Xerna™ TME Panel is a machine learning-based transcriptomic biomarker designed to predict therapeutic response in multiple cancers.

Introduction: Most predictive biomarkers approved for clinical use measure single analytes such as genetic alteration or protein overexpression. We developed and validated a novel biomarker with the aim of achieving broad clinical utility. The Xerna™ TME Panel is a pan-tumor, RNA expression-based classifier, designed to predict response to multiple tumor microenvironment (TME)-targeted therapies, including immunotherapies and anti-angiogenic agents.

Amyloid Fibrils of Stefin B Show Anisotropic Properties.

Human stefin B, a member of the cystatin family of cysteine protease inhibitors, tends to form amyloid fibrils under relatively mild conditions, which is why it is used as a model protein to study amyloid fibrillation. Here, we show for the first time that bundles of amyloid fibrils, i.e.

Robust Depth Image Acquisition Using Modulated Pattern Projection and Probabilistic Graphical Models.

Depth image acquisition with structured light approaches in outdoor environments is a challenging problem due to external factors, such as ambient sunlight, which commonly affect the acquisition procedure. This paper presents a novel structured light sensor designed specifically for operation in outdoor environments. The sensor exploits a modulated sequence of structured light projected onto the target scene to counteract environmental factors and estimate a spatial distortion map in a robust manner.

Amino acid substitutions [K16A] and [K28A] distinctly affect amyloid β-protein oligomerization.

Amyloid β-protein (A β) assembles into oligomers that play a seminal role in Alzheimer's disease (AD), a leading cause of dementia among the elderly. Despite undisputed importance of A β oligomers, their structure and the basis of their toxicity remain elusive. Previous experimental studies revealed that the [K16A] substitution strongly inhibits toxicity of the two predominant A β alloforms in the brain, A β 40 and A β 42, whereas the [K28A] substitution exerts only a moderate effect.

Assembly of Stefin B into Polymorphic Oligomers Probed by Discrete Molecular Dynamics.

Assembly of an amyloidogenic protein stefin B into molten globule oligomers is studied by efficient discrete molecular dynamics. Consistent with in vitro findings, tetramers form primarily through dimer association, resulting in a decreased trimer abundance. Oligomers up to heptamers display elongated rod-like morphologies akin to protofibrils, whereas larger oligomers, decamers through dodecamers, form elongated, branched, as well as annular structures, providing structural insights into pore forming ability and toxicity of amyloidogenic proteins.

Amyloid fibrils compared to peptide nanotubes.

Prefibrillar oligomeric states and amyloid fibrils of amyloid-forming proteins qualify as nanoparticles. We aim to predict what biophysical and biochemical properties they could share in common with better researched peptide nanotubes. We first describe what is known of amyloid fibrils and prefibrillar aggregates (oligomers and protofibrils): their structure, mechanisms of formation and putative mechanism of cytotoxicity.

The role of initial oligomers in amyloid fibril formation by human stefin B.

Oligomers are commonly observed intermediates at the initial stages of amyloid fibril formation. They are toxic to neurons and cause decrease in neural transmission and long-term potentiation. We describe an in vitro study of the initial steps in amyloid fibril formation by human stefin B, which proved to be a good model system.

Modulated acquisition of spatial distortion maps.

This work discusses a novel approach to image acquisition which improves the robustness of captured data required for 3D range measurements. By applying a pseudo-random code modulation to sequential acquisition of projected patterns the impact of environmental factors such as ambient light and mutual interference is significantly reduced. The proposed concept has been proven with an experimental range sensor based on the laser triangulation principle.

Image cytometric nuclear texture features in inoperable head and neck cancer: a pilot study.

Background: Image cytometry can measure numerous nuclear features which could be considered a surrogate end-point marker of molecular genetic changes in a nucleus. The aim of the study was to analyze image cytometric nuclear features in paired samples of primary tumor and neck metastasis in patients with inoperable carcinoma of the head and neck. MATERIALS AND METHODS.

Malignancy associated changes in epithelial cells of buccal mucosa: a potential cancer detection test.

Objective: To analyze the presence of malignancy associated changes (MACs) in normal buccal mucosa cells of lung and breast cancer patients and their relationship to tumor subtype, stage and size.

Study Design: Buccal mucosa smears of 107 lung cancer and 100 breast cancer patients and corresponding healthy subjects were collected, stained by the DNA-specific Feulgen-thionin method and scanned using an automated high-resolution cytometer. Nuclear texture features of a minimum of 500 nuclei per slide were calculated, and statistical classifiers using Gaussian models of class-probability distribution were designed, trained and tested in 3 parts: (1) ability to separate cancer patient samples from controls, (2) cross-validation of classifiers for different cancer types, and (3) correlation of MAC expression with tumor subtype, stage and size.

Value of image cytometry in the subclassification of rhabdomyosarcoma.

Objective: To test the discriminatory capability of nuclear features in the subclassification of rhabdomyosarcoma (RMS) and especially to differentiate embryonal from alveolar RMS.

Study Design: The study included 42 patients with RMS. We performed the analysis on Feulgen-stained filtrates of cell suspensions prepared from deparaffinized tissue sections.

Hydrolysis profiles of formalin fixed paraffin-embedded tumors based on IOD (integrated optical density) and nuclear texture feature measurements.

The aim of the study was to determine optimal hydrolysis time for the Feulgen DNA staining of archival formalin fixed paraffin-embedded surgical samples, prepared as single cell suspensions for image cytometric measurements. The nuclear texture features along with the IOD (integrated optical density) of the tumor nuclei were analysed by an automated high resolution image cytometer as a function of duration of hydrolysis treatment (in 5 N HCl at room temperature). Tissue blocks of breast carcinoma, ovarian serous carcinoma, ovarian serous tumor of borderline malignancy and leiomyosarcoma were included in the study.

Detection of compact low-chromatin areas in cell nuclei images.

When analysing some DNA stained human cell nuclei using a light microscope or an quantitative image cytometer, compact low-chromatin areas (CLCA) can be observed. We are still not certain about the meaning and source of this phenomena. To enable the detection of CLCA by an image cytometer, a special image processing algorithm has to be developed and new nuclear cell features have to be designed.

3D presentation of the nuclear cell features in quantitative cytometry.

The use of an image cytometer in analysis of smears and needle aspirates provides valuable information to a cytologist. It allows to combine the overall impression, formed by visually inspecting the cells, with measured and numerically expressed nuclear cell features. Both types of information can be used efficiently only if presented to the expert in an appropriate way.