9,290 research outputs found
Development of Porous Rubber Pavement for the Canadian Climate
Permeable pavement usage in North America has increased over the last decade as a viable stormwater management system. Porous Rubber Pavement (PRP) is a new material in this category which has been currently utilized as a pavement surface material for low-traffic areas and pedestrian walkways. This material consists of recycled crumb rubber aggregates, granite aggregates and polyurethane as a binder and is proportioned to attain a very high percentage of interconnected air voids (up to 45%). As a new pavement material in North America, the properties and performance of PRP are not thoroughly understood for cold climate conditions. This research aimed to understand the properties and performance of PRP and improve its performance as a pavement surface material for the Canadian climate. This objective is achieved through an evaluation of existing sites and mixes, developing new mixes through an experimental design process, and evaluating new mixes in the laboratory facilities. Some of the mixes were selected to apply in the trial section to assess field performance. Finally, recommendations and guidelines are developed for this climatic zone. Through the experimental design, four new mixes were developed using different proportions of stone aggregates, rubber aggregates and polyurethane binder. Also, using the proportion of the Control Mix, four polyurethane binders were used to make four different mixes to determine the different binder effects in PRPs. In the next stage of research, two trial sections were constructed using selected mixes along with the Control Mix. In addition, samples were also prepared from the field mixes to test their properties in the laboratory. Then the field performance of the various mixes was evaluated over a series of months. They were initially tested immediately following construction before fully opening for traffic. Then three weeks after construction and after seven months when the sections had experienced their first winter. Preliminary field investigations showed that with the current commercial mix, the achieved elastic modulus of PRP surfaces ranged between 37 MPa and 33 MPa. Besides, frictional values ranged between 57 BPN and 74 BPN. Higher IRI values were calculated for both sites, ranging between 7.56 m/km to 15.77 m/km. The average infiltration rate for the pavement surface areas was found to be 30836 mm/hr.
The mechanical properties and durability of the Control Mix and newly developed mixes were investigated. The tensile and compressive strength of the mixes were found to be higher when the percentages of stone aggregates and binders were increased in the mixes. Additionally, an increase in air voids in the samples reduced the materials' tensile and compressive strength. Concerning the types of binder and sources, the obtained results showed no considerable influence of different types of binder in compressive strength test results, whereas binder sources influenced the tensile strength of the PRP materials. PRP samples with varying compositions retained more than 70% of their tensile strength after conditioning with five freeze-thaw cycles. However, due to the variety of binders used, retained tensile strength for PRP samples varied, and some showed retained tensile strength below 70%.
The durability study showed that the granite stones that were used for all the sample preparation were not strong enough to withstand higher abrasion loss. However, PRPs with different compositions showed good rutting resistance, ranging from 0.3mm to 2.8mm in different mixes. Moisture-induced damage, stripping related abrasion was also found to be very small in PRP mixes, ranging from 2.6% to 0.1%. Also, the use of different binders from different sources showed that the B2—aliphatic binder could withstand more rutting than other binders. A Los Angeles abrasion tester tested unconditioned and conditioned samples to determine the materials' ravelling resistance. The result showed that abrasion loss increased in the samples after conditioning with five freeze-thaw cycles. However, it was consistent with the mix types. On the other hand, abrasion loss of samples with different binders occurred differently in the conditioned and unconditioned situations and was inconsistent in the mixes.
Subgrade samples were collected from sites A and B during the trial section construction. The bearing capacity of subgrade soil for Site B was found to be higher than that of Site A. Subsequently, the performance of the mixes in the sections was evaluated through a series of field testing. The LWD results showed that the stiffness modulus differed for the same mixes at Site A and Site B. Besides, all the mixes showed higher stiffness in the 2nd field test than the 1st since compaction occurred on the pavement after opening for traffic. Nevertheless, after experiencing their first winter, a reduction in stiffness was observed for all mixes in the 3rd test. The BPT test revealed that a higher frictional value of PRP mixes was associated with a higher percentage of rubber aggregates and a lower percentage of binder in the mixes. At the same time, a reduction in BPN values was observed in the 2nd test than in the 1st since the sections were further compacted and polished after opening for traffic. In addition, the surface ravelling and transported loose particles affected the frictional values in the 3rd test, increasing the BPN numbers. Initial rut depths on Site A for different mixes ranged from -7.0 mm to -8.7mm, and the range was -5.8 mm to -10.7mm for Site B. However, after fully opening for traffic, greater rut depths were observed on each section due to the additional compaction under the wheel paths. The permeability of the PRP sections ranged from 28368 mm/h to 45605 mm/h, which is higher than the highest rainfall rate in Canada (298.8 mm/h). However, most of the sections showed higher permeability in the 2nd test. After the first winter, the permeability of some of the sections was found to be further increased, whereas others were found to be decreased due to the influence of site surroundings. In the 1st and 2nd field tests, no visible surface distress was observed at Site A and Site B. A small amount of surface distress was observed after the first winter (seven months after the construction), which included a slight loss of coarse aggregate, minor ravelling, small cracking, and rutting. Throughout the trial section construction process, it was also observed that by improving the construction methods and making slight modifications during the construction process (like increased compaction), the performance of PRPs could be further enhanced.
Finally, a set of recommendations and guidelines were developed for using the PRP in the Canadian climate
Homeostasis in Immunity-Related Pupal Tissues of the Malaria Mosquito Anopheles gambiae and its regulation by the NF-kappaB-like Factor Rel2
Die Haut ist eine oft übersehene Komponente des angeborenen Immunsystems der Mücken. Die Haut der Mücke bildet eine physische Barriere, die die mikrobielle Homöostase aufrechterhält, das Eindringen von Toxinen wie Insektiziden verhindert und das Austrocknen verhindert. Die am meisten untersuchten Akteure des Immunsystems von Stechmücken sind das Fettgewebe und die Blutzellen, aber die Hauttalg-Fabriken, die Oenozyten, werden in Studien nur selten berücksichtigt.
Mückenpuppen haben aktiv funktionierende immunitätsbezogene Organe, einschließlich derjenigen, die Hautbarrieren produzieren. Ihre biologische Rolle in diesem Entwicklungsstadium ist kaum bekannt, aber der Übergang von der Puppen- zur Erwachsenenhaut und die Auffälligkeit der talgproduzierenden Zellen machen dieses Stadium zu einem vielversprechenden Entwicklungsstadium für die Untersuchung der Hautbildung.
Mit Hilfe der Transkriptomanalyse beschreiben wir die Rolle der Blutzellen bei der Entwicklung des chitinösen Teils der Insektenhaut, die Beteiligung des Fettkörpers an der Immunität und bestätigen die Rolle der talgproduzierenden Zellen im Lipidstoffwechsel. Darüber hinaus beschreiben wir talgsezernierende Zellen als einen bedeutenden Wirkungsort des NF-kappaB-ähnlichen IMD-Rel2-Pathway, in dem der Transkriptionsfaktor Rel2 die Retinoid-Homöostase reguliert. Schließlich bestätigen wir eine 100 Jahre alte Beobachtung, wonach sebumsezernierende Zellen der Stechmücke ihren Zellinhalt in einem Netzwerk von Vesikeln absondern. Wir beschreiben extrazelluläres Chromatin als Fracht in diesem Vesikelnetzwerk und sein antimikrobielles Potenzial.The skin is an often overlooked component of the mosquito's innate immune system. The mosquito skin provides a physical barrier that maintains microbial homeostasis, prevents the entry of toxins like insecticides, and avoids desiccation. The most studied players in the immune system of mosquitoes are the adipose tissue and blood cells, but studies rarely consider the skin sebum factories, oenocytes.
Mosquito pupae have actively functional immunity-related organs, including those producing skin barriers. Their biological roles at this developmental stage are poorly understood, but the pupae-to-adult metamorphic skin transition and the conspicuity of sebum-secreting cells make it a promising developmental stage to study skin formation.
We use transcriptomics to describe the role of blood cells in the development of the chitinous section of the insect skin, the involvement of the fat body in immunity, and confirm the lipid metabolism role of sebum-secreting cells. Furthermore, we describe sebum-secreting cells as a significant action site of the NF-kappaB-like IMD-Rel2 pathway where the transcription factor Rel2 regulates retinoid homeostasis. Finally, we confirm a 100-year-old observation of how mosquito sebum-secreting cells secrete their cellular contents in a network of vesicles. We describe extracellular chromatin as cargo inside this vesicle network and its antimicrobial potential
Quantum dots based superluminescent diodes and photonic crystal surface emitting lasers
This thesis reports the design, fabrication, and electrical and optical characterisations of GaAs-based quantum dot (QD) photonic devices, specifically focusing on superluminescent diodes (SLDs) and photonic crystal surface-emitting lasers (PCSELs). The integration of QD active regions in these devices is advantageous due to their characteristics such as temperature insensitivity, feedback insensitivity, and ability to utilise the ground state (GS) and excited state (ES) of the dots.
In an initial study concerning the fabrication of QD-SLDs, the influence of ridge waveguide etch depth on the electrical and optical properties of the devices are investigated. It is shown that the output power and modal gain from shallow etched ridge waveguide is higher than those of deep etched waveguides. Subsequently, the thermal performance of the devices is analysed. With increased temperature over 170 ºC, the spectral bandwidth is dramatically increased by thermally excited carrier transition in excited states of the dots.
Following this, an investigation of a high dot density hybrid quantum well/ quantum dot (QW/QD) active structure for broadband, high-modal gain SLDs is presented. The influence of the number of QD layers on the modal gain of hybrid QW/QD structures is analysed. It is shown that higher number of dot layer provides higher modal gain value, however, there is lack of emission from QW due to the requirement of large number of carriers to saturate the QD. Additionally, a comparison is made between “unchirped QD” and “ chirped QD” of hybrid QW/QD structure in terms of modal gain and spectral bandwidth. It is showed that “chirped” of the QD can improve the “flatness” of the spectral bandwidth.
Lastly, the use of self-assembled InAs QD as the active material in epitaxially regrown GaAs-based PCSELs is explored for the first time. Initially, it is shown that both GS and ES lasing can be achieved for QD-PCSELs by changing the grating period of the photonic crystal (PC). The careful design of these grating periods allows lasing from neighbouring devices at GS ( ~1230 nm) and ES (~1140 nm), 90 nm apart in wavelength. Following this, the effect of device area, PC etch depth, PC atom shape (circle or triangle or orientation) on lasing performance is presented. It is shown that lower threshold current density and higher slope efficiencies is achieved with increasing the device size. The deeper PC height device has higher output power due to more suitable height and minimal distance to active region. The triangular atom shape has slightly higher slope efficiency compared to triangular atom shape which is attributed to breaking in-plane symmetry and increase out-of-plane emission
Neuroanatomical and gene expression features of the rabbit accessory olfactory system. Implications of pheromone communication in reproductive behaviour and animal physiology
Mainly driven by the vomeronasal system (VNS), pheromone
communication is involved in many species-specific fundamental innate socio-sexual behaviors such as mating and
fighting, which are essential for animal reproduction and survival. Rabbits are a unique model for studying
chemocommunication due to the discovery of the rabbit mammary pheromone, but paradoxically there has been a
lack of knowledge regarding its VNS pathway. In this work, we aim at filling this gap by approaching the system
from an integrative point of view, providing extensive anatomical and genomic data of the rabbit VNS, as well as
pheromone-mediated reproductive and behavioural studies. Our results build strong foundation for further
translational studies which aim at implementing the use of pheromones to improve animal production and welfare
Towards personalized immunotherapy : development of in vitro models for imaging natural killer cell behavior in the tumor microenvironment
Tremendous advances in the tumor immunology field have transformed immunotherapy
from a promising approach to a standard clinical practice. However, a subset of cancer
patients is non-responsive to immunotherapy. More research is therefore needed to
understand the mechanisms underlying tumor resistance to immunotherapeutic treatments.
The aim of this doctoral work was to develop new tools to study the mechanisms of cancer
immunosurveillance and to test immunotherapeutic treatments in vitro. In this thesis, I
describe the methods developed, and I discuss the main biological findings obtained by
using these methods.
The thesis is organized as follows. A short historical background of immunotherapy is
provided in Chapter 1. Chapter 2 describes the principles of NK cell-mediated cancer
immunosurveillance, and provides an overview on rare cancers, mainly focusing on
sarcoma. The research aims are listed in Chapter 3. In Chapter 4, I describe the cell culture
methods and cell analysis techniques relevant for my doctoral work. In Chapter 5, I
describe the methods we developed to culture tumor spheroids in vitro using ultrasonic
standing waves in microwell chips, focusing on the theory, design, and applications.
Chapter 6 and Chapter 7 focus on the biological findings obtained using our platform in
combination with traditional immunological methods, followed by future implementations
discussed in Chapter 8. The constituent papers are provided at the end of the thesis.
In Paper I, we combined the use of the microwell chip, ultrasonic standing waves and a
protein-repellent polymer coating to enable the production of spheroids from multiple cell
types. In absence of cell adhesion to the chip, spheroids could be collected and further
analyzed by off-the-chip techniques.
In Paper II, we designed a novel multichambered microwell chip to perform multiplexed
fluorescence screening of two- or three-dimensional cell cultures. The platform allows the
direct assessment of drug or immune cell cytotoxic efficacy, making it a promising tool for
individualized cytotoxicity tests for personalized medicine.
In Paper III, we investigate the function of PVR receptors in NK cells interacting with
renal carcinoma spheroids, and the impact of PVR in NK cell-based cellular
immunotherapy. We demonstrated that variations in PVR expression are primarily
recognized by the inhibitory receptor TIGIT, while DNAM-1 strongly contributes to NK
cell activation mainly through PVR-independent mechanisms. We performed NK
cell-based cytotoxicity assays against renal carcinoma spheroids in the microwell chip.
Anti-TIGIT treatment was effective only for TIGIThigh NK cells both when used as
monotherapy or in combination with other drugs, suggesting that only a fraction of patients
might respond to anti-TIGIT therapy.
In Paper IV, a similar approach was used with primary sarcomas. We cultured
patient-derived sarcoma spheroids and tested NK cell-based immunotherapy in the
microwell chip, either alone or in combination with antibody therapy, and we identified
promising treatment combinations.
In Paper V, we applied the use of expansion microscopy to visualize NK cells infiltrating
renal carcinoma spheroids. In conclusion, our multi-disciplinary work shows the
development of new imaging-based platform and its use to study the mechanisms of NK
cell-mediated tumor surveillance and for personalized therapy
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After Creation: Intergovernmental Organizations and Member State Governments as Co-Participants in an Authority Relationship
This is a re-amalgamation of what started as one manuscript and became two when the length proved to be more than any publisher wanted to consider. The splitting consisted of removing what are now Parts 3, 4, and 5 so that the manuscript focused on the outcome-related shared beliefs holding an authority relationship together. Those parts were last worked on in 2018. The rest were last worked on in late 2021 but also remain incomplete.
The relational approach adopted in this study treats intergovernmental organizations and the governments of member states as co-participants in an authority relationship with the governments of their member states. Authority relationships link two types of actor, defined by their authority-holder or addressee role in the relationship, through a set of shared beliefs about why the relationship exists and how the participants should fulfill their respective roles. The IGO as authority holder has a role that includes a right to instruct other actors about what they should or should not do; the governments of member states as addressees are expected to comply with the instructions. Three sets of shared beliefs provide the conceptual “glue” holding the relationship together. The first defines the goal of the collective effort, providing both the rationale for having the authority relationship and providing a lode star for assessments of the collective effort’s success or lack of success. The second set defines the shared understanding about allocation of roles and the process of interaction by establishing shared expectations about a) the selection process by which particular actors acquire authority holder roles, b) the definitions identifying one or more categories of addressees expected to follow instructions, and c) the procedures through which the authority holder issues instructions. The third set focus on the outcomes of cooperation through the relationship by defining a) the substantive areas in which the authority holder may issue instructions, b) the bases for assessing the relevance actions mandated in instructions for reaching the goal, and c) the relative efficacy of action paths chosen for reaching the goal as compared to other possible action paths.
Using an authority relationship framework for analyzing cooperation through IGOs highlights the inherently bi-directional nature of IGO-member government activity by viewing their interaction as involving a three-step process in which the IGO as authority holder decides when to issue what instruction, the member state governments as followers react to the instruction with anything from prompt and full compliance through various forms of pushback to outright rejection, and the IGO as authority holder responds to how the followers react with efforts to increase individual compliance with instructions and reinforce continuing acceptance of the authority relationship. Foregrounding the dynamics produced by the interaction of these two streams of perception and action reveals more clearly how far intergovernmental organizations acquire capacity to operate as independent actors, the dynamic ways they maintain that capacity, and how much they influence member governments’ beliefs and actions at different times. The approach fosters better understanding of why, when, and for how long governments choose cooperation through an IGO even in periods of rising unilateralism
II tüüpi kollageeni neoepitoop C2C uriinis kui põlve osteoartriidi diagnoosimise ja kulu prognoosimise biomarker
Väitekirja elektrooniline versioon ei sisalda publikatsiooneOsteoartriit (OA) on sagedasim liigeshaigus, tabades ligi poolt miljardit inimest maailmas. Põlv on üks peamisi kahjustuskohti. Haiguse kaasaegse käsitluse järgi arenevad kahjustused molekulaarsetest muutustest kuni kudede (kõhr, luu, sünoviaalkest, menisk, sidemed) struktuuri muutusteni. OA on aastate jooksul ebaühtlase kiirusega süvenev haigus, mille puhul stabiilsemad perioodid vahelduvad kiiremate muutustega, kulgedes varajases järgus haigustunnusteta. Seetõttu pakuvad kudede ainevahetuse muutusi peegeldavad molekulaarsed markerid varajast hoiatust koekahjustuse tekkest, võimalust hinnata haiguse kulgu ning tulevikus ka ravivastust. Kuna II tüüpi kollageen (Kol2) on kõhre peamine struktuurne komponent, on OA hindamiseks loodud mitmeid Kol2 lammutamist mõõtvaid teste. Käesolevas uurimuses hindasime OA uue biomarkeri, uC2C kasutusvõimalusi põlve OA (pOA) korral. uC2C on Kol2 lõhustumise neoepitoop C2C uriinis. Võrdlesime uC2C väärtusi röntgenleiu, kõhre otsese vaatlusleiu ja patsiendi kliinilise seisundiga, kasutades erinevaid statistilisi mudeleid. Selgus, et uC2C on sobiv kandidaat pOA varajase diagnostilise testi arendamiseks. C2C sisaldus tõuseb juba haiguse varajases järgus ja on seotud haiguse mitme põhiprotsessiga: kõhre lammutamise ja luukasviste tekkega põlveliigese eri osades. uC2C on hea progressioonimarker naistel: uC2C kõrgem algväärtus ennustab naistel väga hästi (>90%) pOA teket või süvenemist järgneva 3 aasta jooksul. uC2C tase on kõrgem suuremate röntgenmuutuste korral, seega uC2C tase on seotud pOA raskusastmega. uC2C väärtused on suurimad kOA lõppjärgus olevatel haigetel, kes jõuavad liigeseasenduseni suhteliselt noorelt (50–70 a vanuses). Pärast põlveliigese asendamist võib C2C eritumine uriiniga väheneda, suureneda või jääda muutumatuks. Seega ei peata liigeseasendus paljudel juhtudel Kol2 lammutamist organismis ja OA on süsteemsem haigus, kui on seni arvatud. uC2C näib olevat naistel võrreldes meestega parem pOA biomarker.Osteoarthritis (OA) is the most common joint disease, affecting about half a billion people worldwide. The knee is one of the main sites of impairment. According to the new approach to the disease, the alterations develop from the molecular level to structural changes in tissues (cartilage, bone, synovium, meniscus, ligaments). OA is a disease with an alternating course, with no signs of disease at an early stage. Therefore, molecular markers that reflect changes in tissue metabolism provide an early warning of tissue damage, an opportunity to assess the course of the disease, and a response to future treatment. Because type II collagen (Col2) is a major structural component of cartilage, several tests have been developed to measure Col2 degradation. In the current study, we evaluated the potential use of a new OA biomarker, C2C, in knee OA (kOA). uC2C is a Col2 cleavage neoepitope in urine. We compared uC2C values with X-ray findings, direct visual assessment of cartilage, and clinical status using different statistical models. uC2C is a good candidate for the development of an early diagnostic test for kOA. The level of uC2C is increased in the early stages of kOA and is related to several main processes of kOA: the cartilage lesions and the osteophytes in distinct knee compartments. uC2C is a good marker of progression in women–a higher baseline uC2C is an excellent predictor (> 90%) of the initiation or worsening of kOA over the next 3 years. uC2C is higher in higher X-ray grades, so uC2C levels are associated with the severity of kOA. uC2C values are highest in patients with end-stage kOA who reach joint replacement at a relatively young age (50-70 years). After knee replacement, urinary excretion of C2C may decrease, increase, or remain unchanged. Thus, in many cases, joint replacement does not stop the breakdown of Col2 in the body, and OA is a more systemic disease than previously thought. uC2C appears to be a better biomarker of pOA in women than in men.https://www.ester.ee/record=b550707
Hunting Wildlife in the Tropics and Subtropics
The hunting of wild animals for their meat has been a crucial activity in the evolution of humans. It continues to be an essential source of food and a generator of income for millions of Indigenous and rural communities worldwide. Conservationists rightly fear that excessive hunting of many animal species will cause their demise, as has already happened throughout the Anthropocene. Many species of large mammals and birds have been decimated or annihilated due to overhunting by humans. If such pressures continue, many other species will meet the same fate. Equally, if the use of wildlife resources is to continue by those who depend on it, sustainable practices must be implemented. These communities need to remain or become custodians of the wildlife resources within their lands, for their own well-being as well as for biodiversity in general. This title is also available via Open Access on Cambridge Core
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