Logarithmic rate dependence in deforming granular materials

Rate-independence for stresses within a granular material is a basic tenet of many models for slow dense granular flows. By contrast, logarithmic rate dependence of stresses is found in solid-on-solid friction, in geological settings, and elsewhere. In this work, we show that logarithmic rate-dependence occurs in granular materials for plastic (irreversible) deformations that occur during shearing but not for elastic (reversible) deformations, such as those that occur under moderate repetitive compression. Increasing the shearing rate, \Omega, leads to an increase in the stress and the stress fluctuations that at least qualitatively resemble what occurs due to an increase in the density. Increases in \Omega also lead to qualitative changes in the distributions of stress build-up and relaxation events. If shearing is stopped at t=0, stress relaxations occur with \sigma(t)/ \sigma(t=0) \simeq A \log(t/t_0). This collective relaxation of the stress network over logarithmically long times provides a mechanism for rate-dependent strengthening.Comment: 4 pages, 5 figures. RevTeX

Silicon isotopic systematics of deep-sea sponge grounds in the North Atlantic

© 2019 Elsevier Ltd Reconstruction of silica cycling in the oceans is key to a thorough understanding of past climates because of the inherent links between the biogeochemistry of silicifiers and sequestration of organic carbon. Diatoms are one of the most important phytoplankton groups in determining export production from surface waters, and rely largely on upwelling deeper waters as a source of dissolved silicon, an essential nutrient for their growth. Quantification of changes in deep water dissolved silicon concentrations in the past allows a more robust understanding of changes in surface nutrient supply and whole-ocean silicon cycling, but cannot be achieved using surface-derived geochemical archives. In the last few years, there has been increasing focus on the use of geochemical archives in siliceous skeletal elements, or spicules, from seafloor-dwelling sponges to fill this gap. The stable silicon isotopic composition of spicules has been shown to be a function of ambient dissolved silicon, providing a potential archive for past changes in bottom water nutrients. However, biomineralisation processes impact silicon isotope fractionation and silica formed by atypical processes (derived from carnivorous sponges, hypersilicified spicules, and giant basal spicules) result in anomalous geochemical signatures. Furthermore, there is considerable scatter in the calibration between spicule silicon isotopes and dissolved silicon in seawater, even when the atypical groups have been removed. Here, we explore this variability further, by examining aggregation and assemblage-level differences in isotopic fractionation, using silicon isotopic measurements of specimens from two monospecific sponge groups (Pheronema carpenteri and Vazella pourtalesi), and one mixed-species population (genus Geodia) from the North Atlantic. Our new data reveal that variability within the monospecific aggregations is less than mixed-species assemblage, pointing towards a genetic control in isotopic fractionation. However, there is still variability within the monospecific aggregations, which cannot be explained by macroscale environmental differences: such variability is likely a reflection of the physiological health of the individuals, or highly localised heterogeneities in sponge habitats. Other challenges remain in the interpretation of spicule silicon isotopes as proxies for dissolved silicon changes through time, especially when investigating periods of Earth history that extend back considerably further than the residence time of dissolved silicon in the oceans. Despite all the questions still surrounding the use of sponge silicon isotopes in palaeoceanographic applications, they are still the only known archive of bottom water dissolved silicon. Continued efforts to understanding sponge biomineralisation and to incorporate silicon isotopes into oceanic models will help to improve further the reliability of the archive

The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation

Fine control of macrophage activation is needed to prevent inflammatory disease, particularly at barrier sites such as the lungs. However, the dominant mechanisms that regulate the activation of pulmonary macrophages during inflammation are poorly understood. We found that alveolar macrophages (AlvMs) were much less able to respond to the canonical type 2 cytokine IL-4, which underpins allergic disease and parasitic worm infections, than macrophages from lung tissue or the peritoneal cavity. We found that the hyporesponsiveness of AlvMs to IL-4 depended upon the lung environment but was independent of the host microbiota or the lung extracellular matrix components surfactant protein D (SP-D) and mucin 5b (Muc5b). AlvMs showed severely dysregulated metabolism relative to that of cavity macrophages. After removal from the lungs, AlvMs regained responsiveness to IL-4 in a glycolysis-dependent manner. Thus, impaired glycolysis in the pulmonary niche regulates AlvM responsiveness during type 2 inflammation

Evolutionary Conservation of the Functional Modularity of Primate and Murine LINE-1 Elements

LINE-1 (L1) retroelements emerged in mammalian genomes over 80 million years ago with a few dominant subfamilies amplifying over discrete time periods that led to distinct human and mouse L1 lineages. We evaluated the functional conservation of L1 sequences by comparing retrotransposition rates of chimeric human-rodent L1 constructs to their parental L1 counterparts. Although amino acid conservation varies from ∼35% to 63% for the L1 ORF1p and ORF2p, most human and mouse L1 sequences can be functionally exchanged. Replacing either ORF1 or ORF2 to create chimeric human-mouse L1 elements did not adversely affect retrotransposition. The mouse ORF2p retains retrotransposition-competency to support both Alu and L1 mobilization when any of the domain sequences we evaluated were substituted with human counterparts. However, the substitution of portions of the mouse cys-domain into the human ORF2p reduces both L1 retrotransposition and Alu trans-mobilization by 200–1000 fold. The observed loss of ORF2p function is independent of the endonuclease or reverse transcriptase activities of ORF2p and RNA interaction required for reverse transcription. In addition, the loss of function is physically separate from the cysteine-rich motif sequence previously shown to be required for RNP formation. Our data suggest an additional role of the less characterized carboxy-terminus of the L1 ORF2 protein by demonstrating that this domain, in addition to mediating RNP interaction(s), provides an independent and required function for the retroelement amplification process. Our experiments show a functional modularity of most of the LINE sequences. However, divergent evolution of interactions within L1 has led to non-reciprocal incompatibilities between human and mouse ORF2 cys-domain sequences

Concurrent use of prescription drugs and herbal medicinal products in older adults: A systematic review

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The use of herbal medicinal products (HMPs) is common among older adults. However, little is known about concurrent use with prescription drugs as well as the potential interactions associated with such combinations. Objective Identify and evaluate the literature on concurrent prescription and HMPs use among older adults to assess prevalence, patterns, potential interactions and factors associated with this use. Methods Systematic searches in MEDLINE, PsycINFO, EMBASE, CINAHL, AMED, Web of Science and Cochrane from inception to May 2017 for studies reporting concurrent use of prescription medicines with HMPs in adults (≥65 years). Quality was assessed using the Joanna Briggs Institute checklists. The Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre) three stage approach to mixed method research was used to synthesise data. Results Twenty-two studies were included. A definition of HMPs or what was considered HMP was frequently missing. Prevalence of concurrent use by older adults varied widely between 5.3% and 88.3%. Prescription medicines most combined with HMPs were antihypertensive drugs, beta blockers, diuretics, antihyperlipidemic agents, anticoagulants, analgesics, antihistamines, antidiabetics, antidepressants and statins. The HMPs most frequently used were: ginkgo, garlic, ginseng, St John’s wort, Echinacea, saw palmetto, evening primrose oil and ginger. Potential risks of bleeding due to use of ginkgo, garlic or ginseng with aspirin or warfarin was the most reported herb-drug interaction. Some data suggests being female, a lower household income and less than high school education were associated with concurrent use. Conclusion Prevalence of concurrent prescription drugs and HMPs use among older adults is substantial and potential interactions have been reported. Knowledge of the extent and manner in which older adults combine prescription drugs will aid healthcare professionals can appropriately identify and manage patients at risk.Peer reviewedFinal Published versio

Phonon-assisted carrier transport through a lattice-mismatched interface

We showed the distinctive unconventional junction effect of MoS2 junctions: a lattice mismatched MoS2. It is unique to observe the difference originated from the atomic interrelation at the interface. The results revealed the dominant scattering source at the conventional naturally stepwise junction, while the misorientationally stacked layer exhibited effectively decoupled behavior and a significantly smaller junction resistance via phonon assist carrier. Therefore, our finding in this paper clearly shows the different mechanisms in carrier transport at both junction interface of MoS2

Supplier-induced demand for psychiatric admissions in Northern New England

The development of hospital service areas (HSAs) using small area analysis has been useful in examining variation in medical and surgical care; however, the techniques of small area analysis are underdeveloped in understanding psychiatric admission rates. We sought to develop these techniques in order to understand the relationship between psychiatric bed supply and admission rates in Northern New England. Our primary hypotheses were that there would be substantial variation in psychiatric admission across geographic settings and that bed availability would be positively correlated with admission rates, reflecting a supplier-induced demand phenomenon. Our secondary hypothesis was that the construction of psychiatric HSAs (PHSAs) would yield more meaningful results than the use of existing general medical hospital service areas

Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the Cancer Prevention Study II cohort

INTRODUCTION: Vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis and is over-expressed in breast cancer. At least four polymorphisms in the VEGF gene have been associated with changes in VEGF expression levels: -2578C/A, -1154G/A and -634G/C are all located in the promoter region; and +936C/T is located in the 3'-untranslated region. METHOD: We examined the association between these four VEGF polymorphisms and risk for breast cancer among postmenopausal women in CPS-II (Cancer Prevention Study II) Nutrition Cohort. This cohort was established in 1992 and participants were invited to provide a blood sample between 1998 and 2001. Included in this analysis were 501 postmenopausal women who provided a blood sample and were diagnosed with breast cancer between 1992 and 2001 (cases). Control individuals were 504 cancer-free postmenopausal women matched to the cases with respect to age, race/ethnicity, and date of blood collection (controls). RESULTS: We found no association between any of the polymorphisms examined and overall breast cancer risk. However, associations were markedly different in separate analyses of invasive cancer (n = 380) and in situ cancer (n = 107). The -2578C and -1154G alleles, which are both hypothesized to increase expression of VEGF, were associated with increased risk for invasive breast cancer (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.00–2.14 for -2578 CC versus AA; OR 1.64, 95% CI 1.02–2.64 for -1154 GG versus AA) but they were not associated with risk for in situ cancer. The +936C allele, which is also hypothesized to increase VEGF expression, was not clearly associated with invasive breast cancer (OR 1.21, 95% CI 0.88–1.67 for +936 CC versus TT/CT), but it was associated with reduced risk for in situ cancer (OR 0.59, 95% CI 0.37–0.93 for CC versus TT/CT). The -634 C/G polymorphism was not associated with either invasive or in situ cancer. CONCLUSION: Our findings provide limited support for the hypothesis that the -2578C and -1154G VEGF alleles are associated with increased risk for invasive but not in situ breast cancer in postmenopausal women

Genomic Regions Associated with Multiple Sclerosis Are Active in B Cells

More than 50 genomic regions have now been shown to influence the risk of multiple sclerosis (MS). However, the mechanisms of action, and the cell types in which these associated variants act at the molecular level remain largely unknown. This is especially true for associated regions containing no known genes. Given the evidence for a role for B cells in MS, we hypothesized that MS associated genomic regions co-localized with regions which are functionally active in B cells. We used publicly available data on 1) MS associated regions and single nucleotide polymorphisms (SNPs) and 2) chromatin profiling in B cells as well as three additional cell types thought to be unrelated to MS (hepatocytes, fibroblasts and keratinocytes). Genomic intervals and SNPs were tested for overlap using the Genomic Hyperbrowser. We found that MS associated regions are significantly enriched in strong enhancer, active promoter and strong transcribed regions (p = 0.00005) and that this overlap is significantly higher in B cells than control cells. In addition, MS associated SNPs also land in active promoter (p = 0.00005) and enhancer regions more than expected by chance (strong enhancer p = 0.0006; weak enhancer p = 0.00005). These results confirm the important role of the immune system and specifically B cells in MS and suggest that MS risk variants exert a gene regulatory role. Previous studies assessing MS risk variants in T cells may be missing important effects in B cells. Similar analyses in other immunological cell types relevant to MS and functional studies are necessary to fully elucidate how genes contribute to MS pathogenesis