Integrating biological knowledge into variable selection : an empirical Bayes approach with an application in cancer biology

Background: An important question in the analysis of biochemical data is that of identifying subsets of molecular variables that may jointly influence a biological response. Statistical variable selection methods have been widely used for this purpose. In many settings, it may be important to incorporate ancillary biological information concerning the variables of interest. Pathway and network maps are one example of a source of such information. However, although ancillary information is increasingly available, it is not always clear how it should be used nor how it should be weighted in relation to primary data. Results: We put forward an approach in which biological knowledge is incorporated using informative prior distributions over variable subsets, with prior information selected and weighted in an automated, objective manner using an empirical Bayes formulation. We employ continuous, linear models with interaction terms and exploit biochemically-motivated sparsity constraints to permit exact inference. We show an example of priors for pathway- and network-based information and illustrate our proposed method on both synthetic response data and by an application to cancer drug response data. Comparisons are also made to alternative Bayesian and frequentist penalised-likelihood methods for incorporating network-based information. Conclusions: The empirical Bayes method proposed here can aid prior elicitation for Bayesian variable selection studies and help to guard against mis-specification of priors. Empirical Bayes, together with the proposed pathway-based priors, results in an approach with a competitive variable selection performance. In addition, the overall procedure is fast, deterministic, and has very few user-set parameters, yet is capable of capturing interplay between molecular players. The approach presented is general and readily applicable in any setting with multiple sources of biological prior knowledge

Manganese Oxide Thin Films Prepared by Nonaqueous Sol-Gel Processing: Preferential Formation of Birnessite

High quality manganese oxide thin films with smooth surfaces and even thicknesses have been prepared with a nonaqueous sol–gel process involving reduction of tetraethylammonium permanganate in methanol. Spin-coated films have been cast onto soft glass, quartz, and Ni foil substrates, with two coats being applied for optimum crystallization. The addition of alkali metal cations as dopants results in exclusive formation of the layered birnessite phase. By contrast, analogous reactions in bulk sol–gel reactions yield birnessite, tunneled, and spinel phases depending on the dopant cation. XRD patterns confirm the formation of well-crystallized birnessite. SEM images of Li-, Na-, and K–birnessite reveal extremely smooth films having uniform thickness of less than 0.5 μm. Thin films of Rb– and Cs–birnessite have more fractured and uneven surfaces as a result of some precipitation during the sol–gel transformation. All films consist of densely packed particles of about 0.1 μm. When tetrabutylammonium permanganate is used instead of tetraethylammonium permanganate, the sol–gel reaction yields amorphous manganese oxide as the result of diluted Mn sites in the xerogel film. Bilayer films have been prepared by casting an overcoat of K–birnessite onto an Na–birnessite film. However, Auger depth profiling indicates considerable mixing between the adjacent layers

Long noncoding RNAs in liver cancer: what we know in 2014.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer with an estimated over half a million new cases diagnosed annually. Due to the difficulty in early diagnosis and lack of effective treatment options, HCC is currently ranked as the second highest neoplastic-related mortality in the world, with an extremely low 5-year survival rate of between 6 and 11%. Long noncoding RNAs (lncRNAs), are genes lacking protein coding ability, have recently emerged as pivotal participants in biological processes, often dysregulated in a range of cancers, including HCC. AREAS COVERED: In this review, we highlight the recent findings of lncRNAs in HCC pathogenesis, with particular attention on epigenetic events. In silico analysis was utilized to emphasize intrinsic linkages within the ncRNA families associated with hepatocarcinogenesis. EXPERT OPINION: While our understanding of lncRNAs in the onset and progression of HCC is still in its infancy, there is no doubt that understanding the activities of ncRNAs will certainly secure strong biomarkers and improve treatment options for HCC patients

Toward tactilely transparent gloves: Collocated slip sensing and vibrotactile actuation

Tactile information plays a critical role in the human ability to manipulate objects with one\u27s hands. Many environments require the use of protective gloves that diminish essential tactile feedback. Under these circumstances, seemingly simple tasks such as picking up an object can become very difficult. This paper introduces the SlipGlove, a novel device that uses an advanced sensing and actuation system to return this vital tactile information to the user. Our SlipGlove prototypes focus on providing tactile cues associated with slip between the glove and a contact surface. Relative motion is sensed using optical mouse sensors embedded in the glove\u27s surface. This information is conveyed to the wearer via miniature vibration motors placed inside the glove against the wearer\u27s skin. The collocation of slip sensing and tactile feedback creates a system that is natural and intuitive to use. We report results from a human subject study demonstrating that the SlipGlove allows the wearer to approach the capabilities of bare skin in detecting and reacting to fingertip slip. Users of the SlipGlove also had significantly faster and more consistent reaction to fingertip slip when compared to a traditional glove design. The SlipGlove technology allows us to enhance human perception when interacting with real environments and move toward the goal of a tactilely transparent glove

Autonomic nervous system involvement in the giant axonal neuropathy (GAN) KO mouse: implications for human disease

Giant axonal neuropathy (GAN) is an inherited severe sensorimotor neuropathy. The aim of this research was to investigate the neuropathologic features and clinical autonomic nervous system (ANS) phenotype in two GAN knockout (KO) mouse models. Little is known about ANS involvement in GAN in humans, but autonomic signs and symptoms are commonly reported in early childhood

Co-Producing a Shared Characterization of Depredation in the Gulf of Mexico Reef Fish Fishery: Comprehensive Report

Depredation, defined as the partial or complete removal of a hooked fish by a non-target species, is a cryptic form of mortality that can affect the accuracy of stock assessments and species management efforts. Accounting for depredation is crucial to minimize uncertainty in stock assessment models and to obtain accurate and reliable fisheries catch data. If these interactions are frequent, failure to properly quantify this form of mortality can lead to the underestimation of reef fish population removals, inappropriate harvest recommendations, and stakeholder unrest. In recent years, depredation has escalated in the Gulf of Mexico (GoM) reef fish fishery. Although GoM reef fish fishery stakeholders (fishermen) have actively pushed for resource managers to implement solutions to address these increasingly pervasive interactions, a comprehensive characterization of this issue is lacking, and trends surrounding GoM reef fish depredation – as well as factors that impact depredation – have not been adequately described or evaluated. Therefore, the objective of this project was to co-produce a shared characterization of the impacts of depredation in the GoM reef fish fishery. To accomplish this, we employed a three-phased approach consisting of synthesis (phase 1), survey (phase 2), and feedback (phase 3). During phase 1, we synthesized data from the NOAA Fisheries Southeast Fisheries Science Center (SEFSC) GoM Reef Fish Observer Program, the largest and longest depredation-related dataset available. Marked increases in depredation were shown starting in 2017 for both bottom longline and vertical longline, particularly in the Eastern GoM. To complement the analysis of the commercial sector from phase 1, we designed and implemented an electronic survey of private recreational anglers in phase 2. Survey results demonstrate that anglers across the GoM routinely experience depredation and have identified a variety of influential factors such as geographic location and depth. Surprisingly, depredation has not affected fishing behavior for the majority of those surveyed. Findings from the commercial fishery (phase 1) and private recreational fishery (phase 2) were then presented to a representative group of (predominantly) charter-for-hire fishermen during an in-person, collaborative participatory modeling workshop (phase 3). These stakeholders provided unique insights, suggesting that factors like the length of the red snapper fishing season, recreational angler high-grading, and a diminished GoM shrimp trawl fleet, have led to increases in depredation. Perhaps more importantly, these stakeholders noted a growing disconnect between their on-the-water observations (i.e., increased depredation), and what they perceived as an increasing desire from NOAA Fisheries and the general public to protect all sharks. Notably, these sentiments resulted in a lack of trust with respect to shark science, stock assessments, and resource management. Ultimately, this planning project led to a deeper understanding of shark depredation in the GoM commercial, private recreational, and charter-for-hire fisheries. Project findings formed the basis of a comprehensive Research and Development Plan and an Application Plan. In addition, data and insights from this planning project contributed to a peer-reviewed depredation review (Mitchell et al. 2022), a stock assessment report (Drymon et al. 2022), a manuscript in prep (Duffin et al.), five conference presentations, and three outreach products.

A case of recurrent giant cell tumor of bone with malignant transformation and benign pulmonary metastases

Giant cell tumor (GCT) of bone is a locally destructive tumor that occurs predominantly in long bones of post-pubertal adolescents and young adults, where it occurs in the epiphysis. The majority are treated by aggressive curettage or resection. Vascular invasion outside the boundary of the tumor can be seen. Metastasis, with identical morphology to the primary tumor, occurs in a few percent of cases, usually to the lung. On occasion GCTs of bone undergo frank malignant transformation to undifferentiated sarcomas. Here we report a case of GCT of bone that at the time of recurrence was found to have undergone malignant transformation. Concurrent metastases were found in the lung, but these were non-transformed GCT

High-Intensity Radiated Field Fault-Injection Experiment for a Fault-Tolerant Distributed Communication System

Safety-critical distributed flight control systems require robustness in the presence of faults. In general, these systems consist of a number of input/output (I/O) and computation nodes interacting through a fault-tolerant data communication system. The communication system transfers sensor data and control commands and can handle most faults under typical operating conditions. However, the performance of the closed-loop system can be adversely affected as a result of operating in harsh environments. In particular, High-Intensity Radiated Field (HIRF) environments have the potential to cause random fault manifestations in individual avionic components and to generate simultaneous system-wide communication faults that overwhelm existing fault management mechanisms. This paper presents the design of an experiment conducted at the NASA Langley Research Center's HIRF Laboratory to statistically characterize the faults that a HIRF environment can trigger on a single node of a distributed flight control system