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Biomedical subjects

Z Yuan

Publications and source records attributed to Z Yuan.

At least 37 records · Page 2Linked to original sources

Integration of titrimetric measurement, off-gas analysis and NOx- biosensors to investigate the complexity of denitrification processes.

The denitrification process, namely the reduction of nitrate (NO3-) to nitrogen gas (N2), often cannot be simply modelled as a single step process. For a more complete and comprehensive model the intermediates, particularly nitrite (NO2-) and nitrous oxide (N2O), need to be investigated. This paper demonstrates the integration of titrimetric measurements and off-gas analysis with on-line nitrite plus nitrate (NOx-) biosensors, highlighting the necessity of measuring process intermediates with high time-scale resolution to study and understand the kinetics of denitrification. Investigation of activated sludge from a full-scale treatment plant showed a significant accumulation of NO2-, which appeared to impact on the overall denitrification rate measured as NOx- reduction or N2 production. A different sludge obtained from a lab-scale bioreactor produced N2O instead of N2 as the end product of denitrification. The two examples both illustrate the complexity of denitrification and stress the need for the more versatile and detailed measurement procedures, as presented in this paper.

Bioreactors↗

Comparison of methods for the determination of K(L)aO2 for respirometric measurements.

The mass transfer coefficient for oxygen in water (K(L)aO2) is an important parameter for respirometric studies. But determination of K(L)aO2 in process conditions is not straightforward, In this paper, two distinct procedures for determining K(L)aO2 in process conditions are outlined and tested. The off-gas method relies on a gas mass balance over a bioreactor while the non-steady state methods rely on analysing DO recovery after perturbation. Various means for inducing perturbation are tested and compared. K(L)aO2 values for a bioreactor are determined by the listed methods. It was found that the off-gas method resulted in the highest K(L)aO2 for the given reactor, while the non-steady state method, whereby perturbation is caused by exogenous activity on acetate, resulted in the lowest K(L)aO2. It is shown that the gas mass balancing technique is robust to unexpected exogenous activity (caused by for example, the oxidation of storage polymers formed or nitrite accumulated), while the non-steady state methods that involve inducing perturbations by exogenous activity appear susceptible to such continued exogenous activity in the DO recovery period.

Ammonia↗

Alpha-substituted hydroxamic acids as novel bacterial deformylase inhibitor-based antibacterial agents.

We report the synthesis and biological activity of analogues of VRC3375 (N-hydroxy-3-R-butyl-3-[(2-S-(tert-butoxycarbonyl)-pyrrolidin-1-ylcarbonyl]propionamide), an orally active peptide deformylase inhibitor. This study explores the structure-activity relationship of various chelator groups, alpha substituents, P(2)' and P(3)' substituents in order to achieve optimal antibacterial activity with minimal toxicity liability.

Amidohydrolases↗

T helper 2 immunity to hepatitis B surface antigen primed by gene-gun-mediated DNA vaccination can be shifted towards T helper 1 immunity by codelivery of CpG motif-containing oligodeoxynucleotides.

Gene-gun-mediated DNA immunization usually induces predominant T helper 2 (Th2) type immune response. As oligodeoxynucleotides (ODN)-containing unmethylated CpG motifs can activate the innate immune system in a Th1-biased way, the potential of codelivery of CpG motifs-containing ODN (CpG-ODN) with plasmid DNA to switch the gene-gun-mediated Th2 immune response was evaluated in this study. Here we show that codelivery of CpG-ODN with plasmid DNA at certain ratio (10/1) can enhance the Th1 humoral and cell-mediated immune responses in gene-gun-mediated DNA immunization in BALB/c mice, including increasing the hepatitis B surface antigen-specific total immunoglobulin G (IgG), IgG2a subclass, cytotoxic T-cell lymphocyte activity as well as interferon-gamma (IFN-gamma) secretion. Taken together, these results demonstrate that codelivery of CpG-ODN with recombinant plasmid DNA by gene gun can shift the gene-gun-mediated DNA immune response from Th2 towards Th1.

Adjuvants, Immunologic↗

Constitutive model development and micro-structural topology optimisation for nafion hydrogel membranes with ionic clustering.

The deployment of electroactive ionic polymer hydrogel-metal composites in artificial muscle and BioMEMS applications has recently been intensively investigated. In order to analyse their electromechanical responses to externally applied electrical fields, it is critical to develop a constitutive model linking the macro-mechanical moduli with the micro-mechanical characteristics, and to determine the geometric size and shape of the micro-structural cluster and investigate the effect of cluster morphology on the effective electro-elastic moduli of the polymer hydrogels. As a typical ionic polymer-based hydrogel, the Nafion membrane is studied in this work. Based on the Biot poroelasticity theory, a multi-scale constitutive model which includes both macro and micro characteristics is developed using an asymptotic homogenisation method. The effect of water-volume fraction on the effective elastic moduli of the hydrogel membrane is examined for different equivalent weights. Numerical investigations show that the simulated effective constitutive moduli agree well with experimental data. The presently developed constitutive model is thus validated. In order to determine the micro-structural shape of the polymer skeleton subject to fluid pressure, a representative volume element (RVE) is designed by topology optimisation of the periodic microstructures of the Nafion hydrogels, through the minimisation of the electro-elastic interaction energy between the polymer-based fluorocarbon matrix and the surrounding fluid. This optimal RVE correctly predicts the geometric shapes of the clusters.

Compressive Strength↗

Age-related decreases in the response of aquaporin-5 to acetylcholine in rat parotid glands.

Aquaporin-5 (AQP5) is important in salivary fluid secretion in response to cholinergic and adrenergic stimuli in rat parotid glands. We hypothesized that expression and function of AQP5 might change with age. Acetylcholine and epinephrine induced increases in AQP5 levels in the apical plasma membranes of both young adult and senescent rats. The stimulatory effect of acetylcholine, but not that of epinephrine, on AQP5 levels in the apical plasma membranes of the cells decreased markedly during aging. The quinuclidine derivative, SNI-2011, induced a persistent increase in AQP5 levels in the apical plasma membrane in the cells of both these rats. The amounts of M(3)-muscarinic receptor and Gq proteins did not decrease during aging. The age-related alteration in the responsiveness of AQP5 in the cells to these stimuli might account for the concomitant changes in nitric oxide synthase activity. These results suggest that SNI-2011 might have therapeutic benefit for the treatment of age-related xerostomia.

Acetylcholine↗

The effect of GAOs (glycogen accumulating organisms) on anaerobic carbon requirements in full-scale Australian EBPR (enhanced biological phosphorus removal) plants.

Glycogen-accumulating organisms (GAOs) were present in six full-scale plants investigated and in all but one made a significant contribution to the amount of volatile fatty acid (VFA) taken up anaerobically. While most plants surveyed contain GAOs, it was demonstrated that it is possible for a full-scale plant to operate with an insignificant GAO population. "Candidatus Accumulibacter phosphatis" were the significant polyphosphate-accumulating organisms (PAOs) in all plants surveyed. "Candidatus Competibacter phosphatis" were found in all plants along with other possible GAOs that were observed but not identified. A significant GAO population will increase the carbon requirements by removing VFA that could otherwise have been used by PAOs. Process optimization minimizing GAOs in full-scale plants would lead to a more efficient use of VFA.

Bioreactors↗

Improving titrimetric techniques by modelling pH change in activated sludge systems.

Existing titrimetric techniques rely on a well defined hydrogen ion production rate. In particular, they are only suitable in circumstances in which constant background pH influencing reactions take place. This is rarely the case due to the presence of the carbonate acid/base system. In this paper, a model, which describes the influence of the nitrification process on pH and accounts for the action of the carbonate system, is presented. The validity of the model is tested by comparison of model predictions for the important state variables with that of experimental data from a batch oxidation of ammonium nitrogen. The two cases studied are the responses of an endogenously respiring nitrifying sludge to: an ammonium chloride pulse and a pulse of both bicarbonate and ammonium chloride. The results are most encouraging as the dynamic HPR response is mirrored by the model simulation. Furthermore, using the model for data interpretation, the initial nitrogen substrate levels are recovered. It is shown that this could not have been achieved in either case using existing titrimetric techniques.

Bioreactors↗

Integrated control of nitrate recirculation and external carbon addition in a predenitrification system.

The integrated control of nitrate recirculation and external carbon addition in a predenitrification biological wastewater treatment system is studied. The proposed control structure consists of four feedback control loops, which manipulate the nitrate recirculation and the carbon dosage flows in a highly coordinated manner such that the consumption of external carbon is minimised while the nitrate discharge limits (based on both grab and composite samples) are met. The control system requires the measurement of the nitrate concentrations at the end of both the anoxic and the aerobic zones. Distinct from ordinary control systems, which typically minimise the variation in the controlled variables, the proposed control system essentially maximises the diurnal variation of the effluent nitrate concentration and through this maximises the use of influent COD for denitrification, thus minimising the requirement for external carbon source. Simulation studies using a commonly accepted simulation benchmark show that the controlled system consistently achieves the designated effluent quality with minimum costs.

Bioreactors↗

Lymphatic transport of pericardial effusate in sheep.

In this report, we quantified fluid loss from the pericardial cavity during simulated saline effusions and determined what proportion of this loss occurred through lymphatics. Fifty or 100 ml of Ringers lactate solution [containing 0.5% sheep albumin and (131)I-human serum albumin (HSA)] was injected into the pericardial cavity of sheep. Pericardial pressures, systemic arterial pressures, and plasma/pericardial fluid concentrations of the radioactive tracer were measured. Lymph transport of pericardial fluid was estimated from the plasma recovery of tracer using a mass balance equation. Plasma recoveries were corrected for tracer loss using a coefficient of elimination calculated from the plasma disappearance curve of intravenously administered (125)I-HSA. Over 4 h, 27.6 +/- 4.9 (+/-SE) and 36.7 +/- 4.2 ml were lost from the pericardial cavity in the 50- and 100-ml effusion series, respectively, of which 5.2 +/- 0.8 (20.2 +/- 3.8% of volume lost) and 7.7 +/- 1.6 ml (21.5 +/- 3.3% of volume lost) could be attributed to lymphatic transport. We conclude that lymphatic transport is one of the factors that contribute to pericardial "reserve" function by helping to restore pericardial fluid volume to resting levels.

Animals↗

A framework for extreme-event control in wastewater treatment.

In this paper an approach to extreme event control in wastewater treatment plant operation by use of automatic supervisory control is discussed. The framework presented is based on the fact that different operational conditions manifest themselves as clusters in a multivariate measurement space. These clusters are identified and linked to specific and corresponding events by use of principal component analysis and fuzzy c-means clustering. A reduced system model is assigned to each type of extreme event and used to calculate appropriate local controller set points. In earlier work we have shown that this approach is applicable to wastewater treatment control using look-up tables to determine current set points. In this work we focus on the automatic determination of appropriate set points by use of steady state and dynamic predictions. The performance of a relatively simple steady-state supervisory controller is compared with that of a model predictive supervisory controller. Also, a look-up table approach is included in the comparison, as it provides a simple and robust alternative to the steady-state and model predictive controllers. The methodology is illustrated in a simulation study.

Aerobiosis↗

A hedging point strategy--balancing effluent quality, economy and robustness in the control of wastewater treatment plants.

An operational space map is an efficient tool to compare a large number of operational strategies to find an optimal choice of setpoints based on a multicriterion. Typically, such a multicriterion includes a weighted sum of cost of operation and effluent quality. Due to the relative high cost of aeration such a definition of optimality result in a relatively high fraction of the effluent total nitrogen in the form of ammonium. Such a strategy may however introduce a risk into operation because a low degree of ammonium removal leads to a low amount of nitrifiers. This in turn leads to a reduced ability to reject event disturbances, such as large variations in the ammonium load, drop in temperature, the presence of toxic/inhibitory compounds in the influent etc. Hedging is a risk minimisation tool, with the aim to "reduce one's risk of loss on a bet or speculation by compensating transactions on the other side" (The Concise Oxford Dictionary (1995)). In wastewater treatment plant operation hedging can be applied by choosing a higher level of ammonium removal to increase the amount of nitrifiers. This is a sensible way to introduce disturbance rejection ability into the multi criterion. In practice, this is done by deciding upon an internal effluent ammonium criterion. In some countries such as Germany, a separate criterion already applies to the level of ammonium in the effluent. However, in most countries the effluent criterion applies to total nitrogen only. In these cases, an internal effluent ammonium criterion should be selected in order to secure proper disturbance rejection ability.

Automation↗

Combined hydraulic and biological modelling and full-scale validation of SBR process.

The biological reactions during the settling and decant periods of Sequencing Batch Reactors (SBRs) are generally ignored as they are not easily measured or described by modelling approaches. However, important processes are taking place, and in particular when the influent is fed into the bottom of the reactor at the same time (one of the main features of the UniFed process), the inclusion of these stages is crucial for accurate process predictions. Due to the vertical stratification of both liquid and solid components, a one-dimensional hydraulic model is combined with a modified ASM 2d biological model to allow the prediction of settling velocity, sludge concentration, soluble components and biological processes during the non-mixed periods of the SBR. The model is calibrated on a full-scale UniFed SBR system with tracer breakthrough tests, depth profiles of particulate and soluble compounds and measurements of the key components during the mixed aerobic period. This model is then validated against results from an independent experimental period with considerably different operating parameters. In both cases, the model is able to accurately predict the stratification and most of the biological reactions occurring in the sludge blanket and the supernatant during the non-mixed periods. Together with a correct description of the mixed aerobic period, a good prediction of the overall SBR performance can be achieved.

Bioreactors↗

Benchmarking nitrogen removal suspended-carrier biofilm systems using dynamic simulation.

We are witnessing an enormous growth in biological nitrogen removal from wastewater. It presents specific challenges beyond traditional COD (carbon) removal. A possibility for optimised process design is the use of biomass-supporting media. In this paper, attached growth processes (AGP) are evaluated using dynamic simulations. The advantages of these systems that were qualitatively described elsewhere, are validated quantitatively based on a simulation benchmark for activated sludge treatment systems. This simulation benchmark is extended with a biofilm model that allows for fast and accurate simulation of the conversion of different substrates in a biofilm. The economic feasibility of this system is evaluated using the data generated with the benchmark simulations. Capital savings due to volume reduction and reduced sludge production are weighed out against increased aeration costs. In this evaluation, effluent quality is integrated as well.

Benchmarking↗

The fasciated ear2 gene encodes a leucine-rich repeat receptor-like protein that regulates shoot meristem proliferation in maize.

The ability to initiate organs throughout the lifecycle is a unique feature of plant development that is executed by groups of stem cells called meristems. The balance between stem cell proliferation and organ initiation is carefully regulated and ensures that organs can be initiated in regular geometric patterns. To understand how this regulation is achieved, we isolated a novel mutant of maize, fasciated ear2 (fea2), which causes a massive overproliferation of the ear inflorescence meristem and a more modest effect on floral meristem size and organ number. We cloned the fea2 gene using transposon tagging, and it encodes a membrane localized leucine-rich repeat receptor-like protein that is most closely related to CLAVATA2 from Arabidopsis. These findings provide evidence that the CLAVATA pathway for regulation of meristem size is functionally conserved throughout the angiosperms. A possible connection of fea2 to the control of crop yields is discussed.

Amino Acid Sequence↗

Separation of six uremic middle molecular compounds by high performance liquid chromatography and analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

BACKGROUND: Since the postulation of uremic middle molecule (UMM) hypothesis made by Babb et al. [Trans-Am Soc Artif Intern Organs 18 (1972) 98], there has been great interest in the separation and identification of the role of UMM. However, few of the compounds isolated from UMM fractions were demonstrated to play an important role in humans. Thus, the separation and identification of the real UMM is essential for UMM research. METHODS: Urine and serum samples from uremic patients and healthy subjects were separated by gel permeation chromatography. Two presumed UMM fractions, A and B, were obtained from uremic sera and urine, normal urine, but not normal sera. Fraction A was further isolated by anion exchange chromatography and a series of sub-peaks were obtained. The sub-fraction A-3 obtained in the second step was desalted on a Sephadex G-15 column, and characterized by IR, UV and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Further separation of sub-fraction A-3 was performed by high performance liquid chromatography (HPLC). RESULTS: By gel permeation chromatography, two UMM peaks (A and B) were detected at 206 nm in normal urine, uremic sera, but they were barely noticed in the profile of normal sera. In contrast, the absorption at 206 nm of fractions A and B from uremic serum and urine were smaller than that of fractions A and B from normal urine. Fractions A from different origins were resolved into eight to nine sub-peaks at 230 nm by anion exchange chromatography. One of these sub-peaks, A-3, was detected in uremic serum and normal urine, but is undetectable in uremic urine. After desalting, sub-fraction A-3 was separated into two parts designated as A-3-I and A-3-II. MALDI-TOF-MS revealed that fraction A-3-I and A-3-II from two origins were identical, respectively-fraction A-3-I contained three components with MW 839.69, 1007.94 and 2015.16 and fraction A-3-II consisted of another three components with MW 873.69, 1106.67 and 1680.28. Six middle molecular compounds in sub-fraction A-3 were thoroughly resolved by HPLC. CONCLUSION: Our results demonstrated that the UMM sub-fraction A-3 contains the real UMM in the MW range of 800-2015 Da. By multi-step chromatographic isolation, six real middle molecular compounds were purified and characterized with MALDI-TOF-MS. It is likely that three of these UMM compounds are important, as they readily accumulated in sera of uremic patients, but are normally excreted in healthy subjects.

Adult↗

Deformylase as a novel antibacterial target.

Bacterial genomics has revealed a plethora of previously unknown targets of potential use in the discovery of novel antibacterial drugs. However, so far little has emerged from this approach. Peptide deformylase is an interesting target that was discovered more than 30 years ago, but was not exploited until recently. The reawakening of interest in this target resulted from an improved understanding of the enzyme, making it a more tractable and attractive target. Information on the properties of the enzyme, such as its three-dimensional structure, the activity of inhibitors, its resistance and suitability as a target are discussed.

Journal Article↗

Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K.

We have shown previously that the AKT2 pathway is essential for cell survival and important in malignant transformation. In this study, we demonstrate elevated kinase levels of AKT2 and phosphatidylinositol-3-OH kinase (PI3K) in 32 of 80 primary breast carcinomas. The majority of the cases with the activation are estrogen receptor alpha (ERalpha) positive, which prompted us to examine whether AKT2 regulates ERalpha activity. We found that constitutively activated AKT2 or AKT2 activated by epidermal growth factor or insulin-like growth factor-1 promotes the transcriptional activity of ERalpha. This effect occurred in the absence or presence of estrogen. Activated AKT2 phosphorylates ERalpha in vitro and in vivo, but it does not phosphorylate a mutant ERalpha in which ser-167 was replaced by Ala. The PI3K inhibitor, wortmannin, abolishes both the phosphorylation and transcriptional activity of ERalpha induced by AKT2. However, AKT2-induced ERalpha activity was not inhibited by tamoxifen but was completely abolished by ICI 164,384, implicating that AKT2-activated ERalpha contributes to tamoxifen resistance. Moreover, we found that ERalpha binds to the p85alpha regulatory subunit of PI3K in the absence or presence of estradiol in epithelial cells and subsequently activates PI3K/AKT2, suggesting ERalpha regulation of PI3K/AKT2 through a nontranscriptional and ligand-independent mechanism. These data indicate that regulation between the ERalpha and PI3K/AKT2 pathway (ERalpha-PI3K/AKT2-ERalpha) may play an important role in pathogenesis of human breast cancer and could contribute to ligand-independent breast cancer cell growth.

Androstadienes↗