Cost Drivers of Operation Charges and Variation over Time: An Analysis Based on Semiparametric SUR Models

Although building operating charges have turned out to be a major determinant of profitability for real estate investments, there is a noticeable lack of reports or studies that analyze these costs with state-of-the-art statistical techniques. Specifically, past studies usually assume linear relationships between costs and building attributes, they do not control for cluster-specific or longitudinal effects and do not account for the simultaneous structure of cost categories. Therefore, in this study we provide a novel approach to real estate cost benchmarking: We analyze the effects of building attributes on electricity, heating and maintenance costs for office buildings in Germany in a multivariate structured additive regression (STAR) model simultaneously, modeling potentially nonlinear effects as P(enalized)-Splines and controlling for cluster-specific and individual heterogeneity in a three-way random effects structure. This way, we gain insights into how building attributes influence costs, and how cost levels vary across cities, companies and buildings. We furthermore derive quality-adjusted time indices for the two major German submarkets, the former German Democratic Republic and the old West German states. The results obtained can be used to derive portfolio allocation strategies and for planning, constructing, operating and redeveloping real estate

Identification of human in vitro metabolites of the haemoglobin S polymerization inhibitor voxelotor for doping control purposes

Voxelotor (GBT440) is a haemoglobin S polymerization inhibitor used to treat anaemia in sickle cell disease. Due to an increase of arterial oxygen saturation as well as serum erythropoietin and haemoglobin, the World Anti-Doping Agency included voxelotor in the list of prohibited substances and methods in 2023. The objective of the present study was to identify and characterize metabolites of voxelotor to detect a potential misuse by athletes. The biotransformation was studied in vitro using the human hepatocellular cell line HepG2 and pooled human liver microsomes. The metabolites were analysed using high-performance liquid chromatography (high-resolution) mass spectrometry. In total, three phase I metabolites and six phase II metabolites (resulting from glucuro-conjugation and O-methylation) were formed by the HepG2 cells in a time-dependent manner, and two phase I metabolites were generated by the liver microsomes, among them one also found in the HepG2 incubations. A reduced metabolite and the glucuro-conjugate of a reduced metabolite were the most abundant formed by HepG2 cells. In addition, metabolites resulting from mono-hydroxylation, reduction and O-methylation in different combinations were identified. Voxelotor was also found as glucuro-conjugate with a low abundance. With the spectrometric behaviour of voxelotor and its in vitro metabolites described herein, an implementation in doping control screening and, consequently, a detection of an abuse in an athlete urine sample might be possible

Localized Plasticity in the Streamlined Genomes of Vinyl Chloride Respiring Dehalococcoides

Vinyl chloride (VC) is a human carcinogen and widespread priority pollutant. Here we report the first, to our knowledge, complete genome sequences of microorganisms able to respire VC, Dehalococcoides sp. strains VS and BAV1. Notably, the respective VC reductase encoding genes, vcrAB and bvcAB, were found embedded in distinct genomic islands (GEIs) with different predicted integration sites, suggesting that these genes were acquired horizontally and independently by distinct mechanisms. A comparative analysis that included two previously sequenced Dehalococcoides genomes revealed a contextually conserved core that is interrupted by two high plasticity regions (HPRs) near the Ori. These HPRs contain the majority of GEIs and strain-specific genes identified in the four Dehalococcoides genomes, an elevated number of repeated elements including insertion sequences (IS), as well as 91 of 96 rdhAB, genes that putatively encode terminal reductases in organohalide respiration. Only three core rdhA orthologous groups were identified, and only one of these groups is supported by synteny. The low number of core rdhAB, contrasted with the high rdhAB numbers per genome (up to 36 in strain VS), as well as their colocalization with GEIs and other signatures for horizontal transfer, suggests that niche adaptation via organohalide respiration is a fundamental ecological strategy in Dehalococccoides. This adaptation has been exacted through multiple mechanisms of recombination that are mainly confined within HPRs of an otherwise remarkably stable, syntenic, streamlined genome among the smallest of any free-living microorganism

Cost Drivers of Operation Charges and Variation over Time: An Analysis Based on Semiparametric SUR Models

Although building operating charges have turned out to be a major determinant of profitability for real estate investments, there is a noticeable lack of reports or studies that analyze these costs with state-of-the-art statistical techniques. Specifically, past studies usually assume linear relationships between costs and building attributes, they do not control for cluster-specific or longitudinal effects and do not account for the simultaneous structure of cost categories. Therefore, in this study we provide a novel approach to real estate cost benchmarking: We analyze the effects of building attributes on electricity, heating and maintenance costs for office buildings in Germany in a multivariate structured additive regression (STAR) model simultaneously, modeling potentially nonlinear effects as P(enalized)-Splines and controlling for cluster-specific and individual heterogeneity in a three-way random effects structure. This way, we gain insights into how building attributes influence costs, and how cost levels vary across cities, companies and buildings. We furthermore derive quality-adjusted time indices for the two major German submarkets, the former German Democratic Republic and the old West German states. The results obtained can be used to derive portfolio allocation strategies and for planning, constructing, operating and redeveloping real estate.Benchmarking, operating charges, P-Splines, random effects, seemingly unrelated regression, structured additive regression

Agreement of steroid profiles in Athlete Biological Passport residues and corresponding serum samples

The steroid module of the Athlete Biological Passport (ABP) is based on the analysis of six endogenous steroids in urine samples and a Bayesian statistical approach. However, the urinary steroid concentrations may be affected by confounders like microbial degradation, possible co-administration of diuretics as masking agents, insufficient conjugate hydrolysis or UGT2B17 gene polymorphisms affecting glucuronidation. Therefore, it can be helpful to use other matrices (ABP blood and serum samples) to quantify steroids and thereby support noticeable deviations in the Athlete Biological Passport, for example, abnormally increased urinary testosterone/epitestosterone (T/E) ratios. Aim of the study was to investigate the feasibility to re-use plasma obtained from athlete ABP blood samples for measuring a steroid profile. Therefore, testosterone, androstenedione, cortisol and cortisone were quantified in 36 intra-individual matching ABP blood and serum samples. The steroid levels measured in both matrices showed a high agreement indicating a good stability uninfluenced by storage temperature and duration. Our results pointed out the possibility to expand the athlete ABP blood analysis for steroid profiling

Detection of 18-methyl steroids: case report on a forensic urine sample and corresponding dietary supplements

The detection of a putative 18-methyl-19-nortestosterone metabolite in a forensic bodybuilder's urine sample collected as part of a criminal proceeding has triggered a follow-up investigation. Four different dietary supplements in the possession of the suspect were examined with regard to possible precursor steroids. This led to the detection of the declared ingredient methoxydienone, which was confirmed by both, GC–MSMS and LC-HRMSMS. As neither 18-methyl-testosterone, nor 18-methyl-19-nortestosterone were detectable in the supplements, the possibility that the metabolite originates from methoxydienone was investigated. For this purpose, the metabolic fate of methoxydienone was studied in vitro using human HepG2 cells and in vivo by a single oral administration. While the 18-methyl-19-nortestosterone metabolite was not generated by HepG2 cells incubated with methoxydienone, it was observed in the urine samples collected at 2, 6, 10 and 24 h after methoxydienone administration. Moreover, the potential binding of methoxydienone as ligand to the human androgen receptor was modelled in silico in comparison with 18-methylnandrolone, for which androgen receptor activation had been shown in an in vitro approach before. In conclusion, we could ascribe the presence of the 18-methyl-19-nortestosterone metabolite in a forensic urine sample to originate from methoxydienone present in dietary supplements. Methoxydienone was observed to slowly degrade by demethylation of the methoxy substituent in liquid solutions. While no compound-specific intermediates were identified that allowed differentiation from other 18-methyl steroids, the 18-methyl-19-nortestosterone metabolite proved to be a suitable marker for reliable detection in doping analysis

Supplemental material for Influence of estrogen on individual exercise motivation and bone protection in ovariectomized rats

<p>Supplemental material for Influence of estrogen on individual exercise motivation and bone protection in ovariectomized rats by Sebastian T Müller, Annekathrin M Keiler, Kristin Kräker, Oliver Zierau, Ricardo Bernhardt in Laboratory Animals</p

Hemodynamic influence of design parameters of novel venous valve prostheses

Venous ulcers of the lower limbs are one clinical manifestation of chronic venous insufficiency. Currently, there is no venous valve prosthesis available. This study presents novel venous valve prostheses made of threedimensional electrospun fibrous nonwoven leaflets. The aim of this study was to prove the feasibility of the manufacturing process as well as to investigate design features of the venous valve prostheses from a hemodynamic point of view. An adapted pulse duplicator system (ViVitrolabs, Victoria, BC, CA) was used for characterization of the hydrodynamic performance. For eight different venous valve prototypes flow rate, effective orifice area and regurgitation fraction was investigated in vitro. In particular, tricusp valve designs showed an up to 40% higher effective orifice area as well as 15% higher maximum flowrate compared to bicusp valve designs. However, the regurgitation fraction of the bicusp valve designs is up to 86% lower compared to tricusp valve. Additionally, the hemodynamic performance of the tricuspid valves showed a high sensitivity regarding the leaflet length. Bicuspid valves are less sensitive to changes of design parameters, more sufficient and therefore highly reliable