An evaluation of geomorphological contributions to mountain highway design with particular reference to the Lower Himalayas

Mass movement, fluvial erosion, sediment transport and earthworks - induced instability, often pose major problems for highway design and construction in mountain terrain. This thesis examines the contribution that geomorphological techniques can make to the evaluation of these hazards for highway design purposes in the Lower Himalaya. A review of the consequences of geomorphological hazards to highway stability is illustrated by reference to selected mountain roads in India and Nepal. The design, stability and construction costs of these roads are discussed in respect to their status or function in the road network and, more particularly, the severity of hazards and terrain conditions they encounter. Techniques of hazard and terrain assessment for highway design purposes are examined and tested in the remainder of the thesis. Techniques of medium-scale (1: 10 000-1: 50 000) landslide hazard mapping and large-scale (greater than 1: 10 000) geomorphological ground survey are discussed and tested in the Dharan-Dhankuta area of Nepal, in terms of their ability to provide useful information for alignment design, road stabilization and protection works. The contribution of geomorphological ground survey to highway design is critically assessed by reference to the Dharan-Dhankuta road, and its stability following a high magnitude storm in 1984. A proforma method for assessing flooding, erosion and sediment hazards in small mountain channels is developed. Discharge data for the 1984 storm are derived from these proformas and used to test a number of selected ungauged catchment equations, and to develop empirical relationships between peak discharge and catchment variables for purposes of high magnitude runoff prediction from small catchments. In addition, low-cost, low technology methods for monitoring discharge, slope erosion, sediment transport and mass movement are tested in terms of their ability to provide meaningful data in the short-term for design purposes. Finally, optimum strategies of hazard and terrain assessment for highway design are proposed. The potential for further application of geomorphological techniques and expertise to mountain highway design is discussed

Design and development of an on-line vending system for selling prepaid electricity via the Internet

The sale of prepaid electricity is prevalent in South Africa due to the current economic, social, and political conditions. The system currently used for the distribution of tokens for prepaid electricity, CVS, has a design flaw that leads to many security vulnerabilities. The design flaw is that the security devices that generate the tokens are distributed in the field and operate independently of centralised control. This was done because of the limited communication infrastructure in South Africa 10 years ago, but is no longer necessary. An improvement to the system is suggested that removes the security vulnerabilities by making the system on-line. By employing the communication infrastructure that is available today to provide access to the security devices, the security devices can be located in a secure environment. Changing the mode of operation to on-line also has other advantages such as simplifying auditing and removing synchronisation problems. This improved system works by communicating on-line with a centralised server and database for every transaction that a customer makes. By doing this, all of the parties involved are kept up to date with the most recent transactions. There can no longer be financial discrepancies and the risk of all parties involved is thus reduced. It is no longer meaningful to steal the vending machines because they no longer have the ability to generate tokens independently. In order to implement such a system, however, there are many security aspects that need to be addressed, such as the confidentiality of the information within the system and proving that a transaction did occur between two specific parties. To this end, cryptographic functions and protocols are selected that meet the requirements of the system. Public key cryptography was found to be a necessary ingredient in making the system work effectively and efficiently. In order to use public key cryptography in the new system, Public Key Infrastructure is required to manage public keys and provide authentication services. A suitable system is developed and described that employs certificate authorities and X.509 certificates. The procedures that are required from each party are listed. A set of messages that is required for the functions of the system is given. For each message, the contents of the message is given, the parts of the message that must be encrypted are defined and the parts of the message that must be digitally signed are given. Finally, the security of the individual parts of the system is critically analysed to show that all of the design goals have been achieved. Particular attention is given to the authentication of parties involved in the communication. The security of the system as a whole is also evaluated with respect to the X.810 security framework and it is shown that the system is robust from a security perspective. The result of the research is a system that meets the required functionality to replace the existing system, and at the same time meets all of the security requirements. It is shown that the proposed system does not have the security flaws of the existing system and thus is more effective in its purpose of vending prepaid electricity.Dissertation (MEng (Electronic))--University of Pretoria, 2007.Electrical, Electronic and Computer Engineeringunrestricte

An Africa-wide genomic evolution of insecticide resistance in the malaria vector Anopheles funestus involves selective sweeps, copy number variations, gene conversion and transposons

Insecticide resistance in malaria vectors threatens to reverse recent gains in malaria control. Deciphering patterns of gene flow and resistance evolution in malaria vectors is crucial to improve control strategies and preventing malaria resurgence. A genome-wide survey of Anopheles funestus genetic diversity Africa-wide revealed evidences of a major division between southern Africa and elsewhere, associated with different population histories. Three genomic regions exhibited strong signatures of selective sweep, each spanning major resistance loci (CYP6P9a/b, GSTe2 and CYP9K1). However, a sharp regional contrast was observed between populations correlating with gene flow barriers. Signatures of complex molecular evolution of resistance were detected with evidence of copy number variation, transposon insertion and a gene conversion between CYP6P9a/b paralog genes. Temporal analyses of samples before and after bed net scale up suggest that these genomic changes are driven by this control intervention. Multiple independent selective sweeps at the same locus in different parts of Africa suggests that local evolution of resistance in malaria vectors may be a greater threat than trans-regional spread of resistance haplotypes

Do Women in Nepal Like Playing a Mobile Game? MANTRA: A Mobile Gamified App for Improving Healthcare Seeking Behavior in Rural Nepal

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A simple and effective F0 knockout method for rapid screening of behaviour and other complex phenotypes.

Hundreds of human genes are associated with neurological diseases, but translation into tractable biological mechanisms is lagging. Larval zebrafish are an attractive model to investigate genetic contributions to neurological diseases. However, current CRISPR-Cas9 methods are difficult to apply to large genetic screens studying behavioural phenotypes. To facilitate rapid genetic screening, we developed a simple sequencing-free tool to validate gRNAs and a highly effective CRISPR-Cas9 method capable of converting >90% of injected embryos directly into F0 biallelic knockouts. We demonstrate that F0 knockouts reliably recapitulate complex mutant phenotypes, such as altered molecular rhythms of the circadian clock, escape responses to irritants, and multi-parameter day-night locomotor behaviours. The technique is sufficiently robust to knockout multiple genes in the same animal, for example to create the transparent triple knockout crystal fish for imaging. Our F0 knockout method cuts the experimental time from gene to behavioural phenotype in zebrafish from months to one week

Multi‐omics analysis identifies a CYP9K1 haplotype conferring pyrethroid resistance in the malaria vector Anopheles funestus in East Africa

Metabolic resistance to pyrethroids is a menace to the continued effectiveness of malaria vector controls. Its molecular basis is complex and varies geographically across Africa. Here, we used a multi-omics approach, followed-up with functional validation to show that a directionally selected haplotype of a cytochrome P450, CYP9K1 is a major driver of resistance in Anopheles funestus. A PoolSeq GWAS using mosquitoes alive and dead after permethrin exposure, from Malawi and Cameroon, detected candidate genomic regions, but lacked consistency across replicates. Targeted sequencing of candidate resistance genes detected several SNPs associated with known pyrethroid resistance QTLs. The most significant SNPs were in the cytochrome P450 CYP304B1 (Cameroon), CYP315A1 (Uganda) and the ABC transporter gene ABCG4 (Malawi). However, when comparing field resistant mosquitoes to laboratory susceptible, the pyrethroid resistance locus rp1 and SNPs around the ABC transporter ABCG4 were consistently significant, except for Uganda where SNPs in the P450 CYP9K1 was markedly significant. In vitro heterologous metabolism assays with recombinant CYP9K1 revealed that it metabolises type II pyrethroid (deltamethrin; 64% depletion) but not type I (permethrin; 0%), while moderately metabolising DDT (17%). CYP9K1 exhibited reduced genetic diversity in Uganda underlying an extensive selective sweep. Furthermore, a glycine to alanine (G454A) amino acid change in CYP9K1 was fixed in Ugandan mosquitoes but not in other An. funestus populations. This study sheds further light on the evolution of metabolic resistance in a major malaria vector by implicating more genes and variants that can be used to design field-applicable markers to better track resistance Africa-wide

Molecular drivers of insecticide resistance in the Sahelo-Sudanian populations of a major malaria vector Anopheles coluzzii

Background: Information on common markers of metabolic resistance in malaria vectors from countries sharing similar eco-climatic characteristics can facilitate coordination of malaria control. Here, we characterized populations of the major malaria vector Anopheles coluzzii from Sahel region, spanning four sub-Saharan African countries: Nigeria, Niger, Chad and Cameroon. Results: Genome-wide transcriptional analysis identified major genes previously implicated in pyrethroid and/or cross-resistance to other insecticides, overexpressed across the Sahel, including CYP450s, glutathione S-transferases, carboxylesterases and cuticular proteins. Several, well-known markers of insecticide resistance were found in high frequencies—including in the voltage-gated sodium channel (V402L, I940T, L995F, I1527T and N1570Y), the acetylcholinesterase-1 gene (G280S) and the CYP4J5-L43F (which is fixed). High frequencies of the epidemiologically important chromosomal inversion polymorphisms, 2La, 2Rb and 2Rc, were observed (~80% for 2Rb and 2Rc). The 2La alternative arrangement is fixed across the Sahel. Low frequencies of these inversions (C), between Forkhead box L1 and c-EST putative binding sites, were responsible for the high overexpression of GSTe2 in the resistant mosquitoes. Transgenic flies expressing CYP6Z2 exhibited marginal resistance towards 3-phenoxybenzylalcohol (a primary product of pyrethroid hydrolysis by carboxylesterases) and a type II pyrethroid, α-cypermethrin. However, significantly higher mortalities were observed in CYP6Z2 transgenic flies compared with controls, on exposure to the neonicotinoid, clothianidin. This suggests a possible bioactivation of clothianidin into a toxic intermediate, which may make it an ideal insecticide against populations of An. coluzzii overexpressing this P450. Conclusions: These findings will facilitate regional collaborations within the Sahel region and refine implementation strategies through re-focusing interventions, improving evidence-based, cross-border policies towards local and regional malaria pre-elimination

The influence of oxygen isotope exchange between CO2 and H2O in natural CO2-rich spring waters: implications for geothermometry

Oxygen isotope ratio (δ18O) value deviations from the Meteoric Water Line with no significant change in the hydrogen isotope (δ2H) composition have been reported in naturally occurring CO2-rich waters from around the world. Here we review the effects of oxygen isotope exchange with CO2, high temperature equilibration with bedrock minerals and mineral dissolution and precipitation reactions on the CO2-rich water isotopic composition. We present two case studies from Daylesford (Australia) and Pah Tempe (Utah, USA) mineral springs, where we use a numerical geochemical modelling approach to resolve the influence of low temperature water-rock interactions and CO2 equilibration on the observed oxygen isotope ranges observed in the mineral waters. In both cases, we find that mineral dissolution – precipitation reactions are unlikely to have a significant effect on the groundwater isotopic compositions, and that the observed δ18O values in natural CO2 springs can be simply explained by equilibrium fractionation between water and free phase CO2. Traditionally, the interaction of CO2 and water in a natural CO2-rich groundwater setting has only been associated with water 18O depletion and this is the first study to consider 18O enrichment. We establish that in a natural setting, CO2 and water equilibration can result in water 18O depletion or enrichment, and that the change in the oxygen isotope composition ultimately depends on the initial CO2 and water δ18O values. Our new conceptual model therefore provides a mechanism to explain water 18O enrichment at ambient temperatures. This finding is critical for the use of δ18O in groundwater geothermometry and for the interpretation of natural water circulation depths: we argue that in some cases, natural waters previously interpreted as geothermal based on their oxygen isotope composition may actually have acquired their isotopic signature through interaction with CO2 at ambient temperatures

Terrain hazard around the Ok Tedi copper mine, Papua New Guinea

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Gene conversion explains elevated diversity in the immunity modulating APL1 gene of the malaria vector Anopheles funestus

Leucine rich repeat proteins and antimicrobial peptides are key component of the innate immune response to Plasmodium and other microbial pathogens in Anopheles mosquitoes. The APL1 gene of the malaria vector Anopheles funestus has exceptional levels of non-synonymous polymorphism across the range of An. funestus with an average πn of 0.027 versus a genome-wide average of 0.002, and πn is consistently high in populations across Africa. Elevated APL1 diversity was consistent between independent pooled-template and target-enrichment datasets, however no link between APL1 diversity and insecticide-resistance was observed. Although lacking the diversity of APL1, two further mosquito innate immunity genes of the gambicin anti-microbial peptide family had πn/πs ratios greater than one, possibly driven by either positive or balancing selection. Cecropin antimicrobial peptides were expressed much more highly than other anti-microbial peptide genes, a result discordant with current models of anti-microbial peptide activity. The observed APL1 diversity likely results from gene conversion between paralogues, as evidenced by shared polymorphisms, overlapping read mappings, and recombination events among paralogues. In conclusion, we hypothesise that higher gene expression of APL1 than its paralogues is correlated with a more open chromatin formation which enhances gene conversion and elevated diversity at this locus