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To develop effective therapeutic strategies for protein misfolding diseases, a promising route is to identify compounds that inhibit the formation of protein oligomers. To achieve this goal, we report a structure.activity relationship (SAR) approach based on chemical kinetics to estimate quantitatively how small molecules modify the reactive flux toward oligomers. We use this estimate to derive ch
Climate change is expected to severely affect cropping systems and food production in many parts of the world unless local adaptation can ameliorate these impacts. Ensembles of crop simulation models can be useful tools for assessing if proposed adaptation options are capable of achieving target yields, whilst also quantifying the share of uncertainty in the simulated crop impact resulting from th
Chromosomal rearrangements (e.g., fusions/fissions) have the potential to drive speciation. However, their accumulation in a population is generally viewed as unlikely, because chromosomal heterozygosity should lead to meiotic problems and aneuploid gametes. Canonical meiosis involves segregation of homologous chromosomes in meiosis I and sister chromatid segregation during meiosis II. In organism
Although democratic innovations (DIs) are spread all over the world, there is little research on the institutional outcomes of implementing such innovations in governmental organisations. To remedy this, it is important to focus on cases where DIs have been implemented and formally connected to the policymaking process over a longer period. Reykjavik provides such a case. Drawing on observations a
Meteorological extreme events such as El Niño events are expected to affect tropical forest net primary production (NPP) and woody growth, but there has been no large-scale empirical validation of this expectation. We collected a large high-temporal resolution dataset (for 1-13 years depending upon location) of more than 172 000 stem growth measurements using dendrometer bands from across 14 regio
There are many indicators that the representative democratic system is currently facing serious legitimacy challenges. Two central indicators of these challenges are changing patterns of political participation and a decline in system support. Against this backdrop, a growing number of governments claim that democratic innovations (DIs) could reconnect institutions with citizens. This thesis focus
STUDY QUESTION: Does chemotherapy exposure (with or without alkylating agents) or primary diagnosis affect spermatogonial quantity in human prepubertal testicular tissue? SUMMARY ANSWER: Spermatogonial quantity is significantly reduced in testes of prepubertal boys treated with alkylating agent therapies or with hydroxyurea for sickle cell disease. WHAT IS KNOWN ALREADY: Cryopreservation of sperma
The Estonian Citizens’ Assembly (ECA) was initiated in late 2012 as a direct consequence of a legitimacy crisis of Estonian political parties and representative institutions. The spark igniting this crisis was the unravelling of a scheme of illegal party financing. The response from the governmental institutions took the form of a democratic innovation drawing on public crowd-sourcing and delibera
We demonstrate covariant beam-physics simulation through multipole magnets using Hamiltonians relying on canonical momentum. Space-charge interaction using the Lienard-Wiechert potentials is also discussed. This method is compared with conventional nonlinear Lie-operator tracking and the TraceWin software package.
Background: High-circulating level of parathyroid hormone (PTH) is associated with elevated mortality in dialysis patients. The Japanese Society for Dialysis Therapy guideline suggests a lower PTH target than other international guidelines; thus, PTH control may differ in Japan compared with other regions, and be associated with mortality. Methods: We analyzed data from hemodialysis patients with
Background: An increased Head Shaft Angle (HSA) has been reported as a risk factor for hip displacement in children with cerebral palsy (CP) but opinions differ in the literature. The purpose of this study was to re-evaluate the relationship between HSA and hip displacement in a different population of children with CP. Methods: The Cerebral Palsy Integrated Pathway Scotland surveillance programme
The derivation of dopamine neurons from human embryonic stem cells (hESCs) now offers a promising alternative to fetal tissue for cell replacement therapy (CRT) in Parkinson´s disease (PD). Using the appropriate chemical cues in vitro, hESCs can be patterned towards bona-fide ventral midbrain (VM) DA neurons that survive, reinnervate, release DA and provide functional recovery when transplanted in
Background: Worsening heart failure complicated by congestion, hypotension, and renal dysfunction is difficult to manage, increasingly common and predicts a poor outcome. Novel therapies are required to facilitate diuresis and implementation of disease-modifying interventions in preparation for hospital discharge. Accordingly, we investigated the haemodynamic and renal effects of the Reitan Cathet
Anisotropy of gravitational wave (GW) emission results in a net momentum gained by the black hole (BH) merger product, leading to a recoil velocity up to ∼103 km s−1, which may kick it out of a globular cluster (GC). We estimate GW kick retention fractions of merger products assuming different models for BH spin magnitude and orientation. We check how they depend on BH–BH merger time and propertie
In this paper, we discuss how the structural and observational properties of globular clusters (GCs) can be used to infer the presence of a black hole system (BHS) inhabiting their inner regions. We propose a novel way to define the BHS size as the radius from the GC centre within which half of the mass is in stellar mass BHs and the remaining half is in other stars. Using this definition, similar
The first neutron star-neutron star (NS-NS) merger was discovered on August 17, 2017 through gravitational waves (GW170817) and followed with electromagnetic observations. This merger was detected in an old elliptical galaxy with no recent star formation. We perform a suite of numerical calculations to understand the formation mechanism of this merger. We probe three leading formation mechanisms o
There have been increasing theoretical speculations and observational indications that certain globular clusters (GCs) could contain a sizeable population of stellar mass black holes (BHs). In this paper, we shortlist at least 29 Galactic GCs that could be hosting a subsystem of BHs (BHS). In a companion paper, we analysed results from a wide array of GC models (simulated with the MOCCA code for c
