Engineering tolerance into transplanted beta cell lines.

In this paper we explore the possibility of improving, by genetic engineering, the resistance of insulin-secreting cells to the metabolic and inflammatory stresses that are anticipated to limit their function and survival when encapsulated and transplanted in a type 1 diabetic environment. We show that transfer of the Bcl-2 antiapoptotic gene, and of genes specifically interfering with cytokine intracellular signaling pathways, greatly improves resistance of the cells to metabolic limitations and inflammatory stresses.

IL-17F co-expression improves cell growth characteristics and enhances recombinant protein production during CHO cell line engineering.

The generation of a high productivity cell line is a critical step in the production of a therapeutic protein. Many innovative engineering strategies have been devised in order to maximize the expression rate of production cells for increased process efficiency. Less effort has focused on improvements to the cell line generation process, which is typically long and laborious when using mammalian cells. Based on unexpected findings when generating stable CHO cell lines expressing human IL-17F, we studied the benefit of expressing this protein during the establishment of production cell lines. We demonstrate that IL-17F expression enhances the rate of selection and overall number of selected cell lines as well as their transgene expression levels. We also show that this benefit is observed with different parental CHO cell lines and selection systems. Furthermore, IL-17F expression improves the efficiency of cell line subcloning processes. IL-17F can therefore be exploited in a standard manufacturing process to obtain higher productivity clones in a reduced time frame.

Vegetation succession and diversity on Teuravuoma experimental drainage area in northern Finland

Tiivistelmä: Kasvillisuuden sukkessio ja monimuotoisuus Teuravuoman koeojitusalueella Pohjois-Suomessa

Effect of drainage maintenance on the nutrient status on drained Scots pine mires

Tiivistelmä: Kunnostusojituksen vaikutus rämeiden ravinnetilaan

Audit report on the Missouri Valley Drainage District for the year ended June 30, 2012

Audit report on the Missouri Valley Drainage District for the year ended June 30, 2012

Charts of the climatic impact of the drainage of mires in Finland

Tiivistelmä: Karttoja suo-ojitusten vaikutuksesta Suomen ilmastoon

Evaluating Roadway Subsurface Drainage Practices, 2013

The bearing capacity and service life of a pavement is affected adversely by the presence of undrained water in the pavement layers. In cold winter climates like in Iowa, this problem is magnified further by the risk of frost damage when water is present. Therefore, well-performing subsurface drainage systems form an important aspect of pavement design by the Iowa Department of Transportation (DOT). However, controversial findings are also reported in the literature regarding the benefits of subsurface drainage. The goal of this research was not to investigate whether subdrains are needed in Iowa pavements, but to conduct an extensive performance review of primary interstate pavement subdrains in Iowa, determine the cause of the problem if there are drains that are not functioning properly, and investigate the effect of poor subdrain performance due to improper design, construction, and maintenance on pavement surface distresses, if any. An extensive literature review was performed covering national-level and state-level research studies mainly focusing on the effects of subsurface drainage on performance of asphalt and concrete pavements. Several studies concerning the effects of a recycled portland cement concrete (RPCC) subbase on PCC pavement drainage systems were also reviewed. A detailed forensic test plan was developed in consultation with the project technical advisory committee (TAC) for inspecting and evaluating the Iowa pavement subdrains. Field investigations were conducted on 64 selected (jointed plain concrete pavement/JPCP and hot-mix asphalt/HMA) pavement sites during the fall season of 2012 and were mainly focused on the drainage outlet conditions. Statistical analysis was conducted on the compiled data from field investigations to further investigate the effect of drainage on pavement performance. Most Iowa subsurface drainage system outlet blockage is due to tufa, sediment, and soil. Although higher blockage rates reduce the flow rate of water inside outlet pipes, it does not always stop water flowing from inside the outlet pipe to outside the outlet pipe unless the outlet is completely blocked. Few pavement surface distresses were observed near blocked subsurface drainage outlet spots. More shoulder distresses (shoulder drop or cracking) were observed near blocked drainage outlet spots compared to open ones. Both field observations and limited performance analysis indicate that drainage outlet conditions do not have a significant effect on pavement performance. The use of RPCC subbase in PCC pavements results in tufa formation, a primary cause of drainage outlet blockage in JPCP. Several useful recommendations to potentially improve Iowa subdrain performance, which warrant detailed field investigations, were made

Evaluating Roadway Subsurface Drainage Practices: Tech Transfer Summary, 2013.

The bearing capacity and service life of a pavement is affected adversely by the presence of undrained water in the pavement layers. In cold winter climates like in Iowa, this problem is magnified further by the risk of frost damage when water is present. Therefore, well-performing subsurface drainage systems form an important aspect of pavement design by the Iowa Department of Transportation (DOT). However, controversial findings are also reported in the literature regarding the benefits of subsurface drainage. The goal of this research was not to investigate whether subdrains are needed in Iowa pavements, but to conduct an extensive performance review of primary interstate pavement subdrains in Iowa, determine the cause of the problem if there are drains that are not functioning properly, and investigate the effect of poor subdrain performance due to improper design, construction, and maintenance on pavement surface distresses, if any. An extensive literature review was performed covering national-level and state-level research studies mainly focusing on the effects of subsurface drainage on performance of asphalt and concrete pavements. Several studies concerning the effects of a recycled portland cement concrete (RPCC) subbase on PCC pavement drainage systems were also reviewed. A detailed forensic test plan was developed in consultation with the project technical advisory committee (TAC) for inspecting and evaluating the Iowa pavement subdrains. Field investigations were conducted on 64 selected (jointed plain concrete pavement/JPCP and hot-mix asphalt/HMA) pavement sites during the fall season of 2012 and were mainly focused on the drainage outlet conditions. Statistical analysis was conducted on the compiled data from field investigations to further investigate the effect of drainage on pavement performance. Most Iowa subsurface drainage system outlet blockage is due to tufa, sediment, and soil. Although higher blockage rates reduce the flow rate of water inside outlet pipes, it does not always stop water flowing from inside the outlet pipe to outside the outlet pipe unless the outlet is completely blocked. Few pavement surface distresses were observed near blocked subsurface drainage outlet spots. More shoulder distresses (shoulder drop or cracking) were observed near blocked drainage outlet spots compared to open ones. Both field observations and limited performance analysis indicate that drainage outlet conditions do not have a significant effect on pavement performance. The use of RPCC subbase in PCC pavements results in tufa formation, a primary cause of drainage outlet blockage in JPCP. Several useful recommendations to potentially improve Iowa subdrain performance, which warrant detailed field investigations, were made.

MM-GBSA binding free energy decomposition and T cell receptor engineering.

Recognition by the T-cell receptor (TCR) of immunogenic peptides (p) presented by class I major histocompatibility complexes (MHC) is the key event in the immune response against virus infected cells or tumor cells. The major determinant of T cell activation is the affinity of the TCR for the peptide-MHC complex, though kinetic parameters are also important. A study of the 2C TCR/SIYR/H-2Kb system using a binding free energy decomposition (BFED) based on the MM-GBSA approach had been performed to assess the performance of the approach on this system. The results showed that the TCR-p-MHC BFED including entropic terms provides a detailed and reliable description of the energetics of the interaction (Zoete and Michielin, 2007). Based on these results, we have developed a new approach to design sequence modifications for a TCR recognizing the human leukocyte antigen (HLA)-A2 restricted tumor epitope NY-ESO-1. NY-ESO-1 is a cancer testis antigen expressed not only in melanoma, but also on several other types of cancers. It has been observed at high frequencies in melanoma patients with unusually positive clinical outcome and, therefore, represents an interesting target for adoptive transfer with modified TCR. Sequence modifications of TCR potentially increasing the affinity for this epitope have been proposed and tested in vitro. T cells expressing some of the proposed TCR mutants showed better T cell functionality, with improved killing of peptide-loaded T2 cells and better proliferative capacity compared to the wild type TCR expressing cells. These results open the door of rational TCR design for adoptive transfer cancer therapy.

Superior venous drainage in the "LifeBox": a portable extracorporeal oxygenator with a self-expanding venous cannula.

BACKGROUND: In an experimental setting, the performance of the LifeBox, a new portable extracorporeal membrane oxygenator (ECMO) system suitable for patient transport, is presented. Standard rectilinear percutaneous cannulae are normally employed for this purpose, but have limited flow and pressure delivery due to their rigid structure. Therefore, we aimed to determine the potential for flow increase by using self-expanding venous cannulae. METHODS: Veno-arterial bypass was established in three pigs (40.6+/-5.1 kg). The venous line of the cardiopulmonary bypass was established by cannulation of the external jugular vein. The arterial side of the circulation was secured by cannulation of the common carotid artery. Two different venous cannulae (SmartCanula 18/36F 430mm and Biomedicus 19F) were examined for their functional integrity when used in conjunction with the centrifugal pump (500-3000 RPM) of the LifeBox system. RESULTS: At 1500, 2000, 2500, and 3000 RPM, the blood flow increased steadily for each cannula, but remained higher in the self-expanding cannula. That is, the 19F rectilinear cannula achieved a blood flow of 0.93+/-0.14, 1.47+/-0.37, 1.9+/-0.68, and 1.5+/-0.9 l/min, respectively, and the 18/36F self-expanding cannula achieved 1.1+/-0.1, 1.9+/-0.33, 2.8+/-0.39 and 3.66+/-0.52 l/min. However, when tested for venous line pressure, the standard venous cannula achieved -29+/-10.7mmHg while the self-expanding cannula achieved -13.6 +/-4.3mmHg at 1500 RMP. As the RPM increased from 2500 to 3000, the venous line pressure accounted for -141.9+/-20 and -98+/-7.3mmHg for the 19F rectilinear cannula and -30.6+/-6.4 and -45+/-11.6mmHg for the self-expanding cannula. CONCLUSION: The self-expanding cannula exhibited superior venous drainage ability when compared to the performance of the standard rectilinear cannula with the use of the LifeBox. The flow rate achieved was approximately 40% greater than the standard drainage device, with a maximal pump flow recorded at 4.3l/min.

2013 Iowa DOT Engineering Intern Development and Management Program, 13-464, 2013

The Institute for Transportation (InTrans) at Iowa State University (ISU) developed an internship mentoring program in collaboration with the Iowa Department of Transportation (DOT) to provide additional mentorship to both student interns and Iowa DOT intern managers. For the summer 2013 Iowa DOT Engineering Intern Development and Management Program, this report summarizes the following: * Mentoring activities conducted by ISU; * Results of the different intern program success assessments that were conducted; * Experiences, lessons learned, and recommendations; * Program benefits that were realized.

Application of metabolic engineering to the production of scopolamine

Scopolamine is an alkaloid widely used in medicine for its anticholinergic activity. The aim of this review is to show that metabolic engineering techniques constitute a suitable tool to improve the production of tropane alkaloids, focusing in particular on scopolamine. We present an overview of results obtained by various research groups, including our own, who have studied the overexpression of genes involved in the biosynthesis of scopolamine in different plant species that produce tropane alkaloids. Experiments carried out to improve production in hairy root cultures will also be described, as well as those attempting to biotransform hyoscyamine into scopolamine in roots and transgenic tobacco cells.

Estimating Design-Flood Discharges for Streams in Iowa Using Drainage-Basin and Channel-Geometry Characteristics, HR-322, 1993

Drainage-basin and channel-geometry multiple-regression equations are presented for estimating design-flood discharges having recurrence intervals of 2, 5, 10, 25, 50, and 100 years at stream sites on rural, unregulated streams in Iowa. Design-flood discharge estimates determined by Pearson Type-III analyses using data collected through the 1990 water year are reported for the 188 streamflow-gaging stations used in either the drainage-basin or channel-geometry regression analyses. Ordinary least-squares multiple-regression techniques were used to identify selected drainage-basin and channel-geometry regions. Weighted least-squares multiple-regression techniques, which account for differences in the variance of flows at different gaging stations and for variable lengths in station records, were used to estimate the regression parameters. Statewide drainage-basin equations were developed from analyses of 164 streamflow-gaging stations. Drainage-basin characteristics were quantified using a geographic-information-system (GIS) procedure to process topographic maps and digital cartographic data. The significant characteristics identified for the drainage-basin equations included contributing drainage area, relative relief, drainage frequency, and 2-year, 24-hour precipitation intensity. The average standard errors of prediction for the drainage-basin equations ranged from 38.6% to 50.2%. The GIS procedure expanded the capability to quantitatively relate drainage-basin characteristics to the magnitude and frequency of floods for stream sites in Iowa and provides a flood-estimation method that is independent of hydrologic regionalization. Statewide and regional channel-geometry regression equations were developed from analyses of 157 streamflow-gaging stations. Channel-geometry characteristics were measured on site and on topographic maps. Statewide and regional channel-geometry regression equations that are dependent on whether a stream has been channelized were developed on the basis of bankfull and active-channel characteristics. The significant channel-geometry characteristics identified for the statewide and regional regression equations included bankfull width and bankfull depth for natural channels unaffected by channelization, and active-channel width for stabilized channels affected by channelization. The average standard errors of prediction ranged from 41.0% to 68.4% for the statewide channel-geometry equations and from 30.3% to 70.0% for the regional channel-geometry equations. Procedures provided for applying the drainage-basin and channel-geometry regression equations depend on whether the design-flood discharge estimate is for a site on an ungaged stream, an ungaged site on a gaged stream, or a gaged site. When both a drainage-basin and a channel-geometry regression-equation estimate are available for a stream site, a procedure is presented for determining a weighted average of the two flood estimates.

Multiplan Spreadsheets for Highway and Hydraulic Engineering Computations in County Engineering Offices, HR-284, 1987

Multiplan spreadsheet solutions were developed for a set of hydraulic and highway engineering computations of common interest to county engineers. These include earthwork, vertical and horizontal curves, staking superelevated curves and sign inventories for highways. The hydraulic applications were ditch flow, runoff, culvert size and stage discharge.