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North American drinking water utilities are currently re-evaluating their disinfection strategies for controlling microbiological growth in distribution systems. Most water systems in North America use free chlorine as a secondary disinfectant. Since chlorine is known to form potentially carcinogenic byproducts in drinking water, utilities are looking for an alternative to maintain a disinfectant residual in the distribution system. The objective of this study was to evaluate the response of model drinking water distribution systems to a change in disinfectant from either free chlorine or chloramines to chlorine dioxide, in terms of its impact on microbiological water quality (bulk water and biofilm). Switching from a chlorine residual of 0.5 mg/L to a chlorine dioxide residual of 0.25 mg/L did not impact (negatively or positively) microbial water quality as quantified by heterotrophic and total cell counts (sample size = 8 data points). Thus, on the basis of the mass of disinfectant applied, chlorine dioxide was more efficient than free chlorine at controlling microbiological growth in the model distribution system. Similarly, chlorine dioxide was more efficient than chloramines, as a chlorine dioxide residual of 0.25 mg/L inactivated 0.75–1 log more suspended organisms than 1.0 mg/L residual of chloramines. Therefore, under the tested conditions, chlorine showed similar or better disinfection efficiency than free chlorine and chloramines, respectively.

The impact of supplementing a raw drinking water source with reuse water was examined. Reuse water produced from municipal wastewater by a membrane bioreactor and reverse osmosis (MBR-RO) system was blended with untreated Lake Ontario water, then subjected to conventional water treatment processes, and evaluated in terms of disinfection by-products (DBPs), nitrate, and coliforms. The addition of reuse water to the lake water improved water quality in terms of total organic carbon (TOC) and bromide, which resulted in reduced trihalomethane (THM) formation. This appeared to be entirely due to dilution with no specific impact from the conventional treatment process. Nitrate levels in the reuse water (1.4 mg/L) were higher than the lake water (0.4 mg/L) and, therefore, an increase in the reuse water : lake water blend ratio resulted in a linear increase in nitrate levels. The conventionally treated blend water was shown to meet typical drinking water regulations for THMs, haloacetic acids (HAAs), total coliform, and nitrate. Key words: water reuse, drinking water supplement, reverse osmosis, membrane bioreactor, conventional water treatment, disinfection by-products, nitrate.

A simplified computational model of the ultraviolet (UV) disinfection dose delivered to wastewater was developed and the model outputs were compared with pilot-scale biodosimetry data. The model assumed plug flow, an assumption that may apply for some open channel UV reactors designed for wastewater disinfection and in which case may eliminate the need for involved and expensive computational fluid dynamics analyses of flow patterns. The reactor residence times derived from this assumption were combined with the output from a two-dimensional, point-source summation UV irradiance model to calculate UV dose. The output from the irradiance model was adapted to account for the cross-sectional distribution of UV irradiance within the reactor. Two UV reactor configurations were modeled and pilot-tested at two UV transmittance (UVT) values that are typical for wastewater. The simplified model predicted doses that fell within the range of the observed UV doses under some flow and UVT conditions, however it did so inconsistently and over-predicted the doses at the highest tested flow rates. This was concluded to be due to a breakdown of the simplified plug flow assumption due to deviations in the velocity field distribution at higher flows. Therefore, while this modeling approach may provide "back of the envelope" initial estimates of the UV doses supplied to wastewater and may allow a qualitative evaluation of the effect of adjusting UV reactor design parameters (e.g., channel width, lamp spacing) on the resulting UV dose, the precise quantitative prediction of UV dose must continue to rely on more sophisticated models. Key words: ultraviolet disinfection, computational modeling, wastewater treatment.

By using a homology-based bioinformatics approach, a structural model of the vaccinia virus (VV) I7L proteinase was developed. A unique chemical library of ∼51,000 compounds was computationally queried to identify potential active site inhibitors. The resulting biased subset of compounds was assayed for both toxicity and the ability to inhibit the growth of VV in tissue culture cells. A family of chemotypically related compounds was found which exhibits selective activity against orthopoxviruses, inhibiting VV with 50% inhibitory concentrations of 3 to 12 μM. These compounds exhibited no significant cytotoxicity in the four cell lines tested and did not inhibit the growth of other organisms such as Saccharomyces cerevisiae , Pseudomonas aeruginosa , adenovirus, or encephalomyocarditis virus. Phenotypic analyses of virus-infected cells were conducted in the presence of active compounds to verify that the correct biochemical step (I7L-mediated core protein processing) was being inhibited. Electron microscopy of compound-treated VV-infected cells indicated a block in morphogenesis. Compound-resistant viruses were generated and resistance was mapped to the I7L open reading frame. Transient expression with the mutant I7L gene rescued the ability of wild-type virus to replicate in the presence of compound, indicating that this is the only gene necessary for resistance. This novel class of inhibitors has potential for development as an efficient antiviral drug against pathogenic orthopoxviruses, including smallpox.

Drinking water utilities may be required to change disinfectant to improve water quality and meet more stringent disinfection regulations. This research was conducted to assess and compares chlorin...

A bench-scale study was conducted using water from a drinking water treatment facility on Lake Ontario to investigate water quality and disinfection impacts of chlorine contamination in a chlorine dioxide solution applied for primary disinfection. Levels of chlorine contamination were varied between 0% (pure chlorine dioxide) and 20%, with a chlorine dioxide dose of 1 mg/L. The chlorine did not significantly affect the rate of chlorine dioxide decay in the water. The chlorine reduced chlorite formation, but led to a corresponding increase in chlorate formation. Trihalomethane and haloacetic acid concentrations varied with the amount of free chlorine present in the chlorine dioxide solution. Levels of Bacillus subtilis endospore inactivation were similar for solutions containing pure chlorine dioxide and a 20%:80% chlorine:chlorine dioxide mass ratio (for the same total chlorine concentration). Since chlorine alone has been reported to be very ineffective against these endospores, the results suggest that the disinfection effectiveness of the mixture was greater than the effectiveness predicted from each of the two disinfectants acting alone. Key words: chlorine dioxide, chlorine, disinfection, by-products, inactivation, drinking water.

Synthetic water matrices containing ammonia, bicarbonate, hydrogen peroxide, and natural organic matter were studied to identify the effects of these compounds (individually and in combination) on bromate formation. Ammonia alone was observed to significantly reduce bromate formation through the sequestering of brominated intermediates as bromamines. Natural organic matter reacted quickly with bromamines, which could impair the ability of ammonia to block bromate formation. Bicarbonate was observed to generally promote bromate formation in otherwise pure water, but bicarbonate worked synergistically with ammonia to reduce bromate formation by a greater factor than ammonia alone, due to OH radical scavenging. Experiments showed that hydrogen peroxide lowered the effectiveness of ammonia to block bromate formation.

Drinking water utilities may have to consider changing disinfectant to improve water quality and meet more stringent disinfection regulations. The objective of this study was to evaluate the response of a full-scale drinking water distribution system to a change in disinfectant from chlorine to chlorine dioxide, in terms of its impact on microbiological stability and disinfection by-product formation. Chlorine dioxide residuals were consistently present above detection limits throughout the distribution system (>0.20 mg/L). Over a study period of 3.5 months, no degradation of bacterial water quality occurred after implementing the new disinfectant. Chlorine dioxide maintained total bacteria (microscopic counts) and heterotrophic plate count levels below 2 x 105 cells/mL and 1000 CFU/mL, respectively. The change in disinfectant from chlorine to chlorine dioxide led to an 85% reduction in trihalomethanes (i.e., from 30 to 5 μμg/L) and a 60% reduction in haloacetic acids (i.e., from 20 to 8 μμg/L). Chlorine dioxide represents a valuable tool to produce high quality water and is a strong alternative to chlorine for certain distribution systems. Key words: distribution system, chlorine dioxide, drinking water quality, disinfection by-products.

Chlorine dioxide (ClO2) inactivation of Bacillus subtilis ATCC 19659 spores was examined at pilot-scale during periods representative of winter and summer temperature extremes at the Britannia Water Treatment Plant in Ottawa, Canada. In addition, bench-scale experiments using the same source water (Ottawa River, Ontario, Canada), as well as buffered and unbuffered laboratory waters were conducted using B. subtilis spores. Bench-scale inactivation of B. subtilis spores by ClO2 was similar to reported values for Cryptosporidium parvum (both organisms being more resistant to ClO2 than Giardia lamblia), suggesting the possibility that these spores may be used as potential indicators for protozoan parasites. Additionally, spore inactivation was observed to be influenced by pH in laboratory (distilled deionised water) water but not in Ottawa River water. At pilot-scale, spore inactivation was influenced by water temperature: a ClO2 dose of 2.5 mg/L resulted in a spore inactivation of approximately 2.0 log10 and 0.5 log10 at water temperatures of 23.2d egrees C and 5.2 degrees C, respectively. Chlorite concentrations remained below both the US EPA maximum contaminant level of 1.0 mg/L and the maximum contaminant level goal of 0.8 mg/L for up to 2.0log10 B. subtilis inactivation.

Factorial experiments were conducted using source waters from seven drinking water treatment plants in Ontario, Canada to develop statistically based model equations capable of predicting chlorine dioxide consumption and chlorite and chlorate formation upon chlorine dioxide application. The equations address raw water quality and operational parameters including pH, temperature, chlorine dioxide concentration, reaction time and water organic content (as described by non-purgeable organic carbon x ultraviolet absorbance measured at 254 nm, NPOC x UV254). Terms describing two-factor interaction effects were also included, improving the accuracy of the predictive equations in fitting measured response concentrations as evaluated through internal and external validations. Nearly 80% of the predictions for chlorine dioxide consumption and chlorite formation were observed to be within 20% of the measured levels. Over 90% of the predicted chlorate levels were within +/- 0.1 mg/L of the measured levels. Chlorine dioxide concentration and NPOC x UV254 were key parameters when developing the predictive models.

Cryptosporidium parvum , which is resistant to chlorine concentrations typically used in water treatment, is recognized as a significant waterborne pathogen. Recent studies have demonstrated that chlorine dioxide is a more efficient disinfectant than free chlorine against Cryptosporidium oocysts. It is not known, however, if oocysts from different suppliers are equally sensitive to chlorine dioxide. This study used both a most-probable-number–cell culture infectivity assay and in vitro excystation to evaluate chlorine dioxide inactivation kinetics in laboratory water at pH 8 and 21°C. The two viability methods produced significantly different results ( P < 0.05). Products of disinfectant concentration and contact time ( Ct values) of 1,000 mg · min/liter were needed to inactivate approximately 0.5 log 10 and 2.0 log 10 units (99% inactivation) of C. parvum as measured by in vitro excystation and cell infectivity, respectively, suggesting that excystation is not an adequate viability assay. Purified oocysts originating from three different suppliers were evaluated and showed marked differences with respect to their resistance to inactivation when using chlorine dioxide. Ct values of 75, 550, and 1,000 mg · min/liter were required to achieve approximately 2.0 log 10 units of inactivation with oocysts from different sources. Finally, the study compared the relationship between easily measured indicators, including Bacillus subtilis (aerobic) spores and Clostridium sporogenes (anaerobic) spores, and C. parvum oocysts. The bacterial spores were found to be more sensitive to chlorine dioxide than C. parvum oocysts and therefore could not be used as direct indicators of C. parvum inactivation for this disinfectant. In conclusion, it is suggested that future studies address issues such as oocyst purification protocols and the genetic diversity of C. parvum , since these factors might affect oocyst disinfection sensitivity.

Experiments were undertaken with the primary objective of developing kinetic relationships for the formation of cyanogen chloride (CNCl), which could then be integrated into a multi-constituent water quality model. The use of ozone in combination with monochloramine has been reported in the literature to enhance CNCl formation. A procedure to determine C t, a surrogate used to estimate the level of microbial inactivation achieved, was also developed using a semi-batch methodology. Water collected from the Mannheim Water Treatment Plant (WTP) (Waterloo, Ontario, Canada) at 7°C and 20°C was ozonated using a semi-batch procedure to achieve a desired level of inactivation. A series of specific steps were then followed to simulate treatment at the Mannheim WTP as closely as possible at bench-scale. Three different levels of microbial inactivation were selected to simulate 0.5-log Giardia inactivation, and both 1.0-log and 3.0-log Cryptosporidium inactivation. Kinetic relationships were developed which...

Chlorite, chlorate, and trihalomethane (THM) formation was measured following the disinfection of drinking water using chlorine dioxide either alone, or followed by chlorine or monochloramine. Chlorine dioxide doses were selected to provide a range of Giardia inactivation levels as calculated using CT values (disinfectant concentration × contact time) presented in the US Surface Water Treatment Rule. Experiments were conducted at bench-scale in batch reactors, using water obtained from two river sources. Dose requirements did not vary greatly when disinfecting at 1°C versus 25°C, since the higher CT requirements in the cold (due to slower disinfection kinetics) were offset by greater chlorine dioxide stability at low temperature. Higher doses were required at pH 9 compared to pH 6, due to chlorine dioxide disproportionation at the higher pH. Greater formation of chlorite and chlorate was observed at the higher pH. Temperature exerted a relatively small effect on chlorite and chlorate formation, following ...

The importance of operators' knowledge in the production of high-quality water and the need for consistent high-level expertise have fueled propositions for the application of computer technology, including knowledge-based expert systems (KBES), as a means of enhancing drinking water treatment operations. With this in mind, the authors have developed CHLOROS, a knowledge-based system which integrates both expert system and hypertext technologies in a WindowsTM environment. Designed as an off-line tool, the system does not directly control operations related to drinking water disinfection, but rather has been intended to assist treatment plant operations personnel. It is believed that CHLOROS will serve as a practical tool for water utilities because it creates a consistent decision-making environment, captures and preserves the expertise of human experts, and reduces the amount of manual effort and time that may be expended by searching through manuals and literature for information that is required to support the choice of control parameters.Key words: knowledge-based systems, expert system, hypertext system, disinfection, chlorination, chloramination.

The recognition that chlorine disinfection of drinking water may not be effective in controlling pathogens such as Cryptosporidium may lead to the greater use of stronger alternative disinfectants, such as chlorine dioxide. Typical chlorine dioxide residual concentration requirements for disinfection may extend to less than 0.1 mg l−1, thus requiring very good quantitation methods for optimal process control. Traditional methods have been cumbersome and sometimes inaccurate. This study examined three spectrophotometric methods for measuring chlorine dioxide in the

This study examined the rejection of selected pharmaceutically active (PhAC) and endocrine disrupting compounds (EDCs) when using nanofiltration as a function of naturally occurring dissolved organic matter (DOM), colloidal particles, cations and their interactions. Lake Ontario water served as a source of natural DOM and colloidal particles. PhAC/EDC rejection experiments were conducted using raw Lake Ontario water and Lake Ontario water that was pre-treated with either ultrafiltration to remove colloidal particles, or fluidized ion exchange resins to remove DOM. Additionally, the concentration of cations (Ca(2+), Mg(2+), and Na(+)) in the raw and pre-treated water matrices was varied. While ionic PhACs and EDCs exhibited high rejections from all the water matrices examined, neutral compounds were most effectively rejected in water containing DOM and no colloids, and least effectively rejected from colloid-containing water with increased cations but no DOM. The presence of DOM significantly improved compound rejection and the increase in cation concentration significantly decreased rejection. The presence of colloids had comparatively little effect except to mitigate the impact of increased cation concentration, apparently providing some cation-buffering capacity. The sequence in which constituents are removed from waters during treatment may significantly impact PhAC and EDC removal, especially of neutral compounds.

Formation of nine N-nitrosamines has been investigated when seven different source waters representing various qualities were each treated with eleven bench-scale disinfection processes, without addition of nitrosamine precursors. These disinfection treatments included chlorine (OCl-), chloramine (NH2Cl), chlorine dioxide (ClO2), ozone (O3), ultraviolet (UV), advanced oxidation processes (AOP), and combinations. The total organic carbon (TOC) of the seven source waters ranged from 2 to 24 mg x L(-1). The disinfected water samples and the untreated source waters were analyzed for nine nitrosamines using a solid phase extraction and liquid chromatography-tandem mass spectrometry method. Prior to any treatment, N-nitrosodimethylamine (NDMA) was detected ranging from 0 to 53 ng x L(-1) in six of the seven source waters, and its concentrations increased in the disinfected water samples (0-118 ng x L(-1)). N-nitrosodiethylamine (NDEA), N-nitrosomorpholine (NMor), and N-nitrosodiphenylamine (NDPhA) were also identified in some of the disinfected water samples. NDPhA (0.2-0.6 ng x L(-1)) was formed after disinfection with OCl-, NH2Cl, O3, and MPUV/OCl-. NMEA was produced with OCl- and MPUV/OCl-, and NMor formation was associated with O3. In addition, UVtreatment alone degraded NDMA; however, UV/ OCl- and AOP/OCl- treatments produced higher amounts of NDMA compared to UV and AOP alone, respectively. These results suggest that UV degradation or AOP oxidation treatment may provide a source of NDMA precursors. This study demonstrates that environmental concentrations and mixtures of unknown nitrosamine precursors in source waters can form NDMA and other nitrosamines.

On-line particle count and turbidity data was used to monitor the impacts of transient particulate water quality events on the inactivation of indigenous total coliform bacteria by a pilot-scale ultraviolet (UV) disinfection unit at two drinking water treatment plants (referred to as WTPs ‘A’ and ‘B’). The intent of the study was to assess the performance of UV disinfection when exposed to temporary ‘worst case’ particulate water quality conditions in a drinking water treatment context. The pilot unit was installed downstream of a poorly operating filter at WTP ‘A’ and downstream of an intentionally destabilized Actiflo® system at WTP ‘B’. In each case, elevated particle content (turbidity up to 2.9 NTU) did not cause observable adverse effects on the UV disinfection of total coliform bacteria over the test periods, even when a particle extraction technique was applied to count particle-associated bacteria in the water samples.

Studies have shown that viruses are frequently attached onto or enmeshed within suspended particles in natural water and wastewater and that this viral–particle association can impede disinfection processes in some circumstances. This article summarizes the current state of knowledge of the occurrence of particle-associated viruses in the aquatic environment and the reported subsequent impacts on disinfection processes. The intention is that this article will help guide future research and aid regulators attempting to address the disinfection of particle-laden waters.

Haloacetic acids (HAAs) are produced by the reaction of chlorine with natural organic matter and are regulated disinfection by-products of health concern. Biofilms in drinking water distribution systems and in filter beds have been associated with the removal of some HAAs, however the removal of all six routinely monitored species (HAA6) has not been previously reported. In this study, bench-scale glass bead columns were used to investigate the ability of a drinking water biofilm to degrade HAA6. Monochloroacetic acid (MCAA) and monobromoacetic acid (MBAA) were the most readily degraded of the halogenated acetic acids. Trichloroacetic acid (TCAA) was not removed biologically when examined at a 90% confidence level. In general, di-halogenated species were removed to a lesser extent than the mono-halogenated compounds. The order of biodegradability by the biofilm was found to be monobromo > monochloro > bromochloro > dichloro > dibromo > trichloroacetic acid.

A bench-scale study was conducted to determine the inactivation of adenovirus (Ad) types 2, 5, and 41 by ultraviolet (UV) light, chlorine, and monochloramine. The motivation for this study was to determine whether UV disinfection followed by chlorine or monochloramine for a very short contact time (e.g., a minute) could satisfy regulatory requirements for four-log virus inactivation. In order to overcome the difficulty Ad 41 presents for enumeration of the virus in cell culture, a technique was used that combined immunofluorescent staining of viral antigen with traditional scoring of cytopathic effect. A UV dose of 40 mJ∕ cm2 (millijoules per square centimeter) (applied using a collimated beam apparatus) achieved approximately one-log inactivation of adenovirus types 2, 5 and 41, confirming previous research. Ad 41 was found to be more UV resistant to UV light than Ad 2 or Ad 5 at UV doses >70 mJ∕ cm2 to a statistically significant degree (95% confidence); however, at lower UV doses there were no statisti...

This bench-scale study investigated the passage of particle-associated bacteriophage through a dual-media (anthracite-sand) filter over a complete filter cycle and the effect on subsequent ultraviolet (UV) disinfection. Two model viruses, bacteriophages MS2 and T4, were considered. The water matrix was de-chlorinated tap water with either kaolin or Aldrich ® humic acid (AHA) added and coagulated with alum to form floc before filtration. The turbidity of the influent flocculated water was 6.4 ± 1.5 NTU . Influent and filter effluent turbidity and particle counts were measured as well as headloss across the filter media. Filter effluent samples were collected for phage enumeration during three filter cycle stages: (i) filter ripening; (ii) stable operation; and (iii) end of filter cycle. Stable filter operation was defined according to a filter effluent turbidity goal of 0.3 NTU . Influent and filter effluent samples were subsequently exposed to UV light (254 nm) at 40 mJ / cm 2 using a low pressure UV collimated beam. The study found statistically significant differences ( α = 0.05 ) in the quantity of particle-associated phage present in the filter effluent during the three stages of filtration. There was reduced UV disinfection efficiency due to the presence of particle-associated phage in the filter effluent in trials with bacteriophage MS2 and humic acid floc. Unfiltered influent water samples also resulted in reduced UV inactivation of phage relative to particle-free control conditions for both phages. Trends in filter effluent turbidity corresponded with breakthrough of particle-associated phage in the filter effluent. The results therefore suggest that maintenance of optimum filtration conditions upstream of UV disinfection is a critical barrier to particle-associated viruses.

This research was conducted to assess the impact of various disinfectants on bacterial water quality within model distribution systems (i.e. annular reactors). After colonization with non-disinfected water, annular reactors were treated with relatively low doses of chlorine (0.4 mg/l), chlorine dioxide (0.15 mg/l), or chloramines (0.9 mg/l). Under the tested conditions, bacterial inactivation varied as a function of disinfectant type (ranking by efficiency per mg of oxidant: ClO2 > Cl2 > ClNH2) and sample type (bulk water vs. biofilm). Depending on the disinfectant, the log inactivation of suspended and attached bacteria were 0.7–1.2 and 0.5–1.0, respectively. The characterization of microbial communities in drinking water can be performed using biochemical and/or molecular methods. In this study, biochemical tests were used, showing that pseudomonad and pseudomonad-like bacteria, as in other studies, were the most predominant micro-organisms (e.g. Pseudomonas fluorescens, Brevundimonas vescularis). The ratio Gram-positive to Gram-negative organisms was 1 to 3. No drastic differences were observed between the non-treated and disinfected pipes. Based on the bacteriological data presented in these experiments, chlorine dioxide represents an alternative to chlorine for certain distribution systems.

Aims: To investigate the impact of iron particles in groundwater on the inactivation of two model viruses, bacteriophages MS2 and T4, by 254-nm ultraviolet (UV) light. Methods and Results: One-litre samples of groundwater with high iron content (from the Indianapolis Water Company, mean dissolved iron concentration 1·3 mg l−1) were stirred vigorously while exposed to air, which oxidized and precipitated the dissolved iron. In parallel samples, ethylenediaminetetra-acetic acid (EDTA) was added to chelate the iron and prevent formation of iron precipitate. The average turbidity in the samples without EDTA (called the ‘raw’ samples) after 210 min of stirring was 2·7 ± 0·1 NTU while the average turbidity of the samples containing EDTA (called the ‘preserved’ samples) was 1·0 ± 0·1 NTU. ‘Raw’ and ‘preserved’ samples containing bacteriophage MS2 were exposed to 254-nm UV light at doses of 20, 40, or 60 mJ (cm2)−1, while samples containing bacteriophage T4 were exposed to 2 or 5 mJ (cm2)−1, using a low pressure UV collimated beam. The UV inactivation of both phages in the ‘raw’ groundwater was lower than in the EDTA-‘preserved’ groundwater to a statistically significant degree (α = 0·05), due to the association of phage with the UV-absorbing iron precipitate particles. A phage elution technique confirmed that a large fraction of the phage that survived the UV exposures were particle-associated. Conclusions: Phages that are associated with iron oxide particles in groundwater are shielded from UV light to a measurable and statistically significant degree at a turbidity level of 2·7 NTU when the phage particle association is induced under experimental conditions. Significance and Impact of the Study: While the particle association of the phage in this study was induced experimentally, the findings provide further evidence that certain particles in natural waters and wastewaters (e.g. iron oxide particles) may have the potential to shield viruses from UV light.

We report a systematic analysis of the P1' and P2' substrate specificity of TNF-alpha converting enzyme (TACE) using a peptide library and a novel analytical method, and we use the substrate specificity information to design novel reverse hydroxamate inhibitors. Initial truncation studies, using the amino acid sequence around the cleavage site in precursor-TNF-alpha, showed that good turnover was obtained with the peptide DNP-LAQAVRSS-NH2. Based on this result, 1000 different peptide substrates of the form Biotin-LAQA-P1'-P2'-SSK(DNP)-NH2 were prepared, with 50 different natural and unnatural amino acids at P1' in combination with 20 different amino acids at P2'. The peptides were pooled, treated with purified microsomal TACE, and the reaction mixtures were passed over a streptavidin affinity column to remove unreacted substrate and the N-terminal biotinylated product. C-terminal cleavage products not binding to streptavidin were subjected to liquid chromatography/mass spectrometry analysis where individual products were identified and semiquantitated. 25 of the substrates were resynthesized as discrete peptides and assayed with recombinant TACE. The experiments show that recombinant TACE prefers lipophilic amino acids at the P1' position, such as phenylglycine, homophenylalanine, leucine and valine. At the P2' position, TACE can accommodate basic amino acids, such as arginine and lysine, as well as certain non-basic amino acids such as citrulline, methionine sulfoxide and threonine. These substrate preferences were used in the design of novel reverse hydroxamate TACE inhibitors with phenethyl and 5-methyl-thiophene-methyl side-chains at P1', and threonine and nitro-arginine at P2'.

This study investigated whether colloid-sized particles can enmesh and protect viruses from 254-nm ultraviolet (UV) light and sought to determine the particle characteristics (e.g. size, chemical composition) that are most relevant in causing a protective effect. Two viral surrogates (MS2 coliphage and bacteriophage T4), three types of particles (kaolin clay, humic acid powder, and activated sludge), two coagulants (alum and ferric chloride), two filtration conditions (none and 0.45 microm), and two UV doses (40 and 80 mJ/cm2 for MS2 coliphage; 2 and 7 mJ/cm2 for bacteriophage T4) were considered in a series of bench-scale UV collimated beam experiments. Transmission electron microscopy was used to qualitatively confirm the phage particle-association after coagulation. Humic acid and activated sludge floc particles shielded both viral surrogates to a statistically significant degree (with99% confidence) relative to particle-free control conditions, while the kaolin clay particles provided no significant protection. The results of the study suggest that particles2 microm in diameter are large enough to protect viruses from UV light and that particulate chemical composition (e.g. UV-absorbing organic content) may be a critical factor in the survival of particle-associated viruses during UV disinfection.

A membrane bioreactor and reverse osmosis (MBR-RO) system was developed to assess potential reuse applications of municipal wastewater. The objective of the study was to examine the water quality throughout the system with a focus on waterborne pathogens, disinfection by-products (DBPs) and nitrate. This paper will discuss the presence of these contaminants in MBR effluent and focus on their subsequent removal by RO. This study has shown that high quality reuse water can be produced from municipal wastewater through the use of an MBR-RO system. The water meets California Title 22 reuse regulations for non-potable applications and US EPA drinking water limits for trihalomethanes (THM) (80 microg/L), haloacetic acids (HAA) (60 microg/L), chlorite (1.0 mg/L), total coliform (not detectable), viruses (not detectable), and nitrate/nitrite (10 mg N/L). However, THM formation (182-689 microg/L) attributed to cleaning of the MBR with chlorine and incomplete removal by subsequent RO treatment resulted in reuse water with THM levels (40.2+/-19.9 microg/L) high enough to present a potential concern when considering drinking water applications. Nitrate levels of up to 3.6 mg N/L, which resulted from incomplete removal by the RO membrane, are also a potential concern. A denitrification step in the MBR should be considered in potable water applications.

The drinking water industry is closely examining options to maintain disinfection in distribution systems. In particular this research compared the relative efficiency of the chlorite ion (ClO2-) to chlorine dioxide (ClO2) for biofilm control. Chlorite levels were selected for monitoring since they are typically observed in the distribution system as a by-product whenever chlorine dioxide is applied for primary or secondary disinfection. Previous research has reported the chlorite ion to be effective in mitigating nitrification in distribution systems. Annular reactors (ARs) containing polycarbonate and cast iron coupons were used to simulate water quality conditions in a distribution system. Following a 4 week acclimation period, individual ARs operated in parallel were dosed with high (0.25mg/l) and low (0.1mg/l) chlorite concentrations and with high (0.5 mg/l) and low (0.25mg/l) chlorine dioxide concentrations, as measured in the effluent of the AR. Another set of ARs that contained cast iron and polycarbonate coupons served as controls and did not receive any disinfection. The data presented herein show that the presence of chlorite at low concentration levels was not effective at reducing heterotrophic bacteria. Log reductions of attached heterotrophic bacteria for low and high chlorite ranged between 0.20 and 0.34. Chlorine dioxide had greater log reductions for attached heterotrophic bacteria ranging from 0.52 to 1.36 at the higher dose. The greatest log reduction in suspended heterotrophic bacteria was for high dose of ClO2 on either cast iron or polycarbonate coupons (1.77 and 1.55). These data indicate that it would be necessary to maintain a chlorine dioxide residual concentration in distribution systems for control of microbiological regrowth.

This objective of this study was to explore the practicality of monitoring naturally occurring organisms to predict drinking water treatment plant performance, in this case for the reduction of Cryptosporidium. Surface and ground water from seven drinking water treatment plants across North America that use chlorine dioxide were surveyed for aerobic and anaerobic bacterial spore concentrations. The concentrations of total spores were usually high enough in both raw and treated water to allow 4- to 5-log reductions to be observed across the treatment train by filtering up to 2 l of sample. These results suggested that naturally occurring treatment-resistant spores could be candidates as indicators of treatment performance. However, to be useful as indicators for Cryptosporidium reduction, the organisms would have to exhibit similar resistances to disinfection (chlorine dioxide in this case) in order to be useful. The inactivation kinetics of seven of the most common species were determined, and all were observed to be considerably more susceptible to chlorine dioxide inactivation than Cryptosporidium as reported in the literature. This study therefore did not identify an appropriate ambient microbial indicator for Cryptosporidium control.

Ammonia can inhibit the formation of bromate in ozonated drinking water by reacting with free bromine (HOBr/OBr-), an intermediate in bromate formation, to form bromamines. Bromamines do not participate in bromate formation, however, they will decay due to autonomous decomposition and through reaction with ozone and hydroxyl radicals. The reaction with ozone controls the overall decay rate. This reaction also results in a net loss of ammonia from the system, leading to the possibility that all ammonia may be oxidized before the ozone residual in the water is eliminated, allowing bromate formation to resume. This paper presents a review of our understanding of bromamine chemistry and identifies areas that are not adequately understood, which may prevent an accurate estimation of ammonia's impact on bromate formation.

Based on previous studies showing the efficacy of FactorIXa (FIXa) blockade using an active site-blocked form of this coagulation enzyme, we speculated that partial inhibition of the intrinsic coagulation pathway would offer a novel approach to attenuate intravascular clot formation without promoting untoward bleeding. Here we describe the anticoagulant activity of TTP889, a small molecule partial inhibitor of FIXa activity. TTP889 is orally absorbed with a PK profile that is conducive to once daily dosing. It is selective for FIXa in that it shows little to no activity against several other proteases in the clotting cascade including FXa, FXIa, FXIIa or FVIIa in a unique clotting assay. In vivo, TTP889 inhibited fibrin deposition in a rat arteriovenous (A/V) shunt model. In this model, vehicle treated rats had 104mg ± 43 of fibrin deposited on a silk thread after a 15 minute shunt while TTP889 treated rats had significantly less fibrin deposited (39mg ± 18 p=

The total synthesis of (±)-isolobophytolide ( 20 ) has been achieved via a route involving piallyl palladium initiated macrocyclization of sulfone ester 8 and subsequent carboxy inversion of the macrocyclic acid 11 to introduce the C-14 lactone oxygen. Lactone α-methylenation was effected by dehydration of the hydroxymethyl derivative 19 with 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho- p -toluenesulfonate-CuCl 2 .

La copulation entre le (benzenesulfonyl-8 dimethyl-2,6 [perhydro pyrannyl-2oxy]-1) octadiene-2,6 et le methyl-2 α-[trimethylsilyl-3 propargyl] oxirannemethanol conduit au benzenesulfonyl-7 dimethyl-9,13 [perhydro pyrannyl-2 oxy]-14 octadiene-8,12yne-1diol-4,5 (precurseur de synthese des ceurbranolides)

Chouinard, in [8], proved the following remarkable result.Theorem. Let k be a field of characteristic p and G be any finite group. Then a (finitely generated left) kG-module is protective if and only if it is free on restriction to all the elementary abelian p-subgroups of G.

A new procedure for lactone α-methylenation is described in which α-hydroxymethyl lactones are dehydrated with cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate-CuCl2 in acetonitrile.

Purified preparations of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), and interleukin 3 (IL-3 or multi-CSF) alone and in combination, have been compared for their stimulatory effects on human granulocyte-macrophage colony forming cells (GM-CFC). In cultures of unseparated normal human bone marrow, the combinations of G-CSF plus IL-3 and GM-CSF plus IL-3 stimulated additive numbers of GM colonies, while GM-CSF plus G-CSF stimulated greater than additive numbers of GM colonies, compared with the sum of the colony formation obtained with each factor alone. Cultures of unseparated bone marrow, harvested from patients four to six days after administration of 5-fluorouracil (5-FU), resulted in additive GM colony formation with GM-CSF plus G-CSF, GM-CSF plus IL-3, and G-CSF plus IL-3. In order to address the possibility of secondary factor involvement in the synergistic interaction of GM-CSF and G-CSF, CD33+/CD34+ colony forming cells were separated from normal and post FU marrow by two color fluorescence activated cell sorting. In cultures of CD33+/CD34+ cells the combination of GM-CSF plus G-CSF stimulated a synergistic increase in GM colonies while GM-CSF plus IL-3 stimulated additive numbers of colonies. These results suggest that GM-CSF, G-CSF, and IL-3 stimulate distinct populations of GM-CFC. Furthermore GM-CSF and G-CSF interact synergistically and this action is a direct effect on progenitor cells not stimulated by GM-CSF or G-CSF alone.