Quantum spin liquid states in the two dimensional kagome antiferromagnets, ZnxCu4-x(OD)6Cl2

A three-dimensional system of interacting spins typically develops static long-range order when it is cooled. If the spins are quantum (S = 1/2), however, novel quantum paramagnetic states may appear. The most highly sought state among them is the resonating valence bond (RVB) state in which every pair of neighboring quantum spins form entangled spin singlets (valence bonds) and the singlets are quantum mechanically resonating amongst all the possible highly degenerate pairing states. Here we provide experimental evidence for such quantum paramagnetic states existing in frustrated antiferromagnets, ZnxCu4-x(OD)6Cl2, where the S = 1/2 magnetic Cu2+ moments form layers of a two-dimensional kagome lattice. We find that in Cu4(OD)6Cl2, where distorted kagome planes are weakly coupled to each other, a dispersionless excitation mode appears in the magnetic excitation spectrum below ~ 20 K, whose characteristics resemble those of quantum spin singlets in a solid state, known as a valence bond solid (VBS), that breaks translational symmetry. Doping nonmagnetic Zn2+ ions reduces the distortion of the kagome lattice, and weakens the interplane coupling but also dilutes the magnetic occupancy of the kagome lattice. The VBS state is suppressed and for ZnCu3(OD)6Cl2 where the kagome planes are undistorted and 90% occupied by the Cu2+ ions, the low energy spin fluctuations in the spin liquid phase become featureless

A global bond: Explaining the safe-haven status of US Treasury securities

This article offers new theoretical and empirical insights to explain the resilience of US Treasury securities as the world’s premier safe or “risk-free” asset. The standard explanation of resilience emphasizes the relative safety of US Treasuries due to a shortage of safe assets in the global political economy. The analysis here goes beyond the standard explanation to highlight the importance of domestic politics in reinforcing the safe status of US Treasury securities. In particular, the research shows how a formidable “bond” of interests unites domestic and foreign owners of the public debt and works to sustain US power in global finance. Foreigners, who now own roughly half of the US public debt, have something to gain from their domestic counterparts. The top 1% of US households, which dominate domestic ownership of US Treasuries, has considerable political clout, thus alleviating foreign concerns about the creditworthiness of the US federal government. Domestic owners, in turn, benefit from the seemingly insatiable foreign appetite for US Treasury securities. In supplying the US federal government and US households with cheap credit, foreign investors in US Treasuries help to deflect challenges to the top 1% within the wealth and income hierarchy

Metabolic profiling of HepG2 cells incubated with S(−) and R(+) enantiomers of anti-coagulating drug warfarin

Warfarin is a commonly prescribed oral anticoagulant with narrow therapeutic index. It achieves anti-coagulating effects by interfering with the vitamin K cycle. Warfarin has two enantiomers, S(−) and R(+) and undergoes stereoselective metabolism, with the S(−) enantiomer being more effective. We reported the intracellular metabolic profile in HepG2 cells incubated with S(−) and R(+) warfarin by GCMS. Chemometric method PCA was applied to analyze the individual samples. A total of 80 metabolites which belong to different categories were identified. Two batches of experiments (with and without the presence of vitamin K) were designed. In samples incubated with S(−) and R(+) warfarin, glucuronic acid showed significantly decreased in cells incubated with R(+) warfarin but not in those incubated with S(−) warfarin. It may partially explain the lower bio-activity of R(+) warfarin. And arachidonic acid showed increased in cells incubated with S(−) warfarin but not in those incubated with R(+) warfarin. In addition, a number of small molecules involved in γ-glutamyl cycle displayed ratio variations. Intracellular glutathione detection further validated the results. Taken together, our findings provided molecular evidence on a comprehensive metabolic profile on warfarin-cell interaction which may shed new lights on future improvement of warfarin therapy

In Vivo Analysis of the Notch Receptor S1 Cleavage

A ligand-independent cleavage (S1) in the extracellular domain of the mammalian Notch receptor results in what is considered to be the canonical heterodimeric form of Notch on the cell surface. The in vivo consequences and significance of this cleavage on Drosophila Notch signaling remain unclear and contradictory. We determined the cleavage site in Drosophila and examined its in vivo function by a transgenic analysis of receptors that cannot be cleaved. Our results demonstrate a correlation between loss of cleavage and loss of in vivo function of the Notch receptor, supporting the notion that S1 cleavage is an in vivo mechanism of Notch signal control

Recent and Projected Increases in Atmospheric CO2 Concentration Can Enhance Gene Flow between Wild and Genetically Altered Rice (Oryza sativa)

Although recent and projected increases in atmospheric carbon dioxide can alter plant phenological development, these changes have not been quantified in terms of floral outcrossing rates or gene transfer. Could differential phenological development in response to rising CO2 between genetically modified crops and wild, weedy relatives increase the spread of novel genes, potentially altering evolutionary fitness? Here we show that increasing CO2 from an early 20th century concentration (300 µmol mol−1) to current (400 µmol mol−1) and projected, mid-21st century (600 µmol mol−1) values, enhanced the flow of genes from wild, weedy rice to the genetically altered, herbicide resistant, cultivated population, with outcrossing increasing from 0.22% to 0.71% from 300 to 600 µmol mol−1. The increase in outcrossing and gene transfer was associated with differential increases in plant height, as well as greater tiller and panicle production in the wild, relative to the cultivated population. In addition, increasing CO2 also resulted in a greater synchronicity in flowering times between the two populations. The observed changes reported here resulted in a subsequent increase in rice dedomestication and a greater number of weedy, herbicide-resistant hybrid progeny. Overall, these data suggest that differential phenological responses to rising atmospheric CO2 could result in enhanced flow of novel genes and greater success of feral plant species in agroecosystems

Accounting For Alignment Uncertainty in Phylogenomics

Uncertainty in multiple sequence alignments has a large impact on phylogenetic analyses. Little has been done to evaluate the quality of individual positions in protein sequence alignments, which directly impact the accuracy of phylogenetic trees. Here we describe ZORRO, a probabilistic masking program that accounts for alignment uncertainty by assigning confidence scores to each alignment position. Using the BALIBASE database and in simulation studies, we demonstrate that masking by ZORRO significantly reduces the alignment uncertainty and improves the tree accuracy

It’s not the size, it’s the relationship: from ‘small states’ to asymmetry

Debate about the definition of “small state” has produced more fragmentation than consensus, even as the literature has demonstrated its subjects’ roles in joining international organizations propagating norms, executing creative diplomacy, influencing allies, avoiding and joining conflicts, and building peace. However, work on small states has struggled to identify commonalities in these states’ international relations, to cumulate knowledge, or to impact broader IR theory. This paper advocates a changed conceptual and definitional framework. Analysis of “small states” should pivot to examine the dynamics of the asymmetrical relationships in which these states are engaged. Instead of seeking an overall metric for size as the relevant variable—falling victim in a different way Dahl’s “lump-of-power fallacy,” we can recognize the multifaceted, variegated nature of power, whether in war or peacetime

Growth Inhibition and Apoptosis Induced by Osthole, A Natural Coumarin, in Hepatocellular Carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed tumors worldwide and is known to be resistant to conventional chemotherapy. New therapeutic strategies are urgently needed for treating HCC. Osthole, a natural coumarin derivative, has been shown to have anti-tumor activity. However, the effects of osthole on HCC have not yet been reported. METHODS AND FINDINGS: HCC cell lines were treated with osthole at various concentrations for 24, 48 and 72 hours. The proliferations of the HCC cells were measured by MTT assays. Cell cycle distribution and apoptosis were determined by flow cytometry. HCC tumor models were established in mice by subcutaneously injection of SMMC-7721 or Hepa1-6 cells and the effect of osthole on tumor growths in vivo and the drug toxicity were studied. NF-κB activity after osthole treatment was determined by electrophoretic mobility shift assays and the expression of caspase-3 was measured by western blotting. The expression levels of other apoptosis-related genes were also determined by real-time PCR (PCR array) assays. Osthole displayed a dose- and time-dependent inhibition of the HCC cell proliferations in vitro. It also induced apoptosis and caused cell accumulation in G2 phase. Osthole could significantly suppress HCC tumor growth in vivo with no toxicity at the dose we used. NF-κB activity was significantly suppressed by osthole at the dose- and time-dependent manner. The cleaved caspase-3 was also increased by osthole treatment. The expression levels of some apoptosis-related genes that belong to TNF ligand family, TNF receptor family, Bcl-2 family, caspase family, TRAF family, death domain family, CIDE domain and death effector domain family and CARD family were all increased with osthole treatment. CONCLUSION: Osthole could significantly inhibit HCC growth in vitro and in vivo through cell cycle arrest and inducing apoptosis by suppressing NF-κB activity and promoting the expressions of apoptosis-related genes

Seasonality in Human Zoonotic Enteric Diseases: A Systematic Review

BACKGROUND: Although seasonality is a defining characteristic of many infectious diseases, few studies have described and compared seasonal patterns across diseases globally, impeding our understanding of putative mechanisms. Here, we review seasonal patterns across five enteric zoonotic diseases: campylobacteriosis, salmonellosis, vero-cytotoxigenic Escherichia coli (VTEC), cryptosporidiosis and giardiasis in the context of two primary drivers of seasonality: (i) environmental effects on pathogen occurrence and pathogen-host associations and (ii) population characteristics/behaviour. METHODOLOGY/PRINCIPAL FINDINGS: We systematically reviewed published literature from 1960-2010, resulting in the review of 86 studies across the five diseases. The Gini coefficient compared temporal variations in incidence across diseases and the monthly seasonality index characterised timing of seasonal peaks. Consistent seasonal patterns across transnational boundaries, albeit with regional variations was observed. The bacterial diseases all had a distinct summer peak, with identical Gini values for campylobacteriosis and salmonellosis (0.22) and a higher index for VTEC (Gini  0.36). Cryptosporidiosis displayed a bi-modal peak with spring and summer highs and the most marked temporal variation (Gini = 0.39). Giardiasis showed a relatively small summer increase and was the least variable (Gini = 0.18). CONCLUSIONS/SIGNIFICANCE: Seasonal variation in enteric zoonotic diseases is ubiquitous, with regional variations highlighting complex environment-pathogen-host interactions. Results suggest that proximal environmental influences and host population dynamics, together with distal, longer-term climatic variability could have important direct and indirect consequences for future enteric disease risk. Additional understanding of the concerted influence of these factors on disease patterns may improve assessment and prediction of enteric disease burden in temperate, developed countries