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Frontotemporal dementia (FTD) is the second most prevalent type of early-onset dementia and up to 40% of cases are familial forms. One of the genes mutated in patients is CHMP2B, which encodes a protein found in a complex important for maturation of late endosomes, an essential process for recycling membrane proteins through the endolysosomal system. Here, we have generated a CHMP2B-mutated human

The commercial production of bioethanol from lignocellulosic biomass such as wheat straw requires utilizing a microorganism that can withstand all the stressors encountered in the process while fermenting all the sugars in the biomass. Therefore, it is essential to develop tools for monitoring and controlling the cellular fitness during both cell propagation and sugar fermentation to ethanol. In t

Fatty acids are produced by eukaryotes like baker's yeast Saccharomyces cerevisiae mainly using a large multifunctional type I fatty acid synthase (FASI) where seven catalytic steps and a carrier domain are shared between one or two protein subunits. While this system may offer efficiency in catalysis, only a narrow range of fatty acids are produced. Prokaryotes, chloroplasts and mitochondria rely

This paper explores the dark gothic fantasy world of The Witcher 3: The Wild Hunt, an open-world video game from 2015. Using The Witcher 3 as a case study, the paper examines the moral dimensions of player interaction within the game beyond dialogue trees and NPC interaction. By investigating how the player is presented with monsters and animals within the game world, the paper makes an argument f

This paper investigates employment outcomes for a large sample of Ph.D. students who were enrolled in a doctoral training program in Italy in the period 2008–14. The empirical analysis is based on survey data obtained from a questionnaire distributed to 23,500 individuals in 2016. In Italy, student enrolment in a Ph.D. involves a university-based selection process; most students then receive eithe

As novelty is a core value in science, a reliable approach to measuring the novelty of scientific documents is critical. Previous novelty measures however had a few limitations. First, the majority of previous measures are based on recombinant novelty concept, attempting to identify a novel combination of knowledge elements, but insufficient effort has been made to identify a novel element itself

Risk plays a fundamental role in scientific discoveries, and thus it is critical that the level of risk can be systematically quantified. We propose a novel approach to measuring risk entailed in a particular mode of discovery process – knowledge recombination. The recombination of extant knowledge serves as an important route to generate new knowledge, but attempts of recombination often fail. Dr

We formulate probabilistic numerical approximations to solutions of ordinary differential equations (ODEs) as problems in Gaussian process (GP) regression with nonlinear measurement functions. This is achieved by defining the measurement sequence to consist of the observations of the difference between the derivative of the GP and the vector field evaluated at the GP—which are all identically zero

This paper is concerned with sigma-point methods for filtering in nonlinear systems, where the process and measurement noise are heavy tailed and enter the system non-additively. The problem is approached within the framework of assumed density filtering and the necessary statistics are approximated using sigma-point methods developed for Student's t-distribution. This leads to UKF/CKF-type of fil

This letter presents the development of novel iterated filters and smoothers that only require specification of the conditional moments of the dynamic and measurement models. This leads to generalizations of the iterated extended Kalman filter, the iterated extended Kalman smoother, the iterated posterior linearization filter, and the iterated posterior linearization smoother. The connections to t

Despite the ubiquity of the Gaussian process regression model, few theoretical results are available that account for the fact that parameters of the covariance kernel typically need to be estimated from the data set. This article provides one of the first theoretical analyses in the context of Gaussian process regression with a noiseless data set. Specifically, we consider the scenario where the

There is a growing interest in probabilistic numerical solutions to ordinary differential equations. In this paper, the maximum a posteriori estimate is studied under the class of ν times differentiable linear time-invariant Gauss–Markov priors, which can be computed with an iterated extended Kalman smoother. The maximum a posteriori estimate corresponds to an optimal interpolant in the reproducin

The aim of this article is to design a moment transformation for Student-t distributed random variables, which is able to account for the error in the numerically computed mean. We employ Student-t process quadrature, an instance of Bayesian quadrature, which allows us to treat the integral itself as a random variable whose variance provides information about the incurred integration error. Advant

In this paper, we propose a new framework for solving state estimation problems with an additional sparsity-promoting $L-1$-regularizer term. We first formulate such problems as minimization of the sum of linear or nonlinear quadratic error terms and an extra regularizer, and then present novel algorithms which solve the linear and nonlinear cases. The methods are based on a combination of the ite

This paper proposes a novel algorithm for target tracking with direction-of-arrival measurements, modeled by von Mises-Fisher distributions. The algorithm makes use of the assumed density framework with Gaussian distributions, in which the posterior probability density of the target state is approximated by a Gaussian density. A key component of this algorithm is that the proposed Bayesian model o

In this letter, we analyze certain student's t-filters for linear Gaussian systems with misspecified noise covariances. It is shown that under appropriate conditions, the filter both estimates the state and re-scales the noise covariance matrices in a Kullback-Leibler optimal fashion. If the noise covariances are misscaled by a common scalar, then the re-scaling is asymptotically exact. We also co

This letter proposes a new algorithm for Gaussian process classification based on posterior linearization (PL). In PL, a Gaussian approximation to the posterior density is obtained iteratively using the best possible linearization of the conditional mean of the labels and accounting for the linearization error. PL has some theoretical advantages over expectation propagation (EP): all calculated co

Owing to their millisecond-scale temporal resolution, magnetoencephalography (MEG) and electroencephalography (EEG) are well-suited tools to study dynamic functional connectivity between regions in the human brain. However, current techniques to estimate functional connectivity from MEG/EEG are based on a two-step approach; first, the MEG/EEG inverse problem is solved to estimate the source activi

This paper considers approximate smoothing for discretely observed non-linear stochastic differential equations. The problem is tackled by developing methods for linearising stochastic differential equations with respect to an arbitrary Gaussian process. Two methods are developed based on (1) taking the limit of statistical linear regression of the discretised process and (2) minimising an upper b