@phdthesis{PerezChaparro2022,
  author    = {P{\´e}rez Chaparro, Camilo Germ{\´a}n Alberto},
  title     = {Non-HIV comorbidities and exercise in German people living with HIV},
  doi       = {10.25932/publishup-56084},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-560842},
  school      = {Universit{\"a}t Potsdam},
  pages     = {149},
  year      = {2022},
  abstract  = {The post-antiretroviral therapy era has transformed HIV into a chronic disease and non-HIV comorbidities (i.e., cardiovascular and mental diseases) are more prevalent in PLWH. The source of these non-HIV comorbidities aside from traditional risk factor include HIV infection, inflammation, distorted immune activation, burden of chronic diseases, and unhealthy lifestyle like sedentarism. Exercise is known for its beneficial effects in mental and physical health; reasons why exercise is recommended to prevent and treat difference cardiovascular and mental diseases in the general population. This cumulative thesis aimed to comprehend the relation exercise has to non-HIV comorbidities in German PLWH. Four studies were conducted to 1) understand exercise effects in cardiorespiratory fitness and muscle strength on PLWH through a systematic review and meta-analyses and 2) determine the likelihood of German PLWH developing non-HIV comorbidities, in a cross-sectional study. Meta-analytic examination indicates PLWH cardiorespiratory fitness (VO2max SMD = 0.61 ml·kg·min-1, 95\% CI: 0.35-0.88, z = 4.47, p < 0.001, I2 = 50\%) and strength (of remark lowerbody strength by 16.8 kg, 95\% CI: 13-20.6, p< 0.001) improves after an exercise intervention in comparison to a control group. Cross-sectional data suggest exercise has a positive effect on German PLWH mental health (less anxiety and depressive symptoms) and protects against the development of anxiety (PR: 0.57, 95\%IC: 0.36 - 0.91, p = 0.01) and depression (PR: 0.62, 95\%IC: 0.41 - 0.94, p = 0.01). Likewise, exercise duration is related to a lower likelihood of reporting heart arrhythmias (PR: 0.20, 95\%IC: 0.10 - 0.60, p < 0.01) and exercise frequency to a lower likelihood of reporting diabetes mellitus (PR: 0.40, 95\%IC: 0.10 - 1, p < 0.01) in German PLWH. A preliminary recommendation for German PLWH who want to engage in exercise can be to exercise ≥ 1 time per week, at an intensity of 5 METs per session or > 103 MET·min·day-1, with a duration ≥ 150 minutes per week. Nevertheless, further research is needed to comprehend exercise dose response and protective effect for cardiovascular diseases, anxiety, and depression in German PLWH.},
  language  = {en}
}
@phdthesis{Hoelscher2020,
  author    = {Hoelscher, Matthijs Pieter},
  title     = {The production of antimicrobial polypeptides in chloroplasts},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xiii, 114},
  year      = {2020},
  abstract  = {Plants are an attractive platform for the production of medicinal compounds because of their potential to generate large amounts of biomass cheaply. The use of chloroplast transformation is an attractive way to achieve the recombinant production of proteins in plants, because of the chloroplasts' high capacity to produce foreign proteins in comparison to nuclear transformed plants. In this thesis, the production of two different types of antimicrobial polypeptides in chloroplasts is explored. The first example is the production of the potent HIV entry inhibitor griffithsin. Griffithsin has the potential to prevent HIV infections by blocking the entry of the virus into human cells. Here the use of transplastomic plants as an inexpensive production method for griffithsin was explored. Transplastomic plants grew healthily and were able to accumulate griffithsin to up to 5\% of the total soluble protein. Griffithsin could easily be purified from tobacco leaf tissue and had a similarly high neutralization activity as griffithsin recombinantly produced in bacteria. Griffithsin could be purified from dried tobacco leaves, demonstrating that dried leaves could be used as a storable starting material for griffithsin purification, circumventing the need for immediate purification after harvest. The second example is the production of antimicrobial peptides (AMPs) that have the capacity to kill bacteria and are an attractive alternative to currently used antibiotics that are increasingly becoming ineffective. The production of antimicrobial peptides was considerably more challenging than the production of griffithsin. Small AMPs are prone to degradation in plastids. This problem was overcome by fusing AMPs to generate larger polypeptides. In one approach, AMPs were fused to each other to increase size and combine the mode of action of multiple AMPs. This improved the accumulation of AMPs but also resulted in impaired plant growth. This was solved by the use of two different inducible systems, which could largely restore plant growth. Fusions of multiple AMPs were insoluble and could not be purified. In addition to fusing AMPs to each other, the fusion of AMPs to small ubiquitin-like modifier (SUMO), was tested as an approach to improve the accumulation, facilitate purification, and reduce the toxicity of AMPs to chloroplasts. Fusion of AMPs to SUMO indeed increased accumulation while reducing the toxicity to the plants. SUMO fusions produced inside chloroplasts could be purified, and SUMO could be efficiently cleaved off with the SUMO protease. Such fusions therefore provide a promising strategy for the production of AMPs and other small polypeptides inside chloroplasts.},
  language  = {en}
}
@phdthesis{Gopalakrishnan2016,
  author    = {Gopalakrishnan, Sathej},
  title     = {Mathematical modelling of host-disease-drug interactions in HIV disease},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-100100},
  school      = {Universit{\"a}t Potsdam},
  pages     = {121},
  year      = {2016},
  abstract  = {The human immunodeficiency virus (HIV) has resisted nearly three decades of efforts targeting a cure. Sustained suppression of the virus has remained a challenge, mainly due to the remarkable evolutionary adaptation that the virus exhibits by the accumulation of drug-resistant mutations in its genome. Current therapeutic strategies aim at achieving and maintaining a low viral burden and typically involve multiple drugs. The choice of optimal combinations of these drugs is crucial, particularly in the background of treatment failure having occurred previously with certain other drugs. An understanding of the dynamics of viral mutant genotypes aids in the assessment of treatment failure with a certain drug combination, and exploring potential salvage treatment regimens. Mathematical models of viral dynamics have proved invaluable in understanding the viral life cycle and the impact of antiretroviral drugs. However, such models typically use simplified and coarse-grained mutation schemes, that curbs the extent of their application to drug-specific clinical mutation data, in order to assess potential next-line therapies. Statistical models of mutation accumulation have served well in dissecting mechanisms of resistance evolution by reconstructing mutation pathways under different drug-environments. While these models perform well in predicting treatment outcomes by statistical learning, they do not incorporate drug effect mechanistically. Additionally, due to an inherent lack of temporal features in such models, they are less informative on aspects such as predicting mutational abundance at treatment failure. This limits their application in analyzing the pharmacology of antiretroviral drugs, in particular, time-dependent characteristics of HIV therapy such as pharmacokinetics and pharmacodynamics, and also in understanding the impact of drug efficacy on mutation dynamics. In this thesis, we develop an integrated model of in vivo viral dynamics incorporating drug-specific mutation schemes learned from clinical data. Our combined modelling approach enables us to study the dynamics of different mutant genotypes and assess mutational abundance at virological failure. As an application of our model, we estimate in vivo fitness characteristics of viral mutants under different drug environments. Our approach also extends naturally to multiple-drug therapies. Further, we demonstrate the versatility of our model by showing how it can be modified to incorporate recently elucidated mechanisms of drug action including molecules that target host factors. Additionally, we address another important aspect in the clinical management of HIV disease, namely drug pharmacokinetics. It is clear that time-dependent changes in in vivo drug concentration could have an impact on the antiviral effect, and also influence decisions on dosing intervals. We present a framework that provides an integrated understanding of key characteristics of multiple-dosing regimens including drug accumulation ratios and half-lifes, and then explore the impact of drug pharmacokinetics on viral suppression. Finally, parameter identifiability in such nonlinear models of viral dynamics is always a concern, and we investigate techniques that alleviate this issue in our setting.},
  language  = {en}
}