Comparative physical genome mapping of malaria vectors Anopheles sinensis and Anopheles gambiae.

BACKGROUND: Anopheles sinensis is a dominant natural vector of Plasmodium vivax in China, Taiwan, Japan, and Korea. Recent genome sequencing of An. sinensis provides important insights into the genomic basis of vectorial capacity. However, the lack of a physical genome map with chromosome assignment and orientation of sequencing scaffolds hinders comparative analyses with other genomes to infer evolutionary changes relevant to the vector capacity. RESULTS: Here, a physical genome map for An. sinensis was constructed by assigning 52 scaffolds onto the chromosomes using fluorescence in situ hybridization (FISH). This chromosome-based genome assembly composes approximately 36% of the total An. sinensis genome. Comparisons of 3955 orthologous genes between An. sinensis and Anopheles gambiae identified 361 conserved synteny blocks and 267 inversions fixed between these two lineages. The rate of gene order reshuffling on the X chromosome is approximately 3.2 times higher than that on the autosomes. CONCLUSIONS: The physical map will facilitate detailed genomic analysis of An. sinensis and contribute to understanding of the patterns and mechanisms of large-scale genome rearrangements in anopheline mosquitoes.

Graph-Based Imputation Methods and Their Applications to Single Donors and Families.

The outcome of Hematopoietic Stem Cell (HSCT) and organ transplant is strongly affected by the matching of the HLA alleles of the donor and the recipient. However, donors and sometimes recipients are often typed at low resolution, with some alleles either missing or ambiguous. Thus, imputation methods are required to detect the most probably high-resolution HLA haplotypes consistent with a typing. Such imputation algorithms require predefined haplotype frequencies. As such, the phasing of the typing is required for both imputation and frequency generation.We have developed a new approach to HLA haplotype and genotype imputation, where first all candidate phases of a typing are explicated, and then the ambiguity within each phase is solved. This ambiguity is solved through a graph structure of all partial haplotypes and the haplotypes consistent with them.This phasing approach was used to produce an imputation algorithm (GRIMM-Graph Imputation and Matching). GRIMM was then combined with the possibility of combining information from multiple races to produce MR-GRIMM (Multi-Race GRIMM). When family information is available, the phasing of each family member can be restricted by the others. We propose GRAMM (GRaph-bAsed faMily iMputation) to phase alleles in family pedigree HLA typing data and in mother-cord blood unit pairs. Finally, we combined MR-GRIMM with an expectation-maximization (EM) algorithm to estimate haplotype frequencies sharing information between races to produce MR-GRIMME (MR-GRIMM EM).We have shown that these algorithms naturally combine information between races and family members. The accuracy of each of these algorithms is significantly better than its current parallel methods. MR-GRIMM leads to high accuracy in matching predictions. GRAMM better imputes family members than either MR-GRIMM or any existing algorithm and has practically no phasing errors. MR-GRIMME obtains a higher likelihood than existing algorithms.MR-GRIMM, MR-GRIMME, and GRAMM are available as servers or through stand-alone versions in GITHUB and PyPi, as detailed in the appropriate sections.

GRAMM: A new method for analysis of HLA in families.

Recently, haplo-identical transplantation with multiple HLA mismatches has become a viable option for stem cell transplants. Haplotype sharing detection requires the imputation of donor and recipient. We show that even in high-resolution typing when all alleles are known, there is a 15% error rate in haplotype phasing, and even more in low-resolution typings. Similarly, in related donors, the parents' haplotypes should be imputed to determine what haplotype each child inherited. We propose graph-based family imputation (GRAMM) to phase alleles in family pedigree HLA typing data, and in mother-cord blood unit pairs. We show that GRAMM has practically no phasing errors when pedigree data are available. We apply GRAMM to simulations with different typing resolutions as well as paired cord-mother typings, and show very high phasing accuracy, and improved allele imputation accuracy. We use GRAMM to detect recombination events and show that the rate of falsely detected recombination events (false-positive rate) in simulations is very low. We then apply recombination detection to typed families to estimate the recombination rate in Israeli and Australian population datasets. The estimated recombination rate has an upper bound of 10%-20% per family (1%-4% per individual).

Evaluation of Relative Sensitivity Factors for Elemental Analysis of Aluminum and Magnesium Using Glow Discharge Mass Spectrometry with a Fast-Flow Grimm-type Ion Source.

Relative sensitivity factors on glow discharge mass spectrometry were evaluated for unalloyed and alloyed metals of aluminum and magnesium using a glow discharge mass spectrometer operated with fast flow Grimm-type source. All the elements measured could be classified into two groups, i.e. a group of elements could be determined with repeatability equal to or less than 15% relative standard deviation, while another group could be determined with RSDs of greater than 15%. The latter is mainly due to the instability of discharge condition and elemental segregation onto certified reference materials.

THE ULTIMATE INSIGHT: THE PATIENT'S AWARENESS OF MOTHER'S FILICIDAL WISHES.

The author reviews myths and traditional tales in which the protagonist is a filicidal mother. In a displaced form, filicidal mothers appear as the ubiquitous witches of folklore. This imago is universal in fantasies and pavor nocturnus in children, regardless of the quality of care of the real maternal figures. To this phenomenon-the result of defensive externalization of primitive fears-a fundamental dimension is added when this dread seems corroborated by the mother's manifestly murderous wishes and behavior. Clinical examples of this pathogenic circumstance are provided, with comments on the development of dissociation versus repression, depending on the severity of early traumas. The evolution of symptoms and character disorder in adulthood is discussed, as well as interpretive and technical dilemmas posed by these patients.

Hollow Cathode Discharges: Analytical Applications.

The low pressure glow discharges considered in this paper are the hollow cathode (Paschen), and the flat cathode (Grimm). Both discharges have similar voltage-current characteristics which are responsible for their radiation stability. The analytical sample is supplied to the discharge through a sputtering mechanism which provides a stable and non-selective source of particles. Some of the fundamental properties of the glow discharge and sputtering phenomena will be discussed, including the relation between the geometry of the discharge, and the nature and pressure of sustaining gas, and current, on the emission characteristics of the discharges. These will he followed by a description of the conventional instrumentation developed for analytical purposes using the hollow cathode and flat discharge. A description of the hollow cathode developed at the National Bureau of Standards (NBS) will follow. The techniques used for the introduction of various conductive and nonconductive materials into the discharge will be discussed. The use of these discharges will be illustrated with examples taken from the literature and from the measurements performed at NBS. The paper will conclude with a discussion of possible future developments of low pressure glow discharges. A collection of references to works on low pressure glow discharges, containing 690 entries, concludes this work.