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Search Results: 1 - 10 of 89342 matches for " Ute I. Schwarz "
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Clinical and Genetic Determinants of Warfarin Pharmacokinetics and Pharmacodynamics during Treatment Initiation
Inna Y. Gong,Ute I. Schwarz,Natalie Crown,George K. Dresser,Alejandro Lazo-Langner,GuangYong Zou,Dan M. Roden,C. Michael Stein,Marc Rodger,Philip S. Wells,Richard B. Kim,Rommel G. Tirona
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0027808
Abstract: Variable warfarin response during treatment initiation poses a significant challenge to providing optimal anticoagulation therapy. We investigated the determinants of initial warfarin response in a cohort of 167 patients. During the first nine days of treatment with pharmacogenetics-guided dosing, S-warfarin plasma levels and international normalized ratio were obtained to serve as inputs to a pharmacokinetic-pharmacodynamic (PK-PD) model. Individual PK (S-warfarin clearance) and PD (Imax) parameter values were estimated. Regression analysis demonstrated that CYP2C9 genotype, kidney function, and gender were independent determinants of S-warfarin clearance. The values for Imax were dependent on VKORC1 and CYP4F2 genotypes, vitamin K status (as measured by plasma concentrations of proteins induced by vitamin K absence, PIVKA-II) and weight. Importantly, indication for warfarin was a major independent determinant of Imax during initiation, where PD sensitivity was greater in atrial fibrillation than venous thromboembolism. To demonstrate the utility of the global PK-PD model, we compared the predicted initial anticoagulation responses with previously established warfarin dosing algorithms. These insights and modeling approaches have application to personalized warfarin therapy.
$p$-adic superspaces and Frobenius
A. Schwarz,I. Shapiro
Mathematics , 2006,
Abstract: The notion of a $p$-adic superspace is introduced and used to give a transparent construction of the Frobenius map on $p$-adic cohomology of a smooth projective variety over $\zp$ (the ring of $p$-adic integers), as well as an alternative construction of the crystalline cohomology of a smooth projective variety over $\fp$ (finite field with $p$ elements).
Supergeometry and Arithmetic Geometry
A. Schwarz,I. Shapiro
Mathematics , 2006, DOI: 10.1016/j.nuclphysb.2006.08.024
Abstract: We define a superspace over a ring $R$ as a functor on a subcategory of the category of supercommutative $R$-algebras. As an application the notion of a $p$-adic superspace is introduced and used to give a transparent construction of the Frobenius map on $p$-adic cohomology of a smooth projective variety over the ring of $p$-adic integers.
Some remarks on Gopakumar-Vafa invariants
A. Schwarz,I. Shapiro
Mathematics , 2004,
Abstract: We show that Gopakumar-Vafa invariants can be expressed in terms of the cohomology ring of moduli space of D-branes without reference to the sl_2 \times sl_2 action. We also give a simple construction of this action.
Cells determine cell density using a small protein bound to a unique tissue-specific phospholipid
Christopher J. Petzold,Richard I. Schwarz
PeerJ , 2015, DOI: 10.7717/peerj.192
Abstract: Cell density is the critical parameter controlling tendon morphogenesis. Knowing its neighbors allows a cell to regulate correctly its proliferation and collagen production. A missing link to understanding this process is a molecular description of the sensing mechanism. Previously, this mechanism was shown in cell culture to rely on a diffusible factor (SNZR [sensor]) with an affinity for the cell layer. This led to purifying conditioned medium over 4 columns and analyzing the final column fractions for band intensity on SDS gels versus biological activity – a 16 kD band strongly correlated between assays. N-terminal sequencing – EPLAVVDL – identified a large gene (424 AA), extremely conserved between chicken and human. In this paper we probe whether this is the correct gene. Can the predicted large protein be cleaved to a smaller protein? EPLAVVDL occurs towards the C-terminus and cleavage would create a small 94 AA protein. This protein would run at ~10 kD, so what modifications or cofactor binding accounts for its running at 16 kD on SDS gels? This protein has no prominent hydrophobic regions, so can it be secreted? To validate its role, the chicken cDNA for this gene was tagged with myc and his and transfected into a human osteosarcoma cell line (U2OS). U2OS cells expressed the gene but not passively: differentiating into structures resembling spongy bone and expressing alkaline phosphatase, an early bone marker. Intracellularly, two bands were observed by Western blotting: the full length protein and a smaller form (26 kD). Outside the cell, a small band (28 kD) was detected, although it was 40% larger than expected, as well as multiple larger bands. These larger forms could be converted to the predicted smaller protein (94 AA + tags) by changing salt concentrations and ultrafiltering – releasing a cofactor to the filtrate while leaving a protein factor in the retentate. Using specific degradative enzymes and mass spectrometry, the bone cofactor was identified as a lipid containing a ceramide phosphate, a single chained glycerol lipid and a linker. Tendon uses a different cofactor made up of two fatty acid chains linked directly to the phosphate yielding a molecule about half the size. Moreover, adding the tendon factor/cofactor to osteosarcoma cells causes them to stop growing, which is opposite to its role with tendon cells. Thus, the cofactor is cell type specific both in composition and in the triggered response. Further support of its proposed role came from frozen sections from 5 week old mice where an antibody to the factor stained strongly
Collective effects in cellular structure formation mediated by compliant environments: a Monte Carlo study
I. B. Bischofs,U. S. Schwarz
Physics , 2005, DOI: 10.1016/j.actbio.2006.01.002
Abstract: Compliant environments can mediate interactions between mechanically active cells like fibroblasts. Starting with a phenomenological model for the behaviour of single cells, we use extensive Monte Carlo simulations to predict non-trivial structure formation for cell communities on soft elastic substrates as a function of elastic moduli, cell density, noise and cell position geometry. In general, we find a disordered structure as well as ordered string-like and ring-like structures. The transition between ordered and disordered structures is controlled both by cell density and noise level, while the transition between string- and ring-like ordered structures is controlled by the Poisson ratio. Similar effects are observed in three dimensions. Our results suggest that in regard to elastic effects, healthy connective tissue usually is in a macroscopically disordered state, but can be switched to a macroscopically ordered state by appropriate parameter variations, in a way that is reminiscent of wound contraction or diseased states like contracture.
Cell organization in soft media due to active mechanosensing
I. B. Bischofs,U. S. Schwarz
Quantitative Biology , 2003, DOI: 10.1073/pnas.1233544100
Abstract: Adhering cells actively probe the mechanical properties of their environment and use the resulting information to position and orient themselves. We show that a large body of experimental observations can be consistently explained from one unifying principle, namely that cells strengthen contacts and cytoskeleton in the direction of large effective stiffness. Using linear elasticity theory to model the extracellular environment, we calculate optimal cell organization for several situations of interest and find excellent agreement with experiments for fibroblasts, both on elastic substrates and in collagen gels: cells orient in the direction of external tensile strain, they orient parallel and normal to free and clamped surfaces, respectively, and they interact elastically to form strings. Our method can be applied for rational design of tissue equivalents. Moreover our results indicate that the concept of contact guidance has to be reevaluated. We also suggest that cell-matrix contacts are upregulated by large effective stiffness in the environment because in this way, build-up of force is more efficient.
Functional promiscuity in a mammalian chemosensory system: extensive expression of vomeronasal receptors in the main olfactory epithelium of mouse lemurs
Philipp Hohenbrink,Silke Dempewolf,Nicholas I. Mundy,Ute Radespiel
Frontiers in Neuroanatomy , 2014, DOI: 10.3389/fnana.2014.00102
Abstract: The vomeronasal organ (VNO) is functional in most terrestrial mammals, though progressively reduced in the primate lineage, and is used for intraspecific communication and predator recognition. Vomeronasal receptor (VR) genes comprise two families of chemosensory genes (V1R and V2R) that have been considered to be specific for the VNO. However, recently a large number of VRs were reported to be expressed in the main olfactory epithelium (MOE) of mice, but there is little knowledge of the expression of these genes outside of rodents. To explore the function of VR genes in mammalian evolution, we analyzed and compared the expression of 64 V1R and 2 V2R genes in the VNO and the MOE of the grey mouse lemur (Microcebus murinus), the primate with the largest known VR repertoire. We furthermore compared expression patterns in adults of both sexes and seasons, and in an infant. A large proportion (83% – 97%) of the VR loci was expressed in the VNO of all individuals. The repertoire in the infant was as rich as in adults, indicating reliance on olfactory communication from early postnatal development onwards. In concordance with mice, we also detected extensive expression of VRs in the MOE, with proportions of expressed loci in individuals ranging from 29% to 45%. TRPC2, which encodes a channel protein crucial for signal transduction via VRs, was co-expressed in the MOE in all individuals indicating likely functionality of expressed VR genes in the MOE. In summary, the large VR repertoire in mouse lemurs seems to be highly functional. Given the differences in the neural pathways of MOE and VNO signals, which project to higher cortical brain centers or the limbic system, respectively, this raises the intriguing possibility that the evolution of MOE-expression of VRs enabled mouse lemurs to adaptively diversify the processing of VR-encoded olfactory information.
Effect of Alligator Pepper on Litter Weight of Rats Fed on High Glycemic Index Diet  [PDF]
Ute Inegbenebor, Festus Eghomwanre
Food and Nutrition Sciences (FNS) , 2017, DOI: 10.4236/fns.2017.88056
Abstract: This study was carried out to find out if alligator pepper can prevent the development of fetal macrosomia in Sprague-Dawley rats fed with high glycemic index diet. Fifteen adult female Sprague-Dawley rats of proven fertility were acclimatized for a period of two weeks in a well-ventilated laboratory and fed with grower’s mash and water ad libitum. Thereafter, they were randomly placed in separate cages after which a male Sprague-Dawley rat of proven fertility was introduced into each of the cages containing the female rats. They were left in the cages for three days during, which mating was confirmed to have occurred. The male rats were then withdrawn from the female rats, which were placed in separate maternity cages. The female rats were randomly allocated to three groups A, B and C so there were 5 pregnant rats in each group. The rats in group A were fed with 50 g of grower’s mash daily while the rats in groups B and C were fed with 50 g of cooked fermented cassava respectively. All rats were given water ad libitum throughout the duration of the experiment. The rats in groups A and B were intraperitoneally injected with 13.3 ml per Kg body weight of distilled water while the rats in group C were intraperitoneally injected with 13.3 mg/Kg body weight of aqueous extract of alligator pepper respectively. They were observed for 18 - 25 days. The litters of the rats in group B had a significantly higher mean weight than the rats in group A while the litters of the rats in group C had a significantly lower mean weight than the rats in groups B. It was concluded that intraperitoneally injected aqueous extract of alligator pepper, in the first trimester of pregnancy, can prevent the development of fetal macrosomia in Sprague-Dawley rats.
Electronic Structure and Heavy Fermion Behavior in LiV_2O_4
D. J. Singh,P. Blaha,K. Schwarz,I. I. Mazin
Physics , 1999, DOI: 10.1103/PhysRevB.60.16359
Abstract: First principles density functional calculations of the electronic and magnetic properties of spinel-structure LiV$_{2}$O$_{4}$ have been performed using the full potential linearized augmented planewave method. The calculations show that the electronic structure near the Fermi energy consists of a manifold of 12 bands derived from V $t_{2g}$ states, weakly hybridized with O p states. While the total width of this active manifold is approximately 2 eV, it may be roughly decomposed into two groups: high velocity bands and flatter bands, although these mix in density functional calculations. The flat bands, which are the more atomic-like lead to a high density of states and magnetic instability of local moment character. The value of the on-site exchange energy is sensitive to the exact exchange correlation parameterization used in the calculations, but is much larger than the interaction between neighboring spins, reflecting the weak coupling of the magnetic system with the high velocity bands. A scenario for the observed heavy fermion behavior is discussed in which conduction electrons in the dispersive bands are weakly scattered by local moments associated with strongly correlated electrons in the heavy bands.This is analogous to that in conventional Kondo type heavy fermions, but is unusual in that both the local moments and conduction electrons come from the same d-manifold.
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