2개의 분리판 사이에서 분사되는 평행 3중 분류에 의한 비정상 난류 유동장 해석

유근종,최훈기,정지훈 國立 昌原大學校 產業技術硏究院 2004 産技硏論文集 Vol.18 No.-

LES is applied to analyze unsteady turbulent triple-jet water flows which are commonly found in thermal stripping phenomena. Current analyses performed to find effect of different SGS models on flow field with partition plates. LES tends to predict higher level of RMS temperatures compared to those of experiment indicating very active mixing effect among triple jets. The LES is found to be able to provide reliable frequency information of temperature fluctuation. The different SGS models show no significant difference in prediction ability, while Smagorinky-Lilly model yields slightly stronger mixing activity.

혈청이 마우스 간 세포주 BNL CL.2의 Nitric Oxide 생성에 미치는 영향

유지창,정헌택,김유현,진효상,김신무,배현옥 THE KOREAN SOCIETY FOR BIOMEDICAL LABORATORY SCIEN 1999 Journal of biomedical laboratory sciences Vol.5 No.1

마우스 간 세포주인 BNL CL.2의 시험관내 배양에서 혈청과 IFN-γ가 세포주의 nitric oxide(NO) 생성과 세포 손상에 미치는 영향을 알아보기 위한 실험을 하였다. 혈청이 공급된 배양에서 IFN-γ에 의한 세포 생존율은 거의 변동이 없었으나, 혈청을 제거한 배양에서는 약 65%의 생존율이 유지되었으며, NO 생성 억제제인 N -monomethy-L-arginine (NMA)의 첨가는 농도 의존적으로 세포의 생존율을 감소시켰다. 혈청이 제거된 BNL CL.2세포주는 IFN-γ단독 처리에서도 NO 를 생성할 수 있었으며, IFN-γ와 lipopolysaccharide (LPS)의 복합 처리는 세포주의 NO 생성을 상승적으로 증가시켰다. 또한 protein tyrosine kinase (PTK) inhibitor인 herbimycin A와 genistein에 의해서 NO 생성이 억제되어 PTK의 활성이 혈청이 고갈된 BNL CL.2 세포에서 NO의 생성에 중요한 역할을 담당하고 있기 때문으로 판단된다. IFN-γ의 독성은 혈청을 제거시킬 때 NO 생성 억제제에 상승적으로 간 세포를 손상시키며, 이때 NO가 IFN-γ에 의해 유도된 손상을 어느 정도 억제시키는 것을 알 수 있었다. Nitric oxide (NO) plays an important role in immunologic defense, and influences upon the functioning of secretory tissues and cells. It also exhibits cytotoxic/cytostatic activity as one of major operating effectors of the cellular immunity system. We investigated the effects of serum on the cell damages and NO production in the mouse liver cell line BNL CL.2 to establish the role of NO. We observed that, when BNL CL.2 cells were cultured in serum-free medium, they were induced to cell damage by the stimulation of IFN-γalone or IFN-γplus LPS. Serumstarved cells showed large amount of nitrite accumulation and NO synthase (NOS) expression in response to IFN-γalone in dose-and time-dependent manners, but serum-supplied cells did not. The production of NO was blocked by protein tyrosine kinase (PTK) inhibitors, genistein and herbimycin. These results suggest that the deprivation of serum in the BNL CL.2 cell culture medium might primed with the cells to produce NO when the cells are triggered by IFN-γ and the involvement of PTK signal transduction pathway in the expression of NOS gene in murine hepatocytes.

胎盤組織 Guanine Aminohydrolase에 關한 硏究

유지헌,林圭,郭相太,黃炳斗 충남대학교 의과대학 지역사회의학연구소 1987 충남의대잡지 Vol.14 No.2

Guanine aminohydrolase(EC 3.5.4.3, GAH) has been purified from human term placenta approximately 1,280-fold with a 10% yield by combination of ultracentrifuge, ammonium sulfate precipitate, Sephacryl S-300 chromatography, calcium phosphate gel adsorption, DEAEcellulose chromatography and hydroxyapatite chromatography, and then its properties were investigated. 1. The purified enzyme appeared single protein band by SDS/polyacrylamide gel electrophoresis. 2. The enzyme showed a pH optimum around 5.6-8.6. It was heat labile, inactivated by heat-treatment for 10 minutes at 70℃, and irreversively denatured by freezing and was stable at 4℃ for at least 1 month. 3. Copper ion (Cu^2+) was a potent inhibitor, the activity being inhibited upto 75% at 2 mM concentraion and the inhibition was completely recovered its activity by additon of 4 mM EDTA, and zinc ion (Zn^2+ also inhibited upto 40% at 2 mM concentration. The other ions did not almost inhibit. 4. The apparent Km value for guanine was 4 X 10^-5M, and the enzyme activity was completely inhibited by 0. 5 mM of p-hydroxymercuribenzoic acid, but all of the activity was recovered in adding 10 mM mercaptoethanol. 5. The molecular weight of the enzyme showed 170,000 by Sephacryl S-300 chromatography, and 55,000 by SDS-polyacrylamide gel electrophoresis. And the properties such as above results of guanine aminohydrolase of human term placenta are compared with those of guanine aminohydrolase of other tissues.

수지진동증후군의 진단시 냉각부하검사에 의한 수지피부온도의 평가

유철인,이지호,이충렬,이헌,최영희,김양호 大韓産業醫學會 2002 대한직업환경의학회지 Vol.14 No.2

목 적 : 진동에 폭로된 근로자들을 대상으로 진동장해의 유무를 평가하고 냉각부하 후 수지피부온도를 측정하여 수지진동증후군의 유형별로 결과를 평가하여 향후 수지진동증후군 진단의 객관적인 지표로 사용하기 위한 기본적인 자료를 확보하고자 본연구를 실시하였다. 방 법 : 진동에 폭로된 근로자 58명을 대상으로 설문조사와 이학적 검사를 실시하였으며 Stock-holm-revised vibration syndrome classification system에 따라 근로자를 평가하였다. 평가 후 연구대상자들을 말초혈관증상군, 말초신경증상군, 특별한 중상이 없는 무증상군으로 분류하여, 10 ℃에서 10분간 냉각부하하면서 수지피부온도를 측정하고, 측정된 수지피부온도를 이용하여 5분 회복율과 10분 회복율을 산출하여 각 군별로 비교하였다. 결 과 : 연구대상자들을 분류한 결과 말초혈관장해를 호소하는 군이 33명이었으며, 말초신경장해만 있는 군은 18명이었으며, 특별한 증상이 없는 무증상군이 7명이었다. 수지냉각부하검사결과 냉각부하가 끝난 다음 5분, 10분 후에 측정한 피부온도와 5분 회복율, 10분 회복율은 혈관증상군이 신경증상군과 무증상군에 비하여 통계적으로 유의하게 낮았다(P<0.05). 결 론 : 냉각부하시 수지피부온도를 이용한 회복율은 수지진동증후군의 말초혈관장해 진단에 객관적인 지표로 사용할 수 있을 것으로 추정된다. Objectives : Various objective tests have been widely used worldwide for diagnosing the hand-arm vibration syndrome. Among these, the cold provocation test has been frequently used to confirm the presence of Raynaud's phenomenon. This study was carried out in order to evaluate finger skin temperature by cold provacation test(10 ℃ for 10 minute) for the diagnosis of hand-arm vibration syndrome Methods : Fifty-eight workers who had been to exposed local vibration were examined. Information concerning age, occupation, types of vibration tools used, presence of subjective symptoms such as vibration induced white finger(VWF), and numbness and tingling were collected. The subjects were classified into three groups according to their symptoms(Vascular, Neural, and No symptom group). In order to examine the applicability of the cold provocation test using water at 10 ℃ for 10 minute, we compared finger skin temperature between the groups. Results : The mean value of the finger skin temperature at 5 minutes and 10 minutes after cold provocation as well as the recovery rate in the vascular group were significantly lower than that seen in the other groups. Conclusions : The evaluation of finger skin temperature by cold provocation test is very useful method for the diagnosis of hand-arm vibration syndrome. The test results will assist in confirming the diagnosis of the hand-arm vibration syndrome.

정신분열병 환자에서 Risperidone에 의해 유발된 조증 2례

정두훈,윤도준,유희정,송지영 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.2

저자들은 정 신분열병 환자에서 risperidone에 의해 유발된 조증, 경조증 각 1례를 경험하였기에 국내에서는 최초로. 문헌고찰과 함께 보고한다. 증례 1은 22세의 여자 긴장형 정신분열병 환자로 3년전 발병 당시 약물치료후 유지요법 없이 지내다가 4∼5개월 전부터 사회적 위축, 식사량 저하. 말수가 줄어드는 등의 음성증상이 심해져 외래에서 risperidone 2mg을 일 주일간 처방하였다. 환자는 약물순응도가 낮아서 모두 6회에 걸쳐 억지로 투약하여 이 기간에 총 6∼8mg복용후 2∼3일 만에 조증이 발생되었다. 입원후 risperidone을 중단하고 lithium과 고용량의 정형 항정신병약물(chlorpromazine 1200mg 또는 haloperidol 20mg)을 10일간 투여하여 일부 조증이 호전되었다. 증례 2는 29세 남자로 3년 전부터 피해망상, 독극망상을 보이는 망상형 정신분열 병으로 항정신병약물을 처음 투여한 환자였다. 38일간 2mg 사용 시에는 양성증상 및 음성증상의 호전을 보이다가 3mg으로 증량된 후 일 주일만에 뚜렷한 경조증을 보였다. Risperidone을 중단하고 chlorpromazine 300mg을 투여하자 5일 만에 경조증이 완전히 회복되었다. 두 예 모두 risperidone 단독투여에 의한 것이었고, 기분안정제 병합투여, 약물남용 정신질환의 병력이나 가족력, 동반 신체질환은 없었다. Risperidone의 세로토닌(5-HT₂) 차단효과는 도파민(D₂) 차단작용과 함께 정신분열 병에서 음성증상과 정동중상을 호전시킬 뿐 아니라 항우울효과를 나타내며. 일부 환자에서 조증 및 경조증을 유발시키는 것으로 보인다. 기분장애와 분열정동장애에서도 risperidone에 의해 조증이 유발 또는 기존 조증중상이 악화되었다는 증례보고가 있고. 강박장애 등 다른 정신질환으로도 적응증이 확대되고 있으므로, 임상의들은 드물지만 이런 정신과적 부작용의 발생 가능성에 대해 알아야 하겠고. 특히 기분장애나 분열정동장애에서 사용할 경우 기분안정제의 병합투여와 최소 치료용량으로 서서히 증량할 것을 권하는 바이다. 또한 조증유발의 위험인자가 있는 경우는 기분안정효과가 있는 clozapine의 사용이 권장된다. We report the first two cases of manic and hypomanic episodes respectively induced by risperidone treatment done to schizophrenics in Korea. One case was a 22-year-old woman with catatonic schizophrenia. Since 3 years ago, she had shown psychotic symptoms, but with was poor treatment compliance. She had mainly negative symptoms such as social withdrawal, decreased food intake, mutism, and symptoms had been worsened since last 4-5 months. Prior to closed ward admission, she was prescribed 2mg/d of risperidone for a week at OPD. Two days artier taking medicine totally 6-8mg, she revealed manic features. After hospitalization, risperidone was discontinued and then, lithium 900mg/d and high dosage of conventional antipsychotics(chlorpromazine 1200mg/d or haloperidol 20mg/d) were prescribed . About on the l0th day of hospitalization, there was limited improvement of her manic symptoms. The other case was a 29-year-old man with a 3-year history of paranoid schizophrenia. He was never exposed to antipsychotics before. His main symptoms were delusions of being poisoned and of persecution. His positive and also negative symptoms were alleviated by 38 days of risperidone 2mg/d trial. However, one week after dosage increment to 3mg/d, hypomanic symptoms appeared. Risperidone medication was discontinued and was replaced by chlorpromazine 300mg/d. The hypomanic episode was resolved over 5 days. In both of the two cases, manic episodes occurred by monotherapy of risperidone without mood stabilizer, and there were no history of substance abuse and other psychiatric disorders, family history of psychiatric disorders, and comorbid physical illnesses. It is hypothesized that the potent blockade effect on serotonin(5-HT₂) receptor of risperidone causes antidepressant effect as well as therapeutic effect for negative and affective symptoms in schizophrenia. Risperidone would induce manic or hypomanic features in schizophrenic patin of preexisting manic symptoms by risperidone treatment in mood disorder and schizoaffective disorder. Risperidone is being used more widely, even for obsessive-compulsive disorder and other psychiatric disorders. It is necessary for clinicians to recognize manic switch, one of psychiatric side effects by risperidon trial. It is recommended that the combination of mood stabilizer wish risperidone or usage of talc minimum effective dose of risperidone may bewefal especially in the patients with mood disorders or schizoaffective disorders. Clozapine which has mood-stabilizing properties is also beneficial in risk groups of risperidone-induced mania.

초고속 광통신망을 위한 1×N Splitter 설계 및 제작

이상훈,지유강,박수봉 東新大學校 2003 論文集 Vol.13 No.-

In this paper, we fabricated channel waveguide using a BPSG thin flim to develop 1×N optical splitters for optical communication networks by Flame Hydrolysis Deposition(FHD) method. The thickness and reflective index of thin film on channel optical waveguide is measured by prism coupler. And splitter is designed l×N splitter that curved ratio and offset of S-type bent waveguide on branching point of 1x2 splitter by beam propagating method(BPM). The results of curved ratio and offset is 40mm and 0.35㎛ respectively. 1×2 Splitter is simulated to design with core structure of 8.0x8.0, ㎛, reflective index difference 0.29%. 1×32 Splitter is measured core structure of 7.8×8.0㎛, core index of 1.4477, base index of 1.4429, base thickness of 23.4㎛ by prism coupler and optical properties is measured insertion loss of ≤17.3dB, uniformity of 1.8dB, polarization dependent loss of 0.3dB and Return loss of ≥55dB in 1310~1550㎚. 1×N Splitter is measured that near-field pattern on etch port is observed single mode by end-fire coupling. It is confirmed that the 1×N optical splitter can realize highly 2×N optical splitter and N-channel WDM, density wavelength division multiplexer(WDM) el. and WDM-based interconnect optical networks.

유기용제노출이 직업적 청력손실에 미치는 영향

이지호,고영주,이헌,강정학,유철인,이충렬,김양호 大韓産業醫學會 2000 대한직업환경의학회지 Vol.12 No.4

목적 : 산업 장에서 노출되는 유기용제가 청력역치에 어떠한 영향을 미치는가를 5년 동안의 추적조사를 통하여 파악하고자 하였다. 방 법 : 유기용제와 소음에 동시에 노출된 근로자 43명과 소음노출수준, 연령, 근무경력을 짝짓기 한소음노출군을 대상으로 문진과 이경검사, 소음노출 수준, 유기용제노출수준을 조사하였다. 결과 : 1. 전체 근로자의 각 주파수별 청력역치 변화양상에서 500Hz∼2000Hz에서는 추적기간 동 소음동안 현저한 변화가 없었고, 4000Hz 및 8000Hz에서는 역치가 증가하는 경향을 나타내었다. 2.유기용제와 소음에 동시에 노출된군에서 소음 노출군에 비해 4000Hz 이상에서 청력역치가 높게 나타났으나, 통계적인 유의성은 없었다(p(0.05). 3.반복측정 분산분석 법으로 각 주파수별 평균청력 역치의 연차적 변화에 미치는 영향을 분석한 결과 유기용제 노출은 통계적으로 유의한 영향이 없었으나(p)0.05), 소음노출수준은 250Hz, 2000Hz 및 4000Hz에서, 연령은 250Hz와 500Hz에서 통계학적으로 유의한 영향을 미치는 것으로 나타났다(p(0.05). 4.소음노출군파 동시노출군 각각에서의 청력역치 변화량을 paired t-test로 비교한 결과 250Hz∼4000Hz에서는 통계학적 유의성이 없었으며(p(0.1), 8000Hz에서만 경계치 (p=0.0884)의 유의성을 나타내었다. 5.요인들의 영향을 보정한 상태에서 관찰하기 위해 관찰기간동안의 청력역치변화량을 종속변수로 두고 일반선형모형을 이용하여 주파수별로 관찰한 결과 8000Hz에서만 모델에 통계학적 유의성이 있었으며 (p(0.05), 여기서 소음노출수준이 통계학적으로 유의한 영향을 미치는 것으로 나타났고(p(0.05), 유기용제노출은 경 계수준이 었다(p=0.087). 결론 : 청력에 대한 유기용제의 영향이 소음과 연령에 비해 상대적으로 미미하여 명확한 결론에 이르지는 못하였으나, 다소 영향이 있는 것으로 생각되어 유기용제의 영향에 대한 추가연구가 필요할 것으로 판단된다. 또한 보다 효과적인 근로자들의 청력관리를 위해서는 소음 외 산업 장에서 동시에 노출되는 여러 유해물질들을 고려하여야 할 것이다. Objectives : This study was to evaluate the impacts of simultaneous exposure to noise and mixed solvents on workers'hearing threshold level (HTL) over five-year period. Methods : The study was conducted by interview and annual audiometric test on workers in ship building industry from 1994 to 1998. The cases(workers who exposed to noise and mixed solvent simultaneously) were 43 male workers and controls (workers who exposed to nolle) were selected by matching method with regard to age, sex, carrier, and noise exposure level. To assess the impacts of solvent exposure on hearing threshold level, with considering other factors, general liner model was used. Results : 1. The audiogram of all subjects showed typical sensorineural hearing loss pattern. The mean HTLe were increased at high frequency (4000HB and 8000Hz) for study period. 2. The HTLs of cases were more increased than those of controls at high frequencies (4000Hz and 8000Hz), but there was not statlstical significance. 3. The impact of age on the HTL was statistically significant at 250Hz and 500Hz (p(0.05), and the impact of noise on the HTL was statistically significant at 250Hz, 2000Hz and 4000Hz (p(0.05), but the impact solvent exposure on the HTL was not significant. 4. The changes in HTLs of cases were higher than those of controls at high frequency, there were not statistical significance at 4000Hz, but only at 8000Hz (p=0.087). 5. Statistical analysis of the general linear model implicated that the changes in HTL was impacted by noise exposure bevel significantly (p=0.031) and Impacted by solvent exposure weakly (p=0.087) at 8000Hz. Conclusions : The results of this study suggest that workers who simultaneously exposed to noise and mixed solvent were at risk for more affected HTL than those exposed to noise exposure only, but we could not find definitive evidence. Further detailed studies must be made in large number of workers.

한국에서의 양극성장애와 Borna Disease Virus와의 관련성

김지관,정성훈,이유철,조유진 대한생물치료정신의학회 2001 생물치료정신의학 Vol.7 No.1

It has been known that Borna disease virus(BDV) naturally infects horses and sheep, and causes a sporadic neurological disease. There have been many studies of the relation between this virus and human neurological and psychiatric disease, but the definite result remains uncertain, yet. Here, by using a nested reverse trancription-polymerase chain reaction (RT-PCR) technique in the p40 regions, we tried to demonstrate that BDV RNA was present in the peripheral blood mononuclear cells of bipolar patients. In an examination of a total of 38 bipolar patients from 4 different hospitals in Taegu, Republic of Korea, BDV genomic RNA was detected in the p40 region in only one case. These data do not support an etiologic association between BDV infection and bipolar disorder in humans.

울산 석유화학공단 인근 어린이들의 혈액상변화 및 면역기능

이충렬,유철인,이지호,이헌,김양호 대한산업의학회 2001 대한직업환경의학회지 Vol.13 No.2

목적 : 지역 특성상 휘발성 유기화합물, 분진, 악취 등 환경오염의 영향을 많이 받는 것으로 추정되는 울산석유화학공단 인근 어린이들의 혈액상 변화, 계절 차이에 의한 혈액상 변화와 면역기능에 미치는 영향을 평가하기 위하여 본 연구를 실시하였다. 방법 : 2000년 4월, 7월, 10월 3회에 걸쳐 석유화학공단 인근 A 초등학생 46명(남자 32명, 여자 14명), B 초등학생 97명(남자 49명, 여자 48명)과 교외지역의 A 초등학생 95명(남자 47명, 여자 48명)을 대상으로 일반혈액검사, 백혈구 백분율 검사를 실시하였으며 7월 조사 때는 B 및 C 초등학생 11세 남자 각각 25명을 대상으로 면역학적 기능검사를 실시하였다. 결과 : 3차례에 걸쳐 진행된 검사결과는 계절별로 다른 양상을 보여 주었다. 즉, 총백혈구수, 호중구수, 림프구수는 A와 C 초등학생은 7월 조사에서는 감소되었다 다시 10월 조사 때는 다시 증가하는 경향을 보여주며, B초등학생은 계절별 변화가 거의 없는 것으로 나타났다. 적혈구수는 B와 C 초등학생은 7월 조사시 감소되었다가 10월 조사 때는 다시 증가하는 양상을 보여주나 A 초등학생은 갈수록 감소하는 경향을 보여주었다. 혈색소량의 변화는 적혈구수의 변화와 유사하였다 혈소판수는 모두 7월 조사 때는 감 소되었다가 10월 조사 때는 다시 증가하는 양상을 보여주었다. 조사시기에 따라 각 학교 어린이들간에 혈구세포수의 차이가 있음을 구명하기 위하여 generalized linear model의 repeated measures ANOVA를 시도한 결과 연령과 성을 공변인으로 보정한 후의 P 값에서 조사시기의 차이와 학교간 차이의 교호작용변수(interaction variable)는 모든 혈구세포에서 유의한 것으로 나타났다(P<0.05). 이는 조사시기에 따라 각 학교어린이들간에 혈구세포수의 차이가 유의하게 다르다는 것을 의미한다. 면역기능 평가를 위하여 혈중 immunoglobulin 측정 및 림프구 아형 분포분석을 B 및 C 초등학생 6학년 남학생 각 25명, 총 50명을 대상으로 실시하였으나 모두 정상범위이었고 학교간 차이도 없었다. 결론 : 휘발성 유기화합물 같은 물질에 쉽게 영향을 받을 수 있는 백혈구와 적혈구 등의 혈구세포는 조사시기에 따라 각 학교어린이들간에 혈구세포수의 차이가 유의하게 나타남은 각 학교 어린이들간에 조사시기에 따라 혈구세포수에 영향을 주는 휘발성 유기화합물의 노출량의 차이가 중요한 원인 중 하나일 것으로 추정된다. 향후 혈구세포의 변화의 원인이라 추정되는 휘발성 유기화합물의 기중 농도측정이나 체내 생체지표검사를 통한 노출원 조사를 병행하는 추가적 조사가 필요한 것으로 사료된다. Objectives : To evaluate the hematological changes and the immunological function of children living near the petrochemical estate in Ulsan. Methods : The study subjects comprised of 238 children who consisted of 143 children living near the petrochemical estate and 95 children living in a suburban area. We conducted the hematological examination 3 times, in April, July and October. Also we evaluated the immunological function of some children in July. To confirm differences between schools repeated measures ANOVA of generalized linear model was done controlling age and sex as covariates. Results : The blood cell counts of children showed differences between schools in accordance with the survey month. The total WBC, neutrophil, and lymphocyte counts of children living in a suburban area decreased in July and increased in October again, but those of some children living near the petrochemical estate did not changed distinctly. The RBC counts of children living in a suburban area decreased in July and increased in October again, but those of some children living near the petrochemical estate decreased as time passed. The changes of the amount of hemoglobin of all study subjects were similar with those of RBC. The platelet counts of all study subjects decreased in July and increased in October again. In the generalized linear model, school was a significant independent variable for the total WBC, RBC, and platelet counts, and sex was a significant independent variable for the RBC counts. Age was a significant independent variable for the iymphocyte and platelet counts. P values of all blood cell were statistically significant in interaction variable between the survey month and school, and those of the total WBC, neutrophil, and iymphocyte counts were statistically significant in interaction variable between the survey month and age. The immunological function showed no significant difference between study groups. Conclusions : The total WBC and RBC counts which would be easily affected by volatile organic compounds (VOCs) in the atmosphere showed differences between schools in accordance with the survey month. This suggests that the amounts of exposure to VOCs are different among each school children in different months. To ascertain the hematological changes by VOCs, an additional study evaluating the concentrations of atmosphere of VOCs and biological monitoring of some VOCs is needed.

대량의 각혈로 사망한 장티푸스 1예

한상우,유진홍,권순석,김성훈,박지찬,홍은정,최경성,박용완,장준희,안지원,박유경,강지영,박상미,신완식 대한감염학회 2004 감염과 화학요법 Vol.36 No.5

We experienced a 25 year-old male patient with typhoid fever complicated with massive hemoptysis. Pulmonary complication in typhoid fever is very rare and to our knowledge, there has been no report of hemoptysis as a main cause of death with this disease. We herein report a rare case of typhoid fever.