Target System Research Articles

Open LEARN: Open access linear accelerator education and augmented reality Navigator

PurposeTo create an open-access Linear Accelerator Education and Augmented Reality Navigator (Open LEARN) via 3D printable objects and interactive augmented reality assets. MethodsThis study describes an augmented reality linear accelerator (linac) model accessible through a QR code and a smartphone to address the challenges of medical physics and radiation oncology trainees in low-to-middle-income countries. ResultsMajor components of a generic linear accelerator are modeled as individual objects. These objects can be 3D printed for hands-on learning and used as interactive 3D assets within the augmented reality app. In the AR app, descriptions are displayed to navigate the components spatially and textually. Items modeled include the treatment couch, klystron, circulator, RF waveguides, electron gun, waveguide, beam steering assemblies, target, collimators, multi-leaf collimators, and imaging systems. The linear accelerator is rendered at nearly 100% of its actual size, allowing users to change magnification and view objects from different angles. ConclusionsThe augmented reality linear accelerators and 3D-printed objects make these complex machines easily accessible with smartphones and 3D-printing technologies, facilitating education and training through physical and virtual interaction.

Interactive probes: Towards action-level evaluation for dialogue systems

Measures of ‘humanness’, ‘coherence’ or ‘fluency’ are the mainstay of dialogue system evaluation, but they don’t target system capabilities and rarely offer actionable feedback. Reviewing recent work in this domain, we identify an opportunity for evaluation at the level of action sequences, rather than the more commonly targeted levels of whole conversations or single responses. We introduce interactive probes, an evaluation framework inspired by empirical work on social interaction that can help to systematically probe the capabilities of dialogue systems. We sketch some first probes in the domains of tellings and repair, two sequence types ubiquitous in human interaction and challenging for dialogue systems. We argue interactive probing can offer the requisite flexibility to keep up with developments in interactive language technologies and do justice to the open-endedness of action formation and ascription in interaction.

Theoretical study on precise regulation of ESIPT reaction based on ICT effect of o-carborane derivatives

The unique stereocarborane fluorophore design has attracted widespread attention because of its ability to effectively enhance the performance of thin-film fluorescence sensors. This study provides a detailed theoretical investigation of the excited-state intramolecular proton transfer (ESIPT) reactions of three o-carborane derivatives, NaCBO, PaCBO and PyCBO, using density functional theory and time-dependent density functional theory. We found that as the number of benzene rings in the electron donor groups increases, the interaction between the first excited-state electron donor–acceptor fragments is enhanced, weakening the intramolecular hydrogen bonding strength, which in turn inhibits the ESIPT. Notice that the intramolecular charge transfer (ICT) is proportional to the interaction between electron donor and acceptor fragments with the analysis of electron structure. The higher the ICT level of the target system, the more unstable the keto form generated by ESIPT. Therefore, the ESIPT can be precisely manipulated by rationally adjusting the ICT effect. Furthermore, with increasing solvent polarity, the photophysical properties of the chromophores exhibit non-solvatochromism. This is attributed to the rigid o-carborane structure, which serves as a spatial scaffold to increase the adaptability of the molecule to the environment. This study is expected to provide theoretical guidance and new ideas for preparing high-performance thin-film fluorescence sensing.

Using Hardware Events to Detect Side-Channel Attacks

The article discusses the monitoring system being developed by authors for the detection of Side-Channel Attacks, SCA. The theoretical justification of the chosen method of detecting SCA attacks is given: analysis of hardware events of the target system. The architecture of the monitoring system is described, including low-level data collection processes and an expert system that analyzes the collected data. The results of the proof-of-concept on various classes of SCA-attacks are presented. The paper considers a class of attacks on side-channels that use the processor cache to obtain secret information. A method of countering attacks of this class based on the use of a hardware event mechanism is proposed. As a result of the analysis of existing hardware events, predicates have been built for the Intel architecture, allowing one to identify the suspicious behavior of programs in the Linux OS environment. To test the proposed method, a prototype monitoring system was implemented that successfully coped with the detection of simulated SCA-attacks. The advantages and disadvantages of this method are considered, and the direction of further research is indicated.

Synthesis, Hemolytic Activity, and In Silico Studies of New Bile Acid Dimers Connected with a 1,2,3-Triazole Ring.

The synthesis of bile acid conjugates plays a significant role in pharmacology and organic chemistry. These complex compounds are widely studied due to their potential therapeutic applications (e.g., drug carriers or antibacterial agents) and their impact on interactions with biological target systems. It is important to determine the biological activity of the obtained conjugates with potential pharmacological applications. The research aimed to synthesize acyl conjugates of bile acids, determine the influence of acyl groups on potential antibacterial activity and evaluate the impact of conjugation on hemolytic activity. New acetyl bile acid acetyl dimers were synthesized using the "Click Chemistry" reaction, aiming to investigate their hemolytic and antibacterial activity. The structures of all compounds were confirmed through spectral analysis techniques, including 1H and 13C nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), and electrospray ionization-mass spectrometry (ESI-MS). The PM5 semiempirical method was also used to estimate the heat of formation of individual conjugates, and the prediction of activity spectra for substances (PASS) technique was used to determine the pharmacokinetic potential of compounds. Docking studies indicate that obtained conjugates have the potential ability to inhibit the biosynthesis of Lipid II and block DNA gyrase. These compounds can therefore be treated as potential candidates for antibacterial compounds. Research findings suggest that conjugating bile acids and their derivatives through 1,2,3-triazole ring, results in final products with reduced hemolytic activity.

Non-collocated control of an anti-stable system of coupled strings under delayed displacements/velocities feedback

In this paper, we consider the non-collocated stabilization of three coupled wave equations with different speeds and joint anti-dampings. These anti-dampings put all eigenvalues of the system in the right complex plane. By designing two invertible transformations, the wave system is converted into an equivalent system with damping terms at the joint points. The feedback controllers with displacements/velocities are designed to obtain the target system. The well-posedness and exponential stability of the closed-loop system are established using the PDE approach, based on the exponential stability of the target system. Simulation results are presented to verify the effectiveness of the feedback control law.

From Conventional to Cutting-edge: A Comprehensive Review on Drug Delivery Systems

: The essential need for efficacious conveyance of therapeutics to specific tissues or cells, refinement of drug formulations, and the scalability of industrial production drives the pre-sent-day demand for enhanced drug delivery systems (DDS). Newly devised drugs often exhibit suboptimal biopharmaceutical properties, resulting in diminished patient adherence and adverse side effects. The paramount importance of site-specific drug delivery lies in its capacity to facili-tate the targeted administration of diverse therapeutic agents, catering to both localized ailments and systemic treatments. Alongside targeted drug delivery strategies encompassing ligand-based targeting and stimuli-responsive systems, the advent of cutting-edge nanotechnologies such as nanoparticles, liposomes, and micelles has marked a paradigm shift. Additionally, personalized medicines have emerged as a consequential facet of drug delivery, emphasizing the customization of treatment approaches. Researchers have explored an excess of methodologies in the advance-ment of these formulation technologies, including stimuli-responsive drug delivery, 3D printing, gene delivery, and various other innovative approaches. This comprehensive review aims to pro-vide a holistic understanding of the past, present, and future of drug delivery systems, offering in-sights into the transformative potential of emerging technologies.

Initial Clinical Experience With a Novel Robotically Assisted Platform for Combined Mini-Percutaneous Nephrolithotomy and Flexible Ureteroscopic Lithotripsy.

We sought to evaluate the technical feasibility of performing a combined robotically assisted mini-percutaneous nephrolithotomy (PCNL) and flexible ureteroscopy (URS) procedure by a single urologist using the MONARCH Platform, Urology (Johnson & Johnson MedTech, Redwood City, California). In this prospective, first-in-human clinical trial, 13 patients underwent robotically-assisted PCNL for renal calculi at the University of California-Irvine, Department of Urology. Successful completion of the procedure was assessed as the primary endpoint. Postoperative adverse events were monitored for 30 days following the completion of the procedure. Stone ablation efficiency was evaluated on postoperative day 30 with low-dose 2-3 mm slice CT scans. Patients were classified according to the maximum length of their residual stone fragments as either absolute stone-free (Grade A), < 2 mm remnants (Grade B), or 2.1-4.0 mm remnants (Grade C). The combined robotic mini-PCNL and URS procedure was successfully completed in 12 of 13 procedures. No robotic device-related adverse events occurred. Preoperative stone burden was quantified by both maximum linear measurement (median 32.8 mm) as well as by CT-based volume (median 1645.9 mm3). Using the unique robotically assisted targeting system, percutaneous access was gained directly through the center of the renal papilla in a single pass in all cases. Median operative time was 187 minutes (range: 83-383 minutes). On postoperative day 30, a 98.7% (range: 72.9%-100.0%) volume reduction was achieved, with 5 Grade A (38.5%), 1 Grade B (7.7%), and 2 Grade C (15.4%). Three patients experienced complications (2 grade 1 and one grade 2 Clavien-Dindo). Our preliminary investigation demonstrates the safety, efficacy, and feasibility of a unique robotic-assisted combined mini-PCNL and URS platform.

Sustainability in occupational dermatology : Starting points, challenges, and potentials for sustainable care of work-related skin diseases

Sustainability is becoming increasingly important in healthcare and has moved into focus at various levels. This article aims to provide an overview of guiding principles, concepts, and target systems of sustainability and to transfer these to occupational dermatology. Current and future starting points are outlined for various levels, e.g., politics, research, industry, and patient care, in order to link sustainability and occupational dermatology in astructured and systematic way and to transform the structures of patient care in occupational dermatology care towards sustainability. Using the specific example of protective gloves, which is apivotal personal protective measure to prevent work-related hand eczema, starting points, potentials, and challenges are analyzed and specific possibilities and perspectives for more ecologically sustainable action are presented.

An efficient gene targeting system using Δku80 and functional analysis of Cyp51A in Trichophyton rubrum

Trichophyton rubrum is one of the most frequently isolated fungi in patients with dermatophytosis. Despite its clinical significance, the molecular mechanisms of drug resistance and pathogenicity of T. rubrum remain to be elucidated because of the lack of genetic tools, such as efficient gene targeting systems. In this study, we generated a T. rubrum strain that lacks the nonhomologous end-joining-related gene ku80 (Δku80) and then developed a highly efficient genetic recombination system with gene targeting efficiency that was 46 times higher than that using the wild-type strain. Cyp51A and Cyp51B are 14-α-lanosterol demethylase isozymes in T. rubrum that promote ergosterol biosynthesis and are the targets of azole antifungal drugs. The expression of cyp51A mRNA was induced by the addition of the azole antifungal drug efinaconazole, whereas no such induction was detected for cyp51B, suggesting that Cyp51A functions as an azole-responsive Cyp51 isozyme. To explore the contribution of Cyp51A to susceptibility to azole drugs, the neomycin phosphotransferase (nptII) gene cassette was inserted into the cyp51A 3′-untranslated region of Δku80 to destabilize the mRNA of cyp51A. In this mutant, the induction of cyp51A mRNA expression by efinaconazole was diminished. The minimum inhibitory concentration for several azole drugs of this strain was reduced, suggesting that dermatophyte Cyp51A contributes to the tolerance for azole drugs. These findings suggest that an efficient gene targeting system using Δku80 in T. rubrum is applicable for analyzing genes encoding drug targets.

An improved histogram algorithm for DOA estimation based on single vector acoustic system

The integration of a singular vector acoustic system onto an unmanned underwater platform can lead to achieving unambiguous direction finding across the entire space. To enhance the direction-finding capabilities of the single vector acoustic system for low noise target, a refined histogram algorithm utilizing coherent spectrum weighting is suggested. A comparative evaluation and analysis of the target azimuth estimation performance of the enhanced histogram algorithm, traditional frequency-weighted histogram algorithm, and energy-weighted histogram algorithm are carried out. Through computer simulations, it is observed that the three Direction of Arrival (DOA) algorithms exhibit comparable direction-finding capabilities for wideband signals, whereas for single-frequency signals, the improved histogram algorithm surpasses the two conventional algorithms in direction-finding accuracy. Specifically, at a signal-to-noise ratio (SNR) of −40 dB, the azimuth estimation root mean square error (RMSE) is approximately 2°. Findings from sea trials indicate that the improved histogram algorithm displays a narrower spectral peak width and robust resistance to noise interference, thereby substantiating the effectiveness of the enhanced histogram algorithm.

Simulating polarization characteristics of arbitrary-layer target systems’ infrared radiation by photon tracing strategy

It remains a big challenge to simulate and perceive polarization characteristics of coated targets’ infrared radiations, especially for the targets coated with several layers. In this paper, an arbitrary-layer radiational target system model (ARTSmodel) is constructed based on photon trace strategy (PTS) and Monte Carlo algorithm (MCA) to resolve this problem by continually tracing the evolution of the radiating photons’ state of polarization (SoP). In the proposed ARTSmodel, multiple scattering events among different coat layers are well represented, and the wide-band property of the radiations is accounted as well. Additionally, the infrared radiations are regarded as photon packages, and continually traced until they leave the topmost layer and get captured by the sensors bestrewing the entirely upper hemisphere space, whose values will form an upper-hemisphere-space polarization data (UPD) distribution. The UPD is compared with the analytic method and empirical data, and the consistency of results evidences the effectiveness and reliability of the proposed model. Moreover, the UPD and its representation in the Poincare sphere demonstrate that the proposed model provides a new and practicable way to coated target identification and analysis.

Structure of a truncated human GlcNAc-1-phosphotransferase variant reveals the basis for its hyperactivity

Mutations that cause loss of function of GlcNAc-1-phosphotransferase (PTase) lead to the lysosomal storage disorder mucolipidosis II. PTase is the key enzyme of the mannose 6-phosphate (M6P) targeting system that is responsible for tagging lysosomal hydrolases with the M6P moiety for their delivery to the lysosome. We had previously generated a truncated hyperactive form of PTase termed S1S3 which was shown to notably increase the phosphorylation level of secreted lysosomal enzymes and enhance their uptake by cells. Here, we report the 3.4Å cryo-EM structure of soluble S1S3 lacking both transmembrane domains and cytosolic tails. The structure reveals a high degree of conservation of the catalytic core to full-length PTase. In this dimeric structure, the EF-hand of one protomer is observed interacting with the conserved region four of the other. In addition, we present a high-quality EM 3D map of the UDP-GlcNAc bound form of the full-length soluble protein showing the key molecular interactions between the nucleotide sugar donor and side chain amino acids of the protein. Finally, although the domain organization of S1S3 is very similar to that of the Drosophila melanogaster (fruit fly) PTase homolog, we establish that the latter does not act on lysosomal hydrolases.

Laser-assisted bioprinting of targeted cartilaginous spheroids for high density bottom-up tissue engineering

Multicellular spheroids such as microtissues and organoids have demonstrated great potential for tissue engineering applications in recent years as these 3D cellular units enable improved cell-cell and cell-matrix interactions. Current bioprinting processes that use multicellular spheroids as building blocks have demonstrated limited control on post printing distribution of cell spheroids or moderate throughput and printing efficiency. In this work, we presented a laser-assisted bioprinting approach able to transfer multicellular spheroids as building blocks for larger tissue structures. Cartilaginous multicellular spheroids formed by human periosteum derived cells (hPDCs) were successfully bioprinted possessing high viability and the capacity to undergo chondrogenic differentiation post printing. Smaller hPDC spheroids with diameters ranging from ∼100 to 150µm were successfully bioprinted through the use of laser-induced forward transfer method (LIFT) however larger spheroids constituted a challenge. For this reason a novel alternative approach was developed termed as laser induced propulsion of mesoscopic objects (LIPMO) whereby we were able to bioprint spheroids of up to 300µm. Moreover, we combined the bioprinting process with computer aided image analysis demonstrating the capacity to 'target and shoot', through automated selection, multiple large spheroids in a single sequence. By taking advantage of target and shoot system, multilayered constructs containing high density cell spheroids were fabricated.

Decision-making based on Markov decision process in integrated artificial reasoning framework—Part I: Theory

This paper presents a decision-making framework based on an integrated artificial reasoning framework and Markov decision process (MDP). The integrated artificial reasoning framework provides a physics-based approach that converts system information into state transition models, and the analysis result will be represented by the transition probabilities that can be used with an MDP to find a traceable and explainable optimal pathway. A dynamic Bayesian network (DBN) is well suited for representing the structure of an MDP. The causality information among process variables (or among subsystems) is mathematically represented in a DBN by the conditional probabilities of the node’s states provided different probabilities of the parent node’s states. To define node states in a physically understandable manner, we used multilevel flow modeling (MFM). An MFM follows the fundamental energy and mass conservation laws and supports the selection of process variables that represent the system of interest so that causal relations among process variables are properly captured. An MFM-based DBN supports developing state transition models in an MDP to capture the effect of process variables of system having physical relations. The operators of the target system can capture stochastic system dynamics as multiple subsystem state transitions based on their physical relations and uncertainties coming from component degradation or random failures. We analyzed a simplified exemplary system to illustrate an optimal operational policy using the suggested approach.

Multifunctional Iron Oxide Nanoparticles as Promising Magnetic Biomaterials in Drug Delivery: A Review.

A wide range of applications using functionalized magnetic nanoparticles (MNPs) in biomedical applications, such as in biomedicine as well as in biotechnology, have been extensively expanding over the last years. Their potential is tremendous in delivery and targeting systems due to their advantages in biosubstance binding. By applying magnetic materials-based biomaterials to different organic polymers, highly advanced multifunctional bio-composites with high specificity, efficiency, and optimal bioavailability are designed and implemented in various bio-applications. In modern drug delivery, the importance of a successful therapy depends on the proper targeting of loaded bioactive components to specific sites in the body. MNPs are nanocarrier-based systems that are magnetically guided to specific regions using an external magnetic field. Therefore, MNPs are an excellent tool for different biomedical applications, in the form of imaging agents, sensors, drug delivery targets/vehicles, and diagnostic tools in managing disease therapy. A great contribution was made to improve engineering skills in surgical diagnosis, therapy, and treatment, while the advantages and applicability of MNPs have opened up a large scope of studies. This review highlights MNPs and their synthesis strategies, followed by surface functionalization techniques, which makes them promising magnetic biomaterials in biomedicine, with special emphasis on drug delivery. Mechanism of the delivery system with key factors affecting the drug delivery efficiency using MNPs are discussed, considering their toxicity and limitations as well.

Domain-Agnostic Representation of Side-Channels.

Side channels are unintended pathways within target systems that leak internal target information. Side-channel sensing (SCS) is the process of exploiting side channels to extract embedded target information. SCS is well established within the cybersecurity (CYB) domain, and has recently been proposed for medical diagnostics and monitoring (MDM). Remaining unrecognised is its applicability to human-computer interaction (HCI), among other domains (Misc). This article analyses literature demonstrating SCS examples across the MDM, HCI, Misc, and CYB domains. Despite their diversity, established fields of advanced sensing and signal processing underlie each example, enabling the unification of these currently otherwise isolated domains. Identified themes are collating under a proposed domain-agnostic SCS framework. This SCS framework enables a formalised and systematic approach to studying, detecting, and exploiting of side channels both within and between domains. Opportunities exist for modelling SCS as data structures, allowing for computation irrespective of domain. Future methodologies can take such data structures to enable cross- and intra-domain transferability of extraction techniques, perform side-channel leakage detection, and discover new side channels within target systems.

Identifying Target Molecule and Trace Amount of the Byproduct by Two-Dimensional Self-Assembly with Different Solution Concentrations.

Scanning tunneling microscopy (STM) is a powerful way to realize the recognition of self-assembled nanostructures on the atomic scale. In this article, dihexadecyl 6,9-bis((4-(hexadecyloxy)phenyl)ethynyl) phenanthro[9,10-c]thiophene-1,3-dicarboxylate (D-PT) and dihexadecyl 6-bromo-9-((4-(hexadecyloxy) phenyl)ethynyl)phenanthrol[9,10-c]thiophene-1,3-dicarboxylate (S-BrPT) with different substituents were chosen as the target system. D-PT with four side chains as the target molecule and S-BrPT with three side chains and a bromine substituent as the byproduct were mixed in a molar concentration ratio of 20:1. The effect of solution concentration on the molecular self-assembly of the mixture was investigated by STM at the hexadecane/HOPG interface. At high concentrations, only D-PT molecules formed a dimer pattern resulting from the intermolecular van der Waals force and self-adaption. Further diluting the solution, D-PT formed the coexisting dimer and linear structures, in which the linear pattern was formed via solvent coadsorption. At low concentrations, S-BrPT molecules forming N-shaped dimers appeared and filled the linear structure fabricated by D-PT molecules. With further decrease in the concentration, S-BrPT molecules formed N-shaped dimers covering almost half of the surface area, resulting from the C-Br···π and Br···H-C bonds. At very low concentrations, S-BrPT molecules formed N-shaped dimers to arrange the matrix architecture due to the coadsorption of more hexadecane molecules. Density functional theory (DFT) calculations demonstrated that the stronger intermolecular C-Br···π and Br···H-C bonds were significant factors in determining the formation of N-shaped dimers and the stability of this nanostructure. This work enriches the diversity of self-assembled motifs and provides a strategy to characterize different symmetric molecules with trace amounts in a mixed system by STM.

A Comprehensive Review on the Nanotechnology-based Intranasal Drug Delivery Systems for Brain Targeting

A Comprehensive Review on the Nanotechnology-based Intranasal Drug Delivery Systems for Brain Targeting

Robust anti-disturbance interval type-2 fuzzy control for interconnected nonlinear PDE systems via conjunct observer

This paper investigates a robust anti-disturbance interval type-2 (IT2) fuzzy control for interconnected nonlinear partial differential equation (PDE) systems subject to parameter uncertainties by the conjunct observer. First, an IT2 fuzzy model is adopted to remodel the target system. Second, a state observer with mismatched premise variables is constructed to solve the problem that the original system and the observer do not share a uniform premise variable. Moreover, a disturbance observer is designed to estimate the unknown external disturbances, which can be modeled by exogenous PDE systems. Then, utilizing the conjunct observation information, an anti-disturbance IT2 fuzzy control strategy is proposed to attenuate the effect of disturbances on the system performance while ensuring that the closed-loop system is stable. Finally, simulation results verify the effectiveness of the proposed method.