Probing the cancer genome

A report on the Keystone Symposium 'Cancer Genomics and Epigenomics', Taos, USA, 19-24 February 2008

The Barycentric Coordinates Solution to the Optimal Road Junction Problem

The road junction location problems, first posited by Fermat and later generalized by Simpson, is a fundamental component of optimal network design. The barycentric resection formulas of plane surveying provide a solution of elegant simplicity to this problem. Prerequisite junction point angles for the application of the resection formulas are obtained directly from Launhardt's original analytical development of this fundamental problem in route location

Estimation of Turn Location Parameters for Cable Settings

Managers of cable yarding systems, confronted with inherently high owning and operating costs in a very competitive economic environment, need timely, inexpensive and accurate estimates of yarding production. Yarding time, and thereby production, depend on the location of the turn relative to the landing to which it must be transported. Among the important location attributes of a turn are distance and slope to the landing. For all of the turns on a setting the frequency distributions of these attributes are described by turn location parameters. Among the turn location parameters (TLPs) used by forest engineers are average yarding distance and average yarding slope. The assumptions under which a relatively new class of TLP estimators has been developed are discussed in this paper. Recognition of these assumptions and full appreciation of the limitations thereby imposed on the use of the estimators are essential to judicious application of the methodology. Formulas and procedures are given for calculation of numerical estimates and, in order to clarify and illustrate their use, an example is given

Average Yarding Distance for Row Thinning of Plantations

An average yarding distance model for rectilinear skidtrail layout from a centralized landing is given. The model is appropriate to the evaluation of some row thinning designs in plantations. The theoretical basis for formulas used in the model is briefly described. The model was coded for computer solution and applied to a hypothetical example the results of which are presented

Activating Mutations in ERBB2 and Their Impact on Diagnostics and Treatment

Despite the ongoing “war on cancer,” cancer remains one of the major causes of human morbidity and mortality. A new paradigm of targeted therapies holds the most promise for the future, making identification of tumor-specific therapeutic targets of prime importance. ERBB2/HER2, best known for its role in breast cancer tumorigenesis, can be targeted by two types of pharmacological manipulation: antibody therapy against the extracellular receptor domain and small molecule compounds against the intracellular tyrosine kinase domain. Aberrant activation of ERBB2 by gene amplification has been shown to participate in the pathophysiology of breast, ovarian, gastric, colorectal, lung, brain, and head and neck tumors. However, the advent of next-generation sequencing technologies has enabled efficient identification of activating molecular alterations of ERBB2. In this review, we will focus on the functional role of these somatic mutations that cause ERBB2 receptor activation. We will additionally discuss the current preclinical and clinical therapeutic strategies for targeting mutationally activated ERBB2

On the segmentation and classification of hand radiographs

This research is part of a wider project to build predictive models of bone age using hand radiograph images. We examine ways of finding the outline of a hand from an X-ray as the first stage in segmenting the image into constituent bones. We assess a variety of algorithms including contouring, which has not previously been used in this context. We introduce a novel ensemble algorithm for combining outlines using two voting schemes, a likelihood ratio test and dynamic time warping (DTW). Our goal is to minimize the human intervention required, hence we investigate alternative ways of training a classifier to determine whether an outline is in fact correct or not. We evaluate outlining and classification on a set of 1370 images. We conclude that ensembling with DTW improves performance of all outlining algorithms, that the contouring algorithm used with the DTW ensemble performs the best of those assessed, and that the most effective classifier of hand outlines assessed is a random forest applied to outlines transformed into principal components

SNP panel identification assay (SPIA): a genetic-based assay for the identification of cell lines

Translational research hinges on the ability to make observations in model systems and to implement those findings into clinical applications, such as the development of diagnostic tools or targeted therapeutics. Tumor cell lines are commonly used to model carcinogenesis. The same tumor cell line can be simultaneously studied in multiple research laboratories throughout the world, theoretically generating results that are directly comparable. One important assumption in this paradigm is that researchers are working with the same cells. However, recent work using high throughput genomic analyses questions the accuracy of this assumption. Observations by our group and others suggest that experiments reported in the scientific literature may contain pre-analytic errors due to inaccurate identities of the cell lines employed. To address this problem, we developed a simple approach that enables an accurate determination of cell line identity by genotyping 34 single nucleotide polymorphisms (SNPs). Here, we describe the empirical development of a SNP panel identification assay (SPIA) compatible with routine use in the laboratory setting to ensure the identity of tumor cell lines and human tumor samples throughout the course of long term research use

Suitability versus fidelity for rating single-photon guns

The creation of specified quantum states is important for most, if not all, applications in quantum computation and communication. The quality of the state preparation is therefore an essential ingredient in any assessment of a quantum-state gun. We show that the fidelity, under the standard definitions is not sufficient to assess quantum sources, and we propose a new measure of suitability that necessarily depends on the application for the source. We consider the performance of single-photon guns in the context of quantum key distribution (QKD) and linear optical quantum computation. Single-photon sources for QKD need radically different properties than sources for quantum computing. Furthermore, the suitability for single-photon guns is discussed explicitly in terms of experimentally accessible criteria.Comment: 4 pages, 2 figures Revised per referee suggestion

Effect of Thiamine Status on Probability of Lake Ontario Chinook Salmon Spawning in the Upper and Lower Sections of Salmon River, New York

Consumption of thiaminase-containing forage fishes reduces egg and muscle thiamine content and impairs the spawning migration of Cayuga Lake (New York) rainbow trout Oncorhynchus mykiss. Because some Chinook salmon O. tshawytscha from Lake Ontario have been shown to produce eggs low in thiamine, we examined the relationship between the migration of Chinook salmon and the thiamine content of their eggs spawned in the lower and upper sections of the Salmon River, a major tributary to Lake Ontario, in 2003–2006. Eggs from the upper section of the river were collected from 79 salmon returning to the state hatchery 25 river kilometers from the mouth. Eggs from 25 salmon in the lower section were collected from redds or females angled on redds approximately 1–3 km from the mouth. For all years combined, we found the mean thiamine concentration in eggs spawned in the lower section to be significantly lower than that for eggs spawned in the upper section; however, the annual differences in thiamine content of eggs between the upper and lower sections were significant only in 2003 and 2006. Binary logistic regression showed that the odds of spawning in the upper section was increased by 96% (95% confidence interval, 21–217%) for every nanomole of increase in the thiamine content of eggs. Therefore, the migratory achievement of Chinook salmon was significantly dependent on their thiamine status

2015 Update on Acute Adverse Reactions to Gadolinium based Contrast Agents in Cardiovascular MR. Large Multi-National and Multi-Ethnical Population Experience With 37788 Patients From the EuroCMR Registry

Objectives: Specifically we aim to demonstrate that the results of our earlier safety data hold true in this much larger multi-national and multi-ethnical population. Background: We sought to re-evaluate the frequency, manifestations, and severity of acute adverse reactions associated with administration of several gadolinium- based contrast agents during routine CMR on a European level. Methods: Multi-centre, multi-national, and multi-ethnical registry with consecutive enrolment of patients in 57 European centres. Results: During the current observation 37788 doses of Gadolinium based contrast agent were administered to 37788 patients. The mean dose was 24.7 ml (range 5–80 ml), which is equivalent to 0.123 mmol/kg (range 0.01 - 0.3 mmol/kg). Forty-five acute adverse reactions due to contrast administration occurred (0.12 %). Most reactions were classified as mild (43 of 45) according to the American College of Radiology definition. The most frequent complaints following contrast administration were rashes and hives (15 of 45), followed by nausea (10 of 45) and flushes (10 of 45). The event rate ranged from 0.05 % (linear non-ionic agent gadodiamide) to 0.42 % (linear ionic agent gadobenate dimeglumine). Interestingly, we also found different event rates between the three main indications for CMR ranging from 0.05 % (risk stratification in suspected CAD) to 0.22 % (viability in known CAD). Conclusions: The current data indicate that the results of the earlier safety data hold true in this much larger multi-national and multi-ethnical population. Thus, the “off-label” use of Gadolinium based contrast in cardiovascular MR should be regarded as safe concerning the frequency, manifestation and severity of acute events