Azimuth and Range Optimization of the Velocity Azimuth Display (VAD) Algorithm in the WSR-88D

The Velocity Azimuth Display (VAD) algorithm occasionally produces inaccurate wind estimates for the VAD Wind Profile (VWP) product of the Weather Surveillance Radar 1988 Doppler (WSR-88D) System. Weather forecasters have observed differences between the radar\u27s wind profiles and wind profiles produced by rawinsondes and vertical wind profilers, when radiation and subsidence inversions in the atmosphere caused the radar beam to super refract. This thesis sought to improve the operational use of the VWP product for the WSR-88D near Denver, CO, by finding the optimal VAD algorithm Azimuth and Range parameter settings to overcome data contamination by hills located at the default range used by the algorithm. The WSR-88D Algorithm Testing and Display System (WATADS) processed 24 weeks of archived (level II) VAD wind data, which was verified by rawinsonde and vertical wind profiler data. Azimuth optimization was unsuccessful. However, reducing the range not only provided an average improvement in the accuracy of winds obtained under super refractive conditions, but also in the accuracy of those winds obtained when the atmosphere was not super refractive. In the overall average, the range which produced the most improvement over default range (30 km) accuracy was 28 km. The 26 km range also performed well

Use of a scanning optical profilometer for toolmark characterization

An optical profilometer has been used to obtain 3-dimensional data for use in two research projects concerning toolmark quantification and identification. In the first study quantitative comparisons between toolmarks made using data from the optical system proved superior to similar data obtained using a stylus profilometer. In the second study the ability of the instrument to obtain accurate data from two surfaces intersecting at a high angle (approximately 90 degrees) is demonstrated by obtaining measurements from the tip of a flat screwdriver. The data obtained was used to produce a computer generated virtual tool, which was then employed to create virtual tool marks. How these experiments were conducted and the results obtained will be presented and discussed

Validation of Tool Mark Comparisons Obtained Using a Quantitative, Comparative, Statistical Algorithm

A statistical analysis and computational algorithm for comparing pairs of tool marks via profilometry data is described. Empirical validation of the method is established through experiments based on tool marks made at selected fixed angles from 50 sequentially manufactured screwdriver tips. Results obtained from three different comparison scenarios are presented and are in agreement with experiential knowledge possessed by practicing examiners. Further comparisons between scores produced by the algorithm and visual assessments of the same tool mark pairs by professional tool mark examiners in a blind study in general show good agreement between the algorithm and human experts. In specific instances where the algorithm had difficulty in assessing a particular comparison pair, results obtained during the collaborative study with professional examiners suggest ways in which algorithm performance may be improved. It is concluded that the addition of contextual information when inputting data into the algorithm should result in better performance

Hyperglycemia modulates extracellular amyloid-β concentrations and neuronal activity in vivo

Epidemiological studies show that patients with type 2 diabetes (T2DM) and individuals with a diabetes-independent elevation in blood glucose have an increased risk for developing dementia, specifically dementia due to Alzheimer’s disease (AD). These observations suggest that abnormal glucose metabolism likely plays a role in some aspects of AD pathogenesis, leading us to investigate the link between aberrant glucose metabolism, T2DM, and AD in murine models. Here, we combined two techniques — glucose clamps and in vivo microdialysis — as a means to dynamically modulate blood glucose levels in awake, freely moving mice while measuring real-time changes in amyloid-β (Aβ), glucose, and lactate within the hippocampal interstitial fluid (ISF). In a murine model of AD, induction of acute hyperglycemia in young animals increased ISF Aβ production and ISF lactate, which serves as a marker of neuronal activity. These effects were exacerbated in aged AD mice with marked Aβ plaque pathology. Inward rectifying, ATP-sensitive potassium (K(ATP)) channels mediated the response to elevated glucose levels, as pharmacological manipulation of K(ATP) channels in the hippocampus altered both ISF Aβ levels and neuronal activity. Taken together, these results suggest that K(ATP) channel activation mediates the response of hippocampal neurons to hyperglycemia by coupling metabolism with neuronal activity and ISF Aβ levels

Chemical Explosion, Covid-19, and Environmental Justice: insights From Low-Cost air Quality Sensors

OBJECTIVES: to examine the impact of the Intercontinental Terminals Company (ITC) fire and COVID-19 on airborne particulate matter (PM) concentrations and the PM disproportionally affecting communities in Houston using low-cost sensors. METHODS: We compared measurements from a network of low-cost sensors with a separate network of monitors from the Environmental Protection Agency (EPA) in the Houston metropolitan area from Mar 18, 2019, to Dec 31, 2020. Further, we examined the associations between neighborhood-level sociodemographic status and air pollution patterns by linking the low-cost sensor data to EPA environmental justice screening and mapping systems. FINDINGS: We found increased PM levels during ITC fire and pre-COVID-19, and lower PM levels after the COVID-19 lockdown, comparable to observations from the regulatory monitors, with higher variations and a greater number of locations with high PM levels detected. In addition, the environmental justice analysis showed positive associations between higher PM levels and the percentage of minority, low-income population, and demographic index. IMPLICATION: Our study indicates that low-cost sensors provide pollutant measures with higher spatial variations and a better ability to identify hot spots and high peak concentrations. These advantages provide critical information for disaster response and environmental justice studies. SYNOPSIS: We used measurements from a low-cost sensor network for air pollution monitoring and environmental justice analysis to examine the impact of anthropogenic and natural disasters

Anti-tumor activity and mechanistic characterization of APE1/Ref-1 inhibitors in bladder cancer

Bladder cancer is the ninth most common cause of cancer-related deaths worldwide. Although cisplatin is used routinely in treating bladder cancer, refractory disease remains lethal for many patients. The recent addition of immunotherapy has improved patient outcomes; however, a large cohort of patients does not respond to these treatments. Therefore, identification of innovative molecular targets for bladder cancer is crucial. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in both DNA repair and activation of transcription factors through reduction-oxidation (redox) regulation. High APE1/Ref-1 expression is associated with shorter patient survival time in many cancer types. In this study, we found high APE1/Ref-1 expression in human bladder cancer tissue relative to benign urothelium. Inhibition of APE1/Ref-1 redox signaling using APE1/Ref-1-specific inhibitors attenuates bladder cancer cell proliferation in monolayer, in three-dimensional cultures, and in vivo. This inhibition corresponds with an increase in apoptosis and decreased transcriptional activity of NF-κB and STAT3, transcription factors known to be regulated by APE1/Ref-1, resulting in decreased expression of downstream effectors survivin and Cyclin D1 in vitro and in vivo. We also demonstrate that in vitro treatment of bladder cancer cells with APE1/Ref-1 redox inhibitors in combination with standard-of-care chemotherapy cisplatin is more effective than cisplatin alone at inhibiting cell proliferation. Collectively, our data demonstrate that APE1/Ref-1 is a viable drug target for the treatment of bladder cancer, provide a mechanism of APE1/Ref-1 action in bladder cancer cells, and support the use of novel redox-selective APE1/Ref-1 inhibitors in clinical studies. SIGNIFICANCE: This work identifies a critical mechanism for APE1/Ref-1 in bladder cancer growth and provides compelling preclinical data using selective redox activity inhibitors of APE1/Ref-1 in vitro and in vivo

Analysis of antibiotic resistance genes in multidrug-resistant acinetobacter sp. isolates from military and civilian patients treated at the Walter Reed Army Medical Center

Military medical facilities treating patients injured in Iraq and Afghanistan have identified a large number of multidrug-resistant (MDR) Acinetobacter baumannii isolates. In order to anticipate the impact of these pathogens on patient care, we analyzed the antibiotic resistance genes responsible for the MDR phenotype in Acinetobacter sp. isolates collected from patients at the Walter Reed Army Medical Center (WRAMC). Susceptibility testing, PCR amplification of the genetic determinants of resistance, and clonality were determined. Seventy-five unique patient isolates were included in this study: 53% were from bloodstream infections, 89% were resistant to at least three classes of antibiotics, and 15% were resistant to all nine antibiotics tested. Thirty-seven percent of the isolates were recovered from patients nosocomially infected or colonized at the WRAMC. Sixteen unique resistance genes or gene families and four mobile genetic elements were detected. In addition, this is the first report of blaOXA-58-like and blaPER-like genes in the U.S. MDR A. baumannii isolates with at least eight identified resistance determinants were recovered from 49 of the 75 patients. Molecular typing revealed multiple clones, with eight major clonal types being nosocomially acquired and with more than 60% of the isolates being related to three pan-European types. This report gives a “snapshot” of the complex genetic background responsible for antimicrobial resistance in Acinetobacter spp. from the WRAMC. Identifying genes associated with the MDR phenotype and defining patterns of transmission serve as a starting point for devising strategies to limit the clinical impact of these serious infections. © 2006, American Society for Microbiolog

NUScon: a community-driven platform for quantitative evaluation of nonuniform sampling in NMR

Although the concepts of nonuniform sampling (NUS) and non-Fourier spectral reconstruction in multidimensional NMR began to emerge 4 decades ago (Bodenhausen and Ernst, 1981; Barna and Laue, 1987), it is only relatively recently that NUS has become more commonplace. Advantages of NUS include the ability to tailor experiments to reduce data collection time and to improve spectral quality, whether through detection of closely spaced peaks (i.e., “resolution”) or peaks of weak intensity (i.e., “sensitivity”). Wider adoption of these methods is the result of improvements in computational performance, a growing abundance and flexibility of software, support from NMR spectrometer vendors, and the increased data sampling demands imposed by higher magnetic fields. However, the identification of best practices still remains a significant and unmet challenge. Unlike the discrete Fourier transform, non-Fourier methods used to reconstruct spectra from NUS data are nonlinear, depend on the complexity and nature of the signals, and lack quantitative or formal theory describing their performance. Seemingly subtle algorithmic differences may lead to significant variabilities in spectral qualities and artifacts. A community-based critical assessment of NUS challenge problems has been initiated, called the “Nonuniform Sampling Contest” (NUScon), with the objective of determining best practices for processing and analyzing NUS experiments. We address this objective by constructing challenges from NMR experiments that we inject with synthetic signals, and we process these challenges using workflows submitted by the community. In the initial rounds of NUScon our aim is to establish objective criteria for evaluating the quality of spectral reconstructions. We present here a software package for performing the quantitative analyses, and we present the results from the first two rounds of NUScon. We discuss the challenges that remain and present a roadmap for continued community-driven development with the ultimate aim of providing best practices in this rapidly evolving field. The NUScon software package and all data from evaluating the challenge problems are hosted on the NMRbox platform