The tRNA project

part of autobiography of Dr. Milton TaylorSummary of studies done with tRNA to examine whether tRNA modifications played a role in differentiation and virus restriction

Suppression of ribosomal protein synthesis and protein translation factors by Peg-interferon alpha/ribavirin in HCV patients blood mononuclear cells (PBMC)

<p>Abstract</p> <p>Background</p> <p>We have previously reported the induction of many interferon stimulated genes (ISGs) in PBMC collected from patients infected with HCV at various times after initiation of interferon-ribavirin treatment using DNA microarrays to identify changes in gene expression with time. Almost as many genes are down regulated (suppressed) during interferon-ribavirin treatment as are up regulated.</p> <p>Methods</p> <p>DNA microarrays were analyzed by different software, including MAS5 (Affymetrix-Kegg) and GSEA (gene set enrichment analysis) to identify specific pathways both up regulated and down regulated. Data was assessed from a clinical trial, which was a microarray analysis from 68 patients.</p> <p>Results</p> <p>Up regulated genes included genes associated with NF-kb, toll like receptor cytokine -cytokine interaction, and complement and adhesion pathways. The most prominent pathway down regulated was that for ribosomal structural proteins, and eukaryotic translational factors. Down regulation of ribosomal protein genes continued through the treatment up to the last measurement, which was at day 28.</p> <p>Conclusions</p> <p>This suppression of the protein synthetic apparatus might explain the long-term side effects of interferon-ribavirin, and explain a non-specific effect of interferon-ribavirin on viral protein synthesis. There was no evidence for unique transcription factors or micro RNA involvement.</p

From Shepherd to Professor

The autobiography of Dr. Milton Taylor from childhood in Scotland, through life on commune in England, then immigration to Israel. becoming a shepherd on a kibbutz, leaving Israel and immigrating to the USA. Education in USA at Cornell and Stanford Universities, and research and teaching until retirement at Indiana University Bloomington

The quantum metrology triangle and the re-definition of the SI ampere and kilogram; Analysis of a reduced set of observational equations

We have developed a set of seven observational equations that include all of the physics necessary to relate the most important of the fundamental constants to the definitions of the SI kilogram and ampere. We have used these to determine the influence of alternative definitions being considered for the SI kilogram and ampere on the uncertainty of three of the fundamental constants (h, e and mu). We have also reviewed the experimental evidence for the exactness of the quantum metrology triangle resulting from experiments combining the quantum Hall effect, the Josephson effects and single-electron tunnelling.Comment: 16 pages, 3 figures & 5 table

A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

Zeta function regularization for a scalar field in a compact domain

We express the zeta function associated to the Laplacian operator on $S^1_r\times M$ in terms of the zeta function associated to the Laplacian on $M$, where $M$ is a compact connected Riemannian manifold. This gives formulas for the partition function of the associated physical model at low and high temperature for any compact domain $M$. Furthermore, we provide an exact formula for the zeta function at any value of $r$ when $M$ is a $D$-dimensional box or a $D$-dimensional torus; this allows a rigorous calculation of the zeta invariants and the analysis of the main thermodynamic functions associated to the physical models at finite temperature.Comment: 19 pages, no figures, to appear in J. Phys.

Casimir effect: running Newton constant or cosmological term

We argue that the instability of Euclidean Einstein gravity is an indication that the vacuum is non perturbative and contains a condensate of the metric tensor in a manner reminiscent of Yang-Mills theories. As a simple step toward the characterization of such a vacuum the value of the one-loop effective action is computed for Euclidean de Sitter spaces as a function of the curvature when the unstable conformal modes are held fixed. Two phases are found, one where the curvature is large and gravitons should be confined and another one which appears to be weakly coupled and tends to be flat. The induced cosmological constant is positive or negative in the strongly or weakly curved phase, respectively. The relevance of the Casimir effect in understanding the UV sensitivity of gravity is pointed out.Comment: Final, slightly extended version, to appear in Classical and Quantum Gravit

Neptune to the Common-wealth of England (1652): the republican Britannia and the continuity of interests

In the seventeenth century, John Kerrigan reminds us, “models of empire did not always turn on monarchy”. In this essay, I trace a vision of “Neptune’s empire” shared by royalists and republicans, binding English national interest to British overseas expansion. I take as my text a poem entitled “Neptune to the Common-wealth of England”, prefixed to Marchamont Nedham’s 1652 English translation of Mare Clausum (1635), John Selden’s response to Mare Liberum (1609) by Hugo Grotius. This minor work is read alongside some equally obscure and more familiar texts in order to point up the ways in which it speaks to persistent cultural and political interests. I trace the afterlife of this verse, its critical reception and its unique status as a fragment that exemplifies the crossover between colonial republic and imperial monarchy at a crucial moment in British history, a moment that, with Brexit, remains resonant