Thesis advisor: Thomas M. Crea / Few studies have examined drivers of healthcare trust and vaccine hesitancy in the context of low- and middle-income countries (LMIC) where healthcare systems are most fragile. This study focuses on healthcare trust and vaccine hesitancy in Sierra Leone, a country that has a history of infectious disease outbreaks. This study examines drivers and impacts of healthcare mistrust in caregivers of children and Covid-19 vaccine intention and behavior both for caregivers and for their children. This study also examines current community members trust in healthcare providers, including doctors, nurses, and traditional healers. This study uses two data sets: quantitative data for Aim 1 and Aim 3 come from a two-wave longitudinal NICHD-funded study (#R01HD096699; PIs: Thomas M. Crea, PhD, MSW and John S. Schieffelin, MD) and includes a sample of EVD-infected (n=222), EVD-affected (n=208), and control children (n=233) and their caregivers (n=663). Qualitative data were used for Aims 2 and 3 and were collected in August of 2023 in Freetown, Sierra Leone, as part of a study funded through Boston College Vice Provost Office (PI: Oladoyin Okunoren, LCSW). This study has three specific aims: AIM 1: Examine the influence of mental health and healthcare trust on Covid-19 vaccine behavior and intention among caregivers. AIM 2: Explore healthcare perceptions, utilization, and trust in Sierra Leone, and implications for vaccine uptake and intention. AIM 3: Explore community and healthcare worker perceptions of traditional healers within healthcare interventions before and after EVD. / Thesis (PhD) — Boston College, 2024. / Submitted to: Boston College. Graduate School of Social Work. / Discipline: Social Work.

Over the past few decades researchers and industrial professionals alike have realized the vast potential of monoclonal antibodies to treat diseases ranging from arthritis, immune and infectious diseases to cancer. There are a number of antibodies on the market that constitute a large portion of the biopharmaceutical niche in the drug industry. Blockbuster drugs (selling greater than $1 billion/year), include antibodies such as Avastin (bevacizumab), Herceptin (trastuzumab), Rituxan (rituximab), Humira (adalimumab) and Remicade (infliximab), which are cornerstones in this type of sector. With the cost of development to market approval rising astronomically for a new drug, new ways to produce and process these molecules becomes a paramount objective to ultimately help both patients and drug developers. Plants, such as Nicotiana benthamiana, offer a unique production platform due to their recently found ability to produce large amounts of therapeutic proteins in a quick manner. While production would be simple and cheap, purification would not be due to the presence of toxic compounds in ground plant tissue. The current methods to purify these molecules from plant extract include expensive affinity column steps (Protein A/G) that are difficult to scale-up to bed volumes that would be necessary for this technology. In the following paper, a method to purify a monoclonal antibody by non-Protein A/G resins is accomplished and compared to purification by Protein A. The modified process involved an UF/DF step, a precipitation of native impurities step using a charged polymer, hydrophobic interaction chromatography and hydrophobic charge induction chromatography. The yield of this modified process was 19.0%. This process compared favorably with Protein A due to the fact that even with washing steps including NaCl and Tween-20, the Protein A elution fraction still contained a large portion of host cell impurities. A chromatography step would need to be included before Protein A to both protect the column resin and provide a more purified immunoglobulin. / Master of Science

Yes / Coronavirus is the most dangerous virus in the world wide and it can easy spread between people, animals and plants because it is existing on one strand of RNA (Ribonucleic Acid) and it can duplicate faster than any virus. The source of coronavirus is still unknown, but some sources said that it came from seafood market and other sources said that it came from bat and snakes. It starts in Wuhan; China and every day the fatality increases. The symptoms are like a SARS-CoV (acute respiratory syndrome coronavirus)) and MERS-CoV (Middle East Respiratory Syndrome Coronavirus). By using nucleotide sequence of coronavirus from NCBI (National Center for Biotechnology Information) and some programs that ran on Matlab, the results show that there are some differences and similarities between coronavirus and other viruses such as Ebola, Flu-b, Hepatitis B, HIV and Zika especially for DEBs (distinct excluded blocks) program that shows at 5bp (base pair) there is a common with slightly difference between coronavirus “cgggg” and Ebola virus “cgtgg”. The aim from this study is to find a way to help doctors and scientists to stop spreading the coronavirus or to destroy it.

LLM / Department of Public Law / Human rights are those inalienable rights of an individual by virtue of being a human being. They are guaranteed by various domestic and international instruments. This research argues that despite the existence of these instruments and wide acceptances of international human rights standards that seek to protect the right to healthcare, the people infected with Ebola Virus Disease (EVD) are victims of a wide range of constraints to their right to healthcare as a result of the failure by the governments of the respective nations where the impacts of the EVD are mostly felt to discharge their obligations under those instruments. The rights of the people infected with EVD are often violated because of their presumed or known EVD status, causing them to suffer both the burden of the disease and the social burden of discrimination and stigmatisation which could deter the infected persons from accessing available treatment. This would invariably contribute to the spread of the disease. The research further exposes the dilemma posed by the EVD to the healthcare system, where healthcare providers are caught between the rock of selfpreservation from a highly virulent disease and the hard place of discharging their Hippocratic Oath which prescribes ethical guidelines for the discharge of the duties of the medical profession. The present research, which is novel in the field of medico-legal research, seeks to proffer answers to this conundrum.

Les fièvres hémorragiques à virus Lassa (LASV) et Ebola (EBOV) représentent un important problème de santé publique en Afrique. Les réponses immunes et la pathogenèse associées à ces maladies sont peu connues. Les cellules NK ont un rôle important dans la réponse immune innée par leurs propriétés cytotoxiques, mais également dans l’induction des réponses adaptatives par leur production de cytokines et leurs interactions avec les cellules dendritiques (DC) et les macrophages. Ce projet s’attache à comprendre le rôle des cellules NK dans le contrôle de la réplication virale et dans l’induction des réponses immunitaires au cours de ces infections. Un modèle in vitro de coculture de cellules NK humaines avec des DC et macrophages autologues a été développé. L’activation des cellules NK et leurs fonctions ont été analysées après l’infection par LASV et EBOV. Par ailleurs, les réponses des cellules NK en réponse à LASV ont été comparées avec celles induites lors de l’infection par le virus Mopeia (MOPV), très proche de LASV mais non pathogène pour l’homme. Les macrophages, mais pas les DC, infectés par LASV ou MOPV induisent l’activation et l’augmentation des capacités cytotoxiques des cellules NK. Toutefois, les cellules NK ne sont pas capables de lyser les cellules infectées et ne produisent pas d’IFN-γ. Les cellules NK s’activent et sont capables de lyser les cellules infectées en présence de macrophages mais également de DC infectés par des LASV mutants. Cependant, les IFN de type I sécrétés en grande quantité en réponse à ces virus ne sont pas impliqués dans l’activation des cellules NK. L’infection par EBOV n’induit qu’une très faible activation des cellules NK en présence de DC ou macrophages et ne conduit pas à la sécrétion de cytokines, ni à la modification du potentiel cytotoxique.Ces résultats permettent d’améliorer la compréhension des réponses immunes et des mécanismes de pathogenèse mis en place lors des fièvres hémorragiques Lassa et Ebola. / The hemorrhagic fevers caused by Lassa (LASV) and Ebola (EBOV) viruses are important problems of public health in Africa. The immune responses and the pathogenesis associated with these diseases are unknown. NK cells are at the crossroads between the innate and adaptive immune responses through their abilities to secrete cytokines and kill the infected cells. The interactions between NK cells and dendritic cells (DC) or macrophages potentiate the immune responses. This project aims to understand the role of NK cells in the control of viral replication and in the induction of immune responses during LASV and EBOV infection.An in vitro model of coculture of human NK cells with autologous DC or macrophages has been set up. Cell activation, cytokine production, proliferation and NK cell-mediated killing were analyzed after the infection with LASV or EBOV. In addition, NK cell functions in response to LASV were compared with those induced during Mopeia virus (MOPV) infection, closely related to LASV but not pathogenic for humans.Here, we show that LASV- or MOPV-infected macrophages, but not DC, induce the activation of NK cells and the increase of their cytotoxic capacity. This process involves cell contact and type I IFN. However, these cells are neither able to kill the infected cells nor produce IFN-γ. NK cells are activated and are able to kill the infected cells when stimulated by mutated LASV-infected macrophages and DC. Surprisingly, the type I IFN which are secreted in high amounts in response to these viruses are not involved in NK cell activation. EBOV infection does not lead to NK cell activation in the presence of DC. EBOV-infected macrophages induce low NK cell activation without cytokine production or cytotoxicity.These results allow to better understand the immune responses and the mechanisms of pathogenesis associated with Lassa and Ebola hemorrhagic fevers.

Hepatitis C virus (HCV) is one of the leading causes of hepatocellular carcinoma worldwide. HCV-neutralizing antibody AP33 recognizes a linear, highly conserved epitope on the viral entry protein E2, disrupting the interaction with the cellular receptor CD81 that leads to viral entry. AP33-related anti-idiotypes (Ab₂s) have the potential to carry the internal image of the antigen E2, eliciting the production of AP33-like antibodies in humans. This study reports the mid-resolution structure of the Fab fragment of anti-idiotype A164.3 and the high-resolution structure of the Fab fragment of AP33 in complex with the Fv fragment of anti-idiotype B2.1A. Analysis of the structures and comparison with the previously published structure of AP33 in complex with a peptide corresponding to the E2 epitope, suggests that while A164.3 does not mimic the antigen E2, B2.1A is characterized by high surface complementarity with AP33 and functional antigen mimicry. Thus, B2.1A can be classified as an Ab₂-β, a subgroup of anti-idiotypes carrying the internal image of the antigen. Preliminary binding studies show that AP33 binds B2.1A with nanomolar affinity, supporting the role of B2.1A as an idiotypic vaccine candidate. Zaire ebola virus causes severe, often lethal hemorrhagic fever in humans. Ebola virus polymerase cofactor VP35 is a multifunctional protein involved in, among other functions, dsRNA binding and inhibition of the host's interferon pathways. VP35 contains an N-terminal oligomerization domain and a C-terminal dsRNA-binding domain (RBD). Preliminary results on the oligomerization domain of VP35 suggest that this region contains a coiled-coil motif, as previously reported. In order to validate a recently-discovered dsRNA end-capping pocket as a drug target, the structure of VP35 RBD I278A mutant was solved at high resolution, showing that even a small perturbation in the binding pocket can cause dramatic binding impairment due to loss of contacts with dsRNA.

Some Epidemic models with fractional derivatives were proved to be well-defined, well-posed and more accurate [34, 51, 116], compared to models with the conventional derivative. An Ebola epidemic model with non-linear transmission is fully analyzed. The model is expressed with the conventional time derivative with a new parameter included, which happens to be fractional (that derivative is called the 􀀀derivative). We proved that the model is well-de ned and well-posed. Moreover, conditions for boundedness and dissipativity of the trajectories are established. Exploiting the generalized Routh-Hurwitz Criteria, existence and stability analysis of equilibrium points for the Ebola model are performed to show that they are strongly dependent on the non-linear transmission. In particular, conditions for existence and stability of a unique endemic equilibrium to the Ebola system are given. Numerical simulations are provided for particular expressions of the non-linear transmission, with model's parameters taking di erent values. The resulting simulations are in concordance with the usual threshold behavior. The results obtained here may be signi cant for the ght and prevention against Ebola haemorrhagic fever that has so far exterminated hundreds of families and is still a ecting many people in West-Africa and other parts of the world. The full comprehension and handling of the phenomenon of shattering, sometime happening during the process of polymer chain degradation [129, 142], remains unsolved when using the traditional evolution equations describing the degradation. This traditional model has been proved to be very hard to handle as it involves evolution of two intertwined quantities. Moreover, the explicit form of its solution is, in general, impossible to obtain. We explore the possibility of generalizing evolution equation modeling the polymer chain degradation and analyze the model with the conventional time derivative with a new parameter. We consider the general case where the breakup rate depends on the size of the chain breaking up. In the process, the alternative version of Sumudu integral transform is used to provide an explicit form of the general solution representing the evolution of polymer sizes distribution. In particular, we show that this evolution exhibits existence of complex periodic properties due to the presence of cosine and sine functions governing the solutions. Numerical simulations are performed for some particular cases and prove that the system describing the polymer chain degradation contains complex and simple harmonic poles whose e ects are given by these functions or a combination of them. This result may be crucial in the ongoing research to better handle and explain the phenomenon of shattering. Lastly, it has become a conjecture that power series like Mittag-Le er functions and their variants naturally govern solutions to most of generalized fractional evolution models such as kinetic, di usion or relaxation equations. The question is to say whether or not this is always true! Whence, three generalized evolution equations with an additional fractional parameter are solved analytically with conventional techniques. These are processes related to stationary state system, relaxation and di usion. In the analysis, we exploit the Sumudu transform to show that investigation on the stationary state system leads to results of invariability. However, unlike other models, the generalized di usion and relaxation models are proven not to be governed by Mittag-Le er functions or any of their variants, but rather by a parameterized exponential function, new in the literature, more accurate and easier to handle. Graphical representations are performed and also show how that parameter, called ; can be used to control the stationarity of such generalized models. / Mathematical Sciences / Ph. D. (Applied Mathematics)

Les virus sont au centre de problème de santé publique. En raison de l'apparition de nouveaux virus et pour certains de leur résistance aux traitements existants il est toujours d’actualité de développement de nouveaux agents antiviraux. En général, la stratégie de lutte contre les infections virales est basée sur la vaccination ou sur l'activité des petites molécules, interférant avec un ou plusieurs processus biologiques participant au cycle de vie du virus. Dans ce contexte, nous avons conçu et synthétisé des petites bibliothèques de molécules visant des propriétés anti-filovirus. Dans ce projet de recherche, nous avons mis l'accent sur le développement de composés ciblant la protéine Niemann-Pick C1, les protéases cathepsine et le processus de réplication. Lors du développement des inhibiteurs de Neimann-Pick C1 plus de 70 composés ont été synthétisés, portant le squelette pipérazine. Afin d'obtenir des inhibiteurs de cystéine cathepsines pouvant être impliqués dans la réplication du virus Ebola, nous avons synthétisé une petite bibliothèque de composés porteurs de groupement 1,3,5-triazine et possédant des activité de l’ordre du nanomolaire sur les cathepsines B, K, L et S. Enfin, pour inhiber la réplication du virus en ciblant SAH hydrolase, nous avons proposé une série de C-nucléosides carbocyclic ayant motif de 4-aza-7,9-dideazaadenosine. / The viruses cause the problem of public health. Due to the appearance of new viruses and their resistance to existing treatments there is still relevant to develop new antivirals. Generally, the strategy to combat viral infections is based on vaccination or on the activity of small molecules, interfering with one or more biological processes participating in virus life cycle. In this context, we took an effort to design and synthesize the library of small molecules possessing anti-filovirus properties. In this research project, we were focused on the developing of compounds targeting Niemann-Pick C1 protein, cathepsin proteases and replication process. In our effort into the development of the inhibitors of Neimann-Pick C1 we prepared the series of about 70 compounds, having in common the piperazine moiety. Diverse 1,4-N,N - substituents of piperazine, differencing in a size and shape were studied. In order to obtain efficient cysteine cathepsins inhibitors, we synthesized the small library of compounds bearing 1,3,5-triazine moiety. Finally, to inhibit the virus replication by targeting SAH hydrolase, we proposed the series of carbocyclic C-nucleosides having motif of 4-aza-7,9-dideazaadenosine.

2D molybdenum disulfide (MoS₂) gives a new inspiration for the field of nanoelectronics, photovoltaics, and sensorics. However, the most common processing technology, e.g., liquid‐phase based scalable exfoliation used for device fabrication, leads to the number of shortcomings that impede their large area production and integration. Major challenges are associated with the small size and low concentration of MoS₂ flakes, as well as insufficient control over their physical properties, e.g., internal heterogeneity of the metallic and semiconducting phases. Here it is demonstrated that large semiconducting MoS₂ sheets (with dimensions up to 50 µm) can be obtained by a facile cathodic exfoliation approach in nonaqueous electrolyte. The synthetic process avoids surface oxidation thus preserving the MoS₂ sheets with intact crystalline structure. It is further demonstrated at the proof‐of‐concept level, a solution‐processed large area (60 × 60 µm) flexible Ebola biosensor, based on a MoS₂ thin film (6 µm thickness) fabricated via restacking of the multiple flakes on the polyimide substrate. The experimental results reveal a low detection limit (in femtomolar–picomolar range) of the fabricated sensor devices. The presented exfoliation method opens up new opportunities for fabrication of large arrays of multifunctional biomedical devices based on novel 2D materials.

Hur myndigheter kommunicerar under kristider spelar en avgörande roll för hur både samhälle och näringsliv hanterar en kris. Denna deskriptiva studie undersöker hur Folkhälsomyndigheten kommunicerat under två pandemier, Covid-19 och Ebola, för att beskriva hur en svensk myndighet kommunikativt hanterat allvarliga kriser. Studien har tillämpat en kvantitativ innehållsanalys för att granska en större mängd publikationer och mäta teoretiskt intressanta egenskaper i Folkhälsomyndighetens kommunikation. För att fylla vad vi menar är en forskningslucka, den kvantitativa retorikanalysen, har operationaliseringar av centrala retoriska begrepp gjorts. Två urval har gjorts från Folkhälsomyndighetens nyhetsarkiv; ett totalurval av Ebola-publikationer (N=12) och ett slumpmässigt urval av Covid-19-publikationer (n=83), vilket sammantaget resulterade i 95 analysenheter. Dataanalys av publikationerna genomfördes i dataanalysprogrammet SPSS. Vår studie fann att Folkhälsomyndighetens riskkommunikation var dynamisk och anpassades utefter hur allvarlig en kris var och hur den utvecklades. Exempelvis manifesterade myndigheten risker när utvecklingen av Covid-19 var oroväckande och tvärtom, när pandemin var mindre allvarlig under sommarmånaderna. Myndigheten axlar huvudsakligen en rådgivande roll i kristider, i närmare 9 av 10 fall framkommer en eller flera uppmaningar om hur samhället bör förhålla sig till Covid-19. Vidare visar analysen att myndigheten vilade sin argumentation på sakliga eller statistiska bevis (ex. dokument eller forskningsrapporter) i mer än 70 procent av fallen, vilket tyder på ett rationellt övertygande. Studien visar prov på hur en kvantitativ retorikanalys kan genomföras och fyller därmed en forskningslucka. Vidare diskuteras vilka för- och nackdelar som uppstår när teoretiska begrepp omvandlas (operationaliseras) till mätbara variabler. / How authorities communicate during times of crisis plays a crucial part in how society and commerce manages a crisis. This descriptive analysis examines how the Swedish public health authority Folkhälsomyndigheten has communicated during two pandemics, Covid-19 and Ebola, in goal of depicturing how a Swedish government agency has communicated whilst handling a serious risk to public health. The study has applied a quantitative content analysis to examine a large number of publications and measure theoretically interesting properties in Folkhälsomyndigheten’s communication. Central rhetorical concepts have been operationalized and measured in order to fill what we perceive to be a research method gap, the quantitative rhetorical analysis. Two samples have been drawn from Folkhälsomyndigheten’s news archive; a complete sample of Ebola publications (N=12), and a sample of Covid-19 publications (n=83), resulting in a total of 95 units. The data analysis of the publications was performed using the data analysis program SPSS. Our study found that Folkhälsomyndigheten’s risk communication was dynamic and adapted to how severe a crisis was and how it developed. For example, the agency manifested the risks when Covid-19’s development was alarming, and the other way around when the development was less alarming during summer months. The agency primarily holds an advisory role in times of crisis; in almost 9 out of 10 cases one or more appeals or guidelines to the general public is apparent, on how society should adapt to Covid-19. Furthermore, our analysis shows that the agency bases their arguments on facts and statistics evidence (e.g. documentation or research reports) in more than 70 percent of the cases. Which suggests a rational persuasion tactic. The study exemplifies how a quantitative rhetorical analysis can be executed, and thus fills a research gap. In addition, the study discusses the pros and cons of converting (operationalizing) theoretical concepts to measurable variables.