Visualizing displacements and stresses that were calculated using interval methods and finite elements for a system with uncertainty in forces and geometry

Interval methods are currently one of three methods available to model uncertainty in a system. In this thesis interval methods along with finite elements were used to model the uncertainty in beams and a square plate. Intervals defined the upper and lower bounds of uncertain lengths, widths and forces. Care had to be taken to reduce the dependency in the equations in order to obtain sharper bounds on the solution. Using the symbolic notation in Matlab, sharper bounds were calculated for the displacements and the stresses. The life and reliability of the system were computed using stochastic methods. The results were then displayed in the virtual environment. The virtual reality program contains a menu option that allows the user to change the reliability of the part, the life, the applied stress, the stress deviation, the force and the tolerance and observe the resulting stress distribution and displacements on the square plate. The plate was also shown with neighboring pieces so that a designer could view the gap between the displaced square plate and the nearest neighboring part

Childhood experiences and sleep problems: A cross-sectional study on the indirect relationship mediated by stress, resilience and anxiety

Background: Childhood experiences either adverse (ACE) or benevolent (BCE) can indirectly impact sleep quality in adult life, which in turn are modulated by the interplay of a variety of factors such as depression, anxiety, resilience and mental health problems. / Methods: A cross-sectional observational study was conducted across the UK and the Middle Eastern countries during the COVID-pandemic on 405 participants. An online survey used a combination of questionnaires to assess ACE and BCEs. The following tools were then used to assess the contribution of resilience, stress, depression and anxiety respectively: Brief Resilience Scale (BRS), Perceived Stress Scale (PSS-10), Patient Health Questionnaire-2 (PHQ-2) and General Anxiety Disorder-2 (GAD-2) scale on childhood experiences. The extent of sleep disturbances experienced over a period of seven days was assessed using the PROMIS Sleep Disturbance Short-Form Tool. A serial-parallel mediation model was used to evaluate the impact of the mediators on childhood experiences and sleep quality. / Results: Over 50% of the cohort were from Middle Eastern countries. Four or more BCEs were experienced by 94.3% of the cohort. In contrast, 67.9% of participants experienced at least one ACE before the age of 18 years, with moderate levels of stress, mild depression and anxiety were reported in 3.7%, 13% and 20% of participants respectively. Whilst 25.4% of participants reported having had four or more ACEs, with higher reports in the middle easter countries (32%). ACEs were found to correlate with sleep disturbance whilst BCEs showed an inverse correlation. The relationship between ACE and sleep disturbances was shown to be mediated by stress, and anxiety, but not by resilience or depression. Resilience and stress, and resilience and anxiety serially mediated the interaction between ACE and sleep disturbance. With regards to BCE, an inverse association with sleep disturbance was recorded with similar mediators of stress and anxiety observed. / Conclusion: This study confirms the negative effects of ACEs, and the positive effects of BCEs on sleep in adulthood which are both mediated predominantly by psychological resilience, anxiety and stress. Strategies aimed at improving psychological resilience as well as addressing stress and anxiety may help improve sleep quality

Salt polygons and porous media convection

From fairy circles to patterned ground and columnar joints, natural patterns spontaneously appear in many complex geophysical settings. Here, we investigate the origins of polygonally patterned crusts of salt playa and salt pans. These beautifully regular features, approximately a meter in diameter, are found worldwide and are fundamentally important to the transport of salt and dust in arid regions. We show that they are consistent with the surface expression of buoyancy-driven convection in the porous soil beneath a salt crust. By combining quantitative results from direct field observations, analog experiments, and numerical simulations, we further determine the conditions under which salt polygons should form, as well as how their characteristic size emerges

Characterization of Schistosome Tegumental Alkaline Phosphatase (SmAP)

Schistosomes are parasitic platyhelminths that currently infect over 200 million people globally. The parasites can live for years in a putatively hostile environment - the blood of vertebrates. We have hypothesized that the unusual schistosome tegument (outer-covering) plays a role in protecting parasites in the blood; by impeding host immunological signaling pathways we suggest that tegumental molecules help create an immunologically privileged environment for schistosomes. In this work, we clone and characterize a schistosome alkaline phosphatase (SmAP), a predicted ∼60 kDa glycoprotein that has high sequence conservation with members of the alkaline phosphatase protein family. The SmAP gene is most highly expressed in intravascular parasite life stages. Using immunofluorescence and immuno-electron microscopy, we confirm that SmAP is expressed at the host/parasite interface and in internal tissues. The ability of living parasites to cleave exogenous adenosine monophosphate (AMP) and generate adenosine is very largely abolished when SmAP gene expression is suppressed following RNAi treatment targeting the gene. These results lend support to the hypothesis that schistosome surface enzymes such as SmAP could dampen host immune responses against the parasites by generating immunosuppressants such as adenosine to promote their survival. This notion does not rule out other potential functions for the adenosine generated e.g. in parasite nutrition

Synovial tissue atlas in juvenile idiopathic arthritis reveals pathogenic niches associated with disease severity

Precision application of targeted therapies is urgently needed to improve long-term clinical outcomes for children affected by inflammatory arthritis, known as juvenile idiopathic arthritis (JIA). Progress has been hampered by our limited understanding of the cellular basis of inflammation in the target tissue of the disease, the synovial membrane. Here, we analyzed biopsies from the inflamed joints of treatment-naïve children with JIA, early in the course of their disease, using single-cell RNA sequencing, multiplexed immunofluorescence, and spatial transcriptomics to establish a cellular atlas of the JIA synovium. We identified distinct spatial tissue niches, composed of specific stromal and immune cell populations. In addition, we localized genes linked to arthritis severity and disease risk to effector cell populations, including tissue resident SPP1+ macrophages and fibrin-associated myeloid cells. Combined analyses of synovial fluid and peripheral blood from matched individuals revealed differences in cellular composition, signaling pathways, and transcriptional programs across these distinct anatomical compartments. Furthermore, our analysis revealed several pathogenic cell populations that are shared with adult-onset inflammatory arthritis, as well as age-associated differences in tissue vascularity, prominence of innate immunity, and enrichment of TGF-β–responsive stromal subsets that up-regulate expression of disease risk–associated genes. Overall, our findings demonstrate the need for age-specific analyses of synovial tissue pathology to guide targeted treatment strategies in JIA

Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci.

We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A PERFORMANCE NARRATIVA DE UMA BLOGUEIRA: "TORNANDO-SE PRETA EM UM SEGUNDO NASCIMENTO"

A web 2.0 propicia aos sujeitos sociais a possibilidade de contar suas histórias assim como de vê-las discutidas em novas formas de interação. Este artigo almeja apresentar os posicionamentos interacionais que constroem a performance narrativa de co-construção de raça de uma mulher negra no blog "Eu, Mulher Preta". O estudo se ampara nos aportes teóricos dos novos letramentos digitais, na concepção de raça proposta pelas Teorias Queer e na teorização de narrativa como performance. Para analisar a narrativa da blogueira como performance, o quadro analítico se ancora no construto de posicionamento interacional e nas pistas que marcam tal posicionamento na encenação da performance. Os resultados indicam que a narradora se posiciona interacionalmente como mulher preta. Identificamos, porém, um posicionamento interacional anterior ao renascimento como negra: o de mulher "branc[a] meio suj[a]". Observamos ainda que tais posicionamentos refletem duas performances discursivas conflitantes, uma que se aproxima e valoriza a negritude e outra que se distancia de sua origem. Esta investigação, baseando-se nas Teorias Queer, possibilita, também, tratar a questão racial como um traço performativo, colocando-a ao lado de gênero e sexualidade