Kepler-432: a red giant interacting with one of its two long period giant planets

We report the discovery of Kepler-432b, a giant planet ($M_b = 5.41^{+0.32}_{-0.18} M_{\rm Jup}, R_b = 1.145^{+0.036}_{-0.039} R_{\rm Jup}$) transiting an evolved star $(M_\star = 1.32^{+0.10}_{-0.07} M_\odot, R_\star = 4.06^{+0.12}_{-0.08} R_\odot)$ with an orbital period of $P_b = 52.501129^{+0.000067}_{-0.000053}$ days. Radial velocities (RVs) reveal that Kepler-432b orbits its parent star with an eccentricity of $e = 0.5134^{+0.0098}_{-0.0089}$, which we also measure independently with asterodensity profiling (AP; $e=0.507^{+0.039}_{-0.114}$), thereby confirming the validity of AP on this particular evolved star. The well-determined planetary properties and unusually large mass also make this planet an important benchmark for theoretical models of super-Jupiter formation. Long-term RV monitoring detected the presence of a non-transiting outer planet (Kepler-432c; $M_c \sin{i_c} = 2.43^{+0.22}_{-0.24} M_{\rm Jup}, P_c = 406.2^{+3.9}_{-2.5}$ days), and adaptive optics imaging revealed a nearby (0\farcs87), faint companion (Kepler-432B) that is a physically bound M dwarf. The host star exhibits high signal-to-noise asteroseismic oscillations, which enable precise measurements of the stellar mass, radius and age. Analysis of the rotational splitting of the oscillation modes additionally reveals the stellar spin axis to be nearly edge-on, which suggests that the stellar spin is likely well-aligned with the orbit of the transiting planet. Despite its long period, the obliquity of the 52.5-day orbit may have been shaped by star-planet interaction in a manner similar to hot Jupiter systems, and we present observational and theoretical evidence to support this scenario. Finally, as a short-period outlier among giant planets orbiting giant stars, study of Kepler-432b may help explain the distribution of massive planets orbiting giant stars interior to 1 AU.Comment: 22 pages, 19 figures, 5 tables. Accepted to ApJ on Jan 24, 2015 (submitted Nov 11, 2014). Updated with minor changes to match published versio

Geochemical evidence for the application of nanoparticulate colloidal silica gel for in-situ containment of legacy nuclear wastes

Colloidal silica is a nanoparticulate material that could have a transformative effect on environmental risk management at nuclear legacy sites through their use in in-situ installation of injectable hydraulic barriers. In order to utilize such nanoparticulate material as a barrier, we require detailed understanding of its impact on the geochemistry of radionuclides in the environment (e.g. fission products such as Sr and Cs). Here we show, through combining leaching experiments with XAS analyses, that colloidal silica induces several competing effects on the mobility of Sr and Cs. First, cations within the colloidal silica gel compete with Sr and Cs for surface complexation sites. Second, an increased number of surface complexation sites is provided by the silica nanoparticles and finally, the elevated pH within the colloidal silica increases the surface complexation to clay minerals and the silica nanoparticles. XAS analyses show that Sr and Cs complex predominantly with the clay mineral phases in the soil through inner-sphere surface complexes (Sr) and through complexation on the clay basal surfaces at Si vacancy sites (Cs). For binary soil – colloidal silica gel systems, a fraction of the Sr and Cs complexes with the amorphous silica-like surfaces through the formation of outer-sphere surface complexes. Importantly, the net effect of nanoparticulate colloidal silica gel is to increase the retention of Sr and Cs, when compared to untreated soil and waste materials. Our research opens the door to applications of colloidal silica gel to form barriers within risk management strategies at legacy nuclear sites

An Analysis of the Legal, Social, and Political Issues Raised by Asbestos Litigation

This Special Project examines the most important issues of the asbestos problem and advocates a congressional solution (1) to relieve the courts of the thousands of present and potential asbestos cases, (2) to protect future claimants\u27 rights to adequate compensation, and (3) to provide for equitable participation by all responsible parties, which, in addition to asbestos manufacturers,include the federal government, insurance companies, and the tobacco industry. The first six parts of the Special Project examine the various issues of asbestos litigation: theories of liability in products liability suits against asbestos manufacturers, causation,defenses, statutory limitations on actions, collateral estoppel, and punitive damages. The Special Project then discusses in parts VIII,IX, and X the methods used by asbestos manufacturers to attempt to spread their liability through asserting insurer liability, the exclusive remedy of workers\u27 compensation, and indemnity and contribution from the United States. Finally, the Special Project evaluates and analyzes recent developments in the asbestos litigation area, including proposals for federal legislative compensation programs and business alternatives available to asbestos manufacturers facing enormous asbestos-related liabilities... This Special Project critically has examined the most important issues concerning the asbestos problem. It has considered the complex legal, legislative, and social questions that society must confront in order to resolve this predicament. Only swift action by Congress in the form of a fair and comprehensive compensation scheme for victims of asbestos-related disabilities will initiate a solution to this difficult and pervasive problem

Nanopore native RNA sequencing of a human poly(A) transcriptome

High-throughput complementary DNA sequencing technologies have advanced our understanding of transcriptome complexity and regulation. However, these methods lose information contained in biological RNA because the copied reads are often short and modifications are not retained. We address these limitations using a native poly(A) RNA sequencing strategy developed by Oxford Nanopore Technologies. Our study generated 9.9 million aligned sequence reads for the human cell line GM12878, using thirty MinION flow cells at six institutions. These native RNA reads had a median length of 771 bases, and a maximum aligned length of over 21,000 bases. Mitochondrial poly(A) reads provided an internal measure of read-length quality. We combined these long nanopore reads with higher accuracy short-reads and annotated GM12878 promoter regions to identify 33,984 plausible RNA isoforms. We describe strategies for assessing 3′ poly(A) tail length, base modifications and transcript haplotypes

Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis.

Tuberculosis (TB) is responsible for enormous global morbidity and mortality, and current treatment regimens rely on the use of drugs that have been in use for more than 40 years. Owing to widespread resistance to these therapies, new drugs are desperately needed to control the TB disease burden. Herein, we describe the rapid synthesis of analogues of the sansanmycin uridylpeptide natural products that represent promising new TB drug leads. The compounds exhibit potent and selective inhibition of Mycobacterium tuberculosis, the etiological agent of TB, both in vitro and intracellularly. The natural product analogues were also shown to be nanomolar inhibitors of Mtb phospho-MurNAc-pentapeptide translocase, the enzyme responsible for the synthesis of lipid I in mycobacteria. This work lays the foundation for the development of uridylpeptide natural product analogues as new TB drug candidates that operate through the inhibition of peptidoglycan biosynthesis

Comparison of three methods for detection of gametocytes in Melanesian children treated for uncomplicated malaria

Background: Gametocytes are the transmission stages of Plasmodium parasites, the causative agents of malaria. As their density in the human host is typically low, they are often undetected by conventional light microscopy. Furthermore, application of RNA-based molecular detection methods for gametocyte detection remains challenging in remote field settings. In the present study, a detailed comparison of three methods, namely light microscopy, magnetic fractionation and reverse transcriptase polymerase chain reaction for detection of Plasmodium falciparum and Plasmodium vivax gametocytes was conducted.Methods. Peripheral blood samples from 70 children aged 0.5 to five years with uncomplicated malaria who were treated with either artemether-lumefantrine or artemisinin-naphthoquine were collected from two health facilities on the north coast of Papua New Guinea. The samples were taken prior to treatment (day 0) and at pre-specified intervals during follow-up. Gametocytes were measured in each sample by three methods: i) light microscopy (LM), ii) quantitative magnetic fractionation (MF) and, iii) reverse transcriptase PCR (RTPCR). Data were analysed using censored linear regression and Bland and Altman techniques.Results: MF and RTPCR were similarly sensitive and specific, and both were superior to LM. Overall, there were approximately 20% gametocyte-positive samples by LM, whereas gametocyte positivity by MF and RTPCR were both more than two-fold this level. In the subset of samples collected prior to treatment, 29% of children were positive by LM, and 85% were gametocyte positive by MF and RTPCR, respectively.Conclusions: The present study represents the first direct comparison of standard LM, MF and RTPCR for gametocyte detection in field isolates. It provides strong evidence that MF is superior to LM and can be used to detect gametocytaemic patients under field conditions with similar sensitivity and specificity as RTPCR

Incorporation of uranium into hematite during crystallization from ferrihydrite

Ferrihydrite was exposed to U(VI)-containing cement leachate (pH 10.5) and aged to induce crystallization of hematite. A combination of chemical extractions, TEM, and XAS techniques provided the first evidence that adsorbed U(VI) (≈3000 ppm) was incorporated into hematite during ferrihydrite aggregation and the early stages of crystallization, with continued uptake occurring during hematite ripening. Analysis of EXAFS and XANES data indicated that the U(VI) was incorporated into a distorted, octahedrally coordinated site replacing Fe(III). Fitting of the EXAFS showed the uranyl bonds lengthened from 1.81 to 1.87 Å, in contrast to previous studies that have suggested that the uranyl bond is lost altogether upon incorporation into hematite the results of this study both provide a new mechanistic understanding of uranium incorporation into hematite and define the nature of the bonding environment of uranium within the mineral structure. Immobilization of U(VI) by incorporation into hematite has clear and important implications for limiting uranium migration in natural and engineered environments. © 2014 American Chemical Society

Advancing Drug Innovation for Neglected Diseases—Criteria for Lead Progression

The current drug R&D pipeline for most neglected diseases remains weak, and unlikely to support registration of novel drug classes that meet desired target product profiles in the short term. This calls for sustained investment as well as greater emphasis in the risky upstream drug discovery. Access to technologies, resources, and strong management as well as clear compound progression criteria are factors in the successful implementation of any collaborative drug discovery effort. We discuss how some of these factors have impacted drug discovery for tropical diseases within the past four decades, and highlight new opportunities and challenges through the virtual North–South drug discovery network as well as the rationale for greater participation of institutions in developing countries in product innovation. A set of criteria designed to facilitate compound progression from screening hits to drug candidate selection is presented to guide ongoing efforts

Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.This study was funded by the UK Medical Research Council through grants MC_UU_12015/1, MC_PC_13046, MC_PC_13048 and MR/L00002/1. This work was supported by the MRC Metabolic Diseases Unit (MC_UU_12012/5) and the Cambridge NIHR Biomedical Research Centre and EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant 115372). Funding for the InterAct project was provided by the EU FP6 program (grant LSHM_CT_2006_037197). This work was funded, in part, through an EFSD Rising Star award to R.A.S. supported by Novo Nordisk. D.B.S. is supported by Wellcome Trust grant 107064. M.I.M. is a Wellcome Trust Senior Investigator and is supported by the following grants from the Wellcome Trust: 090532 and 098381. M.v.d.B. is supported by a Novo Nordisk postdoctoral fellowship run in partnership with the University of Oxford. I.B. is supported by Wellcome Trust grant WT098051. S.O'R. acknowledges funding from the Wellcome Trust (Wellcome Trust Senior Investigator Award 095515/Z/11/Z and Wellcome Trust Strategic Award 100574/Z/12/Z)