The Inflationary Perturbation Spectrum

Motivated by the prospect of testing inflation from precision cosmic microwave background observations, we present analytic results for scalar and tensor perturbations in single-field inflation models based on the application of uniform approximations. This technique is systematically improvable, possesses controlled error bounds, and does not rely on assuming the slow-roll parameters to be constant. We provide closed-form expressions for the power spectra and the corresponding scalar and tensor spectral indices.Comment: 4 pages, 1 figur

Water in Deep Eutectic Solvents: New Insights From Inelastic Neutron Scattering Spectroscopy

The effect of water on the physicochemical properties of deep eutectic solvents (DES) is a trending research topic. In this work, inelastic neutron scattering (INS) spectroscopy, was used to probe intermolecular interactions in the water-deep eutectic solvent mixtures for the cases of choline chloride (the hydrogen bond acceptor) and three different hydrogen bond donors, with different degrees of acidity: urea, glycerol and lactic acid. It was found that quenching samples in liquid nitrogen is a procedure that may retain the liquid phase morphology of DES at the low temperatures required by INS spectroscopy. The three studied systems share the preference of water molecules to bind to chloride anion, as predicted by numerous molecular dynamics simulations. Despite this similarity, the three systems present several distinct INS features upon water addition that are related to their unique properties and structure at the molecular level. In the choline chloride:urea system, water molecules promote a strengthening of hydrogen bonds with the NH and OH donors, while for the choline chloride:lactic acid system INS probed the existence of solvated DES clusters instead of specifically interfering water molecules. This study takes advantage from the unique capabilities of INS and paves the way for future studies in these systems.publishe

Prevalence and Determinants of Vitamin D Deficiency in 1825 Cape Town Primary Schoolchildren: A Cross-Sectional Study

Vitamin D deficiency (25-hydroxyvitamin D[25(OH)D] <50 nmol/L) is common among adults in Cape Town, South Africa, but studies investigating vitamin D status of children in this setting are lacking. We conducted a cross-sectional study to determine the prevalence and determinants of vitamin D deficiency in 1825 Cape Town schoolchildren aged 6–11 years. Prevalence of vitamin D deficiency was 7.6% (95% Confidence Interval [CI] 6.5% to 8.9%). Determinants of vitamin D deficiency included month of sampling (adjusted odds ratio [aOR] for July–September vs. January–March 10.69, 95% CI 5.02 to 22.77; aOR for October–December vs. January–March 6.73, 95% CI 2.82 to 16.08), older age (aOR 1.25 per increasing year, 95% CI: 1.01–1.53) and higher body mass index (BMI; aOR 1.24 per unit increase in BMI-for-age Z-score, 95% CI: 1.03–1.49). In a subset of 370 participants in whom parathyroid hormone (PTH) concentrations were measured; these were inversely related to serum 25(OH)D concentrations (p < 0.001). However, no association between participants with hyperparathyroidism (PTH >6.9 pmol/L) and vitamin D deficiency was seen (p = 0.42). In conclusion, we report that season is the major determinant of vitamin D status among Cape Town primary schoolchildren, with prevalence of vitamin D deficiency ranging from 1.4% in January–March to 22.8% in July–September

Restarted Q-Arnoldi-type methods exploiting symmetry in quadratic eigenvalue problems

The final publication is available at Springer via http://dx.doi.org/ 10.1007/s10543-016-0601-5.We investigate how to adapt the Q-Arnoldi method for the case of symmetric quadratic eigenvalue problems, that is, we are interested in computing a few eigenpairs of with M, C, K symmetric matrices. This problem has no particular structure, in the sense that eigenvalues can be complex or even defective. Still, symmetry of the matrices can be exploited to some extent. For this, we perform a symmetric linearization , where A, B are symmetric matrices but the pair (A, B) is indefinite and hence standard Lanczos methods are not applicable. We implement a symmetric-indefinite Lanczos method and enrich it with a thick-restart technique. This method uses pseudo inner products induced by matrix B for the orthogonalization of vectors (indefinite Gram-Schmidt). The projected problem is also an indefinite matrix pair. The next step is to write a specialized, memory-efficient version that exploits the block structure of A and B, referring only to the original problem matrices M, C, K as in the Q-Arnoldi method. This results in what we have called the Q-Lanczos method. Furthermore, we define a stabilized variant analog of the TOAR method. We show results obtained with parallel implementations in SLEPc.This work was supported by the Spanish Ministry of Economy and Competitiveness under Grant TIN2013-41049-P. Carmen Campos was supported by the Spanish Ministry of Education, Culture and Sport through an FPU Grant with reference AP2012-0608.Campos, C.; Román Moltó, JE. (2016). Restarted Q-Arnoldi-type methods exploiting symmetry in quadratic eigenvalue problems. BIT Numerical Mathematics. 56(4):1213-1236. https://doi.org/10.1007/s10543-016-0601-5S12131236564Bai, Z., Su, Y.: SOAR: a second-order Arnoldi method for the solution of the quadratic eigenvalue problem. SIAM J. Matrix Anal. Appl. 26(3), 640–659 (2005)Bai, Z., Day, D., Ye, Q.: ABLE: an adaptive block Lanczos method for non-Hermitian eigenvalue problems. SIAM J. Matrix Anal. Appl. 20(4), 1060–1082 (1999)Bai, Z., Ericsson, T., Kowalski, T.: Symmetric indefinite Lanczos method. In: Bai, Z., Demmel, J., Dongarra, J., Ruhe, A., van der Vorst, H. (eds.) Templates for the solution of algebraic eigenvalue problems: a practical guide, pp. 249–260. Society for Industrial and Applied Mathematics, Philadelphia (2000)Balay, S., Abhyankar, S., Adams, M., Brown, J., Brune, P., Buschelman, K., Dalcin, L., Eijkhout, V., Gropp, W., Kaushik, D., Knepley, M., McInnes, L.C., Rupp, K., Smith, B., Zampini, S., Zhang, H.: PETSc users manual. Tech. Rep. ANL-95/11 - Revision 3.6, Argonne National Laboratory (2015)Benner, P., Faßbender, H., Stoll, M.: Solving large-scale quadratic eigenvalue problems with Hamiltonian eigenstructure using a structure-preserving Krylov subspace method. Electron. Trans. Numer. Anal. 29, 212–229 (2008)Betcke, T., Higham, N.J., Mehrmann, V., Schröder, C., Tisseur, F.: NLEVP: a collection of nonlinear eigenvalue problems. ACM Trans. Math. Softw. 39(2), 7:1–7:28 (2013)Campos, C., Roman, J.E.: Parallel Krylov solvers for the polynomial eigenvalue problem in SLEPc (2015, submitted)Day, D.: An efficient implementation of the nonsymmetric Lanczos algorithm. SIAM J. Matrix Anal. Appl. 18(3), 566–589 (1997)Hernandez, V., Roman, J.E., Vidal, V.: SLEPc: a scalable and flexible toolkit for the solution of eigenvalue problems. ACM Trans. Math. Softw. 31(3), 351–362 (2005)Hernandez, V., Roman, J.E., Tomas, A.: Parallel Arnoldi eigensolvers with enhanced scalability via global communications rearrangement. Parallel Comput. 33(7–8), 521–540 (2007)Jia, Z., Sun, Y.: A refined variant of SHIRA for the skew-Hamiltonian/Hamiltonian (SHH) pencil eigenvalue problem. Taiwan J. Math. 17(1), 259–274 (2013)Kressner, D., Roman, J.E.: Memory-efficient Arnoldi algorithms for linearizations of matrix polynomials in Chebyshev basis. Numer. Linear Algebra Appl. 21(4), 569–588 (2014)Kressner, D., Pandur, M.M., Shao, M.: An indefinite variant of LOBPCG for definite matrix pencils. Numer. Algorithms 66(4), 681–703 (2014)Lancaster, P.: Linearization of regular matrix polynomials. Electron. J. Linear Algebra 17, 21–27 (2008)Lancaster, P., Ye, Q.: Rayleigh-Ritz and Lanczos methods for symmetric matrix pencils. Linear Algebra Appl. 185, 173–201 (1993)Lu, D., Su, Y.: Two-level orthogonal Arnoldi process for the solution of quadratic eigenvalue problems (2012, manuscript)Meerbergen, K.: The Lanczos method with semi-definite inner product. BIT 41(5), 1069–1078 (2001)Meerbergen, K.: The Quadratic Arnoldi method for the solution of the quadratic eigenvalue problem. SIAM J. Matrix Anal. Appl. 30(4), 1463–1482 (2008)Mehrmann, V., Watkins, D.: Structure-preserving methods for computing eigenpairs of large sparse skew-Hamiltonian/Hamiltonian pencils. SIAM J. Sci. Comput. 22(6), 1905–1925 (2001)Parlett, B.N.: The symmetric Eigenvalue problem. Prentice-Hall, Englewood Cliffs (1980) (reissued with revisions by SIAM, Philadelphia)Parlett, B.N., Chen, H.C.: Use of indefinite pencils for computing damped natural modes. Linear Algebra Appl. 140(1), 53–88 (1990)Parlett, B.N., Taylor, D.R., Liu, Z.A.: A look-ahead Lánczos algorithm for unsymmetric matrices. Math. Comput. 44(169), 105–124 (1985)de Samblanx, G., Bultheel, A.: Nested Lanczos: implicitly restarting an unsymmetric Lanczos algorithm. Numer. Algorithms 18(1), 31–50 (1998)Sleijpen, G.L.G., Booten, A.G.L., Fokkema, D.R., van der Vorst, H.A.: Jacobi-Davidson type methods for generalized eigenproblems and polynomial eigenproblems. BIT 36(3), 595–633 (1996)Stewart, G.W.: A Krylov-Schur algorithm for large eigenproblems. 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Lifestyle and Genetic Factors Modify Parent-of-Origin Effects on the Human Methylome

BACKGROUND: parent-of-origin effects (POE) play important roles in complex disease and thus understanding their regulation and associated molecular and phenotypic variation are warranted. Previous studies mainly focused on the detection of genomic regions or phenotypes regulated by POE. Understanding whether POE may be modified by environmental or genetic exposures is important for understanding of the source of POE-associated variation, but only a few case studies addressing modifiable POE exist. METHODS: in order to understand this high order of POE regulation, we screened 101 genetic and environmental factors such as ‘predicted mRNA expression levels’ of DNA methylation/imprinting machinery genes and environmental exposures. POE-mQTL-modifier interaction models were proposed to test the potential of these factors to modify POE at DNA methylation using data from Generation Scotland: The Scottish Family Health Study(N=2315). FINDINGS: a set of vulnerable/modifiable POE-CpGs were identified (modifiable-POE-regulated CpGs, N=3). Four factors, ‘lifetime smoking status’ and ‘predicted mRNA expression levels’ of TET2, SIRT1 and KDM1A, were found to significantly modify the POE on the three CpGs in both discovery and replication datasets. We further identified plasma protein and health-related phenotypes associated with the methylation level of one of the identified CpGs. INTERPRETATION: the modifiable POE identified here revealed an important yet indirect path through which genetic background and environmental exposures introduce their effect on DNA methylation, motivating future comprehensive evaluation of the role of these modifiers in complex diseases. FUNDING: NSFC (81971270),H2020-MSCA-ITN(721815), Wellcome (204979/Z/16/Z,104036/Z/14/Z), MRC (MC_UU_00007/10, MC_PC_U127592696), CSO (CZD/16/6,CZB/4/276, CZB/4/710), SFC (HR03006), EUROSPAN (LSHG-CT-2006-018947), BBSRC (BBS/E/D/30002276), SYSU, Arthritis Research UK, NHLBI, NIH

Genetic variants in the KIF6 region and coronary event reduction from statin therapy

A single nucleotide polymorphism (SNP) in KIF6, a member of the KIF9 family of kinesins, is associated with differential coronary event reduction from statin therapy in four randomized controlled trials; this SNP (rs20455) is also associated with the risk for coronary heart disease (CHD) in multiple prospective studies. We investigated whether other common SNPs in the KIF6 region were associated with event reduction from statin therapy. Of the 170 SNPs in the KIF6 region investigated in the Cholesterol and Recurrent Events trial (CARE), 28 were associated with differential event reduction from statin therapy (Pinteraction < 0.1 in Caucasians, adjusted for age and sex) and were further investigated in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI22) and West of Scotland Coronary Prevention Study (WOSCOPS). These analyses revealed that two SNPs (rs9462535 and rs9471077), in addition to rs20455, were associated with event reduction from statin therapy (Pinteraction < 0.1 in each of the three studies). The relative risk reduction ranged from 37 to 50% (P < 0.01) in carriers of the minor alleles of these SNPs and from −4 to 13% (P > 0.4) in non-carriers. These three SNPs are in high linkage disequilibrium with one another (r2 > 0.84). Functional studies of these variants may help to understand the role of KIF6 in the pathogenesis of CHD and differential response to statin therapy

Evaluation of night-time aerosols measurements and lunar irradiance models in the frame of the first multi-instrument nocturnal intercomparison campaign

The first multi-instrument nocturnal aerosol optical depth (AOD) intercomparison campaign was held at the high-mountain Izaña Observatory (Tenerife, Spain) in June 2017, involving 2-min synchronous measurements from two different types of lunar photometers (Cimel CE318-T and Moon Precision Filter Radiometer, LunarPFR) and one stellar photometer. The Robotic Lunar Observatory (ROLO) model developed by the U.S. Geological Survey (USGS) was compared with the open-access ROLO Implementation for Moon photometry Observation (RIMO) model. Results showed rather small differences at Izaña over a 2-month time period covering June and July, 2017 (±0.01 in terms of AOD calculated by means of a day/night/day coherence test analysis and ± 2% in terms of lunar irradiance). The RIMO model has been used in this field campaign to retrieve AOD from lunar photometric measurements. No evidence of significant differences with the Moon's phase angle was found when comparing raw signals of the six Cimel photometers involved in this field campaign. The raw signal comparison of the participating lunar photometers (Cimel and LunarPFR) performed at coincident wavelengths showed consistent measurements and AOD differences within their combined uncertainties at 870 nm and 675 nm. Slightly larger AOD deviations were observed at 500 nm, pointing to some unexpected instrumental variations during the measurement period. Lunar irradiances retrieved using RIMO for phase angles varying between 0° and 75° (full Moon to near quarter Moon) were compared to the irradiance variations retrieved by Cimel and LunarPFR photometers. Our results showed a relative agreement within ± 3.5% between the RIMO model and the photometer-based lunar irradiances. The AOD retrieved by performing a Langley-plot calibration each night showed a remarkable agreement (better than 0.01) between the lunar photometers. However, when applying the Lunar-Langley calibration using RIMO, AOD differences of up to 0.015 (0.040 for 500 nm) were found, with differences increasing with the Moon's phase angle. These differences are thought to be partly due to the uncertainties in the irradiance models, as well as instrumental deficiencies yet to be fully understood. High AOD variability in stellar measurements was detected during the campaign. Nevertheless, the observed AOD differences in the Cimel/stellar comparison were within the expected combined uncertainties of these two photometric techniques. Our results indicate that lunar photometry is a more reliable technique, especially for low aerosol loading conditions. The uncertainty analysis performed in this paper shows that the combined standard AOD uncertainty in lunar photometry is dependent on the calibration technique (up to 0.014 for Langley-plot with illumination-based correction, 0.012–0.022 for Lunar-Langley calibration, and up to 0.1 for the Sun-Moon Gain Factor method). This analysis also corroborates that the uncertainty of the lunar irradiance model used for AOD calculation is within the 5–10% expected range. This campaign has allowed us to quantify the important technical difficulties that still exist when routinely monitoring aerosol optical properties at night-time. The small AOD differences observed between the three types of photometers involved in the campaign are only detectable under pristine sky conditions such as those found in this field campaign. Longer campaigns are necessary to understand the observed discrepancies between instruments as well as to provide more conclusive results about the uncertainty involved in the lunar irradiance models.This work has been developed within the framework of the activities of the World Meteorological Organization (WMO) Commission for Instruments and Methods of Observations (CIMO) Izaña Testbed for Aerosols and Water Vapour Remote Sensing Instruments. AERONET sun photometers at Izaña have been calibrated within the AERONET Europe TNA, supported by the European Union’s Horizon 2020 research and innovation program under grant agreement no. 654109 (ACTRIS‒2). CE318-T linearity check has been performed as part of the ESA-funded project “Lunar spectral irradiance measurement and modelling for absolute calibration of EO optical sensors” under ESA contract number: 4000121576/17/NL/AF/hh. LunarPFR has been performing measurements since 2014 in Norway thanks to Svalbard Science Forum funded project, 2014–2016. The authors would like to thank AERONET team for their support and also to NASA’s Navigation and Ancillary Information Facility (NAIF) at the Jet Propulsion Laboratory to help the implementation of the “SPICE” ancillary information system used in this study. We also thank Izaña's ITs for their work to implement the RIMO model in the free-access server. Special thanks should be given to Tom Stone, who has kindly provided us with the USGS/ROLO irradiance values used in the model comparison analysis. This work has also received funding from the European Union’s Horizon 2020 research and innovation programme and from Marie Skłodowska-Curie Individual Fellowships (IF) ACE-GFAT (grant agreement no. 659398). The authors are grateful to Spanish MINECO (CTM2015-66742-R) and Junta de Castilla y León (VA100P17)

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Unlocking preservation bias in the amber insect fossil record through experimental decay.

Fossils entombed in amber are a unique resource for reconstructing forest ecosystems, and resolving relationships of modern taxa. Such fossils are famous for their perfect, life-like appearance. However, preservation quality is vast with many sites showing only cuticular preservation, or no fossils. The taphonomic processes that control this range are largely unknown; as such, we know little about potential bias in this important record. Here we employ actualistic experiments, using, fruit flies and modern tree resin to determine whether resin type, gut microbiota, and dehydration prior to entombment affects decay. We used solid phase microextraction gas chromatography-mass spectrometry (SPME GC-MS) to confirm distinct tree resin chemistry; gut microbiota of flies was modified using antibiotics and categorized though sequencing. Decay was assessed using phase contrast synchrotron tomography. Resin type demonstrates a significant control on decay rate. The composition of the gut microbiota was also influential, with minor changes in composition affecting decay rate. Dehydration prior to entombment, contrary to expectations, enhanced decay. Our analyses show that there is potential significant bias in the amber fossil record, especially between sites with different resin types where ecological completeness and preservational fidelity are likely affected