Modeling intra-tumor protein expression heterogeneity in tissue microarray experiments

Tissue microarrays (TMAs) measure tumor-specific protein expression via high-density immunohistochemical staining assays. They provide a proteomic platform for validating cancer biomarkers emerging from large-scale DNA microarray studies. Repeated observations within each tumor result in substantial biological and experimental variability. This variability is usually ignored when associating the TMA expression data with patient survival outcome. It generates biased estimates of hazard ratio in proportional hazards models. We propose a Latent Expression Index (LEI) as a surrogate protein expression estimate in a two-stage analysis. Several estimators of LEI are compared: an empirical Bayes, a full Bayes, and a varying replicate number estimator. In addition, we jointly model survival and TMA expression data via a shared random effects model. Bayesian estimation is carried out using a Markov chain Monte Carlo method. Simulation studies were conducted to compare the two-stage methods and the joint analysis in estimating the Cox regression coefficient. We show that the two-stage methods reduce bias relative to the naive approach, but still lead to under-estimated hazard ratios. The joint model consistently outperforms the two-stage methods in terms of both bias and coverage property in various simulation scenarios. In case studies using prostate cancer TMA data sets, the two-stage methods yield a good approximation in one data set whereas an insufficient one in the other. A general advice is to use the joint model inference whenever results differ between the two-stage methods and the joint analysis. Copyright © 2008 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58565/1/3217_ftp.pd

Comparison of methods for estimating the effect of salvage therapy in prostate cancer when treatment is given by indication

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102122/1/sim5890.pd

Evaluation of Crop Production and Water Use Efficiency of Autumn-Sown Annual Forage Crops on the Rainfed Region of Loess Plateau China

The Loess Plateau is one of the most important rainfed regions in China, but rainfall is the most significant factor limiting crop production. In this region rainfall from July to September accounts for 56% of the annual total, providing enough water resources for the growth of autumn-sown crops. Although increasing forage production with autumn sown crops is considered an important means of balancing crop forage and livestock management, suitable species with high yields and good water use efficiency (WUE) are not well defined. The relationship between yield and water use efficiency has been shown to vary with plant species and harvest time (Siahpoosh et al. 2011), indicating that good water management can increase yields. It is therefore necessary to establish efficient water management strategies to increase the yield of autumn-sown crops. The objective of this study was to evaluate annual production of forage crops under autumn sowing conditions and identify their optimal WUE, based on crop production and evapo-transpiration (ET)

Relation of Residue Biomass after Defoliation to Regrowth Dry Matter, WSC and Grain Yield of Winter Wheat

The importance of defoliation height on final yield in dual-purpose wheat is inconsistent. In one study no difference in final wheat yield following a severe grazing at 2 cm compared to light grazing at 6 cm was found (Dann et al. 1983). In contrast, clipping at 3 cm above ground level significantly reduced grain yield compared to 7 cm (Arzadun et al. 2006). An explanation for these inconsistent results may be an underestimation of the value of the remaining biomass and its role in the regrowth process (Fulkerson and Donaghy 2001). In this study, the percentage of residue biomass remaining after defoliation was considered when examining the effect of defoliation height on dry matter accumulation and water-soluble carbohydrate (WSC) during wheat regrowth on the Loess plateau, China

Hybrid Group IV Nanophotonic Structures Incorporating Diamond Silicon-Vacancy Color Centers

We demonstrate a new approach for engineering group IV semiconductor-based quantum photonic structures containing negatively charged silicon-vacancy (SiV$^-$) color centers in diamond as quantum emitters. Hybrid SiC/diamond structures are realized by combining the growth of nanoand micro-diamonds on silicon carbide (3C or 4H polytype) substrates, with the subsequent use of these diamond crystals as a hard mask for pattern transfer. SiV$^-$ color centers are incorporated in diamond during its synthesis from molecular diamond seeds (diamondoids), with no need for ionimplantation or annealing. We show that the same growth technique can be used to grow a diamond layer controllably doped with SiV$^-$ on top of a high purity bulk diamond, in which we subsequently fabricate nanopillar arrays containing high quality SiV$^-$ centers. Scanning confocal photoluminescence measurements reveal optically active SiV$^-$ lines both at room temperature and low temperature (5 K) from all fabricated structures, and, in particular, very narrow linewidths and small inhomogeneous broadening of SiV$^-$ lines from all-diamond nano-pillar arrays, which is a critical requirement for quantum computation. At low temperatures (5 K) we observe in these structures the signature typical of SiV$^-$ centers in bulk diamond, consistent with a double lambda. These results indicate that high quality color centers can be incorporated into nanophotonic structures synthetically with properties equivalent to those in bulk diamond, thereby opening opportunities for applications in classical and quantum information processing

Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli

AbstractSonic Hedgehog (Shh) signals are transduced into nuclear ratios of Gli transcriptional activator versus repressor. The initial part of this process is accomplished by Shh acting through Patched (Ptc) to regulate Smoothened (Smo) activity. The mechanisms by which Ptc regulates Smo, and Smo activity is transduced to processing of Gli proteins remain unclear. Recently, a forward genetic approach in mice identified a role for intraflagellar transport (IFT) genes in Shh signal transduction, downstream of Patched (Ptc) and Rab23. Here, we show that the retrograde motor for IFT is required in the mouse for the phenotypic expression of both Gli activator and repressor function and for effective proteolytic processing of Gli3. Furthermore, we show that the localization of Smo to primary cilia is disrupted in mutants. These data indicate that primary cilia act as specialized signal transduction organelles required for coupling Smo activity to the biochemical processing of Gli3 protein

Archangel: A Hybrid UAV-based Human Detection Benchmark with Position and Pose Metadata

Learning to detect objects, such as humans, in imagery captured by an unmanned aerial vehicle (UAV) usually suffers from tremendous variations caused by the UAV's position towards the objects. In addition, existing UAV-based benchmark datasets do not provide adequate dataset metadata, which is essential for precise model diagnosis and learning features invariant to those variations. In this paper, we introduce Archangel, the first UAV-based object detection dataset composed of real and synthetic subsets captured with similar imagining conditions and UAV position and object pose metadata. A series of experiments are carefully designed with a state-of-the-art object detector to demonstrate the benefits of leveraging the metadata during model evaluation. Moreover, several crucial insights involving both real and synthetic data during model optimization are presented. In the end, we discuss the advantages, limitations, and future directions regarding Archangel to highlight its distinct value for the broader machine learning community.Comment: Submission to IEEE Acces

Photocathode device using diamondoid and cesium bromide films

A photocathode structure is presented that shows promise for use in high brightness electron sources. The structure consists of a metal substrate, a monolayer of a diamondoid derivative, and a thin film of cesium bromide. Diamondoid monolayers reduce the energy spread of electron emitters, while cesium bromide increases the yield and stability of cathodes. We demonstrate that the combined structure retains these properties, producing an emitter with lower energy spread than the corresponding cesium bromide emitter (1.06?eV versus 1.45?eV) and higher yield and stability than un-coated diamondoid emitters

Quantifying Behavioral Sensation Seeking With the Aroma Choice Task

Our goal was to develop a behavioral measure of sensation seeking (SS). The Aroma Choice Task (ACT) assesses preference for an intense, novel, varied, and risky (exciting) option versus a mild, safe (boring) option using real-time odorant delivery. A total of 147 healthy young adults completed 40 binary choice trials. We examined (1) intensity and pleasantness of odorants, (2) stability of responding, (3) association with SS self-report, and (4) association with self-reported illicit drug use. Participants’ preference for the “exciting” option versus the safe option was significantly associated with self-reported SS (p < .001) and illicit drug use (p = .041). Odorant ratings comported with their intended intensity. The ACT showed good internal, convergent, and criterion validity. We propose that the ACT might permit more objective SS assessment for investigating the biological bases of psychiatric conditions marked by high SS, particularly addiction. The ACT measures SS behaviorally, mitigating some self-report challenges and enabling real-time assessment, for example, for functional magnetic resonance imaging (fMRI)