Stereoselective synthesis of 5-substituted pyrrolo[1,2-c]imidazol-3-ones. Access to aldosterone synthase inhibitors and chiral precatalysts

Compounds containing the pyrrolidine moiety are key substructures of compounds with biological activity and organocatalysts. In particular, annulated chiral pyrrolidines with alpha stereogenic centers have aldostereone synthase inhibition activity. In addition, 5-substituted pyrroloimidazol(in)ium salts precursors to N-heterocyclic carbene (NHC) precatalysts are rare due to a lack of convenient synthetic routes to access them. In this thesis is described a rapid synthesis of NHC precursors and a possible route to 5-substituted pyrroloimidazole biologically active compounds. The method involves the preparation of chiral saturated and achiral unsaturated pyrrolo[I,2- c]imidazol-3-ones from N-Cbz-protected t-Butyl proline carboxamide. The resulting starting materials may be used to prepare the target chiral annulated imidazol(in)ium products by a two-step sequence involving first stereoselective lithiation-substitution, followed by POCh induced salt formation.

Aboriginal women in education : Honouring our experiences a vision of access to and success within the university

This thesis explores Aboriginal women's access to and success within universities through an examination of Aboriginal women's educational narratives, along with input from key service providers from both the Aboriginal and non-Aboriginal community. Implemented through the Wildfire Research Method, participants engaged in a consensusbased vision of accessible education that honours the spiritual, emotional, intellectual, and physical elements necessary for the success of Aboriginal women in university. This study positions Aboriginal women as agents of social change by allowing them to define their own needs and offer viable solutions to those needs. Further, it connects service providers from the many disconnected sectors that implicate Aboriginal women's education access. The realities of Aboriginal women are contextualized through historical, sociocultural, and political analyses, revealing the need for a decolonizing educational approach. This fosters a shift away from a deficit model toward a cultural and linguistic assets based approach that emphasizes the need for strong cultural identity formation. Participants revealed academic, cultural, and linguistic barriers and offered clear educational specifications for responsive and culturally relevant programming that will assist Aboriginal women in developing and maintaining strong cultural identities. Findings reveal the need for curriculum that focuses on decolonizing and reclaiming Aboriginal women's identities, and program outcomes that encourage balance between two worldviews-traditional and academic-through the application of cultural traditions to modern contexts, along with programming that responds to the immediate needs of Aboriginal women such as childcare, housing, and funding, and provide an opportunity for universities and educators to engage in responsive and culturally grounded educational approaches.

Whither RDS? An investigation of respondent driven sampling as a method of recruiting mainstream marijuana users.

Background: An important challenge in conducting social research of specific relevance to harm reduction programs is locating hidden populations of consumers of substances like cannabis who typically report few adverse or unwanted consequences of their use. Much of the deviant, pathologized perception of drug users is historically derived from, and empirically supported, by a research emphasis on gaining ready access to users in drug treatment or in prison populations with higher incidence of problems of dependence and misuse. Because they are less visible, responsible recreational users of illicit drugs have been more difficult to study. Methods: This article investigates Respondent Driven Sampling (RDS) as a method of recruiting experienced marijuana users representative of users in the general population. Based on sampling conducted in a multi-city study (Halifax, Montreal, Toronto, and Vancouver), and compared to samples gathered using other research methods, we assess the strengths and weaknesses of RDS recruitment as a means of gaining access to illicit substance users who experience few harmful consequences of their use. Demographic characteristics of the sample in Toronto are compared with those of users in a recent household survey and a pilot study of Toronto where the latter utilized nonrandom self-selection of respondents. Results: A modified approach to RDS was necessary to attain the target sample size in all four cities (i.e., 40 'users' from each site). The final sample in Toronto was largely similar, however, to marijuana users in a random household survey that was carried out in the same city. Whereas well-educated, married, whites and females in the survey were all somewhat overrepresented, the two samples, overall, were more alike than different with respect to economic status and employment. Furthermore, comparison with a self-selected sample suggests that (even modified) RDS recruitment is a cost-effective way of gathering respondents who are more representative of users in the general population than nonrandom methods of recruitment ordinarily produce. Conclusions: Research on marijuana use, and other forms of drug use hidden in the general population of adults, is important for informing and extending harm reduction beyond its current emphasis on 'at-risk' populations. Expanding harm reduction in a normalizing context, through innovative research on users often overlooked, further challenges assumptions about reducing harm through prohibition of drug use and urges consideration of alternative policies such as decriminalization and legal regulation.

Fabrication and Characterization of All-Fiber Components for Optical Access Networks

This Thesis deals with the fabrication and characterization of novel all-fiber components for access networks. All fiber components offer distinctive advantages due to low forward and backward losses, epoxy free optical path and high power handling. A novel fabrication method for monolithic 1x4 couplers, which are vital components in distributed passive optical networks, is realized. The fabrication method differs from conventional structures with a symmetric coupling profile and hence offers ultra wideband performance and easy process control. New structure for 1x4 couplers, by fusing five fibers is proposed to achieve high uniformity, which gives equivalent uniformity performance to 1x4 planar lightwave splitters, isolation in fused fiber WDM is improved with integration of long period gratings. Packaging techniques of fused couplers are analyzed for long term stability.

Markov chain montecarlo method applied to rounding zeros of compositional data: first approach

As stated in Aitchison (1986), a proper study of relative variation in a compositional data set should be based on logratios, and dealing with logratios excludes dealing with zeros. Nevertheless, it is clear that zero observations might be present in real data sets, either because the corresponding part is completely absent –essential zeros– or because it is below detection limit –rounded zeros. Because the second kind of zeros is usually understood as “a trace too small to measure”, it seems reasonable to replace them by a suitable small value, and this has been the traditional approach. As stated, e.g. by Tauber (1999) and by Martín-Fernández, Barceló-Vidal, and Pawlowsky-Glahn (2000), the principal problem in compositional data analysis is related to rounded zeros. One should be careful to use a replacement strategy that does not seriously distort the general structure of the data. In particular, the covariance structure of the involved parts –and thus the metric properties– should be preserved, as otherwise further analysis on subpopulations could be misleading. Following this point of view, a non-parametric imputation method is introduced in Martín-Fernández, Barceló-Vidal, and Pawlowsky-Glahn (2000). This method is analyzed in depth by Martín-Fernández, Barceló-Vidal, and Pawlowsky-Glahn (2003) where it is shown that the theoretical drawbacks of the additive zero replacement method proposed in Aitchison (1986) can be overcome using a new multiplicative approach on the non-zero parts of a composition. The new approach has reasonable properties from a compositional point of view. In particular, it is “natural” in the sense that it recovers the “true” composition if replacement values are identical to the missing values, and it is coherent with the basic operations on the simplex. This coherence implies that the covariance structure of subcompositions with no zeros is preserved. As a generalization of the multiplicative replacement, in the same paper a substitution method for missing values on compositional data sets is introduced

Barreras en el acceso a la dirección escolar : diferencias entre profesoras y directoras de centros de Educación Infantil y Primaria. 'Barriers in the access to school management : differences between teachers and head-teachers from early childhood and elementary education schools'.

Resumen tomado de la publicación. Con el apoyo económico del departamento MIDE de la UNED

Select-divide-and-conquer method for large-scale configuration interaction

A select-divide-and-conquer variational method to approximate configuration interaction (CI) is presented. Given an orthonormal set made up of occupied orbitals (Hartree-Fock or similar) and suitable correlation orbitals (natural or localized orbitals), a large N-electron target space S is split into subspaces S0,S1,S2,...,SR. S0, of dimension d0, contains all configurations K with attributes (energy contributions, etc.) above thresholds T0={T0egy, T0etc.}; the CI coefficients in S0 remain always free to vary. S1 accommodates KS with attributes above T1≤T0. An eigenproblem of dimension d0+d1 for S0+S 1 is solved first, after which the last d1 rows and columns are contracted into a single row and column, thus freezing the last d1 CI coefficients hereinafter. The process is repeated with successive Sj(j≥2) chosen so that corresponding CI matrices fit random access memory (RAM). Davidson's eigensolver is used R times. The final energy eigenvalue (lowest or excited one) is always above the corresponding exact eigenvalue in S. Threshold values {Tj;j=0, 1, 2,...,R} regulate accuracy; for large-dimensional S, high accuracy requires S 0+S1 to be solved outside RAM. From there on, however, usually a few Davidson iterations in RAM are needed for each step, so that Hamiltonian matrix-element evaluation becomes rate determining. One μhartree accuracy is achieved for an eigenproblem of order 24 × 106, involving 1.2 × 1012 nonzero matrix elements, and 8.4×109 Slater determinants

Drying method influences the development of germinability, dessication tolerance and subsequent longevity of immature seeds of sumauma (Ceiba pentandra (L.) Gaertn. [Bombacaceae])

The ability to germinate, tolerate desiccation and survive in air-dry storage was investigated during early seed development in planta and subsequent ex planta maturation of sumauma (Ceiba pentandra). Immature fruits were collected on three different dates (i.e. from about 5 days before until 7 days after mass maturity). Immature fresh seeds were not able to germinate. Fruits or seeds were subjected immediately after each collection to three different drying treatments with progressively slower rates of dessication: (i) seeds were extracted from the fruits and dried immediately; (ii) fruits were dried in a thin layer; (iii) fruits were dried in a tied polyethylene bag (with 10 holes of 1cm diameter). Drying was in a room maintained at 25 degrees C +/- 3 degrees C and 65%+/- 5% r.h. For treatment (i) the seeds were dried for 6 days in order to reduce moisture content to around 13% ( +/- 2%) moisture content. For treatments (ii) and (iii) the fruits were subjected to different periods of drying depending upon collection date. The results of these post-collection treatments showed generally that the more immature the seeds the slower the rate of drying that is required to improve ability to germinate, ability to tolerate desiccation and potential longevity, but at the third harvest, 7 days after mass maturity, the intermediate drying rate treatment was the most beneficial. Thus post fruit collection treatments can be modified depending upon the stage of seed development in order to provide good to high quality seeds of sumauma when collection has to be made at a site with difficult access at less than ideal times. The results are relevant to seed collection practices for both forestry and ex situ plant biodiversity conservation.

Forty-eight hour access to primary care: practice factors predicting patients' perceptions

Background: The government has proposed a 48-hour target for GP availability. Although many practices are moving towards delivering that goal, recent national patient surveys have reported a deterioration in patients' reports of doctor availability. What practice factors contribute to patients' perceptions of doctor availability? Method: A cross sectional patient survey (11 000 patients from 54 inner London practices, 7247 (66%) respondents) using the General Practice Assessment Survey. We asked patients how soon they could be seen in their practice following non-urgent consultation requests and related their aggregated responses to the characteristics of their practice. Results: Three factors relating to practice administration and appointments systems operation independently predicted patients' reports of doctor availability. These were the proportion of patients asked to attend the surgery and wait to be seen, the proportion of patients seen using an emergency surgery arrangement, and the extent of practice computerization. Conclusion: Some practices may have difficulty in meeting the target for GP availability. Meeting the target will involve careful review of practice administrative procedures.

Measuring departures from Hardy-Weinberg: a Markov chain Monte Carlo method for estimating the inbreeding coefficient

Many well-established statistical methods in genetics were developed in a climate of severe constraints on computational power. Recent advances in simulation methodology now bring modern, flexible statistical methods within the reach of scientists having access to a desktop workstation. We illustrate the potential advantages now available by considering the problem of assessing departures from Hardy-Weinberg (HW) equilibrium. Several hypothesis tests of HW have been established, as well as a variety of point estimation methods for the parameter which measures departures from HW under the inbreeding model. We propose a computational, Bayesian method for assessing departures from HW, which has a number of important advantages over existing approaches. The method incorporates the effects-of uncertainty about the nuisance parameters--the allele frequencies--as well as the boundary constraints on f (which are functions of the nuisance parameters). Results are naturally presented visually, exploiting the graphics capabilities of modern computer environments to allow straightforward interpretation. Perhaps most importantly, the method is founded on a flexible, likelihood-based modelling framework, which can incorporate the inbreeding model if appropriate, but also allows the assumptions of the model to he investigated and, if necessary, relaxed. Under appropriate conditions, information can be shared across loci and, possibly, across populations, leading to more precise estimation. The advantages of the method are illustrated by application both to simulated data and to data analysed by alternative methods in the recent literature.

Determination of the density of the multiple access interference of a CDMA system from its moments

A standard CDMA system is considered and an extension of Pearson's results is used to determine the density function of the interference. The method is shown to work well in some cases, but not so in others. However this approach can be useful in further determining the probability of error of the system with minimal computational requirements.

A method to assess individual research outputs

We present here a straightforward method which can be used to obtain a quantitative indication of an individual research output for an academic. Different versions, selections and options are presented to enable a user to easily calculate values both for stand-alone papers and overall for the collection of outputs for a person. The procedure is particularly useful as a metric to give a quantitative indication of the research output of a person over a time window. Examples are included to show how the method works in practice and how it compares to alternative techniques.

The XWS open access catalogue of extreme European windstorms from 1979 to 2012

The XWS (eXtreme WindStorms) catalogue consists of storm tracks and model-generated maximum 3 s wind-gust footprints for 50 of the most extreme winter windstorms to hit Europe in the period 1979–2012. The catalogue is intended to be a valuable resource for both academia and industries such as (re)insurance, for example allowing users to characterise extreme European storms, and validate climate and catastrophe models. Several storm severity indices were investigated to find which could best represent a list of known high-loss (severe) storms. The best-performing index was Sft, which is a combination of storm area calculated from the storm footprint and maximum 925 hPa wind speed from the storm track. All the listed severe storms are included in the catalogue, and the remaining ones were selected using Sft. A comparison of the model footprint to station observations revealed that storms were generally well represented, although for some storms the highest gusts were underestimated. Possible reasons for this underestimation include the model failing to simulate strong enough pressure gradients and not representing convective gusts. A new recalibration method was developed to estimate the true distribution of gusts at each grid point and correct for this underestimation. The recalibration model allows for storm-to-storm variation which is essential given that different storms have different degrees of model bias. The catalogue is available at www.europeanwindstorms.org.