Deploying speaker verification techniques to vision-based RPA detect and avoid

Detect and Avoid (DAA) technology is widely acknowledged as a critical enabler for unsegregated Remote Piloted Aircraft (RPA) operations, particularly Beyond Visual Line of Sight (BVLOS). Image-based DAA, in the visible spectrum, is a promising technological option for addressing the challenges DAA presents. Two impediments to progress for this approach are the scarcity of available video footage to train and test algorithms, in conjunction with testing regimes and specifications which facilitate repeatable, statistically valid, performance assessment. This paper includes three key contributions undertaken to address these impediments. In the first instance, we detail our progress towards the creation of a large hybrid collision and near-collision encounter database. Second, we explore the suitability of techniques employed by the biometric research community (Speaker Verification and Language Identification), for DAA performance optimisation and assessment. These techniques include Detection Error Trade-off (DET) curves, Equal Error Rates (EER), and the Detection Cost Function (DCF). Finally, the hybrid database and the speech-based techniques are combined and employed in the assessment of a contemporary, image based DAA system. This system includes stabilisation, morphological filtering and a Hidden Markov Model (HMM) temporal filter.

Epidemiology and Treatment Options of Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) is caused by an autoimmune inflammation of the small bile ducts. It results to destruction of bile ducts, accumulation of the bile in the liver, and cirrhosis. The prevalence and incidence of PBC is increasing in the Western world. The prevalence is highest in the USA (402 per million) and incidence in Scotland (49/million/year). Our aim was to assess the epidemiology of PBC in Finland. Patients for the epidemiological study were searched from the hospital discharge records from year 1988 to 1999.The prevalence rose from 103 to 180/million from 1988 to 1999, an annual increase of 5.1%. The incidence rose from 12 to 17 /million/year, an annual increase of 3.5%. The age at death increased markedly from 65 to 76 years. The risk of liver related deaths diminished over time. The treatment of PBC is based on Ursodeoxycholic acid (UDCA). During 20 years 50% of patients end up with cirrhosis. Our treatment option was to combine budesonide, a potent corticosteroid with a high first pass metabolism in the liver, to UDCA and evaluate the liver effects and systemic effects such as bone mass density (BMD) changes. Our aim was to find out if combination of laboratory tests would serve as a surrogate marker for PBC and help reducing the need for liver biopsy. Non-cirrhotic PBC patients were randomized to receive budesonide 6 mg/day combined to UDCA 15 mg /kg/day or UDCA alone for three years. The combination therapy with UDCA and budesonide was effective: stage improved 22%, fibrosis 25%, and inflammation 32%. In the UDCA group the changes were: 20% deterioriation in stage and 70% in fibrosis, but a 10% improvement in inflammation. BMD in femoral neck decreased by 3.6% in the combination group and by 1.9% in the UDCA group. The reductions in lumbar spine were 2.8% and 0.7%. Pharmacokinetics did not differ between the stages of PBC. HA, PIIINP, bile acids, and AST were significantly different within stages I-III and could differentiate the mild fibrosis (F0F1) from the moderate (F2F3). The combination of these individual markers (PBC-score) further improved the accuracy. The area under the ROC of the PBC score, using a cut of value 66, had a sensitivity of 81.4% and a specificity of 65.2% to classify the stage of PBC. The prevalence of PBC in Finland increases, which results from increasing incidence and improved survival. The combination of budesonide and UDCA improves liver histology compared to UDCA alone in non-cirrhotic stages of PBC. The treatment may reduce BMD. Hyaluronic acid, PIIINP, AST, and bile acids may serve as tools to monitor the treatment response in the early stages of PBC. The budesonide and UDCA combination therapy is an option for those patients who do not receive full response from UDCA and are still at the non-cirrhotic stage of PBC.

Carbon sequestration versus bioenergy: A case study from South India exploring the relative land-use efficiency of two options for climate change mitigation

This case study has been carried out as a comparison between two different land-use strategies for climate change mitigation, with possible application within the Clean Development Mechanisms. The benefits of afforestation for carbon sequestration versus for bioenergy production are compared in the context of development planning to meet increasing domestic and agricultural demand for electricity in Hosahalli village, Karnataka, India. One option is to increase the local biomass based electricity generation, requiring an increased biomass plantation area. This option is compared with fossil based electricity generation where the area is instead used for producing wood for non-energy purposes while also sequestering carbon in the soil and standing biomass. The different options have been assessed using the PRO-COMAP model. The ranking of the different options varies depending on the system boundaries and time period. Results indicate that, in the short term (30 years) perspective, the mitigation potential of the long rotation plantation is largest, followed by the short rotation plantation delivering wood for energy. The bioenergy option is however preferred if a long-term view is taken. Short rotation forests delivering wood for short-lived non-energy products have the smallest mitigation potential, unless a large share of the wood products are used for energy purposes (replacing fossil fuels) after having served their initial purpose. If managed in a sustainable manner all of these strategies can contribute to the improvement of the social and environmental situation of the local community. (C) 2009 Elsevier Ltd. All rights reserved.

Anti-TNF treatment in juvenile idiopathic arthritis and associated uveitis : Clinical perspectives on growth, uveitis, and drug survival

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of childhood chronic arthritides, associated with chronic uveitis in 20% of cases. For JIA patients responding inadequately to conventional disease-modifying anti-rheumatic drugs (DMARDs), biologic therapies, anti-tumor necrosis factor (anti-TNF) agents are available. In this retrospective multicenter study, 258 JIA-patients refractory to DMARDs and receiving biologic agents during 1999-2007 were included. Prior to initiation of anti-TNFs, growth velocity of 71 patients was delayed in 75% and normal in 25%. Those with delayed growth demonstrated a significant increase in growth velocity after initiation of anti-TNFs. Increase in growth rate was unrelated to pubertal growth spurt. No change was observed in skeletal maturation before and after anti-TNFs. The strongest predictor of change in growth velocity was growth rate prior to anti-TNFs. Change in inflammatory activity remained a significant predictor even after decrease in glucocorticoids was taken into account. In JIA-associated uveitis, impact of two first-line biologic agents, etanercept and infliximab, and second-line or third-line anti-TNF agent, adalimumab, was evaluated. In 108 refractory JIA patients receiving etanercept or infliximab, uveitis occurred in 45 (42%). Uveitis improved in 14 (31%), no change was observed in 14 (31%), and in 17 (38%) uveitis worsened. Uveitis improved more frequently (p=0.047) and frequency of annual uveitis flares was lower (p=0.015) in those on infliximab than in those on etanercept. In 20 patients taking adalimumab, 19 (95%) had previously failed etanercept and/or infliximab. In 7 patients (35%) uveitis improved, in one (5%) worsened, and in 12 (60%) no change occurred. Those with improved uveitis were younger and had shorter disease duration. Serious adverse events (AEs) or side-effects were not observed. Adalimumab was effective also in arthritis. Long-term drug survival (i.e. continuation rate on drug) with etanercept (n=105) vs. infliximab (n=104) was at 24 months 68% vs. 68%, and at 48 months 61% vs. 48% (p=0.194 in log-rank analysis). First-line anti-TNF agent was discontinued either due to inefficacy (etanercept 28% vs. infliximab 20%, p=0.445), AEs (7% vs. 22%, p=0.002), or inactive disease (10% vs. 16%, p=0.068). Females, patients with systemic JIA (sJIA), and those taking infliximab as the first therapy were at higher risk for treatment discontinuation. One-third switched to the second anti-TNF agent, which was discontinued less often than the first. In conclusion, in refractory JIA anti-TNFs induced enhanced growth velocity. Four-year treatment survival was comparable between etanercept and infliximab, and switching from first-line to second-line agent a reasonable therapeutic option. During anti-TNF treatment, one-third with JIA-associated anterior uveitis improved.

Thrombophilia and direct thrombin inhibitor lepirudin clinical and monitoring aspects

Thrombophilia (TF) predisposes both to venous and arterial thrombosis at a young age. TF may also impact the thrombosis or stenosis of hemodialysis (HD) vascular access in patients with end-stage renal disease (ESRD). When involved in severe thrombosis TF may associate with inappropriate response to anticoagulation. Lepirudin, a potent direct thrombin inhibitor (DTI), indicated for heparin-induced thrombocytopenia-related thrombosis, could offer a treatment alternative in TF. Monitoring of narrow-ranged lepirudin demands new insights also in laboratory. The above issues constitute the targets in this thesis. We evaluated the prevalence of TF in patients with ESRD and its impact upon thrombosis- or stenosis-free survival of the vascular access. Altogether 237 ESRD patients were prospectively screened for TF and thrombogenic risk factors prior to HD access surgery in 2002-2004 (mean follow-up of 3.6 years). TF was evident in 43 (18%) of the ESRD patients, more often in males (23 vs. 9%, p=0.009). Known gene mutations of FV Leiden and FII G20210A occurred in 4%. Vascular access sufficiently matured in 226 (95%). The 1-year thrombosis- and stenosis-free access survival was 72%. Female gender (hazards ratio, HR, 2.5; 95% CI 1.6-3.9) and TF (HR 1.9, 95% CI 1.1-3.3) were independent risk factors for the shortened thrombosis- and stenosis-free survival. Additionally, TF or thrombogenic background was found in relatively young patients having severe thrombosis either in hepatic veins (Budd-Chiari syndrome, BCS, one patient) or inoperable critical limb ischemia (CLI, six patients). Lepirudin was evaluated in an off-label setting in the severe thrombosis after inefficacious traditional anticoagulation without other treatment options except severe invasive procedures, such as lower extremity amputation. Lepirudin treatments were repeatedly monitored clinically and with laboratory assessments (e.g. activated partial thromboplastin time, APTT). Our preliminary studies with lepirudin in thrombotic calamities appeared safe, and no bleeds occurred. An effective DTI lepirudin calmed thrombosis as all patients gradually recovered. Only one limb amputation was performed 3 years later during the follow-up (mean 4 years). Furthermore, we aimed to overcome the limitations of APTT and confounding effects of warfarin (INR of 1.5-3.9) and lupus anticoagulant (LA). Lepirudin responses were assessed in vitro by five specific laboratory methods. Ecarin chromogenic assay (ECA) or anti-Factor IIa (anti-FIIa) correlated precisely (r=0.99) with each other and with spiked lepirudin in all plasma pools: normal, warfarin, and LA-containing plasma. In contrast, in the presence of warfarin and LA both APTT and prothrombinase-induced clotting time (PiCT®) were limited by non-linear and imprecise dose responses. As a global coagulation test APTT is useful in parallel to the precise chromogenic methods ECA or Anti-FIIa in challenging clinical situations. Lepirudin treatment requires multidisciplinary approach to ensure appropriate patient selection, interpretation of laboratory monitoring, and treatment safety. TF seemed to be associated with complicated thrombotic events, in venous (BCS), arterial (CLI), and vascular access systems. TF screening should be aimed to patients with repeated access complications or prior unprovoked thromboembolic events. Lepirudin inhibits free and clot-bound thrombin which heparin fails to inhibit. Lepirudin seems to offer a potent and safe option for treatment of severe thrombosis. Multi-centered randomized trials are necessary to assess the possible management of complicated thrombotic events with DTIs like lepirudin and seek prevention options against access complications.

Analytical modelling of integrated solar drying system

The drying of fruit and vegetables is a subject of great importance. Dried fruit and vegetables have gained commercial importance, and their growth on a commercial scale has become an important sector of the agricultural industry. However, food drying is one of the most energy intensive processes of the major industrial process and accounts for up to 15 % of all industrial energy usage. Due to increasingly high electricity prices and environmental concern, a dryer using traditional energy sources is not a feasible option anymore. Therefore, an alternative/renewable energy source is needed. In this regard, an integrated solar drying system that includes highly efficient double-pass counter flow v-groove solar collector, conical-shaped rock-bed thermal storage, auxiliary heater, the centrifugal fan and the drying chamber has been designed and constructed. Mathematical model for all the individual components as well as an integrated model combining all components of the drying system has been developed. Mathematical equations were solved using MATLAB program. This paper presents the analytical model and key finding of the simulation.

Modelling conical rock-bed solar thermal storage tank

An important application of solar thermal storage is for power generation or process heating. Low-temperature thermal storage in a packed rock bed is considered the best option for thermal storage for solar drying applications. In this chapter, mathematical formulations for conical have been developed. The model equations are solved numerically for charging/discharging cycles utilizing MATLAB. Results were compared with rock-bed storage with standard straight tank. From the simulated results, the temperature distribution was found to be more uniform in the truncated conical rock-bed storage. Also, the pressure drop over a long period of time in the conical thermal storage was as low as 25 Pa. Hence, the amount of power required from a centrifugal fan would be significantly lower. The flow of air inside the tank is simulated in SolidWorks software. From flow simulation, 3D modelling of flow is obtained to capture the actual scenario inside the tank.

Mathematical modelling of rock-bed solar thermal storage tank

An important application of thermal storage is solar energy for power generation or process heating. Low temperature thermal storage in a packed rock bed is considered best option for thermal storage for solar drying applications. In this paper, mathematical formulations for conical and cylindrical rock bed storage tanks have been developed. The model equations are solved numerically for charging/discharging cycles. From the simulated results, it was observed that for the same aspect ratio between the diameter and the length of the thermal storages, the conical thermal storage had better performance. The temperature distribution was found to be more uniform in the truncated conical shape rock bed storage. Also, the pressure drop over long period of time in the conical thermal storage was lower than that of the cylindrical thermal storage. Hence, the amount of power required from a centrifugal fan was lower.

Approaches for improving the safety and efficacy of adenoviral gene therapy

Cancer is a devastating disease with poor prognosis and no curative treatment, when widely metastatic. Conventional therapies, such as chemotherapy and radiotherapy, have efficacy but are not curative and systemic toxicity can be considerable. Almost all cancers are caused due to changes in the genetic material of the transformed cells. Cancer gene therapy has emerged as a new treatment option, and past decades brought new insights in developing new therapeutic drugs for curing cancer. Oncolytic viruses constitute a novel therapeutic approach given their capacity to replicate in and kill specifically tumor cells as well as reaching tumor distant metastasis. Adenoviral gene therapy has been suggested to cause liver toxicity. This study shows that new developed adenoviruses, in particular Ad5/19p-HIT, can be redirected towards kidney while adenovirus uptake by liver is minimal. Moreover, low liver transduction resulted in a favorable tumor to liver ratio of virus load. Further, we established a new immunocompetent animal model Syrian hamsters. Wild type adenovirus 5 was found to replicate in Hap-T1 hamster tumors and normal tissues. There are no antiviral drugs available to inhibit adenovirus replication. In our study, chlorpromazine and cidofovir efficiently abrogated virus replication in vitro and showed significant reduction in vivo in tumors and liver. Once safety concerns were addressed together with the new given antiviral treatment options, we further improved oncolytic adenoviruses for better tumor penetration, local amplification and host system modulation. Further, we created Ad5/3-9HIF-Δ24-VEGFR-1-Ig, oncolytic adenovirus for improved infectivity and antiangiogenic effect for treatment of renal cancer. This virus exhibited increased anti-tumor effect and specific replication in kidney cancer cells. The key player for good efficacy of oncolytic virotherapy is the host immune response. Thus, we engineered a triple targeted adenovirus Ad5/3-hTERT-E1A-hCD40L, which would lead to tumor elimination due to tumor-specific oncolysis and apoptosis together with an anti-tumor immune response prompted by the immunomodulatory molecule. In conclusion, the results presented in this thesis constitute advances in our understanding of oncolytic virotherapy by successful tumor targeting, antiviral treatment options as a safety switch in case of replication associated side-effects, and modulation of the host immune system towards tumor elimination.  

Microvascular reconstruction in extremity soft tissue sarcoma surgery

Soft tissue sarcomas (STS) are rare tumors of soft tissue occurring most frequently in the extremities. Modern treatment of extremity STS is based on limb-sparing surgery combined with radiotherapy. To prevent local recurrence, a healthy tissue margin of 2.5 cm around the resected tumor is required. This results in large defects of soft tissue and bone, necessitating the use of reconstructive surgery to achieve wound closure. When local or pedicled soft tissue flaps are unavailable, reconstruction with free flaps is used. Free flaps are elevated at a distant site, and have their blood flow restored at the recipient site through microvascular anastomosis. When limb-sparing surgery is made impossible, amputation is the only option. Proximal amputation such as forequarter amputation (FQA) causes considerable morbidity, but is nevertheless warranted for carefully selected patients for cure or palliation. 116 patients treated in 1985 - 2006 were included in the study. Of these, 93 patients treated with limb-sparing surgery and microvascular reconstructive surgery after resection of extremity STS. 25 patients who underwent FQA were also included. Patients were identified and their medical records retrospectively reviewed. In all, 105 free flap procedures were performed for 103 patients. A total of 95 curatively treated STS patients were included in survival analysis. The latissimus dorsi, used in 56% of cases, was the most frequently used free flap. Free flap success rate was 96%. There were 9% microvascular anastomosis complications and 15% wound complications. For curatively treated STS patients, local recurrence-free survival at 5 years was 73.1%, metastasis-free survival 58.3%, and overall disease-specific survival 68.9%. Functional results were good, with 75% of patients regaining normal or near-normal function after lower extremity, and 55% after upper extremity STS resection. Among curatively treated forequarter amputees, 5-year disease-free survival was 44%. In the palliatively treated group median time until disease death was 14 months. Microvascular reconstruction after extremity soft tissue sarcoma resection is safe and reliable, and produces well-healing wounds allowing early oncological treatment. Oncological outcome after these procedures is comparable to that of other extremity sarcoma patients. Functional results are generally good. Forequarter amputation is a useful treatment option for soft tissue tumors of the shoulder girdle and proximal upper extremity. When free flap coverage of extended forequarter amputation is required, the preferable flap is a fillet flap from the amputated extremity. Acceptable oncological outcome is achieved for curatively treated FQA patients. In the palliatively treated patient considerable periods of increased quality of life can be achieved.

Modulation of growth by aromatase inhibitor treatment in boys: Efficacy and safety

Without estrogen action, the fusion of the growth plates is postponed and statural growth continues for an exceptionally long time. Aromatase inhibitors, blockers of estrogen biosynthesis, have therefore emerged as a new potential option for the treatment of children with short stature. We investigated the efficacy of the aromatase inhibitor letrozole in the treatment of boys with idiopathic short stature (ISS) using a randomised, placebo-controlled, double-blind research setting. A total of 30 boys completed the two-year treatment. By decreasing estrogen-mediated central negative feedback, letrozole increased gonadotrophin and testosterone secretion in pubertal boys, whereas the pubertal increase in IGF-I was inhibited. Treatment with letrozole effectively delayed bone maturation and increased predicted adult height by 5.9 cm (P0.001), while placebo had no effect on either parameter. The effect of letrozole treatment on near-final height was studied in another population, in boys with constitutional delay of puberty, who received letrozole (n=9) or placebo (n=8) for one year, in combination with low-dose testosterone for six months during adolescence. The mean near-final height of boys randomised to receive testosterone and letrozole was significantly greater than that of boys who received testosterone and placebo (175.8 vs. 169.1 cm, P=0.04). As regards safety, treatment effects on bone health, lipid metabolism, insulin sensitivity, and body composition were monitored in boys with ISS. During treatment, no differences in bone mass accrual were evident between the treatment groups, as evaluated by dual-energy x-ray absorptiometry measurements of the lumbar spine and femoral neck. Bone turnover and cortical bone growth, however, were affected by letrozole treatment. As indicated by differences in markers of bone resorption (U-INTP) and formation (S-PINP and S-ALP), the long-term rate of bone turnover was lower in letrozole-treated boys, despite their more rapid advancement in puberty. Letrozole stimulated cortical bone growth in those who progressed in puberty: the metacarpal index (MCI), a measure of cortical bone thickness, increased more in letrozole-treated pubertal boys than in placebo-treated pubertal boys (25% vs. 9%, P=0.007). The change in MCI correlated positively with the mean testosterone-to-estradiol ratio. In post-treatment radiographic evaluation of the spine, a high rate of vertebral deformities - mild anterior wedging and mild compression deformities - were found in both placebo and letrozole groups. In pubertal boys with ISS treated with letrozole, stimulated testosterone secretion was associated with a decrease in the percentage of fat mass and in HDL-cholesterol, while LDL-cholesterol and triglycerides remained unchanged. Insulin sensitivity, as evaluated by HOMA-IR, was not significantly affected by the treatment. In summary, treatment with the aromatase inhibitor letrozole effectively delayed bone maturation and increased predicted adult height in boys with ISS. Long-term follow-up data of boys with constitutional delay of puberty, treated with letrozole for one year during adolescence, suggest that the achieved gain in predicted adult height also results in increased adult height. However, until the safety of aromatase inhibitor treatment in children and adolescents is confirmed, such treatment should be considered experimental.

Scattering and Refraction as Contrast Mechanisms in X-Ray Imaging

Differentiation of various types of soft tissues is of high importance in medical imaging, because changes in soft tissue structure are often associated with pathologies, such as cancer. However, the densities of different soft tissues may be very similar, making it difficult to distinguish them in absorption images. This is especially true when the consideration of patient dose limits the available signal-to-noise ratio. Refraction is more sensitive than absorption to changes in the density, and small angle x-ray scattering on the other hand contains information about the macromolecular structure of the tissues. Both of these can be used as potential sources of contrast when soft tissues are imaged, but little is known about the visibility of the signals in realistic imaging situations. In this work the visibility of small-angle scattering and refraction in the context of medical imaging has been studied using computational methods. The work focuses on the study of analyzer based imaging, where the information about the sample is recorded in the rocking curve of the analyzer crystal. Computational phantoms based on simple geometrical shapes with differing material properties are used. The objects have realistic dimensions and attenuation properties that could be encountered in real imaging situations. The scattering properties mimic various features of measured small-angle scattering curves. Ray-tracing methods are used to calculate the refraction and attenuation of the beam, and a scattering halo is accumulated, including the effect of multiple scattering. The changes in the shape of the rocking curve are analyzed with different methods, including diffraction enhanced imaging (DEI), extended DEI (E-DEI) and multiple image radiography (MIR). A wide angle DEI, called W-DEI, is introduced and its performance is compared with that of the established methods. The results indicate that the differences in scattered intensities from healthy and malignant breast tissues are distinguishable to some extent with reasonable dose. Especially the fraction of total scattering has large enough differences that it can serve as a useful source of contrast. The peaks related to the macromolecular structure come to angles that are rather large, and have intensities that are only a small fraction of the total scattered intensity. It is found that such peaks seem to have only limited usefulness in medical imaging. It is also found that W-DEI performs rather well when most of the intensity remains in the direct beam, indicating that dark field imaging methods may produce the best results when scattering is weak. Altogether, it is found that the analysis of scattered intensity is a viable option even in medical imaging where the patient dose is the limiting factor.

Investing in the future: Norway, climate change, and fossil fuel divestment

The fossil fuel divestment movement has undergone explosive growth over the last few years - expanding from encouraging educational institutions to adopt ethical investment policies to focusing upon cities, pension funds and philanthropic charities. The fossil fuel divestment movement has attained global ambitions - challenging sovereign wealth funds and national governments to engage in fossil fuel divestment, and pushing for fossil fuel divestment at international climate talks - such as the Paris Climate Summit in 2015. By exploring and analysing a key campaign to 'Divest Norway', this chapter considers the efforts to globalise and internationalise the fossil fuel divestment campaign. Part 1 explores the origins of the fossil fuel divestment movement, and the application of such strategies in a variety of contexts. Part 2 looks at the campaign to divest Norway's sovereign wealth fund of fossil fuel investments. There has been much discussion as to whether the bold decision of Norway to engage in coal divestment will encourage and inspire other sovereign wealth funds to engage in fossil fuel divestment. The conclusion considers the efforts to introduce fossil fuel divestment as a policy initiative for nation states as a policy option in international climate law.

Inflammatory meditated mechanisms of cisplatin resistance in non-small cell lung cancer

The majority of non-small cell lung cancer (NSCLC) patients present with advanced stage disease, where chemotherapy is usually the most common treatment option. While somewhat effective, patients treated with cisplatin-based chemotherapy will eventually develop resistance. Multiple pathways have been implicated in chemo-resistance, however the critical underlying mechanisms have yet to be elucidated. The aim of this project is to determine the role of inflammatory mediators in cisplatin resistance.

Formation of structure in dark energy cosmologies

Acceleration of the universe has been established but not explained. During the past few years precise cosmological experiments have confirmed the standard big bang scenario of a flat universe undergoing an inflationary expansion in its earliest stages, where the perturbations are generated that eventually form into galaxies and other structure in matter, most of which is non-baryonic dark matter. Curiously, the universe has presently entered into another period of acceleration. Such a result is inferred from observations of extra-galactic supernovae and is independently supported by the cosmic microwave background radiation and large scale structure data. It seems there is a positive cosmological constant speeding up the universal expansion of space. Then the vacuum energy density the constant describes should be about a dozen times the present energy density in visible matter, but particle physics scales are enormously larger than that. This is the cosmological constant problem, perhaps the greatest mystery of contemporary cosmology. In this thesis we will explore alternative agents of the acceleration. Generically, such are called dark energy. If some symmetry turns off vacuum energy, its value is not a problem but one needs some dark energy. Such could be a scalar field dynamically evolving in its potential, or some other exotic constituent exhibiting negative pressure. Another option is to assume that gravity at cosmological scales is not well described by general relativity. In a modified theory of gravity one might find the expansion rate increasing in a universe filled by just dark matter and baryons. Such possibilities are taken here under investigation. The main goal is to uncover observational consequences of different models of dark energy, the emphasis being on their implications for the formation of large-scale structure of the universe. Possible properties of dark energy are investigated using phenomenological paramaterizations, but several specific models are also considered in detail. Difficulties in unifying dark matter and dark energy into a single concept are pointed out. Considerable attention is on modifications of gravity resulting in second order field equations. It is shown that in a general class of such models the viable ones represent effectively the cosmological constant, while from another class one might find interesting modifications of the standard cosmological scenario yet allowed by observations. The thesis consists of seven research papers preceded by an introductory discussion.