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Les paragangliomes et phéochromocytomes (PPGL) sont des tumeurs neuroendocrines rares dont les formes métastatiques sont fréquemment associées à des déficits héréditaires en succinate déshydrogénase (SDH), une enzyme majeure du cycle de Krebs et de la chaîne respiratoire mitochondriale. La ferroptose, un mécanisme de mort cellulaire régulé par le fer et caractérisé par l’accumulation toxique de peroxydes lipidiques non contrôlés émerge actuellement comme une voie de mort cellulaire potentiellement exploitable dans les PPGL. Le diméthylfumarate (DMF), un activateur du facteur nucléaire érythroïde 2 lié au facteur 2 (NRF2) connu pour son rôle dans la modulation du stress oxydatif, suscite un intérêt croissant en tant qu’inducteur de la ferroptose.

Les phéochromocytomes et paragangliomes (PPGL) sont des tumeurs neuroendocrines, métastatiques dans 15 % des cas. Aucun critère anatomopathologique ne permet de prédire leur malignité, ce qui nécessite un suivi à vie. Les PPGL présentent une forte prédisposition génétique, et une mutation SDHB entraine un risque accru de forme agressive. Ainsi, déterminer le statut génétique et le risque de malignité des patients atteints de PPGL est un défi majeur.

Les paragangliomes et phéochromocytomes (PPGL) sont des tumeurs neuroendocrines rares, très vascularisées, se développant aux dépens des paraganglions des systèmes nerveux sympathique et parasympathique (depuis la tête et le cou jusqu’au pelvis) et de la médullosurrénale. Ils sont métastatiques dans environ 15 % des cas. Il s’agit des tumeurs humaines présentant le plus fort degré d’héritabilité avec près de 40 % des patients porteurs d’une mutation constitutionnelle sur l’un des 20 gènes de prédisposition identifiés à ce jour. La présence d’une mutation du gène SDHBest spécifiquement associée à l’apparition de formes métastatiques et de particulièrement mauvais pronostic.

The present work proposes a modified Pressure-Implicit Split-Operator (PISO) solver integrating the recent Immersed Boundary Method (IBM) proposed by [1] in order to perform reliable simulations of incompressible flows around bluff bodies using the open source toolbox OpenFOAM version 2.2 ( [2] ). The (IBM) allows for a precise representation of fixed and moving solid obstacles embedded in the physical domain, using uniform or stretched Cartesian meshes. Owing to this feature, the maximum level of accuracy and scalability of the numerical solvers can be systematically achieved. An iterative scheme based on sub-iterations between (IBM) and pressure correction has been implemented in the native (PISO) solver of OpenFOAM. This allows one to use fast optimized Poisson solvers while satisfying simultaneously the divergence-free flow state and the no-slip condition at the body surface. To compute the divergence of the momentum equation (in the PISO loop) and the interpolation of the fluxes, we propose an hybrid calculation with an analytical resolution (using the kernel function equation) of the quantities involving the force term (singular quantities). A careful and original verification study has been carried out which allows to estimate three different errors related to the discretization and to the (IBM). Various 2D and 3D well-documented test cases of academic flows around fixed or moving solid bodies (cylinder and sphere) have been simulated and carefully validated against existing data from the literature in a large range of Reynolds numbers, R e = 30 − 3900 and in the frame of DNS and DDES OpenFOAM native models. [ABSTRACT FROM AUTHOR]

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors of neural crest origin. These tumors are caused by germline or somatic mutations in known susceptibility genes in up to 70% of cases. Over the past few years, the emergence of high-throughput technologies has enabled the unprecedented characterization of genomic alterations in PCC/PGL, and has improved our understanding of the molecular mechanisms that distinguish the different tumor subtypes. Integrated genomic analyses have shown that the mutation status of PCC/PGL susceptibility genes strongly correlates with multi-omics data. These observations not only emphasize the role of the long-standing susceptibility genes as the main drivers of PCC/PGL tumorigenesis, but also illustrate the functional interdependence between genomic and epigenomic alterations. In this review, we discuss the genomic landscape underlying PCC/PGL, its functional consequences for tumorigenesis and tumor progression, and the potential clinical relevance of this knowledge for the application of precision medicine for patients with PCC/PGL.

Les progrès dans la compréhension de l’oncogenèse des phéochromocytomes et des paragangliomes métastatiques (PPGLm) mutés SDHBnous permettent d’envisager le recours à de nouvelles thérapies ciblées dans cette pathologie rare dont le pronostic reste réservé.

A variety of carboxylic acids, alcohols and alkanes were studied using photoacoustic spectroscopy (PAS) with an excitation wavelength of 3.39 µm. The analytical potential of this method was estimated with different organic compounds dissolved in chloroform. A detection limit of 0.25% with a signal to noise ratio of 6 was achieved.

Large values (nearly 3000 cm-1) of absorption coefficients β (unaccessible by conventional spectrometric methods), were measured for pure monounsaturated oleic acid (C18 : l) at 3.39 µm (C-H stretch vibration) using He-Ne laser in combination with a novel, compact optothermal sensor. Failure (except in a low concentration range) of C-H stretch vibration to follow Lambert-Beer's law was observed for solutions of C18 : 1 in chloroform. At 3.39 µm minimum detectable concentration of C18 : 1 in chloroform is 0.35 %.

We consider a free-surface liquid layer convecting under an applied horizontal temperature gradient. The surface gets slightly titled by an angle which depends on layer thickness through competing capillary and gravity effects. This result might be of some interest in Marangoni solidification set ups. It also opens up a new way of accurately measuring the surface-tension temperature coefficient.

AbstractMitochondrial complex II, or succinate dehydrogenase, is a key enzymatic complex involved in both the tricarboxylic acid (TCA) cycle and oxidative phosphorylation as part of the mitochondrial respiratory chain. Germline succinate dehydrogenase subunit A (SDHA) mutations have been reported in a few patients with a classical mitochondrial neurodegenerative disease. Mutations in the genes encoding the three other succinate dehydrogenase subunits (SDHB, SDHC and SDHD) have been identified in patients affected by familial or ‘apparently sporadic’ paraganglioma and/or pheochromocytoma, an autosomal inherited cancer-susceptibility syndrome. These discoveries have dramatically changed the work-up and genetic counseling of patients and families with paragangliomas and/or pheochromocytomas. The subsequent identification of germline mutations in the gene encoding fumarase – another TCA cycle enzyme – in a new hereditary form of susceptibility to renal, uterine and cutaneous tumors has highlighted the potential role of the TCA cycle and, more generally, of the mitochondria in cancer.Copyright © 2005 S. Karger AG, Basel

The application of the DEM to engineering problems involving the dynamic behaviour of discontinuous media has necessitated the introduction of moving boundary surfaces. In this paper a method is presented for modelling three-dimensional moving boundary surfaces within the discrete element framework. The surfaces of boundary objects are discretized into triangular planar surfaces using the finite wall method. Wall elements are grouped and each group is associated with a single discrete boundary object which may move independently. Movement comprises any combination of translation and rotation of wall element groups, subject to a given acceleration and velocity during a calculation cycle. The scheme is explicit due to rigidity of the wall elements which are stationary fixed in position and orientation over a time step. Any in-plane velocity is handled as a contact point velocity within a calculation cycle. The kinematic conditions at each calculation cycle may be pre-defined or returned from a separate calculation of rigid body motion of the boundary object. The method provides a means for coupling sphere-based particle dynamics with rigid body dynamics and structural analysis of boundary components. Copyright © 2001 John Wiley & Sons, Ltd.

The discrete element method for analysis of the dynamic behaviour of discontinuous media is well established. However, its application to engineering problems is still limited to simplified representations of structural boundaries and their kinematics. In this paper a method is developed for representing three-dimensional boundaries of arbitrary geometry and for modelling the interaction between boundary objects and particles within the discrete element modelling framework. The approach, which we term the finite wall method, uses planar triangular elements to approximate the boundary surface topology. Any number of wall elements can be used to model the shape of the structure. A contact detection scheme is presented for boundary surfaces and spheres based on a series of vector projections to reduce the problem dimensionally. The algorithm employs spatial sporting to obtain the set of potential contacts between spheres and wall elements prior to contact resolution. In a further stage, all possible contact conditions including contact with surfaces, edges and corners are explicitly determined. Part I of this two-part series of papers describes the finite wall method for representation of surface geometry and fully elaborates the method for detecting and resolving contact between boundary wall elements and spheres. In Part II the finite wall method is extended to apply kinematics to linearly independent boundary objects using combinations of translational and rotational motion. An approach is developed for coupling the DEM with the FEM for the purpose of optimising the design of structures which are dynamically interacting with particulate media. Copyright © 2001 John Wiley & Sons, Ltd.

Shaking separation of paddy and brown rice is investigated using a numerical model and by experiment at the same scale. The numerical model employs the discrete element method with two-dimensional circular particles representing rice grains. The indents on the experimental separation plate were modelled using a method of ‘virtual’ walls whereby only particles in contact with the base of the separation plate were affected by the walls which were positioned at regular intervals along the base. Exit of a particle from an indent was modelled as removal of a virtual wall once the particle-wall contact exceeded a threshold value. The model was validated against experimental results at the macroscopic scale in terms of mean particle distance from the sides and base of the separation plate, and the free surface profile. Particle movement in the experiments was tracked using a high speed video camera. There was good agreement between the results of the simulation and the experiment. The time required to achieve maximum separation of brown and paddy rice was the same in both experiment and simulation. The simulation also showed the same wave-like behaviour of the grain assembly as in the experiment.

Objective.To evaluate the prognostic significance of and predictive value for survival of CA 125 and TPS levels after three chemotherapy courses in ovarian cancer patients.

Aqueous solutions of sodium hydroxide were used to debran whole sorghum and millet grains. The alkali solution was effective in dissolving the pericarp, leaving the kernel free of pericarp. Various combinations of concentration of sodium hydroxide (3, 6, and 10%, w/w) and soaking duration (5, 8, and 10 min) were investigated. Two cultivars of sorghum (Dionje and Jumbo) and one cultivar of pearl millet (IM) were used in the study. A 10% aqueous solution of sodium hydroxide at 60°C was most effective in dissolving the pericarp of both sorghum and millet after 10 min of soaking, resulting in ˜90% yield of clean endosperm for all grain types. The debranning process reduced the fiber content (measured as crude fiber) of sorghum cultivars Dionje and Jumbo by 37.6 and 41.8%, respectively; and pearl millet by 32%.

An earlier paper modelling the monotectic interface [Derby and Favier, Acta Met. 31 (1983) 1123] implied that the liquid phase in irregular monotectics will be in advance of the average interface position. Such a geometry suggests a gradient effect on the fibrous irregular structure. Experiments in the Cu-Pb and pseudobinary Al-In-Sn irregular monotectics reveal a growth law of λυ1/2G1/31/3= constant relating fibre spacing (λ), growth rate (ν) and temperature gradient (G). This is compared with the similar laws reported in some facetted/non-facetted eutectics.

Inclusive distributions of ρ0 and ω mesons have been measured in deep inelastic μ-p interactions at 280 GeV/c. A comparison of the ρ0 cross sections with other leptoproduction experiments is presented. The ω results represent the first observation of this inclusive channel in high energy leptoproduction. The ρ0 and ω yields are found to be equal as may be expected from the available density of states in isospin space. This contrasts with spin angular momentum where the vector to pseudoscalar meson ratio is suppressed relative to the available number of spin states.

TheW andQ2 dependence of the fragmentation functions and of the average multiplicity of charged pions is investigated, using data from the NA9 experiment at the CERN SPS on muon-proton scattering at 280 GeV. A significant increase of pion production with increasingW is observed at fixedQ2, leading to a rise of the average charged pion multiplicity, linear in lnW2, and of the pion fragmentation function in the central region, i.e. at small |xF|. This increase can be understood from the kinematic widening of the cms rapidity range proportional to lnW2 and the observedW independent height of the rapidity distribution. At fixedW, a rise of the average charged pion multiplicity withQ2 is observed. This rise appears to be weaker than that observed for all charged hadrons implying a stronger rise withQ2 for kaons and protons.

The hadronic distributions inQ2,y, z, pT and ? in deep inelastic muon proton scattering have been studied to search for higher twist effects in the hadronic final state. The expected effects are not observed.

Using a lead glass detector installed in the EMC forward spectrometer radiative photons have been measured in 200 GeV muon-hydrogen collisions. The results are compared with the standard QED one photon emission theory of Mo and Tsai and also with the more recent predictions of a multiphoton emission theory of Chahine. We conclude that there is no evidence for any deviation from the standard theory, in terms of the yield and angular distribution of photons with fractional energy,z>0.7.

Multiblock copolymers of styrene and a-methylstyrene (¯Mn ? 70.000 g.mole-1) with various a-methylstyrene contents were synthetized by anionic polymerization. The glass transition temperatures (Tg) of these copolymers have been measured by D.T.A. A single Tg was observed over the whole composition range. This Tg obeys the derived GORDON and TAYLOR equation. Moreover these copolymers are heat resistant up to temperatures of at least 280°C.

A consecutive, unselected series of 1812 cases of head trauma in children less than 15 years of age and admitted hospital over a period of 8.5 years was studied. Data concerning the grade of energy involved, the ages of the victims, the types of pathologies caused and the clinical features noted were collected and statistically analysed. Babies and toddlers (0–3 years) were shown to sustain rather low-energy trauma and suffer more skull fractures, more subdural haematomas and more benign injuries. They lost consciousness less frequently and were less frequently in coma than the other children. By contrast, they had more frequent signs of lateralization, and early seizures were much more frequent in babies than in other children. Young children (3–9 years) had rather higher-energy accidents, frequently lost consciousness, were more frequently in coma and have more frequently had a free interval associated with the development of brain swelling. They did not suffer subdural effusion or contrecoup lesions. Schoolchildren (9–15 years) were statistically more or less like young adults: the clinical sequences of trauma were more severe than in the other children, mortality was a little bit higher, the risk of extradural haematoma was higher, and they rarely suffered subdural haematomas or contrecoup lesions. Traffic accidents, with higher energy involved, were more severe.

Children aged 0–15 years hospitalized in Geneva for head trauma during the last quarter of a century are reviewed. More than half of the severely injured children were not from Geneva area. New methods of management have been introduced progressively. The cases are divided in four successive time periods and classified according to their pathology. A continuous improvement in mortality is obvious, decreasing from 29.4% to 2.2%, but climbing again to 15.2% in the last period, probably due to more severe pathologies. For the Geneva area the mortality decreased progressively from 10.4/100 000 to 3.5/100 000 annually, due to better organization and management, but also to a drop in the incidence of severe cases from 35.5–13.5/100 000 per year. A decrease in the number of traffic accidents is responsible for this. However, the number of handicapped children has not changed.

The Bose-Einstein correlation has been observed for pions in deep inelastic µp interactions at 280 GeV. The importance of non-interference correlations in the sample of like charge pion pairs and in the sample used for reference is discussed. The pion emission region is found to be roughly spherical in the pair rest frame with a radius of 0.46–0.84 fm and the chaos factor ? is 0.60–1.08.

Results are presented from a study of deep inelastic 280 GeV muon-nucleon interactions on the transverse momenta and jet properties of the final state hadrons. The results are analysed in a way which attempts to separate the contributions of hard and soft QCD effects from those that arise from the fragmentation process. The fragmentation models with which the data are compared are the Lund string model, the independent jet model, the QCD parton shower model including soft gluon interference effects, and the firestring model. The discrimination between these models is discussed. Various methods of analysis of the data in terms of hard QCD processes are presented. From a study of the properties of the jet profiles a value of as, to leading order, is determined using the Lund string model, namely as=0.29±0.01 (stat.) ±0.02 (syst.), forQ2~20 GeV2.

The working range and instrumentation of an air conditioning and thin layer drying apparatus are described. Particular attention is paid to the measurement of air humidity through the use of a differential psychrometer. The effect of drying depth is examined in relation to the drying of large samples for subsequent work on quality. The bed depth and boundary layer resistance errors are examined theoretically and experimentally. The bed depth error predominates even for layers one seed deep. For a 4 mm bed depth of barley, theory predicts a bed depth error of less than 5% at air velocities greater than 0·08 m/s. The theoretical prediction for the boundary layer effect indicates an error of less than 1% at velocities above 0·01 m/s. A method of continuously monitoring the aerodynamic force on a sample by means of a pressure differential is also described and shown to be effective in determining true sample weight. Copyright 1993, 1999 Academic Press

A series of 20 hemispheric tumors in children less than 16 years of age, over a period of 20 years, is presented. Among them, 8 were oligodendroglial tumors, a proportion well above the level reported in the literature. The World Health Organization (WHO) classification, which includes mixed oligoastrocytomas, in the oligodendrogliomas was used. This addition does not explain this unusually high proportion. Selection of cases and the correct histological diagnosis are probably important.

The efficacy of a single intravenous bolus of anisoylated plasminogen streptokinase activator complex (APSAC 30U in 4 to 5 minutes) versus an intravenous infusion of streptokinase (1.5 × 106U in 60 minutes) was assessed in 86 patients with evolving myocardial infarction of < 6 hours duration in a cooperative randomised study. The patency of the infarct-related artery was assessed by coronary angiography at, on average, 90 minutes after therapy (mean time: APSAC 95 minutes, streptokinase 105 minutes). The treatment groups were similar with respect to sex, age, location of myocardial infarction and the delay from onset of pain to treatment. The 90-minute patency rate (grade 2 to 3) was 71.8% in the APSAC group and 55.8% in the streptokinase group; the difference was not statistically significant. There was no difference between the drop in fibrinogen concentrations in the 2 groups at 3 or 24 hours. The minimal concentration obtained at the first assessment was ±0.2 g/L in the streptokinase group and 0.5 g/L in the APSAC group. One patient in the APSAC group, who had a previous meningeal bleeding, had a non-fatal cerebrovascular accident. In a subgroup of 38 patients who had 3 control coronary angiograms at 90 minutes, 24 hours and 3 weeks, the patency rate was 63, 82 and 93%, respectively, in the APSAC group and 48, 88 and 92%, respectively, in the streptokinase group (the difference was not statistically significant). None of the patients in the APSAC group presented with reocclusion, whilst 3 patients in the streptokinase group had reocclusions. Thus, APSAC seems a promising new agent that is easier to apply than other thrombolytic agents and is at least as effective as streptokinase.

A quantitative model for change in germination rate of barley (Hordeum vulgare L.) during and after loss of primary dormancy is presented. Change in mean germination time on a logarithmic scale is normally distributed within the period of after-ripening and the standard deviation of this distribution is shown to be a quantitative function of after-ripening temperature. The rate of change of mean germination time is in inverse proportion to the product of the standard deviation and a parameter which is characteristic of the seed population. The latter parameter is the rate constant for change in probit cumulative germination as a negative linear function of the logarithm of mean germination time. A model based solely on dormancy loss is combined with an existing model of change in probit viability as a function of mean germination time to produce a model which predicts the time to and optimum value of mean germination rate of a population as it after-ripens. The model provides a quantitative link between the effect of pre-germination and germination environments on total and rate of germination of an initially dormant population. Experimental data from dormant barley (cv. Triumph) stored at 27, 38, 45, 50 and 60 °C, and germinated at 18 °C were used to validate the model. The data show that germination rate continues to increase after primary dormancy is lost until it reaches an upper limit determined by the intrinsic germinative vigour of the seed lot. Rate of loss of primary dormancy and increase in germination rate thus appear to be quantitatively linked as a function of after-ripening temperature and factors which may be specific to the mode of induction of dormancy within a seed lot prior to harvest.Copyright 1995, 1999 Academic Press

The oil-point, which indicates the threshold pressure at which oil emerges from a seed kernel during mechanical seed-oil expression, is theoretically related to the kernel density of an oilseed thereby enabling its evaluation from initial bulk properties of a bed of seeds. A method for dynamically determining the applied pressure at the oil-point by precise sensing of the oil (pore) pressure is presented. This measurement permits experimental validation of the hypothesis that the oil-point generally occurs at the point where the bed density approaches the kernel density of the constituent seed or material particle. The effect of bulk compression on bulk density, volumetric strain, bed compressibility and specific energy of compression up to the oil-point was examined for rapeseed, soybean, groundnut, palm kernel, and cashew and melon seed before and after pretreatment by heating or size reduction. It was found that oil-seeds can be characterized objectively as hard or soft using bed compressibility and specific energy of compression at the oil-point. In addition the ratio of maximum pore pressure to applied pressure was positively correlated with seed oil content. The effect of particle size reduction and heating was generally to increase bed compressibility and lower the applied pressure at the oil point. The results show that the effect of pre-treatments on the mechanical properties of seed beds must be taken into account when considering the efficacy of mechanical expression of oil from oil-seeds.

The general charge properties of the hadronic final state produced inµ+p andµ+d interactions at 280 GeV are investigated. Quark charge retention and local charge compensation is observed. The ratioF2n/F2p of the neutron to proton structure function is derived from the measurement of the average hadronic charge in µd interactions.

Final data measured with the EMC forward spectrometer are presented on the production of forward charged hadrons in µp and µd scattering at incident beam energies between 100 and 280 GeV. The large statistic of 373 000 events allows a study of the semi-inclusive hadron production as a function ofz,pT2 and T2> in smallQ2,xBj andW bins. Charge multiplicity ratios and differences as a function ofz andxBj are given forp, d andn-targets. From the differences of charge multiplicities the ratio of the valence quark distributions of the protondv(x)/uv(x) is determined for the first time in charged lepton scattering. The Gronau et al. sum rule is tested, the measured sum being 0.31±0.06 stat. ±0.05 syst., compared with the theoretical expectation of 2/7˜0.286. The measured sum corresponds to an absolute value of the ratio of thed andu quark charge of 0.44±0.10 stat.±0.08 syst.

A comparison is made between the properties of the final state hadrons produced in 280 GeV µp interactions and ine+e- annihilation. The Lund model of hadroproduction is used as an aid in understanding the differences observed. The hadron distributions from µp ande+e- interactions are consistent with the quark parton model assumption of environmental independence, provided that the differences in heavy quark production and hard QCD effects in the two processes are taken into account. A comparison with aK+p experiment is also made. Values are also determined for the Lund model parameters sq = 0.410 ± 0.002 ± 0.020 GeV and s' = 0.29-0.15 -0.13+0.09+0.10 GeV, controlling the transverse momenta in fragmentation and intrinsic transverse momenta of the struck quark respectively.

New results on proton and antiproton production in the target and current fragmentation regions of high energy muon-nucleon scattering are presented. Proton and antiproton production is investigated as a function of Feynmanx and rapidity. No significant difference is observed between production on hydrogen and deuterium targets. Correlations betweenpp, and pairs are analysed and the results are compared with the predictions of the Lund fragmentation model.

The multiplicity distributions of charged hadrons produced in the deep inelastic muon-proton scattering at 280 GeV are analysed in various rapidity intervals, as a function of the total hadronic centre of mass energy W ranging from 4–20 GeV. Multiplicity distributions for the backward and forward hemispheres are also analysed separately. The data can be well parameterized by binomial distributions, extending their range of applicability to the case of lepton-proton scattering. The energy and the rapidity dependence of the parameters is presented and a smooth transition from the negative binomial distribution via Poissonian to the ordinary binomial is observed.

The production of strange particles has been studied in a 280 GeV muon nucleon scattering experiment with acceptance and particle identification over a large kinematical range. The data show that at large values ofxBj the interactions take place mostly on au valence quark in agreement with the basic quarkparton model predictions. This feature results in a strong forward-backward asymmetry in the distribution of strangeness along the rapidity axis. The data are compatible with a strange to non-strange quark suppression factor of ˜0.3 and with a strong suppression of strange diquarks. The distributions ofK+K- pairs show that the two kaons are preferentially produced at neighbouring values of rapidity.

A study of the distribution of the azimuthal angle ? of charged hadrons in deep inelastic µ-p scattering is presented. The dependence of the moments of this distribution on the Feynmanx variable and the momentum transverse to the virtual photon indicates that non-zero moments arise mainly from the effects of the intrinsicKT of the struck quark with T2>>?(0.44 GeV)2, and to a lesser extent from QCD processes. No significant variation withQ2 orW2 is observed.

Dimuon and trimuon events have been studied in deep inelastic muon scattering on an iron target at an incident muon energy of 200 GeV. The events are shown to originate mainly from charm production. Comparison of the measured cross sections with data taken at higher muon energies shows that charm production originates predominantly from transverse virtual photons. Within the framework of the photon gluon fusion model this indicates that the parity of the gluon is odd.