Living room and seating alcove, Ocean View Farmhouse, Mt. Mee

As seen from main deck. Stone fireplace on right.

Living room and seating alcove, Ocean View Farmhouse, Mt. Mee

Leadlight window to living room with seating alcove beyond.

Living room and seating alcove beyond, Ocean View Farmhouse, Mt. Mee

As seen from main deck.

Living room and seating alcove, Ocean View Farmhouse, Mt. Mee

As seen from steps of main deck.

A combinatorial approach to the chemical synthesis and biological evaluation of 3,4,5-trisubstiituted furan-2(5H)-ones

Many important natural products contain the furan-2(5H)-one structure. The structure of this molecule lends itself to manipulation using combinatorial techniques due to the presence of more than one site for the attachment of different suhstituents. By developing different reaction schemes at the three sites available for attachment on the furan-2(5H)-one scaffold, combinatorial chemistry techniques can be employed to assemble libraries of novel furan 2(5H)-ones. These libraries can then be entered into various biological screening programmes. This approach will enable a vast diversity or compounds to be examined, in the hope or finding new biologically active Iead structures. The work in this thesis has investigated the potential that combinatorial chemistry has in the quest for new biologically active lead structures based on the furan-2(5H)-one structure. Different reactions were investigated with respect to their suitability for inclusion in a library. Once sets of reactions at the various sites had been established, the viability of these reactions in the assembly of combinatorial libraries was investigated. Purification methods were developed, and the purified products entered into suitable biological screening tests. Results from some of these tests were optimised using structure activity relationships, and the resulting products re-screened. The screening tests performed were for anticancer and antimicrobial activity, cholecystokinin (CCK-B) antagonism and anti-inflammatory activity (in the quest for novel cyclo-oxygenase (COX-2) selective non-steroidal anti-inflammatory drugs). It has been shown that many reactions undergone by the furan-2(5H)-one structure are suitable for the assembly of a combinatorial library. Investigation into the assembly of different libraries has been carried out with initial screening results included. From this work, further investigation into combinatorial library assembly and structure activity relationships of screened reaction products can be undertaken.

Retinal and systemic vascular function in health and disease: the effect of smoking and coronary artery disease

The purpose of the following studies was to explore the effect of systemic vascular and endothelial dysfunction upon the ocular circulation and functionality of the retina. There are 6 principal sections to the present work. Retinal vessel activity in smokers and non-smokers: the principal findings of this work were: chronic smoking affects retinal vessel motion at baseline and during stimulation with flickering light; chronic smoking leads to a vaso-constrictory shift in retinal arteriolar reactivity to flicker; retinal arteriolar elasticity is decreased in chronic smokers. The effect of acute smoking on retinal vessel dynamics in smokers and non-smokers: the principal finding of this work was that retinal reactivity in chronic smokers is blunted when exposed to clicker light provocation immediately after smoking one cigarette. Ocular blood flow in coronary artery disease: The principal findings of this work were: retrobulbar and retinal blood flow is preserved in CAD patients, despite a change pulse wave transmission; arterial retinal response to flickering light provocation is significantly delayed in CAD patients; retinal venular diameters are significantly dilated in CAD patients. Autonomic nervous system function and peripheral circulation in CAD: The principal findings in this work were: CAD patients demonstrate a sympathetic overdrive during a 24 period; a delay in peripheral vascular reactivity (nail-fold capillaries) as observed in patients suffering from CAD could be caused by either arteriosclerotic changes of the vascular walls or due to systemic haemodynamic changes. Visual function in CAD: The principal findings in this work were: overall visual function in CAD patients is preserved, despite a decrease in contrast sensitivity; applying a filtering technique selecting those with greater coefficient of variance which in turn represents a decrease in reliability, some patients appear to have an impaired visual function as assessed using FDT visual field evaluation. Multiple functional, structural and biochemical vascular endothelial dysfunctions in patients suffering from CAD: relationships and possible implications: The principal findings of this work were: BMI significantly correlated with vWF (a marker of endothelial function) in CAD patients. Retinal vascular reactivity showed a significant correlation with peripheral reactivity parameters in controls which lacked in the CAD group and could reflect a loss in vascular endothelial integrity; visual field parameters as assessed by frequency doubling technology were strongly related with systemic vascular elasticity (ambulatory arterial stiffness index) in controls but not CAD patients.

Induction of placental heme oxygenase-1 is protective against TNFα-induced cytotoxicity and promotes vessel relaxation

Background: Pregnancy is characterized by an inflammatory-like process and this may be exacerbated in preeclampsia. The heme oxygenase (HO) enzymes generate carbon monoxide (CO) that induces blood vessel relaxation and biliverdin that acts as an endogenous antioxidant. Materials and Methods: We examined the expression and localization of HO-1 and HO-2 in normal and preeclamptic placenta using reverse transcription polymerase chain reaction (RT-PCR), RNase protection assay, immunoblotting and immunohistochemistry. In addition, the effect of HO activation on tumor necrosis factor-alpha (TNF) induced placental damage and on feto-placental circulation was studied. Results: We provide the first evidence for the role of HO as an endogenous placental factor involved with cytoprotection and placental blood vessel relaxation. HO-1 was significantly higher at term, compared with first trimester placentae indicating its role in placental vascular development and regulation. HO-1 predominantly localized in the extravascular connective tissue that forms the perivascular contractile sheath around the developing blood vessels. HO-2 was localized in the capillaries, as well as the villous stroma, with weak staining of trophoblast. Induction of HO-1 caused a significant attenuation of TNF-mediated cellular damage in placental villous explants, as assessed by lactate dehydrogenase leakage (p 0.01). HO-1 protein was significantly reduced in placentae from pregnancies complicated with preeclampsia, compared with gestationally matched normal pregnancies. This suggests that the impairment of HO-1 activation may compromise the compensatory mechanism and predispose the placenta to cellular injury and subsequent maternal endothelial cell activation. Isometric contractility studies showed that hemin reduced vascular tension by 61% in U46619-preconstricted placental arteries. Hemininduced vessel relaxation and CO production was inhibited by HO inhibitor, tin protoporphyrin IX. Conclusions: Our findings establish HO-1 as an endogenous system that offers protection against cytotoxic damage in the placenta, identifies the HO-CO pathway to regulate feto-placental circulation and provides a new approach to study the disease of preeclampsia.

Corporate governance and finance in Poland and Russia

This book provides a comparative analysis of the emerging corporate control structures in the transition economies. It details characteristics of corporate governance in the two largest transition economies: Russia and Poland. It explores what kind of ownership structures are emerging in these two countries and to what degree they are they path-dependent and conditional on the initial choice of privatisation methods - fast ownership transfer through the mass privatisation programme and loans-for-equity scheme in Russia, and a more 'organic' growth of the new private sector in Poland. It examines the directions of the subsequent, post-privatisation, secondary ownership flows in both countries and the impact of the government on corporations, implied both by the residual shareholding of the state and by its regulatory and administrative actions.

Public libraries and the right to the [smart] city

The future of public libraries has been threatened by funding cuts and new digital technologies which have led many people to question their traditional role and purpose. However, freedom of information, ready access to knowledge and information literacy in all its digital and analog guises are more important than ever. Thus, public libraries remain significant spaces and places where people can socially interact and learn. In many countries public libraries are reinventing themselves and part of this process has been the redesign of library services and the design and construction of new library building and facilities that articulate the values, purpose and role of what has been termed 'the next library'. Following discussion of new library developments in London, Birmingham and Worcester in the UK, Aarhus in Denmark and Helsinki in Finland, the article concludes that public libraries are now both social and media spaces as well as being important physical places that can help city dwellers decide what type of urban world they want to see.

Codon-precise, synthetic, antibody fragment libraries built using automated hexamer codon additions and validated through next generation sequencing

We have previously described ProxiMAX, a technology that enables the fabrication of precise, combinatorial gene libraries via codon-by-codon saturation mutagenesis. ProxiMAX was originally performed using manual, enzymatic transfer of codons via blunt-end ligation. Here we present Colibra™: an automated, proprietary version of ProxiMAX used specifically for antibody library generation, in which double-codon hexamers are transferred during the saturation cycling process. The reduction in process complexity, resulting library quality and an unprecedented saturation of up to 24 contiguous codons are described. Utility of the method is demonstrated via fabrication of complementarity determining regions (CDR) in antibody fragment libraries and next generation sequencing (NGS) analysis of their quality and diversity.

Visible and Invisible Bulgarian Heritage (One research under the Bulgarian Heritage published on the Web)

This paper dials with presentations of the Bulgarian Cultural and Historical Heritage in the Cyberspace. The study was taking place at the Information management course with bachelor students in Information Technologies, Information Brokerage and Information Security at the University of Library Studies and Information Technologies. The students describe about 300 different objectives – cultural and historical, material and immaterial.

Profile of planning: A study of a three-year project on the implementation of collaborative library media programs

The implementation of collaborative planning and teaching models in ten flexibly scheduled elementary and middle school library media centers was studied to determine which factors facilitated the collaborative planning process and to learn what occurs when library media specialists (LMSs) and classroom teachers (CTs) plan together. In this qualitative study, 61 principals, CTs, and LMSs were interviewed on a range of topics including the principal's role, school climate, the value of team planning, the importance of information literacy instruction, and the ideal learning environment. Other data sources were observations, videotapes of planning sessions, and documents. This three-year school reform effort was funded by the Library Power Project to improve library programs, to encourage collaborative planning, and to increase curricular integration of information literacy skills instruction. ^ The findings included a description of typical planning sessions and the identification of several major factors which impacted the success of collaborative planning: the individuals involved, school climate, time for planning, the organization of the school, the facility and collection, and training. Of these factors, the characteristics and actions of the people involved were most critical to the implementation of the innovation. The LMS was the pivotal player and, in the views of CTs, principals, and LMSs themselves, must be knowledgeable about curriculum, the library collection, and instructional design and delivery; must be open and welcoming to CTs and use good interpersonal skills; and must be committed to information literacy instruction and willing to act as a change agent. The support of the principal was vital; in schools with successful programs, the principal served as an advocate for collaborative planning and information literacy instruction, provided financial support for the library program including clerical staff, and arranged for LMSs and CTs to have time during the school day to plan together. ^ CTs involved in positive planning partnerships with LMSs were flexible, were open to change, used a variety of instructional materials, expected students to be actively involved in their own learning, and were willing to team teach with LMSs. Most CTs planning with LMSs made lesson plans in advance and preferred to plan with others. Also, most CTs in this study planned with grade level or departmental groups, which expedited the delivery of information literacy instruction and the effective use of planning time. ^ Implications of the findings of this research project were discussed for individual schools, for school districts, and for colleges and universities training LMSs, CTs, and administrators. Suggestions for additional research were also included. ^

Financial aid and the persistence of associate of arts graduates transferring to a senior university

This study examined the effects of financial aid on the persistence of associate of arts graduates transferring to a senior university in one of four consecutive fall semesters (1998-2001). Situated in an international metropolitan area in the southeastern United States, the institution where the study was conducted is a large public research university identified as a Hispanic Serving Institution. Archival databases served as the source of information on the academic and social background of the 4,669 participants in the study. Data from institutional financial aid records were pooled with the data in the student administrative system.^ For purposes of this study, persistence was defined as ongoing progress until completing the baccalaureate degree. Student social background variables used in the study were gender, ethnicity, age, and income, with GPA and part-time or full-time enrollment status being the academic variables. Amount and type of aid, including grants, loans, scholarships, and work study were incorporated in the models to determine the effect of financial aid on the persistence of these transfer students. Because the dependent variable persistence had three possible outcomes (graduated, still enrolled, dropped out) multinomial logistic regression was the appropriate technique for analyzing the data; four multinomial models were employed in the analysis.^ Findings suggest that grants awarded based on the financial need of students and loans were effective in encouraging the persistence of students, but scholarships and work study were not effective.^

Analytical approximations to predict performance measures of manufacturing systems with job failures and parallel processing

Parallel processing is prevalent in many manufacturing and service systems. Many manufactured products are built and assembled from several components fabricated in parallel lines. An example of this manufacturing system configuration is observed at a manufacturing facility equipped to assemble and test web servers. Characteristics of a typical web server assembly line are: multiple products, job circulation, and paralleling processing. The primary objective of this research was to develop analytical approximations to predict performance measures of manufacturing systems with job failures and parallel processing. The analytical formulations extend previous queueing models used in assembly manufacturing systems in that they can handle serial and different configurations of paralleling processing with multiple product classes, and job circulation due to random part failures. In addition, appropriate correction terms via regression analysis were added to the approximations in order to minimize the gap in the error between the analytical approximation and the simulation models. Markovian and general type manufacturing systems, with multiple product classes, job circulation due to failures, and fork and join systems to model parallel processing were studied. In the Markovian and general case, the approximations without correction terms performed quite well for one and two product problem instances. However, it was observed that the flow time error increased as the number of products and net traffic intensity increased. Therefore, correction terms for single and fork-join stations were developed via regression analysis to deal with more than two products. The numerical comparisons showed that the approximations perform remarkably well when the corrections factors were used in the approximations. In general, the average flow time error was reduced from 38.19% to 5.59% in the Markovian case, and from 26.39% to 7.23% in the general case. All the equations stated in the analytical formulations were implemented as a set of Matlab scripts. By using this set, operations managers of web server assembly lines, manufacturing or other service systems with similar characteristics can estimate different system performance measures, and make judicious decisions - especially setting delivery due dates, capacity planning, and bottleneck mitigation, among others.

Correspondence of historic salinity fluctuations in Florida Bay, USA, to atmospheric variability and anthropogenic changes

Florida Bay is a highly dynamic estuary that exhibits wide natural fluctuations in salinity due to changes in the balance of precipitation, evaporation and freshwater runoff from the mainland. Rapid and large-scale modification of freshwater flow and construction of transportation conduits throughout the Florida Keys during the late nineteenth and twentieth centuries reshaped water circulation and salinity patterns across the ecosystem. In order to determine long-term patterns in salinity variation across the Florida Bay estuary, we used a diatom-based salinity transfer function to infer salinity within 3.27 ppt root mean square error of prediction from diatom assemblages from four ~130 year old sediment records. Sites were distributed along a gradient of exposure to anthropogenic shifts in the watershed and salinity. Precipitation was found to be the primary driver influencing salinity fluctuations over the entire record, but watershed modifications on the mainland and in the Florida Keys during the late-1800s and 1900s were the most likely cause of significant shifts in baseline salinity. The timing of these shifts in the salinity baseline varies across the Bay: that of the northeastern coring location coincides with the construction of the Florida Overseas Railway (AD 1906–1916), while that of the east-central coring location coincides with the drainage of Lake Okeechobee (AD 1881–1894). Subsequent decreases occurring after the 1960s (east-central region) and early 1980s (southwestern region) correspond to increases in freshwater delivered through water control structures in the 1950s–1970s and again in the 1980s. Concomitant increases in salinity in the northeastern and south-central regions of the Bay in the mid-1960s correspond to an extensive drought period and the occurrence of three major hurricanes, while the drop in the early 1970s could not be related to any natural event. This paper provides information about major factors influencing salinity conditions in Florida Bay in the past and quantitative estimates of the pre- and post-South Florida watershed modification salinity levels in different regions of the Bay. This information should be useful for environmental managers in setting restoration goals for the marine ecosystems in South Florida, especially for Florida Bay.