Early tumor response to intraarterial or intravenous administration of carboplatin to treat naturally occurring lower urinary tract carcinoma in dogs.

BackgroundSurvival times and tumor responses associated with malignant neoplasia of the lower urinary tract are poor despite the vast array of current treatments. Therefore, the evaluation of alternative treatments, such as intraarterial administration of chemotherapy (IAC) should be considered.ObjectiveTo describe a technique for superselective catheterization for IAC and to evaluate initial tumor response by ultrasonography after both IAC and intravenous administration of chemotherapy (IVC).AnimalsClient-owned dogs with lower urinary tract neoplasia treated with either IVC (n = 15) or IAC (n = 11).MethodsRetrospective study. An arterial approach via the carotid or femoral artery was utilized to obtain superselective access and administer chemotherapy in the IAC cases. Medical record review was performed, data were recorded, and recorded variables were evaluated statistically.ResultsIntraarterial chemotherapy was successfully administered in all cases. There was a significantly greater decrease in longest unidimensional measurement in the IAC group as compared to the IVC group (P = .013). The IAC group was also significantly more likely to have a tumor response as assessed by modified RECIST guidelines (P = .049). Dogs in the IAC group were significantly less likely to develop anemia (P = .001), lethargy (P = .010) and anorexia (P = .024).Conclusion and clinical importanceThis study demonstrated the feasibility and efficacy of performing IAC for lower urinary tract neoplasia. Further investigation is necessary as the follow-up time was short and the impact on long-term outcome and survival was not determined

On the complexity of computing real radicals of polynomial systems

International audienceLet f= (f1, ..., fs) be a sequence of polynomials in Q[X1,...,Xn] of maximal degree D and V⊂ Cn be the algebraic set defined by f and r be its dimension. The real radical re associated to f is the largest ideal which defines the real trace of V . When V is smooth, we show that re , has a finite set of generators with degrees bounded by V. Moreover, we present a probabilistic algorithm of complexity (snDn )O(1) to compute the minimal primes of re . When V is not smooth, we give a probabilistic algorithm of complexity sO(1) (nD)O(nr2r) to compute rational parametrizations for all irreducible components of the real algebraic set V ∩ Rn. Experiments are given to show the efficiency of our approaches

Impact of baryon physics on dark matter structures: a detailed simulation study of halo density profiles

The back-reaction of baryons on the dark matter halo density profile is of great interest, not least because it is an important systematic uncertainty when attempting to detect the dark matter. Here, we draw on a large suite of high resolution cosmological hydrodynamical simulations, to systematically investigate this process and its dependence on the baryonic physics associated with galaxy formation. The inclusion of baryons results in significantly more concentrated density profiles if radiative cooling is efficient and feedback is weak. The dark matter halo concentration can in that case increase by as much as 30 (10) per cent on galaxy (cluster) scales. The most significant effects occur in galaxies at high redshift, where there is a strong anti-correlation between the baryon fraction in the halo centre and the inner slope of both the total and the dark matter density profiles. If feedback is weak, isothermal inner profiles form, in agreement with observations of massive, early-type galaxies. However, we find that AGN feedback, or extremely efficient feedback from massive stars, is necessary to match observed stellar fractions in groups and clusters, as well as to keep the maximum circular velocity similar to the virial velocity as observed for disk galaxies. These strong feedback models reduce the baryon fraction in galaxies by a factor of 3 relative to the case with no feedback. The AGN is even capable of reducing the baryon fraction by a factor of 2 in the inner region of group and cluster haloes. This in turn results in inner density profiles which are typically shallower than isothermal and the halo concentrations tend to be lower than in the absence of baryons.Comment: 20 pages, 14 figures, 1 table. MNRAS in press. Version 2: added a few references

TSPY potentiates cell proliferation and tumorigenesis by promoting cell cycle progression in HeLa and NIH3T3 cells

BACKGROUND: TSPY is a repeated gene mapped to the critical region harboring the gonadoblastoma locus on the Y chromosome (GBY), the only oncogenic locus on this male-specific chromosome. Elevated levels of TSPY have been observed in gonadoblastoma specimens and a variety of other tumor tissues, including testicular germ cell tumors, prostate cancer, melanoma, and liver cancer. TSPY contains a SET/NAP domain that is present in a family of cyclin B and/or histone binding proteins represented by the oncoprotein SET and the nucleosome assembly protein 1 (NAP1), involved in cell cycle regulation and replication. METHODS: To determine a possible cellular function for TSPY, we manipulated the TSPY expression in HeLa and NIH3T3 cells using the Tet-off system. Cell proliferation, colony formation assays and tumor growth in nude mice were utilized to determine the TSPY effects on cell growth and tumorigenesis. Cell cycle analysis and cell synchronization techniques were used to determine cell cycle profiles. Microarray and RT-PCR were used to investigate gene expression in TSPY expressing cells. RESULTS: Our findings suggest that TSPY expression increases cell proliferation in vitro and tumorigenesis in vivo. Ectopic expression of TSPY results in a smaller population of the host cells in the G(2)/M phase of the cell cycle. Using cell synchronization techniques, we show that TSPY is capable of mediating a rapid transition of the cells through the G(2)/M phase. Microarray analysis demonstrates that numerous genes involved in the cell cycle and apoptosis are affected by TSPY expression in the HeLa cells. CONCLUSION: These data, taken together, have provided important insights on the probable functions of TSPY in cell cycle progression, cell proliferation, and tumorigenesis

Transiting Exoplanet Studies and Community Targets for JWST's Early Release Science Program

This is a white paper that originated from an open discussion at the Enabling Transiting Exoplanet Science with JWST workshop held November 16 - 18, 2015 at STScI (http://www.stsci.edu/jwst/science/exoplanets). Accepted for publication in PASPThis is the author accepted manuscript. The final version is available from IOP Publishing via the DOI in this record.The James Webb Space Telescope will revolutionize transiting exoplanet atmospheric science due to its capability for continuous, long-duration observations and its larger collecting area, spectral coverage, and spectral resolution compared to existing space-based facilities. However, it is unclear precisely how well JWST will perform and which of its myriad instruments and observing modes will be best suited for transiting exoplanet studies. In this article, we describe a prefatory JWST Early Release Science (ERS) program that focuses on testing specific observing modes to quickly give the community the data and experience it needs to plan more efficient and successful future transiting exoplanet characterization programs. We propose a multi-pronged approach wherein one aspect of the program focuses on observing transits of a single target with all of the recommended observing modes to identify and understand potential systematics, compare transmission spectra at overlapping and neighboring wavelength regions, confirm throughputs, and determine overall performances. In our search for transiting exoplanets that are well suited to achieving these goals, we identify 12 objects (dubbed "community targets") that meet our defined criteria. Currently, the most favorable target is WASP-62b because of its large predicted signal size, relatively bright host star, and location in JWST's continuous viewing zone. Since most of the community targets do not have well-characterized atmospheres, we recommend initiating preparatory observing programs to determine the presence of obscuring clouds/hazes within their atmospheres. Measurable spectroscopic features are needed to establish the optimal resolution and wavelength regions for exoplanet characterization. Other initiatives from our proposed ERS program include testing the instrument brightness limits and performing phase-curve observations.(Abridged)K.B.S. recognizes support from the Sagan Fellowship Program, supported by NASA and administered by the NASA Exoplanet Science Institute (NExScI)

AMP-activated protein kinase inhibits K_v1.5 channel currents of pulmonary arterial myocytes in response to hypoxia and inhibition of mitochondrial oxidative phosphorylation

KEY POINTS: Progression of hypoxic pulmonary hypertension is thought to be due, in part, to suppression of voltage‐gated potassium channels (K(v)) in pulmonary arterial smooth muscle by hypoxia, although the precise molecular mechanisms have been unclear. AMP‐activated protein kinase (AMPK) has been proposed to couple inhibition of mitochondrial metabolism by hypoxia to acute hypoxic pulmonary vasoconstriction and progression of pulmonary hypertension. Inhibition of complex I of the mitochondrial electron transport chain activated AMPK and inhibited K(v)1.5 channels in pulmonary arterial myocytes. AMPK activation by 5‐aminoimidazole‐4‐carboxamide riboside, A769662 or C13 attenuated K(v)1.5 currents in pulmonary arterial myocytes, and this effect was non‐additive with respect to K(v)1.5 inhibition by hypoxia and mitochondrial poisons. Recombinant AMPK phosphorylated recombinant human K(v)1.5 channels in cell‐free assays, and inhibited K(+) currents when introduced into HEK 293 cells stably expressing K(v)1.5. These results suggest that AMPK is the primary mediator of reductions in K(v)1.5 channels following inhibition of mitochondrial oxidative phosphorylation during hypoxia and by mitochondrial poisons. ABSTRACT: Progression of hypoxic pulmonary hypertension is thought to be due, in part, to suppression of voltage‐gated potassium channels (K(v)) in pulmonary arterial smooth muscle cells that is mediated by the inhibition of mitochondrial oxidative phosphorylation. We sought to determine the role in this process of the AMP‐activated protein kinase (AMPK), which is intimately coupled to mitochondrial function due to its activation by LKB1‐dependent phosphorylation in response to increases in the cellular AMP:ATP and/or ADP:ATP ratios. Inhibition of complex I of the mitochondrial electron transport chain using phenformin activated AMPK and inhibited K(v) currents in pulmonary arterial myocytes, consistent with previously reported effects of mitochondrial inhibitors. Myocyte K(v) currents were also markedly inhibited upon AMPK activation by A769662, 5‐aminoimidazole‐4‐carboxamide riboside and C13 and by intracellular dialysis from a patch‐pipette of activated (thiophosphorylated) recombinant AMPK heterotrimers (α2β2γ1 or α1β1γ1). Hypoxia and inhibitors of mitochondrial oxidative phosphorylation reduced AMPK‐sensitive K(+) currents, which were also blocked by the selective K(v)1.5 channel inhibitor diphenyl phosphine oxide‐1 but unaffected by the presence of the BK(Ca) channel blocker paxilline. Moreover, recombinant human K(v)1.5 channels were phosphorylated by AMPK in cell‐free assays, and K(+) currents carried by K(v)1.5 stably expressed in HEK 293 cells were inhibited by intracellular dialysis of AMPK heterotrimers and by A769662, the effects of which were blocked by compound C. We conclude that AMPK mediates K(v) channel inhibition by hypoxia in pulmonary arterial myocytes, at least in part, through phosphorylation of K(v)1.5 and/or an associated protein

Bayesian inference of galaxy formation from the K-band luminosity function of galaxies: tensions between theory and observation

We conduct Bayesian model inferences from the observed K-band luminosity function of galaxies in the local Universe, using the semi-analytic model (SAM) of galaxy formation introduced in Lu et al (2011). The prior distributions for the 14 free parameters include a large range of possible models. We find that some of the free parameters, e.g. the characteristic scales for quenching star formation in both high-mass and low-mass halos, are already tightly constrained by the single data set. The posterior distribution includes the model parameters adopted in other SAMs. By marginalising over the posterior distribution, we make predictions that include the full inferential uncertainties for the colour-magnitude relation, the Tully-Fisher relation, the conditional stellar mass function of galaxies in halos of different masses, the HI mass function, the redshift evolution of the stellar mass function of galaxies, and the global star formation history. Using posterior predictive checking with the available observational results, we find that the model family (i) predicts a Tully-Fisher relation that is curved; (ii) significantly over predicts the satellite fraction; (iii) vastly over predicts the HI mass function; (iv) predicts high-z stellar mass functions that have too many low mass galaxies and too few high mass ones. and (v) predicts a redshift evolution of the stellar mass density and the star formation history that are in moderate disagreement. These results suggest that some important processes are still missing in the current model family and we discuss a number of possible solutions to solve the discrepancies, such as interactions between galaxies and dark matter halos, tidal stripping, the bimodal accretion of gas, preheating, and a redshift-dependent initial mass function.Comment: 45 pages, 12 figures, MNRAS in pres

Molecular Mining of Alleles in Water Buffalo Bubalus bubalis and Characterization of the TSPY1 and COL6A1 Genes

discovered in the process. gene in water buffalo, which localized to the Y chromosome.The MASA approach enabled us to identify several genes, including two of clinical significance, without screening an entire cDNA library. Genes identified with TGG repeats are not part of a specific family of proteins and instead are distributed randomly throughout the genome. Genes showing elevated expression in the testes and spermatozoa may prove to be potential candidates for in-depth characterization. Furthermore, their possible involvement in fertility or lack thereof would augment animal biotechnology

The transiting exoplanet community early release science program for JWST

The James Webb Space Telescope (JWST) presents the opportunity to transform our understanding of planets and the origins of life by revealing the atmospheric compositions, structures, and dynamics of transiting exoplanets in unprecedented detail. However, the high-precision, time-series observations required for such investigations have unique technical challenges, and prior experience with other facilities indicates that there will be a steep learning curve when JWST becomes operational. In this paper we describe the science objectives and detailed plans of the Transiting Exoplanet Community Early Release Science (ERS) Program, which is a recently approved program for JWST observations early in Cycle 1. The goal of this project, for which the obtained data will have no exclusive access period, is to accelerate the acquisition and diffusion of technical expertise for transiting exoplanet observations with JWST, while also providing a compelling set of representative datasets that will enable immediate scientific breakthroughs. The Transiting Exoplanet Community ERS Program will exercise the time-series modes of all four JWST instruments that have been identified as the consensus highest priorities, observe the full suite of transiting planet characterization geometries (transits, eclipses, and phase curves), and target planets with host stars that span an illustrative range of brightnesses. The observations in this program were defined through an inclusive and transparent process that had participation from JWST instrument experts and international leaders in transiting exoplanet studies. Community engagement in the project will be centered on a two-phase Data Challenge that culminates with the delivery of planetary spectra, time-series instrument performance reports, and open-source data analysis toolkits in time to inform the agenda for Cycle 2 of the JWST mission