Distribution of Hβ hyperfine couplings in a tyrosyl radical revealed by 263 GHz ENDOR spectroscopy

1H ENDOR spectra of tyrosyl radicals (Y∙) have been the subject of numerous EPR spectroscopic studies due to their importance in biology. Nevertheless, assignment of all internal 1H hyperfine couplings has been challenging because of substantial spectral overlap. Recently, using 263 GHz ENDOR in conjunction with statistical analysis, we could identify the signature of the Hβ2 coupling in the essential Y122 radical of Escherichia coli ribonucleotide reductase, and modeled it with a distribution of radical conformations. Here, we demonstrate that this analysis can be extended to the full-width 1H ENDOR spectra that contain the larger Hβ1 coupling. The Hβ2 and Hβ1 couplings are related to each other through the ring dihedral and report on the amino acid conformation. The 263 GHz ENDOR data, acquired in batches instead of averaging, and data processing by a new “drift model” allow reconstructing the ENDOR spectra with statistically meaningful confidence intervals and separating them from baseline distortions. Spectral simulations using a distribution of ring dihedral angles confirm the presence of a conformational distribution, consistent with the previous analysis of the Hβ2 coupling. The analysis was corroborated by 94 GHz 2H ENDOR of deuterated Y∙122. These studies provide a starting point to investigate low populated states of tyrosyl radicals in greater detail

Distribution of H-beta Hyperfine Couplings in a Tyrosyl Radical Revealed by 263 GHz ENDOR Spectroscopy

1H ENDOR spectra of tyrosyl radicals (Y∙) have been the subject of numerous EPR spectroscopic studies due to their importance in biology. Nevertheless, assignment of all internal 1H hyperfine couplings has been challenging because of substantial spectral overlap. Recently, using 263 GHz ENDOR in conjunction with statistical analysis, we could identify the signature of the Hβ2 coupling in the essential Y122 radical of Escherichia coli ribonucleotide reductase, and modeled it with a distribution of radical conformations. Here, we demonstrate that this analysis can be extended to the full-width 1H ENDOR spectra that contain the larger Hβ1 coupling. The Hβ2 and Hβ1 couplings are related to each other through the ring dihedral and report on the amino acid conformation. The 263 GHz ENDOR data, acquired in batches instead of averaging, and data processing by a new “drift model” allow reconstructing the ENDOR spectra with statistically meaningful confidence intervals and separating them from baseline distortions. Spectral simulations using a distribution of ring dihedral angles confirm the presence of a conformational distribution, consistent with the previous analysis of the Hβ2 coupling. The analysis was corroborated by 94 GHz 2H ENDOR of deuterated Y∙122. These studies provide a starting point to investigate low populated states of tyrosyl radicals in greater detail

Bayesian optimization to estimate hyperfine couplings from 19F ENDOR spectra

ENDOR spectroscopy is a fundamental method to detect nuclear spins in the vicinity of paramagnetic centers and their mutual hyperfine interaction. Recently, site-selective introduction of 19F as nuclear labels has been proposed as a tool for ENDOR-based distance determination in biomolecules, complementing pulsed dipolar spectroscopy in the range of angstrom to nanometer. Nevertheless, one main challenge of ENDOR still consists of its spectral analysis, which is aggravated by a large parameter space and broad resonances from hyperfine interactions. Additionally, at high EPR frequencies and fields (⩾94 GHz/3.4 Tesla), chemical shift anisotropy might contribute to broadening and asymmetry in the spectra. Here, we use two nitroxide-fluorine model systems to examine a statistical approach to finding the best parameter fit to experimental 263 GHz 19F ENDOR spectra. We propose Bayesian optimization for a rapid, global parameter search with little prior knowledge, followed by a refinement by more standard gradient-based fitting procedures. Indeed, the latter suffer from finding local rather than global minima of a suitably defined loss function. Using a new and accelerated simulation procedure, results for the semi-rigid nitroxide-fluorine two and three spin systems lead to physically reasonable solutions, if minima of similar loss can be distinguished by DFT predictions. The approach also delivers the stochastic error of the obtained parameter estimates. Future developments and perspectives are discussed

Quantum Eavesdropping without Interception: An Attack Exploiting the Dead Time of Single Photon Detectors

The security of quantum key distribution (QKD) can easily be obscured if the eavesdropper can utilize technical imperfections of the actual implementation. Here we describe and experimentally demonstrate a very simple but highly effective attack which even does not need to intercept the quantum channel at all. Only by exploiting the dead time effect of single photon detectors the eavesdropper is able to gain (asymptotically) full information about the generated keys without being detected by state-of-the-art QKD protocols. In our experiment, the eavesdropper inferred up to 98.8% of the key correctly, without increasing the bit error rate between Alice and Bob significantly. Yet, we find an evenly simple and effective countermeasure to inhibit this and similar attacks

Hacking commercial quantum cryptography systems by tailored bright illumination

The peculiar properties of quantum mechanics allow two remote parties to communicate a private, secret key, which is protected from eavesdropping by the laws of physics. So-called quantum key distribution (QKD) implementations always rely on detectors to measure the relevant quantum property of single photons. Here we demonstrate experimentally that the detectors in two commercially available QKD systems can be fully remote-controlled using specially tailored bright illumination. This makes it possible to tracelessly acquire the full secret key; we propose an eavesdropping apparatus built of off-the-shelf components. The loophole is likely to be present in most QKD systems using avalanche photodiodes to detect single photons. We believe that our findings are crucial for strengthening the security of practical QKD, by identifying and patching technological deficiencies.Comment: Revised version, rewritten for clarity. 5 pages, 5 figures. To download the Supplementary information (which is in open access), go to the journal web site at http://dx.doi.org/10.1038/nphoton.2010.21

Feasibility of free space quantum key distribution with coherent polarization states

We demonstrate for the first time the feasibility of free space quantum key distribution with continuous variables under real atmospheric conditions. More specifically, we transmit coherent polarization states over a 100m free space channel on the roof of our institute's building. In our scheme, signal and local oscillator are combined in a single spatial mode which auto-compensates atmospheric fluctuations and results in an excellent interference. Furthermore, the local oscillator acts as spatial and spectral filter thus allowing unrestrained daylight operation.Comment: 12 pages, 8 figures, extensions in sections 2, 3.1, 3.2 and 4. This is an author-created, un-copyedited version of an article accepted for publication in New Journal of Physics (Special Issue on Quantum Cryptography: Theory and Practice). IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from i

Razvoj matriksnih sustava za transdermalnu isporuku pentazocina: In vitro/in vivo ispitivanje

The present study aimed to develop hydroxypropyl methylcellulose based transdermal delivery of pentazocine. In formulations containing lower proportions of polymer, the drug released followed the Higuchi kinetics while, with an increase in polymer content, it followed the zero-order release kinetics. Release exponent (n) values imply that the release of pentazocine from matrices was non-Fickian. FT-IR, DSC and XRD studies indicated no interaction between drug and polymer. The in vitro dissolution rate constant, dissolution half-life and pharmacokinetic parameters (Cmax, tmax, AUC(s), t1/2, Kel, and MRT) were evaluated statistically by two-way ANOVA. A significant difference was observed between but not within the tested products. Statistically, a good correlation was found between per cent of drug absorbed from patches vs. Cmax, and AUC(s). A good correlation was also observed when per cent drug released was correlated with the blood drug concentration obtained at the same time point. The results of this study indicate that the polymeric matrix films of pentazocine hold potential for transdermal drug delivery.U radu je opisan razvoj transdermalnih sustava na bazi hidroksipropil metilceluloze za isporuku pentazocina. U pripravcima koji sadrže manje udjele polimera, otpuštanje lijeka slijedilo je Higuchijevu kinetiku. Međutim, ako je udio polimera veći oslobađanje je najbolje odgovaralo kinetici nultog reda. Vrijednost eksponenta n implicira da oslobađanje pentazocina iz matriksa nije po Fickovom zakonu. FT-IR, DSC i X RD studije ukazuju da nema interakcije između ljekovite tvari i polimera. In vitro konstanta oslobađanja, poluvrijeme oslobađanja i farmakokinetički parametri (Cmax, tmax, AUC(s), t1/2, Kel, i MRT) procijenjeni su statistički koristeći ANOVA program. Značajna razlika primijećena je između, ali ne i unutar testiranih pripravaka. Pronađena je dobra korelacija između lijeka apsorbiranog iz flastera i Cmax i AUC(s) te oslobođenog lijeka i koncentracije lijeka u krvi. Rezultati ukazuju da su polimerni matriksni filmovi pentazocina potencijalno dobri sustavi za transdermalnu primjenu lijeka

Controlling a superconducting nanowire single-photon detector using tailored bright illumination

We experimentally demonstrate that a superconducting nanowire single-photon detector is deterministically controllable by bright illumination. We found that bright light can temporarily make a large fraction of the nanowire length normally-conductive, can extend deadtime after a normal photon detection, and can cause a hotspot formation during the deadtime with a highly nonlinear sensitivity. In result, although based on different physics, the superconducting detector turns out to be controllable by virtually the same techniques as avalanche photodiode detectors. As demonstrated earlier, when such detectors are used in a quantum key distribution system, this allows an eavesdropper to launch a detector control attack to capture the full secret key without being revealed by to many errors in the key.Comment: Expanded discussions, updated references. 9 pages, 8 figure

Critical analysis of the Bennett-Riedel attack on secure cryptographic key distributions via the Kirchhoff-law-Johnson-noise scheme

Recently, Bennett and Riedel (BR) (http://arxiv.org/abs/1303.7435v1) argued that thermodynamics is not essential in the Kirchhoff-law–Johnson-noise (KLJN) classical physical cryptographic exchange method in an effort to disprove the security of the KLJN scheme. They attempted to demonstrate this by introducing a dissipation-free deterministic key exchange method with two batteries and two switches. In the present paper, we first show that BR's scheme is unphysical and that some elements of its assumptions violate basic protocols of secure communication. All our analyses are based on a technically unlimited Eve with infinitely accurate and fast measurements limited only by the laws of physics and statistics. For non-ideal situations and at active (invasive) attacks, the uncertainly principle between measurement duration and statistical errors makes it impossible for Eve to extract the key regardless of the accuracy or speed of her measurements. To show that thermodynamics and noise are essential for the security, we crack the BR system with 100% success via passive attacks, in ten different ways, and demonstrate that the same cracking methods do not function for the KLJN scheme that employs Johnson noise to provide security underpinned by the Second Law of Thermodynamics. We also present a critical analysis of some other claims by BR; for example, we prove that their equations for describing zero security do not apply to the KLJN scheme. Finally we give mathematical security proofs for each BR-attack against the KLJN scheme and conclude that the information theoretic (unconditional) security of the KLJN method has not been successfully challenged.Laszlo B. Kish, Derek Abbott, Claes G. Granqvis

Intravitreal bevacizumab (Avastin®) for diabetic retinopathy at 24-months: The 2008 Juan Verdaguer-planas lecture

Diabetic retinopathy (DR) remains the major threat to sight in the working age population. Diabetic macular edema (DME) is a manifestation of DR that produces loss of central vision. Proliferative diabetic retinopathy (PDR) is a major cause of visual loss in diabetic patients. In PDR, the growth of new vessels is thought to occur as a result of vascular endothelial growth factor (VEGF) release into the vitreous cavity as a response to ischemia. Furthermore, VEGF increases vessel permeability leading to deposition of proteins in the interstitium that facilitate the process of angiogenesis and macular edema. This review demonstrates multiple benefits of intravitreal bevacizumab (IVB) on DR including DME and PDR at 24 months of follow up. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse diabetic macular edema. Therefore, in the future this new therapy could replace or complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to pan-retina photocoagulation so that more selective therapy may be applied. In addition, we report a series of patients in which tractional retinal detachment developed or progressed after adjuvant preoperative IVB in severe PDR. © 2010 Bentham Science Publishers Ltd