Emerging evidence for CHFR as a cancer biomarker : from tumor biology to precision medicine

Novel insights in the biology of cancer have switched the paradigm of a "one-size-fits-all" cancer treatment to an individualized biology-driven treatment approach. In recent years, a diversity of biomarkers and targeted therapies has been discovered. Although these examples accentuate the promise of personalized cancer treatment, for most cancers and cancer subgroups no biomarkers and effective targeted therapy are available. The great majority of patients still receive unselected standard therapies with no use of their individual molecular characteristics. Better knowledge about the underlying tumor biology will lead the way toward personalized cancer treatment. In this review, we summarize the evidence for a promising cancer biomarker: checkpoint with forkhead and ring finger domains (CHFR). CHFR is a mitotic checkpoint and tumor suppressor gene, which is inactivated in a diverse group of solid malignancies, mostly by promoter CpG island methylation. CHFR inactivation has shown to be an indicator of poor prognosis and sensitivity to taxane-based chemotherapy. Here we summarize the current knowledge of altered CHFR expression in cancer, the impact on tumor biology and implications for personalized cancer treatment

{HST Studies of the WLM Galaxy. II. The Star Formation History from Field Stars

HST F555W and F814W photometry of a portion of the WLM galaxy are presented. The distance modulus is determined via fitting of the entire color-magnitude diagram to be (m-M)_0 = 24.88 +/- 0.09, which is consistent with the RGB tip distance. The galaxy's measurable star formation history appears to have begun no more than 12 Gyr ago, with about half of WLM's total star formation (by mass) formed before 9 Gyr ago. The star formation rate gradually decreased, until a recent increase in activity starting between 1 and 2.5 Gyr ago. This is still continuing to the present time, and is concentrated in the bar of the galaxy, as shown by the difference in recent star formation rates in the three WF chips.Comment: 20 pages, 7 figures to be published in Ap

Turbulent superfluid profiles in a counterflow channel

We have developed a two-dimensional model of quantised vortices in helium II moving under the influence of applied normal fluid and superfluid in a counterflow channel. We predict superfluid and vortex-line density profiles which could be experimentally tested using recently developed visualization techniques.Comment: 3 double figures, 9 page

Flow Phase Diagram for the Helium Superfluids

The flow phase diagram for He II and $^3$He-B is established and discussed based on available experimental data and the theory of Volovik [JETP Letters {\bf{78}} (2003) 553]. The effective temperature - dependent but scale - independent Reynolds number $Re_{eff}=1/q=(1+\alpha')/\alpha$, where $\alpha$ and $\alpha'$ are the mutual friction parameters and the superfluid Reynolds number characterizing the circulation of the superfluid component in units of the circulation quantum are used as the dynamic parameters. In particular, the flow diagram allows identification of experimentally observed turbulent states I and II in counterflowing He II with the turbulent regimes suggested by Volovik.Comment: 2 figure

Investigating The Possible Anomaly Between Nebular and Stellar Oxygen Abundances in the Dwarf Irregular Galaxy WLM

We obtained new optical spectra of 13 H II regions in WLM with EFOSC2; oxygen abundances are derived for nine H II regions. The temperature-sensitive [O III] 4363 emission line was measured in two bright H II regions HM7 and HM9. The direct oxygen abundances for HM7 and HM9 are 12+log(O/H) = 7.72 +/- 0.04 and 7.91 +/- 0.04, respectively. We adopt a mean oxygen abundance of 12+log(O/H) = 7.83 +/- 0.06. This corresponds to [O/H] = -0.83 dex, or 15% of the solar value. In H II regions where [O III] 4363 was not measured, oxygen abundances derived with bright-line methods are in general agreement with direct values of the oxygen abundance to an accuracy of about 0.2 dex. In general, the present measurements show that the H II region oxygen abundances agree with previous values in the literature. The nebular oxygen abundances are marginally consistent with the mean stellar magnesium abundance ([Mg/H] = -0.62). However, there is still a 0.62 dex discrepancy in oxygen abundance between the nebular result and the A-type supergiant star WLM15 ([O/H] = -0.21). Non-zero reddening values derived from Balmer line ratios were found in H II regions near a second H I peak. There may be a connection between the location of the second H I peak, regions of higher extinction, and the position of WLM15 on the eastern side of the galaxy.Comment: Accepted, Ap.J.; 19 pages (AASTeX 5.2) with 6 figures. Full paper with color figures at http://www.astro.umn.edu/~hlee

What next for preimplantation genetic screening? High mitotic chromosome instability rate provides the biological basis for the low success rate

Preimplantation genetic screening is being scrutinized, as recent randomized clinical trials failed to observe the expected significant increase in live birth rates following fluorescence in situ hybridization (FISH)-based screening. Although these randomized clinical trials are criticized on their design, skills or premature stop, it is generally believed that well-designed and well-executed randomized clinical trials would resolve the debate about the potential benefit of preimplantation genetic screening. Since FISH can analyze only a limited number of chromosomal loci, some of the embryos transferred might be diagnosed as ‘normal’ but in fact be aneuploid for one or more chromosomes not tested. Hence, genome-wide array comparative genome hybridization screening enabling aneuploidy detection of all chromosomes was thought to be a first step toward a better design. We recently showed array screening indeed enables accurate determination of the copy number state of all chromosomes in a single cell. Surprisingly, however, this genome-wide array screening revealed a much higher frequency and complexity of chromosomal aberrations in early embryos than anticipated, with imbalances in a staggering 90% of all embryos. The mitotic error rate in cleavage stage embryos was proven to be higher than the meiotic aneuploidy rate and as a consequence, the genome of a single blastomere is not representative for the genome of the other cells of the embryo. Hence, potentially viable embryos will be discarded upon screening a single blastomere. This observation provides a biological basis for the failure of the randomized clinical trials to increase baby-take-home rates using FISH on cleavage stage embroys

Building a Professional Identity and an Academic Career Track in Translational Medicine

Biomedical scientists aim to contribute to further understanding of disease pathogenesis and to develop new diagnostic and therapeutic tools that relieve disease burden. Yet the majority of biomedical scientists do not develop their academic career or professional identity as “translational scientists,” and are not actively involved in the continuum from scientific concept to development of new strategies that change medical practice. The collaborative nature of translational medicine and the lengthy process of bringing innovative findings from bench to bedside conflict with established pathways of building a career in academia. This collaborative approach also poses a problem for evaluating individual contributions and progress. The traditional evaluation of scientific success measured by the impact and number of publications and grants scientists achieve is inadequate when the product is a team effort that may take decades to complete. Further, where scientists are trained to be independent thinkers and to establish unique scientific niches, translational medicine depends on combining individual insights and strengths for the greater good. Training programs that are specifically geared to prepare scientists for a career in translational medicine are not widespread. In addition, the legal, regulatory, scientific and clinical infrastructure and support required for translational research is often underdeveloped in academic institutions and funding organizations, further discouraging the development and success of translational scientists in the academic setting. In this perspective we discuss challenges and potential solutions that could allow for physicians, physician scientists and basic scientists to develop a professional identity and a fruitful career in translational medicine

A Spitzer/IRAC Census of the Asymptotic Giant Branch Populations in Local Group Dwarfs. I. WLM

We present Spitzer/IRAC observations at 3.6 and 4.5 microns along with optical data from the Local Group Galaxies Survey to investigate the evolved stellar population of the Local Group dwarf irregular galaxy WLM. These observations provide a nearly complete census of the asymptotic giant branch (AGB) stars. We find 39% of the infrared-detected AGB stars are not detected in the optical data, even though our 50% completeness limit is three magnitudes fainter than the red giant branch tip. An additional 4% of the infrared-detected AGBs are misidentified in the optical, presumably due to reddening by circumstellar dust. We also compare our results with those of a narrow-band optical carbon star survey of WLM, and find the latter study sensitive to only 18% of the total AGB population. We detect objects with infrared fluxes consistent with them being mass-losing AGB stars, and derive a present day total mass-loss rate from the AGB stars of 0.7-2.4 x 10^(-3) solar masses per year. The distribution of mass-loss rates and bolometric luminosities of AGBs and red supergiants are very similar to those in the LMC and SMC and the empirical maximum mass-loss rate observed in the LMC and SMC is in excellent agreement with our WLM data.Comment: Accepted by ApJ, 34 pages, 13 figures, version with high-resolution figures available at: http://webusers.astro.umn.edu/~djackson

Building a Professional Identity and an Academic Career Track in Translational Medicine

Biomedical scientists aim to contribute to further understanding of disease pathogenesis and to develop new diagnostic and therapeutic tools that relieve disease burden. Yet the majority of biomedical scientists do not develop their academic career or professional identity as “translational scientists,” and are not actively involved in the continuum from scientific concept to development of new strategies that change medical practice. The collaborative nature of translational medicine and the lengthy proce