289 resultados para Intellectual property disputes


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Introspection is the process by which individuals question their attitudes; either questioning why they hold their attitudes (Why introspection), or how they feel about a particular attitude object (How introspection). Previous research has suggested that Why-introspection induces attitude change, and that Why and How introspection influence attitude-behaviour consistency,persuasion, and other effects. Generally, psychologists have assumed that affective and cognitive attitude bases are the mechanism by which introspection leads to these effects. Leading perspectives originating from these findings suggest that either Why introspection changes the content of cognitive attitude bases (the skewness hypothesis), or increases the salience of cognitive attitude bases (the dominance hypothesis); whereas How introspection may increase the salience of affective attitude bases (another part of the dominance hypothesis). However, direct evidence for these mechanisms is lacking, and the distinction between structural and meta bases has not been considered. Two studies investigated this gap in the existing literature. Both studies measured undergraduate students’ attitudes and attitude bases (both structural and meta, affective and cognitive) before and after engaging in an introspection manipulation (Why introspection / How introspection / control), and after reading a (affective / cognitive) persuasive passage about the attitude object. No evidence was found supporting either the skewness or dominance hypotheses. Furthermore, previous introspection effects were not replicated in the present data. Possible reasons for these null findings are proposed, and several unexpected effects are examined.

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Background: There is growing evidence that individual EEG differences may aid in classifying patients with major depressive disorder (MDD) and also help predict clinical response to antidepressant treatment. This study aims to compare the effectiveness of EEG frequency band power, alpha asymmetry and prefrontal theta cordance towards escitalopram response prediction and MDD diagnosis, in a multi-site initiative. Methods: Resting EEG (eyes open and closed) was recorded from 64 electrodes in 44 depressed patients and 20 healthy controls at baseline, 2 weeks post-treatment and 8 weeks post-treatment. Clinical response was measured as change from baseline MADRS of 50% or more. EEG measures were analyzed (1) at baseline (2) at 2 weeks post-treatment and (3) as an ‘‘early change” variable defined as change in EEG from baseline to 2 weeks post-treatment. Results: At baseline, responders exhibited greater absolute alpha power in the left hemisphere versus the right while non-responders showed the opposite. Responders further exhibited a cortical asymmetry of greater right relative to left activity in parietal areas. Groups also differed in baseline relative delta power with responders showing greater power in the right hemisphere versus the left while non-responders showed the opposite. At 2 weeks post-treatment, responders exhibited greater absolute beta power in the left hemisphere relative to right and the opposite was noted for non-responders. The opposite pattern was noted for absolute and relative delta power at 2 weeks post-treatment. Responders exhibited early reduction in relative alpha power and early increments in relative theta power. Non-responders showed a significant early increase in prefrontal theta cordance. Absolute delta power helped distinguish MDD patients from healthy controls. Conclusions: Hemispheric asymmetries in the alpha and delta bands at pre-treatment baseline and at 2 weeks post-treatment have moderate to moderately strong predictive utility towards antidepressant treatment response. These findings have significant potential for improving clinical practice in psychiatry by eventually guiding clinical choice of treatments. This would greatly benefit patients awaiting relief from depressive symptoms as treatment optimization would help overcome problems associated with delayed recovery. Our results also indicate that resting EEG activity may have clinical utility in predicting MDD diagnosis.

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For the SNO+ neutrinoless double beta decay search, various backgrounds, ranging from impurities present naturally to those produced cosmogenically, must be understood and reduced. Cosmogenic backgrounds are particularly difficult to reduce as they are continually regenerated while exposed to high energy cosmic rays. To reduce these cosmogenics as much as possible the tellurium used for the neutrinoless double beta decay search will be purified underground. An analysis of the purification factors achievable for insoluble cosmogenic impurities found a reduction factor of $>$20.4 at 50\% C.L.. During the purification process the tellurium will come into contact with ultra pure water and nitric acid. These liquids both carry some cosmogenic impurities with them that could be potentially transferred to the tellurium. A conservative limit is set at $<$18 events in the SNO+ region of interest (ROI) per year as a result of contaminants from these liquids. In addition to cosmogenics brought underground, muons can produce radioactive isotopes while the tellurium is stored underground. A study on the rate at which muons produce these backgrounds finds an additional 1 event per year. In order to load the tellurium into the detector, it will be combined with 1,2-butanediol to form an organometallic complex. The complex was found to have minimal effect on the SNO+ acrylic vessel for 154 years.

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In my thesis I argue for the use of system designs that: a) open access to a variety of users and allow for collaboration and idea exchange, while at the same time, b) are designed to motivate and engage users. To exemplify my proposed systems design, I created an interactive and open digital history project focused on Romanian culture and identity during Communism, from 1947, when the Communist Party took power by forcing the King to abdicate, until the revolution in 1989, which marked the end of Communism in Romania (Gilberg, 1990, Boia, 2014). In my project, I present the possibility to recreate Habermas’ notion of public sphere and “the unforced force of the better argument” (Habermas, 1989) and Dewey’s (2004) understanding of democracy as a mode of associated living imbued of the spirit of inquiry within contemporary digital history projects. Second, I outline system designs that motivate and engage users, by satisfying the basic psychological needs outlined in Ryan and Deci’s (2000) self-determination theory: autonomy, competence, and relatedness. Two more concepts are included to complete the proposed digital history project design: presence (Ryan, Rigby, & Przybylski, 2006) and learner hero (Rigby & Przybylski, 2009).

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Multi-frequency eddy current measurements are employed in estimating pressure tube (PT) to calandria tube (CT) gap in CANDU fuel channels, a critical inspection activity required to ensure fitness for service of fuel channels. In this thesis, a comprehensive characterization of eddy current gap data is laid out, in order to extract further information on fuel channel condition, and to identify generalized applications for multi-frequency eddy current data. A surface profiling technique, generalizable to multiple probe and conductive material configurations has been developed. This technique has allowed for identification of various pressure tube artefacts, has been independently validated (using ultrasonic measurements), and has been deployed and commissioned at Ontario Power Generation. Dodd and Deeds solutions to the electromagnetic boundary value problem associated with the PT to CT gap probe configuration were experimentally validated for amplitude response to changes in gap. Using the validated Dodd and Deeds solutions, principal components analysis (PCA) has been employed to identify independence and redundancies in multi-frequency eddy current data. This has allowed for an enhanced visualization of factors affecting gap measurement. Results of the PCA of simulation data are consistent with the skin depth equation, and are validated against PCA of physical experiments. Finally, compressed data acquisition has been realized, allowing faster data acquisition for multi-frequency eddy current systems with hardware limitations, and is generalizable to other applications where real time acquisition of large data sets is prohibitive.

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Exposure to the antiepileptic drug valproic acid (VPA) is associated with an increased risk of congenital malformations including heart, skeletal and most frequently neural tube defects. Although the mechanisms contributing to its teratogenesis are not well understood, VPA was previously shown to increase homologous recombination (HR)-mediated DNA repair and decrease protein expression of the transcription factor NF-κB/p65. The studies in this thesis utilized in vivo and in vitro models to evaluate the expression of HR mediators, investigate the implications of decreased p65 including DNA binding and transcriptional activation, and the expression and histone acetyltransferase activity of Cbp/p300 with an aim to provide mechanistic insight into VPA-mediated alterations. The first study demonstrated that following maternal administration of VPA, mouse embryonic mRNA expression of HR mediators Rad51, Brca1 and Brca2 exhibited temporal and tissue-specific alterations. Protein expression of Rad51 was similarly altered and preceded increased cleavage of caspase-3 and PARP; indicative of apoptosis. The second study confirms previous findings of decreased total cellular p65 protein using P19 cells, but is the first to demonstrate that nuclear p65 protein is unchanged. NF-κB DNA binding was decreased following VPA exposure and maybe mediated by decreased p50 protein, which dimerizes with p65 prior to DNA binding. Transcriptional activity of NF-κB was also increased with VPA exposure which was not due to increased p65 phosphorylation at Ser276. Furthermore, the transcriptional activation capacity was unaffected by VPA exposure as combined exposure to VPA and TNFα additively increased NF-κB activity. The third study demonstrated that VPA exposure in P19 cells decreased Cbp/p300 total cellular and nuclear protein attributed primarily to ubiquitin proteasome-mediated degradation. Histone acetyltransferase (HAT) activity of p300 was decreased proportionately to nuclear protein following VPA exposure. Inhibition of Cbp/p300 HAT activity decreased p65 total cellular protein, increased caspase-3 cleavage and ROS similar to VPA exposures. Furthermore, pre-treatment with the antioxidant enzyme catalase attenuated the increase in caspase-3 cleavage, but not p65 protein. Overall, this thesis demonstrates that VPA exposure impacts the expression and activity of the transcription factor NF-κB and transcriptional co-activators/HATs Cbp/p300, which has implications for downstream VPA targets including Rad51, Brca1 and Brca2.

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The real-time optimization of large-scale systems is a difficult problem due to the need for complex models involving uncertain parameters and the high computational cost of solving such problems by a decentralized approach. Extremum-seeking control (ESC) is a model-free real-time optimization technique which can estimate unknown parameters and can optimize nonlinear time-varying systems using only a measurement of the cost function to be minimized. In this thesis, we develop a distributed version of extremum-seeking control which allows large-scale systems to be optimized without models and with minimal computing power. First, we develop a continuous-time distributed extremum-seeking controller. It has three main components: consensus, parameter estimation, and optimization. The consensus provides each local controller with an estimate of the cost to be minimized, allowing them to coordinate their actions. Using this cost estimate, parameters for a local input-output model are estimated, and the cost is minimized by following a gradient descent based on the estimate of the gradient. Next, a similar distributed extremum-seeking controller is developed in discrete-time. Finally, we consider an interesting application of distributed ESC: formation control of high-altitude balloons for high-speed wireless internet. These balloons must be steered into a favourable formation where they are spread out over the Earth and provide coverage to the entire planet. Distributed ESC is applied to this problem, and is shown to be effective for a system of 1200 ballons subjected to realistic wind currents. The approach does not require a wind model and uses a cost function based on a Voronoi partition of the sphere. Distributed ESC is able to steer balloons from a few initial launch sites into a formation which provides coverage to the entire Earth and can maintain a similar formation as the balloons move with the wind around the Earth.

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Anxiety disorders are the most prevalent form of psychopathology among children and adolescents. Because demand for treatment far exceeds availability, there is a need for alternative approaches that are engaging, accessible, cost-effective, and incorporate practice to reach as many youth as possible. One novel approach is a video game intervention called MindLight that uses two evidence-based strategies to target childhood anxiety problems. Using neurofeedback mechanics to train players to: (1) attend to positive rather than threatening stimuli and (2) down-regulate arousal during stressful situations, MindLight teaches children how to practice overcoming anxious thoughts and arousal in a fun and engaging context. The present study examined the effectiveness of MindLight versus online cognitive-behavioural therapy (CBT) based psychoeducation sessions as a comparison in reducing anxiety in a sample of 144 anxious children, which was measured in three ways: (1) anxiety symptoms, (2) state anxiety in response to stress, and (3) psychophysiological arousal in response to stress. Children between the ages of 8.05–17.78 years (M=13.61, SD=1.79) were randomly assigned to play MindLight or complete psychoeducation for five hours over three weeks. State anxiety and psychophysiological arousal were assessed in response to two stress tasks before and after exposure to MindLight or psychoeducation. Anxiety symptoms were also measured via a questionnaire. Overall, participants showed significant reductions in anxiety symptoms and state anxiety in response to stress, but not psychophysiological arousal in response to stress. Moreover, the magnitude of reductions in anxiety did not differ between interventions but by age and sex. Specifically, older participants showed a greater decrease in severity of state anxiety in response to a social stressor than younger participants and girls showed a greater decrease in severity of state anxiety in response to a cognitive stressor than boys. The present study suggests that playing MindLight results in similar reductions in anxiety as one of the more common means of delivering CBT principles to youth.

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The purpose of this research is to investigate potential methods to produce an ion-exchange membrane that can be integrated directly into a polydimethylsiloxane Lab-on-a-Chip or Micro-Total-Analysis-System. The majority of microfluidic membranes are based on creating microporous structures, because it allows flexibility in the choice of material such that it can match the material of the microfluidic chip. This cohesion between the material of the microfluidic chip and membrane is an important feature to prevent bonding difficulties which can lead to leaking and other practical problems. However, of the materials commonly used to manufacture microfluidic chips, there are none that provide the ion-exchange capability. The DuPont product Nafion{TM} is chosen as the ion-exchange membrane, a copolymer with high conductivity and selectivity to cations and suitable for many applications such as electrolysis of water and the chlor-alkali process. The use of such an ion-exchange membrane in microfluidics could have multiple advantages, but there is no reversible/irreversible bonding that occurs between PDMS and Nafion{TM}. In this project multiple methods of physical entrapment of the ion-exchange material inside a film of PDMS are attempted. Through the use of the inherent properties of PDMS, very inexpensive sugar granulate can be used to make an inexpensive membrane mould which does not interfere with the PDMS crosslinking process. After dissolving away this sacrificial mould material, Nafion{TM} is solidified in the irregular granulate holes. Nafion{TM} in this membrane is confined in the irregular shape of the PDMS openings. The outer structure of the membrane is all PDMS and can be attached easily and securely to any PDMS-based microfluidic device through reversible or irreversible PDMS/PDMS bonding. Through impedance measurement, the effectiveness of these integrated membranes are compared against plain Nafion{TM} films in simple sodium chloride solutions.

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The heat transfer from a hot primary flow stream passing over the outside of an airfoil shaped strut to a cool secondary flow stream passing through the inside of that strut was studied experimentally and numerically. The results showed that the heat transfer on the inside of the strut could be reliably modeled as a developing flow and described using a power law model. The heat transfer on the outside of the strut was complicated by flow separation and stall on the suction side of the strut at high angles of attack. This separation was quite sensitive to the condition of the turbulence in the flow passing over the strut, with the size of the separated wake changing significantly as the mean magnitude and levels of anisotropy were varied. The point of first stall moved by as much as 15% of the chord, while average heat transfer levels changed by 2-5% as the inlet condition was varied. This dependence on inlet conditions meant that comparisons between experiment and steady RANS based CFD were quite poor. Differences between the CFD and experiment were attributed to anisotropic and unsteady effects. The coupling between the two flows was shown to be quite low - that is to say, heat transfer coefficients on both the inner and outer surfaces of the strut were relatively unaffected by the temperature of the strut, and it was possible to predict the temperature on the strut surface quite reliably using heat transfer data from decoupled tests, especially for CFD simulations.

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GM2 gangliosidoses is a family of severe, neurodegenerative disorders resulting from a deficiency in the β-hexosaminidase A (Hex A) enzyme. This disorder is typically caused by a mutation to either the HEXA gene, causing Tay Sachs disease, or a mutation to the HEXB gene, causing Sandhoff disease. The HEXA and HEXB genes are required to produce the α and β subunits of the Hex A enzyme respectively. Using a Sandhoff disease (SD) mouse model (Hexb-/-) we tested the potential of a low dose of systemically delivered single stranded adeno-associated virus 9 (ssAAV9) expressing human HEXB and human HEXA cDNA under the control of a single promoter through the use of a bicistronic vector design with a P2A linker to correct the neurological phenotype. Neonatal mice were injected with either this ssAAV9-HexB-P2A-HexA vector (HexB-HexA) or a vehicle solution via the superficial temporal vein. HexB-HexA treatment alone conferred an increase in survival of 56% compared to vehicle-injected controls and biochemical analysis of the brain tissue and serum revealed an increase in HexA activity and a decrease in brain GM2 ganglioside buildup. Additionally, treatments with the non-steroidal anti-inflammatory drug indomethacin (Indo), the histone deactylase inhibitor ITF2357 (ITF) and the pharmacological chaperone pyrimethamine (Pyr) were tested. The anti-inflammatory treatments of Indo and ITF conferred an increase in survival of 12% and 8% respectively while causing no alteration in the HexA activity or GM2 ganglioside buildup. Pyr had no observable effect on disease progression. Lastly HexB-HexA treatment was tested in conjunction with Indo, ITF and Pyr individually. Additive increases in survival and behavioural testing results were observed with Indo and ITF treatments while no additional benefit to HexA activity or GM2 ganglioside levels in the brain tissue was observed. This indicates the two treatments slowed the progression of the disease through a different mechanism than the reduction of the GM2 ganglioside substrate. Pyr treatment was shown to have no effect when combined with HexB-HexA treatment. This study demonstrates the potential amelioration of SD with a novel AAV9 gene therapy approach as well as helped to identify the additive potential of anti-inflammatory treatments in gene therapy of GM2 gangliosidoses.

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Breast cancer is the most frequently diagnosed cancer in women, accounting for over 25% of cancer diagnoses and 13% of cancer-related deaths in Canadian women. There are many types of therapies for treatment or management of breast cancer, with chemotherapy being one of the most widely used. Taxol (paclitaxel) is one of the most extensively used chemotherapeutic agents for treating cancers of the breast and numerous other sites. Taxol stabilizes microtubules during mitosis, causing the cell cycle to arrest until eventually the cell undergoes apoptosis. Although Taxol has had significant benefits in many patients, response rates range from only 25-69%, and over half of Taxol-treated patients eventually acquire resistance to the drug. Drug resistance remains one of the greatest barriers to effective cancer treatment, yet little has been discerned regarding resistance to Taxol, despite its widespread clinical use. Kinases are known to be heavily involved in cancer development and progression, and several kinases have been linked to resistance of Taxol and other chemotherapeutic agents. However, a systematic screen for kinases regulating Taxol resistance is lacking. Thus, in this study, a set of kinome-wide screens was conducted to interrogate the involvement of kinases in the Taxol response. Positive-selection and negative-selection CRISPR-Cas9 screens were conducted, whereby a pooled library of 5070 sgRNAs targeted 507 kinase-encoding genes in MCF-7 breast cancer cells that were Taxol-sensitive (WT) or Taxol-resistant (TxR) which were then treated with Taxol. Next generation sequencing (NGS) was performed on cells that survived Taxol treatment, allowing identification and quantitation of sgRNAs. STK38, Blk, FASTK and Nek3 stand out as potentially critical kinases for Taxol-induced apoptosis to occur. Furthermore, kinases CDKL1 and FRK may have a role in Taxol resistance. Further validation of these candidate kinases will provide novel pre-clinical data about potential predictive biomarkers or therapeutic targets for breast cancer patients in the future.

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The photochemistry of the polar regions of Earth, as well as the interstellar medium, is driven by the effect of ultraviolet radiation on ice surfaces and on the materials trapped within them. While the area of ice photochemistry is vast and much research has been completed, it has only recently been possible to study the dynamics of these processes on a microscopic level. One of the leading techniques for studying photoreaction dynamics is Velocity Map Imaging (VMI). This technique has been used extensively to study several types of reaction dynamics processes. Although the majority of these studies have utilized molecular beams as the main medium for reactants, new studies showed the versatility of the technique when applied to molecular dynamics of molecules adsorbed on metal surfaces. Herein the development of a velocity map imaging apparatus capable of studying the photochemistry of condensed phase materials is described. The apparatus is used to study of the photo-reactivity of NO2 condensed within argon matrices to illustrate its capabilities. A doped ice surface is formed by condensing Ar and NO2 gas onto a sapphire rod which is cooled using a helium compressor to 20 K. The matrix is irradiated using an Nd:YAG laser at 355 nm, and the resulting NO fragment is state-selectively ionized using an excimer-pumped dye laser. In all, we are able to detect transient photochemically generated species and can collect information on their quantum state and kinetic energy distribution. It is found that the REMPI spectra changes as different sections of the dissociating cloud are probed. The rotational and translational energy populations are found to be bimodal with a low temperature component roughly at the temperature of the matrix, and a second component with much higher temperature, the rotational temperature showing a possible population inversion, and the translational temperature of 100-200 K. The low temperature translational component is found to dominate at long delay times between dissociation and ionization, while at short time delays the high temperature component plays a larger role. The velocity map imaging technique allows for the detection of both the axial and radial components of the translational energy. The distribution of excess energy over the rotational, electronic and translational states of the NO photofragments provides evidence for collisional quenching of the fragments in the Ar-matrix prior to their desorption.

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ABSTRACT The purpose of this study was to examine the technical adequacy of the Developmental Reading Assessment (Beaver & Carter, 2004). Internal consistency analysis, factor analysis, and linear regression analyses were used to test whether the DRA is a statistically reliable measuring of reading comprehension for Grades 7 and 8 students. Correlational analyses, decision consistency analyses, and a focus group of experienced Intermediate (Grades 7 and 8) teachers examined whether there is evidence that the results from the DRA provide valid interpretations regarding students’ reading skills and comprehension. Results indicated that, as currently scored, internal consistency is low and skewness of distribution is high. Factor analyses did not replicate those cited by the DRA developers to prove construct validity. Two-way contingency analyses determined that decision consistency did not vary greatly between the DRA, EQAO, scores and report card marks. Views expressed during the focus group echoed many of the challenges to validity found in the statistical analysis. The teachers found that the DRA was somewhat useful, as there were limited alternative reading assessments available for the classroom, but did not endorse it strongly. The study found little evidence that the DRA provides valid interpretations regarding Intermediate students’ reading skills. Indicated changes to the structure and administration procedures of the DRA may ameliorate some of these issues.

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Underground hardrock mining can be very energy intensive and in large part this can be attributed to the power consumption of underground ventilation systems. In general, the power consumed by a mine’s ventilation system and its overall scale are closely related to the amount of diesel power in operation. This is because diesel exhaust is a major source of underground air pollution, including diesel particulate matter (DPM), NO2 and heat, and because regulations tie air volumes to diesel engines. Furthermore, assuming the size of airways remains constant, the power consumption of the main system increases exponentially with the volume of air supplied to the mine. Therefore large diesel fleets lead to increased energy consumption and can also necessitate large capital expenditures on ventilation infrastructure in order to manage power requirements. Meeting ventilation requirements for equipment in a heading can result in a similar scenario with the biggest pieces leading to higher energy consumption and potentially necessitating larger ventilation tubing and taller drifts. Depending on the climate where the mine is located, large volumes of air can have a third impact on ventilation costs if heating or cooling the air is necessary. Annual heating and cooling costs, as well as the cost of the associated infrastructure, are directly related to the volume of air sent underground. This thesis considers electric mining equipment as a means for reducing the intensity and cost of energy consumption at underground, hardrock mines. Potentially, electric equipment could greatly reduce the volume of air needed to ventilate an entire mine as well as individual headings because they do not emit many of the contaminants found in diesel exhaust and because regulations do not connect air volumes to electric motors. Because of the exponential relationship between power consumption and air volumes, this could greatly reduce the amount of power required for mine ventilation as well as the capital cost of ventilation infrastructure. As heating and cooling costs are also directly linked to air volumes, the cost and energy intensity of heating and cooling the air would also be significantly reduced. A further incentive is that powering equipment from the grid is substantially cheaper than fuelling them with diesel and can also produce far fewer GHGs. Therefore, by eliminating diesel from the underground workers will enjoy safer working conditions and operators and society at large will gain from a smaller impact on the environment. Despite their significant potential, in order to produce a credible economic assessment of electric mining equipment their impact on underground systems must be understood and considered in their evaluation. Accordingly, a good deal of this thesis reviews technical considerations related to the use of electric mining equipment, especially ones that impact the economics of their implementation. The goal of this thesis will then be to present the economic potential of implementing the equipment, as well as to outline the key inputs which are necessary to support an evaluation and to provide a model and an approach which can be used by others if the relevant information is available and acceptable assumptions can be made.