Cells exhibiting strong p16INK4a promoter activation in vivo display features of senescence

The activation of cellular senescence throughout the lifespan promotes tumor suppression, whereas the persistence of senescent cells contributes to aspects of aging. This theory has been limited, however, by an inability to identify and isolate individual senescent cells within an intact organism. Toward that end, we generated a murine reporter strain by “knocking-in” a fluorochrome, tandem-dimer Tomato (tdTom), into exon 1α of the p16 INK4a locus. We used this allele (p16 tdTom ) for the enumeration, isolation, and characterization of individual p16 INK4a -expressing cells (tdTom + ). The half-life of the knocked-in transcript was shorter than that of the endogenous p16 INK4a mRNA, and therefore reporter expression better correlated with p16 INK4a promoter activation than p16 INK4a transcript abundance. The frequency of tdTom + cells increased with serial passage in cultured murine embryo fibroblasts from p16 tdTom/+ mice. In adult mice, tdTom + cells could be readily detected at low frequency in many tissues, and the frequency of these cells increased with aging. Using an in vivo model of peritoneal inflammation, we compared the phenotype of cells with or without activation of p16 INK4a and found that tdTom + macrophages exhibited some features of senescence, including reduced proliferation, senescence-associated β-galactosidase (SA-β-gal) activation, and increased mRNA expression of a subset of transcripts encoding factors involved in SA-secretory phenotype (SASP). These results indicate that cells harboring activation of the p16 INK4a promoter accumulate with aging and inflammation in vivo, and display characteristics of senescence

The intermediate-age open cluster NGC 2112

We report on $BVI$ CCD photometry of a field centered on the region of the intermediate-age open cluster NGC 2112 down to V=21. Due to the smaller field coverage, we are able to limit the effect of field star contamination which hampered in the past precise determinations of the cluster age and distance. This way, we provide updated estimates of NGC 2112 fundamental parameters. Having extended the photometry to the $I$ pass-band, we are able to construct a colour-colour diagram, from which we infer a reddening $E_{B-V}= 0.63\pm0.14$ mag. The comparison of the Colour-Magnitude Diagram (CMD) with theoretical isochrones leads to a distance of $850 \pm 100$ pc, and an age of $2.0 \pm 0.3$ Gyr. While the distance is in agreement with previous determinations, the age turns out to be much better constrained and significantly lower than previous estimates.Comment: 7 pages, 7 eps figures, in press in MNRA

Cost model relationships between textile manufacturing processes and design details for transport fuselage elements

Textile manufacturing processes offer potential cost and weight advantages over traditional composite materials and processes for transport fuselage elements. In the current study, design cost modeling relationships between textile processes and element design details were developed. Such relationships are expected to help future aircraft designers to make timely decisions on the effect of design details and overall configurations on textile fabrication costs. The fundamental advantage of a design cost model is to insure that the element design is cost effective for the intended process. Trade studies on the effects of processing parameters also help to optimize the manufacturing steps for a particular structural element. Two methods of analyzing design detail/process cost relationships developed for the design cost model were pursued in the current study. The first makes use of existing databases and alternative cost modeling methods (e.g. detailed estimating). The second compares design cost model predictions with data collected during the fabrication of seven foot circumferential frames for ATCAS crown test panels. The process used in this case involves 2D dry braiding and resin transfer molding of curved 'J' cross section frame members having design details characteristic of the baseline ATCAS crown design

V4332 Sagittarii revisited

The eruption of V4332 Sgr discovered in February 1994 shows striking similarities to that of V838 Mon started in January 2002. The nature of these eruptions is, however, enigmatic and unclear. We present new photometric and spectroscopic data on V4332 Sgr obtained in April-May 2003 at the SAAO. The obtained spectrum shows an unusual emission-line component superimposed on an early M-type stellar spectrum. The emission-line spectrum is of very low excitation and is dominated by lines from neutral elemets (NaI, FeI, CaI) and molecular bands (TiO, ScO, AlO). We also analyse all the observational data, mainly photometric measurements, available for V4332 Sgr. This allows us to follow the evolution of the effective temperature, radius and luminosity of the object since February 1994 till 2003. We show that the observed decline of V4332 Sgr can be accounted for by a gravitational contraction of an inflated stellar envelope. The combined optical and infrared photometry in 2003 shows that apart from the M-type stellar component there is a strong infrared excess in the KLM bands. This excess was absent in the 2MASS measurements done in 1998 but was probably starting to appear in K in 1999 when the object was observed in the DENIS survey. We interpret the results in terms of a stellar merger scenario proposed by Soker & Tylenda. The infrared excess is likely to be due to a disc-like structure which is either of protostellar nature or has been produced during the 1994 eruption and stores angular momentum from the merger event.Comment: 11 pages, 5 figures, accepted in Astronomy & Astrophysic

The Journal of the Friends' Historical Society vol. 3 No. 3

1. Notices. 2. Notes and Queries. 3. Letter from William Penn. 4. David Lloyd II. 5. Friends on the Atlantic. 6. King's Briefs the Forerunners of Mutual Insurance Societies. 7. Whitefield's Estimate of Quakerism. 8. Earlham College Library, Richmond, Ind. 9. Editors' Notes. 10. Large Gatherings of Friends. 11. Meeting Records I. 12. Friends in Current Literature. 13. A Quotation in the London Y.M. Epistle. 14. List of Officers for 1906-7. 15. Accounts and Balance Sheet for 1905

Far infrared mapping of three Galactic star forming regions : W3(OH), S 209 & S 187

Three Galactic star forming regions associated with W3(OH), S209 and S187 have been simultaneously mapped in two trans-IRAS far infrared (FIR) bands centered at ~ 140 and 200 micron using the TIFR 100 cm balloon borne FIR telescope. These maps show extended FIR emission with structures. The HIRES processed IRAS maps of these regions at 12, 25, 60 & 100 micron have also been presented for comparison. Point-like sources have been extracted from the longest waveband TIFR maps and searched for associations in the other five bands. The diffuse emission from these regions have been quantified, which turns out to be a significant fraction of the total emission. The spatial distribution of cold dust (T < 30 K) for two of these sources (W3(OH) & S209), has been determined reliably from the maps in TIFR bands. The dust temperature and optical depth maps show complex morphology. In general the dust around S209 has been found to be warmer than that in W3(OH) region.Comment: Accepted for publication in Journal of Astrophysics and Astronomy (20 pages including 8 figures & 3 tables

Chemotherapy and Stem Cell Transplantation Increase p16

AbstractThe expression of markers of cellular senescence increases exponentially in multiple tissues with aging. Age-related physiological changes may contribute to adverse outcomes in cancer survivors. To investigate the impact of high dose chemotherapy and stem cell transplantation on senescence markers in vivo, we collected blood and clinical data from a cohort of 63 patients undergoing hematopoietic cell transplantation. The expression of p16INK4a, a well-established senescence marker, was determined in T-cells before and 6months after transplant. RNA sequencing was performed on paired samples from 8 patients pre- and post-cancer therapy. In patients undergoing allogeneic transplant, higher pre-transplant p16INK4a expression was associated with a greater number of prior cycles of chemotherapy received (p=0.003), prior autologous transplantation (p=0.01) and prior exposure to alkylating agents (p=0.01). Transplantation was associated with a marked increase in p16INK4a expression 6months following transplantation. Patients receiving autologous transplant experienced a larger increase in p16INK4a expression (3.1-fold increase, p=0.002) than allogeneic transplant recipients (1.9-fold increase, p=0.0004). RNA sequencing of T-cells pre- and post- autologous transplant or cytotoxic chemotherapy demonstrated increased expression of transcripts associated with cellular senescence and physiological aging. Cytotoxic chemotherapy, especially alkylating agents, and stem cell transplantation strongly accelerate expression of a biomarker of molecular aging in T-cells

Triggered massive-star formation on the borders of Galactic HII regions. IV- Star formation at the periphery of Sh2-212

Aims: We wish to establish whether sequential star formation is taking place at the periphery of the Galactic HII region Sh2-212. Methods: We present CO millimetre observations of this region obtained at the IRAM 30-m telescope to investigate the distribution of associated molecular material. We also use deep JHK observations obtained at the CFHT to study the stellar content of the region, and radio observations obtained at the VLA to look for the presence of an ultra-compact (UC) HII region and for maser emission. Results: In the optical, Sh2-212 is spherically symmetric around its central exciting cluster. This HII region is located along a molecular filament. A thin, well-defined half ring of molecular material surrounds the brightest part of the HII region at the rear and is fragmented. The most massive fragment (~200 solar masses) contains a massive young stellar object displaying a near-IR excess; its spectral energy distribution indicates a high-mass (~14solar masses), high-temperature (~30000K), and high-luminosity (~17000 solar luminosities) source. This object ionizes a UC HII region. Conclusions: Sh2-212 is a good example of massive-star formation triggered via the collect and collapse process. The massive YSO observed at its periphery is a good candidate for a massive star formed in isolation.Comment: 12 pages, 14 figures. To be published in A&