Application of Monoclonal Antibody G250 Recognizing Carbonic Anhydrase IX in Renal Cell Carcinoma

Monoclonal antibody G250 (mAbG250) recognizes a determinant on carbonic anhydrase IX (CAIX). CAIX is expressed by virtually all renal cell carcinomas of the clear cell type (ccRCC), but expression in normal tissues is restricted. The homogeneous CAIX expression in ccRCC and excellent targeting capability of mAbG250 in animal models led to the initiation of the clinical evaluation of mAbG250 in (metastatic) RCC (mRCC) patients. Clinical studies confirmed the outstanding targeting ability of mAbG250 and cG250 PET imaging, as diagnostic modality holds great promise for the future, both in detecting localized and advanced disease. Confirmation of the results obtained in the non-randomized clinical trials with unmodified cG250 is needed to substantiate the value of cG250 treatment in mRCC. cG250-Based radio immuno-therapy (RIT) holds promise for treatment of patients with small-volume disease, and adjuvant treatment with unmodified cG250 may be of value in selected cases. In the upcoming years, ongoing clinical trials should provide evidence for these assumptions. Lastly, whether cG250-based RIT can be combined with tyrosine kinase inhibitors, which constitutes the current standard treatment for mRCC, needs to be established.     

Source Identification of Size-Segregated Aerosol in Münster,Germany, by Factor Analysis

Sources of size-segregated PM ₁₀ , as collected with a five stage Berner type impactor during six intensive measurement campaigns between January 2006 and August 2007 in Münster, NW Germany, were studied by applying factor analysis. PM samples were collected twice a day, each with a sampling duration of 5 to 7.5 hours. Samples were analyzed for water soluble ions, Ca²⁺, Cl^?, Mg²⁺, Na⁺, NH⁺ ₄ , NO^? ₃ , SO^2? ₄, and elemental and organic carbon. Positive matrix factorization (PMF) was used for source apportionment where each size class accounted for a single variable. Five factors were identified of which at least four could be found during each season. Traffic, ammonium nitrate, and long distance transport showed a weekly cycle, whereas the factor representing power generation and industrial products seemed to be relatively stable through the week. Sea salt particles were independent of the day of week. The five factors do not only have a similar composition, but also a similar size distribution, throughout all seasons of the year. Particles from long-distance transport were identified in the accumulation mode while PM originating from power generation were characterized by a larger diameter. Sea salt aerosol consisted mainly of coarse particles, ammonium nitrate is mainly found in the largest size fraction. Even without a detailed chemical trace elements analysis, precise PM source apportionment was accomplished.     

Reverse Engineering and Redesign: Courses to Incrementally and Systematically Teach Design

A variety of design‐process and design‐methods courses exist in engineering education. The primary objective of such courses is to teach engineering design fundamentals utilizing repeatable design techniques. By so doing, students obtain (1) tools they may employ during their education, (2) design experiences to understand the “big picture” of engineering, and (3) proven methods to attack open‐ended problems. While these skills are worthwhile, especially as design courses are moved earlier in curricula, many students report that design methods are typically taught at a high‐level and in a compartmentalized fashion. Often, the students' courses do not include opportunities to obtain incremental concrete experiences with the methods. Nor do such courses allow for suitable observation and reflection as the methods are executed. In this paper, we describe a new approach for teaching design methods that addresses these issues. This approach incorporates hands‐on experiences through the use of “reverse‐engineering” projects. As the fundamentals of design techniques are presented, students immediately apply the methods to actual, existing products. They are able to hold these products physically in their hands, dissect them, perform experiments on their components, and evolve them into new successful creations. Based on this reverse‐engineering concept, we have developed and tested new courses at The University of Texas, MIT, and the United States Air Force Academy. In the body of this paper, we present the structure of these courses, an example of our teaching approach, and an evaluation of the results.     

Germline mosaicism in 4q35 facioscapulohumeral muscular dystrophy (FSHD1A) occurring predominantly in oogenesis

The presence of gamma-glutamyl transpeptidase (GGT) in boar spermatozoa and the potential role of the GGT at sperm penetration were examined using in vitro matured porcine oocytes. In the first experiment, GGT of boar spermatozoa was examined using a histochemical stain. GGT was detected in the midpiece and the acrosome regions of boar spermatozoa. In the second experiment, porcine oocytes matured in vitro were injected with approximately 40 pl of 10 mM HEPES solution alone or HEPES containing 0.5 U/ml GGT or 1 mM guanosine-5'-O-(3'-thiotriphosphate) (GTP-gamma-S; G-protein activator). When GGT was injected into oocytes, the incidence of oocytes activated (23.7 +/- 1.4%) was not different (P > 0.05) from HEPES-injected controls (24.9 +/- 1.3%) at 6 h after injection. Injected GTP-gamma-S, however, activated 76.0 +/- 5.3% of oocytes at 6 h after injection, but extrusion of the second polar body was very low (2.8 +/- 4.8%). Total content of glutathione (GSH) and glutathione disulfide (GSSG) did not differ (P > 0.05) between GTP-gamma-S injected oocytes (4.2 +/- 0.7 pmol/oocyte) and noninjected oocytes (4.0 +/- 0.1 pmol/oocyte) at 6 h after injection. However, the total content of GSH and GSSG was lower (P < 0.01) in GGT-injected oocytes (2.1 +/- 0.2 pmol/oocyte) than HEPES-injected oocytes (3.4 +/- 0.2 pmol/oocyte) at 6 h after injection. In the third experiment, in vitro matured porcine oocytes were injected with about 40 pl of 10 mM HEPES solution alone or HEPES containing 0.5 U/ml GGT and then inseminated. At 12 h after insemination, the incidence of male pronuclear formation was significantly lower in oocytes injected with GGT as compared with injected control oocytes. These results demonstrated that (1) GGT was present on the surface of spermatozoa, (2) total oocyte content of GSH and GSSG was decreased by microinjection of GGT but not by that of GTP-gamma-S, and (3) male pronuclear formation was inhibited in GGT-injected oocytes. These results suggest that sperm GGT may be a limiting factor for male pronuclear formation in polyspermic oocytes.