1,150 research outputs found
Vascular Endothelial Growth Factor mRNA Isoforms 120 and 164 are Differentially Regulated Prior to Ovulation
Vascular Endothelial Growth Factor (VEGF) is produced by cells surrounding the egg in the follicle prior to ovulation. If VEGF is inhibited, ovulation does not occur. The VEGF gene can be spliced to produce different protein isoforms which have specific functions. Our objective was to determine if VEGF 120 and 164 mRNA isoforms are differentially regulated in the preovulatory follicle. From our studies, VEGF isoforms are differentially regulated during both CL regression and after a simulated LH surge. Differences observed in VEGF isoform regulation may allow for manipulation of ovulation in the beef cow
Vascular Endothelial Growth Factor mRNA Isoforms 120 and 164 are Differentially Regulated Prior to Ovulation
Vascular Endothelial Growth Factor (VEGF) is produced by cells surrounding the egg in the follicle prior to ovulation. If VEGF is inhibited, ovulation does not occur. The VEGF gene can be spliced to produce different protein isoforms which have specific functions. Our objective was to determine if VEGF 120 and 164 mRNA isoforms are differentially regulated in the preovulatory follicle. From our studies, VEGF isoforms are differentially regulated during both CL regression and after a simulated LH surge. Differences observed in VEGF isoform regulation may allow for manipulation of ovulation in the beef cow
Moduli Spaces of Cold Holographic Matter
We use holography to study (3+1)-dimensional N=4 supersymmetric Yang-Mills
theory with gauge group SU(Nc), in the large-Nc and large-coupling limits,
coupled to a single massless (n+1)-dimensional hypermultiplet in the
fundamental representation of SU(Nc), with n=3,2,1. In particular, we study
zero-temperature states with a nonzero baryon number charge density, which we
call holographic matter. We demonstrate that a moduli space of such states
exists in these theories, specifically a Higgs branch parameterized by the
expectation values of scalar operators bilinear in the hypermultiplet scalars.
At a generic point on the Higgs branch, the R-symmetry and gauge group are
spontaneously broken to subgroups. Our holographic calculation consists of
introducing a single probe Dp-brane into AdS5 times S^5, with p=2n+1=7,5,3,
introducing an electric flux of the Dp-brane worldvolume U(1) gauge field, and
then obtaining explicit solutions for the worldvolume fields dual to the scalar
operators that parameterize the Higgs branch. In all three cases, we can
express these solutions as non-singular self-dual U(1) instantons in a
four-dimensional space with a metric determined by the electric flux. We
speculate on the possibility that the existence of Higgs branches may point the
way to a counting of the microstates producing a nonzero entropy in holographic
matter. Additionally, we speculate on the possible classification of
zero-temperature, nonzero-density states described holographically by probe
D-branes with worldvolume electric flux.Comment: 56 pages, 8 PDF images, 4 figure
Disposition Index, Glucose Effectiveness, and Conversion to Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study (IRAS)
Towards strange metallic holography
We initiate a holographic model building approach to `strange metallic'
phenomenology. Our model couples a neutral Lifshitz-invariant quantum critical
theory, dual to a bulk gravitational background, to a finite density of gapped
probe charge carriers, dually described by D-branes. In the physical regime of
temperature much lower than the charge density and gap, we exhibit anomalous
scalings of the temperature and frequency dependent conductivity. Choosing the
dynamical critical exponent appropriately we can match the non-Fermi liquid
scalings, such as linear resistivity, observed in strange metal regimes. As
part of our investigation we outline three distinct string theory realizations
of Lifshitz geometries: from F theory, from polarised branes, and from a
gravitating charged Fermi gas. We also identify general features of
renormalisation group flow in Lifshitz theories, such as the appearance of
relevant charge-charge interactions when . We outline a program to
extend this model building approach to other anomalous observables of interest
such as the Hall conductivity.Comment: 71 pages, 8 figure
A One Health overview, facilitating advances in comparative medicine and translational research.
Table of contentsA1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J. BergmanA5 Successful immunotherapy with a recombinant HER2-expressing Listeria monocytogenes in dogs with spontaneous osteosarcoma paves the way for advances in pediatric osteosarcomaNicola J. Mason, Josephine S. Gnanandarajah, Julie B. Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne PatersonA6 Human clinical development of ADXS-HER2Daniel O'ConnorA7 Leveraging use of data for both human and veterinary benefitLaura S. TremlA8 Biologic replacement of the knee: innovations and early clinical resultsJames P. StannardA9 Mizzou BioJoint Center: a translational success storyJames L. CookA10 University and industry translational partnership: from the lab to commercializationMarc JacobsA11 Beyond docking: an evolutionarily guided OneHealth approach to drug discoveryGerald J. Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew SkaffA12 Challenges and opportunities for data applications in animal health: from precision medicine to precision husbandryAmado S. GuloyA13 A cloud-based programmable platform for healthHarlen D. HaysA14 Comparative oncology: One Health in actionAmy K. LeBlancA15 Companion animal diseases bridge the translational gap for human neurodegenerative diseaseJoan R. Coates, Martin L. Katz, Leslie A. Lyons, Gayle C. Johnson, Gary S. Johnson, Dennis P. O'BrienA16 Duchenne muscular dystrophy gene therapyDongsheng DuanA17 Polycystic kidney disease: cellular mechanisms to emerging therapiesJames P. CalvetA18 The domestic cat as a large animal model for polycystic kidney diseaseLeslie A. Lyons, Barbara GandolfiA19 The support of basic and clinical research by the Polycystic Kidney Disease FoundationDavid A. BaronA20 Using naturally occurring large animal models of human disease to enable clinical translation: treatment of arthritis using autologous stromal vascular fraction in dogsMark L. WeissA21 Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based productsDebra A. WebsterA22 Regenerative medicine approaches to Type 1 diabetes treatmentFrancis N. KaranuA23 The zoobiquity of canine diabetes mellitus, man's best friend is a friend indeed-islet transplantationEdward J. RobbA24 One Medicine: a development model for cellular therapy of diabetesRobert J. Harman
Time dependent solitons of noncommutative Chern-Simons theory coupled to scalar fields
We study one- and two-soliton solutions of noncommutative Chern-Simons theory
coupled to a nonrelativistic or a relativistic scalar field. In the
nonrelativistic case, we find a tower of new stationary time-dependent
solutions, all with the same charge density, but with increasing energies. The
dynamics of these solitons cannot be studied using traditional moduli space
techniques, but we do find a nontrivial symplectic form on the phase space
indicating that the moduli space is not flat. In the relativistic case we find
the metric on the two soliton moduli space.Comment: 22 pages, 2 figures, JHEP3 style. v2: This paper is a thoroughly
revised version. We thank P.A. Horvathy, L. Martina and P.C. Stichel for
illuminating comments that led us to reconsider some of our previously
reported results; see note added at the end of the paper. v3:
Acknowledgements adde
The Influence of the Degree of Heterogeneity on the Elastic Properties of Random Sphere Packings
The macroscopic mechanical properties of colloidal particle gels strongly
depend on the local arrangement of the powder particles. Experiments have shown
that more heterogeneous microstructures exhibit up to one order of magnitude
higher elastic properties than their more homogeneous counterparts at equal
volume fraction. In this paper, packings of spherical particles are used as
model structures to computationally investigate the elastic properties of
coagulated particle gels as a function of their degree of heterogeneity. The
discrete element model comprises a linear elastic contact law, particle bonding
and damping. The simulation parameters were calibrated using a homogeneous and
a heterogeneous microstructure originating from earlier Brownian dynamics
simulations. A systematic study of the elastic properties as a function of the
degree of heterogeneity was performed using two sets of microstructures
obtained from Brownian dynamics simulation and from the void expansion method.
Both sets cover a broad and to a large extent overlapping range of degrees of
heterogeneity. The simulations have shown that the elastic properties as a
function of the degree of heterogeneity are independent of the structure
generation algorithm and that the relation between the shear modulus and the
degree of heterogeneity can be well described by a power law. This suggests the
presence of a critical degree of heterogeneity and, therefore, a phase
transition between a phase with finite and one with zero elastic properties.Comment: 8 pages, 6 figures; Granular Matter (published online: 11. February
2012
Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours
BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of γ-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of γ-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent γ-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and γ-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0534-2) contains supplementary material, which is available to authorized users
FindFoci: a focus detection algorithm with automated parameter training that closely matches human assignments, reduces human inconsistencies and increases speed of analysis
Accurate and reproducible quantification of the accumulation of proteins into foci in cells is essential for data interpretation and for biological inferences. To improve reproducibility, much emphasis has been placed on the preparation of samples, but less attention has been given to reporting and standardizing the quantification of foci. The current standard to quantitate foci in open-source software is to manually determine a range of parameters based on the outcome of one or a few representative images and then apply the parameter combination to the analysis of a larger dataset. Here, we demonstrate the power and utility of using machine learning to train a new algorithm (FindFoci) to determine optimal parameters. FindFoci closely matches human assignments and allows rapid automated exploration of parameter space. Thus, individuals can train the algorithm to mirror their own assignments and then automate focus counting using the same parameters across a large number of images. Using the training algorithm to match human assignments of foci, we demonstrate that applying an optimal parameter combination from a single image is not broadly applicable to analysis of other images scored by the same experimenter or by other experimenters. Our analysis thus reveals wide variation in human assignment of foci and their quantification. To overcome this, we developed training on multiple images, which reduces the inconsistency of using a single or a few images to set parameters for focus detection. FindFoci is provided as an open-source plugin for ImageJ
- …