225 research outputs found
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Blocks to thyroid cancer cell apoptosis can be overcome by inhibition of the MAPK and PI3K/AKT pathways
Current treatment for recurrent and aggressive/anaplastic thyroid cancers is ineffective. Novel targeted therapies aimed at the inhibition of the mutated oncoprotein BRAFV600E have shown promise in vivo and in vitro but do not result in cellular apoptosis. TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a tumor-selective manner by activating the extrinsic apoptotic pathway. Here, we show that a TRAIL-R2 agonist antibody, lexatumumab, induces apoptosis effectively in some thyroid cancer cell lines (HTh-7, TPC-1 and BCPAP), while more aggressive anaplastic cell lines (8505c and SW1736) show resistance. Treatment of the most resistant cell line, 8505c, using lexatumumab in combination with the BRAFV600E inhibitor, PLX4720, and the PI3K inhibitor, LY294002, (triple-drug combination) sensitizes the cells by triggering both the extrinsic and intrinsic apoptotic pathways in vitro as well as 8505c orthotopic thyroid tumors in vivo. A decrease in anti-apoptotic proteins, pAkt, Bcl-xL, Mcl-1 and c-FLIP, coupled with an increase in the activator proteins, Bax and Bim, results in an increase in the Bax to Bcl-xL ratio that appears to be critical for sensitization and subsequent apoptosis of these resistant cells. Our results suggest that targeting the death receptor pathway in thyroid cancer can be a promising strategy for inducing apoptosis in thyroid cancer cells, although combination with other kinase inhibitors may be needed in some of the more aggressive tumors initially resistant to apoptosis
Tomographie ultrasonore pour les arbres sur pied
Ultrasonic tomography on standing trees. Ultrasonic tomography was used for the detection of degradation of transversal section of a beech, attacked by white decay. The image reconstruction of the transversal section of the tree in 2D was obtained with a software, which used the values of ultrasonic velocities measured at different heights from the ground. The attacked wood is characterised by low velocities. The measurements were performed with special transducers of 1 MHz, without damaging the bark of the tree. To improve the readings of the signals, a frequency analysis was performed. The ultrasonic tomographies were compared with the corresponding photographic images and with data obtained with a âResistographâ. A good agreement between ultrasonic tomographies and photographs was observed. The image resolution is between 4 and 5 cm. Presently, this is the best resolution ever obtained with an acoustic nondestructive method on a standing tree
On the connection between the number of nodal domains on quantum graphs and the stability of graph partitions
Courant theorem provides an upper bound for the number of nodal domains of
eigenfunctions of a wide class of Laplacian-type operators. In particular, it
holds for generic eigenfunctions of quantum graph. The theorem stipulates that,
after ordering the eigenvalues as a non decreasing sequence, the number of
nodal domains of the -th eigenfunction satisfies . Here,
we provide a new interpretation for the Courant nodal deficiency in the case of quantum graphs. It equals the Morse index --- at a
critical point --- of an energy functional on a suitably defined space of graph
partitions. Thus, the nodal deficiency assumes a previously unknown and
profound meaning --- it is the number of unstable directions in the vicinity of
the critical point corresponding to the -th eigenfunction. To demonstrate
this connection, the space of graph partitions and the energy functional are
defined and the corresponding critical partitions are studied in detail.Comment: 22 pages, 6 figure
Deontological issues - possible misdiagnosis of cerebral metastases
Authors analyses a number of 4588 (52, 24% over 50 years old) patients operated for cerebral tumors in the Clinic Emergency Hospital âBagdasar-Arseniâ from Bucharest, between 2000-2010, with peculiar attention to the concordance between the preoperative and postoperative diagnosis, related to the actual policy to evaluate a neurosurgical patient before surgery. 903 cases were cerebral metastases and 69,5% aged over 50 years old. In 9,7% of cases we recorded a preoperative misdiagnosis of a metastasis due to few main reasons: unavailable information about a present primitive cancer, treacherous MRI image with a single confusing appearance of a cerebral lesion, age less than 50 years old, clinical presentation and biological evaluation inconsistent with malignancy. Authors point that these situations can have serious consequences related to professional competence, deterioration of the patient-doctor relationship, increasing costs for completion of diagnosis and treatment, and inadequate information about patientâs prognosis
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Overview of the SMART-BEAR Technical Infrastructure
This paper describes a cloud-based platform that offers evidence-based, personalised interventions powered by Artificial Intelligence to help support efficient remote monitoring and clinician-driven guidance to people over 65 who suffer or are at risk of hearing loss, cardiovascular diseases, cognitive impairments, balance disorders, and mental health issues. This platform has been developed within the SMART-BEAR integrated project to power its large-scale clinical pilots and comprises a standards-based data harmonisation and management layer, a security component, a Big Data Analytics system, a Clinical Decision Support tool, and a dashboard component for efficient data collection across the pilot sites
Computational horizons in cancer (CHIC) : developing meta- and hyper-multiscale models and repositories for in Silico Oncology - a brief technical outline of the project
This paper briefly outlines the aim, the objectives, the architecture and the main building blocks of the ongoing large scale integrating transatlantic research project CHIC (http://chic-vph.eu/)
Compact Polyelectrolyte Complexes: âSaloplasticâ Candidates for Biomaterials
Precipitates of polyelectrolyte complexes were transformed into rugged shapes suitable for bioimplants by ultracentrifugation in the presence of high salt concentration. Salt ions dope the complex, creating a softer material with viscous fluid-like properties. Complexes that were compacted under the centrifugal field (CoPECs) were made from poly(diallyldimethyl ammonium), PDADMA, as polycation, and poly(styrene sulfonate), PSS, or poly(methacrylic acid), PMAA, as polyanion. Dynamic mechanical testing revealed a rubbery plateau at lower frequencies for PSS/PDADMA with moduli that decreased with increasing salt concentration, as internal ion pair cross-links were broken. CoPECs had significantly lower modulii compared to similar polyelectrolyte complexes prepared by the âmultilayering â method. The difference in mechanical properties was ascribed to higher water content (located in micropores) for the former and, more importantly, to their nonstoichiometric polymer composition. The modulus of PMAA/PDADMA CoPECs, under physiological conditions, demonstrated dynamic mechanical properties that were close to those of the nucleus pulposus in an intervertebral disk
Mineral Preservatives in the Wood of Stradivari and Guarneri
Following the futile efforts of generations to reach the high standard of excellence achieved by the luthiers in Cremona, Italy, by variations of design and plate tuning, current interest is being focused on differences in material properties. The long-standing question whether the wood of Stradivari and Guarneri were treated with wood preservative materials could be answered only by the examination of wood specimens from the precious antique instruments. In a recent communication (Nature, 2006), we reported about the degradation of the wood polymers in instruments of Stradivari and Guarneri, which could be explained only by chemical manipulations, possibly by preservatives. The aim of the current work was to identify the minerals from the small samples of the maple wood which were available to us from the antique instruments. The ashes of wood from one violin and one cello by Stradivari, two violins by Guarneri, one viola by H. Jay, one violin by Gand-Bernardel were analyzed and compared with a variety of commercial tone woods. The methods of analysis were the following: back-scattered electron imaging, X-ray fluorescence maps for individual elements, wave-length dispersive spectroscopy, energy dispersive X-ray spectroscopy and quantitative microprobe analysis. All four Cremonese instruments showed the unmistakable signs of chemical treatments in the form of chemicals which are not present in natural woods, such as BaSO4, CaF2, borate, and ZrSiO4. In addition to these, there were also changes in the common wood minerals. Statistical evaluation of 12 minerals by discriminant analysis revealed: a. a difference among all four Cremona instruments, b. the difference of the Cremonese instruments from the French and English antiques, and c. only the Cremonese instruments differed from all commercial woods. These findings may provide the answer why all attempts to recreate the Stradivarius from natural wood have failed. There are many obvious implications with regard to how the green tone wood should be treated, which chould lead to changes in the practice of violin-making. This research should inspire others to analyze more antique violins for their chemical contents
Characterisation and categorisation of the diversity in viscoelastic vibrational properties between 98 wood types
International audienceContext Increased knowledge on diversity in wood properties would have implications both for fundamental research and for promoting a diversification of uses as material. *Aims The objective is to contribute to overcoming the critical lack of data on the diversity of wood dynamic mechanical/viscoelastic vibrational properties, by testing lesser-known species and categorizing sources of variability. *Methods Air-dry axial specific dynamic modulus of elasticity (E'/Îł) and damping coefficient (tanÎŽ) were measured on a wide sampling (1792 specimens) of 98 wood types from 79 species. An experimental device and protocol was designed for conducting systematic (i.e. rapid and reproducible) characterizations. *Results Diversity at the specimens' level corroborates the "standard" relationship between tanÎŽ and E'/Îł, which is discussed in terms of orientation of wood elements and of chemical composition. Diversity at the species level is expressed on the basis of results for normal heartwood, with specific gravity (Îł) ranging from 0.2 to 1.3. Axial E'/Îł ranges from 9 to 32 GPa and tanÎŽ from 4Ă10-3 to 19Ă10-3. Properties distribution follows a continuum, but with group characteristics. The lowest values of tanÎŽ are only found in certain tropical hardwoods. Results can also suggest alternative species for musical instruments making
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