Toward the prediction of class I and II mouse major histocompatibility complex-peptide-binding affinity:in silico bioinformatic step-by-step guide using quantitative structure-activity relationships

Quantitative structure-activity relationship (QSAR) analysis is a cornerstone of modern informatics. Predictive computational models of peptide-major histocompatibility complex (MHC)-binding affinity based on QSAR technology have now become important components of modern computational immunovaccinology. Historically, such approaches have been built around semiqualitative, classification methods, but these are now giving way to quantitative regression methods. We review three methods--a 2D-QSAR additive-partial least squares (PLS) and a 3D-QSAR comparative molecular similarity index analysis (CoMSIA) method--which can identify the sequence dependence of peptide-binding specificity for various class I MHC alleles from the reported binding affinities (IC50) of peptide sets. The third method is an iterative self-consistent (ISC) PLS-based additive method, which is a recently developed extension to the additive method for the affinity prediction of class II peptides. The QSAR methods presented here have established themselves as immunoinformatic techniques complementary to existing methodology, useful in the quantitative prediction of binding affinity: current methods for the in silico identification of T-cell epitopes (which form the basis of many vaccines, diagnostics, and reagents) rely on the accurate computational prediction of peptide-MHC affinity. We have reviewed various human and mouse class I and class II allele models. Studied alleles comprise HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3101, HLA-A*6801, HLA-A*6802, HLA-B*3501, H2-K(k), H2-K(b), H2-D(b) HLA-DRB1*0101, HLA-DRB1*0401, HLA-DRB1*0701, I-A(b), I-A(d), I-A(k), I-A(S), I-E(d), and I-E(k). In this chapter we show a step-by-step guide into predicting the reliability and the resulting models to represent an advance on existing methods. The peptides used in this study are available from the AntiJen database (http://www.jenner.ac.uk/AntiJen). The PLS method is available commercially in the SYBYL molecular modeling software package. The resulting models, which can be used for accurate T-cell epitope prediction, will be made are freely available online at the URL http://www.jenner.ac.uk/MHCPred.

The Point of Continuity Property: Descriptive Complexity and Ordinal Index

∗ Supported by D.G.I.C.Y.T. Project No. PB93-1142

Hybrid tilted fiber grating based refractive index and liquid level sensing system

We report a refractive index (RI) and liquid level sensing system based on a hybrid grating structure comprising of a 45° and an 81° tilted fiber gratings (TFGs) that have been inscribed into a single mode fiber in series. In this structure, the 45°-TFG is used as a polarizer to filter out the transverse electric (TE) component and enable the 81°-TFG operating at single polarization for RI and level sensing. The experiment results show a lower temperature cross-sensitivity, only about 7.33 pm/°C, and a higher RI sensitivity, being around 180 nm/RIU at RI=1.345 and 926 nm/RIU at RI=1.412 region, which are significantly improved in comparison with long period fiber gratings. The hybrid grating structure has also been applied as a liquid level sensor, showing 3.06 dB/mm linear peak ratio sensitivity.

Optical sensor based on hybrid LPG/FBG in D-fiber for simultaneous refractive index and temperature measurement

A dual-parameter optical sensor has been realized by UV-writing a long-period and a Bragg grating structure in D-fiber. The hybrid configuration permits the detection of the temperature from the latter and measuring the external refractive index from the former responses, respectively. The employment of the D-fiber allows as effective modification and enhancement of the device sensitivity by cladding etching. The grating sensor has been used to measure the concentrations of aqueous sugar solutions, demonstrating the potential capability to detect concentration changes as small as 0.01%.

Low thermal sensitivity grating devices based on ex-45° tilting structure capable of forward-propagating cladding modes coupling

The authors describe a detailed investigation on tilted fiber Bragg grating (TFBG) structures with tilted angles exceeding 45°. In contrast to the backward mode coupling mechanism of Bragg gratings with normal and small tilting structures, the ex-45° TFBGs facilitate the light coupling to the forward-propagating cladding modes. The authors have also theoretically and experimentally examined the mode coupling transition of TFBGs with small, medium, and large tilt angles. In particular, experiments are conducted to investigate the spectra and far-field distribution, as well as temperature, strain, and refractive-index sensitivities of ex-45° devices. It has been revealed that these ex-45° gratings exhibit ultralow thermal sensitivity. As in-fiber devices, they may be superior to conventional Bragg and long-period gratings when the low thermal cross sensitivity is required. © 2006 IEEE.

Refractive index sensor based on a pair of hybrid 45° and 81° tilted fiber gratings

A hybrid structure comprising of a 45° and an 81° TFG based RI sensor has been demonstrated. The experiment results show a higher RI sensitivity, being around 180nm/RIU at RI=1.345 and 926nm/RIU at RI=1.412 region. © 2014 OSA.

Refractive index and temperature sensitivity characteristics of a micro-slot fiber Bragg grating

Fabrication and characterization of a UVinscribed fiber Bragg grating (FBG) with a micro-slot liquid core is presented. Femtosecond (fs) laser patterning/chemical etching technique was employed to engrave a micro-slot with dimensions of 5.74 μm(h) × 125 μm(w) × 1388.72 μm(l) across the whole grating. The device has been evaluated for refractive index (RI) and temperature sensitivities and exhibited distinctive thermal response and RI sensitivity beyond the detection limit of reported fiber gratings. This structure has not just been RI sensitive, but also maintained the robustness comparing with the bare core FBGs and long-period gratings with the partial cladding etched off. © 2012 Optical Society of America.

Differences between younger and older adults in the structure of suicidal intent and its correlates

OBJECTIVE: To analyze differences in the variables associated with severity of suicidal intent and in the main factors associated with intent when comparing younger and older adults. DESIGN: Observational, descriptive cross-sectional study. SETTING: Four general hospitals in Madrid, Spain. PARTICIPANTS: Eight hundred seventy suicide attempts by 793 subjects split into two groups: 18-54 year olds and subjects older than 55 years. MEASUREMENTS: The authors tested the factorial latent structure of suicidal intent through multigroup confirmatory factor analysis for categorical outcomes and performed statistical tests of invariance across age groups using the DIFFTEST procedure. Then, they tested a multiple indicators-multiple causes (MIMIC) model including different covariates regressed on the latent factor "intent" and performed two separate MIMIC models for younger and older adults to test for differential patterns. RESULTS: Older adults had higher suicidal intent than younger adults (z = 2.63, p = 0.009). The final model for the whole sample showed a relationship of intent with previous attempts, support, mood disorder, personality disorder, substance-related disorder, and schizophrenia and other psychotic disorders. The model showed an adequate fit (chi²[12] = 22.23, p = 0.035; comparative fit index = 0.986; Tucker-Lewis index = 0.980; root mean square error of approximation = 0.031; weighted root mean square residual = 0.727). All covariates had significant weights in the younger group, but in the older group, only previous attempts and mood disorders were significantly related to intent severity. CONCLUSIONS: The pattern of variables associated with suicidal intent varies with age. Recognition, and treatment of geriatric depression may be the most effective measure to prevent suicidal behavior in older adults.

Land Policy and Farm Structure: Challenges and Opportunities for Agriculture in the Western Balkan

Although Western Balkan countries are quite different, they can all be characterised by their one shared goal, to achieve the quickest possible accession to the European Union. Even though agriculture plays an important key role within all Western Balkan states, it’s share is the highest in Albania and only Serbia has a trade surplus. Land is a key production factor but all the analysed countries can be characterized by fragmented land structure and low average farm sizes. Mostly based on land ownership issues, a land reform index can be calculated. The major contribution of this paper to the literature is the reevaluated land reform index for the Western Balkans.

Reformed county government structure and service delivery performance: An integrated study of Florida counties

The most fundamental and challenging function of government is the effective and efficient delivery of services to local taxpayers and businesses. Counties, once known as the “dark continent” of American government, have recently become a major player in the provision of services. Population growth and suburbanization have increased service demands while the counties' role as service provider to incorporated residents has also expanded due to additional federal and state mandates. County governments are under unprecedented pressure and scrutiny to meet citizens' and elected officials' demands for high quality, and equitable delivery of services at the lowest possible cost while contending with anti-tax sentiments, greatly decreased state and federal support, and exceptionally costly and complex health and public safety problems. ^ This study tested the reform government theory proposition that reformed structures of county government positively correlate with efficient service delivery. A county government reformed index was developed for this dissertation comprised of form of government, home-rule status, method of election, number of government jurisdictions, and number of elected officials. The county government reform index and a measure of relative structural fragmentation were used to assess their impact on two measures of service output: mean county road pavement condition and county road maintenance expenditures. The study's multi-level design triangulated results from different data sources and methods of analysis. Data were collected from semi-structured interviews of county officials, secondary archival sources, and a survey of 544 elected and appointed officials from Florida's 67 counties. The results of the three sources of data converged in finding that reformed Florida counties are more likely than unreformed counties to provide better road service and to spend less on road expenditures. The same results were found for unfragmented Florida counties. Because both the county government reform index and the fragmentation variables were specified acknowledging the reform theory as well as elements from the public-choice model, the results help explain contradicting findings in the urban service research. ^ Therefore, as suggested by the corroborated findings of this dissertation, reformed as well as unfragmented counties are better providers of road maintenance service and do so in a less costly manner. These findings hold although the variables were specified to capture theoretical arguments from the consolidated as well as the public-choice theories suggesting a way to advance the debate from the consolidated-fragmented dichotomy of urban governance. ^

Hurricane disturbance and recovery of energy balance, CO2 fluxes and canopy structure in a mangrove forest of the Florida Everglades

Eddy covariance (EC) estimates of carbon dioxide (CO2) fluxes and energy balance are examined to investigate the functional responses of a mature mangrove forest to a disturbance generated by Hurricane Wilma on October 24, 2005 in the Florida Everglades. At the EC site, high winds from the hurricane caused nearly 100% defoliation in the upper canopy and widespread tree mortality. Soil temperatures down to -50 cm increased, and air temperature lapse rates within the forest canopy switched from statically stable to statically unstable conditions following the disturbance. Unstable conditions allowed more efficient transport of water vapor and CO2 from the surface up to the upper canopy layer. Significant increases in latent heat fluxes (LE) and nighttime net ecosystem exchange (NEE) were also observed and sensible heat fluxes (H) as a proportion of net radiation decreased significantly in response to the disturbance. Many of these impacts persisted through much of the study period through 2009. However, local albedo and MODIS (Moderate Resolution Imaging Spectro-radiometer) data (the Enhanced Vegetation Index) indicated a substantial proportion of active leaf area recovered before the EC measurements began 1 year after the storm. Observed changes in the vertical distribution and the degree of clumping in newly emerged leaves may have affected the energy balance. Direct comparisons of daytime NEE values from before the storm and after our measurements resumed did not show substantial or consistent differences that could be attributed to the disturbance. Regression analyses on seasonal time scales were required to differentiate the storm's impact on monthly average daytime NEE from the changes caused by interannual variability in other environmental drivers. The effects of the storm were apparent on annual time scales, and CO2 uptake remained approximately 250 g C m-2 yr-1 lower in 2009 compared to the average annual values measured in 2004-2005. Dry season CO2 uptake was relatively more affected by the disturbance than wet season values. Complex leaf regeneration dynamics on damaged trees during ecosystem recovery are hypothesized to lead to the variable dry versus wet season impacts on daytime NEE. In contrast, nighttime CO2 release (i.e., nighttime respiration) was consistently and significantly greater, possibly as a result of the enhanced decomposition of litter and coarse woody debris generated by the storm, and this effect was most apparent in the wet seasons compared to the dry seasons. The largest pre- and post-storm differences in NEE coincided roughly with the delayed peak in cumulative mortality of stems in 2007-2008. Across the hurricane-impacted region, cumulative tree mortality rates were also closely correlated with declines in peat surface elevation. Mangrove forest-atmosphere interactions are interpreted with respect to the damage and recovery of stand dynamics and soil accretion processes following the hurricane.

Using Florida Keys Reference Sites As a Standard for Restoration of Forest Structure in Everglades Tree Islands

In south Florida, tropical hardwood forests (hammocks) occur in Everglades tree islands and as more extensive forests in coastal settings in the nearby Florida Keys. Keys hammocks have been less disturbed by humans, and many qualify as “old-growth,” while Everglades hammocks have received much heavier use. With improvement of tree island condition an important element in Everglades restoration efforts, we examined stand structure in 23 Keys hammocks and 69 Everglades tree islands. Based on Stand Density Index and tree diameter distributions, many Everglades hammocks were characterized by low stocking and under-representation in the smaller size classes. In contrast, most Keys forests had the dense canopies and open understories usually associated with old-growth hardwood hammocks. Subject to the same caveats that apply to off-site references elsewhere, structural information from mature Keys hammocks can be helpful in planning and implementing forest restoration in Everglades tree islands. In many of these islands, such restoration might involve supplementing tree stocking by planting native trees to produce more complete site utilization and a more open understory.

Changes in Community Structure of Sediment Bacteria Along the Florida Coastal Everglades Marsh–Mangrove–Seagrass Salinity Gradient

Community structure of sediment bacteria in the Everglades freshwater marsh, fringing mangrove forest, and Florida Bay seagrass meadows were described based on polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) patterns of 16S rRNA gene fragments and by sequencing analysis of DGGE bands. The DGGE patterns were correlated with the environmental variables by means of canonical correspondence analysis. There was no significant trend in the Shannon–Weiner index among the sediment samples along the salinity gradient. However, cluster analysis based on DGGE patterns revealed that the bacterial community structure differed according to sites. Not only were these salinity/vegetation regions distinct but the sediment bacteria communities were consistently different along the gradient from freshwater marsh, mangrove forest, eastern-central Florida Bay, and western Florida Bay. Actinobacteria- and Bacteroidetes/Chlorobi-like DNA sequences were amplified throughout all sampling sites. More Chloroflexi and members of candidate division WS3 were found in freshwater marsh and mangrove forest sites than in seagrass sites. The appearance of candidate division OP8-like DNA sequences in mangrove sites distinguished these communities from those of freshwater marsh. The seagrass sites were characterized by reduced presence of bands belonging to Chloroflexi with increased presence of those bands related to Cyanobacteria, γ-Proteobacteria, Spirochetes, and Planctomycetes. This included the sulfate-reducing bacteria, which are prevalent in marine environments. Clearly, bacterial communities in the sediment were different along the gradient, which can be explained mainly by the differences in salinity and total phosphorus.

Building an index of well-being for children living in Ireland: conceptual, measurement and policy considerations

This study conceptualised and measured children’s well-being in Ireland and considered how such conceptualisations and approaches to the measurement of well-being might inform social policy for children and families living in Ireland. This research explored what is meant by children’s well-being and how it can be conceptualised and measured so as to reflect the multi-dimensionality of the concept. The study developed an index of well-being that was both theoretically and methodologically robust and could be meaningfully used to inform social policy developments for children and their families. For the first time, an index of well-being for children was developed using an explicitly articulated unifying theory of children’s well-being. Moreover, for the first time an index of wellbeing was developed for 13-year old children living in Ireland using data from Wave 2 of the national longitudinal study of children. The Structural Model of Child Well-being (SMCW), the theoretical framework that underpins the development of this study’s index, offers a comprehensive understanding of well-being. The SMCW builds on, and integrates, a range of already-established theories concerning children’s development, their agency, rights and capabilities into a unifying theory that explains well-being in its entirety. This conceptualisation of well-being moves beyond the narrow focus on child development adopted in some recent studies of children’s well-being and which perpetuate individualised and self-responsibilising conceptualisations of well-being. This study found that the SMCW can be meaningfully applied, both theoretically and operationally, to the construction of an index of well-being for children. While it was not the purpose of this study to validate the SMCW, in the process of developing the index, I concluded that there was a theoretical ‘fit’ between the conceptual orientation of the SMCW and the wider children’s well-being literature. The ‘nested’ structure of the SMCW facilitated the identification of domains, sub-domains and indicators of well-being reflecting typical conventions of index construction. The findings from the resulting index, in both its categorical and continuous forms, demonstrated how a comprehensive theory of well-being can be used to illustrate how children are faring and which children are experiencing poorer or better well-being. Furthermore, this study demonstrated how the SMCW and the resultant index can be meaningfully used to support the implementation and review of the national policy framework for children and young people in Ireland.

Juniperus navicularis - a study of Portuguese population structure and fitness

Juniperus navicularis Gand. is a dioecious endemic conifer that constitutes the understory of seaside pine forests in Portugal, areas currently threatened by increasing urban expansion. The aim of this study is to assess the conservation status of previously known populations of this species located on its core area of distribution. The study was performed in south-west coast of Portugal. Three populations varying in size and pine density were analyzed. Number of individuals, population density, spatial distribution and individual characteristics of junipers were estimated. Female cone, seed characteristics and seed viability were also evaluated. Results suggest that J. navicularis populations are vulnerable because seminal recruitment is scarce, what may lead to a reduction of genetic variability due solely to vegetative propagation. This vulnerability seems to be strongly determined by climatic constraints toward increasing aridity. Ratio between male and female shrubs did not differ from 1:1 in any population. Deviations from 1:1 between mature and non-mature plants were found in all populations, denoting population ageing. Very low seed viability was observed. A major part of described Juniperus navicularis populations have disappeared through direct habitat loss to urban development, loss of fitness in drier and warmer locations and low seed viability. This study is the first to address J. navicularis conservation, and represents a valuable first step toward this species preservation.