Attenuation of Bleomycin-Induced Pulmonary Fibrosis by AAV-Based Knockdown of Lysophosphatidic Acid Receptor 5 Suraj Parajuli : LPA5 in pulmonary fibrosis

SURAJ PARAJULI 가천대학교 메디컬캠퍼스 일반대학원 2024 국내석사

Attenuation of Bleomycin-Induced Pulmonary Fibrosis by AAV-Based Knockdown of Lysophosphatidic Acid Receptor 5 Suraj Parajuli Department of Pharmaceutical Life Science, College of Pharmacy, Gachon University Idiopathic pulmonary fibrosis (IPF) is one of the highly devastating interstitial lung diseases that is characterized by scar tissue in the lungs. The levels of LPA were found to be increased in both human patients and animal models. LPA1/2/3 was found to have a pathogenic effect on IPF. Additionally, LPA5 was overexpressed in the lungs of bleomycin (BLM)-induced IPF mice and BLM-induced lung fibrosis was inhibited by LPA5 antagonists, suggesting a pathogenic role of LPA5. This study aims to reaffirm the pathogenic role of LPA5 using Adeno-Associated Virus (AAV)-mediated knockdown of LPA5. To induce IPF, male C57BL/6J mice received an intratracheal injection of 1 mg/kg BLM. For LPA5 knockdown, AAV bearing shLPA5 or shNC was injected intravenously into mice via the tail vein. Based on the experimental design of prophylactic and therapeutic effect, the AAV injection into mice was administered 7 days before and 3 and 7 days after BLM administration, and mice were sacrificed at 14 or 21 days after BLM administration. The collected lung tissue samples were stained with Hematoxylin and eosin (H&E), Masson-Trichrome staining (MTS), and Immunofluorescence assay (IFA). The prophylactic effect of AAV-bearing LPA5 shRNA was identified and reduced the extent of fibrosis with a significant decrease in the Ashcroft score and collagen deposition. Similarly, the therapeutic effect of AAV-bearing LPA5 shRNA has also been identified as having a promising role in reducing IPF-induced pulmonary damage. However, it has also been identified that AAV was not able to block the activity of receptors within 7 days, due to which the therapeutic effect of AAV-mediated knockdown of LPA5 was determined by prolonging AAV vector incubation time. Moreover, with the increase in the experimental time frame, the lung damage was reversed. As, the pathogenicity of lung fibrosis is involved with different underlying mechanisms. So, SMAD2 activation was determined, as it has already been found to be pathogenic in numerous fibrosis diseases. In this study, it has been demonstrated that pSMAD2 was activated in BLM-induced IPF lungs whereas suppressing LPA5 activity reduced pSMAD2 upregulation in injured lungs. These results suggest that targeting LPA5 using shLPA5 AAV might be a potential strategy for IPF drug development. Keywords: Lysophosphatidic acid receptor 5 (LPA5), Idiopathic pulmonary fibrosis, Bleomycin, Adeno Associated Virus, Collagen, SMAD2.

Genome analysis of Streptomyces peucetius : cytochrome P450, regulatory elements and secondary metabolites

Parajuli, Niranjan Sunmoon Univ. 2004 국내박사

Roll-to-Roll gravure printed 4-bit ALU : the first step for sustainable green foundry for manufacturing sub-penny disposable 4-bit processors

Parajuli, Sajjan Sungkyunkwan University 2023 국내박사

A sub-penny flexible microprocessor (spFM) can let everything become smart objects for cooperatively assisting human’s valuable life through innovative healthcare, Internet of Things, and wearable electronics. To provide spFM on everything, billions of the spFM are needed per day. However, current photolithography-based manufacturing technologies will emit huge greenhouse-gas (GG) that would act as a counter blow in assisting the human’s valuable life. In this thesis, as the first step of sustainable green foundry with dramatically reduced GG emission, a roll-to-roll (R2R) gravure printing system demonstrates its potential to print the spFM on poly(ethylene terephthalate) (PET) film by integrating 12 thin film transistors (TFTs) to wirelessly show function of generating “1” and “0”, called 1-bit code generator for blinking QR code, 46 TFTs to show 1-bit arithmetic logic unit (ALU), and 156 TFTs for 4-bit ALU. Especially, all R2R gravure printed 4-bit arithmetic logic unit (ALU) is imbedded in PC to demonstrate its function. The 1-bit code generator, 1-bit ALU, and 4-bit ALU were all continuously printed up to seven layers in-line on PET film with a printing speed of 5.4 m/min starting from gate electrodes and bus lines, dielectric layers, active layers, junction insulator layers, drain-source electrodes, p-type dopant, and n-type dopant while maintaining constant ink transfer rate and overlay printing registration accuracy. The R2R gravure printed 1-bit code generator, 1-bit ALU, and 4-bit ALU were consisted with complementary single-walled carbon nanotube (SWCNT)-based logic gates. The device yields of the R2R gravure printed 1-bit code generator, 1-bit ALU, and 4-bit ALU were respectively 90%, 60% and 20% along a printed length of 10 m. As a result, this thesis proved, for the first time in the world, that the sustainable R2R printing foundry can be practically realized by starting a service to manufacture flexible electronic devices with the integration of 156 TFTs and will be expandable for fabricating sophisticated circuits such as processors and microcontrollers which would make the realization of IoT more feasible. 1페니 이하의 유연한 마이크로프로세서(spFM)는 혁신적인 헬스케어, 사물 인터넷 및 웨어러블 전자장치를 통해 모든 것이 인간의 소중한 생명을 협력적으로 돕는 스마트 사물이 될 수 있다. 이러한 모든 스마트 사물에 spFM을 공급하기 위해서는 하루에 수십억 개의 spFM이 필요하다. 그러나, 현재의 포토리소그래피 기반의 제조 기술을 이용하여 하루에 수십억 개의 spFM을 제조하면 인간의 소중한 생명을 돕는 데 오히려 작용하는 거대한 온실 가스를 방출할 것이다. 본 논문에서는 온실가스 배출량을 획기적으로 줄인 지속가능한 친환경 파운드리의 첫번째 단계로 롤투롤(R2R) 그라비아 인쇄 시스템을 이용하여 첫 단계로 12개의 박막트랜지스터(TFTs)를 통합하여 1-bit 라고 불리는 “1”과 “0”을 생성하여 QR코드를 점멸시키기 위한 코드 발생기 기능을 무선으로 보여줌으로써 폴리(에틸렌테레프탈레이트) 필름에 spFM을 인쇄할 수 있는 가능성을 보여주었다. 1-bit 코드 발생기를 시작으로 1-bit 산술논리연산장치(ALU)를 표시하기 위한 46개의 TFTs, 4-bit 산술논리연산장치를 표시하기 위한 156개의 TFTs를 연속적으로 개발하여, 인쇄 파운드리로서 논리회로를 집적하기 위한 기술을 개선하였다. 특히, R2R 그라비아 인쇄로 4비트 산술 논리 장치(ALU)를 제조한후 PC에 내장하여 4-bit ALU의 기능을 입증하였다. 1-bit 코드 생성기, 1-bit ALU, 4-bit ALU는 게이트 전극과 버스 라인부터 유전체증, 활성층, 접합 인슐레이터층, 드레인-소스 전극, p-type 도펀트, n-type 도펀트까지 5.4m/min의 인쇄속도로 PET 필름에 일정한 잉크 전이율과 중첩 인쇄정합 정확도를 유지하면서 7단까지 연속적으로 인쇄하였다. 다른 CMOS 논리소자와 유사하게 R2R 그라비아 인쇄 1비트 코드 생성기, 1-bit ALU 및 4-bit ALU도 상호보완적인 단일벽 탄소나노튜브 기반 논리게이트로 구성되었다. R2R 그라비아 인쇄 1-bit 코드생성기, 1-bit ALU 및 4-bit ALU의 장치 수율은 각각 10m 인쇄길이를 따라 90%, 60%, 그리고 20% 였다. 이에 본 논문은 156개의 TFT를 집적한 유연 전자기기 제조 서비스를 시작함으로써 지속가능한 R2R 인쇄 파운드리가 실질적으로 실현될 수 있음을 세계 최초로 입증하였으며, 이를 통해 사물인터넷의 실현 가능성을 높일 수 있는 프로세서 및 마이크로컨트롤러 등의 정교한 회로를 지속가능한 친환경 파운드리로제작할 수 있게 되었다.

Fiscal decentralization in Nepal : The case of Banepa municipality

Mahesh Parajuli Sungkyunkwan University 2019 국내석사

Fiscal Decentralization is a high policy agenda in most countries around the world assuming to achieve efficiency and good governance values such as accountability, transparency and less corruption. Several studies demonstrated the mixed results while evaluating components and influence of fiscal decentralization especially in developing countries as its highly contextual nature. Nepal has been implementing fiscal decentralization policy since two decades. In case of Nepal, little number of researches has been done to analyze the process of fiscal decentralization as well as its influence at local level. In addition, almost no study has been carried out about how a municipality incorporated fiscal decentralization process at local level in Nepal. To address this knowledge gap, this thesis examined the major components of fiscal decentralization and its influence at municipal level. Banepa Municipality of Nepal was selected for this qualitative case study research. In-depth interviews of seven officials and document analysis were done for data collection and triangulation. The findings are optimistic but mixed. The fiscal decentralization is positively evolving in the period of more than three decades in Banepa municipality. In terms of appropriateness of various components of fiscal decentralization, there is certainly some progress. But, study also found some serious deficiencies such as unfunded mandates, vertical imbalances and local capacity crunch inside the components of fiscal decentralization. Influences of fiscal decentralization are mostly positive on accountability, corruption control, democracy building but mixed in terms of efficiency. Apart from these, the study found one clear contribution of fiscal decentralization in Banepa municipality is growth of people's participation. Similarly, the thesis concluded that capacity development should be integral component of fiscal decentralization in order to make it more effective. This research helped to understand the real situation of fiscal decentralization at municipal level and highlighted the need to improve the components of fiscal decentralization. Further, it is a value addition as a holistic understanding from the bottom on fiscal decentralization in scholar community.

Genome analyses of Streptomyces peucetius: cytochrome P450, regulatory elements and secondary metabolites : Streptomyces peucetius 지놈분석: cytochrome P450, 조절기작 및 이차대사 관련 유전자

Niranjan Parajuli 선문대학교 대학원 2004 국내박사

The main objective of the present study was genome analyses of Streptomyces peucetius ATCC 27952. We have determined the genome sequence of 8.7 Mb chromosome of organism, which produces clinically important anthracyline chemotherapeutic agents of the polyketide class of antibiotics, daunorubicin and doxorubicin. The cytochrome P450 (CYP) superfamily is represented by 19 sequences in the S. peucetius. CYP252A1 is the new family found in S. peucetius, which shares 38% identity to CYP51 from Streptomyces coelicolor A3 (2). Although two ferredoxins and four ferredoxin reductases have been identified so far, only one ferredoxin reducatse was found in cluster of CYP147F1 in S. peucetius. CYP105P2 (cytochrome P450) from S. peucetius was cloned and expressed in E. coli. In our best knowledge, cis-5,6,7,8,9-pentahydroxycinnamic acid is a novel compound, which was isolated by enzymatic reaction by CYP105P2 with 7-ethoxycoumarin. Other hydroxylated derivatives of cinnamic acid, benzoic acid and salicylic acid were also isolated using the same enzyme upon respective substances. Effect of CYP105P2 on durg metabolism was also studied. Several regulatory genes are analysed from S. peucetius. These include afsR, afsK, abaA, abaB, adsA, vbrA, pknG and rarA. We also analyzed other genes from this genome, which have ability to enhance secondary metabolites production. These include SAM (S-adenosylmethionine synthetase), ppGpp and sodN. afsR, global regulatory gene (2.9 kb) was cloned and expressed in Streptomyces species under the control of ermE* promoter. Actinorhodin production was found to increase by 3 fold in S. lividans GIBR (transfromant of afsR in S. lividans TK24) with respect to S. lividans IBR (Control, transfromant of pIBR25 in S. lividans TK24). For the first time, the conserved regions of afsR from S. achromogens (rubradirin producer), and S. clavuligerous (clavulinic acid producer) were cloned and sequenced. S. peucetius genome shows the homologue gene clusters of some notable polyketide sysnthases (PKSs) including filpin, actinonycin, amphotericin, spinosad, nystatin, oleandomycin, aureothin, vicenistatin, pristinamycin and virginiamycin. We have also compared the daunorubicin and doxorubicin (DNR/DXR) biosynthetic gene cluster of two strains (29050 and 27952). Our sequence analyses revealed that dpsF is clustered with dpsE, dpsA and dpsB in contrast to biosynthetic pathway proposed by Hutchison et al. We also extended our study to dTDP-L-rhamnose biosynthetic gene cluster from Thermus caldophilus GK24. Thermophilic glucose-1-phosphate thymidylyltransferase (stRmlA), encoding 356 amino acids with a calculated molecular weight 38 kDa was expressed under the control of the tac promoter in E. coli. The expressed enzyme, stRmlA is thermostable up to 70°C and apparently retained its activity even up to 90°C. stRmlA showed its thermal activity up to 90°C only in the presence of dTTP and dTMP, thermal activity being the highest at 70°C. Unlike other mesophilic counterparts, it showed catalytic activity on a wide range of pH (2-13), and separately, in the presence of various metal ions. In an attempt to characterize peculiar thermal behavior of stRmlA, we compared codon sequence, nucleotide frequency, secondary structure, and tertiary structure with various other mesophilic counterparts. The future perspectives of this study are discussed in each chapter. 본 학위논문은 Streptomyces peucetius ATCC 27952 지놈분석 관련 연구이다. 의약품으로 중요한 polyketide 계열 항암제로서 anthracycline 화학요법 치료제인 doxorubicin 과 daunorubicin 을 생산하는 균주로서, 균주의 8.7 Mb chromosome 에 해당하는 지놈을 염기서열분석 하였다. cytochrome P450 (CYP) superfamily 가 S. peucetius 에서 19 개의 염기서열이 분석되었다. 그 중 CYP252A1 은 S. peucetius 에서 발견된 새로운 유형이며, Streptomyces coelicolor A3 (2)에 있는 CYP51 과는 38% 의 유사성이 있다 . 두개의 ferrodoxin 과 ferodoxin reductase 유사 유전자가 아직 반응성은 확인되지 않았지만 , 그 중에 하나는 CYP147F1 과 집단으로 있다. CYP105P2 (cytochrome P450 )는 재조합하여 E. coli 에서 발현되었다. 발현된 CYP105P2 는 7-ethoxycoumarin 과 반응하여 효소의 반응성을 확인하였으며, 반응 결과물은 아직까지 보고되지 않은 cis-5,6,7,8,9-pentahydroxycinnamic acid 로 분석되었다. 그 외에 cinnamic acid, benzoic acid 및 salicyclic acid 도 반응하여 벤젠링에 모두 hydroxylation 되는 같은 결과를 얻었다. Drug metabolism 에 대한 CYP105P의 반응성도 역시 조사했다. 여러개의 조절기작 유전자가 S. peucetius 에서 분석되었다. 이들은 afsR, afsK, abaA, abaB, adsA, vbrA pknG 및 rarA 와 유사성이 있는 유전자들이며, 이들 유전자 외에 이차대사물질 생산에 영향을 주는 다른 유전자들도 분석 되었다. 이들은 SAM synthetase, ppGpp 및 sodN 등과 유사성이 있는 유전자들을 찾았다. 조절기작 유전자인 afsR (2.9 kb) 는 ermE* promoter 에 조절되는 방선균 벡터에 재조합하여 발현하였다. S. lividance 에 afsR 재조합 벡터를 전이된 균주인 S. lividance GIBR 3 배정도의 actinorhodin 생산량이 증가하였다. 기존에 알려져 있는 afsR 유전자를 비교하여 유사성이 높은 영역으로부터 디자인된 primer 를 제작하여 PCR 방법으로 S. achromogenes (rubradirin 생산균주 ) 및 S. clavuligerous (clavulinic acid 생산균주 ) 로 부터 afsR 유사 유전자를 클론하여 염기서열분석하여 afsR 유사 유전자를 확보 할 수 있다. S. peucetius 지놈에는 filipin, actinonycin, amphotericin, spinosad, nystatin, oleandromycin, aureothin, vicenistatin, pristinamycin 및 virginiamycin 을 포함해서 여러개의 새로운 polyketide synthase (PKS)의 유사 유전자 집단들이 있다. 특히 S. peucetius 계열의 균주인 ATCC 29050 및 ATCC 27952 에 있는 daunorubicin (DNR) 및 doxorubicin (DXR) 생합성 유전자 집단을 비교하였다. ATCC 27952 에서 분석된 결과는 Hutchinson 그룹에서 발표된 생합성 유전자 집단과는 달리 dpsF 가 dpsE, dpsA 및 dpsB 와 함께 집단화 되어 있다. Thermus caldophilus GK24 로부터 dTDP-L-rhamnose 생합성 유전자 집단을 연구하였다. 열적 안정 효소인 glucose-1-phosphate thymidylytransferase (stRmlA) 는 356 개의 아미노산으로 구성되어 있고, 분자량은 38 kDa 으로 E. coli 에서 tac promoter 를 가진 벡터에서 발현하였다. 발현된 stRmlA 는 70℃ 이상 열적으로 안정성을 보여주고 있으며, 90℃이상에서도 여전히 반응성이 남아 있다. stRmlA 은 단지 dTTP 및 dTMP 존재할 때 90℃에서 열적 안정성을 보여주고 있다. 다른 일반적인 온도에 작용하는 효소들과 달리, 이 효소는 pH 가 2 에서 13 까지 넓은 영역에서도 효소의 반응성을 보여주고 있으며, 여러 금속 이온에서도 같은 반응성을 갖는다. stRmlA 의 특별한 열에 안정한 이유를 분석하기 위해, 여러 가지 다른 mesophilic 효소와 함께 코돈 분석비교, 핵산빈도 (nucleotide frequency), 이차구조 및 삼차구조를 비교하였다.

Study on Health Risk Reduction by Indoor Air Quality Improvement Using Displacement Exhaust in a Single Cell House of Himalayan Region : 히말라야 지역 싱글 셀 하우스의 치환 배기를 적용한 실내 공기 질과 건강 위해성 개선에 관한 연구

Indira Parajuli Baral The Graduate School,Incheon National University 2017 국내박사

개발 도상국 사람들의 대부분은 싱글 셀 하우스 (SCH) 공간에서 거주하고 있으며 요리, 생활, 아이들이 공부하는 공간을 위해 SCH를 이용하고 있다. 실내 공기질 (IAQ)에 악영향을 주는 극한 기후 조건에 대처하기 위해, 일반적으로 장작 및 기타 바이오 매스를 요리와 난방 목적으로 사용하고 있다. 여성과 5세 미만의 어린이 및 가족 모든 구성원은 발열지역에 둘러앉아 편안한 열기를 찾게 된다. 보통 사람들은 배기가 되지 않는 방에서 극한 추위를 극복하기 위해 스토브를 이용하는 동안 문과 창문을 닫는 것을 선호한다. 따라서 장작 연소 중 방출되는 유해 오염 물질이 쉽게 배출될 수 없으며 실내 환경을 악화시키고 가옥 속에 축적되어 거주자에게 매우 위험하게 된다. 이러한 유형의 오염 물질은 발암성 및 비발암성 모두를 포함한 다양한 형태의 건강 위험을 야기하게 된다. 단기 및 장기적인 건강 영향을 모니터링 하기 위해 조리와 난방을 목적으로 장작을 사용하는 장소인 SCH의 IAQ및 실내기후를 모니터링 하였다. SCH 8 시간 평균 일산화탄소 (CO) 및 24 시간 평균 미세 먼지(PM2.5) 농도는 각각 25.11ppm 및 34μg/m3 으로 나타내고 있다. SCH 의 CO농도 및 PM2.5 농도의 하루 중 최대값은 40ppm 및 793.8μg/m3로 정점을 이루며, 이는 CO 및 PM2.5에 대한 안전성을 위해 규정한 값보다 각각 3.6배, 32 배 높은 값이다. SCH에서 조리와 같은 활동을 마친 후에도 난방과 같이 불은 하루 14 시간까지 사용되어, 건강기준에 비해 농도가 지속적으로 높아 진다. 노출 분석 데이터에 따르면 일산화탄소 (CO), 이산화탄소 (CO2) 및 PM2.5에 대한 평균 노출량은 각각 248.59mg, 96195.19mg 및 6849.74μg이며, SCH 거주자가 하루 흡입하는 양이다. 모니터링 조건에 따라 전체적인 공기 품질 지수(AQI)는 150~430이며, AQI 도 유해한 수준이다. 또한 열적 쾌적 상태는 15.89±1.77 ℃이며, 최저 온도는 12 ℃, 최대 값은 21 ℃ 인 것으로 나타났다. 실내 열 조건은 겨울 20 ℃ 이하로 열 쾌적성 기준보다 낮으며, 이것은 규정된 표준인 ASHRAE55 와 ISO7730보다 낮은 수준이다. 본 연구의 결과 중 하나로 배기가스 배기량은 0.5m이 해결책으로 제시되고 있다. 적절한 환기 결과는 치환배기를 이용하여 점유 구역을 개선하기 위해 SCH에서 7 l/s 공기량으로 배기한 것으로 나타났으며, 이 환기율은 혼합 환기 모드의 88 %보다 작은 수치이다. CFD 시뮬레이션을 이용한 민감도 분석과 Design Ease 6.0을 이용한 통계 분석을 통해 온도 중간대 높이가 SCH 높이의 22 %로 나타났다. 치환배기 시뮬레이션의 깊이는 오염 물질을 추출하고 온도를 최적화하는 스택 최적의 깊이가 SCH 높이의 15 %인 것으로 나타났다. 따라서 치환배기를 이용한 것이 에너지 효율이 높고, 오염 물질 농도를 5배 낮추는데 도움이 된다. 연구 결과에 따라 거주지역 오염 물질을 제거하기 위해 배기가스 방출의 적용을 권장하며 IAQ를 개선하고 주민의 건강 위해성을 줄이며 SCH의 열 손실을 방지하기 위해 상부 구역을 단열 층으로 이용하는 것이 효과적이다. 핵심어: 싱글 셀 하우스, 실내 공기 질, 건강 위해성 분석, 치환배기, 히말라야 지역 Majority of the people in developing countries are residing in a single cell house (SCH) scheme. People are using a single space for cooking, living and the space for their children to study. People use firewood and other types of biomass in general for cooking and for heating purpose to cope with extreme cold climatic condition, which badly affects the indoor air quality (IAQ). All members of the family including women and <5 years age children are found to be sitting around the firing area for comfortable heat. Usually, people preferred to close the door and windows even during firing stove to cope with the extreme cold condition in a non-vented room. The hazardous pollutants released during firewood burning cannot exit out rather it is accumulated inside the house that cause ill indoor environment every time, which is very risky for the dwellers. These types of pollutants are causing various kinds of health risk including both carcinogenic and non- carcinogenic; short term as well as long term health impacts. The monitoring system is developed to find the IAQ and the microclimatic situation of the SCH, where people used firewood for cooking and heating purposes. The 8-hours mean Carbon Monoxide (CO) and 24-hours mean Particulates Matter size below 2.5µm (PM2.5) concentration in SCH is 25.11ppm and 34.5µg/m3. These pollutants level in SCH is peaked by 40ppm and 793.8µg/m3 respectively for CO and PM2.5 which is found to be 3.6, 32 folds higher than the prescribed value for the safe health for CO and PM2.5 respectively. Concentration is continuously higher than safe value prescribed for the health up to 14-hours a day as people continue to fire even after cooking also to heat the space. The exposure analysis data show that the mean exposure concentration for CO, Carbon dioxide (CO2) and PM2.5 are 248.59mg, 96195.19mg and 6849.74µg, respectively, which are inhaled by the dwellers throughout a day. The overall air quality index (AQI) is also found 150-430 for different monitoring conditions cases. Thus, the AQI is in the state of unhealthy level and hazardous conditions. Moreover, the thermal comfort situation is found to be 15.89±1.77°C with minimum temperature of 12°C and maximum of 21°C. The indoor thermal condition is also below the thermal comfort standard i.e. less than 20°C in winter, which is below the prescribed standard ASHRAE 55 and ISO 7730. The displacement exhaust at temperature neutral height as one of the outcomes of this study, with the depth of 0.5m is proposed as solution. The adequate ventilation result shows that it is required to suck only 7l/s air from the enclosure to clean the occupied zone with the displacement principle. This ventilation rate is 88% less than mixing ventilation mode. The temperature neutral height is obtained to be 22% of the SCH height with the sensitivity analysis using CFD simulation and the statistical analysis using statistical software, the Design Ease 6.0. The depth of the stack simulation shows that the optimal depth of the stack to extract the pollutants and to optimize the temperature is found to be 15% of the height of the enclosure. Hence, this ventilation system is energy efficient, which helps to reduce the pollutants concentration five folds less. Based on findings, the study recommends for the application of the displacement exhaust to purge the occupants’ zone pollutants. Hence, it helps to improve IAQ and reduce the health risk of the dwellers and by using the upper zone as an insulation layer to prevent the heat loss from enclosure. Keywords: Single Cell House, Indoor Air Quality, Health Risk Analysis/Reduction, Temperature Neutral Height, Displacement Exhaust, Himalayan Region

Stimulation of T cells by dendritic cells treated with galectin-3

Parajuli, Nirmala 서울대학교 대학원 2005 국내석사

Oncology Nurses’ Confidence in Providing Palliative Care

Parajuli, Jyotsana The Pennsylvania State University ProQuest Dissert 2019 해외박사(DDOD)

Background: The number of people with cancer continues to increase in the United States with the graying of baby boom generation resulting in an increased demand for cancer care. Patients with cancer suffer from complex health issues including high symptom burden, psychological distress, and diminished quality of life. Palliative care can help manage symptom burden and improve the quality of lives of patients with cancer and their families. Oncology nurses are consistent providers of care to patients with cancer throughout the illness trajectory. They play a crucial role in providing palliative care to patients with cancer. However, most often oncology nurses lack education and training in providing appropriate palliative care and feel stressed when providing palliative care. Little is known about the confidence of oncology nurses in delivering palliative care to patients with cancer.Purpose: The purpose of this study was to examine oncology nurses’ confidence in providing the eight domains of palliative care as posited by the National Consensus Project for Quality Palliative Care (NCP) guidelines. One of the main purposes of this study was also to validate the Palliative Care Nursing Self-Competence (PCNSC) Scale in oncology nurses’ population in the United States.Methods: A descriptive correlational design using an online survey methodology was employed. Registered nurses who provided care to patients with cancer were recruited from the Oncology Nursing Society (ONS) listserv. Participants completed an online survey that consisted of a demographic form, a confidence scale, and two open ended questions. Data were analyzed using descriptive and correlational statistics and multiple regression analysis. All data were analyzed using Statistical Package for Social Sciences, SPSS.Results: The results of this study revealed that most of the oncology nurses were somewhat confident to confident in providing palliative care. Results of correlational analysis and multiple regression analysis revealed that years of experience as an oncology nurse and palliative care training were associated with nurses’ confidence in providing palliative care to patients with cancer. The results of the confirmatory factor analysis revealed that the PCNSC scale retained the same 10 factor structure as the original PCNSC scale. In terms of meaning of the term “palliative care”, most participants regarded it as “symptom management” and oncology nurses needed to learn more about several areas of palliative care that were consistent with NCP’s 8 domains of palliative care which are structure and process of care, physical aspects of care, psychological and psychiatric aspects of care, social aspects of care, spiritual, religious, and existential aspects of care, care of the patients nearing the end of life, and ethical and legal aspects of care.Conclusions: To our knowledge this is the first nationally representative study that examined oncology nurses’ confidence in providing palliative care. The results of this study will help design interventions geared towards enhancing oncology nurses’ confidence in providing palliative care to patients with cancer and their families.

Understanding Complex Traits in Alfalfa Through Transcriptomics, Genomics, and Proteomics

Parajuli, Atit Washington State University ProQuest Dissertations 2023 해외박사(DDOD)

Alfalfa (Medicago sativa L.) is a perennial, outcrossing legume crop predominantly grown for hay, silage, or pasture. Genetic improvement in Alfalfa in terms of hay yield is still comparable to 30 years ago. Under a variety of growing conditions, forage yield in Alfalfa is stymied by biotic and abiotic stresses including heat, salt, drought, and disease. To overcome such stresses, Alfalfa uses a differential gene expression pathway which is under the control of transcription factors that contribute to tolerance of stresses. The Alfalfa breeding program is mainly focused on developing synthetic varieties through recurrent phenotypic selection exploiting additive genetic effects. The production of hybrid Alfalfa breeding programs uses synthetic varieties as the most feasible means for genetic gain. High heterozygosity of the plants and severe inbreeding depression upon selfing precludes the development of inbred lines for hybrid production. However, quantifying inbreeding depression through fitness and vigor traits expressed as weak and strong plants can help map these traits using association study. Identifying these genetic variants paves the way for the elimination of deleterious alleles and eventually the development of inbred alfalfa lines for hybrid production. However, genetic regions identified through association study do not always translate to actual functional proteins as they are not always linked to genes or genetic variants responsible for traits of interest. As the protein's biological function is strongly dependent on its 3D structure, associating proteins directly with phenotype could help assess the effect of mutation on protein function. To understand the role of transcription factors in stress tolerance, we identified and performed transcriptome analysis of Basic-leucine zipper (bZIP) transcription factors that have played a critical role in regulating growth and development and mediating the responses to abiotic stress in several species, including Arabidopsis thaliana, Oryza sativa, Lotus japonicus, and Medicago truncatula. We identified 237 bZIP genes that were differentially expressed in response to ABA, cold, drought, and salt stresses, indicating a likely role in abiotic stress signaling and/or tolerance. These expressions were further validated through RT-qPCR analysis. Next, a genome-wide association study was performed to map genetic loci associated with Alfalfa for plant vigor trait using 534 plants collected from three locations (Washington, Wisconsin, and Utah) over three generations of selfing. These plants were selected based on plant health of strong and weak within the same line. A total of 11 genetic loci were identified using 588,136 Single nucleotide polymorphisms (SNPs). Gene ontology analysis of significant loci associated them with genes involved in stress response, defense responses against pathogens, and plant reproduction. Finally, we attempted the first-ever association study between features from alphafold predicted 3D structure of protein and phenotype, to link non-synonymous mutation to phenotypes. We used 154 genes, including significant genes from the GWAS study, after filtering 591,919 SNPs, to predict protein 3D structures that identified the five significant GWAS hits. However, two more genes with the lowest p-values (Nod 19, Cytochrome P450) were also identified which play key roles in plant growth and development and also in stress tolerance. This association study is a promising way to narrow down causal mutations from SNP GWAS through stringent filtering of SNPs.