Mercury emission estimates from fires: an initial inventory for the United States

Recent studies have shown that emissions of mercury (Hg), a hazardous air pollutant, from fires can be significant. However, to date, these emissions have not been well-quantified for the entire United States. Daily emissions of Hg from fires in the lower 48 states of the United States (LOWER48) and in Alaska were estimated for 2002-2006 using a simple fire emissions model. Emission factors of Hg from fires in different ecosystems were compiled from published plume studies and from soil-based assessments. Annual averaged emissions of Hg from fires in the LOWER48 and Alaska were 44 (20-65) metric tons yr(-1), equivalent to approximately 30% of the U.S. EPA 2002 National Emissions Inventory for Hg. Alaska had the highest averaged monthly emissions of all states; however, the emissions have a high temporal variability. Emissions from forests dominate the inventory, suggesting that Hg emissions from agricultural fires are not significant on an annual basis. The uncertainty in the Hg emission factors due to limited data leads to an uncertainty in the emission estimates on the order of +/-50%. Research is still needed to better constrain Hg emission factors from fires, particularly in the eastern U.S. and for ecosystems other than forests.     

Effect of chain length on the rate of quaternization of alkyl amines

Trialkyl amines from triethyl to tristearylamine were quaternized with benzyl chloride and compared for the effect of chain length on the rate of quaternization. Triethylamine reacted about twice as fast as tripropylamine with virtually no chain-length effect from propyl to stearyl. Results are compared to previous rate studies on steric hindrance and chain-length dependence.     

Successful term pregnancy after Mustard operation for transposition of the great arteries

Transposition of the great arteries is a complex cardiac malformation with poor prognosis without surgical correction. Since the introduction of surgical procedures such as the intra-auricular reorientation of the venous return (Mustard procedure), an increasing number of patients may reach adulthood and experience pregnancy. Because long-term complications after the Mustard operation include systemic heart failure, arrhythmias, venous return stenosis and pulmonary edema, hemodynamic changes during pregnancy and delivery may potentially engender life-threatening complications in these patients. We report the case of a 24-year-old primigravida who underwent a Mustard procedure at the age of 2 years for transposition of the great vessels, and who carried out a full-term pregnancy. The pregnancy was uneventful until the 34th week, when the woman developed signs of moderate right ventricular failure and frequent episodes of accelerated junctional rhythm. Digitalisation improved symptoms and elicited return to normal sinus rhythm. The patient delivered at term by elective cesarean section, under close hemodynamic monitoring.     

Chemoproteomic Profiling Reveals that Anticancer Natural Product Dankastatin B Covalently Targets Mitochondrial VDAC3**

Chlorinated gymnastatin and dankastatin alkaloids derived from the fungal strain Gymnascella dankaliensis have been reported to possess significant anticancer activity but their mode of action is unknown. These members possess electrophilic functional groups that can might undergo covalent bond formation with specific proteins to exert their biological activity. To better understand the mechanism of action of this class of natural products, we mapped the proteome-wide cysteine reactivity of the most potent of these alkaloids, dankastatin B, by using activity-based protein profiling chemoproteomic approaches. We identified a primary target of dankastatin B in breast cancer cells as cysteine C65 of the voltage-dependent anion-selective channel on the outer mitochondrial membrane VDAC3. We demonstrated direct and covalent interaction of dankastatin B with VDAC3. VDAC3 knockdown conferred hypersensitivity to dankastatin B-mediated antiproliferative effects in breast cancer cells, thus indicating that VDAC3 was at least partially involved in the anticancer effects of this natural product. Our study reveals a potential mode of action of dankastatin B through covalent targeting of VDAC3 and highlights the utility of chemoproteomic approaches in gaining mechanistic understanding of electrophilic natural products.     

Kinetics and preparation of amine oxides

A kinetic model for the oxidation of dimethyllaurylamine to its amine oxide with hydrogen peroxide was developed. It is a second-order reaction where k=.0250, .0079 and .0037 kg per mol/min at 75, 60 and 50°C, respectively. Amine oxides ofN-lauryl morpholine, piperidine and 3-methyl piperidine were synthesized, and their rates of formation were determined. Compared to dimethyllaurylamine, the piperidines react slower, while the morpholine reaction is much faster.     

Comparison of commercially available quaternary ammonium structures for phase transfer catalysis

A variety of commercially available tetralkyl (R₁R₂R₃R₄N⁺) ammonium chlorides and methyl sulfate salts were examined under phase transfer conditions. For conversion of benzyl chloride to benzyl acetate with aqueous potassium acetate, tri C_8–10 methyl ammonium chloride was the most efficient, with tri C_16–18 methyl ammonium chloride was next. The alkyl trimethyl ammonium chlorides (particularly C_12–14 trimethyl) performed well for the oxidation of benzyl alcohol to benzaldehyde with sodium hypochlorite. Trimethyl tallow, C_16–18 partially unsaturated, ammonium chloride was the catalyst of choice for the dichlorocarbene addition to cyclohexene.     

High occurrence of hepatitis E virus in samples from wastewater treatment plants in Switzerland and comparison with other enteric viruses

Hepatitis E virus (HEV) is responsible for many enterically transmitted viral hepatitides around the world. It is currently one of the waterborne diseases of global concern. In industrialized countries, HEV appears to be more common than previously thought, even if it is rarely virulent. In Switzerland, seroprevalence studies revealed that HEV is endemic, but no information was available on its environmental spread. The aim of this study was to investigate –using qPCR– the occurrence and concentration of HEV and three other viruses (norovirus genogroup II, human adenovirus-40 and porcine adenovirus) in influents and effluents of 31 wastewater treatment plants (WWTPs) in Switzerland. Low concentrations of HEV were detected in 40 out of 124 WWTP influent samples, showing that HEV is commonly present in this region. The frequency of HEV occurrence was higher in summer than in winter. No HEV was detected in WWTP effluent samples, which indicates a low risk of environmental contamination. HEV occurrence and concentrations were lower than those of norovirus and adenovirus. The autochthonous HEV genotype 3 was found in all positive samples, but a strain of the non-endemic and highly pathogenic HEV genotype I was isolated in one sample, highlighting the possibility of environmental circulation of this genotype. A porcine fecal marker (porcine adenovirus) was not detected in HEV positive samples, indicating that swine are not the direct source of HEV present in wastewater. Further investigations will be necessary to determine the reservoirs and the routes of dissemination of HEV.     

Discovery and Characterization of ACT‐451840: an Antimalarial Drug with a Novel Mechanism of Action

More than 40 % of the world's population is at risk of being infected with malaria. Most malaria cases occur in the countries of sub‐Saharan Africa, Central and South America, and Asia. Resistance to standard therapy, including artemisinin combinations, is increasing. There is an urgent need for novel antimalarials with new mechanisms of action. In a phenotypic screen, we identified a series of phenylalanine‐based compounds that exhibit antimalarial activity via a new and yet unknown mechanism of action. Our optimization efforts culminated in the selection of ACT‐451840 [(S,E)‐N‐(4‐(4‐acetylpiperazin‐1‐yl)benzyl)‐3‐(4‐(tert‐butyl)phenyl)‐N‐(1‐(4‐(4‐cyanobenzyl)piperazin‐1‐yl)‐1‐oxo‐3‐phenylpropan‐2‐yl)acrylamide] for clinical development. Herein we describe our optimization efforts from the screening hit to the potential drug candidate with respect to antiparasitic activity, drug metabolism and pharmacokinetics (DMPK) properties, and in vivo pharmacological efficacy.     

Long-term electrocardiography. Detection of low-grade myocardial infarction: sensitivity of 9 bipolar leads

The sensitivity of ambulatory electrocardiography (Holter ECG) for detecting ischaemia is relatively low. A case report of an inferior infarction missed by three-lead Holter monitoring that included a modified lead aVF especially places its sensitivity for detecting inferior ischaemia and infarction in question. Therefore, the present study evaluated the sensitivity of nine bipolar Holter leads for detecting isolated inferior Q-wave infarctions, and compared the sensitivity of the modified leads II, III, and aVF of the Holter ECG with the sensitivity of the "corresponding" leads of the standard ECG. METHODS: Sixteen patients, each of whom had a pathological Q-wave (> 0.04 s and > 0.1 mV) in at least two of the three standard ECG leads II, III, and aVF but in none of the other standard leads, were studied for the presence of a pathological Q-wave on the modified Holter leads II, III, aVF, CM2, CM5, CR4, Frank Z, Nehb D, and inverse Nehb J. RESULTS: Of the nine Holter leads, modified lead III provided the highest sensitivity for detecting inferior Q-wave infarctions, followed by lead Frank Z; leads CR 4 and inverse Nehb J were only slightly less sensitive. In contrast, modified leads II and aVF were significantly less sensitive than modified lead III. Modified bipolar lead aVF of the Holter ECG was significantly less sensitive than the "corresponding" lead aVF of the standard ECG, whereas modified leads II and III provided similar sensitivities for detecting inferior Q-wave infarctions as the "corresponding" leads of the standard ECG. CONCLUSIONS: The significantly lower sensitivity of modified lead aVF for detecting inferior Q-wave infarctions compared with standard lead aVF shows that the sensitivity of a Holter ECG lead cannot be deduced from that of the "corresponding" standard ECG lead. Moreover, the significantly higher sensitivity of modified lead III compared with modified leads II and aVF shows that lead selection is important for Holter monitoring.