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Targeted therapy to overcome the blood-brain barrier in treating Glioblastoma
Glioblastoma represents a challenge in oncology, characterized by its aggressive nature and resistance to conventional therapies. This thesis conducts a comprehensive examination of Glioblastoma, with a primary focus on advancing therapeutic strategies through precision medicine and sophisticated drug delivery mechanisms. The inquiry starts with an exhaustive analysis of the intricate blood-brain barrier, a vital neurovascular interface critical for understanding drug delivery complexities to the central nervous system. Subsequently, the study delves into Glioblastoma, elucidating its etiological foundations, molecular intricacies, clinical presentations, and existing treatment paradigms.
The core of this research centers on the exploration of state-of-the-art targeted therapies, encompassing molecular-level targeting, immunotherapeutic modalities, and synergistic therapeutic approaches. It dissects a range of strategies aimed at enhancing drug delivery, including chemical disruption techniques, innovative delivery methodologies, and bioengineered approaches.
Furthermore, it underscores the transformative potential of nanotechnology, emphasizing nanocarriers as precision tools poised to revolutionize GBM therapy.
The literature review is conducted meticulously, drawing from renowned databases like PubMed, NCBI, NIH/National Cancer Institute, JSTOR, and BioMed Central. Additionally, reputable national and international health institute websites, along with carefully selected books from the campus library, contribute to the diverse and robust foundation of credible information.
The discussion segment dissects the challenges inherent in GBM targeted treatment, underscores the burgeoning domain of precision medicine, highlights the paradigm-shifting role of theranostics,
and outlines a roadmap for future prospects in this intricate landscape
Generation and expression of a mutated murine tRNA-guanine transglycosylase variant
Translation of messenger RNA carrying the nucleic code for protein synthesis is one of the vital bioprocesses of living organisms. This translation is mediated by transfer RNA, which allocates specific amino acids to the growing chain by decoding the genetic code. The tRNAs with the G34U35N36 anticodon sequence are recognised by an enzyme called tRNA-guanine transglycosylase, which catalyses the exchange of guanine with queuine. TGT enzyme is found in all three domains of life and is involved in post-transcriptional modification. TGT is of keen interest in the development of therapeutics against shigellosis, since the genetic inactivation of TGT leads to decreased pathogenicity in Shigella. For understanding the differences between bacterial and eukaryotic TGT, studies have been performed in the past, which show remarkable resemblance. On the contrary, some pronounced structural contrast can also be observed. One prominent difference is that the bacterial TGT contains a short turn of three amino acids, whereas, in eukaryotes, this turn is replaced by an extended loop of more than 45 amino acids. The function of this loop in eukaryotic TGT is not known. The loop is a highly flexible region and, thus, is not structurally solved. To elucidate the function of this loop, a TGT mutant lacking this loop was generated, expressed and purified. TGT mutant was expressed in different bacterial cell strains. For the purification, different chromatography techniques were utilised. The mutation resulted in a low yield of the protein in comparison to the wild-type TGT. This leads to the inference that the loop influences the physicochemical characteristics of the protein
Development of programmes to investigate the antimicrobial efficacy of domestic dishwashers
Dishwashers have undergone a drastic change both in design and programme variation since their conception. Trends in water and energy conservation, as well as the public perception of topics such as environment protection, have pushed for a dishwashing service that delivers highly efficient cleaning while remaining ecologically friendly.
Over the years, different methods have been used to assess the combined effects of different factors that play a role in the antimicrobial efficacy of domestic dishwashers. However, the extent of their individual capabilities remained unknown, as no factor could be tested separately with the commercially available settings.
With the aid of a dishwasher with programmable parameters, a method was developed that would allow for the testing of the different factors in a way that separates their microbicidal activities from one another as much as possible. The work of cleaning agents was excluded from any trials, as they are expected to only benefit the microbial reduction. Furthermore, the methodology used in this thesis work presents an opportunity to investigate the energy consumption levels of different steps in traditional dishwashing processes and find potential targets for future reduction in water and energy usage.
The study discovered that mechanical action, water quantity and the duration of the main cleaning cycle induce an equal reduction of around 4 logarithmic steps, when tested at room temperature. The main source of energy consumption during these experiments was found to be the spray arm pump with values 0.06 and 1.27 Wh per minute for the lowest and highest setting tested, respectively.
The temperature increases caused the largest change in both logarithmic reduction and energy consumption. The highest achieved logarithmic reduction occurred during tests with a cleaning temperature of 75 ℃, with the value being roughly doubled to that of the tests at room temperature. The energy consumption values also drastically increase to a mean of 37 Wh during the heating part of the cycle.
Overall, this method shows potential for discovering a combination of settings that can reduce the general energy consumption while retaining the antimicrobial efficacy of current programmes
5/2022 Erste Änderungssatzung zur Prüfungsordnung für den Masterstudiengang Bionics der Fakultät Technologie und Bionik der Hochschule Rhein-Waal vom 06.08.2019, Amtliche Bekanntmachung Nr. 28/2019, vom 26.01.2022
Physiologically structured population model of Dikerogammarus villosus in River Rhine: Analysis of sensitivity and uncertainty
In this research, we coupled all biological processes of individual level i.e., growth, mortality,and reproduction to establish a Physiologically structured population model (PSPM) and simulate physiologically structured population dynamics of Dikerogammarus villosus (killer shrimp) in River Rhine. In order to study the influence of the changes of model parameters on the model results, we divided the physiological population model of killer shrimp into four levels,first level: Function-Level, second Level: Individual-level, third Level: Cohort-level and fourth Level: Population-level. And studied the effect of each level by slightly changing the values (±10%) of the parameters. And the sensitivity index of each parameter is obtained by calculating the different final results of the model. In this study, the parameters with the most important
effects on the three important physiological processes of growth, death and reproduction were successfully identified, and the parameters with the highest sensitivity were also identified. Finding high-sensitivity parameters can help researchers effectively improve model accuracy and reduce uncertainty. It can also simplify the model, allowing researchers to focus on highly sensitive parameters.
Key words: Dikerogammarus villosus, Physiologically structured population model, PSPM,Sensitivity Analysis
Wie der Darm unsere Psyche beeinflusst-Modulation des Mikrobioms als geeigneter Therapieansatz für psychische Krankheiten?
Die Prävalenz von psychischen Erkrankungen ist in der Bevölkerung weit verbreitet und in den letzten Jahren stark angestiegen. Jährlich sind etwa 27,8 % der Erwachsenen in Deutschland von psychischen Erkrankungen betroffen. Dabei sind die Rückfallquoten und die Wahrscheinlichkeit einer Chronifizierung dieser Krankheiten sehr hoch. Auch besteht die Problematik, dass es wenige Anlaufstellen für die Betroffenen gibt, lange Wartezeiten in Kauf genommen werden müssen und herkömmliche medikamentöse Therapien teilweise starke Nebenwirkungen hervorrufen.
In dieser Masterthesis wurde der Zusammenhang zwischen psychischen Krankheiten, dem Mikrobiom und Stoffwechselparametern untersucht, um zu klären, ob eine Modulation des Darm Mikrobioms durch Präbiotika und Probiotika einen geeigneten Behandlungsansatz für die Therapie von psychischen Erkrankungen wie Depressionen, Angststörungen, Schizophrenie oder Anorexia nervosa darstellen könnte. Dazu wurden insgesamt 55 Artikel analysiert. Die Abundanz von Darmmikroben auf Phylum-, Familien- und Gattungsebene, die Konzentrationsveränderung von Stoffwechselparametern, die Auswirkungen bestimmter Mikroorganismen auf die Stoffwechselparameter und der Effekt von Prä- und Probiotika auf das Mikrobiom und die Verhaltensweisen der Patienten bzw. der Tiere wurden in den Studien verglichen.
Es konnte eine Korrelation zwischen der relativen Häufigkeit bestimmter Mikroorganismen, den von ihnen produzierten Metaboliten und dem Auftreten der untersuchten psychischen Erkrankungen festgestellt werden. Durch die Supplementation mit Prä- und Probiotika und insbesondere durch Lactobacillus spp. und Bifidobacterium spp., konnten die Symptome abgeschwächt werden. Vor allem der kombinierte Einsatz von Pro- und Präbiotika hat sich als effektiv erwiesen.
Die Behandlung von psychischen Erkrankungen ausschließlich durch den Einsatz von Prä- und Probiotika ist häufig nicht ausreichend. In Kombination mit herkömmlichen Behandlungsmethoden ist die gezielte Modulation des Mikrobioms als sinnvoll zu bewerten.
Insgesamt ist dieses Themenfeld jedoch noch wenig erforscht und die Literatur liefert teilweise widersprüchliche Ergebnisse, wodurch zukünftig weitere Untersuchungen erforderlich sind
The Effect of Risk and Uncertainity on Purchasing Decisions
The end of 2019 has brought upon the world a new virus called Covid-19 that has quickly evolved into a pandemic at the start of 2020. To control the spread of the virus, countries around the world were forced to implement various strict measures that includes travel bans, lockdowns, and limited social contacts. As per pervious pandemics, this crisis had severe consequences on economy, consumer behavior, purchasing decisions and people’s mental and physical wellbeing. Consumers were forced to adapt and find alternatives that would fit the “new norm”. This added to the psychological distress people were experi-encing and in turn increased their feeling of risk and uncertainty. Thus, this research con-ducts a semi-structured exploratory in-depth interview (N=16) to profoundly investigate the effect of risk and uncertainty on consumers’ purchasing decisions in Germany. Find-ings of this study suggests that consumers with high uncertainty avoidance and high per-ceived risk are more likely to have a changed behavior. Their purchasing decisions are more oriented toward necessities and self-development products. On the other hand, con-sumers with low uncertainity avoidance and risk perception have experiences less change in terms of consumer behavior and purchasing decisions. The results of this research would help companies understand consumers’ psychological needs which is often ne-glected in literature to provide the needed products and services. It would also benefit the academic and professional world by knowing what to expect during crisis and if changed behaviors will continue after the pandemic is over
12/2022 Erste Änderungssatzung zur Praktikumsordnung für den Bachelorstudiengang Kindheitspädagogik der Fakultät Gesellschaft und Ökonomie an der Hochschule Rhein-Waal vom 19.05.2022
The design and build of a robust syringe pump for extension/contraction of artificial muscles
Field of bionics has been a great source of inspiration for mankind; and even the recent scientific discoveries of the past decades, has increased importance of this field in the modern life.
In this growing trend, more and more scientists are trying to surf over the waves of bio-inspired solutions, but the fundamental differences between nature’s point of view and man-kind, on managing the resources and solving problems, has made the traditional equipment’s of scientist, obsolete; especially when it come to actuation methods.
Since the traditional device and component are not suitable for cutting edge fields, such as bio-inspired robotic, artificial muscles, soft robotic and so on; this thesis has offered an especially designed syringe pump, to fulfill this need.
Starting from the basic constraints and expectations for such syringe pump, a morphological box has been shaped in this project; and along with having an eye over relatively similar products in the market, borders of “design function” has been drawn.
By considering the available equipment and tools for production of such device, the “design concept” of this thesis has been formed.
And finally, after days of manufacturing, the prototype of this concept has been brought to life.
In this syringe pump, a stepper motor (NEMA-17) is controlled by combination of computer, Arduino UNO and microstep driver DM542; by powering this stepper, a lead screw will be driven. Designing an aluminum structure and connecting a lead-nut to the lead-screw; linear displacement can be produced.
This linear displacement is responsible for movement of a tray, which is holding onto the end of syringe’s plunger; and by clamping the cylinder to the designed station of the thesis; with this configuration, desired static pressure can be produced by displacing the plunger.
Having this static pressure, is the key feature for simulating many different biomimetics projects, such as soft robotics and artificial muscles.
As the results, this thesis has achieve the high precision and resolution of “100 m” for each 5 steps of stepper motor, equivalent to 9° of rotation.
Furthermore, the prototype have easily and quickly delivered 300 mmHg (39.99Kpa), by using only a single 20ml syringe; and reached the highest speed of 750 rpm for the stepper motor
Start-up and operation of a continuous stirred tank reactor performing stable anammox process with Candidatus Brocadia fulgida
Nitrogen removal from wastewater is an energy and resource intense operation. In response, anaerobic ammonium oxidising (anammox) bacteria are being increasingly applied as a cost effective and sustainable wastewater treatment. Despite their utilisation worldwide, very little is understood about kinetic parameters and factors impacting their niche differentiation.
The lack of enriched planktonic cultures is limiting further investigations into anammox bacteria and the optimisation of wastewater treatment. In this study, a Continuously Stirred
Tank Reactor (CSTR) inoculated with Candidatus Brocadia fulgida to obtain an enriched planktonic culture. Ca. Brocadia fulgida was selected due to Ca. Brocadias widespread application in Wastewater Treatment Plants (WWTPs), and the lack of planktonic cultures of
this anammox species. The cultivation of anammox bacteria is a time-consuming operation, due to the slow growth rate. This operation was conducted for 84 days, and variety of analytical and microbial techniques were used to monitor bioreactor performance and anammox bacteria enrichment. An analysis of consumption and production patterns was performed to investigate anammox metabolism. Changes in the microbial community were also assessed, which indicated a culture enriched in anammox bacteria. The establishment of a planktonic culture enriched in Ca. Brocadia fulgida in a CSTR was not achieved, and further research is needed in order to successfully apply this innovative approach to anammox bacteria cultivation