The connection between C-reactive protein (CRP) and atherosclerosis lies on three grounds. First, the concentration of CRP in the serum, which is measured by using highly sensitive (a.k.a. 'hs') techniques, correlates with the occurrence of cardiovascular disease. Second, although CRP binds only to Fcγ receptor-bearing cells and, in general, to apoptotic and damaged cells, almost every type of cultured mammalian cells has been shown to respond to CRP treatment. Many of these responses indicate proatherogenic functions of CRP but are being reinvestigated using CRP preparations that are free of endotoxins, sodium azide, and biologically active peptides derived from the protein itself. Third, CRP binds to modified forms of low-density lipoprotein (LDL), and, when aggregated, CRP can bind to native LDL as well. Accordingly, CRP is seen with LDL and damaged cells at the atherosclerotic lesions and myocardial infarcts. In experimental rats, human CRP was found to increase the infarct size, an effect that could be abrogated by blocking CRP-mediated complement activation. In the Apob 100/100 Ldlr -/- murine model of atherosclerosis, human CRP was shown to be atheroprotective, and the importance of CRP-LDL interactions in this protection was noted. Despite all this, at the end, the question whether CRP can protect humans from developing atherosclerosis remains unanswered.

Oxidized low-density lipoproteins (OxLDL) mediate many of the pathological events associated with atherosclerosis. Oxysterols, the major cytotoxic component of OxLDL, induce apoptosis in macrophages by a calcium flux mediated activation of cytosolic phospholipase A2 resulting in the release of arachidonic acid (AA). Inhibition of AA metabolism has been shown to protect macrophages from oxysterol-induced apoptosis. The current study explores the steps in the oxysterol-induced apoptosis signaling pathway in murine macrophages subsequent to the liberation of AA. To elucidate this mechanism, two oxysterols, 7-ketocholesterol and 25-hydroxycholesterol (25-OHC), were used to induce apoptosis in murine macrophage cell lines (P388D1, and Raw 264.7) and mouse peritoneal macrophages (MPMs). Pharmacological inhibition of eicosanoid synthesis or genetic knockout of important eicosanoid biosynthetic genes had no significant effect on the induction of apoptosis by oxysterols in macrophages. The induction of apoptosis in macrophage cell lines and MPMs by oxysterols and OxLDL was suppressed by Sandoz 58-035, an inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT). Furthermore, in comparison to wild-type MPMs, ACAT-1 deficient MPMs were found to be resistant to apoptosis induced by oxysterols or OxLDL. Macrophages treated with 7KC accumulated ACAT-derived cholesteryl and 7-ketocholesteryl esters. An inhibitor of cholesterol trafficking, U18666A, specifically prevented the accumulation of cholesteryl esters, but not 7-ketocholesteryl esters nor the induction of apoptosis. An inhibitor of cPLA2 prevented the accumulation of 7-ketocholesteryl esters. This inhibition was reversed by supplementing oleic acid or AA; however, only AA supplementation restored the induction of apoptosis. These results suggest that oxysterols not only initiate the apoptosis pathway by activating cPLA2, but also participate in the downstream signaling pathway when esterified by ACAT to form arachidonyl oxysterols. We also demonstrate that macrophages lacking the cannabinoid type-2 (CB2) receptor have reduced levels of apoptosis when treated with oxysterols or OxLDL in comparison to wild-type macrophages and that a CB2 specific antagonist blocks oxysterol-induced apoptosis in macrophages suggesting that the CB2 receptor is involved in this pathway, perhaps by interacting with the arachidonyl oxysterols.

<p> This study examines the problem of "rurbanization," which is a term that has been applied to the process by which rural areas are being changed by urban influences. This implies more than the traditional geographic concept of land-use change at the rural-urban fringe, but is concerned with bagic changes in the agricultural industry relating to appearance, land use, nengity and social structure.</p> <p> In rural Southern Ontario, there are two main phenomena occurring to effect these changes: the increage in part-time farming and in low-density residences. This study is concerned more specifically with an examination of these two phenomena. Its two main objectives are to gee how these two are interrelated and how they have affected agriculture and rural society. </p> <p> The study achieveg thege objectives through the use of a questionnaire admtnigtered to residents of Brantford township, a rural area with a thriving agricultural industry, but at the same time under considerable stress from urban pressures. Three types of residents were surveyed: full- time farmers, part-time farmers and non-farmers. The data collected was subjected to discriminant and cross-tabulation analyses in order to observe similarities and differences among the three groups . These similarities and differences allowed inferences concerning the acceptance or rejection of six postulated hypotheses. </p> <p> The following general conclusions result from the analysis: </p> <p> Part-time farmers and rural non-farmers are predominantly former urbanites who have migrated to rural areas. Both groups share similar occupations and have lived at the rural location for a similar length of time, but non-farmers tend to be older an to have been born and raised on a farm. However, there does exist a significant minority of part-time farmers who ere former full-time farmers. Both phenomena appear to be fairly permanent arrangements as the overwhelming majority of both groups wished to maintain their present status. </p> <p>Full-time farmers tend to have a larger size of holding than part-time farmers. Part-time farmers place less emphasis on livestock and tobacco as the predominant crop than do full-time farmers, and tend to place a greater emphasis upon corn and mixed grains as cash crops. The type and quality of land that is occupied and the attitude toward the preservation of agricultural land do not vary significantly by group. All three groups were strongly in favour of preservation of land for farming. The participation rates of part time and non farmers in the rural organizations of the township and in the urban organizations of nearby towns are not significantly different from those of full-time farmers. </p> <p> The study has confirmed some of the findings of other researchers and has in turn shed some new light on the "rurbanization" problem. Urban out-migration has been found to be the most important cause of the problem. Thus, the problem appears to be the result of a social phenomenon rather than a physical one, and the phenomena causing the problem appear to be persistent and permanent. It may also be noted that the choice of alternative, either part-time farming or non-farming residency, is somehow related to the age and location of birth and childhood of the urban out-migrant. Significantly, more part-time farmers were born in city and more non-farmers were born on a farm. It may be argued that is precisely opposite to the situation that might be expected. / Thesis / Bachelor of Arts (BA)

Background Patterns of dyslipidemia and incidence of hypertension have been rarely reported in Asian populations with inconsistent findings. To accumulate further evidence in Asian populations, the study aimed to investigate the relationship between lipid profiles and hypertension in Chinese adult males. Methods We conducted a cross-sectional study based on the data from the DATADRYAD database. The overall population was divided into hypertensive and non-hypertensive groups based on baseline blood pressure levels. For continuous variables, Mann-Whitney test was performed between two groups, while Kruskal-Wallis and Dunn tests were used among multiple groups. The chi-square test was carried out for dichotomous variables. Spearman's correlation coefficient was employed to assess the association between systolic blood pressure (SBP), diastolic blood pressure (DBP) and lipid profiles, whereas the relationship between lipid profiles and the incidence of hypertension was evaluated using multivariate logistic regression. The Bayesian network (BN) model was adopted to investigate the relationship between clinical characteristics and hypertension, and the importance of related predictor to the incidence of hypertension was obtained to make conditional probability analysis. Results Finally, totally 62,957 participants were included in this study. In the lipid profiles, total cholesterol (TC), low-density cholesterol (LDL-c), and non- high-density lipoprotein cholesterol (non-HDL-c) were higher in the hypertensive population (p <0.001). In the fully multivariate model, for every 1 mg/dl increase in TC, LDL-c and non-HDL, the risk of hypertension increased by 0.2% [1.002 (1.001–1.003)], 0.1% [1.001 (1.000–1.002)], and 0.1% [1.001 (1.000–1.002)]. Meanwhile, HDL-c became positively associated with the incidence of hypertension (p for trend < 0.001) after adjusting for the body mass index (BMI), and 1 mg/dl increment in HDL-c increased the risk of hypertension by 0.2% [1.002 (1.000–1.002)] after fully adjusting for multiple variables. Furthermore, the BN showed that the importance of age, BMI, fasting plasma glucose (FPG), and TC to the effect of hypertension is 43.3, 27.2, 11.8, and 5.1%, respectively. Conclusion Elevated TC, LDL-c, and non-HDL-c were related to incidence of hypertension in Chinese adult males, whereas triglycerides (TG) was not significantly associated. The relationship between HDL-c and hypertension incidence shifted from no association to a positive correlation after adjusting for the BMI. Moreover, the BN model displayed that age, the BMI, FPG, and TC were strongly associated with hypertension incidence.

Background: Dyslipidemia is strongly associated with the development of hypertension. In our previous study, it was shown that elevated TC, LDL-c, and non-HDL-c were associated with the prevalence of hypertension in Chinese men, whereas the relationship between HDL-c and hypertension shifted from no association to a positive association after adjusting for the BMI. To further accumulate epidemiological evidence in Asian women, this study aimed to investigate the relationship between lipid profile and prevalence of hypertension in Chinese adult women. Methods: This is a cross-sectional study including 54,099 Chinese women aged>20 years at 32 health screening centers in 11 cities from 2010-2016. The original data were obtained from DATADRYAD database (www.datadryad.org). Besides, the overall women were classified into non-hypertensive and hypertensive groups based on baseline blood pressure levels. Differences between the two groups were examined by Man-Whitney test or Chi-square test. Spearman’s correlation coefficient was employed to evaluate the correlation between systolic blood pressure (SBP), diastolic blood pressure (DBP) and lipid profiles. Multivariate logistic regression was performed to estimate the relationship between different lipid levels and the prevalence of hypertension. Odds ratios (ORs) and 95% confidence intervals (CIs) indicated the risk of lipid and hypertension. Bayesian model (BN) model was constructed to further assess the relationship between baseline characteristics and the prevalence of hypertension, as well as the importance of each variable for the prevalence of hypertension. Results: Compared to the non-hypertensive population, the hypertensive population was older, and had the higher body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), serum creatinine (Scr), fasting blood glucose (FPG), blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and non-high-density lipoprotein cholesterol (non-HDL-c), but HDL-c and the presence concerning the family history of diabetes were lower. Multivariate logistic regression analysis revealed that TC, LDL-c, and non-HDL-c showed a positive trend with hypertension risk (p for trend < 0.05) whereas TC and HDL-c were not significantly associated with hypertension prevalence. Moreover, each 1 mg/dl increase in TC, LDL, and non-HDL hypertension prevalence increased by 0.2% [1.002 (1.000-1.003)], 0.2% [1.002 (1.000- 1.004)], and 0.2% [1.002(1.001-1.004)], respectively. BN suggested that the importance of age, BMI, FPG, non-HDL-c on the prevalence of hypertension was 52.73%, 24.98%, 11.22%, and 2.34%, respectively. Conclusion: Overall, in Chinese adult women, TC, LDL-c and non-HDL-c levels were higher and HDL-c level was lower in the hypertensive population, whereas TG did not differ significantly from the non-hypertensive population. Meanwhile, TC, LDL-c, and non-HDL-c were positively associated with prevalence of hypertension, and HDL-c was negatively associated with prevalence of hypertension but became nonsignificant after full adjustment for variables. Moreover, BN model suggested that age, BMI, FPG, and non-HDL-c had a greater effect on the development of hypertension.

The historical concentration of French mobility policies in urban areas has resulted into a high dependence of the private-car system in low density territories. Therefore, and especially in these areas, mobility is now threatened by a double constraint of carbon. This double constraint is due to the need to curb down green-house gases emissions as well as the expected decrease of oil production from European suppliers in the next decades. In order to face these issues, the Mobility Orientation Law (MOL) was promulgated in 2019 in France. Through a case study of Hauts-de-France low-density inter-municipalities,  this master thesis aims to analyse the effects of this law on geographical inequalities of mobility and on low-carbon mobility in low-density territories.  First, this study explores  the different levers brought by the MOL to these areas. From governance, planning, cooperation and financial evolutions to an analysis of the impulsion of mobility concerns in French low density inter-municipalities, this master thesis sheds light on first key elements raised by the law. Then, this study digs into the possible evolutions of the mobility policies in Hauts-de-France low-density inter-municipalities, based on the current situation in experienced territories. Depending on the polarity of the inter-municipalities, different scenarios of mobility policies evolutions are defined. This enables a better comprehension of the estimated effects from the law on geographical inequalities on mobility and on low-carbon mobility in low-density territories. In fact, the MOL brings necessary but insufficient conditions to the reduction of geographical inequalities and Green House Gazes emissions. / Rörligheten hotas i dag av en dubbel begränsning av karbon. Klimatförändringarna och oljetoppen tvingar oss att förändra våra mobilitetsvanor i grunden. Detta gäller särskilt i områden med låg befolkningstäthet där människor huvudsakligen använder privatbilar. I Frankrike infördes lagen om mobilitetsorientering 2019. Det är en bred lag som tar upp behovet av att utveckla mobilitetsalternativ i dessa områden. Ett viktigt inslag i denna lag är möjligheten att överföra kompetens om rörlighet till mellankommunal nivå.  Denna masteruppsats syftar till att undersöka om och hur lagen om mobilitetsorientering bidrar till att lösa geografiska ojämlikheter i fråga om rörlighet och främja utövandet av koldioxidsnål rörlighet i franska mellankommuner med låg befolkningstäthet. Den bygger huvudsakligen på en studie i Hauts-de-France. Vissa av resultaten kan dock överföras till andra regioner.   Ett frågeformulär skickades ut till 49 nya lokala aktörer inom mobilitet i Hauts-de-France-regionen. Dessa nya lokala aktörer är mellankommuner med låg befolkningstäthet. Vi fick 41 svar från dem. Vi intervjuade också 6 intressanta erfarna  mellankommuner från ett urval av 19 erfarna mellankommuner med låg befolkningstäthet som redan hade kompetens om rörlighet. Dessutom samlade vi in information om dessa mellankommuner med låg befolkningstäthet genom tillgänglig information på Internet och interna källor. Därefter byggde vi upp ett panorama över dessa områden.  Med utgångspunkt i detta panorama analyserade vi de olika åtgärder som lagen medför. Det finns fem huvudsakliga åtgärder som handlar om styrning, planering, samarbete, finansiering och medvetenhet. Lagen ger nya lokala intressenter i områden med låg befolkningstäthet större inflytande. Den ger nya planerings- och samverkansverktyg. Den ger otillräckliga finansiella verktyg men ökar definitivt medvetenheten om rörlighet.   Därefter föreslår vi perspektiv för utvecklingen av rörlighetspolitiken i mellankommuner med låg befolkningstäthet för att mer ingående analysera lagens möjliga effekter på geografiska ojämlikheter i fråga om rörlighet och rörlighet med låga koldioxidutsläpp. Vi definierar tre scenarier baserade på mellankommunens polaritet och på vår panorama.   På det hela taget skapar denna lag nödvändiga men otillräckliga förutsättningar för att möta det dubbla begränsning av karbon och de geografiska ojämlikheterna. Det är dock viktigt att understryka att det inte verkar vara möjligt att utveckla en hållbar rörlighet och samtidigt behålla samma samhälle. Rörlighet kan ses som en konsekvens av hur mänsklig verksamhet utvecklas i vårt samhälle. Eftersom miljöhänsyn kommer att tvinga mänsklig verksamhet att förändras kommer även den resulterande rörligheten att förandras. Denna lag är därför ett första bra steg mot en systemisk förändring.

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In this research study, a strategy was used for assigning stiffness values to various layers of the pavement system so that there are negligible tensile stresses in the subgrade and base layers. The stiffnesses of the aggregate base layers were assigned double the values of the corresponding subgrade materials. The layer thicknesses were designed to achieve surface deflection values within the acceptable limit. An innovative design procedure was developed for designing pavement sections covering various layer thicknesses, material and environmental variables. The designed sections were compared with the American Association of State Highway and Transportation Officials (AASHTO) procedure and the differences were critiqued. Porous asphalt layer was used as the surface course for all pavement sections. The calculations validated the general principle of pavement design, as the subgrade stiffness decreased the base thickness increased for the same surface course thickness and traffic. Structural design of 63 pavements sections was accomplished representing various temperature and materials including additives. Low Density Polyethylene, performance graded asphalt, different soils, aggregates, lime and cement were the component materials utilized in this research study. An explanation on the mechanics of the mixtures is given in the results and discussion section. / Civil Engineering

The liver regulates inflammation during sepsis, and most liver functions are carried out by hepatocytes. Bacterial lipids, including lipopolysaccharide (LPS) and lipoteichoic acid (LTA), can be cleared by hepatocytes, but the underlying mechanisms are uncertain. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates uptake of LPS by hepatocytes, but it is unknown whether LTA uptake is similarly regulated. Therefore, our objectives were to characterize the PCSK9-regulated pathway of bacterial lipid uptake by hepatocytes by identifying whether low-density lipoprotein (LDL) receptor (LDLR) and LDLR-related protein 1 (LRP1) are the target receptors, and by determining which lipoproteins are involved. To study this pathway, we assessed the uptake of fluorescently-labeled LPS or LTA by human HepG2 hepatocytes using flow cytometry. We pre-treated HepG2 cells with PCSK9, alone or in combination with anti-LDLR or anti-LRP1 antibodies, in order to identify the PCSK9-regulated receptors that are involved, and utilized media containing normal serum or lipoprotein-deficient serum to investigate the lipoprotein- dependence of this pathway. We also determined the roles of LDL and HDL in bacterial lipid uptake through a series of add-back experiments to lipoprotein-deficient serum, and blocked LDLR to confirm that LDLR mediates LDL-dependent uptake. The HepG2 cell response to variable degrees of bacterial lipid uptake was also assessed in a subset of experiments by measuring several cytokines and extracellular alanine aminotransferase (ALT) activity in the cell culture supernatant. We found that PCSK9 regulates LDLR-mediated uptake of both LPS and LTA through an LDL-dependent mechanism, while LRP1 is not involved. Increased bacterial lipid uptake did not result in any hepatocellular injury or cytokine production, as measured by ALT activity and interleukin (IL)-6, IL-8, IL-10, and IL-17 concentrations. In conclusion, we completed our objective of characterizing the PCSK9-regulated pathway of bacterial lipid uptake, and provide supporting evidence for targeting PCSK9 as a novel therapeutic avenue in sepsis. / Thesis / Master of Science (MSc) / Bacterial compounds stimulate inflammation that can be overwhelming during sepsis. Understanding the processes behind uptake and clearance of these compounds may lead to better sepsis treatments. Therefore, our goal was to understand how uptake of two bacterial compounds, lipopolysaccharide and lipoteichoic acid, occurs by liver cells called hepatocytes. Hepatocytes are naturally equipped to clear foreign compounds, so understanding their role in clearing bacterial compounds is important. Another goal was to identify the role of the protein PCSK9 in this uptake process, as treatments targeting PCSK9 could be applied to sepsis once we understand its role in this disease. Our research demonstrates the negative role of PCSK9 in regulating uptake of lipopolysaccharide and lipoteichoic acid through a lipoprotein receptor called LDLR, and identifies the role of lipoproteins in this process. These findings further our understanding of the hepatocyte response to bacterial compounds in relation to sepsis, and identify PCSK9 as a potential target for new sepsis therapies.