Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer

Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) prolongs overall survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, men with low PSMA expression are excluded from RLT. We explored the effect of androgen receptor blockade with enzalutamide on PSMA expression. Assessment of PSMA and androgen receptor (AR) expression on the human PC cell lines 22Rv1, C4-2, and LNCaP by immunohistochemistry and flow cytometry revealed low (22Rv1) and high (C4-2 and LNCaP) PSMA expression, and high, comparable AR positivity. Treatment with enzalutamide increased PSMA levels in 22Rv1, C4-2, and LNCaP (2.2/2.3/2.6-fold, p = 0.0005/0.03/0.046) after one week compared to DMSO-treated controls as assessed by flow cytometry. NOD/Scid mice bearing 22Rv1 tumors were treated with enzalutamide for two weeks. Positron emission tomography/computed tomography (PET/CT) demonstrated higher tumor uptake of ⁶⁸Ga-PSMA after enzalutamide treatment (p = 0.004). Similarly, a clinical case with low baseline PSMA avidity demonstrated increased uptake of ⁶⁸Ga-PSMA after enzalutamide on PET/CT and post-therapeutic ¹⁷⁷Lu-PSMA scintigraphy in a patient with mCRPC. Enzalutamide induced PSMA expression in the 22Rv1 xenograft model and in an mCRPC patient, both with low baseline tumoral PSMA levels. Therefore, enzalutamide pre-treatment might render patients with low PSMA expression eligible for ¹⁷⁷Lu-PSMA RLT.     

Phase separation of binary blends in polymer nanoparticles

Polymer blends in nanoparticles have been studied by transmission electron microscopy (TEM) and photoluminescence (PL) spectroscopy. The TEM studies show that blend particles formed from two immiscible polymers by the miniemulsion process exhibit biphasic morphologies. The fact that no core-shell type but Janus-like structures were found indicates that the surface free energies between both polymers and the solution-water interface (including the surfactant molecules) are similar; therefore, the blend morphology and composition of the individual phases are mainly determined by the interaction between the two polymer components. Both the TEM studies and the PL experiments provide strong evidence that phase separation in these particles strictly follows the Flory-Huggins theory. This highlights the applicability of the nanoparticle approach to fabricate blend systems with well-controllable properties and to study structure-property relationships under well-defined conditions.     

In situ applications of a new diver-operated motorized microsensor profiler

Microsensors are powerful tools for microenvironment studies, however their use has often been restricted to laboratory applications due to the lack of adequate equipment for in situ deployments. Here we report on new features, construction details, and examples of applications of an improved diver-operated motorized microsensor profiler for underwater field operation to a water depth of 25 m. The new motorized profiler has a final precision of 5 microm, and can accommodate amperometric Clark-type microsensors for oxygen and hydrogen sulfide, potentiometric microsensors (e.g., for pH, Ca2+), and fiber-optic irradiance microsensors. The profiler is interfaced by a logger with a signal display, and has pushbuttons for underwater operation. The system can be pre-programmed to autonomous operation or interactively operated by divers. Internal batteries supply power for up to 24 h of measurements and 36 h of data storage (max. 64 million data points). Two flexible stands were developed for deployment on uneven or fragile surfaces, such as coral reefs. Three experimental pilot studies are presented, where (1) the oxygen distribution in a sand ripple was 3-D-mapped, (2) the microenvironment of sediment accumulated on a stony coral was studied, and (3) oxygen dynamics during an experimental sedimentation were investigated. This system allows SCUBA divers to perform a wide array of in situ measurements, with deployment precision and duration similar to those possible in the laboratory.     

Tin(IV) oxide coatings from hybrid organotin/polymer nanoparticles

Tin dioxide coatings are widely applied in glasses and ceramics to improve not only optical, but also mechanical properties. In this work, we report a new method to prepare SnO(2) coatings from aqueous dispersions of polymer/organotin hybrid nanoparticles. Various liquid organotin compounds were encapsulated in polymeric nanoparticles synthesized by miniemulsion polymerization. Large amounts of tetrabutyltin and bis(tributyltin) could be successfully incorporated in cross-linked and noncross-linked polystyrene nanoparticles that served as sacrificial templates for the formation of tin oxide coatings after etching with oxygen plasma or calcination. Cross-linked polystyrene particles containing bis(tributyltin)--selected for having a high boiling point--were found to be especially suited for the oxide coating formation. The content of metal in the particles was up to 12 wt %, and estimations by thermogravimetrical indicated that at least 96% of the total organotin compound was converted to SnO(2). The resulting coatings were mainly identified as tetragonal SnO(2) (cassiterite) by X-ray diffraction, although a coexistence of this phase with orthorhombic SnO(2) was observed for samples prepared with bis(tributyltin).     

Development of Mechanically Biologically Treated Municipal Solid Waste under Different Vegetation Types

The use of mechanically biologically treated (MBT) waste as cover material for landfills during the aftercare period has gained in importance since the previous decade. The question arises how such materials change their properties under open field conditions. For field experiments, two MBT plants in Austria with related landfills were selected. A cover layer consisting of MBT material was applied on the surface and planted with grass and rape. The development without any vegetation served as a reference. Leaching, mineralization, and humification of waste organic matter were quantified. The impact of time, sampling depth, respective oxygen supply, and vegetation on the material was investigated. Intensive grass vegetation promoted mineralization and humification. Leaching of salts and the transformation of nitrogen were mainly influenced by time and depth. Aerobic conditions advanced degradation of still-reactive material. Under aerobic conditions, the remaining respiration activity was about two times lower than in the anaerobic zones. It was proven that well stabilized MBT material can be used as a cover layer with adequate vegetation.     

Identification of combustion intermediates in isomeric fuel-rich premixed butanol-oxygen flames at low pressure

Laminar premixed low-pressure flames fueled by either one of the four isomers of butanol were investigated by a molecular-beam photoionization mass spectrometer using vacuum ultraviolet (VUV) synchrotron radiation as the ionization source. The photoionization efficiency (PIE) spectra of most flame intermediates were measured between 7.75 and 11.00 eV. By comparing the resulting PIE spectra to known ionization energies (IEs) or known PIE spectra of pure substances, most hydrocarbon and oxygenated combustion intermediates, including some radicals, in the mass range from m/z=15 to 106 were assigned and identified in the four butanol flames. The results show that the higher-mass oxygenated species in butanol flames are strongly affected by the fuel structure, while many hydrocarbon isomers appear almost independent of the fuel structure. The respective dissociation mechanisms of the fuels, including complex fission, simple fission, and H-atom abstraction, are in good agreement with previous results from nonpremixed butanol flames.     

A meta-analysis of acupuncture techniques for smoking cessation

OBJECTIVE: To determine the effectiveness of acupuncture for smoking cessation and to examine whether any individual aspect of trials is associated with an effect. DATA SOURCES: All randomised controlled trials of acupuncture for smoking cessation that were listed in computerised databases or reference lists of relevant articles. STUDY SELECTION: All randomised single-blind studies that compared acupuncture with sham acupuncture. DATA EXTRACTION: Methodological data were extracted for quality assessment. Outcome data were extracted for rates of total smoking cessation at three intervals: early after treatment and after six and 12 months follow up. DATA SYNTHESIS: Results were expressed as odds ratios of success over failure in intervention over control groups. The combined odds ratio for all studies was calculated. Repeated meta-analyses were subsequently performed on subsets of studies combined according to defined characteristics: acupuncture technique, number of attendances, country of origin, status of journal, and control procedure. The overall quality of studies was poor. The combined odds ratio for smoking cessation calculated for the earliest results after the end of treatment was 1.20 (95% confidence intervals (95% CIs) = 0.98 to 1.48). The combined odds ratio for smoking cessation after six months was 1.29 (95% CI = 0.82 to 2.01), and after 12 months was 1.03 (95% CI = 0.73 to 1.46). There were no significant effects of relevance among subsets of studies grouped according to defined characteristics. CONCLUSIONS: Acupuncture was not superior to sham acupuncture for smoking cessation; no particular aspect of acupuncture technique was associated with a positive effect. The conclusions are limited by methodological inadequacies of studies and by the absence of testable hypotheses; design of future trials should avoid these deficiencies.     

Glycoarrays by a New Tandem Noncovalent-Covalent Modification of Polystyrene Microtiter Plates and their Interrogation with Live Cells

Glycoarrays-easier than ever: Glycoarrays were fabricated on polystyrene microtiter plates with great ease by using a tandem process that combined hydrophobic adsorption and thiourea bridging. They were validated by testing specific bacterial adhesion and its inhibition.     

Combustion chemistry and flame structure of furan group biofuels using molecular-beam mass spectrometry and gas chromatography – Part I: Furan

Fuels of the furan family, i.e. furan itself, 2-methylfuran (MF), and 2,5-dimethylfuran (DMF) are being proposed as alternatives to hydrocarbon fuels and are potentially accessible from cellulosic biomass. While some experiments and modeling results are becoming available for each of these fuels, a comprehensive experimental and modeling analysis of the three fuels under the same conditions, simulated using the same chemical reaction model, has – to the best of our knowledge – not been attempted before. The present series of three papers, detailing the results obtained in flat flames for each of the three fuels separately, reports experimental data and explores their combustion chemistry using kinetic modeling. The first part of this series focuses on the chemistry of low-pressure furan flames. Two laminar premixed low-pressure (20 and 40 mbar) flat argon-diluted (50%) flames of furan were studied at two equivalence ratios (? = 1.0 and 1.7) using an analytical combination of high-resolution electron–ionization molecular-beam mass spectrometry (EI-MBMS) in Bielefeld and gas chromatography (GC) in Nancy. The time-of-flight MBMS with its high mass resolution enables the detection of both stable and reactive species, while the gas chromatograph permits the separation of isomers. Mole fractions of reactants, products, and stable and radical intermediates were measured as a function of the distance to the burner. A single kinetic model was used to predict the flame structure of the three fuels: furan (in this paper), 2-methylfuran (in Part II), and 2,5-dimethylfuran (in Part III). A refined sub-mechanism for furan combustion, based on the work of Tian et al. [Combust. Flame 158 (2011) 756–773] was developed which was then compared to the present experimental results. Overall, the agreement is encouraging. The main reaction pathways involved in furan combustion were delineated computing the rates of formation and consumption of all species. It is seen that the predominant furan consumption pathway is initiated by H-addition on the carbon atom neighboring the O-atom with acetylene as one of the dominant products.