The Microbial Ecology of Bacterial Vaginosis: A Fine Scale Resolution Metagenomic Analysis

The vaginal microbiota play an important protective role in maintaining the health of women. Disruption of the mutualistic relationship that exists between bacterial communities in the vagina and their hosts can lead to bacterial vaginosis (BV), a condition in which lactic acid producing bacteria are supplanted by a diverse array of strictly anaerobic bacteria. BV has been shown to be an independent risk factor for adverse outcomes including preterm delivery and low infant birth weight, acquisition of sexually transmitted infections and HIV, and development of pelvic inflammatory disease. National surveys indicate the prevalence of BV among U.S. women is 29.2%, and yet, despite considerable effort, the etiology of BV remains unknown. Moreover, there are no broadly effective therapies for the treatment of BV, and reoccurrence is common. In the proposed research we will test the overarching hypothesis that vaginal microbial community dynamics and activities are indicators of risk to BV. To do this, we propose to conduct a high resolution prospective study in which samples collected daily from 200 reproductive-age women over two menstrual cycles are used to capture molecular events that take place before, during, and after the spontaneous remission of BV episodes. We will use modern genomic technologies to obtain the data needed to correlate shifts in vaginal microbial community composition and function, metabolomes, and epidemiological and behavioral metadata with the occurrence of BV to better define the syndrome itself and identify patterns that are predictive of BV. The three specific aims of the research are: (1) Evaluate the association between the dynamics of vaginal microbial communities and risk to BV by characterizing the community composition of vaginal specimens archived from a vaginal douching cessation study in which 33 women self-collected vaginal swabs twice-weekly for 16 weeks; (2) Enroll 135 women in a prospective study in which self-collected vaginal swab samples and secretions are collected daily along with data on the occurrence of BV, vaginal pH, and information on time varying habits and practices; (3) Apply model-based statistical clustering and classification approaches to associate the microbial community composition and function, with metadata and clinical diagnoses of BV. The large body of information generated will facilitate understanding vaginal microbial community dynamics, the etiology of BV, and drive the development of better diagnostic tools for BV. Furthermore, the information will enable a more personalized and effective treatment of BV and ultimately help prevent adverse sequelae associated with this highly prevalent disruption of the vaginal microbiome

Computer Program for Assessing the Economic Feasibility of Solar Energy for Single Family Residences and Light Commercial Applications

Computer program, SHCOST, was used to perform economic analyses of operational test sites. The program allows consideration of the economic parameters which are important to the solar system user. A life cycle cost and cash flow comparison is made between a solar heating system and a conventional system. The program assists in sizing the solar heating system. A sensitivity study and plot capability allow the user to select the most cost effective system configuration

Plane strain fracture toughness and mechanical properties of 5Al-2.5Sn ELI titanium at room and cryogenic temperatures Final report

Plane strain fracture toughness and mechanical properties of titanium alloy at room and cryogenic temperature

Plane strain fracture toughness of 2219-T87 aluminum alloy at room and cryogenic temperatures

Tensile strength, yield strength, and plane strain fracture toughness of aluminum alloy at room and cryogenic temperature

Supersonic particles probes : : measurement ofinternal wall losses

Issued as Progress reports [nos. 1-7], and Final report, Project E-19-678 (subproject E-16-633

Frequency response in short thermocouple wires

Theoretical expressions are derived for the steady state frequency response of a thermocouple wire. In particular, the effects of axial heat conduction are demonstrated for a nonuniform wire with unequal material properties and wire diameters across the junction. The amplitude ratio at low frequency omega approaches 0 agrees with the results of Scadron and Warshawsky (1952) for a steady state temperature distribution. Moreover, the frequency response for a nonuniform wire in the limit of infinite length l approaches infinity is shown to reduce to a simple expression that is analogous to the classic first order solution for a thermocouple wire with uniform properties. Theoretical expressions are also derived for the steady state frequency response of a supported thermocouple wire. In particular, the effects of axial heat conduction are demonstrated for both a supported one material wire and a two material wire with unequal material properties across the junction. For the case of a one material supported wire, an exact solution is derived which compares favorably with an approximate expression that only matches temperatures at the support junction. Moreover, for the case of a two material supported wire, an analytical expression is derived that closely correlates numerical results. Experimental measurements are made for the steady state frequency response of a supported thermocouple wire. In particular, the effects of axial heat conduction are demonstrated for both a supported one material wire (type K) and a two material wire (type T) with unequal material properties across the junction. The data for the amplitude ratio and phase angle are correlated to within 10 pct. with the theoretical predictions of Forney and Fralick (1991). This is accomplished by choosing a natural frequency omega sub n for the wire data to correlate the first order response at large gas temperature frequencies. It is found that a large bead size, however, will increase the amplitude ratio at low frequencies but decrease the natural frequency of the wire. The phase angle data are also distorted for imperfect junctions

Mutations of penicillin acylase residue B71 extend substrate specificity by decreasing steric constraints for substrate binding

Two mutant forms of penicillin acylase from Escherichia coli strains, selected using directed evolution for the ability to use glutaryl-L-leucine for growth [Forney, Wong and Ferber (1989) Appl. Environ. Microbiol. 55, 2550-2555], are changed within one codon, replacing the B-chain residue Phe(B71) with either Cys or Leu. Increases of up to a factor of ten in k(cat)/K-m values for substrates possessing a phenylacetyl leaving group are consistent with a decrease in K-s. Values of k(cat/)K(m) for glutaryl-L-leucine are increased at least 100-fold. A decrease in k(cat)/K-m for the CySB71 mutant with increased pH is consistent with binding of the uncharged glutaryl group. The mutant proteins are more resistant to urea denaturation monitored by protein fluorescence, to inactivation in the presence of substrate either in the presence of urea or at high pH, and to heat inactivation. The crystal structure of the Leu(B71) mutant protein, solved to 2 X resolution, shows a flip of the side chain of Phe(B256) into the periphery of the catalytic centre, associated with loss of the pi-stacking interactions between Phe(B256) and Phe(B71). Molecular modelling demonstrates that glutaryl-L-leucine may bind with the uncharged glutaryl group in the S-1 subsite of either the wild-type or the Leu(B71) mutant but with greater potential freedom of rotation of the substrate leucine moiety in the complex with the mutant protein. This implies a smaller decrease in the conformational entropy of the substrate on binding to the mutant proteins and consequently greater catalytic activity

Three-wire Thermocouple: Frequency Response in Constant Flow

Theory and experimental measurements are compared with a novel three-wire thermocouple. Signals from three wires of unequal diameters arc recorded from the thermocouple suspended in constant flow with a periodic temperature fluctuation. It is demonstrated that the reconstructed signal from the three-wire thermocouple requires no compensation for omega less than or equal to 5(sub omega1), where omega, is the natural frequency of the smaller wire. The latter result represents a significant improvement compared to previous work with two-wire thermocouples. A correction factor has also been derived to account for wires of arbitrary diameter