Spatial Properties of Entangled Two-Photon Absorption.

We experimentally study entangled two-photon absorption in rhodamine 6G as a function of the spatial properties of a high flux of broadband entangled photon pairs. We first demonstrate a key signature dependence of the entangled two-photon absorption rate on the type of entangled pair flux attenuation: linear, when the laser pump power is attenuated, and quadratic, when the pair flux itself experiences linear loss. We then perform a fluorescence-based Z-scan measurement to study the influence of beam waist size on the entangled two-photon absorption process and compare this to classical single- and two-photon absorption processes. We demonstrate that the entangled two-photon absorption shares a beam waist dependence similar to that of classical two-photon absorption. This result presents an additional argument for the wide range of contrasting values of quoted entangled two-photon absorption cross sections of dyes in literature.

Dynamics of the femtosecond laser-triggered spark gap.

We present space and time resolved measurements of the air hydrodynamics induced by femtosecond laser pulse excitation of the air gap between two electrodes at high potential difference. We explore both plasma-based and plasma-free gap excitation. The former uses the plasma left in the wake of femtosecond filamentation, while the latter exploits air heating by multiple-pulse resonant excitation of quantum molecular wavepackets. We find that the cumulative electrode-driven air density depression channel plays the dominant role in the gap evolution leading to breakdown. Femtosecond laser heating serves mainly to initiate the depression channel; the presence of filament plasma only augments the early heating.

JUNO, the receptor of sperm IZUMO1, is expressed by the human oocyte and is essential for human fertilisation.

STUDY QUESTION: Is JUNO protein present at the surface membrane of human oocytes and involved in the fertilisation process? SUMMARY ANSWER: JUNO protein is expressed on the plasma membrane of human oocytes and its inhibition by a monoclonal antibody completely blocks gamete fusion. WHAT IS KNOWN ALREADY: Fusion of gamete membranes is the culminating event of the fertilisation process, but its molecular mechanisms are poorly understood. Until now, three molecules have been shown to be essential: CD9 tetraspanin in the oocyte, Izumo1 protein on the sperm and Juno, its corresponding receptor on the oocyte. Oocyte CD9 and sperm IZUMO1 have been identified in human gametes and their interaction is also well-conserved among several mammalian species. The presence of JUNO on human oocytes, however, has not yet been reported, nor has its role in fertilisation been investigated. STUDY DESIGN, SIZE, DURATION: We selected an anti-human JUNO antibody in order to investigate the presence of JUNO on the oocyte membrane surface and studied its potential involvement in gamete membrane interaction during fertilisation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Monoclonal antibodies against human JUNO (anti-hJUNO mAb) were produced by immunisation of mice with HEK cells transfected with the putative human JUNO sequence (HEK-hJUNO). These antibodies were used for immunostaining experiments and in vitro fertilisation assays with human gametes (GERMETHEQUE Biobank). MAIN RESULTS AND THE ROLE OF CHANCE: Three hybridoma supernatants, verified by immunostaining, revealed specifically HEK-hJUNO cells. The three purified monoclonal antibodies, FJ2E4 (IgG1), FJ8E8 (IgG1) and FJ4F5 (IgG2a), recognised the soluble recombinant human JUNO protein and, in a western blot of HEK-hJUNO extracts, a protein with an expected MW of 25 kDa. In addition, soluble recombinant human IZUMO protein inhibited the binding of anti-hJUNO mAbs to cells expressing hJUNO. Using these anti-hJUNO mAbs in immunostaining, we identified the presence of JUNO protein at the plasma membrane of human oocytes. Furthermore, we revealed a progressive expression of JUNO according to oocyte maturity. Finally, we showed that human zona-free oocytes, inseminated in the presence of anti-hJUNO mAb, were not fertilised by human sperm. These results suggest that, as seen in the mouse, JUNO is indeed involved in human gamete membrane fusion during fertilisation. LARGE-SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In accordance with French bioethics laws, functional tests were performed using zona-free oocytes, which of course does not fully encompass all normal in vivo physiological conditions. However, these in vitro tests do provide direct information regarding sperm-oocyte membrane interactions. WIDER IMPLICATIONS OF THE FINDINGS: Mechanisms of gamete fusion appear to be homologous between mice and humans. However, some differences do exist and analysing the human mechanisms is essential. In fact, this is the first report describing the presence of JUNO on human oocytes and its involvement in human fertilisation. This discovery allows further examination of the understanding of molecular mechanisms that drive gamete fusion: a crucial challenge at a time when infertility affects 16% of reproductively active couples. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Agence Nationale pour la Recherche, Grant no. ANR-13-BVS5-0004, and by Association Institut du Cancer et d'Immunogénétique (ICIG). There are no competing interests.

Impact of cancer chemotherapy before ovarian cortex cryopreservation on ovarian tissue transplantation.

STUDY QUESTION: How efficacious is transplantation of ovarian cortex previously exposed to chemotherapy? SUMMARY ANSWER: Prior exposure to chemotherapy did not disrupt the function of cryopreserved ovarian tissue after transplantation. WHAT IS KNOWN ALREADY: Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) is an efficacious technique for restoration of female fertility. At least 130 children have been born following this procedure. To date, little is known about the efficacy of OTT in patients exposed to cancer chemotherapy prior to OTC. STUDY DESIGN, SIZE, DURATION: This study evaluates the recovery of ovarian function and fertility in 31 consecutive patients who had received OTT, between 2005 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Thirty one patients, wanting children, were transplanted with autologous ovarian cortex, among which 22 patients (71%) had been exposed to chemotherapy before OTC. Recovery of ovarian function was considered total once menstruation occurred. Ovarian function recovery (OFR), ovarian graft survival, and incidence of pregnancy were related to previous chemotherapy exposure, type of chemotherapy and graft characteristics (number of grafted fragments and follicular density). MAIN RESULTS AND ROLE OF CHANCE: The amount of ovarian tissue collected was the only parameter to show any significant change between patients with versus without previous chemotherapy. At 1 year after OTT, the cumulative incidence of OFR was 83% (93% in patients exposed to chemotherapy and 67% in others (P = 0.14)). A low follicular density (<0.3 foll/mm2) in the transplant and a low number of grafted fragments (<16) were significantly associated with a delayed OFR. Graft survival at 2 years after OTT was 77%. It was significantly lower in patients exposed to bifunctional alkylating agents before ovarian cryopreservation and in patients with a low follicular density. The proportion of women who succeeded in having at least one live birth was 23% in the total population, 0% (0/9) in the group 'no previous chemotherapy', and 32% (7/22) in the group 'previous chemotherapy'. The cumulative incidence of pregnancy (Kaplan-Meier) at 3 years after OTT was 36% overall and 49% in case of previous chemotherapy, with no difference related to previous chemotherapy exposure. In total there were 13 pregnancies and 8 births in 7 patients. LIMITATIONS, REASONS FOR CAUTION: The pathology in the two groups of patients was not comparable. In the group of patients who had chemotherapy before OTC, there were 95% of hematological malignancies. In the group of patients who did not have chemotherapy before OTC only 1 out of 9 patients had a malignant hematological disease while 44% had some pathology affecting the ovaries. Few women are available for study and only large changes are likely to have statistical significance. WIDER IMPLICATIONS OF THE FINDINGS: These results suggest that prior cancer chemotherapy should no longer be considered a limitation to cryopreservation of ovarian tissue and current recommendations in this regard should be revised. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Agence de la Biomédecine (France's biomedical office). There are no competing interests to report. TRIAL REGISTRATION NUMBER: NCT02184806.

Short-pulse lasers for weather control.

Filamentation of ultra-short TW-class lasers recently opened new perspectives in atmospheric research. Laser filaments are self-sustained light structures of 0.1-1 mm in diameter, spanning over hundreds of meters in length, and producing a low density plasma (1015-1017 cm-3) along their path. They stem from the dynamic balance between Kerr self-focusing and defocusing by the self-generated plasma and/or non-linear polarization saturation. While non-linearly propagating in air, these filamentary structures produce a coherent supercontinuum (from 230 nm to 4 µm, for a 800 nm laser wavelength) by self-phase modulation (SPM), which can be used for remote 3D-monitoring of atmospheric components by Lidar (Light Detection and Ranging). However, due to their high intensity (1013-1014 W cm-2), they also modify the chemical composition of the air via photo-ionization and photo-dissociation of the molecules and aerosols present in the laser path. These unique properties were recently exploited for investigating the capability of modulating some key atmospheric processes, like lightning from thunderclouds, water vapor condensation, fog formation and dissipation, and light scattering (albedo) from high altitude clouds for radiative forcing management. Here we review recent spectacular advances in this context, achieved both in the laboratory and in the field, reveal their underlying mechanisms, and discuss the applicability of using these new non-linear photonic catalysts for real scale weather control.

Gas-Solid Phase Transition in Laser Multiple Filamentation.

While propagating in transparent media, near-infrared multiterawatt (TW) laser beams break up in a multitude of filaments of typically 100-200 um diameter with peak intensities as high as 10 to 100 TW/cm^{2}. We observe a phase transition at incident beam intensities of 0.4 TW/cm^{2}, where the interaction between filaments induce solidlike two-dimensional crystals with a 2.7 mm lattice constant, independent of the initial beam diameter. Below 0.4 TW/cm^{2}, we evidence a mixed phase state in which some filaments are closely packed in localized clusters, nucleated on inhomogeneities (seeds) in the transverse intensity profile of the beam, and other are sparse with almost no interaction with their neighbors, similar to a gas. This analogy with a thermodynamic gas-solid phase transition is confirmed by calculating the interaction Hamiltonian between neighboring filaments, which takes into account the effect of diffraction, Kerr self-focusing, and plasma generation. The shape of the effective potential is close to a Morse potential with an equilibrium bond length close to the observed value.

Growth arrest specific 1 (Gas1) and glial cell line-derived neurotrophic factor receptor α1 (Gfrα1), two mouse oocyte glycosylphosphatidylinositol-anchored proteins, are involved in fertilisation.

Recently, Juno, the oocyte receptor for Izumo1, a male immunoglobulin, was discovered. Juno is an essential glycosylphosphatidylinositol (GIP)-anchored protein. This result did not exclude the participation of other GIP-anchored proteins in this process. After bibliographic and database searches we selected five GIP-anchored proteins (Cpm, Ephrin-A4, Gas1, Gfra1 and Rgmb) as potential oocyte candidates participating in fertilisation. Western blot and immunofluorescence analyses showed that only three were present on the mouse ovulated oocyte membrane and, of these, only two were clearly involved in the fertilisation process, namely growth arrest specific 1 (Gas1) and glial cell line-derived neurotrophic factor receptor α1 (Gfrα1). This was demonstrated by evaluating oocyte fertilisability after treatment of oocytes with antibodies against the selected proteins, with their respective short interference RNA or both. Gfrα1 and Gas1 seem to be neither redundant nor synergistic. In conclusion, oocyte Gas1 and Gfrα1 are both clearly involved in fertilisation.

Spin-Glass Model Governs Laser Multiple Filamentation.

We show that multiple filamentation patterns in high-power laser beams can be described by means of two statistical physics concepts, namely, self-similarity of the patterns over two nested scales and nearest-neighbor interactions of classical rotators. The resulting lattice spin model perfectly reproduces the evolution of intense laser pulses as simulated by the nonlinear Schrödinger equation, shedding new light on multiple filamentation. As a side benefit, this approach drastically reduces the computing time by 2 orders of magnitude as compared to the standard simulation methods of laser filamentation.

Laser filamentation as a new phase transition universality class.

We show that the onset of laser multiple filamentation can be described as a critical phenomenon that we characterize both experimentally and numerically by measuring a set of seven critical exponents. This phase transition deviates from any existing universality class and offers a unique perspective of conducting two-dimensional experiments of statistical physics at a human scale.

Reversibility of laser filamentation.

We investigate the reversibility of laser filamentation, a self-sustained, non-linear propagation regime including dissipation and time-retarded effects. We show that even losses related to ionization marginally affect the possibility of reverse propagating ultrashort pulses back to the initial conditions, although they make it prone to finite-distance blow-up susceptible to prevent backward propagation.

Mid-infrared laser filamentation in molecular gases.

We observed the filamentation of mid-infrared ultrashort laser pulses (3.9 µm, 80 fs) in molecular gases. It efficiently generates a broadband supercontinuum over two octaves in the 2.5-6 µm spectral range, with a red-shift up to 500 nm due to the Raman effect, which dominates over the blue shift induced by self-steepening and the gas ionization. As a result, the conversion efficiency into the Stokes region (4.3-6 µm) 65% is demonstrated.

High-field quantum calculation reveals time-dependent negative Kerr contribution.

The exact quantum time-dependent optical response of hydrogen under strong-field near-infrared excitation is investigated and compared to the perturbative model widely used for describing the effective atomic polarization induced by intense laser fields. By solving the full 3D time-dependent Schrödinger equation, we exhibit a supplementary, quasi-instantaneous defocusing contribution missing in the weak-field model of polarization. We show that this effect is far from being negligible, in particular when closures of ionization channels occur and stems from the interaction of electrons with their parent ions. It provides an interpretation of the higher-order Kerr effect recently observed in various gases.

Impact of the hypoxic microenvironment on spermatogonial stem cells in culture.

The stem cell niche plays a crucial role in the decision to either self-renew or differentiate. Recent observations lead to the hypothesis that O2 supply by blood and local O2 tension could be key components of the testicular niche of spermatogonial stem cells (SSCs). In this study, we investigated the impact of different hypoxic conditions (3.5%, 1%, and 0.1% O2 tension) on murine and human SSCs in culture. We observed a deleterious effect of severe hypoxia (1% O2 and 0.1% O2) on the capacity of murine SSCs to form germ cell clusters when plated at low density. Severe effects on SSCs proliferation occur at an O2 tension ≤1% and hypoxia was shown to induce a slight differentiation bias under 1% and 0.1% O2 conditions. Exposure to hypoxia did not appear to change the mitochondrial mass and the potential of membrane of mitochondria in SSCs, but induced the generation of mitochondrial ROS at 3.5% and 1% O2. In 3.5% O2 conditions, the capacity of SSCs to form colonies was maintained at the level of 21% O2 at low cell density, but it was impossible to amplify and maintain stem cell number in high cell density culture. In addition, we observed that 3.5% hypoxia did not improve the maintenance and propagation of human SSCs. Finally, our data tend to show that the transcription factors HIF-1α and HIF-2α are not involved in the SSCs cell autonomous response to hypoxia.

Direct amplitude shaping of high harmonics in the extreme ultraviolet.

We demonstrate direct amplitude shaping of high harmonics (HHs) using a reflective micromirror array based on micro-electromechanical-system (MEMS) technology. We show independent control over the intensity of each HH in the observed range (14 - 36 eV). These results are used to calculate the control achieved over the temporal structure of the attosecond pulses in the train.

Ultrafast laser spectroscopy and control of atmospheric aerosols.

We review applications of ultrafast laser pulses for aerosol analysis via linear and non-linear spectroscopy, including the most advanced techniques like coherent control of molecular excited states. We also discuss the capability of such pulses to influence the nucleation of atmospheric aerosols by assisting condensation of water in air.

Coherent manipulation of free amino acids fluorescence.

Coherent manipulation of molecular wavepackets in biomolecules might contribute to the quest towards label-free cellular imaging and protein identification. We report the use of optimally tailored UV laser pulses in pump-probe depletion experiments that selectively enhance or decrease fluorescence between two aromatic amino acids: tryptophan (Trp) and tyrosine (Tyr). Selective fluorescence modulation is achieved with a contrast of ~35%. A neat modification of the time-dependent fluorescence depletion signal of Trp is observed, while the Tyr transient trace remains unchanged. The mechanism invoked for explaining the change of the depletion of Trp is a less efficient coupling between the fluorescing state and the higher non-radiative excited states by the optimally shaped pulse, than by the reference pulse.

Cardiovascular findings in women suffering from Turner syndrome requesting oocyte donation.

BACKGROUND: Through oocyte donation (OD), women with Turner syndrome (TS) may achieve motherhood. However, this population has a high prevalence of cardiac malformations and carry a risk for aortic dissection that is increased by pregnancy. Until recently, the necessity for a specialized cardiac evaluation before pregnancy was underestimated as was the need for follow-up through adulthood. The aim of this study was to evaluate the follow-up (mainly cardiovascular) of women with TS requesting OD. METHODS: Disease monitoring since diagnosis and prior cardiac evaluations conducted out of our centre were assessed in 25 women with TS who requested OD. New cardiac evaluations using echocardiography and magnetic resonance imaging were performed by our specialized cardiologist in 18 of these patients. RESULTS: We observed that the medical follow-up of women with TS was often deficient throughout adulthood. Most of the prior cardiac evaluations performed by cardiologists not accustomed to women with TS, either before (n = 8) or when starting OD (n = 12), were considered normal. However, when revaluated by a cardiologist who is familiar with TS, seven women were diagnosed with a bicuspid aortic valve and thus excluded from OD. In addition, when appropriate screening was conducted by our referent cardiologist before OD no cardiac complication was observed during pregnancy or delivery. CONCLUSIONS: Careful follow-up, including cardiac evaluation, should be recommended for women diagnosed with TS, before and after puberty. Moreover, assessment of cardiovascular parameters by a cardiologist familiar with TS should be routinely repeated before undertaking OD.

From higher-order Kerr nonlinearities to quantitative modeling of third and fifth harmonic generation in argon.

The recent measurement of negative higher-order Kerr effect (HOKE) terms in gases has given rise to a controversial debate, fed by its impact on short laser pulse propagation. By comparing the experimentally measured yield of the third and fifth harmonics, with both an analytical and a full comprehensive numerical propagation model, we confirm the absolute and relative values of the reported HOKE indices.

Transition from plasma-driven to Kerr-driven laser filamentation.

While filaments are generally interpreted as a dynamic balance between Kerr focusing and plasma defocusing, the role of the higher-order Kerr effect (HOKE) is actively debated as a potentially dominant defocusing contribution to filament stabilization. In a pump-probe experiment supported by numerical simulations, we demonstrate the transition between two distinct filamentation regimes at 800 nm. For long pulses (1.2 ps), the plasma substantially contributes to filamentation, while this contribution vanishes for short pulses (70 fs). These results confirm the occurrence, in adequate conditions, of filamentation driven by the HOKE rather than by plasma.

Modelling of HNO3-mediated laser-induced condensation: a parametric study.

Based on both static (extended Köhler) and dynamic modelling, we investigate the influence of temperature, humidity, HNO(3) initial concentration, as well as of the particle concentration, on the efficiency of HNO(3)-mediated laser-induced condensation. This mechanism is most efficient for low temperatures, high HNO(3) concentration, and relative humidities. It is, however, still active up to 30 °C, down to 70% relative humidity, and below the ppm level of HNO(3). Furthermore, lower particle concentration minimizing the depletion of both HNO(3) and water vapor is more favourable to particle growth.