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Biomedical subjects

M D Kennedy

Publications and source records attributed to M D Kennedy.

10 recordsLinked to original sources

Optimising the operation of a MBR pilot plant by quantitative analysis of the membrane fouling mechanism.

In order to optimize some operational conditions of MBR systems, a MBR pilot plant equipped with a submerged hollow fibre membrane module was employed in this study. The pilot MBR was fed with real municipal wastewater and the filtration flux, backwashing interval, aeration frequency and temperature were varied. A filtration flux below 25 I/m2h is generally recommended, at below this flux, the MBR operated at sub-critical flux conditions, the filter cake was minimized and membrane fouling was mainly attributed to the membrane pore blocking. Moreover, the membrane fouling, at below 25 I/m2h, was more reversible to backwashing; above this value, backwashing became less efficient to clean the membrane. Less frequent backwashing (e.g. 600 s filtration/45 s backwashing) decreased the amount of fouling irreversible to backwashing and its performance was superior to that of frequent backwashing (e.g. 200 s filtration/15 s backwashing). The MBR suffered more fouling at low temperature conditions (e.g. at 13-14 degrees C) than at high temperature conditions (e.g. at 17-18 degrees C). A conceptual model was built up and successfully interpreted this temperature effect.

Bacteria, Aerobic↗

Calibrating a side-stream membrane bioreactor using Activated Sludge Model No. 1.

Membrane bioreactors (MBRs) are attracting global interest but the mathematical modeling of the biological performance of MBRs remains very limited. This study focuses on the modeling of a side-stream MBR system using the Activated Sludge Model No. 1 (ASM1), and compares the results with the modeling of traditional activated sludge processes. ASM1 parameters relevant for the long-term biological behaviour in MBR systems were calibrated (i.e. Y(H) = 0.72 gCOD/gCOD, Y(A) = 0.25 gCOD/gN, b(H) = 0.25 d(-1), b(A) = 0.080 d(-1) and f(p) = 0.06), and generally agreed with the parameters in traditional activated sludge processes, with the exception that a higher autotrophic biomass decay rate was observed in the MBR. Influent wastewater characterization was proven to be a critical step in model calibration, and special care should be taken in characterizing the inert particulate COD (X(I)) concentration in the MBR influent. It appeared that the chemical-biological method was superior to the physical-chemical method. A sensitivity analysis for steady-state operation and DO dynamics suggested that the biological performance of the MBR system (the sludge concentration, effluent quality and the DO dynamics) are very sensitive to the parameters (i.e. Y(H), Y(A), b(H), b(A) micro(maxH) and micro(maxA), and influent wastewater components (X(I), S(s), X(s) and S(NH)).

Biomass↗

Modelling the biological performance of a side-stream membrane bioreactor using ASM1.

Membrane bioreactors (MBRs) are attracting global interest but the mathematical modeling of the biological performance of MBRs remains very limited. This study focuses on the modelling of a side-stream MBR system using Activated Sludge Model No. 1 (ASM1), and comparing the results with the modelling of traditional activated sludge processes. ASM1 parameters relevant for the long-term biological behaviour in MBR systems were calibrated (i.e. Y(H) = 0.72gCOD/gCOD, Y(A) = 0.25gCOD/gN, b(H) = 0.25 d(-1), b(A) = 0.080 d(-1) and f(P) = 0.06), and generally agreed with the parameters in traditional activated sludge processes, with the exception that a higher autotrophic biomass decay rate was observed in the MBR. A sensitivity analysis for steady state operation and DO dynamics suggested that the biological performance of the MBR system (the sludge concentration, effluent quality and the DO dynamics) are very sensitive to the parameters(i.e. Y(H), Y(A), b(H), b(A), micro(maxH) and micro(maxA)), and influent wastewater components(X(I), S(S), X(S), S(NH)).

Biomass↗

A comparison of critical velocity estimates to actual velocities in predicting simulated rowing performance.

The most accurate critical velocity (CV) estimate for the prediction of velocity during a simulated 2,000-m rowing race and the relationship to aerobic power were studied. Sixteen male rowers completed randomized maximal exertion trials (200, 400, 600, 800, 1,000, and 1,200 m), a maximal oxygen consumption (VO(2)max) on a Concept II rowing machine, and an actual 2,000-m simulated rowing race. Three mathematical models were applied to 4 rowing distance combinations producing 12 CV estimates. Seven of the 12 possible CV estimates were not significantly different from actual 2,000-m velocity. Comparison of the 3 CV models using all 6 trial distances revealed that the nonlinear model produced a CV estimate lower than the 2 linear CV models. CV was significantly correlated to VO(2)max (r = 0.91) and the mean velocity achieved during the 2,000-m simulated rowing race (r = 0.97). VO(2)max was significantly correlated to 2,000-m simulated rowing race velocity (r = 0.93).

Adult↗

Riboflavin-mediated delivery of a macromolecule into cultured human cells.

Cell surface receptors for the vitamins folic acid and biotin have been previously reported to mediate the endocytosis of vitamin-conjugated macromolecules into cultured cells. To evaluate whether a similar uptake pathway for riboflavin-conjugated macromolecules might exist, riboflavin was covalently linked to bovine serum albumin (BSA) via the vitamin's ribityl side chain, and uptake of the protein by cultured human cells was examined. Whereas unconjugated BSA was not internalized by KB, A549, SK-LU-1 or SK-OV cells, riboflavin-conjugated BSA was readily internalized (>106 molecules/cell). Analysis of the uptake pathway revealed that the riboflavin-BSA conjugate likely docks on cells at a carrier/transport protein that is distinct from the uptake pathway for free riboflavin and then enters via normal membrane cycling. Evidence for this contention is: (i) the internalized conjugate accumulates in endosomal compartments, (ii) uptake into cells is halted at temperatures near 0 degreesC where membrane trafficking is abrogated, (iii) cell association is inhibited by unlabeled riboflavin-BSA, but not by free riboflavin, and (iv) cellular uptake of [3H]riboflavin is only partially inhibited by riboflavin-BSA. Regardless of the pathway of internalization, these data demonstrate that riboflavin conjugation can facilitate protein entry into human cells in culture.

Binding Sites↗

Optimization of folate-conjugated liposomal vectors for folate receptor-mediated gene therapy.

A folate-targeted transfection complex that is internalized by certain cancer cells and displays several properties reminiscent of enveloped viruses has been developed. These liposomal vectors are comprised of a polycation-condensed DNA plasmid associated with a mixture of neutral and anionic lipids supplemented with folate-poly(ethylene glycol)-dioleylphosphatidylethanolamine for tumor cell-specific targeting. N-Citraconyl-dioleylphosphatidylethanolamine is also included for pH-dependent release of endosome-entrapped DNA into the cytoplasm, and a novel plasmid containing a 366-bp segment from SV40 DNA has been employed to facilitate transport of the plasmid into the nucleus. Because formation of the DNA core is an important step in the assembly of liposomal vectors, considerable effort was devoted to comparing the transfection efficiencies of various DNA condensing agents. It was found that complexation of plasmid DNA with high molecular weight polymers such as acylated-polylysine and cationic dendrimers leads to higher folate-mediated transfection efficiency than DNA complexed with unmodified polylysine. In contrast, compaction of plasmid DNA with small cationic molecules such as spermine, spermidine, or gramicidin S yields only weakly active folate-targeted liposomal vectors. Compared to analogous liposomal vector preparations lacking an optimally compacted DNA core, a cell-specific targeting ligand, a caged fusogenic lipid, and a nucleotide sequence that facilitates nuclear uptake, these modified liposomal vectors display greatly improved transfection efficiencies and target cell specificity.

Anions↗

Folate-targeted enzyme prodrug cancer therapy utilizing penicillin-V amidase and a doxorubicin prodrug.

In antibody-targeted enzyme prodrug therapy, a monoclonal antibody (mAb) covalently linked to an enzyme is commonly exploited to concentrate the enzyme on the tumor cell surface prior to administration of a relatively nontoxic prodrug. The tumor-localized enzyme then converts the prodrug into a cytotoxic agent, which in turn diffuses into the tumor causing localized cell death. In this paper, we have substituted folic acid for the mAb as a mean of delivering an attached enzyme, penicillin-V amidase (PVA), to folate receptor (FR)-positive tumor cells. The enzyme PVA is capable of converting a doxorubicin-N-p-hydroxyphenoxyacetamide prodrug (DPO) into its potent parent drug, doxorubicin. For PVA targeting, each PVA molecule was covalently labeled with three molecules of folic acid via the formation of amide bonds. In vitro binding assays showed that folate-PVA-125I conjugates bind specifically to KB cells (FR-positive tumor cells) but not to A549 cells (FR-negative tumor cells). Moreover, in a series of in vitro cytotoxicity tests, folate-PVA conjugates were found to kill folate receptor positive but not receptor negative cells, and when bound to FR-positive cells, folate-PVA conjugates rendered the DPO prodrug as toxic as free doxorubicin (IC50, approximately 0.6 microM). Finally, preliminary in vivo plasma clearance studies in normal mice revealed that i.v. administered folate-PVA-125I and PVA-125I are both cleared from the blood within a 24 h time period, removing concern that nonspecifically trapped folate-PVA might activate prodrug in nontargeted tissues. In view of the fact that only a small number of folate-PVA molecules are required to mediate killing of target cells in vitro, these data argue that folate-targeted enzyme prodrug therapy should be considered for tumor eradication in vivo.

Animals↗

Assessing communication in children with psychiatric and communication disorders.

This article presents issues related to the communication assessment of children with psychiatric and communication disorders. Challenges inherent in assessing this population are discussed. Frequently used assessment instruments and procedures are described. Consideration is given to the assessment of very young or low-functioning children and older or high-functioning children.

Adolescent↗

Play-language relationships in young children with developmental delays: implications for assessment.

The purpose of this longitudinal study was to determine whether the reported parallels between symbolic play and normal language development were evidenced in 6 children with developmental delays of varying etiologies. Subjects' play and language behavior over a 6-month period was videotaped and analyzed during free play and modeling tasks. Although results supported the correspondences previously reported between normal language development and symbolic play, the variability across observations in the present subjects was more marked than expected. Implications for clinical assessment are discussed.

Child, Preschool↗

Developmental outcome in 49,XXXXY Klinefelter syndrome.

The developmental histories of two males who have 49 XXXXY Klinefelter syndrome are described. Now aged 16 and six, they have been followed since the ages of four and two, respectively. They have many of the typical physical characteristics described in the literature, but their mental retardation is not as severe as has been reported. Both are moderately delayed in their general development and their personalities and learning styles are more similar to XXY Klinefelter individuals. These two case studies demonstrate previously unreported potential in individuals with this disorder, and the authors discuss the implications of this finding.

Adolescent↗