Letrozole treatment of pubertal female mice results in activational effects on reproduction, metabolism and the gut microbiome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women that is comprised of two out of the following three features: hyperandrogenism, oligo- or amenorrhea, or polycystic ovaries. In addition to infertility, many women with PCOS have metabolic dysregulation that increases the risk of developing type 2 diabetes, hypertension, and non-alcoholic fatty liver disease. Changes in the gut microbiome are associated with PCOS and gut microbes may be involved in the pathology of this disorder. Since PCOS often manifests in the early reproductive years, puberty is considered to be a critical time period for the development of PCOS. Exposure to sex steroid hormones during development results in permanent, organizational effects, while activational effects are transient and require the continued presence of the hormone. Androgens exert organizational effects during prenatal or early post-natal development, but it is unclear whether androgen excess results in organizational or activational effects during puberty. We recently developed a letrozole-induced PCOS mouse model that recapitulates both reproductive and metabolic phenotypes of PCOS. In this study, we investigated whether letrozole treatment of pubertal female mice exerts organizational or activational effects on host physiology and the gut microbiome. Two months after letrozole removal, we observed recovery of reproductive and metabolic parameters, as well as diversity and composition of the gut microbiome, indicating that letrozole treatment of female mice during puberty resulted in predominantly activational effects. These results suggest that if exposure to excess androgens during puberty leads to the development of PCOS, reduction of androgen levels during this time may improve reproductive and metabolic phenotypes in women with PCOS. These results also imply that continuous letrozole exposure is required to model PCOS in pubertal female mice since letrozole exerts activational rather than organizational effects during puberty

MEK inhibitors cobimetinib and trametinib, regressed a gemcitabine-resistant pancreatic-cancer patient-derived orthotopic xenograft (PDOX).

A pancreatic ductal adenocarcinoma (PDAC), obtained from a patient, was grown orthotopically in the pancreatic tail of nude mice to establish a patient-derived orthotopic (PDOX) model. Seven weeks after implantation, PDOX nude mice were divided into the following groups: untreated control (n = 7); gemcitabine (100 mg/kg, i.p., once a week for 2 weeks, n = 7); cobimetinib (5 mg/kg, p.o., 14 consecutive days, n = 7); trametinib (0.3 mg/kg, p.o., 14 consecutive days, n = 7); trabectedin (0.15 mg/kg, i.v., once a week for 2 weeks, n = 7); temozolomide (25 mg/kg, p.o., 14 consecutive days, n = 7); carfilzomib (2 mg/kg, i.v., twice a week for 2 weeks, n = 7); bortezomib (1 mg/kg, i.v., twice a week for 2 weeks, n = 7); MK-1775 (20 mg/kg, p.o., 14 consecutive days, n = 7); BEZ-235 (45 mg/kg, p.o., 14 consecutive days, n = 7); vorinostat (50 mg/kg, i.p., 14 consecutive days, n = 7). Only the MEK inhibitors, cobimetinib and trametinib, regressed tumor growth, and they were more significantly effective than other therapies (p < 0.0001, respectively), thereby demonstrating the precision of the PDOX models of PDAC and its potential for individualizing pancreatic-cancer therapy

A millimeter-wave kinetic inductance detector camera for long-range imaging through optical obscurants

Millimeter-wave imaging provides a promising option for long-range target detection through optical obscurants such as fog, which often occur in marine environments. Given this motivation, we are currently developing a 150 GHz polarization-sensitive imager using a relatively new type of superconducting pair-breaking detector, the kinetic inductance detector (KID). This imager will be paired with a 1.5 m telescope to obtain an angular resolution of 0.09° over a 3.5° field of view using 3,840 KIDs. We have fully characterized a prototype KID array, which shows excellent performance with noise strongly limited by the irreducible fluctuations from the ambient temperature background. Full-scale KID arrays are now being fabricated and characterized for a planned demonstration in a maritime environment later this year

Strong field double ionization of H2 : Insights from nonlinear dynamics

The uncorrelated (``sequential'') and correlated (``nonsequential'') double ionization of the H2 molecule in strong laser pulses is investigated using the tools of nonlinear dynamics. We focus on the phase-space dynamics of this system, specifically by finding the dynamical structures that regulate these ionization processes. The emerging picture complements the recollision scenario by clarifying the distinct roles played by the recolliding and core electrons. Our analysis leads to verifiable predictions of the intensities where qualitative changes in ionization occur. We also show how these findings depend on the internuclear distance

Constraining Intra-cluster Gas Models with AMiBA13

Clusters of galaxies have been used extensively to determine cosmological parameters. A major difficulty in making best use of Sunyaev-Zel'dovich (SZ) and X-ray observations of clusters for cosmology is that using X-ray observations it is difficult to measure the temperature distribution and therefore determine the density distribution in individual clusters of galaxies out to the virial radius. Observations with the new generation of SZ instruments are a promising alternative approach. We use clusters of galaxies drawn from high-resolution adaptive mesh refinement (AMR) cosmological simulations to study how well we should be able to constrain the large-scale distribution of the intra-cluster gas (ICG) in individual massive relaxed clusters using AMiBA in its configuration with 13 1.2-m diameter dishes (AMiBA13) along with X-ray observations. We show that non-isothermal beta models provide a good description of the ICG in our simulated relaxed clusters. We use simulated X-ray observations to estimate the quality of constraints on the distribution of gas density, and simulated SZ visibilities (AMiBA13 observations) for constraints on the large-scale temperature distribution of the ICG. We find that AMiBA13 visibilities should constrain the scale radius of the temperature distribution to about 50% accuracy. We conclude that the upgraded AMiBA, AMiBA13, should be a powerful instrument to constrain the large-scale distribution of the ICG.Comment: Accepted for publication in The Astrophysical Journal, 12 pages, 9 figure

Epithelial Migration and Non-adhesive Periderm Are Required for Digit Separation during Mammalian Development.

The fusion of digits or toes, syndactyly, can be part of complex syndromes, including van der Woude syndrome. A subset of van der Woude cases is caused by dominant-negative mutations in the epithelial transcription factor Grainyhead like-3 (GRHL3), and Grhl3-/-mice have soft-tissue syndactyly. Although impaired interdigital cell death of mesenchymal cells causes syndactyly in multiple genetic mutants, Grhl3-/- embryos had normal interdigital cell death, suggesting alternative mechanisms for syndactyly. We found that in digit separation, the overlying epidermis forms a migrating interdigital epithelial tongue (IET) when the epithelium invaginates to separate the digits. Normally, the non-adhesive surface periderm allows the IET to bifurcate as the digits separate. In contrast, in Grhl3-/- embryos, the IET moves normally between the digits but fails to bifurcate because of abnormal adhesion of the periderm. Our study identifies epidermal developmental processes required for digit separation

Constraining the LRG Halo Occupation Distribution using Counts-in-Cylinders

The low number density of the Sloan Digital Sky Survey (SDSS) Luminous Red Galaxies (LRGs) suggests that LRGs occupying the same dark matter halo can be separated from pairs occupying distinct dark matter halos with high fidelity. We present a new technique, Counts-in-Cylinders (CiC), to constrain the parameters of the satellite contribution to the LRG Halo-Occupation Distribution (HOD). For a fiber collision-corrected SDSS spectroscopic LRG subsample at 0.16 < z < 0.36, we find the CiC multiplicity function is fit by a halo model where the average number of satellites in a halo of mass M is = ((M - Mcut)/M1)^alpha with Mcut = 5.0 +1.5/-1.3 (+2.9/-2.6) X 10^13 Msun, M1 = 4.95 +0.37/-0.26 (+0.79/-0.53) X 10^14 Msun, and alpha = 1.035 +0.10/-0.17 (+0.24/-0.31) at the 68% and 95% confidence levels using a WMAP3 cosmology and z=0.2 halo catalog. Our method tightly constrains the fraction of LRGs that are satellite galaxies, 6.36 +0.38/-0.39, and the combination Mcut/10^{14} Msun + alpha = 1.53 +0.08/-0.09 at the 95% confidence level. We also find that mocks based on a halo catalog produced by a spherical overdensity (SO) finder reproduce both the measured CiC multiplicity function and the projected correlation function, while mocks based on a Friends-of-Friends (FoF) halo catalog has a deficit of close pairs at ~1 Mpc/h separations. Because the CiC method relies on higher order statistics of close pairs, it is robust to the choice of halo finder. In a companion paper we will apply this technique to optimize Finger-of-God (FOG) compression to eliminate the 1-halo contribution to the LRG power spectrum.Comment: 40 pages, 9 figures, submitted to Astrophysical Journa

Player Autonomy in Sport: Impact of Coach’s Passion

While motivation is a critical factor in all sports, at the highest level of performance it is what makes the difference between success and failure. Motivation can be either intrinsic or extrinsic, but intrinsic motivation is often more potent of the two. Self-Determination Theory (SDT) posits that human motivation is linked to inherent psychological needs. When SDT is applied to movement, it is suggested that regularity of physical activity participation is influenced by intrinsic motivation and perceived autonomy. In sports, coaches play a unique role in an athlete's performance and are directly responsible for the social environment and perceived autonomy for athletes. The type of passion a coach exhibits influences their coaching style and impacts an athlete's perception of autonomy. As a result, there is debate as to which types of passion have the most influence on coaching styles and in turn, an athlete’s perceived autonomy. The purpose of this thesis is to examine the affects of coach's passion, a strong inclination or emotion toward something, on a player's perceived autonomy, and whether obsessive passion is more detrimental than no passion at all. Using a systematic literature review, and the PRISMA guidelines, this study analyzed 23 peer-reviewed journal articles, from 1985 to present, relating to SDT, the dualistic model of passion, and intrinsic motivation. The findings suggest that harmonious passion leads to the greatest autonomy and intrinsic motivation, and it can overcome the negative effects of obsessive passion. These results provide insight as to how coaches should optimize their coaching techniques to train their athletes to maximize performance. Implications suggest that coaches learn to recognize when they are exhibiting obsessive behaviors and actively attempt to reduce it by engaging in more harmonious actions.Kinesiology and Health Educatio

Exploring the Energetics of Intracluster Gas with a Simple and Accurate Model

The state of the hot gas in clusters of galaxies is investigated with a set of model clusters, created by assuming a polytropic equation of state (Gamma=1.2) and hydrostatic equilibrium inside gravitational potential wells drawn from a dark matter simulation. Star formation, energy input, and nonthermal pressure support are included. To match the gas fractions seen in non-radiative hydrodynamical simulations, roughly 5% of the binding energy of the dark matter must be transferred to the gas during cluster formation; the presence of nonthermal pressure support increases this value. In order to match X-ray observations, scale-free behavior must be broken. This can be due to either variation of the efficiency of star formation with cluster mass M_500, or the input of additional energy proportional to the formed stellar mass M_F. These two processes have similar effects on X-ray scalings. If 9% of the gas is converted into stars, independent of cluster mass, then feedback energy input of 1.2e-5*M_Fc^2 (or ~1.0 keV per particle) is required to match observed clusters. Alternatively, if the stellar mass fraction varies as M_500^-0.26 then a lower feedback of 4e-6*M_Fc^2 is needed, and if the stellar fraction varies as steeply as M_500^-0.49 then no additional feedback is necessary. The model clusters reproduce the observed trends of gas temperature and gas mass fraction with cluster mass, as well as observed entropy and pressure profiles; thus they provide a calibrated basis with which to interpret upcoming SZ surveys. One consequence of the increased gas energy is that the baryon fraction inside the virial radius is less than roughly 90% of the cosmic mean, even for the most massive clusters.Comment: Accepted by ApJ; 28 pages, 12 figure

The ELIXR Galaxy Survey. II: Baryons and Dark Matter in an Isolated Elliptical Galaxy

The Elliptical Isolated X-ray (ElIXr) Galaxy Survey is a volume-limited (<110Mpc) study of optically selected, isolated, Lstar elliptical galaxies, to provide an X-ray census of galaxy-scale (virial mass, Mvir < 1e13 Msun) objects, and identify candidates for detailed hydrostatic mass modelling. In this paper, we present a Chandra and XMM study of one such candidate, NGC1521, and constrain its distribution of dark and baryonic matter. We find a morphologically relaxed hot gas halo, extending almost to R500, that is well described by hydrostatic models similar to the benchmark, baryonically closed, Milky Way-mass elliptical galaxy NGC720. We obtain good constraints on the enclosed gravitating mass (M500=3.8e12+/-1e12 Msun, slightly higher than NGC\thin 720), and baryon fraction (fb500=0.13+/-0.03). We confirm at 8.2-sigma the presence of a dark matter (DM) halo consistent with LCDM. Assuming a Navarro-Frenk-White DM profile, our self-consistent, physical model enables meaningful constraints beyond R500, revealing that most of the baryons are in the hot gas. Within the virial radius, fb is consistent with the Cosmic mean, suggesting that the predicted massive, quasi-hydrostatic gas halos may be more common than previously thought. We confirm that the DM and stars conspire to produce an approximately powerlaw total mass profile (rho \propto r^-alpha) that follows the recently discovered scaling relation between alpha and optical effective radius. Our conclusions are insensitive to modest, observationally motivated, deviations from hydrostatic equilibrium. Finally, after correcting for the enclosed gas fraction, the entropy profile is close to the self-similar prediction of gravitational structure formation simulations, as observed in massive galaxy clusters.Comment: Accepted for publication in the Astrophysical Journal. Minor modifications to match accepted version. Conclusions unchanged. 18 pages, 11 figures and 3 table