• 대한비뇨기종양학회지
• /
• 제15권3호
• /
• pp.178-186
• /
• 2017

Purpose: Poloxamer 407 (P407) thermo-sensitive hydrogel formulations were developed to enhance the retention time in the urinary bladder after intravesical instillation. Materials and Methods: P407 hydrogels (P407Gels) containing 0.2 w/w% fluorescein isothiocyanate dextran (FD, MW 4 kDa) as a fluorescent probe were prepared by the cold method with different concentrations of the polymer (20, 25, and 30 w/w%). The gel-forming capacities were characterized in terms of gelation temperature (G-Temp), gelation time (G-Time), and gel duration (G-Dur). Homogenous dispersion of the probe throughout the hydrogel was observed by using fluorescence microscopy. The in vitro bladder simulation model was established to evaluate the retention and drug release properties. P407Gels in the solution state were administered to nude mice via urinary instillation, and the in vivo retention behavior of P407Gels was visualized by using an in vivo imaging system (IVIS). Results: P407Gels showed a thermo-reversible phase transition at $4^{\circ}C$ (refrigerated; sol) and $37^{\circ}C$ (body temperature; gel). The G-Temp, G-Time, and G-Dur of FD-free P407Gels were approximately $10^{\circ}C-20^{\circ}C$, 12-30 seconds, and 12-35 hours, respectively, and were not altered by the addition of FD. Fluorescence imaging showed that FD was spread homogenously in the gelled P407 solution. In a bladder simulation model, even after repeated periodic filling-emptying cycles, the hydrogel formulation displayed excellent retention with continuous release of the probe over 8 hours. The FD release from P407Gels and the erosion of the gel, both of which followed zero-order kinetics, had a linear relationship ($r^2=0.988$). IVIS demonstrated that the intravesical retention time of P407Gels was over 4 hours, which was longer than that of the FD solution (<1 hour), even though periodic urination occurred in the mice. Conclusions: FD release from P407Gels was erosion-controlled. P407Gels represent a promising system to enhance intravesical retention with extended drug delivery.

• 응용통계연구
• /
• 제23권5호
• /
• pp.871-882
• /
• 2010

동물종양 실험에서는 종양발생 시간이 직접 관찰되지 않고 단지 자연사로 인한 관찰 시점이나 강제적으로 희생시킨 시점 이전에 종양이 발생했는지 유무만을 알 수 있다. 이와 같은 형태의 결측을 가진 자료를 분석하기 위해 3단계(건강$\rightarrow$종양발생$\rightarrow$사망) 모형이 널리 사용되고 있다. 본 논문에서는 자연사로 인한 사망 시간이 종속적인 중도절단으로 작용하여 사망 시간과 종양발생 시간이 종속될 때, 이를 모형에 반영하기 위해 감마 프레일티 효과를 도입하였다. 모수 추정은 종양발생 시간과 프레일티 효과의 결측을 다루기 위해 EM 알고리즘 방법을 사용하였다. 제안한 추정량의 소표본 성질을 살펴보기 위해 제안한 방법을 Lindsey와 Ryan (1993, 1994)의 방광암 자료에 적용하여 모수를 추정하였으며, 그 추정값을 바탕으로 모의실험을 수행하였다.

• 융합신호처리학회논문지
• /
• 제8권1호
• /
• pp.6-14
• /
• 2007

요역동학검사는 하부요로계의 이상증상을 진단하기위하여 수행된다. 일반적으로 임상에서 행해지는 요역동학검사에서는 침습적인 방법으로 방광을 채운 후 배뇨하는 절차를 거친다. 하지만 이러한 방법은 카테터를 삽입해야하므로 환자에게 고통을 수반하게 한다. 본 연구에서는 비침습적이고 보다 편리한 방법으로 하부요로계의 기능을 평가할 수 있는 시스템을 구현하고자 하였다. 비침습적인 방법으로 하부요로증상(lower urinary tract symptoms, LUTS)의 진단을 위하여 배뇨시 요속, 요류음, 비침습적 방광내압을 측정할 수 있는 시스템을 구현하였다. 구현된 시스템은 센서부, 신호처리부, FPGA를 이용한 시스템 제어부 그리고 PC모니터링 프로그램으로 구성하였다. 그리고 구현된 계측시스템의 평가를 위하여 FPGA 시스템 제이부의 시뮬레이션을 수행하였고 인체의 하부요로계를 모식화한 실험장치를 구현하였다. 실험장치를 이용한 측정부의 평가결과 요속측정부의 평균에러율이 1.08%, 계수변화율이 1.48로 평가되었다. 그리고 비침습적 방광내압부는 평균에러율이 2.41%, 계수변화율이 2.81로 나타났다. 요류음신호의 시간영역과 주파수영역에서의 분석위해 평균실효치전력(average RMS power)과 주파수영역에서의 중심주파수(median frequency, MF)를 분석하였으며, 그 결과 $60{\sim}160Hz$의 중심주파수대에서 폐색을 가장 잘 반영하였다.

• Journal of applied mathematics & informatics
• /
• 제39권5_6호
• /
• pp.785-804
• /
• 2021

The proposal of new families has been worked out by many authors over recent years. Many ways to generate new families have been developed as the methods of addition, linear combination, composition and, one of the newer, the T-X family of distributions. Using this latter method, Korkmaz et al. (2018) proposed a new class called Weibull Marshall-Olkin-G (WMO-G) family. In the present work, we propose a new distribution, based on the WMO-G family, using the Lomax distribution as baseline, called Weibull Marshall-Olkin Lomax (WMOL) distribution. The hazard rate function of this distribution can be increasing, decreasing, bathtub-shaped, decreasing-increasing-decreasing and unimodal. Some properties of the proposed model are developed. Besides that, we consider method of maximum likelihood for estimating the unknown parameters of the WMOL distribution. We provide a simulation study in order to verify the asymptotic properties of the maximum likelihood estimates. The applicability of the new distribution to modeling real life data is proved by two real data sets.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권12호
• /
• pp.7473-7482
• /
• 2013

The G-protein coupled receptor 87 (GPR87) is a recently discovered orphan GPCR which means that the search of their endogenous ligands has been a novel challenge. GPR87 has been shown to be overexpressed in squamous cell carcinomas (SCCs) or adenocarcinomas in lungs and bladder. The 3D structure of GPR87 was here modeled using two templates (2VT4 and 2ZIY) by a threading method. Functional assignment of GPR87 by SVM revealed that along with transporter activity, various novel functions were predicted. The 3D structure was further validated by comparison with structural features of the templates through Verify-3D, ProSA and ERRAT for determining correct stereochemical parameters. The resulting model was evaluated by Ramachandran plot and good 3D structure compatibility was evidenced by DOPE score. Molecular dynamics simulation and solvation of protein were studied through explicit spherical boundaries with a harmonic restraint membrane water system. A DRY-motif (Asp-Arg-Tyr sequence) was found at the end of transmembrane helix3, where GPCR binds and thus activation of signals is transduced. In a search for better inhibitors of GPR87, in silico modification of some substrate ligands was carried out to form polar interactions with Arg115 and Lys296. Thus, this study provides early insights into the structure of a major drug target for SCCs.