The aim of the present study was to use gastrointestinal simulation technology and in vitro-in vivo correlation (IVIVC) as tools to investigate a possible extension of biowaiver criteria to BCS class II drugs using carbamazepine (CBZ) as a candidate compound. Gastrointestinal simulation based on the advanced compartmental absorption and transit model implemented in GastroPlus was used. Actual in vitro and in vivo data generated in CBZ bioequivalence studies were used for correlation purposes. The simulated plasma profile, based on the CBZ physicochemical and pharmacokinetic properties, was almost identical with that observed in vivo. Parameter sensitivity analysis (PSA) indicated that the percent of drug absorbed is relatively insensitive to the variation of the input parameters. Additionally, plasma concentration-time profiles were simulated based on dissolution profiles observed under the different experimental conditions. Regardless of the differences observed in vitro, the predicted pharmacokinetic profiles were similar in the extent of drug exposure (AUC) while there were certain differences in parameters defining the drug absorption rate (C(max)t(max)). High level A IVIVC was established for the pooled data set (r = 0.9624), indicating that 1% SLS may be considered as the universal biorelevant dissolution medium for both the IR and CR CBZ tablets. The proposed methodology involving gastrointestinal simulation technology and IVIVC suggests that there is a rationale for considering CBZ biowaiver extension and introduction of the wider dissolution specifications for CBZ immediate release tablets.

We present a systematic study of the crystal-field interactions in the LiRF 4 (R = Gd, Ho, Er, Tm, and Yb) family of rare-earth magnets. Using detailed inelastic neutron scattering measurements, we have been able to quantify the transition energies and wave functions for each system. This allows us to quantitatively describe the high-temperature susceptibility measurements for the series of materials and make predictions based on a mean-field approach for the low-temperature thermal and quantum phase transitions. We show that coupling between crystal field and phonon states leads to line-shape broadening in LiTmF 4 and level splitting in LiYbF 4 . Furthermore, using high-resolution neutron scattering from LiHoF 4 , we find anomalous broadening of crystal-field excitations which we attribute to magnetoelastic coupling.

Electric-field-dependent pulse measurements are reported in the charge-ordered state of α-(BEDT-TTF)2I3. At low electric fields up to about 50 V/cm only negligible deviations from Ohmic behavior can be identified with no threshold field. At larger electric fields and up to about 100 V/cm a reproducible negative differential resistance is observed with a significant change in shape of the measured resistivity in time. These changes critically depend whether constant voltage or constant current is applied to the single crystal. At high enough electric fields the resistance displays a dramatic drop down to metallic values and relaxes subsequently in a single-exponential manner to its low-field steady-state value. We argue that such an electric-field induced negative differential resistance and switching to transient states are fingerprints of cooperative domain-wall dynamics inherent to two-dimensional bond-charge density wave with ferroelectric-like nature.

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We present direct local-probe evidence for strongly hybridized nuclear-electronic spin states of an Ising ferromagnet LiHoF 4 in a transverse magnetic field. The nuclear-electronic states are addressed via a magnetic resonance in the GHz frequency range using coplanar resonators and a vector network analyzer. The magnetic resonance spectrum is successfully traced over the entire field-temperature phase diagram, which is remarkably well reproduced by mean-field calculations. Our method can be directly applied to a broad class of materials containing rare-earth ions for probing the substantially mixed nature of the nuclear and electronic moments. DOI: 10.1103/PhysRevB.94.214433 The compound LiHoF 4 is widely regarded as a prototypical system realizing the transverse-field Ising model [1]. The ground state in zero field is ferromagnetically ordered, while applying a relatively small transverse field induces a zerotemperature quantum phase transition at H c = 4.95 T into a quantum paramagnet [2], as shown in Fig. 1. Meanwhile, the hyperfine coupling strength of a Ho 3+ ion is exceptionally large, with a coupling constant A = 39(1) mK [3,4]. The resulting strong hybridization between the electronic and nuclear magnetic moments [5] leads to two dramatic effects close to the quantum critical point: (i) significant modification of the low-temperature magnetic phase boundary (see Fig. 1) [2]; and (ii) incomplete mode softening of the low-energy electronic excitations at the critical point [6]. Therefore, this system provides a rare opportunity to explore the quantum phase transition of a magnet coupled to a nuclear spin bath [2,[6][7][8].The impact of strong hybridization has also been highlighted for magnetic-ion diluted insulators, such as LiYF 4 :Ho 3+ , using magnetic resonance [9,10]. A similar line of effort has achieved more recently single-molecule magnetic resonance with a rare-earth ion [11]. Furthermore, strong hybridization is of great interest in quantum information science [12][13][14]. As much as these examples focus on the single-ion limit, the other limiting case of many-body systems, such as LiHoF 4 , provides a very different and complementary perspective. While in the long-range-ordered state the hybridization is suppressed, an applied transverse field introduces quantum fluctuations enhancing the hybridization towards H c .However, probing directly the strongly hybridized states in LiHoF 4 using spectroscopic methods, at the lowest-energy scale, has so far been restricted to the thermal paramagnetic phase in the single-ion limit. The involved energy scale is too low to be resolved by neutron scattering [6,7]. Magnetic resonance on 165 Ho nuclei would provide a direct way of probing the hybridized nuclear-electronic states. However, the resonance in the ordered phase is expected around the * ivankowacevic@gmail.com † peter.babkevich@gmail.com ‡ minki.jeong@gmail.com frequency of 4.5 GHz in zero field, which does not fall into the operating frequencies of conventional nuclear magnetic resonance (NM...

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Intrusion Detection Systems (IDSs) automatically analyze event logs and network traffic in order to detect malicious activity and policy violations. Because IDSs have a large number of false positives and false negatives and the technical nature of their alerts requires a lot of manual analysis, the researchers proposed approaches that automate the analysis of alerts to detect large-scale attacks and predict the attacker’s next steps. Unfortunately, many such approaches use unique datasets and success metrics, making comparison difficult. This survey provides an overview of the state of the art in detecting and projecting cyberattack scenarios, with a focus on evaluation and the corresponding metrics. Representative papers are collected while using Google Scholar and Scopus searches. Mutually comparable success metrics are calculated and several comparison tables are provided. Our results show that commonly used metrics are saturated on popular datasets and cannot assess the practical usability of the approaches. In addition, approaches with knowledge bases require constant maintenance, while data mining and ML approaches depend on the quality of available datasets, which, at the time of writing, are not representative enough to provide general knowledge regarding attack scenarios, so more emphasis needs to be placed on researching the behavior of attackers.

We present a systematic study of the phase diagram of LiHo x Y 1−x F 4 (0.25 x 1) Ising ferromagnets obtained from neutron scattering measurements and mean-field calculations. We show that while the thermal phase transition decreases linearly with dilution, as predicted by mean-field theory, the critical transverse field at the quantum critical point is suppressed much faster. This behavior is related to competition between off-diagonal dipolar coupling and quantum fluctuations that are tuned by doping and applied field, respectively. In this paper, we quantify the deviation of the experimental results from mean-field predictions, with the aim that this analysis can be used in future theoretical efforts towards a quantitative description.