Artificial Intelligence-Based Anomaly Detection Technology over Encrypted Traffic: A Systematic Literature Review.

As cyber-attacks increase in unencrypted communication environments such as the traditional Internet, protected communication channels based on cryptographic protocols, such as transport layer security (TLS), have been introduced to the Internet. Accordingly, attackers have been carrying out cyber-attacks by hiding themselves in protected communication channels. However, the nature of channels protected by cryptographic protocols makes it difficult to distinguish between normal and malicious network traffic behaviors. This means that traditional anomaly detection models with features from packets extracted a deep packet inspection (DPI) have been neutralized. Recently, studies on anomaly detection using artificial intelligence (AI) and statistical characteristics of traffic have been proposed as an alternative. In this review, we provide a systematic review for AI-based anomaly detection techniques over encrypted traffic. We set several research questions on the review topic and collected research according to eligibility criteria. Through the screening process and quality assessment, 30 research articles were selected with high suitability to be included in the review from the collected literature. We reviewed the selected research in terms of dataset, feature extraction, feature selection, preprocessing, anomaly detection algorithm, and performance indicators. As a result of the literature review, it was confirmed that various techniques used for AI-based anomaly detection over encrypted traffic were used. Some techniques are similar to those used for AI-based anomaly detection over unencrypted traffic, but some technologies are different from those used for unencrypted traffic.

Effect of the Interaction between Transition Metal Redox Center and Cyanide Ligand on Structural Evolution in Prussian White Cathodes.

Transition metal (TM) based Prussian whites, comprising a cyanide anion ((C≡N)-) and TM cations in an alternative manner, have been widely adopted as cathode materials for rechargeable batteries. Prussian whites are characterized by the TM electronic states that exclusively adopt low spin (LS) toward the C atom and high spin (HS) toward the N atom through the hybridized covalent bonding in the TM─C≡N─TM unit with the average oxidation states of the TM ions being 2+, considerably affecting the phase transition behavior upon the release and storage of carrier ions; however, there have been only a few studies on their associated features. Herein, Prussian whites with different HS TM ions were synthesized via coprecipitation and the phase transition behavior controlled by the π electron interaction between the cyanide anions and TM ions during battery operations was investigated. In situ X-ray characterizations reveal that the combined effect of π backdonation in the LS Fe-C unit and π donation in the HS TM-N unit effectively controls the bond length of the TM─C≡N─TM building unit, thus markedly influencing the lattice volume of a series of Prussian white cathodes during the charge/discharge process. This study presents a comprehensive understanding of the structure-property relationship of the Prussian white cathodes involving π electron interactions during battery operations.

Generating ICS Anomaly Data Reflecting Cyber-Attack Based on Systematic Sampling and Linear Regression.

Cyber threats to industrial control systems (ICSs) have increased as information and communications technology (ICT) has been incorporated. In response to these cyber threats, we are implementing a range of security equipment and specialized training programs. Anomaly data stemming from cyber-attacks are crucial for effectively testing security equipment and conducting cyber training exercises. However, securing anomaly data in an ICS environment requires a lot of effort. For this reason, we propose a method for generating anomaly data that reflects cyber-attack characteristics. This method uses systematic sampling and linear regression models in an ICS environment to generate anomaly data reflecting cyber-attack characteristics based on benign data. The method uses statistical analysis to identify features indicative of cyber-attack characteristics and alters their values from benign data through systematic sampling. The transformed data are then used to train a linear regression model. The linear regression model can predict features because it has learned the linear relationships between data features. This experiment used ICS_PCAPS data generated based on Modbus, frequently used in ICS. In this experiment, more than 50,000 new anomaly data pieces were generated. As a result of using some of the new anomaly data generated as training data for the existing model, no significant performance degradation occurred. Additionally, comparing some of the new anomaly data with the original benign and attack data using kernel density estimation confirmed that the new anomaly data pattern was changing from benign data to attack data. In this way, anomaly data that partially reflect the pattern of the attack data were created. The proposed method generates anomaly data like cyber-attack data quickly and logically, free from the constraints of cost, time, and original cyber-attack data required in existing research.

InZnTiON Channel Layer for Highly Stable Thin-Film Transistors and Light-Emitting Transistors.

In this study, we incorporated TiN as a carrier suppressor into an amorphous InZnO channel to achieve stable channels for thin-film transistors (TFTs) and light-emitting transistors (LETs). The low electronegativity and standard electrode potential of the Ti dopant led to a reduction in the number of oxygen vacancies in the InZnO channel. Moreover, the substitution of nitrogen into the oxygen sites of InZnO effectively decreased the excess electrons. As a result, the cosputtering of the TiN dopant resulted in a decrease in the carrier concentration of the InZnO channel, serving as an effective carrier suppressor. Due to the distinct structures of TiN and InZnO, the TiN-doped InZnO channel exhibited a completely amorphous structure and a featureless surface morphology. The presence of oxygen vacancies in the InZnO channel creates trap states for electrons and holes. Consequently, the TFT with the InZnTiON channel demonstrated an improved subthreshold swing and enhanced stability during the gate bias stress test. Furthermore, the threshold voltage shift (ΔVth) changed from 3.29 to 0.86 V in the positive bias stress test and from -0.92 to -0.09 V in the negative bias stress test. Additionally, we employed an InZnTiON channel in LETs as a substitute for organic semiconductors. The reduction in the number of oxygen vacancies effectively prevented exciton quenching caused by hole traps within the vacancies. Consequently, appropriate TiN doping in the InZnO channel enhanced the intensity of the LET devices.

Maternal Embryonic Leucine Zipper Kinase is Associated with Metastasis in Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) has high relapse and metastasis rates and a high proportion of cancer stem-like cells (CSC), which possess self-renewal and tumor initiation capacity. MELK (maternal embryonic leucine zipper kinase), a protein kinase of the Snf1/AMPK kinase family, is known to promote CSC maintenance and malignant transformation. However, the role of MELK in TNBC metastasis is unknown; we sought to address this in the current study. We found that MELK mRNA levels were higher in TNBC tumors [8.11 (3.79-10.95)] than in HR+HER2- tumors [6.54 (2.90-9.26)]; P < 0.001]. In univariate analysis, patients with breast cancer with high-MELK-expressing tumors had worse overall survival (P < 0.001) and distant metastasis-free survival (P < 0.01) than patients with low-MELK-expressing tumors. In a multicovariate Cox regression model, high MELK expression was associated with shorter overall survival after adjusting for other baseline risk factors. MELK knockdown using siRNA or MELK inhibition using the MELK inhibitor MELK-In-17 significantly reduced invasiveness, reversed epithelial-to-mesenchymal transition, and reduced CSC self-renewal and maintenance in TNBC cells. Nude mice injected with CRISPR MELK-knockout MDA-MB-231 cells exhibited suppression of lung metastasis and improved overall survival compared with mice injected with control cells (P < 0.05). Furthermore, MELK-In-17 suppressed 4T1 tumor growth in syngeneic BALB/c mice (P < 0.001). Our findings indicate that MELK supports metastasis by promoting epithelial-to-mesenchymal transition and the CSC phenotype in TNBC. Significance: These findings indicate that MELK is a driver of aggressiveness and metastasis in TNBC.

Overcoming the imatinib-resistant BCR-ABL mutants with new ureidobenzothiazole chemotypes endowed with potent and broad-spectrum anticancer activity.

The design of kinase inhibitors targeting the oncogenic kinase BCR-ABL constitutes a promising paradigm for treating chronic myeloid leukaemia (CML). Nevertheless, the efficacy of imatinib, the first FDA-approved targeted therapy for CML, is curbed by the emergence of resistance. Herein, we report the identification of the 2-methoxyphenyl ureidobenzothiazole AK-HW-90 (2b) as a potent pan-BCR-ABL inhibitor against imatinib-resistant mutants, particularly T315I. A concise array of six compounds 2a-f was designed based on our previously reported benzothiazole lead AKE-5l to improve its BCR-ABLT315I inhibitory activity. Replacing the 6-oxypicolinamide moiety of AKE-5l with o-methoxyphenyl and changing the propyl spacer with phenyl afforded 2a and AK-HW-90 (2b) with IC50 values of 2.0 and 0.65 nM against BCR-ABLT315I, respectively. AK-HW-90 showed superior anticancer potency to imatinib against multiple cancer cells (NCI), including leukaemia K-562. The obtained outcomes offer AK-HW-90 as a promising candidate for the treatment of CML and other types of cancer.

Structural Evolution of Mg-Doped Single-Crystal LiCoO2 Cathodes: Importance of Morphology and Mg-Doping Sites.

Layered lithium cobalt oxide (LiCoO2, LCO), which serves as a structural motif for the widely adopted layered cathodes in lithium-ion batteries, has a long history, and its unstable phase transition during high-voltage operation (∼4.5 V) remains an intractable problem. Many research strategies, such as surface coating and immobile ion doping, have been proposed to address this issue, but a clear understanding of the effects has not been demonstrated because of various potential parameters (e.g., particle size, shape, and dopant content). Herein, we report a molten salt synthesis method that produces sphere-like single-crystal magnesium (Mg)-doped LCO. In situ X-ray diffraction and X-ray absorption fine structure analyses confirmed that the lattice strain was effectively alleviated by the effects of both the particle shape and Mg doping compared to the plate-like and sphere-like single-crystal LCO samples. Furthermore, the preference for Mg doping in the Co site (3b) rather than in the Li site (3a) in the LCO framework is systematically revealed, and a clear understanding of Mg doping that suppresses the monoclinic phase transition is discussed in detail.

Metal-Coordinated Phthalocyanines as Platform Molecules for Understanding Isolated Metal Sites in the Electrochemical Reduction of CO2.

Single-atom catalysts (SACs) of non-precious transition metals (TMs) often show unique electrochemical performance, including the electrochemical carbon dioxide reduction reaction (CO2RR). However, the inhomogeneity in their structures makes it difficult to directly compare SACs of different TM for their CO2RR activity, selectivity, and reaction mechanisms. In this study, the comparison of isolated TMs (Fe, Co, Ni, Cu, and Zn) is systematically investigated using a series of crystalline molecular catalysts, namely TM-coordinated phthalocyanines (TM-Pcs), to directly compare the intrinsic role of the TMs with identical local coordination environments on the CO2RR performance. The combined experimental measurements, in situ characterization, and density functional theory calculations of TM-Pc catalysts reveal a TM-dependent CO2RR activity and selectivity, with the free energy difference of ΔG(*HOCO) - ΔG(*CO) being identified as a descriptor for predicting the CO2RR performance.

Highly stretchable transparent bar coated Ag NW/PEDOT:PSS hybrid electrode for wearable and stretchable devices.

In this study, we demonstrated poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT:PSS) as a composite with Ag nanowire (Ag NW) to enhance the stretchability of the Ag NW network electrode. The composite Ag NW/PEDOT:PSS hybrid ink (AP ink) was prepared at a ratio of 1 : 10, 1 : 20, and 1 : 30, respectively and bar coated on polyurethane substrate. The different ink ratios were studied and optimized with a sheet resistance of 14.93 Ω sq-1. and a transmittance of 88.6% showing a high performance in mechanical stress tests such as bending, folding, rolling, twisting, and stretching. It also showed a conductive bridge effect where the PEDOT:PSS acted as an anchor or support to Ag NW during mechanical strain and PEDOT:PSS also enhanced the electrical conductivity of the Ag NW. Therefore, to prove the real time performance of the electrode as a wearable device, we fabricated transparent electroluminescence devices and thin film heater devices which are highly flexible and demonstrated excellent performance proving that the AP electrode is more suitable candidate for future wearable transparent devices.

Ancient genomes from the Himalayas illuminate the genetic history of Tibetans and their Tibeto-Burman speaking neighbors.

Present-day Tibetans have adapted both genetically and culturally to the high altitude environment of the Tibetan Plateau, but fundamental questions about their origins remain unanswered. Recent archaeological and genetic research suggests the presence of an early population on the Plateau within the past 40 thousand years, followed by the arrival of subsequent groups within the past 10 thousand years. Here, we obtain new genome-wide data for 33 ancient individuals from high elevation sites on the southern fringe of the Tibetan Plateau in Nepal, who we show are most closely related to present-day Tibetans. They derive most of their ancestry from groups related to Late Neolithic populations at the northeastern edge of the Tibetan Plateau but also harbor a minor genetic component from a distinct and deep Paleolithic Eurasian ancestry. In contrast to their Tibetan neighbors, present-day non-Tibetan Tibeto-Burman speakers living at mid-elevations along the southern and eastern margins of the Plateau form a genetic cline that reflects a distinct genetic history. Finally, a comparison between ancient and present-day highlanders confirms ongoing positive selection of high altitude adaptive alleles.

Hepatitis B virus X protein promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells by regulating SOCS1.

Hepatocellular carcinoma (HCC), a primary type of liver cancer, is one of the leading causes of cancer related deaths worldwide. HCC patients have poor prognosis due to intrahepatic and extrahepatic metastasis. Hepatitis B virus (HBV) infection is one of the major causes of various liver diseases including HCC. Among HBV gene products, HBV X protein (HBx) plays an important role in the development and metastasis of HCC. However, the mechanism of HCC metastasis induced by HBx has not been elucidated yet. In this study, for the first time, we report that HBx interacts with the suppressor of cytokine signaling 1 (SOCS1) which negatively controls NF-κB by degrading p65, a subunit of NF-κB. NF-κB activates the transcription of factors associated with epithelial-mesenchymal transition (EMT), a crucial cellular process associated with invasiveness and migration of cancer cells. Here, we report that HBx physically binds to SOCS1, subsequently prevents the ubiquitination of p65, activates the transcription of EMT transcription factors and enhance cell migration and invasiveness, suggesting a new mechanism of HBV-associated HCC metastasis. [BMB Reports 2022; 55(5): 220-225].

Drug-drug interactions in atrial fibrillation patients receiving direct oral anticoagulants.

Polypharmacy is common in patients with atrial fibrillation (AF), making these patients vulnerable to the occurrence of potential drug-drug interactions (DDIs). We assessed the risk of ischemic stroke and major bleeding in the context of concomitant treatment with potential DDIs in patients with AF prescribed direct oral anticoagulants (DOACs). Using the common data model (CDM) based on an electronic health record (EHR) database, we included new users of DOACs from among patients treated for AF between January 2014 and December 2017 (n = 1938). The median age was 72 years, and 61.8% of the patients were males, with 28.2% of the patients having a CHA2DS2-VASc score in category 0-1, 49.4% in category 2-3, and 22.4% in category ≥ 4. The CHA2DS2-VASc score was significantly associated with ischemic stroke occurrence and hospitalization for major bleeding. Multiple logistic regression analysis showed that increased risk of ischemic stroke and hospitalization for major bleeding was associated with the number of DDIs regardless of comorbidities: ≥ 2 DDIs was associated with ischemic stroke (OR = 18.68; 95% CI, 6.22-55.27, P < 0.001) and hospitalization for major bleeding (OR = 5.01; 95% CI, 1.11-16.62, P < 0.001). DDIs can cause reduced antithrombotic efficacy or increased risk of bleeding in AF patients prescribed DOACs.

Transparent and Flexible SiOC Films on Colorless Polyimide Substrate for Flexible Cover Window.

We fabricated transparent and flexible silicon oxycarbide (SiOC) hard coating (HC) films on a colorless polyimide substrate to use as cover window films for flexible and foldable displays using a reactive roll-to-roll (R2R) sputtering system at room temperature. At a SiOC thickness of 100 nm, the R2R-sputtered SiOC film showed a high optical transmittance of 87.43% at a visible range of 400 to 800 nm. The R2R-sputtered SiOC films also demonstrated outstanding flexibility, which is a key requirement of foldable and flexible displays. There were no cracks or surface defects on the SiOC films, even after bending (static folding), folding (dynamic folding), twisting, and rolling tests. Furthermore, the R2R-sputtered SiOC film showed good scratch resistance in a pencil hardness test (550 g) and steel wool test under a load of 250 g. To test the impact protection ability, we compared the performance of thin-film heaters (TFHs) and oxide-semiconductor-based thin-film transistors (TFTs) with and without SiOC cover films. The similar performance of the TFHs and TFTs with the SiOC cover window films demonstrate that the R2R-sputtered SiOC films offer promising cover window films for the next generation of flexible or foldable displays.

High-resolution UV spectroscopy of 1-indanol.

We report on rotationally resolved laser induced fluorescence (LIF) and vibrationally resolved resonance-enhanced multiphoton ionization (REMPI) spectroscopy of the chiral molecule 1-indanol. Spectra of the S1← S0 electronic transition are recorded in a jet-cooled, pulsed molecular beam. Using two time-delayed pulsed lasers, the lifetimes of the S1 state of the two most stable conformers, referred to as eq1 and ax2, have been determined. The S1← S0 origin bands of these conformers as well as the transition to a vibrationally excited level in the S1 state of eq1 are recorded with full rotational resolution (25 MHz observed linewidth) by measuring the LIF intensity following excitation with a tuneable, narrowband cw laser. On selected rotationally resolved electronic transitions, Lamb-dips are measured to confirm the Lorentzian lifetime-contribution to the observed lineshapes. The rotationally resolved S1← S0 origin band of a neon-complex of eq1 is measured via LIF as well. The fit of the rotationally resolved LIF spectra of the origin bands to those of an asymmetric rotor yields a standard deviation of about 6 MHz. The resulting spectroscopic parameters are tabulated and compared to the outcome of ab initio calculations. For both conformers as well as for the Ne-eq1 complex, the geometric structures in the S0 and S1 states are discussed. For all systems, the transition dipole moment is mainly along the a-axis, the contributions along the b- and c-axes being about one order of magnitude smaller.

Experimental test of Babinet's principle in matter-wave diffraction.

We report on an experimental test of Babinet's principle in quantum reflection of an atom beam from diffraction gratings. The He beam is reflected and diffracted from a square-wave grating at near grazing-incidence conditions. According to Babinet's principle the diffraction peak intensities (except for the specular-reflected beam) are expected to be identical for any pair of gratings of complementary geometry. We observe conditions where Babinet's principle holds and also where it fails. Our data indicate breakdown conditions when either the incident or a diffracted beam propagates close to the grating surface. At these conditions, the incident or the diffracted He beam is strongly affected by the dispersive interaction between the atoms and the grating surface. Babinet's principle is also found to break down, when the complementary grating pair shows a large asymmetry in the strip widths. For very small strip widths, edge diffraction from half planes becomes dominant, whereas for the complementary wide strips the atom-surface interactions leads to a strong reduction of all non-specular diffraction peak intensities.

Structural Basis for Design of New Purine-Based Inhibitors Targeting the Hydrophobic Binding Pocket of Hsp90.

Inhibition of the molecular chaperone heat shock protein 90 (Hsp90) represents a promising approach for cancer treatment. BIIB021 is a highly potent Hsp90 inhibitor with remarkable anticancer activity; however, its clinical application is limited by lack of potency and response. In this study, we aimed to investigate the impact of replacing the hydrophobic moiety of BIIB021, 4-methoxy-3,5-dimethylpyridine, with various five-membered ring structures on the binding to Hsp90. A focused array of N7/N9-substituted purines, featuring aromatic and non-aromatic rings, was designed, considering the size of hydrophobic pocket B in Hsp90 to obtain insights into their binding modes within the ATP binding site of Hsp90 in terms of π-π stacking interactions in pocket B as well as outer α-helix 4 configurations. The target molecules were synthesized and evaluated for their Hsp90α inhibitory activity in cell-free assays. Among the tested compounds, the isoxazole derivatives 6b and 6c, and the sole six-membered derivative 14 showed favorable Hsp90α inhibitory activity, with IC50 values of 1.76 µM, 0.203 µM, and 1.00 µM, respectively. Furthermore, compound 14 elicited promising anticancer activity against MCF-7, SK-BR-3, and HCT116 cell lines. The X-ray structures of compounds 4b, 6b, 6c, 8, and 14 bound to the N-terminal domain of Hsp90 were determined in order to understand the obtained results and to acquire additional structural insights, which might enable further optimization of BIIB021.

Internal dynamics of inorganic and methylmercury in a marine fish: Insights from mercury stable isotopes.

Mercury isotope ratios in fish tissues have been used to infer sources and biogeochemical processes of mercury in aquatic ecosystems. More experimental studies are however needed to understand the internal dynamics of mercury isotopes and to further assess the feasibility of using fish mercury isotope ratios as a monitoring tool. We exposed Olive flounder (Paralichthys olivaceus) to food pellets spiked with varying concentrations (400, 1600 ng/g) of methylmercury (MeHg) and inorganic mercury (IHg) for 10 weeks. Total mercury (THg), MeHg concentrations, and mercury isotope ratios (δ202Hg, Δ199Hg, Δ200Hg) were measured in the muscle, liver, kidney, and intestine of fish. Fish fed mercury unamended food pellets and MeHg amended food pellets showed absence of internal δ202Hg and Δ199Hg fractionation in all tissue type. For fish fed IHg food pellets, the δ202Hg and Δ199Hg values of intestine equilibrated to those of the IHg food pellets. Kidney, muscle, and liver exhibited varying degrees of isotopic mixing toward the IHg food pellets, consistent with the degree of IHg bioaccumulation. Liver showed additional positive δ202Hg shifts (∼0.63‰) from the binary mixing line between the unamended food pellets and IHg food pellets, which we attribute to redistribution or biliary excretion of liver IHg with a lower δ202Hg to other tissues. Significant δ202Hg fractionation in the liver and incomplete isotopic equilibration in the muscle indicate that these tissues may not be suitable for source monitoring at sites heavily polluted by IHg. Instead, fish intestine appears to be a more suitable proxy for identifying IHg sources. The results from our study are essential for determining the appropriate fish tissues for monitoring environmental sources of IHg and MeHg.

The increased risk of bleeding due to drug-drug interactions in patients administered direct oral anticoagulants.

INTRODUCTION: Direct oral anticoagulants (DOACs) have the potential to increase bleeding due to drug-drug interactions (DDIs). In the present study, the risk of bleeding was evaluated when drugs with potential DDIs were simultaneously prescribed with DOACs. MATERIALS AND METHODS: The present study included patients with non-valvular atrial fibrillation (AF) and venous thromboembolism (VTE) who were newly prescribed DOACs between January 2014 and December 2016. RESULTS: The study included 115,362 patients with AF or VTE who were newly administered DOACs (median age, 73 years, range, 19-108 years; males, 53.0%; AF, 81.9%). A total of 7001 any bleeding (6.1%) and 2283 major bleeding (2.0%) events occurred with DOAC prescriptions. Based on multiple logistic regression analysis, the number of DDIs was significantly associated with bleeding events independent of CHA2DS2-VASc score and Charlson Comorbidity Index (CCI). The rates of exposure to DDI drugs associated with any bleeding and major bleeding were 56.7% and 66.1%, respectively. The most common DDI drugs showed similar distributions in any or major bleeding; non-steroidal anti-inflammatory drugs (NSAIDs), antiplatelet agents, diltiazem, and amiodarone were frequently prescribed. CONCLUSIONS: Physicians prescribing DOACs for AF or VTE should be aware of the increasing risk of bleeding associated with drugs having potential DDIs regardless of comorbidities.

Scattering of adiabatically aligned molecules by nonresonant optical standing waves.

We study the effect of rotational state-dependent alignment in the scattering of molecules by optical fields. CS2 molecules in their lowest few rotational states are adiabatically aligned and transversely accelerated by a nonresonant optical standing wave. The width of the measured transverse velocity distribution increases to 160 m/s with the field intensity, while its central peak position moves from 10 to -10 m/s. These changes are well reproduced by numerical simulations based on the rotational state-dependent alignment but cannot be modeled when ignoring these effects. Moreover, the molecular scattering by an off-resonant optical field amounts to manipulating the translational motion of molecules in a rotational state-specific way. Conversely, our results demonstrate that scattering from a nonresonant optical standing wave is a viable method for rotational state selection of nonpolar molecules.