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Supplemental Digital Content is available in the text., Major adverse cardiovascular events are closely associated with 24-hour blood pressure (BP). We determined outcome-driven thresholds for 24-hour mean arterial pressure (MAP), a BP index estimated by oscillometric devices. We assessed the association of major adverse cardiovascular events with 24-hour MAP, systolic BP (SBP), and diastolic BP (DBP) in a population-based cohort (n=11 596). Statistics included multivariable Cox regression and the generalized R2 statistic to test model fit. Baseline office and 24-hour MAP averaged 97.4 and 90.4 mm Hg. Over 13.6 years (median), 2034 major adverse cardiovascular events occurred. Twenty-four-hour MAP levels of

Objectives To compare the effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament (ACL) reconstruction animal model. Methods Anterior cruciate ligament reconstruction using the plantaris tendon as graft material was performed on both knees of 24 rabbits (48 knees) to mimic ACL reconstruction by two different suspensory fixation devices for graft fixation. For the adjustable fixation device model (Socket group; group S), a 5 mm deep socket was created in the lateral femoral condyle (LFC) of the right knee. For the fixed-loop model (Tunnel group; group T), a femoral tunnel penetrating the LFC was created in the left knee. Animals were sacrificed at four and eight weeks after surgery for histological evaluation and biomechanical testing. Results Histologically, both groups showed a mixture of direct and indirect healing patterns at four weeks, whereas only indirect healing patterns were observed in both groups at eight weeks. No significant histological differences were seen between the two groups at four and eight weeks in the roof zone (four weeks, S: mean 4.8 sd 1.7, T: mean 4.5 sd 0.5, p = 0.14; eight weeks, S: mean 5.8 sd 0.8, T: mean 4.8 sd 1.8, p = 0.88, Mann-Whitney U test) or side zone (four weeks, S: mean 5.0 sd 1.2, T: mean 4.8 sd 0.4, p = 0.43; eight weeks, S: mean 5.3 sd 0.8,T: mean 5.5 sd 0.8, p = 0.61, Mann-Whitney U test) . Similarly, no significant difference was seen in the maximum failure load between group S and group T at four (15.6 sd 9.0N and 13.1 sd 5.6N) or eight weeks (12.6 sd 3.6N and 17.1 sd 6.4N, respectively). Conclusion Regardless of bone tunnel configuration, tendon-bone healing after ACL reconstruction primarily occurred through indirect healing. No significant histological or mechanical differences were observed between adjustable and fixed-loop femoral cortical suspension methods. Cite this article: Y. Sato, R. Akagi, Y. Akatsu, Y. Matsuura, S. Takahashi, S. Yamaguchi, T. Enomoto, R. Nakagawa, H. Hoshi, T. Sasaki, S. Kimura, Y. Ogawa, A. Sadamasu, S. Ohtori, T. Sasho. The effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament reconstruction: An animal study. Bone Joint Res 2018;7:327–335. DOI: 10.1302/2046-3758.75.BJR-2017-0238.R2.

形態: 図版あり, Physical characteristics: Original contains illustrations, Accepted: 2018-03-25, 資料番号: PA1920025000

In most anterior cruciate ligament (ACL) reconstructions, grafts are fixed to the femoral side first followed by the tibial side. Various techniques have been reported to achieve optimal tension on the grafts, but once the grafts are fixed it is difficult to adjust graft tension further. To enable post fixation tension control we have invented a new graft configuration using an adjustable loop-device (TightRopeTM, Arthrex, FL, USA) on the tibial side. In this paper, biomechanical properties of this configuration using soft tissue were examined in terms of graft diameter and various suture techniques (referred to as base suture) to make a closed circle to support TightRopeTM. Two experiments were conducted under different conditions. In each experiment, cyclic load, followed by a pull-to-failure load, was applied to the grafts and elongation and failure mode were recorded. (1) To evaluate the effects of diameter, 5.0 or 6.0 mm grafts were prepared by a single locking loop stitch as the base suture (SLL5, SLL6). (2) To evaluate different base sutures, 5.0 mm tendons were used, and grafts were prepared using five kinds of base sutures (SLL, ZLL: zigzag locking loop, DZLL: double zigzag locking loop, DK: double Krackow, DK w/o TR: double Krackow without TightRopeTM). In the first experiment, tearing was observed in 2 of 6 cases in the SLL5 test group, whereas no tearing was observed with SLL6. In the second experiment, no tearing was observed with DZLL or DK. Elongation was smaller in these two groups compared to the other groups. Mechanical strength decreases with a smaller graft diameter. Biomechanical properties differed with different base sutures and, among them, the double-zigzag-suture stitch and double Krackow provided less elongation and higher ultimate load in this graft configuration.

Objectives The aim of this study was to investigate the effect of granulocyte-colony stimulating factor (G-CSF) on mesenchymal stem cell (MSC) proliferation in vitro and to determine whether pre-microfracture systemic administration of G-CSF (a bone marrow stimulant) could improve the quality of repaired tissue of a full-thickness cartilage defect in a rabbit model. Methods MSCs from rabbits were cultured in a control medium and medium with G-CSF (low-dose: 4 μg, high-dose: 40 μg). At one, three, and five days after culturing, cells were counted. Differential potential of cultured cells were examined by stimulating them with a osteogenic, adipogenic and chondrogenic medium. A total of 30 rabbits were divided into three groups. The low-dose group (n = 10) received 10 μg/kg of G-CSF daily, the high-dose group (n = 10) received 50 μg/kg daily by subcutaneous injection for three days prior to creating cartilage defects. The control group (n = 10) was administered saline for three days. At 48 hours after the first injection, a 5.2 mm diameter cylindrical osteochondral defect was created in the femoral trochlea. At four and 12 weeks post-operatively, repaired tissue was evaluated macroscopically and microscopically. Results The cell count in the low-dose G-CSF medium was significantly higher than that in the control medium. The differentiation potential of MSCs was preserved after culturing them with G-CSF. Macroscopically, defects were filled and surfaces were smoother in the G-CSF groups than in the control group at four weeks. At 12 weeks, the quality of repaired cartilage improved further, and defects were almost completely filled in all groups. Microscopically, at four weeks, defects were partially filled with hyaline-like cartilage in the G-CSF groups. At 12 weeks, defects were repaired with hyaline-like cartilage in all groups. Conclusions G-CSF promoted proliferation of MSCs in vitro. The systemic administration of G-CSF promoted the repair of damaged cartilage possibly through increasing the number of MSCs in a rabbit model. Cite this article: T. Sasaki, R. Akagi, Y. Akatsu, T. Fukawa, H. Hoshi, Y. Yamamoto, T. Enomoto, Y. Sato, R. Nakagawa, K. Takahashi, S. Yamaguchi, T. Sasho. The effect of systemic administration of G-CSF on a full-thickness cartilage defect in a rabbit model MSC proliferation as presumed mechanism: G-CSF for cartilage repair. Bone Joint Res 2017;6:123–131. DOI: 10.1302/2046-3758.63.BJR-2016-0083.

Matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) are thought to play critical roles in cartilage degradation at the early phase of osteoarthritis (OA). The aim of this study is to examine the effect of chemically modified Mmp13 or Adamts5 small interfering RNA (siRNA), alone or in combination, in a mouse OA model. OA pathology was surgically induced in 9-week-old male C57/BL6 mice (n = 64) via destabilization of the medial meniscus (DMM). We used chemically modified siRNA (Accell siRNAs®) for Mmp13 and Adamts5, as well as a non-targeting control and evaluated their combined and individual effects after injection in the DMM model. The control group (n = 16) was injected with non-targeting siRNA and the normal group (n = 16) did not undergo any surgical induction or intra-articular injection. Histological assessment of the articular cartilage was conducted at 4 and 8 weeks post-DMM surgery to evaluate OA progression. Significant improvement in the histological score was observed at 8 weeks after DMM in all three siRNA-treated groups compared to the control siRNA-injected group. The score of the combined group was significantly lower than that of the Adamts5 siRNA-only group. No significant differences were noted between the Mmp13 siRNA-only group and the combined group. Combined intra-articular injection of Mmp13 and Adamts5 siRNA resulted in almost the same inhibitory effects as Mmp13 siRNA alone on cartilage degradation at the early phase of OA.

Objective We investigated the effect of administration of intra-articular mesenchymal stem cells (MSCs) on cartilage repair at different timings, and the distribution of MSCs in the knee. Design A partial thickness cartilage defect (PTCD) was created on the medial femoral condyle in 14-week-old Sprague-Dawley rats. Intra-articular injection of 1 × 106 MSCs was performed at 3 time points, namely at the time of surgery (0w group), at 1 week after surgery (1w group), and at 2 weeks after surgery (2w group). For the control, 50 μL phosphate-buffered saline was injected at the time of surgery. The femoral condyles were collected at 6 weeks after creation of PTCD and assessed histologically. To investigate the distribution of MSCs, fluorescent-labeled MSCs were injected into the knee joint. Results In the control group, the cartilage lesion was distinguishable from surrounding cartilage. In the 0w group, hypocellularity and a slight decrease in safranin O stainability were observed around the injured area, but cartilage was restored to a nearly normal condition. In contrast, in the 1w and 2w groups, the cartilage surface was irregular and safranin O stainability in the injured and surrounding areas was poor. Histological score in the 0w group was significantly better than in the control, 1w, and 2w groups. At 1 day postinjection, fluorescent-labeled MSCs were mostly distributed in synovium. However, no migration into the PTCD was observed. Conclusions Early intra-articular injection of MSCs was effective in enhancing cartilage healing in a rat PTCD model. Injected MSCs were distributed in synovium, not in cartilage surrounding the PTCD.

SummaryObjectiveTo examine whether the detection of osteophytes anywhere in the knee could serve as a pre-radiographic biomarker for osteoarthritis (OA) development.MethodsBaseline magnetic resonance imaging (MRIs) of 132 participants in the Osteoarthritis Initiative (OAI) were studied. Based on radiographs, 66 knees were assessed as osteoarthritis-free (no-osteoarthritis [NOA], or Kellgren/Lawrence [K/L] severity grade 0/1 both at baseline and 48 months), and another 66 knees were assessed as having radiographic OA changes (pre-radiographic osteoarthritis [PROA], or with K/L grade 0/1 at baseline and grade ≥2 at 48 months). Using baseline MRI data, we examined eight sites of osteophyte formation: the medial and lateral femoral condyle (MFC and LFC, respectively); medial and lateral tibial plateau (MTP and LTP, respectively); medial and lateral facets of the patellofemoral joint (PM and PL, respectively); tibial spine (TS); and femoral intercondylar notch (IC). Knee joint osteophyte size was assessed via the 8-point marginal osteophytes item of the whole-organ magnetic resonance imaging score (WORMS). The frequencies and distributions of osteophytes were compared between groups.ResultsMild-size osteophytes (defined as score ≥2) were observed more frequently at the MFC (P = 0.00278), MTP (P = 0.0046), TS (P = 0.0146), PM (P

The objectives of this study are (1) to examine age-dependent longitudinal differences in histological responses after creation of partial-thickness articular cartilage defects (PTCDs) in rats and to use this model (2) to objectively evaluate the effectiveness of interventions for cartilage repair. Linear PTCDs were created at a depth of 100 μm in the weight-bearing region of the medial femoral condyle in rats of different ages (3 weeks, 6 weeks, 10 weeks and 14 weeks). One day, one week, two weeks, four weeks and twelve weeks after PTCD generation, spontaneous healing was evaluated histologically and immunohistochemically. Effects of interventions comprising mesenchymal stem cells (MSCs) or platelet-rich plasma (PRP) or both on 14-week-old PTCD rats were evaluated and compared with natural courses in rats of other ages. Younger rats exhibited better cartilage repair. Cartilage in 3-week-old and 6-week-old rats exhibited nearly normal restoration after 4–12 weeks. Cartilage in 14-week-old rats deteriorated over time and early signs of cartilage degeneration were observed. With injection of MCSs alone or MSCs + PRP, 14-week-old PTCD rats showed almost the same reparative cartilage as 6-week-old rats. With injection of PRP, 14-week-old PTCD rats showed almost the same reparative cartilage as 10-week-old rats. This model will be of great use to objectively compare the effects of interventions for small cartilage lesions and may help to advance the development of disease-modifying osteoarthritis drugs.

2005，2006年に，東京都多摩地域の半促成および露地栽培において，Oidium属Reticuloidium亜属菌（OR菌）によるキュウリうどんこ病の発生状況を調査した結果，5市2町11圃場の6品種で発生が確認され，本菌が広範に分布することが明らかとなった．本菌の発生は，多くは5月上旬～6月中旬で，その後は従来のOidium属Fibroidium亜属菌（OF菌）が優占したが，それぞれは単独で発生し，両種が混発することは少なかった．圃場（品種：南極2号，京涼み）におけるOR菌の発病状況は，発病葉率21.8～39.0％，発病度5.8～12.8に達した．OR菌の形態的特徴はいずれも既知の日本産Oidium属Reticuloidium亜属菌と一致したが，分生子柄のfoot-cellの大きさは菌株によりやや異なった．品種によるOR菌に対する感受性の差異は，OF菌とほぼ同様の傾向であったが，湧泉に対しては，菌株により異なった．

Nedocromil sodium has a number of known hydrate states, a monohydrate, a trihydrate and a heptahemihydrate, including an amorphous state. Effect of grinding on the hydration states of nedocromil sodium crystals was studied. After grinding the trihydrate, heptahemihydrate was observed in the ground sample, even though, the water content in the ground sample was not sufficient to cover the heptahemihydrate’s hydration level. On the other hand, in the ground heptahemihydrate, trihydrate was existed. Apparent activation energies (ΔE) for hydrates, monohydrate→anhydrate, trihydrate→monohydrate and heptahemihydrate→amorphous(anhydrate), were calculated using TG data. ΔE for the dehydration of heptahemihydrate was significantly lower than that of other hydrates. Obtained ΔE data explained the inter-conversion behavior of nedocromil sodium induced by grinding.

The Chinese Meishan pig is prolific breed and it is considered that this pig has a capacity with higher rates of embryonic survival. The oviductal secretory cells may affect the embryonic development and survival. The aim of the present study was to investigate the ultrastructural features of secretory cells in the various regions of the Chinese Meishan pig oviduct during the follicular and luteal phases of the oestrous cycle. In the ampullar secretory cells, numerous secretory granules with moderately electron-dense matrices were present in the supranuclear cytoplasm and exocytosis of secretory granules was observed. The number of secretory granules was dramatically reduced in the ampullar secretory cells in the luteal phase. During the follicular phase in the fimbrial epithelium, the secretory cells contained rough endoplasmic reticulum and Golgi apparatus, but most cells had few small granules. In the luteal phase, the secretory cells in the ampullar and fimbrial epithelia extended beyond the luminal border of the ciliated cells. In the isthmus, many granules were present in the cytoplasm of secretory cells throughout the oestrous cycle, but the number of secretory granules was reduced in the luteal phase. The cytomorphometric data revealed that the height of ciliated cells decreased substantially in the fimbriae and ampulla at the luteal phase, while that of non-ciliated cells was less affected. These results suggest that the drastic reduction of cell height of ciliated cells cause the extrusion of most secretory cells beyond the ciliated cells in the fimbriae and ampulla during the luteal phase. In summary, our ultrastructural observations of Chinese Meishan pig oviduct revealed marked cyclic changes in the ultrastructural features of secretory cells. In particular, the ultrastructural features and the numbers of secretory granules were distinctive for each particular segment. These findings should provide insight into the regional and cellular differences in functions of secretory cells of the Chinese Meishan pig oviduct.

The present study was conducted to examine the relationship between the oxygen consumption rate and sex ratio of bovine in vitro fertilized embryos on each day of blastocyst formation. The quality of blastocysts collected on day 7, 8, and 9 after in vitro fertilization (IVF) were categorized as ranks A and B (excellent and good, respectively) based on microscopic observation of the morphology. The oxygen consumption rate and sex of individual blastocysts were evaluated using two novel techniques: scanning electrochemical microscopy (SECM) and loop-mediated isothermal amplification (LAMP), respectively. The oxygen consumption rates of embryos of rank A were significantly higher (p < 0.05) than those of rank B, irrespective of the day of blastocyst appearance after IVF. Neither did the proportion of male embryos of ranks A and B differ significantly from each other at any of the days examined, nor from the average proportion (53%). The oxygen consumption rate of embryos of rank B collected on day 8 was significantly higher (p < 0.05) in female embryos than in male embryos collected on the same day. However, there were no apparent differences of oxygen consumption rates at each day of blastocyst appearance between male and female embryos of rank A. These results indicate that the oxygen consumption rate of individual embryos reflects their quality but does not correlate with the sex ratio of embryos of excellent quality.

Background and Study Aims: The outcome of stenting gastric outlet stricture is favorable compared with a bypass operation which has significant morbidity and mortality. In Japan, this procedure is particularly complicated by a lack of enteral stents. We report some technical stratagems for stent placement for gastric outlet strictures. Patients and Methods: Between February 1993 and July 2001, 23 patients with gastric outlet strictures (14 men, nine women; mean age 72 years) underwent stent placement using an esophageal stent system. The Ultraflex or Z-stents were used in 18 or five patients, respectively. With the Ultraflex, we increased the length of the delivery system. Some patients underwent stent placement with the help of endoscopic assistance with a grasping forceps or a home-made sheath. Results: The metal stent was successfully inserted in all patients. There were no complications during the procedure. Migration occurred in two out of five patients treated with the Z-stent, whereas there was no migration in patients treated with the Ultraflex stent. In two patients, curable pancreatitis was caused by pressure on the duodenal papilla. One of these patients also experienced bile stasis which required biliary decompression. There were three cases of obstruction, caused by tumor ingrowth (1), hyperplasia (1) and stent fracture (1); recanalization by an additional stent placement and/or cutting stent filaments was successful. All the patients died, with a median survival period of 52 days. There was no procedure-related mortality. Conclusions: With some technical modification, stent placement for gastric outlet stricture, even using an esophageal stent, is feasible. This procedure offers good palliation with no major complications.

Percutaneous microwave coagulation for recanalizing stents occluded by tumor ingrowth has been reported. With this technique, however, the percutaneous drain diminishes the quality of life in patients with unresectable tumors and a limited prognosis. Transpapillary microwave ablation was attempted in three patients with occluded stents. After a sheath had been inserted into the proximal hepatic duct across the occluded region, a microwave electrode was introduced into the intrahepatic duct via the sheath. We used microwave therapy with an output power of 40 W, based on our previous in vitro study. Except in one patient, the stents were successfully recanalized with one or two attempts. In one patient who underwent ablation in the intrahepatic duct, a 1.8-mm electrode enabled recanalization of the stent. In another who underwent ablation in the extrahepatic duct, however, a larger electrode was required. There were no procedure-related complications. Transpapillary microwave coagulation of occluded stents appears to be an alternative to percutaneous microwave coagulation with an electrode fitting the stent size. The technique might be easier with the use of a redesigned electrode with a guide wire lumen.

The relation between atomic ordering and martensitic transformation temperature, M s , in Ag-Zn-Al alloys was examined mainly by means of electrical resistivity measurements. Disordered bcc phase was frozen-in by quenching from a temperature above the critical temperature for ordering, T c . In a Ag-22.3at%Zn-8.9at%Al alloy, the M s temperature has been found to decrease by aging in the parent phase at temperatures between 253 and 293K. The resistivity also decreased in accord with the M s temperature. This indicates that atomic ordering proceeds by aging. The relation between the decrease in the reverse transformation temperature, A f . and the degree of long range order was obtained. In a Ag-11.0at%Zn-15.5at%Al alloy, in which the M s temperature in the as-quenched state is higher and the T c temperature is lower than that of the former alloy, aging in the martensite phase was performed. In this case, the aging brought about the increase in the A f temperature. This is in contrast to the results of aging in the parent phase. Furthermore, the effect of aging in the parent phase at temperatures higher than T c was examined. Both the transformation temperature and the resistivity were found to become higher. These changes are due to lowering in the degree of short range order.

In a previous paper, it has been pointed out that the rubber effect and stabilization of the martensite phase are caused by short range reordering during aging [K. Marukawa, K. Tsuchiya, Scripta Metall. Mater. 32 (1995) 77]. This view was further examined by experimental and theoretical studies. It has been found that the change in electrical resistivity produced by aging is well correlated with magnitudes of these effects. The relation between the short range order parameters and the representative quantities of these effects was formulated on the basis of thermodynamics. Quantitative evaluation was performed by numerical calculations utilizing the Monte Carlo method. It was found that the rubber effect is prominent when the aging temperature is in the vicinity of the order–disorder transition temperature. It was also shown that in most cases disordering or lowering in the long range order causes the stabilization.

The relation between the degree of long-range order and the martensitic transformation temperature was examined by means of electrical resistivity measurements and electron microscopic observations in Ag–Zn–Al alloys having a composition near Ag2(Zn, Al). The disordered state of the β phase (bcc structure) can be frozen by quenching from a temperature above the critical temperature for ordering. By aging at or around the room temperature, atomic ordering is developed. The ordered structure after aging in the parent phase was found to be the C11b structure. Specimens in the disordered β phase transform to the martensitic phase on cooling below room temperature. It has been found that the martensitic transformation temperature is lowered by aging at temperatures between 253 and 293 K. This indicates that ordering brings about the decrease in the transformation temperature. The resistivity of the β phase measured at the aging temperature and that of the martensitic phase at liquid nitrogen temperature also decrease by aging. The resistivity change was related to the degree of long range order and the decrease in the transformation temperature was expressed as a function of the degree of order.

GRAFT coronary arteriaosclerosis (GCA) is the major determinant of long-term survival following heart transplantation. GCA consists of concentric intimal arterial lesions that are diffusely distributed within epicardial and intramural coronary arteries of engrafted hearts and may result in myocardial ischemia, infarction, and sudden death. The clinical diagnosis of GCA is often delayed until late progress of GCA because patients with denervated engrafted hearts do not experience anginal symptoms, and the diffuse and concentric nature of occlusive lesions may obscure the early angiographic findings. In addition, therapeutic interventions for GCA such as angioplasty and coronary bypass grafting are limited because of the diffuse nature of the process. Therapeutic options are, therefore, limited, and retransplantation is often the last choice. Recent reports have suggested GCA is a type of chronic vascular rejection. It remains controversial whether established GCA can be improved by modification in immunosuppressive therapy. Previously our study indicated that multiglycosidorum tripterygium (MT) has effective immunosuppressive effect and could prevent the development of GCA following transplantation. The purpose of this study was to examine whether the therapy of MT initiated after GCA was already established could halt or reverse the progress of GCA in a rat allograft model.

The critical temperature for the order-disorder transition, T c , and the ordered domain structure of the B2 phase have been investigated by electrical resistivity measurements and electron microscopic observations in Ag-Zn alloys containing 38, 40 and 42 at%Zn. Specimens quenched from the disordered β phase were all found to be ordered in the B2 structure. Resistivity change measured during aging of the B2 phase shows a plateau at the initial stage of aging. This indicates the degree of order reaches the equilibrium value immediately after the start of aging. The B2 domain size as measured after aging and quenching increases as the aging temperature increases. However, it takes a smaller value when the aging temperature is beyond T c . Values of T c were determined by monitoring the domain size as 441, 405 and 367 K for the 42, 40 and 38Zn alloys, respectively. The ragging or fluctuating of anti-phase domain boundaries was recognized in the specimens aged at a temperature just below T c . The activation energy for the domain growth was obtained by measuring growth rates as 49.3 kJ/mol, which was judged to correspond to the migration energy of excess vacancies.

This paper reports on the excellent performance of V-band monolithic high electron-mobility transistor (HEMT) oscillators, and discusses oscillation characteristics on drain bias. With regard to output characteristics, double-hetero (DH) HEMT (especially with a high-density Si-planar doped layer) are superior to single-hetero (SH) HEMT's. A monolithic microwave integrated circuit (MMIC) oscillator has been developed with a planar doped DH HEMT and has achieved the peak output power of 11.1 dBm at a 55.9-GHz oscillation frequency. Phase noise of -85 dBc/Hz at 100-kHz offset and -103 dBc/Hz at 1-MHz offset have been achieved at a drain voltage of 5.5 V and a gate voltage of 0 V. These characteristics have been achieved without any buffer amplifiers of dielectric resonators. This study has revealed that the phase noise decreases as drain voltage increases. This phenomenon is caused by lower pushing figure and lower noise level at a low-frequency range obtained under a high drain voltage. It is because the depletion layer in the channel is extended to the drain electrode with increase of drain voltage, resulting in the small fluctuation of the gate-to-source capacitance. We also investigate low-frequency noise spectra of AlGaAs-InGaAs-GaAs DH HEMT's with different bias conditions. The low-frequency noise decreases for more than 3 V of the drain voltage. A unique mechanism is proposed to explain this phase noise reduction at high drain voltage.

The effects of steroid hormones (oestradiol and progesterone) on the appearance of a golden hamster oviduct-specific glycoprotein (GHOGP) in the epithelium of the oviduct of the newborn golden hamster were investigated by immunoblotting and immunohistochemical staining with a GHOGP-specific monoclonal antibody. Newborn golden hamsters (1.5 days old) were injected daily with oestradiol (1 microgram) or progesterone (10 microgram). An oviductal extract of oestradiol-treated golden hamsters for 4 days apparently immunoreacted with the monoclonal antibody on a broad band with a molecular mass of more than 200 kDa by immunoblotting under reducing conditions. This broad band was consistent with the migration of GHOGP in an extract of adult oviducts. Consecutive daily injections of oestradiol induced the appearance of GHOGP in undifferentiated epithelial cells of the oviduct of neonates. In oviducts of oestradiol-injected animals, GHOGP was first detected in the Golgi region and then increased in amount to fill the supranuclear cytoplasm of the epithelial cells. The inductive effect of oestradiol was dose-dependent. In contrast, consecutive daily injections of progesterone had no effect on the appearance of GHOGP in the oviductal epithelium. The effects of oestradiol and progesterone in organ culture of oviducts were examined in vitro, by culturing oviductal organs from 1.5-day-old newborn golden hamsters in chemically defined medium supplemented with oestradiol or progesterone for 2 days and then subjected to immunohistochemical staining. The immunoreaction was detected only in the epithelial cells of oestradiol-treated oviducts at concentrations of > 0.01 ng ml-1, but not in the cells of untreated and progesterone-treated oviducts. These results indicate that the production of GHOGP in the epithelial cells of the oviduct of newborn golden hamsters is induced by oestradiol both in vivo and in vitro. It is suggested that oestradiol may be involved in the synthesis of GHOGP in the oviduct during postnatal development of golden hamsters.

We report measurements of branching fractions of ? lepton decays to final states with a KS0 meson using a 669fb-1 data sample accumulated with the Belle detector at the KEKB asymmetric-energy e+e- collider. The inclusive branching fraction is measured to be B(?-?KS0X-??)=(9. 15�0.01�0.15)�10-3, where X- can be anything; the exclusive branching fractions are B(?-??-KS0??)=(4.16�0. 01�0.08)�10-3, B(?-?K-KS0??)=(7.40�0. 07�0.27)�10-4, B(?-??-KS0?0??)=(1. 93�0.02�0.07)�10-3, B(?-?K-KS0?0??)=(7. 48�0.10�0.37)�10-4, B(?-??-KS0KS0??)=(2. 33�0.03�0.09)�10-4, B(?-??-KS0KS0?0??) =(2.00�0.22�0.20)�10-5, where the first uncertainty is statistical and the second is systematic. For each mode, the accuracy is improved over that of pre-B-factory measurements by a factor ranging from five to ten. In ?-??-KS0KS0?0?? decays, clear signals for the intermediate states ?-??-f1(1285)?? and ?-?K*- KS0?0?? are observed. � 2014 American Physical Society.

We report the results of a search for the X(1835) state in the process e+e-?J/?X(1835) using a data sample of 672 fb-1 collected with the Belle detector at and near the � (4S) resonance at the KEKB asymmetric-energy e+e- collider. No significant evidence is found for this process, and an upper limit is set on its cross section times the branching fraction: ?Born(e+e-?J/?X(1835))�B(X(1835)??3 charged tracks)

We search for the charmless B0 decay with final state particles p???-? using the full data sample that contains 772�106BB? pairs collected at the ?(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. This decay is predicted to proceed predominantly via the b?s? radiative penguin process with a high energy photon. No significant signal is found. We set an upper limit of 6.5�10-7 for the branching fraction of B0?p???-? at the 90% confidence level. � 2014 American Physical Society.

Partial thickness articular cartilage injuries (PTCIs) were not previously thought to heal spontaneously. Immature rats have the capacity for spontaneous repair of PTCIs, although it is a long-term process. Our aim has been to examine the spontaneous repair response mechanism in immature rats. Single linear PTCIs were created in 3-week-old and 12-week-old rats in the direction of joint motion. On day 1 and at 1, 2, and 4 weeks after PTCI, evaluations of histological changes and immunohistology at the injury site and in the surrounding cartilage were performed. Anti-CD105 and anti-CD166 antibodies (as stem cell markers to identify mesenchymal stem cells in reparative cartilage tissue) were used for immunohistological evaluations. To determine whether endogenous repair ability existed in articular cartilage, an ex vivo experiment was also carried out. Femoral condyles with PTCIs were incubated in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum for 1 day and for 1 and 2 weeks. Histological changes were subsequently examined. Immature cartilage showed a higher repair response than did mature cartilage, and the response occurred immediately after PTCI. In immature rats, CD105- and CD166-positive cells were found in the superficial and transitional zones of the articular cartilage. Few CD166-positive cells were identified in mature articular cartilage. No significant in vivo differences in the spontaneous repair responses to PTCIs were observed between mature and immature groups. Thus, the repair response to PTCIs seems to be associated not only with CD105- and CD166-positive cells, but also with other perichondral factors.

Summary Objective Osteoarthritis (OA) leads to pain and loss of function in affected joints. Gait disturbance results from these symptoms of OA, and gait analysis can be important to evaluate the progression of OA. The purpose of this study was to analyze gait pattern in a rodent model of OA and to assess the effects of intra-articular injection of hyaluronan (IAI-HA) by gait analysis, along with histological evaluation. Design OA was induced by destabilization of the medial meniscus (DMM) of C57BL/6 mice. IAI-HA started 3 weeks after DMM surgery. Mice were allocated to three groups and were given either 800-kDa HA (800-HA), 6000-kDa HA (6000-HA) or saline. We compared these three groups with a sham group by gait analysis using CatWalk™. Histological evaluation was performed to assess articular cartilage changes in the knee joints. Results Mice injected with 800-HA or 6000-HA showed gait patterns similar to that of the sham mice, while the saline-injected group showed gait disturbances 12 and 16 weeks after DMM surgery. Histological changes in articular cartilage were similar among the 800-HA, 6000-HA and saline-treated groups, demonstrating OA progression throughout the experimental time points. Positive gait-related effects of IAI-HA might occur by its pain relieving effect and/or by preventing contracture. Conclusion IAI-HA prevented gait disturbances in the DMM model, but did not prevent histological changes associated with OA progression.

Rapid progress in industrialization and urbanization has resulted in the concentration of economic growth and social functions in the urban areas. In most urban cities, it has become more and more certain that the increase of energy consumption is causing environmental problems including the temperature rise in the urban atmosphere (urban heat island) and air pollution. The present paper reports on the results of field observation and three-dimensional computer simulation of the urban heat island in the Tokyo metropolitan area. The three-dimensional governing equations for the urban atmospheric boundary layer were formulated by virtue of the vorticity-velocity vector potential method. Particular attention was focused on the representation of a buoyancy term in the equation of motion in the vertical direction, thereby describing the cross-over effect and stratified inversion layer near the ground surface. The vorticity-velocity potential method is superior from the viewpoint of numerical stability and suitable for the simulation of an urban heat island. A survey on the energy consumption was first made in the Tokyo metropolitan area. Next, these data were used for the three-dimensional simulations. In order to evaluate the validity of the present model to simulate the urban heat island, the simulation was carried out by initializing it with the same meteorological conditions as those used for the observation day. The simulation results were then compared with the field observation data for the surface temperature. Quite a good agreement was obtained between the present simulation and the observed data, thereby assuring the present model. Further future prediction of the urban heat island was performed for an energy release rate five times as much as the present rate, which corresponds to the year 2031 if the present consumption rate is maintained until then.

Serum is an essential requirement for the growth and long-term survival of human endothelial cells, even in the presence of such defined elements such as polypeptide growth factors and hormones. A polypeptide from fetal bovine serum was isolated and characterized on the basis of long-term survival of human endothelial cells in serum-free culture. The endothelial cell viability maintaining factor has been purified to homogeneity by a combination of polyethylene glycol precipitation, hydroxylapatite, gel permeation and reverse-phase high performance liquid chromatography. The final purified endothelial cell viability maintaining factor has a molecular weight of 65 000 (reduced) and has been identified as bovine apolipoprotein H by amino-terminal amino acid sequence analysis and Western blot analysis. Endothelial cell viability maintaining factor improved a long-term viability of human endothelial cells at maximal concentrations of 2.5–5 μg protein/ml in serum-free medium.

Regional distribution of cerebral blood flow was determined semi-quantitatively with 99 Tc m -HMPAO brain SPET under basal conditions in Type 1 (insulin-dependent) diabetic patients of recent onset and longer disease duration, and related to metabolic control and history of hypoglycaemic events. Long-term diabetic patients showed significantly more alterations in regional cerebral blood flow than diabetics of recent onset and healthy controls. Regional hypoperfusion, predominantly localized in the fronto-temporal cortex, was almost exclusively observed in patients with long-term diabetes. The latter finding was related to lower HbA1c levels (i.e. better metabolic control) and to the frequency of impending hypoglycaemia, but not to age of the patient, duration of diabetes or to chronic diabetes complications. The incidence of hypoperfusion was comparable in patient groups with or without a medical history of hypoglycaemic coma. However, regions of hypoperfusion were larger in the patients who had experienced hypoglycaemic coma. It is concluded that regional cerebral hypoperfusion in long-term Type 1 (insulin-dependent) diabetics, as evidenced by HMPAO-SPET, can be related to the frequency and degree of hypoglycaemic events and to tight metabolic control, which is however at the expense of an increased risk of recurrent hypoglycaemia

Epithelial cells of the mammalian oviduct play an important role in reproductive and developmental events that occur there. Oviductal epithelial cells from several mammalian species can be isolated and cultured in serum or serum-free medium in vitro and cell culture of bovine oviductal epithelial cells (BOEC) has been described by many investigators. Cultured BOEC show a wide variety of secretory activities and these secretory factors may influence early embryonic development or sperm function. Monolayer cultures of BOEC have been widely used for in vitro co-culture of bovine preimplantation embryos. The use of BOEC co-culture systems has improved embryonic development in nearly all the studies conducted. In addition, interaction of bovine spermatozoa with BOEC, in a similar manner to that observed for spermatozoa in vivo, induced specific changes in sperm capacitation and consequently improved the fertilizing capacity of bovine spermatozoa in vitro. Thus co-culture systems with BOEC may not only offer an excellent model for studying the mechanisms of capacitation and acrosome reaction of bovine spermatozoa but also provide a useful tool for the improvement of embryo development in vitro.

The purpose of this study was to characterise dose distribution in linear accelerator-based intracranial stereotactic radiosurgery using the dynamic conformal arc technique, and to validate the pertinence of dose prescription to the specific percentage isodose surface (IDS).73 plans for brain metastases were reviewed and replanned with a uniform method for target definition and treatment planning.In all cases except 1 the dose prescription to the 80% IDS satisfied the criteria of the standardised prescription IDS as previously proposed. However, both of the planning target volume (PTV) coverage values for the 80% and 90% IDSs and the PTV D99 and D95 (IDS receiving at least 99% or 95% of the PTV) were inconsistent and significantly increased as a function of the PTV size. The 80% IDS for a PTV of more than 5 cm(3) achieved adequate PTV coverage without a leaf margin. The dose conformity for 80% IDS gradually worsened as the PTV increased, whereas that for the PTV D99 or D95 improved as a function of the PTV size. The addition of a leaf margin attained 100% PTV coverage for 80% IDS, while leading to a poorer dose conformity.The dose prescription to the specific percentage IDS does not necessarily guarantee consistent target coverage, D99 and D95, and desirable dose conformity in proportion to the target volume. The dose prescription and evaluation at the specific target coverage would therefore be preferable as an objective method in order to report the "marginal dose" and to clearly compare the planning parameters with those from other modalities.

Inhibitory PAS (Per/Arnt/Sim) domain protein (IPAS) is a dominant negative transcription factor that represses hypoxia-inducible factor 1 (HIF-1) activity. In this study, we show that IPAS also functions as a pro-apoptotic protein through binding to pro-survival Bcl-2 family members. In a previous paper, we reported that NF-κB-dependent IPAS induction by cobalt chloride repressed the hypoxic response in PC12 cells. We found that prolonged incubation under the same conditions caused apoptosis in PC12 cells. Repression of IPAS induction protected cells from apoptosis. Furthermore, knockdown of IPAS recovered cell viability. EGFP-IPAS protein was localized in both the nucleus and the cytoplasm, with a large fraction associated with mitochondria. Mitochondrial IPAS induced mitochondria depolarization and caspase-3 activation. Immunoprecipitation assays revealed that IPAS is associated with Bcl-x(L), Bcl-w and Mcl-1. The association of IPAS with Bcl-x(L) was also observed in living cells by the FLIM-based FRET analysis, indicating direct binding between the two proteins. IPAS contributed to dysfunction of Bcl-x(L) by inhibiting the interaction of Bcl-x(L) with Bax. These results demonstrate that IPAS functions as a dual function protein involved in transcription repression and apoptosis.