGaAs/GaAsSb type-II quantum wells.

Nanoimprint lithography manufacturing equipment utilizes a patterning technology that involves the field-by-field deposition and exposure of a low viscosity resist deposited by jetting technology onto the substrate. The patterned mask is lowered into the fluid which then quickly flows into the relief patterns in the mask by capillary action. Following this filling step, the resist is crosslinked under UV radiation, and then the mask is removed, leaving a patterned resist on the substrate. The technology faithfully reproduces patterns with a higher resolution and greater uniformity compared to those produced by photolithography equipment. Additionally, as this technology does not require an array of widediameter lenses and the expensive light sources necessary for advanced photolithography equipment, NIL equipment achieves a simpler, more compact design, allowing for multiple units to be clustered together for increased productivity. In this paper, we review the progress and status of the FPA-1100NR2 mask replication system and also discuss the methods used on wafer imprint systems to extend the life of a replica mask. Criteria that are crucial to the success of a replication platform include image placement (IP) accuracy and critical dimension uniformity (CDU). Data is presented on both of these subjects. With respect to image placement, an IP accuracy (after removing correctables) of 0.8nm in X, 1.0nm in Y has been demonstrated. Particle adders were studied by cycling the tool for more than 16000 times and measuring particle adders. Additionally, new methods, including on-tool wafer inspection and in-situ mask cleaning are being studied to further extend the replica mask life.

We present an experimental result of absorption and external quantum efficiency measurements of an InAs/GaSb Type II superlattice (T2SL). The probed T2SL sample consisted of a 6 μm cutoff p–i–n diode having a 300-period superlattice with a 9-monolayer (ML) GaSb /0.9 ML InSb/7 ML InAs on a p-type GaSb substrate.\nThe absorption quantum efficiency is estimated from the sample transmission at 87 K. We prepared three T2SL samples using GaSb substrates of different thicknesses: 150, 100, and 50 μm. By comparing the transmission spectra of these samples to that of a 100 μm thick GaSb substrate, we derived the absorption coefficient and the absorption quantum efficiency of the T2SL sample. We also discuss the refractive index of T2SL using a thin-film interference method together with the transmission measurements.\nThe external quantum efficiency is measured with a p–i–n detector using the T2SL sample having the same design. The detector consists of a 50-period p-type (Be: 1 × 1017 cm−3) SL, a 200-period undoped SL as absorbing layer, and a 50-period n-type (Si: 1 × 1017 cm−3) SL. The detector responsivity is 0.4 A/W at 4.5 μm and the quantum efficiency is 17% at 30 K.\nThe absorption quantum efficiency was 25% at 4.5 μm when we employed the complete T2SL (300-period T2SL). However, it became 18% when we used the absorption layer (200-period T2SL), which is consistent with the measured external quantum efficiency. This result suggests that almost all the carriers generated in the absorption layer are collected., 資料番号: PA1510066000

Liquid crystals (LCs) of large macrocyclic compounds are a plausible platform in which to organize included guest molecules regularly in a flowable medium. Herein, a series of metallomacrocycles with different peripheral alkyl chains were synthesized through a 3:3 self-assembly based on metal complexation between naphthalene-2,7-dihydroxamic acid and Cu2+ ions. The crystallinity and liquid crystallinity of the macrocycles sharply depend on the structure of the peripheral alkyl chains. The metallomacrocycle with six hexyl chains has only the crystalline phase, whereas the metallomacrocycles with more and longer side chains exhibit LC mesophases. Most notably, oligo(ethylene glycol) side chains effectively assemble the macrocycle into an ordered lamellar structure.

Short wavelength infrared (SWIR) focal plane array (FPA), has an attractive application such as night vision, chemical sensing, remote monitoring of infrastructure and so on. In spite of the many trials on alternative material, FPA with HgCdTe (MCT) keep predominant position in SWIR region, especially over wavelength of 1.7μm. However, MCT is not suitable for commercial application due to its containing environmentally hazardous substances. For a commercial use, so far, Sumitomo Electric has developed FPA with InGaAs/GaAsSb type-II quantum well structures, which are based on maturity of III-V compound semiconductor epitaxial and device fabrication technology. Recently, we have successfully extended cutoff-wavelength up to 2.5μm, which showed comparable spectral range to MCT. By adopting asymmetrically the thicker layer of InGaAs in quantum wells, we modified spectral response related to the type-II transition in the quantum well. The 250-pair InGaAs/GaAsSb quantum wells structure lattice-matched InP substrates were grown by metal organic vaper phase epitaxy. The p-n junction of each pixel was formed by selective zinc diffusion. Dark current density was less than 1μA/cm2 at 213K, which means comparably to low dark current of MCT. Temperature dependence of dark current density showed diffusion current limited mode. These results means InGaAs/GaAsSb type-II FPA is a promising candidate for commercial applications. In the presentation, we will report the characteristics of InGaAs/GaAsSb type-II quantum well and the operational results of SWIR FPA.

Turner syndrome results from the entire or partial loss of the second X chromosome, and is associated with a number of medical problems. Affected women require long-term medical follow-up. This study investigated the status of medical follow-up focusing on the transition for young adult women with Turner syndrome (TS). The clinical profiles of 63 women with TS over the age of 16 were retrospectively examined. Thirty-three women are continuously followed by pediatric endocrinologists at our pediatric division. Twenty women were transferred to gynecologists as primary care physicians. Eight young adult women dropped out of the regular health check-up from our pediatric division even though 7 women were undergoing estrogen replacement therapy. We further reviewed the complications and management of the 33 women who were continuously followed at our pediatric division. A high incidence of obesity and liver dysfunction were observed in this age group (23.5±8.7). Nineteen out of 33 women consulted a cardiologist in the adult care division for cardiovascular complications. In the analysis of 20 women who were transferred to gynecologists, mainly two gynecologists accepted the transfer and have become accustomed to clinical care for TS. Seven women who were followed by the gynecologist in our facility were adequately managed for lifelong complications. Since there is no clear framework for transition in Japan, coordination with other specialists, especially gynecologists, is essential for the successful management of adult women with TS. Patient education and provision of information are required for establishing self-advocacy, which will prevent drop-out.

The authors estimate signal-to-noise ratios (SNRs) and contrasts for both InGaAs SWIR camera (cut-off wavelength λ co ~1.7 μm) and type II superlattice (T2SL) SWIR camera (λ co ~2.3 μm), under such situations as human skin as an object and vegetation as surroundings which are illuminated only by OH night airglow. In estimating the number of signal electrons, the measured spectral properties of quantum efficiencies for both InGaAs and T2SL detectors are used along with reflectance spectra of human skin and materials, while atmospheric transmission spectra are calculated with MODTRAN. As to noise electrons, shot noise resulting from dark current of InGaAs or T2SL detector is added to photon noise and ROIC (Read-Out Integrated Circuit) noise. The SNR values for the T2SL camera are found larger than those for the InGaAs camera. The contrasts of human skin vs surroundings are positive for the T2SL camera, while those for the InGaAs camera are negative.

One of JAXA’s future missions, using an imaging Fourier Transform Spectrometer (FTS), requires the focal plane array (FPA) that has high sensitivity up to the very long-wavelength infrared (VLWIR) region. Since a Type-II superlattice (T2SL) is the only known infrared material to exhibit performance that is theoretically predicted to be higher than that of HgCdTe additionally the cutoff wavelength can be tailored in the wavelength region of 3-30 μm, we started the research and development of the T2SL detector in 2009. In order to confirm our final goal, which is to realize the FPA with a cutoff wavelength of 15 μm, we first fabricated the 320 × 256 (QVGA format) InAs/GaInSb T2SL FPA with a cutoff wavelength of 15 μm, and the large-format 640 × 512 (VGA format) T2SL FPA is followed because the other missions, using an infrared imager, require the large-format FPA. The noise-equivalent delta temperature measured with F1.4 optics was 0.15 K for QVGA format T2SL FPA at 77 K. It was 0.35 K for VGA format T2SL FPA at 77 K, but there is non-uniformity, and further improvements are necessary to achieve high performance FPAs.

In the short wavelength infrared (SWIR) region, InGaAs/GaAsSb type-II quantum well absorption structures are proposed as an attractive material for realizing low dark current. Recently QVGA format (array size 320×256) focal plane array (FPA) with cutoff-wavelength of 2.35 μm was demonstrated for commercial use by our group. We succeeded in extending cut-off wavelength of FPA consisting of InGaAs/GaAsSb type-II quantum well up to 2.5 μm. The 250-pairs InGaAs/GaAsSb quantum well structure lattice matched to InP substrate was grown by metal organic vapor phase epitaxy (MOVPE). The p-n junction of each pixel was formed by selective zinc diffusion method. Dark current of pixel showed the diffusion current limited mode and slightly better than that of HgCdTe with a same cutoff-wavelength. We present the electrical and optical characteristics of InGaAs/GaAsSb type-II quantum well FPA with cutoff-wavelength of 2.5 μm.

The zebrafish has been considered as a suitable animal model for drug discovery, especially for evaluation of the teratogenicity, due to their small size, rapid development, transparency, and developmental similarities to mammalian development. These features of zebrafish make it possible to maintain them in culture plates, evaluate the teratogenicity in short term, conduct morphological assessment of each organ without any autopsy operation. The purpose of the present study was to improve an evaluation method for the teratogenicity of test compounds with high throughput ability and prediction rateusing zebrafish embryos. In this study, we established a modified evaluation method as using non-dechorionated embryos and observation a limited number of parameters without grading. Zebrafish embryos were exposed to test compounds from 5-6 to 144 hr post-fertilization, (hpf) corresponding to the organogenesis period. Morphological changes or functional abnormalities induced by test compound treatments were assessed and scored at 11 endpoints, and the potential of teratogenicity was judged based on the score. As a validation assay of the system, the potentials of 59 known teratogenic or non-teratogenic test compounds were evaluated using the present standard zebrafish assay, and the teratogenicity was correctly predicted in 90% (53/59) of all compounds with low false negative and false positive rates. These results indicated that the evaluation method using zebrafish for the teratogenicity we have improved was a valuable tool for early stage screening in drug discovery.

Clobazam (CLB) is known to increase hepatobiliary thyroxine (T4) clearance in Sprague-Dawley (SD) rats, which results in hypothyroidism followed by thyroid follicular cell hypertrophy. However, the mechanism of the acceleration of T4-clearance has not been fully investigated. In the present study, we tried to clarify the roles of hepatic UDP-glucronosyltransferase (UGT) isoenzymes (UGT1A and UGT2B) and efflux transporter (multidrug resistance-associated protein-2; MRP2) in the CLB-induced acceleration of T4-clearance using two mutant rat strains, UGT1A-deficient mutant (Gunn) and MRP2-deficient mutant (EHBR) rats, especially focusing on thyroid morphology, levels of circulating hormones (T4 and triiodothyronine (T3)) and thyroid-stimulating hormone (TSH), and mRNA or protein expressions of UGTs (Ugt1a1, Ugt1a6, and Ugt2b1/2) and MRP2 (Mrp). CLB induced thyroid morphological changes with increases in TSH in SD and Gunn rats, but not in EHBR rats. T4 was slightly decreased in SD and Gunn rats, and T3 was decreased in Gunn rats, whereas these hormones were maintained in EHBR rats. Hepatic Ugt1a1, Ugt1a6, Ugt2b1/2, and Mrp2 mRNAs were upregulated in SD rats. In Gunn rats, UGT1A mRNAs (Ugt1a1/6) and protein levels were quite low, but UGT2B mRNAs (Ugt2b1/2) and protein were prominently upregulated. In SD and Gunn rats, MRP2 mRNA and protein were upregulated to the same degree. These results suggest that MRP2 is an important contributor in development of the thyroid cellular hypertrophy in CLB-treated rats, and that UGT1A and UGT2B work in concert with MRP2 in the presence of MRP2 function to enable the effective elimination of thyroid hormones.

We present the development status of Type II superlattice (T2SL) infrared detector in JAXA. Since 2009, we have started a basic research on InAs/GaSb T2SL infrared detectors. Our final goal is to realize the T2SL array detector having a cutoff wave length of λc=15 μm. In order to confirm a technical feasibility of 15 μm cutoff T2SL detector, we fabricated T2SL samples having a different thickness of InAs/ 7 monolayers (ML) GaSb. These crystals are designed for the cutoff wavelength from 6 μm to 15 μm. The X-ray Diffraction measurement shows a mismatch between the substrate and superlattice layers is below 0.006%. The surface morphology of the samples with an atomic force microscope is 1.5-3.3 A RMS for 5×5 μm square regions. We also fabricated single pixel detectors with these crystals. We show the results of the spectral response measurement using a FTIR system. We also show the development status of an array detector. The array detector having the cutoff wavelength of 6 μm is successfully demonstrated. However, further improvements are required for a future 15 μm cutoff array detector.

HgCdTe (MCT) is predominantly used for infrared imaging applications even in SWIR region. However, MCT is expensive and contains environmentally hazardous substances. Therefore, its application has been restricted mainly military and scientific use and was not spread to commercial use. InGaAs/GaAsSb type-II quantum well structures are considered as an attractive material for realizing low dark current PDs owing to lattice-matching to InP substrate. Moreover, III-V compound material systems are suitable for commercial use. In this report, we describe successful operation of focal plane array (FPA) with InGaAs/GaAsSb quantum wells and mention improvement of optical characteristics. Planar type pin-PDs with 250-pairs InGaAs(5nm)/GaAsSb(5nm) quantum well absorption layer were fabricated. The p-n junction was formed in the absorption layer by the selective diffusion of zinc. Electrical and optical characteristics of FPA or pin-PDs were investigated. Dark current of 1μA/cm 2 at 210K, which showed good uniformity and led to good S/N ratio in SWIR region, was obtained. Further, we could successfully reduce of stray light in the cavity of FPA with epoxy resin. As a result, the clear image was taken with 320x256 format and 7% contrast improvement was achieved. Reliability test of 10,000 heat cycles was carried out. No degradations were found in FPA characteristics of the epoxy coated sample. This result means FPA using InGaAs/GaAsSb type-II quantum wells is a promising candidate for commercial applications.

The cutoff wavelength of 6μm is preferable for the full usage of the atmospheric window in the mid-wavelength region. An InAs/GaSb type-II superlattice (T2SL) is the only known infrared material that has a theoretically predicted high performance and also the cutoff wavelength can be easily controlled by changing the thickness of InAs and GaSb. In this study, we used a p-i-n structure with InAs/GaSb T2SL absorber and also barrier layers which was grown on a Tedoped GaSb substrate by molecular beam epitaxy. A mesa-type focal plane array (FPA) with 320×256 pixels and 30μm pixel pitch was fabricated. Mesa structures were formed by inductively coupled plasma reactive ion etching with halogen gas mixture. Prior to the deposition of the SiO2 passivation film, N2 plasma treatment was applied for reducing the dark currents. Measured dark current of the sensor was 4x10-7A/cm2 at temperature of 77K and reverse bias of -20mV. The quantum efficiency was 0.35 and the detectivity was 4.1x1012cm/Hz1/2W. The sensor array was hybridized with the commercially available readout integrated circuit using indium bumps. The noise equivalent differential temperature measured with F/2.3 optics was 31mK at 77K. The operability was over 99%. This FPA is suitable for full usage of the atmospheric window in the mid-wavelength region.

Stray light in focal plane array (FPA) deteriorates the accuracy of hyper spectral imaging. Multiple reflections between FPA window and peripheral region of a sensor chip are considered to be the major sources of stray light. One idea for suppressing the stray light is to shield the incident light on the peripheral region of the sensor chip by narrowing the FPA window. However, it is limited by the tolerance of assembly. In this study we have examined an epoxy coating on the peripheral region such as ROIC contact pad area, AlN substrate and bonding wire. Sensor chip with InGaAs/GaAsSb type-II quantum well structures, which has the cut-off wavelength of 2.35 μm, 320×256 pixels were bonded to ROIC through indium bumps, assembled to AlN substrate and to a four stage TEC. To avoid the degradation by the stress to the chip and bonding wire, low elastic modulus epoxy was selected. Stray light suppression was confirmed by the sensor signal output of epoxy coated samples, 3% contrast improvement was achieved. Further, reliability test of 10,000 heat cycles between -75°C and 25°C was carried out. No degradations were found in sensor characteristics of the epoxy coated sample. These results suggest that the epoxy coating in SWIR FPA is effective in suppressing the stray light and suitable for hyper spectral imaging.

Historical control data on rabbit prenatal developmental toxicity studies, performed between 1994-2010, were obtained from 20 laboratories, including 11 pharmaceutical and chemical companies and nine contract laboratories, in Japan. In this paper, data were incorporated from a laboratory if the information was based on 10 studies or more. Japanese White rabbits and New Zealand White rabbits were used for prenatal developmental toxicity studies. The data included maternal reproductive findings at terminal cesarean sections and fetal findings including spontaneous incidences of morphological alterations. No noticeable differences between strains or laboratories were observed in the maternal reproductive and fetal developmental data. The inter-laboratory variations in the incidences of fetal external, visceral, and skeletal alterations seem to be due to differences in the selection of observation parameters, observation criteria, and classification of the findings, and terminology of fetal alterations.

In squid jigging operations for neon flying squid ( Ommastrephes bartramii ), 30–40% of hooked squid are estimated to fall off (i.e., become detached) from the jigs during the drum-hauling process, caused by breakage/severance of the hooked tentacle(s). Reducing fall-off events can lead to higher productivity and more efficient use of the squid resource. In the present study, there were 950 fall-off events either directly observed or assessed from the residue of tentacle(s) left on the jigs compared with the 1720 total captures, which comprises 35.6% of 2670 total hooked squids. The fall-off ratio according to the mantle length ( ML ) was examined using logistic curve analysis and a higher fall-off ratio for smaller squid was confirmed through size selectivity curve analysis. F 50 , the 50% probability of fall off from the jig, was estimated to be 37.4 cm ML . The breaking strength of a single tentacle was determined to be similar to the body weight ( BW ) of squid smaller than 41.4 cm ML , indicating a high possibility of tentacle breakage in the case of 1 tentacle grabbing the jig for smaller-sized squid.