Vector bundles on manifolds: the cohomology of projective algebraic varieties

This Thesis looks at different areas of mathematics which require the notion of a differentiable manifold. The first three chapters contain various materials such as differentiable manifolds, submanifolds, tangent bundles, differential forms, integrations, Stokes' theorem, and certain concepts of Riemannian geometry. In the last chapter, we show that the kernel of a given elliptic operator L is finite dimensional. We also show that on compact differentiable manifolds for each de Rham cohomology class a there exists a unique harmonic form y, showing that the de Rham cohomology is finite dimensional

High-mobility group box 1, an endogenous ligand of toll-like receptors 2 and 4, induces astroglial inflammation via nuclear factor kappa B pathway

Background: Neuroinflammation has a definitive role in neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease. In addition to its pathoge- nic ligands, toll-like receptors (TLRs) can be activated by damaged endogenous molecules that induce inflammatory signalling pathways such as high-mobility group box 1 protein (HMGB1).  Materials and methods: Using an ex-vivo rat optic nerve (RON) model, we sought to determine the effects of lipopolysaccharides (LPS; TLR4 agonist), zymosan (TLR2 agonist) or HMGB1 — with or without TLR2/4 antagonists, on the expression of glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (NF-ҡβ) for signalling pathway and astrocyte reactivity, using double immunohistochemistry; as well as on the modulation of the neurotoxicity. HMGB1-treated RON had significantly higher expression and co-localisation of GFAP and NF-ҡβ as compared to the un- treated control, which was a similar result to those treated with LPS and zymosan.  Results: Moreover, the HMGB1-induced inflammation was blocked by TLR2/4 antagonists (p = 0.05). However, the HMGB1-induced cell death was unblocked by TLR antagonists. Overall, HMGB1 endogenously mediates the signalling me- chanisms of neuroinflammation through TLR2/4.  Conclusions: Whereas, the neuronal death mechanism resulting from HMGB1 could be caused by a different signalling pathway. Gaining an understanding of these mechanisms may help researchers discover new therapeutic targets for neurodegenerative diseases.

Validation and improvement of a rear-end conflict prediction model

as attached.

Ligands of toll-like receptors 2/4 differentially alter markers of inflammation, adhesion and angiogenesis by monocytes from women with pre-eclampsia in co-culture with endothelial cells

Pre-eclampsia (PE) is characterized by an exaggerated systemic inflammatory response and generalized endothelial dysfunction. We have recently demonstrated that fibrinogen, an endogenous ligand of Toll-like receptor (TLR) 4, activates monocytes from women with pre-eclampsia (Al-ofi et al., 2014). Using an experimental co-culture model of primary human monocytes (derived from 9 women with PE (GA = 33.18 ± 5.8) and 9 normotensive pregnant women, NP (GA = 33.15 ± 4.0)) and human umbilical venous endothelial cells (HUVECs), we compared the effects of fibrinogen and lipopolysaccharide (LPS, bacterial ligand to TLR4) on the expression levels of inflammatory cytokines (IL-6 and IL-1β), chemokines (IL-8 and MCP-1), and anti-angiogenic factor (soluble fms-like tyrosine kinase-1,sFLT-1), as well as the soluble vascular cell adhesion molecule-1 (sVCAM-1). Cytokines, VEGF and sVCAM-1 were measured in the supernatant media by cytometric array. The levels of sFLT-1 were measured by ELISA. Fibrinogen induced greater expression levels of IL-1β and VCAM-1 from PE HUVEC-monocyte co-culture than from NP HUVEC-monocyte co-culture (P < 0.05), similar to the effects of LPS. In contrast, unlike LPS, fibrinogen suppressed IL-6, IL-8, MCP-1 and sFLT-1 production by co-cultures that included PE monocytes compared to those with NP monocytes (P < 0.05). In conclusion, fibrinogen promotes monocyte-endothelial cell adhesion and angiogenesis and suppresses the expression of some inflammatory markers in pre-eclampsia. Although the physiological implications of these intriguing observations are unclear our findings suggest that fibrinogen contributes to the regulation of cell adhesion, angiogenesis and inflammation by mechanisms not wholly dependent on TLR4 stimulation

Monocyte Subpopulations from Pre-Eclamptic Patients Are Abnormally Skewed and Exhibit Exaggerated Responses to Toll-Like Receptor Ligands

The leading cause of pregnancy-associated mortality and morbidity is pre-eclampsia (PE). Although information regarding the etiology of this disease is scant, its pathophysiology is characterized by abnormal placentation, endothelial dysfunction as well as an exaggerated inflammatory response. Clinical evidence also indicates that the abundance of many immune cells at the feto-maternal interface and in the circulation of PE patients is abnormal, when compared with normal pregnant (NP) controls. In addition, the phenotype and function of some of these cells is altered. To further characterize the systemic effects of PE on circulating cells, we analyzed monocytic subpopulations in NP and PE patients by flow cytometry. We found that non-classical CD14lowCD16+ monocytes are significantly increased in women with PE and they display irregular expression of several chemokine receptors and antigen presentation molecules. The most striking phenotypic difference among the cell surface molecules was the marked upregulation of TLR4 expression, where both CD14highCD16+ and CD14lowCD16+ monocytes demonstrated higher levels than their NP counterparts. Stimulation of PE monocytes with TLR ligands resulted in profound secretion of various cytokines in comparison with NP controls. These data suggest that PE monocytes are hyper-responsive to TLR ligands and this may contribute to exacerbation of the disease

POLA KOMUNIKASI LINTAS BUDAYA SANTRI DI PONDOK PESANTREN (STUDI KASUS PONDOK PESANTREN MODERN DEA MALELA)

Penelitian ini bertujuan mendeskirpsikan dan memahami pola komunikasi lintas budaya Santri di Pondok Pesantren Modern Dea Malela dan hambatan yang dialami Santri dalam berkomunikasi lintas budaya dengan Santri lainnya. Penelitian ini merupakan penelitian deskriptif dengan menggunakan pendekatan kualitatif agar dapat memperoleh keterangan yang lebih luas dan mendalam mengenai hal-hal yang menjadi pembahasan dalam penelitian ini. Teknik yang digunakan dalam pengumpulan data antara lain observasi, wawancara, dan dokumentasi. Adapun teknik analisis data yang digunakan dalam penelitian ini adalah teknik analisis data dari Miles dan Huberman, yaitu: Reduksi data, penyajian data, dan verifikasi atau kesimpulan. Hasil Penelitian ini menunjukkan bahwa komunikasi lintas budaya merupakan proses pertukaran pikiran dan makna antara orang-orang yang berbeda budaya. Ketika komunikasi tersebut terjadi antara orang-orang yang berbeda bangsa (internasional), antar etnik (interetnical), kelompok ras (interracial), atau komunikasi bahasa (intercommunal) disebut komunikasi lintas budaya. Komunikasi lintas budaya dari anggota budaya yang berbeda berperan terjadinya tingkah laku manusia, misalnya tingkah laku santri asing menyamahi budaya setempat atau budaya di Indonesia, sehingga santri asing berperilaku berdasarkan budaya setempat. Kata Kunci: Komunikasi; Lintas Budaya; Santri; Pondok Pesantren

Ursodeoxycholic Acid Improves Mitochondrial Function and Redistributes Drp1 in Fibroblasts from Patients with either Sporadic or Familial Alzheimer's Disease

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Mitochondrial abnormalities have been identified in many cell types in AD, with deficits preceding the development of the classical pathological aggregations. Ursodeoxycholic acid (UDCA), a treatment for primary biliary cirrhosis, improves mitochondrial function in fibroblasts derived from Parkinson's disease (PD) patients as well as several animal models of AD and PD. In this paper, we investigated both mitochondrial function and morphology in fibroblasts from patients with both sporadic and familial AD. We show that both sporadic AD (sAD) and PSEN1 fibroblasts share the same impairment of mitochondrial membrane potential and alterations in mitochondrial morphology. Mitochondrial respiration, however, was decreased in sAD fibroblasts and increased in PSEN1 fibroblasts. Morphological changes seen in AD fibroblasts include reduced mitochondrial number and increased mitochondrial clustering around the cell nucleus as well as an increased number of long mitochondria. We show here for the first time in AD patient tissue that treatment with UDCA increases mitochondrial membrane potential and respiration as well as reducing the amount of long mitochondria in AD fibroblasts. In addition we show reductions in Dynamin-related protein 1 (Drp1) level; particularly the amount localised to mitochondria in both sporadic AD and familial patient fibroblasts. Drp1 protein amount and localization were increased after UDCA treatment. The restorative effects of UDCA are abolished when Drp1 is knocked down. This paper highlights the potential use of UDCA as a treatment for neurodegenerative disease