Transcriptional Regulation by DAX-1 in Pluripotent and Differentiated Cells

DAX-1, an orphan nuclear hormone receptor, acts mainly as a repressor through transcriptional protein complexes. Its unique structure and specific expression raises questions as to what its precise interactions are and how it mediates its repressive function. While it is known to play a role in sexual development and adrenal insufficiency, expression in certain types of cancer suggests additional functions and interactions. Knock in of DAX-1 into a low-DAX-1 expressing cancer cell line has been previously observed to increase apoptosis, while, inversely, down in a high-DAX-1 expressing cancer cell line shows a decrease in apoptosis. Target genes that belong to the TNFα and BCL-2 families have shown changes in expression correlating to the modified levels of DAX-1 in knock-down experiments. Direct regulation of BCL-2, one of the target genes of interest, was investigated further based on mirrored expression changes of DAX-1 in knock-down and knock in experiments through ChIP experiments. These findings emphasize a significant role of DAX-1 in moderating apoptosis in a breast cancer cell line. In the context of undifferentiated mouse embryonic stem cells, Dax-1 is highly expressed and has been shown to be an important contributor to the pluripotent state. Potential downstream targets of Dax-1 were previously identified based on significant changes in expression when Dax-1 expression was down regulated. Two methods, siRNA and CRISPR-Cas9, were used to decrease Dax-1 expression in the E14 mouse embryonic stem cell line. Direct interactions and other novel stem cell factors were confirmed using analysis of publically available ChiP-seq data. Ultimately, while Dax-1 is not a master regulator, its transcriptional control of specific genes that are key in the maintenance of pluripotency is an important component of stem cell growth and differentiation. Bioinformatic analysis of ChIP-seq experiments brought to light general patterns as to how Dax-1 contributes to pluripotency, and additional ontologies of Dax-1 target genes for future studies

ZAP-70 Phosphorylation and other prognostic factors in adult B-chronic lymphocytic leukaemia patients

AbstractB chronic lymphocytic leukaemia (B-CLL) is a disease with an enormously heterogeneous prognosis. Due to lack of effective treatments and the heterogeneity in its course, B-CLL has remained largely incurable. In the last two decades a number of biological markers have been recognised as prognostic parameters to replace clinical staging, chief among them is ZAP-70 (a T-cell cytoplasmic tyrosine protein) albeit without a full understanding of the mechanism involved.The aim of this thesis was to identify reliable prognostic factors that could be used in the management of B-CLL patients. Seventy-six B-CLL patients were studied over 30 months using a random stratified method of sampling, whereby adult B-CLL patients were recruited at different stages of the disease. Retrospective studies enabled some patients to be studied for up to 192 months. ZAP-70 expression was demonstrated in some B-CLL cells and was examined for possible phosphorylation following B-CLL cells stimulation, implying its involvement in cell signalling. Through the use of a novel method developed during the present study, B-CLL cells were stimulated via the SDF1-α-CD184 signalling pathway resulting in ZAP-70 phosphorylation. Its expression and phosphorylation was investigated alongside other prognostic factors and also correlated with B-CLL progression. More importantly, this study demonstrated that ZAP-70 positive cells are more responsive to signals derived from their surrounding environment, such as SDF-1α.In conclusion ZAP-70, CD38, and CD23 expressions together with IgVH gene mutational status were confirmed as indicators of poor prognosis. Response to external stimuli by some B-CLL cells, resulting in ZAP-70 phosphorylation represents the most novel aspect of this thesis and demonstrates ZAP-70 involvement in B-CLL signalling. Additionally, raised NK: B-CLL and T: B-CLL cell ratios were identified as good modifiable variable predictors of time to treatment that could be used for monitoring and therapeutic purposes. Since B-CLL is an incurable disease, the identification of prognostic factors could help in deciding the best time for intervention in B-CLL patients

Teaching English as a Second Language in an Urban Public University in Sri Lanka : A Reflective Paper

The purpose of this Master of Arts (MA) thesis is threefold: First, this reflective paper provides a critical literature review on English Language Teaching (ELT) in Sri Lanka. Second, this reflective paper presents seven guiding principles which will steer my English as a Second Language (ESL) teaching in an urban public university in Sri Lanka. Third, drawing from the seven guiding principles, this reflective paper presents a complete syllabus and three assignments as concrete examples (attached as appendixes) which will be implemented in a College of Humanities and Social Sciences in an urban public university in Sri Lanka. The importance of the present reflective paper can be summarized under four main points: First, the critical literature review could help researchers and practitioners to better understand the complex linguistic situation and ELT in Sri Lanka. Second, based on the seven guiding principles I will have a new syllabus which will be implemented in my ESL classes in an urban public university in Sri Lanka. After the implementation of the syllabus, I will reflect on my experience of implementing the syllabus and improve the syllabus further. Third, the seven guiding principles which will inform my future practice as an ESL teacher are transferable to English dominated post-colonial countries such as India, Pakistan, Bangladesh and so on. As a novice ESL teacher in an urban public university in Sri Lanka, one of the challenges I faced was the lack of a formal syllabus for my ESL classes. It gave rise to multiple issues in relation to teaching methodology, lesson planning, and teaching materials, resulting in the dissatisfaction of my students and myself. It was the lack of a formal syllabus for my ESL classes that motivated me to design a syllabus for an intermediate level ESL course in an urban public university in Sri Lanka. I believe that the new syllabus steered by the seven guiding principles presented in this MA thesis will create a new synergy in my future ESL classrooms

Pengaruh Model Pembelajaran Bersiklus (Learning Cycle 5E) Terhadap Kemampuan Berpikir Kritis Siswa

The aim of this study was to determine the effect of the 5E Learning Cycle model on critical thinking skills in Grade VII students of SMPN 9 East Kupang in the academic year 2019/2020. This study also aims to determine the level of significance of the two methods in improving critical thinking skills. One of the efforts to overcome this is by implementing the 5 E learning cycle (1 Engagement, Exploration, Exploration, Elaboration, Evaluation) learning model. This research is used quasi-experimental with a posttest-only control group design. The population is class VII, and the sample consist of class VIIA that the experimental class, and class VIIB is the control class. The instrument used was an essay test of critical thinking skills. The normality test used the Kolmogorov Smirnov test, and the homogeneity test used the homogeneity of variances test. Based on the t-test results using the Independent Sample Test with the assistance of SPSS version 25, there is a significant value of 0.000 or less than 0.05. , this shows that there is an influence on students' critical thinking

Hubungan Kesiapan Mengajar Dan Proses Praktik Pengalaman Lapangan Dengan Keterampilan Dasar Mengajar Mahasiswa Pendidikan Biologi

Mahasiwa calon guru harus menguasai keterampilan dasar mengajar yang diperoleh  melalui program pengajaran dan pelatihan di kampus maupun praktik lapangan di sekolah. Penelitian bertujuan mencari hubungan antara kesiapan mengajar dan pelaksanaan pengalaman praktik lapangan dengan keterampilan dasar mengajar mahasiwa. Penelitian ex post facto dengan desain korelasi, variabel (X1) kesiapan mengajar dan (X2) pelaksanaan pengalaman lapangan (PPL)  dan keterampilan dasar mengajar (Y). Sampel adalah mahasiswa program studi pendidikan biologi yang melaksanakan PPL berjumlah 26 orang. Pengumpulan data menggunakan angket, data dianalisis dengan statistik inferensial berbantuan SPSS. Hasil pengujian hipotesis pertama menunjukkan nilai sig = 0,003 lebih kecil dari a = 0,05 terdapat hubungan yang positif dan signifikan antara kesiapan mengajar dengan keterampilan mengajar mahasiswa PPL, dengan koefisien hubungan sedang. Pengujian hipotesis kedua menunjukkan nilai sig = 0,005 lebih kecil dari a = 0,05 Artinya terdapat hubungan yang positif dan signifikan antara proses pelaksanaan PPL dengan keterampilan dasar mengajar, kooefesien hubungan sedang. hipotesis ketiga menunjukkan nilai sig. F Perubahan 0,002 lebih kecil dari nilai a = 0,05 Hal ini berarti terdapat hubungan yang positif dan signifikan antara kesiapan mengajar dengan proses pelaksanaan PPL dengan keterampilan dasar mengajar mahasiswa PPL. Semakin baik kesiapan mengajar mahasiswa dalam pelaksanaan PPL maka akan semakin meningkat keterampilan dasar mengajarnya

DAYA KECAMBAH KABESAK (Acacia leucophloea) DAN ASAM JAWA (Tamarindus indica) MENGGUNAKAN VARIASI BAHAN DAN WAKTU PERENDAMAN

Pada pembudidayaan jenis tanaman kehutanan lokal perlu pengetahuan mengenai teknik perkecambahan yang tepat, untuk memperoleh semai secara cepat dalam jumlah banyak. Tanaman Kabesak (Acacia leucophloea) dan asam jawa (Tamarindus indica) merupakan tanaman yang memiliki manfaat penting secara ekonomis dan ekologis karena itu pemahaman teknik perkecambahan yang tepat penting diketahui. Penelitian ini mengkaji pengaruh bahan perendaman dan waktu perendaman terhadap daya kecambah kabesak dan asam jawa. Rancangan percobaan yang digunakan dalam penelitian ini adalah rancangan acak lengkap (RAL) dengan 2 perlakuan (faktorial) dan 3 ulangan. Faktor perlakukan pertama adalah bahan perendaman yaitu monosodium glutamat, urine sapi dan air panas. Faktor kedua adalah waktu perendaman yaitu 6 jam, 12 jam dan 24 jam. Perlakuan diujikan masing-masing ke benih kabesak dan asam jawa. Parameter pengamatan dalam penelitian ini adalah daya kecambah benih kabesak dan asam jawa. Hasil uji daya kecambah benih kabesak menunjukkan perendaman dengan air panas menghasilkan daya kecambah tertinggi dibanding perlakuan perendaman dengan bahan lainnya terhadap benih kabesak. Interaksi terbaik untuk bahan perendaman dan lama perendaman terhadap daya kecambah kabesak yaitu perlakuan perendaman dengan air panas selama 12 jam. Untuk uji daya kecambah Asam jawa diketahui bahwa bahan perendaman tidak mempengaruhi secara signifikan terhadap daya kecambah benih tersebut. Daya kecambah Asam jawa dipengaruhi oleh lama perendaman, dengan lama perendaman terbaik selama 6 jam. Kata kunci:  asam jawa, kabesak, monosodium Glutamat, semai, uri

The implementation strategies of village government policies in supporting the success of village-owned enterprises

BUMDes as one of the business entities operating in the village of Kuta, Kanatang District, East Sumba Regency. The BUMDes management policy strategy should remain oriented to the aspirations of the existing community then discussed together in joint deliberation to determine priority programs in accordance with the wishes of the local community, and in implementing existing programs it must be carried out professionally and transparently. The method used in this study is a descriptive qualitative research method that points to the object or problem to be studied which produces qualitative data using purposive sampling technique. that the village government uses are program strategies, strategies to increase supporting resources and organizational strategies. The supporting factor for the village government in supporting the success of BUMDes is the participation of the community.According to Law Number 6 of 2014 concerning Villages, it is explained that Village is a legal community unit that has territorial boundaries authorized to regulate and manage government affairs. One of the government policies to make it easier for villages to manage their existing potential is that village governments are encouraged to have Village-Owned Enterprises (BUMDes). The success of Village-Owned Enterprises is on the shoulders of the government in the village itself. In the existing program implementation strategy, the village government must understand the local village situation and must be ready to improvise with any changes in the situation without ignoring the goals that have been previously set. A factor or variable does not determine the success of Village-Owned Enterprises. However, it is determined and influenced by various existing factors, such as the village government's need for a helpful policy strategy to succeed in an existing program. Implementing existing programs must be done professionally and transparently. The research method was descriptive qualitative using a purposive sampling technique. The research results proved that Village-Owned Enterprises has not been entirely successful because only a few programs have just been implemented. Additionally, the village government used several strategies, including program strategies, strategies for increasing supporting resources, and organizational strategies