Poiseuille geometry shear flow apparatus for small-angle scattering experiments

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Temporally delayed linear modelling (TDLM) measures replay in both animals and humans

There are rich structures in off-task neural activity which are hypothesised to reflect fundamental computations across a broad spectrum of cognitive functions. Here, we develop an analysis toolkit - Temporal Delayed Linear Modelling (TDLM) for analysing such activity. TDLM is a domain-general method for finding neural sequences that respect a pre-specified transition graph. It combines nonlinear classification and linear temporal modelling to test for statistical regularities in sequences of task-related reactivations. TDLM is developed on the non-invasive neuroimaging data and is designed to take care of confounds and maximize sequence detection ability. Notably, as a linear framework, TDLM can be easily extended, without loss of generality, to capture rodent replay in electrophysiology, including in continuous spaces, as well as addressing second-order inference questions, e.g., its temporal and spatial varying pattern. We hope TDLM will advance a deeper understanding of neural computation and promote a richer convergence between animal and human neuroscience

Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy

Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P<0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P<0.01) and thymidine kinase activity (P<0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P<0.05) in the rats treated with cyclosporine as compared to the vehicle. These results show that cyclosporine treatment causes an increase in the hepatic content of estrogen receptor activity that is associated with an enhanced potential for a regenerative response. These effects of cyclosporine treatment on the sex hormone receptor levels in liver may explain the mechanisms responsible for some of the untoward effects of treatment with this agent. © 1990 Plenum Publishing Corporation

Green's relations and stability for subsemigroups

We prove new results on inheritance of Green's relations by subsemigroups in the presence of stability of elements. We provide counterexamples in other cases to show in particular that not all right-stable semigroups are embeddable in left-stable semigroups. This is carried out in the context of a survey of the various closely related notions of stability and minimality of Green's classes that have appeared in the literature over the last sixty years, and which have sometimes been presented in different forms

Wavelet-Based Linear-Response Time-Dependent Density-Functional Theory

Linear-response time-dependent (TD) density-functional theory (DFT) has been implemented in the pseudopotential wavelet-based electronic structure program BigDFT and results are compared against those obtained with the all-electron Gaussian-type orbital program deMon2k for the calculation of electronic absorption spectra of N2 using the TD local density approximation (LDA). The two programs give comparable excitation energies and absorption spectra once suitably extensive basis sets are used. Convergence of LDA density orbitals and orbital energies to the basis-set limit is significantly faster for BigDFT than for deMon2k. However the number of virtual orbitals used in TD-DFT calculations is a parameter in BigDFT, while all virtual orbitals are included in TD-DFT calculations in deMon2k. As a reality check, we report the x-ray crystal structure and the measured and calculated absorption spectrum (excitation energies and oscillator strengths) of the small organic molecule N-cyclohexyl-2-(4-methoxyphenyl)imidazo[1,2-a]pyridin-3-amine

The Nature of Notebooks: How Enlightenment Schoolchildren Transformed the Tabula Rasa

John Locke's comparison of the mind to a blank piece of paper, the tabula rasa, was one of the most recognizable metaphors of the British Enlightenment. Though scholars embrace its impact on the arts, humanities, natural sciences, and social sciences, they seldom consider why the metaphor was so successful. Concentrating on the notebooks made and used by the schoolchildren of Enlightenment Scotland, this essay contends that the answer lies in the material and visual conditions that gave rise to the metaphor's usage. By the time students had finished school, they had learned to conceptualize the pages, the script, and the figures of their notebooks as indispensable learning tools that could be manipulated by scores of adaptable folding, writing, and drawing techniques. In this article, I reveal that historicizing the epistemology and manipulability of student manuscript culture makes it possible to see that the success of Locke's metaphor was founded on its appeal to everyday note-keeping activities performed by British schoolchildren

Effects of Global Warming on Ancient Mammalian Communities and Their Environments

Current global warming affects the composition and dynamics of mammalian communities and can increase extinction risk; however, long-term effects of warming on mammals are less understood. Dietary reconstructions inferred from stable isotopes of fossil herbivorous mammalian tooth enamel document environmental and climatic changes in ancient ecosystems, including C(3)/C(4) transitions and relative seasonality.Here, we use stable carbon and oxygen isotopes preserved in fossil teeth to document the magnitude of mammalian dietary shifts and ancient floral change during geologically documented glacial and interglacial periods during the Pliocene (approximately 1.9 million years ago) and Pleistocene (approximately 1.3 million years ago) in Florida. Stable isotope data demonstrate increased aridity, increased C(4) grass consumption, inter-faunal dietary partitioning, increased isotopic niche breadth of mixed feeders, niche partitioning of phylogenetically similar taxa, and differences in relative seasonality with warming.Our data show that global warming resulted in dramatic vegetation and dietary changes even at lower latitudes (approximately 28 degrees N). Our results also question the use of models that predict the long term decline and extinction of species based on the assumption that niches are conserved over time. These findings have immediate relevance to clarifying possible biotic responses to current global warming in modern ecosystems

Chromosome 15q25 (CHRNA3-CHRNA5) Variation Impacts Indirectly on Lung Cancer Risk

Genetic variants at the 15q25 CHRNA5-CHRNA3 locus have been shown to influence lung cancer risk however there is controversy as to whether variants have a direct carcinogenic effect on lung cancer risk or impact indirectly through smoking behavior. We have performed a detailed analysis of the 15q25 risk variants rs12914385 and rs8042374 with smoking behavior and lung cancer risk in 4,343 lung cancer cases and 1,479 controls from the Genetic Lung Cancer Predisposition Study (GELCAPS). A strong association between rs12914385 and rs8042374, and lung cancer risk was shown, odds ratios (OR) were 1.44, (95% confidence interval (CI): 1.29–1.62, P = 3.69×10−10) and 1.35 (95% CI: 1.18–1.55, P = 9.99×10−6) respectively. Each copy of risk alleles at rs12914385 and rs8042374 was associated with increased cigarette consumption of 1.0 and 0.9 cigarettes per day (CPD) (P = 5.18×10−5 and P = 5.65×10−3). These genetically determined modest differences in smoking behavior can be shown to be sufficient to account for the 15q25 association with lung cancer risk. To further verify the indirect effect of 15q25 on the risk, we restricted our analysis of lung cancer risk to never-smokers and conducted a meta-analysis of previously published studies of lung cancer risk in never-smokers. Never-smoker studies published in English were ascertained from PubMed stipulating - lung cancer, risk, genome-wide association, candidate genes. Our study and five previously published studies provided data on 2,405 never-smoker lung cancer cases and 7,622 controls. In the pooled analysis no association has been found between the 15q25 variation and lung cancer risk (OR = 1.09, 95% CI: 0.94–1.28). This study affirms the 15q25 association with smoking and is consistent with an indirect link between genotype and lung cancer risk

Twisting of the DNA-binding surface by a β-strand-bearing proline modulates DNA gyrase activity

DNA gyrase is the only topoisomerase capable of introducing (−) supercoils into relaxed DNA. The C-terminal domain of the gyrase A subunit (GyrA-CTD) and the presence of a gyrase-specific ‘GyrA-box’ motif within this domain are essential for this unique (−) supercoiling activity by allowing gyrase to wrap DNA around itself. Here we report the crystal structure of Xanthomonas campestris GyrA-CTD and provide the first view of a canonical GyrA-box motif. This structure resembles the GyrA-box-disordered Escherichia coli GyrA-CTD, both adopting a non-planar β-pinwheel fold composed of six seemingly spirally arranged β-sheet blades. Interestingly, structural analysis revealed that the non-planar architecture mainly stems from the tilted packing seen between blades 1 and 2, with the packing geometry likely being defined by a conserved and unusual β-strand-bearing proline. Consequently, the GyrA-box-containing blade 1 is placed at an angled spatial position relative to the other DNA-binding blades, and an abrupt bend is introduced into the otherwise flat DNA-binding surface. Mutagenesis studies support that the proline-induced structural twist contributes directly to gyrase’s (−) supercoiling activity. To our knowledge, this is the first demonstration that a β-strand-bearing proline may impact protein function. Potential relevance of β-strand-bearing proline to disease phenylketonuria is also noted

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L