Monitoring, removal and risk assessment of cytostatic drugs in hospital wastewater.

Cytostatic agents are applied in cancer therapy and subsequently excreted into hospital wastewater. As these substances are known to be carcinogenic, mutagenic and toxic for reproduction, they should be removed from wastewater at their source of origin.In this study the fate and effects of the cancerostatic platinum compounds (CPC) cisplatin, carboplatin, oxaliplatin, 5-fluorouracil (5-FU) and the anthracyclines doxorubicin, daunorubicin and epirubicin were investigated in hospital wastewater. Wastewater from the in-patient treatment ward of a hospital in Vienna was collected and monitored for the occurrence of the selected drugs. A calculation model was established to spot the correlation between administered dosage and measured concentrations. To investigate the fate of the selected substances during wastewater treatment, the oncologic wastewater was treated in a pilot membrane bioreactor system (MBR) and in downstream advanced wastewater treatment processes (adsorption to activated carbon and UV-treatment). Genotoxic effects of the oncologic wastewater were assessed before and after wastewater treatment followed by a risk assessment.Monitoring concentrations of the selected cytostatics in the oncologic wastewater were in line with calculated concentrations. Due to different mechanisms (adsorption, biodegradation) in the MBR-system 5 - FU and the anthracyclines were removed < LOD, whereas CPC were removed by 60%. In parallel, genotoxic effects could be reduced significantly by the MBR-system. The risk for humans, the aquatic and terrestrial environment by hospital wastewater containing cytostatic drugs was classified as small in a preliminary risk assessment.     

Enantiospecific Synthesis and Cytotoxicity Evaluation of Oximidine II Analogues

Analogues of the anticancer natural product oximidine II were prepared and evaluated for cytotoxicity. One analogue of oximidine II that carries a C15 allylic amide side chain as well as two analogues with C15 vinyl sulfone side chains were found to lack cytotoxicity against the cancer cell line SK‐Mel‐5, thereby confirming the necessity of the C15 enamide side chain of oximidine II for cytotoxicity. Four analogues, designed by comparative molecular similarity index analysis (CoMSIA), that feature a less complex macrolactone scaffold were prepared and tested. The two analogues carrying a C15 vinyl sulfone group and the two analogues with a C15 oximidine II enamide side chain showed weak cytotoxicity against the SK‐Mel‐5 cell line and other cell lines, indicating that the designed simplified macrocycles cannot replace the oximidine II macrocycle.     

Biomimetic Aerobic C?H Olefination of Cyclic Enaminones at Room Temperature: Development toward the Synthesis of 1,3,5‐Trisubstituted Benzenes

A green and mild protocol for the dehydrogenative olefination of cyclic enaminones was devised via palladium catalysis at room temperature using oxygen as the terminal oxidant. The synthetic utility of the olefinated cyclic enaminones afforded a series of unique 1,3,5‐trisubstituted benzenes via an unanticipated Diels–Alder tandem reaction. The broad substrate scope and good yields achieved with this new protocol provide an alternative pathway for arene functionalization.

     

Characterization and Comparison of High Blocking Voltage IGBTs and IEGTs Under Hard- and Soft-Switching Conditions

The market of converters connected to transmission lines continues to require insulated gate bipolar transistors (IGBTs) with higher blocking voltages to reduce the number of IGBTs connected in series in high-voltage converters. To cope with these demands, semiconductor manufactures have developed several technologies. Nowadays, IGBTs up to 6.5-kV blocking voltage and IEGTs up to 4.5-kV blocking voltage are on the market. However, these IGBTs and injection-enhanced gate transistors (IEGTs) still have very high switching losses compared to low-voltage devices, leading to a realistic switching frequency of up to 1 kHz. To reduce switching losses in high-power applications, the auxiliary resonant commutated pole inverter (ARCPI) is a possible alternative. In this paper, switching losses and on-state voltages of NPT-IGBT (3.3 kV-1200 A), FS-IGBT (6.5 kV-600 A), SPT-IGBT (2.5 kV-1200 A, 3.3 kV-1200 A and 6.5 kV-600 A) and IEGT (3.3 kV-1200 A) are measured under hard-switching and zero-voltage switching (ZVS) conditions. The aim of this selection is to evaluate the impact of ZVS on various devices of the same voltage ranges. In addition, the difference in ZVS effects among the devices with various blocking voltage levels is evaluated.     

Adsorptive removal of refractory sulfur compounds by tantalum oxide modified activated carbons

Adsorptive desulfurization of a model diesel fuel consisting of dibenzothiophene (DBT) or 4,6‐dimethyldibenzothiophene(4,6‐DMDBT) in hexadecane was performed over activated carbons and tantalum oxide modified (Ta‐x/ACC, x= 2, 5 or 10 wt % Ta, Activated Carbon Centaur) activated carbons at 50°C. The adsorption isotherm for ACC followed the Langmuir model while the adsorption on Ta‐5/ACC fitted the Sips equation indicating more than one type of adsorption sites. Characterization studies indicated new types of adsorption site resulting from the incorporation of Ta oxide into the porous structure of the ACC. XPS data suggested interaction of Ta with the S atom in DBT. The heats of adsorption in the liquid phase determined from micro flow calorimetry for DBT in C16 confirmed the interaction of Ta with DBT. Ta‐5/ACC exhibited the highest adsorption capacity for 4,6‐DMDBT compared to literature reports. Competitive adsorption experiments showed the adsorption capacity as follows: quinoline> DBT? naphthalene. © 2017 American Institute of Chemical Engineers AIChE J, 2017     

Interactions between ABC‐transport proteins and the secondary Fusarium metabolites enniatin and beauvericin

Enniatins (ENN) and beauvericin (BEA) exert cytotoxic properties. Here, we observed that their impact on Ca²⁺‐homeostasis can be reversed by exogenous ATP. Thus, we investigated whether membrane‐located ATP‐binding cassette (ABC) transporters influence ENNs‐ and BEA‐induced cytotoxicity. In short‐term exposure assays breast cancer resistance protein (ABCG2)‐overexpression weakly but significantly reduced the cytotoxic activity of BEA but not ENNs. In contrast, multidrug resistance‐associated protein‐1 (ABCC1)‐ and P‐glycoprotein (ABCB1)‐overexpression was not protective under identical conditions. ABCG2‐mediated resistance against BEA was reversible by ABCG2 modulators. In long‐term exposure assays, ABCG2 and ABCB1 significantly protected against ENNs‐ and to a lesser extent BEA‐induced cytotoxicity. Moreover, both fusariotoxins potently inhibited the ABCG2‐ and ABCB1‐mediated efflux of specific fluorescent substrates, with BEA being more effective. Additionally, ATPase and photoaffinity‐labelling assays proofed interaction of both substances with ABCG2 and ABCB1. Remarkably, 2 years selection of KB‐3‐1 cells against both fusariotoxins resulted only in two‐fold ENNs but negligible BEA resistance. Interestingly, the selected sublines displayed upregulation of multidrug resistance proteins and crossresistance to other chemotherapeutics. Summarizing, ABCG2 and ABCB1 slightly but significantly protect human cells against ENNs‐ and BEA‐induced cytotoxicity. However, both mycotoxins potently interact with ABCB1 and ABCG2 transport functions suggesting influences on bioavailability of xenobiotics and pharmaceuticals.     

SiGe channels for VT control of high-k metal gate transistors for 32 nm complementary metal oxide semiconductor technology and beyond

GLOBALFOUNDRIES 32 nm high-k metal gate technology, with SiGe channel for V_T control of P-field effect transistor, is taken into production. This epitaxial channel material is being introduced into high volume manufacturing in complementary metal oxide semiconductor technology. The morphology of the SiGe channel (cSiGe) for narrow width transistors is carefully controlled by process conditions such as epitaxial growth temperature, pre bake condition or in-situ Si recess prior epitaxial deposition. A micro loading effect observed in 28 nm technology was eliminated by an in-situ recess of the silicon before epitaxial deposition. Due to the significant cost of this process step, an epitaxial batch system has been evaluated to reduce the cost of ownership dramatically. Also the cSiGe process has been optimized to minimize the thickness variation of the SiGe channel due to the strong response of V_T to cSiGe thickness.     

Discovery and Characterization of Multiple Classes of Human CatSper Blockers

The cation channel of sperm (CatSper) is a validated target for nonhormonal male contraception, but it lacks selective blockers, hindering studies to establish its role in both motility and capacitation. Via an innovative calcium uptake assay utilizing human sperm we discovered novel inhibitors of CatSper function from a high-throughput screening campaign of 72,000 compounds. Preliminary SAR was established for seven hit series. HTS hits or their more potent analogs blocked potassium-induced depolarization and noncompetitively inhibited progesterone-induced CatSper activation. CatSper channel blockade was confirmed by patch clamp electrophysiology and these compounds inhibited progesterone- and prostaglandin E1-induced hyperactivated sperm motility. One of the hit compounds is a potent CatSper inhibitor with high selectivity for CatSper over hCav1.2, hNav1.5, moderate selectivity over hSlo3 and hERG, and low cytotoxicity and is therefore the most promising inhibitor identified in this study. These new CatSper blockers serve as useful starting points for chemical probe development and drug discovery efforts.     

Comparison of the transient behavior of microchannel and fin-and-tube evaporators

The development of control algorithms for refrigeration systems requires models capable of simulating transient behavior with sensible computational time and effort. The most pronounced dynamics in these systems are found in the condenser and the evaporator, especially the transient behavior of the evaporator is of great importance when designing and tuning controllers for refrigeration systems. Various so called moving boundary models were developed for capturing these dynamics and showed to cover the important characteristics. A factor that has significant influence on the time constant and nonlinear behavior of a system is the amount of refrigerant charge in the evaporator which is considerably reduced when microchannel heat exchangers are utilized. Here a moving boundary model is used and adapted to simulate and compare the transient behavior of a microchannel evaporator with a fin-and-tube evaporator for a residential air-conditioning system. The results are validated experimentally at a test rig.     

Presence of cancerostatic platinum compounds in hospital wastewater and possible elimination by adsorption to activated sludge

Platinum originating from the excreted cancerostatic platinum compounds (CPC) cisplatin, carboplatin and oxaliplatin was monitored over a period of 28 days in the wastewater of the oncologic ward of the Vienna University Hospital. Concentration levels ranging from 4.7 to 145 microg L(-1) were measured by inductively coupled plasma mass spectrometry (ICP-MS). An average ratio of weekly drug emission/drug consumption of 0.27+/-0.12 was assessed. Model studies were carried out for fundamental understanding of CPC interaction with the solid phases present at different stages of the water cycle. Wastewater and activated sludge were spiked with CPC at concentration levels as found in the sewer of the oncologic ward. The platinum concentration remaining in the tested solution was measured after 24 h of incubation. Depending on pH, the three substances exhibited considerably different adsorption rates in wastewater. At pH 7, cisplatin was adsorbed by 88%, whereas only 26% of carboplatin and 54% of oxaliplatin were removed from the aqueous phase. Adsorption by activated sludge was higher, less affected by pH variation and comparable for all investigated CPC (96% for cisplatin, 70% for carboplatin and 74% for oxaliplatin at pH 6.8). In a next step, the dependence of CPC adsorption was tested for wastewater and activated sludge of different sampling sites. Strong variations were found only for wastewater, whereas activated sludge showed more consistent elimination rates (average values: cisplatin 92%, carboplatin 72%, and oxaliplatin 78%). These findings indicate that the major part of the excreted CPC is adsorbed by the solid phase in the water cycle and is thus expected to be removed from the wastewater by sewage treatment plants.