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Malaria was the deadliest infectious disease in colonial Assam, but the malady received less attention from government officials and medical officers than other diseases. Additionally, malaria in Assam has received relatively little attention from modern historians. This project sits at the intersection of medical, colonial, and environmental histories, and contributes to discussions in the history of malaria, Assam, and British India. It explores the history of malaria in colonial Assam between 1826 and 1939. The approach is largely one of historical epidemiology; it analyses mortality and morbidity data on ‘Fevers’ and attempts made by the government and medical officers to understand and prevent the disease. Assam was transformed by British rule, and the trajectories of both malaria and society were strongly influenced by colonial rule during this time period. The ecology of Assam was heavily modified to support the province’s biggest industry- tea. In the process, jungles were cleared, millions of immigrant labourers were recruited, and malaria flourished. Efforts to reduce malaria across the province failed, and public health as a practice was often structured around keeping immigrant labourers healthy and industrial enclaves productive. Exploring anti-malarial measures in the province and the relationship between the creation of medical knowledge and public health praxis, this project touches on the topics of colonial ‘development’, quinine, mosquito control measures, and epidemiology. This dissertation argues that malaria played a pivotal role in the history of colonial Assam; that historians are able to gain some understanding of the presence and effects of the disease even when knowledge in the past was limited; and that perceptions of the disease, attempts to control it, and that both human and non-human factors that contributed to malaria were heavily influenced by colonial forces.

We investigated anammox, denitrification and dissimilatory reduction of nitrite to ammonium (DNRA) activity in the Eastern Tropical South Pacific oxygen minimum zone (OMZ) off northern Chile, at high-depth resolution through the oxycline into the anoxic OMZ core. This was accompanied by high-resolution nutrient and oxygen profiles to link changes in nitrogen transformation rates to physicochemical characteristics of the water column. Denitrification was detected at most depths, but anammox was the most active N-2-producing process, while DNRA was not detectable. Anammox and denitrification were mainly active in the anoxic OMZ core while activity was low to not detectable in the oxycline, except in association with an intrusion of OMZ core water. This indicates that continuous exposure to even submicromolar oxygen levels inhibits the processes either directly or through nitrite limitation. Anammox activity did not peak at the oxic-anoxic boundary but 20-50m below matching the salinity maximum of the Equatorial Subsurface Water. This suggests that water history plays a major role for anammox activity possibly due to slow growth of anammox bacteria. Denitrification peaked deeper than anammox, likely reflecting a shift in the balance between this process and nitrate reduction to nitrite, governed by the relative availability of nitrate and nitrite.

Plasmids were constructed to investigate homologous mitotic recombination in Drosophila cells. Heteroalleles containing truncated but overlapping segments of the bacterial beta-galactosidase gene (lacZ) were positioned either on separate plasmids or as direct repeats on the same chromosome. Recombination reconstituted a functional lacZgene leading to expression of LacZ+activity detectable by histochemical staining. High extrachromosomal recombination (ECR) frequencies between unlinked heteroalleles were observed upon transient co-transfection into Drosophila melanogaster Schneider line 2 (S2) cells. Stably transfected cells containing the lacZ heteroalleles linked on a chromosome exhibited intrachromosomal recombination (ICR) frequencies two orders of magnitude lower than ECR frequencies. Recombination was inducible by exposing the cells to ethyl methanesulphonate or mitomycin C. Recombination products were characterized by multiplex PCR analysis and unequal sister chromatid recombination was found as the predominant mechanism reconstituting the lacZ gene. To investigate recombination in vivo imaginal disc cells from transgenic larvae carrying the reporter gene on the X chromosome were isolated and stained for LacZ+ activity. The presence of a few LacZ+ clones indicated that mitotic recombination events occurred at frequencies two orders of magnitude lower than the corresponding event in cultured cells and late during larval development.

This paper presents a computational algorithm for the detection and compensation for intracellular movement in the FRAP experiments with focal adhesions in living cells. The developed approach is based on the calculation of correlation coefficient. It was validated on the series of the experimental datasets and shows the successful results in the comparison with other widelyestablished methods.

Секция 9. Распознавание образов, информационные системы управления Automotive focal adhesion segmentation and its tracking is a critical part of ac-tin filament treadmilling that is detected by the method of the fluorescent recovery after photobleaching(FRAP). However, the complex processes in live cells exhibit new challenging tasks before the cell image segmentation. In the developed tracking method we propose to use the correlation function to estimate the shift of cell compartments. We employ local thresholding for the fluorescence recovery intensity in order to segment the focal adhesions in the region of interest. We have applied this method for tracking the focal adhesions in HeLa cells.

A novel mathematical approach for quantitative investigation of protein dy- namics in living cells with °uorescence recovery after photobleaching (FRAP) experiments has been developed. Existing FRAP Їtting models are based on the speciЇc chemical reaction equations and often exhausting for parameters Їtting. Our model allows to study di®erent biomolecular processes and can be used as a non-Їtting procedure for quantitative FRAP analysis. The mathematical for- malism is based on the theory of stochastic processes. The derived model was validated on the examples of binding and actin polymerization reactions.

Actin polymerization in cell is a basic biological process relevant to health and disease. We have developed the e±cient stochastic simulation algorithm for modelling actin dynamics regulated by actin-associated proteins. As opposed to other existing actin-cytoskeleton mathematical models, our approach is based on the advanced Monte Carlo simulation schemes and associates the main biochem- ical actin-related reactions, including multistep spontaneous actin nucleation, random and stress-induced Їlament fragmentation, with structural properties of protein Їlaments. Created algorithms were integrated into a freely available software package with user-friendly interface.

The processes of actin polymerization have significant importance for different biological processes, such as cell cytoskeleton formation and cell motility. However, analytical analysis of the experimental data from these systems gives only rough estimations and has many limitations. In this paper the simulation formalism for the subsequent experimental data processing is proposed and the simulation model developed. The validation of the model has been performed by the comparison of the simulated results with the analytical prediction for the simplest situation.

Plastins are members of a family of actin-binding proteins which exhibit a tissue-specific expression pattern. L-plastin, which is specifically expressed in hematopoietic cell lineage, has been proposed to be involved in the control of cell adhesion and motility. This protein is also frequently expressed in cell lines derived from mammary solid tumors and therefore might be involved in cancer invasion and metastasis. We have analysed plastin expression in normal and carcinomatous breast tissues in vivo by immunohistochemistry and immunoblotting approaches using specific plastin isoform antibodies. L-plastin was not detected in normal epithelial cells of the mammary gland whereas a staining of myoepithelial cells was observed in 50% of the cases. In breast carcinomas, a significant immunostaining of malignant epithelial cells was observed in 4 of the 29 cases analysed (13.8%). No correlation between L-plastin expression and tumor size, histological grade or lymph node status was observed. In contrast, L-plastin was found expressed in 4 of the 11 estrogen and progesterone receptors negative tumors (p = 0.039). The potential role of plastin expression in the tumor process is discussed.

We tested six additional chemicals (acetaldehyde, benomyl, diethylstilboestrol, diethylstilboestrol dipropionate, griseofulvin, and mercaptoethanol) for in vitro systems of the coordinated programme to study aneuploidy induction sponsored by the Commission of the European Communities in two in vitro test systems. Using Saccharomyces cerevisiae D61.M (mitotic chromosomal malsegregation assay), benomyl showed a dose-dependent increase in the frequency of chromosomal malsegregation with a lowest effective dose tested (LEDT) of 30 micrograms/ml (0.1 mM). Diethylstilboestrol (DES) showed solvent-dependent effects. DES dissolved in ethanol induced an increase in chromosomal malsegregation as well as in the frequency of total resistant colonies (mutations and recombinations) with a LEDT around 13 micrograms/ml (0.048 mM). Using dimethylsulfoxide as the solvent, no increases were observed with DES up to 333 micrograms/ml (1.24 mM). Acetaldehyde induced an increase in chromosomal malsegregation with the cold treatment protocol (LEDT: 1.25 microliters/ml (21 mM) and 0.75 microliters/ml (13 mM), respectively) but no increase with the overnight protocol (highest dose tested (HDT): 1.75 microliters/ml; 30 mM). Concerning the frequency of total cycloheximide-resistant colonies (mutations and recombinations) increases were obtained with both protocols. The other three compounds were negative when tested up to toxic doses (survival below 10%), up to the maximum solubility in the solvent used or up to heavy precipitation in the incubation mix. The HDT were 333 micrograms/ml (0.88 mM) for diethylstilboestrol dipropionate, 1,600 micrograms/ml (4.5 mM) for griseofulvin and 0.5 microliters/ml (7 mM) for mercaptoethanol. Concerning effects on porcine brain tubulin assembly in vitro, diethylstilboestrol and griseofulvin inhibited the assembly process. The IC30% (30% inhibition concentration) values were 12.5 microM and 100 microM for DES and griseofulvin, respectively. Mercaptoethanol showed no effects up to 50 mM.

Gaulden reported a novel and unexpected mitomycin C (MMC) effect, namely a pronounced retardation of very late prophase and loss of chromosome orientation in neuroblasts of the grasshopper Chortophaga viridifasciate. Because this effect may be due to interactions of MMC with non-DNA targets, MMC was tested for its interaction with porcine brain tubulin assembly in vitro and for the induction of chromosomal malsegregation in the diploid yeast Saccharomyces cerevisiae strain D61.M. A reversible dose-dependent inhibition of tubulin assembly was observed. Since no biological activation system was present in the incubation mixture this inhibition seems to result from an interaction of unactivated MMC with the assembly process. The possible chemical activation of MMC by reduction with 1,4-dithioerythritol (DTE) was investigated by omission of this compound during isolation and polymerization of tubulin. The absence of DTE resulted in a strong reduction of the net tubulin assembly. Also under these conditions MMC led to a dose-dependent inhibition of the assembly, indicating that the effect of MMC on tubulin assembly is independent of a reductive chemical modification. In S. cerevisiae D61.M, MMC did not induce chromosome loss, but induced other genetic events (possibly mutations, deletions or mitotic recombination) as was detected by an increase of the total number and of the frequency of cycloheximide-resistant colonies. This effect could be observed with and without the addition of rat liver S9 as an exogenous activation system.

Three genotoxic carcinogens and eight tumor promoters were tested for induction of aneuploidy, specifically chromosome loss, in Saccharomyces cerevisiae D61.M. This is a heterozygous diploid yeast strain that permits the scoring of segregants expressing three linked recessive markers (cyhR2, ade6, and leu1), two of which (ade6 and leu1) are located close to the centromere on opposite arms of chromosome VII. The centromere marker leu was routinely checked, and a positive control (bavistan) was run with every experiment. The three genotoxic carcinogens aflatoxin B1, benzo(a)pyrene, and 7,12-dimethylbenz(a)anthracene did not induce aneuploidy, independent of the presence or absence of an exogenous metabolic activation system (rat liver homogenate; S9). Four of the eight tumor promoters tested induced chromosome loss but not mitotic recombination or mutation: cholic acid, lithocholic acid, phenobarbital, and saccharin. Diethylstilbestrol (DES) led to positive as well as to negative results in several independent experiments. In the case of the positive experiment, DES also induced putative recombinants. Three tumor promoters induced neither chromosome loss nor mitotic recombination: anthralin, 4,4'-dichloro-diphenyl-ethane (DDT) and gamma-hexachlorcyclohexane (lindane). From our experiments it can be concluded that the hypothesis put forward by Parry et al. [Nature; 294:263-265], according to which tumor promoters induce chromosome loss in yeast, is not correct in a general sense. In our set of eight tumor promoters, only one half distinctly induced chromosome loss.

57 Fe and 197 Au Mossbauer data have been reported and discussed for a variety of catalysts of gold supported on iron oxide. The 57 Fe Mossbauer spectra show that iron is present as ferrihydrite, haematite and goethite in amounts that depend on the conditions of preparation. The highest amount of ferrihydrite is observed in the samples prepared by coprecipitation. The 197 Au Mossbauer spectra reveal the formation of two main gold species, i.e., metallic gold and oxidic trivalent gold. The presence of gold favours the formation of ferrihydrite over that of haematite. No direct correlation was found between catalytic activity towards CO oxidation and the Au species identified by Mossbauer spectroscopy, but catalyst activity was found to increase with the relative amount of ferrihydrite. It is suggested that the ferrihydrite is important for activation of molecular oxygen.