Internal Motility in Stiffening Actin-Myosin Networks

We present a study on filamentous actin solutions containing heavy meromyosin subfragments of myosin II motor molecules. We focus on the viscoelastic phase behavior and internal dynamics of such networks during ATP depletion. Upon simultaneously using micro-rheology and fluorescence microscopy as complementary experimental tools, we find a sol-gel transition accompanied by a sudden onset of directed filament motion. We interpret the sol-gel transition in terms of myosin II enzymology, and suggest a "zipping" mechanism to explain the filament motion in the vicinity of the sol-gel transition.Comment: 4 pages, 3 figure

Statins in Cancer Prevention and Therapy

Statins, a class of HMG-CoA reductase inhibitors best known for their cholesterol-reducing and cardiovascular protective activity, have also demonstrated promise in cancer prevention and treatment. This review focuses on their potential applications in head and neck cancer (HNC), a common malignancy for which established treatment often fails despite incurring debilitating adverse effects. Preclinical and clinical studies have suggested that statins may enhance HNC sensitivity to radiation and other conventional therapies while protecting normal tissue, but the underlying mechanisms remain poorly defined, likely involving both cholesterol-dependent and -independent effects on diverse cancer-related pathways. This review brings together recent discoveries concerning the anticancer activity of statins relevant to HNC, highlighting their anti-inflammatory activity and impacts on DNA-damage response. We also explore molecular targets and mechanisms and discuss the potential to integrate statins into conventional HNC treatment regimens to improve patient outcomes

Optimising Spectroscopic and Photometric Galaxy Surveys: Efficient Target Selection and Survey Strategy

The next generation of spectroscopic surveys will have a wealth of photometric data available for use in target selection. Selecting the best targets is likely to be one of the most important hurdles in making these spectroscopic campaigns as successful as possible. Our ability to measure dark energy depends strongly on the types of targets that we are able to select with a given photometric data set. We show in this paper that we will be able to successfully select the targets needed for the next generation of spectroscopic surveys. We also investigate the details of this selection, including optimisation of instrument design and survey strategy in order to measure dark energy. We use color-color selection as well as neural networks to select the best possible emission line galaxies and luminous red galaxies for a cosmological survey. Using the Fisher matrix formalism we forecast the efficiency of each target selection scenario. We show how the dark energy figures of merit change in each target selection regime as a function of target type, survey time, survey density and other survey parameters. We outline the optimal target selection scenarios and survey strategy choices which will be available to the next generation of spectroscopic surveys.Comment: 16 pages, 22 figures, accepted to MNRAS in dec 201

Yeast cell death during DNA damage arrest is independent of caspase or reactive oxygen species

CDC13 encodes a telomere-binding protein that prevents degradation of telomeres. cdc13-1 yeast grown at the nonpermissive temperature undergo G2/M arrest, progressive chromosome instability, and subsequent cell death. Recently, it has been suggested that cell death in the cdc13-1 mutant is an active process characterized by phenotypic hallmarks of apoptosis and caspase activation. In this work, we show that cell death triggered by cdc13-1 is independent of the yeast metacaspase Yca1p and reactive oxygen species but related to cell cycle arrest per se. Inactivating YCA1 or depleting reactive oxygen species does not increase viability of cdc13-1 cells. In turn, caspase activation does not precede cell death in the cdc13-1 mutant. Yca1p activity assayed by cell binding of mammalian caspase inhibitors is confounded by artifactual labeling of dead yeast cells, which nonspecifically bind fluorochromes. We speculate that during a prolonged cell cycle arrest, cdc13-1 cells reach a critical size and die by cell lysis

Therapy-Induced Cellular Senescence: Potentiating Tumor Elimination or Driving Cancer Resistance and Recurrence?

Cellular senescence has been increasingly recognized as a hallmark of cancer, reflecting its association with aging and inflammation, its role as a response to deregulated proliferation and oncogenic stress, and its induction by cancer therapies. While therapy-induced senescence (TIS) has been linked to resistance, recurrence, metastasis, and normal tissue toxicity, TIS also has the potential to enhance therapy response and stimulate anti-tumor immunity. In this review, we examine the Jekyll and Hyde nature of senescent cells (SnCs), focusing on how their persistence while expressing the senescence-associated secretory phenotype (SASP) modulates the tumor microenvironment through autocrine and paracrine mechanisms. Through the SASP, SnCs can mediate both resistance and response to cancer therapies. To fulfill the unmet potential of cancer immunotherapy, we consider how SnCs may influence tumor inflammation and serve as an antigen source to potentiate anti-tumor immune response. This new perspective suggests treatment approaches based on TIS to enhance immune checkpoint blockade. Finally, we describe strategies for mitigating the detrimental effects of senescence, such as modulating the SASP or targeting SnC persistence, which may enhance the overall benefits of cancer treatment

The Global Star Formation Rate from the 1.4 GHz Luminosity Function

The decimetric luminosity of many galaxies appears to be dominated by synchrotron emission excited by supernova explosions. Simple models suggest that the luminosity is directly proportional to the rate of supernova explosions of massive stars averaged over the past 30 Myr. The proportionality may be used together with models of the evolving 1.4 GHz luminosity function to estimate the global star formation rate density in the era z < 1. The local value is estimated to be 0.026 solar masses per year per cubic megaparsec, some 50% larger than the value inferred from the Halpha luminosity density. The value at z ~ 1 is found to be 0.30 solar masses per year per cubic megaparsec. The 10-fold increase in star formation rate density is consistent with the increase inferred from mm-wave, far-infrared, ultra-violet and Halpha observations.Comment: 10 pages, 2 figures, Astrophysical Journal Letters (in press); new PS version has improved figure placemen

Measurement of radiotherapy x-ray skin dose on a chest wall phantom

Sufficient skin dose needs to be delivered by a radiotherapy chest wall treatment regimen to ensure the probability of a near surface tumor recurrence is minimized. To simulate a chest wall treatment a hemicylindrical solid water phantom of 7.5 cm radius was irradiated with 6 MV x-rays using 20×20 cm2 and 10×20 cm2 fields at 100 cm source surface distance (SSD) to the base of the phantom. A surface dose profile was obtained from 0 to 180°, in 10° increments around the circumference of the phantom. Dosimetry results obtained from radiochromic film (effective depth of 0.17 mm) were used in the investigation, the superficial doses were found to be 28% (of Dmax) at the 0° beam entry position and 58% at the 90° oblique beam position. Superficial dose results were also obtained using extra thin thermoluminescent dosimeters (TLD) (effective depth 0.14 mm) of 30% at 0°, 57% at 90°, and a metal oxide semiconductor field effect transistor (MOSFET) detector (effective depth 0.5 mm) of 43% at 0°, 62% at 90°. Because the differences in measured superficial doses were significant and beyond those related to experimental error, these differences are assumed to be mostly attributable to the effective depth of measurement of each detector. We numerically simulated a bolus on/bolus off technique and found we could increase the coverage to the skin. Using an alternate “bolus on,” “bolus off” regimen, the skin would receive 36.8 Gy at 0° incidence and 46.4 Gy at 90° incidence for a prescribed midpoint dose of 50 Gy. From this work it is evident that, as the circumference of the phantom is traversed the SSD increases and hence there is an inverse square fluence fall-off, this is more than offset by the increase in skin dose due to surface curvature to a plateau at about 90°. Beyond this angle it is assumed that beam attenuation through the phantom and inverse square fall-off is causing the surface dose to reduce

Survey incompleteness and the evolution of the QSO luminosity function

We concentrate on a type of QSO survey which depends on selecting QSO candidates based on combinations of colors. Since QSO's have emission lines and power-law continua, they are expected to yield broadband colors unlike those of stellar photospheres. Previously, the fraction of QSO's expected to be hiding (unselected) within the locus of stellar (U-J, J-F) colors was estimated at about 15 percent. We have now verified that the KK88 survey is at least 11 percent incomplete, but have determined that it may be as much as 34 percent incomplete. The 'missing' QSO's are expected to be predominantly at z less than or = 2.2. We have studied the proper motion and variability properties of all stellar objects with J less than or = 22.5 or F less than or = 21.5 in the SA 57 field which has previously been surveyed with a multicolor QSO search by KK88