Strategic optimization in North West Water Ltd and its effect on distribution optimization

The water industry is heavily regulated, and is in a monopolistic situation, so it is restricted in the charges it can levy, while it has to meet the full demands of its customers. Therefore the economist's approach to optimization, based on the assumption that volume is the sole determinant of cost and revenue changes, cannot be used. Thus an alternative approach is required. The aim of strategic optimization at North West Water Ltd is to produce an operating procedure for the major sources, to meet a declared demand, while maintaining a specified minimum storage volume, at minimum cost.     

Eutrophication and Pathogen Abatement in the San Juan Bay Estuary

The San Juan Bay Estuary is a tropical lagoon system severely impacted by eutrophication and by elevated pathogen concentrations. This investigation examined alternatives for pollution abatement primarily through physical modifications to the system. The investigation included field surveys, computation of pollutant loads, and application of hydrodynamic and eutrophication models. A eutrophication model developed for temperate estuaries was successfully transferred to San Juan Bay Estuary. Results indicate two primary modifications reduce eutrophication. The first clears a constricted channel to the interior of the system and promotes flushing. The second fills deep holes in which anoxic conditions promote sediment nutrient release to the water column. Major reductions in pathogen concentration require regional controls on sources.     

Horn aberrations in Dall's sheep (Ovis dalli) from Yukon Territory, Canada

Horn aberrations in Dall's sheep from the Kluane Lake area of Yukon Territory were of two basic types. In the more prevalent type, the horn was severed at an annual growth check and the terminal segment of the remaining portion formed a short conical protuberance. The second type had characteristics of the first, but in addition, underwent extreme twisting or torquing during subsequent growth. Sheep with aberrant horns represented 2% of the Kluane Lake population or 14% of harvestable rams (greater than or equal to 6 yr old). Deformed horns, occurring in ewes and rams, were generally observed in animals 6 yr or older. Aberrations followed necrosis of the terminal segment of the horn core: cavitation of the sheath between successive periods of growth or the sequestering of portions of necrotic core within the sheath resulted. All sheep examined (eight) had a normal complement of 54 chromosomes.     

General in vivo assay for the study of integrin cell membrane receptor microclustering

A method for measuring the microclustering of a class of cell surface receptors called integrins is reported. Integrins are proteins involved in bidirectional signaling across the cell membrane and are important in cell adhesion, growth, and survival. Their activity is regulated by changes in protein conformation and protein clustering. The developed in vivo clustering assay uses fluorescence resonance energy transfer (FRET) and has the benefit of requiring a single cloning step to generate FRET donors and acceptors that can be used to measure the clustering of a series of integrin mutants. The FRET reporters contain extracellular donor or acceptor fluorescent protein attached to native integrin cytoplasmic and transmembrane domains, and these are expressed along with wild-type or mutant integrins. Expression of the FRET reporters has no affect on the ligand binding properties of coexpressed integrins. FRET values are calculated for cell lines spreading on ligand coated surfaces, and these values are independent of fluorescent protein expression. No FRET is observed in cell lines expressing the reporters in the absence of integrins. Integrin-dependent FRET values increase approximately 2-3-fold when the integrins contain mutations that result in increased ligand binding affinities.     

Enhancement of cisplatin-induced cytotoxicity by 7-hydroxystaurosporine (UCN-01), a new G2-checkpoint inhibitor

DNA-damaging agents arrest cell cycle progression at either G1 or G2. A variety of agents such as caffeine have been shown to abrogate the DNA damage-dependent G2 checkpoint and enhance cytotoxicity. Unfortunately, this strategy has not enhanced therapeutic activity because adequate concentrations of these modulators are not tolerated in vivo. Here, using Chinese hamster ovary cell lines, we show that the potent protein kinase inhibitor 7-hydroxy-staurosporine (UCN-01) abrogates the G2 arrest induced by the DNA-damaging agent cisplatin. UCN-01 not only was effective at inducing mitosis when added to G2-arrested cells but also prevented cells from arresting in G2 when added to S-phase cells. Furthermore, UCN-01 did not cause premature mitosis of S-phase cells; rather, the cells progressed to G2 before undergoing mitosis. These effects were observed at noncytotoxic concentrations of UCN-01 that alone had no effect on cell cycle passage. Furthermore, the same concentrations of UCN-01 that resulted in abrogation of the cisplatin-induced G2 arrest also enhanced cisplatin-induced cytotoxicity, as determined by a colony formation assay. UCN-01 enhanced cisplatin cytotoxicity up to 60-fold and reduced by 3-fold the concentration of cisplatin required to kill 90% of the cells. The concentrations of UCN-01 required for this enhancement have been shown to be well tolerated in animal models, suggesting that this combination may represent an effective strategy for enhancing cisplatin-based chemotherapeutic regimens.     

Large-signal analysis of MOS varactors in CMOS -G/sub m/ LC VCOs

MOS varactors are used extensively as tunable elements in the tank circuits of RF voltage-controlled oscillators (VCOs) based on submicrometer CMOS technologies. MOS varactor topologies include conventional D = S = B connected, inversion-mode (I-MOS), and accumulation-mode (A-MOS) structures. When incorporated into the VCO tank circuit, the large-signal swing of the VCO output oscillation modulates the varactor capacitance in time, resulting in a VCO tuning curve that deviates from the dc tuning curve of the particular varactor structure. This paper presents a detailed analysis of this large-signal effect. Simulated results are compared to measurements for an example 2.5-GHz complementary -G/sub m/ LC VCO using I-MOS varactors implemented in 0.35-/spl mu/m CMOS technology.     

New Insight into the Structure–Activity Relationships of the Selective Excitatory Amino Acid Transporter Subtype 1 (EAAT1) Inhibitors UCPH‐101 and UCPH‐102

In the present study, we made further investigations on the structure–activity requirements of the selective excitatory amino acid transporter 1 (EAAT1) inhibitor, 2‐amino‐4‐(4‐methoxyphenyl)‐7‐(naphthalen‐1‐yl)‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromene‐3‐carbonitrile (UCPH‐101), by exploring 15 different substituents (R¹) at the 7‐position in combination with eight different substituents (R²) at the 4‐position. Among the 63 new analogues synthesized, we identified a number of compounds that unexpectedly displayed inhibitory activities at EAAT1 in light of understanding the structure–activity relationship (SAR) of this inhibitor class extracted from previous studies. Moreover, the nature of the R¹ and R² substituents were observed to contribute to the functional properties of the various analogues in additive and non‐additive ways. Finally, separation of the four stereoisomers of analogue 14 g (2‐amino‐4‐([1,1′‐biphenyl]‐4‐yl)‐3‐cyano‐7‐isopropyl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromene) was carried out, and in agreement with a study of a related scaffold, the R configuration at C4 was found to be mandatory for inhibitory activity, while both the C7 diastereomers were found to be active as EAAT1 inhibitors. A study of the stereochemical stability of the four pure stereoisomers 14 g ‐ A – D showed that epimerization takes places at C7 via a ring‐opening, C?C bond rotation, ring‐closing mechanism.     

Effects of cooking temperatures on the physicochemical properties and consumer acceptance of chicken stock

As a base for sauces, soups, and cooking liquids for meats, grains, and vegetables, stocks can be integral to the overall quality of restaurant menu items, however, science-based studies on the effects of cooking methods on the physiochemical and sensory properties of stock are lacking. The effects of starting (22 °C, 85 °C, and 99 °C) and cooking temperatures (85 °C and 99 °C) of chicken stock on clarity, color, viscosity, protein content, amino acid content, mineral content, and overall liking were measured. Protein content and viscosity were significantly higher for stocks cooked at 99 °C, but no effect on amino acid content, color, or clarity was observed. Calcium concentration in stocks cooked at 99 °C was significantly (P < 0.0001) lower (9.3 and 10.1 mg/mL, for stocks started at temperatures of 22 and 99 °C, respectively) than stock cooked at 85 °C (16.6 and 17.5 mg/mL for stocks started at temperatures of 22 and 85 °C, respectively). Stocks prepared at 99 °C scored higher on overall liking compared to commercial samples and those cooked at 85 °C (P= 0.0101). These data can be used by culinary scientists and professionals to develop more efficient techniques in the kitchen, and by product developers to optimize the overall quality and acceptance of stock. PRACTICAL APPLICATION: This work documents the effects of preparation method on the physical and chemical properties, and consumer acceptance of chicken stock. This information can be used by product developers, culinary scientists, and professional chefs to optimize stock-based products. Culinary educators can use this information to provide students with objective evidence-based rationale for the techniques underlying a celebrated culinary tradition. This is also an example of how research can facilitate collaboration between culinary and food science professionals.     

Ultrathin oxide films by atomic layer deposition on graphene

In this paper, a method is presented to create and characterize mechanically robust, free-standing, ultrathin, oxide films with controlled, nanometer-scale thickness using atomic layer deposition (ALD) on graphene. Aluminum oxide films were deposited onto suspended graphene membranes using ALD. Subsequent etching of the graphene left pure aluminum oxide films only a few atoms in thickness. A pressurized blister test was used to determine that these ultrathin films have a Young's modulus of 154 ± 13 GPa. This Young's modulus is comparable to much thicker alumina ALD films. This behavior indicates that these ultrathin two-dimensional films have excellent mechanical integrity. The films are also impermeable to standard gases suggesting they are pinhole-free. These continuous ultrathin films are expected to enable new applications in fields such as thin film coatings, membranes, and flexible electronics.