CHO cell engineering to prevent polypeptide aggregation and improve therapeutic protein secretion.

The ability to efficiently produce recombinant proteins in a secreted form is highly desirable and cultured mammalian cells such as CHO cells have become the preferred host as they secrete proteins with human-like post-translational modifications. However, attempts to express high levels of particular proteins in CHO cells may consistently result in low yields, even for non-engineered proteins such as immunoglobulins. In this study, we identified the responsible faulty step at the stage of translational arrest, translocation and early processing for such a "difficult-to-express" immunoglobulin, resulting in improper cleavage of the light chain and its precipitation in an insoluble cellular fraction unable to contribute to immunoglobulin assembly. We further show that proper processing and secretion were restored by over-expressing human signal receptor protein SRP14 and other components of the secretion pathway. This allowed the expression of the difficult-to-express protein to high yields, and it also increased the production of an easy-to-express protein. Our results demonstrate that components of the secretory and processing pathways can be limiting, and that engineering of the secretory pathway may be used to improve the secretion efficiency of therapeutic proteins from CHO cells.

In vitro characterization of immune-related properties of human fetal bone cells for potential tissue engineering applications.

We describe herein some immunological properties of human fetal bone cells recently tested for bone tissue-engineering applications. Adult mesenchymal stem cells (MSCs) and osteoblasts were included in the study for comparison. Surface markers involved in bone metabolism and immune recognition were analyzed using flow cytometry before and after differentiation or treatment with cytokines. Immunomodulatory properties were studied on activated peripheral blood mononuclear cells (PBMCs). The immuno-profile of fetal bone cells was further investigated at the gene expression level. Fetal bone cells and adult MSCs were positive for Stro-1, alkaline phosphatase, CD10, CD44, CD54, and beta2-microglobulin, but human leukocyte antigen (HLA)-I and CD80 were less present than on adult osteoblasts. All cells were negative for HLA-II. Treatment with recombinant human interferon gamma increased the presence of HLA-I in adult cells much more than in fetal cells. In the presence of activated PBMCs, fetal cells had antiproliferative effects, although with patterns not always comparable with those of adult MSCs and osteoblasts. Because of the immunological profile, and with their more-differentiated phenotype than of stem cells, fetal bone cells present an interesting potential for allogeneic cell source in tissue-engineering applications.

Engineering Study for the Evaluation of Public Road Administration and Maintenance Alternatives, Executive Summary for HR-265, 1985

Iowa's public road system of 112,000 miles is one of the largest and the best in the nation. It represents a considerable financial investment of taxpayer revenues over the years. And, it requires a sustained investment to preserve an economical level of transport service into the future. In 1982, a Governor's Blue Ribbon Transportation Task Force evaluated the effectiveness of Iowa's entire transportation system. Four important Task Force recommendations dealt with public road administrative issues in Iowa. These issues were related to: 1. design criteria and levels of maintenance 2. consistency in the use of standards among jurisdictions 3. consolidation of maintenance operations at one jurisdictional level and 4. jurisdictional authority for roads. The issues formed the background for Research Project HR-265.

Field Evaluation of Engineering Fabrics for Asphalt Concrete Resurfacing - Audubon County, HR-360, Construction Report, 1994

An asphalt concrete (ACC) overlay is most often the rehabilitative effort used to maintain the serviceability of either an ACC or PCC pavement. The major problem in durability of this ACC overlay comes from reflective cracking. These cracks usually open, allowing water to enter the unsealed crack and strip the ACC in the overlay. The stripping of the ACC allows accelerated deterioration at the crack. Two engineering fabrics were evaluated in this project in order to determine their effectiveness in reducing reflective cracking. These two materials are: PavePrep, Contech Construction Products, Inc., and Pro-Guard, Phillips Fiber Corporation. A 4.2 km (2.6 mi) roadway in Audubon County was selected for the research project. The roadway was divided into eight test sections. Four of the test sections are conventional resurfacing. The other four sections are split between the two engineering fabrics (two Pro-Guard and two PavePrep). A 75 mm (3 in.) thick overlay was placed over the entire project.

Engineering Fabric Repair Prior to Resurfacing - Roadglas - US 30, HR-525, 1992

In Iowa it is normal procedure to either use partial or full-depth patching to repair deteriorated areas of pavement prior to resurfacing. The Owens/Corning Corporation introduced a repair system to replace the patching process. Their Roadglas repair system was used in this research project on US 30 in Story County. It was installed in 1985 and has been observed annually since that time. There were some construction problems with slippage as the roller crossed the abundant Roadglas binder. It appears the Roadglas system has helped to control reflective cracking in the research areas. Since the time when this project was completed it has been reported that Owens/Corning has discontinued production of the Roadglas system.

Concurrent use of cisplatin or cetuximab with definitive radiotherapy for locally advanced head and neck squamous cell carcinomas. Strahlentherapie in Kombination mit platinbasierter Chemotherapie oder Cetuximab zur Behandlung von lokal fortgeschrittenen Plattenepithelkarzinomen im Kopf-Hals-Bereich.

AIM: The goal of the present work was to compare outcomes of definitive concurrent cisplatin-based chemoradiotherapy (CRT) with cetuximab-based bioradiotherapy (BRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Between 2006 and 2012, 265 patients with locally advanced HNSCC were treated at our institution with CRT (n = 194; 73 %) with three cycles of cisplatin (100 mg/m(2), every 3 weeks) or BRT (n = 71; 27 %) with weekly cetuximab. Patients receiving BRT had more pre-existing conditions (Charlson index ≥ 2) than the CRT group (p = 0.005). RESULTS: Median follow-up was 29 months. In all, 56 % of patients treated with CRT received the planned three cycles (92 % at least two cycles) and 79 % patients treated with BRT received six cycles or more. The 2-year actuarial overall survival (OS) and progression-free survival (PFS) were 72 % and 61 %, respectively. In the multivariate analysis (MVA), T4 stage, N2-3 stage, smoking status (current smoker as compared with never smoker), and non-oropharyngeal locations predicted for OS, whereas BRT association with OS was of borderline significance (p = 0.054). The 2-year actuarial locoregional control (LRC) and distant control (DC) rates were 73 and 79 %, respectively. CRT was independently associated with an improved LRC (2-year LRC: 76 % for CRT vs. 61 % for BRT) and DC (2-year LRC: 81 % for CRT vs. 68 % for BRT) in comparison with BRT (p < 0.001 and p = 0.01 in the MVA). Subgroup analyses showed that T4 patients benefited significantly from CRT (vs. BRT) in LRC, while T1-3 did not. BRT patients had more G3-4 skin complications (p < 0.001) and CRT patients had higher rates of feeding tube placement (p = 0.006) and G3-4 gastrointestinal toxicities (p < 0.001). CONCLUSION: This retrospective analysis showed a better LRC in locally advanced HNSCC treated by cisplatin-based CRT than cetuximab-based BRT, and a nonsignificant trend towards an improved OS.

Crystal engineering studies: polymorphs and co-crystals

We review the key topics of one of the areas with the biggest impact of the last years in the chemical and pharmaceutical industry that is Crystal Engineering. The relevance of polymorphs and co-crystals from different points of view is been highlighted and broadly illustrated by means of several recent examples of studies carried out in this field. In addition, the most suitableinstrumental techniques and the intellectual property implications are reviewed.

WISE: Women in Science and Engineering, Fall 2006

Women in Science and Engineering (WISE) Program is to expand and improve educational and professional opportunities for women in all fields of science, technology, engineering and math (STEM) by facilitating individual, institutional, and social change.

WISE: Women in Science and Engineering, Spring 2007

Women in Science and Engineering (WISE) Program is to expand and improve educational and professional opportunities for women in all fields of science, technology, engineering and math (STEM) by facilitating individual, institutional, and social change.

WISE: Women in Science and Engineering, Spring 2009

Women in Science and Engineering (WISE) Program is to expand and improve educational and professional opportunities for women in all fields of science, technology, engineering and math (STEM) by facilitating individual, institutional, and social change.

WISE: Women in Science and Engineering, Winter 2007

Women in Science and Engineering (WISE) Program is to expand and improve educational and professional opportunities for women in all fields of science, technology, engineering and math (STEM) by facilitating individual, institutional, and social change.

WISE: Women in Science and Engineering, Winter 2007-2008

Women in Science and Engineering (WISE) Program is to expand and improve educational and professional opportunities for women in all fields of science, technology, engineering and math (STEM) by facilitating individual, institutional, and social change.

WISE: Women in Science and Engineering, Winter 2009

Women in Science and Engineering (WISE) Program is to expand and improve educational and professional opportunities for women in all fields of science, technology, engineering and math (STEM) by facilitating individual, institutional, and social change.

WISE: Women in Science and Engineering, Winter 2011-2012

Women in Science and Engineering (WISE) Program is to expand and improve educational and professional opportunities for women in all fields of science, technology, engineering and math (STEM) by facilitating individual, institutional, and social change.