Aviation Biofuel Production in Sweden

Civil Aviation is one of the fastest growing sectors on earth, for which emissions currently account for between 2 and 3% of the global total (International Air Transport Association, 2013). Decarbonising the aviation sector is a key challenge on the international agenda, for which sustainable alternative fuels stand as playing a future role. Biofuels for aviation (biojet) have shown to be energy efficient, safe and generate significant emissions savings (Faaij & van dijk, 2012). Efforts are currently underway to accelerate biojet fuel development through establishing global and regional supply chains for commercial production, yet high production costs, relative to fossil based fuel production stands as the fundamental hurdle preventing commercial scale production. The Nordic region is characterised as having good potential for biofuel production, prompting studies throughout Norway, Finland and Denmark. Similar environmental conditions are found within Sweden, yet a Swedish regional investigation into biojet production opportunities is yet to be carried out. This research identifies key opportunities and barriers to establishing a biojet production system within Sweden using available forestry biomass as a feedstock. Findings indicate that the availability of forestry biomass resources, infrastructure and knowledge present within the Swedish system could support the establishment of a biojet system, yet high production costs and a lack of policy support create unfavourable market conditions. Future efforts to establish biojet uptake in Sweden may include lobbying for policy change at the national level to recognize aviation emissions when setting policy targets. The process of facilitating collaboration through linking actors in the field, both within Sweden and throughout the wider Nordic region, is an essential non-technical component to streamline future potential supply chain pathways

Approaches to target WD40 proteins and synthesis and evaluation of chemical tools for on-bead screening

A database consisting of information on human WD40 domains was compiled from literature sources. Data collected included information on function, structure, links to disease and information on molecules known to bind to WD40 domain containing proteins. Curation of the data collected suggested that 21% of WD40 domain containing proteins are linked to cancer, and that only 6% had known small molecule binders. From the database a shortlist of WD40 domain containing proteins that were considered of interest as research targets was produced. It was determined that WD40 Domain Containing Protein 5 (WDR5) was a potential cancer target open to several targeting methods. WDR5 normally plays a structural roll in the formation of a complex containing WDR5, RbBP5, ASH2L, and DPY-30. This complex is required for methylation of H3K4, when MLL1 joins the complex it is able to methylate H3K4me2. It was also recently determined that WDR5 complexes with MYC, another protein with roles in transcriptional control. Both MLL1 and MYC are known to be prominent cancer targets. His-tagged WDR5 was successfully expressed in BL21 (DE3) cell line and purified by a 2 step method. First the protein was purified via His tag - Ni-NTA agarose affinity chromatography, the eluted protein was then further purified via Size Exclusion Chromatography. The first approach targeting WDR5 consisted of a combination of an in-silico approach and a small molecule binder screen. Two in-silico methods, Q-mol and USRCAT, were used to determine small molecules that would potentially bind to WDR5. From this suggested set, 81 compounds were screened against WDR5. Thermal denaturation fluorescence (TDF) was chosen as assay technique. A single compound increased the thermal stability of WDR5 in repeated experiments. This compound, NCI292249, was further characterised in microdialysis experiments where it was determined to have a low affinity of 564 μM to WDR5. In a second approach, in order to target the MYC-WDR5 interaction, a series of truncated peptides derived from the WDR5 binding motif from MYC were produced testing a variation of the One-Bead One-Compound (OBOC) synthesis method derived in this work. These peptide fragments were synthesised using Fmoc solid phase peptide synthesis on TentaGel micobeads experimenting with the SOBOC technique (Scanning OBOC) adapted to produce all possible fragments of a peptide in parallel. The peptide fragments were fluorescently labelled with tetramethylrhodamine and screened against 6XHis-WDR5 isolated on Ni-NTA functionalised agarose beads. The peptide fragments were ranked based on their affinity to the WDR5-coated micro-beads assayed by Confocal Scanning (CONA). The highest affinity peptide found in the CONA screen was further tested for WDR5 binding in solution by fluorescence anisotropy which resulted in an affinity of 96 μM to WDR5. This 7-mer truncate of the MYC peptide was used as input for an in-silico method of peptide optimisation named MorPH. MorPH is a technique developed in the Auer Lab in which amino acids in a peptide are systematically replaced by all commercially available non-natural amino acids in a sequential manner. Each of ~ 1000 modified peptidomimetics are docked in-silico to the target structure. The suggestions from MorPH for the MYC peptide truncate were analysed and the potential replacements discussed in order to plan a possible future synthesis. The MorPH technique was tested experimentally in this thesis in a second example, targeting of Survivin. Survivin is followed as cancer target in the Auer lab and it is found in significantly high concentrations in cancer cell lines and in stem cells. Increased Survivin expression has also been linked to a poor prognosis and reduced patient survivability in the clinic. Several suggestions resulting from the MorPH in-silico screen were synthesised and screened against Survivin. The best-in-series peptide was shown to have a Kd of 2.5 μM, with significantly increased plasma stability. Several chemical tools were developed and characterised for use with on-bead synthesis methods. A contribution was made to a novel synthetic method for isomerically pure rhodamine dyes and their functionalisation[1] (Tetramethylrhodamine was azide-functionalised for use in peptide labelling, based on the azide-alkyne Huisgen cycloaddition reaction). The Auer lab synthesises many of its compounds and libraries using solid phase synthesis techniques. Several compounds exist in literature for the linking of chemicals to a solid-support, all of which are stable to different chemistries and require different conditions to cleave the reaction product from the solid phase. The use of methionine as a linker is described in literature as being highly specific in its cleavage conditions. A series of literature cleavage conditions were tested, the method that offered the highest purity was selected to be improved through further testing. The improved cleavage method was then characterised by cleaving the 20 natural amino acids from the methionine linker. In this experiment it was determined that all amino acids tolerated the new conditions with the exception of methionine, cysteine and tryptophan, which were expected to react poorly to the harsh conditions. This verified that methionine was a suitable alternative to current lab standards for bead linkage

Bacterial Vaginosis (BV) Candidate Bacteria: Associations with BV and Behavioural Practices in Sexually-Experienced and Inexperienced Women

BACKGROUND: In recent years several new fastidious bacteria have been identified that display a high specificity for BV; however no previous studies have comprehensively assessed the behavioural risk associations of these bacterial vaginosis-candidate organisms (BV-COs). METHODS: We examined the associations between 8 key previously described BV-COs and BV status established by Nugent's score (NS). We also examined the sexual practices associated with each BV-CO. We incorporated 2 study populations: 193 from a sexually-inexperienced university population and 146 from a highly sexually-active clinic population. Detailed behavioural data was collected by questionnaire and vaginal smears were scored by the Nugent method. Stored samples were tested by quantitative PCR assays for the 8 BV-COs: Atopobium vaginae, Gardnerella vaginalis, Leptotrichia spp., Megasphaera type I, Sneathia spp., and the Clostridia-like bacteria BVAB1, BVAB2 and BVAB3. Associations between BV-COs and BV and behaviours were examined by univariate and multivariable analyses. RESULTS: On univariate analysis, all BV-COs were more common in BV compared to normal flora. However, only Megasphaera type I, BVAB2, A. vaginae and G. vaginalis were significantly independently associated with BV by multivariable analysis. Six of the eight BV-COs (Megasphaera type I, BVAB2, BVAB3, Sneathia, Leptotrichia and G. vaginalis) were rare or absent in sexually-unexposed women, and demonstrated increasing odds of detection with increasing levels of sexual activity and/or numbers of lifetime sexual partners. Only G. vaginalis and A. vaginae were commonly detected in sexually-unexposed women. Megasphaera type I was independently associated with women-who-have-sex-with women (WSW) and lifetime sexual partner numbers, while unprotected penile-vaginal-sex was associated with BVAB2 detection by multivariate analysis. CONCLUSIONS: Four of eight key BV-COs were significantly associated with BV after adjusting for the presence of other BV-COs. The majority of BV-COs were absent or rare in sexually-unexposed women, and associated with increasing sexual exposure, suggesting potential sexual transmission of BV-COs

Risks for Acquisition of Bacterial Vaginosis Among Women Who Report Sex with Women: A Cohort Study

Bacterial vaginosis (BV) is common in women who have sex with women. While cross-sectional data support a role for sexual transmission, risks for incident BV have not been prospectively studied in this group. at enrollment conferred reduced risk for subsequent BV (HR 0.18 (0.08–0.4)). Detailed analysis of behavioral data suggested a direct dose-response relationship with increasing number of episodes of receptive oral-vulvovaginal sex (HR 1.02 (95% CI, 1.00–1.04).Vaginal detection of several BVAB in BV-negative women predicted subsequent BV, suggesting that changes in vaginal microbiota precede BV by weeks or months. BV acquisition was associated with report of new partner with BV; associations with sexual practices – specifically, receptive oral sex – require further investigation

Barriers to Infectious Disease Care among Lesbians1

Despite the considerable number of women in the United States who identify as lesbian, few data exist that address lesbians' health needs. The Institute of Medicine emphasized that data on sexually transmitted infections, Pap smear screening, and cervical dysplasia among lesbians were needed to guide clinical practice, policy development, and patient education. Use of surveillance data for this purpose is limited because risk classifications exclude same-gender sex among women or subsume it under behavior considered as higher risk. However, sexual transmission of human papillomavirus, HIV, Treponema pallidum, and Trichomonas vaginalis between women has been reported. Data indicate that lesbians receive routine Pap smear screening less frequently than is optimal. Moreover, lesbians commonly report previous pregnancy, induced abortion, and hormonal contraceptive use. Education of lesbians and their care providers should counter assumptions that sex between women confers no risk for transmission of sexually transmitted infections, and lesbians should receive Pap smears according to current guidelines

Managing chronic hepatitis B: A qualitative study exploring the perspectives of people living with chronic hepatitis B in Australia

<p>Abstract</p> <p>Background</p> <p>The implementation of a comprehensive public health response to hepatitis B in Australia is urgently required to reduce the increasing burden of hepatitis B infection on the health system and the community. A significant gap in the public health response to hepatitis B is an understanding of how people with chronic hepatitis B (CHB) respond to CHB.</p> <p>Findings</p> <p>A qualitative study involving semi-structured interviews and focus group discussions was conducted. Interviews were held with 20 people with CHB from three states of Australia. In addition, four focus group discussions were held with a total of 40 community and health workers from culturally and linguistically diverse communities in four Australian states.</p> <p>People with CHB reported no formal or informal pre or post test discussion with little information about hepatitis B provided at the point of diagnosis. Knowledge deficits about hepatitis B were found among most participants. Few resources are available for people with CHB or their families to assist them in understanding the infection and promoting their health and well-being. A lack of confidence in the professional knowledge of service providers was noted throughout interviews.</p> <p>Conclusions</p> <p>People with CHB need culturally and linguistically appropriate education and information, particularly at the point of diagnosis. Primary health care professionals need the knowledge, skills and motivation to provide appropriate information to people with CHB, to ensure they have the capacity to better manage their infection.</p

Risk Behaviors for Reproductive Tract Infection in Women Who Have Sex with Women in Beijing, China

OBJECTIVES: To assess risk behaviors for reproductive tract infections (RTI) including sexually transmitted infections (STI) among women who have sex with women (WSW) in Beijing, China. METHODS: A cross-sectional study of women recruited from venues and internet outreach analyzed using interviews. RESULTS: We recruited 224 WSW, among whom were 37 couples. The average age of participants was 25.6 years. Sex with men in the past year was reported by 10.7% of participants. During the past year, 34.3% (77/224) had had >1 sexual partner and 72.4% (162/224) had ever had >1 sexual partner. Condom use in the last sex with a man was reported by 54.2% (13/24) of women; 12.5% (3/24) reported never having used a condom with a man in the past year. In the past year, 13.4% (30/224) reported using sex toys with their female partners; of these, 43.3% (13/30) reported consistent condom use with the sex toys and 36.7% (11/30) had shared sex toys. Among participants 65.2% (120/184) reported that their "G-spot" had been stimulated during sex, 49.2% (59/120) of whom reported bleeding during or after sex. Only 12.5% (8/64) of those never reporting "G spot" stimulation reported bleeding during or after sex (P<0.001). CONCLUSIONS: WSW in Beijing engaged in high-risk sexual behaviors that may carry a substantial risk of being infected with STI/RTI. To implement STI/RTI prevention and intervention among women, women-women sexual behavior should be considered when doing research and intervention programs

Bacterial vaginosis

Bacterial vaginosis is the most prevalent cause of abnormal vaginal discharge in women of childbearing age. It can have a major impact on quality of life and psychological wellbeing if frequently recurrent and strongly symptomatic. The use of molecular techniques to study the vaginal microbiome is increasing our understanding of the dynamic changes in flora that occur in health and disease. It might soon be possible to separate Gardnerella into different pathogenic and non-pathogenic species. Many groups are studying compounds that can disrupt the biofilm which is dominated by Gardnerella and Atopobium vaginae. Several studies in the last decade support the concept of bacterial vaginosis as a sexually transmitted infection