Soviet-American Arms Negotiations—1960-68: A Prelude For SALT

While we may well be standing on the threshold of a most far-reaching arms agreement today, the postwar history of arms negotiations has been marked by few bright spots

Non-Profit Hospitals Face Structural As Well As Financial Challenges: Lessons from Massachusetts

Like most non-profit hospitals, those of Massachusetts are facing serious financial challenges. While the immediate issue is the shortfall between revenues and expenses, the paper finds that their real problems are structural, evidenced by at least three systemic impediments -uncompensated care, over-utilization of teaching hospitals, and an increasingly unattractive environment for the practice of medicine. Other states whose non-profit hospitals face persistent financial difficulties may find it useful to consider whether structural impediments of the type facing Massachusetts undermine the operating performance of their own institutions

Should Massachusetts Regionalize Public Health?

Amidst rising global concerns about bioterrorism and pandemic flu preparedness, the delivery capacity and effectiveness of public health service assumes increased importance and relevance. In the United States, the lack of a centralized, national public health system has meant that “public health” is the primary responsibility of state and local governments. Many states have established various types of intrastate regional structures to deliver the range of on-going, occasional, and/or episodic services that characterize the world of public health. However, Massachusetts is not among them. Despite its global reputation as a pre-eminent medical center, the state of Massachusetts has a highly balkanized public health system, with a separate health department for each of its 351 cities and towns. This structure reflects the state’s long-standing tradition of weak county government and strong home rule. The result, however, is a state-wide public health system characterized by strong local autonomy, lack of accountability, no credentialing or licensure requirements, disparate delivery capabilities, increased funding problems, and the real potential for ineffectiveness in the event of a devastating disease or attack. This paper examines how public health is currently organized and delivered both nationally and within Massachusetts, and it concludes by identifying criteria and potential regionalization structures that could lead to a more efficient and comprehensive public health delivery capability for the state. The findings have relevance not only for Massachusetts but also any state looking to improve the delivery of its public health services

Senior Recital: Hayden McAfee, horn

This recital is presented in partial fulfillment of requirements for the degree Bachelor of Music in Performance. Mr. McAfee studies horn with Richard Williams.https://digitalcommons.kennesaw.edu/musicprograms/2201/thumbnail.jp

Multi-Segment Radius Measurement Using an Absolute Distance Meter Through a Null Assembly

This system was one of the test methods considered for measuring the radius of curvature of one or more of the 18 segmented mirrors that form the 6.5 m diameter primary mirror (PM) of the James Webb Space Telescope (JWST). The assembled telescope will be tested at cryogenic temperatures in a 17-m diameter by 27-m high vacuum chamber at the Johnson Space Center. This system uses a Leica Absolute Distance Meter (ADM), at a wavelength of 780 nm, combined with beam-steering and beam-shaping optics to make a differential distance measurement between a ring mirror on the reflective null assembly and individual PM segments. The ADM is located inside the same Pressure-Tight Enclosure (PTE) that houses the test interferometer. The PTE maintains the ADM and interferometer at ambient temperature and pressure so that they are not directly exposed to the telescope s harsh cryogenic and vacuum environment. This system takes advantage of the existing achromatic objective and reflective null assembly used by the test interferometer to direct four ADM beamlets to four PM segments through an optical path that is coincident with the interferometer beam. A mask, positioned on a linear slide, contains an array of 1.25 mm diameter circular subapertures that map to each of the 18 PM segments as well as six positions around the ring mirror. A down-collimated 4 mm ADM beam simultaneously covers 4 adjacent PM segment beamlets and one ring mirror beamlet. The radius, or spacing, of all 18 segments can be measured with the addition of two orthogonally-oriented scanning pentaprisms used to steer the ADM beam to any one of six different sub-aperture configurations at the plane of the ring mirror. The interferometer beam, at a wavelength of 687 nm, and the ADM beamlets, at a wavelength of 780 nm, pass through the objective and null so that the rays are normally incident on the parabolic PM surface. After reflecting off the PM, both the ADM and interferometer beams return to their respective instruments on nearly the same path. A fifth beamlet, acting as a differential reference, reflects off a ring mirror attached to the objective and null and returns to the ADM. The spacings between the ring mirror, objective, and null are known through manufacturing tolerances as well as through an in situ null wavefront alignment of the interferometer test beam with a reflective hologram located near the caustic of the null. Since total path length between the ring mirror and PM segments is highly deterministic, any ADM-measured departures from the predicted path length can be attributed to either spacing error or radius error in the PM. It is estimated that the path length measurement between the ring mirror and a PM segment is accurate to better than 100 m. The unique features of this invention include the differential distance measuring capability and its integration into an existing cryogenic and vacuum compatible interferometric optical test

Intramolecular Phenotypic Capacitance in a Modular RNA Molecule

Phenotypic capacitance refers to the ability of a genome to accumulate mutations that are conditionally hidden and only reveal phenotype-altering effects after certain environmental or genetic changes. Capacitance has important implications for the evolution of novel forms and functions, but experimentally studied mechanisms behind capacitance are mostly limited to complex, multicomponent systems often involving several interacting protein molecules. Here we demonstrate phenotypic capacitance within a much simpler system, an individual RNA molecule with catalytic activity (ribozyme). This naturally occurring RNA molecule has a modular structure, where a scaffold module acts as an intramolecular chaperone that facilitates folding of a second catalytic module. Previous studies have shown that the scaffold module is not absolutely required for activity, but dramatically decreases the concentration of magnesium ions required for the formation of an active site. Here, we use an experimental perturbation of magnesium ion concentration that disrupts the folding of certain genetic variants of this ribozyme and use in vitro selection followed by deep sequencing to identify genotypes with altered phenotypes (catalytic activity). We identify multiple conditional mutations that alter the wild-type ribozyme phenotype under a stressful environmental condition of low magnesium ion concentration, but preserve the phenotype under more relaxed conditions. This conditional buffering is confined to the scaffold module, but controls the catalytic phenotype, demonstrating how modularity can enable phenotypic capacitance within a single macromolecule. RNA’s ancient role in life suggests that phenotypic capacitance may have influenced evolution since life’s origins

Mechanisms of Covalent Self-Assembly of the Azoarcus Ribozyme From Four Fragment Oligonucleotides

RNA oligomers of length 40–60 nt can self-assemble into covalent versions of the Azoarcus group I intron ribozyme. This process requires a series of recombination reactions in which the internal guide sequence of a nascent catalytic complex makes specific interactions with a complement triplet, CAU, in the oligomers. However, if the CAU were mutated, promiscuous self-assembly may be possible, lessening the dependence on a particular set of oligomer sequences. Here, we assayed whether oligomers containing mutations in the CAU triplet could still self-construct Azoarcus ribozymes. The mutations CAC, CAG, CUU and GAU all inhibited self-assembly to some degree, but did not block it completely in 100mM MgCl₂. Oligomers containing the CAC mutation retained the most self-assembly activity, while those containing GAU retained the least, indicating that mutations more 5’ in this triplet are the most deleterious. Self-assembly systems containing additional mutant locations were progressively less functional. Analyses of properly self-assembled ribozymes revealed that, of two recombination mechanisms possible for selfassembly, termed ‘tF2’ and ‘R2F2’, the simpler one-step ‘tF2’ mechanism is utilized when mutations exist. These data suggest that self-assembling systems are more facile than previously believed, and have relevance to the origin of complex ribozymes during the RNA World

Telomere Estimates by qPCR in American Kestrel Birds

Telomeres are highly conserved repeated sequences found at the ends of linear chromosomes. Measuring telomere length has been used to estimate the ages of individuals in several species. The research presented here focuses on developing telomere length estimates in the American Kestrel (Falco sparverius), using Quantitative Polymerase Chain Reaction (qPCR). The verification of a primer pair that can amplify a reference gene and serve to normalize the telomere qPCR data is vitally important. The gene for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was preferably chosen because it occurs in a single copy in most birds. However, the Kestrel genome has not been sequenced making primer design challenging. We used a bioinformatics approach to find regions of the GAPDH gene that are conserved between chicken and several species of raptors. We also checked several published GAPDH primers reported in the literature. Here, we report the sequence and efficiency of qPCR primers that can be used for telomere length studies in the American Kestral

Genotype Network Intersections Promote Evolutionary Innovation

Evolutionary innovations are qualitatively novel traits that emerge through evolution and increase biodiversity. The genetic mechanisms of innovation remain poorly understood. A systems view of innovation requires the analysis of genotype networks—the vast networks of genetic variants that produce the same phenotype. Innovations can occur at the intersection of two different genotype networks. However, the experimental characterization of genotype networks has been hindered by the vast number of genetic variants that need to be functionally analyzed. Here, we use high-throughput sequencing to study the fitness landscape at the intersection of the genotype networks of two catalytic RNA molecules (ribozymes). We determined the ability of numerous neighboring RNA sequences to catalyze two different chemical reactions, and we use these data as a proxy for a genotype to fitness map where two functions come in close proximity. We find extensive functional overlap, and numerous genotypes can catalyze both functions. We demonstrate through evolutionary simulations that these numerous points of intersection facilitate the discovery of a new function. However, the rate of adaptation of the new function depends upon the local ruggedness around the starting location in the genotype network. As a consequence, one direction of adaptation is more rapid than the other. We find that periods of neutral evolution increase rates of adaptation to the new function by allowing populations to spread out in their genotype network. Our study reveals the properties of a fitness landscape where genotype networks intersect and the consequences for evolutionary innovations. Our results suggest that historic innovations in natural systems may have been facilitated by overlapping genotype networks