Kidney Injury Caused by Preeclamptic Pregnancy Recovers Postpartum in a Transgenic Rat Model

Preeclampsia (PE) is characterized by the onset of hypertension (≥140/90 mmHg) and presence of proteinuria (>300 mg/L/24 h urine) or other maternal organ dysfunctions. During human PE, renal injuries have been observed. Some studies suggest that women with PE diagnosis have an increased risk to develop renal diseases later in life. However, in human studies PE as a single cause of this development cannot be investigated. Here, we aimed to investigate the effect of PE on postpartum renal damage in an established transgenic PE rat model. Female rats harboring the human-angiotensinogen gene develop a preeclamptic phenotype after mating with male rats harboring the human-renin gene, but are normotensive before and after pregnancy. During pregnancy PE rats developed mild tubular and glomerular changes assessed by histologic analysis, increased gene expression of renal damage markers such as kidney injury marker 1 and connective-tissue growth factor, and albuminuria compared to female wild-type rats (WT). However, four weeks postpartum, most PE-related renal pathologies were absent, including albuminuria and elevated biomarker expression. Only mild enlargement of the glomerular tuft could be detected. Overall, the glomerular and tubular function were affected during pregnancy in the transgenic PE rat. However, almost all these pathologies observed during PE recovered postpartum.     

Probing the Conformation States of Neurotensin Receptor 1 Variants by NMR Site-Directed Methyl Labeling

G protein-coupled receptors (GPCRs) are key players in mediating signal transduction across the cell membrane. However, due to their intrinsic instability, many GPCRs are not suitable for structural investigations. Various approaches have been developed in recent years to remedy this situation, ranging from the use of more native membrane mimetics to protein-stabilization methods. The latter approach typically results in GPCRs that contain various numbers of mutations. However, probing the functionality of such variants by in vitro and in vivo assays is often time consuming. In addition, to validate the suitability of such GPCRs for structural investigations, an assessment of their conformation state is required. NMR spectroscopy has been proven to be suitable to probe the conformation state of GPCRs in solution. Here, by using chemical labeling with an isotope-labeled methyl probe, we show that the activity and the conformation state of stabilized neurotensin receptor 1 variants obtained from directed evolution can be efficiently assayed in 2D NMR experiments. This strategy enables the quantification of the active and inactive conformation states and the derivation of an estimation of the basal as well as agonist-induced activity of the receptor. Furthermore, this assay can be used as a readout when re-introducing agonist-dependent signaling into a highly stabilized, and thus rigidified, receptor by mutagenesis. This approach will be useful in cases where low production yields do not permit the addition of labeled compounds to the growth medium and where 1D NMR spectra of selectively ¹⁹F-labeled receptors are not sufficient to resolve signal overlap for a more detailed analysis.     

Comments on “Necessary and sufficient stability condition of fractional-order interval linear systems” [Automatica 44 (2008), 2985–2988]

This paper shows that the main thesis of the article “Necessary and sufficient stability condition of fractional-order interval linear systems” by Ahn and Chen (Automatica, vol. 44, pp. 2985–2988) is only a sufficient (and not a necessary) condition for the robust stability of fractional-order linear systems.     

Reactive path integral quantum simulations of molecules solvated in superfluid helium

A hybrid ab initio   path integral molecular dynamics/bosonic path integral Monte Carlo simulation method has been developed, implemented and tested, which allows for the reactive simulations of molecules, clusters or complexes solvated by superfluid ⁴${}^4$He. The simulation takes into account “on-the-fly” the electronic structure and thus the chemical reactivity of the solutes, in conjunction with the Bose–Einstein statistics, and thus the superfluid character of this peculiar solvent. This enables investigations into cryochemical reactions taking place in helium nanodroplets, such as those used in helium nanodroplet isolation (HENDI) spectroscopy.     

Spezifische Bedarfe bei zahnärztlichen Patienten mit Demenz und ihre ethischen Implikationen

Definition of the problem

The central foundations of successful dental treatment consist of a trustful patient-dentist relationship, the professional and psychosocial expertise of the team treating the patient, and consideration of ethical aspects both during the therapeutic decision-making process and during the subsequent execution of therapy. This is especially true of the dental treatment of (mostly elder) persons with dementia, calling for an in-depth assessment of the various normative implications.

Arguments

In geriatric dentistry in particular, situational dilemmas regarding treatment often arise from specific constellations (e.?g. greatly reduced potential for dental therapy, lack of ability regarding oral hygiene and lack of individual patient responsibility) combined with an acute need for treatment and the necessary involvement of third parties. These dilemmas frequently place additional professional and normative demands on the dentist. The current contribution discusses this specific situation, first by way of theoretical discourse and subsequently with a case-related approach on the basis of two case histories.

Conclusion

It becomes clear here that classic state-of-the-art therapies are replaced by “compromise treatment” in many cases in geriatric dentistry. Such treatment follows divergent diagnostic and therapeutic rules, poses changed requirements in terms of communication and presents specific ethical challenges and pitfalls.

     

MODELING OF CONTROLLED THERMO-MECHANICAL PROCESSING OF TUBES FOR ENHANCED MANUFACTURING AND PERFORMANCE

1.IntroductionApproximately15milliontonsofsteeltubeandpipeproductsareconsumedintheUnitedStatesannually.Mechanicaltubesarethefeedstocksusedinthemanufactureofrollingelementbearings,hydrauliccylinders,alldagreatvarietyofpowertransmissioncomponents.Steeltubesarealsoemployedinthedrillstringsforoilandnaturalgasexplorationandrecovery.Steelpipesareusedinthetransportofgas,oilandotherfluids.ControlledThermal--MechanicalProcessing(CTMP)involvesprecisecontroloftemperature,mechanicaldeformation,andmicr…     

Cellular analysis by open-source software for affordable cytometry

Image cytometry is an important technique in affordable healthcare and cellular research. Some efforts toward establishing a personal, low-cost cytometer have been described in the literature. However, a self-assembled fluorescence microscope requires software for cytometric analysis. There are some open-source image-based software analysis applications available. However, for a quantitative analysis of images, software that can generate data comparable to those of previously evaluated cytometric analyses programs is required. Hence, the aim of this study is to compare results of a commercially available image cytometry program to data obtained using the open-source software CellProfiler (CP). Leukocytes and fluorescent bead images obtained using a Laser Scanning Cytometer were analyzed by CP and the results compared with those of conventional cytometric analyses' programs. Algorithms were developed enabling the analysis of leukocytes and beads by CP. CP provided similar results to those obtained by the cytometer software. Hallmark parameters, including cell count and fluorescence intensity, revealed a high correlation in the analysis of both programs. Therefore, CP is appropriate for cellular analysis on a self-assembled microscope, thereby enabling affordable cytometry.     

Space-efficient region filling in raster graphics

This paper presents fill algorithms for boundary-defined regions in raster graphics. The algorithms require only a constant-size working memory. The methods presented are based on the so-called seed fill algorithms that use the internal connectivity of the region with a given inner point. Basic methods, as well as additional hcuristics for speeding up the algorithm, are described and verified. Empirical results are used to compare the time complexities of the algorithms for different classes of regions.     

Glyphosate Adsorption from Water Using Hierarchically Porous Metal–Organic Frameworks

The selective removal of one ligand in mixed-ligand MOFs upon thermolysis provides a powerful strategy to introduce additional mesopores without affecting the overall MOF structure. By varying the initial ligand ratio, MOFs of the MIL-125-Ti family with two distinct hierarchical pore architectures are synthesized, resembling either large cavities or branching fractures. The performance of the resulting hierarchically porous MOFs is evaluated toward the adsorptive removal of glyphosate (N-(phosphonomethyl)glycine) from water, and the adsorption kinetics and mechanism are examined. Due to their strong affinity for phosphoric groups, the numerous Ti–OH groups resulting from the selective ligand removal act as natural anchor points for effective glyphosate uptake. The relationships between contact duration, glyphosate concentration, and adsorbent dosage are investigated, and the impact of these parameters on the effectiveness of glyphosate removal from contaminated water samples is examined. The introduction of additional mesopores has increased the adsorption capacities by nearly 3 times with record values exceeding 440.9 mg g⁻¹, which ranks these MOFs among the best-reported adsorbents.