Nanochemistry for Biomedical Sensors and Contrast Agents.

The primary focus of the work described in this dissertation is the coupling of PEBBLE (Photonic Explorers for Biomedical use by Biologically Localized Embedding) nanosensors with new sensing technologies. Included in this body of work is the application of fluorescence anisotropy based measurements to PEBBLE nanosensors, in order to measure analyte concentrations. The advantage of the fluorescence anisotropy technique is that it is a self-referencing measurement; therefore the process of designing fluorescence based nanosensors is streamlined. Separate measurements were performed on poly (acrylamide) PEBBLEs with embedded Calcium Green and Newport Green indicator dyes in order to sense Ca2+(aq.) and Zn2+(aq.), respectively. A sol-gel PEBBLE with the embedded [Ru(dpp)3]2+ indicator dye was used to make O2 measurements in a sealed gas-tight optical cell. A second sensing technique investigated utilizes a new photoacoustic based sensing method that utilizes the pH-sensitive fluorescent indicator dye SNARF-5F. In the experiment, the photoacoustic response of a series of solutions, with the indicator dye dissolved in buffers that ranged in pH from 6 to 9, was consistent with the trend that one would expect based on the absorption of the SNARF-5F dye as a function of pH. This proof-of-principle experiment demonstrates the possibility of creating an in vivo nanoplatform for sensing analyte concentrations in whole, intact tissue using photoacoustic detection. A silver nanoprism colloid was investigated as a potential Surface-Enhanced Raman Scattering (SERS) substrate, with the analyte 4-mercaptopyridine (4-MPy). This analyte was chosen as a test molecule because it could be utilized to develop a SERS based pH nanosensor with the nanoprism colloid. It had been discovered that, while the poly (vinyl pyrrolidone) (PVP) organic capping agent interfered with the acquisition of the SERS signal on the nanoprism colloid, this approach is feasible.Ph.D.ChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/60707/1/horvatht_1.pd

The 1981 Argentina ground data collection

Over 600 fields in the corn, soybean and wheat growing regions of the Argentine pampa were categorized by crop or cover type and ancillary data including crop calendars, historical crop production statistics and certain cropping practices were also gathered. A summary of the field work undertaken is included along with a country overview, a chronology of field trip planning and field work events, and the field work inventory of selected sample segments. LANDSAT images were annotated and used as the field work base and several hundred ground and aerial photographs were taken. These items along with segment descriptions are presented. Meetings were held with officials of the State Secretariat of Agriculture (SEAG) and the National Commission on Space Investigations (CNIE), and their support to the program are described

Effects of Gamma Ray Bursts in Earth Biosphere

We continue former work on the modeling of potential effects of Gamma Ray Bursts on Phanerozoic Earth. We focus on global biospheric effects of ozone depletion and show a first modeling of the spectral reduction of light by NO2 formed in the stratosphere. We also illustrate the current complexities involved in the prediction of how terrestrial ecosystems would respond to this kind of burst. We conclude that more biological field and laboratory data are needed to reach even moderate accuracy in this modelingComment: Accepted for publication in Astrophysics & Space Scienc

A high-throughput LC-MS/MS method for the measurement of the bile acid/salt content in microbiome-derived sample sets

Due to the physicochemical properties of bile acids/salts (i.e., hydrophobic and ionizable), the application of reverse-phase liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based methods are ideally suited for the measurement of these compounds in a host of microbiologically-relevant matrices. Here, we provide a detailed bioanalytical protocol that contains several modifications of a method previously described by Wegner et al. [1]. Briefly, this modified method exhibits the following advantages for the measurement of cholic acid (CA), taurocholic acid (TCA), and deoxycholic acid (DCA) in microbiome-relevant sample matrices: i) fecal sample processing has been streamlined by the elimination of lyophilization and manual homogenization steps; ii) the Sciex 6500 QTRAP hybrid triple-quadrupole/linear ion trap mass spectrometer has sufficient sensitivity to perform the measurement of bile acids/salts in negative ion mode – ammonium adducts of bile acids/salts are not required for detection; and, iii) assay throughput has been boosted by more than 5-fold by shortening the chromatographic duty cycle of a single sample injection from 45 min to 8.4 min. Recently, the method was used to perform 508 sequential injections (72 calibration standards, 52 blank-internal standard sample, and 368 MiniBioReactor Array (MBRA)-derived samples) from four separate batches over a 4-day time period

Detection of ultra-high energy cosmic ray showers with a single-pixel fluorescence telescope

We present a concept for large-area, low-cost detection of ultra-high energy cosmic rays (UHECRs) with a Fluorescence detector Array of Single-pixel Telescopes (FAST), addressing the requirements for the next generation of UHECR experiments. In the FAST design, a large field of view is covered by a few pixels at the focal plane of a mirror or Fresnel lens. We report first results of a FAST prototype installed at the Telescope Array site, consisting of a single 200 mm photomultiplier tube at the focal plane of a 1 m$^2$ Fresnel lens system taken from the prototype of the JEM-EUSO experiment. The FAST prototype took data for 19 nights, demonstrating remarkable operational stability. We detected laser shots at distances of several kilometres as well as 16 highly significant UHECR shower candidates.Comment: Accepted for publication in Astroparticle Physic

Aeroheating Testing and Predictions for Project Orion CEV at Turbulent Conditions

An investigation of the aeroheating environment of the Project Orion Crew Exploration Vehicle was performed in the Arnold Engineering Development Center Hypervelocity Wind Tunnel No. 9 Mach 8 and Mach 10 nozzles and in the NASA Langley Research Center 20 - Inch Mach 6 Air Tunnel. Heating data were obtained using a thermocouple-instrumented approx.0.035-scale model (0.1778-m/7-inch diameter) of the flight vehicle. Runs were performed in the Tunnel 9 Mach 10 nozzle at free stream unit Reynolds numbers of 1x10(exp 6)/ft to 20x10(exp 6)/ft, in the Tunnel 9 Mach 8 nozzle at free stream unit Reynolds numbers of 8 x 10(exp 6)/ft to 48x10(exp 6)/ft, and in the 20-Inch Mach 6 Air Tunnel at free stream unit Reynolds numbers of 1x10(exp 6)/ft to 7x10(exp 6)/ft. In both facilities, enthalpy levels were low and the test gas (N2 in Tunnel 9 and air in the 20-Inch Mach 6) behaved as a perfect-gas. These test conditions produced laminar, transitional and turbulent data in the Tunnel 9 Mach 10 nozzle, transitional and turbulent data in the Tunnel 9 Mach 8 nozzle, and laminar and transitional data in the 20- Inch Mach 6 Air Tunnel. Laminar and turbulent predictions were generated for all wind tunnel test conditions and comparisons were performed with the experimental data to help define the accuracy of computational method. In general, it was found that both laminar data and predictions, and turbulent data and predictions, agreed to within less than the estimated 12% experimental uncertainty estimate. Laminar heating distributions from all three data sets were shown to correlate well and demonstrated Reynolds numbers independence when expressed in terms of the Stanton number based on adiabatic wall-recovery enthalpy. Transition onset locations on the leeside centerline were determined from the data and correlated in terms of boundary-layer parameters. Finally turbulent heating augmentation ratios were determined for several body-point locations and correlated in terms of the boundary-layer momentum Reynolds number

Experimental Investigation of Project Orion Crew Exploration Vehicle Aeroheating in AEDC Tunnel 9

An investigation of the aeroheating environment of the Project Orion Crew Entry Vehicle has been performed in the Arnold Engineering Development Center Tunnel 9. The goals of this test were to measure turbulent heating augmentation levels on the heat shield and to obtain high-fidelity heating data for assessment of computational fluid dynamics methods. Laminar and turbulent predictions were generated for all wind tunnel test conditions and comparisons were performed with the data for the purpose of helping to define uncertainty margins for the computational method. Data from both the wind tunnel test and the computational study are presented herein

Persisting Viral Sequences Shape Microbial CRISPR-based Immunity

Well-studied innate immune systems exist throughout bacteria and archaea, but a more recently discovered genomic locus may offer prokaryotes surprising immunological adaptability. Mediated by a cassette-like genomic locus termed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), the microbial adaptive immune system differs from its eukaryotic immune analogues by incorporating new immunities unidirectionally. CRISPR thus stores genomically recoverable timelines of virus-host coevolution in natural organisms refractory to laboratory cultivation. Here we combined a population genetic mathematical model of CRISPR-virus coevolution with six years of metagenomic sequencing to link the recoverable genomic dynamics of CRISPR loci to the unknown population dynamics of virus and host in natural communities. Metagenomic reconstructions in an acid-mine drainage system document CRISPR loci conserving ancestral immune elements to the base-pair across thousands of microbial generations. This ‘trailer-end conservation’ occurs despite rapid viral mutation and despite rapid prokaryotic genomic deletion. The trailer-ends of many reconstructed CRISPR loci are also largely identical across a population. ‘Trailer-end clonality’ occurs despite predictions of host immunological diversity due to negative frequency dependent selection (kill the winner dynamics). Statistical clustering and model simulations explain this lack of diversity by capturing rapid selective sweeps by highly immune CRISPR lineages. Potentially explaining ‘trailer-end conservation,’ we record the first example of a viral bloom overwhelming a CRISPR system. The polyclonal viruses bloom even though they share sequences previously targeted by host CRISPR loci. Simulations show how increasing random genomic deletions in CRISPR loci purges immunological controls on long-lived viral sequences, allowing polyclonal viruses to bloom and depressing host fitness. Our results thus link documented patterns of genomic conservation in CRISPR loci to an evolutionary advantage against persistent viruses. By maintaining old immunities, selection may be tuning CRISPR-mediated immunity against viruses reemerging from lysogeny or migration

Remote Infrared Imaging of the Space Shuttle During Hypersonic Flight: HYTHIRM Mission Operations and Coordination

The Hypersonic Thermodynamic Infrared Measurements (HYTHIRM) project has been responsible for obtaining spatially resolved, scientifically calibrated in-flight thermal imagery of the Space Shuttle Orbiter during reentry. Starting with STS-119 in March of 2009 and continuing through to the majority of final flights of the Space Shuttle, the HYTHIRM team has to date deployed during seven Shuttle missions with a mix of airborne and ground based imaging platforms. Each deployment of the HYTHIRM team has resulted in obtaining imagery suitable for processing and comparison with computational models and wind tunnel data at Mach numbers ranging from over 18 to under Mach 5. This paper will discuss the detailed mission planning and coordination with the NASA Johnson Space Center Mission Control Center that the HYTHIRM team undergoes to prepare for and execute each mission

Transient ischemic attacks in patients with active and occult cancer.

BACKGROUND AND AIM Paraneoplastic coagulopathy can present as stroke and is associated with specific biomarker changes. Identifying paraneoplastic coagulopathy can help guide secondary prevention in stroke patients, and early cancer detection might improve outcomes. However, unlike ischemic stroke, it remains unclear whether paraneoplastic coagulopathy is associated with transient ischemic attacks (TIA). This study assessed the presence of cancer-related biomarkers in TIA patients and evaluated long-term mortality rates in patients with and without active cancer. METHODS Active cancer was retrospectively identified in consecutive TIA patients treated at a comprehensive stroke center between 2015 and 2019. An association between the presence of cancer and cancer-related biomarkers was assessed using multivariable logistic regression. Long-term mortality after TIA was analyzed using multivariable Cox regression. RESULTS Among 1436 TIA patients, 72 had active cancer (5%), of which 17 were occult (1.2%). Cancer-related TIA was associated with male gender (adjusted odds ratio [aOR] 2.29, 95% CI 1.12-4.68), history of smoking (aOR 2.77, 95% CI 1.34-5.7), elevated D-dimer (aOR 1.77, 95% CI 1.26-2.49), lactate dehydrogenase (aOR 1.003, 95% CI 1.00-1.005), lower leukocyte count (aOR 1.20, 95% CI 1.04-1.38), and lower hemoglobin (aOR 1.02, 95% CI 1.00-1.04). Long-term mortality was associated with both active cancer (adjusted hazard ratios [aHR] 2.47, 95% CI 1.58-3.88) and occult cancer (aHR 3.08, 95% CI 1.30-7.32). CONCLUSION Cancer-related TIA is not uncommon. Biomarkers known to be associated with cancer-related stroke also seem to be present in TIA patients. Early identification would enable targeted treatment strategies and could improve outcomes in this patient population