Large-Scale Calculations of the Double-Beta Decay of 76Ge, 130Te, 136Xe, and 150Nd in the Deformed Self-Consistent Skyrme Quasiparticle Random-Phase Approximation

We use the axially-deformed Skyrme Quasiparticle Random-Phase Approximation (QRPA) together with the SkM* energy-density functional, both as originally presented and with the time-odd part adjusted to reproduce the Gamow-Teller resonance energy in 208Pb, to calculate the matrix elements governing the neutrinoless double-beta decay of 76Ge, 130Te, 136Xe, and 150Nd. Our matrix elements in 130Te and 136Xe are significantly smaller than those of previous QRPA calculations, primarily because of the difference in pairing or deformation between the initial and final nuclei. In 76Ge and 150Nd our results are similar to those of less computationally intensive QRPA calculations. We suspect the 76Ge result, however, because we are forced to use a spherical ground-state, even though the HFB indicates a deformed minimum.Comment: 9 pages, 4 figure

Rate and cost of adaptation in the Drosophila Genome

Recent studies have consistently inferred high rates of adaptive molecular evolution between Drosophila species. At the same time, the Drosophila genome evolves under different rates of recombination, which results in partial genetic linkage between alleles at neighboring genomic loci. Here we analyze how linkage correlations affect adaptive evolution. We develop a new inference method for adaptation that takes into account the effect on an allele at a focal site caused by neighboring deleterious alleles (background selection) and by neighboring adaptive substitutions (hitchhiking). Using complete genome sequence data and fine-scale recombination maps, we infer a highly heterogeneous scenario of adaptation in Drosophila. In high-recombining regions, about 50% of all amino acid substitutions are adaptive, together with about 20% of all substitutions in proximal intergenic regions. In low-recombining regions, only a small fraction of the amino acid substitutions are adaptive, while hitchhiking accounts for the majority of these changes. Hitchhiking of deleterious alleles generates a substantial collateral cost of adaptation, leading to a fitness decline of about 30/2N per gene and per million years in the lowest-recombining regions. Our results show how recombination shapes rate and efficacy of the adaptive dynamics in eukaryotic genomes

The asexual genome of Drosophila

The rate of recombination affects the mode of molecular evolution. In high-recombining sequence, the targets of selection are individual genetic loci; under low recombination, selection collectively acts on large, genetically linked genomic segments. Selection under linkage can induce clonal interference, a specific mode of evolution by competition of genetic clades within a population. This mode is well known in asexually evolving microbes, but has not been traced systematically in an obligate sexual organism. Here we show that the Drosophila genome is partitioned into two modes of evolution: a local interference regime with limited effects of genetic linkage, and an interference condensate with clonal competition. We map these modes by differences in mutation frequency spectra, and we show that the transition between them occurs at a threshold recombination rate that is predictable from genomic summary statistics. We find the interference condensate in segments of low-recombining sequence that are located primarily in chromosomal regions flanking the centromeres and cover about 20% of the Drosophila genome. Condensate regions have characteristics of asexual evolution that impact gene function: the efficacy of selection and the speed of evolution are lower and the genetic load is higher than in regions of local interference. Our results suggest that multicellular eukaryotes can harbor heterogeneous modes and tempi of evolution within one genome. We argue that this variation generates selection on genome architecture

Finite Amplitude Method for Charge-Changing Transitions in Axially-Deformed Nuclei

We describe and apply a version of the finite amplitude method for obtaining the charge-changing nuclear response in the quasiparticle random phase approximation. The method is suitable for calculating strength functions and beta-decay rates, both allowed and forbidden, in axially-deformed open-shell nuclei. We demonstrate the speed and versatility of the code through a preliminary examination of the effects of tensor terms in Skyrme functionals on beta decay in a set of spherical and deformed open-shell nuclei. Like the isoscalar pairing interaction, the tensor terms systematically increase allowed beta-decay rates. This finding generalizes previous work in semimagic nuclei and points to the need for a comprehensive study of time-odd terms in nuclear density functionals.Comment: 11 pages, 8 figures, submitted to Physical Review

Pharmacology of ketoprofen administered orally to pigs : an experimental and clinical study

Ketoprofen is a non-steroidal anti-inflammatory drug belonging to the 2-arylpropionic acid group. It has been widely used in domestic animals because of its anti-inflammatory, antipyretic and analgesic actions. Ketoprofen is a chiral compound existing in two enantiomeric forms, S (+) and R (-) ketoprofen. Each enantiomer has different pharmacodynamic and pharmacokinetic properties. The commercial products in veterinary medicine are 50:50 racemic mixtures of both enantiomers. Ketoprofen undergoes unidirectional chiral inversion from the R- to the S-enantiomer, the extent of inversion being about 70% in pigs. The aims of this thesis research were to investigate the oral bioavailability, enantiospecific plasma concentrations and efficacy of racemic ketoprofen after oral administration in pigs. Total plasma concentrations of ketoprofen were investigated in a randomized crossover design. Racemic ketoprofen was administered at 3 mg/kg and 6 mg/kg po, and 3 mg/kg im and iv. The bioavailability of oral ketoprofen was almost complete. Bioequivalence could not be detected between oral and intramuscular administration routes. Plasma concentrations of S- and R-ketoprofen after oral (4 mg/kg) and intramuscular (3 mg/kg) routes of administration of racemic ketoprofen in pigs were determined in crossover design. S-ketoprofen was the predominant enantiomer in pig plasma after administration of the racemic mixture via both routes. The maximum plasma concentration of S-ketoprofen was more than twice as high as that of R-ketoprofen, and the terminal half-life was approximately three times greater for S-ketoprofen than R-ketoprofen with both administration routes. The mean (± SD) relative bioavailability (po compared to im) was 83 ± 20% and 63 ± 23% for S-ketoprofen and R-ketoprofen, respectively. Although some differences were detected in the plasma concentrations of ketoprofen enantiomers after different routes of administration, they are probably not relevant in clinical use. Thus, the pharmacological effects of racemic ketoprofen are considered to be comparable after intramuscular and oral routes of administration in growing pigs. The efficacy of orally administered racemic ketoprofen in endotoxemia in pigs was assessed in an E. coli endotoxin challenge trial. The growing pigs were challenged intravenously with E. coli endotoxin and one hour after the challenge were treated with ketoprofen at dose rates of 0.5 mg/kg, 1 mg/kg, 2 mg/kg and 4 mg/kg or with tap water. The body temperature was measured and a total clinical score was calculated after assessing the general behaviour, respiratory rate and locomotion of the pigs. Thromboxane B2 and ketoprofen concentrations were analysed from blood samples. Ketoprofen treatment significantly reduced the rectal temperature and total clinical scores, and lowered the blood thromboxane B2 concentrations when compared to the control group. Ketoprofen plasma concentrations were lower than previously reported in healthy pigs after similar doses. Two mg/kg can be considered a sufficient oral dose of ketoprofen for treating endotoxemia in pigs, as increasing the dose above this did not further increase the effect. Lameness is a common problem among sows and gilts. It often leads to poor animal welfare and economic losses because of unplanned culling. Locomotor disorders cause severe pain, and lame animals need to be treated accordingly. A field trial was conducted to examine the efficacy and compare two doses of oral administration of racemic ketoprofen in the treatment of clinical lameness caused by non-infectious musculoskeletal disorders in sows and gilts. Dose rates of 2 mg/kg and 4 mg/kg of oral ketoprofen were compared to placebo treatment over five consecutive days in a double-blinded study. Lameness was assessed with a five-grade scoring system prior to and on the last day of the treatment. This study demonstrated that oral ketoprofen was efficient in alleviating the signs of non-infectious lameness in sows and gilts. The rate of treatment success was 54.3% for the ketoprofen 4 mg/kg group, 53.2% for the ketoprofen 2 mg/kg group and 20.8% for the pigs in the placebo group. There was no difference in efficacy between the two ketoprofen doses. Oral ketoprofen appeared to be a practical way to alleviate pain and improve the welfare of lame sows. The findings support the use of ketoprofen at a dose rate of 2 mg/kg in treating locomotor disorders in pigs.Ketoprofeeni on fenyylipropionihappojohdosten ryhmään kuuluva steroideihin kuulumaton tulehduskipulääke. Sitä käytetään laajalti kotieläimillä sen tulehdusoireita ja kipua poistavan sekä kuumetta alentavan vaikutuksen takia. Ketoprofeenilla on kiraalinen molekyylirakenne ja siitä johtuen se esiintyy kahtena, R(-) ja S(+), enantiomeerina. Enantiomeerit eroavat toisistaan merkittävästi sekä farmakokineettisiltä että dynaamisilta ominaisuuksiltaan. Eläinlääkinnässä kaupallisesti saatavilla olevat valmisteet ovat raseemisia seoksia, joissa on yhtä paljon molempia enantiomeerejä. Ketoprofeenilla tapahtuu inversiota R-ketoprofeenista S-ketoprofeeniksi. Inversioaste on sialla noin 70 %. Tämän väitöskirjatyön tavoitteena oli selvittää suun kautta annetun raseemisen ketoprofeenin hyötyosuus, enantiomeerien plasmapitoisuudet sekä lääkityksen teho sialla. Plasman ketoprofeenipitoisuudet selvitettiin tutkimuksessa, jossa ketoprofeenia annettiin suun kautta sekä lihaksen- ja suonensisäisesti. Suun kautta annetun ketoprofeenin hyötyosuus oli korkea. Enatiomeerien plasmapitoisuudet määritettiinmolemmilla antatavoilla. S-ketoprofeeni oli hallitseva enantiomeeri riippumatta antotavasta. Plasman maksimipitoisuus oli S-ketoprofeenilla yli kaksi kertaa korkeampi ja puoliintumisaika noin kolme kertaa pidempi kuin R-ketoprofeenilla. Relatiivinen hyötyosuus suun kautta annettaessa verrattuna lihaksen sisäiseen antotapaan oli 83 ± 20 % S-ketoprofeenilla ja 63 ± 23 % R-ketoprofeenilla. Antotapa vaikutti enantiomeerien plasmapitoisuuksiin jonkin verran, mutta sillä ei kuitenkaan todennäköisesti ole käytännön vaikutusta. Suun kautta annetun ketoprofeenin tehoa endotoksemian hoidossa tutkittiin altistamalla porsaat E. coli endotoksiinille. Tunnin kuluttua altistuksesta porsaat lääkittiin joko vedellä (kontrolliryhmä) tai ketoprofeenilla, jota käytettiin neljällä eri annostasolla. Tehoa arvioitiin kliinisten oireiden sekä plasman tromboksaani B2- pitoisuuksien perusteella. Ketoprofeeni hoito lievensi kliinisiä oireita sekä alensi kuumetta ja tromboksaani B2-pitoisuuksia verrattuna kontrolliryhmään. Ketoprofeenin plasmapitoisuudet olivat matalampia kuin aiemmin raportoidut arvot terveillä porsailla. 2 mg/kg annos on riittävä endotoksemian hoidossa sialla, sillä annoksen nostaminen ei lisännyt kliinistä tehoa. Emakon ontuminen on yleinen vaiva, joka heikentää eläimen hyvinvointia ja helposti johtaa eläimen ennenaikaiseen poistoon. Ketoprofeenin tehoa sian ontuman hoidossa tutkittiin kahdella eri annostasolla kenttäkokeessa. Verrokkina oli lumelääke. Ontuma arvioitiin viisiportaisella asteikolla ennen lääkitystä ja lääkityksen jälkeen. Ketoprofeeni hoito lievensi merkitsevästi ontuman oireita verrattuna lumelääkkeeseen. Ketoprofeenin annostasot eivät eronneet toisistaan tehon suhteen. Suun kautta annettu raseeminen ketoprofeeni annoksella 2 mg/kg viiden päivän ajan osoittautui käytännössä hyväksi tavaksi lievittää kipuoireita ja parantaa hyvinvointia