Near-ideal spontaneous photon sources in silicon quantum photonics.

While integrated photonics is a robust platform for quantum information processing, architectures for photonic quantum computing place stringent demands on high quality information carriers. Sources of single photons that are highly indistinguishable and pure, that are either near-deterministic or heralded with high efficiency, and that are suitable for mass-manufacture, have been elusive. Here, we demonstrate on-chip photon sources that simultaneously meet each of these requirements. Our photon sources are fabricated in silicon using mature processes, and exploit a dual-mode pump-delayed excitation scheme to engineer the emission of spectrally pure photon pairs through inter-modal spontaneous four-wave mixing in low-loss spiralled multi-mode waveguides. We simultaneously measure a spectral purity of 0.9904 ± 0.0006, a mutual indistinguishability of 0.987 ± 0.002, and  >90% intrinsic heralding efficiency. We measure on-chip quantum interference with a visibility of 0.96 ± 0.02 between heralded photons from different sources.

Mid-infrared coincidence measurements on twin photons at room temperature.

Quantum measurements using single-photon detectors are opening interesting new perspectives in diverse fields such as remote sensing, quantum cryptography and quantum computing. A particularly demanding class of applications relies on the simultaneous detection of correlated single photons. In the visible and near infrared wavelength ranges suitable single-photon detectors do exist. However, low detector quantum efficiency or excessive noise has hampered their mid-infrared (MIR) counterpart. Fast and highly efficient single-photon detectors are thus highly sought after for MIR applications. Here we pave the way to quantum measurements in the MIR by the demonstration of a room temperature coincidence measurement with non-degenerate twin photons at about 3.1 µm. The experiment is based on the spectral translation of MIR radiation into the visible region, by means of efficient up-converter modules. The up-converted pairs are then detected with low-noise silicon avalanche photodiodes without the need for cryogenic cooling.

Temporal electronic phenotyping by mining careflows of breast cancer patients.

In this work we present a careflow mining approach designed to analyze heterogeneous longitudinal data and to identify phenotypes in a patient cohort. The main idea underlying our approach is to combine methods derived from sequential pattern mining and temporal data mining to derive frequent healthcare histories (careflows) in a population of patients. This approach was applied to an integrated data repository containing clinical and administrative data of more than 4000 breast cancer patients. We used the mined histories to identify sub-cohorts of patients grouped according to healthcare activities pathways, then we characterized these sub-cohorts with clinical data. In this way, we were able to perform temporal electronic phenotyping of electronic health records (EHR) data.

AurkA controls self-renewal of breast cancer-initiating cells promoting wnt3a stabilization through suppression of miR-128.

AurkA overexpression was previously found in breast cancer and associated to its ability in controlling chromosome segregation during mitosis, however whether it may affect breast cancer cells, endorsed with stem properties (BCICs), is still unclear. Surprisingly, a strong correlation between AurkA expression and ß-catenin localization in breast cancer tissues suggested a link between AurkA and Wnt signaling. In our study, AurkA knock-down reduced wnt3a mRNA and suppressed metastatic signature of MDA-MB-231 cells. As a consequence, the amount of BCICs and their migratory capability dramatically decreased. Conversely, wnt3a mRNA stabilization and increased CD44(+)/CD24(low/-) subpopulation was found in AurkA-overexpressing MCF7 cells. In vivo, AurkA-overexpressing primary breast cancer cells showed higher tumorigenic properties. Interestingly, we found that AurkA suppressed the expression of miR-128, inhibitor of wnt3a mRNA stabilization. Namely, miR-128 suppression realized after AurkA binding to Snail. Remarkably, a strong correlation between AurkA and miR-128 expression in breast cancer tissues confirmed our findings. This study provides novel insights into an undisclosed role for the kinase AurkA in self-renewal and migration of BCICs affecting response to cancer therapies, metastatic spread and recurrence. In addition, it suggests a new therapeutic strategy taking advantage of miR-128 to suppress AurkA-Wnt3a signaling.

Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase IV 'real life' trial on the variability of response to opioids.

BACKGROUND: Guidelines tend to consider morphine and morphine-like opioids comparable and interchangeable in the treatment of chronic cancer pain, but individual responses can vary. This study compared the analgesic efficacy, changes of therapy and safety profile over time of four strong opioids given for cancer pain. PATIENT AND METHODS: In this four-arm multicenter, randomized, comparative, of superiority, phase IV trial, oncological patients with moderate to severe pain requiring WHO step III opioids were randomly assigned to receive oral morphine or oxycodone or transdermal fentanyl or buprenorphine for 28 days. At each visit, pain intensity, modifications of therapy and adverse drug reactions (ADRs) were recorded. The primary efficacy end point was the proportion of nonresponders, meaning patients with worse or unchanged average pain intensity (API) between the first and last visit, measured on a 0-10 numerical rating scale. (NCT01809106). RESULTS: Forty-four centers participated in the trial and recruited 520 patients. Worst pain intensity and API decreased over 4 weeks with no significant differences between drugs. Nonresponders ranged from 11.5% (morphine) to 14.4% (buprenorphine). Appreciable changes were made in the treatment schedules over time. Each group required increases in the daily dose, from 32.7% (morphine) to 121.2% (transdermal fentanyl). Patients requiring adjuvant analgesics ranged from 68.9% (morphine) to 81.6% (oxycodone), switches varied from 22.1% (morphine) to 12% (oxycodone), discontinuation of treatment from 27% ( morphine) to 14.5% (fentanyl). ADRs were similar except for effects on the nervous system, which significantly prevailed with morphine. CONCLUSION: The main findings were the similarity in pain control, response rates and main adverse reactions among opioids. Changes in therapy schedules were notable over time. A considerable proportion of patients were nonresponders or poor responders. CLINICAL TRIAL REGISTRATION: NCT01809106 (https://clinicaltrials.gov/ct2/show/NCT01809106?term=cerp&rank=2).

High-frequency electro-optic measurement of strained silicon racetrack resonators.

The observation of the electro-optic effect in strained silicon waveguides has been considered a direct manifestation of an induced χ(2) nonlinearity in the material. In this work, we perform high-frequency measurements on strained silicon racetrack resonators. Strain is controlled by a mechanical deformation of the waveguide. It is shown that any optical modulation vanishes, independent of the applied strain, when the applied voltage varies much faster than the carrier effective lifetime and that the DC modulation is also largely independent of the applied strain. This demonstrates that plasma carrier dispersion is responsible for the observed electro-optic effect. After normalizing out free-carrier effects, our results set an upper limit of (8±3) pm/V to the induced high-speed effective χeff,zzz(2) tensor element at an applied stress of -0.5 GPa. This upper limit is about 1 order of magnitude lower than previously reported values for static electro-optic measurements.

Ultra-high-Q thin-silicon nitride strip-loaded ring resonators.

We report on the design, fabrication, and characterization of thin Si3N4 ultra-high-quality (UHQ) factor ring resonators monolithically integrated on a silicon chip. The devices are based on a strip-loaded configuration and operate at both near-infrared (NIR) and third-telecom wavelengths. This approach allows us to use a guiding Si3N4 core that is one order of magnitude thinner than what has been reported in the past for obtaining similar device performances. Our strip-loaded devices benefit from the absence of physically etched lateral boundaries to show minute light scattering and, therefore, reducing significantly scattering-related losses. Consequently, UHQs of 3.7×10(6) in the NIR and high-quality factors of up to 9×10(5) in the C-band were measured for the guiding material thickness of 80 nm and 115 nm, respectively. These first results are subject to further improvements that may allow employing strip-loaded resonators in nonlinear frequency conversion or quantum computing schemes within the desired spectral range provided by the material transparency.

Targeting the EWS-FLI1 transcription factor in Ewing sarcoma.

PURPOSE: Preclinical data indicate there is strong synergism of action against Ewing sarcoma in sequential treatment with trabectedin followed by irinotecan and it appears to be related to a selective blockade of the transcription factor EWS-FLI1. This combination was evaluated in Ewing sarcoma patient who was progressing with standard therapies. METHODS: Trabectedin was given as a 24-h iv infusion on day 1 at the dose of 1 mg/sqm, and irinotecan 75 mg/sqm on day 2 and then on days 2 and 4, every 3 weeks from the seventh course. RESULTS: The therapy was well tolerated with transient hematological toxicity and transaminitis and induced stabilization of the disease lasting for 11 courses, with clinical improvement and marked reduction of the need for opioids. However, shortly before the 12th course, sudden death occurred, possibly due to cerebral stroke, presumably not related to the drug treatment. CONCLUSIONS: The encouraging clinical benefit observed with the combination and its good tolerability deserves further investigation in Ewing sarcoma.

Enhancement of photoluminescence intensity of erbium doped silica containing Ge nanocrystals: distance dependent interactions.

Photo-physical processes in Er-doped silica glass matrix containing Ge nanocrystals prepared by the sol-gel method are presented in this article. Strong photoluminescence at 1.54 µm, important for fiber optics telecommunication systems, is observed from the different sol-gel derived glasses at room temperature. We demonstrate that Ge nanocrystals act as strong sensitizers for Er(3+) ions emission and the effective Er excitation cross section increases by almost four orders of magnitude with respect to the one without Ge nanocrystals. Rate equations are considered to demonstrate the sensitization of erbium luminescence by Ge nanocrystals. Analyzing the erbium effective excitation cross section, extracted from the flux dependent rise and decay times, a Dexter type of short range energy transfer from a Ge nanocrystal to erbium ion is established.

A miRNA Signature in Human Cord Blood Stem and Progenitor Cells as Potential Biomarker of Specific Acute Myeloid Leukemia Subtypes.

MicroRNAs (miRNAs) are important regulators of several cellular processes. During hematopoiesis, specific expression signatures have been reported in different blood cell lineages and stages of hematopoietic stem cell (HSC) differentiation. Here we explored the expression of miRNAs in umbilical cord blood stem (HSC) and progenitor cells (HPC) and compared it to unilineage granulocyte and granulo-monocyte differentiation as well as to primary blasts from patients with acute myeloid leukemia (AML). CD34 + CD38- ad CD34 + CD38 + cells were profiled using a global array consisting of about 2000 miRNAs. An approach combining bioinformatic prediction of miRNA targets with mRNA expression profiling was used to search for putative biologically enriched functions and networks. At least 15 miRNAs to be differentially expressed between HSC and HPC cell population, a cluster of 7 miRNAs are located in the q32 region of human chromosome 14 (miR-377-3p, -136-5p, 376a-3p, 495-3p, 654-3p, 376c-3p and 381-3p) whose expression decreased during the early stages of normal myelopoiesis but were markedly increased in a small set of AML. Interestingly, miR-4739 and -4516, two novel microRNA whose function and targets are presently unknown, showed specific and peculiar expression profile during the hematopoietic stem cells differentiation into unilineages and resulted strongly upregulated in almost all AML subsets. miR-181, -126-5p, -29b-3p and -22-3p resulted dis-regulated in specific leukemias phenotypes. This study provides the first evidence of a miRNA signature in human cord blood stem and progenitor cells with a potential role in hematopoietic stemness properties and possibly in leukemogenesis of specific AML subtypes.

Chaotic dynamics in coupled resonator sequences.

Optically induced thermal and free carrier nonlinearities in silicon micro-ring resonator influence their behavior. They can be either deleterious by making them instable and by driving their resonances out of the designed wavelengths, or enabler of different applications. Among the most interesting one, there are optical bistability and self induced oscillations. These lead to all optical logic, signal modulation, optical memories and applications in neural networks. Here, we theoretically and experimentally demonstrate that when many resonators are coupled together, thermal and free carrier nonlinearities induce also chaos. The chaotic dynamics are deeply analyzed using experimentally reconstructed phase space trajectories and the tool of Lyapunov exponents.

Thermo-optical bistability with Si nanocrystals in a whispering gallery mode resonator.

We report on the observation of optical bistability in an integrated planar microresonator with embedded silicon nanocrystals (Si-ncs). The phenomenon originates from the thermo-optical modulation of the silica-embedded Si-ncs refractive index, which in turn alters the spectral position of the resonator mode. The estimated thermo-optical coefficient of the Si nanocrystalline material, dn/dT≈2.92×10(-5)> K(-1), is an order of magnitude lower than that of bulk silicon. Both time-resolved pump-and-probe experiments and numerical simulations confirm that the silica host is responsible for the heat dissipation from the resonator. Moreover, a negligible Q-factor degradation at pump powers as high as 100 mW, along with the absence of a fast component in time-resolved measurements, confirm the minute contribution from excited carriers effects. These observations, combined with the already published large third-order nonlinearities of Si-ncs (an order of magnitude larger than in bulk Si), make this system an outstanding candidate for low-power on-chip nonlinear comb generation.

Oscillatory vertical coupling between a whispering-gallery resonator and a bus waveguide.

We report on a theoretical and experimental study of the optical coupling between a whispering-gallery type resonator and a waveguide lying on different planes. In contrast to the usual in-plane geometry, the present vertical one is characterized by an oscillatory behavior of the effective coupling as a function of the vertical gap. This behavior manifests itself as oscillations in both the resonance peak waveguide transmission and the mode quality factor. An analytical description based on coupled-mode theory and a two-port beam-splitter model of the waveguide-resonator vertical coupling is developed for arbitrary phase-matching conditions and is successfully used to interpret the experimental observations.

Er-doped light emitting slot waveguides monolithically integrated in a silicon photonic chip.

An integrated erbium-based light emitting diode has been realized in a waveguide configuration allowing 1.54 µm light signal routing in silicon photonic circuits. This injection device is based on an asymmetric horizontal slot waveguide where the active slot material is Er(3+) in SiO2 or Er(3+) in Si-rich oxide. The active horizontal slot waveguide allows optical confinement, guiding and lateral extraction of the light for on-chip distribution. Light is then coupled through a taper section to a passive Si waveguide terminated by a grating which extracts (or inserts) the light signal for measuring purposes. We measured an optical power density in the range of tens of µW/cm(2) which follows a super-linear dependence on injected current density. When the device is biased at high current density, upon a voltage pulse (pump signal), free-carrier and space charge absorption losses become large, attenuating a probe signal by more than 60 dB/cm and thus behaving conceptually as an electro-optical modulator. The integrated device reported here is the first example, still to be optimized, of a fundamental block to realize an integrated silicon photonic circuit with monolithic integration of the light emitter.

Electrical pump & probe and injected carrier losses quantification in Er doped Si slot waveguides.

Electrically driven Er(3+) doped Si slot waveguides emitting at 1530 nm are demonstrated. Two different Er(3+) doped active layers were fabricated in the slot region: a pure SiO(2) and a Si-rich oxide. Pulsed polarization driving of the waveguides was used to characterize the time response of the electroluminescence (EL) and of the signal probe transmission in 1 mm long waveguides. Injected carrier absorption losses modulate the EL signal and, since the carrier lifetime is much smaller than that of Er(3+) ions, a sharp EL peak was observed when the polarization was switched off. A time-resolved electrical pump & probe measurement in combination with lock-in amplifier techniques allowed to quantify the injected carrier absorption losses. We found an extinction ratio of 6 dB, passive propagation losses of about 4 dB/mm, and a spectral bandwidth > 25 nm at an effective d.c. power consumption of 120 µW. All these performances suggest the usage of these devices as electro-optical modulators.

Reconfigurable optical routers based on Coupled Resonator Induced Transparency resonances.

The interferometric coupling of pairs of resonators in a resonator sequence generates coupled ring induced transparency (CRIT) resonances. These have quality factors an order of magnitude greater than those of single resonators. We show that it is possible to engineer CRIT resonances in tapered SCISSOR (Side Coupled Integrated Space Sequence of Resonator) to realize fast and efficient reconfigurable optical switches and routers handling several channels while keeping single channel addressing capabilities. Tapered SCISSORs are fabricated in silicon-on-insulator technology. Furthermore, tapered SCISSORs show multiple-channel switching behavior that can be exploited in DWDM applications.

Erbium emission in MOS light emitting devices: from energy transfer to direct impact excitation.

The electroluminescence (EL) at 1.54 µm of metal­oxide­semiconductor (MOS) devices withEr3C ions embedded in the silicon-rich silicon oxide (SRSO) layer has been investigated under different polarization conditions and compared with that of erbium doped SiO2 layers. EL time-resolved measurements allowed us to distinguish between two different excitation mechanisms responsible for the Er3C emission under an alternate pulsed voltage signal (APV). Energy transfer from silicon nanoclusters (Si-ncs) to Er3C is clearly observed at low-field APV excitation. We demonstrate that sequential electron and hole injection at the edges of the pulses creates excited states in Si-ncs which upon recombination transfer their energy to Er3C ions. On the contrary, direct impact excitation of Er3C by hot injected carriers starts at the Fowler­Nordheim injection threshold (above 5 MV cm(-1)) and dominates for high-field APV excitation.

Photophysics of resonantly and non-resonantly excited erbium doped Ge nanowires.

We have fabricated Er doped germanium nanowires of different diameters by pulsed laser deposition and chemical methods. Er induced photoluminescence emission due to the intra-4f (4)I(13/2)→(4)I(15/2) transition of Er energy levels at 1.53 µm has been achieved at room temperature using both resonant (980 nm) and non-resonant (325 nm) excitation of Er ions. The observed 1.53 µm photoluminescence signal upon non-resonant 325 nm excitation is attributed to the Ge related oxygen deficiency centers surrounding the Ge core. For direct excitation, the infrared photoluminescence characteristics have been studied as a function of Er concentration, photon flux, and diameter of the nanowires. The Er related emission signal is found to be enhanced with increase in Er concentration, pump flux of 980 nm, and the nanowire diameter. The time resolved characteristics of the Er induced emission peak have been studied as a function of the pump flux as well as the diameter of the Ge nanowires.

Second-harmonic generation in silicon waveguides strained by silicon nitride.

Silicon photonics meets the electronics requirement of increased speed and bandwidth with on-chip optical networks. All-optical data management requires nonlinear silicon photonics. In silicon only third-order optical nonlinearities are present owing to its crystalline inversion symmetry. Introducing a second-order nonlinearity into silicon photonics by proper material engineering would be highly desirable. It would enable devices for wideband wavelength conversion operating at relatively low optical powers. Here we show that a sizeable second-order nonlinearity at optical wavelengths is induced in a silicon waveguide by using a stressing silicon nitride overlayer. We carried out second-harmonic-generation experiments and first-principle calculations, which both yield large values of strain-induced bulk second-order nonlinear susceptibility, up to 40 pm V(-1) at 2,300 nm. We envisage that nonlinear strained silicon could provide a competing platform for a new class of integrated light sources spanning the near- to mid-infrared spectrum from 1.2 to 10 µm.

Coupled-resonator-induced-transparency concept for wavelength routing applications.

The presence of coupled resonators induced transparency (CRIT) effects in side-coupled integrated spaced sequence of resonators (SCISSOR) of different radii has been studied. By controlling the rings radii and their center to center distance, it is possible to form transmission channels within the SCISSOR stop-band. Two different methods to exploit the CRIT effect in add/drop filters are proposed. Their performances, e. g. linewidth, crosstalk and losses, are examined also for random variations in the structural parameters. Finally, few examples of high performances mux/demux structures and 2 × 2 routers based on these modified SCISSOR are presented. CRIT based SCISSOR optical devices are particularly promising for ultra-dense wavelength division multiplexing applications.