Sequential generation of linear cluster states from a single photon emitter.

Light states composed of multiple entangled photons-such as cluster states-are essential for developing and scaling-up quantum computing networks. Photonic cluster states can be obtained from single-photon sources and entangling gates, but so far this has only been done with probabilistic sources constrained to intrinsically low efficiencies, and an increasing hardware overhead. Here, we report the resource-efficient generation of polarization-encoded, individually-addressable photons in linear cluster states occupying a single spatial mode. We employ a single entangling-gate in a fiber loop configuration to sequentially entangle an ever-growing stream of photons originating from the currently most efficient single-photon source technology-a semiconductor quantum dot. With this apparatus, we demonstrate the generation of linear cluster states up to four photons in a single-mode fiber. The reported architecture can be programmed for linear-cluster states of any number of photons, that are required for photonic one-way quantum computing schemes.

Boson Sampling with Single-Photon Fock States from a Bright Solid-State Source.

A boson-sampling device is a quantum machine expected to perform tasks intractable for a classical computer, yet requiring minimal nonclassical resources as compared to full-scale quantum computers. Photonic implementations to date employed sources based on inefficient processes that only simulate heralded single-photon statistics when strongly reducing emission probabilities. Boson sampling with only single-photon input has thus never been realized. Here, we report on a boson-sampling device operated with a bright solid-state source of single-photon Fock states with high photon-number purity: the emission from an efficient and deterministic quantum dot-micropillar system is demultiplexed into three partially indistinguishable single photons, with a single-photon purity 1-g^{(2)}(0) of 0.990±0.001, interfering in a linear optics network. Our demultiplexed source is between 1 and 2 orders of magnitude more efficient than current heralded multiphoton sources based on spontaneous parametric down-conversion, allowing us to complete the boson-sampling experiment faster than previous equivalent implementations.

Insomnia and sleep misperception.

Sleep misperception is often observed in insomnia individuals (INS). The extent of misperception varies between different types of INS. The following paper comprised sections which will be aimed at studying the sleep EEG and compares it to subjective reports of sleep in individuals suffering from either psychophysiological insomnia or paradoxical insomnia and good sleeper controls. The EEG can be studied without any intervention (thus using the raw data) via either PSG or fine quantitative EEG analyses (power spectral analysis [PSA]), identifying EEG patterns as in the case of cyclic alternating patterns (CAPs) or by decorticating the EEG while scoring the different transient or phasic events (K-Complexes or sleep spindles). One can also act on the on-going EEG by delivering stimuli so to study their impact on cortical measures as in the case of event-related potential studies (ERPs). From the paucity of studies available using these different techniques, a general conclusion can be reached: sleep misperception is not an easy phenomenon to quantify and its clinical value is not well recognized. Still, while none of the techniques or EEG measures defined in the paper is available and/or recommended to diagnose insomnia, ERPs might be the most indicated technique to study hyperarousal and sleep quality in different types of INS. More research shall also be dedicated to EEG patterns and transient phasic events as these EEG scoring techniques can offer a unique insight of sleep misperception.

[Evaluation of endometrectomy by radiofrequency for premenopausal women: a retrospective study]. / Évaluation de l'endométrectomie par radiofréquence chez les femmes préménopausiques : étude rétrospective sur 90 cas.

OBJECTIVE: In present study, we are assessing the efficiency of endometrial ablation by radiofrequency (Novasure(®)) for the treatment of abnormal uterine bleeding. MATERIAL AND METHODS: A total of 90 patients underwent an endometrial ablation by radiofrequency for uterine bleeding between 2009 and 2012. For the postoperative follow-up, symptoms amelioration and eventual adverse-events were evaluated by a self-administered questionnaire given to all patients after the surgery. RESULT: Sixty-five patients (74%) responded to the questionnaire with an average of 17.5 months. Among them, endometrial bleeding decreased in 92% of the cases (IC 95%; 86-99). The amenorrhea rate was 55% (IC 95%; 43-67) and 36% of the patients presented a diminution of menstrual bleeding after treatment. Thirty-two patients (36%) presented dysmenorrhea before the radiofrequency and 78% of them experienced an amelioration of the symptoms after treatment (IC 95%; 64-93). In 19 patients (21%), the cause of uterine bleeding was adenomyosis, among them, bleeding decreased in 84% of the cases (IC 95%; 71-98) and dysmenorrhea in 70%. (IC 95%; 41-97). Finally, 84% of the patients were satisfied with the result of the treatment. CONCLUSION: Our findings suggest that endometrial radiofrequency is effective for the treatment of menometrorrhagia, dysmenorrhea and also adenomyosis.

[Comparison of three models to predict non-sentinel lymph node status in breast cancer patients with metastatic sentinel lymph nodes: a retrospective study of 77 patients]. / Comparaison de trois modèles prédictifs d'envahissement des ganglions non sentinelles en cas de métastases des ganglions sentinelles dans le cancer du sein: une étude rétrospective sur 77 patientes.

UNLABELLED: Various statistic predictive models have been developed to predict the status of the non-sentinel lymph nodes (NSLN) when the sentinel one was invaded by tumor cells in the case of breast invasive carcinoma. The objective of this study was to compare the accuracy of three of these statistic models: the MSKCC nomogram, the Tenon score and the MDA score. The study was conducted at Croix Rousse Hospital, Lyon, France. OBJECTIVE: When sentinel lymph node is invaded by metastasis, complete lymph node dissection of the axilla can be avoided using statistic predictive models especially when talking about micrometastases and moreover about isolated tumor cells in the sentinel lymph node. Over the different existing models, we tested the three most used ones to determine the model that is most adapted to our everyday practice. METHOD: The study population consisted of 77 women with an invasive breast cancer treated by complete axillary lymph node dissection for metastatic sentinel lymph node. Over the nine models already published, we focused on three of them due to their ease to use as well as their good preliminary results: the Memorial Sloan-Kettering Cancer Center nomogram (MSKCC), the Tenon score and the M.D Anderson score (MDA). Different criteria are used by these models, but all of them take in consideration: tumor size, multifocality, tumor type, lymphovascular invasion, hormonal receptors, number of sentinel lymph node resected, degree of sentinel lymph node invasion (i.e. macrometastasis, micrometastasis or isolated tumor cells) and histologic method used to diagnose sentinel lymph node invasion. These scores are validated depending on their false negative ratio as well as the proportion of patient selected as having a low risk of non-sentinel lymph node invasion. The major criterion for the MSKCC score is the calibration that compares the predicted likelihood of invasion and the histologically proved one. RESULTS: The rate of non-sentinel lymph node invasion was 37.6%. The discrimination of the three models was good with an AUC of 0.74 for both MSKCC nomogram and Tenon score and of 0.72% for MDA score. MSKCC nomogram was well calibrated (P=0.23). The false negative ratio was 0 (CI 95%: 0-18.1%) for MSKCC nomogram, 16.7% (CI 95%: 8.6%-27.8%) for Tenon score and 16% (CI 95%: 6.8-31%) for MDA score. The percentage of patients considered as having a low risk of invasion of the non-sentinel lymph node was 20.5% for MSKCC nomogram, 34.7% for MDA score and 47.4% for Tenon score. CONCLUSION: MSKCC nomogram seems to be the statistic model that is most adapted to the population we studied. To validate the Tenon and MDA score, we should have a most important population.

Destruction of Sun-grazing comet C/2011 N3 (SOHO) within the low solar corona.

Observations of comets in Sun-grazing orbits that survive solar insolation long enough to penetrate into the Sun's inner corona provide information on the solar atmosphere and magnetic field as well as on the makeup of the comet. On 6 July 2011, the Solar Dynamics Observatory (SDO) observed the demise of comet C/2011 N3 (SOHO) within the low solar corona in five wavelength bands in the extreme ultraviolet (EUV). The comet penetrated to within 0.146 solar radius (~100,000 kilometers) of the solar surface before its EUV signal disappeared. Before that, material released into the coma--at first seen in absorption--formed a variable EUV-bright tail. During the final 10 minutes of observation by SDO's Atmospheric Imaging Assembly, ~6 × 10(8) to 6 × 10(10) grams of total mass was lost (corresponding to an effective nucleus diameter of ~10 to 50 meters), as estimated from the tail's deceleration due to interaction with the surrounding coronal material; the EUV absorption by the comet and the brightness of the tail suggest that the mass was at the high end of this range. These observations provide evidence that the nucleus had broken up into a family of fragments, resulting in accelerated sublimation in the Sun's intense radiation field.

Interdigitated coplanar electrodes for enhanced sensitivity in a photorefractive polymer.

Organic photorefractive polymer composites can be made to exhibit near 100% diffraction efficiency and fast writing times, though large external slants are needed to project the applied field onto the grating vector. We show here that the use of interdigitated electrodes on a single plane provides similar performance to these standard devices and geometries but without a external slant angle. This new device's structure also greatly improves the diffraction efficiency and sensitivity compared to less slanted standard devices necessary for some real applications, such as holographic displays, optical coherence imaging, and in-plane switching.

An updatable holographic three-dimensional display.

Holographic three-dimensional (3D) displays provide realistic images without the need for special eyewear, making them valuable tools for applications that require situational awareness, such as medical, industrial and military imaging. Currently commercially available holographic 3D displays use photopolymers that lack image-updating capability, resulting in restricted use and high cost. Photorefractive polymers are dynamic holographic recording materials that allow updating of images and have a wide range of applications, including optical correlation, imaging through scattering media and optical communication. To be suitable for 3D displays, photorefractive polymers need to have nearly 100% diffraction efficiency, fast writing time, hours of image persistence, rapid erasure, and large area-a combination of properties that has not been shown before. Here, we report an updatable holographic 3D display based on photorefractive polymers with such properties, capable of recording and displaying new images every few minutes. This is the largest photorefractive 3D display to date (4 x 4 inches in size); it can be recorded within a few minutes, viewed for several hours without the need for refreshing, and can be completely erased and updated with new images when desired.

Keeping data continuous when analyzing the prognostic impact of a tumor marker: an example with cathepsin D in breast cancer.

The prognostic value of cathepsin D has been recently recognized, but as many quantitative tumor markers, its clinical use remains unclear partly because of methodological issues in defining cut-off values. Guidelines have been proposed for analyzing quantitative prognostic factors, underlining the need for keeping data continuous, instead of categorizing them. Flexible approaches, parametric and non-parametric, have been proposed in order to improve the knowledge of the functional form relating a continuous factor to the risk. We studied the prognostic value of cathepsin D in a retrospective hospital cohort of 771 patients with breast cancer, and focused our overall survival analysis, based on the Cox regression, on two flexible approaches: smoothing splines and fractional polynomials. We also determined a cut-off value from the maximum likelihood estimate of a threshold model. These different approaches complemented each other for (1) identifying the functional form relating cathepsin D to the risk, and obtaining a cut-off value and (2) optimizing the adjustment for complex covariate like age at diagnosis in the final multivariate Cox model. We found a significant increase in the death rate, reaching 70% with a doubling of the level of cathepsin D, after the threshold of 37.5 pmol mg(-1). The proper prognostic impact of this marker could be confirmed and a methodology providing appropriate ways to use markers in clinical practice was proposed.

Combinatorial library of peptide isosters based on Diels-Alder reactions: identification of novel inhibitors against a recombinant cysteine protease from Leishmania mexicana.

A combinatorial split-and-mix library of peptide isosters based on a Diels-Alder reaction was synthesized as a "one-bead-two-compounds" library and encoded by ladder synthesis for facile analysis by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. In the "one-bead-two-compounds" library approach, each bead contains a library member as a putative protease inhibitor along with a fluorescence-quenched substrate for the protease. When the library was screened with CPB2.8 DeltaCTE, a recombinant cysteine protease from L. mexicana, several beads containing compounds with inhibitory activity could be selected from the library and analyzed by MALDI-TOF MS for structure elucidation. Two types of inhibitors were revealed. One novel class of inhibitors had the bicyclic Diels-Alder product isosteric element incorporated internally in a peptide, while the other type was an N-terminal alpha,beta-unsaturated ketone Michael acceptor used as starting material for the Diels-Alder reaction. Selected hit sequences and constructed consensus sequences based on the observed frequencies of amino acids in different subsites were resynthesized and assayed in solution for inhibitor activity and were shown to have IC(50) values in the high nanomolar to low micromolar range.

Substrate specificity of recombinant cysteine proteinase, CPB, of Leishmania mexicana.

The primary S(1) subsite specificity of a recombinant cysteine proteinase, CPB2.8 Delta CTE, of Leishmania mexicana was investigated in a systematic way using a series of peptides derived from Abz-KLRFSKQ-EDDnp in which Arg was substituted by all natural amino acids (where Abz is ortho-amino-benzoyl and EDDnp is N-[2,4-dinitrophenyl]-ethylenediamine). The peptides from this series with charged side chain amino acids, Cys, Cys(SBzl), and Thr(OBzl) were well hydrolysed. All other substitutions resulted in peptides that were resistant or hydrolysed very slowly and inhibited the enzyme with K(i) values in the range of 9--400 nM. Looking for natural substrates for CPB2.8, we observed that the recombinant enzyme failed to release kinin from human kininogen, an activity earlier observed with cruzipain from Trypanosoma cruzi (Del Nery et al., J. Biol. Chem. 272 (1997) 25713.). This lack of activity seems to be a result of the resistance to hydrolysis of the sequence at the N-terminal site of bradykinin in the human kininogen. The preferences for the S(3), S(2) and S(1)'-S(3)' for some amino acids were also examined using substrates derived from Abz-KLRFSKQ-EDDnp with variations at Lys, Leu, Phe, Ser and Lys, using the amino acids Ala, Phe, Leu, His or Pro. Peptides with Phe at P(1)' presented the highest affinity to the leishmanial enzyme. For comparison, some of the obtained peptides were also assayed with recombinant human cathepsin L and cruzain. The best substrates for CPB2.8 Delta CTE were also well hydrolysed by cathepsin L, however, the best inhibitors of the parasite enzyme have low affinity to cathepsin L. These promising data provide leads for the design of anti-parasitic drugs directed against the leishmanial enzyme.

Identification of peptides inhibitory to recombinant cysteine proteinase, CPB, of Leishmania mexicana.

We have identified peptides that are relatively resistant to hydrolysis by a recombinant cysteine proteinase, CPB2.8DeltaCTE, of Leishmania mexicana, and yet exhibit inhibition constant (K(i)) values in the nanomolar range. Common to these peptides is a basic-hydrophobic-hydrophobic motif in the P3-P1 sites, which is also present in the pro-region of the enzyme. A nine-amino acid stretch, FAARYLNGA, which has good homology to the pro-region of mammalian cathepsin L was identified as the part of the pro-region most likely to interact with the active site of the parasite enzyme. This peptide is not hydrolyzed by CPB2.8DeltaCTE and inhibited it with a K(i) of 4 microM. Extension of this sequence at both the N- and C-termini and the introduction of ortho-aminobenzoic acid at the N-terminal site reduced the K(i) value to 30 nM. The best substrate for CPB2.8DeltaCTE was also well hydrolyzed by cathepsin L, however the best inhibitor of the parasite enzyme inhibit poorly cathepsin L, with K(i) value two order of magnitude higher than against the parasite enzyme. These promising data provide insights into the peculiar specificity of the parasite enzyme and will aid the design of antiparasitic drugs directed against the leishmanial enzyme.

[Complete remission after abdominal wall metastasis from uterine cervical cancer on a laparoscopic trochar site: a case report]. / Rémission complète après métastase pariétale sur trajet de trocart de coelioscopie d'un cancer du col utérin. A propos d'un cas.

Abdominal wall metastasis to laparoscopic trochar sites after preoperative staging procedure is rare for uterine cervix cancer. Prognosis is unfavorable. We report a case of metastasis to a laparoscopic trochar site in a patient with a stage IIB cervical cancer with no nodal involvement who is alive four and a half years after radical surgery and radiotherapy.

Expression and characterization of a recombinant cysteine proteinase of Leishmania mexicana.

A major cysteine proteinase (CPB) of Leishmania mexicana, that is predominantly expressed in the form of the parasite that causes disease in mammals, has been overexpressed in Escherichia coli and purified from inclusion bodies to apparent homogeneity. The CPB enzyme, CPB2.8, was expressed as an inactive pro-form lacking the characteristic C-terminal extension (CPB2.8DeltaCTE). Pro-region processing was initiated during protein refolding and proceeded through several intermediate stages. Maximum enzyme activity accompanied removal of the entire pro-region. This was facilitated by acidification. Purified mature enzyme gave a single band on SDS/PAGE and gelatin SDS/PAGE gels, co-migrated with native enzyme in L. mexicana lysates, and had the same N-terminal sequence as the native enzyme. The procedure yielded >3.5 mg of active enzyme per litre of E. coli culture.

The substrate specificity of a recombinant cysteine protease from Leishmania mexicana: application of a combinatorial peptide library approach.

The substrate specificity of CPB2.8DeltaCTE, a recombinant cysteine protease from Leishmania mexicana, was mapped by screening a fluorescence-quenched combinatorial peptide library. Results from library screening indicated a preference for Arg or Lys in the S(3) subsite and for hydrophobic residues, both aliphatic and aromatic, in S(2). The S(1) subsite exhibited a specificity for the basic residues Arg and Lys. Generally, the specificity of the primed subsites was less strict compared with the non-primed side which showed preference for Arg, Lys and Ala in S'(1), Arg, Pro and Gly in S'(2) and Lys, Arg and Ser in S'(4). By contrast, a strict preference for the basic residues Arg and Lys was found for S'(3). Overall, there was a trend for basic residues in alternating subsites and smaller residues in the primed sites compared with the non-primed sites. In addition, there were strict requirements for the amino acids in subsites S(3)--S(1). Fluorescence-quenched peptides from the library with the highest on-resin cleavage were resynthesised and their kinetics of hydrolysis by CPB2.8DeltaCTE assessed in solution phase assays. Several good substrates containing the quintessential dipeptide particular to cathepsin-L-like enzymes, -F-R/K-, in P(2) and P(1) were identified (e.g. Y(NO(2))-EKFR down arrow RGK-K(Abz)G, Abz=2-aminobenzoyl; k(cat)K(m)(-1)=4298 mM(-1)s(-1)). However, novel substrates containing the dipeptide -L/I-Q- in P(2) and P(1) were also well hydrolysed (e.g. Y(NO(2))-YLQ down arrow GIQK-K(Abz)G; k(cat)K(m)(-1)=2583 mM(-1)s(-1)). The effect of utilising different fluorescent donor--quencher pairs on the value of k(cat)K(m)(-1) was examined. Generally, the use of the Abz/Q-EDDnp donor--quencher pair (EDDnp=N-(2,4-dinitrophenyl)ethylenediamine) instead of K(Abz)/Y(NO(2)) resulted in higher k(cat)K(m)(-1) values for analogous substrates.

Transvaginal sonohysterographic evaluation of intrauterine adhesions.

PURPOSE: We assessed the role of preoperative sonohysterography in the diagnosis of intrauterine synechiae. METHODS: Nineteen patients with a suspected diagnosis of intrauterine adhesion underwent hysterosalpingography, transvaginal sonography, and sonohysterography performed in the consultation room. The patients were then treated by hysteroscopy under laparoscopic or ultrasound guidance. RESULTS: Transvaginal sonography showed an abnormal uterine cavity in only 10 cases. The sensitivities of sonohysterography and hysterosalpingography in the diagnosis of intrauterine adhesions were both 100%. Sonohysterography showed complete correlation with hysterosalpingography. CONCLUSIONS: We recommend routine sonohysterography after transvaginal sonography in cases of suspected intrauterine synechiae.

Fluorescence-quenched solid phase combinatorial libraries in the characterization of cysteine protease substrate specificity.

To map the substrate specificity of cysteine proteases, two combinatorial peptide libraries were synthesized and screened using the archetypal protease, papain. The use of PEGA resin as the solid support for library synthesis facilitated the application of an on-resin fluorescence-quenched assay. Results from the screening of library 2 indicated a preference for Pro or Val in the S3 subsite and hydrophobic residues in S2; the most prevalent residue not being Phe but Val. The S1 subsite exhibited a dual specificity for both small, nonpolar residues, Ala or Gly, as well as larger, Gln, and charged residues, Arg. Small residues predominated in the S1'-S4' subsites. Active peptides from the libraries and variations thereof were resynthesized and their kinetics of hydrolysis by papain assessed in solution phase assays. Generally, there was a good correlation between the extent of substrate cleavage on solid phase and the kcat/KM's obtained in solution phase assays. Several good substrates for papain were obtained, the best substrates being Y(NO2)PMPPLCTSMK(Abz) (kcat/KM = 2109 (mM s)-1), Y(NO2)PYAVQSPQK(Abz) (kcat/KM = 1524 (mM s)-1), and Y(NO2)PVLRQQRSK(Abz) (kcat/KM = 1450 (mM s)-1). These results were interpreted in structural terms by the use of molecular dynamics (MD). These MD calculations indicated two different modes for the binding of substrates in the narrow enzyme cleft.

Analysis of organic reactions by thin layer chromatography combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

The products of a wide variety of organic reactions were rapidly identified by their masses through a combination of thin layer chromatography (TLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). Crude mixtures of peptides and glycopeptides, complex carbohydrate reactions, and a classical organic reaction were analysed using the following standard protocol. The components of the reaction mixtures were first separated on the TLC plate, scraped off, extracted and analysed by MALDI-TOFMS. The technique used is easy and applicable to most organic reactions, becoming a very powerful technique in reaction optimization once composition and identity of TLC spots have been established by MS. Moreover, the TLC/MALDI-TOFMS method was used to identify low molecular weight compounds with masses within the matrix region (100-500 u), a goal which is normally difficult to achieve. We successfully detected low molecular weight compounds by suppression of the matrix peaks using a relatively low matrix:analyte ratio (15:1 or lower). Doping both matrix and analyte solutions with [Cs]+ ions resulted in suppression of both [Na]+ and [K]+ peaks, thus enhancing the spectral signals and making identification of low molecular weight compounds more facile.

Fine needle aspiration cytology of a solid papillary carcinoma of the breast. A case report with immunohistochemical studies.

BACKGROUND: Solid papillary carcinoma of the breast was recently described. This tumor display distinctive clinical and morphologic features. It is an intraductal papillary carcinoma frequently associated with mucinous carcinoma and infiltrating ductal carcinoma not otherwise specified. CASE: Fine needle aspiration cytology (FNAC) of a solid papillary carcinoma of the right breast in an 82-year-old female, demonstrated a cellular specimen of discohesive, small, uniform and ovoid tumor cells, with occasional loose cluster. The cytoplasm was abundant and finely granular. The nuclei were round, without marked atypia. The nucleoli were inconspicuous. SCant mucinous material was present. The diagnosis was confirmed histologically and immunohistochemically. CONCLUSION: The cytologic aspects of solid papillary carcinoma of the breast suggest a carcinoma with endocrine differentiation and a weak mucinous component.