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Nuclear receptor-related 1 (Nurr1) protein has been identified as an obligatory transcription factor in midbrain dopaminergic neurogenesis, but the global set of human NURR1 target genes remains unexplored. Here, we identified direct gene targets of NURR1 by analyzing genome-wide differential expression of NURR1 together with NURR1 consensus sites in three human neural stem cell (hNSC) lines. Microarray data were validated by quantitative PCR in hNSCs and mouse embryonic brains and through comparison to published human data, including genome-wide association study hits and the BioGPS gene expression atlas. Our analysis identified ~40 NURR1 direct target genes, many of them involved in essential protein modules such as synapse formation, neuronal cell migration during brain development, and cell cycle progression and DNA replication. Specifically, expression of genes related to synapse formation and neuronal cell migration correlated tightly with NURR1 expression, whereas cell cycle progression correlated negatively with it, precisely recapitulating midbrain dopaminergic development. Overall, this systematic examination of NURR1-controlled regulatory networks provides important insights into this protein’s biological functions in dopamine-based neurogenesis.

The transcription factor Kruppel-like factor 4 (KLF4) is highly expressed and plays an important role in maintaining stemness in embryonic stem cells (ES cells). However, how the expression of KLF4 is regulated has not been well documented. To elucidate the molecular mechanisms controlling the expression of human KLF4 (hKLF4) in ES cells, a 3685-bp DNA fragment upstream of the hKLF4 gene was isolated and the 5′-regulatory region was characterized, from which two regions highly conserved with rodents were identified. In addition, one consensus binding site for members of the TCF family (TBS) was identified within each conserved region. Tcf7l1, a member of the TCF family, is highly expressed in ES cells and has been identified as a crucial regulator of the pluripotency gene regulatory network in ES cells. Therefore, the possible transcriptional mechanisms by which Tcf7l1 regulates hKLF4 expression in ES cells were investigated. In the present study, gel retardation showed that Tcf7l1 preferentially bound to...

Patient Initials or Identifier Number JCD ### Relevant Clinical History and Physical Exam A 53-year-old man was admitted for effort chest pain for 2 months ago. His coronary risk factor was hypertension. He had previous history of CTO and underwent PCI at LCX 1 year ago. Baseline coronary

Patient initials or identifier number LJS ### Relevant clinical history and physical exam A 70-year-old female was admitted with chest pain for 2 days. Since last month, he has suffered from crescendo chest pain. The ECG showed ST elevation on inferior lead and biomarker was elevated. ###

Background The self-expandable COMPLETE™ stent (Medtronic) has greater elasticity, allowing it to regain its shape after the compression force reduces, and has higher trackability, thus is easier to maneuver through tortuous vessels, whereas the balloon-expandable SCUBA™ stent (Medtronic) has higher radial stiffness and can afford more accurate placement without geographic miss, which is important in aortoiliac bifurcation lesions. To date, there have been no randomized control trials comparing efficacy and safety between the self-expanding stent and balloon-expandable stent in advanced atherosclerotic iliac artery disease. Methods/design The purpose of our study is to examine primary patency (efficacy) and incidence of stent fracture and geographic miss (safety) between two different major representative stents, the self-expanding nitinol stent (COMPLETE-SE™) and the balloon-expanding cobalt-chromium stent (SCUBA™), in stenotic or occlusive iliac arterial lesions. This trial is designed as a prospective, randomized, multicenter trial to demonstrate a noninferiority of SCUBA™ stent to COMPLETE-SE™ stent following balloon angioplasty in iliac arterial lesions, and a total of 280 patients will be enrolled. The primary end point of this study is the rate of primary patency in the treated segment at 12 months after intervention as determined by catheter angiography, computed tomography angiography, or duplex ultrasound. Discussion The SENS-ILIAC trial will give powerful insight into whether the stent choice according to deployment mechanics would impact stent patency, geographic miss, or stent fracture in patients undergoing stent implantation in iliac artery lesions. Trial registration National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT01834495), registration date: May 8, 2012 Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1435-9) contains supplementary material, which is available to authorized users.

Patient initials or identifier number 01511314 ### Relevant clinical history and physical exam Case summary: A 84 year-old male patient presented with exertional chest pain for several months. His coronary risk factors were hypertesion, hyperlipidemia and smoking. The echocardiography

OBJECTIVE Although several studies have reported an association between microalbuminuria and pulse wave velocity in patients with hypertension or diabetes, there have been no reports of their significance in apparently healthy individuals. METHODS Microalbuminuria and brachial-ankle PWV (baPWV) were investigated in a sample of 3826 nonhypertensive, nondiabetic individuals (3598 men, mean age 50 ± 11.3 years) at Kangbuk Samsung Health Promotion Center between 2006 and 2009. The patients were classified into two groups according to urinary albumin-creatinine ratio (UACR) in morning urine specimens: normoalbuminuria (

A series of amphiphilic graft copolymers based on polyaspartamide were synthesized by a successive aminolysis reaction of polysuccinimide using 2-diisopropylaminoethyl (DIP) and laurylamine as a pH sensitive and hydrophobic group, respectively. The pH-dependent self-assembly behavior of the aqueous copolymer solution was investigated. Nano-aggregation occurred at a pH in the vicinity of the pKa of the DIP group, which was induced by a hydrophilic–hydrophobic shift of the DIP group in solution. The mean diameter of the nano-aggregate could be modulated by changing the composition of both pendants. The mean diameter of the nanoparticles increased with increasing solution pH from 6.5 to 8. At pH 8, the mean diameter of the nanoparticles increased rapidly at the temperature above 45 °C, probably due to the change in hydrophilic–hydrophobic balance of the pH-sensitive DIP moiety. The dissolution of paclitaxel (PTX) into this amphiphilic nanoparticle was attempted and the pH-dependent release behavior was examined with the stability study of the particle. The results showed significantly faster release of PTX at pH 6.5, which is a tumoral acidic pH, than in a neutral physiological pH. These thermo- and pH-sensitive polyaspartamide derivatives have potential use as a tumor-targeting delivery.

요 약 본 논문은 중공을 가진 판재 두 매를 결합하기 위하여 중공 주위를 따라 기존 레이저 용접법 대신 기계적 프레스 결합법을 적용하는 것에 관한 연구이다. 이를 통해 레이저 용접을 적용했을 때 불가피하게 발생하는 열 변형을 효과적으로 없앨 수 있다. 유한요소해석을 통하여 중공형 판재를 기계적으로 결합시킬 수 있는 금형 설계 방법을 제안하였다. 기계적 결합력을 최대화시키는 데 관련 있는 다섯 가지 설계인자를 선택하여 다꾸치 실험법을 적용한 결과 성형 깊이와 펀치모서리 반경이 가장 크게 영향을 미치는 인자로 나타났다 .Abstract This study is to apply the mechanical press joining method to join two kinds of sheet metals with circular holes by mechanical pressing instead of laser beam. Usage of the mechanical pressing avoids the thermal deformation of sheet metals which occurs inevitably in laser joining. A die design has been proposed to make the mechanical press joining applicable with finite element analysis. Five design factors related to the joining force have been selected and applied to the Taguchi method for optimization. Among five factors, 'Forming Depth' and 'Punch Corner Radius' have been revealed to be the most influential ones.

Earthwork is very equipment-intensive task and researches related to automated excavation have been conducted. There is an issue to secure the safety for an automated excavating system. Therefore, this paper focuses on how to improve safety for semi- or fully-automated backhoe excavation. The primary objective of this research is to develop the core technology for automated object detection in excavation work. In order to satisfy the research objective, a diverse sensing technologies are investigated and analysed in terms of functions, durability, and reliability. The authors developed detecting algorithm for the objects using laser sensor and verified its performance by several tests. The results of this study would be the basis for developing the automated object detection system.

BACKGROUND Cardiovascular events are known to occur more frequently in patients with a high morning surge in blood pressure (BP), but the correlation between a morning BP surge and corrected QT dispersion (QTc) has not been confirmed to date. METHODS AND RESULTS The correlation between the morning BP surge and QTc was studied in 82 patients recently diagnosed with high BP (47 males, 35 females). Twenty-four-hours BP monitoring was conducted to classify patients into dipper (n=45) or nondipper (n=37) groups according to the degree of nocturnal BP reduction. QTc was found to be significantly longer in the nondippers compared with the dippers (36.1+/-17.2 vs 47.6+/-20.7, p

It has not been examined whether high Lp(a) levels are able to predict long-term adverse cardiovascular outcomes in patients (pts) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). The aim of this study is to assess the impact of Lp(a) levels on the major clinical

Trimetazidine (VastinanTM) is an anti-ischemic metabolic agent, which improves myocardial glucose utilization through inhibition of fatty acid metabolism, also known as fatty acid oxidation inhibitor. Trimetazidine usually prescribed as a long-term treatment of angina pectoris. The aim of this study

Background There have been few randomized control trials comparing the incidence of stent fracture and primary patency among different self-expanding nitinol stents to date. The SMART™ CONTROL stent (Cordis Corp, Miami Lakes, Florida, United States) has a peak-to-valley bridge and inline interconnection, whereas the COMPLETE™-SE stent (Medtronic Vascular, Santa Rosa, California, United States) crowns have been configured to minimize crown-to-crown interaction, increasing the stent's flexibility without compromising radial strength. Further, the 2011 ESC (European society of cardiology) guidelines recommend that dual antiplatelet therapy with aspirin and a thienopyridine such as clopidogrel should be administered for at least one month after infrainguinal bare metal stent implantation. Cilostazol has been reported to reduce intimal hyperplasia and subsequent repeat revascularization. To date, there has been no randomized study comparing the safety and efficacy of two different antiplatelet regimens, clopidogrel and cilostazol, following successful femoropopliteal stenting. Methods/Design The primary purpose of our study is to examine the incidence of stent fracture and primary patency between two different major representative self-expanding nitinol stents (SMART™ CONTROL versus COMPLETE™-SE) in stenotic or occlusive femoropopliteal arterial lesion. The secondary purpose is to examine whether there is any difference in efficacy and safety between aspirin plus clopidogrel versus aspirin plus cilostazol for one month following stent implantation in femoropopliteal lesions. This is a prospective, randomized, multicenter trial to assess the efficacy of the COMPLETE™-SE versus SMART™ CONTROL stent for provisional stenting after balloon angioplasty in femoropopliteal arterial lesions. The study design is a 2x2 randomization design and a total of 346 patients will be enrolled. The primary endpoint of this study is the rate of binary restenosis in the treated segment at 12 months after intervention as determined by catheter angiography or duplex ultrasound. Discussion This trial will provide powerful insight into whether the design of the COMPLETE™-SE stent is more fracture-resistant or effective in preventing restenosis compared with the SMART™ CONTROL stent. Also, it will determine the efficacy and safety of aspirin plus clopidogrel versus aspirin plus cilostazol in patients undergoing stent implantation in femoropopliteal lesions. Trial registration Registered on 2 April 2012 with the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT01570803).

Recently, it was reported that statins are associated with lower rates of major adverse cardiovascular events and amputations in critical limb ischemia (CLI) patients (pts). However, the impact of statin administration duration on clinical outcomes for pts undergoing percutaneous transluminal

The aim of our study was to assess the relationship between serum gamma-glutamyl transferase (GGT) level within the normal range and incident hypertension according to drinking and obesity status in nonhypertensive individuals. We followed up 4783 normotensive adults (mean age = 44 years) who had serum GGT levels within the normal range at baseline for 3 years. Subjects were divided into four GGT quartile groups according to their serum GGT level at baseline. The overall incidence of hypertension was 8.1%, and the incidence increased with increasing GGT quartile (3.8%, 6.9%, 9.0%, and 12.4% in the lowest, second, third, and highest GGT quartiles, respectively; P < .001). In the logistic regression analysis adjusted for age, sex, body mass index, lifestyle factors, glucose, uric acid, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, high-sensitivity C-reactive protein, and baseline systolic blood pressure, the odds ratio (ORs) for incident hypertension increased with increasing GGT quartile (P for trend = .030). In the above model, the highest quartile group showed increased ORs compared with those in the lowest quartile group (ORs [95% confidence interval], 2.638 [1.259-5.528]). Subgroup analyses revealed a significant association between GGT quartile and the incidence of hypertension in the drinker and non-overweight groups. Our results indicate that elevated serum GGT levels within the normal range are associated with a higher risk of incident hypertension in Korean adults, particularly, in drinkers and non-overweight individuals, suggesting possible different pathophysiologic mechanisms in the incidence of alcohol- and obesity-related hypertension.

There have been limited data comparing efficacy and safety of Biolimus-eluting Stents (BES, BiomatrixTM, Biosensors and NoboriTM, Terumo) with Platinum Chromium Everolimus-eluting Stent (PtCr-EES, Promus ElementTM, Boston Scientific) in a series of Asian population in real world clinical practice.

It has been well known that a major cause of vasospastic angina is endothelial dysfunction and subsequent significant coronary vasoconstriction. Thus, diltiazem and nitrate can be beneficial as selective coronary vasodilators for pts with significant vasoconstriction. However, there is no study

Chronic alcohol consumption is known to be a risk factor of significant coronary artery disease (CAD). However, currently there is no available data with larger study population regarding long-term clinical outcomes of CAS patients (pts) with chronic alcohol consumption in real world clinical

There have been limited data comparing efficacy and safety of Biolimus-eluting Stents (BES, BiomatrixTM, Biosensors and NoboriTM, Terumo) with Zotarolimus-eluting Stent (ZES, Resolute Integrity, Medtronic) in a series of Asian population in real world clinical practice. A total of 626 patients (pts