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PURPOSE To compare image quality in selective intracoronary contrast-injected computed tomography angiography (Selective-CTA) with that in conventional intravenous contrast-injected CTA (IV-CTA). MATERIALS AND METHODS Six pigs (35 to 40 kg) underwent both IV-CTA using an intravenous injection (60 mL) and Selective-CTA using an intracoronary injection (20 mL) through a guide-wire during/after percutaneous coronary intervention. Images of the common coronary artery were acquired. Scans were performed using a combined machine comprising an invasive coronary angiography suite and a 320-channel multi-slice CT scanner. Quantitative image quality parameters of CT attenuation, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), mean lumen diameter (MLD), and mean lumen area (MLA) were measured and compared. Qualitative analysis was performed using intraclass correlation coefficient (ICC), which was calculated for analysis of interobserver agreement. RESULTS Quantitative image quality, determined by assessing the uniformity of CT attenuation (399.06 vs. 330.21, p

BACKGROUND AND OBJECTIVES We sought to investigate an anti-atherosclerotic and anti-inflammatory effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in normoglycemic atherosclerotic rabbit model. METHODS Male New Zealand white rabbits (n=26) were fed with a 1% high-cholesterol diet for 7 weeks followed by normal diet for 2 weeks. After balloon catheter injury, the rabbits were administered with the Dapagliflozin (1mg/kg/day) or control-medium for 8 weeks (n=13 for each group). All lesions were assessed with angiography, optical coherence tomography (OCT), and histological assessment. RESULTS Atheroma burden (38.51±3.16% vs. 21.91±1.22%, p

AimAlthough the atheroprotective effects of statins and angiotensin II receptor blockers (ARBs) are well-established, little is known about their additive effects, especially during the early period of atherosclerosis. The aim of this study was to investigate whether combination of a statin and an ARB exerts synergistic anti-atherosclerotic effects, and to elucidate the mechanisms of combined effects.MethodsAtherosclerotic plaques were developed in arteries of 23 rabbits using a high-cholesterol diet (HCD) and intra-arterial balloon inflation. Rabbits received one of five different treatment strategies for 4 weeks: positive control [n = 5, HCD]; negative control [n = 3, regular chow diet]; statin [n = 5, HCD and rosuvastatin 10 mg]; ARB [n = 5, HCD and olmesartan 20 mg]; and combination [n = 5, HCD and statin+ARB].ResultsHistological analysis demonstrated that development of atherosclerotic plaques was inhibited more in combination group than in statin group (P = 0.001). Although macrophage infiltration identified by RAM11 staining was not significantly different between combination and individual treatment groups (31.76±4.84% [combination] vs. 38.11±6.53% [statin; P = 0.35] or 35.14±2.87% [ARB; P = 0.62]), the relative proportion of pro-inflammatory M1-macrophages was significantly lower in combination group than in ARB group (3.20±0.47% vs. 5.20±0.78%, P = 0.02). Furthermore, M2-macrophage polarization was higher in combination group than in statin group (17.70±3.04% vs. 7.86±0.68%, P = 0.001).ConclusionCombination treatment with a statin and an ARB produced synergistic protective effects for atherosclerosis initiation and progression, which may be attributed to modulation of macrophage characteristics in the early period of atherosclerosis.

Background LAA occlusion has a similar stroke prevention efficacy compared to anticoagulation treatment for non-valvular atrial fibrillation. Objective The objective of this study was to assess the feasibility and safety of a modified Occlutech® left atrial appendage (LAA) closure device in a canine model. Methods The device was implanted in 10 dogs (33±1kg) using fluoroscopy and transesophageal echocardiography (TEE) guidance. The modified Occlutech® LAA occlusion device was compared with the current version, the Watchman device, and the Amplazter cardiac plug (ACP). LAA occlusion and anchoring to the LAA were evaluated. All dogs were assessed using angiography, TEE, and a gross anatomy examination. Results The 10 LAA occlusion devices were to be implanted into 10 dogs (5 modified Occlutech devices, 3 current version of Occlutech devices, 1 Watchman, and 1 ACP). LAA implantation was not performed in one dog due to transeptal puncture failure. The three current version of Occlutech devices were embolized immediately after implantation, so three modified devices of the same size were implanted securely without embolization. The mean implant size was 20.1±2.0mm. The devices chosen were a mean of 23.3±10.6% larger than the measured landing zone diameters. Post-implant angiography and TEE revealed well-positioned devices without pericardial effusion or impingement on surrounding structures. Conclusions The results of this acute animal study suggested that a modified Occlutech® LAA occlusion device was feasible and had greater anchoring performance in canines. Additional large clinical studies are needed to evaluate safety and efficacy.

A 13-year-old castrated male Yorkshire terrier dog had a soft splenic mass, which measured 11 cm in the greatest diameter. Microscopically, the parenchyma of the spleen was completely replaced by myxoid substances. Numerous spindle and stellate cells were loosely arranged in the myxoid stroma, and variable vessels of variable sizes were observed in a loose matrix with poorly defined margins. Immunohistochemical analysis showed that tumor cells were positive for desmin and alpha-SMA, but negative for S-100. Interestingly, intravascular tumor embolus with positive α-SMA expression was observed. This case is meaningful, because angiomyxoma, a rare tumor of dogs, occurs in the spleen. Even in human cases, splenic angiomyxoma was not reported.

Given the lack of promptness and inevitable use of additional contrast agents, the myocardial viability imaging procedures have not been used widely for determining the need to performing revascularization.This study is aimed to evaluate the feasibility of myocardial viability assessment, consecutively with diagnostic invasive coronary angiography (ICA) without use of additional contrast agent, using a novel hybrid system comprising ICA and multislice CT (MSCT).In all, 14 Yucatan miniature swine models (female; age, 3 months; weight, 28-30 kg) were subjected to ICA followed by balloon occlusion (90 minutes) and reperfusion of the left anterior descending coronary artery. Two weeks after induction of myocardial infarction, delayed hyperenhancement (DHE) images were obtained, using a novel combined machine comprising ICA and 320-channel MSCT scanner (Aquilion ONE, Toshiba), after 2, 5, 7, 10, 15, and 20 minutes after conventional ICA. The heart was sliced in 10-mm consecutive sections in the short-axis plane and was embedded in a solution of 1% triphenyltetrazolium chloride (TTC). Infarct size was determined as TTC-negative areas as a percentage of total left ventricular area. On MSCT images, infarct size per slice was calculated by dividing the DHE area by the total slice area (%) and compared with histochemical analyses.Serial MSCT scans revealed a peak CT attenuation of the infarct area (222.5 ± 36.5 Hounsfield units) with a maximum mean difference in CT attenuation between the infarct areas and normal myocardium of at 2 minutes after contrast injection (106.4; P for difference = 0.002). Furthermore, the percentage difference of infarct size by MSCT vs histopathologic specimen was significantly lower at 2 (8.5% ± 1.8%) and 5 minutes (9.5% ± 1.9%) than those after 7 minutes. Direct comparisons of slice-matched DHE area by MSCT demonstrated excellent correlation with TTC-derived infarct size (r = 0.952; P.001). Bland-Altman plots of the differences between DHE by MSCT and TTC-derived infarct measurements plotted against their means showed good agreement between the 2 methods.The feasibility of myocardial viability assessment by DHE using MSCT after conventional ICA was proven in experimental models, and the optimal viability images were obtained after 2 to 5 minutes after the final intracoronary injection of contrast agent for conventional ICA.

Objective Selective catheter-directed intracoronary contrast injected coronary computed tomography angiography (selective CCTA) has recently been introduced for on-site evaluation of coronary artery disease during coronary artery catheterization. In this study, we aimed to develop a feasible protocol for selective CCTA using ultralow-dose contrast medium as compared with conventional intravenous CCTA (IV CCTA). Materials and methods A novel combined system incorporating coronary angiography and a 320-detector row computed tomographic scanner was used to study 4 swine (35-40 kg) under animal institutional review board approval. A selective CCTA scan was simultaneously performed with an injection of 13.13 mgI/mL of modulated contrast medium at multiple different injection rates including 2, 3, and 4 mL/s and different total injection volumes of either 20 or 30 mL. Intravenous CCTA was performed with 60 mL of contrast medium, followed by 30 mL of saline chaser at 5 mL/s. Coronary mean and peak intensity, transluminal attenuation gradient, as well as 3-dimensional maximum intensity projections were obtained. Results Attenuation values (mean ± standard error, in Hounsfield units [HUs]) of selective CCTA for the left anterior descending (LAD) and right coronary artery (RCA) using the various combinations of injection rates and total injection volumes were as follows: 20 mL at 2 mL/s (LAD, 270.3 ± 20.4 HU; RCA, 322.6 ± 7.4 HU), 20 mL at 3 mL/s (LAD, 262.9 ± 20.4 HU; RCA, 264.7 ± 7.4 HU), 30 mL at 3 mL/s (LAD, 276.8 ± 20.4 HU; RCA, 274.0 ± 7.4 HU), 20 mL at 4 mL/s (LAD, 268.0 ± 20.4 HU; RCA, 277.7 ± 7.4 HU), and 30 mL at 4 mL/s (LAD, 251.3 ± 20.4 HU; RCA, 334.7 ± 7.4 HU). The representative protocol of the selective CCTA studies produced results within the optimal enhancement range (approximately 250-350 HU) for all segments, and comparison of transluminal attenuation gradient data with selective CCTA and IV CCTA studies demonstrated that the former method was more homogenous (-1.5245 and -1.7558 for LAD as well as 0.0459 and 0.0799 for RCA, respectively). Notably, the volume of iodine contrast medium used for selective CCTA was reported to be 1.09% (0.2 g) of IV CCTA (24 g). Conclusions The current findings demonstrate the feasibility of selective CCTA using ultralow-dose intracoronary contrast injection. This technique may provide additional means of coronary evaluation in patients who may require strategic planning before a procedure using a combined modality system.

Objectives: This study aimed to survey the characteristics of air quality and meteorological conditions in a greenway park. Methods: We measured meteorological and health related factors, including noise, particulate matter () and selected gaseous air pollutants at three locations in a greenway park and on a general roadside as comparison. The measurements were repeated four times from April to October 2014. Results: The average air temperature in the greenway park was which was lower than on the general roadside. The average concentration in the greenway park was , a level 2-3 times lower than that at the roadside. The noise level at the greenway site was 4.4 dB(A)- 23.0 dB(A) lower than at the roadside. The average CO, , and NOx concentrations in the greenway park were lower than at the roadside. The average phytoncide and anions concentrations in the greenway park were higher than at the roadside. Conclusions: The urban forest of the greenway park may have some impact on air quality and meteorological conditions.

Horse health has become a major concern with the expansion of horse-related industries and sports; the importance of healthy muscles for horse performance and daily activities is undisputed. Here we generated equine-induced pluripotent stem cells (E-iPSCs) by reprogramming equine adipose-derived stem cells (E-ADSCs) into iPSCs using a polycistronic lentiviral vector encoding four transcription factors (i.e., Oct4, Sox2, Klf4, and c-Myc) and then examined their pluripotent characteristics. Subsequently, established E-iPSCs were transplanted into muscle-injured Rag/ mdx mice. The histopathology results showed that E-iPSC-transplanted mice exhibited enhanced muscle regeneration compared to controls. In addition, E-iPSC-derived myofibers were observed in the injured muscles. In conclusion, we show that E-iPSCs could be successfully generated from equine ADSCs and transplanted into injured muscles and that E-iPSCs have the capacity to induce regeneration of injured muscles.

Despite the susceptibility to frequent intrinsic and extrinsic injuries, especially in the inner zone, the meniscus does not heal spontaneously owing to its poor vascularity. In this study, the effect of platelet-rich plasma (PRP), containing various growth factors, on meniscal mechanisms was examined under normal and post-traumatic inflammatory conditions. Isolated primary meniscal cells of New Zealand white (NZW) rabbits were incubated for 3, 10, 14 and 21 days with PRP(-), 10% PRP (PRP(+)), IL(+) or IL(+) PRP(+). The meniscal cells were collected and examined using reverse-transcription polymerase chain reaction (RT-PCR). Culture media were examined by immunoblot analyses for matrix metalloproteinases (MMP) catabolic molecules. PRP containing growth factors improved the cellular viability of meniscal cells in a concentration-dependent manner at Days 1, 4 and 7. However, based on RT-PCR, meniscal cells demonstrated dedifferentiation, along with an increase in type I collagen in the PRP(+) and in IL(+) PRP(+). In PRP(+), the aggrecan expression levels were lower than in the PRP(-) until Day 21. The protein levels of MMP-1 and MMP-3 were higher in each PRP group, i.e., PRP(+) and IL(+) PRP(+), at each culture time. A reproducible 2-mm circular defect on the meniscus of NZW rabbit was used to implant fibrin glue (control) or PRP in vivo. After eight weeks, the lesions in the control and PRP groups were occupied with fibrous tissue, but not with meniscal cells. This study shows that PRP treatment of the meniscus results in an increase of catabolic molecules, especially those related to IL-1 alpha-induced inflammation, and that PRP treatment for an in vivo meniscus injury accelerates fibrosis, instead of meniscal cartilage.

This study aimed to develop a new biodegradable stent for peripheral artery disease (PAD) that could provide sufficient radial force to maintain long-term patency and flexibility. All self-expandable hybrid biodegradable stents were designed by using a knitting structure composed of poly-L-lactic acid (PLLA) and nitinol. Four different types of stents were implanted in 20 iliac arteries in 10 mini pigs as follows: a bare-metal stent (BMS) (group 1,n=5), a drug-free hybrid stent (group 2,n=5), a 50% (50 : 100,w/w) paclitaxel (PTX)/poly-lactide-co-glycolic acid (PLGA; fast PTX-releasing form) hybrid stent (group 3,n=5), and a 30% (30 : 100,w/w) PTX/PLGA (slow PTX-releasing form) hybrid stent (group 4,n=5). We performed follow-up angiography and intravascular ultrasonography (IVUS) at 4 and 8 weeks. In a comparison of groups 1, 2, 3, and 4, less diameter stenosis was observed in the angiographic analysis for group 4 at the 4-week follow-up (19.0% ± 12.7% versus 39.3% ± 18.1% versus 46.8% ± 38.0% versus 4.8% ± 4.2%, resp.;p=0.032). IVUS findings further suggested that the neointima of the patients in group 4 tended to be lesser than those of the others. Our new biodegradable 30% PTX/PLGA (slow-releasing form) stent showed more favorable results for patency than the other stent types.

The basic service model is to be process transmting patient health information from various medical devices to evacuation hospital through gateway collecting it in aerial emergency medicine environments. In this paper, we study on the most secure transmission scheme in case that personal patient informations are transmitted from medical devices to gateway. Moreover we compare and analyze existing methods on secure transmission and suggest an optimal alternative on the basis of international standard, ISO/IEEE 11073.

Platelets are involved in hemostasis, wound healing, and tumor growth. Autologous blood products are commonly used to facilitate healing in a variety of clinical surgery applications. Recently, it was shown that platelet-rich plasma (PRP) has more specific growth factors that participate in the healing process. This study investigated the expression of PRP growth factors and evaluated their potential role in the cartilage regeneration using primary isolated chondrocytes. PRP obtained from New Zealand White rabbit by low speed centrifugation. Extracted PRPs contained 6-10 × 10(6) platelet/μl and concentration of platelets was slightly variable. Primary isolated chondrocytes from the same rabbits were cultured and treated with 0.1-20% PRP. The cells were collected and examined by reverse transcription-polymerase chain reaction and cytochemical staining. The expression of sex determining region Y-box 9, transforming growth factor-beta, vascular endothelial growth factor, and chondromdulin-I was increased in chondrocyte cultures with 10% PRP by time-dependent manner. To maintain the integrity of the cartilage, the proteoglycan contents were also up-regulated from the mRNA of aggrecan and positive Safranin-O staining in PRP concentration- and time-dependent manner. PRP provides crucial growth factors related to chondrocyte proliferation and differentiation through time-sequential modulation. Controlled in vivo trials for cartilage regeneration are needed.

Systemic transplantation of adipose-derived stem cells (ASCs) is emerging as a novel therapeutic option for functional recovery of diverse damaged tissues. This study investigated the effects of systemic transplantation of human ASCs (hASCs) on bone repair. We found that hASCs secrete various bone cell-activating factors, including hepatocyte growth factor and extracellular matrix proteins. Systemic transplantation of hASCs into ovariectomized mice induced an increased number of both osteoblasts and osteoclasts in bone tissue and thereby prevented bone loss. We also observed that conditioned medium from hASCs is capable of stimulating proliferation and differentiation of osteoblasts via Smad/extracellular signal-regulated kinase (ERK)/JNK (c-jun NH(2) -terminal kinase) activation as well as survival and differentiation of osteoclasts via ERK/JNK/p38 activation in vitro. Overall, our findings suggest that paracrine factors secreted from hASCs improve bone repair and that hASCs can be a valuable tool for use in osteoporosis therapy.

Several mammals, including dogs, have been successfully cloned using somatic cell nuclear transfer (SCNT), but the efficiency of generating normal, live offspring is relatively low. Although the high failure rate has been attributed to incomplete reprogramming of the somatic nuclei during the cloning process, the exact cause is not fully known. To elucidate the cause of death in cloned offspring, 12 deceased offspring cloned by SCNT were necropsied. The clones were either stillborn just prior to delivery or died with dyspnea shortly after birth. On gross examination, defects in the anterior abdominal wall and increased heart and liver sizes were found. Notably, a significant increase in muscle mass and macroglossia lesions were observed in deceased SCNT-cloned dogs. Interestingly, the expression of myostatin, a negative regulator of muscle growth during embryogenesis, was down-regulated at the mRNA level in tongues and skeletal muscles of SCNT-cloned dogs compared with a normal dog. Results of the present study suggest that decreased expression of myostatin in SCNT-cloned dogs may be involved in morphological abnormalities such as increased muscle mass and macroglossia, which may contribute to impaired fetal development and poor survival rates.

Castor beans (Ricinus communis) contain ricin, which is one of the most toxic substances of plant origin. Ricin toxicosis has been reported in different countries with usually ingestion of castor beans or plants in both animals and humans. However, ricin toxicosis by ingestion of some products containing castor oil cake has rarely been reported. This paper describes outbreaks of dog death by ricin toxicosis after accidental ingestion of the same soil conditioner. Fifteen dogs showed toxic symptoms such as severe vomiting, abdominal pain and hemorrhagic diarrhea, and then thirteen dogs died in a few days. The soil conditioner dogs ingested consisted of 10% castor oil cake containing ricin. On the basis of clinical signs, laboratory and pathologic findings, a diagnosis of ricin toxicosis was established in the present case. In comparison with previous cases by ingestion of castor beans, the dogs' morbidity was very high in the present case. The ingestion of castor oil cake may be more dangerous to life than the castor beans. It is because mortality by ingestion of castor beans depends on the degree of mastication of the beans, whereas ricin in oil cake is easily absorbed from the stomach and the intestines. As ricin is a heat-labile toxin, products containing ricin or oil cake should be properly treated with heat and have written caution sentences about toxicosis, and be kept out of reach of domestic animals and children.

A. Winkleman 등은 건식 식각(Reactive ion etching)을 이용해 나노 팁을 가지는 실리콘 어레이를 제조한 후† Corresponding Author 표면처리(Silanization)를 하였고, B. Cortese 등은 PDMS Key Words : Carbon Nanotip(탄소 나노팁), HAR Carbon Microneedle(고종횡비 탄소 마이크로니들), MEMS(멤스), Hydrophobicity Control(소수성 제어) 초록: 본 논문에서는 뒷면 노광법과 감광제의 열분해법을 이용하여 다양한 형상을 가지는 탄소 마이크로니들의 제조방법과 제조된 마이크로니들을 사용하여 소수성 표면제어에 대한 연구를 수행하였다. SU-8이 도포된 표면마스크 뒷면으로부터 자외선을 조사하여 다양한 지름, 간격, 그리고 높이를 가지는 폴리머 마이크로니들을 제조하였다. 이 니들은 이후 열처리공정을 통해서 수축, 열변형 등의 형상변화를 거치면서 10이상의 높은 종횡비와 나노사이즈의 뾰족한 팁을 가지는 탄소 재질의 마이크로니들로 변하게 된다. 탄소 마이크로니들을 가지는 석영기판은 친수성 표면을 가지고 있기 때문에 표면에너지가 낮은 물질을 처리하여 소수성 정도를 제어하였다. HMDS처리는 SU-8 니들보다는 탄소 니들의 경우에 표면의 소수성 조절에 효과가 있음을 접촉각의 측정과 XPS 측정결과로부터 확인할 수 있었다. 본 논문에서 제시하는 탄소 마이크로니들의 제조기술과 표면처리기술은 세포분석 및 바이오분야 그리고 자기세정분야 등에서 유용하게 사용될 수 있다. Abstract: This paper reports the fabrication of geometry-controlled carbon microneedles by a backside exposure method and pyrolysis. The SU-8 microneedles are a polymer precursor in a carbonization process, which geometries such as base diameter, spacing, and aspect ratio can be controlled in a photolithography step. Using this fabrication method, highly reproducible carbon microneedles, which have high aspect ratios of more than 10 and very sharp nanotips, can be realized. The quartz surface with carbon microneedles becomes very hydrophilic and its wettability is adjusted by carrying out the silane treatment. In the carbon microneedle array (3 μm × 3 μm), the contact angle is extremly enhanced (~180°); this will be advantageous in developing low-drag microfluidics and labs-on-a-chip as well as in other bio-applications.

Sudden deaths have occurred in feedlot cattle with marked necro-hemorrhagic enteritis of the jejunum, ileum and colon. Suckling beef calves are the most frequently affected. Over-consumption of large amounts of milk, inadequate colostrum intake, chilling and stress are conducive to the development of enterotoxemia. Enterotoxemia caused by Clostridium perfringens type D mostly occurs following a sudden change of diet, particularly to feeds made richer in order to grow the cattle to market weight in feedlots. During July 2006, sudden deaths of cattle occurred in the Youngcheon regional area of Gyeongbuk province. There were no significant clinical signs except anorexia, depression, intermittent diarrhea and mild respiratory failure. Histological findings revealed a prominent intranuclear inclusion as well as infiltration of the globular leukocytes in various organs including the heart, kidneys, liver, spleen and lymph nodes. Spleen and lymphatic tissues showed lymphatic necrosis and a starry sky appearance. In the submucosa of the small intestines, basophilic aggregation was detected with massive infiltration of the globular leukocytes and eosinophils. Gram staining for the tissue sections containing inclusions of the small intestines revealed a positive histochemical reaction. Taken together, we suggest that Clostridium perfringens type D-induced enterotoxemia is determined to be the cause of sudden death of feedlot cattle.

Aims Atherosclerosis is a well-known cause of cardiovascular disease and is associated with a variety of inflammatory reactions. However, an adequate large-animal model of advanced plaques to investigate the pathophysiology of atherosclerosis is lacking. Therefore, we developed and assessed a swine model of advanced atherosclerotic plaques with macrophage polarization. Methods Mini-pigs were fed a 2% high-cholesterol diet for 7 weeks followed by withdrawal periods of 4 weeks. Endothelial denudation was performed using a balloon catheter on 32 coronary and femoral arteries of 8 mini-pigs. Inflammatory proteins (high-mobility group box 1 [HMGB1] or tumor necrosis factor alpha (TNF-α) were injected via a micro-infusion catheter into the vessel wall. All lesions were assessed with angiography and optical coherence tomography and all tissues were harvested for histological evaluation. Results Intima/plaque area was significantly higher in the HMGB1- and TNF-α-injected groups compared to the saline-injected group (p = 0.002). CD68 antibody detection and polarization of M1 macrophages significantly increased in the inflammatory protein-injected groups (p

Senescence marker protein 30 (SMP30), an important aging marker molecule that is highly expressed in the liver, has been known to protect hepatocytes from apoptosis by the synthesis of vitamin C. To explore the function of SMP30 in liver fibrosis, the effect of SMP30 deficiency on liver fibrosis was investigated in SMP30 knockout (KO) mice. Moreover, the in vivo results were further confirmed by way of hepatic stellate cell (HSC) isolation. We demonstrated that carbon tetrachloride (CCl4)-induced liver fibrosis and the nuclear translocation of p-Smad2/3, the immediate downstream of transforming growth factor beta (TGF-β), were significantly inhibited in the liver of SMP30 KO mice compared with wildtype (WT) mice. We also confirmed that both WT and SMP30 KO HSCs did not express SMP30. Finally, we further confirmed that up-regulation of peroxisome proliferator-activated receptor-gamma (PPAR-γ) caused by a lack of vitamin C was the pivotal factor in the mechanisms for attenuated liver fibrosis of SMP30 KO mice, and feeding with vitamin C restored CCl4-induced liver fibrosis in SMP30 KO mice. Conclusion: Vitamin C deficiency by SMP30 depletion attenuated liver fibrosis by way of up-regulated PPAR-γ expression in SMP30 KO mice. Our results provide, for the first time, the possible mechanisms underlying inhibition of HSC activation associated with vitamin C and PPAR-γ up-regulation in liver fibrosis of SMP30 KO mice. (HEPATOLOGY 2010.)

Recently, sputter-deposited MoSi2 films have been successfully used as a barrier material in Nb/MoSi2/Nb Josephson junctions. In this report, we present our study on the deposition conditions of MoSi2 film for electronics application. We investigated the film stress and sheet resistance as a function of deposition conditions. We also studied the micro-structural change in the film according to the deposition conditions using electron microscopes. We suggest that the thermal strain need to be considered in order to get a reliable junction.

We present an electrochemical impedance biosensor utilizing pyrolyzed carbon film as a working electrode material for aptamer-based thrombin detection. Batch-fabricated, smooth thin film carbon electrodes, which are fabricated by photolithography and photoresist thermal decomposition at high temperatures in inert ambient, are obtained for integrated electrochemical biosensors. To confirm the suitability of pyrolyzed carbon for use in an electrochemical biosensor, physical and electrical properties of carbon film pyrolyzed with a positive photoresist, AZ9260, were studied. Film thickness after pyrolysis was between 19% and 15% relative to the initial photoresist thickness and the cross-section was changed from rectangular to round shape due to the photoresist reflow characteristics. Resistivity of carbon thin film pyrolyzed at 1000 °C was 3 mΩ cm, which is comparable to that of highly boron-doped polysilicon. The pyrolysis temperature of 1000 °C was chosen in order to obtain carbon film with high conductivity for use as a working electrode. Thrombin aptamer was grafted onto the pyrolyzed carbon surface using carbodiimide-mediated chemistry, followed by Triton-X 100 and BSA treatment to reduce non-specific binding of thrombin. Electron-transfer resistance changes due to thrombin binding onto the carbon surface were measured using electrochemical impedance spectroscopy techniques. Thrombin concentrations between 0.5 nM and 500 nM were detected by electrochemical measurement. Pyrolyzed carbon can provide a new approach for miniaturization, integration, and low-cost fabrication in electrochemical biosensors.

A thermoelectric flow sensor for small quantity of gas flow rate was fabricated using silicon wafer semiconductor process and bulk micromachining technology. Evanohm R alloy heater and chromel-constantan thermocouples were used as a generation heat unit and sensing parts, respectively. The heater and thermocouples are thermally isolated on the laminated membrane. The characteristics of this sensor were observed in the flow rate range from 0.2 slm to 1.0 slm and the heater power from 0.72 mW to 5.63 mW. The results showed that the sensitivities : voltage difference, : flow rate) were increased in accordance with heater power rise and decreasing of flow rate.

A thin-film multijunction thermal converter was fabricated through the process using 6 inch silicon wafer semiconductor process and bulk micromachining. Evanohm R alloy and chromel-constantan were used as a heater and thermocouple materials, respectively. The temperature coefficient of resistance of Evanohm R heater was about 75.12 ppm/ and the voltage sensitivity of the thermal converter indicated about 5.75 mV/mW in air. The transfer differences, measured by FRDC-DC method in the frequency range from 20 Hz to 10 kHz, showed the value under about 1.36 ppm, 0.83 ppm for the film thickness of 500, 200 nm, respectively. And in case of a 200 nm-thick thermal converter, the AC-DC transfer differences seems to be stabilized below the value of 1 ppm in the frequency range from 1 kHz to 500 kHz.

A chromel-alumel thermoelectric flow sensor using thermal isolation membrane was fabricated. Temperature coefficient of resistance of thin film Pt-heater was about , and Seebeck coefficient of chromel-alumel thermocouple was about . The sensor showed that thermoelectric voltage decreased as thermal conductivity of gas increased, and -flow sensitivity increased as heater voltage increased or the distance between heater and thermocouple decreased. When heater voltage was about 2.5 V, -flow sensitivity and thermal response time of the sensor were about and 0.18 sec., respectively. Linear range in flow sensitivity of the flow sensor was wider than that of Bi-Sb flow sensor.

Developed a new fabrication process for 10-V Josephson junction series arrays (JJAs). A plasma nitridation process is employed for reducing the microwave attenuation in the Josephson microstripline. Improvements of microwave attenuation are about 2 dB for test arrays of 2000, 3000, and 4000 Josephson junctions in a single stripline. We obtained stable quantized voltage steps up to 12 V at 76.4 and 86.8 GHz with step amplitudes of more than 5 /spl mu/A and stability times of more than 5 min. The circuits used 14 648 junctions arranged in 8 parallel paths.

This paper proposes a thick oxide air-bridge structure which can be used as a substrate for RF circuits. The structure was fabricated by anodic reaction, complex oxidation and micromachining technology using TMAH etching. High quality films were obtained by combining low temperature thermal oxidation (, 1 hr at ) and rapid thermal oxidation (RTO) process (, 2 min). This structure is mechanically stable because of thick oxide layer up to and is expected to solve the problem of high dielectric loss of silicon substrate in RF region. The properties of the transmission line formed on the oxidized porous silicon (OPS) air-bridge were investigated and compared with those of the transmission line formed on the OPS layers. The insertion loss of coplanar waveguide (CPW) on OPS air-bridge was (about 2dB) lower than that of CPW on OPS layers. Also, the return loss of CPW on OPS air-bridge was less than about -20 dB at measured frequency region for 2.2 mm. Therefore, this technology is very promising for extending the use of CMOS circuitry to higher RF frequencies.

NiCr-heaters with three different thicknesses ranging from 400 nm to 800 nm were fabricated and their characteristics were compared for the purpose of developing a chromel-alumel multijunction thermal converter for low input voltage with low frequency. The thermoelectric effect-induced AC-DC voltage transfer difference of the thermal converter with a built-in NiCr-heater of 400 nm-thickness was in the DC reversing frequency of with appling and the difference was increased to in the frequency of , when both thermoelectric effects and frequency effects were considered, showing the thermal converter would be suitable for the low input voltage application with low frequency.

A planar Bi-Sb multijunction thermal converter was fabricated on the LPCVD Si/sub 3/N/sub 4//SiO/sub 2//Si/sub 3/N/sub 4/-diaphragm, prepared by silicon bulk micromachining, which thermally isolated a bifilar Pt- or NiCr-heater and the hot junctions of a Bi-Sb thermopile from the silicon substrate. The voltage responsivity, the ac-dc transfer difference, and the fluctuations of the output thermoelectric voltage and heater resistance were discussed to investigate the design factors of a thermal converter. The respective voltage responsivities in air and in a vacuum of the thermal converter with a built-in NiCr-heater were about 14.0 mV/mW and 54.0 mV/mW. The ac-dc voltage and the current transfer differences in air were about /spl plusmn/0.60 ppm and /spl plusmn/0.11 ppm in the dc reversing frequency range from 10 Hz to 10 kHz. They are sufficiently small to be used as practical ac standards. Compared to the thermal converter with a built-in Pt-heater, the thermal converter with a built-in NiCr-heater demonstrated a higher voltage responsivity and smaller ac-dc transfer differences, while exhibiting slightly larger fluctuations in output thermoelectric voltage and in heater resistance.

Apoptosis has a role in many medical disorders and treatments; hence, its non-invasive evaluation is one of the most riveting research topics. Currently annexin V is used as gold standard for imaging apoptosis. However, several drawbacks, including high background, slow body clearance, make it a suboptimum marker for apoptosis imaging. In this study, we radiolabeled the recently identified histone H1 targeting peptide (ApoPep-1) and evaluated its potential as a new apoptosis imaging agent in various animal models. ApoPep-1 (CQRPPR) was synthesized, and an extra tyrosine residue was added to its N-terminal end for radiolabeling. This peptide was radiolabeled with (124)I and (131)I and was tested for its serum stability. Surgery- and drug-induced apoptotic rat models were prepared for apoptosis evaluation, and PET imaging was performed. Doxorubicin was used for xenograft tumor treatment in mice, and the induced apoptosis was studied. Tumor metabolism and proliferation were assessed by [(18)F]FDG and [(18)F]FLT PET imaging and compared with ApoPep-1 after doxorubicin treatment. The peptide was radiolabeled at high purity, and it showed reasonably good stability in serum. Cell death was easily imaged by radiolabeled ApoPep-1 in an ischemia surgery model. And, liver apoptosis was more clearly identified by ApoPep-1 rather than [(124)I]annexin V in cycloheximide-treated models. Three doxorubicin doses inhibited tumor growth, which was evaluated by 30-40% decreases of [(18)F]FDG and [(18)F]FLT PET uptake in the tumor area. However, ApoPep-1 demonstrated more than 200% increase in tumor uptake after chemotherapy, while annexin V did not show any meaningful uptake in the tumor compared with the background. Biodistribution data were also in good agreement with the microPET imaging results. All of the experimental data clearly demonstrated high potential of the radiolabeled ApoPep-1 for in vivo apoptosis imaging.

Recently, the importance of platelet activation in cancer metastasis has become generally accepted. As a result, the development of new platelet inhibitors with minimal adverse effects is now a promising area of targeted cancer therapy. Baicalein is a functional ingredient derived from the root of Scutellaria baicalensis Georgi, a plant used intraditional medicine. The pharmacological effects of this compound including anti-oxidative and anti-inflammatory activities have already been demonstrated. However, its effects on platelet activation are unknown. We therefore investigated the effects of baicalein on ligand-induced platelet aggregation and pulmonary cancer metastasis. In the present study, baicalein inhibited agonist-induced platelet aggregation, granule secretion markers (P-selectin expression and ATP release), [Ca(2+)]i mobilization, and integrin αIIbβ3 expression. Additionally, baicalein attenuated ERK2, p38, and Akt activation, and enhanced VASP phosphorylation. Indeed, baicalein was shown to directly inhibit PI3K kinase activity. Moreover, baicalein attenuated the platelet aggregation induced by C6 rat glioma tumor cells in vitro and suppressed CT26 colon cancer metastasis in mice. These features indicate that baicalein is a potential therapeutic drug for the prevention of cancer metastasis.

A 4-year-old, male, dachshund was referred to a certain local veterinary hospital because of a soft and fluctuant swelling in the left upper cervical region. The swelling was surgically removed and appeared to be filled with bloody mucus. Grossly, the swelling was identified as salivary mucocele and showed small multifocal whitish ossified tissue on its surface. Microscopically, the wall of salivary mucocele appeared as granulation tissue surrounding mucin, which was composed of loose edematous and vascularized connective tissue containing chronic inflammatory cells such as lymphocytes, plasma cells and macrophages. Characteristically, present case had ossifying components formed by metaplastic spindle cells in the wall of salivary mucocele. Therefore, the present case was diagnosed as salivary mucocele with osseous metaplasia in a dog.

We have developed a new fabrication process for integrated Nb/Al/sub 2/O/sub 3//Nb Josephson series arrays using the selective niobium anodization process (SNAP), the image reversal technique (IRT) and lift-off. To avoid chaotic behavior, the critical current of the array was decreased by post-fabrication annealing or the in situ multilayer oxidation process. In the frequency range 70-100 GHz, the array containing 2520 junctions produced stable quantized voltage steps up to 2 V with step widths of 40-100 /spl mu/A and stability times of more than 4 h. >

Purpose Appropriate animal models of atherosclerotic plaque are crucial to investigating the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. We aimed to develop a novel animal model that would be suitable for the study of advanced atherosclerotic lesions in vivo. Materials and Methods Atherosclerotic plaque was induced in 24 iliac arteries from 12 rabbits by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline (n=5), olive oil (n=6), or inflammatory proteins [n=13, high-mobility group protein B1 (HMGB1) n=8 and tumor necrosis factor (TNF)-α n=5] using a Cricket™ Micro-infusion catheter. Optical coherence tomography (OCT) was performed to detect plaque characteristics after 4 weeks, and all tissues were harvested for histological evaluation. Results Advanced plaque was more frequently observed in the group injected with inflammatory proteins. Macrophage infiltration was present to a higher degree in the HMGB1 and TNF-α groups, compared to the oil or saline group (82.1±5.1% and 94.6±2.2% compared to 49.6±14.0% and 46.5±9.6%, p-value

We present a facile, yet versatile carbon nanofabrication method using electron beam lithography and resist pyrolysis. Various resist nanopatterns were fabricated using a negative electron beam resist, SAL-601, and they were then subjected to heat treatment in an inert atmosphere to obtain carbon nanopatterns. Suspended carbon nanostructures were fabricated by the wet-etching of an underlying sacrificial oxide layer. Free-standing carbon nanostructures, which contain 130 nm wide, 15 nm thick, and 4 µm long nanobridges, were fabricated by resist pyrolysis and nanomachining processes. Electron beam exposure dose effects on resist thickness and pattern widening were studied. The thickness of the carbon nanostructures was thinned down by etching with oxygen plasma. An electrical biosensor utilizing carbon nanostructures as a conducting channel was studied. Conductance modulations of the carbon device due to streptavidin–biotin binding and pH variations were observed.

A pair of two-layer-coated totally reflecting thin-film systems that mutually compensate for the polarization changes and have a good stability for the thickness errors is investigated.

Several mammals, including dogs, have been successfully cloned using somatic cell nuclear transfer (SCNT), but the efficiency of generating normal, live offspring is relatively low. Although the high failure rate has been attributed to incomplete reprogramming of the somatic nuclei during the cloning process, the exact cause is not fully known. To elucidate the cause of death in cloned offspring, 12 deceased offspring cloned by SCNT were necropsied. The clones were either stillborn just prior to delivery or died with dyspnea shortly after birth. On gross examination, defects in the anterior abdominal wall and increased heart and liver sizes were found. Notably, a significant increase in muscle mass and macroglossia lesions were observed in deceased SCNT-cloned dogs. Interestingly, the expression of myostatin, a negative regulator of muscle growth during embryogenesis, was down-regulated at the mRNA level in tongues and skeletal muscles of SCNT-cloned dogs compared with a normal dog. Results of the present study suggest that decreased expression of myostatin in SCNT-cloned dogs may be involved in morphological abnormalities such as increased muscle mass and macroglossia, which may contribute to impaired fetal development and poor survival rates.

Introduction Nuclear and optical imaging are complementary in many aspects and there would be many advantages when optical imaging probes are prepared using radionuclides rather than classic fluorophores, and when nuclear and optical dual images are obtained using single imaging probe. Methods The luminescence intensities of various radionuclides having different decay modes have been assayed using luminescence imaging and in vitro luminometer. Radioiodinated Herceptin was injected into a tumor-bearing mouse, and luminescence and microPET images were obtained. The plant dipped in [ 32 P]phosphate solution was scanned in luminescence mode. Radio-TLC plate was also imaged in the same imaging mode. Results Radionuclides emitting high energy β + /β − particles showed higher luminescence signals. NIH3T6.7 tumors were detected in both optical and nuclear imaging. The uptake of [ 32 P]phosphate in plant was easily followed by luminescence imaging. Radio-TLC plate was visualized and radiochemical purity was quantified using luminescence imaging. Conclusion Many radionuclides with high energetic β + or β − particles during decay were found to be imaged in luminescence mode due mainly to Cerenkov radiation. ‘Cerenkov imaging’ provides a new optical imaging platform and an invaluable bridge between optical and nuclear imaging. New optical imaging probes could be easily prepared using well-established radioiodination methods. Cerenkov imaging will have more applications in the research field of plant science and autoradiography.