The adenylate cyclase receptor complex and aqueous humor formation.

The secretory tissue of the eye, the ciliary processes, contains an enzyme receptor complex, composed of membrane proteins, the catalytic moiety of the enzyme adenylate cyclase, a guanyl nucleotide regulatory protein (or N protein), and other features. The enzyme can be activated by well-known neurohumoral or humoral agents, catecholamines, glycoprotein hormones produced by the hypothalamic pituitary axis, and other related compounds, including placental gonadotropin, organic fluorides, and forskolin, a diterpene. These compounds cause the ciliary epithelia to produce cyclic AMP at an accelerated rate. Cyclic AMP, as a second messenger, causes, either directly or indirectly, a decrease in the net rate of aqueous humor inflow that may be modulated by cofactors. Clinical syndromes fit the experimental data so that an integrated explanation can be given for the reduced intraocular pressure witnessed under certain central nervous system and adrenergic influences. The molecular biology of this concept provides important leads for future investigations that bear directly both upon the regulation of intraocular pressure and upon glaucoma

Generation Efficiencies for Propagating Modes in a Supersolid

Using Andreev and Lifshitz's supersolid hydrodynamics, we obtain the propagating longitudinal modes at non-zero applied pressure $P_{a}$ (necessary for solid 4He), and their generation efficiencies by heaters and transducers. For small $P_{a}$, a solid develops an internal pressure $P \sim P_{a}^2$. This theory has stress contributions both from the lattice and an internal pressure $P$. Because both types of stress are included, the normal mode analysis differs from previous works. Not surprisingly, transducers are significantly more efficient at producing elastic waves and heaters are significantly more efficient at producing fourth sound waves. We take the system to be isotropic, which should apply to systems that are glassy or consist of many crystallites; the results should also apply, at least qualitatively, to single-crystal hcp 4He.Comment: 10 pages. Accepted by Physical Review

Thermal Equilibration and Thermally-Induced Spin Currents in a Thin-Film Ferromagnet on a Substrate

Recent spin-Seebeck experiments on thin ferromagnetic films apply a temperature difference $\Delta T_{x}$ along the length $x$ and measure a (transverse) voltage difference $\Delta V_{y}$ along the width $y$. The connection between these effects is complex, involving: (1) thermal equilibration between sample and substrate; (2) spin currents along the height (or thickness) $z$; and (3) the measured voltage difference. The present work studies in detail the first of these steps, and outlines the other two steps. Thermal equilibration processes between the magnons and phonons in the sample, as well as between the sample and the substrate leads to two surface modes, with surface lengths $\lambda$, to provide for thermal equilibration. Increasing the coupling between the two modes increases the longer mode length and decreases the shorter mode length. The applied thermal gradient along $x$ leads to a thermal gradient along $z$ that varies as $\sinh{(x/\lambda)}$, which can in turn produce fluxes of the carriers of up- and down- spins along $z$, and gradients of their associated \textit{magnetoelectrochemical potentials} $\bar{\mu}_{\uparrow,\downarrow}$, which vary as $\sinh{(x/\lambda)}$. By the inverse spin Hall effect, this spin current along $z$ can produce a transverse (along $y$) voltage difference $\Delta V_y$, which also varies as $\sinh{(x/\lambda)}$.Comment: 14 pages, 7 figures, 1 tabl

The transcription factor ATF5: role in cellular differentiation, stress responses, and cancer.

Activating transcription factor 5 (ATF5) is a cellular prosurvival transcription factor within the basic leucine zipper (bZip) family that is involved in cellular differentiation and promotes cellular adaptation to stress. Recent studies have characterized the oncogenic role of ATF5 in the development of several different types of cancer, notably glioblastoma. Preclinical assessment of a systemically deliverable dominant-negative ATF5 (dnATF5) biologic has found that targeting ATF5 results in tumor regression and tumor growth inhibition of glioblastoma xenografts in mouse models. In this review, we comprehensively and critically detail the current scientific literature on ATF5 in the context of cellular differentiation, survival, and response to stressors in normal tissues. Furthermore, we will discuss how the prosurvival role of ATF5 aides in cancer development, followed by current advances in targeting ATF5 using dominant-negative biologics, and perspectives on future research

Andreev-Lifshitz Hydrodynamics Applied to an Ordinary Solid under Pressure

We have applied the Andreev-Lifshitz hydrodynamic theory of supersolids to an ordinary solid. This theory includes an internal pressure $P$, distinct from the applied pressure $P_a$ and the stress tensor $\lambda_{ik}$. Under uniform static $P_{a}$, we have $\lambda_{ik} = (P-P_{a})\delta_{ik}$. For $P_{a} \ne 0$, Maxwell relations imply that $P \sim P_{a}^{2}$. The theory also permits vacancy diffusion but treats vacancies as conserved. It gives three sets of propagating elastic modes; it also gives two diffusive modes, one largely of entropy density and one largely of vacancy density (or, more generally, defect density). For the vacancy diffusion mode (or, equivalently, the lattice diffusion mode) the vacancies behave like a fluid within the solid, with the deviations of internal pressure associated with density changes nearly canceling the deviations of stress associated with strain. We briefly consider pressurization experiments in solid $^4$He at low temperatures in light of this lattice diffusion mode, which for small $P_{a}$ has diffusion constant $D_{L} \sim P_{a}^{2}$. The general principles of the theory -- that both volume and strain should be included as thermodynamic variables, with the result that both $P$ and $\lambda_{ik}$ appear -- should apply to all solids under pressure, especially near the solid-liquid transition. The lattice diffusion mode provides an additional degree of freedom that may permit surfaces with different surface treatments to generate different responses in the bulk.Comment: 10 pages. Accepted by Physical Review

Andreev-Lifshitz Supersolid Hydrodynamics Including the Diffusive Mode

We have re-examined the Andreev-Lifshitz theory of supersolids. This theory implicitly neglects uniform bulk processes that change the vacancy number, and assumes an internal pressure $P$ in addition to lattice stress $\lambda_{ik}$. Each of $P$ and $\lambda_{ik}$ takes up a part of an external, or applied, pressure $P_a$ (necessary for solid 4He). The theory gives four pairs of propagating elastic modes, of which one pair corresponds to a fourth-sound mode, and a single diffusive mode, which has not been analyzed previously. The diffusive mode has three distinct velocities, with the superfluid velocity much larger than the normal fluid velocity, which in turn is much larger than the lattice velocity. The mode structure depends on the relative values of certain kinetic coefficients and thermodynamic derivatives. We consider pressurization experiments in solid 4He at low temperatures in light of this diffusion mode and a previous analysis of modes in a normal solid with no superfluid component.Comment: 8 pages. Accepted by Physical Review

The Economic Impact of Extending Marriage to Same-Sex Couples in Maine

This research study estimates that same-sex marriage in Maine, if permitted, would have a positive impact on the state's economy and budget. The study finds that same-sex weddings and associated tourism would generate $60 million in additional spending in Maine over three years, creating 1,000 new jobs. Due to this spending, the state and Maine counties would see an increase of$3.6 million in revenues over the next three years; the result of an increase of sales tax revenues of approximately $3.1 million and new marriage license fees of$500,000. In calculating the net benefit to the State, the study approximates that half of Maine's 4,644 same-sex couples, or 2,316 couples, would marry in the first three years that marriage is extended to them. The study also estimates that approximately 15,657 same-sex couples from other states would come to Maine to marry

Evidence of Employment Discrimination on the Basis of Sexual Orientation and Gender Identity: Complaints Filed with State Enforcement Agencies, 1999-2007

To more accurately measure the effect of anti-discrimination laws, this report compares sex, race, and sexual orientation complaint rates through a population-adjusted model. Today, twenty states and the District of Columbia prohibit employment discrimination based on sexual orientation. Of those, thirteen also prohibit discrimination on the basis of gender identity. An aggregation of all available state level data reveals that sexual orientation discrimination laws are used at similar frequencies by Lesbian, Gay, and Bisexual (LGB) workers as sex discrimination laws by female workers, both at 5 complaints per every 10,000 workers. Race complaints are filed at the higher rate of 7 per 10,000 workers

Characterizing the role of macrophages in cisplatin-induced kidney injury and progression to chronic kidney disease.

Cisplatin is a commonly used chemotherapeutic for treatment of many solid-organ cancers. Unfortunately, 30% of patients treated with cisplatin develop acute kidney injury (AKI), and even patients who do not develop AKI are at risk for long term declines in kidney function and development of chronic kidney disease (CKD). While traditional rodent toxicity studies have utilized a single, lethal dose of cisplatin, new models of cisplatin-induced kidney injury have revealed that repeated, low doses of cisplatin lead to development of kidney fibrosis. This model can be used to examine AKI-to-CKD transition processes. C57BL/6 mice are one of the most used mouse strains in research; however, they are resistant to chronic kidney disease-associated pathologies. While repeated 7 mg/kg cisplatin doses induce kidney fibrosis in FVB/n mice, we found that treating C57BL/6 mice with this same dosing regimen does not result in kidney fibrosis. Here, we demonstrate that increasing the dose of cisplatin to 9 mg/kg is sufficient to consistently induce fibrosis in C57BL/6 mice. In addition, we present that cohorts of C57BL/6 mice purchased from Jackson one year apart and mice bred in house display variability in renal outcomes following repeated low dose cisplatin treatment. This variability revealed CCL2 as a marker of cisplatin-induced kidney injury through correlation studies. In addition, significant myeloid cell infiltration was observed in the kidney after four doses of 9 mg/kg cisplatin, indicating macrophages are present during the AKI-to-CKD transition. To further evaluate the role of macrophages in cisplatin-induced fibrosis, we used either C57BL/6 mice with Ccr2 genetic knockout or liposome encapsulated clodronate (Clodrosome) to deplete macrophage populations during repeated, 9 mg/kg cisplatin treatments. We found that Ccr2-/- mice had decreased levels of infiltrating macrophages in the kidney following cisplatin treatments. In contrast, Clodrosome treatment depleted resident and M2 macrophages in the kidney following cisplatin treatment. Furthermore, Clodrosome treatment decreased collagen deposition, myofibroblast accumulation, and inflammatory cytokine production, while Ccr2 genetic knockout had no effect on these markers following cisplatin treatment. These data suggest that Clodrosome depletion of resident and M2 macrophages in the kidney attenuates development of renal fibrosis following repeated, low doses of cisplatin