Lundy: An Analysis and Comparative Study of Factors Affecting the Development of the Island from 1577 to 1969, with a Gazetteer of Sites and Monuments.

The dates chosen for the thesis encompass the development of Lundy from an isolated subsistence economy, reliant on the harvesting of sea birds and rabbits, to a small village community with increasing economic dependence on seasonal visitors. This change is considered in the context of a comparative study of small islands, and in relation to the broader context of regional and national economic and social background. These, with new researches and the re-examination of existing texts, have enabled a fuller and more accurate account of Lundy's history than has hitherto been offered. This study concludes that while many factors have shaped. Lundy's development, the most illuminating have been the geography, the nature of the ownership in its response to the island and the dynamics of change, and the effect of external factors in the last two centuries. It is also suggested that the island has been more consistently populated than was previously thought. Claims to extra-ordinary legal status for Lundy are examined, and considered to be without substance. It is found that Lundy's extra-parochial status, and exclusion from administrative processes until the mid-twentieth century, rested on its isolation and lack of importance in terms of size or the value of its resources. This lack of importance has also contributed to the present re-interpretation of island resources. The study exemplifies the proposition that understanding of local history does not rest on a sequence of documented events in one place, but upon the integration of documentary, archaeological, cartographic, photographic and artistic resources taken in the broader context of comparative studies, and a wider understanding of external historical, economic and social circumstances. The systematic cross reference of the gazetteer of the sites and monuments to the main text serves both to illuminate some parts of the history, and to provide a firm base from which future work may proceed

Capillarity-like growth of protein folding nuclei

We analyzed folding routes predicted by a variational model in terms of a generalized formalism of the capillarity scaling theory for 28 two-state proteins. The scaling exponent ranged from 0.2 to 0.45 with an average of 0.33. This average value corresponds to packing of rigid objects.That is, on average the folded core of the nucleus is found to be relatively diffuse. We also studied the growth of the folding nucleus and interface along the folding route in terms of the density or packing fraction. The evolution of the folded core and interface regions can be classified into three patterns of growth depending on how the growth of the folded core is balanced by changes in density of the interface. Finally, we quantified the diffuse versus polarized structure of the critical nucleus through direct calculation of the packing fraction of the folded core and interface regions. Our results support the general picture of describing protein folding as the capillarity-like growth of folding nuclei.Comment: 16 pages,6 figures. Submitted to Proc.Natl.Acad.Sc

Simulation, Experiment, and Evolution: Understanding Nucleation in Protein S6 Folding

In this study, we explore nucleation and the transition state ensemble of the ribosomal protein S6 using a Monte Carlo Go model in conjunction with restraints from experiment. The results are analyzed in the context of extensive experimental and evolutionary data. The roles of individual residues in the folding nucleus are identified and the order of events in the S6 folding mechanism is explored in detail. Interpretation of our results agrees with, and extends the utility of, experiments that shift f-values by modulating denaturant concentration and presents strong evidence for the realism of the mechanistic details in our Monte Carlo Go model and the structural interpretation of experimental f-values. We also observe plasticity in the contacts of the hydrophobic core that support the specific nucleus. For S6, which binds to RNA and protein after folding, this plasticity may result from the conformational flexibility required to achieve biological function. These results present a theoretical and conceptual picture that is relevant in understanding the mechanism of nucleation in protein folding.Comment: PNAS in pres

Phi-values in protein folding kinetics have energetic and structural components

Phi-values are experimental measures of how the kinetics of protein folding is changed by single-site mutations. Phi-values measure energetic quantities, but are often interpreted in terms of the structures of the transition state ensemble. Here we describe a simple analytical model of the folding kinetics in terms of the formation of protein substructures. The model shows that Phi-values have both structural and energetic components. In addition, it provides a natural and general interpretation of "nonclassical" Phi-values (i.e., less than zero, or greater than one). The model reproduces the Phi-values for 20 single-residue mutations in the alpha-helix of the protein CI2, including several nonclassical Phi-values, in good agreement with experiments.Comment: 15 pages, 3 figures, 1 tabl

Worldwide prevalence of tocophobia in pregnant women: systematic review and meta-analysis

Introduction: Tocophobia is defined as a severe fear of pregnancy and childbirth. There is increasing evidence that tocophobia may have short-term and long-term adverse effects on mother and baby. We performed a systematic review and meta-analysis to determine the global prevalence of tocophobia in pregnancy. Material and methods: Relevant articles were identified through searching six relevant databases: MEDLINE, CINAHL, Pubmed, PsycINFO, Maternity & Infant Care and Scopus between 1946 and April 2016. We used search terms for tocophobia prevalence in pregnant women that we agreed with a medical librarian. There were no language restrictions. Two review authors independently assessed data for inclusion, extracted data and assessed quality using a standardized appraisal tool. Meta-analysis was performed to determine the overall pooled-prevalence of tocophobia. Several subgroup and sensitivity analyses were conducted. Results: Thirty-three studies were included in the systematic review from 18 countries of which data from 29 studies were used in the meta-analysis of 853 988 pregnant women. Definition of tocophobia varied, whereas prevalence rates ranged between 3.7 and 43%. The overall pooled prevalence of tocophobia, using a random-effects model, was 14% (95% CI 0.12â 0.16). Significant heterogeneity was observed (I2 = 99.25%, p = 0.00), which was not explained in subgroup analyses including tocophobia definition used, screening trimester and parity. Conclusion: The prevalence of tocophobia is estimated at 14% and appears to have increased in recent years (2000 onwards). Considerable heterogeneity (99.25%) was noted that may be attributed to lack of consensus on the definition of tocophobia, so our results should be interpreted with caution

Polymorphisms on PAI-1 and ACE genes in association with fibrinolytic bleeding after on-pump cardiac surgery

Publisher Copyright: © 2015 Ozolina et al.Background: Carriers of plasminogen activator inhibitor -1 (PAI-1) -675 genotype 5G/5G may be associated with lower preoperative PAI-1 plasma levels and higher blood loss after heart surgery using cardiopulmonary bypass (CPB). We speculate if polymorphisms of PAI-1 -844 A/G and angiotensin converting enzyme (ACE) intron 16 I/D also might promote fibrinolysis and increase postoperative bleeding. Methods: We assessed PAI-1 -844 A/G, and ACE intron 16 I/D polymorphisms by polymerase chain reaction technique and direct sequencing of genomic DNA from 83 open heart surgery patients that we have presented earlier. As primary outcome, accumulated chest tube drainage (CTD) at 4 and 24 h were analyzed for association with genetic polymorphisms. As secondary outcome, differences in plasma levels of PAI-1, t-PA/PAI-1 complex and D-dimer were determined for each polymorphism. SPSS® was used for statistical evaluation. Results: The lowest preoperative PAI-1 plasma levels were associated with PAI-1 -844 genotype G/G, and higher CTD, as compared with genotype A/A at 4 and 24 h after surgery. Correspondingly, 4 h after the surgery CTD was higher in carriers of ACE intron 16 genotype I/I, as compared with genotype D/D. PAI-1 plasma levels and t-PA/PAI-1 complex reached nadir in carriers of ACE intron 16 genotype I/I, in whom we also noticed the highest D-dimer levels immediately after surgery. Notably, carriers of PAI-1 -844 genotype G/G displayed higher D-dimer levels at 24 h after surgery as compared with those of genotype A/G. Conclusions: Increased postoperative blood loss secondary to enhanced fibrinolysis was associated with carriers of PAI-1 -844 G/G and ACE Intron 16 I/I, suggesting that these genotypes might predict increased postoperative blood loss after cardiac surgery using CPB.publishersversionPeer reviewe

Acquired and congenital disorders of sung performance: A review.

Many believe that the majority of people are unable to carry a tune. Yet, this widespread idea underestimates the singing abilities of the layman. Most occasional singers can sing in tune and in time, provided that they perform at a slow tempo. Here we characterize proficient singing in the general population and identify its neuronal underpinnings by reviewing behavioral and neuroimaging studies. In addition, poor singing resulting from a brain injury or neurogenetic disorder (i.e., tone deafness or congenital amusia) is examined. Different lines of evidence converge in indicating that poor singing is not a monolithic deficit. A variety of poor-singing "phenotypes" are described, with or without concurrent perceptual deficits. In addition, particular attention is paid to the dissociations between specific abilities in poor singers (e.g., production of absolute vs. relative pitch, pitch vs. time accuracy). Such diversity of impairments in poor singers can be traced to different faulty mechanisms within the vocal sensorimotor loop, such as pitch perception and sensorimotor integration