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Cancer cells are able to reach distant tissues by migration and invasion processes. Enhanced ability to cope with physical stresses leading to cell membrane damages may offer to cancer cells high survival rate during metastasis. Consequently, down-regulation of the membrane repair machinery may lead to metastasis inhibition. We show that migration of MDA-MB-231 cells on collagen I fibrils induces disruptions of plasma membrane and pullout of membrane fragments in the wake of cells. These cells are able to reseal membrane damages thanks to annexins (Anx) that are highly expressed in invasive cancer cells. In vitro membrane repair assays reveal that MDA-MB-231 cells respond heterogeneously to membrane injury and some of them possess a very efficient repair machinery. Finally, we show that silencing of AnxA5 and AnxA6 leads to the death of migrating MDA-MB-231 cells due to major defect of the membrane repair machinery. Disturbance of the membrane repair process may therefore provide a new avenue for inhibiting cancer metastasis. [ABSTRACT FROM AUTHOR]

This paper presents recent developments at Commissariat à l'Energie atomique, Laboratoire d'Electronique et de Technologie de l'Information infrared laboratory on processing and characterization of p-on- n HgCdTe (MCT) planar infrared focal plane arrays (FPAs) in short-wave infrared (SWIR) spectral band for the astrophysics applications. These FPAs have been grown using both liquid phase epitaxy and molecular beam epitaxy on a lattice-matched CdZnTe substrate. This technology exhibits lower dark current and lower series resistance in comparison with n-on- p vacancy-doped architecture and is well adapted for low flux detection or high operating temperature. This architecture has been evaluated for space applications in long-wave infrared and very-long-wave infrared spectral bands with cut-off wavelengths from 10 μm up to 17 μm at 78 K and is now evaluated for the SWIR range. The metallurgical nature of the absorbing layer is also examined and both molecular beam epitaxy and liquid phase epitaxy have been investigated. Electro-optical characterizations have been performed on individual photodiodes from test arrays, whereas dark current investigation has been performed with a fully functional readout integrated circuit dedicated to low flux operations. [ABSTRACT FROM AUTHOR]

HgCdTe (MCT) is a very versatile material system for infrared (IR) detection, suitable for high performance detection in a wide range of applications and spectral ranges. Indeed, the ability to tailor the cutoff frequency as close as possible to the needs makes it a perfect candidate for high performance detection. Moreover, the high quality material available today, grown either by molecular beam epitaxy or liquid phase epitaxy, allows for very low dark currents at low temperatures, suitable for low flux detection applications such as science imaging. MCT has also demonstrated robustness to the aggressive environment of space and faces, therefore, a large demand for space applications. A satellite may stare at the earth, in which case detection usually involves a lot of photons, called a high flux scenario. Alternatively, a satellite may stare at outer space for science purposes, in which case the detected photon number is very low, leading to low flux scenarios. This latter case induces very strong constraints onto the detector: low dark current, low noise, (very) large focal plane arrays. The classical structure used to fulfill those requirements are usually p/ n MCT photodiodes. This type of structure has been deeply investigated in our laboratory for different spectral bands, in collaboration with the CEA Astrophysics lab. However, another alternative may also be investigated with low excess noise: MCT n/ p avalanche photodiodes (APD). This paper reviews the latest achievements obtained on this matter at DEFIR (LETI and Sofradir common laboratory) from the short wave infrared (SWIR) band detection for classical astronomical needs, to long wave infrared (LWIR) band for exoplanet transit spectroscopy, up to very long wave infrared (VLWIR) bands. The different available diode architectures ( n/ p VHg or p/ n, or even APDs) are reviewed, including different available ROIC architectures for low flux detection. [ABSTRACT FROM AUTHOR]

We report recent developments at Commissariat à l'Energie Atomique-Laboratoire d'Electronique des Technologies de l'Information Infrared Laboratory on the processing and characterization of p-on- n HgCdTe (MCT) planar infrared focal plane arrays (FPAs) operating in the long-wavelength infrared (LWIR) and very-long-wavelength infrared (VLWIR) spectral bands. The active layers in these FPAs were grown by liquid phase epitaxy (LPE) on a lattice-matched CdZnTe substrate. This technological process results in lower dark current and lower serial resistance than for n-on- p vacancy-doped architecture and thus is better adapted for lower flux detection or higher operating temperature. This architecture was evaluated for space applications in the LWIR and VLWIR spectral bands with cutoff wavelengths from 10 to 17 μm at 78 K. Innovations have been introduced to the technological process to form a heterojunction by use of an LPE growth technique. The initial objective was to reduce the dark current at low temperatures, by reducing the transition temperature from diffusion-limited to depletion-limited dark current. Another advantage is that the wider bandgap obtained in the vicinity of the junction ensures less sensitivity to the defects present at the interface between MCT and passivation layers. Electro-optical characterization of p-on- n photodiodes was performed on quarter video graphics array format FPAs with 25 and 30 μm pixel pitches. The results revealed excellent operabilities in current and responsivity, with low dispersion, and noise limited by current shot noise. Studies performed on the dark current show that dark current densities at 78 K are consistent with the heuristic prediction law 'Rule 07'. Below this temperature, dark current varies as a pure diffusion current for a variety of devices from different manufacturers, introducing a temperature range limitation in the description of the 'Rule 07' law. [ABSTRACT FROM AUTHOR]

We describe the layout and unique features of the focal plane system for MIRI. We begin with the detector array and its readout integrated circuit (combining the amplifier unit cells and the multiplexer), the electronics, and the steps by which the data collection is controlled and the output signals are digitized and delivered to the JWST spacecraft electronics system. We then discuss the operation of this MIRI data system, including detector readout patterns, operation of subarrays, and data formats. Finally, we summarize the performance of the system, including remaining anomalies that need to be corrected in the data pipeline. [ABSTRACT FROM AUTHOR]

Development of antibodies (Abs) against factor VIII (FVIII) is a severe complication of haemophilia A treatment. Recent publications suggest that domain specificity of anti-FVIII antibodies, particularly during immune tolerance induction ( ITI), might be related to the outcome of the treatment. Obtaining suitable tools for a fine mapping of discontinuous epitopes could thus be helpful. The aim of this study was to map discontinuous epitopes on FVIII A2 domain using a new epitope prediction functionality of the PEPOP bioinformatics tool and a peptide inhibition assay based on the Luminex technology. We predicted, selected and synthesized 40 peptides mimicking discontinuous epitopes on the A2 domain of FVIII. A new inhibition assays using Luminex technology was performed to identify peptides able to inhibit the binding of anti-A2 Abs to A2 domain. We identified two peptides ( IFKKLYHVWTKEVG and LYSRRLPKGVKHFD) able to block the binding of anti-A2 allo-antibodies to this domain. The three-dimensional representation of these two peptides on the A2 domain revealed that they are localized on a limited region of A2. We also confirmed that residues 484-508 of the A2 domain define an antigenic site. We suggest that dissection of the antibody response during ITI using synthetic peptide epitopes could provide important information for the management of patients with inhibitors. [ABSTRACT FROM AUTHOR]

The motion of ships can cause discomfort and stress in humans, but little is known about the impact on sheep welfare, despite many sheep traveling long distances by ship during live export. We tested whether exposing sheep to roll (side to side movement), heave (up and down movement), and pitch (front to back movement) with similar amplitude and period conditions to a commercial livestock transport vessel would affect their behavior and physiology. Specifically, we tested the effects of these motions and a control treatment on behavior, heart rate variability, rumination, body posture, and balance of sheep. Four sheep (37 ± 0.1 kg) were restrained in pairs in a crate, which was placed on a moveable and programmable platform that generated roll and pitch motions. An electric forklift was used to produce heave motion. The treatments were applied for 30 min each time in a changeover design with 1 repetition over 8 consecutive days. Sheep behavior was recorded continuously from video records, and heart rate monitors were attached to determine heart rate and its variability. Heave reduced the time that sheep spent ruminating, compared with the other 3 treatments (P < 0.001). The 2 sheep spent more time during heave with their heads 1 above the head of the other (P < 0.001) and looking toward their companion (P = 0.02), indicating greater affiliative behavior. Sheep spent more time during heave standing with their back supported on the crate (P = 0.006) and less time lying down (P = 0.01). Roll caused more stepping motions than pitch and control, indicating loss of balance (P < 0.001). Sheep experiencing heave and roll had increased heart rates and reduced interbeat intervals (IBI) compared to the control (P < 0.001). The IBI of sheep in the heave treatment had an increased ratio of low to high frequency duration (P = 0.01), indicating reduced parasympathetic control of stress responses. Therefore, there was both behavioral and physiological evidence that heave and roll caused stress, with sheep experiencing roll apparently coping better by regular posture changes and heave causing the sheep to seek the close presence of their companion. [ABSTRACT FROM AUTHOR]

Aim The need for developing efficient and safe alternatives to parabens has been growing in the cosmetic and pharmaceutical industries. To this end, the antimicrobial activities and safety of methyl-β- d-maltoside, methyl-β- d-maltotrioside and their dodecyl homologues were investigated. Methods and Results Antimicrobial activities of methyl- and dodecyl-β- d-oligomaltoside have been tested on European pharmacopoeia reference strains. When effective, minimal inhibitory concentrations ranged from 32 to 1024 mg l−1. Methyl derivatives exhibited greater antibacterial properties, while their dodecyl homologues were more active on fungal strains. To elucidate the mechanism of action of methyl compounds, enzymatic inhibition assays of key maltose metabolism enzymes have been conducted. Methyl-β-maltotrioside (MeG3) was found to be effective in inhibiting microbial glucoamylase and α-amylase. MeG3 and dodecyl-β-maltotrioside cytotoxicity were also checked on HepG2 cells and were found to be low, compared with benzalkonium chloride or parabens. Conclusion Methyl- and dodecyl-β-maltoside or maltotrioside were found to be active against reference strains used for preservatives efficacy testing. Methyl derivatives could act through an interesting inhibition of the microbial enzymatic metabolism. Significance and Impact of the Study Given their very simple chemical structure, low toxicity and good antimicrobial activity, methyl-β- d-oligomaltosides could represent a valuable alternative to currently used preservatives such as parabens. [ABSTRACT FROM AUTHOR]

We report the first results of work carried out at CEA and Sofradir to build ultralow-dark-current focal-plane arrays (FPAs) in the short-wave infrared range (SWIR) for space applications. These FPAs are designed to detect very low flux in the 2- μm wavelength range. To this end, Sofradir has designed a source follower per detector read-out circuit (ROIC, 384 × 288, 15 μm pitch). This ROIC has been hybridized on different HgCdTe diode configurations processed at CEA-LETI, and low-flux characterizations have been carried out at CEA-IRFU at low temperature (from 60 K to 160 K). Both ion-implanted p/ n and n/ p diodes have been evaluated. The metallurgical nature of the absorbing layer has also been examined, and both molecular-beam epitaxy (MBE) and liquid-phase epitaxy (LPE) have been applied. Dark-current measurements are discussed in comparison with previous results from the literature. State-of-the-art dark currents are recorded for temperatures higher than 120 K. At temperatures lower than 100 K, the decrease in dark current flattens out for both technologies. In this region, currents between 0.4 e/s/pixel and 0.06 e/s/pixel are reported. [ABSTRACT FROM AUTHOR]

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Antibodies (Abs) that block factor VIII (FVIII) activity occur in hemophilia A patients treated with FVIII replacement therapy and severely impair treatment. In this work, we designed and synthesized ten peptides whose sequences are found in putative epitopes at the surface of a1 and C2 domains of the FVIII molecule. These peptides were screened for their ability to inhibit the binding of anti-FVIII Abs from plasmas of hemophilia A patients to FVIII. All peptides were efficient in inhibiting anti-FVIII Abs in plasma from patients with inhibitors, with however different efficiencies. It was found that each tested patient’s plasma had a different profile of reactivity with peptides, consistent with an individual anti-FVIII Ab specificity. The profile of recognized peptides was also changing during the treatment of the patients. Three peptides were used in an affinity chromatography assay to attempt to remove anti-FVIII Abs from patients’ plasma. Anti-FVIII IgGs were significantly captured by the peptide-Sepharose affinity matrixes as assessed by enzyme-linked immunosorbent assay. However, due to the low level of Abs in the plasma samples, other methods (Chromogenic and Bethesda assays) were not sensitive enough to properly detect the reduction of inhibitors. [ABSTRACT FROM AUTHOR]

Reported myocardial pathology resulting from increased levels of catecholamines in vivo has led us to investigate the effect of adrenalin on the gap junction proteins connexin 40 (Cx40) and Cx43 and the possible relationship to vascular toxicity. Adrenalin and its known metabolites, adrenochrome and adrenolutin, were used in this study. Utilizing the A7r5 rat aortic cell line, we evaluated the effects of adrenalin, adrenochrome, and adrenolutin on the expression and function of connexin 40 and 43 that are present in both cardiac and vascular tissues. [ABSTRACT FROM AUTHOR]

The clinical reasoning process is an important aspect of occupational therapy practice. The purpose of this critical, focused ethnography was to compare the clinical reasoning process of an experienced and novice therapist. Individual semi-structured interviews were conducted with an experienced and a novice therapist after each had reviewed a sample case study to help elicit the clinical reasoning process. Observations in the clinical setting were conducted. Themes which emerged include definitions of clinical reasoning, sources used when reasoning, factors influencing clinical reasoning, ability to prioritize, patient viewed as an individual, patients' role in treatment, and clinical reasoning as an evolving process. Similarities and differences between the therapists are noted and discussed. Implications for practice, education, and future research are identified. [ABSTRACT FROM AUTHOR]

We report 11 cases of vermian partial agenesis without posterior fossa cyst or hemispheric abnormalities. Characteristic MR signs were: absence of the posterior lobe, hypoplasia of the anterior lobe, a narrow sagittal cleft separating the hemispheres ("buttocks sign") and fourth ventricle deformity. The main clinical signs were complex oculomotor dysfunction and developmental delay. None of the patients had respiratory symptoms. Consideration is given to the relationship between Joubert syndrome and this entity as well as to embryological data. [ABSTRACT FROM AUTHOR]

Surface-plasmon waveguides based on metallic strips can provide a two-dimensional optical confinement. This concept has been successfully applied to midinfrared quantum cascade lasers, processed as ridge waveguides, to demonstrate that the lateral extension of the optical mode can be influenced solely by the width of the device top contact. In this configuration, the waveguide mode has a reduced interaction with the top metal and the ridge sidewalls. This results in lower propagation losses and higher performances. For devices operating at a wavelength of lambdaap7.5 mum, the room-temperature threshold current density was reduced from 6.3 to 4.4 kA/cm2 with respect to larger devices with full top metallization [ABSTRACT FROM PUBLISHER]

We report the pulsed, room-temperature operation of λ≈7.5 μm quantum cascade lasers (QCLs) in which the optical mode is a surface-plasmon polariton excitation. Previously reported devices based on this concept operate at cryogenic temperatures only. The use of a silver-based electrical contact with reduced optical losses at the QCL emission wavelength allows a reduction of the laser threshold current by a factor of 2 relative to samples with a gold-based contact layer. As a consequence, the devices exhibit room-temperature operation with threshold current densities ∼6.3 kA/cm2. These devices could be used as all-electrical surface-plasmon generators at midinfrared wavelengths. [ABSTRACT FROM AUTHOR]

Surface-plasmon distributed-feedback quantum cascade lasers with a first-order grating realised by the sole patterning of the top metallic contact are demonstrated. The devices have a single-mode emission with a sidemode suppression ratio greater than 20 dB. The emission wavelength at 78 K is centred at λ=7.3 µm and has a tuning rate as a function of temperature ≃0.4 nm/K. [ABSTRACT FROM AUTHOR]

Pulsed laser action above room temperature at λ≃11.3 μm has been achieved in quantum cascade devices grown by metal organic vapour phase epitaxy (MOVPE). The emission wavelength (λ≃11.3 μm) is the longest reported for QC lasers grown with this technique. The peak output power at 77 K is approximately 315 mW, decreasing to ≃ 100 mW at room temperature. The devices display laser operation up to at least 350 K. [ABSTRACT FROM AUTHOR]

The presenilin 1 (PS1) gene, located on chromosome 14, is the major gene involved in the autosomal dominant forms of early onset Alzheimer's disease (AD). In order to estimate the frequency of de novo PS1 mutations, we have sequenced the PS1 open reading frame in 13 clinically diagnosed patients with no affected relatives, who had developed AD before the age of 50. In one case with onset at 37 years, we identified a missense mutation resulting in a methionine to lysine substitution at codon 139 of the PS1 gene. This substitution is the fourth identified at the same codon. This study, in agreement with previous reports, suggests that de novo PS1 mutations can occur but at a low frequency. [ABSTRACT FROM PUBLISHER]