Piston and tilt interferometry for segmented wavefront sensing.

We present a novel interferometric technique dedicated to the measurement of relative phase differences (pistons) and tilts of a periodically segmented wavefront. Potential applications include co-phasing of segmented mirrors of Keck-like telescopes as well as coherent laser beam combining. The setup only requires a holes mask selecting the center part of each element, a diffracting component, and a camera. Recorded interferogram is made of many subareas with sinusoidal fringe pattern. From each pattern, piston is extracted from fringe shift and tilts from fringe frequency and orientation. The pattern analysis is simple enough to enable kilohertz rate operation. The λ ambiguities are solved by a two-wavelength measurement. This technique is compatible with a very high number of elements and can be operated in the presence of atmospheric turbulence.

[Nager syndrome associated with tetralogy of Fallot: A frequent association?]. / Syndrome de Nager associé à une tétralogie de Fallot : une association fréquente ?

Nager syndrome belongs to a heterogeneous group of disorders involving abnormal development of the extremities, face, and jaw: acrofacial dysostosis (AFD). Fewer than 100 cases of Nager syndrome have been reported to date. Recently, mutations in the 1q21.2 region of the SF3B4 gene (splicing factor 3B subunit 4), which encodes a spliceosomal protein (SAP49) involved in the assembly of the spliceosomal complex U2SNP, have been demonstrated in patients with Nager syndrome. We report the case of a child who had a characteristic association (Pierre Robin sequence, bilateral and symmetrical malar hypoplasia, absent thumbs) clinically diagnosed as Nager syndrome. This child also presented tetralogy of Fallot. This combination is unusual; only two other cases have been described. The karyotype and the CGH-array were normal. After the description in 2012 of several mutations in the SF3B4 gene (1q21.2) in Nager syndrome, a genetic search for our patient revealed the mutation c.1229delC. In 2013, other authors showed the presence of these same mutations in the majority of their patients diagnosed as Nager syndrome. The haploinsufficiency of the SF3B4 region seems to be the major cause of Nager syndrome.

Collective phase measurement of an array of fiber lasers by quadriwave lateral shearing interferometry for coherent beam combining.

We present a new configuration of quadriwave lateral shearing interferometer dedicated to phase detection for beam-combining purposes. Assuming that the fibers are disposed in a matrix arrangement, our scheme gives direct access to the phase step between adjacent fibers in two dimensions. Experimentally recorded interferograms are made only of two-wave interference fringes that scroll as the phase evolves in the fibers. This simplicity allows fast treatment by the spatial demodulation process, and the phase map from the fibers can be estimated in real time. No external reference is required, and the technique is fully compatible with a high number of fibers.

Phase and amplitude control of a multimode LMA fiber beam by use of digital holography.

Amplitude and phase control of the output beam of a multimode LMA fiber supporting 4 modes is demonstrated by digital holography in both continuous and ns pulsed regimes at 1064 nm. Our system allows dynamic compensation of beam pointing instabilities, external perturbations introducing low order aberrations and fluctuations of the relative phase of the modes supported by the fiber.

Coherent fiber combining by digital holography.

We present an original technique for coherent beam combining of an array of fiber amplifiers based on self-adaptive digital holography. In this method, the phase errors between the fibers of the array are compensated by using the diffracted phase-conjugated -1 order of a digital hologram. The proposed method is compatible with a large number of fibers and simply implemented with a CCD detector matrix and a spatial light modulator. This concept is analyzed and experimentally demonstrated with three polarization-maintaining passive fibers at 1.06 microm.

Randomized study of recombinant interleukin-2 after autologous bone marrow transplantation for acute leukemia in first complete remission.

Immunological control of acute leukemia may be achieved after allogeneic transplant. Despite promising preliminary results, the impact of immunotherapy with interleukin-2 (r-IL-2) on patients with acute leukemia (AL), in first complete remission (CR1) remains unclear. We conducted a prospective multicenter randomized trial to compare outcome in patients with AL in CR1, treated with autologous bone marrow transplantation (BMT) with or without postgraft r-IL-2. One hundred and thirty patients with AL in CR1 (myeloblastic (AML): N = 78; lymphoblastic (ALL): N = 52) were randomized at time of BMT to receive (N = 65) or not (N = 65) r-IL-2. r-IL-2 (RU 49637 from Roussel Uclaf) was started after hematological recovery, as a five cycle regimen (12 M IU/m2/day continuous infusion on day 1-5, 15-17, 29-31,43-45 and 57-59). The two groups were balanced for patient and transplant characteristics. Analysis was based on an intent to treat. Thirty-eight (59%) of the 65 patients randomized into the study group started r-IL-2 at a median of sixty-eight days (23-140) after transplant and received 77% (16-100) of the scheduled dosage. They received a median of 120 x 10(6) IU/m2 (25-156) over 10 (3-13) days during a total median period of 56 (3-78) days. With a median follow-up of 7 years (5.4-8.1 years), 79 patients relapsed (study group: 43 (66%); control group: 36 (55%): p = NS). Survival and leukemia-free survival estimates were 33% (23-45) versus 43% (22-52) and 29% (19-41) versus 36% (24-51) respectively for study and control groups (all p = NS). These results show that leukemic control after autologous BMT is not increased by r-IL-2 therapy. Further studies should investigate more appropriate r-IL-2 schedules and the possibilities offered by better antigen recognition and activated effector cells.

Parallel regional quantification of choline acetyltransferase and cholinesterase activity in the central nervous system of an invertebrate (Sepia officinalis).

The present study describes (i) a procedure to dissect the central nervous system of the cuttlefish (Cephalopod) into ten, functionally distinct, anatomical regions of interest and (ii) the parallel measurement of acetylcholine synthesis (choline acetyltransferase) and degradation (cholinesterase) activities. Both aspects (dissection and parallel quantification of acetylcholine synthesis and degradation) could be of great importance for quantitative regional studies in neurochemistry in this animal model, it is interesting to study the cellular and molecular mechanisms involved in learning and aging processes. The parallel quantification of acetylcholine synthesis and degradation applicable to any animal model is pivotal since both enzymes are essential for the cholinergic neurotransmission and may be differentially modulated by specific functions such as learning and aging processes. Furthermore, since choline acetyltransferase and cholinesterase show different localization into the brain, their parallel quantification may underlie the involvement of cholinesterase in non-cholinergic functions, which remain unclear throughout the animal kingdom.

Central acetylcholine synthesis and catabolism activities in the cuttlefish during aging.

Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities, measured in 10 central regions of young, middle-aged and old cuttlefish, showed a regional heterogeneity but with different age-related distribution patterns. Maximal acetylcholine synthesis and catabolism were observed in the inferior frontal and the optic lobes. Important age-related decreases in ChAT activities were evidenced in most regions, while only moderate variations were found for AChE. Since the superior frontal lobe is involved in visual learning, the dramatic decrease in ChAT activity observed in this lobe (-77%) could be implicated in the learning deficits reported in senescent Sepia.

The use of a sequential high dose recombinant interleukin 2 regimen after autologous bone marrow transplantation does not improve the disease free survival of patients with acute leukemia transplanted in first complete remission.

We report the outcome of 50 consecutive patients with CR1 acute leukemia (AML = 22; ALL = 28) treated with autologous BMT, after cyclophosphamide and TBI, followed with a sequential high dose rIL2 regimen. rIL-2 (RU 49637 from Roussel-Uclaf, Romainville, France) was started after hematological reconstitution an average of 72 +/- 22 days post transplant. The schedule consisted of a continuous infusion over 5 cycles (Cycle 1: 5 days starting on day 1; cycle 2-5: 2 days starting on day 15, 29, 43 and 57). Patients were treated at 4 different dosages (12 (N = 40), 16 (N = 3), 20 (N = 2), 24 (N = 5) x 10(6) IU/m2/day). Toxicities were mainly related to capillary leak syndrome and thrombocytopenia. Patients received an average of 122 +/- 49 10(6) IU/m2. Two patients with AML died from toxicity. rIL-2 infusion was associated with very a high level of immune stimu-lation of both T-cells (P < 0.05) and natural killer (NK) cells (P < 0.05) and associated cytolytic functions (P < 0.05). With a minimal and median follow-up of 21 and 46 months, 3 year leukemia free survival is 41 +/- 6% overall, 39 +/- 10% and 43 +/- 8% for AML and ALL respectively. Relapse probabilities at 3 years are 59 +/- 11% for AML and 57 +/- 8% for ALL. We conclude that this short infusion of rIL-2 over 2 months, resulting in an increased immune stimulation, is not associated with a better leukemic control for patients with acute leukemia transplanted early after reaching first complete remission.

In vivo binding, pharmacokinetics and metabolism of the selective M2 muscarinic antagonists [3H]AF-DX 116 and [3H]AF-DX 384 in the anesthetized rat.

The pharmacokinetics, in vivo binding and metabolism of two M2 muscarinic receptor antagonists, [3H]AF-DX 116 and [3H]AF-DX 384, were studied in anesthetized rats, which received either the tracer alone or following a saturating injection of atropine. Both radioligands were cleared from the circulation with distribution half-lives of 17 and 14 sec and elimination half-lives of 17 and 40 min for [3H]AF-DX 116 and [3H]AF-DX 384, respectively. A radioactive distribution, predominant in peripheral organs when compared to brain, was found at each time studied after tracer injection. Atropine-displaceable tracer uptake was evidenced at 20-40 min in brain (31%), submandibular glands (26%), spleen (37%) and notably heart (55%) for [3H]AF-DX 116 but only in heart (50%) for [3H]AF-DX 384 at 10-20 min. Regional brain sampling revealed a relatively uniform distribution of [3H]AF-DX 384 and a -45% atropine saturation effect (i.e., specific binding) in the thalamus 20 min after injection. Sequential thin-layer chromatographic studies performed on tissue extracts demonstrated the rapid appearance of labeled metabolites of both radiotracers in brain (but less so in liver) and especially in cardiac tissues, where almost 70% of total radioactivity still corresponded to authentic tracer 40 min after injection. Thus, based on their low blood-brain barrier permeability and the high presence of labeled metabolites in the central nervous system, AF-DX 116 and AF-DX 384 might be more helpful in the study of M2 muscarinic receptors present in heart rather than brain. Labeled with positron emittors, these M2 antagonists might be applicable to the pathophysiological study of disease states, such as cardiomyopathies.

Joint action of combinations of pollutants on the acetylcholinesterase activity of several marine species.

: Acetylcholinesterase (AChE) is used as a specific biomarker of the effects of organophosphorous (OP) and carbamate (C) insecticides on the coastal marine environment. Studies of mixtures (by pairs) of five of these substances showed cumulative, synergistic inhibitory effects in all cases. The strongest synergy was observed in organophosphate-carbamate mixtures (OP-C) and the least in mixtures of substances of the same type (OP-OP, C-C). The intensity of the synergistic effect was directly related to the length of time the enzyme was incubated with the inhibitory mixtures. Among the major organic contaminants of the marine environment, DDT and lindane (organochlorines), as well as atrazine and isoproturon, are not AChE inhibitors and had no effect on the inhibitory action of the OP and C insecticides tested. Among contaminants of metallic origin, zinc chloride, cadmium chloride, tributyltin chloride and methylmercury did not inhibit AChE at the concentrations measured in the different marine compartments (water, sediment, living matter). Mercuric chloride and arsenite had a weak inhibitory action in certain organisms. Zinc chloride, cadmium chloride and arsenic enhanced the inhibitory effects of some OP and C insecticides. The dragonet (Callionymus lyra) proved to be a particularly sensitive target species for monitoring pollutant effects.