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One of the key areas that have attracted attention in the construction industry today is Structural Health Monitoring, more commonly known as SHM. It is a concept developed to monitor the quality and longevity of various engineering structures. The incorporation of such a system would help to continuously track health of the structure, indicate the occurrence/presence of any damage in real time and give us an idea of the number of useful years for the same. Being a recently conceived idea, the state of the art technique in the field is straight forward - populating a given structure with sensors and extracting information from them. In this regard, instrumenting with too many sensors may be inefficient as this could lead to superfluous data that is expensive to capture and process. This research aims to explore an alternate SHM technique that optimizes the data acquisition process by eliminating the amount of redundant data that is sensed and uses this sufficient data to detect and locate the fault present in the structure. Efficient data acquisition requires a mechanism that senses just the necessary amount of data for detection and location of fault. For this reason Compressive Sensing (CS) is explored as a plausible idea. CS claims that signals can be reconstructed from what was previously believed to be incomplete information by Shannon's theorem, taking only a small amount of random and linear non - adaptive measurements. As responses of many physical systems contain a finite basis, CS exploits this feature and determines the sparse solution instead of the traditional least - squares type solution.As a first step, CS is demonstrated by successfully recovering the frequency components of a simple sinusoid. Next, the question of how CS compares with the conventional Fourier transform is analyzed. For this, recovery of temporal frequencies and signal reconstruction is performed using the same number of samples for both the approaches and the errors are compared. On the other hand, the FT error is gradually minimized to match that of CS by increasing the number of regularly placed samples. Once the advantages are established, feasibility of using CS to detect damage in a single degree of freedom system is tested under unforced and forced conditions. In the former scenario, damage is indicated when there is a change in natural frequency of vibration of the system after an impact. In the latter, the system is excited harmonically and damage is detected by a change in amplitude of the system's vibration. As systems in real world applications are predominantly multi-DOF, CS is tested on a 2-DOF system excited with a harmonic forcing. Here again, damage detection is achieved by observing the change in the amplitude of vibration of the system. In order to employ CS for detecting either a change in frequency or amplitude of vibration of a structure subjected to realistic forcing conditions, it would be prudent to explore the reconstruction of a signal which contains multiple frequencies. This is accomplished using CS on a chirp signal. Damage detection is clearly a spatio-temporal problem. Hence it is important to additionally explore the extension of CS to spatial reconstruction. For this reason, mode shape reconstruction of a beam with standard boundary conditions is performed and validated with standard/analytical results from literature. As the final step, the operation deflection shapes (ODS) are reconstructed for a simply supported beam using CS to establish that it is indeed a plausible approach for a less expensive SHM. While experimenting with the idea of spatio-temporal domain, the mode shape as well as the ODS of the given beam are examined under two conditions - undamaged and damaged. Damage in the beam is simulated as a decrease in the stiffness coefficient over a certain number of elements. Although the range of modes to be examined heavily depends on the structure in question, literature suggests that for most practical applications, lower modes are more dominant in indicating damage. For ODS on the other hand, damage is indicated by observing the shift in the recovered spatial frequencies and it is confirmed by the reconstructed response.

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Melanoma is a highly malignant neoplasia with high rates of metastasis in humans and dogs. Regardless of being considered a highly immunogenic neoplasm, the function of the immune system is hampered by the expression of immune checkpoint molecules by the cancer cells. In contrast, soft tissue sarcomas are poorly immunogenic, as Tumor infiltrating Lymphocytes are lacking, or when present they are usually at the periphery of the tumor. Still, soft tissue sarcomas are considered immunosuppressed. Checkpoint molecules from the PD-axis are overexpressed in numerous human malignant neoplasia and have recently gained attention with a few reports in canine tumors. Immunotherapies against these checkpoint molecules have shown great efficacy in humans, but in order to determine translational approaches into canine patients, more research is needed. Here we determined the gene expression of Programed Death receptor-1, and its ligands PD-L1 and PD-L2 in canine tumors with two distinct immune profiles. Our results show that regardless of their immune profiles, melanoma versus soft tissue sarcoma, checkpoint molecules expression was higher in malignant tumors with a higher grade. Additionally, we evaluated the expression of these molecules in a set of patients that received histotripsy, which is a non-invasive and non-thermal ultrasound focused therapy that induces mechanical stress to the cells, leading to liquefactive necrosis. Here we reported a focal decrease of the expression of these checkpoint molecules in tissue sections obtain at the treatment interface, compared to those taken from untreated areas of the tumor. In addition, a positive relationship was noticed between the infiltration of CD3+ T lymphocytes and the expression of these checkpoint molecules in both canine melanoma, and soft tissue sarcoma. Our findings demonstrate that immunotherapies targeting these checkpoint molecules have a great potential for efficacy in canine neoplasia, along or combined with tumor ablation therapies that increased immune cell infiltration in poorly immunogenic neoplasia. / Doctor of Philosophy / Melanoma is a highly malignant tumor and very resistant to therapy for humans and dogs. At the same time, this neoplasia is usually highly infiltrated by cells from the immune system. However, this immune infiltration is often inhibited by molecules expressed by the melanoma cells. In contrast, soft tissue sarcoma is considered poorly immunogenic, as they often contain low levels of immune cell infiltrates but are still considered immune suppressed. In this study, we determined the expression of molecules that inhibit the effect of T lymphocytes, specifically Programed cell death receptor-1, PD-Ligand 1, and PD-Ligand 2 for these neoplasms with distinct immune profiles. We encounter that despite their immune profiles, the expression of these molecules is higher in malignant tumors. Additionally, we evaluated the expression of these molecules in a set of patients that received histotripsy, which is a non-invasive and non-thermal focused ultrasound therapy that induces mechanical stress to the cancerigenous cells, leading to its death (necrosis). Here we reported a focal decrease of the expression of these checkpoint molecules in tissue sections obtain at the treatment interface, compared to those taken from untreated areas of the tumor. In addition, a positive relationship was noticed between the infiltration of T lymphocytes and the expression of these checkpoint molecules in both canine melanoma, and soft tissue sarcoma. Our findings demonstrate that immunotherapies targeting these checkpoint molecules have a great potential for efficacy in canine neoplasms, along or combined with tumor ablation therapies that increased immune cell infiltration in poorly immunogenic neoplasia.

This study explored the effects of lecture speech rate and duration on L1 Chinese listeners' listening comprehension of online L2 English lectures on free-recall and cued-recall questions. There are many factors that may affect a Chinese listener's listening comprehension of online English lectures. The current study focused specifically on the effects of speech rate and duration, and explored the possibility of identifying tools that listeners might use to control these factors during online lectures in order to achieve better learning experiences. Using an exploratory quasi-experimental approach, this study explored the research questions in three phases: 1) An initial quasi-experiment was conducted via Qualtrics and applied as a pilot study; 2) The quasi-experiment was revised, with a new link sent out to potential participants from both the United States and China; and 3) Quasi-experiment responses were collected and analyzed. Based on 28 participant responses, the findings from the current study suggest that the interaction between speech rate and duration impacted L1 Chinese listener's comprehension of online L2 English lectures. The findings also suggest that study participants' responses on various types of questions were affected differently by the speech rate and duration of the lectures. / Doctor of Philosophy / It is assumed that the slower and the shorter the listening material is, the better the foreign language learner's listening comprehension will be. Is this true? This study explored how a lecture's speech rate and duration may affect L1 Chinese listeners' listening comprehension of online L2 English lectures on free-recall and cued-recall questions. It discusses the possibility of identifying tools for listeners to control the speech rate and duration of online lectures in order to help listeners achieve better learning experiences. Using an exploratory quasi-experimental approach, this study explored the research questions in three phases: 1) An initial quasi-experiment was conducted via Qualtrics and applied as a pilot study; 2) The quasi-experiment was revised, with a new link sent out to potential participants from both the United States and China; and 3) Quasi-experiment responses were collected and analyzed. Based on 28 participant responses, the findings from the current study suggest that speech rate and duration worked together to impact L1 Chinese listeners' comprehension of online L2 English lectures. The findings also suggest that study participants' responses on various types of questions were affected differently by the speech rate and duration of the lectures.

<p dir="ltr">Immunotherapy has revolutionized the field of oncology. While a lot of antibodies and small molecule inhibitors have been developed for this, a lot of targets remain undruggable in humans.</p><p dir="ltr">Targeted protein degradation has opened a new horizon in drug discovery where we can target these undruggable proteins. Proteolysis targeting chimeras using the ubiquitin-proteasomal system is one of the most popular TPD strategies that complement lysosomal degradation strategies to degrade intracellular proteins, typically using bifunctional small molecule degraders. Recently, large biomolecular and antibody conjugates have been developed for degrading membrane and extracellular proteins in cells, such as lysosomal targeting chimeras (LYTACs) and genetically encoded LYTACS, among several others. However, larger molecules have limitations in penetrating solid tumors. This dissertation work focused on the development of bifunctional small molecule degraders for programmed death-ligand 1 (PD-L1), a transmembrane protein ligand for the immune checkpoint programmed cell death 1 (PD-1). PD-L1 is highly expressed on several tumors, such as triple-negative breast cancer (TNBC), non-small cell lung carcinoma, and renal cancer, and is known to suppress cancer-killing immune cells via interaction with PD-1 on T-cells. In addition, PD-L1 is also present on macrophages in the tumor microenvironments leading to further immune suppression and acquired resistance to anti-PD-1 therapy is associated with the upregulation of alternative immune checkpoints, thereby reducing anti-tumor efficacy. We have designed and synthesized bifunctional small molecules as PD-L1 degraders with different recruiters and linkers guided by computational studies with known PD-1/PD-L1 structures to show both cell surface and total protein degradation in human TNBC cells. In a separate project, we also developed small molecule conjugates to degrade an intracellular integral membrane protein of the endoplasmic reticulum with an unknown 3D structure, namely Diglyceride acyltransferase 2 (DGAT2). Recently, our lab identified DGAT2 as a new target for combating Alzheimer’s disease. Specifically, DGAT2 catalyzes triacylglycerol (TAG) synthesis using diacylglycerol and fatty acyl CoA as substrates. The accumulation of TAGs, mechanistically linked to DGAT2, results in “fat” or lipid droplets (LDs) inside the cells. Our lab showed that microglial cells (resident immune cells in the brain) accumulate LDs in the postmortem brains of human patients and mouse models (5xFAD) of Alzheimer’s disease and that the LD accumulation is driven by amyloid-beta (Ab) – a hallmark of Alzheimer’s disease – via DGAT2 pathway. Further, these LD-laden microglia have phagocytic defects and are spared Aβ thereby affecting plaque accumulation and clearance. Inhibiting DGAT2 reduces the amount of TAG in the brain, which in turn reduces LDs and restores microglial ability to phagocytose Ab. However, commercially available DGAT2 inhibitors were unable to reduce LD load in older 5xFAD mice. Using AlphaFold’s models of DGAT2, we designed and identified sites to synthesize bifunctional DGAT2 degraders that resulted in reduced LDs in mouse primary microglial cells and enhanced phagocytosis of Aβ plaques in vivo in aged 5xFAD mice. Our approach shows a framework to develop bifunctional small molecule degraders for membrane proteins to potentially combat immune dysregulation in chronic diseases.</p>

This degree project aims to examine teachers' use of translanguaging, whether planned or incidental, and their attitudes and perceptions towards translanguaging in the context of English communicative classrooms in Sweden. In Swedish universities, the target language approach is highly endorsed by educators during English teaching education programs. Although exposure to the target language has been identified as important, comprehension plays a vital role in learning a new language. Translanguaging is an approach that enhances comprehension while allowing for exposure to the target language. This study was conducted through classroom observations followed by qualitative interviews with practicing teachers. Quantitative data from the observations and qualitative data from the interviews highlight the use of translanguaging as well as practicing teachers’ attitudes and perceptions of the approach. Our study showed that, even though teachers were somewhat unfamiliar with translanguaging as a term, they utilized what could be considered translanguaging during their English lessons and held positive attitudes toward the approach. Translanguaging was primarily used to explain and clarify activities. Teachers utilized their own and students' multilingual capabilities to achieve a deeper understanding of topics and to provide instructions.

Multilingualism is a reality in South African classrooms. The Constitution of South Africa (Act 108 of 1996) and the national language policy recognize language rights and aims at supporting, promoting and developing the official languages. However, despite the advantages of mother tongue education, English is often chosen as language of learning and teaching at the cost of the African official languages. This study proposes the accommodation and promotion of multilingualism through blended learning.Blended learning refers to the blending of traditional instruction methods, such as face-to-face instruction, with other forms of instruction such as online learning and teaching. Through a discussion of asynchronous and synchronous learning tools it was established that wikis would be used for this study. In terms of blended learning and learning theories the main emphasis in this study is on socio-constructivism as well as communal constructivism.The empirical research in this study focused on the establishment and testing of a conceptual model for the accommodation and promotion of multilingualism through blended learning in the subject IT. The research took the form of a sequential embedded mixed methods design. Both quantitative and qualitative approaches were used. A questionnaire was used with IT teachers to investigate the language and blended learning context. This was followed up with qualitative research in the form of interviews aimed at provincial and national experts in terms of the subject IT and e-learning. Based on the literature and these two investigations, a conceptual model was developed. The conceptual model’s effectiveness was tested through a quasi-experimental study. A questionnaire was also completed by the respondents at the schools after the completion of the study. Through the testing of the effectiveness of the conceptual model it was found that multilingualism could successfully be accommodated and promoted through this conceptual model.

The aim of this descriptive and evaluative research study is to assess the impact achieved by the DBSA/ SALGA ICT Internship Programme, a national local government internship programme that was undertaken by South African Local Government Association (SALGA) and the Development Bank of Southern Africa (DBSA) Development Fund in partnership with the South African Communication Forum (SACF), Department of Provincial and Local Government (DPLG) and SIEMENS Ltd Training Institute.A supply-side internship programme in nature, its strategic objectives were to train and equip young South Africans with ICT skills, give youth learners workplace experience in the ICT functional area within their respective municipalities, create employment opportunities for youth and economic development for local municipalities in alleviation of scarce-critical ICT skills to capacitate the local government sector.Forty (x40) learners from Further Education and Training (FET) Colleges were recruited from various rural municipalities to undertake ICT training with SIEMENS Training Institute and given workplace experiential learning with fifteen x15 host municipalities under the banner of the South African Local Government Association. This descriptive and evaluative study is undertaken in a case study format with particular interest in the retention levels of graduate learners endowed with scarce skills in the context of the skills challenges facing the local government sector. The study also focuses on unique challenges and interventional measures that could be undertaken by designers of public education and training programmes to ensure efficiency of internship programmes and optimal benefit of publicly-funded internship programmes to youth learners. This research study not only has internal validity in terms of the operational delivery of internship programmes but also external contextual importance for publicly-funded learning and placement programmes within the larger human resources development (HRD) domain and local government sector. In the process of conducting the study, stratified random sampling is utilised due to the multi-stakeholder nature of the programme. A stratified survey sample comprising fifty percent (50%) of the total survey population of forty (40) former ICT learners who participated in the internship programme is selected whilst a sample of sixty percent (60%) of the fifteen (15) host municipalities who participated in the programme is also selected using stratified random sampling. The findings of the study indicate that participation in the DBSA/ SALGA ICT Internship Programme has positively promoted the employability of former ICT learners. All ICT learner respondents confirmed current employment within the ICT functional area. Research findings indicate that the local government sector has derived short term retention and benefit from the programme but has not been able to retain the skills of the majority of former ICT learners in the long term. Although most of the former ICT learners have since migrated out of the local government sector, most former learners are still employed in the ICT field within the public sector and to some extent in the private sector of the South African economy. The study found out that most learners were able to assimilate and find employment within their host municipalities or were able to find ICT-related employment soon after graduation. The research findings of this impact assessment study indicate that the DBSA/ SALGA ICT Internship Programme has positively transformed young inexperienced graduates into responsible young adults through the development of key life skills and work experiences to enable them to successfully navigate the path between the classroom and the challenging world of work. / Mini-dissertation submitted in partial fullfilment of the requirements for the North-West University Yunibesiti Ya Bokone-Bophirima Noordwest-Universiteit Masters Degree in Business Administration (MBA) Human Resource Management (HRM) North-West University (NWU) Graduate School of Business & Government

The nature of the bilingual mental lexicon and how the L1 and the L2 interact in language production and processing has been the focus of decades of research from linguistic, psycholinguistic and neurolinguistic perspectives. In spite of this significant body of evidence, the degree to which the L1 influences L2 production and processing remains an area of debate, especially with respect to formal features such as grammatical gender. While it is clear that non-nativelike production and processing of L2 grammatical gender persist even in highly-proficient adult bilinguals, the underlying representation of the L1 and L2 gender features and how this representation affects the use of gender in the L2 is currently unclear. Furthermore, there is no evidence at present regarding the nature of the L1-L2 grammatical gender system when the L1 and the L2 have asymmetric gender systems (in other words, differ in number of gender values), as is the case with German, which bears three gender values (masculine, feminine and neuter), and Spanish and French, which each display two gender values (masculine and feminine). This dissertation investigates the representation of and interactions between the L1 and the L2 at the level of the formal gender feature, with a particular focus on language pairings with asymmetric gender systems. Through complementary data from L2 production and processing, I examine the representation of the asymmetric grammatical gender systems in the mental lexicon of L1 Spanish-L2 German and L1 French-L2 German bilinguals and the consequences this asymmetry between the L1 and L2 gender systems has on gender use strategies in the L2. From the perspective of bilingual lexical access, this research contributes new evidence to inform existing psycholinguistic theories of L1-L2 gender interactions and also proposes the Asymmetric gender representation hypothesis, a new model to account for the unique integrated nature of the gender system in bilinguals with L1-L2 asymmetric gender systems. From a language acquisition perspective, the present study provides new data on L2 gender use strategies with asymmetric gender systems, formulating the L1 transfer continuum, which extends existing proposals to include the degree of (a)symmetry between the L1 and the L2. This research also connects theoretical proposals regarding gender agreement in functional-lexical code-switches (specifically, switches within the Determiner Phrase such as dieGER-F mesaSPA-F or elSPA-M TischGER-M) to bilinguals’ preferences in code-switching between two languages that display formal gender. Taken together, all of these complementary perspectives addressed in this dissertation offer a well-rounded perspective of grammatical gender in asymmetric gender systems specifically, and contribute novel evidence regarding the interactions between the L1 and the L2 in the bilingual mental lexicon in general.