Discovery and optimization of narrow spectrum inhibitors of Tousled like kinase 2 (TLK2) using quantitative structure activity relationships.

The oxindole scaffold has been the center of several kinase drug discovery programs, some of which have led to approved medicines. A series of two oxindole matched pairs from the literature were identified where TLK2 was potently inhibited as an off-target kinase. The oxindole has long been considered a promiscuous kinase inhibitor template, but across these four specific literature oxindoles TLK2 activity was consistent, while the kinome profile was radically different ranging from narrow to broad spectrum kinome coverage.

Discovery and Optimization of Narrow Spectrum Inhibitors of Tousled Like Kinase 2 (TLK2) Using Quantitative Structure Activity Relationships.

The oxindole scaffold has been the center of several kinase drug discovery programs, some of which have led to approved medicines. A series of two oxindole matched pairs from the literature were identified where TLK2 was a potent off-target kinase. The oxindole has long been considered a promiscuous inhibitor template, but across these 4 specific literature oxindoles TLK2 activity was consistent, while the kinome profile was radically different from narrow to broad spectrum coverage.

Labour market trajectories after part-time sickness absence: a nationwide cohort study from Finland.

Objectives: The use of part-time sickness absence (pSA) enables return to part-time work from full sickness absence. However, subsequent labour market outcomes of pSA users depend on various individual and work-related characteristics. We investigated labour market paths of private and public sector employees after having a pSA spell.

Contribution of compositional changes in the workforce to sickness absence trends in Finland.

In this study, we assessed whether the long-term decrease in sickness absences in Finland is explained by observed and unobserved compositional changes in the workforce. Utilizing register-based panel data on Finnish wage earners aged 30-62, we examined the annual onset of compensated sickness absence (granted after 10 weekdays) in the period 2005-2016. We applied random effects models adjusting for changes in the observed sociodemographic and occupational characteristics of the study population.

Does previous sickness absence affect work participation after vocational labour market training? A difference-in-differences propensity score matching approach.

Background: Reduced work ability is relatively common among job seekers and it can hinder future labour market attachment. A commonly used measure to increase employability is the use of active labour market programmes. While vocational labour market training (LMT) has been shown to be an effective way to increase work participation among job seekers, there is still uncertainty about how LMT works in different population groups, for example, among persons with a work disability history.

Working life expectancy and working years lost among users of part- and full-time sickness absence in Finland.

Objectives: The use of part-time sickness absence (pSA) instead of full-time sickness absence (fSA) is known to increase work participation. Yet, its effect on the total length of working lives remains unclear. We carried out a quasi-experiment to assess the impact of using pSA versus fSA on the length of working lives.

Thermally Sprayed Coatings: Novel Surface Engineering Strategy Towards Icephobic Solutions.

Surface engineering promotes possibilities to develop sustainable solutions to icing challenges. Durable icephobic solutions are under high interest because the functionality of many surfaces can be limited both over time and in icing conditions. To solve this, one potential approach is to use thermally sprayed polymer or composite coatings with multifunctional properties as a novel surface design method.

Multiplexed proteomic analysis of oxidation and concentrations of cerebrospinal fluid proteins in Alzheimer disease.

Background: Carbonylation is an irreversible oxidative modification of proteins that has been linked to various conditions of oxidative stress, aging, physiological disorders, and disease. Increased oxidative stress is thus also considered to play a role in the pathogenesis of age-related neurodegenerative disorders such as Alzheimer disease (AD). In addition, it has recently become evident that the response mechanisms to increased oxidative stress may depend on sex.

Prevalence and natural course of ectopic atrial tachycardia.

Aims: The purpose of this study was to calculate the prevalence of ectopic atrial tachycardia in a population of young asymptomatic males and to assess its natural course both in asymptomatic subjects and in symptomatic hospital patients.

Methods And Results: 12-lead electrocardiograms (ECG) of 3554 consecutive males applying for a pilot's licence were analysed. ECGs of symptomatic arrhythmia patients at two university hospitals were also analysed.