4,083 research outputs found
Three Essays on Fiscal Stress and Financial Stability in State Government Finance
State government finance is a substantial endeavor in the United States. The management of a multitude of revenues and expenditures often involves some level of fiscal stress. In an age of increased public scrutiny, policymakers must be mindful of possible causes of fiscal stress, and the policy options available to mitigate fiscal stress and increase financial stability. This dissertation contains three essays that examine different elements of fiscal stress, and in some cases, the applicable policy responses.
Chapter two examines rainy day funds and their countercyclical goal of reducing recessionary fiscal stress. This essay takes a different approach from much of the literature, by using forecast residuals to quantify fiscal stress as tax revenue volatility and searching for any relationship between rainy day funds and states that had greater volatility. Empirical results indicate states that experience positive residuals, that is actual tax revenues greater than the forecast trend line, had greater rainy day fund balances.
Chapter three focuses on the problem of lost revenues facing states from e-commerce. Due to Supreme Court decisions, businesses that do not have a physical location, or nexus, in a state are not required to collect sales and use taxes. To date, the policy response to lost revenue that has gained the most traction is the Streamlined Sales and Use Tax Agreement. Results indicate that states with local option sales taxes and higher sales tax rates were more likely to adopt this agreement.
Chapter four scrutinizes state unemployment trust funds, which are used to fund state unemployment insurance programs. If state funds run short of money during recessions due to the larger number of individuals drawing benefits, then states must borrow from the federal government’s unemployment trust fund. This creates another liability that must be managed by state governments. Empirical findings show that several features of programs affect balances and the probability of taking a loan from the federal fund including the taxable wage base, weekly benefits, and unemployment tax rates. This dissertation concludes by summarizing the results and exploring future research possibilities on the three essay topics
Cucurbitacin-I (JSI-124) activates the JNK/c-Jun signaling pathway independent of apoptosis and cell cycle arrest in B Leukemic Cells
<p>Abstract</p> <p>Background</p> <p>Cucurbitacin-I (JSI-124) is potent inhibitor of JAK/STAT3 signaling pathway and has anti-tumor activity in a variety of cancer including B cell leukemia. However, other molecular targets of JSI-124 beyond the JAK/STAT3 pathway are not fully understood.</p> <p>Methods</p> <p>BJAB, I-83, NALM-6 and primary CLL cells were treated with JSI-124 as indicated. Apoptosis was measured using flow cytometry for accumulation of sub-G1 phase cells (indicator of apoptosis) and Annexin V/PI staining. Cell cycle was analyzed by FACS for DNA content of G1 and G2 phases. Changes in phosphorylation and protein expression of p38, Erk1/2, JNK, c-Jun, and XIAP were detected by Western blot analysis. STAT3 and c-Jun genes were knocked out using siRNA transfection. VEGF expression was determined by mRNA and protein levels by RT-PCR and western blotting. Streptavidin Pull-Down Assay was used to determine c-Jun binding to the AP-1 DNA binding site.</p> <p>Results</p> <p>Herein, we show that JSI-124 activates c-Jun N-terminal kinase (JNK) and increases both the expression and serine phosphorylation of c-Jun protein in the B leukemic cell lines BJAB, I-83 and NALM-6. JSI-124 also activated MAPK p38 and MAPK Erk1/2 albeit at lower levels than JNK activation. Inhibition of the JNK signaling pathway failed to effect cell cycle arrest or apoptosis induced by JSI-124 but repressed JSI-124 induced c-Jun expression in these leukemia cells. The JNK pathway activation c-Jun leads to transcriptional activation of many genes. Treatment of BJAB, I-83, and NALM-6 cells with JSI-124 lead to an increase of Vascular Endothelial Growth Factor (VEGF) at both the mRNA and protein level. Knockdown of c-Jun expression and inhibition of JNK activation significantly blocked JSI-124 induced VEGF expression. Pretreatment with recombinant VEGF reduced JSI-124 induced apoptosis.</p> <p>Conclusions</p> <p>Taken together, our data demonstrates that JSI-124 activates the JNK signaling pathway independent of apoptosis and cell cycle arrest, leading to increased VEGF expression.</p
Uptake and cytotoxicity of citrate-coated gold nanospheres : comparative studies on human endothelial and epithelial cells
The use of gold nanoparticles (AuNPs) for diagnostic applications and for drug and gene-delivery is currently under intensive investigation. For such applications, biocompatibility and the absence of cytotoxicity of AuNPs is essential. Although generally considered as highly biocompatible, previous in vitro studies have shown that cytotoxicity of AuNPs in certain human epithelial cells was observed. In particular, the degree of purification of AuNPs (presence of sodium citrate residues on the particles) was shown to affect the proliferation and induce cytotoxicity in these cells. To expand these studies, we have examined if the effects are related to nanoparticle size (10, 11 nm, 25 nm), to the presence of sodium citrate on the particles' surface or they are due to a varying degree of internalization of the AuNPs. Since two cell types are present in the major barriers to the outside in the human body, we have also included endothelial cells from the vasculature and blood brain barrier.
Results
Transmission electron microscopy demonstrates that the internalized gold nanoparticles are located within vesicles. Increased cytotoxicity was observed after exposure to AuNPs and was found to be concentration-dependent. In addition, cell viability and the proliferation of both endothelial cells decreased after exposure to gold nanoparticles, especially at high concentrations. Moreover, in contrast to the size of the particles (10 nm, 11 nm, 25 nm), the presence of sodium citrate on the nanoparticle surface appeared to enhance these effects. The effects on microvascular endothelial cells from blood vessels were slightly enhanced compared to the effects on brain-derived endothelial cells. A quantification of AuNPs within cells by ICP-AES showed that epithelial cells internalized a higher quantity of AuNPs compared to endothelial cells and that the quantity of uptake is not correlated with the amount of sodium citrate on the nanoparticles’ surface.
Conclusions
In conclusion the higher amount of citrate on the particle surface resulted in a higher impairment of cell viability, but did not enhance or reduce the uptake behavior in endothelial or epithelial cells. In addition, epithelial and endothelial cells exhibited different uptake behaviors for citrate-stabilized gold nanoparticles, which might be related to different interactions occurring at the nanoparticle-cell-surface interface. The different uptake in epithelial cells might explain the higher reduction of proliferation of these cells after exposure to AuNPs treatment although more detailed investigations are necessary to determine subcellular events. Nevertheless an extrinsic effect of sodium-citrate stabilized particles could not be excluded. Thus, the amount of sodium citrate should be reduced to a level on which the stability of the particles and the safety for biomedical applications are guaranteed
Antigen depot is not required for alum adjuvanticity
Alum adjuvants have been in continuous clinical use for more than 80 yr. While the prevailing theory has been that depot formation and the associated slow release of antigen and/or inflammation are responsible for alum enhancement of antigen presentation and subsequent T- and B-cell responses, this has never been formally proven. To examine antigen persistence, we used the chimeric fluorescent protein EαGFP, which allows assessment of antigen presentation in situ, using the Y-Ae antibody. We demonstrate that alum and/or CpG adjuvants induced similar uptake of antigen, and in all cases, GFP signal did not persist beyond 24 h in draining lymph node antigen-presenting cells. Antigen presentation was first detectable on B cells within 6–12 h of antigen administration, followed by conventional dendritic cells (DCs) at 12–24 h, then finally plasmacytoid DCs at 48 h or later. Again, alum and/or CpG adjuvants did not have an effect on the magnitude or sequence of this response; furthermore, they induced similar antigen-specific T-cell activation in vivo. Notably, removal of the injection site and associated alum depot, as early as 2 h after administration, had no appreciable effect on antigen-specific T- and B-cell responses. This study clearly rules out a role for depot formation in alum adjuvant activity
Opposing Effects of Omega-3 and Omega-6 Long Chain Polyunsaturated Fatty Acids on the Expression of Lipogenic Genes in Omental and Retroperitoneal Adipose Depots in the Rat
This study aimed to determine the effect of varying dietary intake of the major n-3 PUFA in human diets, α-linolenic acid (ALA; 18 : 3n-3), on expression of lipogenic genes in adipose tissue. Rats were fed diets containing from 0.095%en to 6.3%en ALA and a constant n-6 PUFA level for 3 weeks. Samples from distinct adipose depots (omental and retroperitoneal) were collected and mRNA expression of the pro-lipogenic transcription factors Sterol-Retinoid-Element-Binding-Protein1c (SREBP1c) and Peroxisome Proliferator Activated Receptor-γ (PPARγ), lipogenic enzymes Sterol-coenzyme Desaturase1 (SCD-1), Fatty Acid Synthase (FAS), lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (G3PDH) and adipokines leptin and adiponectin determined by qRT-PCR. Increasing dietary ALA content resulted in altered expression of SREBP1c, FAS and G3PDH mRNA in both adipose depots. SREBP1c mRNA expression was related directly to n-6 PUFA concentrations (omental, r2 = .71; P < .001; Retroperitoneal, r2 = .20; P < .002), and inversely to n-3 PUFA concentrations (omental, r2 = .59; P < .001; Retroperitoneal, r2 = .19; P < .005) independent of diet. The relationship between total n-6 PUFA and SREBP1c mRNA expression persisted when the effects of n-3 PUFA were controlled for. Altering red blood cell concentrations of n-3 PUFA is thus associated with altered expression of lipogenic genes in a depot-specific manner and this effect is modulated by prevailing n-6 PUFA concentrations
Parallel Analysis: a Method for Determining Significant Principal Components
Numerous ecological studies use Principal Components Analysis (PCA) for exploratory analysis and data reduction. Determination of the number of components to retain is the most crucial problem confronting the researcher when using PCA. An incorrect choice may lead to the underextraction of components, but commonly results in overextraction. Of several methods proposed to determine the significance of principal components, Parallel Analysis (PA) has proven consistently accurate in determining the threshold for significant components, variable loadings, and analytical statistics when decomposing a correlation matrix. In this procedure, eigenvalues from a data set prior to rotation are compared with those from a matrix of random values of the same dimensionality (p variables and n samples). PCA eigenvalues from the data greater than PA eigenvalues from the corresponding random data can be retained. All components with eigenvalues below this threshold value should be considered spurious. We illustrate Parallel Analysis on an environmental data set.
We reviewed all articles utilizing PCA or Factor Analysis (FA) from 1987 to 1993 from Ecology, Ecological Monographs, Journal of Vegetation Science and Journal of Ecology. Analyses were first separated into those PCA which decomposed a correlation matrix and those PCA which decomposed a covariance matrix. Parallel Analysis (PA) was applied for each PCA/FA found in the literature. Of 39 analyses (in 22 articles), 29 (74.4%) considered no threshold rule, presumably retaining interpretable components. According to the PA results, 26 (66.7%) overextracted components. This overextraction may have resulted in potentially misleading interpretation of spurious components. It is suggested that the routine use of PA in multivariate ordination will increase confidence in the results and reduce the subjective interpretation of supposedly objective methods
New Constraints on the Lyman Continuum Escape Fraction at z~1.3
We examine deep far-ultraviolet (1600 Angstrom) imaging of the Hubble Deep
Field-North (HDFN) and the Hubble Ultra Deep Field (HUDF) to search for leaking
Lyman continuum radiation from starburst galaxies at z~1.3. There are 21
(primarily sub-L*) galaxies with spectroscopic redshifts between 1.1<z<1.5 and
none are detected in the far-UV. We fit stellar population templates to the
galaxies' optical/near-infrared SEDs to determine the starburst age and level
of dust attenuation, giving an accurate estimate of the intrinsic Lyman
continuum ratio, f_1500/f_700, and allowing a conversion from f_700 limits to
relative escape fractions. We show that previous high-redshift studies may have
underestimated the amplitude of the Lyman Break, and thus the relative escape
fraction, by a factor of ~2. Once the starburst age and intergalactic HI
absorption are accounted for, 18 galaxies in our sample have limits to the
relative escape fraction, f_esc,rel < 1.0 with some limits as low as f_esc,rel
< 0.10 and a stacked limit of f_esc,rel < 0.08. This demonstrates, for the
first time, that most sub-L* galaxies at high redshift do not have large escape
fractions. When combined with a similar study of more luminous galaxies at the
same redshift we show that, if all star-forming galaxies at z~1 have similar
relative escape fractions, the value must be less than 0.14 (3 sigma). We also
show that less than 20% (3 sigma) of star-forming galaxies at z~1 have relative
escape fractions near unity. These limits contrast with the large escape
fractions found at z~3 and suggest that the average escape fraction has
decreased between z~3 and z~1. (Abridged)Comment: Accepted for publication in ApJ. aastex format. 39 pages, 11 figure
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