Family Size Evolution in Drosophila Chemosensory Gene Families: A Comparative Analysis with a Critical Appraisal of Methods

Gene turnover rates and the evolution of gene family sizes are important aspects of genome evolution. Here, we use curated sequence data of the major chemosensory gene families from Drosophila-the gustatory receptor, odorant receptor, ionotropic receptor, and odorant-binding protein families-to conduct a comparative analysis among families, exploring different methods to estimate gene birth and death rates, including an ad hoc simulation study. Remarkably, we found that the state-of-the-art methods may produce very different rate estimates, which may lead to disparate conclusions regarding the evolution of chemosensory gene family sizes in Drosophila. Among biological factors, we found that a peculiarity of D. sechellia's gene turnover rates was a major source of bias in global estimates, whereas gene conversion had negligible effects for the families analyzed herein. Turnover rates vary considerably among families, subfamilies, and ortholog groups although all analyzed families were quite dynamic in terms of gene turnover. Computer simulations showed that the methods that use ortholog group information appear to be the most accurate for the Drosophila chemosensory families. Most importantly, these results reveal the potential of rate heterogeneity among lineages to severely bias some turnover rate estimation methods and the need of further evaluating the performance of these methods in a more diverse sampling of gene families and phylogenetic contexts. Using branch-specific codon substitution models, we find further evidence of positive selection in recently duplicated genes, which attests to a nonneutral aspect of the gene birth-and-death process.

Comment on reversal of hypogonadotropic hypogonadism in a Chinese cohort.

The reversal of congenital hypogonadotropic hypogonadism (CHH) is a relatively recent phenomenon that has gained increasing attention over the past 10 years. Yet to date, only one prospective study has been conducted estimating that 10% (95% confidence interval [CI]: 2%-18%) of cases undergo reversal. [1] Other retrospective studies have reported rates in the range of 5%-8% [2],[3] and a recent study showed 44/308 (14%, 95% CI: 11%-19%) CHH patients underwent reversal. [4] Moreover, a time-to-event analysis in this large cohort revealed a lifetime reversal incidence of 22%. The article by Mao and colleagues presented in this issue is a meaningful contribution to our understanding of reversal as it examines the largest retrospective cohort to date. [5] Interestingly, they report the rate of reversal as 5% (95% CI: 3%-8%) in this Chinese cohort. It is difficult to reconcile the discrepancies in rates of reversibility and direct comparisons are hampered by the variable definitions employed. Using a novel definition for reversal (i.e, either endogenous testosterone (T) >270 ng dl−1 , serum T gradually increasing above 150 ng dl−1 with increased testicular volume, or normal spontaneous sperm production/normal erectile function/ejaculation), Mao and colleagues posit that testicular size and triptorelin-stimulated LH levels are reliable predictive factors for reversal. However, these cannot be considered as hard and fast rules for predicting reversal as the groups intersect - akin to the overlap observed between CHH patients and those with delayed puberty. Indeed, the fact that approximately half (44%, 95% CI: 25%-66%) of the reversal patients in the study by Mao et al.[5] were diagnosed between 17 and 19 years of age, underscores the challenge in differentiating CHH from extreme normal variants of puberty. This study further lends credence the recently reported observations that reversals may relapse. [4],[6] The notion that reversal may not be lasting highlights the vulnerability of the reproductive axis among CHH patients. While the mechanism(s) for relapse are unclear, it seems plausible that environmental, metabolic or psychiatric stressors could contribute. The factors that Mao and colleagues identify as significantly different in cases of reversal, were not informative for identifying those cases that relapsed back to a hypogonadal state. Notably, reversal has been reported in probands harboring mutations in genes underlying CHH. [1],[3],[4],[6] Unfortunately, comprehensive genetic screening on the Chinese cohort is not available. The reversal phenomenon is fascinating for its glimpse into the plasticity of the neuroendocrine control of reproduction. Future directions will almost certainly include investigation of specific genetic signatures and novel biomarkers for predicting reversal (and relapse). Yet CHH is a rare condition and to fully elucidate the biology of reversible CHH, it will be important to harmonize definitions of what constitutes a reversal, carefully phenotype patients and chart the natural history of their CHH. In this way, this unique human disease model may offer further insights into the control of human reproduction and provide opportunities to translate discoveries into enhanced approaches to improve the care and quality of life for these patients.

Effect of the MC1R gene on sexual dimorphism in melanin-based colorations.

Variants of the melanocortin-1 receptor (MC1R) gene result in abrupt, naturally selected colour morphs. These genetic variants may differentially affect sexual dimorphism if one morph is naturally selected in the two sexes but another morph is naturally or sexually selected only in one of the two sexes (e.g. to confer camouflage in reproductive females or confer mating advantage in males). Therefore, the balance between natural and sexual selections can differ between MC1R variants, as suggest studies showing interspecific correlations between sexual dimorphism and the rate of nonsynonymous vs. synonymous amino acid substitutions at the MC1R. Surprisingly, how MC1R is related to within-species sexual dimorphism, and thereby to sex-specific selection, has not yet been investigated. We tackled this issue in the barn owl (Tyto alba), a species showing pronounced variation in the degree of reddish pheomelanin-based coloration and in the number and size of black feather spots. We found that a valine (V)-to-isoleucine (I) substitution at position 126 explains up to 30% of the variation in the three melanin-based colour traits and in feather melanin content. Interestingly, MC1R genotypes also differed in the degree of sexual colour dimorphism, with individuals homozygous for the II MC1R variant being 2 times redder and 2.5 times less sexually dimorphic than homozygous individuals for the VV MC1R variant. These findings support that MC1R interacts with the expression of sexual dimorphism and suggest that a gene with major phenotypic effects and weakly influenced by variation in body condition can participate in sex-specific selection processes.

Particle Size Analysis of Pharmaceutical Powders by Laser Diffraction

Raaka-aineen hiukkaskoko on lääkekehityksessä keskeinen materiaaliparametri. Lääkeaineen partikkelikoko vaikuttaa moneen lääketuotteen tärkeään ominaisuuteen, esimerkiksi lääkkeen biologiseen hyväksikäytettävyyteen. Tässä diplomityössä keskityttiin jauhemaisten lääkeaineiden hiukkaskoon määrittämiseen laserdiffraktiomenetelmällä. Menetelmä perustuu siihen, että partikkeleista sironneen valon intensiteetin sirontakulmajakauma on riippuvainen partikkelien kokojakaumasta. Työn kirjallisuusosassa esiteltiin laserdiffraktiomenetelmän teoriaa. PIDS (Polarization Intensity Differential Scattering) tekniikka, jota voidaan käyttää laserdiffraktion yhteydessä, on myös kuvattu kirjallisuusosassa. Muihin menetelmiin perustuvista analyysimenetelmistä tutustuttiin mikroskopiaan sekä aerodynaamisen lentoajan määrittämiseen perustuvaan menetelmään. Kirjallisuusosassa esiteltiin myös partikkelikoon yleisimpiä esitystapoja. Työn kokeellisen osan tarkoituksena oli kehittää ja validoida laserdiffraktioon perustuva partikkelikoon määritysmenetelmä tietylle lääkeaineelle. Menetelmäkehitys tehtiin käyttäen Beckman Coulter LS 13 320 laserdiffraktoria. Laite mahdollistaa PIDS-tekniikan käytön laserdiffraktiotekniikan ohella. Menetelmäkehitys aloitettiin arvioimalla, että kyseinen lääkeaine soveltuu parhaiten määritettäväksi nesteeseen dispergoituna. Liukoisuuden perusteella väliaineeksi valittiin tällä lääkeaineella kyllästetty vesiliuos. Dispergointiaineen sekä ultraäänihauteen käyttö havaittiin tarpeelliseksi dispergoidessa kyseistä lääkeainetta kylläiseen vesiliuokseen. Lopuksi sekoitusnopeus näytteensyöttöyksikössä säädettiin sopivaksi. Validointivaiheessa kehitetyn menetelmän todettiin soveltuvan hyvin kyseiselle lääkeaineelle ja tulosten todettiin olevan oikeellisia sekä toistettavia. Menetelmä ei myöskään ollut herkkä pienille häiriöille.

Differential Dimerization of Variants Linked to Enhanced S-Cone Sensitivity Syndrome (ESCS) Located in the NR2E3 Ligand-Binding Domain.

NR2E3 encodes the photoreceptor-specific nuclear hormone receptor that acts as a repressor of cone-specific gene expression in rod photoreceptors, and as an activator of several rod-specific genes. Recessive variants located in the ligand-binding domain (LBD) of NR2E3 cause enhanced short wavelength sensitive- (S-) cone syndrome (ESCS), a retinal degeneration characterized by an excess of S-cones and non-functional rods. We analyzed the dimerization properties of NR2E3 and the effect of disease-causing LBD missense variants by bioluminescence resonance energy transfer (BRET(2) ) protein interaction assays. Homodimerization was not affected in presence of p.A256V, p.R039G, p.R311Q, and p.R334G variants, but abolished in presence of p.L263P, p.L336P, p.L353V, p.R385P, and p.M407K variants. Homology modeling predicted structural changes induced by NR2E3 LBD variants. NR2E3 LBD variants did not affect interaction with CRX, but with NRL and rev-erbα/NR1D1. CRX and NRL heterodimerized more efficiently together, than did either with NR2E3. NR2E3 did not heterodimerize with TLX/NR2E1 and RXRα/NR2C1. The identification of a new compound heterozygous patient with detectable rod function, who expressed solely the p.A256V variant protein, suggests a correlation between LBD variants able to form functional NR2E3 dimers and atypical mild forms of ESCS with residual rod function.

Population Size and Civil Conflict Risk: Is There A Causal Link?

[spa] La estimación del impacto del tamaño de la populación sobre la probabilidad de conflicto civil se complica por el sesgo de endogeneidad y las variables omitidas. Este artículo trata el problema de causalidad utilizando métodos de variables instrumentales en un panel de 37 países del África Sub-sahariana en el período 1981-2004. Encontramos que un aumento de la población en un 1% aumenta la probabilidad de conflicto civil por un 5.2%.

Pricing of Product Variants

Työn tutkimusongelma oli selventää, tutkia ja analysoida dynaamisen hinnoittelun tekijät ja mahdollisuudet tuotevarianttien hinnoittelussa. Tutkimusongelman selvittämiseksi työlle asetettiin 8 tavoitetta - Saada selville miksi tuotevarianttien hinnoittelu on ongelmallista - Esittää kuinka tuotevarianttien hinnat teoreettisesti tulisi asettaa - Tunnistaa tuotevarianttien hinnoittelun ulottuvuudet ja selvittää dynaamisen hinnoittelun edut staattiseen hinnoitteluun verrattuna - Esitellä analyysikehikko hinnoittelun tilan analysointiin - Tunnistaa dynaamisen hinnoittelun tuotevarianteille suomat mahdollisuudet - Etsiä soveltuvat hinnoittelumenetelmät tuotevarianttien dynaamiseen hinnoitteluun - Analysoida tuotevariantteja myyvän yrityksen hinnoittelu - Tunnistaa ja arvioida dynaamisen hinnoittelun edut yritykselle Diplomityössä käytettiin useita tutkimusmenetelmiä. Perustieto haettiin kirjallisuustutkimuksella ja sitä täydennettiin haastatteluilla. Tutkimusprosessi alkoi tutkimuksella tuotevarianttien hinnoittelusta ja kirjallisuuden perusteella luotiin näkökulma ja yleiset kehityssuunnat tarkempaa tutkimusta varten. Kaksi tärkeintä tuotevariaatioiden hinnoitteludimensiota tunnistettiin ja niiden analysointia varten luotiin nelikenttämalli. Kirjallisuustutkimuksen ja tarkemman kohdeyrityksen tarkastelun perusteella dynaaminen tuotelinjahinnoittelu on tuotevarianttien dynaamisen hinnoittelun tavoitetila. Nelikenttämallia käytettiin kohdeyrityksen hinnoittelun tilan arviointiin ja dynaamisen hinnoittelun suurimmat hyödyt löydettiin. Tutkimuksen päätulokset ovat - Hinnoittelun dynaamisuutta tulee tuotevarianteilla tutkia hinnoittelun älykkyyden ja kehittyneisyyden kanssa - Tuotevariaatioiden hinnoittelun tavoitetila on dynaaminen tuotelinjahinnoittelu - Hinnoittelun kehittäminen staattisesta dynaamiseen tuo huomattavia etuja - Tärkein etu on parempi hintojen hallinta ja mahdollisuus johtaa hintoja tehokkaasti. Tämän vuoksi hinnoitteluanalyysissa havaittiin selvästi lisääntyneitä voittoja - Hinnoittelun älykkyyden nostaminen hyödyttää yritystä ja saa aikaan lisäyksen voitoissa

Cooperative games with size-truncated information

[Eng] We study the marginal worth vectors and their convex hull, the socalled Weber set, from the original coalitional game and the transformed one, which is called the Weber set of level k. We prove that the core of the original game is included in each of the Weber set of level k, for any k, and that the Weber sets of consecutive levels form a chain if and only if the original game is 0-monotone. Even if the game is not 0-monotone, the intersection of the Weber sets for consecutive levels is always not empty, what is not the case for non-consecutive ones. Spanish education system.

Cooperative games with size-truncated information

[Eng] We study the marginal worth vectors and their convex hull, the socalled Weber set, from the original coalitional game and the transformed one, which is called the Weber set of level k. We prove that the core of the original game is included in each of the Weber set of level k, for any k, and that the Weber sets of consecutive levels form a chain if and only if the original game is 0-monotone. Even if the game is not 0-monotone, the intersection of the Weber sets for consecutive levels is always not empty, what is not the case for non-consecutive ones. Spanish education system.

Multisensory stimulation can induce an illusion of larger belly size in immersive virtual reality

Body change illusions have been of great interest in recent years for the understanding of how the brain represents the body. Appropriate multisensory stimulation can induce an illusion of ownership over a rubber or virtual arm, simple types of out-of-the-body experiences, and even ownership with respect to an alternate whole body. Here we use immersive virtual reality to investigate whether the illusion of a dramatic increase in belly size can be induced in males through (a) first person perspective position (b) synchronous visual-motor correlation between real and virtual arm movements, and (c) self-induced synchronous visual-tactile stimulation in the stomach area.

Segmentation model for small and medium size business sector: Case Oy Compaq Computer Ab

Markkinasegmentointi nousi esiin ensi kerran jo 50-luvulla ja se on ollut siitä lähtien yksi markkinoinnin peruskäsitteistä. Suuri osa segmentointia käsittelevästä tutkimuksesta on kuitenkin keskittynyt kuluttajamarkkinoiden segmentointiin yritys- ja teollisuusmarkkinoiden segmentoinnin jäädessä vähemmälle huomiolle. Tämän tutkimuksen tavoitteena on luoda segmentointimalli teollismarkkinoille tietotekniikan tuotteiden ja palveluiden tarjoajan näkökulmasta. Tarkoituksena on selvittää mahdollistavatko case-yrityksen nykyiset asiakastietokannat tehokkaan segmentoinnin, selvittää sopivat segmentointikriteerit sekä arvioida tulisiko tietokantoja kehittää ja kuinka niitä tulisi kehittää tehokkaamman segmentoinnin mahdollistamiseksi. Tarkoitus on luoda yksi malli eri liiketoimintayksiköille yhteisesti. Näin ollen eri yksiköiden tavoitteet tulee ottaa huomioon eturistiriitojen välttämiseksi. Tutkimusmetodologia on tapaustutkimus. Lähteinä tutkimuksessa käytettiin sekundäärisiä lähteitä sekä primäärejä lähteitä kuten case-yrityksen omia tietokantoja sekä haastatteluita. Tutkimuksen lähtökohtana oli tutkimusongelma: Voiko tietokantoihin perustuvaa segmentointia käyttää kannattavaan asiakassuhdejohtamiseen PK-yritys sektorilla? Tavoitteena on luoda segmentointimalli, joka hyödyntää tietokannoissa olevia tietoja tinkimättä kuitenkaan tehokkaan ja kannattavan segmentoinnin ehdoista. Teoriaosa tutkii segmentointia yleensä painottuen kuitenkin teolliseen markkinasegmentointiin. Tarkoituksena on luoda selkeä kuva erilaisista lähestymistavoista aiheeseen ja syventää näkemystä tärkeimpien teorioiden osalta. Tietokantojen analysointi osoitti selviä puutteita asiakastiedoissa. Peruskontaktitiedot löytyvät mutta segmentointia varten tietoa on erittäin rajoitetusti. Tietojen saantia jälleenmyyjiltä ja tukkureilta tulisi parantaa loppuasiakastietojen saannin takia. Segmentointi nykyisten tietojen varassa perustuu lähinnä sekundäärisiin tietoihin kuten toimialaan ja yrityskokoon. Näitäkään tietoja ei ole saatavilla kaikkien tietokannassa olevien yritysten kohdalta.

Comparing N = 1 effect size indices in presence of autocorrelation

Generalization from single-case designs can be achieved by means of replicating individual studies across different experimental units and settings. When replications are available, their findings can be summarized using effect size measurements and integrated through meta-analyses. Several procedures are available for quantifying the magnitude of treatment"s effect in N = 1 designs and some of them are studied in the current paper. Monte Carlo simulations were employed to generate different data patterns (trend, level change, slope change). The experimental conditions simulated were defined by the degrees of serial dependence and phases" length. Out of all the effect size indices studied, the Percent of nonoverlapping data and standardized mean difference proved to be less affected by autocorrelation and perform better for shorter data series. The regression-based procedures proposed specifically for single-case designs did not differentiate between data patterns as well as simpler indices.

Particle shape and orientation in laser diffraction and static image analysis size distribution analysis of micrometer sized rectangular particles

Laser diffraction (LD) and static image analysis (SIA) of rectangular particles [United States Pharmacopeia, USP30-NF25, General Chapter <776>, Optical Miroscopy.] have been systematically studied. To rule out sample dispersion and particle orientation as the root cause of differences in size distribution profiles, we immobilize powder samples on a glass plate by means of a dry disperser. For a defined region of the glass plate, we measure the diffraction pattern as induced by the dispersed particles, and the 2D dimensions of the individual particles using LD and optical microscopy, respectively. We demonstrate a correlation between LD and SIA, with the scattering intensity of the individual particles as the dominant factor. In theory, the scattering intensity is related to the square of the projected area of both spherical and rectangular particles. In traditional LD the size distribution profile is dominated by the maximum projected area of the particles (A). The diffraction diameters of a rectangular particle with length L and breadth B as measured by the LD instrument approximately correspond to spheres of diameter ØL and ØB respectively. Differences in the scattering intensity between spherical and rectangular particles suggest that the contribution made to the overall LD volume probability distribution by each rectangular particle is proportional to A2/L and A2/B. Accordingly, for rectangular particles the scattering intensity weighted diffraction diameter (SIWDD) explains an overestimation of their shortest dimension and an underestimation of their longest dimension. This study analyzes various samples of particles whose length ranges from approximately 10 to 1000 μm. The correlation we demonstrate between LD and SIA can be used to improve validation of LD methods based on SIA data for a variety of pharmaceutical powders all with a different rectangular particle size and shape.

Small-size pines suitability for glueboards

The aim of the research was to evaluate the suitability of small-size pine as a raw material for glueboard. A further aim was to investigate claims that dead knots and the twisting of the heartwood cause, quality problems in the but of the small-size pine. The theoretical framework of the study details the whole manufacturing process from raw material to the finished article; the description of the qualities of raw material, the sawing and drying processes as well as the making of the glueboard. The solve the research problem the following figures were calculated: amount of small-size pines, the yield and quality of sawn timber which can be used for making glueboard as well as the variables which affect the various stages of the process. The results show that about half of the timber from the thinning process was suitable material for sawing. The most common problem with the unsuitable timber was form defects of the stem. The average usage ratio of sawing was 2,31 k-m3/m3. 87,97 % of the sawn timber could be used for the production of glueboard. The unsuitability of sawn timber for making glueboard was mainly caused by breakage and the twisting of the heartwood. Dead knots were small and did not effect the quality of the but of the small-size pine. It can therefore be concluded that small-size pine is suitable raw material for glueboard.