Due to their short range (2–500 nm), Auger electrons (Auger e-) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Au-ger e-, it remains challenging to maximize the interaction between Auger e- and DNA. To assess the DNA-damaging effect of Auger e- released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [189, 191Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by im-munofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incuba-tion), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by release of Auger e- very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger e-.

The vast rise in the number of Internet-connected devices necessitates a more accessible spectrum. As a result, Cognitive Radio was already proposed as a solution to the problem of restricted spectrum resources by utilizing available spectrum which is assigned to primary users. This method allows the secondary user to utilize the spectrum whenever the primary user is not using it, and it does so without intruding with the primary user. Whenever the secondary user detects the spectrum, it faced some issues, such as complexity in sensing leading to a lack of noise value, and the primary user is hidden to all secondary users. In order to tackle these challenges, an adaptive threshold matched filter detector and a cooperative matched filter detector are utilized in this paper to detect the spectrum. The probability of detection (Pd), probability of miss detection (Pm), and probability of false alarm (Pf) are the metrics used to assess sensing accuracy. To simulate suggested detectors, the MATLAB R2020a software was utilized. In comparison to earlier studies, the simulation conclusions reveal that the detection process starts with lower SNR values.

For a positive integer k, a radio k-coloring of a simple connected graph G = (V (G), E(G)) is a mapping | f(u) - f(v)| ≥ k +1-d (u , v ) such that f :V (G)→{0,1, 2,...} for each pair of distinct vertices u and v of G, where d(u, v) is the distance between u and v in G. The span of a radio k-coloring f, rck(f), is the maximum integer it assigns to some vertex of G. The radio k-chromatic number, rck(G) of G is min{rck(f)}, where the minimum is taken over all radio k-colorings f of G. If k is the diameter of G, then rck(G) is known as the radio number of G. In this work, we propose four algorithms (two serial algorithms and their parallel versions) which related to the radio k-coloring problem. One of them is an approximate algorithm that determines an upper bound of the radio number of a given graph. The other is an exact algorithm which finds the radio number of a graph G. The approximate algorithm is a polynomial time algorithm while the exact algorithm is an exponential time algorithm. The parallel algorithms are parallelized using the Message Passing Interface (MPI) standard. The experimental results prove the ability of the proposed algorithms to achieve a speedup 7 for 8 processors.

An updated, binary-coded message has been developed for transmission to extraterrestrial intelligences in the Milky Way galaxy. The proposed message includes basic mathematical and physical concepts to establish a universal means of communication followed by information on the biochemical composition of life on Earth, the Solar System’s time-stamped position in the Milky Way relative to known globular clusters, as well as digitized depictions of the Solar System, and Earth’s surface. The message concludes with digitized images of the human form, along with an invitation for any receiving intelligences to respond. Calculation of the optimal timing during a given calendar year is specified for potential future transmission from both the Five-hundred-meter Aperture Spherical radio Telescope in China and the SETI Institute’s Allen Telescope Array in northern California to a selected region of the Milky Way which has been proposed as the most likely for life to have developed. These powerful new beacons, the successors to the Arecibo radio telescope which transmitted the 1974 message upon which this expanded communication is in part based, can carry forward Arecibo’s legacy into the 21st century with this equally well-constructed communication from Earth’s technological civilization.

Radio astronomical observations at millimeter and submillimeter wavelengths are a very important tool of astrophysical research. However, there is a huge area in the northern Eurasia, including the whole Russian territory, which lacks sufficiently large radio telescopes effectively operating at these wavelengths. In this review we describe our long-term efforts to find suitable sites for such radio telescopes in this area, that is, sites with good atmospheric transparency at millimeter and submillimeter waves. We describe methods and instruments used for measurements and evaluations of the atmospheric opacity. They include special radiometric systems, which are used for estimations of the atmospheric opacity from the sky brightness measurements. Evaluation of the precipitable water vapor from such measurements by the artificial neural network is discussed. Alternative approaches use global atmospheric models and signals of the Global Navigation Satellite Systems. To date, a long-term radiometric monitoring has been performed at several candidate sites and atmospheric conditions for many sites have been evaluated using global atmospheric models. Several sites with the best atmospheric transparency at millimeter and submillimeter wavelengths have been selected. They can be effectively used for astronomical observations at least in the major atmospheric transparency windows at 1.3 mm and 0.85 mm. These results can be also used for space communications and radar systems.

Community radios play a paramount role in the development of the community. Community radio stations have been highly engaged in addressing social, economic, cultural, educational, health, environmental, sanitation, and disaster issues effectively and strategically using local languages in context. Community radios are also used to express, and share indigenous views, thoughts, ideas, problems, and perspectives of local people. The purpose of this analysis is to explore the role of community radio for integrated and sustainable development in Ethiopia. It used a systematic narrative review. Nine research works and five assessments report were selected purposively and analyzed in a quantitative approach. Currently, in Ethiopia, there are 50 community radio stations that received broadcast licenses from Ethiopian Broadcast Authority with four types of licensing and broadcasting in 29 local languages. Community radio helps the community to identify their common goals, create holistic plans, monitor the progress of their developmental activities, and guide on sustainable development. It contributes to integrated and sustainable development in a collaborative and creative process that cultivates the social, economic, and political conditions needed for the community to succeed which aimed to improve and sustain the livelihoods of the community. However, the media can’t achieve its target goal to support the development activities and bring holistic development of the community. As a result; this review paper focuses on reviewing how Ethiopians use community radios for holistic development. And it suggested the way how we can use community radios for the prospective holistic development in Ethiopia.

Supernova remnants (SNRs) are an integral part in studying the properties of the Galaxy and its interstellar medium. For the current work, we explore the relation between the observed radio luminosities of SNRs and the physical properties of those SNRs. The physical properties of 54 SNRs are derived from their observed X-ray spectra. Then the observed radio emission is compared to predicted radio emission using the analytic model of . We find the model can be improved significantly by including an interstellar medium density dependence in the efficiency of particle acceleration and magnetic field amplification.

According to the cognitive radio (CR) paradigm, the efficient use of the radio spectrum is achieved by performing four main functions: spectral perception, spectral mobility, decision-making, and cooperation. In this work, a multivariable algorithm that considers geographic mobility (GM) is presented. The decision-making process includes a feedback mechanism for the dynamic selection of reservation channels in a wireless network with cognitive capabilities. Geographic mobility plays a crucial role in how radio takes advantage of its environment; however, it has been scarcely explored in the literature. In the present work, geographic mobility tests were carried out involving the interaction of CR and primary users (PU), where a measurement of the latency time of the proposed algorithm called: Algorithm for Decision-Making with Geographic Mobility (ATDeMoGeo) was evaluated and compared with other algorithms such as: Dijkstra's Algorithm, Analytic Hierarchical Process (AHP), Fuzzy Analytic Hierarchical Process (FAHP) and Decision-Making Algorithm with Modified Dijkstra (ATDDiM). It was found that the proposed algorithm is robust and that it considerably reduces the latency time to accurately determine the best communication channels, thanks to the decision-making function implemented to establish which channels the CRs can occupy. For the selection of the best reserve channels, a series of criteria were considered, such as: signal-to-interference plus noise ratio (SINR), bandwidth (BW), probability of channel availability (AP), estimated channel time of availability (ETA) using the random waypoint mobility model (RWPM). These criteria are evaluated for two types of service, i.e., real time (RT) and best effort (BE). For the evaluation and validation of the ATDeMoGeo algorithm, a network with cognitive characteristics in NS-3 was simulated. The simulation scenarios consisted of a base station (BS) with mobile CRs and PUs. Based on the previous criteria, i.e., BW, SINR, AP and ETA, the BS assesses the spectrum occupancy information obtained by the CRs. The results show that the proposed algorithm can be used without problem for the proposed scenarios with higher speed and accuracy for the selection of better communication channels.

A software defined radio (SDR) is a communication system that makes use of components that can be configured through software, in contrast to traditional systems where these components are variable through hardware, these radio devices are much more versatile, this article describes the factors that must be considered when implementing a communication system based on Software Defined Radios (SDR), in order to reduce the attenuation factors and thus obtain the maximum distance for a transmission of data effectively in the UHF band. The calculations made for the first Fresnel zone and for the design of the Ground Plane type antennas used in the transmission/reception stages of the x40 bladeRF platforms are also presented. The tests were carried out at the facilities of the Huarangal Nuclear Center of the Peruvian Institute of Nuclear Energy, obtaining favorable results that allow ratifying the versatility and performance of the SDRs.

The next generation of wireless and mobile networks will have to handle a significant increase in traffic load compared to the actual one. This situation calls for novel ways to increase spectral efficiency. Therefore in this paper, we propose a wireless spectrum hypervisor architecture that abstracts a radio frequency (RF) front-end into a configurable number of virtual RF front-ends. The proposed architecture has the ability to enable flexible spectrum access in existing wireless and mobile networks, which is a challenging task due to the limited spectrum programmability, $i.e.$, the capability a system has to change the spectral properties of a given signal to fit an arbitrary frequency allocation. The main goal of the proposed approach is to improve spectral efficiency by efficiently using vacant gaps in congested spectrum-bandwidths or adopting network densification through infrastructure sharing. We demonstrate mathematically how our proposed approach works and present several simulation results proving its functionality and efficiency. Additionally, we designed and implemented an open-source and free proof of concept prototype of the proposed architecture, which can be used by researchers and developers to run experiments or extend the concept to other applications. We present several experimental results used to validate the proposed prototype. We demonstrate that the prototype can easily handle up to 12 concurrent physical layers.

: The article presents a brief review of cooling systems of various temperature levels (from 0.1 K to 230 K) for radio astronomical receivers of photonics and electronics. The features of various levels of cooling and the requirements for the design of the cooling system are considered in detail, as well as approaches to designing interfaces for cooled receivers: vacuum, cryogenic, electrical, mechanical, optical, and others required for the effective operation of the receiver,. The presented approaches to design are illustrated by a series of joint developments of the authors carried out over the past 45 years, including those produced last year.

In this paper, we propose, implement, and test two novel downlink LTE scheduling algorithms. The implementation and testing of these algorithms were in Matlab, and they are based on the use of Reinforcement Learning, more specifically, the Qlearning technique for scheduling two types of users. The first algorithm is called a Collaborative scheduling algorithm, and the second algorithm is called a Competitive scheduling algorithm. The first type of the scheduled users is the Primary Users, and they are the licensed subscribers that pay for their service. The second type of the scheduled users is the Secondary Users, and they could be unlicensed subscribers that dont pay for their service, device to device communications, or sensors. Each user whether it is a primary or secondary is considered as an agent. In the Collaborative scheduling algorithm, the primary user agents will collaborate in order to make a joint scheduling decision about allocating the resource blocks to each one of them, then the secondary user agents will compete among themselves to use the remaining resource blocks. In the Competitive scheduling algorithm, the primary user agents will compete among themselves over the available resources, then the secondary user agents will compete among themselves over the remaining resources. Experimental results show that both scheduling algorithms converged to almost ninety percent utilization of the spectrum, and provided fair shares of the spectrum among users.

The article analyzes existing materials and structures with quadratic-nonlinear optical properties that can be used to generate a difference frequency in the terahertz and sub-terahertz frequency ranges. The principle of constructing a nonlinear optical-radio converter, based on an optical focon (a focusing cone), is proposed. Based on the assumption that this focon can be implemented from the metal-organic framework (MOF), we propose a technique for modeling its parameters. The mathematical model of the process of propagation and nonlinear interaction of waves inside the focon is based on a simplification of the nonlinear wave equation. Within the framework of the developed model, the following parameters are approximately determined: the 3D gradient of the linear refractive index and the function determining the geometric profile of the focon, which provide a few-mode-based generation of the difference frequency.

A non-negligible fraction of quasars are red at optical wavelengths, indicating (in the vast majority of cases) that the accretion disc is obscured by a column of dust which extinguishes the shorter-wavelength blue emission. In this paper we summarise recent work by our group, where we find fundamental differences in the radio properties of SDSS optically selected red quasars. We also present new analyses, using a consistent colour-selected quasar parent sample matched to four radio surveys (FIRST, VLA Stripe 82, VLA COSMOS 3 GHz and LoTSS DR1) across a frequency range 150 MHz-3 GHz and four orders of magnitude in radio flux. We show this enhancement is driven by systems with small-scale radio emission (∼kpc) and peaks around the radio-quiet threshold (defined as the ratio of 1.4 GHz luminosity to 6μm luminosity) across the four radio samples. Exploring the potential mechanisms behind this enhancement, we rule out star-formation and propose either small-scale jets or dusty winds interacting with the interstellar medium; this will be tested in detail using new multi-band uGMRT data. Overall our results cannot be explained with a simple viewing angle hypothesis, and so may point towards red quasars representing a key phase in the evolution of galaxies.

The CoDRIVE solution builds on R&D in the development of connected and autonomous vehicles (CAVs). The mainstay of the system is a low-cost GNSS receiver integrated with a MEMS grade IMU powered with CoDRIVE algorithms and high precision data processing software. The solution integrates RFID (radio-frequency identification) localisation information derived from tags installed in the roads around the University of Nottingham. This aids the positioning solution by correcting the long-term drift of inertial navigation technology in the absence of GNSS. The solution is informed of obscuration of GNSS through city models of skyview and elevation masks derived from 360-degree photography. The results show that predictive intelligence of the denial of GNSS and RFID aiding realises significant benefits compared to the inertial only solution. According to the validation, inertial only solutions drift over time, with an overall RMS accuracy over a 300 metres section of GNSS outage of 10 to 20 metres. After deploying the RFID tags on the road, experiments show that the RFID aided algorithm is able to constrain the maximum error to within 3.76 metres, and with 93.9% of points constrained to 2 metres accuracy overall.

An antenna sensor is proposed to execute dual functions of antenna and sensor in the wireless sensor system, in order to reduce data loss and to increase transmission rate by omitting a certain interface. The as-made sensor was test at a center frequency of 46 MHz for measuring human finger postures using principle of dipole antenna. The antenna sensor was attached on a wearable glove. The results showed that the motion sensor can accurately identify finger angles at 0°, 20°, 40°, 60° and 80°.

With the constant growth of Software Defined Radio (SDR) technologies in wireless communications related fields the need for efficient ways to test and evaluate the Physical Layer (PHY) protocols developed for these technologies in real life traffic scenarios become more critical. This paper proposes a software testbed that enhances the creation of network environments that allow feeding GNU Radio applications with test traffic in a simple way and through an interoperable interface. This makes possible the use of any traffic generator, existent one or custom built to evaluate the GNU Radio application. In addition, the paper proposes an efficient way to collect PHY layer specific monitoring data that improves the performance of the critical components of the message delivery path by employing the Protocol Buffers library. The paper considers the entire testing and evaluation ecosystem and demonstrates how PHY layer specific monitoring information is collected, handled, stored, and processed as time series allowing complex visualization and real time monitoring.

In 2011, by 1.3 mm wavelength VLBI radio wave observations of the SgrA*, Fish, V. L. et al showed that the emissions tightly related to the formation of a black hole shadow have a remarkably large time-varying feature within a region of less than 50 μas. The present paper suggests that the origin of the time variation in the observed emission is due to effects of the orbital motion of the existing super-massive black hole binary orbiting at SgrA* with a period of 2150±2.5 s. This suggestion is based on observations of decameter radio wave pulses from SgrA*. We show a good correlation between the time variation in the coherent flux density of the VLBI results and the time variation model of estimated emission intensities based on the periodic motion of the super-massive black hole binary by applying parameters deduced from the decameter radio wave pulse observation model (DRWP-Model). With further confirmation by Fourier analyses of the potential periodicity of the VLBI data that show the same periods of DRWP Model, we conclude that the time variation detected by the 1.3 mm wavelength radio wave VLBI is evidence of an existing super-massive black hole at Sgr A*.

This paper proposes a cognitive radio engine platform for making exploitation of available frequency channels usable for a tactical wireless sensor network in presence of incumbent communication devices known as the primary user (PU) required to be protected from undesired harmful interference. In the field of tactical communication networks, it is desperate to find available frequencies for opportunistic and dynamic access to channels in which PU is in active. This paper introduces a cognitive engine plaform for determining available channels on the basis of case-based reasoning technique deployable as core functionality on cognitive radio engine to enable dynamic spectrum access (DSA) with high fidelity. Towards this, this paper introduces a plausible learning engine to characterize channel usage pattern to extract best channel candiates for the tactical cognitive radio node (TCRN). Performance of the proposed cognitive engine is verified by conducting simulation tests which confirm the reliability in functional aspect of the proposed cognitive engine covering the learning engine as well as the case-based reasoning engine with showing how well TCRN can avoid the collision against the PU operation considered as the etiquette secondary user (SU) should have.

Radio Occultation (RO) is pivotal for profiling the neutral and ionized atmosphere, with the PlanetiQ mission, via its GNOMES satellites, striving to establish an advanced atmospheric observing system. However, an assessment of the spatiotemporal distributions of PlanetiQ observations and comparisons with reliable datasets are lacking. This study addresses this gap by examining the temporal and spatial distribution of RO observations from PlanetiQ during its initial 198 operational days in 2023, alongside comparisons with COSMIC and Numerical Weather Prediction (NWP) models. Data from GN02, GN03, and GN04 satellites, yielding 1099, 1313, and 1843 RO events per day respectively, were analyzed. The satellite constellation's observations demonstrate a generally well-distributed pattern, albeit minor deficiencies in equatorial and polar regions. Single-profile comparisons with COSMIC data reveal strong correlations for pressure, temperature, Water Vapor Pressure (WVP), and refractivity profiles, with temperature exhibiting larger variations (RMSE = 1.24°C). Statistical analyses confirm statistically insignificant differences between PlanetiQ and COSMIC profiles at the same spatio-temporal coordinates. Comparisons with NWP models show slight differences with GFS, with overall RMSE values of 0.23 mb (WVP), 0.6 mb (pressure), 1.3 (refractivity), and 1.5°C (temperature). However, assessments against GFS/ECMWF models indicate overall compatibility, with insignificant differences between PlanetiQ profiles and models observations.

Radio communication system in an underground mine is one of the very essential systems for the underground mine. It is required that the radio communication system must be reliable from the starting to construct the underground mine to the closure of the mine. However, underground mine radio communication systems reliability is required to be tested on an active radio communication system in a real environment. In the study was suggested a new research methodology that is studied reliability using dynamic system modeling on Vensim software instead of traditional method to study the reliability of radio communication systems calculating large-scale differential equations. In other words, we suggest a new research methodology. The Motorola Dimetra (TETRA) radio communication system's availability readiness information was used to simulate the reliability of the underground mine radio communication system probability of reliability using Vensim software for system dynamic modeling.Also, the factors that affect the reliability of underground mining radio communication systems was studied. The study was determined factors that affect the underground mine radio communication system from the following risks. The study was in the examples of the Oyu Tolgoi underground mine. The factors that affect the reliable operation of the underground mine radio communication system were determined using the failure statistics of TETRA radio communication system in the Oyu Tolgoi mine in 2015-2018.

We report an all-optical radio-frequency (RF) spectrum analyzer with a bandwidth greater than 5 terahertz (THz), based on a 50-cm long spiral waveguide in a CMOS-compatible high-index doped silica platform. By carefully mapping out the dispersion profile of the waveguides for different thicknesses, we identify the optimal design to achieve near zero dispersion in the C-band. To demonstrate the capability of the RF spectrum analyzer, we measure the optical output of a femtosecond fiber laser with an ultrafast optical RF spectrum in the terahertz regime.

The launch of the RadioAstron space radio telescope provides a unique opportunity to study the extreme high brightness temperature of Active Galactic Nuclei (AGNs) with unprecedented long baselines of up to 28 Earth diameters. A coordinated ground-based flux density monitoring of RadioAstron targets is essential to determine the effect of interstellar scintillation (ISS) on the Space Very Long Baseline Interferometry (SVLBI) visibilities. Moreover, a combination/comparison of scintillation with SVLBI observations is expected to reveal the relative influence of source brightness temperature, compactness, and properties of the interstellar medium on the observed variability at centimeter wavelengths. In 2014 we started a RadioAstron target triggered flux monitoring with the Effelsberg 100-m radio telescope in support of this SVLBI mission. A total of 112 targets were observed during the five-session monitoring performed so far. In this paper we present a statistical study on the short-term flux density variability of the sample, which is focused on the variability characteristics and derived physical properties of the observed sources.

The pointing accuracy of large radio telescopes is affected by antenna structure errors, installation errors, servo errors, gravity, and varying environmental factors. It is hard to estimate the pointing error of radio telescopes under solar radiation via the traditional multi-parameter static pointing models, due to the time-varying characteristics of the dynamic pointing error. There is still no effective way to estimate the dynamic pointing error of large radio telescopes under solar radiation up to now. To estimate the dynamic pointing error of large radio telescopes under solar radiation, a new way based on digital twin(DT) is tried in this paper. The operational framework of the DT system of large radio telescopes is introduced first. Then, the Wuqing 70-m radio telescope(WRT70) is taken as the research object, the digital models of which are created. Finally, the reliability of the WRT70's DT system is verified and the dynamic pointing error of WRT70(staying at the position of the elevation angle of 90° and the azimuth angle of 180°) on two sunny days in different seasons is estimated by the created DT system. The research results show that the pointing error of large radio telescopes under solar radiation fluctuates greatly and the seasonal differences are very striking. The maximum elevation pointing error of WRT70 under solar radiation around the winter solstice is over 40 arcsec, which should never be ignored. The way is feasible to estimate the dynamic pointing error of large radio telescopes staying at a specific position under solar radiation via constructing a DT system in this paper, but it is not yet able to estimate effectively the dynamic pointing error of large radio telescopes being in action. It is expected to establish a dynamic pointing error model and calibrate the dynamic pointing errors of large radio telescopes being in action by DT technology in the future.

The transition region is a very thin but most peculiar layer in the solar atmosphere, located between the solar chromosphere and the corona. It is a key region for understanding the coronal heating, the solar eruptions triggering, and the origin of solar winds. Here, the gradients of all physical parameters are very high, including plasma density, ionization degree, temperature, and magnetic fields, etc. Therefore, the transition region should be highly dynamic, such as fast energy releasing and transporting, plasma heating, and even particle accelerating. They include two physical aspects: thermal and non-thermal processes. The thermal processes can be observed from the ultraviolet (UV) and extreme ultraviolet (EUV) emission by multi-wavelength images. The non-thermal processes, however, should be related to radio emissions especially at millimeter wavelengths, and the frequency range should span from several GHz to beyond 300 GHz, and the emission mechanism should be highly related to the magnetic fields and variations. The ultra-wide broadband spectral observations at millimeter wavelengths with high spectral resolutions may provide rich dynamic information about the transition region, such as non-thermal energy release and transmission, the flows of plasma and energetic particles, the magnetic fields and their variations, the generation and transportation of various waves, and the formation and evolution of the source regions of solar eruptions. Here, we discussed the spectral characteristics of millimeter-wave emission from the transition region and proposed a new conception of ultra-wide broadband millimeter-wave spectrometers to observe them.

For the elimination of radio-frequency interference (RFI) in a passive microwave radiometer, the threshold level is generally calculated from the mean value and standard deviation. However, a serious problem that can arise is an error in the retrieved brightness temperature from a higher threshold level owing to the presence of RFI. In this paper, we propose a method to detect and mitigate RFI contamination using the threshold level from statistical criteria based on a spectrogram technique. Mean and skewness spectrograms are created from a brightness temperature spectrogram by shifting the 2-D window to discriminate the form of the symmetric distribution as a natural thermal emission signal. From the remaining bins of the mean spectrogram eliminated by RFI-flagged bins in the skewness spectrogram for data captured at 0.1-s intervals, two distribution sides are identically created from the left side of the distribution by changing the standard position of the distribution. Simultaneously, kurtosis calculations from these bins for each symmetric distribution are repeatedly performed to determine the retrieved brightness temperature corresponding to the closest kurtosis value of three. The performance is evaluated using experimental data, and the error in the retrieved brightness temperature is observed to be less than approximately 3 K from a window with a size of 100 × 100 time-frequency bins according to the RFI levels and cases.

Over the past decade, our knowledge of the $\gamma$-ray sky has been revolutionized by ground- and space-based observatories by detecting photons up to several hundreds of tera-electron volt (TeV) energies. A major population of the $\gamma$-ray bright objects are active galactic nuclei (AGN) with their relativistic jets pointed along our line-of-sight. Gamma-ray emission is also detected from nearby mis-aligned AGN such as radio galaxies. While the TeV-detected radio galaxies ($TeVRad$) only form a small fraction of the $\gamma$-ray detected AGN, their multi-wavelength study offers a unique opportunity to probe and pinpoint the high-energy emission processes and sites. Even in the absence of substantial Doppler beaming $TeVRad$ are extremely bright objects in the TeV sky (luminosities detected up to $10^{45}~erg~s^{-1}$), and exhibit flux variations on timescales shorter than the event-horizon scales (flux doubling timescale less than 5 minutes). Thanks to the recent advancement in the imaging capabilities of high-resolution radio interferometry (millimeter very long baseline interferometry, mm-VLBI), one can probe the scales down to less than 10 gravitational radii in $TeVRad$, making it possible not only to test jet launching models but also to pinpoint the high-energy emission sites and to unravel the emission mechanisms. This review provides an overview of the high-energy observations of $TeVRad$ with a focus on the emitting sites and radiation processes. Some recent approaches in simulations are also sketched. Observations by the near-future facilities like Cherenkov Telescope Array, short millimeter-VLBI, and high-energy polarimetry instruments will be crucial for discriminating the competing high-energy emission models.

Modern radio spectrometers make measurement of polarized intensity as a function of Faraday depth possible. I investigate the effect of depolarization along a model line of sight. I model sightlines with two components informed by observations: a diffuse interstellar medium with a lognormal electron density distribution and a narrow, denser component simulating a spiral arm or H~{\sc ii} region, all with synchrotron-emitting gas mixed in. I then calculate the polarized intensity from 300-1800 MHz and calculate the resulting Faraday depth spectrum. The idealized synthetic observations show far more Faraday complexity than is observed in Global Magneto-Ionic Medium Survey observations. In a model with a very nearby H~{\sc ii} region observed at low frequencies, most of the effects of a ``depolarization wall'' are evident: the H~{\sc ii} region depolarizes background emission and less (but not zero) information from beyond the H~{\sc ii} region reaches the observer. In other cases, the effects are not so clear, as significant amounts of information reach the observer even through significant depolarization, and it is not clear that low-frequency observations sample largely different volumes of the interstellar medium than high-frequency observations. The observed Faraday depth can be randomized such that it does not always have any correlation with the true Faraday depth.

The explosive emergence of wireless technologies and standards, covering licensed and unlicensed spectrum bands has triggered the appearance of a huge amount of wireless technologies, with many of them coexisting in the same band. Unfortunately, the wireless spectrum is a scarce resource, and the available frequency bands will not scale with the foreseen demand for new capacity. Certain parts of the spectrum, in particular the license-free ISM bands, are overcrowded, while other parts, mostly licensed bands, may be significantly underutilized. As such, there is a need to introduce more advanced techniques to access and share the wireless medium, either to improve the coordination within a given band, or to explore the possibilities of intelligently using unused spectrum in underutilized (licensed) bands. Therefore, in this paper, we present a SDR based framework that can be employed to devise disruptive techniques to optimize the sub-optimal use of radio spectrum that exists today. Additionally, we describe two use cases for the proposed framework.

Abstract: We review the development and application of an organic polymer-gel capable of producing fixed, three-dimensional fluorescent images of complex radiation fields. The gel consists for more than 99% of γ-ray-polymerized (~15% conversion) tertiary-butyl acrylate (TBA) containing ~100 ppm of a fluorogenic compound, e.g. maleimido-pyrene (MPy). The radio-fluorogenic effect depends on copolymerization of the MPy into growing chains of TBA on radiation-induced polymerization. This converts the maleimido residue, which quenches the pyrene fluorescence, into a succinimido moeity (SPy), which doesn't. The intensity of the fluorescence is proportional to the yield of free-radicals formed and hence to the local dose deposited. Because the SPy moieties are built into the cross-linked polymer matrix the image is fixed. The method of preparing the gel and imaging the radiation-induced fluorescence are presented and discussed. The effect is illustrated with fluorescent images of the energy deposited in the gel by beams of X-rays, electrons and protons as well as a radioactive isotope.

Neonatal drug information (DI) is essential for safe and effective pharmacotherapy in (pre)term neonates. Such information is usually absent from drug labels, making formularies a crucial part of the neonatal clinician’s toolbox. Several formularies exist worldwide, but they have never been fully mapped nor compared for content, structure and workflow. The objective of this review was to identify neonatal formularies, explore (dis)similarities, and raise awareness of their existence.Neonatal formularies were identified through self-acquaintance, experts and structured search. A questionnaire was sent to all identified formularies to provide details on formulary function. An original extraction tool was employed to collect DI from the formularies on the 10 most commonly used drugs in pre(term) neonates.Eight different neonatal formularies were identified worldwide (Europe, USA, Australia-New Zealand, Middle East). Six responded to the questionnaire and were compared for structure and content. Each formulary has its own workflow, monograph template and style, and update routine. Focus on certain aspects of DI also varies, as well as the type of initiative and funding.Clinicians should be aware of the various formularies available and their differences in characteristics and content to use them properly for the benefit of their patients.

Recombinant α1-microglobulin (A1M) is proposed as protector during 177Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of 177Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but, the radioprotecting action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after 177Lu-octreotate and/or A1M administration. Mice were injected with 177Lu-octreotate and/or A1M, while control mice received saline or A1M vehicle solution. Bone marrow, kidney medulla, and kidney cortex were sampled after 24 hours or 7 days. Differential protein expression was analyzed with tandem mass spectrometry. Dosimetric estimation was based on 177Lu activity in kidney. PHLDA3 was the most prominent radiation responsive protein in kidney tissue. In general, no statistically significant difference in expression of radiation-related proteins was observed between the irradiated groups. Most canonical pathways were identified in bone marrow from the 177Lu-octreotate+A1M group. Altogether, tissue-dependent proteomic response followed exposure to 177Lu-octreotate alone or together with A1M. Combining 177Lu-octreotate with A1M did not inhibit the radiation induced protein expression early after exposure, and late effects should be further studied.

The article proposes to use a radio holography for the detection and identification of unmanned aerial vehicles (UAVs).

This paper presents several novel designs of underwater portable radio antennas operating in the 2 MHz, 50 MHz and 2.4 GHz bands and efficient for launching surface electromagnetic waves at the seawater/air interface. The antenna operation is enabled by an impedance matching antenna enclosure, which is filled with de-ionized water. Enhanced coupling to surface electromagnetic waves is based on the field enhancement at the antenna tip. These design features allow us to reduce antenna dimensions and improve the coupling of electromagnetic energy to the surrounding saltwater medium. Since surface wave propagation length far exceeds the skin depth of conventional radio waves at the same frequency, this technique is useful for broadband underwater wireless communication over distances, which far exceed the skin depth in seawater. We conclude that the developed broadband underwater radio communication technique will be useful in networking of unmanned underwater vehicles.

We propose a 10-Gb/s 64-quadrature amplitude modulation (QAM) signal-based Radio over Fiber (RoF) system for 50 km of standard single mode fiber length which utilizes Reinforcement Learning (RL) SARSA based decision method to indicate an effective decision which mitigates nonlinearity. By utilizing RL-SARSA algorithm, the results demonstrate that significant reduction can be obtained in terms of bit error rate.

Machine learning (ML) methodologies have been looked upon recently as a potential candidate for mitigating nonlinearity issues in optical communications. In this paper, we experimentally demonstrate a 40-Gb/s 256-quadrature amplitude modulation (QAM) signal-based Radio over Fiber (RoF) system for 50 km of standard single mode fiber length which utilizes support vector machine (SVM) decision method to indicate an effective nonlinearity mitigation. The influence of different impairments in the system is evaluated that includes the influences of Mach-Zehnder Modulator nonlinearities, in-phase and quadrature phase skew of the modulator. By utilizing SVM, the results demonstrated in terms of bit error rate and eye linearity suggest that impairments are significantly reduced and licit input signal power span of 5dBs is enlarged to 15 dBs.

In radiotherapy, accurate deposition of energy to the targeted volume is vital to ensure effective treatment. Gel dosimeters are attractive detection systems, as tissue substitutes with potential to yield three-dimensional dose distributions. Radio-fluorogenesis is creation fluorescent chemical products in response to energy deposition from high-energy radiation. This report shares studies of a radio-fluorogenic gel dosimetry system, gelatin with coumarin-3-carboxlyic acid (C3CA), for the quantification of imparted energy. Aqueous solutions exposed to ionizing radiation result in the production of hydroxyl free radicals through water radiolysis. Interactions between hydroxyl free radicals and coumarin-3-carboxylic acid produce a fluorescent product. 7-hydroxy-coumarin-3-carboxylic acid has a blue (445 nm) emission, following UV to near UV (365–405 nm) excitation. Effects of C3CA concentration and pH buffers were investigated for this system. The response of the system was explored with respect to strength, type, and exposure rate of high-energy radiation. Results show a linear dose response relationship with a dose-rate dependency and no energy or type dependencies. This report supports the utility of gelatin-C3CA for phantom studies of radio-fluorogenic processes.

The polarised emission from AGN jets carries information about the physical conditions at the emitting plasma elements while its temporal evolution probes the physical processes that introduce variability and dynamically modify the local conditions. Here we present the analysis of multi-frequency radio linear and circular polarisation datasets with the aim to exactly quantify the conditions in blazar jets. Our analysis includes both the careful treatment of observational datasets and numerical modelling for the reproduction of synthetic polarisation curves that can be compared to the observed ones. In our approach the variability is attributed to traveling shocks. The emission from the cells of our jet model is computed with radiative transfer of all Stokes parameters. The model also accounts for Faraday effects which map the low-energy particle populations. We present two extreme cases in terms of the significance of Faraday conversion in the production of circular polarisation. As we show, in both regimes the model gives realistic reproduction of the observed emission.

In this research paper, design and development of pyramidal horn antenna for J-band application is reported. It is particularly designed for 17 dB gain and half beam width about 25 degrees at 6.93 GHz. Horn aperture, horn axial length and distance from the throat of the antenna to aperture are the main design constraints which are calculated and used for the antenna design and simulation. Beam width in E-plane and H-plane horn is calculated and it is 19.18 dB and 22.86 dB respectively. The reported antenna design shows good performance for J-band in radiometry, satellite, and radar applications.

Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 120 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.

We present a study of the radio variability of bright, $S_{1.4}\geq100$ mJy, high-redshift quasars at $z\geq3$ on timescales up to 30--40 years. The study involved simultaneous RATAN-600 measurements at frequencies of 2.3, 4.7, 8.2, 11.2, and 22.3 GHz in 2017--2020. In addition, data from the literature were used. We have found that the variability index $V_S$ of the quasars ranges from 0.02 to 0.96, with about half of the objects in the sample showing a variability index in the range of 0.25--0.50, which is comparable to that of the blazars at lower redshifts. The distribution of $V_S$ at 22.3 GHz is significantly different from that at 2.3--11.2 GHz, which may be attributed to the fact that a compact AGN core dominates at the source's rest frame frequencies greater than 45 GHz, leading to higher variability indices obtained at 22.3 GHz (the $V_S$ distribution peaks around 0.4) compared to the lower frequencies (the $V_S$ distribution peaks around 0.1--0.2). Several source groups with distinctive variability characteristics were found using cluster analysis of quasars. We propose 7 new candidates for gigahertz peaked-spectrum (GPS) sources and 5 new megahertz peaked-spectrum (MPS) sources based on their spectrum shape and variability features. Only 6 out of 23 sources previously reported as GPS demonstrate a low variability level typical of classical GPS sources ($V_{S} < 0.25$) at 4.7--22.3~GHz. When excluding the highly variable peaked-spectrum blazars, we expect no more than 20\% of the sources in the sample to be GPS candidates and no more than 10\% to be MPS candidates.

This paper is a detailed study on radio frequency identification (RFID) technology focused on its application for warehouse traceability in the company FRUMECAR. It highlights the importance of controlling the traceability of items in warehouses or logistics companies, highlighting the need for reliable, real-time information to effectively manage inventory and resolve incidents quickly. The paper discusses in depth what RFID is, its types, main components such as tags, readers, and antennas, as well as discussing how it works, advantages, disadvantages, and specific applications. It also examines factors such as return on investment, cost feasibility, and environmental factors that influence the implementation of RFID systems. The paper presents a practical approach, proposing RFID-based solutions to improve traceability in FRUMECAR, analyzing the current state of the company and its warehouses, with the aim of implementing an efficient system that allows real-time tracking of products.

Ozonated sunflower oil (OSO) is renowned for its diverse therapeutic benefits. Nonetheless, the consequences of extended dietary intake of OSO have yet to be thoroughly investigated. Herein, the effect of 2-year dietary supplementation of OSO was examined on the zebrafish survivability, obesity, skeletal deformities, swimming behavior, and liver, kidney, ovary, and testis function. Results showed that the zebrafish feed supplemented with 20% (wt/wt) OSO for 2 years emerged with higher survivability and body weight management compared to sunflower oil (SO) and normal diet (ND) supplemented zebrafish. Radio imaging (X-ray) based analysis revealed 2.6o and 15.2o lower spinal curvature in the OSO-supplemented groups than in SO and ND-supplemented groups; consistently, OSO-supplemented zebrafish showed better swimming behavior. The histology analysis of the liver revealed a least fatty liver change and interleukin 6 (IL-6) generation in the OSO-supplemented group. Additionally, a significantly lower level of reactive oxygen species (ROS), apoptotic, and senescent cells were observed in the liver of the OSO-supplemented zebrafish. Also, no adverse effect on the kidney, testis, and ovary morphology was detected during 2 years of OSO consumption. Moreover, lower senescence with diminished ROS and apoptosis was noticed in the kidney and ovary in response to OSO consumption. The OSO supplementation was found to be effective in countering age-associated dyslipidemia by alleviating total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDL-C) and elevating high-density lipoproteins (HDL-C)/TC levels. Conclusively, prolonged OSO consumption showed no adverse effect on the morphology and functionality of vital organs; in fact, OSO supplementation displayed a protective effect against age-associated detrimental effects on spinal deformities, vital organ functionality, cell senescence, and survivability of zebrafish.

This paper presents a novel sensor for the detection and characterization of regions of air turbulence that would be of use to improve UAV stability in bad weather. It consists of a combined Schlieren imager and a Radar Acoustic Sounding System (RASS) to produce dual modality “images” of air movement within the measurement volume. The ultrasound modulated Schlieren imager consists of a strobed point light source, parabolic mirror, light-block and camera which are controlled by two laptops. It provides a fine scale projection of the acoustic pulse modulated air turbulence through the measurement volume. The narrow beam 40 kHz/ 17 GHz RASS produces spectra based on Bragg enhanced Doppler radar reflections from the acoustic pulse as it travels. Tests using artificially generated air vortices showed some disruption of the Schlieren image and of the RASS spectrogram. This should allow the higher resolution Schlieren images to identify the turbulence mechanisms that are disrupting the RASS spectra.

The azimuth wheel-rail of large aperture radio telescope is the key component, it not only sup-ports the whole weight of the antenna, but also directly affects the pointing performance of the antenna with its surface accuracy. The whole weight of the radio telescope is hundreds or even thousands of tons, its azimuth frame rollers have great contact stress with the wheel-rail surface, repeated rolling can cause rolling contact fatigue on the wheel-rail surface, resulting in wear, cracks and other damage to the wheel-rail, and even lead to failure or fracture of the wheel-rail in serious cases, so it is very important to monitor the damage of the antenna wheel-rail. In order to visually detect the use of antenna wheel-rail surface, this paper proposed the method using electromagnetic ultrasonic detection to detect the damage of antenna wheel-rail surface for the first time. Based on the electromagnetic ultrasonic nondestructive testing principle, the simplified wheel-rail model containing wear, corrosion and crack damage is simulated. The results show that this method can effectively detect the surface damage of the antenna wheel-rail surface, and it can provide an important reference for the research of wheel-rail damage detection of large radio telescope.

In order to monitor the diversity of terrestrial biomes, the Earth Exploration Satellite Services demand a high data rate for downlink transmissions while sharing their frequency spectrum with, and suffering interferences from, cellular Base Stations. Both highlight the dilemmas of spectral efficiency (bps/Hz) and spectral coexistence. Our research aims to mitigate interference on low orbit satellite downlinks using Cognitive Radio (CR) and Adaptive MODulation and CODing (MODCOD) techniques. To fulfill this: 1) we present CR approaches to enhance spectrum exploitation. Next, 2) we detail Adaptive MODCOD (ACM) technique to increase RF power and spectral efficiencies. Then, 3) we suggest the solution by combining 1) and 2). Afterwards, 4) we analyze it by monitoring the signal to interference plus noise ratio and the CR/MODCOD strategy. Finally, 5) we provide case studies to demonstrate the strategy’s effectiveness through the practical operation of satellite services, and 6) we conduct a bench test of the communication system.

Objective: to evaluate the feasibility of the intra-operative application of a specimen PET/CT imager in a clinical setting. Materials and methods: this is a pilot analysis performed in three patients who received an intra-operative administration of 68Ga-PSMA-11 (n=2) and 68Ga-DOTA-TOC (n=1), respectively. Patients were administrated with PET radiopharmaceuticals to perform radio-guided surgery with a beta-probe detector during radical prostatectomy for prostate cancer (PCa) and salvage lymphadenectomy for recurrent neuroendocrine tumor (NET) of the ileum, respectively. All procedures have been performed within two ongoing clinical trials in our Institute (NCT05596851 and NCT05448157). Pathologic assessment with immunohistochemistry (PSMA-staining and SSA immunoreactivity) was considered as standard of truth. Specimen images were compared with baseline PET/CT images and histopathological analysis. Results: Patients received 1 MBq/Kg of 68Ga-PSMA-11 (PCa) or 1.2 MBq/Kg of 68Ga-DOTA-TOC (NET) prior to surgery. Specimens were collected, positioned in the dedicated specimen container, and scanned to obtain high resolution PET/CT images. In all cases a perfect match was observed between the findings detected by the specimen imager and histopathology. Overall, the PET spatial resolution was sensibly higher for the specimen images compared to the baseline whole-body PET/CT images. Furthermore, the use of the PET/CT specimen imager did not significantly interfere with any procedures, and the overall length of the surgery was not affected using the PET/CT specimen imager. Finally, the radiation exposure of the operating theater staff was lower than 40 µSv per procedure (range 26 – 40 Sv). Conclusion: the image acquisition of specimens obtained by patients who received intra-surgery injection of 68Ga-PSMA-11 and 68Ga-DOTA-TOC was feasible and reliable also in a live-experience session and has been easily adapted to surgery daily-practice. The high sensitivity, together with the evaluation of intra-lesion tumor heterogeneity, were the most relevant results since the data derived from specimen PET/CT imaging matched perfectly with the histopathological analysis.

M87 is the best available source for studying the AGN jet-launching region. To enrich our knowledge of this region, with quasi-simultaneous observations using VLBA at 22, 43 and 86~GHz, we capture the images of the radio jet in M87 on a scale within several thousand R_s. Based on the images, we analyze the transverse jet structure and obtain the spectral-index distribution in the jet. We find that the absorption is enhanced at the collimation regions and the interruption of the jet. The external medium, which may not be uniform, may have contributed a lot to the absorption in the jet-launching region. Additionally, the temporal morphology of the jet in its launching region may be largely affected by the local, short-lived kink instability growing in itself.

The Square Kilometre Array (SKA) will be both the largest radio telescope ever constructed and the largest Big Data project in the known Universe. The first phase of the project will generate on the order of 5 zettabytes of data per year. A critical task for the SKA will be its ability to process data for science, which will need to be conducted by science pipelines. Together with polarization data from the LOFAR Multifrequency Snapshot Sky Survey (MSSS), we have been developing a realistic SKA-like science pipeline that can handle the large data volumes generated by LOFAR at 150 MHz. The pipeline uses task-based parallelism to image, detect sources, and perform Faraday Tomography across the entire LOFAR sky. The project thereby provides a unique opportunity to contribute to the technological development of the SKA telescope, while simultaneously enabling cutting-edge scientific results. In this paper, we provide an update on current efforts to develop a science pipeline that can enable tight constraints on the magnetised large-scale structure of the Universe.

Long-range radio transmissions open new sensor application fields, in particular for environment monitoring. As an example, the {\sl LoRa} radio protocol enables to connect remote sensors at distance as long as ten kilometers in line-of-sight. However, the large area covered also bring several difficulties, such as the placement of sensing devices in regard to geography topology, or the variability of communication latency. Sensing the environment also carries constraints related to the interest of sensing points in relation with a physical phenomenon. Criteria for designs are thus evolving a lot from the existing methods, especially in complex terrains. This article describes simulation techniques based on geography analysis to compute long-range radio coverages and radio characteristics in these situations. As radio propagation is just a particular case of physical phenomena, it is shown how a unified approach also allows to characterize the behavior of potential physical risks. The case of heavy rainfall and flooding is investigated. Geography analysis is achieved using segmentation tools to produce cellular systems which are in turn translated into code for high-performance computations. The paper provides results from practical complex terrain experiments using LoRa, that confirm the accuracy of the simulation, scheduling characteristics for sample networks, and performance tables for simulations on middle range Graphics Processing Units (GPUs).

Overactive bladder (OAB) is characterized by urinary urgency and increased urinary frequency, and can impact quality of life significantly. Tamsulosin and mirabegron combination therapy has been studied as a safe and effective treatment option for patients with OAB. This study evaluated the effects of combining these two drugs on their pharmacokinetics and safety profiles in healthy Korean males. In this open-label, fixed-sequence, 3-period, drug-drug interaction phase 1 study, a total of 36 male participants were administered multiple doses of tamsulosin alone (0.2 mg once daily), mirabegron alone (50 mg once daily), and a combination of both drugs. The results showed that the combination of tamsulosin and mirabegron increased tamsulosin exposure in the plasma by approximately 40%. In contrast, the maximum plasma concentration of mirabegron reduced by approximately 17%, when administered along with tamsulosin. No clinically significant changes in safety profiles, vital signs, or clinical laboratory test results were observed in this study. In conclusion, there were no clinically relevant drug-drug interactions between tamsulosin and mirabegron in terms of pharmacokinetics, safety, and tolerability, suggesting that their combination therapy could be a promising treatment option for patients with OAB.

The drug discovery process is a rigorous and time-consuming endeavor, typically requiring several years of extensive research and development. Although classical machine learning (ML) has proven successful in this field, its computational demands in terms of speed and resources are significant. In recent years, researchers have sought to explore the potential benefits of quantum computing (QC) in the context of ML, leading to the emergence of Quantum Machine Learning (QML) as a distinct research field. The objective of the current study is twofold: first, to present a review of the proposed QML algorithms for application in the drug discovery pipeline, and second, to compare QML algorithms with their classical and hybrid counterparts in terms of their efficiency. A query-based search of various databases took place, and five different categories of algorithms were identified in which QML was implemented. The majority of QML applications in drug discovery are primarily focused on the initial stages of the drug discovery pipeline, particularly with regard to the identification of novel drug-like molecules. Comparison results revealed that QML algorithms are strong rivals against the classical ones and a hybrid solution is the recommended approach at present.

Maximizing the indications potential and revenue from drugs that are already marketed offers a new take on the famous mantra of the Nobel Prize-winning pharmacologist, Sir James Black, “The most fruitful basis for the discovery of a new drug is to start with an old drug”. However, rational design of drug mixtures poses formidable challenges because of the lack of or limited information about in vivo cell regulation, mechanisms of genetic pathway activation, and in vivo pathway interactions. Most of the repositioned drugs therefore are the result of “serendipity” - based on late phase clinical studies of unexpected findings. One of the reasons that the connection between drug candidates and their potential adverse drug reactions or new applications could not be identified earlier is that the underlying mechanism associating them is either very intricate and unknown or dispersed and buried in a sea of information. Discovery of such multi-domain pharmacomodules - pharmacologically relevant sub-networks of biomolecules and/or pathways - from collection of databases by independent/simultaneous mining of multiple datasets is an active area of research. Here, while presenting some of the promising bioinformatics approaches and pipelines, we summarize and discuss the current and evolving landscape of computational drug repositioning.

Coronavirus disease (COVID-19) is the current global public health threat with no specific, effective, and approved treatment available till date. The outbreak of COVID-19 has led the world into an unimagined and uncertain situation by disrupting the economies, claiming human lives, and leaving many into secondary mental health problems. As per the latest WHO report, approximately 8.2 million people are infected, and nearly 0.44 million lives are lost to COVID. The infection has spread to over 200 countries and territories around the world. The world is in search of efficient diagnostics and therapeutics, including vaccines, biologics and drugs. With the rapid increase in rates of infection and time constraints, drug repurposing seems to be a potential and viable option to find the promising anti-COVID therapeutics. In the wake of a rapid increase in the number of clinical trials involving drugs for repurposing, we aim to provide information on the safety concerns related to the drugs currently investigated in trials. This review also highlights the possible mechanisms of actions, adverse drug reactions, and contraindications of the drugs under repurposing evaluation.

Inhibitors of the factor FXI represent a new class of anticoagulant agents that are facing the clinical approval for the treatment of acute coronary syndrome (ACS), venous thromboembolism (VTE), and stroke prevention of atrial fibrillation (AF). These new inhibitors include chemical small molecules (asundexian and milvexian), monoclonal antibodies (abelacimab, osocimab, and xisomab), and antisense oligonucleotides (IONIS-FXIRX and fesomersen), and thus with very peculiar and different pharmacokinetic and pharmacodynamic properties. Besides their clinical efficacy and safety, based on their pharmacological heterogeneity, the use of these drugs in patients with comorbidities may undergo to drug-drug interactions (DDI) with other concomitant therapies. Although only few clinical evidence are available, it is possible to predict clinical relevant DDI by taking into consideration their pharmacokinetic properties, such as the CYP450-dependent metabolism, the interaction with drug transporters and/or the route of elimination. These characteristics may be useful to differentiate their use with the direct oral anticoagulant (DOAC) anti -FXa (rivaroxaban, apixaban, edoxaban) and thrombin (dabigatran), whose pharmacokinetics are strongly dependent from P-gp inhibitors/inducers. In the present review, we summarize the current clinical evidence on DDI of new anti FXI with CYP450/P-gp inhibitors and inducers and indicate potential differences with DOAC anti FXa.

Of the manifold concepts in drug discovery and design, covalent drugs have re-emerged as one of the most promising over the past 20-or so years. All such drugs harness the ability of a covalent bond to drive an interaction between a target biomolecule, typically a protein, and a small molecule. Formation of a covalent bond necessarily prolongs target engagement, opening avenues to targeting shallower binding sites, protein complexes, and other difficult to drug manifolds, amongst other virtues. This opinion piece discusses frameworks around which to develop covalent drugs. Our argument, based on results from our research program on natural electrophile signaling, is that targeting specific residues innately involved in native signaling programs are ideally poised to be targeted by covalent drugs. We outline ways to identify electrophile-sensing residues, and discuss how studying ramifications of innate signaling by endogenous molecules can provide a means to predict drug mechanism and function and assess on- versus off-target behaviors.

Recently, NOAA has included GNSS (Global Navigation Satellite System) Radio Occultation (RO) data as one of the crucial long-term observables for weather and climate applications. To include more GNSS RO data in the numerical weather prediction system, the NOAA Commercial Weather Data Pilot program (CWDP) started to explore the commercial RO data available on the market. After two rounds of pilot studies, the CDWP decided to award the first Indefinite Delivery Indefinite Quantity (IDIQ) contract to GeoOptics and Spire Incs. in 2020. This study examines the quality of Spire data products for weather and climate applications. Spire RO data are collected from commercial CubeSats through careful comparison with the data from Formosa Satellite Mission 7–Constellation Observing System for Meteorology, Ionosphere, and Climate-2 (COSMIC-2), ERA-5, and high-quality radiosonde data. The results demonstrated that although with lower Signal-Noise-Ratio (SNR) in general, the pattern of the lowest penetration height for Spire is similar to those for COSMIC-2. The Spire and COSMIC-2 penetrate heights are between 0.6 and 0.8 km altitude at the tropical oceans. Although using different GNSS RO receivers, the precision of Spire STRASP receivers is of the same quality as those of COSMIC-2 Global Positioning System - GPS, GALILEO, and GLObal NAvigation Satellite System – GLONASS (TGRS) receivers. The retrieval accuracy from Spire is very compatible with those from COSMIC-2. We validated Spire temperature and water vapor profiles by comparing them with collocated radiosonde data. Generally, over the height region between 8 km and 16.5 km, the Spire temperature profiles match those from RS41 RAOB very well with temperature biases &lt; 0.02 K. Over the height range from 17.8 to 26.4 km, the temperature differences are ~-0.034 K with RS41 RAOB being warmer. We also estimated the error covariance matrix for Spire, COSMIC-2, and KOMPSAT-5. Results showed that the COSMIC-2 estimated error covariance values are slightly more significant over the oceans at the mid-latitudes (45oN-30oN and 30oS-45oS), which may also be owing to COSMIC-2 SNR being lower at those latitudinal zones.

Whistler mode waves play a major role in regulating the lifetime of trapped electrons in the Earth's radiation belts. Specifically, whistler mode hiss waves are one of the mechanisms that maintains the slot region between the inner and outer radiation belts. The generation mechanism of hiss is a topic still under debate with at least three prominent theories present in the literature. Lightning generated whistlers in their ducted or non-ducted modes, are considered to be one of the possible sources of hiss. We present a study of new observations from the Radio Receiver Instrument (RRI) on the Enhanced Polar Outflow Probe (ePOP: currently known as SWARM-E). RRI consists of two orthogonal dipole antennas, which enables polarization measurements, when the satellite boresight is parallel to the geomagnetic field. Here we present 75 passes of ePOP - RRI from 2014 - 2018, in which lightning whistlers and hiss waves were observed. In more than 50% of those passes hiss is found to co-exist with the lightning whistlers. Moreover, the whistler observations are correlated with observations of wave power at the lower-hybrid resonance. The observations and a whistler mode ray-tracing study suggest that multiple-hop lightning induced whistlers can be a source of hiss and plasma instabilities in the magnetosphere.

DARPA, the Defense Advanced Research Projects Agency from the United States, has started the Spectrum Collaboration Challenge with the aim to encourage research and development of coexistence and collaboration techniques of heterogeneous networks in the same wireless spectrum bands. Team SCATTER has been participating in the challenge since its beginning, back in 2016. SCATTER’s open-source software-defined physical layer (SCATTER PHY) has been developed as a standalone application, with the ability to communicate with higher layers of SCATTER’s system via ZeroMQ, and uses USRP X310 software-defined radio devices to send and receive wireless signals. SCATTER PHY relies on USRP’s ability to schedule timed commands, uses both physical interfaces of the radio devices, utilizes the radio’s internal FPGA board to implement custom high-performance filtering blocks in order to increase its spectral efficiency as well as enable reliable usage of neighboring spectrum bands. This paper describes the design and main features of SCATTER PHY and showcases the experiments performed to verify the achieved benefits.

Use of Machine Learning (ML) methodologies in optical communications has paved a new pathway. In this paper, firstly, we discuss the use of ML methodologies for reducing optical fiber nonlinearities, nonlinearity compensation, fault detection and optical performance monitoring. Then we present our recent work where we compare RL-SARSA and SVM based method with conventional method. The results show that RL-SARSA and SVM methods are successful candidates in mitigating the nonlinearities in proposed system as compared to conventional optical communication system.

The last 20 years have seen significant advancements in polymeric drug delivery methods. A formulation or a system that makes it possible for a medicinal ingredient to be injected into the body is known as polymeric drug delivery1. The key choice for many novel medication delivery methods is made achievable by biodegradable and bio-reducible polymers. The research's prospects for practical applications have necessitated the field's development—the choice for a lot of new drug delivery systems. The prospects of the research for practical applications are required for the development in the field. Polymeric drug delivery methods have been developed from natural polymers like arginine, chitosan2, dextrin, polysaccharides, poly (glycolic acid), poly (lactic acid), and hyaluronic acid. Regarding polymeric drug delivery1, synthetic polymers such as poly(2-hydroxyethyl methacrylate), poly(N-isopropyl acrylamide), poly(ethylenimine), dendritic polymers, biodegradable, and bioabsorbable polymers have all been considered. Polymeric drug delivery has also been addressed by focusing on drug-free macromolecular therapies, biomimetic and bio-related polymeric systems, and targeting polymeric drug delivery. Pharmaceutical fields are seeing a tremendous rise in the development of polymeric drug delivery methods based on natural and manmade polymers. The successful advancements in the utilization of biocompatible and bio-related copolymers and dendrimers in cancer treatment, including their application as vehicle systems for highly effective anticancer medications3. A new paradigm for the development of polymeric drug and gene delivery systems will be possible through the fusion of viewpoints from the synthetic and biological domains.

The practical application of a pH-responsive Nanoparticle Drug Delivery System (NDDS) in cancer treatment is often hampered by several issues such as the protection of therapeutic molecules from external stresses, inefficient targeted delivery, sustained drug release, and poor efficacy. This study presents an effective design strategy for the synthesis of a pH-sensitive controlled hydrophobic drug delivery method based on the formulation of chitosan (CS)-coated mesoporous silica nanoparticles (MSNs) through the sol-gel method, where hydrolysis takes place in the acidic medium followed by polycondensation of the hydrolyzed products. For this purpose, NH2 modified-MSNs were prepared by using tetraethyl orthosilicate (TEOS) as precursor and cetyltrimethylammonium bromide (CTAB) as a template, and 3-aminopropyltriethoxysilane (APTES) for amine modification, followed by hydrophobic drug loading and CS coating of various concentrations. Camptothecin (CPT) was used as a model drug. Fabricated monodispersed functionalized nanoparticles had sizes ranging from 200nm to 245nm with an encapsulation efficiency as high as 90%. The highest encapsulation efficiency was found for 1% CS coating, which released 50% drug in 120h at pH 6.4 and 20% at pH 7.4 respectively. These nanoformulations exhibited pH-responsive release patterns of CPT under two different pH values (pH=7.4 and pH=6.4). These results contribute to the optimization of NDDS, with potential implications for nanoformulations designed for controlled and sustained drug release particularly to tumors without affecting healthy cells owing to differences in the pH of the tumor microenvironment and the normal physiological environment of cells.

We discuss further details on the concepts of “drug-likeness”, “lead-likeness”, and “natural product-likeness”. The discussion will first focus on natural products as drugs, then a discussion of previous studies in which the complexities of the scaffolds and chemical space of naturally occurring compounds have been compared with synthetic, semi-synthetic compounds and FDA-approved drugs. This is followed by guiding principles for designing “drug-like” natural product libraries for lead compound discovery purposes. We end up by presenting a tool for measuring “natural product-likeness” of compounds and a brief presentation of machine learning approaches and a binary quantitative structure-activity relationship (QSAR) for classifying drugs from non-drugs and natural compounds from non-natural ones, respectively.

Background: no reports have examined the profile of drug-induced dysphagia in detail. The goal of this study was to investigate if there are any differences in the profiles of drug-induced dysphagia. Methods: This study used the Japanese Adverse Drug Event Report (JADER) database. Further, reported odds ratios (RORs) were used to analyze data on adverse drug events from 2004 to 2021. The top ten drugs with the most drug-induced dysphagia occurrences were used as target drugs. The association between RORs and drug-induced dysphagia caused by the target drugs was evaluated, and the age distribution and time of onset of drug-induced dysphagia for each drug were compared. RORs were the primary endpoint. Moreover, age and time of onset of drug-induced dysphagia were secondary outcomes. Results: In total, 756,965 reports were analyzed. All the target drugs were associated with drug-induced dysphagia. Among them, cevimeline was a novel finding, as no dysphagia was observed during the clinical trial. For most drugs, the onset of drug-induced dysphagia was occurring within approximately 25 days of administration. However, even after long-term use, paroxetine and milnacipran were associated with drug-induced dysphagia. Conclusion: The onset profile of drug-induced dysphagia may differ from one drug to the next.

Drug repurposing is a valuable tool for combating the slowing rates of novel therapeutic discovery. The Computational Analysis of Novel Drug Opportunities (CANDO) platform performs shotgun repurposing of 2030 indications/diseases using 3733 drugs/compounds to predict interactions with 46,784 proteins and relating them via proteomic interaction signatures. An accuracy is calculated by comparing interaction similarities of drugs approved for the same indications. We performed a unique subset analysis by breaking down the full protein library into smaller subsets and then recombining the best performing subsets into larger supersets. Up to 14% improvement in accuracy is seen upon benchmarking the supersets, representing a 100–1000 fold reduction in the number of proteins considered relative to the full library. Further analysis revealed that libraries comprised of proteins with more equitably diverse ligand interactions are important for describing compound behavior. Using one of these libraries to generate putative drug candidates against malaria results in more drugs that could be validated in the biomedical literature than the list suggested by the full protein library. Our work elucidates the role of particular protein subsets and corresponding ligand interactions that play a role in drug repurposing, with implications for drug design and machine learning approaches to improve the CANDO platform.

The proliferation of radio frequency devices in today's society, especially in smart homes, Internet of Things devices, and smartphones, underscores the urgent need for robust identification methods to strengthen cybersecurity. This paper delves into the field of radio frequency fingerprinting to propose a Bluetooth device identification method based on the application of the Jensen-Shannon divergence to the statistical distribution of noise in Bluetooth signals. A detailed case study is performed to investigate the Bluetooth radio frequency noise recorded at 5 Gsps from different devices is investigated to define a statistical radio frequency fingerprint for each Bluetooth device. A noise model is used to extract a unique, universal, persistent, recoverable, and robust statistical radio frequency fingerprint that identifies each Bluetooth device. Then, using the Jensen-Shannon divergence, different noise signals provided by each Bluetooth device are compared with the statistical radio frequency fingerprint of all devices and a membership resolution is declared. The study shows that the proposed method can discriminate between devices of the same brand and model, achieving an identification effectiveness of 99.5 \%. By leveraging the statistical radio frequency fingerprint of Bluetooth devices, this research not only contributes to the advancement of the field of implicit device authentication systems based on wireless communication but also provides valuable insights into the practical implementation of radio frequency identification techniques that could be useful in forensic processes.

Radio techniques are widely used in wildlife tracking. Currently, the most common tracking methods include radio tracking (operating on VHF and UHF frequencies), satellite tracking (e.g., Argos satellite Doppler-based positioning system), and Global Navigation Satellite System (GNSS) tracking. One of the radio tracking systems is the Radio-Frequency Identification (RFID) system, characterized by small dimensions and a long operational period due to energy-efficient features. The advantages of RFID make it possible to apply this technique to track oak acorns in the process of zoochoric dispersal. In our study, we explored the potential applications of RFID systems for monitoring the dispersal of oak acorns. We developed a tracking system based on a semi-passive RFID tag, which we tested under laboratory and quasi-realistic conditions. The obtained results confirm the feasibility of using our system in radio tracking small objects such as oak acorns.

As an established and widely available infrastructure, wireless local area networks (WLANs) have emerged as a viable option for indoor localization of both mobile and stationary users. In planning a mobile communications network and radio system design, the critical role of coverage prediction becomes evident, empowering network operators to optimize cellular networks and elevate the overall customer experience. Moreover, WLANs present several challenges that must be fulfilled when it comes to localization based on Wi-Fi signals to get a proper coverage prediction map. This paper presents a study based on application of the extra trees regression (ETR) for indoor localization by using coverage prediction maps. The aim of the proposed method is to accurately estimate a user’s position within a radio environment map (REM) area using collected received signal strength indicator (RSSI) values. The proposed scheme investigates several machine learning (ML) regression algorithms for localization, where the training dataset is obtained from the REM by using the nearest neighbors method. Parameter tuning is conducted to optimize the performance of the ETR scheme by using 10-fold cross-validation. In the numerical results, we first demonstrate the effectiveness of utilizing ML regression techniques for generating coverage maps, which enables accurate estimation of the Wi-Fi signal strength in indoor environments. Then, we showcase the superior performance of the proposed ETR-based method compared to several other ML schemes for indoor localization using the REM. ML algorithms, including decision tree regression and the ETR, are compared to evaluate the system model. Based on error metrics, the proposed ETR-based approach exhibits the best performance among the evaluated techniques. The combination of coverage map generation and localization using regression techniques offers a powerful approach for analyzing the radio frequency (RF) environment in indoor spaces.

Abstract- Cognitive radio (CR) play an important role in improving spectral efficiency (SE) of wireless communication, meanwhile, intelligent reflecting surface (IRS) is an effective technology to improve the secrecy performance of wireless communication system by adjusting the phase shift and amplitude of channel. Thus, we consider an IRS-aided multiple-input single-output (MISO) CR systems to enhance secrecy rate, which is consists of a single eavesdropping link, a primary network containing the primary receiver (PR), and secondary network including secondary receiver (SR) and the SR transmitter (SR-TX). Specifically, we minimize the transmit power of SR subject to secrecy capacity constraint and interference temperature (IT) constraint on PR, by jointly optimizing the beamforming vector and artificial noise (AN) constraints matrix at SR-TX as well as the phase shift matrix of IRS. Numerical results show that the different values of transmit antennas at the SR-TX and the number of IRS elements can significantly decrease the transmit power under the condition of ensuring secure communication.

In cognitive radio systems, identifying spectrum opportunities is fundamental to efficiently use the spectrum. Spectrum occupancy prediction is a convenient way of revealing opportunities based on previous occupancies. Studies have demonstrated that usage of the spectrum has a high correlation over multidimensions which includes time, frequency, and space. Accordingly, recent literature uses tensor-based methods to exploit the multidimensional spectrum correlation. However, these methods share two main drawbacks. First, they are computationally complex. Second, they need to re-train the overall model when no information is received from any base station for any reason. Different than the existing works, this paper proposes a method for dividing the multidimensional correlation exploitation problem into a set of smaller sub-problems. This division is achieved through composite two-dimensional (2D)-long short-term memory (LSTM) models. Extensive experimental results reveal a high detection performance with more robustness and less complexity attained by the proposed method. The real-world measurements provided by one of the leading mobile network operators in Turkey validate these results.

Introduction: Atrial fibrillation (AF) is a common cardiac arrhythmia whose prevalence rises with age and is linked to increased morbidity and mortality due to the risk of thromboembolism. Management typically involves anticoagulation and rhythm control, but the treatment of elderly patients with multiple comorbidities requires careful consideration of drug side effects and interactions. Cibenzoline, a Vaughan-Williams class IA antiarrhythmic, is effective against AF but has risks of toxicity, especially in older people and those with renal impairment, due to its renal excretion and prolonged half-life in these populations. Discussion: This paper presents a case of an 80-year-old woman with paroxysmal AF who suffered cardiac arrest due to cibenzoline toxicity despite receiving standard adjusted dosages. The patient's cibenzoline blood concentration was significantly higher than the therapeutic range, leading to cardiotoxicity, which was exacerbated by drug interactions with bisoprolol and edoxaban, both metabolized by the CYP3A4 enzyme. Venoarterial extracorporeal membrane oxygenation (V-A ECMO) and intra-aortic balloon pump (IABP) successfully managed the cardiac arrest. This case emphasizes the unpredictable pharmacokinetics of cibenzoline in elderly patients with renal impairment and the need for vigilant therapeutic drug monitoring to avoid adverse events. Conclusions: Cibenzoline can pose a significant risk of severe toxicity in elderly patients with renal impairment, and drug interactions may potentiate this risk. The paper underscores the importance of careful dose adjustment and monitoring of drug levels in this population. In cases of cibenzoline-induced cardiac arrest, V-A ECMO and IABP are effective treatment modalities. The case study serves as a critical reminder for clinicians to remain vigilant for drug-induced complications and to apply aggressive supportive treatments when necessary.

Pancreatic cancer is an intractable disease with the worst prognosis of all cancers. The currently used treatment regimens do not significantly impact patient survival, and therefore, effective treatment strategies are urgently needed. Drug repurposing, which identifies new indications for existing and approved drugs, has proven to be a promising approach to anti-cancer drug discovery. Indeed the antihelmintic drug, pyrvinium pamoate has shown promise as an anti-pancreatic cancer drug, but to date, the inhibition of mitochondrial function is the only mechanism of action described in pancreatic cancer. This study showed, using pancreatic cancer 2D cell cultures and 3D spheroids, that pyrvinium pamoate exhibited short- and long-term cytotoxicity, inhibited epithelial-to-mesenchymal transition and cell invasion and migration. Mechanistically, pyrvinium pamoate induced DNA damage, inhibited the PI3K/AKT cell survival pathway, and triggered cell cycle arrests, as well as apoptotic and autophagic cell death. Importantly, pyrvinium pamoate acted synergistically with the first-line drug, gemcitabine in 2D and 3D pancreatic cancer cell culture models. This study provided evidence that pyrvinium pamoate is effective as a single agent and in combination with gemcitabine for the treatment of pancreatic cancer.

Mosquitoes conveying Plasmodium store parasites into the skin of the mammalian host. Parasites make a trip through the circulation system to the liver, where they cross a few hepatocytes prior to building up a disease. Inside the last hepatocyte the parasite goes through morphogenesis and afterward abiogenetically partitions to become more than 20,000 blood-infective parasites, called merozoites. On account of P. vivax, P. ovale, and P. cynomolgi, the parasites can stay lethargic in the liver in structures called hypnozoites. The merozoites are delivered once again into the circulation system, where they start the repetitive blood stage. Inside erythrocytes, a little division of parasites separate into male or female gametocytes. These gametocytes are ingested by the mosquito during blood taking care of, where they will duplicate explicitly, in the long run prompting the arrangement of sporozoites

Our bodies produce a host of electrophilic species that can label specific endogenous proteins in cells. The signaling roles of these molecules are underactive debate. However, in our opinion it is becoming increasingly likely that electrophiles can rewire cellular signaling processes at endogenous levels. Attention is turning more to understanding how nuanced electrophile signaling in cells is. In this perspective, we describe recent work from our laboratory that has started to inform on different levels of context-specific regulation of proteins by electrophiles. We discuss the relevance of these data to the field, and to the broader application of electrophile signaling to precision medicine development, beyond the traditional views of their pleiotropic cytotoxic roles.

Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer; presents novel nanomedicine therapeutics aimed to improve the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for clinical application of nanomedicine in management of LC resistance.

The up-and-coming microfluidic technology is the most promising platform for designing anti-cancer drugs and new point-of-care diagnostics. Compared to conventional drug screening methods based on Petri dishes and animal studies, drug delivery in microfluidic systems has many advantages. For instance, these platforms offer high throughput drug screening, require a small amount of samples, provide an in vivo-like microenvironment for cells, and eliminate ethical issues associated with animal studies. Multiple cell cultures in microfluidic chips could better mimic the 3D tumor environment using low reagents consumption. The clinical experiments have shown that combinatorial drug treatments have a better therapeutic effect than monodrug therapy. So many attempts were performed in this field in the last decade. This review highlights the applications of microfluidic chips in anti-cancer drug screening and systematically categorizes these systems as a function of sample size and combination of drug screening. Finally, it provides a perspective on the future of the clinical applications of microfluidic systems for anti-cancer drug development.

Overexpression of BRF2, a selective subunit of RNA polymerase III, has been shown to be crucial in the development of several types of cancers, including breast cancer and lung squamous cell carcinoma . Predominately, BRF2 acts as a central redox-sensing transcription factor (TF) and is involved in rescuing oxidative stress (OS) -induced apoptosis. Here, we showed a novel link between BRF2 and DNA damage response. Due to the lack of BRF2 specific inhibitors, through virtual and molecular dynamics screening, we identified potential drug candidates that interfere with BRF2-TATA-binding Protein (TBP)-DNA complex interactions based on binding energy, intermolecular, and torsional energy parameters. We experimentally tested Bexarotene as a potential BRF2 inhibitor. We found that Bexarotene (Bex) treatment resulted in a dramatic decline in oxidative stress (Tert-butylhydroquinone (tBHQ))-induced levels of BRF2 and consequently, lead to a decrease in cellular proliferation of cancer cells which may in part be due to drug pretreatment induced reduction of ROS generated by the oxidizing agent. Our data thus, provide the first experimental evidence that BRF2 is a novel player in DNA damage response pathway and Bexarotene can be used as a potential inhibitor to treat cancers with the specific elevation of oxidative stress.

Background: drugs provide a significant benefit; however, their use implies an intrinsic potential danger, with the possibility to cause unwanted effects. These effects are known as adverse drug reactions (ADRs). Post-marketing drug safety surveillance detects unknown risks that have not been identified in clinical trials and it is necessary to monitor marketed medications under real-life practice. Due to the scarce information about fixed combination of ciprofloxacin 0.3% / dexamethasone 0.1% (SDO), we performed a drug safety surveillance study. (2) Methods: A prospective non-controlled drug safety surveillance study was conducted in Peruvian population. A total of 236 patients prescribed SDO were included derivates from 12 sites. Patients' standardized information was collected through two phone calls, including demographics, medical history, prescribing patterns of SDO, concomitant medication, and ADRs in detail. The ADRs were classified by causality and severity, followed by outcome measures to identify new risk. (3) Results: 236 patients prescribed with SDO participated in the study and 220 were included. A total of 82 ADRs/220 patients were reported after the use of SDO, presenting a ratio 0.37 ADR/patient. The most frequent ADR with SDO administration was eye irritation (30%). The totality of the ADR was classified as non-serious, and the 97.5% (n=80) was classified as mild and 2.5% as moderate (n=2). No cases under the severe category were identified. (4) Conclusion: No new risks were found in the population where this study was conducted.

The recent covid crisis has proven important lessons for academia and industry regarding digital reorganization. Among fascinating lessons from these times is the huge potential of data analytics and artificial intelligence. The crisis exponentially accelerated the adoption of analytics and artificial intelligence, and this momentum is predicted to continue into the 2020s and over. Moreover, drug development is a costly and time-consuming business, and only a minority of approved drugs return the revenue that exceeds the research and development costs. As a result, there is a huge drive to make drug discovery cheaper and faster. With modern algorithms and hardware, it is not too surprising that the new technologies of artificial intelligence and other computational simulation tools can help drug developers. In only two years of covid research, many novel molecules have been designed/identified using artificial intelligence methods with astonishing results in terms of time and effectiveness. This paper will review the most significant research on artificial intelligence in the de novo drug design for COVID-19 pharmaceutical research.

The gate resistance is a parasitic element in transistors for RF and millimeter-wave circuits that can negatively impact power gain and noise figure. To develop accurate device models, a reliable measurement methodology is crucial. This article reviews the standard measurement methodology used in the literature and proposes also an additional method, which is evaluated using suitable test structures in a 16nm FinFET process. The advantages and disadvantages of the two approaches are discussed along with their respective application scenarios

A case study is presented which demonstrates the value and validity of a novel approach to the use of consolidated amateur (‘ham’) radio reception reports as indicators of the presence of intense ionospheric sporadic E (Es). It is shown that the use of amateur data can provide an important supplement to other techniques, allowing the detection and tracking of Es where no suitable ionosonde or other measurements are available. The effectiveness of the approach is demonstrated by reference to ionosonde data, and the advantages and limitations of the technique are discussed.

Radio Frequency Interference (RFI) detection and characterization play a critical role to in ensuring the security of all wireless communication networks. Advances in Machine Learning (ML) have led to the deployment of many robust techniques dealing with various types of RFI. To sidestep an unavoidable complicated feature extraction step in ML, this paper proposes an efficient end-to-end method using the latest advances in deep learning to extract the appropriate features of the RFI signal. Moreover, this study utilizes the benefits of transfer learning to determine both the type of received RFI signals and their modulation types. To this end, the scalogram of the received signals is used as the input of the pre-trained convolutional neural networks (CNN), followed by a fully-connected classifier. This study considers a digital video stream as the signal of interest (SoI), transmitted in a real-time satellite-to-ground communication using DVB-S2 standards. To create the RFI dataset, the SoI is combined with three well-known jammers namely, continuous-wave interference (CWI), multi- continuous-wave interference (MCWI), and chirp interference (CI). This study investigated four well-known pre-trained CNN architectures, namely, AlexNet, VGG-16, GoogleNet, and ResNet-18, for the feature extraction to recognize the visual RFI patterns directly from pixel images with minimal preprocessing. Moreover, the robustness of the proposed classifiers is evaluated by the data generated at different signal to noise ratios (SNR).

A cognitive radio sensor network (CRSN) based Smart Grid (SG) is a new paradigm for a modern SG. It is totally different from the traditional power grid and also different from the conventional SG that uses a static resource allocation technique to allocate resources to sensor nodes and communication devices in the SG network. Due to the challenges associated with competitive sensor nodes and communication devices in accessing and utilizing radio resources, the need for dynamic radio resource allocation (RRA) has been proposed as a solution for allocating radio resources to sensor nodes in a CRSN based smart grid ecosystem (network). These challenges include energy/power constraints, poor quality of service (QoS), interference, delay, spectrum efficiency issues, and excessive spectrum hand-offs. Hence, the optimization of resource allocation criteria, such as energy efficiency, throughput maximization, QoS guarantee, fairness, priority, interference mitigation/avoidance, etc., will go a long way in addressing the problems of RRA in a CRSN based SG. Consequently, this work explores RRA in CRSNs for SGs. Various resource allocation schemes, as well as its architecture in a CRSN for SG environment, are presented. The work reported in this paper introduces a model called the “guaranteed network connectivity channel allocation” for throughput maximization (GNC-TM) and optimal spectrum band determination in RRA for improved throughput criteria in CRSNs for SGs. The results show that the model outperforms the existing protocol in terms of throughput and error probability. Finally, the contribution to knowledge and future research direction, such as energy efficiency and hybrid energy harvesting schemes are highlighted.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients’ access to best care. A modified Delphi methodology was used to confirm strong consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian patients and their health care providers request improvements in timely access to life-saving therapeutics in line with other countries. Clinicians expect urgent improvements in our health systems to give our patients their best chance of survival.

The emergence of resistance to first-line antimalarial drugs calls for development of new therapies for drug-resistant malaria. The efficacy of quinoline-based antimalarial drugs has prompted the development of novel quinolines. A panel of 4-aminoquinoline hydrazone analogues were tested on Plasmodium falciparum strains: IC50 values after a 48-hour cycle ranged from 0.60 - 49 µM, while the 72-hour cycle ranged from 26-219 nM on the multi-drug resistant K1 strain. Time-course assays were carried out to define the activity of the lead compounds which inhibited over 50 % growth in 24 hours and 90% growth in 72 hours. Cytotoxicity assays with HepG2 cells showed IC50 values of 0.87-11.1 M, whereas in MDBK cells IC50 values ranged from 1.66-11.7 M. High selectivity indices were observed for the lead compounds screened at 72 hours on P. falciparum. Analyses of stage-specificity revealed that the ring stage of the parasite life cycle were most affected. Based on antimalarial efficacy and in vitro safety profiles, lead compound 4-(2-benzylidenehydrazinyl)-6-methoxy-2-methylquinoline 2 was progressed to drug combination studies for the detection of synergism, with a combinatory index of 0.599 at IC90 for the combination of with artemether, indicating a synergistic antimalarial activity. Compound 2 was screened on different strains of P. falciparum (3D7, Dd2) which maintained similar activity to K1, suggesting no cross-resistance between multi-drug resistance and sensitive parasite strains. In vivo analysis with 2 showed suppression of parasitaemia with P. yoelii NL treated mice (20 mg/kg and 5 mg/kg).

Covid-19 is one of humanity’s biggest threat in the 21st century with WHO figures reporting 636 million cases and up to 6.6 million deaths globally. SARS-CoV-2, the virus that causes the Covid-19 disease, is characterized by high mutation which contributes to its rapid spread. While several vaccines have been produced to minimize the severity of the coronavirus and diverse treatment regimens have been approved by the US FDA under Emergency Use Authorization (EUA), SARS-CoV-2 viral mutations continue to derail the efforts of scientists as the emerging variants evade the recommended therapies. Nonetheless, diverse computational models exist that offer an opportunity to overcome the barriers involved in developing new drugs. In this review, the focus is on the use of various virtual screening techniques like molecular docking, molecular dynamics simulations, QSAR, pharmacophore modeling, and homology modeling in repurposing SARS-CoV-2 therapeutics. The results have been promising from the computer-aided drug design (CADD) studies in suggesting potential compounds for treatment of Covid-19 and helping in bringing the pandemic under control.

Background &amp; Aim: Drug sustainability (DS) is a surrogate marker for treatment efficacy. We aimed to compare the DS of two main biologics used to treat moderate-to-severe ulcerative colitis (UC), infliximab (IFX) and vedolizumab (VDZ), in a real-world setting. Methods: We conducted a retrospective cohort study at a tertiary medical center in Israel. We included patients treated between Dec 1st, 2017, and May 1st, 2021, who were followed for up to 300 weeks. DS was defined as corticosteroid, surgical, and hospitalization-free treatment. Results: 217 patients with UC were included. VDZ had a significantly longer median DS of 265.6 weeks compared to IFX's 106.5 weeks (p=0.001) in treatment-naïve patients, even when adjusting for disease severity (HR 0.55 95 CI 0.3-0.98, p=0.042). In treatment-experienced patients, DS was comparable between IFX and VDZ (p=0.593). Conclusion: VDZ showed significantly longer DS in treatment-naïve patients with UC compared to IFX, also when adjusted for disease severity. There was no difference in DS between VDZ and IFX in treatment-experienced patients and patients switching from one drug to another. VDZ may be a suitable first-line treatment for biologic-naïve patients with moderate-to-severe UC.

The worldwide outbreak of SARS-CoV-2 in early 2020 caused numer- ous deaths and unprecedented measures to control its spread. We employed our Computational Analysis of Novel Drug Opportunities (CANDO) multiscale therapeutic discovery, repurposing, and design platform to identify small molecule inhibitors of the virus to treat its resulting indication, COVID-19. Initially, few experimental studies existed on SARS-CoV-2, so we optimized our drug candidate prediction pipelines using results from two independent high-throughput screens against prevalent human coronaviruses. Ranked lists of candidate drugs were generated using our open source cando.py software based on viral protein inhibition and proteomic interaction similarity. For the former viral protein inhibition pipeline, we computed interaction scores between all compounds in the corresponding candidate library and eighteen SARS-CoV proteins using an interaction scoring protocol with extensive parameter optimization which was then applied to the SARS-CoV-2 proteome for prediction. For the latter similarity based pipeline, we computed interaction scores between all compounds and human protein structures in our libraries then used a consensus scoring approach to identify candidates with highly similar proteomic interaction signatures to multiple known anti-coronavirus actives. We published our ranked candidate lists at the very beginning of the COVID-19 pandemic. Since then, 51 of our 276 predictions have demonstrated anti-SARS-CoV-2 activity in published clinical and experimental studies. These results illustrate the ability our platform to rapidly respond to emergent pathogens and provide greater evidence that treating compounds in a multitarget context more accurately describes their behavior in biological systems.

Although marketing authorization holders (MAHs) are involved in monitoring medication safety, it was unclear how they experience their role and current monitoring activities in pregnancy. Therefore, a qualitative study using online focus groups with MAHs and the Belgian umbrella organisation of MAHs was conducted in June-July 2021. In total, 38 representatives of nine organisations participated. Overall, participants reported multiple difficulties with data collection, including underreporting, collection of incomplete information and loss to follow-up. The limited number of high-quality data collected, the unknown denominator and the lack of comparator data complicate MAHs’ data processing activities, preventing them to timely provide evidence in the pregnancy label. Three ‘conflicts’ inherent to the specific position of MAHs were identified explaining the difficulties they experience, i.e., 1) mistrust from patients and healthcare professionals (HCPs); 2) MAHs’ legal obligations and regulatory framework; 3) MAHs’ position outside the healthcare context. To overcome these barriers, MAHs suggested that data registration should occur in close collaboration with patients and HCPs, organized within the healthcare context and performed by using a user-friendly system. In conclusion, the reported difficulties and underlying conflicts of MAHs highlight the need for more effective, collaborative data collection strategies to generate new evidence on this topic.

In this paper, we propose a lightweight physical layer aided authentication and key agreement (PL-AKA) protocol in the internet of things (IoT). Conventional evolved packet system AKA (EPS-AKA) used in long-term evolution (LTE) systems may suffer from congestions in core networks by the large signaling overhead as the number of IoT devices increases. Thus, in order to alleviate the overhead, we consider a cross-layer authentication by integrating physical layer approaches to cryptography-based schemes. To demonstrate the feasibility of the PL-AKA, universal software radio peripheral (USRP) based tests are conducted as well as numerical simulations. The proposed scheme shows a significant reduction in signaling overhead compared to the conventional EPS-AKA in both simulation and experiment. Therefore, the proposed lightweight PL-AKA has the potential for practical and efficient implementation of large-scale IoT networks.

During the recent years, there has been a tremendous increase in use of mobile phones which resulted in an increase of the exposure to electromagnetic radiations in our life. Human saliva is considered as a potential source of biomarkers to monitor changes that occur under pathological conditions. The main objective of the current experiment was to determine the effect of mobile phone radiation on general health, electrolytes and salivary function among Islamic University students who use mobile phones. A questionnaire was designed and applied to 167 healthy and 36 deaf female students to select cases whose meeting the inclusion criteria. A total of 103 students who met the inclusion criteria were included to investigate the influence of mobile phone radiations on their general health. For assessment of salivary parameters, a total of 55 students were chosen and classified into three groups. Group I was the control group, which included 17 deaf students who did not use the mobile phone at all. Group II was healthy students who have mobile phone for less than 5 years. Group III was healthy students who have mobile phone for 5 years or more. Descriptive data that included mean, standard deviation, and percentages was calculated for each group. Multiple group comparisons were made by one-way analysis of variance (ANOVA) followed by Tukey test for pairwise comparisons. Categorical data were analyzed by Chi square (χ2) test. For all the tests, a P value of 0.05 or less was considered for statistical significance. The results showed that the participants who use mobile phone had several problems in their health including dry mouth, bad odor from mouth, drooling of saliva, as well as ear and eye pain. The majority of the participants who use mobile phone complained of headache, anxiety, insomnia and forgetfulness as compared to deaf participants. Also, the study showed that there was no significant difference between salivary pH in all tested groups. Regarding to salivary flow rate, the differences were no significant in all tested groups. In addition, this study has also shown that there was significant difference between the salivary Na+ and K+ levels of the three groups. Salivary level of Na+ and K+ were significantly lower in mobile phone users when compared to non users of mobile phone.

Movement disorders can be associated with various drugs and systemic diseases, posing diagnostic challenges for clinicians. This review explores the spectrum of movement disorders associated with pharmacological agents and medical conditions. Drug-induced movement disorders encompass a broad range of conditions resulting from exposure to medications that affect several neurotransmitters. Neuroleptic medications can lead to tardive dyskinesia, characterized by involuntary, repetitive movements. Antipsychotics and antiemetics, including metoclopramide, may induce acute dystonic reactions. Other drugs, such as dopamine receptor-blocking agents, can contribute to drug-induced parkinsonism. Beyond medications, movement disorders can also arise secondary to systemic diseases. Metabolic disorders like Wilson's disease, characterized by copper accumulation, may manifest as chorea or dystonia. Inflammatory conditions such as rheumatoid arthritis and systemic lupus erythematosus can result in secondary movement disorders due to autoimmune-mediated processes affecting the central nervous system. Movement disorders linked to drugs or systemic diseases often necessitate a thorough clinical evaluation, including detailed medication histories and comprehensive systemic assessments. Neuroimaging, laboratory investigations, and, in some cases, cerebrospinal fluid analyses and electrodiagnostic studies help in establishing accurate diagnoses. Management involves addressing the underlying cause, modifying medications, and employing symptomatic treatments.

The lungs of tuberculosis (TB) patients contain a spectrum of granulomatous lesions ranging from solid and well vascularized cellular granulomas, to avascular caseous granulomas. In solid granulomas, current therapy kills actively replicating (AR) intracellular bacilli, while in low vascularized caseous granulomas the low oxygen tension stimulates aerobic and microaerophilic AR bacilli to transit into non-replicating (NR), drug-tolerant, extracellular stages. These stages, which do not have genetic mutations and are often referred to as persisters, are difficult to eradicate due to low drug penetration inside caseum and mycobacterial cell walls. The sputum of TB patients contains also viable bacilli called differentially detectable (DD) cells that, unlike persisters, grow in liquid, but not in solid media. This review provides a comprehensive update on drug combinations killing in vitro AR and drug-tolerant bacilli (persisters and DD cells), and sterilizing Mycobacterium tuberculosis-infected BALB/c and caseum-forming C3HeB/FeJ mice. These observations have been important for testing new drug combinations in noninferiority clinical trials, in order to shorten duration of current regimens against TB. In 2022, the World Health Organization, based on one of this trial, supported the use of a 4-month regimen for treatment of drug-susceptible TB as a possible alternative to the current 6-month regimen.

The release of drugs from core/shell nanoparticles (NPs) is a crucial factor in ensuring high re-producibility, stability, and quality control. It serves as the scientific basis for the development of nanocarriers. Several factors, such as composition, composition ratio, ingredient interactions, and preparation methods, influence the drug release from these carrier systems. The objective of our study was to investigate and discuss the relationship between modifications of core/shell NPs as multifunctional drug delivery systems and the properties and kinetics of drug release using an in vitro drug release model. In this paper, we prepared four core/shell NPs consisting of a super-paramagnetic iron oxide NPs (Fe3-δO4) core encapsulated by a biocompatible thermo-responsive copolymer, poly(2-(2-methoxy) ethyl methacrylate-oligo (ethylene glycol) methacrylate) or P(MEO2MAx-OEGMA100-x) (where x and 100-x represent the molar fractions of MEO2MA and OEGMA, respectively), and loaded with doxorubicin (DOX). Colloidal behavior measurements in water and PBS as a function of temperature showed an optimization of the lower critical solu-tion temperature (LCST) depending on the molar fractions of MEO2MA and OEGMA used to form each NPs. In vitro studies of doxorubicin release as a function of temperature demonstrated a high control of release based on the LCST. A temperature of approximately 45°C for 60 h was sufficient to release 100 % of the DOX loaded in the NPs for each sample. In conclusion, external stimuli can be used to modulate the drug release behavior. Core/shell NPs hold great promise as a technique for multifunctional drug delivery systems.

The multifactorial nature of some diseases, and in particular neurodegenerative diseases such as Alzheimer’s disease, frequently requires the use of several drugs. These drug cocktails are not without drawbacks in terms of increased adverse effects, drug-drug interactions or adherence to treatment. The concept of pleiotropic drugs, which combine, within a single molecule, several activities directed against distinct therapeutic targets, makes it possible to overcome some of these problems. In addition, these pleiotropic drugs, generally, lead to the expression of a synergy of effects, sometimes greater than that observed with a combination of drugs. This article will review, through recent examples, the different kinds of pleiotropic drugs being studied or already present on the market of medicines.

This study proposes an innovative pharmacovigilance approach, VIGI-4, leveraging ChatGPT Teams Pro version. Our method involves aggregating data from all phase 4 studies published in February 2024 to identify adverse reactions. These results are categorized by disease state alphabetically, demonstrating the method's capacity to generate structured and easily navigable outputs. The results section is tailored to exemplify the valuable, actionable insights attainable through our workflow. This research emphasizes the game-changing potential of integrating advanced technologies such as ChatGPT into pharmacovigilance, signaling a new era in safeguarding drug safety.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic presented a new challenge in modern medicine. The development of vaccines was followed by massive population vaccinations. A few reports on post-vaccination allergic reactions have made patients and medical personnel uneasy as to anti-COVID-19 vaccines’ allergising potential. Most of the studies in this area to date have been small, and some that were based on global databases skipped most of the allergic diseases and concentrated only on anaphylaxis. We aimed to analyse the incidence of serious allergic reactions based on the EudraVigilance (EV) database, regardless of the reported symptoms and allergy mechanism. Methods: The total number of administrated vaccine doses was extracted on the 5th October 2023 from Vaccine Tracker and included all administrations since vaccinations began in the European Economic Area (EEA). Data on serious allergic reactions to COVID-19 vaccines was extracted from the EudraVigilance database with the same time point. The code names of 147 allergic symptoms or diseases were used. Results: The frequency of serious allergic reactions per 100,000 administered vaccine doses was 1.53 for Comirnaty, 2.16 for Spikevax, 88.6 for Vaxzevria, 2.11 for Janssen, 7.9 for Novavax, 13.3 for VidPrevtyn Beta and 3.1 for Valneva. The most prevalent reported reactions were oedema (0.46) and anaphylaxis (0.40). Only 6% of these reactions were delayed hypersensitivity-oriented. Conclusions: The overall frequency of potential serious allergic reactions to COVID-19 is very rare. Therefore, COVID-19 vaccines seem to be safe for human use. The lowest frequency of allergic reaction was observed for Comirnaty and the highest for Vaxzevria.

This report provides a comprehensive overview of occupational asthma and respiratory hypersensitivity, focusing on some chemicals used in the workplace Includes numerous case studies and research papers related to occupational exposure methacrylates, such as HEMA-HPMA, and respiratory hypersensitivity are discussed And the relationship is explored The book also examines asthma pathophysiology, emerging drug delivery systems used to treat asthma, and the potential of nanoparticles , dendrimers and micellar systems have to improve pulmonary drug delivery in detail The worldwide prevalence of asthma is highlighted, with higher rates in high-GDP countries. The book highlights the need to improve asthma diagnosis, treatment and biomarkers, particularly in rural and low-income countries where the disease is often underdiagnosed and inadequately treated, and discusses the role of inflammation in asthma, in particular secondary inflammation characterized by specific cytokines and inflammation cells In addition, the paper explores various drug delivery methods, such as parenteral and parenteral drugs, pressurized inhalers (pMDIs), dry powder inhalers ( DPIs), nebulizers, nanoparticles, liposomes, micellar systems, microparticles , dendrimers, and gene therapy . These systems aim to increase pulmonary delivery of drugs and improve clinical outcomes. The potential of dendrimer bilirubin-based nanoparticles and micellar systems in the treatment of asthma and lung inflammatory diseases, including asthma, has been discussed in summary, this paper provides an overview of occupational asthma and respiratory hypersensitivity, and this discussion highlights the association between methacrylate exposure and respiratory hypersensitivity.

Animal trypanosomiasis (AT) is a complex of veterinary diseases known under various names such as nagana, surra, dourine and mal de caderas, depending on the country, the infecting trypanosome species and the host. AT is caused by parasites of the genus Trypanosoma, and the main species infecting domesticated animals are T. brucei brucei, T. b. rhodesiense, T. congolense, T. vivax, T. evansi and T. equiperdum. AT transmission, again depending on species, is through tsetse flies or common Stomoxys and tabanid flies or through copulation. Therefore, the geographical spread of all forms of AT together is not restricted to the habitat of a single vector like the tsetse fly and currently includes almost all of Africa, and most of South America and Asia. The disease is a threat to millions of companion and farm animals in these regions, creating a financial burden in the billions of dollars to developing economies as well as serious impacts on livestock rearing and food production. Despite the scale of these impacts, control of AT is neglected and under-resourced, with diagnosis and treatments being woefully inadequate and not improving for decades. As a result, neither the incidence of the disease, nor the effectiveness of treatment is documented in most endemic countries, although it is clear that there are serious issues of resistance to the few old drugs that are available. In this review we particularly look at the drugs, their application to the various forms of AT, and their mechanisms of action and resistance. We also discuss the spread of veterinary trypanocide resistance and its drivers, and highlight current and future strategies to combat it.

Intermolecular interactions are the fabrics underlying almost all processes in living organisms, where two cornerstone concepts, intermolecular binding affinity (K d ) and binding energy (ΔG), have long been established to physically describe the strengths of biomolecular interactions, e.g., drug-target K d and ΔG to describe the strength of drug-target interaction. The past two-three years saw a big step forward in the use of artificial intelligence (AI) in structural biology (e.g., AlphaFold for protein structure prediction) and drug discovery & design. In light of the roles of K d and ΔG in drug discovery & design, the speed of this AI progress raises a question of what’s next for its practical application in the pharmaceutical industry, in addition to a system-wide account of biomolecular structures and motions. Last August, the concept of a general intermolecular binding affinity calculator (GIBAC) was for the first time coined and proposed in an MDPI-published preprint. Here, this article puts forward an updated conceptual and practical framework of GIBAC, including its inception, definition, construction, practical applications, technical challenges and limitations, and future directions. Moreover, this article argues that the time is now ripe for the construction of such an accurate, precise and efficient GIBAC to be on the agenda of the entire drug discovery & design community, to ensure its applicability & reliability, and to enhance its value in drug R&D in future.