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ObjectiveOur aim is to validate the process steps implemented by the French CATI platform to assess amyloid status, obtained from 18F-Florbetapir PET scans, in a cohort of 318 cognitively normal subjects participating in the INSIGHT-preAD study. Our objective was to develop a method with partial volume effect correction (PVEC) on untransformed PET images, using an automated pipeline (“RACHEL”) adapted to large series of patients and including quality checks of results.MethodsWe compared RACHEL using different options (with and without PVEC, different sets of regions of interest), to two other methods validated in the literature, referred as the “AVID” and “CAEN” methods. A standard uptake value ratio (SUVR) was obtained with the different methods for participants to another French study, IMAP, including 26 normal elderly controls (NEC), 11 patients with mild cognitive impairment (MCI) and 16 patients with Alzheimer’s disease (AD). We determined two cutoffs for RACHEL method by linear correlation with the other methods and applied them to the INSIGHT-preAD subjects.ResultsRACHEL including PVEC and a combination of the whole cerebellum and the pons as a reference region allowed the best discrimination between NEC and AD participants. A strong linear correlation was found between RACHEL and the other two methods and yielded the two cutoffs of 0.79 and 0.88. According to the more conservative threshold, 19.8% of the INSIGHT-preAD subjects would be considered amyloid positive, and 27.7% according to the more liberal threshold.ConclusionsWith our method, we clearly discriminated between NEC with negative amyloid status and patients with clinical AD. Using a linear correlation with other validated cutoffs, we could infer our own positivity thresholds and apply them to an independent population. This method might be useful to the community, especially when the optimal cutoff could not be obtained from a population of healthy young adults or from correlation with post-mortem results.

The unpolarized and polarized Beam Char\\-ge Asymmetries (BCAs) of the \\(\\vv{e}^{\\pm}p \\to e^{\\pm}p \\gamma\\) process off unpolarized hydrogen are discussed. The measurement of BCAs with the CLAS12 spectrometer at the Thomas Jefferson National Accelerator Facility, using polarized positron and electron beams at 10.6 GeV is investigated. This experimental configuration allows to measure azimuthal and \\(t\\)-dependences of the unpolarized and polarized BCAs over a large \\((x_B,Q^2)\\) phase space, providing a direct access to the real part of the Compton Form Factor (CFF) \\({\\mathcal H}\\). Additionally, these measurements confront the Bethe-Heitler dominance hypothesis and eventual effects beyond leading twist. The impact of potential positron beam data on the determination of CFFs is also investigated within a local fitting approach of experimental observables. Positron data are shown to strongly reduce correlations between CFFs and consequently improve significantly the determination of \\(\\Re {\\rm e} [\\mathcal{H}]\\).

We propose to use the High Momentum Spectrometer of Hall C combined with the Neutral Particle Spectrometer (NPS) to perform high precision measurements of the Deeply Virtual Compton Scattering (DVCS) cross section using a beam of positrons. The combination of measurements with oppositely charged incident beams is the only unambiguous way to disentangle the contribution of the DVCS\\(^2\\) term in the photon electroproduction cross section from its interference with the Bethe-Heitler amplitude. This provides a stronger way to constrain the Generalized Parton Distributions of the nucleon. A wide range of kinematics accessible with an 11 GeV beam off an unpolarized proton target will be covered. The \\(Q^2-\\)dependence of each contribution will be measured independently.

Positron beams, both polarized and unpolarized, are identified as essential ingredients for the experimental program at the next generation of lepton accelerators. In the context of the Hadronic Physics program at the Jefferson Laboratory (JLab), positron beams are complementary, even essential, tools for a precise understanding of the electromagnetic structure of the nucleon, in both the elastic and the deep-inelastic regimes. For instance, elastic scattering of (un)polarized electrons and positrons off the nucleon allows for a model independent determination of the electromagnetic form factors of the nucleon. Also, the deeply virtual Compton scattering of (un)polarized electrons and positrons allows us to separate unambiguously the different contributions to the cross section of the lepto-production of photons, enabling an accurate determination of the nucleon Generalized Parton Distributions (GPDs), and providing an access to its Gravitational Form Factors. Furthermore, positron beams offer the possibility of alternative tests of the Standard Model through the search of a dark photon or the precise measurement of electroweak couplings. This letter proposes to develop an experimental positron program at JLab to perform unique high impact measurements with respect to the two-photon exchange problem, the determination of the proton and the neutron GPDs, and the search for the \\(A^{\\prime}\\) dark photon.

Liver X receptors (LXRs) have been proposed to have some anticancer properties, through molecular mechanisms that remain elusive. Here we report for the first time that LXR ligands induce caspase-1-dependent cell death of colon cancer cells. Caspase-1 activation requires Nod-like-receptor pyrin domain containing 3 (NLRP3) inflammasome and ATP-mediated P2 × 7 receptor activation. Surprisingly, LXR β is mainly located in the cytoplasm and has a non-genomic role by interacting with pannexin 1 leading to ATP secretion. Finally, LXR ligands have an antitumoral effect in a mouse colon cancer model, dependent on the presence of LXR β , pannexin 1, NLRP3 and caspase-1 within the tumor cells. Our results demonstrate that LXR β , through pannexin 1 interaction, can specifically induce caspase-1-dependent colon cancer cell death by pyroptosis.

In this paper, a wideband small cavity-backed magneto-electric (ME) antenna is proposed. This antenna is linearly polarized and designed to cover all the Global Navigation Satellite System (GNSS) bands. It exhibits small external dimensions of 90 × 90 × 40 mm3 (0.34 × 0.34 × 0.15 λ3 at lowest frequency) and achieves a wide impedance bandwidth of 40.5% (from 1.14 to 1.72 GHz) due to the excitation of a third resonance of the ME structure. It also provides a regular broadside gain of 5.2 dBi and stable radiation pattern in both E and H planes of the antenna.

Postanthesis growth of tomato (Solanum lycopersicon) as of many types of fruit relies on cell division and cell expansion, so that some of the largest cells to be found in plants occur in fleshy fruit. Endoreduplication is known to occur in such materials, which suggests its involvement in cell expansion, although no data have demonstrated this hypothesis as yet. We have analyzed pattern formation, cell size, and ploidy in tomato fruit pericarp. A first set of data was collected in one cherry tomato line throughout fruit development. A second set of data was obtained from 20 tomato lines displaying a large weight range in fruit, which were compared as ovaries at anthesis and as fully grown fruit at breaker stage. A remarkable conservation of pericarp pattern, including cell layer number and cell size, is observed in all of the 20 tomato lines at anthesis, whereas large variations of growth occur afterward. A strong, positive correlation, combining development and genetic diversity, is demonstrated between mean cell size and ploidy, which holds for mean cell diameters from 10 to 350 [micro]m (i.e. a 32,000-times volume variation) and for mean ploidy levels from 3 to 80 C. Fruit weight appears also significantly correlated with cell size and ploidy. These data provide a framework of pericarp patterning and growth. They strongly suggest the quantitative importance of polyploidy-associated cell expansion as a determinant of fruit weight in tomato.

The omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has anti-inflammatory and anti-cancer properties. Among pro-inflammatory mediators, tumor necrosis factor α (TNFα) plays a paradoxical role in cancer biology with induction of cancer cell death or survival depending on the cellular context. The objective of the study was to evaluate the role of TNFα in DHA-mediated tumor growth inhibition and colon cancer cell death. The treatment of human colorectal cancer cells, HCT-116 and HCT-8 cells, with DHA triggered apoptosis in autocrine TNFα-dependent manner. We demonstrated that DHA-induced increased content of TNFα mRNA occurred through a post-transcriptional regulation via the down-regulation of microRNA-21 (miR-21) expression. Treatment with DHA led to nuclear accumulation of Foxo3a that bounds to the miR-21 promoter triggering its transcriptional repression. Moreover, inhibition of RIP1 kinase and AMP-activated protein kinase α reduced Foxo3a nuclear-cytoplasmic shuttling and subsequent increase of TNFα expression through a decrease of miR-21 expression in DHA-treated colon cancer cells. Finally, we were able to show in HCT-116 xenograft tumor-bearing nude mice that a DHA-enriched diet induced a decrease of human miR-21 expression and an increase of human TNFα mRNA expression limiting tumor growth in a cancer cell-derived TNFα dependent manner. Altogether, the present work highlights a novel mechanism for anti-cancer action of DHA involving colon cancer cell death mediated through autocrine action of TNFα.

The organoleptic quality of tomato fruit involves a set of attributes (flavour, aroma, texture) that can be evaluated either by sensory analyses or by instrumental measures. In order to study the genetic control of this characteristic, a recombinant inbred line (RIL) population was developed from an intraspecific cross between a cherry tomato line with a good overall aroma intensity and an inbred line with medium flavour but bigger fruits. A total of 38 traits involved in organoleptic quality were evaluated. Physical traits included fruit weight, diameter, colour, firmness, and elasticity. Chemical traits were dry matter weight, titratable acidity, pH, and the contents of soluble solids, sugars, lycopene, carotene, and 12 aroma volatiles. A panel of trained assessors quantified sensory attributes: flavour (sweetness and sourness), aroma (overall aroma intensity, together with candy, lemon, citrus fruit, and pharmaceutical aromas) and texture (firmness, meltiness, mealiness, juiciness, and skin difficult to swallow). RILs showed a large range of variation. Molecular markers were used to map a total of 130 quantitative trait loci (QTL) for the 38 traits. They were mainly distributed in a few chromosome regions. Major QTLs (R2 >30%) were detected for fruit weight, diameter, colour, firmness, meltiness, and for six aroma volatiles. The relationships between instrumental measures and sensory traits were analysed with regard to the QTL map. A special insight was provided about the few regions where QTLs are related to multiple traits. A few examples are shown to illustrate how the simultaneous analysis of QTL segregation for related traits may aid in understanding the genetic control of quality traits and pave the way towards QTL characterization.