Commercial investigation results for the generic bioprocessing apparatus flown on United States Microgravity Laboratory-1

The Generic Bioprocessing Apparatus (BPA) payload was developed by BioServe to support the commercial flight development needs of our specialized consortia comprised of business, academic, and government entities. The consortia have commitments to explore commercial opportunities in bioprocessing, biomedical models, and closed agricultural systems. In addition, some members of BioServe have interests in the development and/or qualification of enabling flight hardware used in life sciences space flight testing. Some business and academic entities have interests in more than one of these consortia. To aid in payload development, flight, and analysis, each consortium member contributes resources ranging from proprietary expertise and materials, to hardware and cash. Professionals from business, academia, and government often interact with each other via graduate research assistants who do much of the 'hands-on' payload preparation and subsequent data analyses. The GBA supported research, testing, and development activities for each different BioServe consortium. It produced an environment in which professionals from diverse backgrounds came together with a single focus. And, it provided a truly novel learning environment for a youthful new cadre of space professionals committed to the exploration of commercial opportunities presented by space. Since the GBA supported a large number of different experiments, this paper briefly describes the payload characteristics and the essential operations of the payload. A summary of the experiments is presented. Finally, a few of the experiments are described in detail highlighting some novel effects of space flight on life science systems. Portions of the reported work have or will appear in appropriate archival journals as cited in the bibliography. In several instances, data collected from USML-1 have been supplemented with related data collected on more recent STS missions

Autonomous support for microorganism research in space

A preliminary design for performing on-orbit, autonomous research on microorganisms and cultured cells/tissues is presented. An understanding of gravity and its effects on cells is crucial for space exploration as well as for terrestrial applications. The payload is designed to be compatible with the COMmercial Experiment Transported (COMET) launch vehicle, an orbiter middeck locker interface, and with Space Station Freedom. Uplink/downlink capabilities and sample return through controlled reentry are available for all carriers. Autonomous testing activities are preprogrammed with inflight reprogrammability. Sensors for monitoring temperature, pH, light, gravity levels, vibration, and radiation are provided for environmental regulation and experimental data collection. Additional experiment data acquisition includes optical density measurement, microscopy, video, and file photography. Onboard full data storage capabilities are provided. A fluid transfer mechanism is utilized for inoculation, sampling, and nutrient replenishment of experiment cultures. In addition to payload design, representative experiments were developed to ensure scientific objectives remained compatible with hardware capabilities. The project is defined to provide biological data pertinent to extended duration crewed space flight including crew health issues and development of a Controlled Ecological Life Support System (CELSS). In addition, opportunities are opened for investigations leading to commercial applications of space, such as pharmaceutical development, modeling of terrestrial diseases, and material processing

New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel

Although the treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, it is entering a new era with the development of new strategies and trial designs. Because there is an increasing number of novel therapeutic agents and potential combinations available to test in patients with PDAC, the identification of robust prognostic and predictive markers and of new targets and relevant pathways is a top priority as well as the design of adequate trials incorporating molecular-driven hypothesis. We presently report a consensus strategy for research in pancreatic cancer that was developed by a multidisciplinary panel of experts from different European institutions and collaborative groups involved in pancreatic cancer. The expert panel embraces the concept of exploratory early proof of concept studies, based on the prediction of response to novel agents and combinations, and randomised phase II studies permitting the selection of the best therapeutic approach to go forward into phase III, where the recommended primary end point remains overall survival. Trials should contain as many translational components as possible, relying on standardised tissue and blood processing and robust biobanking, and including dynamic imaging. Attention should not only be paid to the pancreatic cancer cells but also to microenvironmental factors and stem/stellate cell

Pancreatobiliary versus intestinal histologic type of differentiation is an independent prognostic factor in resected periampullary adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Resectable adenocarcinomas in the pancreatic head, by definition "periampullary", originate from ampullary, duodenal, biliary, or ductal pancreatic epithelium. Typically, periampullary adenocarcinomas have either intestinal or pancreatobiliary type of differentiation, and the type of differentiation might be prognostically more important than the anatomic site of origin. The aim of the study was to determine whether the histologic type of differentiation is an independent prognostic factor in periampullary adenocarcinoma, and whether tumour origin predicts the prognosis in pancreatobiliary type carcinomas independently of resection margin involvement, tumour size, nodal involvement, perineural and vascular infiltration, and degree of differentiation.</p> <p>Methods</p> <p>Histopathologic variables in 114 consecutively resected periampullary adenocarcinomas of pancreatobiliary (n = 67) and intestinal (n = 47) type differentiation were evaluated using a standardized, systematic protocol for evaluation of the resected specimen (study group). Histologic type of differentiation and tumour origin were compared as predictors of survival, and the results were validated by comparison with a historical control group consisting of 99 consecutive pancreaticoduodenectomies performed before standardization of histopathologic evaluation. Associations between histopathologic variables were evaluated by Chi-square and Mann-Whitney tests. Survival was estimated by the Kaplan-Meier method, comparing curves using log-rank test, and by univariate and multivariable Cox regression analysis.</p> <p>Results</p> <p>Both in the study group (n = 114) and in the historical control group (n = 99), the histologic type of differentiation independently predicted survival, while tumour origin predicted survival only in univariate analysis. Independent adverse predictors of survival in the study group were pancreatobiliary type differentiation (p < 0.001; HR 3.1; CI 1.8–5.1), regional lymph node involvement (p < 0.001; HR 2.5; CI 1.5–4.4), vessel involvement (p = 0.012; HR 1.9; CI 1.2–3.1), and increasing tumour diameter (measured in cm, p = 0.011; HR 1.3; CI 1.1–1.5). For pancreatobiliary differentiated adenocarcinomas (n = 67), lymph node status, vessel involvement, and tumour diameter remained independent prognostic factors, while tumour origin did not independently predict the prognosis due to significant association with tumour size (p < 0.001) and lymph node involvement (p = 0.004).</p> <p>Conclusion</p> <p>Pancreatobiliary versus intestinal type of differentiation independently predicts poor prognosis after pancreaticoduodenectomy for periampullary adenocarcinoma. Lymph node involvement, vessel infiltration, and increasing tumour diameter are adverse predictors of survival in tumours with pancreatobiliary differentiation.</p

Incidence, mechanism and prognostic value of activated AKT in pancreas cancer

When activated, the serine/threonine kinase AKT mediates an antiapoptotic signal implicated in chemoresistance of various cancers. The mechanism(s) of AKT activation are unknown, though overexpression of HER-2/neu has been implicated in breast cancer. Therefore, we determined the incidence of activated AKT in human pancreatic cancer, whether HER-2/neu is involved in AKT activation, and if AKT activation is associated with biologic behaviour. HER-2/neu expression and AKT activation were examined in seven pancreatic cancer cell lines by Western blotting. The in vitro effect of HER-2/neu inhibition on AKT activation was similarly determined. Finally, 78 pancreatic cancer specimens were examined for AKT activation and HER-2/neu overexpression, and correlated with the clinical prognostic variable of histologic grade. HER-2/neu was overexpressed in two of seven cell lines; these two cell lines demonstrated the highest level of AKT activation. Inhibition of HER-2/neu reduced AKT activation in vitro. AKT was activated in 46 out of 78 (59%) of the pancreatic cancers; HER-2/neu overexpression correlated with AKT activation (P=0.015). Furthermore, AKT activation was correlated with higher histologic tumour grade (P=0.047). Thus, it is concluded that AKT is frequently activated in pancreatic cancer; this antiapoptotic signal may be mediated by HER-2/neu overexpression. AKT activation is associated with tumour grade, an important prognostic factor

Techniques for the Determination of Local Dynamic Pressure and Angle of Attack on a Horizontal Axis Wind Turbine

Data from the National Renewable Energy Laboratory`s Combined Experiment has been utilized to develop techniques for indirectly calculating the instantaneous local dynamic pressure and angle of attack on a horizontal axis wind turbine. First, an analytic model based upon inflow geometry relative to the wind turbine was developed for both parameters. Second, dynamic pressure and angle of attack were inferred from the pressure required to normalize the blade stagnation point to C{sub p} = 1.0. Third, rotor blade pressure profiles were compared to those from wind tunnel tests to determine angle of attack. Test results are shown over a variety of typical inflow conditions and are corroborated by measured data. Differences between the calculated and measured values are also discussed