190 research outputs found
After House Bill 920: An Analysis of Needed Real Property Tax Reform
This Note will analyze the current state of real property tax law in Ohio and its relationship to H.B. 920. The tax reform provision of H.B. 920 will be separately analyzed from both the historical perspective surrounding its passage and the technical perspective of its mathematical calculations. A further analysis of the relationship between taxation by uniform rule under Article XII, Β§ 2 of the Ohio Constitution will be undertaken. The conclusion will focus on a constitutionally valid solution to the problem of property tax reform while, at the same time, noting several essential and unusual questions
Universal Heat Conduction in YBa_2Cu_3O_6.9
The thermal conductivity of YBa_2Cu_3O_6.9 was measured at low temperatures
in untwinned single crystals with concentrations of Zn impurities from 0 to 3%
of Cu. A linear term kappa_0/T = 0.19 mW/K^2.cm is clearly resolved as T -> 0,
and found to be virtually independent of Zn concentration. The existence of
this residual normal fluid strongly validates the basic theory of transport in
unconventional superconductors. Moreover, the observed universal behavior is in
quantitative agreement with calculations for a gap function of d-wave symmetry.Comment: Latex file, 4 pages, 3 EPS figures, to appear in Physical Review
Letter
PAR2 modulators derived from GB88
PAR2 antagonists have potential for treating inflammatory, respiratory, gastrointestinal, neurological, and metabolic disorders, but few antagonists are known. Derivatives of GB88 (3) suggest that all four of its components bind at distinct PAR2 sites with the isoxazole, cyclohexylalanine, and isoleucine determining affinity and selectivity, while the C-terminal substituent determines agonist/antagonist function. Here we report structurally similar PAR2 ligands with opposing functions (agonist vs antagonist) upon binding to PAR2. A biased ligand AY117 (65) was found to antagonize calcium release induced by PAR2 agonists trypsin and hexapeptide 2f-LIGRLO-NH2 (IC50 2.2 and 0.7 mu M, HT29 cells), but it was a selective PAR2 agonist in inhibiting cAMP stimulation and activating ERK1/2 phosphorylation. It showed antiinflammatory properties both in vitro and in vivo
Thermal Conductivity across the Phase Diagram of Cuprates: Low-Energy Quasiparticles and Doping Dependence of the Superconducting Gap
Heat transport in the cuprate superconductors YBaCuO and
LaSrCuO was measured at low temperatures as a function of
doping. A residual linear term kappa_{0}/T is observed throughout the
superconducting region and it decreases steadily as the Mott insulator is
approached from the overdoped regime. The low-energy quasiparticle gap
extracted from kappa_{0}/T is seen to scale closely with the pseudogap. The
ubiquitous presence of nodes and the tracking of the pseudogap shows that the
overall gap remains of the pure d-wave form throughout the phase diagram, which
excludes the possibility of a complex component (ix) appearing at a putative
quantum phase transition and argues against a non-superconducting origin to the
pseudogap. A comparison with superfluid density measurements reveals that the
quasiparticle effective charge is weakly dependent on doping and close to
unity.Comment: 12 pages, 9 figure
Hrs and SNX3 Functions in Sorting and Membrane Invagination within Multivesicular Bodies
After internalization, ubiquitinated signaling receptors are delivered to early endosomes. There, they are sorted and incorporated into the intralumenal invaginations of nascent multivesicular bodies, which function as transport intermediates to late endosomes. Receptor sorting is achieved by Hrsβan adaptor-like protein that binds membrane PtdIns3P via a FYVE motifβand then by ESCRT complexes, which presumably also mediate the invagination process. Eventually, intralumenal vesicles are delivered to lysosomes, leading to the notion that EGF receptor sorting into multivesicular bodies mediates lysosomal targeting. Here, we report that Hrs is essential for lysosomal targeting but dispensable for multivesicular body biogenesis and transport to late endosomes. By contrast, we find that the PtdIns3P-binding protein SNX3 is required for multivesicular body formation, but not for EGF receptor degradation. PtdIns3P thus controls the complementary functions of Hrs and SNX3 in sorting and multivesicular body biogenesis
Interleukin-4 Alters Early Phagosome Phenotype by Modulating Class I PI3K Dependent Lipid Remodeling and Protein Recruitment
Phagocytosis is a complex process that involves membranelipid remodeling and the attraction and retention of key effector proteins. Phagosome phenotype depends on the type of receptor engaged and can be influenced by extracellular signals. Interleukin 4 (IL-4) is a cytokine that induces the alternative activation of macrophages (MΦs) upon prolonged exposure, triggering a different cell phenotype that has an altered phagocytic capacity. In contrast, the direct effects of IL-4 during phagocytosis remain unknown. Here, we investigate the impact of short-term IL-4 exposure (1 hour) during phagocytosis of IgG-opsonized yeast particles by MΦs. By time-lapse confocal microscopy of GFP-tagged lipid-sensing probes, we show that IL-4 increases the negative charge of the phagosomal membrane by prolonging the presence of the negatively charged second messenger PI(3,4,5)P3. Biochemical assays reveal an enhanced PI3K/Akt activity upon phagocytosis in the presence of IL-4. Blocking the specific class I PI3K after the onset of phagocytosis completely abrogates the IL-4-induced changes in lipid remodeling and concomitant membrane charge. Finally, we show that IL-4 direct signaling leads to a significantly prolonged retention profile of the signaling molecules Rac1 and Rab5 to the phagosomal membrane in a PI3K-dependent manner. This protracted early phagosome phenotype suggests an altered maturation, which is supported by the delayed phagosome acidification measured in the presence of IL-4. Our findings reveal that molecular differences in IL-4 levels, in the extracellular microenvironment, influence the coordination of lipid remodeling and protein recruitment, which determine phagosome phenotype and, eventually, fate. Endosomal and phagosomal membranes provide topological constraints to signaling molecules. Therefore, changes in the phagosome phenotype modulated by extracellular factors may represent an additional mechanism that regulates the outcome of phagocytosis and could have significant impact on the net biochemical output of a cell
Repression of the type I interferon pathway underlies MYC & KRAS-dependent evasion of NK & B cells in pancreatic ductal adenocarcinoma
MYC is implicated in the development and progression of Pancreatic cancer, yet the precise level of MYC deregulation required to contribute to tumour development has been difficult to define. We used modestly elevated expression of human MYC, driven from the Rosa26 locus, to investigate the pancreatic phenotypes arising in mice from an approximation of MYC trisomy. We show that this level of MYC alone suffices to drive pancreatic neuroendocrine tumours, and to accelerate progression of KRAS-initiated precursor lesions to metastatic pancreatic ductal adenocarcinoma. Our phenotype exposed suppression of the Type I Interferon pathway by the combined actions of MYC and KRAS and we present evidence of repressive MYC/MIZ1 complexes binding directly to the promoters of type I Interferon regulators IRF5, IRF7, STAT1 and STAT2. De-repression of Interferon regulators allows pancreatic tumour infiltration of B and NK cells, resulting in increased survival
ERK5 MAP Kinase Regulates Neurogenin1 during Cortical Neurogenesis
The commitment of multi-potent cortical progenitors to a neuronal fate depends on the transient induction of the basic-helix-loop-helix (bHLH) family of transcription factors including Neurogenin 1 (Neurog1). Previous studies have focused on mechanisms that control the expression of these proteins while little is known about whether their pro-neural activities can be regulated by kinase signaling pathways. Using primary cultures and ex vivo slice cultures, here we report that both the transcriptional and pro-neural activities of Neurog1 are regulated by extracellular signal-regulated kinase (ERK) 5 signaling in cortical progenitors. Activation of ERK5 potentiated, while blocking ERK5 inhibited Neurog1-induced neurogenesis. Furthermore, endogenous ERK5 activity was required for Neurog1-initiated transcription. Interestingly, ERK5 activation was sufficient to induce Neurog1 phosphorylation and ERK5 directly phosphorylated Neurog1 in vitro. We identified S179/S208 as putative ERK5 phosphorylation sites in Neurog1. Mutations of S179/S208 to alanines inhibited the transcriptional and pro-neural activities of Neurog1. Our data identify ERK5 phosphorylation of Neurog1 as a novel mechanism regulating neuronal fate commitment of cortical progenitors
Coherent elastic neutrino-nucleus scattering: Terrestrial and astrophysical applications
Coherent elastic neutrino-nucleus scattering (CENS) is a process in which neutrinos scatter on a nucleus which acts as a single particle. Though the total cross section is large by neutrino standards, CENS has long proven difficult to detect, since the deposited energy into the nucleus is keV. In 2017, the COHERENT collaboration announced the detection of CENS using a stopped-pion source with CsI detectors, followed up the detection of CENS using an Ar target. The detection of CENS has spawned a flurry of activities in high-energy physics, inspiring new constraints on beyond the Standard Model (BSM) physics, and new experimental methods. The CENS process has important implications for not only high-energy physics, but also astrophysics, nuclear physics, and beyond. This whitepaper discusses the scientific importance of CENS, highlighting how present experiments such as COHERENT are informing theory, and also how future experiments will provide a wealth of information across the aforementioned fields of physics
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