A note on the expectations hypothesis at the founding of the Fed

One of the most influential tests of the expectations hypothesis is Mankiw and Miron (1986), who found that the spread between the long-term and short-term rates provided predictive power for the short-term rate before the Fed's founding but not after. They suggested that the failure of the expectations hypothesis after the Fed's founding was due to the Fed's practice of smoothing short-term interest rates. We show that their finding that the expectations hypothesis fares better prior to the Fed's founding is due to the fact that the test they employ tends to generate results that are more favorable to the expectations hypothesis during periods when there is extreme volatility in the short-term rate. (Earlier version titled: The expectations theory and the founding of the Fed: another look at the evidence)Interest rates ; Rational expectations (Economic theory) ; Federal Reserve System - History

Regulation of AQP0 water permeability is enhanced by cooperativity.

Aquaporin 0 (AQP0), essential for lens clarity, is a tetrameric protein composed of four identical monomers, each of which has its own water pore. The water permeability of AQP0 expressed in Xenopus laevis oocytes can be approximately doubled by changes in calcium concentration or pH. Although each monomer pore functions as a water channel, under certain conditions the pores act cooperatively. In other words, the tetramer is the functional unit. In this paper, we show that changes in external pH and calcium can induce an increase in water permeability that exhibits either a positive cooperativity switch-like increase in water permeability or an increase in water permeability in which each monomer acts independently and additively. Because the concentrations of calcium and hydrogen ions increase toward the center of the lens, a concentration signal could trigger a regulatory change in AQP0 water permeability. It thus seems plausible that the cooperative modes of water permeability regulation by AQP0 tetramers mediated by decreased pH and elevated calcium are the physiologically important ones in the living lens

Nanodiamonds carrying quantum emitters with almost lifetime-limited linewidths

Nanodiamonds (NDs) hosting optically active defects are an important technical material for applications in quantum sensing, biological imaging, and quantum optics. The negatively charged silicon vacancy (SiV) defect is known to fluoresce in molecular sized NDs (1 to 6 nm) and its spectral properties depend on the quality of the surrounding host lattice. This defect is therefore a good probe to investigate the material properties of small NDs. Here we report unprecedented narrow optical transitions for SiV colour centers hosted in nanodiamonds produced using a novel high-pressure high-temperature (HPHT) technique. The SiV zero-phonon lines were measured to have an inhomogeneous distribution of 1.05 nm at 5 K across a sample of numerous NDs. Individual spectral lines as narrow as 354 MHz were measured for SiV centres in nanodiamonds smaller than 200 nm, which is four times narrower than the best SiV line previously reported for nanodiamonds. Correcting for apparent spectral diffusion yielded a homogeneous linewith of about 200 MHz, which is close to the width limit imposed by the radiative lifetime. These results demonstrate that the direct HPHT synthesis technique is capable of producing nanodiamonds with high crystal lattice quality, which are therefore a valuable technical material

Malondialdehyde Acetaldehyde Adducts (MAA-Adducts) Direct Distinctive Pro-Inflammatory Responses in Endothelial and Macrophage Cell Lines

Chronic inflammation plays a critical role in the pathogenesis of atherosclerosis. At present, the mechanism(s) by which inflammation contributes to this disease isnot entirely understood. Inflammation is known to induce oxidative stress, of which one consequence is lipid peroxidation. This process leads to the production of malondialdehyde (MDA), which can subsequently break down to form acetaldehyde (AA). These two aldehyde by-products can covalently interact with the ε-amino group of lysineswithin proteins and lipoproteins leading to the formation of highly immunogenic malondialdehyde-acetaldehyde adducts (MAA-adducts). The aim of this study was to determine the in-vitro cytokine response of endothelial cells and macrophages treated with MAA-modified human serum albumin (HSA-MAA) and low-density lipoprotein (LDL-MAA). In addition, cells isolated from mice with exposure to MAA and high fat diets were stained and imaged for uptake of the modified macromolecules of interest. We found that exposure of endothelial cells resulted in increased expression of IL-6, TNF-α, ICAM-1, VCAM-1, and MCP-1 in response to incubation with HSA-MAA; whereas, the same treatment of macrophages resulted in increased expression of IL-6, TNF-α, and IL-1b. LDL-MAA incubationresulted in increased TNF-α expression in macrophages, but MCP-1 was elevated in endothelial cells. Interestingly, the quantitative and qualitative uptake of triglycerides was increased in both endothelial and macrophage cells when exposed to LDL-MAA compared to LDL alone. The results of these studies demonstrate that different MAA-adducts elicit unique responses in different cell types. Additionally, the presence of MAA appears to modulate the cells leading to increased uptake of triglycerides and further progression of the inflammatory response.https://digitalcommons.unmc.edu/emet_posters/1003/thumbnail.jp

Allosteric Mechanism of Water Channel Gating by Ca2+–calmodulin

Calmodulin (CaM) is a universal regulatory protein that communicates the presence of calcium to its molecular targets and correspondingly modulates their function. This key signaling protein is important for controlling the activity of hundreds of membrane channels and transporters. However, our understanding of the structural mechanisms driving CaM regulation of full-length membrane proteins has remained elusive. In this study, we determined the pseudo-atomic structure of full-length mammalian aquaporin-0 (AQP0, Bos Taurus) in complex with CaM using electron microscopy to understand how this signaling protein modulates water channel function. Molecular dynamics and functional mutation studies reveal how CaM binding inhibits AQP0 water permeability by allosterically closing the cytoplasmic gate of AQP0. Our mechanistic model provides new insight, only possible in the context of the fully assembled channel, into how CaM regulates multimeric channels by facilitating cooperativity between adjacent subunits

Southern Hemisphere forcing of South Asian monsoon precipitation over the past ~1 million years

The orbital-scale timing of South Asian monsoon (SAM) precipitation is poorly understood. Here we present new SST and seawater δ18O (δ18Osw) records from the Bay of Bengal, the core convective region of the South Asian monsoon, over the past 1 million years. Our records reveal that SAM precipitation peaked in the precession band ~9 kyrs after Northern Hemisphere summer insolation maxima, in phase with records of SAM winds in the Arabian Sea and eastern Indian Ocean. Precession-band variance, however, accounts for ~30% of the total variance of SAM precipitation while it was either absent or dominant in records of the East Asian monsoon (EAM). This and the observation that SAM precipitation was phase locked with obliquity minima and was sensitive to Southern Hemisphere warming provides clear evidence that SAM and EAM precipitation responded differently to orbital forcing and highlights the importance of internal processes forcing monsoon variability

The synthetic Tie2 agonist peptide vasculotide protects against vascular leakage and reduces mortality in murine abdominal sepsis

Introduction: Angiopoietin-1 (Angpt1), the natural agonist ligand for the endothelial Tie2 receptor, is a non-redundant endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte-endothelium interactions. Here we evaluate the efficacy of a novel polyethylene glycol (PEG)-clustered Tie2 agonist peptide, vasculotide (VT), to protect against vascular leakage and mortality in a murine model of polymicrobial abdominal sepsis. Methods: Polymicrobial abdominal sepsis in C57BL6 mice was induced by cecal-ligation-and-puncture (CLP). Mice were treated with different dosages of VT or equal volume of phosphate-buffered saline (PBS). Sham-operated animals served as time-matched controls. Results: Systemic administration of VT induced long-lasting Tie2 activation in vivo. VT protected against sepsis-induced endothelial barrier dysfunction, as evidenced by attenuation of vascular leakage and leukocyte transmigration into the peritoneal cavity. Histological analysis revealed that VT treatment ameliorated leukocyte infiltration in kidneys of septic mice, probably due to reduced endothelial adhesion molecule expression. VT-driven effects were associated with significantly improved organ function and reduced circulating cytokine levels. The endothelial-specific action of VT was supported by additional in vitro studies showing no effect of VT on either cytokine release from isolated peritoneal macrophages, or migratory capacity of isolated neutrophils. Finally, administration of VT pre-CLP (hazard ratio 0.39 [95% confidence interval 0.19-0.81] P < 0.001) and post-CLP reduced mortality in septic mice (HR 0.22 [95% CI 0.06-0.83] P < 0.05). Conclusions: We provide proof of principle in support of the efficacious use of PEGylated VT, a drug-like Tie2 receptor agonist, to counteract microvascular endothelial barrier dysfunction and reduce mortality in a clinically relevant murine sepsis model. Further studies are needed to pave the road for clinical application of this therapeutic concept

UVA and Seasonal Patterning of 56 370 Myocardial Infarctions Across Scotland, 2000–2011

Background: Myocardial infarction exhibits seasonal patterning, with higher amplitude at increased latitude. Epidemiological evidence suggests that sunlight is protective against cardiovascular disease, independent of ambient temperature, but ultraviolet B–mediated vitamin D production has been discounted as causal. We aimed to determine whether ultraviolet A is associated with the seasonal patterning of myocardial infarction. Methods and Results: Routine hospitalization data were used to determine monthly incidence of myocardial infarction in Scotland between 2000 and 2011. Small‐area–level aggregated data were obtained on ambient temperature from the Meteorological Office and ultraviolet A and ultraviolet B irradiance from NASA satellites. Autoregressive distributed lag models were run for ultraviolet A and myocardial infarction, including adjustment for ambient temperature and ultraviolet B. Monthly incidence of myocardial infarction displayed winter peaks and summer troughs superimposed on the underlying trend, with a mean amplitude of 0.31 (95% CI: 0.21, 0.41) myocardial infarctions per 100 000 population per month. Ultraviolet A exposure was inversely associated with myocardial infarction independent of ambient temperature (coefficient, −0.05; 95% CI, −0.09, −0.01; P=0.015) and ultraviolet B UVB (coefficient, −0.05; 95% CI, −0.09, −0.02; P=0.004). Conclusions: Further research is required to explore whether an ultraviolet‐mediated mechanism different to vitamin D, such as nitric oxide–mediated vasodilatation, may play a causal role in the seasonal and geographical patterning of myocardial infarction