Independent trapping and manipulation of microparticles using dexterous acoustic tweezers

An electronically controlled acoustic tweezer was used to demonstrate two acoustic manipulation phenomena: superposition of Bessel functions to allow independent manipulation of multiple particles and the use of higher-order Bessel functions to trap particles in larger regions than is possible with first-order traps. The acoustic tweezers consist of a circular 64-element ultrasonic array operating at 2.35MHz which generates ultrasonic pressure fields in a millimeter-scale fluid-filled chamber. The manipulation capabilities were demonstrated experimentally with 45 and 90-lm-diameter polystyrene spheres. These capabilities bring the dexterity of acoustic tweezers substantially closer to that of optical tweezers

Plasma proteome correlates of lipid and lipoprotein: biomarkers of metabolic diversity and inflammation in children of rural Nepal.

Proteins involved in lipoprotein metabolism can modulate cardiovascular health. While often measured to assess adult metabolic diseases, little is known about the proteomes of lipoproteins and their relation to metabolic dysregulation and underlying inflammation in undernourished child populations. The objective of this population study was to globally characterize plasma proteins systemically associated with HDL, LDL, and triglycerides in 500 Nepalese children. Abnormal lipid profiles characterized by elevated plasma triglycerides and low HDL-cholesterol (HDL-C) concentrations were common, especially in children with subclinical inflammation. Among 982 proteins analyzed, the relative abundance of 11, 12, and 52 plasma proteins was correlated with LDL-cholesterol (r = -0.43∼0.70), triglycerides (r = -0.39∼0.53), and HDL-C (r = -0.49∼0.79) concentrations, respectively. These proteins included apolipoproteins and numerous unexpected intracellular and extracellular matrix binding proteins, likely originating in hepatic and peripheral tissues. Relative abundance of two-thirds of the HDL proteome varied with inflammation, with acute phase reactants higher by 4∼40%, and proteins involved in HDL biosynthesis, cholesterol efflux, vitamin transport, angiogenesis, and tissue repair lower by 3∼20%. Untargeted plasma proteomics detects comprehensive sets of both known and novel lipoprotein-associated proteins likely reflecting systemic regulation of lipoprotein metabolism and vascular homeostasis. Inflammation-altered distributions of the HDL proteome may be predisposing undernourished populations to early chronic disease

Apoptosis Induction by MEK Inhibition in Human Lung Cancer Cells Is Mediated by Bim

AZD6244 (ARRY-142886) is an inhibitor of MEK1/2 and can inhibit cell proliferation or induce apoptosis in a cell-type dependent manner. The precise molecular mechanism of AZD6244-induced apoptosis is not clear. To investigate mechanisms of AZD6244 induced apoptosis in human lung cancer, we determined the molecular changes of two subgroups of human lung cancer cell lines that are either sensitive or resistant to AZD6244 treatment. We found that AZD6244 elicited a large increase of Bim proteins and a smaller increase of PUMA and NOXA proteins, and induced cell death in sensitive lung cancer cell lines, but had no effect on other Bcl-2 related proteins in those cell lines. Knockdown of Bim by siRNA greatly increased the IC50 and reduced apoptosis for AZD6244 treated cells. We also found that levels of endogenous p-Thr32-FOXO3a and p-Ser253-FOXO3a were lower in AZD6244-sensitive cells than in AZD6244-resistant cells. In the sensitive cells, AZD6244 induced FOXO3a nuclear translocation required for Bim activation. Moreover, the silencing of FOXO3a by siRNA abrogated AZD6244-induced cell apoptosis. In addition, we found that transfection of constitutively active AKT up-regulated p-Thr32-FOXO3a and p-Ser253-FOXO3a expression and inhibited AZD6244-induced Bim expression in sensitive cells. These results show that Bim plays an important role in AZD6244-induced apoptosis in lung cancer cells and that the PI3K/AKT/FOXO3a pathway is involved in Bim regulation and susceptibility of lung cancer cells to AZD6244. These results have implications in the development of strategies to overcome resistance to MEK inhibitors

A Preliminary Survey of Interprofessional Education

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153603/1/jddj002203372006704tb04096x.pd

Herschel SPIRE-FTS Observations of Excited CO and [CI] in the Antennae (NGC 4038/39): Warm and Cold Molecular Gas

We present Herschel SPIRE-FTS observations of the Antennae (NGC 4038/39), a well studied, nearby ($22$ Mpc) ongoing merger between two gas rich spiral galaxies. We detect 5 CO transitions ($J=4-3$ to $J=8-7$), both [CI] transitions and the [NII]$205\mu m$ transition across the entire system, which we supplement with ground based observations of the CO $J=1-0$, $J=2-1$ and $J=3-2$ transitions, and Herschel PACS observations of [CII] and [OI]$63\mu m$. Using the CO and [CI] transitions, we perform both a LTE analysis of [CI], and a non-LTE radiative transfer analysis of CO and [CI] using the radiative transfer code RADEX along with a Bayesian likelihood analysis. We find that there are two components to the molecular gas: a cold ($T_{kin}\sim 10-30$ K) and a warm ($T_{kin} \gtrsim 100$ K) component. By comparing the warm gas mass to previously observed values, we determine a CO abundance in the warm gas of $x_{CO} \sim 5\times 10^{-5}$. If the CO abundance is the same in the warm and cold gas phases, this abundance corresponds to a CO $J=1-0$ luminosity-to-mass conversion factor of $\alpha_{CO} \sim 7 \ M_{\odot}{pc^{-2} \ (K \ km \ s^{-1})^{-1}}$in the cold component, similar to the value for normal spiral galaxies. We estimate the cooling from H$_2$, [CII], CO and [OI]$63\mu m$to be$\sim 0.01 L_{\odot}/M_{\odot}$. We compare PDR models to the ratio of the flux of various CO transitions, along with the ratio of the CO flux to the far-infrared flux in NGC 4038, NGC 4039 and the overlap region. We find that the densities recovered from our non-LTE analysis are consistent with a background far-ultraviolet field of strength$G_0\sim 1000$. Finally, we find that a combination of turbulent heating, due to the ongoing merger, and supernova and stellar winds are sufficient to heat the molecular gas.Comment: 50 pages, 15 figures, 8 tables, Accepted for publication in The Astrophysical Journa

Investigating Multiple Candidate Genes and Nutrients in the Folate Metabolism Pathway to Detect Genetic and Nutritional Risk Factors for Lung Cancer

Purpose: Folate metabolism, with its importance to DNA repair, provides a promising region for genetic investigation of lung cancer risk. This project investigates genes (MTHFR, MTR, MTRR, CBS, SHMT1, TYMS), folate metabolism related nutrients (B vitamins, methionine, choline, and betaine) and their gene-nutrient interactions. Methods: We analyzed 115 tag single nucleotide polymorphisms (SNPs) and 15 nutrients from 1239 and 1692 non-Hispanic white, histologically-confirmed lung cancer cases and controls, respectively, using stochastic search variable selection (a Bayesian model averaging approach). Analyses were stratified by current, former, and never smoking status. Results: Rs6893114 in MTRR (odds ratio [OR] = 2.10; 95% credible interval [CI]: 1.20–3.48) and alcohol (drinkers vs. non-drinkers, OR = 0.48; 95% CI: 0.26–0.84) were associated with lung cancer risk in current smokers. Rs13170530 in MTRR (OR = 1.70; 95% CI: 1.10–2.87) and two SNP*nutrient interactions [betaine*rs2658161 (OR = 0.42; 95% CI: 0.19–0.88) and betaine*rs16948305 (OR = 0.54; 95% CI: 0.30–0.91)] were associated with lung cancer risk in former smokers. SNPs in MTRR (rs13162612; OR = 0.25; 95% CI: 0.11–0.58; rs10512948; OR = 0.61; 95% CI: 0.41–0.90; rs2924471; OR = 3.31; 95% CI: 1.66–6.59), and MTHFR (rs9651118; OR = 0.63; 95% CI: 0.43–0.95) and three SNP*nutrient interactions (choline*rs10475407; OR = 1.62; 95% CI: 1.11–2.42; choline*rs11134290; OR = 0.51; 95% CI: 0.27–0.92; and riboflavin*rs8767412; OR = 0.40; 95% CI: 0.15–0.95) were associated with lung cancer risk in never smokers. Conclusions: This study identified possible nutrient and genetic factors related to folate metabolism associated with lung cancer risk, which could potentially lead to nutritional interventions tailored by smoking status to reduce lung cancer risk

Multi-Modal Data Collection for Measuring Health, Behavior, and Living Environment of Large-Scale Participant Cohorts: Conceptual Framework and Findings from Deployments

As mobile technologies become ever more sensor-rich, portable, and ubiquitous, data captured by smart devices are lending rich insights into users' daily lives with unprecedented comprehensiveness, unobtrusiveness, and ecological validity. A number of human-subject studies have been conducted in the past decade to examine the use of mobile sensing to uncover individual behavioral patterns and health outcomes. While understanding health and behavior is the focus for most of these studies, we find that minimal attention has been placed on measuring personal environments, especially together with other human-centric data modalities. Moreover, the participant cohort size in most existing studies falls well below a few hundred, leaving questions open about the reliability of findings on the relations between mobile sensing signals and human outcomes. To address these limitations, we developed a home environment sensor kit for continuous indoor air quality tracking and deployed it in conjunction with established mobile sensing and experience sampling techniques in a cohort study of up to 1584 student participants per data type for 3 weeks at a major research university in the United States. In this paper, we begin by proposing a conceptual framework that systematically organizes human-centric data modalities by their temporal coverage and spatial freedom. Then we report our study design and procedure, technologies and methods deployed, descriptive statistics of the collected data, and results from our extensive exploratory analyses. Our novel data, conceptual development, and analytical findings provide important guidance for data collection and hypothesis generation in future human-centric sensing studies.This work was supported by Whole Communities—Whole Health, a research grand challenge at the University of Texas at Austin, and National Science Foundation Award SES-1758835.Office of the VP for Researc

Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences (SPARCS) are oriented inversely in 3' untranslated regions of specific genes enriched for regulation by STAT1 and EZH2. Derepression of these loci results in double-stranded RNA generation following IFN-γ exposure due to bi-directional transcription from the STAT1-activated gene promoter and the 5' long terminal repeat of the antisense ERV. Engagement of MAVS and STING activates downstream TBK1, IRF3, and STAT1 signaling, sustaining a positive feedback loop. SPARCS induction in human tumors is tightly associated with major histocompatibility complex class 1 expression, mesenchymal markers, and downregulation of chromatin modifying enzymes, including EZH2. Analysis of cell lines with high inducible SPARCS expression reveals strong association with an AXL/MET-positive mesenchymal cell state. While SPARCS-high tumors are immune infiltrated, they also exhibit multiple features of an immune-suppressed microenviroment. Together, these data unveil a subclass of ERVs whose derepression triggers pathologic innate immune signaling in cancer, with important implications for cancer immunotherapy