Stereoselective synthesis of a Glc-NAc conjugate as potential modulator of carbohydrate metabolism and Regio- and stereoselective behaviour of carbapyranose 1,2-epoxides with α-gluco and β-manno configuration

The first part of the present work thesis concerns the synthesis of a Glc-NAc-Conjugated Lactate Dehydrogenase Inhibitor as promising anticancer agent. It was widely demonstrated that solid tumors have an enormous consumption of glucose and are characterized by a “metabolic switch”, because tumor cells use as principal source of energy aerobic glycolysis, instead of oxidative phosphorylation. Besides, cancer cells overexpress the glucose transporter GLUT-1 and enzymes of glycolysis, including Lactate Dehydrogenase Isoform A (LDH-A), which has recently emerged as a new potential target in the anticancer therapy, because of its key role in glycolysis progression. On the basis of these evidences, N-hydroxyindole-based (NHI) LDH-A inhibitors were synthesized in our Department. Recently the research team where I carried out my thesis converted one of these NHI-based LDH-A inhibitors into the corresponding glucose-conjugate and the preliminary studies on its anticancer activity demonstrated that this activity depends on a dual-targeting mechanism, which involves both LDH-A and glucose transporter GLUT-1. On account of this, our goal was synthesizing the corresponding Glc-NAc-conjugate, since the N-acetylglucosamine group, as reported, plays a very important biological role and appears to be involved in determining some features of cancer cells. The second part of this work thesis concerns regioselective studies of the nucleophilic addition reactions to carbapyranose-1,2-epoxide with α-gluco and β-manno configuration. Ring-opening reactions of carbapyranose-1,2-epoxide with β-manno configuration had been widely studied because these epoxides were opened efficiently with attack at C(1) (sterically and electronically favoured) to give 1,2-trans-diaxial carba-α-manno derivatives with both oxygen and nitrogen nucleophiles. Instead carbapyranose-1,2-epoxide with α-gluco configuration did not give such good results, because nucleophiles attack was often unregioselective. Precedent studies, finalyzed to the synthesis of useful α-manno glycoconjugates confirmed these kinds of behaviour, besides in our studies on epoxides with α-gluco configuration it was observed an undesired intramolecular addition process with the internal nucleophile C(5)-CH2OR, that allows the formation of a bicyclic byproduct. The first goal of my thesis was to minimize or to avoid the formation of this bicyclic byproduct, in order to better study and direct the stereo- and regioselectivity of nucleophilic addition reaction on these substrates. For these reasons, first we introduced different bulky protecting groups on the C(6) position, then, we introduced a deoxy-methyl group on C(6) position. On the one hand, introduction of bulky protective groups on C(6) position still have not allowed to obtain regioselective results in nucleophilic addition reactions with O-nucleophiles, however reduced formation of the bicyclic compound was achieved. On the other hand, the introduction of a methyl substituent on C(5) position completely avoids the formation of the bicyclic compound but still affords unregioselective results in nucleophilic addition reactions. More interesting, the use of alcohols different from MeOH efficiently influences the regio- and stereoselectivity of the ring opening process. A very nice result was obtained under methanolysis using LiClO4 as the coordinating agent: in these reaction conditions we observed a completely C(1) regio- and stereoselective nucleophilic addition process

Optical memories and switching dynamics of counterpropagating light states in microresonators

The Kerr nonlinearity can be a key enabler for many digital photonic circuits as it allows access to bistable states needed for all-optical memories and switches. A common technique is to use the Kerr shift to control the resonance frequency of a resonator and use it as a bistable, optically-tunable filter. However, this approach works only in a narrow power and frequency range or requires the use of an auxiliary laser. An alternative approach is to use the asymmetric bistability between counterpropagating light states resulting from the interplay between self- and cross-phase modulation, which allows light to enter a ring resonator in just one direction. Logical HIGH and LOW states can be represented and stored as the direction of circulation of light, and controlled by modulating the input power. Here we study the switching speed, operating laser frequency and power range, and contrast ratio of such a device. We reach a bitrate of 2 Mbps in our proof-of-principle device over an optical frequency range of 1 GHz and an operating power range covering more than one order of magnitude. We also calculate that integrated photonic circuits could exhibit bitrates of the order of Gbps, paving the way for the realization of robust and simple all-optical memories, switches, routers and logic gates that can operate at a single laser frequency with no additional electrical power.Comment: 10 pages, 10 figure

Kerr-mediated symmetry breaking of counterpropagating light in microresonators

Nonlinear Optics has been a source of surprises for physicists for almost a century comprising both fundamental physics and real-world applications. To access optical nonlinearities, significant light intensities are required; thus nonlinear optics often involves a resonant cavity to amplify the light intensity. Microresonators have proven to be an ideal platform for this kind of experiment since the cavity mode area can be as small as a few µm2 and their high Q-factor traps light for many round trips while more light is coupled in. Also, light interacts with the nonlinear material, of which the resonator is made, for the whole round trip. However, the interaction between counter-propagating light in microresonators is still a relatively unexplored field. This thesis reports on the first observation of Kerr-induced spontaneous symmetry breaking in a microresonator, whereby light can circulate in only one direction inside the resonator. I develop a theoretical model describing the steady-state solutions and the dynamics of how the symmetry-broken regime responds to the input changes. I show experimentally how the symmetry breaking can be used to realise all-optical isolator, circulators, memories and logic gates. These devices, based on the Kerr-nonreciprocity, represent a promising alternative for the realisation of integrated all-optical passive photonics circuits

Symmetry Breaking of Counter-Propagating Light in a Nonlinear Resonator

Spontaneous symmetry breaking is a concept of fundamental importance in many areas of physics, underpinning such diverse phenomena as ferromagnetism, superconductivity, superfluidity and the Higgs mechanism. Here we demonstrate nonreciprocity and spontaneous symmetry breaking between counter-propagating light in dielectric microresonators. The symmetry breaking corresponds to a resonance frequency splitting that allows only one of two counter-propagating (but otherwise identical) states of light to circulate in the resonator. Equivalently, this effect can be seen as the collapse of standing waves and transition to travelling waves within the resonator. We present theoretical calculations to show that the symmetry breaking is induced by Kerr-nonlinearity-mediated interaction between the counter-propagating light. Our findings pave the way for a variety of applications including optically controllable circulators and isolators, all-optical switching, nonlinear-enhanced rotation sensing, optical flip-flops for photonic memories as well as exceptionally sensitive power and refractive index sensors

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

Interplay of Polarization and Time-Reversal Symmetry Breaking in Synchronously Pumped Ring Resonators

Optically induced breaking of symmetries plays an important role in nonlinear photonics, with applications ranging from optical switching in integrated photonic circuits to soliton generation in ring lasers. In this work we study for the first time the interplay of two types of spontaneous symmetry breaking that can occur simultaneously in optical ring resonators. Specifically we investigate a ring resonator (e.g. a fiber loop resonator or whispering gallery microresonator) that is synchronously pumped with short pulses of light. In this system we numerically study the interplay and transition between regimes of temporal symmetry breaking (in which pulses in the resonator either run ahead or behind the seed pulses) and polarization symmetry breaking (in which the resonator spontaneously generates elliptically polarized light out of linearly polarized seed pulses). We find ranges of pump parameters for which each symmetry breaking can be independently observed, but also a regime in which a dynamical interplay takes place. Besides the fundamentally interesting physics of the interplay of different types of symmetry breaking, our work contributes to a better understanding of the nonlinear dynamics of optical ring cavities which are of interest for future applications including all-optical logic gates, synchronously pumped optical frequency comb generation, and resonator-based sensor technologies

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

Coherent suppression of backscattering in optical microresonators

As light propagates along a waveguide, a fraction of the field can be reflected by Rayleigh scatterers. In high quality-factor whispering-gallery-mode microresonators, this intrinsic backscattering is primarily caused by either surface or bulk material imperfections. For several types of microresonator-based experiments and applications, minimal backscattering in the cavity is of critical importance, and thus the ability to suppress the backscattering is essential. We demonstrate that introducing an additional scatterer in the near-field of a high-quality-factor microresonator can coherently suppress the amount of backscattering in a microresonator by more than 30 dB. The method relies on controlling the scatterer's position in order for the intrinsic and scatterer-induced backpropagating fields to destructively interfere. This technique is useful in microresonator applications where backscattering is currently limiting the performance of devices, such as ring-laser gyroscopes and dual frequency combs that both suffer from injection locking. Moreover, these findings are of interest for integrated photonic circuits in which backreflections could negatively impact the stability of laser sources or other components

Counterpropagating light in ring resonators : switching fronts, plateaus, and oscillations

We characterize the formation of robust stationary states formed by light plateaus separated by two local switching fronts in only one of two counterpropagating fields in ring resonators with normal dispersion. Such states are due to global cross coupling and allow for frequency combs to switch from one field to the other by simply tuning the input laser frequency. Exact expressions for the distance between fronts and for plateau powers are provided in excellent agreement with simulations. These demonstrate an unusual high degree of control over pulse and plateau duration in one of the fields upon changes of one of the input laser frequencies. We identify a wide parameter region in which light plateaus are self-starting and are the only stable solution. For certain values of the detunings we find multistable states of plateaus with switching fronts, slowly oscillating homogeneous states and nonoscillating homogeneous states of the counterpropagating fields. Robustness and multistability of these unusual single-field front solutions are provided in parameter ranges that are experimentally achievable in a wide variety of ring resonators

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