Preimplantation genetic diagnosis: Analysis of gene expression, nuclear DNA and cytoplasmic DNA

Preimplantation genetic diagnosis (PGD) following in vitro fertilization (IVF) offers couples at risk for transmitting genetic disorders the opportunity to identify affected embryos prior to replacement. In particular, embryo gender determination permits screening for X-linked diseases of unknown etiology. Analysis of embryos can be performed by polymerase chain reaction (PCR) amplification of material obtained by micromanipulation. This approach provides an alternative to the termination of an established pregnancy following chorionic villi sampling or amniocentesis. ^ Lately, the focus of preimplantation diagnosis and intervention has been shifting toward an attempt to correct cytoplasmic deficiencies. Accordingly, it is the aim of this investigation to develop methods to permit the examination of single cells or components thereof for clinical evaluation. In an attempt to lay the groundwork for precise therapeutic intervention for age related aneuploidy, transcripts encoding proteins believed to be involved in the proper segregation of chromosomes during human oocyte maturation were examined and quantified. Following fluorescent rapid cycle RT-PCR analysis it was determined that the concentration of cell cycle checkpoint gene transcripts decreases significantly as maternal age increases. Given the well established link between increasing maternal age and the incidence of aneuploidy, these results suggest that the degradation of these messages in aging oocytes may be involved with inappropriate chromosome separation during meiosis. ^ In order to investigate the cause of embryonic rescue observed following clinical cytoplasmic transfer procedures and with the objective of developing a diagnostic tool, mtDNA concentrations in polar bodies and subcellular components were evaluated. First, the typical concentration of mtDNA in human and mouse oocytes was determined by fluorescent rapid cycle PCR. Some disparity was noted between the copy numbers of individual cytoplasmic samples which may limit the use of the current methodology for the clinical assessment of the corresponding oocyte. ^

Temporal Mining for Distributed Systems

Many systems and applications are continuously producing events. These events are used to record the status of the system and trace the behaviors of the systems. By examining these events, system administrators can check the potential problems of these systems. If the temporal dynamics of the systems are further investigated, the underlying patterns can be discovered. The uncovered knowledge can be leveraged to predict the future system behaviors or to mitigate the potential risks of the systems. Moreover, the system administrators can utilize the temporal patterns to set up event management rules to make the system more intelligent. With the popularity of data mining techniques in recent years, these events grad- ually become more and more useful. Despite the recent advances of the data mining techniques, the application to system event mining is still in a rudimentary stage. Most of works are still focusing on episodes mining or frequent pattern discovering. These methods are unable to provide a brief yet comprehensible summary to reveal the valuable information from the high level perspective. Moreover, these methods provide little actionable knowledge to help the system administrators to better man- age the systems. To better make use of the recorded events, more practical techniques are required. From the perspective of data mining, three correlated directions are considered to be helpful for system management: (1) Provide concise yet comprehensive summaries about the running status of the systems; (2) Make the systems more intelligence and autonomous; (3) Effectively detect the abnormal behaviors of the systems. Due to the richness of the event logs, all these directions can be solved in the data-driven manner. And in this way, the robustness of the systems can be enhanced and the goal of autonomous management can be approached. This dissertation mainly focuses on the foregoing directions that leverage tem- poral mining techniques to facilitate system management. More specifically, three concrete topics will be discussed, including event, resource demand prediction, and streaming anomaly detection. Besides the theoretic contributions, the experimental evaluation will also be presented to demonstrate the effectiveness and efficacy of the corresponding solutions.

Three essays on the economics of defense contracting, output and income inequality

This dissertation analyzes both the economics of the defense contracting process and the impact of total dollar obligations on the economies of U.S. states. Using various econometric techniques, I will estimate relationships across individual contracts, state level output, and income inequality. I will achieve this primarily through the use of a dataset on individual contract obligations. ^ The first essay will catalog the distribution of contracts and isolate aspects of the process that contribute to contract dollar obligations. Accordingly, this study describes several characteristics about individual defense contracts, from 1966-2006: (i) the distribution of contract dollar obligations is extremely rightward skewed, (ii) contracts are unevenly distributed in a geographic sense across the United States, (iii) increased duration of a contract by 10 percent is associated with an increase in costs by 4 percent, (iv) competition does not seem to affect dollar obligations in a substantial way, (v) contract pre-payment financing increases the obligation of contracts from anywhere from 62 to 380 percent over non-financed contracts. ^ The second essay will turn to an aggregate focus, and look the impact of defense spending on state economic output. The analysis in chapter two attempts to estimate the state level fiscal multiplier, deploying Difference-in-Differences estimation as an attempt to filter out potential endogeneity bias. Interstate variation in procurement spending facilitates utilization of a natural experiment scenario, focusing on the spike in relative spending in 1982. The state level relative multiplier estimate here is 1.19, and captures the short run, impact effect of the 1982 spending spike. ^ Finally I will look at the relationship between defense contracting and income inequality. Military spending has typically been observed to have a negative relationship with income inequality. The third chapter examines the existence of this relationship, combining data on defense procurement with data on income inequality at the state level, in a longitudinal analysis across the United States. While the estimates do not suggest a significant relationship exists for the income share of the top ten percent of households, there is a significant positive relationship for the income share of top one percent households for an increase in defense procurement.^

Understanding Antenatal Genetics Services in Sri Lanka: Current Landscape of Screening and Diagnostic Services and Contextual Factors Influencing Their Availability and Uptake

Background: Too little information is available on Sri Lanka’s current capacity to provide community genetic services—antenatal genetic services in particular—to understand whether building that capacity could further improve and reduce disparity in maternal and child health. This qualitative research project seeks to gather information on congenital disorders, routine antenatal care, and the current state of antenatal screening testing services within that routine antenatal to assess the feasibility of and the need for scaling up antenatal genetics services in Sri Lanka. Methods: Nineteen key informant (KI) interviews were conducted with stakeholders in antenatal care and genetic services. Seven focus group discussions were held with a total of 56 Public Health Midwives (PHMs), the health workers responsible for antenatal care at the field level. Transcripts for all interviews and FGDs were analyzed for key themes, and themes were categorized to address the specific aims of the project. Results: Antenatal genetic services play a minor role in antenatal care, with screening and diagnostic procedures available in the private sector and paid for out-of-pocket. KIs and PHMs expect that demand for antenatal genetic services will increase as patients’ purchasing power and knowledge grow but note that prohibitive abortion laws limit the ability of patients to act on test results. Genetic services compete for limited financial and human resources in the free public health system, and inadequate information on the prevalence of congenital disorders limits the ability to understand whether funding for services related to those disorders should be increased. A number of alternatives to scaling up antenatal genetic services within the free health system might be better suited to the Sri Lankan structural and social context. Conclusions: Scaling up antenatal genetic services within the public health system is not feasible in the current financial, legal, and human resource context. Yet current availability and utilization patterns contribute to regional and economic disparities, suggesting that stasis will not bring continued improvements in maternal and child health. More information on the burden of congenital disorders is necessary to fully understand if and how antenatal genetic service availability should be increased in Sri Lanka, but even before that information is gathered, examination of policies for patient referral, termination of pregnancy, and government support for individuals with genetic disease are steps that might bring extend improvements and reduce disparity in maternal and child health.

Three Essays on the Economics of Defense Contracting, Output and Income Inequality

This dissertation analyzes both the economics of the defense contracting process and the impact of total dollar obligations on the economies of U.S. states. Using various econometric techniques, I will estimate relationships across individual contracts, state level output, and income inequality. I will achieve this primarily through the use of a dataset on individual contract obligations. The first essay will catalog the distribution of contracts and isolate aspects of the process that contribute to contract dollar obligations. Accordingly, this study describes several characteristics about individual defense contracts, from 1966-2006: (i) the distribution of contract dollar obligations is extremely rightward skewed, (ii) contracts are unevenly distributed in a geographic sense across the United States, (iii) increased duration of a contract by 10 percent is associated with an increase in costs by 4 percent, (iv) competition does not seem to affect dollar obligations in a substantial way, (v) contract pre-payment financing increases the obligation of contracts from anywhere from 62 to 380 percent over non-financed contracts. The second essay will turn to an aggregate focus, and look the impact of defense spending on state economic output. The analysis in chapter two attempts to estimate the state level fiscal multiplier, deploying Difference-in-Differences estimation as an attempt to filter out potential endogeneity bias. Interstate variation in procurement spending facilitates utilization of a natural experiment scenario, focusing on the spike in relative spending in 1982. The state level relative multiplier estimate here is 1.19, and captures the short run, impact effect of the 1982 spending spike. Finally I will look at the relationship between defense contracting and income inequality. Military spending has typically been observed to have a negative relationship with income inequality. The third chapter examines the existence of this relationship, combining data on defense procurement with data on income inequality at the state level, in a longitudinal analysis across the United States. While the estimates do not suggest a significant relationship exists for the income share of the top ten percent of households, there is a significant positive relationship for the income share of top one percent households for an increase in defense procurement.

Radiocarbon dating and alkenone-based proxies of sediment core GeoB7702-3

In this study we utilize two organic geochemical proxies, the Uk'37 index and TEX86, to examine past sea surface temperatures (SST) from a site located near the Nile River Delta in the eastern Mediterranean (EM) Sea. The Uk'37 and TEX86 records generally are in agreement and indicate SST ranges of 14°C-26°C and 14°C-28°C, respectively, during the last 27 cal ka. During the Holocene, TEX86-based SST estimates are usually higher than Uk'37-based SST estimates, which is likely due to seasonal differences between the timing of the haptophyte and crenarchaeota blooms in the EM and is related to the onset of the modern flow regime of the Nile River. Both records show that SST varied on centennial to millennial timescales in response to global climate events, i.e., cooling during the Last Glacial Maximum (LGM), Heinrich event 1 (H1), and the Younger Dryas (YD) and warming during the Bølling-Allerød and in the early Holocene during deposition of sapropel S1. The H1 cooling was particularly severe and is marked by a drop in SST of ~4.5°C in comparison to pre-H1 SST, with temperatures >1°C cooler than during the LGM. In contrast to high-latitude and western Mediterranean records, which indicate both an abrupt onset and termination of the YD event, the transition from the YD to the Holocene was much more gradual in the EM.

Kaolinite/Chlorite ratio of sediment core GeoTü SL143

The ratio between the clay minerals kaolinite and chlorite has been investigated in high resolution in a late Quaternary sediment core from the central Aegean Sea. The record spans the last ca. 105 ka. The kaolinite/chlorite ratio was used to reconstruct the fine-grained aeolian dust influx from the North African deserts, mainly derived from desiccated lake depressions. It therewith can be used as a proxy for wind activity, aridity and vegetation cover in the source area. The data document three major humid phases in North Africa bracketing the formation of sapropel layers S4, S3 and S1. They occur at >105-95 ka, 83.5-72 ka and 14-2 ka. The first two phases are characterised by relatively abrupt lower and upper boundaries suggesting a non-linear response of vegetation to precipitation, with critical hydrological thresholds. In contrast, the onset and termination of the last humid period were more gradual. Highest kaolinite/chlorite ratios indicating strongest aeolian transport and aridity occur during Marine Isotope Stage (MIS) 5b, at ca. 95-84 ka. The long-term decrease in kaolinite/chlorite ratios during the last glacial period indicates a gradual decline of deflatable lake sediments in the source areas.

Isotope analysis and heat flow measurements of Maria S. Merian cruise MSM21/4 on the western Svalbard margin

Methane hydrate is an ice-like substance that is stable at high-pressure and low temperature in continental margin sediments. Since the discovery of a large number of gas flares at the landward termination of the gas hydrate stability zone off Svalbard, there has been concern that warming bottom waters have started to dissociate large amounts of gas hydrate and that the resulting methane release may possibly accelerate global warming. Here, we can corroborate that hydrates play a role in the observed seepage of gas, but we present evidence that seepage off Svalbard has been ongoing for at least three thousand years and that seasonal fluctuations of 1-2°C in the bottom-water temperature cause periodic gas hydrate formation and dissociation, which focus seepage at the observed sites.

Deuterium isotope ratios of Victoria Lower Glacier Ice Core

The Little Ice Age (LIA) is one of the most prominent climate shifts in the past 5000 yrs. It has been suggested that the LIA might be the most recent of the Dansgaard-Oeschger events, which are better known as abrupt, large scale climate oscillations during the last glacial period. If the case, then according to Broecker (2000a, 2000b) Antarctica should have warmed during the LIA, when the Northern Hemisphere was cold. Here we present new data from the Ross Sea, Antarctica, that indicates surface temperatures were ~2 °C colder during the LIA, with colder sea surface temperatures in the Southern Ocean and/or increased sea-ice extent, stronger katabatic winds, and decreased snow accumulation. Whilst we find there was large spatial and temporal variability, overall Antarctica was cooler and stormier during the LIA. Although temperatures have warmed since the termination of the LIA, atmospheric circulation strength has remained at the same, elevated level. We conclude, that the LIA was either caused by alternative forcings, or that the sea-saw mechanism operates differently during warm periods.

Magnetostratigraphy of ODP Leg 178 holes

We present revised magnetostratigraphic interpretations for Ocean Drilling Program Sites 1095, 1096, and 1101, cored in sediment drifts located off the Pacific margin of the Antarctic Peninsula. The revised interpretations incorporate a variety of observations and results obtained since the end of Leg 178, of which the most significant are new paleomagnetic measurements from U-channel samples, composite depth scales that allow stratigraphic correlation between multiple holes cored at a site, and revised biostratigraphic interpretations. The U-channel data, which include more than 102,000 paleomagnetic observations from more than 13,400 intervals along U-channel samples, are included as electronic files. The magnetostratigraphic records at all three sites are consistent with sedimentation being continuous over the intervals cored, although the data resolution does not preclude short hiatuses less than a few hundred thousand years in duration. The magnetostratigraphic records start at the termination of Subchron C4Ar.2n (9.580 Ma) at ~515 meters composite depth (mcd) for Site 1095, at the onset of Subchron C3n.2n (4.620 Ma) at ~489.68 mcd for Site 1096, and at the onset of Subchron C2An.1n (3.040 Ma) at 209.38 meters below seafloor for Site 1101. All three sites provide paleomagnetic records that extend upward through the Brunhes Chron.

Mitigating Social Risk in the Extractive Sector: Developing Intercultural Competence as a Tool for Negotiating Western-Indigenous Perspectives within the Undergraduate Mining Engineering Curriculum

Drawing upon critical, communications, and educational theories, this thesis develops a novel framing of the problem of social risk in the extractive sector, as it relates to the building of respectful relationships with indigenous peoples. Building upon Bakhtin’s dialogism, the thesis demonstrates the linkage of this aspect of social risk to professional education, and specifically, to the undergraduate mining engineering curriculum, and develops a framework for the development of skills related to intercultural competence in the education of mining engineers. The knowledge of social risk, as well as the level of intercultural competence, of students in the mining engineering program, is investigated through a mixture of surveys and focus groups – as is the impact of specific learning interventions. One aspect of this investigation is whether development of these attributes alters graduates’ conception of their identity as mining engineers, i.e. the range and scope of responsibilities, and understanding of to whom responsibilities are owed, and their role in building trusting relationships with communities. Survey results demonstrate that student openness to the perspectives of other cultures increases with exposure to the second year curriculum. Students became more knowledgeable about social dimensions of responsible mining, but not about cultural dimensions. Analysis of focus group data shows that students are highly motivated to improve community perspectives and acceptance. It is observed that students want to show respect for diverse peoples and communities where they will work, but they are hampered by their inability to appreciate the viewpoints of people who do not share their values. They embrace benefit sharing and environmental protection as norms, but they mistakenly conclude that opposition to mining is rooted in a lack of education rather than in cultural values. Three, sequential, threshold concepts are identified as impeding development of intercultural competence: Awareness and Acknowledgement of Different Forms of Knowledge; Recognition that Value Systems are a Function of Culture; Respect for varied perceptions of Social Wellbeing and Quality of Life. Future curriculum development in the undergraduate mining engineering program, as well as in other educational programs relevant to the extractive sector, can be effectively targeted by focusing on these threshold concepts.

The Economic Case for Electric Mining Equipment and Technical Considerations Relating to their Implementation

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.

Cape Breton Provides Pointers for the Adjustment Programs Required by the Decline of the Old Economy (Working Paper 14)

The Cape Breton Development Corporation need not, should not, be dying in the way it is. “Devco” has been widely represented as a failure dragged out too long. In fact it had for a time considerable success in a role too difficult to be often attempted. The main failure was in the political will to stick to its purpose. This commentary is in three parts. The first, major section discusses the purpose of Devco and the policies that served the purpose quite well but were maintained for little more than a decade. It suggests that the benefits would have been greater if Devco had been started earlier in the period of postwar prosperity. The second section comments on the enfeeblement of Devco in the 1980s. The removal of its development function also weakened, and has eventually led to the abandonment of, Devco’s social purpose in the operation of coal mining. Third, a short epilogue pointing out that, while the Cape Breton case is extreme, there will be increasing need to moderate the socially disruptive consequences of accelerating economic change. There are lessons from the Devco experience: the longer remedial action is delayed, the more difficult and expensive it becomes, and the more necessary for its effectiveness is a steady political will.

Tianjin sales of land by auctions:Italian Colonialism in the early twentieth century China

s a signatory to the Boxer Protocol in 1901, Italy came into possession of the Tianjin concession, its only colonial possession in China. The Italian settlement was situated on the Hai River, and most of the land consisted of cemeteries and salt deposits. Italian administration of the settlement encountered many difficulties. Expropriation of land from the Chinese occupants was not easy, and it proved equally difficult to attract Italian investors. However despite the fact that Italian public opinion supported the abandonment of the concession, the Italian government was ultimately obliged to undertake a project for its urban development. Success in Tianjin became a national challenge for Italy, with the National Trust providing the necessary economic support. The history of the Italian settlement in Tianjin therefore sheds light on the politics of colonialism and on Italy's economic and political agendas at the turn of the twentieth century.

Surface modifications of nanocrystalline diamond films and their functionalization with phthalocyanines

Boron-doped diamond is a promising electrode material for a number of applications providing efficient carrier transport, a high stability of the electrolytic performance with time, a possibility for dye-sensitizing with photosensitive molecules, etc. It can be functionalized with electron donor molecules, like phthalocyanines or porphyrins, for the development of light energy conversion systems. For effective attachment of such molecules, the diamond surface has to be modified by plasma- or photo-chemical processes in order to achieve a desired surface termination. In the present work, the surface modifications of undoped and boron-doped nanocrystalline diamond (NCD) films and their functionalization with various phthalocyanines (Pcs) were investigated. The NCD films have been prepared by hot filament chemical vapor deposition (HFCVD) on silicon substrates and were thereafter subjected to modifications with O2 or NH3 plasmas or UV/O3 treatments for exchange of the H-termination of the as-grown surface. The effectiveness of the modifications and their stability with time during storage under different ambients were studied by contact angle measurements and X-ray photoelectron spectroscopy (XPS). Furthermore, the surface roughness after the modifications was investigated with atomic force microscopy (AFM) and compared to that of as-grown samples in order to establish the appearance of etching of the surface during the treatment. The as-grown and the modified NCD surfaces were exposed to phthalocyanines with different metal centers (Ti, Cu, Mn) or with different side chains. The results of the Pc grafting were investigated by XPS and Raman spectroscopy. XPS revealed the presence of nitrogen stemming from the Pc molecules and traces of the respective metal atoms with ratios close to those in the applied Pc. In a next step Raman spectra of Ti-Pc, Cu-Pc and Mn-Pc were obtained with two different excitation wavelengths (488 and 785 nm) from droplet samples on Si after evaporation of the solvent in order to establish their Raman fingerprints. The major differences in the spectra were assigned to the effect of the size of the metal ion on the structure of the phthalocyanine ring. The spectra obtained were used as references for the Raman spectra of NCD surfaces grafted with Pc. Finally, selected boron doped NCD samples were used after their surface modification and functionalization with Pc for the preparation of electrodes which were tested in a photoelectrochemical cell with a Pt counter electrode and an Ag/AgCl reference electrode. The light sources and electrolytes were varied to establish their influence on the performance of the dye-sensitized diamond electrodes. Cyclic voltammetry measurements revealed broad electrochemical potential window and high stability of the electrodes after several cycles. The open circuit potential (OCP) measurements performed in dark and after illumination showed fast responses of the electrodes to the illumination resulting in photocurrent generation.