Reproduction and population structure in European aspen

The European aspen (Populus tremula) is a keystone species for biodiversity in boreal forests. However, the future of aspen may be threatened, because large aspens have mostly been removed from managed forests, whereas regeneration and the long-term persistence of mature trees are subjects of concern in protected areas. Aspen is a pioneer tree, and it can reproduce both sexually by seed and asexually by root suckers. Through asexual reproduction aspen forms clones, groups of genetically identical trees (ramets). In my thesis, I have studied the structure of aspen populations in terms of number, size, clonal and demographic properties. Additionally, I have investigated the emergence and survival of seedlings as well as the seed quantity and quality in crosses between the European and hybrid aspen. To study the regeneration and population structure, mature aspens were recorded in old-growth and managed forests in eastern Finland based on a large-scale inventory (11 400 ha). In addition, small aspen trees were surveyed on sample plots. Clonal structure was investigated both by morphological characters and by DNA-based markers (microsatellites). Seedling emergence and survival was studied with two sowing experiments. With crosses between European and hybrid aspens we wanted to study whether elevated temperatures due to climate change would benefit the different crosses of European and hybrid aspen unequally and thus affect the gene flow between the two species. The average volumes of mature aspen were 5.3 m3/ha in continuous old-growth, and 0.8 m3/ha in managed forests. Results indicate also that large aspen trees in managed forests are a legacy of the past less intensively managed forest landscapes. Long-term persistence of aspen in protected areas can only be secured by restoration measures creating sufficiently large gaps for regeneration. More emphasis should be given to sparing aspens in thinnings and to retaining of mature aspens in regeneration cutting in managed forests. Aspen was found to be spatially aggregated in the landscape. This could be explained by site type, disturbance history and / or limitations in seed dispersal. Clonal structure does not explain the spatial aggregation, since average size of the clones was only 2.3 ramets, and most clones (70 %) consisted of just one ramet. The small size of the clones suggests that most of them are relatively young. Therefore, sexual reproduction may be more common than has previously been thought. Seedling emergence was most successful in mineral soil especially, when the site had been burned. Only few seedlings occurred on humus. Survival of the seedlings was low, and strongly dependent on moisture, but also on seedbed conditions. The seeds were found to maintain their germinability longer than has earlier been thought to be possible. Interspecific crosses produced more seeds with higher quality than intraspecific crosses. When temperature was elevated, germination of hybrid aspen seeds increased more than seeds from P. tremula x P. tremula crosses. These results suggest that hybrid aspen may have a significant genetic impact on the European aspen, and this effect may become strengthened by climate warming.

GATA Transcription Factors in Tissue Homeostasis and Pathology of the Gastrointestinal Tract and Liver

Mammalian gastrointestinal tract and liver are self-renewing organs that are able to sustain themselves due to stem cells present in their tissues. In constant, inflammation-related epithelial damage, vigorous activation of stem cells may lead to their uncontrolled proliferation, and further, to cancer. GATA-4, GATA-5, and GATA-6 regulate cell proliferation and differentiation in many mammalian organs. Lack of GATA-4 or GATA-6 leads to defective endodermal development and cell differentiation. GATA-4 and GATA-5 are considered the ones with tumor suppressive functions, whereas GATA-6 is more related to tumor promotion. In the digestive system their roles in inflammation and tumor-related molecular pathways remain unclear. In this study, we examined the GATA-related molecular pathways involved in normal tissue organization and renewal and in inflammation-related epithelial repair in the gastrointestinal tract and liver. The overall purpose of this study was to elucidate the relation of GATA factors to gastrointestinal and hepatic disease pathology and to evaluate their possible clinical significance in tumor biology. The results indicated distinct expression patterns for GATA-4, GATA-5, and GATA-6 in the human and murine gastrointestinal tract and liver, and their involvement in the regulation of intestine-specific genes. GATA-5 was confined to the intestines of suckling mice, suggesting an association with postnatal enzymatic changes. GATA-4 was upregulated in bowel inflammation concomitantly with TGF-β signaling. In gastrointestinal tumors, GATA-4 was restricted to benign neoplasias of the stomach, while GATA-6 was detected especially at the invasive edges of malignant tumors throughout the gut. In the liver, GATA-4 was upregulated in pediatric tumors along with erythropoietin (Epo), which was detected also in the sera of tumor patients. Furthermore, GATA-4 was enhanced in areas of vigorous hepatic regeneration in patients with tyrosinemia type I. These results suggest a central role for GATA-4 in pediatric tumor biology of the liver. To conclude, GATA-4, GATA-5, and GATA-6 are associated with normal gastrointestinal and hepatic development and regeneration. The appearance of GATA-4 along with TGF-β-signaling in the inflammatory bowel suggests a protective role in the response to inflammation-related epithelial destruction. However, in extremely malignant pediatric liver tumors, GATA-4 function is unlikely to be tumor-suppressing, probably due to the nature of the very primitive multipotent tumor cells. GATA-4, along with its possible downstream factor Epo, could be utilized as novel hepatic tumor markers to supplement the present diagnostics. They could also serve a function in future biological therapies for aggressive pediatric tumors.

SSMBS: a web server to locate sequentially separated motifs in biological sequences

The identification of sequence (amino acids or nucleotides) motifs in a particular order in biological sequences has proved to be of interest. This paper describes a computing server, SSMBS, which can locate anddisplay the occurrences of user-defined biologically important sequence motifs (a maximum of five) present in a specific order in protein and nucleotide sequences. While the server can efficiently locate motifs specified using regular expressions, it can also find occurrences of long and complex motifs. The computation is carried out by an algorithm developed using the concepts of quantifiers in regular expressions. The web server is available to users around the clock at http://dicsoft1.physics.iisc.ernet.in/ssmbs/.

Health-Related Quality of Life, Costs and Treatment of Inflammatory Rheumatic Diseases in Routine Practice : With special emphasis on biological drugs

Rheumatoid arthritis (RA) and other chronic inflammatory joint diseases already begin to affect patients health-related quality of life (HRQoL) in the earliest phases of these diseases. In treatment of inflammatory joint diseases, the last two decades have seen new strategies and treatment options introduced. Treatment is started at an earlier phase; combinations of disease-modifying anti-rheumatic drugs (DMARDs) and corticosteroids are used; and in refractory cases new drugs such as tumour necrosis factor (TNF) inhibitors or other biologicals can be started. In patients with new referrals to the Department of Rheumatology of the Helsinki University Central Hospital, we evaluated the 15D and the Stanford Health Assessment Questionnaire (HAQ) results at baseline and approximately 8 months after their first visit. Altogether the analysis included 295 patients with various rheumatic diseases. The mean baseline 15D score (0.822, SD 0.114) was significantly lower than for the age-matched general population (0.903, SD 0.098). Patients with osteoarthritis (OA) and spondyloarthropathies (SPA) reported the poorest HRQoL. In patients with RA and reactive arthritis (ReA) the HRQoL improved in a statistically significant manner during the 8-month follow-up. In addition, a clinically important change appeared in patients with systemic rheumatic diseases. HAQ score improved significantly in patients with RA, arthralgia and fibromyalgia, and ReA. In a study of 97 RA patients treated either with etanercept or adalimumab, we assessed their HRQoL with the RAND 36-Item Health Survey 1.0 (RAND-36) questionnaire. We also analysed changes in clinical parameters and the HAQ. With etanercept and adalimumab, the values of all domains in the RAND-36 questionnaire increased during the first 3 months. The efficacy of each in improving HRQoL was statistically significant, and the drug effects were comparable. Compared to Finnish age- and sex-matched general population values, the HRQoL of the RA patients was significantly lower at baseline and, despite the improvement, remained lower also at follow-up. Our RA patients had long-standing and severe disease that can explain the low HRQoL also at follow-up. In a pharmacoeconomic study of patients treated with infliximab we evaluated medical and work disability costs for patients with chronic inflammatory joint disease during one year before and one year after institution of infliximab treatment. Clinical and economic data for 96 patients with different arthritis diagnoses showed, in all patients, significantly improved clinical and laboratory variables. However, the medical costs increased significantly during the second period by 12 015 (95% confidence interval, 6 496 to 18 076). Only a minimal decrease in work disability costs occurred mean decrease 130 (-1 268 to 1 072). In a study involving a switch from infliximab to etanercept, we investigated the clinical outcome in 49 patients with RA. Reasons for switching were in 42% failure to respond by American College of Rheumatology (ACR) 50% criteria; in 12% adverse event; and in 46% non-medical reasons although the patients had responded to infliximab. The Disease Activity Score with 28 joints examined (DAS28) allowed us to measure patients disease activity and compare outcome between groups based on the reason for switching. In the patients in whom infliximab was switched to etanercept for nonmedical reasons, etanercept continued to suppress disease activity effectively, and 1-year drug survival for etanercept was 77% (95% CI, 62 to 97). In patients in the infliximab failure and adverse event groups, DAS28 values improved significantly during etanercept therapy. However, the 1-year drug survival of etanercept was only 43% (95% CI, 26 to 70) and 50% (95% CI, 33 to 100), respectively. Although the HRQoL of patients with inflammatory joint diseases is significantly lower than that of the general population, use of early and aggressive treatment strategies including TNF-inhibitors can improve patients HRQoL effectively. Further research is needed in finding new treatment strategies for those patients who fail to respond or lose their response to TNF-inhibitors.

Cereal alkylresorcinols as dietary biomarkers-absorption and occurrence in biological membranes

Several studies link the consumption of whole-grain products to a lowered risk of chronic diseases, such as certain types of cancer, type II diabetes, and cardiovascular diseases. However, the final conclusions of the exact protective mechanisms remain unclear, partly due to a lack of a suitable biomarker for the whole-grain cereals intake. Alkylresorcinols (AR) are phenolic lipids abundant in the outer parts of wheat and rye grains usually with homologues of C15:0- C25:0 alkyl chains, and are suggested to function as whole-grain biomarkers. Mammalian lignan enterolactone has also previously been studied as a potential whole-grain biomarker. In the present work a quantified gas chromatography-mass spectrometry method for the analysis of AR in plasma, erythrocytes, and lipoproteins was developed. The method was used to determine human and pig plasma AR concentrations after the intake of whole-grain wheat and rye products compared to low-fibre wheat bread diets to assess the usability of AR as biomarkers of whole-grain intake. AR plasma concentrations were compared to serum ENL concentrations. AR absorption and elimination kinetics were investigated in a pig model. AR occurrence in human erythrocyte membranes and plasma lipoproteins were determined, and the distribution of AR in blood was evaluated. Plasma AR seem to be absorbed via the lymphatic system from the small intestine, like many other lipophilic compounds. Their apparent elimination half-life is relatively short and is similar to that of tocopherols, which have a similar chemical structure. Plasma AR concentrations increased significantly after a one- to eight-week intake of whole-grain wheat and further on with whole-grain rye bread. The concentrations were also higher after habitual Finnish diet compared to diet with low-fibre bread. Inter-individual variation after a one-week intake of the same amount of bread was high, but the mean plasma AR concentrations increased with increasing AR intake. AR are incorporated into erythrocyte membranes and plasma lipoproteins, and VLDL and HDL were the main AR carriers in human plasma. Based on these studies, plasma AR could function as specific biomarkers of dietary whole-grain products. AR are exclusively found in whole-grains and are more suitable as specific biomarkers of whole-grain intake than previously investigated mammalian lignan enterolactone, that is formed from several plants other than cereals in the diet. Plasma AR C17:0/C21:0 -ratio could distinguish whether whole-grain products in the diet are mainly wheat or rye. AR could be used in epidemiological studies to determine whole-grain intake and to better assess the role of whole-grains in disease prevention.

Bio-inspired multifunctional metallic foams through the fusion of different biological solutions

Nature is a school for scientists and engineers. Inherent multiscale structures of biological materials exhibit multifunctional integration. In nature, the lotus, the water strider, and the flying bird evolved different and optimized biological solutions to survive. In this contribution, inspired by the optimized solutions from the lotus leaf with superhydrophobic self-cleaning, the water strider leg with durable and robust superhydrophobicity, and the lightweight bird bone with hollow structures, multifunctional metallic foams with multiscale structures are fabricated, demonstrating low adhesive superhydrophobic self-cleaning, striking loading capacity, and superior repellency towards different corrosive solutions. This approach provides an effective avenue to the development of water strider robots and other aquatic smart devices floating on water. Furthermore, the resultant multifunctional metallic foam can be used to construct an oil/water separation apparatus, exhibiting a high separation efficiency and long-term repeatability. The presented approach should provide a promising solution for the design and construction of other multifunctional metallic foams in a large scale for practical applications in the petro-chemical field. Optimized biological solutions continue to inspire and to provide design idea for the construction of multiscale structures with multifunctional integration. Inspired by the optimized biological solutions from the lotus leaf with superhydrophobic self-cleaning, the water strider leg with durable and robust superhydrophobicity, and the lightweight bird bone with hollow structures, multifunctional metallic foams with multiscale structures are fabricated, demonstrating low adhesive superhydrophobic self-cleaning, striking loading capacity, stable corrosion resistance, and oil/water separation.

A Method to Find Sequentially Separated Motifs in Biological Sequences (SSMBS)

Sequence motifs occurring in a particular order in proteins or DNA have been proved to be of biological interest. In this paper, a new method to locate the occurrences of up to five user-defined motifs in a specified order in large proteins and in nucleotide sequence databases is proposed. It has been designed using the concept of quantifiers in regular expressions and linked lists for data storage. The application of this method includes the extraction of relevant consensus regions from biological sequences. This might be useful in clustering of protein families as well as to study the correlation between positions of motifs and their functional sites in DNA sequences.

Biological mechanisms behind clozapine-induced agranulocytosis

Clozapine is the most effective drug in treating therapy-resistant schizophrenia and may even be superior to all other antipsychotics. However, its use is limited by a high incidence (approximately 0.8%) of a severe hematological side effect, agranulocytosis. The exact molecular mechanism(s) of clozapine-induced agranulocytosis is still unknown. We investigated the mechanisms behind responsiveness to clozapine therapy and the risk of developing agranulocytosis by performing an HLA (human leukocyte antigens) association study in patients with schizophrenia. The first group comprised patients defined by responsiveness to first-generation antipsychotics (FGAs) (n= 19). The second group was defined by a lack of response to FGAs but responsiveness to clozapine (n=19). The third group of patients had a history of clozapine-induced granulocytopenia or agranulocytosis (n=26). Finnish healthy blood donors served as controls (n= 120). We found a significantly increased frequency of HLA-A1 among patients who were refractory to FGAs but responsive to clozapine. We also found that the frequency of HLA-A1 was low in patients with clozapine-induced neutropenia or agranulocytosis. These results suggest that HLA-A1 may predict a good therapeutic outcome and a low risk of agranulocytosis and therefore HLA typing may aid in the selection of patients for clozapine therapy. Furthermore, in a subgroup of schizophrenia, HLA-A1 may be in linkage disequilibrium with some vulnerability genes in the MHC (major histocompatibility complex) region on chromosome 6. These genes could be involved in antipsychotic drug response and clozapine-induced agranulocytosis. In addition, we investigated the effect of clozapine on gene expression in granulocytes by performing a microarray analysis on blood leukocytes of 8 schizophrenic patients who had started clozapine therapy for the first time. We identified an altered expression in 4 genes implicated in the maturation or apoptosis of granulocytes: MPO (myeloperoxidase precursor), MNDA (myeloid cell nuclear differentiation antigen), FLT3LG (Fms-related tyrosine kinase 3 ligand) and ITGAL (antigen CD11A, lymphocyte function-associated antigen 1). The altered expression of these genes following clozapine administration may suggest their involvement in clozapine-induced agranulocytosis. Finally, we investigated whether or not normal human bone marrow mesenchymal stromal cells (MSC) are sensitive to clozapine. We treated cultures of human MSCs and human skin fibroblasts with 10 µM of unmodified clozapine and with clozapine bioactivated by oxidation. We found that, independent of bioactivation, clozapine was cytotoxic to MSCs in primary culture, whereas clozapine at the same concentration stimulated the growth of human fibroblasts. This suggests that direct cytotoxicity to MSCs is one possible mechanism by which clozapine induces agranulocytosis.

Biological and environmental determinants

This chapter describes biological and environmental determinants of the health of Australians, providing a background to the development of successful public health activity. You will recall from the introduction to Section 2 that health determinants are the biomedical, genetic, behavioural, socioeconomic and environmental factors that impact on health and wellbeing. These determinants can be influenced by interventions and by resources and systems (Australian Institute of Health and Welfare (AIHW) AIHW 2012a). Many factors combine to affect the health of individuals and communities. People’s circumstances and the environment determine whether a population is healthy or not. Factors such as where people live, the state of their environment, genetics, their education level and income, and their relationships with friends and family are all likely to impact on their health. The determinants of population health reflect the context of people’s lives; however, people have limited control over many of these determinants (WHO 2007).

Chemical modifications of natural triterpenes—glycyrrhetinic and boswellic acids: evaluation of their biological activity

Synthetic analogues of naturally occurring triterpenoids; glycyrrhetinic acid, arjunolic acid, and boswellic acids, by modification of A-ring with a cyano- and enone-functionality, have been reported. A novel method of synthesis of α-cyanoenones from isoxazoles is reported. Bioassays using primary mouse macrophages and tumor cell lines indicate potent anti-inflammatory and cytotoxic activities associated with cyano-enones of boswellic acid and glycyrrhetinic acid.

Characterization of LRRTM and NGR gene families: Expression and functions

Some leucine-rich repeat (LRR) -containing membrane proteins are known regulators of neuronal growth and synapse formation. In this work I characterize two gene families encoding neuronal LRR membrane proteins, namely the LRRTM (leucine-rich repeat, transmembrane neuronal) and NGR (Nogo-66 receptor) families. I studied LRRTM and NGR family member's mRNA tissue distribution by RT-PCR and by in situ hybridization. Subcellular localization of LRRTM1 protein was studied in neurons and in non-neuronal cells. I discovered that LRRTM and NGR family mRNAs are predominantly expressed in the nervous system, and that each gene possesses a specific expression pattern. I also established that LRRTM and NGR family mRNAs are expressed by neurons, and not by glial cells. Within neurons, LRRTM1 protein is not transported to the plasma membrane; rather it localizes to endoplasmic reticulum. Nogo-A (RTN4), MAG, and OMgp are myelin-associated proteins that bind to NgR1 to limit axonal regeneration after central nervous system injury. To better understand the functions of NgR2 and NgR3, and to explore the possible redundancy in the signaling of myelin inhibitors of neurite growth, I mapped the interactions between NgR family and the known and candidate NgR1 ligands. I identified high-affinity interactions between RTN2-66, RTN3-66 and NgR1. I also demonstrate that Rtn3 mRNA is expressed in the same glial cell population of mouse spinal cord white matter as Nogo-A mRNA, and thus it could have a role in myelin inhibition of axonal growth. To understand how NgR1 interacts with multiple structurally divergent ligands, I aimed first to map in more detail the nature of Nogo-A:NgR1 interactions, and then to systematically map the binding sites of multiple myelin ligands in NgR1 by using a library of NgR1 expression constructs encoding proteins with one or multiple surface residues mutated to alanine. My analysis of the Nogo-A:NgR1 -interactions revealed a novel interaction site between the proteins, suggesting a trivalent Nogo-A:NgR1-interaction. Our analysis also defined a central binding region on the concave side of NgR1's LRR domain that is required for the binding of all known ligands, and a surrounding region critical for binding MAG and OMgp. To better understand the biological role of LRRTMs, I generated Lrrtm1 and Lrrtm3 knock out mice. I show here that reporter genes expressed from the targeted loci can be used for maping the neuronal connections of Lrrtm1 and Lrrtm3 expressing neurons in finer detail. With regard to LRRTM1's role in humans, we found a strong association between a 70 kb-spanning haplotype in the proposed promoter region of LRRTM1 gene and two possibly related phenotypes: left-handedness and schizophrenia. Interestingly, the responsible haplotype was linked to phenotypic variability only when paternally inherited. In summary, I identified two families of neuronal receptor-like proteins, and mapped their expression and certain protein-protein interactions. The identification of a central binding region in NgR1 shared by multiple ligands may facilitate the design and development of small molecule therapeutics blocking binding of all NgR1 ligands. Additionally, the genetic association data suggests that allelic variation upstream of LRRTM1 may play a role in the development of left-right brain asymmetry in humans. Lrrtm1 and Lrrtm3 knock out mice developed as a part of this study will likely be useful for schizophrenia and Alzheimer s disease research.

CNS injury, γ1 laminin, and its KDI peptide

Nisäkkäillä keskushermoston uudistuminen on rajallista. Keskushermostovamman jälkeen aktivoituu monien paranemista edistävien tekijöiden lisäksi myös estäviä tekijöitä. Monella molekyylillä, kuten laminiinilla, on keskushermoston paranemista tehostava vaikutus. Laminiinit ovat myös kehon tyvikalvojen oleellisia rakennuskomponentteja. Keskushermoston laminiinit ovat tärkeitä sikiökehityksen aikana, esimerkiksi hermosäikeiden ohjauksessa. Myöhemmin ne osallistuvat veriaivoesteen ylläpitoon sekä vammojen jälkeiseen kudosreaktioon. Väitöskirjatutkimuksessani olen selvittänyt lamiiniinien, erityisesti γ1 laminiinin ja sen KDI peptidin, ekspressiota keskushermoston vammatilanteissa. Kokeellisessa soluviljelmäasetelmassa, joka simuloi vammautunutta keskushermostoympäristöä, osoitimme että KDI peptidi voimistaa sekä hermosolujen selviytymistä että hermosäikeiden kasvua. Kainihappo on glutamaattianalogi, ja glutamaattitoksisuudella uskotaan olevan tärkeä merkitys keskushermoston eri vamma- ja sairaustilanteissa tapahtuvassa hermosolukuolemassa. Toisessa väitöskirjani osatyössä osoitimme eläinmallissa KDI peptidin suojaavan rotan aivojen hippokampuksen hermosoluja kainihapon aiheuttamalta solutuholta. Elektrofysiologisilla mittauksilla osoitimme kolmannessa osatyössäni, että KDI peptidi estää glutamaattireseptorivirtoja ja suojaa siten glutamaattitoksisuudelta. Aivoveritulpan aiheuttama aivovaurio on yleinen syy aivohalvaukseen. Viimeisessä osatyössäni tutkimme eläinmallissa laminiinien ekspressiota iskemian vaurioittamassa aivokudoksessa. Laminiiniekspression todettiin voimistuvan vaurion jälkeen sekä tyvikalvo- että soluväliainerakenteissa. Vaurion ympärillä havaittiin astrosyyttejä, jotka jo melko aikaisessa vaiheessa vamman jälkeen ekspressoivat γ1 laminiinia ja KDI peptidiä. Tästä voidaan päätellä laminiinien osallistuvan aivoiskeemisen vaurion patofysiologiaan. Yleisesti väitöskirjatyöni kartoitti laminiinien ekspressiota sekä terveessä että vammautuneessa keskushermostossa. Väitöskirjatyöni tukee hypoteesia, jonka mukaan KDI peptidi suojaa keskushermostoa vaurioilta.

Role of γ1 Laminin and Its KDI Peptide in the Central Nervous System

Since the 1980 s, laminin-1 has been linked to regeneration of the central nervous system (CNS) and promotion of neuronal migration and axon guidance during CNS development. In this thesis, we clarify the role of γ1 laminin and its KDI tripeptide in development of human embryonic spinal cord, in regeneration of adult rat spinal cord injury (SCI), in kainic acid-induced neuronal death, and in the spinal cord tissue of amyotrophic lateral sclerosis (ALS). We demonstrated that γ1 laminin together with α1, β1, and β3 laminins localize at the floor plate region in human embryonic spinal cord. This localization of γ1 laminin is in spatial and temporal correlation with development of the spinal cord and indicates that γ1 laminin may participate in commissural axon guidance during the embryonic development of the human CNS. With in vitro studies using the Matrigel culture system, we demonstrated that the KDI tripeptide of γ1 laminin provides a chemotrophic guidance cue for neurites of the human embryonic dorsal spinal cord, verifying the functional ability of γ1 laminin to guide commissural axons. Results from our experimental SCI model demonstrate that the KDI tripeptide enhanced functional recovery and promoted neurite outgrowth across the mechanically injured area in the adult rat spinal cord. Furthermore, our findings indicate that the KDI tripeptide as a non-competitive inhibitor of the ionotropic glutamate receptors can provide when administered in adequate concentrations an effective method to protect neurons against glutamate-induced excitotoxic cell death. Human postmortem samples were used to study motor neuron disease, ALS (IV), and the study revealed that in human ALS spinal cord, γ1 laminin was selectively over-expressed by reactive astrocytes, and that this over-expression may correlate with disease severity. The multiple ways by which γ1 laminin and its KDI tripeptide provide neurotrophic protection and enhance neuronal viability suggest that the over-expression of γ1 laminin may be a glial attempt to provide protection for neurons against ALS pathology. The KDI tripeptide is effective therapeutically thus far in animal models only. However, because KDI containing γ1 laminin exists naturally in the human CNS, KDI therapies are unlikely to be toxic or allergenic. Results from our animal models are encouraging, with no toxic side-effects detected even at high concentrations, but the ultimate confirmation can be achieved only after clinical trials. More research is still needed until the KDI tripeptide is refined into a clinically applicable method to treat various neurological disorders.

A FEM-Based Forward Solver for Studying the Forward Problem of Electrical Impedance Tomography (EIT) with A Practical Biological Phantom

A Finite Element Method based forward solver is developed for solving the forward problem of a 2D-Electrical Impedance Tomography. The Method of Weighted Residual technique with a Galerkin approach is used for the FEM formulation of EIT forward problem. The algorithm is written in MatLAB7.0 and the forward problem is studied with a practical biological phantom developed. EIT governing equation is numerically solved to calculate the surface potentials at the phantom boundary for a uniform conductivity. An EIT-phantom is developed with an array of 16 electrodes placed on the inner surface of the phantom tank filled with KCl solution. A sinusoidal current is injected through the current electrodes and the differential potentials across the voltage electrodes are measured. Measured data is compared with the differential potential calculated for known current and solution conductivity. Comparing measured voltage with the calculated data it is attempted to find the sources of errors to improve data quality for better image reconstruction.