Machine learning techniques for the prediction of indoor gamma-ray dose rates - Strengths, weaknesses and implications for epidemiology.

We investigate methods that improve the estimation of indoor gamma ray dose rates at locations where measurements had not been made. These new predictions use a greater range of modelling techniques and larger variety of explanatory variables than our previous examinations of this subject. Specifically, we now employ three types of machine learning models in addition to the geostatistical, nearest neighbour and other earlier models.

Gene model for the ortholog in .

Gene model for the ortholog of Myc ( ) in the May 2011 (Agencourt dana_caf1/DanaCAF1) Genome Assembly (GenBank Accession: GCA_000005115.1 ) of . This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.

An accessible digital imaging workflow for multiplexed quantitative analysis of adult eye phenotypes in .

The compound eye of has long been a model for studying genetics, development, neurodegeneration, and heterochromatin. Imaging and morphometry of adult and other insects is hampered by the low throughput, narrow focal plane, and small image sensors typical of stereomicroscope cameras. When data collection is distributed among many individuals or extended time periods, these limitations are compounded by inter-operator variability in lighting, sample positioning, focus, and post-acquisition processing.

Effects of stopping criterion on the growth of trees in regression random forests.

Random forests are a powerful machine learning tool that capture complex relationships between independent variables and an outcome of interest. Trees built in a random forest are dependent on several hyperparameters, one of the more critical being the node size. The original algorithm of Breiman, controls for node size by limiting the size of the parent node, so that a node cannot be split if it has less than a specified number of observations.

Smoothing Lexis diagrams using kernel functions: A contemporary approach.

Lexis diagrams are rectangular arrays of event rates indexed by age and period. Analysis of Lexis diagrams is a cornerstone of cancer surveillance research. Typically, population-based descriptive studies analyze multiple Lexis diagrams defined by sex, tumor characteristics, race/ethnicity, geographic region, etc.

Cost-effectiveness analysis under multiple effectiveness outcomes: A probabilistic approach.

Probability based criteria are proposed for the assessment of cost-effectiveness of a new treatment compared to a standard treatment when there are multiple effectiveness measures. Depending on the preferences of a policy maker, there are several options to define such criteria. Two such metrics are investigated in detail.

Alternative stopping rules to limit tree expansion for random forest models.

Random forests are a popular type of machine learning model, which are relatively robust to overfitting, unlike some other machine learning models, and adequately capture non-linear relationships between an outcome of interest and multiple independent variables. There are relatively few adjustable hyperparameters in the standard random forest models, among them the minimum size of the terminal nodes on each tree. The usual stopping rule, as proposed by Breiman, stops tree expansion by limiting the size of the parent nodes, so that a node cannot be split if it has less than a specified number of observations.

Student Attitudes Contribute to the Effectiveness of a Genomics CURE.

The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit. We found, in general, that the attitudes students bring with them into the classroom contribute to two outcome measures, namely, learning as assessed by a pre- and postquiz and perceived self-reported benefits.

Facilitating Growth through Frustration: Using Genomics Research in a Course-Based Undergraduate Research Experience.

A hallmark of the research experience is encountering difficulty and working through those challenges to achieve success. This ability is essential to being a successful scientist, but replicating such challenges in a teaching setting can be difficult. The Genomics Education Partnership (GEP) is a consortium of faculty who engage their students in a genomics Course-Based Undergraduate Research Experience (CURE).

A genetic screen in Drosophila reveals novel cytoprotective functions of the autophagy-lysosome pathway.

The highly conserved autophagy-lysosome pathway is the primary mechanism for breakdown and recycling of macromolecular and organellar cargo in the eukaryotic cell. Autophagy has recently been implicated in protection against cancer, neurodegeneration, and infection, and interest is increasing in additional roles of autophagy in human health, disease, and aging. To search for novel cytoprotective features of this pathway, we carried out a genetic mosaic screen for mutations causing increased lysosomal and/or autophagic activity in the Drosophila melanogaster larval fat body.

Nutrient-dependent regulation of autophagy through the target of rapamycin pathway.

In response to nutrient deficiency, eukaryotic cells activate macroautophagy, a degradative process in which proteins, organelles and cytoplasm are engulfed within unique vesicles called autophagosomes. Fusion of these vesicles with the endolysosomal compartment leads to breakdown of the sequestered material into amino acids and other simple molecules, which can be used as nutrient sources during periods of starvation. This process is driven by a group of autophagy-related (Atg) proteins, and is suppressed by TOR (target of rapamycin) signalling under favourable conditions.

Mechanisms of TSC-mediated control of synapse assembly and axon guidance.

Tuberous sclerosis complex is a dominant genetic disorder produced by mutations in either of two tumor suppressor genes, TSC1 and TSC2; it is characterized by hamartomatous tumors, and is associated with severe neurological and behavioral disturbances. Mutations in TSC1 or TSC2 deregulate a conserved growth control pathway that includes Ras homolog enriched in brain (Rheb) and Target of Rapamycin (TOR). To understand the function of this pathway in neural development, we have examined the contributions of multiple components of this pathway in both neuromuscular junction assembly and photoreceptor axon guidance in Drosophila.

Thinking globally and acting locally with TOR.

The target of rapamycin (TOR) pathway regulates ribosome biogenesis, protein synthesis, nutrient import, autophagy and cell cycle progression. After 30 years of concentrated attention, how TOR controls these processes is only now beginning to be understood. Recent advances have identified a wide array of TOR inputs, including amino acids, oxygen, ATP and growth factors, as well the regulatory proteins that facilitate their effects on TOR.

HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth.

The division, differentiation, and function of stem cells and multipotent progenitors are influenced by complex signals in the microenvironment, including oxygen availability. Using a genetic "knock-in" strategy, we demonstrate that targeted replacement of the oxygen-regulated transcription factor HIF-1alpha with HIF-2alpha results in expanded expression of HIF-2alpha-specific target genes including Oct-4, a transcription factor essential for maintaining stem cell pluripotency. We show that HIF-2alpha, but not HIF-1alpha, binds to the Oct-4 promoter and induces Oct-4 expression and transcriptional activity, thereby contributing to impaired development in homozygous Hif-2alpha KI/KI embryos, defective hematopoietic stem cell differentiation in embryoid bodies, and large embryonic stem cell (ES)-derived tumors characterized by altered cellular differentiation.

Mxi1 is induced by hypoxia in a HIF-1-dependent manner and protects cells from c-Myc-induced apoptosis.

HIF-1, a hypoxia inducible transcription factor, plays a pivotal role in the cellular response to hypoxia by activating genes involved in glucose metabolism, vascular remodeling, and erythropoiesis. We identified Mxi1, a c-Myc antagonist, as a novel target gene induced in hypoxia. Mxi1 was not induced in cells deficient in ARNT (HIF-1beta), suggesting that Mxi1 is a transcriptional target of the HIF-1 complex.

Akt and hypoxia-inducible factor-1 independently enhance tumor growth and angiogenesis.

Recent reports have suggested that phosphatidylinositol 3-kinase/Akt signaling can induce angiogenesis and tumor growth by activating the hypoxia-inducible factor-1 (HIF-1). However, the absence of specific biochemical inhibitors of HIF-1 signaling has prevented a direct test of the requirement for HIF-1 activity in Akt-dependent tumorigenesis. To genetically test the relationship between HIF-1 and Akt, activated Akt was expressed in a hepatoma cell line lacking HIF-1.

A novel hypoxia-inducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets.

Hypoxia triggers a reversible inhibition of protein synthesis thought to be important for energy conservation in O2-deficient environments. The mammalian target of rapamycin (mTOR) pathway integrates multiple environmental cues to regulate translation in response to nutrient availability and stress, suggesting it as a candidate for O2 regulation. We show here that hypoxia rapidly and reversibly triggers hypophosphorylation of mTOR and its effectors 4E-BP1, p70S6K, rpS6, and eukaryotic initiation factor 4G.

Loss of pVHL is sufficient to cause HIF dysregulation in primary cells but does not promote tumor growth.

Inactivation of the von Hippel-Lindau (VHL) gene is associated with the development of highly vascularized tumors. pVHL targets the alpha subunits of hypoxia inducible factor (HIF) for ubiquitin-mediated degradation in an oxygen-dependent manner. Although pVHL-deficient tumor cell lines demonstrate constitutive stabilization and activation of HIF, it has yet to be shown that loss of murine Vhl alone is sufficient to dysregulate HIF.

Phosphatidylinositol 3-kinase/Akt signaling is neither required for hypoxic stabilization of HIF-1 alpha nor sufficient for HIF-1-dependent target gene transcription.

The serine/threonine kinase Akt/PKB and the oxygen-responsive transcription factor HIF-1 share the ability to induce such processes as angiogenesis, glucose uptake, and glycolysis. Akt activity and HIF-1 are both essential for development and implicated in tumor growth. Upon activation by products of phosphatidylinositol 3-kinase (PI3K), Akt phosphorylates downstream targets that stimulate growth and inhibit apoptosis.

The role of ARNT2 in tumor angiogenesis and the neural response to hypoxia.

The Hypoxia-Inducible Factor-1 (HIF-1) activates the transcription of many genes required for cellular and organismal responses to oxygen deprivation. The HIF-1 complex is composed of the ubiquitously expressed basic helix-loop-helix/PAS (bHLH/PAS) proteins HIF-1alpha and Arylhydrocarbon Receptor Nuclear Translocator (ARNT). ARNT2 is a conserved ARNT homolog that is highly expressed in neurons, suggesting that ARNT2/HIF-1alpha heterodimers mediate transcriptional responses to oxygen deprivation in the nervous system.