Young Workers, Old Workers, and Convergence

The human capital of young and old workers are imperfect substitutes both in production and in on-the-job training. This helps explain why capital does not flow from rich to poor countries, causing instantaneous convergence of per capita output. If each generation chooses its human capital optimally given that of the previous and succeeding generations, human capital follows a unique rational- expectations path. For moderate substitutability, human capital within each sector oscillates relative to that in other sectors, but aggregate human capital converges to the steady state monotonically, at rates consistent with those observed empirically.

Experience with Ada on the F-18 High Alpha Research Vehicle Flight Test Program

Considerable experience was acquired with Ada at the NASA Dryden Flight Research Facility during the on-going High Alpha Technology Program. In this program, an F-18 aircraft was highly modified by the addition of thrust-vectoring vanes to the airframe. In addition, substantial alteration was made in the original quadruplex flight control system. The result is the High Alpha Research Vehicle. An additional research flight control computer was incorporated in each of the four channels. Software for the research flight control computer was written in Ada. To date, six releases of this software have been flown. This paper provides a detailed description of the modifications to the research flight control system. Efficient ground-testing of the software was accomplished by using simulations that used the Ada for portions of their software. These simulations are also described. Modifying and transferring the Ada for flight software to the software simulation configuration has allowed evaluation of this language. This paper also discusses such significant issues in using Ada as portability, modifiability, and testability as well as documentation requirements

Investigating the role of cAMP in mycobacterial antimicrobial drug tolerance by the discovery of a novel cAMP-phosphodiesterase

M. tuberculosis, the causative agent of Tuberculosis (TB), is an ancient pathogen that has plagued mankind for over 70,000 years. In 2018, TB was responsible globally for 10 million new infections and 1.5 million deaths - more than any other infectious disease. M. tuberculosis bacilli have evolved to thrive in the harsh, nutrient limited environment within the host alveolar macrophage and evade the constant pressure of immune cell mediated killing. This evolution has led to the bacilli developing phenotypic adaptions that concurrently, drastically decrease their susceptibility to many antimicrobials. The basis for phenotypic adaptions is signalling to detect an environmental stimulus and to mediate an appropriate response. To this end, M. tuberculosis and other mycobacteria have evolved a robust cyclic AMP (cAMP) signalling system with multiple cAMP producing and cAMP binding effector proteins. Several of these proteins have already been shown to regulate virulence, carbon metabolism and essential gene expression. However, the link between cAMP signalling and antimicrobial susceptibility in mycobacteria has not previously been investigated. In this project, I identified a new cAMP degrading phosphodiesterase enzyme (Rv1339) and used it as a tool to significantly decrease intrabacterial levels of cAMP in mycobacteria. The effect of this in M. smegmatis mc2155 was to increase antimicrobial susceptibility. By using a combination of metabolomics, RNA-sequencing, antimicrobial susceptibility assays and bioenergetics analysis, I was able to characterise the potential mechanism behind this increased susceptibility. I was also able to begin preliminary work required to investigate this link in M. tuberculosis H37Rv. This work represents a proof-of-concept that targeting cAMP signalling is a promising new avenue for antimicrobial development, and expands our understanding of cAMP signalling in mycobacteria.Open Acces

Defective RNAs of Semliki Forest virus

This thesis describes an investigation into the mouse-protecting nucleotide sequences of defective interfering (Dl) Semliki Forest virus (SFV) RNA was extracted from tissue culture preparations of Dl SFV and reverse transcribed Putative Dl SFV cDNA was amplified by the polymerase chain reaction using primers specific for the termini of the virion RNA A number of molecular clones were constructed from the products of amplification and the nucleotide sequences of two of these clones were determined (pSFVDI-6 2146 nts and pSFVDI-19 1244 nts) Both pSFVDI-6 and pSFVDI-19 were derived from three noncontiguous regions of the SFV genome comprising the 5' and 3' termini and part of the nsP2 coding region RNA transcribed from these clones was transfected into SFV-infected BHK-21 cells to produce genetically homogeneous Dl SFV preparations These preparations were stable on serial passage and interfered with virus multiplication m vitro The transfection technique was also used in a preliminary investigation of the regulatory elements of the SFV genome A 388- nucleotide region within the nsP2 gene of SFV was tentatively defined as containing all or part of a packaging signal since Dl SFV clones lacking this region were not propagated as virions. To determine the biological activity of the cloned Dl SFV preparations in vivo they were mixed with 10 LD₁₀, SFV and inoculated into adult mice by the intranasal route The Dl SFV preparation derived from pSFVDI-19 typically conferred 75% protection against the lethal encephalitis that normally follows infection with SFV. whereas the Dl SFV preparation derived from pSFVDI-6 was non-protecting However, it should be noted that the concentration of Dl SFV in these cloned preparations was not standardised Modulation of infection in vivo was independent of the antigenic load and mice were susceptible to subsequent lethal challenge A preliminary experiment suggested that propagation of Dl SFV genomes was cell-specific because genomes derived from pSFVDI-19, but not pSFVDI-6, could be detected in mouse brain tissue following intracerebral coinoculation of SFV with the cloned Dl SFV preparations

Simulated holographic three-dimensional intensity shaping of evanescent-wave fields

The size of bright structures in traveling-wave light fields is limited by diffraction. This in turn limits a number of technologies, for example, optical trapping. One way to beat the diffraction limit is to use evanescent waves instead of traveling waves. Here we apply a holographic algorithm, direct search, to the shaping of complex evanescent-wave fields. We simulate three-dimensional intensity shaping of evanescent-wave fields using this approach, and we investigate some of its limitations. (c) 2008 Optical Society of America.</p

Ultrafast dynamic conductivity and scattering rate saturation of photoexcited charge carriers in silicon investigated with a midinfrared continuum probe

We employ ultra-broadband terahertz-midinfrared probe pulses to characterize the optical response of photoinduced charge-carrier plasmas in high-resistivity silicon in a reflection geometry, over a wide range of excitation densities (10^{15}-10^{19} cm^{-3}) at room temperature. In contrast to conventional terahertz spectroscopy studies, this enables one to directly cover the frequency range encompassing the resultant plasma frequencies. The intensity reflection spectra of the thermalized plasma, measured using sum-frequency (up-conversion) detection of the probe pulses, can be modeled well by a standard Drude model with a density-dependent momentum scattering time of approx. 200 fs at low densities, reaching approx. 20 fs for densities of approx. 10^{19} cm^{-3}, where the increase of the scattering rate saturates. This behavior can be reproduced well with theoretical results based on the generalized Drude approach for the electron-hole scattering rate, where the saturation occurs due to phase-space restrictions as the plasma becomes degenerate. We also study the initial sub-picosecond temporal development of the Drude response, and discuss the observed rise in the scattering time in terms of initial charge-carrier relaxation, as well as the optical response of the photoexcited sample as predicted by finite-difference time-domain simulations.Comment: 9 pages, 4 figure

HBsAg-vectored DNA vaccines elicit concomitant protective responses to multiple CTL epitopes relevant in human disease.

Vaccines capable of controlling neoplastic and infectious diseases which depend on the cellular immune response for their resolution, have proven difficult to develop. We, and others, have previously demonstrated that the potent immunogenicity of hepatitis B surface antigen (HBsAg), the already- licensed human vaccine for hepatitis B infection, may be exploited to deliver foreign antigens for cytotoxic T-lymphocyte (CTL) induction. In this study we demonstrate that recombinant (r) HBsAg DNA delivering a CTL polyepitope appended at the C&#x27; terminus elicits concomitant responses to multiple epitopes restricted through a diversity of MHC class I haplotypes, which are relevant in a number of human diseases. We show that the rHBsAg DNA vaccine elicits concomitant protection against neoplastic and infectious disease. These studies vindicate the use of HBsAg as a powerful vector to deliver CTL responses to foreign antigens, and have implications for a multi-disease vaccine applicable to the HLA-polymorphic human population