Traceable clonal culture and chemodrug assay of heterogeneous prostate carcinoma PC3 cells in microfluidic single cell array chips

Cancer heterogeneity has received considerable attention for its role in tumor initiation and progression, and its implication for diagnostics and therapeutics in the clinic. To facilitate a cellular heterogeneity study in a low cost and highly efficient manner, we present a microfluidic platform that allows traceable clonal culture and characterization. The platform captures single cells into a microwell array and cultures them for clonal expansion, subsequently allowing on-chip characterization of clonal phenotype and response against drug treatments. Using a heterogeneous prostate cancer model, the PC3 cell line, we verified our prototype, identifying three different sub-phenotypes and correlating their clonal drug responsiveness to cell phenotype.     

Microfluidic device capable of medium recirculation for non-adherent cell culture

We present a microfluidic device designed for maintenance and culture of non-adherent mammalian cells, which enables both recirculation and refreshing of medium, as well as easy harvesting of cells from the device. We demonstrate fabrication of a novel microfluidic device utilizing Braille perfusion for peristaltic fluid flow to enable switching between recirculation and refresh flow modes. Utilizing fluid flow simulations and the human promyelocytic leukemia cell line, HL-60, non-adherent cells, we demonstrate the utility of this RECIR-REFRESH device. With computer simulations, we profiled fluid flow and concentration gradients of autocrine factors and found that the geometry of the cell culture well plays a key role in cell entrapping and retaining autocrine and soluble factors. We subjected HL-60 cells, in the device, to a treatment regimen of 1.25% dimethylsulfoxide, every other day, to provoke differentiation and measured subsequent expression of CD11b on day 2 and day 4 and tumor necrosis factor-alpha (TNF-α) on day 4. Our findings display perfusion sensitive CD11b expression, but not TNF-α build-up, by day 4 of culture, with a 1:1 ratio of recirculation to refresh flow yielding the greatest increase in CD11b levels. RECIR-REFRESH facilitates programmable levels of cell differentiation in a HL-60 non-adherent cell population and can be expanded to other types of non-adherent cells such as hematopoietic stem cells.     

Cultural heritage and the attractiveness of cities: evidence from recreation trips

Many cities are trying to attract tourists by investing in urban amenities. Cultural heritage is an important example, and substantial investments are needed to keep ancient inner cities and characteristic monumental buildings in good shape. The costs of these policies are usually clear, and the benefits are often much more difficult to assess. This paper attempts to fill part of this gap by studying the destination choices of urban recreation trips that have urban recreation as the main travel motive. We estimate a discrete choice model for destination choice that takes into account the potential importance of unobserved characteristics. The model allows us to compute the marginal willingness-to-travel for destinations offering more cultural heritage, which we measure as the area of the inner city that has a protected status because of the cultural heritage that is present there.     

Cheaper patents

The 1883 Patents Act in Britain provides perspective for modern patent policy reforms because it radically changed incentives for inventors by reducing filing fees by 84 percent. Patents increased 2.5-fold after the reform, which was evenly distributed across the geography of inventors, the organization of invention and sectors. By realizing a large demand for cheaper patents the reform increased the propensity to patent and shifted inventive activity inside the patent system. It did not increase innovation as measured by changes in the distribution of high and low value patents and citations to English inventor patents in the United States.     

Quantification of the physiological loading of one week of "pre-season" and one week of "in-season" training in professional soccer players

The aim of this study was to quantify the physiological loads of programmed "pre-season" and "in-season" training in professional soccer players. Data for players during each period were included for analysis (pre-season, n = 12; in-season, n = 10). We monitored physiological loading of training by measuring heart rate and rating of perceived exertion (RPE). Training loads were calculated by multiplying RPE score by the duration of training sessions. Each session was sub-categorized as physical, technical/tactical, physical and technical/tactical training. Average physiological loads in pre-season (heart rate 124 ± 7 beats · min(-1); training load 4343 ± 329 Borg scale · min) were higher compared with in-season (heart rate 112 ± 7 beats · min(-1); training load 1703 ± 173 Borg scale · min) (P < 0.05) and there was a greater proportion of time spent in 80-100% maximum heart rate zones (18 ± 2 vs. 5 ± 2%; P < 0.05). Such differences appear attributable to the higher intensities in technical/tactical sessions during pre-season (pre-season: heart rate 137 ± 8 beats · min(-1); training load 321 ± 23 Borg scale · min; in-season: heart rate 114 ± 9 beats · min(-1); training load 174 ± 27 Borg scale · min; P < 0.05). These findings demonstrate that pre-season training is more intense than in-season training. Such data indicate that these adjustments in load are a direct attempt to deliver training to promote specific training adaptations.     

Continuing Education and the Redrawing of Boundaries

Continuing education, broadly defined to include both vocational and non-vocational kinds of provision, is having an increasing impact within higher education. Its further expansion is now part of government strategy. This expansion will not be achieved without difficulties, and it poses considerable and varied challenges to those who work in higher education. In this paper, we focus on the effects that continuing education is having on established boundaries within higher education — boundaries between different sectors and types of provision, between different subjects and ways of teaching, and between higher education staff and their different skills. As the provision of continuing education increases, existing boundaries will change, become more permeable or be broken down altogether while new divisions and distinctions are created and built up.     

IS THERE REAL OPINION CHANGE?

Public opinion research in general and the study of opinionchange in particular have frequently been challenged as unreliable.Attitudinal measurements are characterized as merely reflectingnon-attitudes, labile moods, and/or methodological artefacts.Given this basis, the measurement of opinion change is seenas a product of random variations and systematic biases ratherthan as reliably measuring true change. However, most opinionchange is (1) not chaotic, but slow and steady and (2) largelyexplicable. Even opinion change that is rapid and/or multi-directionalcan be plausibly explained. Measurement variation does howeveroften distort time series and greatly complicates the reliableassessment of true change.     

Applying scientific openmindedness to religion and science education

Mahner's and Bunge's two main theses are nearly correct as social reports but the extent to which they are wrong is philosophically very important. I draw attention to a philosophically superior way of viewing the essential relation between science and religion which can have a humane or benign influence upon how both science and religion are taught. On the one hand, science does not need to fight religion nor try to suppress it. A generous openness of mind, which distinguishes the critical rationality implicit in the advance of science, deserves to be applied without acrimony to any systems of thought that purport to explain the universe. On the other hand, religions have no need to fear the growth of scientific knowledge, provided science is not confused, as Mahner and Bunge confuse it, with its materialistic interpretation.