Controlling the Influent Load to Wastewater Treatment Plants

The need for control of the influent load to a wastewater treatment plant (WWTP) is becoming more important. One reason for this is that there are a number of things that cannot be achieved with plant-focused control. For instance it is hard to avoid sludge loss as a result of poor settling or reducing a too high influent flow rate by in-plant control actions. It is also difficult to reduce the effects of a toxin in the influent, if the entire influent is to be biologically treated. Optimisation of the various parts of the collection system, with respect to locally defined objectives, may be counter-productive as it may increase the effluent loads when taking the whole system into account. This is typically the case as optimisation of the control of the sewer net with respect to combined sewer overflows (CSOs) leads to an increased flow to the WWTP. Equalization basins are used to control the flow rate or the load in the sewer net as well as at the WWTPs. The focus has recently been shifted from only reducing the amount of CSOs to reduce the effluent load from the sewer and the WWTP. To minimize the total load from the system the methods previously used to optimise the individual sub-systems must be used together and information from various parts of the system should be available system wide. Due to the cost associated with the construction of equalization basins, the current approach is to increase storage volume by constructing and controlling gates in the sewer net. The potential of system wide control is difficult to estimate, which is exemplified by a discussion on some existing implementations. In this thesis an equalization basin is modelled and used with an existing model of a WWTP. This system is operated with some commonly applied control strategies of equalization basins to estimate the result of control during ideal conditions. Without control of the basin, the possible benefit of construction, or providing an equal amount of storage capacity in the sewer net, is evaluated

Designed oligomers of cyanovirin-N show enhanced HIV neutralization

Cyanovirin-N (CV-N) is a small, cyanobacterial lectin that neutralizes many enveloped viruses, including human immunodeficiency virus type I (HIV-1). This antiviral activity is attributed to two homologous carbohydrate binding sites that specifically bind high mannose glycosylation present on envelope glycoproteins such as HIV-1 gp120. We created obligate CV-N oligomers to determine whether increasing the number of binding sites has an effect on viral neutralization. A tandem repeat of two CV-N molecules (CVN_2) increased HIV-1 neutralization activity by up to 18-fold compared to wild-type CV-N. In addition, the CVN_2 variants showed extensive cross-clade reactivity and were often more potent than broadly neutralizing anti-HIV antibodies. The improvement in activity and broad cross-strain HIV neutralization exhibited by these molecules holds promise for the future therapeutic utility of these and other engineered CV-N variants

Cross-Reactive Human IgM-Derived Monoclonal Antibodies that Bind to HIV-1 Envelope Glycoproteins

Elicitation of antibodies with potent and broad neutralizing activity against HIV by immunization remains a challenge. Several monoclonal antibodies (mAbs) isolated from humans with HIV-1 infection exhibit such activity but vaccine immunogens based on structures containing their epitopes have not been successful for their elicitation. All known broadly neutralizing mAbs (bnmAbs) are immunoglobulin (Ig) Gs (IgGs) and highly somatically hypermutated which could impede their elicitation. Ig Ms (IgMs) are on average significantly less divergent from germline antibodies and are relevant for the development of vaccine immunogens but are underexplored compared to IgGs. Here we describe the identification and characterization of several human IgM-derived mAbs against HIV-1 which were selected from a large phage-displayed naive human antibody library constructed from blood, lymph nodes and spleens of 59 healthy donors. These antibodies bound with high affinity to recombinant envelope glycoproteins (gp140s, Envs) of HIV-1 isolates from different clades. They enhanced or did not neutralize infection by some of the HIV-1 primary isolates using CCR5 as a coreceptor but neutralized all CXCR4 isolates tested although weakly. One of these antibodies with relatively low degree of somatic hypermutation was more extensively characterized. It bound to a highly conserved region partially overlapping with the coreceptor binding site and close to but not overlapping with the CD4 binding site. These results suggest the existence of conserved structures that could direct the immune response to non-neutralizing or even enhancing antibodies which may represent a strategy used by the virus to escape neutralizing immune responses. Further studies will show whether such a strategy plays a role in HIV infection of humans, how important that role could be, and what the mechanisms of infection enhancement are. The newly identified mAbs could be used as reagents to further characterize conserved non-neutralizing, weakly neutralizing or enhancing epitopes and modify or remove them from candidate vaccine immunogens