Immunohistochemical Evaluation of TNF Expression in Canine Cystic Endometrial Hyperplasia

Tumour Necrosis Factor (TNF) has been identified in the uterus of several species, and altered TNF expression is reported in some pathological conditions. This study sought to evaluate TNF expression in canine cystic endometrial hyperplasia (CEH; n=20) and compare it with expression in postpartum samples (PP; n=5).This work was supported by Portuguese Foundation for Science and Technology, Center for Studies in Education, Technologies and by Health and by strategic project PEst-OE/CED/UI4016/201

Probing material nonlinearity at various depths by time reversal mirrors

International audienceIn this letter, the time reversal mirror is used to focus elastic energy at a prescribed location and to analyze the amplitude dependence of the focus signal, thus providing the nonlinearity of the medium. By varying the frequency content of the focused waveforms, the technique can be used to probe the surface, by penetrating to a depth defined by the wavelength of the focused waves. The validity of this concept is shown in the presence of gradual and distributed damage in concrete by comparing actual results with a reference nonlinear measurement and X ray tomography images

Validation and data characteristics of methane and nitrous oxide profiles observed by MIPAS and processed with Version 4.61 algorithm

The ENVISAT validation programme for the atmospheric instruments MIPAS, SCIAMACHY and GOMOS is based on a number of balloon-borne, aircraft, satellite and ground-based correlative measurements. In particular the activities of validation scientists were coordinated by ESA within the ENVISAT Stratospheric Aircraft and Balloon Campaign or ESABC. As part of a series of similar papers on other species [this issue] and in parallel to the contribution of the individual validation teams, the present paper provides a synthesis of comparisons performed between MIPAS CH4 and N2O profiles produced by the current ESA operational software (Instrument Processing Facility version 4.61 or IPF v4.61, full resolution MIPAS data covering the period 9 July 2002 to 26 March 2004) and correlative measurements obtained from balloon and aircraft experiments as well as from satellite sensors or from ground-based instruments. In the middle stratosphere, no significant bias is observed between MIPAS and correlative measurements, and MIPAS is providing a very consistent and global picture of the distribution of CH4 and N2O in this region. In average, the MIPAS CH4 values show a small positive bias in the lower stratosphere of about 5%. A similar situation is observed for N2O with a positive bias of 4%. In the lower stratosphere/upper troposphere (UT/LS) the individual used MIPAS data version 4.61 still exhibits some unphysical oscillations in individual CH4 and N2O profiles caused by the processing algorithm (with almost no regularization). Taking these problems into account, the MIPAS CH4 and N2O profiles are behaving as expected from the internal error estimation of IPF v4.61 and the estimated errors of the correlative measurements

Intensity-Based Registration of Freehand 3D Ultrasound and CT-scan Images of the Kidney

This paper presents a method to register a pre-operative Computed-Tomography (CT) volume to a sparse set of intra-operative Ultra-Sound (US) slices. In the context of percutaneous renal puncture, the aim is to transfer planning information to an intra-operative coordinate system. The spatial position of the US slices is measured by optically localizing a calibrated probe. Assuming the reproducibility of kidney motion during breathing, and no deformation of the organ, the method consists in optimizing a rigid 6 Degree Of Freedom (DOF) transform by evaluating at each step the similarity between the set of US images and the CT volume. The correlation between CT and US images being naturally rather poor, the images have been preprocessed in order to increase their similarity. Among the similarity measures formerly studied in the context of medical image registration, Correlation Ratio (CR) turned out to be one of the most accurate and appropriate, particularly with the chosen non-derivative minimization scheme, namely Powell-Brent's. The resulting matching transforms are compared to a standard rigid surface registration involving segmentation, regarding both accuracy and repeatability. The obtained results are presented and discussed

Differences and homologies of chromosomal alterations within and between breast cancer cell lines: A clustering analysis

BACKGROUND: The MCF7 (ER+/HER2-), T47D (ER+/HER2-), BT474 (ER+/HER2+) and SKBR3 (ER-/HER2+) breast cancer cell lines are widely used in breast cancer research as paradigms of the luminal and HER2 phenotypes. Although they have been subjected to cytogenetic analysis, their chromosomal abnormalities have not been carefully characterized, and their differential cytogenetic profiles have not yet been established. In addition, techniques such as comparative genomic hybridization (CGH), microarray-based CGH and multiplex ligation-dependent probe amplification (MLPA) have described specific regions of gains, losses and amplifications of these cell lines; however, these techniques cannot detect balanced chromosomal rearrangements (e.g., translocations or inversions) or low frequency mosaicism. RESULTS: A range of 19 to 26 metaphases of the MCF7, T47D, BT474 and SKBR3 cell lines was studied using conventional (G-banding) and molecular cytogenetic techniques (multi-color fluorescence in situ hybridization, M-FISH). We detected previously unreported chromosomal changes and determined the content and frequency of chromosomal markers. MCF7 and T47D (ER+/HER2-) cells showed a less complex chromosomal make up, with more numerical than structural alterations, compared to BT474 and SKBR3 (HER2+) cells, which harbored the highest frequency of numerical and structural aberrations. Karyotype heterogeneity and clonality were determined by comparing all metaphases within and between the four cell lines by hierarchical clustering. The latter analysis identified five main clusters. One of these clusters was characterized by numerical chromosomal abnormalities common to all cell lines, and the other four clusters encompassed cell-specific chromosomal abnormalities. T47D and BT474 cells shared the most chromosomal abnormalities, some of which were shared with SKBR3 cells. MCF7 cells showed a chromosomal pattern that was markedly different from those of the other cell lines. CONCLUSIONS: Our study provides a comprehensive and specific characterization of complex chromosomal aberrations of MCF7, T47D, BT474 and SKBR3 cell lines. The chromosomal pattern of ER+/HER2- cells is less complex than that of ER+/HER2+ and ER-/HER2+ cells. These chromosomal abnormalities could influence the biologic and pharmacologic response of cells. Finally, although gene expression profiling and aCGH studies have classified these four cell lines as luminal, our results suggest that they are heterogeneous at the cytogenetic level

Non Destructive Evaluation of Containment Walls in Nuclear Power Plants

Two functions are regularly tested on the containment walls in order to anticipate a possible accident. The first is mechanical to resist at a possible internal over-pressure and the second is to prevent leakage. The reference accident LLOCA (Large Loss of Coolant Accident) is the rupture of a pipe in the primary circuit of a nuclear plant. In this case, the pressure and temperature can reach 5 bar and 180°C in 20 seconds. The national project ‘Non-destructive testing of the containment structures of nuclear plants’ aims at studying the non-destructive techniques capable to evaluate the concrete properties and its damaging or progression of cracks. This 4-year-project is segmented into two parts. The first consists in developing and selecting the most relevant NDEs (Non Destructive Evaluations) in the laboratory to reach these goals. These evaluations are developed in conditions representing the real conditions of the stresses generated during ten-yearly visits of the plants or those related to an accident. The second part consists in applying the selected techniques to two containment structures under pressure. The first (technique) is proposed by the ONERA (National Office for Aerospace Studies and Research of France) and the second is a mock-up of a containment wall on a 1/3 scale made by EDF (Electricity of France) within the VeRCoRs program. Communication bears on the part of the project that concerns the damaging and cracking follow-up. The tests are done in bending on 3 or 4 points in order to study the cracks’ generation, their propagation, as well as their opening and closing. The mostly ultrasonic techniques developed concern linear or non-linear acoustic: acoustic emission [1], LOCADIFF (Locating with diffuse ultrasound) [2], energy diffusion, surface waves velocity and attenuation, DAET (Dynamic Acousto-Elasticity Testing) [3]. The data contribute to providing the mapping of the parameters searched for, either in volume, in surface or globally. Image correlation is an important additional asset to validate the coherence of the data. The spatial normalization of the data allows proposing algorithms on the combination of the experimental data. The tests results are presented and they show the capacity and the limits of the evaluation of the volume, surface or global data. A data fusion procedure is associated with these results

Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal community study of predictive factors

BACKGROUND Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes. METHODS We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders. FINDINGS Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores. INTERPRETATION The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention

Amyotrophic lateral sclerosis transcriptomics reveals immunological effects of low-dose interleukin-2

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease causing upper and lower motor neuron loss and currently no effective disease-modifying treatment is available. A pathological feature of this disease is neuroinflammation, a mechanism which involves both CNS-resident and peripheral immune system cells. Regulatory T-cells are immune-suppressive agents known to be dramatically and progressively decreased in patients with amyotrophic lateral sclerosis. Low-dose interleukin-2 promotes regulatory T-cell expansion and was proposed as an immune-modulatory strategy for this disease. A randomized placebo-controlled pilot phase-II clinical trial called Immuno-Modulation in Amyotrophic Lateral Sclerosis was carried out to test safety and activity of low-dose interleukin-2 in 36 amyotrophic lateral sclerosis patients (NCT02059759). Participants were randomized to 1MIU, 2MIU-low-dose interleukin-2 or placebo and underwent one injection daily for 5 days every 28 days for three cycles. In this report, we describe the results of microarray gene expression profiling of trial participants' leukocyte population. We identified a dose-dependent increase in regulatory T-cell markers at the end of the treatment period. Longitudinal analysis revealed an alteration and inhibition of inflammatory pathways occurring promptly at the end of the first treatment cycle. These responses are less pronounced following the end of the third treatment cycle, although an activation of immune-regulatory pathways, involving regulatory T-cells and T helper 2 cells, was evident only after the last cycle. This indicates a cumulative effect of repeated low-dose interleukin-2 administration on regulatory T-cells. Our analysis suggested the existence of inter-individual variation amongst trial participants and we therefore classified patients into low, moderate and high-regulatory T-cell-responders. NanoString profiling revealed substantial baseline differences between participant immunological transcript expression profiles with the least responsive patients showing a more inflammatory-prone phenotype at the beginning of the trial. Finally, we identified two genes in which pre-treatment expression levels correlated with the magnitude of drug responsiveness. Therefore, we proposed a two-biomarker based regression model able to predict patient regulatory T-cell-response to low-dose interleukin-2. These findings and the application of this methodology could be particularly relevant for future precision medicine approaches to treat amyotrophic lateral sclerosis

The immune cell landscape in kidneys of patients with lupus nephritis.

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies

Influences of tongue biomechanics on speech movements during the production of velar stop consonants: a modeling study

This study explores the following hypothesis: forward looping movements of the tongue that are observed in VCV sequences are due partly to the anatomical arrangement of the tongue muscles and how they are used to produce a velar closure. The study uses an anatomically based 2D biomechanical tongue model. Tissue elastic properties are accounted for in finite-element modeling, and movement is controlled by constant-rate control parameter shifts. Tongue raising and lowering movements are produced by the model with the combined actions of the genioglossus, styloglossus and hyoglossus. Simulations of V1CV2 movements were made, where C is a velar consonant and V is [a], [i] or [u]. If V1 is one of the vowels [a] and [u], the resulting trajectories describe movements that begin to loop forward before consonant closure and continue to slide along the palate during the closure. This prediction is in agreement with classical data published in the literature. If V1 is vowel [i], we observe a small backward movement. This is also in agreement with some measurements on human speakers, but it is also in contradiction with the original data published by Houde (1967). These observations support the idea that the biomechanical properties of the tongue could be the main factor responsible for the forward loops when V1 is a back vowel. In the left [i] context, it seems that additional factors have to be taken into considerations, in order to explain the observations made on some speaker