Twin-tunnelling-induced ground movements in clay

Modern tunnelling methods aim to reduce ground movements arising from the construction process. In clay strata the usual method of construction is by tunnel boring machine, which allows close control of the tunnelling process; however, any movements have the potential to cause damage to existing structures at, and below, the ground surface. The construction of underground rail systems often comprises two tunnels running in opposite directions. Common practice for assessing construction-generated movements around these tunnels is to make predictions based upon individual tunnel construction and utilise superposition to generate a total deformation profile. This approach does not take into account the strain- or stress-dependent effects between tunnel constructions. A delay may result in unanticipated ground movements generated by the construction of the second tunnel. The effect of this delay on the ground movements arising between the first and the second tunnel construction process was investigated in a series of plane strain centrifuge tests. The ground movements at and below the surface were monitored and were assessed against superposition-based predictions for surface settlement with the outcomes highlighting some inconsistencies. A procedure for predicting both surface and subsurface vertical settlement profiles in the plane transverse to the advancing tunnels in clay is suggested

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

Personhood, consciousness, and god : how to be a proper pantheist

© Springer Nature B.V. 2018In this paper I develop a theory of personhood which leaves open the possibility of construing the universe as a person. If successful, it removes one bar to endorsing pantheism. I do this by examining a rising school of thought on personhood, on which persons, or selves, are understood as identical to episodes of consciousness. Through a critique of this experiential approach to personhood, I develop a theory of self as constituted of qualitative mental contents, but where these contents are also capable of unconscious existence. On this theory, though we can be conscious of our selves, consciousness turns out to be inessential to personhood. This move, I then argue, provides resources for responding to the pantheist’s problem of God’s person.Peer reviewedFinal Accepted Versio

International Veterinary Epilepsy Task Force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Multiple dimensions of mediation within transnational advertising production: cultural intermediaries as shapers of emerging cultural capital

The paper re-conceptualizes cultural intermediaries as shapers of “emerging cultural capital” (Prieur, A., and M. Savage. 2013. “Emerging Forms of Cultural Capital.” European Societies 15 (2): 246–267; Savage, M., F. Devine, N. Cunningham, M. Taylor, Y. Li, J. Hjellbrekke, and A. Miles. 2013. “A New Model of Social Class? Findings from the BBC’s Great British Class Survey Experiment.” Sociology 47 (2): 219–250) and re-frames their practice of signification and negotiation as informed by “multiple dimensions of mediation.” Drawing on a case study of Nike’s transnational advertising production and interviews with key actors within the context of production, the paper examines how the creative/cultural labour process cuts across global and national fields of cultural production and consumption through which popular culture and middle-brow tastes were mediated, signified and represented. In particular, a television campaign for the Japanese youth market was critically analysed to reveal how specific new tastes, lifestyles and consumption practices were legitimized as emerging forms of cultural capital. Consequently, their taste-making practices are profoundly implicated in symbolic struggles and cultural changes emerging within/from the increasingly “globalizing” field of cultural production

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells

Cancer Appetite and Symptom Questionnaire (CASQ) for Brazilian Patients: Cross-Cultural Adaptation and Validation Study

Background Appetite and symptoms, conditions generally reported by the patients with cancer, are somewhat challenging for professionals to measure directly in clinical routine (latent conditions). Therefore, specific instruments are required for this purpose. This study aimed to perform a cultural adaptation of the Cancer Appetite and Symptom Questionnaire (CASQ), into Portuguese and evaluate its psychometric properties on a sample of Brazilian cancer patients. Methods This is a validation study with Brazilian cancer patients. The face, content, and construct (factorial and convergent) validities of the Cancer Appetite and Symptom Questionnaire, the study tool, were estimated. Further, a confirmatory factor analysis (CFA) was conducted. The ratio of chi-square and degrees of freedom (χ2 /df), comparative fit index (CFI), goodness of fit index (GFI) and root mean square error of approximation (RMSEA) were used for fit model assessment. In addition, the reliability of the instrument was estimated using the composite reliability (CR) and Cronbach’s alpha coefficient (α), and the invariance of the model in independent samples was estimated by a multigroup analysis (Δχ2). Results Participants included 1,140 cancer patients with a mean age of 53.95 (SD = 13.25) years; 61.3% were women. After the CFA of the original CASQ structure, 2 items with inadequate factor weights were removed. Four correlations between errors were included to provide adequate fit to the sample (χ2 /df = 8.532, CFI = .94, GFI = .95, and RMSEA = .08). Themodel exhibited a low convergent validity (AVE = .32). The reliability was adequate (CR = .82 α = .82). The refined model showed strong invariance in two independent samples (Δχ2 : λ: p = .855; i: p = .824; Res: p = .390). A weak stability was obtained between patients undergoing chemotherapy and radiotherapy (Δχ2 : λ: p = .155; i: p < .001; Res: p < .001), and between patients undergoing chemotherapy combined with radiotherapy and palliative care (Δχ2 : λ: p = .058; i: p < .001; Res: p < .001). Conclusion The Portuguese version of the CASQ had good face and construct validity and reliability. However, the CASQ still presented invariance in independent samples of Brazilian patients with cancer. However, the tool has low convergent validity and weak invariance in samples with different treatment

Modulation of the surface proteome through multiple ubiquitylation pathways in African Trypanosomes

Recently we identified multiple suramin-sensitivity genes with a genome wide screen in Trypanosoma brucei that includes the invariant surface glycoprotein ISG75, the adaptin-1 (AP-1) complex and two deubiquitylating enzymes (DUBs) orthologous to ScUbp15/HsHAUSP1 and pVHL-interacting DUB1 (type I), designated TbUsp7 and TbVdu1, respectively. Here we have examined the roles of these genes in trafficking of ISG75, which appears key to suramin uptake. We found that, while AP-1 does not influence ISG75 abundance, knockdown of TbUsp7 or TbVdu1 leads to reduced ISG75 abundance. Silencing TbVdu1 also reduced ISG65 abundance. TbVdu1 is a component of an evolutionarily conserved ubiquitylation switch and responsible for rapid receptor modulation, suggesting similar regulation of ISGs in T. brucei. Unexpectedly, TbUsp7 knockdown also blocked endocytosis. To integrate these observations we analysed the impact of TbUsp7 and TbVdu1 knockdown on the global proteome using SILAC. For TbVdu1, ISG65 and ISG75 are the only significantly modulated proteins, but for TbUsp7 a cohort of integral membrane proteins, including the acid phosphatase MBAP1, that is required for endocytosis, and additional ISG-related proteins are down-regulated. Furthermore, we find increased expression of the ESAG6/7 transferrin receptor and ESAG5, likely resulting from decreased endocytic activity. Therefore, multiple ubiquitylation pathways, with a complex interplay with trafficking pathways, control surface proteome expression in trypanosomes

Evaluating the Role of Micronutrients and Hormones in Cognitive Function: A Comparative Study in Children with Learning Disabilities Undergoing Speech Therapy

Children with learning difficulties have significant challenges, affecting their cognitive ability and general development. Recent studies have highlighted the importance of micronutrients and hormonal balances in determining cognitive ability. However, knowledge of the connection between these physiological markers and mental processes in children with learning impairments is still growing. Objectives: The main aim of this research was to assess the concentrations of essential micronutrients (specifically Vitamin D, C, B vitamins, Magnesium, and Zinc) as well as hormones (Thyroxine, Epinephrine, and Norepinephrine) in children who have been identified with learning difficulties. In addition, the research's objective was to compare the aforementioned biochemical levels with those of a control group with comparable age and sex characteristics. One of the study's primary objectives was to investigate the correlation between the aforementioned biochemical parameters and cognitive abilities, as assessed by the Language Proficiency Test (LPT) scores in children undergoing speech treatment. Materials and Methods: 160 children between the ages of 6 and 13 were enrolled in this comparative cross-sectional study, which was structured into control, pre-test, and post-test cohorts. A comprehensive biochemical analysis was gathered from anthropometric measurements, demographic data, and blood samples. The objective of this methodology was to offer a comprehensive comprehension of the possible biochemical elements that impact the cognitive development of children who have learning disabilities. Cognitive functions were assessed using the LPT. The data analysis was conducted using SPSS software, with one-way ANOVA and Pearson's correlation coefficient as principal statistical instruments. Results: The study unveiled significant variations in the concentrations of diverse micronutrients and hormones among the various categories. The control group generally exhibited elevated concentrations of zinc, magnesium, and vitamin D. Significant variability in Thyroxine and Catecholamine levels suggested distinct physiological conditions among the groups. Notably, the post-test group, which underwent speech therapy and received nutritional counseling, demonstrated enhanced scores on the LPT compared to the pre-test group. Conclusion: This study's findings highlight the significant influence of micronutrients and hormones on the cognitive functionality of children with learning disabilities. The positive association observed between improved levels of nutrients and higher LPT scores in the post-test group emphasizes the effectiveness of integrated therapeutic approaches. The study advocates for including nutritional and hormonal evaluations in managing learning disabilities, pointing towards the necessity of comprehensive and holistic treatment methodologies