Can Zipf's law be adapted to normalize microarrays?

BACKGROUND: Normalization is the process of removing non-biological sources of variation between array experiments. Recent investigations of data in gene expression databases for varying organisms and tissues have shown that the majority of expressed genes exhibit a power-law distribution with an exponent close to -1 (i.e. obey Zipf's law). Based on the observation that our single channel and two channel microarray data sets also followed a power-law distribution, we were motivated to develop a normalization method based on this law, and examine how it compares with existing published techniques. A computationally simple and intuitively appealing technique based on this observation is presented. RESULTS: Using pairwise comparisons using MA plots (log ratio vs. log intensity), we compared this novel method to previously published normalization techniques, namely global normalization to the mean, the quantile method, and a variation on the loess normalization method designed specifically for boutique microarrays. Results indicated that, for single channel microarrays, the quantile method was superior with regard to eliminating intensity-dependent effects (banana curves), but Zipf's law normalization does minimize this effect by rotating the data distribution such that the maximal number of data points lie on the zero of the log ratio axis. For two channel boutique microarrays, the Zipf's law normalizations performed as well as, or better than existing techniques. CONCLUSION: Zipf's law normalization is a useful tool where the Quantile method cannot be applied, as is the case with microarrays containing functionally specific gene sets (boutique arrays)

Evaluation of Weight Change During Carboplatin Therapy in Dogs With Appendicular Osteosarcoma.

BackgroundThe prevalence of cancer cachexia in veterinary medicine has not been studied widely, and as of yet, no definitive diagnostic criteria effectively assess this syndrome in veterinary patients.Objectives(1) To determine the patterns of weight change in dogs with appendicular osteosarcoma treated with amputation and single-agent carboplatin during the course of adjuvant chemotherapy; and (2) to determine whether postoperative weight change is a negative prognostic indicator for survival time in dogs with osteosarcoma.AnimalsEighty-eight dogs diagnosed with appendicular osteosarcoma. Animals were accrued from 3 veterinary teaching hospitals.MethodsRetrospective, multi-institutional study. Dogs diagnosed with appendicular osteosarcoma and treated with limb amputation followed by a minimum of 4 doses of single-agent carboplatin were included. Data analyzed in each patient included signalment, tumor site, preoperative serum alkaline phosphatase activity (ALP), and body weight (kg) at each carboplatin treatment.ResultsA slight increase in weight occurred over the course of chemotherapy, but this change was not statistically significant. Weight change did not have a significant effect on survival. Institution, patient sex, and serum ALP activity did not have a significant effect on survival.Conclusions and clinical importanceWeight change was not a prognostic factor in these dogs, and weight loss alone may not be a suitable method of determining cancer cachexia in dogs with appendicular osteosarcoma

Diffusion of noble gases in subduction zone hydrous minerals

Subduction of atmospheric noble gases has been considered to play an important role in altering the primordial isotopes of Earth’s mantle over geological time. Analysis of natural samples and experiments indicate that large quantities of noble gases can be dissolved in volatile-bearing hydrous minerals in the subduction slabs. To quantitatively investigate the recycling efficiency of noble gases and relevant consequences on the mantle noble gas isotopic evolution, the diffusivities of noble gases in these minerals are needed. In this study, diffusion of He, Ne, Ar, Kr and Xe in lizardite, antigorite and tremolite have been calculated by first-principles methods based on density functional theory. Our results disclose that diffusion is slower with increasing radius of the noble gas atom (DHe > DNe > DAr > DKr > DXe) as expected. The common ring-structures in hydrous silicate minerals provide incorporation sites for the noble gas atoms and control their mobility. The diffusion activation energies are 84.9, 157.3, 287.5, 347.4, 414.9 kJ/mol from He to Xe in lizardite, and despite the very similar lattice structure between lizardite and antigorite, the activation energies are found to be significantly higher in antigorite, which are 120.6, 267.3, 449.6, 497.9 and 550.0 kJ/mol, respectively. In tremolite, the energy barriers are 93.6, 158.2, 266.3, 322.2 and 385.0 kJ/mol, which are also found to be in very good agreement with available experimental values and similar to those in lizardite. We also calculated diffusion activation energies at higher pressures (1 GPa for liazardite, 3 GPa for antigorite and tremolite) to better understand how much noble gases can be preserved against diffusive loss during subduction. Our result show that the oceanic crust and the lithospheric mantle of the subduction slab play different roles in delivering noble gases into the mantle. We find that all Ar, Kr, Xe and possibly part of the Ne can be entrained by the serpentine-dominated lithospheric mantle into the deep mantle due to the high diffusive energy barriers in antigorite. In contrast, noble gases in the amphibole-enriched oceanic crust would be characterized by fractionated noble gas signature, with the concentrations of retained noble gases in the crust following their respective ionic radius (Ne < Ar < Kr < Xe)

A systematic review and meta-analyses of pregnancy and fetal outcomes in women with multiple sclerosis: a contribution from the IMI2 ConcePTION project.

Neurologists managing women with Multiple Sclerosis (MS) need information about the safety of disease modifying drugs (DMDs) during pregnancy. However, this knowledge is limited. The present study aims to summarize previous studies by performing a systematic review and meta-analyses. The terms "multiple sclerosis" combined with DMDs of interest and a broad profile for pregnancy terms were used to search Embase and Medline databases to identify relevant studies published from January 2000 to July 2019.1260 studies were identified and ten studies met our inclusion criteria. Pooled risk ratios (RR) of pregnancy and birth outcomes in pregnancies exposed to DMDs compared to those not exposed were calculated using a random effects model. For spontaneous abortion RR = 1.14, 95% CI 0.99-1.32, for preterm births RR = 0.93, 95% CI 0.72-1.21 and for major congenital malformations RR = 0.86, 95% CI 0.47-1.56. The most common major congenital malformations reported in MS patients exposed to MS drugs were atrial septal defect (ASD) (N = 4), polydactyly (N = 4) and club foot (N = 3), which are among the most prevalent birth defects observed in the general population. In conclusion, interferons, glatiramer acetate or natalizumab, do not appear to increase the risk for spontaneous abortions, pre-term birth or major congenital malformations. There were very few patients included that were exposed to fingolimod, azathioprine and rituximab; therefore, these results cannot be generalized across drugs. Future studies including internal comparators are needed to enable treating physicians and their patients to decide on the best treatment options

Assessing the Health of Richibucto Estuary with the Latent Health Factor Index

The ability to quantitatively assess the health of an ecosystem is often of great interest to those tasked with monitoring and conserving ecosystems. For decades, research in this area has relied upon multimetric indices of various forms. Although indices may be numbers, many are constructed based on procedures that are highly qualitative in nature, thus limiting the quantitative rigour of the practical interpretations made from these indices. The statistical modelling approach to construct the latent health factor index (LHFI) was recently developed to express ecological data, collected to construct conventional multimetric health indices, in a rigorous quantitative model that integrates qualitative features of ecosystem health and preconceived ecological relationships among such features. This hierarchical modelling approach allows (a) statistical inference of health for observed sites and (b) prediction of health for unobserved sites, all accompanied by formal uncertainty statements. Thus far, the LHFI approach has been demonstrated and validated on freshwater ecosystems. The goal of this paper is to adapt this approach to modelling estuarine ecosystem health, particularly that of the previously unassessed system in Richibucto in New Brunswick, Canada. Field data correspond to biotic health metrics that constitute the AZTI marine biotic index (AMBI) and abiotic predictors preconceived to influence biota. We also briefly discuss related LHFI research involving additional metrics that form the infaunal trophic index (ITI). Our paper is the first to construct a scientifically sensible model to rigorously identify the collective explanatory capacity of salinity, distance downstream, channel depth, and silt-clay content --- all regarded a priori as qualitatively important abiotic drivers --- towards site health in the Richibucto ecosystem.Comment: On 2013-05-01, a revised version of this article was accepted for publication in PLoS One. See Journal reference and DOI belo

Structure evolution of nanodiamond aggregates: a SANS and USANS study

Ultra-small-angle neutron scattering (USANS) and small-angle neutron scattering (SANS) measurements, covering length scales from micrometres to nanometres, were made to investigate the structure of nanodiamonds (NDs) and their suspensions. These nanodiamonds were produced by two different techniques, namely by the detonation method and by the laser ablation of a carbon-hydrocarbon mixture. The (U)SANS results indicated the presence of structures four orders of magnitude larger than the dimensions of a single ND particle, consisting of aggregations of ND particles. This aggregation of the ND particles was studied by employing the contrast variation technique. Two different solvents, namely H2O and dimethyl sulfoxide (and their deuterated counterparts), were used to understand the role of hydrogen in the shape and size of the aggregates. The analysis of experimental data from SANS measurements also reveals the ND particles to have an ellipsoidal structure. Using a defined shape model and the SANS contrast variation technique, it was possible to characterize the non-diamond outer shell of the particles and determine the outer layer thickness. This clarification of the structure of the NDs will allow better preparation of suspensions/samples for various applications. Understanding the structure of NDs at multiple length scales also provides crucial knowledge of particle-particle interaction and its effect on the aggregation structures

A suffix tree or not a suffix tree?

In this paper we study the structure of suffix trees. Given an unlabeled tree τ on n nodes and suffix links of its internal nodes, we ask the question ”Is τ a suffix tree?”, i.e., is there a string S whose suffix tree has the same topological structure as τ? We place no restrictions on S, in particular we do not require that S ends with a unique symbol. This corresponds to considering the more general definition of implicit or extended suffix trees. Such general suffix trees have many applications and are for example needed to allow efficient updates when suffix trees are built online. Deciding if τ is a suffix tree is not an easy task, because, with no restrictions on the final symbol, we cannot guess the length of a string that realizes τ from the number of leaves. And without an upper bound on the length of such a string, it is not even clear how to solve the problem by an exhaustive search. In this paper, we prove that τ is a suffix tree if and only if it is realized by a string S of length n−1, and we give a linear-time algorithm for inferring S when the first letter on each edge is known. This generalizes the work of I et al. [Discrete Appl. Math. 163, 2014]

Holographic flows to IR Lifshitz spacetimes

Recently we studied `vanishing' horizon limits of `boosted' black D3-brane geometry \cite{hsnr}. The type IIB solutions obtained by taking these special double limits were found to describe nonrelativistic Lifshitz spacetimes at zero temperature. In the present work we study these limits for TsT black-hole solutions which include $B$-field. The new Galilean solutions describe a holographic RG flow from Schr\"odinger ($a=2$) spacetime in UV to a Lifshitz universe ($a=3$) in the IR.Comment: 10 pages; v2: A bad typo in eq.8 corrected; v3: Discussion and reference on Kaigorodov spaces included, correction in sec-3, to be published in JHE

Three geographically separate domestications of Asian rice

Domesticated rice (Oryza sativa L.) accompanied the dawn of Asian civilization(1) and has become one of world's staple crops. From archaeological and genetic evidence various contradictory scenarios for the origin of different varieties of cultivated rice have been proposed, the most recent based on a single domestication(2,3). By examining the footprints of selection in the genomes of different cultivated rice types, we show that there were three independent domestications in different parts of Asia. We identify wild populations in southern China and the Yangtze valley as the source of the japonica gene pool, and populations in Indochina and the Brahmaputra valley as the source of the indica gene pool. We reveal a hitherto unrecognized origin for the aus variety in central India or Bangladesh. We also conclude that aromatic rice is a result of a hybridization between japonica and aus, and that the tropical and temperate versions of japonica are later adaptations of one crop. Our conclusions are in accord with archaeological evidence that suggests widespread origins of rice cultivation(1,4). We therefore anticipate that our results will stimulate a more productive collaboration between genetic and archaeological studies of rice domestication, and guide utilization of genetic resources in breeding programmes aimed at crop improvement.European Research Council [339941]info:eu-repo/semantics/publishedVersio