Γ-stochastic neighbour embedding for feed-forward data visualization

t-distributed Stochastic Neighbour Embedding (t-SNE) is one of the most popular nonlinear dimension reduction techniques used in multiple application domains. In this paper we propose a variation on the embedding neighbourhood distribution, resulting in Γ-SNE, which can construct a feed-forward mapping using an RBF network. We compare the visualizations generated by Γ-SNE with those of t-SNE and provide empirical evidence suggesting the network is capable of robust interpolation and automatic weight regularization

Design and synthesis of lactams derived from mucochloric and mucobromic acids as pseudomonas aeruginosa quorum sensing inhibitors

© 2018 by the authors. Bacterial infections, particularly hospital-acquired infections caused by Pseudomonas aeruginosa, have become a global threat with a high mortality rate. Gram-negative bacteria including P. aeruginosa employ N-acyl homoserine lactones (AHLs) as chemical signals to regulate the expression of pathogenic phenotypes through a mechanism called quorum sensing (QS). Recently, strategies targeting bacterial behaviour or QS have received great attention due to their ability to disarm rather than kill pathogenic bacteria, which lowers the evolutionary burden on bacteria and the risk of resistance development. In the present study, we report the design and synthesis of N-alkyl- and N-aryl 3,4 dichloro- and 3,4-dibromopyrrole-2-one derivatives through the reductive amination of mucochloric and mucobromic acid with aliphatic and aromatic amines. The quorum sensing inhibition (QSI) activity of the synthesized compounds was determined against a P. aeruginosa MH602 reporter strain. The phenolic compounds exhibited the best activity with 80% and 75% QSI at 250 µM and were comparable in activity to the positive control compound Fu-30. Computational docking studies performed using the LasR receptor protein of P. aeruginosa suggested the importance of hydrogen bonding and hydrophobic interactions for QSI

Cerebellar-dependent delay eyeblink conditioning in adolescents with Specific Language Impairment

Cerebellar impairments have been hypothesized as part of the pathogenesis of Specific Language Impairment (SLI), although direct evidence of cerebellar involvement is sparse. Eyeblink Conditioning (EBC) is a learning task with well documented cerebellar pathways. This is the first study of EBC in affected adolescents and controls. 16 adolescent controls, 15 adolescents with SLI, and 12 adult controls participated in a delay EBC task. Affected children had low general language performance, grammatical deficits but no speech impairments. The affected group did not differ from the control adolescent or control adult group, showing intact cerebellar functioning on the EBC task. This study did not support cerebellar impairment at the level of basic learning pathways as part of the pathogenesis of SLI. Outcomes do not rule out cerebellar influences on speech impairment, or possible other forms of cerebellar functioning as contributing to SLI

A population-based study of anxiety as a precursor for depression in childhood and adolescence

BACKGROUND: Anxiety and depression co-occur in children and adolescents with anxiety commonly preceding depression. Although there is some evidence to suggest that the association between early anxiety and later depression is explained by a shared genetic aetiology, the contribution of environmental factors is less well examined and it is unknown whether anxiety itself is a phenotypic risk factor for later depression. These explanations of the association between early anxiety and later depression were evaluated. METHODS: Anxiety and depressive symptoms were assessed longitudinally in a U.K. population-based sample of 676 twins aged 5–17 at baseline. At baseline, anxiety and depression were assessed by parental questionnaire. Depression was assessed three years later by parental and adolescent questionnaire. RESULTS: Shared genetic effects between early anxiety and later depression were found. A model of a phenotypic risk effect from early anxiety on later depression provided a poor fit to the data. However, there were significant genetic effects specific to later depression, showing that early anxiety and later depression do not index entirely the same genetic risk. CONCLUSIONS: Anxiety and depression are associated over time because they share a partly common genetic aetiology rather than because the anxiety phenotype leads to later depression

High field level crossing studies on spin dimers in the low dimensional quantum spin system Na2_2T2_2(C2_2O4_4)3_3(H2_2O)2_2 with T=Ni,Co,Fe,Mn

In this paper we demonstrate the application of high magnetic fields to study the magnetic properties of low dimensional spin systems. We present a case study on the series of 2-leg spin-ladder compounds Na$_2$T$_2$(C$_2$O$_4$)$_3$(H$_2$O)$_2$ with T = Ni, Co, Fe and Mn. In all compounds the transition metal is in the $T^{2+}$ high spin configuation. The localized spin varies from S=1 to 3/2, 2 and 5/2 within this series. The magnetic properties were examined experimentally by magnetic susceptibility, pulsed high field magnetization and specific heat measurements. The data are analysed using a spin hamiltonian description. Although the transition metal ions form structurally a 2-leg ladder, an isolated dimer model consistently describes the observations very well. This behaviour can be understood in terms of the different coordination and superexchange angles of the oxalate ligands along the rungs and legs of the 2-leg spin ladder. All compounds exhibit magnetic field driven ground state changes which at very low temperatures lead to a multistep behaviour in the magnetization curves. In the Co and Fe compounds a strong axial anisotropy induced by the orbital magnetism leads to a nearly degenerate ground state and a strongly reduced critical field. We find a monotonous decrease of the intradimer magnetic exchange if the spin quantum number is increased

Sexual selection protects against extinction

Reproduction through sex carries substantial costs, mainly because only half of sexual adults produce offspring. It has been theorised that these costs could be countered if sex allows sexual selection to clear the universal fitness constraint of mutation load. Under sexual selection, competition between (usually) males, and mate choice by (usually) females create important intraspecific filters for reproductive success, so that only a subset of males gains paternity. If reproductive success under sexual selection is dependent on individual condition, which depends on mutation load, then sexually selected filtering through ‘genic capture’ could offset the costs of sex because it provides genetic benefits to populations. Here, we test this theory experimentally by comparing whether populations with histories of strong versus weak sexual selection purge mutation load and resist extinction differently. After evolving replicate populations of the flour beetle Tribolium castaneum for ~7 years under conditions that differed solely in the strengths of sexual selection, we revealed mutation load using inbreeding. Lineages from populations that had previously experienced strong sexual selection were resilient to extinction and maintained fitness under inbreeding, with some families continuing to survive after 20 generations of sib × sib mating. By contrast, lineages derived from populations that experienced weak or non-existent sexual selection showed rapid fitness declines under inbreeding, and all were extinct after generation 10. Multiple mutations across the genome with individually small effects can be difficult to clear, yet sum to a significant fitness load; our findings reveal that sexual selection reduces this load, improving population viability in the face of genetic stress

‘You’re just chopped off at the end’: Retired servicemen’s identity work struggles in the military to civilian transition

Promoting positive transition to retirement and cultural adaption for ex-service personnel has been identified as a priority for both social-science research and for public health policy in the UK. The Royal British Legion (RBL) aims to provide support to service and retired service personnel, but to date the transition to retirement experiences of older (60-plus) ex- service personnel remain under-researched. In this article, we employ a symbolic interactionist theoretical framework to examine older servicemen’s experiences and identity challenges post-retirement from the British armed forces. Data were collected primarily through semi-structured, focus-group interviews with 20 former servicemen. Here, we focus specifically upon the challenges encountered by these ex-servicemen in the retirement transition from military to civilian life, a time of identity flux of sociological interest. To navigate this period of identity change and challenge, many participants constructed a ‘modified military self’ through involvement with the RBL as a key social support network. For many retired personnel the RBL offered a form of identification and group identity that resonated strongly with earlier experiences of comradeship in the military

Epigenetic silencing of DSC3 is a common event in human breast cancer

INTRODUCTION: Desmocollin 3 (DSC3) is a member of the cadherin superfamily of calcium-dependent cell adhesion molecules and a principle component of desmosomes. Desmosomal proteins such as DSC3 are integral to the maintenance of tissue architecture and the loss of these components leads to a lack of adhesion and a gain of cellular mobility. DSC3 expression is down-regulated in breast cancer cell lines and primary breast tumors; however, the loss of DSC3 is not due to gene deletion or gross rearrangement of the gene. In this study, we examined the prevalence of epigenetic silencing of DSC3 gene expression in primary breast tumor specimens. METHODS: We used bisulfite genomic sequencing to analyze the methylation state of the DSC3 promoter region from 32 primary breast tumor specimens. We also used a quantitative real-time RT-PCR approach, and analyzed all breast tumor specimens for DSC3 expression. Finally, in addition to bisulfite sequencing and RT-PCR, we used an in vivo nuclease accessibility assay to determine the chromatin architecture of the CpG island region from DSC3-negative breast cancer cells lines. RESULTS: DSC3 expression was downregulated in 23 of 32 (72%) breast cancer specimens comprising: 22 invasive ductal carcinomas, 7 invasive lobular breast carcinomas, 2 invasive ductal carcinomas that metastasized to the lymph node, and a mucoid ductal carcinoma. Of the 23 specimens showing a loss of DSC3 expression, 13 (56%) were associated with cytosine hypermethylation of the promoter region. Furthermore, DSC3 expression is limited to cells of epithelial origin and its expression of mRNA and protein is lost in a high proportion of breast tumor cell lines (79%). Lastly, DNA hypermethylation of the DSC3 promoter is highly correlated with a closed chromatin structure. CONCLUSION: These results indicate that the loss of DSC3 expression is a common event in primary breast tumor specimens, and that DSC3 gene silencing in breast tumors is frequently linked to aberrant cytosine methylation and concomitant changes in chromatin structure

Television viewing in Thai infants and toddlers: impacts to language development and parental perceptions

<p>Abstract</p> <p>Background</p> <p>Effects of television to language development in infants and toddlers, especially in the Asian children, are inconclusive. This study aimed to (a) study time spent on television in Thai infants and toddlers (age < 2 years), (b) investigate the association between time spent on television (as recommended by the American Academy of Paediatrics (AAP), < 2 hours per day) and language development in Thai 2-year-old children, and (c) explore parental perceptions on television toward their child's development.</p> <p>Methods</p> <p>Two hundred and sixty children and their parents were recruited into the study. Time spent on television and parental perceptions on television viewing toward their child's development were recorded during face-to-face and telephone interviews. Language development was assessed at the age of 2 years using the Clinical Linguistic Auditory Milestone Scale (CLAMS), and parents' report. Association between delayed language development and time spent on television viewing, as well as other various parameters such as gender, maternal education and family income, were analysed using a multivariate logistic regression model.</p> <p>Results</p> <p>Most Thai infants and toddlers watched television at the age of 6 months, 1 year and 2 years old (98.0, 95.3 and 96.7%, respectively). On average, 1-year-old children watched television 1.23 ± 1.42 hours per day. This increased to 1.69 ± 1.56 hours per day when they were 2 years old. However, watching television longer than 2 hours per day did not associate with delayed language development. On multivariate logistic regression analysis, gender (male) was the only significant factor associated with delayed language development (OR = 6.9, 95% CI = 1.5–31.3). Moreover, 75%, 71%, and 66% of Thai parents believed that television viewing yielded benefits to children's developments.</p> <p>Conclusion</p> <p>Thai children commenced watching television at an early age and the amount of television viewing time increased by age. Most parents had positive perceptions to television viewing. The study found no association between time spent on television viewing (≥ 2 hours per day) and delayed language development at the age of 2 years.</p> <p>Gender (male) was the only variable associated with delayed language development.</p

Widespread Translocation from Autosomes to Sex Chromosomes Preserves Genetic Variability in an Endangered Lark

Species that pass repeatedly through narrow population bottlenecks (<100 individuals) are likely to have lost a large proportion of their genetic variation. Having genotyped 92 Raso larks Alauda razae, a Critically Endangered single-island endemic whose world population in the Cape Verdes over the last 100 years has fluctuated between about 15 and 130 pairs, we found variation at 7 of 21 microsatellite loci that successfully amplified, the remaining loci being monomorphic. At 6 of the polymorphic loci variation was sex-linked, despite the fact that these microsatellites were not sex-linked in the other passerine birds where they were developed. Comparative analysis strongly suggests that material from several different autosomes has been recently transferred to the sex chromosomes in larks. Sex-linkage might plausibly allow some level of heterozygosity to be maintained, even in the face of persistently small population sizes