Receptor tyrosine kinase and p16/CDKN2 expression in a case of tripe palms associated with non-small-cell lung cancer

Background: Tripe palms is a descriptive term for a cutaneous paraneoplastic keratoderma. Tripe palms are frequently associated with gastric and pulmonary carcinoma. The pathogenetic mechanism remains unknown. Objective: To determine the influence of receptor tyrosine kinases, which are both expressed in pulmonary carcinomas and in human skin, we performed expression studies on epidermal growth factor receptor (EGFR), HER2, HERS in a skin sample of tripe palms obtained from a patient with non-small-cell lung cancer with lymph node involvement. Two months after diagnosis, the patient had developed palmoplantar `tripe palms'. Additionally, the expression of SRC, c-myc and p16/CDKN2 were studied. Method: Conventional reverse-transcription polymerase chain reaction was performed on a tissue sample of tripe palms. Results: Weak expression of HER2 and of p16/CDKN2 was found. EGFR, HERS, c-myc and SRC were not expressed. Conclusion: Receptor tyrosine kinases of subclass I, the tyrosine kinase SRC and the oncogene c-myc play no major role in the pathogenesis of this case of tripe palms. Copyright (C) 2000 S. Karger AG. Basel

Pediatric Bone Age Assessment Using Deep Convolutional Neural Networks

Skeletal bone age assessment is a common clinical practice to diagnose endocrine and metabolic disorders in child development. In this paper, we describe a fully automated deep learning approach to the problem of bone age assessment using data from Pediatric Bone Age Challenge organized by RSNA 2017. The dataset for this competition is consisted of 12.6k radiological images of left hand labeled by the bone age and sex of patients. Our approach utilizes several deep learning architectures: U-Net, ResNet-50, and custom VGG-style neural networks trained end-to-end. We use images of whole hands as well as specific parts of a hand for both training and inference. This approach allows us to measure importance of specific hand bones for the automated bone age analysis. We further evaluate performance of the method in the context of skeletal development stages. Our approach outperforms other common methods for bone age assessment.Comment: 14 pages, 9 figure

Particle interactions and lattice dynamics: Scenarios for efficient bidirectional stochastic transport?

Intracellular transport processes driven by molecular motors can be described by stochastic lattice models of self-driven particles. Here we focus on bidirectional transport models excluding the exchange of particles on the same track. We explore the possibility to have efficient transport in these systems. One possibility would be to have appropriate interactions between the various motors' species, so as to form lanes. However, we show that the lane formation mechanism based on modified attachment/detachment rates as it was proposed previously is not necessarily connected to an efficient transport state and is suppressed when the diffusivity of unbound particles is finite. We propose another interaction mechanism based on obstacle avoidance that allows to have lane formation for limited diffusion. Besides, we had shown in a separate paper that the dynamics of the lattice itself could be a key ingredient for the efficiency of bidirectional transport. Here we show that lattice dynamics and interactions can both contribute in a cooperative way to the efficiency of transport. In particular, lattice dynamics can decrease the interaction threshold beyond which lanes form. Lattice dynamics may also enhance the transport capacity of the system even when lane formation is suppressed.Comment: 25 pages, 17 figures, 2 table

Single-Bottleneck Approximation for Driven Lattice Gases with Disorder and Open Boundary Conditions

We investigate the effects of disorder on driven lattice gases with open boundaries using the totally asymmetric simple exclusion process as a paradigmatic example. Disorder is realized by randomly distributed defect sites with reduced hopping rate. In contrast to equilibrium, even macroscopic quantities in disordered non-equilibrium systems depend sensitively on the defect sample. We study the current as function of the entry and exit rates and the realization of disorder and find that it is, in leading order, determined by the longest stretch of consecutive defect sites (single-bottleneck approximation, SBA). Using results from extreme value statistics the SBA allows to study ensembles with fixed defect density which gives accurate results, e.g. for the expectation value of the current. Corrections to SBA come from effective interactions of bottlenecks close to the longest one. Defects close to the boundaries can be described by effective boundary rates and lead to shifts of the phase transitions. Finally it is shown that the SBA also works for more complex models. As an example we discuss a model with internal states that has been proposed to describe transport of the kinesin KIF1A.Comment: submitted to J. Stat. Mec

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

Microdissection of human chromosomes by a laser microbeam

A laser microbeam apparatus, based on an excimer laser pumped dye laser is used to microdissect human chromosomes and to isolate a single chromosome slice

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

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

β-glucan-dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment

The initial host response to fungal pathogen invasion is critical to infection establishment and outcome. However, the diversity of leukocyte-pathogen interactions is only recently being appreciated. We describe a new form of interleukocyte conidial exchange called "shuttling." In Talaromyces marneffei and Aspergillus fumigatus zebrafish in vivo infections, live imaging demonstrated conidia initially phagocytosed by neutrophils were transferred to macrophages. Shuttling is unidirectional, not a chance event, and involves alterations of phagocyte mobility, intercellular tethering, and phagosome transfer. Shuttling kinetics were fungal-species-specific, implicating a fungal determinant. β-glucan serves as a fungal-derived signal sufficient for shuttling. Murine phagocytes also shuttled in vitro. The impact of shuttling for microbiological outcomes of in vivo infections is difficult to specifically assess experimentally, but for these two pathogens, shuttling augments initial conidial redistribution away from fungicidal neutrophils into the favorable macrophage intracellular niche. Shuttling is a frequent host-pathogen interaction contributing to fungal infection establishment patterns

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes