MCMC-ODPR : primer design optimization using Markov Chain Monte Carlo sampling

Background Next generation sequencing technologies often require numerous primer designs that require good target coverage that can be financially costly. We aimed to develop a system that would implement primer reuse to design degenerate primers that could be designed around SNPs, thus find the fewest necessary primers and the lowest cost whilst maintaining an acceptable coverage and provide a cost effective solution. We have implemented Metropolis-Hastings Markov Chain Monte Carlo for optimizing primer reuse. We call it the Markov Chain Monte Carlo Optimized Degenerate Primer Reuse (MCMC-ODPR) algorithm. Results After repeating the program 1020 times to assess the variance, an average of 17.14% fewer primers were found to be necessary using MCMC-ODPR for an equivalent coverage without implementing primer reuse. The algorithm was able to reuse primers up to five times. We compared MCMC-ODPR with single sequence primer design programs Primer3 and Primer-BLAST and achieved a lower primer cost per amplicon base covered of 0.21 and 0.19 and 0.18 primer nucleotides on three separate gene sequences, respectively. With multiple sequences, MCMC-ODPR achieved a lower cost per base covered of 0.19 than programs BatchPrimer3 and PAMPS, which achieved 0.25 and 0.64 primer nucleotides, respectively. Conclusions MCMC-ODPR is a useful tool for designing primers at various melting temperatures at good target coverage. By combining degeneracy with optimal primer reuse the user may increase coverage of sequences amplified by the designed primers at significantly lower costs. Our analyses showed that overall MCMC-ODPR outperformed the other primer-design programs in our study in terms of cost per covered base

Timely Permanency for Children in Foster Care: Revisiting Core Assumptions about Children’s Options and Outcomes

The Adoption and Safe Families Act (ASFA, 1997) represented an emerging consensus that foster care should not be a long-term solution for children. Foster care is intended to provide a temporary living arrangement until permanency can be achieved, but, at the time ASFA was passed, some children were spending large proportions of their childhoods in temporary homes. In many cases, these children had a permanency plan of reunification that had little chance of being realized. Thus, the overarching goals of ASFA were to reduce the amount of time children spent “in limbo” and to promote permanency, while maintaining explicit preferences for family preservation and reunification

Archaeogenetic evidence of ancient Nubian barley evolution from six to two-row indicates local adaptation

Background Archaeobotanical samples of barley (Hordeum vulgare L.) found at Qasr Ibrim display a two-row phenotype that is unique to the region of archaeological sites upriver of the first cataract of the Nile, characterised by the development of distinctive lateral bracts. The phenotype occurs throughout all strata at Qasr Ibrim, which range in age from 3000 to a few hundred years. Methodology and Findings We extracted ancient DNA from barley samples from the entire range of occupancy of the site, and studied the Vrs1 gene responsible for row number in extant barley. Surprisingly, we found a discord between the genotype and phenotype in all samples; all the barley had a genotype consistent with the six-row condition. These results indicate a six-row ancestry for the Qasr Ibrim barley, followed by a reassertion of the two-row condition. Modelling demonstrates that this sequence of evolutionary events requires a strong selection pressure. Conclusions The two-row phenotype at Qasr Ibrim is caused by a different mechanism to that in extant barley. The strength of selection required for this mechanism to prevail indicates that the barley became locally adapted in the region in response to a local selection pressure. The consistency of the genotype/phenotype discord over time supports a scenario of adoption of this barley type by successive cultures, rather than the importation of new barley varieties associated with individual cultures

Measuring human rights abuse from access to information requests

Existing measures of human rights abuses are often only available at the country-year level. Several more fine-grained measures exhibit spatio-temporal inaccuracies or reporting biases due to the primary sources upon which they rely. To address these challenges, and to increase the diversity of available human rights measures more generally, this study provides the first quantitative effort to measure human rights abuses from textual records of citizen-government interactions. Using a dataset encompassing over 1.5 million access-to-information (ATI) requests made to the Mexican federal government from June 2003 onward, supervised classification is used to identify the subset of these requests that pertain to human rights abuses of various types. The results from this supervised machine learning exercise are validated against (i) gold standard ATI requests pertaining to past human rights abuses in Mexico and (ii) several accepted external measures of sub-national and sub-annual human rights abuses. In doing so, we demonstrate that the measurement of human rights abuses from citizen-submitted ATI request texts can provide measures of human rights abuse that exhibit both high validity and notable spatio-temporal specificity, relative to existent human rights datasets and variables

Learning from the children : exploring preschool children's encounters with ICT at home

This paper is an account of our attempts to understand preschool children's experiences with information and communication technologies (ICT) at home. Using case study data, we focus on what we can learn from talking directly to the children that might otherwise have been overlooked and on describing and evaluating the methods we adopted to ensure that we maximised the children's contributions to the research. By paying attention to the children's perspectives we have learned that they are discriminating users of ICT who evaluate their own performances, know what gives them pleasure and who differentiate between operational competence and the substantive activities made possible by ICT

Determining Optimum Soil Type and Salinity for Rearing the Federally Endangered Salt Creek Tiger Beetle, \u3ci\u3eCicindela (Ellipsoptera) nevadica lincolniana\u3c/i\u3e Casey (Coleoptera: Carabidae: Cicindelinae)

Effective rearing methods are needed to recover the federally endangered Salt Creek tiger beetle, Cicindela (Ellipsoptera) nevadica lincolniana Casey, a subspecies that occurs exclusively in saline wetlands and seeps along Little Salt Creek in Lancaster County, Nebraska. Experiments were initiated to determine soil type and salinity concentrations appropriate for stimulating female oviposition in laboratory settings to produce larvae and/or adults for reintroduction to native habitats. In 2013, there were highly significant differences between native soil and a sand/loess soil mixture, but no differences between two salinity levels, 0.354 M and 0.5 M. In 2014, using only a sand/loess soil mixture, there were again no differences between the test salinity levels. A sand/loess soil mixture of either 0.354M or 0.5M salinity was determined to be optimum for egg production

Determining Optimum Soil Type and Salinity for Rearing the Federally Endangered Salt Creek Tiger Beetle, \u3ci\u3eCicindela (Ellipsoptera) nevadica lincolniana\u3c/i\u3e Casey (Coleoptera: Carabidae: Cicindelinae)

Effective rearing methods are needed to recover the federally endangered Salt Creek tiger beetle, Cicindela (Ellipsoptera) nevadica lincolniana Casey, a subspecies that occurs exclusively in saline wetlands and seeps along Little Salt Creek in Lancaster County, Nebraska. Experiments were initiated to determine soil type and salinity concentrations appropriate for stimulating female oviposition in laboratory settings to produce larvae and/or adults for reintroduction to native habitats. In 2013, there were highly significant differences between native soil and a sand/loess soil mixture, but no differences between two salinity levels, 0.354 M and 0.5 M. In 2014, using only a sand/loess soil mixture, there were again no differences between the test salinity levels. A sand/loess soil mixture of either 0.354M or 0.5M salinity was determined to be optimum for egg production

Remasking of Candida albicans β-Glucan in Response to Environmental pH Is Regulated by Quorum Sensing

Candida albicans is a commensal yeast of the human gut which is tolerated by the immune system but has the potential to become an opportunistic pathogen. One way in which C. albicans achieves this duality is through concealing or exposing cell wall pathogen-associated molecular patterns (PAMPs) in response to host-derived environment cues (pH, hypoxia, and lactate). This cell wall remodeling allows C. albicans to evade or hyperactivate the host’s innate immune responses, leading to disease. Previously, we showed that adaptation of C. albicans to acidic environments, conditions encountered during colonization of the female reproductive tract, induces significant cell wall remodeling resulting in the exposure of two key fungal PAMPs (β-glucan and chitin). Here, we report that this pH-dependent cell wall remodeling is time dependent, with the initial change in pH driving cell wall unmasking, which is then remasked at later time points. Remasking of β-glucan was mediated via the cell density-dependent fungal quorum sensing molecule farnesol, while chitin remasking was mediated via a small, heat-stable, nonproteinaceous secreted molecule(s). Transcript profiling identified a core set of 42 genes significantly regulated by pH over time and identified the transcription factor Efg1 as a regulator of chitin exposure through regulation of CHT2. This dynamic cell wall remodeling influenced innate immune recognition of C. albicans, suggesting that during infection, C. albicans can manipulate the host innate immune responses

Examining Neolithic Building and Activity Areas through Historic Cultural Heritage in Jordan: A Combined Ethnographic, Phytolith and Geochemical Investigation

The INEA project (Identifying activity areas in Neolithic sites through Ethnographic Analysis of phytoliths and geochemical residues, https://research.bournemouth. ac.uk/2014/07/inea-project-2/) develops and applies a method that combines the analysis of plant remains (silica phytoliths) and geochemical residues to inform on construction methods and the use of space in recently abandoned historical villages and Neolithic settlements. It is a collaborative project based at Bournemouth University, in partnership with the Council for British Research in the Levant

Drivers of international variation in prevalence of disabling low back pain: Findings from the cultural and psychosocial influences on disability study

Background: Wide international variation in the prevalence of disabling low back pain (LBP) among working populations is not explained by known risk factors. It would be useful to know whether the drivers of this variation are specific to the spine or factors that predispose to musculoskeletal pain more generally.Methods: Baseline information about musculoskeletal pain and risk factors was elicited from 11 710 participants aged 20-59 years, who were sampled from 45 occupational groups in 18 countries. Wider propensity to pain was characterized by the number of anatomical sites outside the low back that had been painful in the 12 months before baseline (\u27pain propensity index\u27). After a mean interval of 14 months, 9055 participants (77.3%) provided follow-up data on disabling LBP in the past month. Baseline risk factors for disabling LBP at follow-up were assessed by random intercept Poisson regression.Results: After allowance for other known and suspected risk factors, pain propensity showed the strongest association with disabling LBP (prevalence rate ratios up to 2.6, 95% CI: 2.2-3.1; population attributable fraction 39.8%). Across the 45 occupational groups, the prevalence of disabling LBP varied sevenfold (much more than within-country differences between nurses and office workers), and correlated with mean pain propensity index (r = 0.58).Conclusions: Within our study, major international variation in the prevalence of disabling LBP appeared to be driven largely by factors predisposing to musculoskeletal pain at multiple anatomical sites rather than by risk factors specific to the spine.Significance: Our findings indicate that differences in general propensity to musculoskeletal pain are a major driver of large international variation in the prevalence of disabling low back pain among people of working age