Entropy, Ergodicity and Stem Cell Multipotency

Populations of mammalian stem cells commonly exhibit considerable cell-cell variability. However, the functional role of this diversity is unclear. Here, we analyze expression fluctuations of the stem cell surface marker Sca1 in mouse hematopoietic progenitor cells using a simple stochastic model and find that the observed dynamics naturally lie close to a critical state, thereby producing a diverse population that is able to respond rapidly to environmental changes. We propose an information-theoretic interpretation of these results that views cellular multipotency as an instance of maximum entropy statistical inference.Comment: 6 pages, 3 figure

Search for an exosphere in sodium and calcium in the transmission spectrum of exoplanet 55 Cancri e

[Abridged] The aim of this work is to search for an absorption signal from exospheric sodium (Na) and singly ionized calcium (Ca$^+$) in the optical transmission spectrum of the hot rocky super-Earth 55 Cancri e. Although the current best-fitting models to the planet mass and radius require a possible atmospheric component, uncertainties in the radius exist, making it possible that 55 Cancri e could be a hot rocky planet without an atmosphere. High resolution (R$\sim$110000) time-series spectra of five transits of 55 Cancri e, obtained with three different telescopes (UVES/VLT, HARPS/ESO 3.6m & HARPS-N/TNG) were analysed. Targeting the sodium D lines and the calcium H and K lines, the potential planet exospheric signal was filtered out from the much stronger stellar and telluric signals, making use of the change of the radial component of the orbital velocity of the planet over the transit from -57 to +57 km/sec. Combining all five transit data sets, we detect a signal potentially associated with sodium in the planet exosphere at a statistical significance level of 3$\sigma$. Combining the four HARPS transits that cover the calcium H and K lines, we also find a potential signal from ionized calcium (4.1 $\sigma$). Interestingly, this latter signal originates from just one of the transit measurements - with a 4.9$\sigma$ detection at this epoch. Unfortunately, due to the low significance of the measured sodium signal and the potentially variable Ca$^+$ signal, we estimate the p-values of these signals to be too high (corresponding to <4$\sigma$) to claim unambiguous exospheric detections. By comparing the observed signals with artificial signals injected early in the analysis, the absorption by Na and Ca$^+$ are estimated to be at a level of approximately 2.3$\times 10^{-3}$ and 7.0$\times 10^{-2}$ respectively, relative to the stellar spectrum.Comment: 15 pages, 8 figures, submission updated after English language editing, submission updated to correct a mistaken cross-reference noticed in A&A proo

CD44 targeted delivery of siRNA by using HA-decorated nanotechnologies for KRAS silencing in cancer treatment

KRAS is a small GTPase that regulates cell proliferation and survival. In tumors, the KRAS gene is mutated, and leading to unregulated tumor growth. Despite the recognized importance of KRAS in cancer, attempts to develop small molecule inhibitors have proved unsuccessful. An alternative strategy is gene silencing and the use of small nucleic acid sequences (e.g. siRNA, shRNA), has been reported to successfully downregulate KRAS. In this study we developed ternary nanocomplexes to deliver an anti-KRAS siRNA to colorectal cancer cells, exploiting the interaction of hyaluronic acid (HA) with CD44 as a means to achieve selective targeting of CD44-positive cancer cells. Two different polycations, poly(hexamethylene biguanide) and chitosan, were complexed with siRNA and coated with HA. Physico-chemical properties and stability of nanoparticles were characterized, including size, surface charge, and degree of siRNA protection. We demonstrate nanoparticle internalization (flow cytometry), siRNA cytosolic release (confocal microscopy) and KRAS silencing (RT-qPCR) in CD44+/KRAS+ colorectal cancer cell line, HCT-116. Further we demonstrate that the uptake of HA-decorated nanoparticles in cancer cells is higher when co-cultured with fibroblasts

Spectroscopic Transit Search: a self-calibrating method for detecting planets around bright stars

We search for transiting exoplanets around the star $\beta$ Pictoris using high resolution spectroscopy and Doppler imaging that removes the need for standard star observations. These data were obtained on the VLT with UVES during the course of an observing campaign throughout 2017 that monitored the Hill sphere transit of the exoplanet $\beta$ Pictoris b. We utilize line profile tomography as a method for the discovery of transiting exoplanets. By measuring the exoplanet distortion of the stellar line profile, we remove the need for reference star measurements. We demonstrate the method with white noise simulations, and then look at the case of $\beta$ Pictoris, which is a $\delta$ Scuti pulsator. We describe a method to remove the stellar pulsations and perform a search for any transiting exoplanets in the resultant data set. We inject fake planet transits with varying orbital periods and planet radii into the spectra and determine the recovery fraction. In the photon noise limited case we can recover planets down to a Neptune radius with an $\sim$80% success rate, using an 8 m telescope with a $R\sim 100,000$ spectrograph and 20 minutes of observations per night. The pulsations of $\beta$ Pictoris limit our sensitivity to Jupiter-sized planets, but a pulsation removal algorithm improves this limit to Saturn-sized planets. We present two planet candidates, but argue that their signals are most likely caused by other phenomena. We have demonstrated a method for searching for transiting exoplanets that (i) does not require ancillary calibration observations, (ii) can work on any star whose rotational broadening can be resolved with a high spectral dispersion spectrograph and (iii) provides the lowest limits so far on the radii of transiting Jupiter-sized exoplanets around $\beta$ Pictoris with orbital periods from 15 days to 200 days with >50% coverage.Comment: Accepted for publication in A&A, 8 pages, 8 figures. The Github repository can be found at https://github.com/lennartvansluijs/Spectroscopic-Transit-Searc

Discovery of a New WZ Sagittae Type Cataclysmic Variable in the Kepler/K2 Data

We identify a new, bright transient in the Kepler/K2 Campaign 11 field. Its light curve rises over seven magnitudes in a day and then declines three magnitudes over a month before quickly fading another two magnitudes. The transient was still detectable at the end of the campaign. The light curve is consistent with a WZ~Sge type dwarf nova outburst. Early superhumps with a period of 82 minutes are seen in the first 10 days and suggest that this is the orbital period of the binary which is typical for the WZ~Sge class. Strong superhump oscillations develop ten days after peak brightness with periods ranging between 83 and 84 minutes. At 25 days after the peak brightness a bump in the light curve appears to signal a subtle rebrightening phase implying that this was an unusual type-A outburst. This is the only WZ~Sge type system observed by Kepler/K2 during an outburst. The early rise of this outburst is well-fit with a broken power law. In first 10 hours the system brightened linearly and then transitioned to a steep rise with a power law index of 4.8. Looking at archival Kepler/K2 data and new TESS observations, a linear rise in the first several hours at the initiation of a superoutburst appears to be common in SU~UMa stars.Comment: 11 pages, 14 figures, 2 tables, accepted to appear in the Monthly Notices of the Royal Astronomical Societ

Lipogenesis by Isolated Human Apocrine Sweat Glands: Testosterone Has no Effect During Long-Term Organ Maintenance

Lipid synthesis by freshly isolated human apocrine glands has been measured by the incorporation of [U-14C] acetate. Incorporation is linear over 6h at 1010 ± 282 pmol/mg wet weight/h (n = 11; mean ± sem). The lipid classes, as percentages of the total lipid synthesized, were found by TLC to be cholesterol 12.3 ± 2.0, mono-glycerides 7.5 ± 1.5, 1,2 di-glycerides 3.0 ± 0.9, 1,3 di-glycerides 3.5 ± 0.5, tri-glycerides 28.4 ± 1.8, free fatty acids 2.0 ± 0.4, lysolecithin 15.4 ± 3.9, sphingomyelin 9.9 ± 4.3, phosphatidyl-choline 8.4 ± 0.4, phosphatidyl-ethanolamine -inositol and -serine 1.8 ± 0.1, phosphatidic acid and cardiolipin 3.3 ± 0.5, and unidentified 3.3 ± 0.5 (mean ± sem, n = 5); Glands were maintained on permeable supports. After 10 d maintenance, electron microscopy showed that the cellular architecture had been preserved, that the ATP contents were the same as in freshly isolated glands, and that [U-14]C] acetate incorporation was not significantly altered at 851 ± 237 pmol/mg/h (n = 18). The addition of 3μM testosterone had no effect on acetate incorporation at 844 ± 231 pmol/mg/h (n = 18). The lipid classes and their proportions were similar to the values for fresh glands after 10 d maintenance both with and without testosterone

K2: Background Survey - The search for undiscovered transients in Kepler/K2 data

The K2 mission of the Kepler Space Telescope offers a unique possibility to examine sources of both Galactic and extragalactic origin with high-cadence photometry. Alongside the multitude of supernovae and quasars detected within targeted galaxies, it is likely that Kepler has serendipitously observed many transients throughout K2. Such events will likely have occurred in background pixels, coincidentally surrounding science targets. Analysing the background pixels presents the possibility to conduct a high-cadence survey with areas of a few square degrees per campaign. We demonstrate the capacity to independently recover key K2 transients such as KSN 2015K and SN 2018oh. With this survey, we expect to detect numerous transients and determine the first comprehensive rates for transients with lifetimes of <1 d.This research was supported by an Australian Government Research Training Program (RTP) Scholarship and utilizes data collected by the K2 missio