Fischell Department of Bioengineering Research Works

Permanent URI for this collectionhttp://hdl.handle.net/1903/6627

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    Decrease of resistance to air flow with nasal strips as measured with the airflow perturbation device
    (Springer Nature, 2004-10-22) Wong, Lily S; Johnson, Arthur T
    Nasal strips are used by athletes, people who snore, and asthmatics to ease the burden of breathing. Although there are some published studies that demonstrate higher flow with nasal strips, none had directly measured the effect of the strips on nasal resistance using the airflow perturbation device (APD). The APD is an inexpensive instrument that can measure respiratory resistance based on changes in mouth pressure and rate of airflow. This study tested forty-seven volunteers (14 men and 33 women), ranging in age from 17 to 51. Each volunteer was instructed to breathe normally into the APD using an oronasal mask with and without nasal strips. The APD measured respiratory resistance during inhalation, exhalation, and an average of the two. Results of a paired mean t-test comparing nasal strip against no nasal strip were statistically significant at the p = 0.05 level. The Breathe Right™ nasal dilator strips lowered nasal resistance by an average of 0.5 cm H20/Lps from an average nasal resistance of 5.5 cm H20/Lps. Nasal strips reduce nasal resistance when measured with the APD. The effect is equal during exhalation and during inhalation.
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    Maximum static inspiratory and expiratory pressures with different lung volumes
    (Springer Nature, 2006-05-05) Lausted, Christopher G; Johnson, Arthur T; Scott, William H; Johnson, Monique M; Coyne, Karen M; Coursey, Derya C
    Maximum pressures developed by the respiratory muscles can indicate the health of the respiratory system, help to determine maximum respiratory flow rates, and contribute to respiratory power development. Past measurements of maximum pressures have been found to be inadequate for inclusion in some exercise models involving respiration. Maximum inspiratory and expiratory airway pressures were measured over a range of lung volumes in 29 female and 19 male adults. A commercial bell spirometry system was programmed to occlude airflow at nine target lung volumes ranging from 10% to 90% of vital capacity. In women, maximum expiratory pressure increased with volume from 39 to 61 cmH2O and maximum inspiratory pressure decreased with volume from 66 to 28 cmH2O. In men, maximum expiratory pressure increased with volume from 63 to 97 cmH2O and maximum inspiratory pressure decreased with volume from 97 to 39 cmH2O. Equations describing pressures for both sexes are: Pe/Pmax = 0.1426 Ln( %VC) + 0.3402 R2 = 0.95 Pi/Pmax = 0.234 Ln(100 - %VC) - 0.0828 R2 = 0.96 These results were found to be consistent with values and trends obtained by other authors. Regression equations may be suitable for respiratory mechanics models.
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    A finite element model for protein transport in vivo
    (Springer Nature, 2007-06-28) Sadegh Zadeh, Kouroush; Elman, Howard C; Montas, Hubert J; Shirmohammadi, Adel
    Biological mass transport processes determine the behavior and function of cells, regulate interactions between synthetic agents and recipient targets, and are key elements in the design and use of biosensors. Accurately predicting the outcomes of such processes is crucial to both enhancing our understanding of how these systems function, enabling the design of effective strategies to control their function, and verifying that engineered solutions perform according to plan. A Galerkin-based finite element model was developed and implemented to solve a system of two coupled partial differential equations governing biomolecule transport and reaction in live cells. The simulator was coupled, in the framework of an inverse modeling strategy, with an optimization algorithm and an experimental time series, obtained by the Fluorescence Recovery after Photobleaching (FRAP) technique, to estimate biomolecule mass transport and reaction rate parameters. In the inverse algorithm, an adaptive method was implemented to calculate sensitivity matrix. A multi-criteria termination rule was developed to stop the inverse code at the solution. The applicability of the model was illustrated by simulating the mobility and binding of GFP-tagged glucocorticoid receptor in the nucleoplasm of mouse adenocarcinoma. The numerical simulator shows excellent agreement with the analytic solutions and experimental FRAP data. Detailed residual analysis indicates that residuals have zero mean and constant variance and are normally distributed and uncorrelated. Therefore, the necessary and sufficient criteria for least square parameter optimization, which was used in this study, were met.The developed strategy is an efficient approach to extract as much physiochemical information from the FRAP protocol as possible. Well-posedness analysis of the inverse problem, however, indicates that the FRAP protocol provides insufficient information for unique simultaneous estimation of diffusion coefficient and binding rate parameters. Care should be exercised in drawing inferences, from FRAP data, regarding concentrations of free and bound proteins, average binding and diffusion times, and protein mobility unless they are confirmed by long-range Markov Chain-Monte Carlo (MCMC) methods and experimental observations.
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    Synthetic biology: enormous possibility, exaggerated perils
    (Springer Nature, 2008-04-25) Russ, Zachary N
    The following essay was written by a freshman undergraduate student majoring in Bioengineering at the University of Maryland, Mr. Zachary Russ. Mr. Russ was one of 94 students who submitted a 1000 to 1200 word essay to the 3rd Annual Bioethics Essay Contest sponsored by the Institute of Biological Engineering (IBE). A group of professionals in Biological Engineering assessed and ranked the essays in a blinded process. Five semi-finalists were invited to present their essays at a session at the annual meeting of IBE in Chapel Hill, NC on March 8, 2008. Five judges scored the presentations at the annual meeting and selected Mr. Russ's contribution as the overall winner (1st Place). Below is his essay.
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    Testing limits to airflow perturbation device (APD) measurements
    (Springer Nature, 2008-10-31) Lopresti, Erika R; Johnson, Arthur T; Koh, Frank C; Scott, William H; Jamshidi, Shaya; Silverman, Nischom K
    The Airflow Perturbation Device (APD) is a lightweight, portable device that can be used to measure total respiratory resistance as well as inhalation and exhalation resistances. There is a need to determine limits to the accuracy of APD measurements for different conditions likely to occur: leaks around the mouthpiece, use of an oronasal mask, and the addition of resistance in the respiratory system. Also, there is a need for resistance measurements in patients who are ventilated. Ten subjects between the ages of 18 and 35 were tested for each station in the experiment. The first station involved testing the effects of leaks of known sizes on APD measurements. The second station tested the use of an oronasal mask used in conjunction with the APD during nose and mouth breathing. The third station tested the effects of two different resistances added in series with the APD mouthpiece. The fourth station tested the usage of a flexible ventilator tube in conjunction with the APD. All leaks reduced APD resistance measurement values. Leaks represented by two 3.2 mm diameter tubes reduced measured resistance by about 10% (4.2 cmH2O·sec/L for control and 3.9 cm H2O·sec/L for the leak). This was not statistically significant. Larger leaks given by 4.8 and 6.4 mm tubes reduced measurements significantly (3.4 and 3.0 cm cmH2O·sec/L, respectively). Mouth resistance measured with a cardboard mouthpiece gave an APD measurement of 4.2 cm H2O·sec/L and mouth resistance measured with an oronasal mask was 4.5 cm H2O·sec/L; the two were not significantly different. Nose resistance measured with the oronasal mask was 7.6 cm H2O·sec/L. Adding airflow resistances of 1.12 and 2.10 cm H2O·sec/L to the breathing circuit between the mouth and APD yielded respiratory resistance values higher than the control by 0.7 and 2.0 cm H2O·sec/L. Although breathing through a 52 cm length of flexible ventilator tubing reduced the APD measurement from 4.0 cm H2O·sec/L for the control to 3.6 cm H2O·sec/L for the tube, the difference was not statistically significant. The APD can be adapted for use in ventilated, unconscious, and uncooperative patients with use of a ventilator tube and an oronasal mask without significantly affecting measurements. Adding a resistance in series with the APD mouthpiece has an additive effect on resistance measurements, and can be used for qualitative calibration. A leak size of at least the equivalent of two 3.2 mm diameter tubes can be tolerated without significantly affecting APD measurements.
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    Microbial nar-GFP cell sensors reveal oxygen limitations in highly agitated and aerated laboratory-scale fermentors
    (Springer Nature, 2009-01-15) Garcia, Jose R; Cha, Hyung J; Rao, Govind; Marten, Mark R; Bentley, William E
    Small-scale microbial fermentations are often assumed to be homogeneous, and oxygen limitation due to inadequate micromixing is often overlooked as a potential problem. To assess the relative degree of micromixing, and hence propensity for oxygen limitation, a new cellular oxygen sensor has been developed. The oxygen responsive E. coli nitrate reductase (nar) promoter was used to construct an oxygen reporter plasmid (pNar-GFPuv) which allows cell-based reporting of oxygen limitation. Because there are greater than 109 cells in a fermentor, one can outfit a vessel with more than 109 sensors. Our concept was tested in high density, lab-scale (5 L), fed-batch, E. coli fermentations operated with varied mixing efficiency – one verses four impellers. In both cases, bioreactors were maintained identically at greater than 80% dissolved oxygen (DO) during batch phase and at approximately 20% DO during fed-batch phase. Trends for glucose consumption, biomass and DO showed nearly identical behavior. However, fermentations with only one impeller showed significantly higher GFPuv expression than those with four, indicating a higher degree of fluid segregation sufficient for cellular oxygen deprivation. As the characteristic time for GFPuv expression (approx 90 min.) is much larger than that for mixing (approx 10 s), increased specific fluorescence represents an averaged effect of oxygen limitation over time and by natural extension, over space. Thus, the pNar-GFPuv plasmid enabled bioreactor-wide oxygen sensing in that bacterial cells served as individual recirculating sensors integrating their responses over space and time. We envision cell-based oxygen sensors may find utility in a wide variety of bioprocessing applications.
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    Mapping the moral boundaries of biological engineering
    (Springer Nature, 2009-05-08) Russ, Zachary N
    The following essay was written by a sophomore undergraduate student majoring in Bioengineering at the University of Maryland, Mr. Zachary Russ. Mr. Russ was one of 174 students who submitted a 1000–1200 word essay to the 4th Annual Bioethics Contest sponsored by the Institute of Biological Engineering (IBE). A group of professionals in Biological Engineering assessed and ranked the essays in a blinded process. Five semi-finalists were invited to present their essays at a session at the annual meeting of IBE in Santa Clara, CA on March 21, 2009. Five judges scored all the presentation at the annual meeting and selected Mr. Russ's contribution as the overall winner (1st Place).
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    Analysis of recent segmental duplications in the bovine genome
    (Springer Nature, 2009-12-01) Liu, George E; Ventura, Mario; Cellamare, Angelo; Chen, Lin; Cheng, Ze; Zhu, Bin; Li, Congjun; Song, Jiuzhou; Eichler, Evan E
    Duplicated sequences are an important source of gene innovation and structural variation within mammalian genomes. We performed the first systematic and genome-wide analysis of segmental duplications in the modern domesticated cattle (Bos taurus). Using two distinct computational analyses, we estimated that 3.1% (94.4 Mb) of the bovine genome consists of recently duplicated sequences (≥ 1 kb in length, ≥ 90% sequence identity). Similar to other mammalian draft assemblies, almost half (47% of 94.4 Mb) of these sequences have not been assigned to cattle chromosomes. In this study, we provide the first experimental validation large duplications and briefly compared their distribution on two independent bovine genome assemblies using fluorescent in situ hybridization (FISH). Our analyses suggest that the (75-90%) of segmental duplications are organized into local tandem duplication clusters. Along with rodents and carnivores, these results now confidently establish tandem duplications as the most likely mammalian archetypical organization, in contrast to humans and great ape species which show a preponderance of interspersed duplications. A cross-species survey of duplicated genes and gene families indicated that duplication, positive selection and gene conversion have shaped primates, rodents, carnivores and ruminants to different degrees for their speciation and adaptation. We identified that bovine segmental duplications corresponding to genes are significantly enriched for specific biological functions such as immunity, digestion, lactation and reproduction. Our results suggest that in most mammalian lineages segmental duplications are organized in a tandem configuration. Segmental duplications remain problematic for genome and assembly and we highlight genic regions that require higher quality sequence characterization. This study provides insights into mammalian genome evolution and generates a valuable resource for cattle genomics research.
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    Complete genomic sequence analysis of infectious bronchitis virus Ark DPI strain and its evolution by recombination
    (2008-12-22) Ammayappan, Arun; Upadhyay, Chitra; Gelb, Jack Jr.; Vakharia, Vikram N
    An infectious bronchitis virus Arkansas DPI (Ark DPI) virulent strain was sequenced, analyzed and compared with many different IBV strains and coronaviruses. The genome of Ark DPI consists of 27,620 nucleotides, excluding poly (A) tail, and comprises ten open reading frames. Comparative sequence analysis of Ark DPI with other IBV strains shows striking similarity to the Conn, Gray, JMK, and Ark 99, which were circulating during that time period. Furthermore, comparison of the Ark genome with other coronaviruses demonstrates a close relationship to turkey coronavirus. Among non-structural genes, the 5'untranslated region (UTR), 3C-like proteinase (3CL pro) and the polymerase (RdRp) sequences are 100% identical to the Gray strain. Among structural genes, S1 has 97% identity with Ark 99; S2 has 100% identity with JMK and 96% to Conn; 3b 99%, and 3C to N is 100% identical to Conn strain. Possible recombination sites were found at the intergenic region of spike gene, 3'end of S1 and 3a gene. Independent recombination events may have occurred in the entire genome of Ark DPI, involving four different IBV strains, suggesting that genomic RNA recombination may occur in any part of the genome at number of sites. Hence, we speculate that the Ark DPI strain originated from the Conn strain, but diverged and evolved independently by point mutations and recombination between field strains.