The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Adenomyosis, endometriosis, endometritis, and typical endometrial hyperplasia are common non-cancerous diseases of the endometrium that afflict many women with life-impacting consequences. The mammalian target of the rapamycin (mTOR) pathway interacts with estrogen signaling and is known to be dysregulated in endometrial cancer. Based on this knowledge, we attempt to investigate the role of mTOR signaling in benign endometrial diseases while focusing on how the interplay between mTOR and eukaryotic translation initiation factors (eIFs) affects their development. In fact, mTOR overactivity is apparent in adenomyosis, endometriosis, and typical endometrial hyperplasia, where it promotes endometrial cell proliferation and invasiveness. Recent data show aberrant expression of various components of the mTOR pathway in both eutopic and ectopic endometrium of patients with adenomyosis or endometriosis and in hyperplastic endometrium as well. Moreover, studies on endometritis show that derangement of mTOR signaling is linked to the establishment of endometrial dysfunction caused by chronic inflammation. This review shows that inhibition of the mTOR pathway has a promising therapeutic effect in benign endometrial conditions, concluding that mTOR signaling dysregulation plays a critical part in their pathogenesis.     

The Discovery and Structure-Activity Evaluation of (+)-Floyocidin B and Synthetic Analogs

Tuberculosis represents one of the ten most common courses of death worldwide and the emergence of multidrug-resistant M. tuberculosis makes the discovery of novel anti-tuberculosis active structures an urgent priority. Here, we show that (+)-floyocidin B representing the first example of a novel dihydroisoquinoline class of fungus-derived natural products, displays promising antitubercular hit properties. (+)-Floyocidin B was identified by activity-guided extract screening and its structure was unambiguously determined by total synthesis. The absolute configuration was deduced from a key synthesis intermediate by single crystal X-ray diffraction analysis. A hit series was generated by the isolation of further natural congeners and the synthesis of analogs of (+)-floyocidin B. Extensive biological and physicochemical profiling of this series revealed first structure-activity relationships and set the basis for further optimization and development of this novel antitubercular scaffold.     

Effect of binder system on the thermophysical properties of 3D-printed zirconia ceramics

Fabrication of 3D-printed ceramic parts with high complexity and high spatial resolution often demands low wall thickness as well as high stiffness at the green state, whereas printing simpler geometries may tolerate thicker, more compliant walls with the advantage of a rapid binder-burn-out and sintering process. In this work, the influence of the binder system on the thermophysical properties of 3D-printed stabilized zirconia ceramics was investigated. Samples were fabricated with the lithography-based ceramic manufacturing (LCM) technology using two different photosensitive ceramic suspensions (LithaCon 3Y230 and LithaCon 3Y210), with the same ZrO₂ powder. A significant difference in stiffness in the green state (~3 MPa vs. ~32 MPa for LithaCon 3Y230 and LithaCon 3Y210, respectively) was measured, associated with a rather loose or a linked network formed in the binder due to photopolymerization. Both materials reached high relative densities, that is, >99%, exhibiting a homogeneous fine-grained microstructure. No significant differences on the coefficient of thermal expansion (11.18 ppm/K vs. 11.17 ppm/K) or Young's modulus (207 GPa vs. 205 GPa) were measured, thus demonstrating the potential of tailoring binder systems to achieve the required accuracy in 3D-printed parts, without detrimental effects on material's microstructure and thermophysical properties at the sintered state.     

Self-assembled microstructured polymeric and ceramic surfaces

Self-assembled microstructures were manufactured by dip coating of substrates with unfilled and filler-loaded preceramic polymer mixtures in the presence of a solvent and a non-solvent. The nature of the polymers was characterized by their solubility parameters. Variation of the polymer/polymer ratio and the volume fraction of the solvent and/or non-solvent led to different surface structures. Studies of the structure formation mechanism indicate that demixing processes of the polymers are responsible for self-assembly in filler-free mixtures. In filler-loaded mixtures the structure formation process, however, is more complex. The micro-structured polymeric coatings obtained from filler loaded systems were converted into polymer derived ceramic coatings under shape retention. High specific surface areas were measured after thermal conversion.     

Me-DLC films as material for highly sensitive temperature compensated strain gauges

In technical applications strain gauges are widely used. Apart from conventional polymer foil based strain gauges that are glued to the work piece surface, sputtered strain gauges are already commercially used in special applications. Those sputter strain gauges are typically made of NiCr alloy and the sensor layer is as sensitive to strain as the ones used in the glued strain gauges with a gauge factor of 2, but neglecting problems of creeping and swelling of the involved polymer materials. Diamond-like carbon (DLC) films offer significantly higher strain sensitivity, but usually they are also very sensitive to temperature effects. Using metal doped diamond-like carbon (Me-DLC), higher strain sensitivity than conventional metal based systems, in combination with thermal compensation, is possible. The influence of different process parameters on the gauge factor and temperature coefficient of resistance (TCR) of DLC and Me-DLC films produced in industrial sputtering systems was investigated. Gauge factors up to 13 in combination with a high negative TCR in the range of a few thousand ppm/K were reached with sputtered DLC films. The substrate bias voltage in particular showed a strong influence on the resulting gauge factor of the films. For Me-DLC films different deposition methods (dc and rf sputtering) and various doping metals (Ag, Ni, Ti, and W) were investigated. Using dc sputtering of the Me-DLC films only Ni-DLC showed gauge factors slightly higher than 2. Furthermore, only for Ni-DLC zero crossing of the TCR was observed by variation of the metal content. Using rf excitation especially Ni-DLC films showed gauge factors exceeding values of 15 in combination with a TCR close to zero.     

Kinetics of nucleation and crystallization in poly(?-caprolactone) (PCL)

The recently developed differential fast scanning calorimetry (DFSC) is used for a new look at the crystal growth of poly(?-caprolactone) (PCL) from 185 K, below the glass transition temperature, to 330 K, close to the equilibrium melting temperature. The DFSC allows temperature control of the sample and determination of its heat capacity using heating rates from 50 to 50,000 K/s. The crystal nucleation and crystallization halftimes were determined simultaneously. The obtained halftimes cover a range from 3 × 10⁻² s (nucleation at 215 K) to 3 × 10⁹ s (crystallization at 185 K). After attempting to analyze the experiments with the classical nucleation and growth model, developed for systems consisting of small molecules, a new methodology is described which addresses the specific problems of crystallization of flexible linear macromolecules. The key problems which are attempted to be resolved concern the differences between the structures of the various entities identified and their specific role in the mechanism of growth. The structures range from configurations having practically unmeasurable latent heats of ordering (nuclei) to being clearly-recognizable, ordered species with rather sharp disordering endotherms in the temperature range from the glass transition to equilibrium melting for increasingly perfect and larger crystals. The mechanisms and kinetics of growth involve also a detailed understanding of the interaction with the surrounding rigid-amorphous fraction (RAF) in dependence of crystal size and perfection.     

n-Type Doping of Vapor–Liquid–Solid Grown GaAs Nanowires

In this letter, n-type doping of GaAs nanowires grown by metal–organic vapor phase epitaxy in the vapor–liquid–solid growth mode on (111)B GaAs substrates is reported. A low growth temperature of 400°C is adjusted in order to exclude shell growth. The impact of doping precursors on the morphology of GaAs nanowires was investigated. Tetraethyl tin as doping precursor enables heavily n-type doped GaAs nanowires in a relatively small process window while no doping effect could be found for ditertiarybutylsilane. Electrical measurements carried out on single nanowires reveal an axially non-uniform doping profile. Within a number of wires from the same run, the donor concentrations N _D of GaAs nanowires are found to vary from 7 × 10¹⁷ cm^-3 to 2 × 10¹⁸ cm^-3. The n-type conductivity is proven by the transfer characteristics of fabricated nanowire metal–insulator-semiconductor field-effect transistor devices.     

The use of microwave irradiation for the easy synthesis of graphene-supported transition metal nanoparticles in ionic liquids

Stable ruthenium or rhodium metal nanoparticles were supported on chemically derived graphene (CDG) surfaces with small and uniform particle sizes (Ru 2.2 ± 0.4 nm and Rh 2.8 ± 0.5 nm) by decomposition of their metal carbonyl precursors by rapid microwave irradiation in a suspension of CDG in the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate. The graphene-supported hybrid nanoparticles were shown to be active and could be re-used at least 10 times as catalysts for the hydrogenation of cyclohexene and benzene under organic-solvent-free conditions with constant activities up to 1570 mol cyclohexane × (mol metal)⁻¹ × h⁻¹ at 4 bar and 75 °C.     

Modeling and in-depth analysis of the start-up of dividing-wall columns

Saving potentials of up to 30% in capital and operating costs are the driving forces behind the increase in the application of dividing-wall columns in industry. However, a lack of knowledge still exists when dealing with the start-up of dividing-wall columns, which is inherently a strongly nonlinear process. Here, for the first time the start-up of dividing-wall columns is explored, where the starting point is an empty column at ambient conditions. A model is presented which is capable of predicting the dynamic discrete-continuous changes which are characteristic of dividing-wall columns. The proposed process model takes into account the heat transfer across the dividing wall as well as the vapor distribution below the dividing wall. The degree of accuracy of the model is clearly determined by comparing different simplifications, e.g. a constant vapor distribution ratio equal to the steady-state value. The detailed studies were carried out with strict product specifications so that the influence of process parameters could be quantified. The rigorous process model and the obtained simulation results presented in this study provide a promising basis for developing and applying optimal start-up policies for dividing-wall columns.     

Effect of Melt Processing on Crystallization Behavior and Rheology of Poly(3‐hydroxybutyrate) (PHB) and its Blends

Poly(3‐hydroxybutyrate) (PHB) is sensitive to high processing temperatures. This leads to a decrease in molar mass as well as a lower melt viscosity. The crystallization temperature shifts to lower values, and crystallization kinetics is slow. A mixture was developed in order to improve the manufacturing properties and the final product. The blends exhibit a slight reduction in molar mass because they have a lower melting point than pure PHB, and can be extruded at their melt temperature of 170 to 180°C. Then they immediately crystallize at 125 to 100°C. Differential scanning calorimetry (DSC) shows the effect of holding time in the melt on crystallization behavior. It has been shown that the crystallization time has to be longer in the case of PHB and shorter for the blends. Thermal degradation of PHB and its blends has been investigated using thermogravimetry analysis (TG). Derivative thermogravimetry coupled with TG (TG/DTG) curves show three decomposition stages for blends at 290, 340 and 445°C, respectively. Acetic acid, water, carbon dioxide and methane are produced by degradation at a higher temperature.