Rotons and Quantum Evaporation from Superfluid 4He

The probability of evaporation induced by $R^+$ and $R^-$ rotons at the surface of superfluid helium is calculated using time dependent density functional theory. We consider excitation energies and incident angles such that phonons do not take part in the scattering process. We predict sizable evaporation rates, which originate entirely from quantum effects. Results for the atomic reflectivity and for the probability of the roton change-mode reflection are also presented.Comment: 11 pages, REVTEX, 3 figures available upon request or at http://anubis.science.unitn.it/~dalfovo/papers/papers.htm

Resistant starch and exercise independently attenuate weight regain on a high fat diet in a rat model of obesity

<p>Abstract</p> <p>Background</p> <p>Long-term weight reduction remains elusive for many obese individuals. Resistant starch (RS) and exercise may be useful for weight maintenance. The effects of RS, with or without exercise, on weight regain was examined during relapse to obesity on a high carbohydrate, high fat (HC/HF) diet.</p> <p>Methods</p> <p>Obesity-prone rats were fed <it>ad libitum </it>for 16 weeks then weight reduced on a low fat diet to induce a 17% body weight loss (weight reduced rats). Weight reduced rats were maintained on an energy-restricted low fat diet for 18 weeks, with or without a daily bout of treadmill exercise. Rats were then allowed free access to HC/HF diet containing low (0.3%) or high (5.9%) levels of RS. Weight regain, energy balance, body composition, adipocyte cellularity, and fuel utilization were monitored as rats relapsed to obesity and surpassed their original, obese weight.</p> <p>Results</p> <p>Both RS and exercise independently attenuated weight regain by reducing the energy gap between the drive to eat and suppressed energy requirements. Exercise attenuated the deposition of lean mass during relapse, whereas its combination with RS sustained lean mass accrual as body weight returned. Early in relapse, RS lowered insulin levels and reduced the deposition of fat in subcutaneous adipose tissue. Exercise cessation at five weeks of relapse led to increased weight gain, body fat, subcutaneous adipocytes, and decreased lean mass; all detrimental consequences to overall metabolic health.</p> <p>Conclusions</p> <p>These data are the first to show the complimentary effects of dietary RS and regular exercise in countering the metabolic drive to regain weight following weight loss and suggest that exercise cessation, in the context of relapse on a HC/HF diet, may have dire metabolic consequences.</p

Dust in the inner regions of debris disks around A stars

We present infrared interferometric observations of the inner regions of two A-star debris disks, beta Leo and zeta Lep, using the FLUOR instrument at the CHARA interferometer on both short (30 m) and long (>200 m) baselines. For the target stars, the short baseline visibilities are lower than expected for the stellar photosphere alone, while those of a check star, delta Leo, are not. We interpret this visibility offset of a few percent as a near-infrared excess arising from dust grains which, due to the instrumental field of view, must be located within several AU of the central star. For beta Leo, the near-infrared excess producing grains are spatially distinct from the dust which produces the previously known mid-infrared excess. For zeta Lep, the near-infrared excess may be spatially associated with the mid-infrared excess producing material. We present simple geometric models which are consistent with the near and mid-infrared excess and show that for both objects, the near-infrared producing material is most consistent with a thin ring of dust near the sublimation radius with typical grain sizes smaller than the nominal radiation pressure blowout radius. Finally, we discuss possible origins of the near-infrared emitting dust in the context of debris disk evolution models.Comment: 20 pages, 2 figures, to appear in the Astrophysical Journa

Drug discovery for male subfertility using high-throughput screening:a new approach to an unsolved problem

STUDY QUESTIONCan pharma drug discovery approaches be utilized to transform investigation into novel therapeutics for male infertility?SUMMARY ANSWERHigh-throughput screening (HTS) is a viable approach to much-needed drug discovery for male factor infertility.WHAT IS KNOWN ALREADYThere is both huge demand and a genuine clinical need for new treatment options for infertile men. However, the time, effort and resources required for drug discovery are currently exorbitant, due to the unique challenges of the cellular, physical and functional properties of human spermatozoa and a lack of appropriate assay platform.STUDY DESIGN, SIZE, DURATIONSpermatozoa were obtained from healthy volunteer research donors and subfertile patients undergoing IVF/ICSI at a hospital-assisted reproductive techniques clinic between January 2012 and November 2016.PARTICIPANTS/MATERIALS, SETTING, METHODSA HTS assay was developed and validated using intracellular calcium ([Ca2+]i) as a surrogate for motility in human spermatozoa. Calcium fluorescence was detected using a Flexstation microplate reader (384-well platform) and compared with responses evoked by progesterone, a compound known to modify a number of biologically relevant behaviours in human spermatozoa. Hit compounds identified following single point drug screen (10 μM) of an ion channel-focussed library assembled by the University of Dundee Drug Discovery Unit were rescreened to ensure potency using standard 10 point half-logarithm concentration curves, and tested for purity and integrity using liquid chromatography and mass spectrometry. Hit compounds were grouped by structure activity relationships and five representative compounds then further investigated for direct effects on spermatozoa, using computer-assisted sperm assessment, sperm penetration assay and whole-cell patch clamping.MAIN RESULTS AND THE ROLE OF CHANCEOf the 3242 ion channel library ligands screened, 384 compounds (11.8%) elicited a statistically significant increase in calcium fluorescence, with greater than 3× median absolute deviation above the baseline. Seventy-four compounds eliciting ≥50% increase in fluorescence in the primary screen were rescreened and evaluated further, resulting in 48 hit compounds that produced a concentration-dependent increase in [Ca2+]i. Sperm penetration studies confirmed in vitro exposure to two hit compounds (A and B) resulted in significant improvement in functional motility in spermatozoa from healthy volunteer donors (A: 1 cm penetration index 2.54, 2 cm penetration index 2.49; P &lt; 0.005 and B: 1 cm penetration index 2.1, 2 cm penetration index 2.6; P &lt; 0.005), but crucially, also in patient samples from those undergoing fertility treatment (A: 1 cm penetration index 2.4; P = 0.009, 2 cm penetration index 3.6; P = 0.02 and B: 1 cm penetration index 2.2; P = 0.0004, 2 cm penetration index 3.6; P = 0.002). This was primarily as a result of direct or indirect CatSper channel action, supported by evidence from electrophysiology studies of individual sperm.LIMITATIONS, REASONS FOR CAUTIONIncrease and fluxes in [Ca2+]i are fundamental to the regulation of sperm motility and function, including acrosome reaction. The use of calcium signalling as a surrogate for sperm motility is acknowledged as a potential limitation in this study.WIDER IMPLICATIONS OF THE FINDINGSWe conclude that HTS can robustly, efficiently, identify novel compounds that increase [Ca2+]i in human spermatozoa and functionally modify motility, and propose its use as a cornerstone to build and transform much-needed drug discovery for male infertility.</p

Sequential and Batch Processing Methods of the EBP Learning Algorithm

Placental abnormalities can cause Pregnancy-Associated Disorders, including preeclampsia, intrauterine growth restriction, and placental insufficiency, resulting in complications for both the mother and fetus. Trophoblast cells within the labyrinthine layer of the placenta facilitate the exchange of nutrients, gases, and waste between mother and fetus; therefore, the development of this cell layer is critical for fetal development. As trophoblast cells differentiate, it is assumed their metabolism changes with their energy requirements. We hypothesize that proper regulation of trophoblast metabolism is a key component of normal placental development; therefore, we examined the role of AMP-activated kinase (AMPK, PRKAA1/2), a sensor of cellular energy status. Our previous studies have shown that AMPK knockdown alters both trophoblast differentiation and nutrient transport. In this study, AMPKα1/2 shRNA was used to investigate the metabolic effects of AMPK knockdown on SM10 placental labyrinthine progenitor cells before and after differentiation. Extracellular flux analysis confirmed that AMPK knockdown was sufficient to reduce trophoblast glycolysis, mitochondrial respiration, and ATP coupling efficiency. A reduction in AMPK in differentiated trophoblasts also resulted in increased mitochondrial volume. These data indicate that a reduction in AMPK disrupts cellular metabolism in both progenitors and differentiated placental trophoblasts. This disruption correlates to abortive trophoblast differentiation that may contribute to the development of Pregnancy-Associated Disorders

SPICES: Spectro-Polarimetric Imaging and Characterization of Exoplanetary Systems

SPICES (Spectro-Polarimetric Imaging and Characterization of Exoplanetary Systems) is a five-year M-class mission proposed to ESA Cosmic Vision. Its purpose is to image and characterize long-period extrasolar planets and circumstellar disks in the visible (450 - 900 nm) at a spectral resolution of about 40 using both spectroscopy and polarimetry. By 2020/22, present and near-term instruments will have found several tens of planets that SPICES will be able to observe and study in detail. Equipped with a 1.5 m telescope, SPICES can preferentially access exoplanets located at several AUs (0.5-10 AU) from nearby stars ($<$25 pc) with masses ranging from a few Jupiter masses to Super Earths ($\sim$2 Earth radii, $\sim$10 M$_{\oplus}$) as well as circumstellar disks as faint as a few times the zodiacal light in the Solar System

A near-infrared interferometric survey of debris disc stars. II. CHARA/FLUOR observations of six early-type dwarfs

High-precision interferometric observations of six early-type main sequence stars known to harbour cold debris discs have been obtained in the near-infrared K band with the FLUOR instrument at the CHARA Array. The measured squared visibilities are compared to the expected visibility of the stellar photospheres based on theoretical photospheric models taking into account rotational distortion, searching for potential visibility reduction at short baselines due to circumstellar emission. Our observations bring to light the presence of resolved circumstellar emission around one of the six target stars (zeta Aql) at the 5 sigma level. The morphology of the emission source cannot be directly constrained because of the sparse spatial frequency sampling of our interferometric data. Using complementary adaptive optics observations and radial velocity measurements, we find that the presence of a low-mass companion is a likely origin for the excess emission. The potential companion has a K-band contrast of four magnitudes, a most probable mass of about 0.6 Msun, and is expected to orbit between about 5.5 AU and 8 AU from its host star assuming a purely circular orbit. Nevertheless, by adjusting a physical debris disc model to the observed Spectral Energy Distribution of the zeta Aql system, we also show that the presence of hot dust within 10 AU from zeta Aql, producing a total thermal emission equal to 1.69 +- 0.31% of the photospheric flux in the K band, is another viable explanation for the observed near-infrared excess. Our re-interpretation of archival near- to far-infrared photometric measurements shows however that cold dust is not present around zeta Aql at the sensitivity limit of the IRS and MIPS instruments onboard Spitzer, and urges us to remove zeta Aql from the category of bona fide debris disc stars.Comment: 14 pages, accepted for publication in A&

The read-across hypothesis and environmental risk assessment of pharmaceuticals

This article is made available through the Brunel Open Access Publishing Fund. Copyright © 2013 American Chemical Society.Pharmaceuticals in the environment have received increased attention over the past decade, as they are ubiquitous in rivers and waterways. Concentrations are in sub-ng to low μg/L, well below acute toxic levels, but there are uncertainties regarding the effects of chronic exposures and there is a need to prioritise which pharmaceuticals may be of concern. The read-across hypothesis stipulates that a drug will have an effect in non-target organisms only if the molecular targets such as receptors and enzymes have been conserved, resulting in a (specific) pharmacological effect only if plasma concentrations are similar to human therapeutic concentrations. If this holds true for different classes of pharmaceuticals, it should be possible to predict the potential environmental impact from information obtained during the drug development process. This paper critically reviews the evidence for read-across, and finds that few studies include plasma concentrations and mode of action based effects. Thus, despite a large number of apparently relevant papers and a general acceptance of the hypothesis, there is an absence of documented evidence. There is a need for large-scale studies to generate robust data for testing the read-across hypothesis and developing predictive models, the only feasible approach to protecting the environment.BBSRC Industrial Partnership Award BB/ I00646X/1 and BBSRC Industrial CASE Partnership Studentship BB/I53257X/1 with AstraZeneca Safety Health and Environment Research Programme