Steroid biosynthetic enzyme activities in leachate-exposed female perch (Perca fluviatilis) as biomarkers for endocrine disruption

Studies have shown that adult female perch in a freshwater lake, Molnbyggen, Sweden, have a reproductive disorder caused by unidentified endocrine disrupting compounds (EDCs) leaching from a local refuse dump. The adverse effects include shallow open sores, low ratio of sexually mature individuals, low gonadosomatic index and low circulating levels of androgens. We hypothesised that the low androgen levels could be a result of impaired production and/or stimulated excretion of androgens by EDCs. From October 2000 to November 2001, at time-points important in the perch reproductive cycle, adult female perch were collected in Molnbyggen and in the reference lake, Djursj?n. The activities of three key enzymes in androgen biosynthesis: 17alpha-hydroxylase (17OHlase), 17,20-lyase (lyase) and 17beta-hydroxysteroid dehydrogenase (17betaHSD) were determined in head kidney or ovary. The relationship between enzyme activities and plasma steroid concentrations was examined. Ovarian histopathology and the determination of brain aromatase activity were also included in the study. Similar 17OHlase, 17betaHSD and aromatase activities were found in Molnbyggen females and reference fish throughout the year. Head kidney 17OHlase showed a positive correlation to cortisol levels (r=0.754; p<0.001) but not to androgen levels. Molnbyggen females exhibited lower ovarian lyase activity during vitellogenesis than reference fish. Atretic oocytes were on most occasions more frequent in sexually immature than in sexually mature females. The results suggest that neither 17OHlase, 17betaHSD nor aromatase is the target for EDCs disrupting the androgen homeostasis of exposed female perch. Further investigation is needed to establish the role of decreased ovarian lyase activity in endocrine homeostasis, but the possibility of increased excretion of androgens should also be examined.     

Kernel methods in system identification,machine learning and function estimation: A survey

Most of the currently used techniques for linear system identification are based on classical estimation paradigms coming from mathematical statistics. In particular, maximum likelihood and prediction error methods represent the mainstream approaches to identification of linear dynamic systems, with a long history of theoretical and algorithmic contributions. Parallel to this, in the machine learning community alternative techniques have been developed. Until recently, there has been little contact between these two worlds. The first aim of this survey is to make accessible to the control community the key mathematical tools and concepts as well as the computational aspects underpinning these learning techniques. In particular, we focus on kernel-based regularization and its connections with reproducing kernel Hilbert spaces and Bayesian estimation of Gaussian processes. The second aim is to demonstrate that learning techniques tailored to the specific features of dynamic systems may outperform conventional parametric approaches for identification of stable linear systems.     

Synthesis of Novel Pyridine-Carboxylates as Small-Molecule Inhibitors of Human Aspartate/Asparagine-β-Hydroxylase

The human 2-oxoglutarate (2OG)-dependent oxygenase aspartate/asparagine-β-hydroxylase (AspH) is a potential medicinal chemistry target for anticancer therapy. AspH is present on the cell surface of invasive cancer cells and accepts epidermal growth factor-like domain (EGFD) substrates with a noncanonical (i. e., Cys 1–2, 3–4, 5–6) disulfide pattern. We report a concise synthesis of C-3-substituted derivatives of pyridine-2,4-dicarboxylic acid (2,4-PDCA) as 2OG competitors for use in SAR studies on AspH inhibition. AspH inhibition was assayed by using a mass spectrometry-based assay with a stable thioether analogue of a natural EGFD AspH substrate. Certain C-3-substituted 2,4-PDCA derivatives were potent AspH inhibitors, manifesting selectivity over some, but not all, other tested human 2OG oxygenases. The results raise questions about the use of pyridine-carboxylate-related 2OG analogues as selective functional probes for specific 2OG oxygenases, and should aid in the development of AspH inhibitors suitable for in vivo use.     

Location of biomarkers and reagents within agarose beads of a programmable bio-nano-chip

The slow development of cost-effective medical microdevices with strong analytical performance characteristics is due to a lack of selective and efficient analyte capture and signaling. The recently developed programmable bio-nano-chip (PBNC) is a flexible detection device with analytical behavior rivaling established macroscopic methods. The PBNC system employs ≈300 μm-diameter bead sensors composed of agarose "nanonets" that populate a microelectromechanical support structure with integrated microfluidic elements. The beads are an efficient and selective protein-capture medium suitable for the analysis of complex fluid samples. Microscopy and computational studies probe the 3D interior of the beads. The relative contributions that the capture and detection of moieties, analyte size, and bead porosity make to signal distribution and intensity are reported. Agarose pore sizes ranging from 45 to 620 nm are examined and those near 140 nm provide optimal transport characteristics for rapid (<15 min) tests. The system exhibits efficient (99.5%) detection of bead-bound analyte along with low (≈2%) nonspecific immobilization of the detection probe for carcinoembryonic antigen assay. Furthermore, the role analyte dimensions play in signal distribution is explored, and enhanced methods for assay building that consider the unique features of biomarker size are offered.     

Spreading dynamics of a functionalized polymer latex

Functionalized polymer nanoparticles are used as binders for inorganic materials in everyday technologies such as paper and coatings. However, the functionalization can give rise to two opposing effects: It can promote adhesion via specific interactions to the substrate, but a high degree of functionalization can also hamper spreading on substrates. Here, we studied the spreading kinetics of individual functionalized vinyl acetate-co-ethylene polymer nanoparticles on inorganic substrates by atomic force microscopy (AFM) imaging. We found that the kinetics underwent a transition from a fast initial regime to a slower regime. The transition was independent of functionalization of the particles but depended on the wettability of the substrate. Furthermore, the transition from the fast regime to the slow regime occurred at a size-dependent contact angle, leading to a h ～ a(3/2) scaling dependence between the height (h) and the width (a) of the spreading particles. Thereafter, spreading continued on a slower time scale. In the slow regime, the kinetics was blocked by a high degree of functionalization. We interpret the observations in terms of a nanoscale stick-slip transition occurring at interface stress around 6 kPa. We develop models that describe the scaling relations between the particle height and width on different substrates.     

Cost modelling in underpinning projects

Large refurbishment projects are characterized by highly varied costs from one project to another. In Finnish underpinning, only retrospective analysis of costs has been available for the owner’s decision process. In order to develop tools for pre‐tender cost estimating and for comparison of different design solutions and evaluation of tenders of the underpinning project, two different cost models have been developed for research. In both models developed, the minimum data required is the pile length. In the more detailed model, the assessment is based on the design solution, including known pile types and the load transfer classification. Both models are easy to use, and the percentage of explained variance is fairly good in the more detailed model.     

Post-COVID-19 Syndrome: Retinal Microcirculation as a Potential Marker for Chronic Fatigue

Post-COVID-19 syndrome (PCS) is characterized by persisting sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PCS can affect patients with all COVID-19 disease severities. As previous studies have revealed impaired blood flow as a provoking factor triggering PCS, it was the aim of the present study to investigate the potential association between self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT angiography (OCT-A) and quantified using the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic fatigue (CF) was assessed according to the variables of Bell’s score, age and gender. VDs in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed, considering the repetitions (12 times). Seropositivity for autoantibodies targeting G protein-coupled receptors (GPCR-AAbs) was determined by an established cardiomyocyte bioassay. Taking account of the repetitions, a mixed model was performed to detect possible differences in the least square means between the different groups included in the analysis. An age effect in relation to VD was observed between patients and controls (p < 0.0001). Gender analysis showed that women with PCS showed lower VD levels in the SVP compared to male patients (p = 0.0015). The PCS patients showed significantly lower VDs in the ICP as compared to the controls (p = 0.0001 (CI: 0.32; 1)). Moreover, considering PCS patients, the mixed model revealed a significant difference between those with chronic fatigue (CF) and those without CF with respect to VDs in the SVP (p = 0.0033 (CI: −4.5; −0.92)). The model included variables of age, gender and Bell’s score, representing a subjective marker for CF. Consequently, retinal microcirculation might serve as an objective biomarker in subjectively reported chronic fatigue in patients with PCS.     

Effect of dietarytrans fatty acids on microsomal enzymes and membranes

Three groups of rats were maintained on diets containing different proportions oftrans fatty acids (0, 18.3 or 36.6% of the total fatty acids) for eight weeks. No differences in body weight were observed among the three groups, but the fat cell size, determined in epididymal fat, differed significantly between the controls and the rats fed diets containingtrans fatty acids. The supernatant obtained by centrifuging homogenates of liver from the rats at 9000×g (S-9 fraction) was used as an activator in a bacterial test for mutagenicity of 2-aminofluorene and aflatoxin B₁ usingSalmonella typhimurium strains TA 98 and TA 100, respectively. The mutagenicities of 2-aminofluorene in strain TA 98 and of aflatoxin B₁ in strain TA 100 were significantly lower with the liver S-9 fraction from rats fed a diet containing 36.6%trans fatty acids than with the liver S-9 fraction from rats fed a control diet with notrans fatty acids.     

Estimation of Hamaker Constants of Ceramic Materials from Optical Data Using Lifshitz Theory

The Hamaker constants of eight different ceramic materials, 6H-SiC, tetragonal, partially stabilized ZrO₂ (3% Y₂O₃), β-Si₃N₄, α-Al₂O₃, Y₂O₃, sapphire (single-crystal α-Al₂O₃), MgO, MgAl₂O₄, and fused silica, across air, water, and n -dodecane at room temperature and across silica at 2000 K have been calculated from optical data using the Lifshitz theory. Spectroscopic ellipsometry was used to measure the photon energy dependence of the refractive index, n , and the extinction coefficient, k , in the visible and near-UV range on several important ceramic materials. This relatively simple, nondestructive technique has proved to yield reliable optical data on sintered, polycrystalline materials such as Si₃N₄, SiC, ZrO₂, Al₂O₃, and ZnO. For the other materials, Y₂O₃, sapphire, MgO, MgAl₂O₄, and fused silica, optical data from the literature were used to calculate the Hamaker constants. The calculated Hamaker constants were estimated to be accurate within ±10%.