Control of dynamical regimes in optical microresonators exploiting parametric interaction

Microresonators have the ability of strongly enhancing the propagating optical field, enabling nonlinear phenomena, such as bi-stability, self-pulsing and chaotic regimes, at very low powers. It is fundamental to comprehend the mechanisms that generate such dynamics, which are crucial for micro-cavities-based applications in communications, sensing and metrology. The aim of this work is to develop a scheme for the control of nonlinear regimes in microresonators, assuming the interplay between the ultra-fast Kerr effect and a slow intensity-dependent nonlinearity, such as thermo-optical effect. The framework of the coupled-mode theory is applied to model the system, while the bifurcation theory is used to investigate a configuration in which the power and frequency of a weak signal can control the behaviour of a strong pump. In this regards, this study demonstrates that the effect of a parametric interaction, specifically the four-wave mixing, plays a fundamental role in influencing the nature of the stationary states observed in a micro-cavity. The results show possible new strategies for enhanced, low-power, all-optical control of sensors, oscillators and chaos-controlled devices. Moreover, the outcomes provide new understanding of the effect of coherent wave mixing in the thermal stability regions of optical micro-cavities, including optical micro-combs

Parametric control of thermal self-pulsation in micro-cavities

We propose a scheme for bifurcation control in micro-cavities based on the interplay between the ultrafast Kerr effect and a slow nonlinearity, such as thermo-optical, free-carriers-induced, or opto-mechanical one. We demonstrate that Hopf bifurcations can be efficiently controlled with a low energy signal via four-wave mixing. Our results show that new strategies are possible for designing efficient micro-cavity-based oscillators and sensors. Moreover, they provide new understanding of the effect of coherent wave mixing in the thermal stability regions of optical micro-cavities, fundamental for micro-resonator-based applications in communications, sensing, and metrology, including optical micro-combs

Optical multi-stability in a nonlinear high-order microring resonator filter

We theoretically analyze and experimentally demonstrate optical bi-stability and multi-stability in an integrated nonlinear high-order microring resonator filter based on high-index contrast doped silica glass. We use a nonlinear model accounting for both the Kerr and thermal effects to analyze the instability behavior of the coupled-resonator based filter. The model also accurately predicts the multi-stable behavior of the filter when the input frequency is slightly detuned. To understand the role of the intracavity power distribution, we investigate the detuning of the individual rings of the filter from the optical response with a pump–probe experiment. Such a measurement is performed scanning the filter with a low-power probe beam tuned a few free spectral ranges away from the resonance where the pump is coupled. A comprehensive understanding of the relationship between the nonlinear behavior and the intracavity power distribution for the high-order microring resonator filter will help the design and implementation of future all-optical switching systems using this type of filter

Fasting glucose and body mass index as predictors of activity in breast cancer patients treated with everolimus-exemestane: the EverExt study

Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test. Survival predictors were tested in Cox models. Median follow up was 12.4 months (1.0-41.0). The overall cohort showed increasing levels of FG and decreasing BMI (p < 0.001). Lower FG fasting glucose at BR was more commonly associated with C/PR or SD compared with PD (p < 0.001). We also observed a somewhat higher BMI associated with better response (p = 0.052). More patients in the lowest FG category achieved clinical benefit compared to the highest (p < 0.001), while no relevant differences emerged for BMI. Fasting glucose at re-assessment was also predictive of PFS (p = 0.037), as confirmed in models including BMI and line of therapy (p = 0.049). Treatment discontinuation was significantly associated with changes in FG (p = 0.014). Further research is warranted to corroborate these findings and clarify the underlying mechanisms

Effect of biologically oriented preparation technique on the stress concentration of endodontically treated upper central incisor restored with zirconia crown: 3d-fea

The aim of this study was to evaluate the effect of biologically oriented preparation technique on the stress concentration of endodontically treated upper central incisors restored with zirconia crown (yttria-stabilized zirconia polycrystalline ceramic) through finite element analysis (FEA). Four models of maxillary central incisors containing enamel, dentin, periodontal ligament, cortical and medullary bone were created in CAD. Each model received a polymeric core-build up with nanofilled dental resin composite. The evaluated models were SM—preparation in shoulder 90°; CM—chamfer preparation; BOPT—biologically oriented preparation technique and BOPTB—BOPT preparation 1 mm below the cement-enamel junction. All models received zirconia crowns (5Y-TZP), fiberglass post and 1 mm ferrule. The models were imported into the analysis software with parameters for mechanical structural testing using the maximum principal stress and the tensile strength as the analysis criteria. Then, load of 150 N was applied at the cingulum with 45° slope to the long axis of the tooth, with the fixed base for each model. The type of marginal preparation affected the stresses concentration in endodontically treated teeth and in the zirconia crown margin. Considering the stress magnitude only, BOPT is a viable option for anterior monolithic zirconia crowns; however, with the highest stress magnitude at the restoration margin

Laser cavity-soliton microcombs

Microcavity-based frequency combs, or ‘microcombs’1,2, have enabled many fundamental breakthroughs3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 through the discovery of temporal cavity-solitons. These self-localized waves, described by the Lugiato–Lefever equation22, are sustained by a background of radiation usually containing 95% of the total power23. Simple methods for their efficient generation and control are currently being investigated to finally establish microcombs as out-of-the-lab tools24. Here, we demonstrate microcomb laser cavity-solitons. Laser cavity-solitons are intrinsically background-free and have underpinned key breakthroughs in semiconductor lasers22,25,26,27,28. By merging their properties with the physics of multimode systems29, we provide a new paradigm for soliton generation and control in microcavities. We demonstrate 50-nm-wide bright soliton combs induced at average powers more than one order of magnitude lower than the Lugiato–Lefever soliton power threshold22, measuring a mode efficiency of 75% versus the theoretical limit of 5% for bright Lugiato–Lefever solitons23. Finally, we can tune the repetition rate by well over a megahertz without any active feedback

Phase II study of epirubicin, oxaliplatin and docetaxel combination in metastatic gastric or gastroesophageal junction adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>This phase II study was designed to evaluate the activity and safety of a combination of epirubicin, oxaliplatin and docetaxel in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.</p> <p>Methods</p> <p>Forty patients with measurable distant metastases received epirubicin 50 mg/m², docetaxel 60 mg/m²followed by oxaliplatin 100 mg/m²on day 1 of each 21-day cycle. Primary end point was response rates (RR).</p> <p>Results</p> <p>All patients were evaluable. The overall RR was 47.5% (95% confidence interval (CI) 32–63). The disease control was 80%. Median time for response was 6 weeks. Median time to progression was 6.3 months (95% CI 5.4–7.2) and the median overall survival time was 12.1 months (95% CI 10.7–13.5). Grade 3/4 neutropenia occurred in 50% of patients with two episodes of febrile neutropenia (5%). Other non-hematological grade 3 toxicities included sensory neuropathy in two patiens (5%), vomiting and mucositis in two patients (5%) and diarrhea in one patient (2.5%).</p> <p>Conclusion</p> <p>The combination of epirubicin, oxaliplatin and docetaxel was found to be effective and well tolerated in patiens with metastatic gastric or GEJ adenocarcinoma and maybe an appropriate regimen to be used in the neoadjuvant setting and with molecularly targeted agents.</p

Role of gonadotropin-releasing hormone analogues in metastatic male breast cancer: Results from a pooled analysis

Background: Male breast cancer is a rare malignancy. Despite the lack of prospectively generated data from trials in either the adjuvant or metastatic setting, patients are commonly treated with hormone therapies. Much controversy exists over the use of gonadotropin-releasing hormone analogues in metastatic male breast cancer patients. We conducted this study to provide more concrete ground on the use of gonadotropin-releasing hormone analogues in this setting. Methods: We herein present results from a pooled analysis including 60 metastatic male breast cancer patients treated with either an aromatase inhibitor or cyproterone acetate as a monotherapy (23 patients) or combined with a gonadotropin-releasing hormone analogue (37 patients). Results: Overall response rate was 43.5 % in patients treated with monotherapy and 51.3 % with combination therapy (p = 0.6). Survival outcomes favored combination therapy in terms of median progression-free survival (11.6 months versus 6 months; p = 0.05), 1-year progression-free survival rate (43.2 % versus 21.7 %; p = 0.05), median overall survival (29.7 months versus 22 months; p = 0.05), and 2-year survival rate (64.9 % versus 43.5 %; p = 0.05). Conclusions: In metastatic male breast cancer patients, the combined use of gonadotropin-releasing hormone analogues and aromatase inhibitors or antiandrogens seems to be associated with greater efficacy, particularly in terms of survival outcomes, compared with monotherapy. Collectively, these results encourage considering these agents in the metastatic setting

Thermo-optical pulsing in a microresonator filtered fiber-laser: a route towards all-optical control and synchronization

We report on 'slow' pulsing dynamics in a silica resonator-based laser system: by nesting a high-Q rod-resonator inside an amplifying fiber cavity, we demonstrate that trains of microsecond pulses can be generated with repetition rates in the hundreds of kilohertz. We show that such pulses are produced with a period equivalent to several hundreds of laser cavity roundtrips via the interaction between the gain dynamics in the fiber cavity and the thermo-optical effects in the high-Q resonator. Experiments reveal that the pulsing properties can be controlled by adjusting the amplifying fiber cavity parameters. Our results, confirmed by numerical simulations, provide useful insights on the dynamical onset of complex self-organization phenomena in resonator-based laser systems where thermo-optical effects play an active role. In addition, we show how the thermal state of the resonator can be probed and even modified by an external, counter-propagating optical field, thus hinting towards novel approaches for all-optical control and sensing applications

An ontology-based approach supporting holistic structural design with the consideration of safety, environmental impact and cost

Early stage decision-making for structural design critically influences the overall cost and environmental performance of buildings and infrastructure. However, the current approach often fails to consider the multi-perspectives of structural design, such as safety, environmental issues and cost in a comprehensive way. This paper presents a holistic approach based on knowledge processing (ontology) to facilitate a smarter decision-making process for early design stage by informing designers of the environmental impact and cost along with safety considerations. The approach can give a reasoning based quantitative understanding of how the design alternatives using different concrete materials can affect the ultimate overall performance. Embodied CO2 and cost are both considered along with safety criteria as indicative multi-perspectives to demonstrate the novelty of the approach. A case study of a concrete structural frame is used to explain how the proposed method can be used by structural designers when taking multi performance criteria into account. The major contribution of the paper lies on the creation of a holistic knowledge base which links through different knowledge across sectors to enable the structural engineer to come up with much more comprehensive decisions instead of individual single objective targeted delivery