Identifying pathological biomarkers: histochemistry still ranks high in the omics era

In recent years, omic analyses have been proposed as possible approaches to diagnosis, in particular for tumours, as they should be able to provide quantitative tools to detect and measure abnormalities in gene and protein expression, through the evaluation of transcription and translation products in the abnormal vs normal tissues. Unfortunately, this approach proved to be much less powerful than expected, due to both intrinsic technical limits and the nature itself of the pathological tissues to be investigated, the heterogeneity deriving from polyclonality and tissue phenotype variability between patients being a major limiting factor in the search for unique omic biomarkers. Especially in the last few years, the application of refined techniques for investigating gene expression in situ has greatly increased the diagnostic/prognostic potential of histochemistry, while the progress in light microscopy technology and in the methods for imaging molecules in vivo have provided valuable tools for elucidating the molecular events and the basic mechanisms leading to a pathological condition. Histochemical techniques thus remain irreplaceable in pathologist's armamentarium, and it may be expected that even in the future histochemistry will keep a leading position among the methodological approaches for clinical pathology

Non-Uniform Planar Slicing for Robot-Based Additive Manufacturing

Planar slicing algorithms with constant layer thickness are widely implemented for geometry processing in Additive Manufacturing (AM). Since the build direction is fixed, a staircase effect is produced, decreasing the final surface finish. Also, support structures are required for overhanging portions. To overcome such limits, AM is combined with manipulators and working tables with multiple degrees of freedom. This is called Robot-Based Additive Manufacturing (RBAM) and it aims to increase the manufacturing flexibility of traditional printers, enabling the deposition of material in multiple directions. In particular, the deposition direction is changed at each layer requiring non-uniform thickness slicing. The total number of layers, as well as the volume of the support structures and the manufacturing time are reduced, while the surface finish and mechanical performance of the final product are increased. This paper presents an algorithm for non-uniform planar slicing developed in Rhinoceros and Grasshopper. It processes the input geometry and uses parameters to capture manufacturing limits. It mostly targets curved geometries to remove the need for support structures, also increasing the part quality

Interfacial properties of most monofluorinated bile acids deviate markedly from the natural congeners: studies with the Langmuir-Pockels surface balance

We characterized the air-water interfacial properties of four monofluorinated bile acids alone and in binary mixtures with a common lecithin, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), using an automated Langmuir-Pockels surface balance. We compared 7alpha-fluoromurocholic acid (FMCA), 7alpha-fluorohyodeoxycholic acid (FHDCA), 6alpha-fluoroursodeoxycholic acid (FUDCA), and 6alpha-fluorochenodeoxycholic acid (FCDCA) with their natural dihydroxy homologs, murocholic acid (MCA), hyodeoxycholic acid (HDCA), ursodeoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA). For further comparison, two trihydroxy bile acids, 3alpha,6beta,7alpha-trihydroxycholanoic acid [alpha-muricholic acid (alpha-MCA)] and 3alpha,6alpha,7beta-trihydroxycholanoic acid [omega-muricholic acid (omega-MCA)], with isologous OH polar functions to FMCA and FUDCA were also studied. Pressure-area isotherms of MCA, HDCA, UDCA, CDCA, and FMCA displayed sharp collapse points. In contrast, FHDCA, FUDCA, and FCDCA formed monolayers that were less stable than the trihydroxy bile acids, displaying second-order phase transitions in their isotherms. All natural and fluorinated bile acids condensed mixed monolayers with POPC, with maximal effects at molar bile acid concentrations between 30 and 50 mol%. Examination of molecular models revealed that the 7alpha-F atom of the interfacially stable FMCA projects away from the 6beta-OH function, resulting in minimal steric interactions, whereas in FHDCA, FUDCA, and FCDCA, close vicinal interactions between OH and F polar functions result in progressive bulk solubility upon monolayer compression. These results provide a framework for designing F-modified bile acids to mimic or diverge from the natural compounds in vivo

A method for the assessment and compensation of positioning errors in industrial robots

Industrial Robots (IR) are currently employed in several production areas as they enable flexible automation and high productivity on a wide range of operations. The IR low positioning performance, however, has limited their use in high precision applications, namely where positioning errors assume importance for the process and directly affect the quality of the final products. Common approaches to increase the IR accuracy rely on empirical relations which are valid for a single IR model. Also, existing works show no uniformity regarding the experimental procedures followed during the IR performance assessment and identification phases. With the aim to overcome these restrictions and further extend the IR usability, this paper presents a general method for the evaluation of IR pose and path accuracy, primarily focusing on instrumentation and testing procedures. After a detailed description of the experimental campaign carried out on a KUKA KR210 R2700 Prime robot under different operating conditions (speed, payload and temperature state), a novel online compensation approach is presented and validated. The position corrections are processed with an industrial PC by means of a purposely developed application which receives as input the position feedback from a laser tracker. Experiments conducted on straight paths confirmed the validity of the proposed approach, which allows remarkable reductions (in the order of 90%) of the orthogonal deviations and in-line errors during the robot movements

Rasch analysis of the Fatigue Severity Scale in Italian subjects with multiple sclerosis.

To perform a psychometric analysis of the Fatigue Severity Scale (FSS) using Rasch analysis in a sample of Italian subjects with multiple sclerosis

A review of geometry representation and processing methods for cartesian and multiaxial robot-based additive manufacturing

Nowadays, robot-based additive manufacturing (RBAM) is emerging as a potential solution to increase manufacturing flexibility. Such technology allows to change the orientation of the material deposition unit during printing, making it possible to fabricate complex parts with optimized material distribution. In this context, the representation of parts geometries and their subsequent processing become aspects of primary importance. In particular, part orientation, multiaxial deposition, slicing, and infill strategies must be properly evaluated so as to obtain satisfactory outputs and avoid printing failures. Some advanced features can be found in commercial slicing software (e.g., adaptive slicing, advanced path strategies, and non-planar slicing), although the procedure may result excessively constrained due to the limited number of available options. Several approaches and algorithms have been proposed for each phase and their combination must be determined accurately to achieve the best results. This paper reviews the state-of-the-art works addressing the primary methods for the representation of geometries and the subsequent geometry processing for RBAM. For each category, tools and software found in the literature and commercially available are discussed. Comparison tables are then reported to assist in the selection of the most appropriate approaches. The presented review can be helpful for designers, researchers and practitioners to identify possible future directions and open issues

Routinely frozen biopsies of human skeletal muscle are suitable for morphological and immunocytochemical analyses at transmission electron microscopy

The aim of the present investigation was to evaluate whether routinely frozen biopsies of human skeletal muscle may be suitable for morphological and immunocytochemical analyses at transmission electron microscopy. The fixation/embedding protocols we successfully used for decades to process fresh mammalian tissues have been applied to frozen muscle biopsies stored for one to four years in liquid nitrogen. After 2.5% glutaraldehyde -2% paraformaldehyde - 1% OsO4 fixation and embedding in epoxy resin, the ultrastructural morphology of myofibres and satellite cells as well as of their organelles and inclusions proved to be well preserved. As expected, after 4% paraformaldehyde - 0.5% glutaraldehyde fixation and embedding in LR White resin, the morphology of membrane-bounded organelles was relatively poor, although myofibrillar and sarcomeric organization was still recognizable. On the contrary, the myonuclei were excellently preserved and, after conventional staining with uranyl acetate, showed an EDTA-like effect, i.e. the bleaching of condensed chromatin, which allows the visualization of RNP-containing structures. These samples proved to be suitable for immunocytochemical analyses of both cytoskeletal and nuclear components, whereas the poor mitochondrial preservation makes unreliable any in situ investigation on these organelles

Path Approximation Strategies for Robot Manufacturing: A Preliminary Experimental Evaluation

Industrial Robots (IRs) are increasingly adopted for material subtraction or deposition functions owing to their advantages over machine tools, like cost-effectiveness and versatility. Unfortunately, the development of efficient robot manufacturing processes still faces unsolved issues related to the IRs poor positioning accuracy and to the tool path generation process. Novel engineering methods and tools are needed for CAD based programming of accurate paths and continuous robot motions to obtain the required manufacturing quality and tolerances. Within this context, to achieve smoothness along the tool path formed by linear G-code segments, the IR controllers’ approximation strategies, summarily reported in the manufacturer’s manuals, must be considered. The aim of this paper is to present the preliminary work carried out to identify the approximation algorithms of a Kuka IR when executing linear moves. An experimental study is conducted by varying the controller settings and the maximum translational velocity. The robot behavior has been acquired thanks to the controller tracing function and then processed to yield relations readily employable for the interpretation of G-Code commands and the subsequent generation of proper robot motion instructions. The obtained formulas allow to accurately predict the robot geometric path and kinematics within the corner transition between two linear segments