mbs: modifying Hudson's ms software to generate samples of DNA sequences with a biallelic site under selection

<p>Abstract</p> <p>Background</p> <p>The pattern of single nucleotide polymorphisms, or SNPs, contains a tremendous amount of information with respect to the mechanisms of the micro-evolutionary process of a species. The inference of the roles of these mechanisms, including natural selection, relies heavily on computer simulations. A coalescent simulation is extremely powerful in generating a large number of samples of DNA sequences from a population (species) when all mutations are neutral, and Hudson's <b>ms </b>software is frequently used for this purpose.</p> <p>However, it has been difficult to incorporate natural selection into the coalescent framework.</p> <p>Results</p> <p>We herein present a software application to generate samples of DNA sequences when there is a biallelic site targeted by selection. This software application, referred to as <b>mbs</b>, is developed by modifying Hudson's <b>ms</b>. The <b>mbs </b>software is so flexible that it can incorporate any arbitrary histories of population size changes and any mode of selection as long as selection is operating on a biallelic site.</p> <p>Conclusion</p> <p><b>mbs </b>provides opportunities to investigate the effect of any mode of selection on the pattern of SNPs under various demography.</p

Klinische Bedeutung der Bestimmung der Bindung von Trijodthyronin an Serumproteine mittels Dextran-Gel-Filtration

Neben den bewährten älteren Verfahren zur Bestimmung des proteingebundenen127Jods und des Radiojodumsatzes hat sich die gleichzeitige Bestimmung des sog. freien und des proteingebundenen Anteils an in vitro mit Serum inkubiertem L-Trijodthyronin-131Jod mittels Dextran-Gel-Filtration klinisch zur Differentialdiagnose von Hyperthyreose und Euthyreose bewährt. Bei Ausnützung der Verdrängung von proteingebundenem L-Trijodthyronin-131Jod durch nichtmarkiertes Hormon und bei Variation der Dextran-Gel-Menge in der Säule bietet die Methode gute Differenzierungsmöglichkeiten auch für die Schilddrüsenfunktionszustände Euthyreose und Hypothyreose. Bei dem Verfahren wird der Patient nicht mit radioaktivem Jod belastet, ein für die Kinderklinik wichtiger Gesichtspunkt. Manche Störfaktoren, die den131Jodspeicherungstest und die Bestimmung des proteingebundenen Jods (PB127I) verfälschen, haben keinen Einfluß auf die mit der Dextran-Gel-Filtration untersuchten Proteinbindungsverhältnisse für L-Trijodthyronin-131Jod. So hat sich das Verfahren für die Untersuchung von Patienten mit operativ oder durch131Jodbehandlung verkleinerten Schilddrüsen, mit endokrinem Exophthalmus und in Fällen mit vorausgegangener Jodgabe, z. B. in Form von Kontrastmitteln, besonders bewährt. Mit der Bestimmung des sog. freien L-Trijodthyronin-131Jods wird ein physiologisch und pathogenetisch wichtiger Parameter der Schilddrüsenfunktion ermittelt. Die klinische Bedeutung der Bestimmung der Bindungs-und Transportverhältnisse für Trijodthyronin mittels Dextran-Gel-Filtration wird diskutiert.In addition to conventional methods of assay of protein bound iodine (PB127I) and of131iodine turnover in the thyroid, the simultaneous determination of socalled free and protein bound 1-triiodothyronine-131I, added in vitro to serum, using dextran gel filtration was found to be clinically helpful for diagnosis of euthyroidism and hyperthyroidism. Employing discharge effects of non-labelled triiodothyronine on protein bound 1-triiodothyronine-131I and varying the amount of dextran gel in the columns, the method provides reasonably good differentiation of euthyroid and hypothyroid states. No radioactive iodine is given to patients during this procedure, a fact of importance for pediatriciens. Some factors, that influence131iodine uptake or PB127I levels, do not disturb protein binding of 1-triiodothyronine-131I as determined by dextran gel filtration. The latter method was found to be especially useful for the examination of patients with surgically, or by therapy with131iodine dissected thyroid glands, with endocrine exophthalmos, and in cases of previous iodine administration (e.g. X-ray procedures). Determination of socalled free 1-triiodothyronine-131I provides information about a factor of physiological and pathogenetical significance, its clinical meaning is discussed

Refined analytic torsion

Given an acyclic representation $\alpha$ of the fundamental group of a compact oriented odd-dimensional manifold, which is close enough to an acyclic unitary representation, we define a refinement $T_\alpha$ of the Ray-Singer torsion associated to $\alpha$, which can be viewed as the analytic counterpart of the refined combinatorial torsion introduced by Turaev. $T_\alpha$ is equal to the graded determinant of the odd signature operator up to a correction term, the metric anomaly, needed to make it independent of the choice of the Riemannian metric. $T_\alpha$ is a holomorphic function on the space of such representations of the fundamental group. When $\alpha$ is a unitary representation, the absolute value of $T_\alpha$ is equal to the Ray-Singer torsion and the phase of $T_\alpha$ is proportional to the $\eta$-invariant of the odd signature operator. The fact that the Ray-Singer torsion and the $\eta$-invariant can be combined into one holomorphic function allows one to use methods of complex analysis to study both invariants. In particular, using these methods we compute the quotient of the refined analytic torsion and Turaev’s refinement of the combinatorial torsion generalizing in this way the classical Cheeger-Müller theorem. As an application, we extend and improve a result of Farber about the relationship between the Farber-Turaev absolute torsion and the $\eta$-invariant. As part of our construction of $T_\alpha$ we prove several new results about determinants and $\eta$-invariants of non self-adjoint elliptic operators