Keratin 6a marks mammary bipotential progenitor cells that can give rise to a unique tumor model resembling human normal-like breast cancer.

Progenitor cells are considered an important cell of origin of human malignancies. However, there has not been any single gene that can define mammary bipotential progenitor cells, and as such it has not been possible to use genetic methods to introduce oncogenic alterations into these cells in vivo to study tumorigenesis from them. Keratin 6a is expressed in a subset of mammary luminal epithelial cells and body cells of terminal end buds. By generating transgenic mice using the Keratin 6a (K6a) gene promoter to express tumor virus A (tva), which encodes the receptor for avian leukosis virus subgroup A (ALV/A), we provide direct evidence that K6a(+) cells are bipotential progenitor cells, and the first demonstration of a non-basal location for some biopotential progenitor cells. These K6a(+) cells were readily induced to form mammary tumors by intraductal injection of RCAS (an ALV/A-derived vector) carrying the gene encoding the polyoma middle T antigen. Tumors in this K6a-tva line were papillary and resembled the normal breast-like subtype of human breast cancer. This is the first model of this subtype of human tumors and thus may be useful for preclinical testing of targeted therapy for patients with normal-like breast cancer. These observations also provide direct in vivo evidence for the hypothesis that the cell of origin affects mammary tumor phenotypes

Inflammatory biomarker score and cancer: A population-based prospective cohort study

BACKGROUND: Inflammation is associated with cancer but there are conflicting reports on associations of biomarkers of inflammation with cancer risk and mortality. We investigated the associations of C-reactive protein (CRP) and leukocyte count with cancer risk and mortality using individual biomarkers, and an inflammatory score derived from both biomarkers. METHODS: We conducted this analysis among 2,570 men enrolled in the population-based, prospective Kuopio Ischemic Heart Disease Risk Factor Study in Finland. During an average follow-up period of 26 years, 653 cancer cases and 287 cancer deaths occurred. We computed a z-score for each participant, with the combined z-score being the sum of each individual’s CRP and leukocyte z-scores. Multivariable-adjusted Cox proportional hazard model was used to evaluate associations with cancer risk and mortality. RESULTS: Using individual biomarkers, elevated leukocyte count was associated with an increased risk of cancer (RR = 1.31, 95 % CI 1.04-1.66), and cancer mortality (RR=, 95 % CI 1.39, 0.98-1.97). The corresponding results for CRP were (RR = 1.23, 95 % CI 0.97-1.55) for risk and (RR = 1.15, 95 % CI 0.81-1.64) for cancer mortality. Associations of the biomarkers with cancer appeared to be more robust using the combined z-score. HRs comparing men within the highest z-score quartile to those within the lowest z-score quartiles were 1.47 (95 % CI 1.16-1.88, p-trend < 0.01) for cancer risk, and 1.48 (95 % CI 1.03-2.14, p-trend = 0.09) for cancer mortality. CONCLUSION: Our study suggests that inflammation is associated with cancer risk and mortality, and combining inflammatory biomarkers into a score is a robust method of elucidating this association

The limits of the total crystal-field splittings

The crystal-fields causing $|J>$ electron states splittings of the same second moment $\sigma^{2}$ can produce different total splittings $\Delta E$ magnitudes. Based on the numerical data on crystal-field splittings for the representative sets of crystal-field Hamiltonians ${\cal H}_{\rm CF}=\sum_{k}\sum_{q}B_{kq}C_{q}^{(k)}$ with fixed indexes either $k$ or $q$, the potentials leading to the extreme $\Delta E$ have been identified. For all crystal-fields the admissible ranges $(\Delta E_{min},\Delta E_{max})$ have been found numerically for $1\leq J\leq 8$. The extreme splittings are reached in the crystal-fields for which ${\cal H}_{\rm CF}s$ are the definite superpositions of the $C_{q}^{(k)}$ components with different rank $k=2,4$ and 6 and the same index $q$. Apart from few exceptions, the lower limits $\Delta E_{min}$ occur in the axial fields of ${\cal H}_{\rm CF}(q=0)=B_{20}C_{0}^{(2)}+B_{40}C_{0}^{(4)}+B_{60}C_{0}^{(6)}$, whereas the upper limits $\Delta E_{max}$ in the low symmetry fields of ${\cal H}_{\rm CF}(q=1)=B_{21}C_{1}^{(2)}+B_{41}C_{1}^{(4)}+B_{61}C_{1}^{(6)}$. Mixing the ${\cal H}_{\rm CF}$ components with different $q$ yields a secondary effect and does not determine the extreme splittings. The admissible $\Delta E_{min}$ changes with $J$ from $2.00\sigma$ to $2.40\sigma$, whereas the $\Delta E_{max}$ from $2.00\sigma$ to $4.10\sigma$. The maximal gap $\Delta E_{max}-\Delta E_{min}=2.00\sigma$ has been found for the states $|J=4>$. Not all the nominally allowed total splittings, preserving $\sigma^{2}=const$ condition, are physically available, and in consequence not all virtual splittings diagrams can be observed in real crystal-fields.Comment: 30 pages, Appendix (8 pages) and 11 tables; submitted to pss(b

Visiting the iron cage: Bureaucracy and the contemporary workplace

Bureaucracy as an organizational form has always been a controversial issue and placed at the very heart of most discussions within organizational theory. One side of this prolonged discussion praises this administrative form as the ‘rational’ way to run an organization. It provides needed guidance and clarifies responsibilities, which enables employees to become more efficient. However, the opposition claims that in a non-linear world, where industrial organizations are forced to confront the challenging task of sensing and responding to unpredictable, novel situations of highly competitive markets, such an organizational form stifles creativity, fosters de-motivation and causes pressure on employees. Dealing with a bureaucratic form of organization and its consequences begs for a context. It would be appropriate to quit ‘taking sides’ and develop a sound analysis of this phenomenon under the conditions of today’s global workplace environment. This chapter intends to delineate the conditions under which bureaucracy has emerged and the way it has been interpreted since its inception and develop a sound and appropriate analytical approach to its functioning given the prevailing conditions of the contemporary workplace.Publisher's VersionAuthor Post Prin