Thiopurines are a standard treatment for childhood leukemia, but like all chemotherapeutics, their use is limited by inherent or acquired resistance in patients. Recently, the nucleoside diphosphate hydrolase NUDT15 has received attention on the basis of its ability to hydrolyze the thiopurine effector metabolites 6-thio-deoxyGTP (6-thio-dGTP) and 6-thio-GTP, thereby limiting the efficacy of thiop

Cirka 1000 barn föds med hjärtfel i Sverige varje år och idag överlever de flesta och uppnår vuxen ålder. Det finns uppskattningsvis 2.3 miljoner vuxna med medfött hjärtfel i Europa idag, en siffra som förväntas öka. Samtidigt har prevalensen av patienter med komplexa medfödda hjärtfel också ökat de senaste 10 åren. Det finns således ett behov av att öka kunskapen om patofysiologin vid dessa sjukdAround 1000 children are born with a heart disease in Sweden every year and today most of these children survive and reach adult age. There are around 2.3 million grownups with congenital heart disease in Europe today, a number that is expected to continue to increase. Further, the prevalence of patients with complex malformations has been growing significantly the last 10 years. There is thus a n

Nucleotides in the free pool are more susceptible to nonenzymatic methylation than those protected in the DNA double helix. Methylated nucleotides like O6-methyl-dGTP can be mutagenic and toxic if incorporated into DNA. Removal of methylated nucleotides from the nucleotide pool may therefore be important to maintain genome integrity. We show that MutT homologue 1 (MTH1) efficiently catalyzes the h

Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G). Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions. The clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed promising therapeutic properties. Both BoNT/A1 and BoNT/A2 utilize three isoforms of

One of the greatest challenges for the world today is the reduction of greenhouse gas emissions. As buildings contribute to almost a quarter of the greenhouse gas emissions worldwide, reducing the energy use of the existing building stock is an important measure for climate change mitigation. In order to increase the renovation pace, there is a need for a comprehensive technicaldocumentation that

Anthropogenic climate change is one of the most severe environmental challenges facing the planet today, and it is certainly one of the most debated. The built environment is a known major culprit, and cities as consumption centers account for a large share of the world’s consumption-based carbon footprint. It may well be argued that urban communities are at the very core of the climate change pro

This study analyzes the effect of cleaner local energy production on the consumer carbon footprint. The results in consumption based carbon footprint assessments have traditionally indicated that a significant change in consumption patterns or lifestyles would be needed to achieve the often aspired, ambitious 50- 80% cutoffs in the carbon emissions on a community level. However, it is also known t

The housing sector accounts for roughly 30% of the total annual energy consumption in the developed nations. Notwithstanding, sustainable housing management has not received sufficient attention previously, even though the role of housing managers can be considered significant in reducing the energy consumption of existing residential buildings. This study proposes a concept for a comprehensive an

In the European Union (EU), there are a large number of mandatory and voluntary policies applied to improve the environmental life cycle impacts of products. Policies are enacted at both the EU level and among the EU member states, and there is a need to develop a better coordination between the various policies. This contribution outlines the various policies and examines various conceptual appro

In the hadronic decay mode of a pair of W bosons, e+e-→W+W-→q1q̄2q3qbar4, QCD interference effects can mix up the two color singlets q1q̄2 and q3q̄4, i.e., produce hadrons that cannot be uniquely assigned to either of W+ and W-. We show that interference is negligible for energetic perturbative gluon emission, and develop models to help us to estimate the nonperturbative effects. The total contrib

We study the fragmentation of arbitrary parton configurations, with particular emphasis on events where two partons have a small invariant mass. Within the framework of string fragmentation, a natural transition is obtained between two nearby partons (qg or gg) and a single parton (q or g) carrying the full momentum (provided that colours match), i.e. the final state hadrons are distributed in the

We present a detailed model for exclusive properties of initial state parton showers. A numerically efficient algorithm is obtained by tracing the parton showers backwards, i.e. start with the hard scattering partons and then successively reconstruct preceding branchings in falling sequence of spacelike virtualities Q2 and rising sequence of parton energies. We show how the Altarelli-Parisi equati

Objective: To investigate if muscle strength and muscle activation patterns are associated with increased knee abduction during two functional tasks, commonly used in rehabilitation for individuals with anterior cruciate ligament reconstruction (ACLR). Design: Cross-sectional study. Setting: Laboratory. Participants: 24 women and 29 men approximately 7 months after ACLR. Main outcome measures: Iso

The vector and axial-vector two-point functions are calculated to next-to-next-to-leading order in Chiral Perturbation Theory for three light flavours. We also obtain expressions at the same order for the masses, m2 π, m2 Κ and m2 η, and the decay constants, Fπ, FΚ and Fη. We present some numerical results after a simple resonance estimate of some of the new O(p6) constants.

Within Chiral Perturbation Theory (CHPT) we compute the form factors A, V and γ = A/V in the π → lνγ decay to O(p6). A and γ obtain corrections of order 25%.

Background: Inherited retinal degenerations (IRDs) encompass a wide spectrum of genetic ocular diseases characterized by considerable genetic and clinical heterogeneity. Methods: Complete ophthalmic examination and next-generation sequencing. Results: We describe a patient with no family history of vision loss, who at the age of 28 years developed visual impairment consistent with a severe form of