Performance enhancement in the measurement of 5 endogenous steroids by LC-MS/MS combined with differential ion mobility spectrometry

pre-printBackground: Challenges for steroid analysis by LC-MS/MS include low ionization efficiency, endogenous isobars with similar fragmentation patterns and chromatographic retention. Differential ion mobility spectrometry (DMS) provides an additional degree of separation prior to MS/MS detection, and shows promise in improving specificity of analysis. We developed a sensitive and specific method for measurement of corticosterone, 11-deoxycortisol, 11-deoxycorticosterone, 17-hydroxyprogesterone and progesterone in human serum and plasma using an ABSciex 5500 mass spectrometer equipped with a differential ion mobility interface. Methods: 250 μL aliquots of serum were spiked with deuterated internal standards and extracted with MTBE. The samples were analyzed using positivemode electrospray LC-DMS-MS/MS. Themethod was validated and compared with immunoassays and LC-MS/MS methods of reference laboratories. Results: Inter and intra assay imprecision was b10%. Limits of quantification and detection in nmol/L were 0.18, 0.09 for corticosterone and 17-hydroxyprogesterone, 0.30, 0.16 for 11-deoxycortisol, 0.12, 0.06 for progesterone and 0.06, 0.03 for 11-deoxycorticosterone. Comparison for progesterone and 17-hydroxyprogesterone with immunoassay showed slopes of 0.97 and 1.0, intercepts of 0.16 and 0.10 and coefficients of determination (r2) of 0.92 and 0.97, respectively. Progesterone by immunoassay showed positive bias in samples measuring b3.18 nmol/L. Reference intervals for progesterone and 11-deoxycorticosterone in post-menopausal women were found to be b2.88 and b0.28 nmol/L respectively. Conclusions: We developed and validated an LC-DMS-MS/MS method for analysis of five endogenous steroids suitable for routine measurements in clinical diagnostic laboratories. Specificity gained with DMS allows reducing the complexity of sample preparation, decreasing LC run times and increasing speed of the analysis

An Experiential Approach to Mentoring Academic Leaders: Review, Practice, Report

This session presents a leadership development program where new department chairs discuss best practices and realistic challenges with seasoned chairs, helping all to improve their leadership skills through a supportive group process. The program includes a summer book study, monthly meetings, a department chair handbook, and leadership resources

Nebraska Growers’ and Crop Consultants’ Knowledge and Implementation of Integrated Pest Management of Western Bean Cutworm

Western bean cutworm (WBC), Striacosta albicosta (Smith; Lepidoptera: Noctuidae), is a native noctuid pest of corn and dry beans in North America. While this pest has expanded its range greatly in recent years, historically it has consistently caused high yield losses in western Nebraska. A survey was distributed to growers, crop consultants and other agricultural professionals to obtain information about current management practices used for WBC. Questions covered multiple topics including: demographics, scouting practices, degree-day model use, confidence in management knowledge, Bt corn use, insecticide use, and considerations for biological control. There were 95 completed responses received by email. Respondents self-reported a significantly higher yield loss due to WBC in 2016 than in 2015 and 2014. Growers demonstrated less knowledge of WBC identification and management than crop consultants. There were frequent (58.45%) reports of Cry1F Bt corn providing decreased control against WBC. This survey identified major concerns for growers and agricultural professionals in Nebraska for WBC management. An improved understanding of WBC biology and education on management would be most beneficial for growers. Crop consultants would benefit from using more diverse management tactics including: biological control, rotation of insecticide mode-of-action, and diversifying Bt corn types

Interim Leadership Positions: The Kobayashi Maru of Academia?

Leading a department through a transition such as reorganization or restructuring is difficult. When the unit leader is in an interim position, this is even more complicated. This presentation will be led by faculty who were all in interim leadership positions during major transitions in leadership, restructuring, and staff layoffs

In Situ Fabrication and Repair (ISFR) Technologies; New Challenges for Exploration

NASA's human exploration initiative poses great opportunity and great risk for manned missions to the Moon and Mars. Engineers and Scientists at the Marshall Space Flight Center (MSFC) are continuing to evaluate current technologies for in situ resource-based exploration fabrication and repair applications. Several technologies to be addressed in this paper have technology readiness levels (TRLs) that are currently mature enough to pursue for exploration purposes. However, while many technologies offer promising applications, these technologies must be pulled along by the demands and applications of this great initiative. The In Situ Fabrication and Repair (ISFR) Element will supply and push state of the art technologies for applications such as habitat structure development, in situ resource utilization for tool and part fabrication, and repair and non-destructive evaluation W E ) of common life support elements. As an overview of the ISFR Element, this paper will address rapid prototyping technologies, their applications, challenges, and near term advancements. This paper will also discuss the anticipated need to utilize in situ resources to produce replacement parts and fabricate repairs to vehicles, habitats, life support and quality of life elements. Overcoming the challenges of ISFR development will provide the Exploration initiative with state of the art technologies that reduce risk, and enhance supportability

Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis

Rheumatoid arthritis is a chronic inflammatory disease that shows characteristic diurnal variation in symptom severity, where joint resident fibroblast-like synoviocytes (FLS) act as important mediators of arthritis pathology. We investigate the role of FLS circadian clock function in directing rhythmic joint inflammation in a murine model of inflammatory arthritis. We demonstrate FLS time-of-day-dependent gene expression is attenuated in arthritic joints, except for a subset of disease-modifying genes. The deletion of essential clock gene Bmal1 in FLS reduced susceptibility to collagen-induced arthritis but did not impact symptomatic severity in affected mice. Notably, FLS Bmal1 deletion resulted in loss of diurnal expression of disease-modulating genes across the joint, and elevated production of MMP3, a prognostic marker of joint damage in inflammatory arthritis. This work identifies the FLS circadian clock as an influential driver of daily oscillations in joint inflammation, and a potential regulator of destructive pathology in chronic inflammatory arthritis

Radio galaxies and their magnetic fields out to z <= 3

We present polarization properties at 1.4 GHz of two separate extragalactic source populations: passive quiescent galaxies and luminous quasar-like galaxies. We use data from the Wide-Field Infrared Survey Explorer to determine the host galaxy population of the polarized extragalactic radio sources. The quiescent galaxies have higher percentage polarization, smaller radio linear size, and 1.4 GHz luminosity of 6 × 1021 < L1.4 < 7 × 1025 W Hz−1, while the quasar-like galaxies have smaller percentage polarization, larger radio linear size at radio wavelengths, and a 1.4 GHz luminosity of 9 × 1023 < L1.4 < 7 × 1028 W Hz−1, suggesting that the environment of the quasar-like galaxies is responsible for the lower percentage polarization. Our results confirm previous studies that found an inverse correlation between percentage polarization and total flux density at 1.4 GHz. We suggest that the population change between the polarized extragalactic radio sources is the origin of this inverse correlation and suggest a cosmic evolution of the space density of quiescent galaxies. Finally, we find that the extragalactic contributions to the rotation measures (RMs) of the nearby passive galaxies and the distant quasar-like galaxies are different. After accounting for the RM contributions by cosmological large-scale structure and intervening Mg II absorbers we show that the distribution of intrinsic RMs of the distant quasar-like sources is at most four times as wide as the RM distribution of the nearby quiescent galaxies, if the distribution of intrinsic RMs of the WISE–Star sources itself is at least several rad m−2 wide

Prospectus, January 20, 1987

https://spark.parkland.edu/prospectus_1987/1001/thumbnail.jp

Alterations of immune response of non-small lung cancer with azacytidine

Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints - in particular the PD-1/PD-L1 pathway - may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade