80 research outputs found
Dark-Bright Soliton Bound States in a Microresonator
The recent discovery of dissipative Kerr solitons in microresonators has facilitated the development of fully coherent, chip-scale frequency combs. In addition, dark soliton pulses have been observed in microresonators in the normal dispersion regime. Here, we report bound states of mutually trapped dark-bright soliton pairs in a microresonator. The soliton pairs are generated seeding two modes with opposite dispersion but with similar group velocities. One laser operating in the anomalous dispersion regime generates a bright soliton microcomb, while the other laser in the normal dispersion regime creates a dark soliton via Kerr-induced cross-phase modulation with the bright soliton. Numerical simulations agree well with experimental results and reveal a novel mechanism to generate dark soliton pulses. The trapping of dark and bright solitons can lead to light states with the intriguing property of constant output power while spectrally resembling a frequency comb. These results can be of interest for telecommunication systems, frequency comb applications, ultrafast optics and soliton states in atomic physics
Universal symmetry-breaking dynamics for the Kerr interaction of counterpropagating light in dielectric ring resonators
Spontaneous symmetry breaking is an important concept in many areas of physics. A fundamentally simple symmetry-breaking mechanism in electrodynamics occurs between counterpropagating electromagnetic waves in ring resonators, mediated by the Kerr nonlinearity. The interaction of counterpropagating light in bidirectionally pumped microresonators finds application in the realization of optical nonreciprocity (for optical diodes), studies of PT-symmetric systems, and the generation of counterpropagating solitons. Here, we present comprehensive analytical and dynamical models for the nonlinear Kerr interaction of counterpropagating light in a dielectric ring resonator. In particular, we study discontinuous behavior in the onset of spontaneous symmetry breaking, indicating divergent sensitivity to small external perturbations. These results can be applied to realize, for example, highly sensitive near-field or rotation sensors. We then generalize to a time-dependent model, which predicts different types of dynamical behavior, including oscillatory regimes that could enable Kerr-nonlinearity-driven all-optical oscillators. The physics of our model can be applied to other systems featuring Kerr-type interaction between two distinct modes, such as for light of opposite circular polarization in nonlinear resonators, which are commonly described by coupled Lugiato-Lefever equations
Analisis Hukum Islam terhadap penerapan tarif Surge Pricing pada sewa taksi online Uber di wilayah Surabaya
Skripsi ini adalah hasil penelitian lapangan (field research). Rumusan masalahnya: Pertama, bagaimana praktek penerapan tarif surge pricing pada sewa taksi online Uber di wilayah Surabaya. Kedua, bagaimana analisis hukum Islam terhadap penerapan tarif surge pricing pada sewa taksi online Uber di wilayah Surabaya .Data penelitian ini dihimpun melalui observasi, wawancara kemudian dianalisis dengan menggunakan metode deskripsi kualitatif. Penelitian ini menggunakan pola pikir deduktif, yang diawali dengan mengemukakan pengertian-pengertian, teori-teori, atau fakta-fakta yang bersifat umum, yaitu ketentuan-ketentuan hukum Islam mengenai Ija>rah dan Upah dalam hukum Islam yang selanjutnya dipaparkan dari kenyataan yang ada di lapangan mengenai praktik penerapan tarif surge pricing pada sewa taksi online Uber di wilayah Surabaya, kemudian diteliti dan dianalisis.Hasil penelitian menyimpulkan bahwa penerapan tarif surge pricing yang diberlakukan oleh Uber pada saat terjadinya jam jam sibuk yang menggunakan prinsip ekonomi persediaan dan permintaan, dimana jika permintaan sedang tinggi sedangkan persediaan tidak mencukupi maka biaya perjalanan otomatis meningkat. Dalam penerapannya biaya perjalanan akan meingkat antara 1.1x – 5.5x lipat. Hal ini terjadi secara tiba tiba dan menjadikan penumpang membayar biaya yang lebih mahal dibandingkan dengan perjalanan biasa, dan juga hal ini hanya terjadi di wilayah tertentu dan hanya terjadi beberapa menit atau jam saja. Dalam hukum Islam sebernarnya penerapan ini diperbolehkan, akan tetapi harus diberlakukan secara adil, jelas, transparan dan melihat kerelaan antara penumpang dengan driver. Dan dalam hal ini uber juga memberlakukan perjanjian baku yang terdapat pada buku panduan uber yang sedikit menerangkan tentang adanya tarif surge pricing ini, jadi dengan adanya perjanjian baku ini Uber sudah benar dalam penerapan adanya tarif surge pricing ini.Sejalan dengan kesimpulan di atas, maka disarankan kepada Uber supaya memberi fasilitas kepada pelanggan untuk juga mengetahui di mana atau akan terjadinya penerapan tarif surge pricing dan kepada pengguna layanan Uber agar jika terkena penerapan tarif surge pricing untuk bersabar menunggu hingga harga kembali normal atau tetap memesan taksi online uber dengan cepat agar tarif tidak semakin naik, dan juga kepada driver agar tidak memanfaatkan keadaan saat terjadinya penerapan tarif surge pricing
A Kerr Polarization Controller
Kerr-effect-induced changes of the polarization state of light are well known in pulsed laser systems. An example is nonlinear polarization rotation, which is critical to the operation of many types of mode-locked lasers. Here, we demonstrate that the Kerr effect in a high-finesse Fabry-Pérot resonator can be utilized to control the polarization of a continuous wave laser. It is shown that a linearly-polarized input field is converted into a left- or right-circularly-polarized field, controlled via the optical power. The observations are explained by Kerr-nonlinearity induced symmetry breaking, which splits the resonance frequencies of degenerate modes with opposite polarization handedness in an otherwise symmetric resonator. The all-optical polarization control is demonstrated at threshold powers down to 7 mW. The physical principle of such Kerr effect-based polarization controllers is generic to high-Q Kerr-nonlinear resonators and could also be implemented in photonic integrated circuits. Beyond polarization control, the spontaneous symmetry breaking of polarization states could be used for polarization filters or highly sensitive polarization sensors when operated close to the symmetry-breaking point
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Nonlinear enhanced microresonator gyroscope
Optical gyroscopes based on the Sagnac effect have been the mainstay of inertial navigation in aerospace and shipping for decades. These gyroscopes are typically realized either as ring-laser gyroscopes (RLGs) or fiber-optic gyroscopes (FOGs). With the recent rapid progress in the field of ultrahigh-quality optical whispering-gallery mode and ring microresonators, attention has been focused on the development of microresonator-based Sagnac gyroscopes as a more compact alternative to RLGs and FOGs. One avenue that has been explored is the use of exceptional points in non-Hermitian systems to enhance the responsivity to rotation. We use a similar phenomenon, namely, the critical point of a spontaneous symmetry-breaking transition between counterpropagating light, to demonstrate a microresonator gyroscope with a responsivity enhanced by a factor of around 104. We present a proof-of-principle rotation measurement as well as a characterization of the system’s dynamical response, which shows the universal critical behaviors of responsivity enhancement and critical slowing down, both of which are beneficial in an optical gyroscope. We believe that this concept could be used to realize simple and cheap chip-based gyroscopes with sensitivities approaching those of today’s RLGs and FOGs
Chemical Synthesis and Immunological Evaluation of Fragments of the Multiantennary Group-Specific Polysaccharide of Group B Streptococcus.
Group B Streptococcus (GBS) is a Gram-positive bacterium and the most common cause of neonatal blood and brain infections. At least 10 different serotypes exist, that are characterized by their different capsular polysaccharides. The Group B carbohydrate (GBC) is shared by all serotypes and therefore attractive be used in a glycoconjugate vaccine. The GBC is a highly complex multiantennary structure, composed of rhamnose rich oligosaccharides interspaced with glucitol phosphates. We here report the development of a convergent approach to assemble a pentamer, octamer, and tridecamer fragment of the termini of the antennae. Phosphoramidite chemistry was used to fuse the pentamer and octamer fragments to deliver the 13-mer GBC oligosaccharide. Nuclear magnetic resonance spectroscopy of the generated fragments confirmed the structures of the naturally occurring polysaccharide. The fragments were used to generate model glycoconjugate vaccine by coupling with CRM197. Immunization of mice delivered sera that was shown to be capable of recognizing different GBS strains. The antibodies raised using the 13-mer conjugate were shown to recognize the bacteria best and the serum raised against this GBC fragment-mediated opsonophagocytic killing best, but in a capsule dependent manner. Overall, the GBC 13-mer was identified to be a highly promising antigen for incorporation into future (multicomponent) anti-GBS vaccines.Bio-organic Synthesi
A phase I study with MAG-camptothecin intravenously administered weekly for 3 weeks in a 4-week cycle in adult patients with solid tumours
In MAG-camptothecin (MAG-CPT), the topoisomerase inhibitor camptothecin is linked to a water-soluble polymer. Preclinical experiments showed enhanced antitumour efficacy and limited toxicity compared to camptothecin alone. Prior phase I trials guided the regimen used in this study. The objectives were to determine the maximum tolerated dose, dose-limiting toxicities, safety profile, and pharmacokinetics of weekly MAG-CPT. Patients with solid tumours received MAG-CPT intravenously administered weekly for 3 weeks in 4-week cycles. At the starting dose level ( 80 mg m(-2) week(-1)), no dose-limiting toxicities occurred during the first cycle (n = 3). Subsequently, three patients were enrolled at the second dose level ( 120 mg m(-2) week(-1)). Two of three patients at the 80 mg m(-2) week(-1) cohort developed haemorrhagic cystitis ( grade 1/3 dysuria and grade 2/3 haematuria) during the second and third cycles. Next, the 80 mg m(-2) week(-1) cohort was enlarged to a total of six patients. One other patient at this dose level experienced grade 1 haematuria. At 120 mg m(-2) week(-1), grade 1 bladder toxicity occurred in two of three patients. Dose escalation was stopped at 120 mg m(-2) week(-1). Cumulative bladder toxicity was dose-limiting toxicity at 80 mg m(-2) week(-1). Pharmacokinetics revealed highly variable urinary camptothecin excretion, associated with bladder toxicity. Due to cumulative bladder toxicity, weekly MAG-CPT is not a suitable regimen for treatment of patients with solid tumours
Schedule-dependent cytotoxicity of SN-38 in p53 wild-type and mutant colon adenocarcinoma cell lines
In this study the effects of SN-38 on colon adenocarcinoma cell lines expressing wild-type p53 (LS174T) or mutant non-functional p53 (HT29) have been investigated. On exposure to SN-38, HT29 cells rapidly progressed through G1 and S and arrested in G2/M. Release and concomitant increase in apoptosis after 48 h was concentration- and time-dependent (P < 0.001), being more rapid at higher concentrations, but reaching plateau at 10 ng ml–1 with prolonged exposure. LS174T cells showed only a small increase in apoptosis, and only at high concentrations (50–100 ng ml–1). The main effect of SN-38 in LS174T cells was prolonged cell cycle arrest, which was independent of concentration. Arrest occurred in all phases of the cell cycle, with the distribution depending on concentration (P < 0.001) and not duration (P > 0.05). With increasing concentration, LS174T cells arrested in G2/M, S and G1. Cell cycle arrest was coincident with increased p53 expression in each phase of the cell cycle. Expression in G1 increased with time and concentration (P < 0.001, P = 0.01 respectively), whereas in S and G2/M p53 expression increased only with time (P < 0.001). Dose-dependent p53-associated G1 arrest, in the absence of DNA synthesis indicates an additional cytotoxic mechanism for SN-38, which requires higher concentrations than the S phase mechanism, and detection of which seems to involve p53. For incubations with the same ED (exposure × duration), apoptosis in HT29 cells was significantly higher for prolonged exposure to lower concentrations, whereas in LS174T cells there was a trend towards increased apoptosis with shorter exposures to higher concentrations, indicating a schedule effect of SN-38. Although expression of wild-type p53 leads to a more rapid induction of apoptosis, SN-38 cytotoxicity was generally greater in cells with mutant p53, as wild-type cells escaped apoptosis by p53 associated prolonged cell cycle arrest. Thus, pulsed schedules with higher doses may be more effective in cells expressing wild-type p53, whereas continued exposure with protracted schedules may be more active in cells expressing mutant p53. © 1999 Cancer Research Campaig
Membrane transport of camptothecin: facilitation by human P-glycoprotein (ABCB1) and multidrug resistance protein 2 (ABCC2)
BACKGROUND: The purpose of the present study was to continue the investigation of the membrane transport mechanisms of 20-(S)-camptothecin (CPT) in order to understand the possible role of membrane transporters on its oral bioavailability and disposition. METHODS: The intestinal transport kinetics of CPT were characterized using Caco-2 cells, MDCKII wild-type cells and MDCKII cells transfected with human P-glycoprotein (PGP) (ABCB1) or human multidrug resistance protein 2 (MRP2) (ABCC2). The effects of drug concentration, inhibitors and temperature on CPT directional permeability were determined. RESULTS: The absorptive (apical to basolateral) and secretory (basolateral to apical) permeabilities of CPT were found to be saturable. Reduced secretory CPT permeabilities with decreasing temperatures suggests the involvement of an active, transporter-mediated secretory pathway. In the presence of etoposide, the CPT secretory permeability decreased 25.6%. However, inhibition was greater in the presence of PGP and of the breast cancer resistant protein inhibitor, GF120918 (52.5%). The involvement of additional secretory transporters was suggested since the basolateral to apical permeability of CPT was not further reduced in the presence of increasing concentrations of GF120918. To investigate the involvement of specific apically-located secretory membrane transporters, CPT transport studies were conducted using MDCKII/PGP cells and MDCKII/MRP2 cells. CPT carrier-mediated permeability was approximately twofold greater in MDCKII/PGP cells and MDCKII/MRP2 cells than in MDCKII/wild-type cells, while the apparent K(m )values were comparable in all three cell lines. The efflux ratio of CPT in MDCKII/PGP in the presence of 0.2 μM GF120918 was not completely reversed (3.36 to 1.49). However, the decrease in the efflux ratio of CPT in MDCKII/MRP2 cells (2.31 to 1.03) suggests that CPT efflux was completely inhibited by MK571, a potent inhibitor of the Multidrug Resistance Protein transporter family. CONCLUSIONS: The current results provide evidence that PGP and MRP2 mediate the secretory transport of CPT in vitro. However, the involvement of other transporters cannot be ruled out based on these studies. Since these transporters are expressed in the intestine, liver and kidney variations in their expression levels and/or regulation may be responsible for the erratic oral absorption and biliary excretion of CPT observed in human subjects
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