Journals
2009 EN
Dominique Ambard · Fabien Cherblanc
Experimental uniaxial tensile tests have been carried out on annulus tissue samples harvested on pig and lamb lumbar intervertebral discs. When subjecting the samples to loading cycles, the stress-strain curves exhibit strong nonlinearities and hysteresis. This particular behavior results from the anisotropic microstructure of annulus tissue composed of woven oriented collagen fibers embedded in the extracellular matrix. During uniaxial tension, the collagen fibers reorient toward the loading direction increasing its global stiffness. To describe this behavior, we propose a heuristic two-dimensional rheological model based on three mechanical and one geometrical characteristics. The latter one is the fibers orientation angle becoming the key parameter that govern the macroscopic mechanical behavior. The experimental results are used to identify the physical properties associated with the rheological model, leading to an accurate representation of the stress-strain curve over a complete loading cycle. In this framework, the fibers reorientation can solely account for the rigidity increase while the hysteresis is associated with liquid viscous flows through the matrix. Based on this representation, unusual coupling effects between strains and fluid flows can be observed, that would significantly affect the cell nutrients transport mechanisms.
Springer Science+Business Media
Journals
2009 EN
Dominique Ginhac · Jérôme Dubois · Barthélémy Heyrman
+1 more
International audienceA high speed analog VLSI image acquisition and low-level image processing system is presented. The architecture of the chip is based on a dynamically reconfigurable SIMD processor array. The chip features a massively parallel architecture enabling the computation of programmable mask-based image processing in each pixel. Each pixel include a photodiode, an amplifier, two storage capacitors, and an analog arithmetic unit based on a four-quadrant multiplier architecture. A 64 × 64 pixel proof-of-concept chip was fabricated in a 0.35 μm standard CMOS process, with a pixel size of 35 μm × 35 μm. The chip can capture raw images up to 10,000 fps and runs low-level image processing at a framerate of 2,000–5,000 fp
Springer Science+Business Media
Journals
2009 EN
Stefania Millevoi · Sandra Bernat · Dominique Telly
+5 more
Several unclassified variants (UV) of BRCA1 can be deleterious by affecting normal pre-mRNA splicing. Here, we investigated the consequences at the mRNA level of the frequently encountered c.5242C>A UV in BRCA1 exon 18. We show that the c.5242C>A variant induces skipping of exon 18 in UV carriers and in vitro. This alteration predicted to disrupt the first BRCT domain of BRCA1. We show that two splicing repressors, hnRNP A1 and hnRNP H/F, display a significant preference toward binding with the mutated exon 18 and assemble into a protein complex. Sequence analysis of the region surrounding the c.5242C>A change reveals the presence of hnRNP A1 and hnRNP H/F binding sites, which are modified by several UVs. Mutation of these sites alters the RNA binding ability of both splicing regulators. In conclusion, our work supports the model of the pathogenicity of the c.5242C>A BRCA1 variant that induces exon skipping by creating a sequence with silencer properties. We propose that other UVs in exon 18 interfere with splicing complex assembly by perturbing the binding of hnRNP A1 and hnRNP H/F to their respective cis-elements. RNA analysis is therefore necessary for the assessment of the consequences of UVs on splicing of disease-associated genes and to enable adequate genetic counseling for breast/ovarian cancer families.
Springer Science+Business Media
Journals
2009 EN
Laura La Paglia · Anthony Laugé · Jérémie Weber
+5 more
Biallelic inactivation of the ATM gene causes ataxia-telangiectasia (A-T), a complex neurological disease associated with a high risk of leukaemias and lymphomas. Mothers of A-T children, obligate ATM heterozygote mutation carriers, have a breast cancer (BC) relative risk of about 3. The frequency of ATM carriers in BC women with a BC family history has been estimated to be 2.70%. To further our clinical understanding of familial BC and examine whether haematological malignancies are predictive of ATM germline mutation, we estimated the frequency of heterozygote mutation carriers in a series of 122 BC women with a family history of both BC and haematological malignancy and without BRCA1/2 mutation. The gene screening was performed with a new high throughput method, EMMA (enhanced mismatch mutation analysis). Amongst 28 different ATM variants, eight mutations have been identified in eight patients: two mutations leading to a putative truncated protein and six being likely deleterious mutations. One of the truncating mutations was initially interpreted as a missense mutation, p.Asp2597Tyr, but is actually a splice mutation (c.7789G>T/p.Asp2597_Lys2643>LysfsX3). The estimated frequency of ATM heterozygote mutation carriers in our series is 6.56% (95% CI: 2.16-10.95), a significantly higher figure than that observed in the general population, estimated to be between 0.3 and 0.6%. Although a trend towards an increased frequency of ATM carriers was observed, it was not different from that observed in a population of familial BC women not selected for haematological malignancy as the frequency of ATM carriers was 2.70%, a value situated in the confidence interval of our study.
Springer Science+Business Media
Journals
2009 EN
Youlia Kirova · Alexia Savigi · Brigitte SigalZafrani
+6 more
As tumours in BRCA1/2 mutation carriers might be more sensitive to radiation, we investigated after long-term follow-up whether mutation status influenced the rate of ipsilateral and contralateral breast cancers after breast-conserving treatment (BCT). BRCA1 and BRCA2 genes were screened for germline mutations in 131 patients with a family history of breast and/or ovarian cancer who had undergone BCT and radiotherapy. Patients were matched to 261 controls with sporadic breast cancer according to age at diagnosis and year of treatment. Controls were followed up for at least as long as the interval between diagnosis and genetic screening in familial cases. Rates of ipsilateral and contralateral cancer between groups were compared by the log-rank test. The BRCA1/2 mutations occurred in 20.6% of tested patients. Tumours in mutation carriers were more likely to be grade III (P < 10(-4)) and oestrogen receptor negative (P = 0.005) than in non-carriers and controls. Overall median follow-up was 161 months. There was no significant difference in ipsilateral tumours between mutation carriers, non-carriers and controls (P = 0.13). On multivariate analysis, age was the most significant predictor for ipsilateral recurrence (P < 10(-3)). The rate of contralateral cancer was significantly higher in familial cases: 40.7% (mutation carriers), 20% (non-carriers), and 11% (controls) (P < 10(-4)). After 13.4 years of follow-up, the rate of ipsilateral tumours was no higher in mutation carriers than in non-carriers or controls. As tumours in BRCA1/2 mutation carriers might be more sensitive to radiation, BCT is a possible treatment option.
Springer Science+Business Media
Journals
2009 EN
Sabine Rohrmann · Jakob Linseisen · Alina Vrieling
+45 more
To examine the association of baseline and lifetime ethanol intake with cancer of the pancreas in the European Prospective Investigation into Cancer and Nutrition (EPIC).
Springer Science+Business Media
Journals
2009 EN
Frederike L. Büchner · H. Bas BuenodeMesquita · Jakob Linseisen
+47 more
To examine the association between fruit and vegetable consumption and risk of different histological subtypes of lung cancer among participants of the European Prospective Investigation into Cancer and Nutrition study.
Springer Science+Business Media
Journals
2009 EN
Salma Chahed · Éric Marcon · Evren Şahin
+2 more
Home Care (HC) services provide complex and coordinated medical and paramedical care to patients at their homes. As health care services move into the home setting, the need for developing innovative approaches that improve the efficiency of home care organizations increases. We first conduct a literature review of investigations dealing with operation planning within the area of home care management. We then address a particular issue dealing with the planning of operations related to chemotherapy at home as it is an emergent problem in the French context. Our interest is focused on issues specific to the anti-cancer drug supply chain. We identify various models that can be developed and analyze one of them.
Springer Science+Business Media
Journals
2009 EN
Frank Huysentruyt · Beatrijs Moerkerke · Stijn Devaere
+1 more
An ontogenetic series of in-captivity bred Corydoras aeneus was used, in order to study the developmental changes in the external morphology.Allometric growth of several body parts was studied, attempting to reveal important steps in the species' early life history. Based on the external morphology, the different stages during early development of C. aeneus were identified, according to Balon (Journal of the FisheriesResearch Board of Canada 32: 1663 1670, 1975). After hatching, at a SL of 3.5 mm, the developmental state corresponded to an eleutherembryonic phase, followed by the protopterygiolarval phase (4.4-5.7 mmSL), the pterygiolarval phase (5.7-14.0 mm SL) and the juvenile period. In addition, an overall growth curve and inflexion points were determined. As such, ontogenetic changes in growth coefficients k (in SL = b age(k)) were determined. Log transformed data were used for a piecewiselinear regression method, as per regression spline smoothing procedures. This way, the growth curve could be divided into six different intervals of growth rate. Initially, the slope was 0.05 until 0.7 dph, then increasing to 0.18 until 4 dph, and 0.36 until 10 dph. After this, growth rate reached a maximumof 0.76 until 24 dph, slowed down to 0.47 until 37 dph and then finally again slowed down to 0.36. A similar growth analysis was also done on the different body parts and these results were compared to both morphological and data from literature. This led to the conclusion that the inflexion points found during the early development of C. aeneus matched the different key-events known in teleost early life history and development. The transition from endo- to exogenous feeding, at the moment a functional branchial respiratory system becomes increasingly important, was the first point at which allometries changed together with functional demands. A second, similar congruence occurred at the transition to the pterygiolarval phase, when priorities shift towards locomotory needs. Finally, our results also indicated a transition to a carangiform swimming mode at approximately 8 mm SL
Springer Science+Business Media
Journals
2009 EN
Fabrice Guérif · M. Lemseffer · Milène Blanchard
+1 more
While extended culture has been considerably improved, some questions remain regarding the application of Single Blastocyst Transfer (SBT).
Springer Science+Business Media