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  • Mbanzibwa, Deusdedith R (Helsingin yliopisto, 2011)
    Cassava brown streak disease (CBSD) was described for the first time in Tanganyika (now Tanzania) about seven decades ago. Tanganyika (now Tanzania) about seven decades ago. It was endemic in the lowland areas of East Africa and inland parts of Malawi and caused by Cassava brown streak virus (CBSV; genus Ipomovirus; Potyviridae). However, in 1990s CBSD was observed at high altitude areas in Uganda. The causes for spread to new locations were not known.The present work was thus initiated to generate information on genetic variability, clarify the taxonomy of the virus or viruses associated with CBSD in Eastern Africa as well as to understand the evolutionary forces acting on their genes. It also sought to develop a molecular based diagnostic tool for detection of CBSD-associated virus isolates. Comparison of the CP-encoding sequences of CBSD-associated virus isolates collected from Uganda and north-western Tanzania in 2007 and the partial sequences available in Genbank revealed occurrence of two genetically distinct groups of isolates. Two isolates were selected to represent the two groups. The complete genomes of isolates MLB3 (TZ:Mlb3:07) and Kor6 (TZ:Kor6:08) obtained from North-Western (Kagera) and North-Eastern (Tanga) Tanzania, respectively, were sequenced. The genomes were 9069 and 8995 nucleotides (nt), respectively. They translated into polyproteins that were predicted to yield ten mature proteins after cleavage. Nine proteins were typical in the family Potyviridae, namely P1, P3, 6K1, CI, 6K2, VPg, NIa-Pro, NIb and CP, but the viruses did not contain HC-Pro. Interestingly, genomes of both isolates contained a Maf/HAM1-like sequence (HAM1h; 678 nucleotides, 25 kDa) recombined between the NIb and CP domains in the 3’-proximal part of the genomes. HAM1h was also identified in Euphorbia ringspot virus (EuRSV) whose sequence was in GenBank. The HAM1 gene is widely spread in both prokaryotes and eukaryotes. In yeast (Saccharomyces cerevisiae) it is known to be a nucleoside triphosphate (NTP) pyrophosphatase. Novel information was obtained on the structural variation at the N-termini of polyproteins of viruses in the genus Ipomovirus. Cucumber vein yellowing virus (CVYV) and Squash vein yellowing virus (SqVYV) contain a duplicated P1 (P1a and P1b) but lack the HC-Pro. On the other hand, Sweet potato mild mottle virus (SPMMV), has a single but large P1 and has HC-Pro. Both virus isolates (TZ:Mlb3:07 & TZ:Kor6:08) characterized in this study contained a single P1 and lacked the HC-Pro which indicates unique evolution in the family Potyviridae. Comparison of 12 complete genomes of CBSD-associated viruses which included two genomes characterized in this study, revealed genetic identity of 69.0–70.3% (nt) and amino acid (aa) identities of 73.6–74.4% at polyprotein level. Comparison was also made among 68 complete CP sequences, which indicated 69.0-70.3 and 73.6-74.4 % identity at nt and aa levels, respectively. The genetic variation was large enough for dermacation of CBSD-associated virus isolates into two distinct species. The name CBSV was retained for isolates that were related to CBSV isolates available in database whereas the new virus described for the first time in this study was named Ugandan cassava brown streak virus (UCBSV) by the International Committee on Virus Taxonomy (ICTV). The isolates TZ:Mlb3:07 and TZ:Kor6:08 belong to UCBSV and CBSV, respectively. The isolates of CBSV and UCBSV were 79.3-95.5% and 86.3-99.3 % identitical at nt level, respectively, suggesting more variation amongst CBSV isolates. The main sources of variation in plant viruses are mutations and recombination. Signals for recombination events were detected in 50% of isolates of each virus. Recombination events were detected in coding and non-coding (3’-UTR) sequences except in the 5’UTR and P3. There was no evidence for recombination between isolates of CBSV and UCBSV. The non-synonomous (dN) to synonomous (dS) nucleotide substitution ratio (ω) for the HAM1h and CP domains of both viruses were ≤ 0.184 suggesting that most sites of these proteins were evolving under strong purifying selection. However, there were individual amino acid sites that were submitted to adaptive evolution. For instance, adaptive evolution was detected in the HAM1h of UCBSV (n=15) where 12 aa sites were under positive selection (P< 0.05) but not in CBSV (n=12). The CP of CBSV (n=23) contained 12 aa sites (p<0.01) while only 5 aa sites in the CP gene of UCBSV were predicted to be submitted to positive selection pressure (p<0.01). The advantages offered by the aa sites under positive selection could not be established but occurrence of such sites in the terminal ends of UCBSV-HAMIh, for example, was interpreted as a requirement for proteolysis during polyprotein processing. Two different primer pairs that simultaneously detect UCBSV and CBSV isolates were developed in this study. They were used successfully to study distribution of CBSV, UCBSV and their mixed infections in Tanzania and Uganda. It was established that the two viruses co-infect cassava and that incidences of co-infection could be as high as 50% around Lake Victoria on the Tanzanian side. Furthermore, it was revealed for the first time that both UCBSV and CBSV were widely distributed in Eastern Africa. The primer pair was also used to confirm infection in a close relative of cassava, Manihot glaziovii (Müller Arg.) with CBSV. DNA barcoding of M. glaziovii was done by sequencing the matK gene. Two out of seven M. glaziovii from the coastal areas of Korogwe and Kibaha in north eastern Tanzania were shown to be infected by CBSV but not UCBSV isolates. Detection in M. glaziovii has an implication in control and management of CBSD as it is likely to serve as virus reservoir. This study has contributed to the understanding of evolution of CBSV and UCBSV, which cause CBSD epidemic in Eastern Africa. The detection tools developed in this work will be useful in plant breeding, verification of the phytosanitary status of materials in regional and international movement of germplasm, and in all diagnostic activities related to management of CBSD. Whereas there are still many issues to be resolved such as the function and biological significance of HAM1h and its origin, this work has laid a foundation upon which the studies on these aspects can be based.
  • Laiho, Päivi (Helsingin yliopisto, 2005)
  • Ollikainen, Miina (Helsingin yliopisto, 2007)
    Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common known clearly hereditary cause of colorectal and endometrial cancer (CRC and EC). Dominantly inherited mutations in one of the known mismatch repair (MMR) genes predispose to HNPCC. Defective MMR leads to an accumulation of mutations especially in repeat tracts, presenting microsatellite instability. HNPCC is clinically a very heterogeneous disease. The age at onset varies and the target tissue may vary. In addition, families that fulfill the diagnostic criteria for HNPCC but fail to show any predisposing mutation in MMR genes exist. Our aim was to evaluate the genetic background of familial CRC and EC. We performed comprehensive molecular and DNA copy number analyses of CRCs fulfilling the diagnostic criteria for HNPCC. We studied the role of five pathways (MMR, Wnt, p53, CIN, PI3K/AKT) and divided the tumors into two groups, one with MMR gene germline mutations and the other without. We observed that MMR proficient familial CRC consist of two molecularly distinct groups that differ from MMR deficient tumors. Group A shows paucity of common molecular and chromosomal alterations characteristic of colorectal carcinogenesis. Group B shows molecular features similar to classical microsatellite stable tumors with gross chromosomal alterations. Our finding of a unique tumor profile in group A suggests the involvement of novel predisposing genes and pathways in colorectal cancer cohorts not linked to MMR gene defects. We investigated the genetic background of familial ECs. Among 22 families with clustering of EC, two (9%) were due to MMR gene germline mutations. The remaining familial site-specific ECs are largely comparable with HNPCC associated ECs, the main difference between these groups being MMR proficiency vs. deficiency. We studied the role of PI3K/AKT pathway in familial ECs as well and observed that PIK3CA amplifications are characteristic of familial site-specific EC without MMR gene germline mutations. Most of the high-level amplifications occurred in tumors with stable microsatellites, suggesting that these tumors are more likely associated with chromosomal rather than microsatellite instability and MMR defect. The existence of site-specific endometrial carcinoma as a separate entity remains equivocal until predisposing genes are identified. It is possible that no single highly penetrant gene for this proposed syndrome exists, it may, for example be due to a combination of multiple low penetrance genes. Despite advances in deciphering the molecular genetic background of HNPCC, it is poorly understood why certain organs are more susceptible than others to cancer development. We found that important determinants of the HNPCC tumor spectrum are, in addition to different predisposing germline mutations, organ specific target genes and different instability profiles, loss of heterozygosity at MLH1 locus, and MLH1 promoter methylation. This study provided more precise molecular classification of families with CRC and EC. Our observations on familial CRC and EC are likely to have broader significance that extends to sporadic CRC and EC as well.
  • Govindan, Ashokkumar (2014)
    Ubiquitin-mediated proteolysis regulates many basic cellular processes in plant development. Especially, in Arabidopsis thaliana over 1400 genes encode components of the ubiquitin/26S proteasome pathway. Approximately, 90% of the genes encode subunits of the E3 ubiquitin ligases, which confer substrate specificity. However, till now few E3 target proteins were known. Hence, identification and characterization of E3-substrate interaction is essential for understanding the role of ubiquitinylation in various plant developmental pathways. The main objectives of my Master’s thesis were derived from the Flower- specific Ubiquitin Proteasome System (FUPS) research project on the identification of proteins related to FUPS by the candidate and genomic approaches. The candidate approach involved molecular cloning of candidate ubiquitin E3 ligase gene RFI2 and its interaction substrates SLK1 and SLK2 (SLKs). The genomic approach includes genotypic and phenotypic characterization of the Salk T-DNA mutant lines corresponding to the selected FUPS E3 components. The cloning of candidate genes RFI2 and SLKs were done by Gateway cloning technology in order to generate overexpression and inducible expression gene constructs. For functional characterization of candidate proteins in vivo, these constructs were transformed into plants by floral dip Agrobacterium mediated transformation. The yeast two hybrid (Y2H) system was employed to study protein-protein interactions. Genotypic characterization of the selected T-DNA mutant lines was carried out by genetic screening through kanamycin selection. Molecular cloning of candidate genes RFI2 and SLKs into various expression vectors was accomplished. The RFI2 expression constructs were successfully transformed into Arabidopsis plants. The overexpression construct of SLK2 and the RFI2+SLK2 double construct were successfully transformed into root callus. However, the Y2H interaction assay was inconclusive about RFI2-SLK protein interaction, but RFI2 was shown to form homodimers. The transformed plants and the tagged protein constructs of RFI2 and SLK2 will be utilized for protein purification, biochemical assay and in vitro ubiquitination assay to study protein interaction, stability and modification. The genetic screening of T-DNA lines resulted in identification of 10 homozygous lines. In phenotypic analysis of these homozygous lines, early-stage growth and developmental phenotypes such as germination, juvenile leaf emergence, rosette size, colour and root growth were observed. The phenotypic analysis is crucial in identification of the informative phenotype changes in the E3 T-DNA mutant lines. This approach has been successfully employed in understanding of genetic and molecular basis for many biological traits in plants.
  • Mouhu, Katriina (Helsingin yliopisto, 2014)
    Strawberries (Fragaria sp.) are found throughout the Northern Hemisphere, growing in a wide variety of climatic conditions. The economically most important species is the garden strawberry (Fragaria x ananassa Duch.). Strawberries are perennial rosette plants with distinct developmental phases regulated by day length during the growing season. During long days (LDs) in spring and summer, strawberries grow actively with axillary buds developing into stolons called runners. During short days (SDs) in autumn, runner formation is replaced by branch crown formation and an inflorescence is initiated in the shoot meristem of a rosette crown. After winter rest, the inflorescence formed in the previous autumn flowers and vegetative growth is again activated by LDs. The wild strawberry (F. vesca L.) has been used as a model plant in strawberry research for several years. The wild strawberry is a seasonally flowering SD plant, but several perpetually flowering strawberry genotypes have been found. These types differ by a single recessive locus, the SEASONAL FLOWERING LOCUS (SFL), but the regulatory gene behind this trait has not been identified. This thesis aimed to identify the genes related to flowering and vegetative development in the wild strawberry. Expressed sequence tag (EST) sequencing of SD F. vesca and a perpetually flowering genotype were combined with data mining in published Fragaria and Rosaceae EST databases using known Arabidopsis thaliana (L.) Heynh. flowering-related genes as a reference. The results revealed that most genes in the Arabidopsis flowering pathways could be identified among strawberry ESTs, indicating putative conservation in flowering pathway genes between these species. Fragaria vesca TERMINAL FLOWER 1 (FvTFL1), a homologue of the Arabidopsis thaliana TFL1, was confirmed to be the SFL, encoding the flowering repressor in wild strawberry. Fragaria vesca SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (FvSOC1), a homologue of Arabidopsis SOC1, represses flowering via FvTFL1 activation in shoot apices. Both FvSOC1 and FvTFL1 expression are under photoperiodic regulation, controlled at least in part via F. vesca FLOWERING LOCUS T 1 (FvFT1), encoding a putative homologue of the Arabidopsis mobile flowering signal FT, and expressed specifically under LDs. It was concluded that FvTFL1 functions as the flowering repressor and FvTFL1 activation under LDs occurs by FvFT1 via FvSOC1 in wild strawberry. FvSOC1 regulates vegetative growth independently of FvTFL1. FvSOC1 enhanced runner formation from the axillary buds, which involves changes in the levels of gibberellin biosynthesis genes. These results were used to construct a model of the yearly growth cycle in wild strawberry.
  • Kiuru-Kuhlefelt, Sonja (Helsingin yliopisto, 2002)
  • Koivunen, Minni (Helsingin yliopisto, 2006)
    For most RNA viruses RNA-dependent RNA polymerases (RdRPs) encoded by the virus are responsible for the entire RNA metabolism. Thus, RdRPs are critical components in the viral life cycle. However, it is not fully understood how these important enzymes function during viral replication. Double-stranded RNA (dsRNA) viruses perform the synthesis of their RNA genome within a proteinacous viral particle containing an RdRP as a minor constituent. The phi6 bacteriophage is the best-studied dsRNA virus, providing an excellent background for studies of its RNA synthesis. The purified recombinant phi6 RdRP is highly active in vitro and it possesses both RNA replication and transcription activities. The crystal structure of the phi6 polymerase, solved in complex with a number of ligands, provides a working model for detailed in vitro studies of RNA-dependent RNA polymerization. In this thesis, the primer-independent initiation of the phi6 RdRP was studied in vitro using biochemical and structural methods. A C-terminal, four-amino-acid-long loop protruding into the central cavity of the phi6 RdRP has been suggested to stabilize the incoming nucleotides of the initiation complex formation through stacking interactions. A similar structural element has been found from several other viral RdRPs. In this thesis, this so-called initiation platform loop was subjected to site-directed mutagenesis to address its role in the initiation. It was found that the initiation mode of the mutants is primer-dependent, requiring either an oligonucleotide primer or a back-priming initiation mechanism for the RNA synthesis. The crystal structure of a mutant RdRP with altered initiation platform revealed a set of contacts important for primer-independent initiation. Since phi6 RdRP is structurally and functionally homologous to several viral RdRPs, among them the hepatitis C virus RdRP, these results provide further general insight to understand primer-independent initiation. In this study it is demonstrated that manganese phasing could be used as a practical tool for solving structures of large proteins with a bound manganese ion. The phi6 RdRP was used as a case study to obtain phases for crystallographic analysis. Manganese ions are naturally bound to the phi6 RdRP at the palm domain of the enzyme. In a crystallographic experiment, X-ray diffraction data from a phi6 RdRP crystal were collected at a wavelength of 1.89 Å, which is the K edge of manganese. With this data an automatically built model of the core region of the protein could be obtained. Finally, in this work terminal nucleotidyl transferase (TNTase) activity of the phi6 RdRP was documented in the isolated polymerase as well as in the viral particle. This is the first time that such an activity has been reported in a polymerase of a dsRNA virus. The phi6 RdRP used uridine triphosphates as the sole substrate in a TNTase reaction but could accept several heterologous templates. The RdRP was able to add one or a few non-templated nucleotides to the 3' end of the single- or double-stranded RNA substrate. Based on the results on particle-mediated TNTase activity and previous structural information of the polymerase, a model for termination of the RNA-dependent RNA synthesis is suggested in this thesis.
  • Biedzka-Sarek, Marta (Helsingin yliopisto, 2008)
    In complement activation, Factor H (FH) and C4b-binding protein (C4bp) are the key regulators that prevent the complement cascade from attacking host tissues. Some bacteria may bind and deposit these regulators on their own surfaces and thus provide themselves with an efficient means to avoid complement activation. In consequence, bacteria resist complement-mediated lysis and opsonin-dependent phagocytosis. This study has demonstrated that Y. enterocolitica, similar to many other pathogens, recruits both FH and C4bp to its surface to ensure protection against the complement-mediated killing. YadA and Ail, the most crucial serum resistance factors of Y.enterocolitica, mediate the binding of FH and C4bp. FH - YadA interaction involves multiple higher structural motifs on the YadA stalk and the short consensus repeats (SCRs) of the entire polypeptide chain of FH. The Ail binding site on FH has been located to SCRs 6 and 7. The binding site for FH on Ail, however, remains undetermined. Both YadA- and Ail-bound regulators display full cofactor activity for FI-mediated cleavage of C3b/C4b. FH/C4bp-binding characteristics do, however, differ between YadA and Ail. In addition, Ail captures the regulators only in the absence of blocking lipopolysaccharide O-antigen and outer core, whereas YadA binds FH/C4bp independent of the presence of other surface factors Independent of mode of binding, however, YadA and Ail provide Y. enterocolitica a means to avoid complement-mediated lysis, enhancing chances for the bacteria to survive in the host during various phases of infection.
  • Hielm, Sebastian (Helsingin yliopisto, 1999)
  • Santti, Henrikki (Helsingin yliopisto, 2004)
  • Putula, Jaana (Helsingin yliopisto, 2014)
    Neuropeptides orexin-A and orexin-B, and their receptors OX1 and OX2 were first found as regulators of appetite, and later several other functions have been found as well. Orexin peptides and receptors have been researched, especially in the field of drug discovery; however many relevant biochemical properties remain partly unsolved, including the factors determining orexin ligand binding properties and ligand selectivity. The study of these factors was pursued in this thesis. Ligand selectivity was studied with chimaeric orexin receptors. We mapped some of the molecular determinants of orexin receptors that are needed for the selectivity of orexin agonists and OX1-specific antagonist. The second quarter of the orexin receptors seems to be the most important area both for agonist and antagonist selectivity. However, for antagonist selectivity, the third quarter also seems to have a role. Activated orexin receptors cause a strong elevation of intracellular calcium. However, reduction of extracellular calcium attenuates that increase and other orexin receptor signalling, mediated by certain phospholipases and kinases, for instance. It remains unknown, however, how calcium causes these effects. With [125I]-orexin-A, a clear decrease in binding was observed after reduction of the extracellular calcium concentration. Also, we saw a similar reduction in the activities of phospholipase C (PLC) and adenylyl cyclase (AC). The concentration-relationship of calcium was identical for radioligand binding, PLC activation, and AC stimulation, while AC inhibition was more strongly attenuated. When the driving force for calcium influx was reduced with high-K+ medium, the orexin-A-induced PLC activity was more strongly reduced than orexin-A binding. In addition, inhibition of the orexin receptor-operated calcium channels had a more pronounced effect on the PLC activity than on the binding. It is thus suggested that reduction of extracellular calcium concentration both inhibits orexin binding and attenuates enzymatic activity. Orexin-B has higher binding affinity for OX2 than OX1 receptor and [Ala11, D-Leu15]-orexin-B, an orexin-B variant, has been reported to display even higher OX2-selectivity. We observed that [Ala11, D-Leu15]-orexin-B showed much lower OX2-selectivity than originally reported. In addition, the selectivity of both forms of orexin-B was dependent on the cell line. These findings may be caused by biased agonism of the orexin receptor, meaning that the orexin receptor can be found in multiple conformations, each of which can interact differently with an agonist. This result extends our knowledge of orexin ligand binding properties, and the phenomenon should be considered, for instance, when novel agonists for orexin receptors are screened.
  • Forsström, Linda (Helsingin yliopisto, 2012)
    ABSTRACT Idiopathic developmental disorders (DDs) affect ~1% of the population worldwide. This being a considerable amount, efforts are being made to elucidate the disease mechanisms. One or several genetic factors cause 30-40% of DDs, and only 10% are caused by environmental factors. The remaining 50% of DD patients go undiagnosed, mostly due to a lack of diagnostic techniques. The cause in most undiagnosed cases is though to be a genetic factor or a combination of genetic and environmental factors. Despite the surge of new technologies entering the market, their implementation into diagnostic laboratories is hampered by costs, lack of information about the expected diagnostic yield, and the wide range of selection. This study evaluates new microarray methods in diagnosing idiopathic DDs, providing information about their added diagnostic value. Study I analysed 150 patients by array comparative genomic hybridization (array CGH, 44K and 244K), with a subsequent 18% diagnostic yield. These results are supported by other studies, indicating an enourmous added diagnostic value of array CGH, compared with conventional cytogenetic analysis. Nevertheless, 80% of the patients remained undiagnosed in Study I. In an effort to diagnose more patients, in Study IV the resolution was increased from 8.9 Kb of the 244K CGH array to 0.7 Kb, by using a single-nucleotide polymorphism (SNP) array. However, no additional pathogenic changes were detected in the 35 patients assessed, and thus, for diagnostic purposes, an array platform with ca 9 Kb resolution appears adequate. The recent vast increase in reports of detected aberrations and associated phenotypes has enabled characterization of several new syndromes first based on a common aberration and thereafter by delineation of common clinical characteristics. In Study II, a familial deletion at 9q22.2q22.32 with variable penetrance was described. Despite several reports of aberrations in the adjacent area at 9q associated with Gorlin syndrome, the patients in this family had a unique phenotype and did not present with the syndrome. In Study III, a familial duplication of chromosome 6p22.2 was described. The duplication caused increased expression of an important enzyme of the γ-aminobutyric acid (GABA) degradation pathway, causing oxidative stress of the brain, and thus, very likely, the mild mental retardation of these patients. These two case studies attempted to pinpoint candidate genes and to resolve the pathogenic mechanism causing the clinical characteristics of the patients. Presenting rare genetic and clinical findings to the international science and medical community enables interpretation of similar findings in other patients. The added value of molecular karyotyping in patients with idiopathic DD is evident. As a first line of testing, arrays with a median resolution of at least 9 Kb should be considered and further characterization of detected aberrations undertaken when possible. Diagnostic whole-exome sequencing may be the best option for patients who remain undiagnosed after high-resolution array analysis.
  • Loukola, Anu-Maria (Helsingin yliopisto, 2000)
  • Seppälä, Anniina (2013)
    Montmorillonite is a layered swelling clay mineral that has the abilities to absorb water, causing the mineral to swell, and to exchange its structural cations, most commonly Na$^+$ and Ca$^{2+}$. These properties are applied in various fields including the nuclear waste management in Finland. Montmorillonite is the main component of bentonite clay which is planned to be used as a release barrier material in the final repository for spent nuclear fuel. The aim of this work was to study how water is absorbed into the interlayer spaces of Na-montmorillonite. Molecular dynamics simulations were performed on a 3-layered montmorillonite particle surrounded by free water. The amount of water initially present between the layers was varied from none to 1 and 2 water molecules per unit cell. The simulations were performed at two temperatures, 298 K and 323 K, applying CLAYFF force field. The evolution of water content showed practically no absorption at either temperature in the case of completely dry montmorillonite. For the other cases, montmorillonite with water initially present in the interlayers, absorption was observed and it was faster at the higher temperature. The evolution of interlayer thicknesses in each case showed a variation between the two interlayers of the system which was thought to result from the different placement of substitutions in the clay layers.
  • Ilinov, Andrey (Helsingin yliopisto, 2015)
    Nanotechnology became an emerging field during the last few decades. The possibility to create elements having sizes in the nanometer range provides new opportunities for medical applications, various sensors and detectors, and composite materials technologies. However, at the nanoscale the basic physical properties may change unexpectedly including chemical, mechanical, optical and electronic properties. There is still no clear understanding of all possible consequences of miniaturization on the behavior of nanostructures. This thesis is focused on the analysis of mechanical and structural (including sputtering under irradiation) properties of nanorods. By nanorods we imply structures like beams or rods, with their cross-sectional diameter measuring in nanometers and having a length several times larger than the diameter. At such sizes it becomes possible to simulate the structures atom by atom using the molecular dynamics (MD) method. In the first part of the thesis, we analyze the elastic properties of Si nanorods: how the variation in size may change the elastic moduli, the effects of oxidation and intrinsic stresses. We also check the validity of the classical continuum mechanics approach by modeling the same nanorods with the finite elements method (FEM). In the second part we investigate sputtering from Au nanorods under ion irradiation. Recent experiments had shown that there is a big enhancement of sputtering yields from Au nanorods in contrast with those from a flat surface. The yields can be as much as 1000 per individual impact. MD gives us an opportunity to analyze the sputtering process with a femtosecond resolution which is impossible by any of the existing experimental methods. We find that an explosive ejection of nanoclusters is the main factor causing such large sputtering yields.
  • Safi, Elnaz (2014)
    Beryllium (Be) is a strong candidate as plasma-facing material for the main wall of future fusion reactors. Thus, its erosion plays a key role in predicting the reactor's life-time and viability. MD simulations can be a powerful tool to study Be behavior under high plasma particle flux. In this work, beryllium sputtering due to D bombardment is studied using MD simulations. We have analyzed the fundamental mechanisms for Be erosion considering some important parameters that influence the outcome, such as particle flux and surface temperature. It is shown that the Be erosion yield is strongly dependent on the surface temperature and its dependency on the particle flux is negligible. We also show that different species of Be molecules can be sputtered from its surface, mainly due to swift chemical sputtering mechanism.
  • Magarkar, Aniket (Helsingin yliopisto, 2014)
    Drug delivery is a vital issue in pharmaceutical research; once a drug candidate molecule is identified, it must be delivered to the target area of the body where it can take effect. In addition, non-specific distribution of drug molecules to areas other than the drug target must be decreased to avoid unwanted side effects. To achieve this, nanotechnological drug delivery systems can be used. Nanotechnological drug delivery systems come in a wide variety of forms, including liposomes, dendrimers, nanoparticles, and polymeric micelles. Of these, our research is focused on drug delivery liposomes. Drug delivery liposomes are composed of a membrane that forms a closed spherical sack, with a diameter of approximately 100 nm that can contain drug molecules. The criteria for effectiveness of these drug delivery liposomes (DDLs) are structural stability, its lifetime in the bloodstream, the release rate of the encapsulated content and site specific targeting. Cholesterol is one of the crucial lipid components of the DDL known to increase its stability. They also can have a protective polymer coating such as polyethylene glycol (PEG) that protects the DDL from the body s defense mechanisms. Also the DDL can posses targeting moieties, able to direct the PEGylated liposomes to the specific target. In this study we have investigated surface structure of the DDL and its interactions with elements of the blood stream. While it is difficult to determine an accurate picture of the DDL surface and its interactions with ions and bloodstream proteins with atomistic resolution by experiments alone, computational molecular modelling techniques can provide insights into it. Hence, we have used computational modelling and molecular dynamics simulations to understand the role of each component of the DDL in its structure. The three of the five reported studies in this thesis (I, II, III) are focused on how surface charge plays an important role in the liposome, how it is affected by various components of the DDLs, and how the specific interactions of DDLs and ions present in the blood stream influence it. The chapter IV deals with understanding the properties by systematically varying components such as cholesterol and PEG. Also we have produced the first ever model of the first FDA approved drug delivery liposome (DOXIL ®) at atomistic resolution details. The last study (V) deals with the application of molecular dynamics in targeted drug delivery research. In this study we could identify the reason for failure of specific novel targeting peptide (AETP), which is used to functionalize the DDL, by identifying its interactions with the protective PEG polymer.
  • Ilmola, Roni (2015)
    Surface growth by using nanocluster deposition has attracted a lot of attention in recent years due to possibilities to affect electronic properties of the resulting thin films. Industry is interested in this method because with cluster deposition it is possible to manufacture thin films much faster than by using single atom deposition. In some cases, nanocluster deposition is the only method by which thin films have been able to be deposited successfully. I have studied Si20 cluster deposition on the Si(0 0 1) surface. I used molecular dynamics simulations to simulate epitaxial silicon growth at temperatures 300 K, 500 K, 700 K, 1000 K, 1300 K and 1600 K. I used two potential models to do this, the Tersoff and the Stillinger-Weber potentials. This work focuses on the differences in the results of these potential models at various temperatures. All the atoms in the cluster had 1 eV of energy. I observed that the growth is stronger with the Stillinger-Weber potential almost at every temperature. At 300 K no epitaxial growth was seen and at 1600 K the substrate melted. I observed almost complete epitaxial growth with the Stillinger-Weber potential, whereas with the Tersoff potential there was an amorphous layer on top of the crystalline region. The epitaxial growth didn’t originate from the diffusion as much as from the rearrangement of atoms at the amorphous-crystalline interface.
  • Julin, Jan (Helsingin yliopisto, 2011)
    Nucleation is the first step in a phase transition where small nuclei of the new phase start appearing in the metastable old phase, such as the appearance of small liquid clusters in a supersaturated vapor. Nucleation is important in various industrial and natural processes, including atmospheric new particle formation: between 20 % to 80 % of atmospheric particle concentration is due to nucleation. These atmospheric aerosol particles have a significant effect both on climate and human health. Different simulation methods are often applied when studying things that are difficult or even impossible to measure, or when trying to distinguish between the merits of various theoretical approaches. Such simulation methods include, among others, molecular dynamics and Monte Carlo simulations. In this work molecular dynamics simulations of the homogeneous nucleation of Lennard-Jones argon have been performed. Homogeneous means that the nucleation does not occur on a pre-existing surface. The simulations include runs where the starting configuration is a supersaturated vapor and the nucleation event is observed during the simulation (direct simulations), as well as simulations of a cluster in equilibrium with a surrounding vapor (indirect simulations). The latter type are a necessity when the conditions prevent the occurrence of a nucleation event in a reasonable timeframe in the direct simulations. The effect of various temperature control schemes on the nucleation rate (the rate of appearance of clusters that are equally able to grow to macroscopic sizes and to evaporate) was studied and found to be relatively small. The method to extract the nucleation rate was also found to be of minor importance. The cluster sizes from direct and indirect simulations were used in conjunction with the nucleation theorem to calculate formation free energies for the clusters in the indirect simulations. The results agreed with density functional theory, but were higher than values from Monte Carlo simulations. The formation energies were also used to calculate surface tension for the clusters. The sizes of the clusters in the direct and indirect simulations were compared, showing that the direct simulation clusters have more atoms between the liquid-like core of the cluster and the surrounding vapor. Finally, the performance of various nucleation theories in predicting simulated nucleation rates was investigated, and the results among other things highlighted once again the inadequacy of the classical nucleation theory that is commonly employed in nucleation studies.