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RALY RNA Binding Protein-like Reduced Expression is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

  • Cui, Zhi-Wen;Xia, Ye;Ye, Yi-Wang;Jiang, Zhi-Mao;Wang, Ya-Dong;Wu, Jian-Ting;Sun, Liang;Zhao, Jun;Fa, Ping-Ping;Sun, Xiao-Juan;Gui, Yao-Ting;Cai, Zhi-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3403-3408
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    • 2012
  • The molecular mechanisms involved in the progression of clear cell renal cell carcinomas (ccRCCs) are still unclear. The aim of this study was to analyse the relationships between expression of RALYL and clinical characteristics. In 41 paired samples of ccRCCs and adjacent normal tissues, we used real-time qPCR to evaluate the expression of RALYL mRNA. RALYL protein levels were determined in 146 samples of ccRCC and 37 adjacent normal tissues by immunohistochemistry. Statistical analysis was used to explore the relationships between expression of RALYL and the clinical characteristics (gender, age, tumor size, T stage, N stage, M stage, survival times and survival outcome) in ccRCC. In addition, these patients were follow-up period 64 months (range: 4~116months) to investigate the influence on prognosis. We found significantly differences between ccRCC tissues and normal tissues (p<0.001, paired-sample t test) in mRNA levels of RALYL. Immunohistochemistry analyses in 146 ccRCC samples and 37 adjacent normal tissues showed significantly lower RALYL protein levels in ccRCC samples (${\chi}^2$-test, p<0.001), inversely correlating with tumour size (p=0.024), T stage (0.005), N stage (p<0.001) as well as M stage (p=0.019), but not age (p=0.357) and gender (p=0.348). Kaplan-Meier survival analysis demonstrated that people with lower level of RALYL expression had a poorer survival rate than those with a higher level of RALYL expression, significantly different by the log-rank test (p=0.011). Cox regression analysis indicated that RALYL expression (p=0.039), N stage (p=0.008) and distant metastasis (p<0.001) were independent prognosis factors for the overall survival of ccRCC patients. We demonstrated that the expression of RALYL was significantly low in ccRCC and correlated with a poor prognosis in a large number of clinical samples. Our findings showed that RALYL may be a potential therapeutic target as well as a poor prognostic factor.

CT Based 3-Dimensional Treatment Planning of Intracavitary Brachytherapy for Cancer of the Cervix : Comparison between Dose-Volume Histograms and ICRU Point Doses to the Rectum and Bladder

  • Hashim, Natasha;Jamalludin, Zulaikha;Ung, Ngie Min;Ho, Gwo Fuang;Malik, Rozita Abdul;Ee Phua, Vincent Chee
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5259-5264
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    • 2014
  • Background: CT based brachytherapy allows 3-dimensional (3D) assessment of organs at risk (OAR) doses with dose volume histograms (DVHs). The purpose of this study was to compare computed tomography (CT) based volumetric calculations and International Commission on Radiation Units and Measurements (ICRU) reference-point estimates of radiation doses to the bladder and rectum in patients with carcinoma of the cervix treated with high-dose-rate (HDR) intracavitary brachytherapy (ICBT). Materials and Methods: Between March 2011 and May 2012, 20 patients were treated with 55 fractions of brachytherapy using tandem and ovoids and underwent post-implant CT scans. The external beam radiotherapy (EBRT) dose was 48.6Gy in 27 fractions. HDR brachytherapy was delivered to a dose of 21 Gy in three fractions. The ICRU bladder and rectum point doses along with 4 additional rectal points were recorded. The maximum dose ($D_{Max}$) to rectum was the highest recorded dose at one of these five points. Using the HDRplus 2.6 brachyhtherapy treatment planning system, the bladder and rectum were retrospectively contoured on the 55 CT datasets. The DVHs for rectum and bladder were calculated and the minimum doses to the highest irradiated 2cc area of rectum and bladder were recorded ($D_{2cc}$) for all individual fractions. The mean $D_{2cc}$ of rectum was compared to the means of ICRU rectal point and rectal $D_{Max}$ using the Student's t-test. The mean $D_{2cc}$ of bladder was compared with the mean ICRU bladder point using the same statistical test. The total dose, combining EBRT and HDR brachytherapy, were biologically normalized to the conventional 2 Gy/fraction using the linear-quadratic model. (${\alpha}/{\beta}$ value of 10 Gy for target, 3 Gy for organs at risk). Results: The total prescribed dose was $77.5Gy{\alpha}/{\beta}10$. The mean dose to the rectum was $4.58{\pm}1.22Gy$ for $D_{2cc}$, $3.76{\pm}0.65Gy$ at $D_{ICRU}$ and $4.75{\pm}1.01Gy$ at $D_{Max}$. The mean rectal $D_{2cc}$ dose differed significantly from the mean dose calculated at the ICRU reference point (p<0.005); the mean difference was 0.82 Gy (0.48-1.19Gy). The mean EQD2 was $68.52{\pm}7.24Gy_{{\alpha}/{\beta}3}$ for $D_{2cc}$, $61.71{\pm}2.77Gy_{{\alpha}/{\beta}3}$ at $D_{ICRU}$ and $69.24{\pm}6.02Gy_{{\alpha}/{\beta}3}$ at $D_{Max}$. The mean ratio of $D_{2cc}$ rectum to $D_{ICRU}$ rectum was 1.25 and the mean ratio of $D_{2cc}$ rectum to $D_{Max}$ rectum was 0.98 for all individual fractions. The mean dose to the bladder was $6.00{\pm}1.90Gy$ for $D_{2cc}$ and $5.10{\pm}2.03Gy$ at $D_{ICRU}$. However, the mean $D_{2cc}$ dose did not differ significantly from the mean dose calculated at the ICRU reference point (p=0.307); the mean difference was 0.90 Gy (0.49-1.25Gy). The mean EQD2 was $81.85{\pm}13.03Gy_{{\alpha}/{\beta}3}$ for $D_{2cc}$ and $74.11{\pm}19.39Gy_{{\alpha}/{\beta}3}$ at $D_{ICRU}$. The mean ratio of $D_{2cc}$ bladder to $D_{ICRU}$ bladder was 1.24. In the majority of applications, the maximum dose point was not the ICRU point. On average, the rectum received 77% and bladder received 92% of the prescribed dose. Conclusions: OARs doses assessed by DVH criteria were higher than ICRU point doses. Our data suggest that the estimated dose to the ICRU bladder point may be a reasonable surrogate for the $D_{2cc}$ and rectal $D_{Max}$ for $D_{2cc}$. However, the dose to the ICRU rectal point does not appear to be a reasonable surrogate for the $D_{2cc}$.

Foundation Methods for the Soft Ground Reinforcement of Lightweight Greenhouse on Reclaimed Land: A review (간척지 온실 기초 연약지반 보강 방법에 대한 고찰)

  • Lee, Haksung;Kang, Bang Hun;Lee, Su Hwan
    • Journal of Bio-Environment Control
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    • v.29 no.4
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    • pp.440-447
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    • 2020
  • The demand for large-scale horticultural complexes utilizing reclaimed lands is increasing, and one of the pending issues for the construction of large-scale facilities is to establish foundation design criteria. In this paper, we tried to review previous studies on the method of reinforcing the foundation of soft ground. Target construction methods are spiral piles, wood piles, crushed stone piles and PF (point foundation) method. In order to evaluate the performance according to the basic construction method, pull-out resistance, bearing capacity, and settlement amount were measured. At the same diameter, pull-out resistance increased with increasing penetration depth. Simplified comparison is difficult due to the difference in reinforcement method, diameter, and penetration depth, but it showed high bearing capacity in the order of crushed stone pile, PF method, and wood pile foundation. In the case of wood piles, the increase in uplift resistance was different depending on the slenderness ratio. Wood, crushed stone pile and PF construction methods, which are foundation reinforcement works with a bearing capacity of 105 kN/㎡ to 826 kN/㎡, are considered sufficient methods to be applied to the greenhouse foundation. There was a limitation in grasping the consistent trend of each foundation reinforcement method through existing studies. If these data are supplemented through additional empirical tests, it is judged that a basic design guideline that can satisfy the structure and economic efficiency of the greenhouse can be presented.

A Study on LRFD Reliability Based Design Criteria of RC Flexural Members (R.C. 휨부재(部材)의 L.R.F.D. 신뢰성(信賴性) 설계기준(設計基準)에 관한 연구(研究))

  • Cho, Hyo Nam
    • KSCE Journal of Civil and Environmental Engineering Research
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    • v.1 no.1
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    • pp.21-32
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    • 1981
  • Recent trends in design standards development in some European countries and U.S.A. have encouraged the use of probabilistic limit sate design concepts. Reliability based design criteria such as LSD, LRFD, PBLSD, adopted in those advanced countries have the potentials that they afford for symplifying the design process and placing it on a consistent reliability bases for various construction materials. A reliability based design criteria for RC flexural members are proposed in this study. Lind-Hasofer's invariant second-moment reliability theory is used in the derivation of an algorithmic reliability analysis method as well as an iterative determination of load and resistance factors. In addition, Cornell's Mean First-Order Second Moment Method is employed as a practical tool for the approximate reliability analysis and the derivation of design criteria. Uncertainty measures for flexural resistance and load effects are based on the Ellingwood's approach for the evaluation of uncertainties of loads and resistances. The implied relative safety levels of RC flexural members designed by the strength design provisions of the current standard code were evaluated using the second moment reliability analysis method proposed in this study. And then, resistance and load factors corresponding to the target reliability index(${\beta}=4$) which is considered to be appropriate level of reliability considering our practices are calculated by using the proposed methods. These reliability based factors were compared to those specified by our current ultimate strength design provisions. It was found that the reliability levels of flexural members designed by current code are not appropriate, and the code specified resistance and load factors were considerably different from the reliability based resistance and load factors proposed in this study.

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Comparison of the Medication Effects between Milnacipran and Pregabalin in Fibromyalgia Syndrome Using a Functional MRI: a Follow-up Study (섬유근통 환자에 대한 Milnacipran과 Pregabalin 약물치료에 대한 기능적 자기공명영상에서의 후속 영향 비교)

  • Kang, Min Jae;Mun, Chi-Woong;Lee, Young Ho;Kim, Seong-Ho
    • Investigative Magnetic Resonance Imaging
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    • v.18 no.4
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    • pp.341-351
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    • 2014
  • Purpose : In this study, the medication effects of Milnacipran and Pregabalin, as well known as fibromyalgia treatment medicine, in fibromyalgia syndrome patients were compared through the change of BOLD signal in pain related functional MRI. Materials and Methods: Twenty fibromyalgia syndrome patients were enrolled in this study and they were separated into two groups according to the treatment medicine: 10 Milnacipran (MLN) treatment group and 7 Pregabalin (PGB) treatment group. For accurate diagnosis, all patients underwent several clinical tests. Pre-treated and post-treated fMRI image with block-designed pressure-pain stimulation for each group were obtained to conduct the statistical analysis of paired t-test and two sample t-test. All statistical significant level was less than 0.05. Results: In clinical tests, the clinical scores of the two groups were not significantly different at pre-treatment stage. But, PGB treatment group had lower Widespread Pain Index (WPI) and Brief Fatigue Inventory (BFI) score than those of MLN treatment group at post-treatment stage. In functional image analysis, BOLD signal of PGB treatment group was higher BOLD signal at several regions including anterior cingulate and insula than MLN treatment group at post-treatment stage. Also, paired t-test values of the BOLD signal in MLN group decreased in several regions including insula and thalamus as known as 'pain network'. In contrast, size and number of regions in which the BOLD signal decreased in PGB treatment group were smaller than those of MLN treatment group. Conclusion: This study showed that MLN group and PGB group have different medication effects. It is not surprising that MLN and PGB have not the same therapeutic effects since these two drugs have different medicinal mechanisms such as antidepressants and anti-seizure medication, respectively, and different detailed target of fibromyalgia syndrome treatment. Therefore, it is difficult to say which medicine will work better in this study.

The Suppressive Effects of Integrin Antibodies on the Infection of Hantaan Virus in Fibroblasts (한탄바이러스의 섬유아세포 감염에 대한 Integrin 항체의 억제 효과)

  • Park, Ho-Sun;Kim, Ki-Duk;Kim, Sung-Kwang
    • Journal of Yeungnam Medical Science
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    • v.15 no.1
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    • pp.55-66
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    • 1998
  • Pathophysiological mechanism of hemorrhagic fever with renal syndrome (HFRS) is not fully understood. Major clinical findings of HFRS patients are widespread hemorrhage, acute renal failure and shock. Basic lesion is vascular injury with microvascular hemorrhage and relatively little inflammation. According to autopsy findings, renal medulla shows focal hemorrhage, tubular necrosis and interstitial mononuclear infiltrates. The predominant cell type in the renal and pulmonary interstitium is a fibroblast and it participates in the healing process at the injury site by secreting a large amount of extracellular matrix proteins. Cultured human lung fibroblasts and Mongolian gerbil fibroblasts were known to be good host cells for the hantaan virus. It is possible that not only the endothelial cell but also the fibroblast is a target of Hantaan virus and the fibroblast might be involved in the pathogenesis and the healing process in HFRS. Integrins are adhesion molecules, and act as receptors for many extracellular matrix proteins. Recently, there are many reports that cell surface integrins influence on some viral infections or reversely viruses influence on the expression of integrins. The ${\alpha}_5{\beta}_1$ integrin is a major receptor for the fibronectin which is an important extracellular matrix protein secreted by fibroblasts. In this study, the role of ${\alpha}_5{\beta}_1$ integrin in the infection of Hantaan virus was examined by using anti-${\alpha}_5{\beta}_1$, integrin, anti-${\alpha}_5$ integrin and anti-${\beta}_1$, integrin antibodies in chicken embryo fibroblasts (CEF) and Mongolian gerbil fibroblasts(MGF). The treatment of anti-${\alpha}_5{\beta}_1$, integrin antibody in CEF reduced the virion titers 26.8% and the amount of nucleocapsid N protein 32.6% when compared with control CEF. When MGF were treated with anti-${\alpha}_5$, anti-${\beta}_1$ and anti-${\alpha}_5{\beta}_1$ integrin antibodies, virion titers were reduced by 26.5%, 29.4% and 28.7% and the amount of nucleocapsid N protein were reduced by 65.2%, 59.7% and 72.6%. These results suggested that ${\alpha}_5{\beta}_1$ integrin might act as a receptor for the Hantaan virus or blocking of ${\alpha}_5{\beta}_1$ integrin influences on the viral replication in CEF and MGF. It is also possible that the blocking of only one subunit of integrin represents similar results in that of whole molecule.

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Improvement of Melanin Production and Skin Tone by Fullerene Serum (플러린 함유 세럼의 멜라닌색소 및 피부톤 개선 효과)

  • Lim, Hyun-Sook;Lee, Mi-Bun;Lee, Jae-Nam
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.19 no.6
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    • pp.455-464
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    • 2018
  • This study investigated whether the whitening effects of fullerene serum occurred through improvement of melanin production and skin tone and evaluated its potential for use as a cosmetic material for adult women aged 30-55 with dull skin color and pigmentation. Subjects were divided into a control group with fullerene-less serum (B) and an experimental group with serum containing 0.1% fullerene (A) and evaluated over 8 weeks. Visual assessment and measurement of skin conditions (melanin index, skin brightness) were conducted before use of and 4 and 8 weeks after use of the product, and a questionnaire survey and safety assessment were conducted at the end of the experiment. The results revealed that the highest decrease was 0.37% in the experimental group (A) after eight weeks of use of the product, but that this difference was not statistically significant. Moreover, no significant differences were observed upon inter-group comparison. Evaluation of changes in the melanin index and inter-group comparison revealed a significant decline in the experimental group (A) at all time points. Additionally, the $L^*$ value (skin brightness) of the experimental group (A) showed a significant increase (improvement) after eight weeks, while in inter-group comparison revealed a significant increase (improvement) at all time points (4 and 8 weeks later) (p<0.05). Based on a questionnaire survey of efficacy, positive response rates such as improvement of the target parts on week 8 were high in terms of 'improvement of skin color.' Moreover, the safety assessment revealed no adverse reactions. In conclusion, serum containing 0.1% fullerene revealed improved melanin production and skin tone (brightness) and confirmed its potential for use as a cosmetic material with brightening efficacy. Taken together, the results of this study indicate systematic investigation of the effective application and cosmetics formulations of this product are warranted.

A Study on Curriculum Development For Community Health Practitioners (보건진료원 직무교육 교과과정 개선을 위한 일 연구)

  • 조원정;이경자
    • Journal of Korean Academy of Nursing
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    • v.22 no.2
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    • pp.207-226
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    • 1992
  • This study was designed to develop a conceptual framework for the curriculum and develop the details of the learning content for the education of Community Health Practitioners (CHPs). Since education programs for CHPs started 10 years ago, concepts related to CHP services have changed because of changes in society. The objectives of the study were as follows : 1) to analyse the usefulness of the present education program for CHPs, 2) to analyse the Job performance and self -confidence of the CHPs, 3) to identify the health needs of the clients served by the CHPs and the community problems related to health. 4) to develop a conceptual framework for the curriculum, for the education of CHPs, 5) to develops details for the learning content of the education program for CHPs. Phase I of the study was conducted by questionnaires to 150 CHPs who have worked in remote rural areas for more than 2 years. Among them, 147 responded. Data was collected from August 16, to August 25, 1990. In order to identify the health needs of the community people, research within the last five years was reviewed and analyzed. The data on 1, 842 communities gathered by the WHO Nursing Collaborations Center of the College of Nursing, Yonsei University was utilized to identify community problems related to health and the self - confidence in job performance of the CHPs. Psase II of the study consisted of a workshop with 13 professionals including Community Health Practitioners to evaluate the existing education program and a conceptual framework of the curriculum for the job education of CHPs. The results of the study are Summariged below : 1. The only 26 among 45 content items of the education program related to job skills was used by 80% of the responding CHPs. The knowledge of $\ulcorner$Networking community organization$\lrcorner$ was used by only 53.7% of the respondents. Educational content about $\ulcorner$Mental disease$\lrcorner$ was used by less than 50% of CHPs because of a knowledge deficit. 2. The CHPs reported that their activities concentrated on clinical services during the last six months. The survey showed that they seemed to neglect the activities for health promotion and disease prevention. Thus, $\ulcorner$Education for community loaders$\lrcorner$(15.9%), $\ulcorner$Activity for eavironmental health$\lrcorner$(16.3%) and $\ulcorner$Social work for needey people$\lrcorner$(23.3%) were done by less than 30% of CHPs. 3. More than 90% of CHPs reported being self - confident for the activities of $\ulcorner$Health education and counselling$\lrcorner$, $\ulcorner$Medicine prescription$\lrcorner$ and $\ulcorner$Immunization$\lrcorner$. But 50% of CHPs reported that they were not have self - confident in $\ulcorner$Management of water and environmental health$\lrcorner$ and only 25.6% of CHPs could insert an IUD independently. 4. It was identified that respiratory diseases and the gastrointestinal diseases were most common problems for the community people, followed by musculoskeletal and skin problems. 5. The community problems were classified into eight categories : physical environmental problems, environmental hygiene, health problems, health behavior, social problem, lack of resources, financial problem and the problems of the cultural and value system. 6. The conceptual framework consisted of the target population and their health status, nursing process working site and primary health care services such as health promotion, disease prevention, treatment and rehabilitation. 7. The contents of curriculum of education program for CHPs were formulated from the results of this study.

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Airway size in malocclusions with hyperdivergent skeletal pattern (개방교합성 골격헝태를 갖는 부정교합자의 기도크기)

  • Kwak, So-Yeong;Kim, Hyo-Young;Jeon, Young-MI;Kim, Jong-Ghee
    • The korean journal of orthodontics
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    • v.33 no.4 s.99
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    • pp.293-305
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    • 2003
  • The pharynx have significant locations and functions because it forms a part of the unit in which respiration and deglutition are carried out. Because of the closed relationship between the pharynx and the dentofacial and craniofacial structure, many studies are carried out on this subjects. The purpose of this study were to compare the airway size including pharynx, soft palate, tongue and hyoid bone between normal and hyperdivergent skeletal pattern and to evaluate the change of those size in different age. The sample of this study were consisted of 51 subjects in normal group, 52 subjects in hyperdivergent group. Each was divided into two subgroups by age , child group(9-l2yr old) and adult group(18yr old over). The lateral cephalometric radiographs were taken and the distance, angle and ratio of the facial skeleton, pharynx, soft palate, tongue and hyoid bone were measured and evaluated statistically. The result obtained were summarized as follows : 1 SN-Mn angle, FMA, and Pal-Mn angle were significantly larger in child group than adult group, but the lower anterior facial height(LAFH) and facial height ratio(FHR) were significantly smaller in child group than adult group. Occlu-Mn angle was significantly steep in hyperdivergent group than normal, but not significantly different between child group and adult group. 2. Hyperdivergent group and child group had the stronger correlation between SN-Mn angle, FMA, Pal-Mn angle, LAFH and FHR and airway size than normal group and adult group. Hyperdivevgent child group had significant negative correlation between SN-Mn angle, FMA, Pal-Mn angle and sagittal skeletal dimension of nasopharynx and sagittal depth of nasopharyngeal lumen. Significant positive correlation were seen between LAFH and vertical measurement of airway. 3. There was no difference of the linear measurement of airway size between hyperdivergent group and normal group. 4. Adult group had smaller posterior pharyngeal wall, target nasopharyngeal depth longer nasopharyngeal height and longer pharyngeal length than child group. 5. The sagittal measurement of hyoid bone had no difference between child group and adult group. But adult group had larger vertical measurement of hyoid bone than child group.

A Survey of Food and Nutrient Intakes of the Eged People in Rural Area, Gyeongbuk Yecheon (경북 예천 농촌지역 거주노인의 연령대별 영양소 및 식품섭취량 조사)

  • Park, Mi-Yeon;Kim, Gum-Ran;Lee, Da-Jeong;Kim, Jin-Moon;Park, Phil-Sook
    • Journal of Nutrition and Health
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    • v.39 no.1
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    • pp.58-73
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    • 2006
  • This research has done for 262 people of the aged men and women that are more than 65 years old who are live in 9 areas of Yecheon as target; through twice off ace to face interview for 24 hours recall method, the result of food intake for 2 days is as following. In case of energy, the aged men (women) of sixties ingested 67.7 $(72.0)\%$ of Korean RDA by 1,369 (1264) kcal, for the ages of seventies and eighties, 68.9 $(66.9)\%$ of Korean RDA and 76.3 $(65.8)\%$ by each 1,309 (1104) kcal and 1,368 (1052) kcal. The aged men ingested protein $46.0\~49.6 g$ ($70.6\~82.9\%$ of RDA), and aged women ingested protein $32.7\~40.2 g$ ($59.4\~73.0\%$ of RDA). Calcium intake of aged men was 388.8 mg, 319.8 mg, 284.4 mg by age range, and aged women was 291.9 mg ($41.6\%$ of RDA), 246.5 mg ($35.3\%$ of RDA), 240.1 mg ($34.3\%$ of RDA). Iron intake of aged men was $8.6\~8.9 mg$ ($72\~74%$ of RDA), and aged women ingested 8.6 mg ($71.3\%$ of RDA), 7.5 mg (62.6 of RDA$\%$), 6.6 mg ($55.4\%$ of RDA) for iron by age range. Vitamin $B_1$ intake of aged men was $0.62\~0.71 mg$ ($62\~71\%$ of RDA), and aged women's intake was $0.50\~0.60 mg$ ($50\~60\%$ of RDA). Vitamin $B_2$ intake of aged men was $0.59\~0.60 mg$ ($49\%$ of RDA), and aged women's intake was $0.45\~0.50 mg$ ($37\~42\%$ of RDA). Vitamin C intake by age range, in case of aged men (women) in sixties was 53.1 (48.9) mg, in seventies was 49.9 (33.2) mg and more than eighties was 34.1 (33.4) mg. The average food intake by age range, in aged men (women) of sixties was 828.9 (670.8) g and seventies was 726.8 (568.8) g and more than eighties was 656.0 (525.3) g. Plant food intake of aged men was 490.8-569.5 g and aged women was 417.9-537.7 g. Aged men (women) of MAR by age range, sixties was 0.60 (0.58), seventies was 0.59 (0.50) and more than eighties was 0.56 (0.49), respectively. INQ for protein, phosphorus, iron, vitamin A, vitamin B, niacin, vitamin C was more than 1 in 60's and 70's aged men, but there was no nutrients in eighties of aged women. Aged men and women's KDDS points represent average 3.14 and 3.04 (out of 5 points), and while intake of the milk was the most lacking, but intake of the fruit was the most lacking in DDS.