Peripheral arterial occlusive disease (PAOD) often presents as intermittent claudication, which may be caused by impaired vasodilation. Impairment of resistance vessels may contribute to the pathogenesis of PAOD, and explain the poor correlation between resting blood flow and limb function. Collateral function following arterial occlusion is not well defined, however collaterals and arterialized collateral capillaries (ACCs) in male and female animal models exhibit impaired vasodilation following arterial occlusion, which can potentially be improved with exercise training. Furthermore, resistance vessels in the ischemic tree and stem are likely involved in the pathogenesis of PAOD, however the relative importance of each is unknown. Therefore, we measured functional vasodilation in pre-existing collaterals, ACCs, the ischemic tree, and the stem region, 7 and 21-days following spinotrapezius feed artery ligation in male and female BALB/c mice, and with exercise therapy. Vasodilation in ACCs was more impaired in female mice than in males. Generally, vasodilation was impaired at day-7, likely due to impaired endothelium-dependent and smooth muscle-dependent vasodilation in maturing collaterals, and recovered by day-21. Exercise training appears to enhance collateral reactivity, more in ACCs in males than in females, suggesting that its therapeutic benefits are linked not only to structural adaptation but also to vessel functionality. Therefore, future research is required to determine the cause of sex differences in exercise therapy to treat peripheral arterial occlusive disease.

Peripheral arterial occlusive disease (PAOD) is characterized by buildup of atherosclerotic plaque in peripheral arteries that leads to an occlusion that can interrupt the supply of blood to the peripheral tissue, causing downstream tissue ischemia/hypoxia. PAOD is estimated to affect over 200 million patients worldwide. Current surgical revascularization treatments can be effective in about half of the patient population, leading to a significant number of patients with no treatment options beyond pharmacological intervention and lifestyle modification. The decrease in blood flow downstream of the occlusion leads to increased blood pressure gradient in the microvasculature, specifically in vessels that connect arterial trees (known as collaterals), which will structurally enlarge and increase blood flow to the downstream ischemic/hypoxic tissue. Targeting this process, known as arteriogenesis, can provide a potential treatment option for patients suffering from PAOD by redirecting blood flow around an occluded artery and therefore supplying hypoxic tissue with blood. In order to enhance this process, cellular transplantation has been used but the current cell types explored have not been successful in enhancing arteriogenesis. Myoblasts, proliferative muscle progenitor cells, mediate muscle regeneration, and promote angiogenesis (the growth of new capillaries to supply hypoxic tissue). Preliminary data indicates that myoblasts also promote arteriogenesis in obese mice, making them an attractive therapeutic candidate. However, the methods used in the preliminary studies limited our ability to confirm those findings and characterize the cell therapy candidate. Specifically, we lacked a reproducible and optimized method to isolate myogenic cells and characterize these cells during in vitro culture and after in vivo transplantation. Therefore, the 1st Aim of this study was to optimize the isolation to obtain the highest number possible of satellite cell-yielding myofibers by modification of enzymatic and mechanical digestion of extensor digitorum longus muscle. Modifications to this methodology increased myofiber yield by more than 150%. The 2nd Aim was to optimize the expansion of satellite cell-derived myoblasts by modification of culture media supplements to promote cell expansion while minimizing maturation. bFGF and SB 203580 supplementation improved cell proliferation and prevented myogenic cell maturation during 7-days of in vitro culture. The 3rd Aim was to develop a process for evaluating the quantity and identity of isolated myogenic cells before and after transplantation. This was achieved by implementing an immunofluorescent transcription factor labeling protocol to determine cell identity and a live/dead cell viability assay to determine cell viability and quantity. All 3 aims were integrated into a proof-of-concept pilot study on a hindlimb ischemic BALB/c mouse model. While myoblast transplantation failed to increase collateral arteriogenesis in this model, the process developed in this project provides a reproducible framework for future studies on myoblast-enhanced arteriogenesis. Further research on the effects of myoblast transplantation on arteriogenesis may facilitate the development of new therapies that improve the prognosis of patients with PAOD.

This thesis examines the transmission of monetary policy and the effects of persistent cost-push shocks in the presence of high household indebtedness (DTI) and frictions in fixed-rate mortgage (FRM) interest rates. A dynamic stochastic general equilibrium (DSGE) model incorporating housing, household debt, and long-term FRMs is estimated to accomplish this. The key findings can be summarized as follows: (i) A higher DTI leads to a stronger transmission of monetary policy, although this effect is dampened by the degree of interest rate fixation periods. (ii) Cost-push shocks propagates more strongly to inflation when the interest rate fixation periods is longer, resulting in delayed and slightly muted effects on output and consumption compared to adjustable-rate mortgages (ARM). (iii) While stronger responses to inflation help mitigate the cost-push shock, this comes at the expense of a larger output gap but with a slightly faster stabilization of the economy with a somewhat steeper recovery.

Indiana University-Purdue University Indianapolis (IUPUI) / Collateral connections in the brain, also known as Leptomeningeal Anastomoses, are connections between blood vessels originating from different arteries. Despite limited knowledge, they are suggested as an important contributor to cerebral stroke recovery that allows additional blood flow through the affected area. However, few databases and algorithms exist for this specific task of locating them. In this paper, a MATLAB program is developed to find these connections and detect strokes to replace manual labeling by professionals. The limited data available for this study are 23 2D microscopy images of mice cerebral vascular structures highlighted by dyes. In the images, strokes are shown to diminish the pixel count of vessels below 80\% compared to the healthy brain. Stroke classification error is greatly reduced by narrowing the scope from comparing the entire hemisphere to one smaller region. A novel way of finding collateral connections is utilizing connected components. Connected components organize all adjacent pixels into a group. All collateral connections can be found on the border of two neighboring arterial flow regions, and belong to the same group of connected components with the arterial source from each side. Along with finding collateral connections, a newly created coordinate system allows regions to be defined relative to the brain landmarks, based on the brain's center, orientation, and scale. The method newly proposed in this paper combines stroke detection, brain coordinate system extraction, and collateral connection detection in stroke-affected mouse brains using only image processing techniques. This allows a simpler, more explainable result on limited data than other techniques such as supervised machine learning. In addition, the new method does not require ground truth and high image count for training. This automated process was successfully interpreted by medical experts, which allows for further research into automating collateral connection detection in 3D.

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<p>Obemannade flygplan med attackförmåga (UCAV) används i allt större utsträckning i konflikter idag. En av de främsta fördelarna med dessa är att det inte finns någon risk att mista en pilot, då dessa är fjärstyrda. I attacker utförda av amerikanska UCAV:er i framför allt Afghanistan och Pakistan, har collateral damage inträffat vid ett flertal tillfällen. Det innebär att civila oavsiktligt fallit offer för attacker. Enligt krigets lagar kan sådana händelser rättfärdigas av att militär nödvändighet föreligger, men det är tveksamt om det går att hävda det när man inte riskerar egna förluster. Detta innebär i så fall att collateral damage alltid är krigsbrott när det orsakats av UCAV. Då är det viktigt att det går att utkräva ansvar ur obemannade system och det finns farhågor att ansvarsförhållandena blir otydligare när det inte sitter en pilot i flygplanet som ”trycker på knappen”. Men så länge den obemannade farkosten fjärrstyrs och besluten tas av en människa går det inte att se några skillnader i möjligheten till ansvarsutkrävande från bemannade system.</p> / <p>The use of Unmanned combat aerial vehicles (UCAV) has seen an increasing use in modern conflicts. One of the main advantages of these is the fact that there is no risk of losing a pilot, as the aircraft are remote-controlled. The attacks carried out by U.S. UCAVs in Afghanistan and Pakistan have resultet in a number of incients with collateral damage. According to the laws of war, only military necessity can justify such incidents and it is highly doubtful if you can claim such necessity when you do not risk any loss of life yourself. This would mean that collateral damage caused by UCAVs automatically becomes a war crime. This raises the issue of accountability and wether it is possible to extract such from unmanned systems. There are fears that this would be difficult when no pilot is present in the aircraft to ”pull the trigger”. However, as long as operators remotely control the unmanned aircraft and the decision to release weapons in anger are made by humans, there are no differences to be found in terms of accountability between manned and unmanned systems.</p>

Obemannade flygplan med attackförmåga (UCAV) används i allt större utsträckning i konflikter idag. En av de främsta fördelarna med dessa är att det inte finns någon risk att mista en pilot, då dessa är fjärstyrda. I attacker utförda av amerikanska UCAV:er i framför allt Afghanistan och Pakistan, har collateral damage inträffat vid ett flertal tillfällen. Det innebär att civila oavsiktligt fallit offer för attacker. Enligt krigets lagar kan sådana händelser rättfärdigas av att militär nödvändighet föreligger, men det är tveksamt om det går att hävda det när man inte riskerar egna förluster. Detta innebär i så fall att collateral damage alltid är krigsbrott när det orsakats av UCAV. Då är det viktigt att det går att utkräva ansvar ur obemannade system och det finns farhågor att ansvarsförhållandena blir otydligare när det inte sitter en pilot i flygplanet som ”trycker på knappen”. Men så länge den obemannade farkosten fjärrstyrs och besluten tas av en människa går det inte att se några skillnader i möjligheten till ansvarsutkrävande från bemannade system. / The use of Unmanned combat aerial vehicles (UCAV) has seen an increasing use in modern conflicts. One of the main advantages of these is the fact that there is no risk of losing a pilot, as the aircraft are remote-controlled. The attacks carried out by U.S. UCAVs in Afghanistan and Pakistan have resultet in a number of incients with collateral damage. According to the laws of war, only military necessity can justify such incidents and it is highly doubtful if you can claim such necessity when you do not risk any loss of life yourself. This would mean that collateral damage caused by UCAVs automatically becomes a war crime. This raises the issue of accountability and wether it is possible to extract such from unmanned systems. There are fears that this would be difficult when no pilot is present in the aircraft to ”pull the trigger”. However, as long as operators remotely control the unmanned aircraft and the decision to release weapons in anger are made by humans, there are no differences to be found in terms of accountability between manned and unmanned systems.