Mechanistic behaviour and molecular interactions of heat shock protein 47 (HSP47)

This project involves the study of heat shock protein 47 (HSP47), which is a molecular chaperone crucial for collagen biosynthesis. It exhibits a high degree of sequence homology with members of the serine protease inhibitor (serpin) superfamily, though HSP47 does not possess the inhibitory activity. It is a single-substrate chaperone, and binds only to collagen. ‘Knock-out’ of the hsp47 gene impairs the secretion of correctly folded collagen triple helix molecules leading to embryonic lethality in mice. Thus the aim of this project was to elucidate the specific mechanism that governs the binding to and release from collagen at the molecular level, known as the ‘pH-switch mechanism’. Emphasis is given on histidine (His) residues as the HSP47-collagen dissociation pH is similar to the pKa of the imidazole side chain of His residues. Site directed mutagenesis was used to mutate surface His residues, based on a mouse HSP47 homology model. The effects of the mutations on the behaviour of HSP47 were then assessed by collagen binding assays and structural analyses with circular dichroism (CD). All mutants were found to have good solubility and retain their binding ability to collagen like wild-type HSP47 in batch assay, but perturbed behaviour was seen in column experiment. Mutation of His residue at position 191 (H191) causes the shift in the collagen dissociation pH, while mutation of H197 and/or 198 disrupt the specific HSP47-collagen interaction. H191, 197 and 198 are predicted to be located in the region near the C-terminus of strand 3 of β-sheet A (s3A) in the homology model, a region specifically known as the ‘breach cluster’ in serpin nomenclature. The extent of conformational rearrangement of this region was further investigated by means of intrinsic tryptophan fluorescence spectroscopy using a series of single tryptophan (Trp) mutants. Results from analyses performed on the mutants did not contradict the observation seen in His mutational work, as Trp residues in the ‘breach’ cluster are likely to be located in the dynamic region of HSP47 pH-triggered conformational change. In conclusion, this study establishes the importance of His residues in the ‘breach cluster’ to HSP47 pH-switch behaviour. Finally, a model for HSP47 pH-switch mechanism was proposed from data obtained via mutagenesis experiments. The model is hoped to assist future research into HSP47 cellular behaviour and will also be of great use in therapeutic applications involving the molecular chaperone

Soil compaction of peat under the influence of electrokinetic stabilization (EKS) treatment

This study aims to enhance the properties of peat such as, (shear strength, compressibility, permeability and liquid limit). Peat is considered as one of the problematic soil in construction projects all over the world, which covers about 4% land of the whole world while 8% of the total area of Malaysia and about (5.86%) of peat soil existing in Johor state. Low shear strength of peat may lead to massive loss of various sectors contributing toward any economic activities such as construction & agriculture projects. There are several issues related to peat stabilization which has become a priority to ensure that soft soil is stable & capable of supporting a load after treated by a suitable soil stabilization method. The problem can be finally reduced by applying stabilization treatment to enhance its properties. One of the known technique Electrokinetic Stabilization treatment, by applying an electric potential to stabilize soft soil. In this method, aluminum was used as an electrode with various voltage potential in the range of 110 to 150 V was applied on both cathode and anode electrode for the duration of 3 and 6 hours at the testing condition without & with a load of (50 kg). Soil parameters such as, shear strength

Far field imaging of a dielectric inclusion

A non-iterative topological sensitivity framework for guaranteed far field detection of a dielectric inclusion is presented. The cases of single and multiple measurements of the electric far field scattering amplitude at a fixed frequency are taken into account. The performance of the algorithm is analyzed theoretically in terms of resolution, stability, and signal-to-noise ratio.Comment: 6 pages, 5th International Workshop on New Computational Methods for Inverse Problems, ENS Cachan, Franc

Foreign assistance and economic growth: evidence from Pakistan 1972 - 2010

This paper examines the relationship between foreign assistance and economic growth for the period 1972 to 2010. Past literature indicates that due to low domestic resource mobilization Pakistan had to resort to various forms of foreign assistance on a regular basis. Using time series data since 1972 and employing Johansen maximum likelihood procedure we show that foreign assistance in the absence of macroeconomic stabilization and structural reforms has a negative relationship with real per capita GDP. However national savings as percentage of GDP show a positive relationship with real per capita GDP. Pakistan has a long history of dependence on multilateral and bilateral development partners. Over the decades the share of grants as percentage of total foreign assistance has declined forcing the country to procure loans at harsh conditionalties. Given the positive impact of national savings on economic growth there is an urgent need for improving the tax base, promoting instruments that encourage savings culture in the private sector and attracting remittances from abroad. These increased savings would then have to be channelized towards productive investments which in turn require pro market reforms.Foreign assistance, Economic Growth, National Savings

Keberkesanan Khidmat Sokongan Pembelajaran dalam Program Pendidikan Jarak Jauh di UPM

Kajian ini bertujuan untuk mengetahui tahap penggunaan khidmat sokongan dalam pendidikan jarak jauh di Universiti Putra Malaysia (UPM) dengan melihat kepada penggunaan khidmat sokongan secara keseluruhan, perbezaan penggunaan di antara bidang-bidang yang dikaji dan juga hubungan angkubah terpilih dengan pencapaian akademik. Seramai 167 orang pelajar pendidikan jarak jauh yang sedang mengikuti program Bimbingan dan Kaunseling, TESL dan Pengajaran sebagai Bahasa Pertama dipilih sebagai sampel kajian melalui kaedah persampelan stratifikasi rawak mudah. Pengwnpulan data menggunakan soal selidik berstruktur yang ditabdir sendiri oleh responden dengan bantuan pengkaji. Data dianalisis menggunakan program Statistical Package for Social Science (SPSS) for MS Window Release 6.0. Secara keseluruhan, penemuan kajian mendapati tahap hubungan di antara pelajar-pelajar dengan pensyarah dan tutor adalah agak tinggi. Begitu juga hubungan pelajar dengan keluarga dan rakan-rakan juga didapati agak tinggi. Walau bagaimanapun, didapati tahap penggunaan kemudahan perpustakaan dan pusat pelajar adalah rendah. Terdapat perbezaan tahap penggunaan khidmat sokongan di antara ketiga-tiga program. Didapati bahawa tahap penggunaan khidmat sokongan pembelajaran pelajar TESL adalah lebih rendah dibandingkan dengan pelajar program Bimbingan dan Kaunseling dan PBMP. Kajian ini juga mendapati bahawa hubungan rapat di antara pelajar dengan pensyarah mempunyai kesan terhadap pencapaian akademik pelajar. Kajian ini menyimpulkan bahawa khidmat sokongan adalah penting dalam pembe1ajaran secara pendidikan jarak jauh. Hubungan di antara pelajar dengan pensyarah perIu dirancang supaya dapat memberi kesan yang lebih baik dalam pembelajaran melalui sistem ini. Dengan peningakatan kemudahan perpustakaandan pusat pelajar dapat membantu keberkesanan dalam pengajian pelajar. Akhir sekali kemudahan berkomunikasi dan kemudahan fizikal perlu dipertingkatkan lagi bagi meningkatkan keberkesanan pebelajaran melalui sistem ini