CREATING A MULTIVALENT SUBUNIT VACCINE USING TYPE III SECRETION SYSTEM TIP PROTEINS AS ANTIGENS

Many gram-negative bacterial pathogens employ type III secretion systems (TTSS) to transport effector proteins into eukaryotic host cell membranes and cytoplasms to subvert normal cellular functions. TTSSs contain a basal body which spans the inner and outer bacterial membranes and a needle which extends the into extracellular space. With the increasing prevalence of drug resistant bacterial strains, vaccines represent one of the most promising strategies to combat these diseases. Proteins located at the extracellular needle tip of TTSSs appear to be excellent candidates for a sub-unit vaccine approach. These so called tip proteins are surface exposed and regulate the secretion of other effector proteins. This work presents pre-formulation, formulation and animal studies focused on creating a single multivalent sub-unit vaccine for five gram-negative pathogenic systems. In addition, a putative tip protein from Chlamydiae is compared to the other tip proteins using biophysical methods

All-In-One Hand Washing System

The MQP group researched, developed and built a prototype, ran tests on the prototype and ultimately designed a full version of an all-in-one hand washing system. The system is completely touch-free and resource conscious. The system is controlled by a fully programed circuit that runs a 20 second hand wash and dry cycle upon motion sensors being triggered. The unit first dispenses soap along the user’s hands, then delays and allows the user to scrub their hands if wanted, after the delay it then sprays the user’s hands off. At the end of the wash cycle, hand dryers located at the entrance to the device allow the user to dry their hands as they remove them from the device. This unit maintains restroom cleanliness and optimizes the tedious process of hand washing

Biophysical Characterization of Chlamydia trachomatis CT584 Supports Its Potential Role as a Type III Secretion Needle Tip Protein

This is the published version. Copyright American Chemical SocietyChlamydia are obligate intracellular bacterial pathogens that cause a variety of diseases. Likemany Gram-negative bacteria, they employ type III secretion systems (T3SS) for invasion, establishing and maintaining their unique intracellular niche, and possibly cellular exit. Computational structure prediction indicated that ORF CT584 is homologous to other T3SS needle tip proteins. Tip proteins have been shown to be localized to the extracellular end of the T3SS needle and play a key role in controlling secretion of effector proteins. We have previously demonstrated that T3SS needle tip proteins from different bacteria share many biophysical characteristics. To support the hypothesis that CT584 is a T3SS needle tip protein, biophysical properties of CT584 were explored as a function of pH and temperature, using spectroscopic techniques. Far-UV circular dichroism, Fourier transform infrared spectroscopy, UV absorbance spectroscopy, ANS extrinsic fluorescence, turbidity, right angle static light scattering, and analytical ultracentrifugation were all employed to monitor the secondary, tertiary, quaternary, and aggregation behavior of this protein. An empirical phase diagram approach is also employed to facilitate such comparisons. These analyses demonstrate that CT584 shares many biophysical characteristics with other T3SS needle tip proteins. These data support the hypothesis that CT584 is a member of the same functional family, although future biologic analyses are required

Spectral Analysis of the Primary Flight Focal Plane Arrays for the Thermal Infrared Sensor

Thermal Infrared Sensor (TIRS) is a (1) New longwave infrared (10 - 12 micron) sensor for the Landsat Data Continuity Mission, (2) 185 km ground swath; 100 meter pixel size on ground, (3) Pushbroom sensor configuration. Issue of Calibration are: (1) Single detector -- only one calibration, (2) Multiple detectors - unique calibration for each detector -- leads to pixel-to-pixel artifacts. Objectives are: (1) Predict extent of residual striping when viewing a uniform blackbody target through various atmospheres, (2) Determine how different spectral shapes affect the derived surface temperature in a realistic synthetic scene

Formulation and Immunogencity studies of Type III Secretion System needle antigens as Vaccine Candidates

Bacterial infections caused by Shigella flexneri, Salmonella typhimurium and Burkholderia pseudomallei are currently difficult to prevent due to the lack of a licensed vaccine. Here we present formulation and immunogenicity studies for the three type III secretion system (TTSS) needle proteins MxiHΔ5, PrgIΔ5 and BsaLΔ5 (each truncated by five residues at its C terminus) as potential candidates for vaccine development. These antigens are found to be thermally stabilized by the presence of carbohydrates and polyols. Additionally, all adsorb readily to aluminum hydroxide apparently through a combination of hydrogen bonds and/or Van der Waals forces. The interaction of these proteins with the aluminum-based adjuvant changes with time to resulting in varying degrees of irreversible binding. Peptide maps of desorbed protein, however, suggest that chemical changes are not responsible for this irreversible association. The ability of MxiHΔ5 and PrgIΔ5 to elicit strong humoral immune responses was tested in a murine model. When administered intramuscularly as monomers, the needle components exhibited dose dependent immunogenic behavior. The polymerized version of MxiH was exceptionally immunogenic even at low doses. The responses of both monomeric and polymerized forms were boosted by adsorption to an aluminum salt adjuvant

Landsat-8 On-Orbit and Landsat-9 Pre-Launch Sensor Radiometric Characterization

Topics: Landsat 8, 9 Instrument Overview -Operational Land Imager (OLI) -Thermal Infrared Sensor (TIRS); Landsat-8 Instrument Status and On-orbit Radiometric Performance Characterization; Landsat-9 Instrument Status and Pre-launch Radiometric Performance Characterization

Landsat-7 ETM+: 12 years On-Orbit Reflective-Band Radiometric Performance

The Landsat-7 ETM+ sensor has been operating on orbit for more than 12 years and characterizations of its performance have been ongoing over this period. In general, the radiometric performance of the instrument has been remarkably stable: (1) Noise performance has degraded by 2% or less overall, with a few detectors displaying step changes in noise of 2% or less, (2) Coherent noise frequencies and magnitudes have generally been stable, though the within-scan amplitude variation of the 20kHz noise in bands 1 and 8 disappeared with the failure of the scan line corrector and a new similar frequency noise (now about 18kHz) has appeared in two detectors in band 5 and increased in magnitude with time, (3) Bias stability has been better than 0.25 DN out of a normal value of 15 DN in high gain, (4) Relative gains, the differences in response between the detectors in the band, have generally changed by 0.1% or less over the mission, with the exception of a few detectors with a step response change of 1% or less and (5) Gain stability averaged across all detectors in a band, which is related to the stability of the absolute calibration, has been more stable than the techniques used to measure it. Due to the inability to confirm changes in the gain (beyond a few detectors that have been corrected back to the band average), ETM+ reflective band data continues to be calibrated with the pre-launch measured gains. In the worst case some bands may have changed as much as 2% in uncompensated absolute calibration over the 12 years

Medical Students' Exposure to and Attitudes about the Pharmaceutical Industry: A Systematic Review

A systematic review of published studies reveals that undergraduate medical students may experience substantial exposure to pharmaceutical marketing, and that this contact may be associated with positive attitudes about marketing

Disease-Toxicant Interactions in Manganese Exposed Huntington Disease Mice: Early Changes in Striatal Neuron Morphology and Dopamine Metabolism

YAC128 Huntington's disease (HD) transgenic mice accumulate less manganese (Mn) in the striatum relative to wild-type (WT) littermates. We hypothesized that Mn and mutant Huntingtin (HTT) would exhibit gene-environment interactions at the level of neurochemistry and neuronal morphology. Twelve-week-old WT and YAC128 mice were exposed to MnCl2-4H2O (50 mg/kg) on days 0, 3 and 6. Striatal medium spiny neuron (MSN) morphology, as well as levels of dopamine (DA) and its metabolites (which are known to be sensitive to Mn-exposure), were analyzed at 13 weeks (7 days from initial exposure) and 16 weeks (28 days from initial exposure). No genotype-dependent differences in MSN morphology were apparent at 13 weeks. But at 16 weeks, a genotype effect was observed in YAC128 mice, manifested by an absence of the wild-type age-dependent increase in dendritic length and branching complexity. In addition, genotype-exposure interaction effects were observed for dendritic complexity measures as a function of distance from the soma, where only YAC128 mice were sensitive to Mn exposure. Furthermore, striatal DA levels were unaltered at 13 weeks by genotype or Mn exposure, but at 16 weeks, both Mn exposure and the HD genotype were associated with quantitatively similar reductions in DA and its metabolites. Interestingly, Mn exposure of YAC128 mice did not further decrease DA or its metabolites versus YAC128 vehicle exposed or Mn exposed WT mice. Taken together, these results demonstrate Mn-HD disease-toxicant interactions at the onset of striatal dendritic neuropathology in YAC128 mice. Our results identify the earliest pathological change in striatum of YAC128 mice as being between 13 to 16 weeks. Finally, we show that mutant HTT suppresses some Mn-dependent changes, such as decreased DA levels, while it exacerbates others, such as dendritic pathology