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Perfluoroalkyls acids (PFAAs) have been emitted in the environment either as manufacturing by products or through degradation of its precursors. Development of efficient identification and quantification of PFAAs in different environmental media is important for environmental and human health risk assessments. In this study, different extraction methods were developed to determine nine (9) different PFAAs in seawater and seawater sandworm Perinereis wilsoni. P. wilsoni extracted using two methods: manual extraction and accelerated solvent extraction (ASE). Solid phase extraction method was used for the clean-up and preconcentration of PFAAs from the marine water samples. High-performace liquid chromatography–tandem mass spectrometry was used to analyze PFAAs concentrations in the samples. Percent recoveries of surrogate (SUR) in marine water samples were between 52 to 72% (blank), 52 to 88% (1 ng), and 56 to 79% (10 ng). Manual extraction of sandworm resulted in 57 to 93% recovery of SUR compounds. ASE extraction gave higher recoveries of SUR compounds (62 to 92%). The developed analytical methods for seawater and sandworm extraction can assure production of good quality PFAAs data.

The association of sarcopenia with cognitive function in its specific domains remains poorly understood.To investigate the association of sarcopenia and its components with neuropsychological performance among patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD).Cross-sectional design.A memory clinic in Japan.The study included 497 MCI/684 AD patients aged 65-89 years.Patients were assessed for muscle mass by bioelectrical impedance analysis, muscle strength by hand grip strength (HGS), and physical performance by timed up and go test (TUG). Sarcopenia was defined as presence of both low muscle strength and low muscle mass. The patients underwent neuropsychological tests, including logical memory, frontal lobe assessment battery, word fluency test, Raven's colored progressive matrices, digit span, and the Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog).The prevalence of sarcopenia in men and women was 24.1% and 19.5%, respectively. In multiple regression analyses adjusting for confounders, unlike in men, sarcopenia was associated with memory function in women (ADAS-cog, memory domain, coefficient = 1.08, standard error (SE) = 0.36), which was thought likely due to the relationship between HGS and memory function (immediate recall of logical memory, coefficient = 0.07, SE = 0.03; ADAS-cog, memory domain, coefficient = -0.10, SE = 0.03). Of the components of sarcopenia in both sexes, HGS and TUG were associated with visuospatial function and frontal lobe function, respectively.The specific association of sarcopenia and its components with cognitive domains may provide the key to elucidating the muscle-brain interactions in AD.

Background Aging‐related degeneration of elastic fibres causes skin wrinkles and loss of elasticity. A correlation has been reported between dermal elastic fibre degradation and wrinkles. However, the mechanism of wrinkle formation is complex and unclear. To establish methods for treating wrinkles, it is necessary to understand the aging‐related morphological alterations underlying elastin fibre degradation or disappearance. Objectives To image and analyse aging‐related three‐dimensional (3D) morphological alterations of elastic fibres in the eyelid and abdominal skin. Methods Excised human eyelid and abdominal skin tissues were examined. The structure of elastic fibres in the skin tissues was examined via nuclear, tropoelastin and fibrillin‐1 immunostaining. Then, 3D imaging was performed using a confocal laser microscope and tissue decolourization technology. Images were analysed using a computational method. Results The decolourization technology made it possible to image elastin fibres in 3D, and we devised a method for analyzing the elastin fibre structure using computational methods. It was quantitatively shown that the eyelid skin has a more complex fibrous structure than the abdomen, and the fibres became curved, shortened and thickened with age. Conclusions We provide a novel 3D analysis method for elastin fibres and report age‐related alterations in elastin fibre structure in the human eyelid and abdominal skin. This method contributes to the understanding of elastin fibre degeneration in more detail than conventional methods. Applying this 3D analysis method to skin tissues will contribute to a better understanding of age‐related changes in fibres and to the development of novel wrinkle treatments.

Background: Nipple-sparing mastectomy (NSM) is an increasingly popular surgical procedure for treatment of breast cancer. However, NSM is controversial because of its association with locoregional recurrence. We started performing NSM in 1978. Methods: We investigated the surgical safety including nipple necrosis, and nipple–areola recurrence (NAR) and skin flap recurrence (SFR) after NSM for 1071 patients with breast cancer, including 31 with stage 0, 414 with stage 1, 479 with stage 2, 141 with stage 3 and 6 with stage 4, from 1985 to 2017. Our NSM method involved creating a thick skin flap to avoid surgical complications. No patients received radiotherapy. In 1034 patients with stage 1–3 breast cancer treated with NSM who developed NAR or SFR, we evaluated cancer stage, nuclear grade, lymph node metastasis, tumor–nipple–areola distance, and histological classification as tubule forming, solid and scirrhous type. In 748 patients with early stage 1 and 2A breast cancer treated with NSM, NAR and SFR were evaluated for estrogen receptor and HER2 expression. We evaluated disease-free interval and frequency of late NAR and SFR. Results: Median follow-up after NSM was 87 (3–397) months. There was only one case of total nipple necrosis among all 1071 patients. There were 96 patients (9.0%) with local recurrence, including 44 (4.0%) with NAR and 52 (4.8%) with SFR. NAR was seen in 1 (3.1%), 14 (3.4%), 17 (5.1%), 5 (3.4%), 7 (5.0%) and 0 patients with stage 0, 1, 2A, 2B, 3 and 4 cancer, respectively. SFR was seen in 0, 15 (3.6%), 8 (2.7%), 7 (4.8%), 22 (15.6%) and 0 patients with stage 0, 1, 2A, 2B, 3 and 4 cancer, respectively. Median disease-free interval of NAR and SFR was 3.4 (0.96–22.3) and 2.5 (0.21–21.2) years, respectively. Twenty-three (53%), 12 (27.9%) and 6 (14%) patients had NAR at more than 3, 5 and 10 years after NSM, respectively. Twenty (38%), 13 (25%) and 6 (11.5%) patients had SFR at more than 3, 5 and 10 years after NSM, respectively. Therefore, late NAR and SFR were observed. Patients with stage 1–3 cancer treated with NSM who had significantly more frequent NAR, were characterized by high nuclear grade and tubule-forming type cancer. Patients with significantly more frequent SFR were characterized by stage 3 cancer, positive lymph node metastasis and age ≤40 years. Patients with early stage breast cancer treated with NSM with significantly more frequent NAR had negative estrogen receptor expression, positive HER2 expression and shorter tumor–nipple–areola distance (≤2 cm). Overall survival was significantly better in patients with NAR (97% at 5 years and 80% at 10 years) than SFR (71% at 5 years and 50% at 10 years). Regarding SFR, overall survival was significantly worse for multiple (≥2) and diffuse (clinical inflammatory syndrome) recurrence than for single-nodule recurrence. There was no significant difference in prognosis between NAR and single-nodule SFR. Conclusions: Our data showed that clinicopathological features and prognosis differed between patients with NAR and SFR. There was no significant difference in prognosis between NAR and single-nodule SFR. Late NAR and SFR were seen, and careful long-term follow-up observation is necessary after NSM. Citation Format: Sakurai T, Suzuma T, Yoshimura G, Sasaki E, Umemura T, Sakurai T. Clinicopathological features and prognosis of nipple–areola and skin flap recurrence after nipple-sparing mastectomy for breast cancer over 20 years [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-08.

We present here a study of the magnetic properties of the antiferromagnetic dimer material CuVOF$_4$(H$_2$O)$_6\cdot$H$_2$O, in which the dimer unit is composed of two different $S = 1/2$ species, Cu(II) and V(IV). An applied magnetic field of $\mu_0H_{\rm c1} = 13.1(1)~\rm T$ is found to close the singlet-triplet energy gap, the magnitude of which is governed by the antiferromagnetic intradimer, $J_0 \approx 21~\rm K$, and interdimer, $J' \approx 1~\rm K$, exchange energies, determined from magnetometry and electron-spin resonance measurements. The results of density functional theory (DFT) calculations are consistent with the experimental results and predicts antiferromagnetic coupling along all nearest-neighbor bonds, with the magnetic ground state comprising spins of different species aligning antiparallel to one another, while spins of the same species are aligned parallel. The magnetism in this system cannot be accurately described by the overlap between localized V orbitals and magnetic Cu orbitals lying in the Jahn-Teller (JT) plane, with a tight-binding model based on such a set of orbitals incorrectly predicting that interdimer exchange should be dominant. DFT calculations indicate significant spin density on the bridging oxide, suggesting instead an unusual mechanism in which intradimer exchange is mediated through the O atom on the Cu(II) JT axis., Comment: Main - 12 pages, 11 figures. Supplemental Information - 11 pages, 11 figures; V2 - Corrected typo in author list

We have prepared polycrystalline samples of RE2Au3Sn6 (RE = Ce, La) and investigated their magnetic, transport and thermal properties. We found that Ce2Au3Sn6 shows antiferromagnetic transition at T N = 2.54 K, while La2Au3Sn6 shows no phase transition above 0.4 K. The electronic specific heat coefficient of Ce2Au3Sn6 is γ = 350 mJ Ce-mol K2, which indicates that Ce2Au3Sn6 is a heavy fermion compound. The magnetic entropy of Ce2Au3Sn6 at T N is estimated to be 70% of Rln2, which can be attributed to the shielding of the magnetic moment by the Kondo effect.

Magnetic and transport properties of a new cubic compound CeMgZn2 have been examined by measuring the magnetic susceptibility, the magnetization, the electrical resistivity, and the specific heat. CeMgZn2 is a Kondo-lattice compound with trivalent Ce ions. The magnetic susceptibility measured at 0.1 T exhibits a shoulder and a cusp at T N1 = 5.4 K and T N2 = 3.1 K, respectively. T N1 and T N2 correspond to the antiferromagnetic-transition temperatures since these temperatures decrease with increasing magnetic field. The large value of the paramagnetic Curie temperature divided by T N1 (13.5) implies that T N1 is suppressed by geometrical frustration on a face-centered cubic Ce sublattice. The geometrical frustration may also be responsible for the appearance of many magnetic phases in magnetic fields.

Magnetic, transport, and thermal properties of new orthorhombic compounds Ce4Pt9Al13 and Ce4Pt9Al13 have been investigated by the magnetization, the electrical resistivity, and the specific-heat measurements. Ce4Pt9Al13 is a Kondo-lattice compound and shows a ferromagnetic or ferrimagnetic transition at T C = 0.88 K. Pr4Pt9Al13 is an antiferromagnetic compound with the transition temperature at T N = 2.6 K.

We have synthesized polycrystalline samples of a new orthorhombic compound Ce2lr3Sb4 and investigated their physical properties by measuring the magnetization, the electrical resistivity, and the specific heat down to 0.4 K. From the results of electrical resistivity measurements, it was found that Ce2Ir3Sb4 is a Kondo lattice compound. We found that Ce2Ir3Sb4 does not show any phase transition down to 0.4 K. The specific heat peak at 1.3 K is not due to a phase transition but due to the Schottky specific heat caused by the crystalline electric field splitting of the 4f level of Ce ions.

We have synthesized polycrystalline samples of CePtAl2 by arc melting method and examined their magnetic, transport and thermal properties by measuring the magnetization, the electrical resistivity, and the specific heat down to 0.4 K. As a result of these measurements, we found that CePtAl2 is a ferromagnetic Ce-based compound with the Curie-temperature Tc = 2.7 K.

We have fabricated and investigated the optical properties of highly lattice mismatched AlInSb thermophotovoltaic cells grown on GaAs substrates. Defects, such as dislocations and surface damage, were minimized by controlling the strain of the film structure and by using a silicon nitride passivation layer. An output power density of 9.7 mW cm−2 was achieved under 1000 °C blackbody radiation with an incident power density of 1.63 W cm−2, which gave a power conversion efficiency of 0.59 %. Optimal efficiency of above 5% was estimated by a simulation using recombination parameters obtained from electroluminescence analysis. Additionally, a six-fold increase in spectral efficiency was confirmed by using a 3.3 μm monochromatic light source, which indicated that a thermophotovoltaic cell with a high efficiency of more than 30% would be possible in combination with wavelength-selective emitter.

Frankliniella cephalica (Crawford) is an invasive species of thrips found in the islands of Yaeyama in the Okinawa Prefecture, Japan. During the late 1990s to early 2000s, a species of thrips was isolated from wild flowers of Bidens pilosa L. and Ipomoea batatas L. growing close to cultivated fields. They were subsequently identified as F. cephalica using fine morphological characteristics with the help of Steve Nakahara (U.S. Department of Agriculture, Beltsville, MD) and Laurence Mound (CSIRO, Australia). Voucher specimens were deposited in the Laboratory of Insect Resources, Faculty of Agriculture, Tokyo University of Agriculture by Shuji Okajima (2). We investigated the ability of F. cephalica to vector Tomato spotted wilt virus (TSWV) by experimentally determining virus transmission efficiency. Newly hatched larvae as much as 12 h old underwent a viral acquisition-access period (AAP) of 24 h, during which they fed on the leaves of Datura stramonium infected with TSWV-O, a Japanese type isolate. Transmission efficiency of adults 4 days after emergence from molt (14 days after the AAP) was determined by a petunia leaf disk assay (3) in which the adults were individually allowed to feed for successive 24-h inoculation access periods (IAP) on two different leaf disks of Petunia × hybrida cv. Polo Blue. Transmission of the virus by the adults was considered positive if at least one of the leaf disks showed viral necrotic spot. We tested 20 randomly selected leaf disks with clear necrotic spots using a simplified rapid immunofilter paper assay. All selected disks were positive for TWSV. The transmission efficiencies were 24.6% for female (n = 57) and 54.4% for male (n = 125) adults. The efficiency was significantly different between sexes (Fisher's exact probability test, P < 0.001). We also examined changes in the virus infection site at different developmental stages in thrips using immunofluorescence microscopy with a polyclonal antibody to N protein of the virus (4). After a 6-h AAP feeding by first instar larvae, the virus was found initially to infect the epithelial cells and then spread throughout the midgut tissue in the second instar larvae 5 days after acquisition of the virus. In viruliferous adults, the virus was present in the salivary glands and on the basement membrane of the midgut tissue. These data indicate that F. cephalica is a new insect vector for TSWV. F. cephalica is a major insect pest of tropical crops in tropical and subtropical coastal belts (1). The presence of a thrips vector in weed hosts surrounding cultivated fields might increase the chance of crops in this habitat becoming infected with viruses. References: (1) M. Lamberts and J. H. Crane. Page 337 in: Advances in New Crops. J. Janick and J. E. Simon, eds. Timber Press, Portland, OR, 1990. (2) M. Masumoto and S. Okajima. Jpn. J. Appl. Entomol. Zool. 48:225, 2004. (3) T. Sakurai et al. Appl. Entomol. Zool. 39:71, 2004. (4) S. Tsuda et al. Ann. Phytopathol. Soc. Jpn. 60:216, 1994.

A semiconductor device including a substrate having a low substrate surface formed in the substrate with a first gentle slope from the substrate surface; a single crystalline layer formed on the low substrate surface nearly level with the substrate surface and having a gentle slope facing the first gentle slope; an optical semiconductor element is constructed using the single crystalline layer. An electronic semiconductor element is constructed using the substrate surface. A wiring layer connects electrodes of the optical semiconductor element and the electronic semiconductor element through the first and the second gentle slopes.

Introduction: Achievement of a good cosmetic outcome is one of the most important goals of surgical treatment of breast cancer. However, most patients must undergo a mastectomy if the outcome of breast-conserving surgery is discordant. All potential techniques that maintain oncological safety should be considered to maximize the cosmetic outcome for patients who require a mastectomy. We began performing nipple-sparing mastectomy (NSM) in 1978. Recent reports have suggested that NSM is oncologically as safe as mastectomy and affords a better cosmetic outcome. Conversely, the surgical complications and recurrence associated with NSM remain controversial. Objective: In the present study, we review the safety of the NSM surgical technique, discuss nipple–areola recurrence and skin flap recurrence after NSM, and compare recurrence and prognosis between NSM and mastectomy based on our long-term follow-up data. Patients and Methods: We retrospectively analyzed 723 patients with early-stage breast cancer who underwent NSM from 1985 to 2007. The patients' median age, tumor size, and tumor–areola distance were 50 y, 2.1 cm, and 1.5 cm, respectively. We used a thick skin flap method to avoid surgical complications including nipple and skin flap necrosis. We analyzed nipple–areola recurrence and skin flap recurrence after NSM. We also analyzed 100 patients who underwent mastectomy for early-stage breast cancer during the same period as those who underwent NSM. We compared the local recurrence rate (LRR), disease-free survival (DFS) rate, and overall survival (OS) rate among all 723 patients who underwent NSM and 100 patients who underwent mastectomy. No patients in either group received radiotherapy. Results: Among all patients who underwent NSM, stage 0, 1, 2A, and 2B disease was present in 21, 320, 253, and 129 patients, respectively. Notably, no nipple necrosis occurred during the average 114-month follow-up period. Local recurrence developed in 49 patients (6.7%), including recurrence at the nipple–areola complex in 24 (3.3%) and recurrence at the skin flap in 25 (3.4%). The average disease-free interval in patients with nipple–areola recurrence was 50 months, and that in patients with skin flap recurrence was 68 months. The clinical features of nipple–areola recurrence were a low rate of ER positivity (27%), high rate of Her2/neu positivity (60%), Paget type recurrence rate of 52%, and small tumor–areola distance (0.5 cm). The clinical features of skin flap recurrence were a relatively high rate of ER positivity (55%), solitary type recurrence rate of 88%, and diffuse type recurrence rate of 12%. The prognosis of diffuse type skin flap recurrence was significantly worse than that of solitary type recurrence (p = 0.01). There were no significant differences between the NSM and mastectomy groups in the LLR (6.7% vs. 4.0%, respectively), 10-y DFS rate (88% vs. 90%, respectively), or 10-y OS rate (92% vs. 91%, respectively). Conclusion: Our long-term follow-up data show that NSM should be considered as an alternative option for mastectomy when the outcome of breast-conserving surgery is discordant in patients with early-stage breast cancer. Citation Format: Sakurai T, Suzuma T, Yoshimura G, Jinta E, Umemura T, Sakurai T. Long-term follow-up of nipple-sparing mastectomy for early-stage breast cancer without radiotherapy: A single-center study at a Japanese institution. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-12-09.

Feedback-controlled electromigration (FCE) has been employed to control atomic junctions with quantized conductance. An FCE scheme is controlled by many parameters, such as the threshold differential conductance GTH, feedback voltage VFB, and voltage step VSTEP. It is considered possible to achieve a precise and stable control of the quantized conductance by automatically optimizing the FCE parameters. This motivated us to develop an approach based on machine learning (ML) to tune the feedback parameters of FCE. The ML system is composed of three kinds of engines, namely, learning, evaluation, and inference. The learning engine performs the FCE procedure with random parameters, collects various experimental data, and updates the database. Subsequently, four variables and a cost function are defined to evaluate the controllability of the quantized conductance. The evaluation engine scores the experimental data by using the defined cost function. Then, the control quality is evaluated in real time during the FCE procedure. The inference engine selects the new FCE parameter according to the evaluated data. These engines determine the optimal parameters without human intervention and according to the situation. Finally, we actually applied this system to the FCE procedure. The parameter is selected from sample data in the database according to the variation in controllability. As a result, the controllability gradually improves during the FCE procedure that uses the ML system. The results indicate that the proposed ML system can evaluate the controllability of the FCE procedure and change the VFB parameter in real time according to the situation.

Some food-derived opioid peptides have been reported to cause diseases, such as gastrointestinal inflammation, celiac disease, and mental disorders. Bifidobacterium is a major member of the dominant human gut microbiota, particularly in the gut of infants. In this study, we evaluated the potential of Bifidobacterium in the degradation of food-derived opioid peptides. All strains tested showed some level of dipeptidyl peptidase activity, which is thought to be involved in the degradation of food-derived opioid peptides. However, this activity was higher in bifidobacterial strains that are commonly found in the intestines of human infants, such as Bifidobacterium longum subsp. longum, B. longum subsp. infantis, Bifidobacterium breve and Bifidobacterium bifidum, than in those of other species, such as Bifidobacterium animalis and Bifidobacterium pseudolongum. In addition, some B. longum subsp. infantis and B. bifidum strains showed degradative activity in food-derived opioid peptides such as human and bovine milk-derived casomorphin-7 and wheat gluten-derived gliadorphin-7. A further screening of B. bifidum strains revealed some bifidobacterial strains that could degrade all three peptides. Our results revealed the potential of Bifidobacterium species in the degradation of food-derived opioid peptides, particularly for species commonly found in the intestine of infants. Selected strains of B. longum subsp. infantis and B. bifidum with high degradative capabilities can be used as probiotic microorganisms to eliminate food-derived opioid peptides and contribute to host health.

Small-cell lung cancer (SCLC) is a subgroup of lung cancer with a high frequency of liver metastasis, which is a predictor of poor prognosis. Diffuse liver metastases of SCLC with no visible nodular lesions in the liver when examined using computed tomography (CT) are relatively rare; however, a few cases with rapid progression to acute liver failure that were diagnosed after death have been reported. In this paper, we report a 63-year-old man with diffuse liver metastases of SCLC that were histologically diagnosed using a transjugular liver biopsy while the patient was alive, even though no lesions were visible during a contrast-enhanced CT examination.

The vehicle travel velocity at pedestrian contact is considered to be an important parameter that affects the crash outcome. To reduce vehicle/pedestrian impact velocity, a collision damage mitigation braking system (CDMBS) using a sensor for pedestrian protection could be an effective countermeasure. The first purpose of this study is to clarify the relation between vehicle travel velocity and pedestrian injury severity due to differences in pedestrians’ ages in actual traffic accidents. The accident analyses were performed using vehicle-pedestrian accident data in 2009 from the database of the Institute for Traffic Accident Research and Data Analysis (ITARDA) in Japan. The result revealed that the fatality risk became higher with the increase in vehicle travel velocity. The second purpose of this study is to determine the safety performance of production vehicles equipped with the CDMBS for pedestrian protection. It was found that the CDMBS was highly effective in reducing the impact velocity from 50 km/h (vehicle travel velocity) to below 17 km/h, that could result in a significant decrease in fatality risk to be 2% or less. Additionally, the authors investigated a detectable zone with respect to a pedestrian’s position in relation to the vehicle. It was shown that the detectable zones for production vehicles tested were limited to be inside the vehicle front width.

The effect of a thrips-non-transmissible Tomato spotted wilt virus (TSWV) on insect–host interactions between thrips and Arabidopsis thaliana was analysed. A wild-type TSWV virulent isolate and a TSWV isolate that induces mild symptoms on inoculated plants (TSWV-Mo) were used in this study, and TSWV-Mo isolate was obtained by single local lesion isolation using Petunia x hybrid after several passages on Nicotiana rustica plants. In transmission test, although wild-type TSWV (TSWV-wt) was transmitted by two thrips species (transmission ratio; Frankliniella occidentalis, 25%; Thrips tabaci, 10%; and T. palmi, 0%), none of the thrips transmitted TSWV-Mo. Feeding damage by F. occidentalis in A. thaliana plants was more extensive on TSWV-wt-infected plants than on TSWV-Mo-infected plants, despite comparable preference. Among the markers of plant defences, salicylic acid-regulated genes were upregulated threefold to sixfold by TSWV-wt or TSWV-Mo infection. In contrast, jasmonate-regulated genes and jasmonate/ethylene-regulated genes were not affected by the infections. Pull assays showed that adjacent TSWV-Mo-infected plants were preferred over uninfected plants. In conclusion, our results showed that the transmissibility by thrips of TSWV is not related to preference of vector thrips and suggested that TSWV-Mo-infected plants may be used as attractants for behaviour control of thrips.

Background and Purpose Melanin-concentrating hormone receptor 1 (MCH1 receptor) antagonists are being considered as anti-obesity agents. The present study reports a new class of MCH1 receptor antagonists with an 8-methylquinoline scaffold. The molecular mechanism of MCH1 receptor blockade by these antagonists was examined. Experimental Approach The pharmacological properties of the 8-methylquinolines as exemplified by MQ1 were evaluated by use of multiple biophysical and cell-based functional assays. Key Results Multiple signalling pathways for Gαi and Gαq, and β-arrestin were inhibited by MQ1. Furthermore, MQ1 produced an insurmountable antagonism, causing a rightward shift of the curve for concentration-dependent binding of MCH along with a progressive reduction of the maximal response. The dissociation kinetics for MQ1 were determined from washout experiments as well as by affinity selection-MS. In short, MQ1 was shown to be a slowly dissociating reversible MCH1 receptor blocker with a low Koff value. Conclusion and Implications This is the first time that a slowly dissociating negative allosteric modulator of the MCH1 receptor has been demonstrated to inhibit the numerous signalling pathways of this receptor. The characteristics of MQ1 are superior and distinct from previously reported MCH1 receptor antagonists, making members of this chemotype attractive as drug candidates.

Electromagnetic-wave sintering of alumina ceramics using 28 GHz gyrotron has been performed aiming for a high fracture toughness value in order for use as pistons for pressure cells of high-frequency electron spin resonance (ESR) measurements. We have tried to improve the fracture toughness by using nano-sized alumina powder (140 nm in average particle size) having smaller particle size than our previous work (400 nm in average particle size). Rapid densification was observed around the sintering temperature of 1200 °C. We obtained the relative density over 99 % above 1400 °C. It was found that alumina ceramics made in this work at sintering temperatures have smaller grain size and higher density simultaneously as compared to the previous work. These results suggest that alumina ceramics made from powder of smaller particle size sintered by electromagnetic-wave sintering possibly have high fracture toughness which can be used as materials for the pressure cell for ESR.

Introduction: Cosmetic outcome is one of the most important goals of surgical treatment for breast cancer. Therefore, to maximize the cosmetic outcome for patients who require a mastectomy, the actions that can be taken from an oncologically safe perspective must be considered. Recent reports have suggested that nipple-sparing mastectomy (NSM) is oncologically as safe as a standard mastectomy and provides a better cosmetic outcome. However, little is known about the outcome of NSM for patients with multifocal breast cancer. Aim: To determine the oncological and technical outcomes of NSM for patients with multifocal breast cancer compared with NSM for patients with unifocal breast cancer using retrospective long-term follow-up data. Patients and Methods: We retrospectively analyzed 799 patients with primary breast cancer who underwent NSM, including 45 patients with multifocal breast cancer and 754 patients with unifocal breast cancer. The indications for NSM in this study were defined as any stage, any tumor size and any tumor–areola distance. Briefly, NSM was performed when no involvement of the nipple areola complex was revealed by radiographic and clinical examinations. Our surgical notes for NSM comprised a thick skin flap method for conserving the breast volume using subcutaneous fat and avoiding surgical complications including nipple necrosis. No patients received radiotherapy. We compared the local recurrence rate (LRR), disease-free survival (DFS), breast cancer-specific survival (BCSS) and overall survival (OS) between the 45 multifocal breast cancer and 754 unifocal breast cancer cases. Results: The numbers of multifocal breast cancer cases in stages 0, 1, 2A, 2B, 3 and 4 were 1, 17, 12, 8, 7 and 0, respectively. The corresponding numbers of unifocal breast cancer cases were 18, 288, 223, 117, 102 and 6, respectively. The median follow-up periods of the multifocal and unifocal breast cancer cases were 108 and 98 months, respectively. No nipple necrosis was recorded in either group (0/45, 0/754). Regarding NSM for patients with multifocal breast cancer, there were 8 patients (17.7%) with local recurrence, including 4 (8.9%) at the nipple and 4 (8.9%) at the skin flap. In NSM for patients with unifocal breast cancer, there were 63 patients (8.3%) with local recurrence, including 26 (3.4%) at the nipple and 37 (4.9%) at the skin flap. There were significant differences between NSM for patients with multifocal and unifocal breast cancer in the LRR (17.7% vs. 8.3%, p = 0.03) and DFS (10 yr, 72.4% vs. 83.8%, p = 0.04), but no significant differences in the BCSS (10 yr, 83.6% vs. 90.9%, p = 0.18) and OS (10 yr, 83.6% vs. 89.5%, p = 0.32). Conclusions: The present results suggest that NSM for patients with multifocal breast cancer can be technically performed as safely as NSM for patients with unifocal breast cancer. Our long-term follow-up data show that survival after NSM for multifocal breast cancer is equal to that after NSM for unifocal breast cancer. However, careful local observation after NSM is required. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-18-08.