Miracle-dz/UniFAR-FTUs huggingface dataset:
Couplage d’approches expérimentales et modélisatrices pour l'étude des mécanismes d'effet de perturbateurs endocriniens chez la limnée des étangs, Lymnaea stagnalis.

Les produits phytosanitaires contiennent des molecules qui peuvent interferer avec le systeme endocrinien et induire des effets deleteres sur les etres vivants. Ce sont des perturbateurs endocriniens. Afin d’assurer un niveau de protection satisfaisant pour les mollusques aquatiques, une bonne comprehension des perturbations du systeme endocrinien est necessaire. L’organisation pour le developpement et la cooperation economique s’est exprimee en faveur de la mise en place de protocoles standards d’ecotoxicite chez les mollusques, notamment sur la reproduction, dans le cadre des processus d’evaluation du risque ecologique et des autorisations de mise sur le marche de nouvelles molecules. Cette these vise a proposer des tests standards et des outils d’analyse afin d’evaluer les effets de substances chimiques chez un escargot d’eau douce, Lymnaea stagnalis. Une serie de tests de toxicite a ete conduite dans laquelle les limnees ont ete exposees a des androgenes, des oestrogenes et dessolvants. Les effets observes ont ete evalues a l’aide d’approches statistiques standards et d’un modele de toxicokinetique-toxicodynamique (TKTD). Les limnees ont montre une sensibilite uniquement au tributyltin et triphenyltin a des concentrations realistes d’un point de vue environnemental. Le triethylene glycol et l’acetone etaient les solvants les moins nocifs. De plus, le modele TKTD suggere un mecanisme generaliste dans l’action du compose. La manifestation des perturbations endocriniennes chez L. Stagnalis restent evasives et necessitent d’autres recherches. Enfin, la these a montre que
Genomic Ampli fi cation of CD 274 ( PD-L 1 ) in Small-Cell Lung Cancer

Purpose: Programmed death ligand-1 (PD-L1), encoded by the CD274 gene, is a target for immune checkpoint blockade; however, little is known about genomic CD274 alterations. A subset of small-cell lung cancer (SCLC) exhibits increased copy number of chromosome 9p24, on which CD274 resides; however, most SCLCs show low expression of PD-L1. We therefore examined whether CD274 is a target of recurrent genomic alterations. Experimental Design: We examined somatic copy number alterations in two patient cohorts by quantitative real-time PCR in 72 human SCLC cases (cohort 1) and SNP array analysis in 138 human SCLC cases (cohort 2). Whole-genome sequencing revealed the detailed genomic structure underlying focal amplification. PD-L1 expression in amplified cases from cohorts 1 and 2 was further examined by transcriptome sequencing and immunohistochemical (IHC) staining. Results: By examining somatic copy number alterations in two cohorts of primary human SCLC specimens, we observed 9p24 copy number gains (where CD274 resides) and focal, high-level amplification ofCD274.We found evidence for genomic targeting of CD274, suggesting selection during oncogenic transformation. CD274 amplification was caused by genomic rearrangements not affecting the open reading frame, thus leading to massively increased CD274 transcripts and high level expression of PD-L1. Conclusions: A subset (4/210, 1.9%) of human SCLC patient cases exhibits massive expression of PD-L1 caused by focal amplification ofCD274. Such tumorsmay be particularly susceptible to immune checkpoint blockade. Clin Cancer Res; 1–7. 2016 AACR.
A Step-by-Step Clinical Approach for the Management of Neuroendocrine Tumours

Abstract Neuroendocrine tumours (NET) are rare neoplasms, but the incidence is permanently increasing. Most of the NETs are slow proliferating and clinically silent, and for that reason, they are often diagnosed at a stage with advanced disease. The complexity and diversity of the NET-biology require the treatment of patients in specialised centres to guarantee a qualified, multidisciplinary treatment planning. At our institution, we developed an interdisciplinary model for the assessment and treatment of NET. The aim was to adapt the guidelines to the clinical practice, exchange of current knowledge, and a tailored approach to the individual patient. In our team are included medical professionals from pathology, radiology, oncology, gastroenterology, oncological surgery, and nuclear medicine. In this paper, we describe step-by-step a procedural algorithm for the management of patients with neuroendocrine tumours, focusing on midgut-NETs in terms of therapy.
Studies of the Toxicological Potential of Tripeptides (L-Valyl-L-prolyl-L-proline and L-lsoleucyl-L-prolyl-L-proline): VII. Micronucleus Test of Tripeptides-Containing Casein Hydrolysate and Lactobacillus helveticus-fermented Milk Powders in Rats and Mice

The objective of these in vivo experiments was to assess the mutagenic potential of tripeptides as reflected by the ability of the test compound to induce the formation of micronuclei in mouse polychromatic erythrocytes. The test agents used in these experiments were (1) powdered Aspergillus oryzae protease casein hydrolysate (CH) and (2) powdered Lactobacillus helveticus-fermented milk (FM). Both test agents contain two tripeptides, L-valyl-L-prolyl-L-proline (VPP) and L-isoleucyl-L-prolyl-L-proline (IPP). Male Sprague-Dawley rats (five per group) were administered doses of 0, 500, 1000, or 2000 mg (0, 3, 6, or 12 mg VPP plus IPP)/kg body weight (BW)/day CH by oral gavage for 2 days. Male CD-I mice (six per group) received a single oral gavage dose of 0, 500, 1000, or 2000 mg (0, 0.8, 1.6 or 3.3 mg VPP plus IPP)/kg BW of FM. Positive-control agents were cyclophosphamide (10 mg/kg, intraperitoneal [i.p.]) in rats and mitocycin C (2 mg/kg, i.p.) in mice. Twenty-four hours after the second dose of CH, or the dose of cyclophosphamide to rats, or FM or mitocycin C to mice, bone marrow cells were fixed and examined for the presence of polychromatic erythrocytes (PCEs) and the presence or absence of mi-cronucleated PCEs (MNPCEs). Administration of CH to rats and FM to mice produced neither changes in body weights nor signs of systemic toxicity. Similarly, neither CH nor FM caused statistically significant variations in the incidences of either PCEs or MNPCEs. Both positive-control agents caused unequivocal increases in the incidence of MNPCEs and cyclophosphamide significantly reduced the percent of rat erythrocytes appearing as PCEs. The results of these micronucleus assays conducted with either powdered CH or FM in rats and mice, respectively, show that neither form of the tripeptides possesses the potential to induce micronuclei formation in these rodent species.
Mindsets of Commitment and Motivation: Interrelationships and Contribution to Work Outcomes

ABSTRACT Two studies are reported that investigate the relationships among commitment and motivation mindsets and their contribution to work outcomes. Study 1 involved 487 nurses from a hospital in the center of Italy. Results showed that commitment's facets were related to parallel dimensions of work motivation. Study 2 involved 593 nurses from a hospital in the north of Italy. Analyses indicated that commitment and motivation were important antecedents of working attitudes and behaviors. Moreover, self-determined motivation played a critical mediating role in positive behaviors. Findings are discussed in terms of their practical implications for organizations and employees.
Immobilization of pycnoporus coccineus laccase on Eupergit C: Stabilization and treatment of olive oil mill wastewaters

The use of olive oil mill wastewaters (OMW) as an organic fertilizer is limited by their phytotoxic effect, due to the high concentration of phenolic compounds. As an alternative to physico-chemical methods for OMW detoxification, the laccase from Pycnoporus coccineus, a white-rot fungus with the ability to decrease the chemical oxygen demand (COD) and color of the industrial effluent, is being studied. In this work, the P. coccineus laccase was immobilized on two acrylic epoxy-activated resins, Eupergit C and Eupergit C 250L. The highest activity was obtained with the macroporous Eupergit C 250L, reaching 110 U g−1 biocatalyst. A substantial stabilization effect against pH and temperature was obtained upon immobilization. The soluble enzyme maintained ≥80% of its initial activity after 24 h at pH 7.0–10.0, whereas the immobilized laccase kept the activity in the pH range 3.0–10.0. The free enzyme was quickly inactivated at temperatures >50°C, whereas the immobilized enzyme was very stable up to 70°C. Gel filtration profiles of the OMW treated with the immobilized enzyme (for 8 h at room temperature) showed both degradation and polymerization of the phenolic compounds.
Mosaicism and phenotype in ring chromosome 20 syndrome

Ring chromosome 20 [r(20)] syndrome is a rare chromosomal disorder characterized by epilepsy, mild to moderate mental impairment, and malformation. Patients generally show mosaicism in 1–100% of lymphocytes with r(20). We report here a patient with r(20) syndrome who exhibited mild phenotype with the small ratio of mosaicism (13%) with r(20). Although previous small‐scale studies concluded that the mosaicism ratio was unrelated to clinical phenotype, our reassessment of all 57 reported cases has revealed that the ratio is significantly associated with age at seizure onset, intelligence quotient, and malformation, but not with the response of epilepsy to drug treatment. Our results provide important clinical information and prediction for r(20) syndrome.
Gsh‐1, an orphan Hox gene, is required for normal pituitary development.

The anterior pituitary regulates the function of multiple organ systems as well as body growth, and in turn is controlled by peptides released by the hypothalamus. We find that mutation of the Gsh‐1 homeobox gene results in pleiotropic effects on pituitary development and function. Homozygous mutants exhibit extreme dwarfism, sexual infantilism and significant perinatal mortality. The mutant pituitary is small in size and hypocellular, with severely reduced numbers of growth hormone‐ and prolactin‐producing cells. Moreover, the pituitary content of a subset of pituitary hormones, including growth hormone, prolactin and luteinizing hormone, is significantly decreased. The hypothalamus, although morphologically normal, is also perturbed in mutants. The gsh‐1 gene is shown to be essential for growth hormone‐releasing hormone (GHRH) gene expression in the arcuate nucleus of the hypothalamus. Further, sequence and electrophoretic mobility shift data suggest the Gsh‐1 and GHRH genes as potential targets regulated by the Gsh‐1‐encoded protein. The mutant phenotype indicates a critical role for Gsh‐1 in the genetic hierarchy of the formation and function of the hypothalamic‐pituitary axis.
University of Birmingham An investigation of the influence of extracellular matrix anisotropy and cell-matrix interactions on tissue architecture

Mechanical interactions between cells and the ﬁbrous extracellular matrix (ECM) in which they reside play a key role in tissue development. Mechanical cues from the environment (such as stress, strain and ﬁbre orientation) regulate a range of cell behaviours, including proliferation, diﬀerentiation and motility. In turn, the ECM structure is aﬀected by cells exerting forces on the matrix which result in deformation and ﬁbre realignment. In this paper we develop a mathematical model to investigate this mechanical feedback between cells and the ECM. We consider a three-phase mixture of collagen, culture medium and cells, and formulate a system of partial diﬀerential equations which represents conservation of mass and momentum for each phase. This modelling framework takes into account the anisotropic mechanical properties
KLeOS: a personal, mobile, knowledge and learning organisation system

The design of a personal, mobile Knowledge and Learning Organisation System (KLeOS) is described. Studies of adult learning practice showed that learning activity is mobile between locations, time slots, and topic areas. Moreover, learning follows a hierarchical organisation at three operational levels: learning activities are discrete acts, which are grouped to form learning episodes, which in turn are grouped to form learning projects. KLeOS reflects this hierarchical structure and allows the user to organise and manage their learning experiences and resources as a visual timeline. In addition, it incorporates a knowledge map, which is updated as the user progresses through learning experiences. The interface of the organiser is based on the idea of timelines and employs project lines and activity lines to represent the user's learning over a lifetime. The organiser forms a bridge between the timeline and the knowledge map by tagging the nodes of knowledge with the context of the learning episode(s) within which that knowledge was acquired. The architecture of KLeOS allows it to be used on a number of different platforms, thus ensuring mobility.
The seven deadly sins of DNA barcoding

Despite the broad benefits that DNA barcoding can bring to a diverse range of biological disciplines, a number of shortcomings still exist in terms of the experimental design of studies incorporating this approach. One underlying reason for this lies in the confusion that often exists between species discovery and specimen identification, and this is reflected in the way that hypotheses are generated and tested. Although these aims can be associated, they are quite distinct and require different methodological approaches, but their conflation has led to the frequently inappropriate use of commonly used analytical methods such as neighbour‐joining trees, bootstrap resampling and fixed distance thresholds. Furthermore, the misidentification of voucher specimens can also have serious implications for end users of reference libraries such as the Barcode of Life Data Systems, and in this regard we advocate increased diligence in the a priori identification of specimens to be used for this purpose. This commentary provides an assessment of seven deficiencies that we identify as common in the DNA barcoding literature, and outline some potential improvements for its adaptation and adoption towards more reliable and accurate outcomes.
Host manipulation by parasites: a multidimensional phenomenon

Th e diversity of ways in which parasites manipulate the phenotype of their hosts to increase their transmission has been well-documented during the past decades. Parasites clearly have the potential to alter a broad range of phenotypic traits in their hosts, extending from behaviour and colour to morphology and physiology. While the vast majority of studies have concentrated on few, often only one, host characters, there is increasing evidence that manipulative parasites alter multiple characteristics of their host’s phenotype. Th ese alterations can occur simultaneously and/or successively through time, making parasitically modifi ed organisms undoubtedly more complex than traditionally viewed. Here, we briefl y review the multidimensionality of host manipulation by parasites, discuss its possible signifi cance and evolution, and propose directions for further research. Th is view should prove to be an extremely useful approach, generating a series of testable hypotheses regarding the ecology of parasitized hosts, and leading to a better comprehension of complex host–parasite relationships.
An absolute angle recovery method for dual-interferometer-based rotational stages

A new absolute angle recovery method for dual-interferometer-based rotational stages is presented. The high resolution of laser interferometers makes this sensor particularly suitable for high-precision rotational stages (comprising two parallel interferometer heads separated by a fixed distance). However the incremental operation of the sensor results in relative angle reference. The proposed method establishes an absolute angle reference system based on the characteristic movement of the rotational stage throughout the full angular range. The method is successfully applied in a high-precision rotational stage and its performance is evaluated with an external dual-interferometer system showing an accuracy of ±1. 65μrad (3σ).
Evidence of multidimensionality in the ALSFRS-R Scale: a critical appraisal on its measurement properties using Rasch analysis

Objective To examine dimensionality, reliability and validity of the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) using traditional classical test theory methods and Rasch analysis in order to provide a rationale for possible improvement of its metric quality. Methods Methodological research on ALSFRS-R collected in a consecutive sample of 485 patients with amyotrophic lateral sclerosis (ALS) attending three tertiary ALS centres. Results The ALSFRS-R items showed good internal consistency but dimensionality analysis argues against the use of ALSFRS-R as a single score because the scale lacks unidimensionality. Parallel analysis and exploratory factor analysis revealed three factors representing the following domains: (1) bulbar function; (2) fine and gross motor function; and (3) respiratory function. Rasch analysis showed that all items in each domain fitted the respective constructs to measure, except for item No 9 ‘climbing stairs’ and item No 12 ‘respiratory insufficiency’. Rating categories did not comply with the criteria for category functioning. Collapsing the scale's 5 level ratings into 3 levels improved its metric quality. Conclusions The ALSFRS-R fails to satisfy rigorous measurement standards and should be, at least in part, revised. At present, ALSFRS-R should be considered as a profile of mean scores from three different domains (bulbar, motor and respiratory functions) more than a global total score. Further studies on ALSFRS-R using modern psychometric methods are warranted to confirm our findings and refine the metric quality of this scale, through a step by step process.
DNA/polyaniline/gold nanocomposites: An electrical overview

Nanocomposites of conducting polymers /metal nanoparticles (NC) have been considered important candidates for different applications involving determination and quantification of DNA due to their novel properties, viz. electronic, mechanical and optical response. The interaction of components with DNA is a critical step in the optimization of diagnostic applications. In this work, we have studied mechanisms of interaction of polyaniline - gold nanoparticle (PANI-Au) with DNA molecules by optical and electrical impedance spectroscopy. In both responses (absorbance at 318 nm and emission at 440 nm) a similar behavior with variation in the corresponding [P]DNA/[N]PANI-Au ratio is established, in agreement with EIS data, in a strong indication that EIS can be explored as an alternative technique for description of PANI-Au / DNA interactions.
Onset of Primary and Secondary Instabilities of Viscoelastic Fluids Saturating a Porous Layer Heated from below by a Constant Flux

We analyze the thermal convection thresholds and linear characteristics of the primary and secondary instabilities for viscoelastic fluids saturating a porous horizontal layer heated from below by a constant flux. The Galerkin method is used to solve the eigenvalue problem by taking into account the elasticity of the fluid, the ratio between the viscosity of the solvent and the total viscosity of the fluid and the lateral confinement of the medium. For the primary instability, we found out that depending on the rheological parameters, two types of convective structures may appear when the basic conductive solution loses its stability: stationary long wavelength instability as for Newtonian fluids and oscillatory convection. The effect of the lateral confinement of the porous medium by adiabatic walls is to stabilize the oblique and longitudinal rolls and therefore selects transverse rolls at the onset of convection. In the range of the rheological parameters where stationary long wave instability develops first, we use a parallel flow approximation to determine analytically the velocity and temperature fields associated with the monocellular convective flow. The linear stability analysis of the monocellular flow is performed, and the critical conditions above which the flow becomes unstable are determined. The combined influence of the viscoelastic parameters and the lateral confinement on the characteristics of the secondary instability is quantified. The major new findings concerning the secondary instabilities may be summarized as follows: (i) For concentrated viscoelastic fluids, computations showed that the most amplified mode of convection corresponds to oscillatory transverse rolls, which appears via a Hopf bifurcation. This pattern selection is independent of both the fluid elasticity and the lateral confinement of the porous medium. (ii) For diluted viscoelastic fluids, the preferred mode of convection is found to be oscillatory transverse rolls for a very laterally-confined medium. Otherwise, stationary or oscillatory longitudinal rolls may develop depending on the fluid elasticity. Results also showed the destabilizing effect of the relaxation fluid elasticity and the stabilizing effect of the viscosity ratio for the onset of both primary and secondary instabilities.
Differential Effects of Peptide Histidine Isoleucine (PHI) and Related Peptides on Stimulation and Suppression of Neuroblastoma Cell Proliferation

The growth rate of rodent embryonic neuroblasts and human neuroblastoma cell lines is regulated in part by autocrine or paracrine actions of neuropeptides of the family that includes vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), and pituitary adenylate cyclase-activating peptide (PACAP). These peptides act via seven transmembrane G-protein-linked receptors coupled to cAMP elevation, phospholipase C activation, intracellular Ca2+ release, and/or of mitogen-activated protein (MAP) kinase activation. Here we investigated the action of these peptides on the mouse neuroblastoma cell line Neuro2a. PHI and VIP inhibited proliferation at concentrations as low as 10−13 m and 10−10 m, respectively. In contrast, PACAP action was biphasic, with stimulation occurring at subnanomolar doses and inhibition at higher doses. Peptide actions were studied further by measuring cAMP and ERK1/2 MAP kinase activity and by assessing3H-thymidine incorporation in conjunction with a panel of signal transduction pathways inhibitors. The data obtained indicated that the PHI-inhibitory and PACAP-stimulatory activities were mediated by corresponding changes in activity of the MAP kinase pathway and independent of protein kinase A (PKA) or protein kinase C (PKC). In contrast, the inhibitory actions of VIP and PACAP were specifically blocked by antagonists of PKA. Northern blot analysis revealed gene expression for only the PACAP-preferring (PAC1) receptor. However, binding experiments using 125I-labeled PACAP27, PHI, and VIP, demonstrated the presence of PACAP-preferring sites, bivalent VIP/PACAP sites, and PHI-binding sites that did not interact with VIP. The studies demonstrate potent regulatory actions of PACAP, PHI, and VIP on neuroblastoma cell proliferation which appear to be mediated by multiple subsets of receptors which differentially couple to MAP kinase and PKA signaling pathways.