HEPA/Vaccine Plan for Indoor Anthrax Remediation

A mathematical model suggests that a HEPA/vaccine approach is viable for most buildings after a large-scale anthrax attack

[18F]Atorvastatin:synthesis of a potential molecular imaging tool for the assessment of statin-related mechanisms of action

BACKGROUND: Statins are lipid-lowering agents that inhibit cholesterol synthesis and are clinically used in the primary and secondary prevention of cardiovascular diseases. However, a considerable group of patients does not respond to statin treatment, and the reason for this is still not completely understood. [18F]Atorvastatin, the 18F-labeled version of one of the most widely prescribed statins, may be a useful tool for statin-related research. RESULTS: [18F]Atorvastatin was synthesized via an optimized ruthenium-mediated late-stage 18F-deoxyfluorination. The defluoro-hydroxy precursor was produced via Paal-Knorr pyrrole synthesis and was followed by coordination of the phenol to a ruthenium complex, affording the labeling precursor in approximately 10% overall yield. Optimization and automation of the labeling procedure reliably yielded an injectable solution of [18F]atorvastatin in 19% ± 6% (d.c.) with a molar activity of 65 ± 32 GBq·μmol-1. Incubation of [18F]atorvastatin in human serum did not lead to decomposition. Furthermore, we have shown the ability of [18F]atorvastatin to cross the hepatic cell membrane to the cytosolic and microsomal fractions where HMG-CoA reductase is known to be highly expressed. Blocking assays using rat liver sections confirmed the specific binding to HMG-CoA reductase. Autoradiography on rat aorta stimulated to develop atherosclerotic plaques revealed that [18F]atorvastatin significantly accumulates in this tissue when compared to the healthy model. CONCLUSIONS: The improved ruthenium-mediated 18F-deoxyfluorination procedure overcomes previous hurdles such as the addition of salt additives, the drying steps, or the use of different solvent mixtures at different phases of the process, which increases its practical use, and may allow faster translation to clinical settings. Based on tissue uptake evaluations, [18F]atorvastatin showed the potential to be used as a tool for the understanding of the mechanism of action of statins. Further knowledge of the in vivo biodistribution of [18F]atorvastatin may help to better understand the origin of off-target effects and potentially allow to distinguish between statin-resistant and non-resistant patients

Mobility after job loss in Germany: the effects of regional economic opportunities and economic worries on mobility intentions and behaviour

This study examines the impact of local economic opportunity structures on mobility intentions and mobility behaviour subsequent to involuntary job loss in Germany. Previous research has demonstrated that job loss leads to an increased propensity for regional mobility; however, the role of the regional economy as a push factor and its influence on the decision to relocate remains unclear. The focus of the study at hand is on the opportunities provided by locational factors and an examination of the broader context in which regional mobility after job loss occurs. Logistic regression models are set up using data from the German Socio-Economic Panel study, which is complemented by a unique combination of spatial structure indicators. The results demonstrate that job loss has no effect on the mobility intentions of displaced workers. However, it increases the propensity to relocate within Germany. Furthermore, a favourable economic situation in the home region makes mobility intentions of displaced workers less likely. This is indicated by a negative effect of the local GDP and a positive effect of the occupation-specific local unemployment rate. A mediation analysis does not confirm a hypothesised omitted variable bias of economic worries in the effect of regional economic characteristics on the mobility intentions of displaced workers

Navigating Regional Barriers to Job Mobility: The Role of Opportunity Structures in Individual Job-to-Job Transitions

Rickmeier K. Navigating Regional Barriers to Job Mobility: The Role of Opportunity Structures in Individual Job-to-Job Transitions. Social Sciences. 2023;12(5): 295.Job-to-job transitions are associated with career progression and wage gains. Thus, regional differences in job mobility potentially contribute to and reinforce regional and social inequalities. This study aims to close the research gap in the understanding of the regional contexts in which individual job mobility occurs. Using the theoretical concept of regional opportunity structures, three key aspects of region-related job changes are investigated: regional determinants of (1) general job mobility; (2) job mobility with wage gains; and (3) simultaneous job and residential mobility. This study is based on individual data from the German Socio-Economic Panel study, enriched with regional indicators. The results show that job changes are negatively associated with labour market tightness, indicating that workers are less likely to change jobs in regions with a high ratio of job vacancies to unemployed workers. Fewer job-to-job transitions in tighter labour markets suggests that regional factors such as job availability and security play an important role in shaping job mobility, and that policies aimed at promoting job transitions may need to consider the specificities of local labour markets. The effects of other indicators of economic opportunities remain insignificant, and there are no clear effects of other aspects of regional opportunity structures

18^{18}F-labeling of small molecules and peptides

As of 2018, the Food and Drug Administration (FDA) has approved just ten positron-emission-tomography (PET)-tracers, of which six have been developed in the last seven years. The overall low quantity of approved PET-tracers can be partly attributed to the lack of general methods to access potential tracers. The half-life of commonly used radionuclides is below two hours; therefore, the radionuclide should be introduced in the last step of the synthesis. The high density of functional groups on advanced molecular structures can lower the reactivity of fluoride, and can deactivate reagents and catalysts. New methods are required that tolerate high structural complexity and thereby permit access to new tracers. The group of Ritter has developed the highly functional group tolerant ruthenium-mediated radio-deoxyfluorination of phenols. The first chapter of this thesis describes an improved procedure for the ruthenium-mediated radio-deoxyfluorination, which has allowed us to obtain the otherwise inaccessible [18F]atorvastatin. Under basic conditions, selective complexation to the 4-hydroxyphenyl substituent over other aryl substituents in hydroxy-atorvastatin was achieved. The use of protic polar solvents enabled almost quantitative elution of [18F]fluoride from the anion exchange cartridge without the need for inversion. These improvements of the method allowed us to isolate [18F]atorvastatin in 20% radiochemical yield and we could show that it is stable in human and rat serum. Peptides are a favorable platform for the development of PET-tracers, because they can show very selective binding and rapid clearance from the bloodstream. Additionally, rapid synthesis of derivatives by solid phase peptide synthesis (SPPS) enables for the fast screening of a structural library. Over the last decade, many methods for polypeptide labeling with [18F]fluoride have been developed, however, all require the introduction of a prosthetic group that changes the properties of the peptide. The second part of this thesis reports a method that provides access to peptides containing 4-[18F]fluoro-phenylalanine side chains by radio-deoxyfluorination of a tyrosine residue bearing a traceless transition metal activating group. By merely exchanging one hydrogen or hydroxyl substituent of the native peptide structure with fluorine-18, the steric properties of the peptide are barely altered and thus its biological functions are likely preserved. The presented method tolerates all 20 canonical amino acids, allows the labeling on the C- terminus, N- terminus or within the peptide, and enables the labeling precursor to be easily accessed by SPPS using a novel ruthenium-containing amino acid building block

From means to margins: The uneven effects of hiring market concentration on the gender wage gap in Germany

In this paper, we study the impact of monopsony power on the gender wage differentials at various parts of the wage distribution from 2019 to 2022. We are measuring hiring labour market concentration by constructing the HHI on the basis of online job advertisement data from Germany.The wages and a rich set of demographic characteristics are acquired from the German Socio-Economic Panel. With the help of RIF-IV, we establish that the impact of labour market concentration is more pronounced in higher deciles of the distribution for the aggregated sample, reaching -2.4% for the monthly wages and -9.6% for the hourly ones. Respective values for the medians equal to -0.9% and -4.7%. However, disaggregating by sex reveals different distributional effects for women and men. For men, the effects are consistent with the aggregated sample, where the impact is insignificant in the lower deciles and increases towards the upper end. For women, however, the impact is highest at the lower and upper deciles and the set of effects demonstrates a hump-shape. Furthermore, women in western Germany are considerably more affected than women in the East. The findings suggests that hiring labour market concentration contributes to a widening of the gender wage gap especially at the lower end of the wage distribution