699 research outputs found
Trends in Self-Employment Among White and Black Men: 1910-1990
No full textWe examine trends in self-employment among white and black men from 1910 to 1990 using Census and CPS microdata. Self-employment rates fell over most of the century and then started to rise after 1970. For white men, we find that the decline was due to declining rates within industries, but was counterbalanced somewhat by a shift in employment towards high self-employment industries. Recently, the increase in self-employment was caused by an end to the within industry decline and the continuing shift in employment towards high self-employment industries. We find that the trends in self-employment average returns do not easily explain the decline in self-employment from 1950 to 1970, nor the increase from 1970 to 1990. We also find that changes in tax rates, social security benefits, and immigration patterns do not explain the recent upturn in self-employment. For black men, we find that the self-employment rate remained at a level of roughly one-third the white rate from 1910 to 1990. The large and constant gap between the black and the white rates is not due to blacks being concentrated in low self-employment rate industries, but is consistent with job opportunities outside of self-employment increasing relative to those in self-employment. However, more recently the relative earnings of blacks in self-employment rose more than relative earnings for whites the near constancy of the relative self-employment rates more surprising. We also find that absent continuing forces holding down black self-employment, a simple inter-generational model of self-employment suggests that black and white rates would converge quickly.
New Cysteine Derivatives with Antiproliferative Activity on Melanoma Cells
No full textHere we describe the rational design, computer-aided virtual ligand docking and synthesis of 19 nonpeptidic compounds designed to inhibit histone deacetylases and kill melanoma cells. Compounds were derived from cysteine, fused at the S-terminus to 4-butanoyl hydroxamate, and at the N-terminus to 4-(dimethylamino) benzoic acid. The latter was extended by coupling to amines to form a small library of prospective anti-cancer compounds. Four compounds were cytotoxic at sub-micromolar concentrations against cells of a particularly aggressive human melanoma (MM96L), and nine compounds showed selectivities of >= 5: 1 for killing human melanoma instead of normal human fibroblast cells. The most active compounds were shown to cause hyperacetylation of histones due to inhibition of histone deacetylases. Further refinement of these compounds may produce an anti-tumor drug suitable for treating melanoma
Histone deacetylase inhibitors as suppressors of bone destruction in inflammatory diseases
No full textObjectives Despite progress in developing many new anti-inflammatory treatments in the last decade, there has been little progress in finding treatments for bone loss associated with inflammatory diseases, such as rheumatoid arthritis and periodontitis. For instance, treatment of rheumatic diseases with anti-tumour necrosis factor-alpha agents has been largely successful in reducing inflammation, but there have been varying reports regarding its effectiveness at inhibiting bone loss. In addition, there is often a delay in finding the appropriate anti-inflammatory therapy for individual patients, and some therapies, such as disease modifying drugs, take time to have an effect. In order to protect the bone, adjunct therapies targeting bone resorption are being developed. This review focuses on new treatments based on using histone deacetylase inhibitors (HDACi) to suppress bone loss in these chronic inflammatory diseases. Key findings A number of selected HDACi have been shown to suppress bone resorption by osteoclasts in vitro and in animal models of chronic inflammatory diseases. Recent reports indicate that these small molecules, which can be administered orally, could protect the bone and might be used in combination with current anti-inflammatory treatments. Summary HDACi do have potential to suppress bone destruction in chronic inflammatory diseases including periodontitis and rheumatoid arthritis.Melissa D. Cantley, Peter M. Bartold, David P. Fairlie, K.D. Rainsfor and David R. Hayne
Towards a treatment for Alzheimer's disease.
No full textDr David P Fairlie$AUD 179,200.05NHMRC Project GrantsStandard Project Gran
CHARACTERIZING PEPTIDE ALPHA HELICES VIA COLD ION SPECTROSCOPY OF MODEL COMPOUNDS
No full textTethered peptides are synthetic peptides in which a chemical linkage between two remote sites in the peptide sequence bind these sites together. The Fairlie group has devised a tether that locks the pentapeptide ‘core’ into a single turn of an alpha helix, robust to large swings in pH, temperature, and denaturant. By changing the chirality of the amino acids, left- (D) and right-handed (L) helices can be exclusively formed. Catenating these sub-units leads to -helices of greater length.
This talk describes the propensity of these tethered peptides to maintain their alpha helical nature upon the removal of solvent and transition into the gas phase as protonated ions. To this end we explore the structures of three tethered peptides linked together through the formation of a lactam between the lysine and aspartic acid residues, Y[KAAAD]-NH, F[KAAAD]-NH, and YR[KAAAD]-NH (tether denoted by brackets). UV photofragment spectroscopy and IR-UV double resonance methods will be carried out on the cryocooled, protonated ions to probe the hydrogen bonding patterns of these molecules with the goal of elucidating the unique spectroscopic signatures of isolated single-turn alpha helices. The effect of the protonation site and handedness of the helix on the H-bonds in the single turn helices will also be described
Anti-malarial effect of histone deacetylation inhibitors and mammalian tumour cytodifferentiating agents Anna Walduck, Mike J. Kelso, David P. Fairlie, Allan Saul, Peter G. Parsons
No full textThe histones of Plasmodium falciparum represent a potential new target for anti-malarial compounds. A naturally occurring compound, apicidin, has recently been shown to inhibit the in vitro growth of P. falciparum. Apicidin was shown to hyperacetylate histones, suggesting that its mode of action is through histone deacetylase inhibition. We have tested the ability of known histone deacetylase inhibitors, mammalian tumour suppressor compounds, and cytodifferentiating agents to inhibit the in vitro growth of a drug sensitive and resistant strain of P, falciparum. Seven of the tested compounds had mu M IC50 values, and trichostatin A, a histone deacetylation inhibitor and cytodifferentiating agent, was active at low nM concentrations. One compound, suberic acid bisdimethylamide, which selectively arrests tumour cells as opposed to normal mammalian cells, had an in vivo cytostatic effect against the acute murine malaria Plasmodium berghei, and one round of treatment with the compound failed to select for resistant mutations. These results suggest a promising role for histone deacetylase inhibitors and cytodifferentiating agents as antimalarial drug candidates. (C) 2000 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved
Characterizing peptide alpha helices via cold ion spectroscopy of model compounds
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Previous issue date: 6Tethered peptides are synthetic peptides in which a chemical linkage between two remote sites in the peptide sequence bind these sites together. The Fairlie group has devised a tether that locks the pentapeptide ‘core’ into a single turn of an alpha helix, robust to large swings in pH, temperature, and denaturant. By changing the chirality of the amino acids, left- (D) and right-handed (L) helices can be exclusively formed. Catenating these sub-units leads to α-helices of greater length. This talk describes the propensity of these tethered peptides to maintain their alpha helical nature upon the removal of solvent and transition into the gas phase as protonated ions. To this end we explore the structures of three tethered peptides linked together through the formation of a lactam between the lysine and aspartic acid residues, Y[KAAAD]- NH2, F[KAAAD]-NH2, and YR[KAAAD]-NH2 (tether denoted by brackets). UV photofragment spectroscopy and IR-UV double resonance methods will be carried out on the cryocooled, protonated ions to probe the hydrogen bonding patterns of these molecules with the goal of elucidating the unique spectroscopic signatures of isolated single-turn alpha helices. The effect of the protonation site and handedness of the helix on the H-bonds in the single turn helices will also be described
Entrepreneurship, Economic Conditions, and the Great Recession
No full textThe "Great Recession" resulted in many business closings and foreclosures, but what effect did it have on business formation? On the one hand, recessions decrease potential business income and wealth, but on the other hand they restrict opportunities in the wage/salary sector leaving the net effect on entrepreneurship ambiguous. The most up-to-date microdata available – the 1996 to 2009 Current Population Survey (CPS) – are used to conduct a detailed analysis of the determinants of entrepreneurship at the individual level to shed light on this question. Regression estimates indicate that local labor market conditions are a major determinant of entrepreneurship. Higher local unemployment rates are found to increase the probability that individuals start businesses. Home ownership and local home values for home owners are also found to have positive effects on business creation, but these effects are noticeably smaller. Additional regression estimates indicate that individuals who are initially not employed respond more to high local unemployment rates by starting businesses than wage/salary workers. The results point to a consistent picture – the positive influences of slack labor markets outweigh the negative influences resulting in higher levels of business creation. Using the regression estimates for the local unemployment rate effects, I find that the predicted trend in entrepreneurship rates tracks the actual upward trend in entrepreneurship extremely well in the Great Recession.entrepreneurship, great recession, unemployment, self-employment
Mexican-American Entrepreneurship
No full textAlthough business ownership has implications for income inequality, wealth accumulation and job creation, surprisingly little research explores why Mexican-Americans are less likely to start businesses and why the businesses that they start are less successful on average than non-Latino whites. We conduct a comprehensive analysis of Mexican-American entrepreneurship using microdata from the 2000 U.S. Census, the matched and unmatched March and Outgoing Rotation Group Files of the Current Population Survey from 1994 to 2004, and the Legalized Population Survey (LPS). We find that low levels of education and wealth explain the entire gap between Mexican immigrants and non-Latino whites in business formation rates. Nearly the entire gap in business income for Mexican immigrants is explained by low levels of education and limited English language ability. Using the natural experiment created by the Immigration Reform and Control Act (IRCA), we find that legal status represents an additional barrier for Mexican immigrants. A conservative estimate suggests that the lack of legal status reduces business ownership rates by roughly seven-tenths of a percentage point for both men and women. Human and financial capital deficiencies are found to limit business ownership and business success among second and third-generation Mexican-Americans, but to a lesser extent. These findings have implications for the debates over the selection of immigrants and the assimilation of Mexican-Americans in the U.S. economy.Mexican-Americans, entrepreneurship, self-employment
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