Leadership, Wellbeing, and Performance - a Strategic Convergence in the Digital Age?

It is a simple equation: employees expend their time going about their work while their company in return reimburses them monetarily. For most executives there is nothing more to it and so they can otherwise focus all their attention on the one and only business rule which is the maximization of profit for the owners of the company. Yet, since many decades an increasing number of scholars has argued that the differentiation between investments into employees and their welfare and those designed to increase profits is false because it implies a contrariety between these two purposes that does not exist. Rather, they argue, meaningful investments into a company’s workforce may in themselves serve to increase profits because an employee who is better off is more productive. This idea is at the heart of the domain of Strategic Human Resource Management (SHRM) which views employees as a strategic asset and the source of competitive advantage. It is the core premise of this thesis that the notion of SHRM has never been more relevant than today amid the onslaught of Digitalization which appears to overwhelm employees and puts them under increasing strain. To prove this premise, I in the review of literature first seek to identify suitable organizational practices which are designed to support employees to rise above the challenges posed to them, establishing the installation of responsible leadership as the most suitable approach. Second, the review then endeavours to determine a concept that encapsulates the welfare of employees whereby designating psychological wellbeing. Third and last, employee performance is foregrounded as the concept to assess the impact the chosen organizational practices unfold in respect to the organizational goals. These three concepts are subsequently brought into relation with one another whereas the thesis’ four hypotheses are construed: responsible leadership positively influences both psychological wellbeing and employee performance, while wellbeing impacts performance, also in a positive manner. Thus, I expect to identify wellbeing as a full mediator of the nexus between leadership and performance which is the core of the fourth hypothesis. These hypotheses are tested by means of Multilevel Structural Equation Modelling, employing two distinct models and using data collected from 10 companies in Finland via the Exponential research project at Aalto University. While establishing psychological wellbeing as a mediator of the relationship between responsible leadership and employee performance and thereby supporting the thesis’ premise, the underlying nexus between leadership and performance in the direct model appears insignificant, whereas plausible reasons are noted. Generally, I in my thesis substantiate the value that investments in employee welfare can generate for an organization, before the particular background of Digitalization with the continuous introduction of new technology and the transformation of business models. Further, I provide a thorough account of the various disagreements among scholars in the SHRM field, scrutinizing issues such as the possibility of obverse effects of HR practices or the persistence of level issues. By addressing those issues, I furnish proof of the continuous relevance of SHRM and offer a point of departure for like studies

Identification of a Potent Allosteric Inhibitor of Human Protein Kinase CK2 by Bacterial Surface Display Library Screening

Human protein kinase CK2 has emerged as promising target for the treatment of neoplastic diseases. The vast majority of kinase inhibitors known today target the ATP binding site, which is highly conserved among kinases and hence leads to limited selectivity. In order to identify non-ATP competitive inhibitors, a 12-mer peptide library of 6 × 105 variants was displayed on the surface of E. coli by autodisplay. Screening of this peptide library on variants with affinity to CK2 was performed by fluorophore-conjugated CK2 and subsequent flow cytometry. Single cell sorting of CK2-bound E. coli yielded new peptide variants, which were tested on inhibition of CK2 by a CE-based assay. Peptide B2 (DCRGLIVMIKLH) was the most potent inhibitor of both, CK2 holoenzyme and the catalytic CK2α subunit (IC50 = 0.8 µM). Using different ATP concentrations and different substrate concentrations for IC50 determination, B2 was shown to be neither ATP- nor substrate competitive. By microscale thermophoresis (MST) the KD value of B2 with CK2α was determined to be 2.16 µM, whereas no binding of B2 to CK2β-subunit was detectable. To our surprise, besides inhibition of enzymatic activity, B2 also disturbed the interaction of CK2α with CK2β at higher concentrations (≥25 µM)

A π-Halogen Bond of Dibenzofuranones with the Gatekeeper Phe113 in Human Protein Kinase CK2 Leads to Potent Tight Binding Inhibitors

Human protein kinase CK2 is an emerging target for neoplastic diseases. Potent lead structures for human CK2 inhibitors are derived from dibenzofuranones. Two new derivatives, 7,9-dichloro-1,2-dihydro-8-hydroxy-4-[(4-methoxyphenylamino)-methylene]dibenzo[b,d]furan-3(2H)-one (4a) and (E)-1,3-dichloro-6-[(4-methoxyphenylimino)-methyl]dibenzo[b,d]furan-2,7-diol (5) were tested for inhibition of CK2 and induction of apoptosis in LNCaP cells. Both turned out to be tight binding inhibitors, with IC50 values of 7 nM (4a) and 5 nM (5) and an apparent Ki value of 0.4 nM for both. Compounds 4a and 5 reduced cellular CK2 activity, indicating cell permeability. Cell viability was substantially impaired in LNCaP cells, as well as apoptosis was induced, which was not appearing in non-neoplastic ARPE-19 cells. Co-crystallization of 4a and 5 revealed an unexpected π-halogen bond of the chloro substituent at C9 with the gatekeeper amino acid Phe113, leading to an inverted binding mode in comparison to parent compound 4b, with the Cl at C6 instead, which was co-crystallized as a control. This indicates that the position of the chloro substituent on ring A of the dibenzofuran scaffold is responsible for an inversion of the binding mode that enhances potency

ТЕХНОГЕННІ РОДОВИЩА ТА ЇХ КЛАСИФІКАЦІЯ

На багатьох гірничодобувних підприємствах тих, що забезпечують мінера-льною сировиною чорну і кольорову металургію України та країн СНД, виник-ла проблема з розвіданими запасами. Резерв запасів багатьох видів корисних копалини на експлуатованих родовищах недостатній для забезпечення повної проектної потужності. Стан сировинних баз багатьох найважливіших гірничо-добувних регіонів і підприємств, що діють, різко погіршав у зв'язку з висна-женням запасів, зниженням їх якісних і економічних характеристик ускладнен-ням умов відробітку в результаті тривалої і інтенсивної експлуатації раніше освоєних родовищ. Основною причиною ситуації, що створилася, можна назва-ти зниження фінансування геологорозвідувальних робіт для освоєння нових ро-довищ необхідної мінеральної сировини

Functional display of heterotetrameric human protein kinase CK2 on Escherichia coli: a novel tool for drug discovery

Background: Human protein kinase CK2 represents a novel therapeutic target for neoplastic diseases. Inhibitors are in need to explore the druggability and the therapeutic options of this enzyme. A bottleneck in the search for new inhibitors is the availability of the target for testing. Therefore an assay was developed to provide easy access to CK2 for discovery of novel inhibitors. Results: Autodisplay was used to present human CK2 on the surface of Escherichia coli. Heterotetrameric CK2 consists of two subunits, α and β, which were displayed individually on the surface. Co-display of CK2α and CK2β on the cell surface led to the formation of functional holoenzyme, as demonstrated by NaCl dependency of enzymatic activity, which differs from that of the catalytic subunit CK2α without β. In addition interaction of CK2α and CK2β at the cell surface was confirmed by co-immunoprecipitation assays. Surface displayed CK2 holoenzyme enabled an easy IC50 value determination. The IC50 values for the known CK2 inhibitors TBB and Silmitasertib were determined to be 50 and 3.3 nM, respectively. Conclusion: Surface-displayed CK2α and CK2β assembled on the cell surface of E. coli to an active tetrameric holoenzyme. The whole-cell CK2 autodisplay assay as developed is suitable for inhibition studies. Furthermore, it can be used to determine quantitative CK2 inhibition data such as IC50 values. In summary, this is the first report on the functional surface display of a heterotetrameric enzyme on E. coli.<br

Multi-model study of mercury dispersion in the atmosphere: vertical and interhemispheric distribution of mercury species

Atmospheric chemistry and transport of mercury play a key role in the global mercury cycle. However, there are still considerable knowledge gaps concerning the fate of mercury in the atmosphere. This is the second part of a model intercomparison study investigating the impact of atmospheric chemistry and emissions on mercury in the atmosphere. While the first study focused on ground-based observations of mercury concentration and deposition, here we investigate the vertical and interhemispheric distribution and speciation of mercury from the planetary boundary layer to the lower stratosphere. So far, there have been few model studies investigating the vertical distribution of mercury, mostly focusing on single aircraft campaigns. Here, we present a first comprehensive analysis based on various aircraft observations in Europe, North America, and on intercontinental flights. The investigated models proved to be able to reproduce the distribution of total and elemental mercury concentrations in the troposphere including interhemispheric trends. One key aspect of the study is the investigation of mercury oxidation in the troposphere. We found that different chemistry schemes were better at reproducing observed oxidized mercury patterns depending on altitude. High concentrations of oxidized mercury in the upper troposphere could be reproduced with oxidation by bromine while elevated concentrations in the lower troposphere were better reproduced by OH and ozone chemistry. However, the results were not always conclusive as the physical and chemical parameterizations in the chemistry transport models also proved to have a substantial impact on model results

Occurrence and timing of withdrawal of life-sustaining measures in traumatic brain injury patients: a CENTER-TBI study

Funder: National Institute for Health Research (UK)Abstract: Background: In patients with severe brain injury, withdrawal of life-sustaining measures (WLSM) is common in intensive care units (ICU). WLSM constitutes a dilemma: instituting WLSM too early could result in death despite the possibility of an acceptable functional outcome, whereas delaying WLSM could unnecessarily burden patients, families, clinicians, and hospital resources. We aimed to describe the occurrence and timing of WLSM, and factors associated with timing of WLSM in European ICUs in patients with traumatic brain injury (TBI). Methods: The CENTER-TBI Study is a prospective multi-center cohort study. For the current study, patients with traumatic brain injury (TBI) admitted to the ICU and aged 16 or older were included. Occurrence and timing of WLSM were documented. For the analyses, we dichotomized timing of WLSM in early (< 72 h after injury) versus later (≥ 72 h after injury) based on recent guideline recommendations. We assessed factors associated with initiating WLSM early versus later, including geographic region, center, patient, injury, and treatment characteristics with univariable and multivariable (mixed effects) logistic regression. Results: A total of 2022 patients aged 16 or older were admitted to the ICU. ICU mortality was 13% (n = 267). Of these, 229 (86%) patients died after WLSM, and were included in the analyses. The occurrence of WLSM varied between regions ranging from 0% in Eastern Europe to 96% in Northern Europe. In 51% of the patients, WLSM was early. Patients in the early WLSM group had a lower maximum therapy intensity level (TIL) score than patients in the later WLSM group (median of 5 versus 10) The strongest independent variables associated with early WLSM were one unreactive pupil (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.3–12.4) or two unreactive pupils (OR 5.8, CI 2.6–13.1) compared to two reactive pupils, and an Injury Severity Score (ISS) if over 41 (OR per point above 41 = 1.1, CI 1.0–1.1). Timing of WLSM was not significantly associated with region or center. Conclusion: WLSM occurs early in half of the patients, mostly in patients with severe TBI affecting brainstem reflexes who were severely injured. We found no regional or center influences in timing of WLSM. Whether WLSM is always appropriate or may contribute to a self-fulfilling prophecy requires further research and argues for reluctance to institute WLSM early in case of any doubt on prognosis