Synthetic Galectin Inhibitors Selective O-galactosyl aldoximes, multivalent lactosides and galactose-mimicking mannosides

This thesis describes the design, synthesis and evaluation of synthetic inhibitors for the carbohydrate binding proteins called galectins. Potent and selective inhibitors can be used as important research tools in the endeavor to chart the true role of galectins in biological events such as cancer and inflammation and possibly as lead for future galectin targeting drugs. A panel of O-galactosyl aldoximes was synthesized and inhibitors with high affinity and selectivity for galectin-3 and -7 were identified. The best inhibitor for galectin-3, O-(?-D-galactopyranosyl)-indole-3-carbaldoxime, was combined with previously optimized galectin-3 targeting triazoles, in a fragment based approach, to give 3C-triazol-1-yl-O-galactopyranosyl aldoximes with high affinity and selectivity for galectin-3 (Kd down to 11 µM). Furthermore, a glycoside clustering effect was observed for multivalent lactose containing inhibitors and galectin-1. The mechanisms behind this were investigated using mutated galectin-1, lacking the possibility to dimerize. Finally, 1H-[1,2,3]-triazol-1-yl mannosides, with synthetic advantages over galactose based inhibitors, were synthesized and the 4-benzylaminocarbonyl-1H-[1,2,3]-triazol-1-yl ?-D-mannopyranoside (Kd=540 µM, for galectin-9N) compared favorably with its galactoside counterpart

Effects of Reforms in a Corrupt Institution

Corruption is considered a global problem. All over the world it affects people’s lives, for the majority in negative ways. Cleaning up a corrupt state has proved to be difficult; if it does not have a history of continuously being a democracy for a long time it faces an increased chance of being corrupt. Whether a state actively fights corruption through laws and reforms does not always matter. Since the Rose Revolution took place in Georgia about ten years ago the country has fought corruption hard. It is today famous for achieving changes to the better in a faster pace than others seem able to. Ten years ago a wealthy student could buy an education and a diploma. Through this research, based on 41 interviews with stakeholders of the higher education in Georgia, opinions are revealed about the current situation. A lot has happened in Georgia the last ten years; within higher education corruption in terms of bribes seems to have eradicated. What is found out to be the continuous problem is elite corruption and nepotism. These are problems reforms seem to have overseen. It is also believed to be harder to fight than bribery

Outbreaks of African swine fever in domestic pigs in Gulu district, Uganda

The demand for animal products has increased in the last decades, especially for poultry and pork. Pork production has increased drastically globally, and also in Uganda. Thirty-one percent of Uganda´s population lives in poverty. Pig production is believed to play a crucial role in poverty alleviation, because of the ability to convert low quality feed into high quality protein together with high reproductive potential. African swine fever (ASF) is a lethal disease of domestic pigs often characterized by haemorrhagic fever and with mortality rates up to 100%. The disease is endemic in most sub-Saharan countries and since 2007 in the Russian Federation and Caucasus area. ASF is associated with severe sanitary and socio-economic consequences, in countries where it is endemic as well as in areas where it has recently been introduced. The epidemiology, involving a domestic and a sylvatic cycle, is complex. This, together with the absence of vaccine and the marked virus resistance in contaminated animal products, make ASF one of the most feared and therefore important diseases in swine. ASF poses a serious constraint on pig production in Africa, where control is made difficult by several factors, including lack of basic biosecurity measures, traditional free-ranging husbandry system and movements of pigs. The aim of this study was to collect information from the past year´s outbreaks of ASF in Gulu district to better understand the spatial and temporal dynamics of the disease and to clarify modes of transmission. Sixteen villages with history of confirmed outbreaks of ASF were visited and 135 interviews were performed. The average mortality during these outbreaks was estimated at 84.5%. Thirteen blood samples were collected from clinically affected pigs. Out of these, five were PCR-positive. Out of the six blood samples from pigs that survived outbreaks, three were ELISA-positive. The main transmission routes were trade of live pigs and pig products, especially at onset of an outbreak (introduction into a village). When the virus had been introduced into a village, it was probably spread through swill/waste and direct contact between domestic pigs, both of which are facilitated through the traditional free range pig husbandry system and lack of biosecurity. The involvement of wild reservoirs and subclinical carriers was not investigated but is assumed to be less important

Lantbrukares uppfattningar om klimatförändringar : en kvantitativ studie av skånska lantbrukare

In this thesis, farmers` perceptions of climate change have been examined. Questionnaires were sent to 400 cereal farmers in the southernmost county of Sweden, Scania, of whom 221 replied. Four themes have been investigated: the farmers perceptions on past climate changes, their perceptions on future climate changes, their opinions on how the authorities are managing the climate change issue and their opinions on adaptation to climate change. Study results indicate that 9 out of 10 farmers had experienced some type of climate change over the last 15 years. The most common notion was that the climate has become more “periodized” and that winters have become milder. As many as 97% of the farmers thought that the climate will change during the coming 30 years, but only 67% believes that temperatures will rise. There are different opinions on whether climate change will be mostly positive or negative for agriculture in Scania, although most of the farmers think that the negative consequences will dominate. Most respondents think that the amount of information they receive from authorities, about climate change, is satisfactory. However, the majority thinks that the quality, or relevance, of the information is poor. They also think that more should be done in Sweden in order both to mitigate- and adapt to climate change. Large differences occur about the opinions on the EU-membership, in light of climate change, but most respondents are positive towards the membership. Nine out of ten farmers have already started to adapt to climate change or consider doing so. The adaptations preferred by most farmers concern water management. Both improved drainage and expanded irrigation are seen as relevant adaptation measures. Many farmers also consider “reduced soil disturbance” as an adaptation measure to climate change. When it comes to crop choice, it seems as most adaptations are done as preventive measures to reduce risks rather than to take advantage of new opportunities. The results of this study indicate similarities to other studies. In relation to farmers in other contexts i.e. in developed nations, the Scanian farmers are generally more aware of climate change. In some regards the farmers expectations for future climate change are in line with scientific predictions for Scania, but for other aspects, there are discrepancies. The farmers tend to underestimate the future temperature rises but overestimate the increase in periodized and more extreme weather. The current study can be of good value for the authorities engaged in agriculture and climate change related issues. To possess knowledge of the farmers` opinions may facilitate the cooperation between authorities and farmers. This is an aspect of high importance from an agroecological viewpoint, where good communication and integration of different actors in the food system web, is emphasized

Galectin-3-Binding Glycomimetics that Strongly Reduce Bleomycin-Induced Lung Fibrosis and Modulate Intracellular Glycan Recognition

Contains fulltext : 165645.pdf (publisher's version ) (Closed access

Exploring cancer register data to find risk factors for recurrence of breast cancer – application of Canonical Correlation Analysis

BACKGROUND: A common approach in exploring register data is to find relationships between outcomes and predictors by using multiple regression analysis (MRA). If there is more than one outcome variable, the analysis must then be repeated, and the results combined in some arbitrary fashion. In contrast, Canonical Correlation Analysis (CCA) has the ability to analyze multiple outcomes at the same time. One essential outcome after breast cancer treatment is recurrence of the disease. It is important to understand the relationship between different predictors and recurrence, including the time interval until recurrence. This study describes the application of CCA to find important predictors for two different outcomes for breast cancer patients, loco-regional recurrence and occurrence of distant metastasis and to decrease the number of variables in the sets of predictors and outcomes without decreasing the predictive strength of the model. METHODS: Data for 637 malignant breast cancer patients admitted in the south-east region of Sweden were analyzed. By using CCA and looking at the structure coefficients (loadings), relationships between tumor specifications and the two outcomes during different time intervals were analyzed and a correlation model was built. RESULTS: The analysis successfully detected known predictors for breast cancer recurrence during the first two years and distant metastasis 2–4 years after diagnosis. Nottingham Histologic Grading (NHG) was the most important predictor, while age of the patient at the time of diagnosis was not an important predictor. CONCLUSION: In cancer registers with high dimensionality, CCA can be used for identifying the importance of risk factors for breast cancer recurrence. This technique can result in a model ready for further processing by data mining methods through reducing the number of variables to important ones

Non-Glycosidically Linked Pseudodisaccharides: Thioethers, Sulfoxides, Sulfones, Ethers, Selenoethers, and Their Binding to Lectins

Hydrolytically stable non-glycosidically linked tail-to-tail pseudodisaccharides are linked by a single bridging atom remote from the anomeric centre of the constituent monosaccharides. Some such pseudodisaccharides with sulfur or oxygen bridges were found to act as disaccharide mimetics in their binding to the Banana Lectin and to Concanavalin A. A versatile synthetic route to a small library of such compounds is described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69166/1/1951_ftp.pd