Modeling of biocatalytic reactions: A workflow for model calibration, selection and validation using Bayesian statistics

We present a workflow for kinetic modeling of biocatalytic reactions which combines methods from Bayesian learning and uncertainty quantification for model calibration, model selection, evaluation, and model reduction in a consistent statistical framework. Our workflow is particularly tailored to sparse data settings in which a considerable variability of the parameters remains after the models have been adapted to available data, a ubiquitous problem in many real‐world applications. Our workflow is exemplified on an enzyme‐catalyzed two‐substrate reaction mechanism describing the symmetric carboligation of 3,5‐dimethoxy‐benzaldehyde to (R )‐3,3′,5,5′‐tetramethoxybenzoin catalyzed by benzaldehyde lyase from Pseudomonas fluorescens . Results indicate a substrate‐dependent inactivation of enzyme, which is in accordance with other recent studies

New results for two-loop off-shell three-point diagrams

A number of exact results for two-loop three-point diagrams with massless internal particles and arbitrary (off-shell) external momenta are presented. Divergent contributions are calculated in the framework of dimensional regularization.Comment: 10 pages, 3 figures, standard LaTEX (PS-file is also available by anonymous FTP at node VSFYS1.FI.UIB.NO in subdirectory DAVYDYCHEV, the file BERGEN94-03.PS), Bergen Scientific/Technical Report No.1994-0

Uso de microminerais complexados na redução de lesões de casco em reprodutoras suínas/ Use of complexed trace minerals to improve claw lesions in swine sows

As lesões nos cascos em porcas têm alta prevalência no Brasil e resultam em perdas no desempenho produtivo e econômico da produção, além de comprometer o bem-estar dos animais. Vários fatores estão envolvidos em seu desenvolvimento, incluindo o tipo de alojamento, os manejos, os aspectos nutricionais e genéticos. O objetivo deste estudo foi avaliar o efeito dos minerais Zinco, Cobre, Manganês, Cromo e Selênio complexo-aminoácidos na prevalência de lesões nos cascos de matrizes suínas em uma granja localizada no município de Toledo, Paraná. Os minerais foram fornecidos para todo o plantel de fêmeas, totalizando 450 porcas. Foram avaliados os cascos dos membros pélvicos de 10% das matrizes, escolhidas aleatoriamente na maternidade, em dois momentos, sendo 05/12/2020 e 18/08/2021, início e fim do período experimental, respectivamente, totalizando assim 247 dias de tratamento. As lesões foram classificadas conforme área afetada (Crescimento e Erosão da Almofada Plantar, Rachadura entre a Almofada Plantar e Sola, Lesão na Linha Branca, Rachadura Horizontal da Parede do casco, Rachadura Vertical da Parede do casco, Crescimento das Unhas Principais e Crescimento ou Amputação das Unhas Acessórias) e escore de severidade. Houve redução de 17% e 66% na prevalência de lesões totais e severas, respectivamente. O escore médio das lesões diminuiu em todas as áreas, assim como a redução do índice de lesões em 52% e a quantidade de porcas em condições ideais aumentou em 315%, evidenciando, então, que os microminerais complexados com aminoácidos proporcionaram uma redução nas lesões de cascos em fêmeas suínas estudadas

Evidence of Gunn-Peterson damping wings in high-z quasar spectra: strengthening the case for incomplete reionization

The spectra of several high-redshift (z>6) quasars have shown evidence for a Gunn-Peterson (GP) damping wing, indicating a substantial mean neutral hydrogen fraction (x_HI > 0.03) in the z ~ 6 intergalactic medium (IGM). However, previous analyses assumed that the IGM was uniformly ionized outside of the quasar's HII region. Here we relax this assumption and model patchy reionization scenarios for a range of IGM and quasar parameters. We quantify the impact of these differences on the inferred x_HI, by fitting the spectra of three quasars: SDSS J1148+5251 (z=6.419), J1030+0524 (z=6.308), and J1623+3112 (z=6.247). We find that the best-fit values of x_HI in the patchy models agree well with the uniform case. More importantly, we confirm that the observed spectra favor the presence of a GP damping wing, with peak likelihoods decreasing by factors of > few - 10 when the spectra are modeled without a damping wing. We also find that the Ly alpha absorption spectra, by themselves, cannot distinguish the damping wing in a relatively neutral IGM from a damping wing in a highly ionized IGM, caused either by an isolated neutral patch, or by a damped Ly alpha absorber (DLA). However, neutral patches in a highly ionized universe (x_HI < 0.01), and DLAs with the large required column densities (N_HI > few x 10^{20} cm^{-2}) are both rare. As a result, when we include reasonable prior probabilities for the line of sight (LOS) to intercept either a neutral patch or a DLA at the required distance of ~ 40-60 comoving Mpc away from the quasar, we find strong lower limits on the neutral fraction in the IGM, x_HI > 0.1 (at 95% confidence). This strengthens earlier claims that a substantial global fraction of hydrogen in the z~6 IGM is in neutral form.Comment: 18 pages, 7 figures, version accepted for publication in the MNRA

Statistics of low-energy levels of a one-dimensional weakly localized Frenkel exciton: A numerical study

Numerical study of the one-dimensional Frenkel Hamiltonian with on-site randomness is carried out. We focus on the statistics of the energy levels near the lower exciton band edge, i. e. those determining optical response. We found that the distribution of the energy spacing between the states that are well localized at the same segment is characterized by non-zero mean, i.e. these states undergo repulsion. This repulsion results in a local discrete energy structure of a localized Frenkel exciton. On the contrary, the energy spacing distribution for weakly overlapping local ground states (the states with no nodes within their localization segments) that are localized at different segments has zero mean and shows almost no repulsion. The typical width of the latter distribution is of the same order as the typical spacing in the local discrete energy structure, so that this local structure is hidden; it does not reveal itself neither in the density of states nor in the linear absorption spectra. However, this structure affects the two-exciton transitions involving the states of the same segment and can be observed by the pump-probe spectroscopy. We analyze also the disorder degree scaling of the first and second momenta of the distributions.Comment: 10 pages, 6 figure

To whom does the law speak? Canvassing a neglected picture of law’s interpretive field

Among the most common strategies underlying the so-called indeterminacy thesis is the following two-step argument: (1) that law is an interpretive practice, and that evidently legal actors more generally hold different (and competing) theories of meaning, which lead to disagreements as to what the law says (that is, as to what the law is); (2) and that, as there is no way to establish the prevalence of one particular theory of meaning over the other, indeterminacy is pervasive in law. In this paper I offer some reflections to resist this trend. In particular I claim that a proper understanding of law as an authoritative communicative enterprise sheds new light on the relation between the functioning of the law and our theories of interpretation, leading to what can be considered a neglected conclusion: the centrality of the linguistic criterion of meaning in our juridical interpretive practices. In the first part of the chapter I discuss speech-act theory in the study of law, assessing its relevance between alternative options. Then I tackle the ‘to whom does the law speak?’ question, highlighting the centrality of lay-people for our juridical practices. Lastly, I examine the consequences of this neglected fact for our interpretive theories

Functional investigation of two simultaneous or separately segregating DSP variants within a single family support the theory of a dose-dependent disease severity

Desmoplakin (DP) is an important component of desmosomes, essential in cell-cell connecting structures in stress-bearing tissues. Over many hundreds of pathogenic variants in DSP have been associated with different cutaneous and cardiac phenotypes or a combination, known as a cardiocutaneous syndrome. Of less than 5% of the reported DSP variants, the effect on the protein has been investigated. Here, we describe and have performed RNA, protein and tissue analysis in a large family where DSPc.273+5G>A/c.6687delA segregated with palmoplantar keratoderma (PPK), woolly hair and lethal cardiomyopathy, while DSPWT/c.6687delA segregated with PPK and milder cardiomyopathy. hiPSC-derived cardiomyocytes and primary keratinocytes from carriers were obtained for analysis. Unlike the previously reported nonsense variants in the last exon of DSP that bypassed the nonsense-mediated mRNA surveillance system leading to protein truncation, variant c.6687delA was shown to cause loss of protein expression. Patients carrying both variants and having a considerably more severe phenotype were shown to have 70% DP protein reduction, while patients carrying only c.6687delA had 50% protein reduction and a milder phenotype. Analysis of RNA from patient cells did not show any splicing effect of the c.273+5G>A variant. However, a minigene splicing assay clearly showed alternative spliced transcripts originating from this variant. This study shows the importance of RNA and protein analyses to pinpoint the exact effect of DSP variants instead of solely relying on predictions. In addition, the particular pattern of inheritance, with simultaneous or separately segregating DSP variants within the same family, strongly supports the theory of a dose-dependent disease severity

Cidofovir for the Treatment of Recurrent Respiratory Papillomatosis: A Review of the Literature

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90089/1/phco.2005.25.7.977.pd

Quantum Effects in Coulomb Blockade

We review the quantum interference effects in a system of interacting electrons confined to a quantum dot. The review starts with a description of an isolated quantum dot. We discuss the status of the Random Matrix theory (RMT) of the one-electron states in the dot, present the universal form of the interaction Hamiltonian compatible with the RMT, and derive the leading corrections to the universal interaction Hamiltonian. Next, we discuss a theoretical description of a dot connected to leads via point contacts. Having established the theoretical framework to describe such an open system, we discuss its transport and thermodynamic properties. We review the evolution of the transport properties with the increase of the contact conductances from small values to values $\sim e^2/\pi\hbar$. In the discussion of transport, the emphasis is put on mesoscopic fluctuations and the Kondo effect in the conductance.Comment: 169 pages, 28 figures; several references and footnotes are added, and noticed typos correcte