Single Form Research Articles

Pharmacokinetics behavior of four cannabidiol preparations following single oral administration in dogs.

Cannabidiol (CBD) is a natural phytochemical agent and one of the most abundant found in Cannabis sativa. It is known to exhibit pharmacological properties on various condition such as relieving-inflammation, pain, epilepsy, and anxiety effect. There has been an increasing trend globally in the use of CBD as a supplement in pets. Consequently, there are various CBD products being marketed that are specifically available for pets. Veterinarians and pet owners are concerned that following ingestion, different CBD formulations may result in a CBD level circulating in the blood that may affect the safe use and efficacy of CBD in pets. Several pharmacokinetics studies in animals have been mainly conducted with an oily form of CBD. To date, there is a lack of data regarding direct comparisons in animals among the CBD plasma kinetic profiles from an oral administration of the various preparation forms. Therefore, the current study evaluated and compared the plasma CBD levels from a single oral administration using four different CBD preparations-liquid (an oil-based form, a nanoemulsion form, or a water-soluble form) or a semi-solid form (as CBD mixed in a treat) in dogs. In total, 32 healthy, crossbreed dogs were randomly assigned into 4 groups and treated according to a 1-period, 4-treatment parallel-design. The three liquid forms were dosed at 5 mg/kg body weight, while the single semi-solid form was given at 50 mg/treat/dog. The results showed that the CBD plasma profile from the administration of a water-soluble form was comparable to that of the oil-based group. The nanoemulsion-based form tended to be rapidly absorbed and reached its peak sooner than the others. However, the CBD in all preparations reached the maximum plasma concentration within 3 h post-dose, with an average range of 92-314 μg/L. There were significant differences among certain parameters between the liquid and semi-solid forms. This was the first study to provide pharmacokinetics data regarding CBD in water soluble, nanoemulsion-based, and semi-solid forms for dogs as companion animals. The current data should facilitate the scrutiny of CBD plasma profiles based on different formulations via an oral route in dogs.

Springback prediction using point series and deep learning

One of the main challenges that prevent wide adoption of Single Point Incremental Forming (SPIF) is the geometric accuracy of the process resulting primarily from the effect of springback. There are various expedients that can be adopted to address this, but one of the most common is tool path correction. The challenge is then how best to predict springback so as to implement tool path correction. It is established that springback, to a large extent, is related to the geometry of the part to be manufactured. The proposed mechanism uses a novel point series representation to capture local geometries that then form a global bank of geometries for general use. Each point series can then be associated with a predicted springback value generated using deep or machine learning. Experiments are reported using a Long Short Term Memory (LSTM) model coupled with a Multilayer Perception Network (MLP), and a Support Vector Machine (SVM) regression model. A best R2, “Coefficient of Determination”, of 0.9181 was obtained indicating that the proposed approach provided a realistic solution to the current limitations of SPIF.

Simple formulation of no-cloning and no-hiding that admits efficient and robust verification

Incompatibility is a feature of quantum theory that sets it apart from classical theory, and the inability to clone an unknown quantum state is one of the most fundamental instances. The no-hiding theorem is another such instance that arises in the context of the black-hole information paradox, and can be viewed as being dual to no-cloning. Here, we formulate both of these fundamental features of quantum theory in a single form that is amenable to efficient verification, and that is robust to errors arising in state preparation and measurements. We extend the notion of unitarity—an average figure of merit that for quantum theory captures the coherence of a quantum channel—to general physical theories. Then, we introduce the notion of compatible unitarity pair (CUP) sets, that correspond to the allowed values of unitarities for compatible channels in the theory. We show that a CUP set constitutes a simple “fingerprint” of a physical theory, and that incompatibility can be studied through them. We derive information-disturbance constraints on quantum CUP sets that encode both the no-cloning/broadcasting and no-hiding theorems of quantum theory. We then develop randomized benchmarking protocols that efficiently estimate quantum CUP sets and provide simulations using IBMQ of the simplest instance. Finally, we discuss ways in which CUP sets and quantum no-go theorems could provide additional information to benchmark quantum devices. Published by the American Physical Society 2024

Multi-modal fusion network guided by prior knowledge for 3D CAD model recognition

Currently, the 3D CAD model has found extensive use in various applications. The more accurate recognition and more reliable reuse of 3D computer-aided design (CAD) models could significantly save labor costs and time in the production and design of 3D products. However, existing 3D model recognition methods are constrained by a single representation form that lacks supplementary information from multiple sources, and there is a lack of corresponding guidance for relationships between different data. In this paper, we focus on multi-modal information for 3D model representation and propose a Multi-modal Fusion Network (MMFN) guided by prior knowledge for 3D CAD model recognition. In particular, we consider prior knowledge about the class distribution of 3D models: The designed labeling information is utilized as the prior knowledge to guide the multi-modal information fusion via the cross-attention structure. Then, the contrastive learning method is utilized in the optimization step, further increasing the aggregation of similar samples and contributing to enhancing the discriminative capability of features. Finally, we conduct extensive experiments on the public datasets, ModelNet, ShapeNet, and a challenging industrial 3D CAD dataset built by ourselves. Compared to state-of-the-art approaches, our MMFN provides competitive results. The source code has been published on Github: https://github.com/WhiteTJU/MMFN.

Direct Single Crystal to Amorphous Transformation and Memory Effect in AlPO4-17.

Pressure induced amorphization provides a distinct route to prepare novel amorphous materials. Single crystals of the porous aluminophosphate AlPO4-17 directly transform to an amorphous state beginning at 0.6 GPa, without fragmentation into polycrystalline material. Apart from a reduction in dimensions, the amorphous material retains the form of the initial single crystal. Remnant crystalline domains in the amorphous material also preserve the initial orientation of the single crystal. X-ray diffraction indicates the compression of the structure around the empty pores in the xy plane and such an amorphization mechanism is consistent with a direct structural relationship between the single crystal and amorphous forms. The collapse of the initial pore volume is almost complete at 2.5 GPa. A memory effect is observed in the amorphous form, which strongly expands on decompression. The present process opens the way for the synthesis of topologically ordered amorphous materials approaching "perfect glasses" with improved mechanical properties.

Research on Detection System of Intelligent Computer Optimization Algorithm for Concrete Mix Ratio Based on Big Data

PLC is used to complete the control function of the concrete proportioning system. The MCGS (Configuration Software Monitor and Control System) is used to realize the real-time monitoring, data management and fault warning of the whole monitoring system. The material feed and PLC control process in the feed system are emphatically introduced. A concrete proportioning design method based on multiple parameters is proposed. The nonlinear multi-objective optimization model of concrete mix ratio was established by stepwise regression analysis and complex optimization method. The problems of narrow range of variables and single form of objective and constraint in traditional linear optimization methods are solved, which makes the selection of optimal index simpler and more flexible. Through the calculation of examples, it is clear that this method can obtain the mixture that meets the use conditions, and can greatly save the experimental work and construction cost.

Performance Analysis of Multi-Point Incremental Forming Tool using Martensitic AISI 420 Sheet Metals

Incremental Sheet metal Forming (ISF) Process is a suitable process which helps to produce various parts used in automotive sector by rapid prototyping. This method of producing a prototype helps industry in reducing the production cost. In ISF process, a final product is evolved through local deformation of the sheet metal made by the tool. Usually better formability is obtained when the tool makes a better contact with the sheet metal throughout the process. Improved formability elevates dimensional accuracy of the product, thus increases the market value of the product. A new tool with multiple ball ends capable of making multiple mating points over sheet metal was used in this research to enhance the efficiency of formability and surface finish. Ability of the new Multi-Point Incremental Forming Tool (MPIF) was investigated and compared to the existing Single Point Forming Tool (SPIF) based on the formability and surface finish. Forming Limit Diagram (FLD), Strain Distribution (SD) and Scanning Electron Microscope (SEM) were used to examine the formability of the sheet metal. The SEM & 3D-Surface roughness profilometer were used to observe the sheet metals surface finish. In addition to these experimental techniques a simulation results were also used to predict the stress and strain rate during forming process. The experimentation and simulation outcome shows that the MPIF provides superior formability and surface finish.

Chiral separation of D,L‐phenylglycine by cellulose triacetate membranes

AbstractEnantiopure pharmaceuticals are especially important in medicinal applications. Phenylglycine, as a critical pharmaceutical intermediate, is often utilized in single enantiomeric form for drug synthesis. Chiral membrane separation offers advantages such as simple operation, low energy consumption, and scalability, holding great potential for chiral drug separations. In this work, cellulose triacetate (CTA) membranes are prepared via phase inversion and used for permeation experiments driven by a concentration gradient to investigate selective permeation of D,L‐phenylglycine solutions. Scanning electron microscopy reveals surface and cross‐sectional morphologies of the fabricated membranes. After single‐factor optimization, the CTA membrane exhibits an enantiomeric excess of 68.94% for D,L‐phenylglycine separation. The membrane maintains its selective permeation capability after repeated use. This indicates the CTA membrane has favorable chiral selective permeation for D,L‐phenylglycine solutions with stable performance. The chiral carbon on the six‐membered ring of the CTA backbone, as well as the single‐handed helical structure of the backbone, are thought to be responsible for the chiral selectivity of the membrane. This is the first report of using CTA membranes for chiral amino acid separation, providing experimental references and theoretical basis for membrane separation of racemic mixtures. It could facilitate scalable applications of chiral membranes.

Unified approach to artificial compressibility and local low Mach number preconditioning

This paper presents a unified approach to artificial compressibility and local low Mach number preconditioning methods. The numerical formulation is presented, which provides a seamless transition between incompressible and compressible systems. A single preconditioner that can act as the artificial compressibility or the local preconditioning under a given Mach number condition is derived. An artificial compressibility method is proposed for the unified system. The unified preconditioner is applied to the upwind approach, Roe's approximate Riemann solver, and the JST artificial dissipation approach. A Roe average, which can be applied to the unified systems in a single form is derived. The preconditioning matrix is applied to a single solver to analyze problems ranging from incompressible fluid flows to compressible flows with shocks.

In vivo validation of highly customized cranial Ti-6AL-4V ELI prostheses fabricated through incremental forming and superplastic forming: an ovine model study

Cranial reconstructions are essential for restoring both function and aesthetics in patients with craniofacial deformities or traumatic injuries. Titanium prostheses have gained popularity due to their biocompatibility, strength, and corrosion resistance. The use of Superplastic Forming (SPF) and Single Point Incremental Forming (SPIF) techniques to create titanium prostheses, specifically designed for cranial reconstructions was investigated in an ovine model through microtomographic and histomorphometric analyses. The results obtained from the explanted specimens revealed significant variations in bone volume, trabecular thickness, spacing, and number across different regions of interest (VOIs or ROIs). Those regions next to the center of the cranial defect exhibited the most immature bone, characterized by higher porosity, decreased trabecular thickness, and wider trabecular spacing. Dynamic histomorphometry demonstrated differences in the mineralizing surface to bone surface ratio (MS/BS) and mineral apposition rate (MAR) depending on the timing of fluorochrome administration. A layer of connective tissue separated the prosthesis and the bone tissue. Overall, the study provided validation for the use of cranial prostheses made using SPF and SPIF techniques, offering insights into the processes of bone formation and remodeling in the implanted ovine model.

Complementary operation based sizing and scheduling strategy for hybrid hydro-PV-wind generation systems connected to long-distance transmission lines

Wind and solar power are expected to play important roles in many countries to achieve carbon neutrality; however, their inherent instabilities pose significant threats to existing power grids. Because hydropower has been recognized as a viable compensatory resource for solar and wind energy uncertainties, many studies have sought to determine optimal scheduling strategies for hydro-PV, hydro-wind, and hydro-PV-wind systems. However, few studies have simultaneously considered the sizing and scheduling of large-scale hydro-PV-wind hybrid systems connected to long-distance transmission lines. Therefore, this paper develops a mathematical metric to measure the wind and solar output complementarity and incorporates it into a multi-objective sizing and scheduling model for a hybrid hydro-PV-wind system, in which resource complementarity, profit generation, system reliability, and power curtailment trade-offs are concurrently considered. The ɛ-constraint method is employed and decision makers’ attitude parameters are introduced to transform the proposed model into its equivalent single objective form. A case study in China reveals that the maximum wind and solar power output complementarity rate can be at least 0.19 for the studied hybrid hydro-PV-wind system. The incorporation of wind enables the hybrid hydro-PV-wind system to provide 4.11% more load than a hydro-PV system. In addition, if 2% of power curtailment is permitted, 1.53% more load can be served and 14.9% higher profits can be earned. To better explore the application of hybrid systems, management recommendations are provided for system operators, the power industry, and management administrations.

Current Status of Cognition and Clinical Practice of Refractory Cancer Pain in Shanghai: A Questionnaire Survey.

This study aimed to assess the current status of clinical practice of refractory cancer pain (RCP) among a sample of physicians specializing in cancer pain management in Shanghai. From 2019 to 2021, a questionnaire survey was conducted among physicians engaged in diagnosis and treatment of cancer pain through the questionnaire WJX network platform in Shanghai, China. A total of 238 responses participated in the survey. This survey reports physicians' understanding and incidence rate of breakthrough cancer pain (BTCP). The choice of analgesics and satisfaction of analgesic effect were investigated. We also investigated doctors' knowledge of the diagnostic criteria for RCP and their tendency to choose analgesics. Oral immediate-release morphine and intravenous or subcutaneous morphine injection have been the common treatment approach for transient cancer pain exacerbations. The main barriers to pain management are lack of standardized treatment methods for RCP, lack of knowledge related to RCP, and single drug dosage form. Doctors believe the most necessary measures to improve the current situation of poor cancer pain control include improving medical staff's understanding and treatment techniques for RCP, updating treatment techniques and methods, and improving the configuration of drug types in medical institutions. Clinicians expect to improve understanding and treatment techniques through systematic training. Despite multiple available analgesic measures, the treatment of RCP remains challenging. Improving the understanding of medical staff towards RCP, improving treatment techniques, and increasing the accessibility of multiple drug types are important ways to improve the satisfaction of cancer pain management in the future.

Citrus sinensis Peel Extract Synergistically Enhances the Cytotoxic Effect of Chemotherapeutic Agents on HepG2 Cells

Doxorubicin (DOX) and cisplatin (Cis), non-specific chemotherapeutic agents used for hepatocellular carcinoma (HCC), are frequently combined with synthetic or natural agents to enhance their cytotoxic effects. Citrus sinensis peel extract (CPE) serves as a natural source of flavonoids, including sinensetin (SIN), which has the potential to increase the efficacy of DOX and Cis. This study aimed to observe the effect of CPE and SIN one of CPE compounds, in enhancing liver cancer cell susceptibility to doxorubicin and cisplatin. The assays conducted in this study included a phytochemical analysis of CPE using TLC, cell viability assays against HepG2 cells using MTT assay in both single and combination forms, and cell viability assays on Vero cells. The result confirmed the presence of SIN as one of the compounds in CPE. Both CPE and SIN, when used individually, exhibited moderate cytotoxic effects on HepG2 cells with IC50 of 101.09 μg/mL and 83.13 μM, respectively, while showing no cytotoxic effect on Vero cells. Cis demonstrated significant cytotoxicity against HepG2 cells with an IC50 of 7.86 μM. DOX exerted a strong cytotoxic effect on both HepG2 and Vero cells, with the IC50 of 2.52 μM and 13.98 μM. It was observed that CPE was able to synergistically enhance the cytotoxic effects of DOX, and SIN synergistically increased the cytotoxicity of Cis, particularly against HepG2 cells, with CI<1.0.Keywords: CPE, SIN, Cisplatin, Doxorubicin, HCC.

Single-crystal strategy towards enhanced carrier mobility of fluorescent molecules for high-efficiency blue OLEDs

The organic single crystal, due to its long-range ordered molecular arrangement, high quality, low defect state density, and excellent luminescent properties, plays an irreplaceable role in the field of optoelectronics and organic light-emitting diodes. By employing strategies for constructing organic single crystals, it is possible to significantly enhance the carrier mobility and stability of devices, leading to superior optoelectronic properties. In particular, in organic light-emitting diode (OLED) devices, the introduction of an organic single crystal luminescent layer can unlock the potential of luminescent materials, extend their operational lifetimes, and enable them to withstand higher current densities. Here, we have grown high fluorescence quantum yield (PLQY) blue-emitting 1,4-bis (2-methylstyryl) benzene (BMSB) molecules in single crystal form. The average mobility has been improved from non-existent in thin films to 0.188 cm2/(V·s) in crystal devices. Additionally, through the rational design of device structures and the enhancement of electrical properties, we have achieved a transition from non-functional thin film devices to stable blue-emitting crystal devices, achieving a current density of 853.60 mA/cm2.

Numerical analysis of stress & strain and thickness variation in single point incremental forming of tailor welded steel blanks

Numerical analysis of stress & strain and thickness variation in single point incremental forming of tailor welded steel blanks

Dispersion state analysis in hot melt extruded, highly drug-loaded 3D printing filaments applying Raman microscopy

Abstract Objectives Highly drug-loaded polymer formulations are favorable intermediates in pharmaceutical applications, for example, for the individualized production of medicines via 3D printing with the maximum flexibility regarding dose strength and drug combination in a single dosage form. However, high-disperse drug loads are challenging for the process itself and the (intermediate) product properties, making the knowledge about the dispersion state of the drug particles achieved by the production process helpful to overcome such challenges. Methods Therefore, a novel dispersion state analysis technique based on scanning Raman microscopy is proposed in the present study and applied to HPMC filaments loaded with 20 wt%, 40 wt%, and 60 wt% theophylline. The qualitative and quantitative evaluations of the scans were correlated to melt viscosities, process data, and mechanical properties of the filaments. Key findings The analyses revealed not only an increasing particle size reduction with increasing drug load and thus increasing viscosity and mechanical energy input. The particle size reduction also caused a change in the filaments’ mechanical properties from elastic ductile to rigid brittle. Furthermore, an alignment of the elongated drug particles with the frozen three-dimensional flow pattern of the extruder and not only with the extrusion direction was elucidated. Conclusions Therefore, the necessity to investigate the dispersion state further is highlighted for future studies on highly drug-loaded polymer formulations, providing a novel measuring technique applicable to challenging pharmaceutical formulations.

Abstract 1910: Advancing therapeutic interventions for NUT carcinoma: Orchestrating the precision of CRISPR/Cas9-mediated NUTM1 suppression and synergistic ADC strategies

Abstract Purpose: NUT carcinoma (NC) is aggressive carcinoma defined by translocations involving the NUTM1 and frequent squamous differentiation. NUTM1 gene encodes a testicular nuclear protein (NUT), exclusively expressed in the testis. The fusion of NUTM1 leads to abnormal cell growth, resulting in the development of NC. This study aims to discover advanced approaches for inducing the death of cancer cells, specifically targeting those expressing NUT proteins. Methods: Spatial Transcriptome analysis and RNA sequencing were applied to formalin-fixed paraffin-embedded NUTM1 fusion-positive cancer tissues. Virus-like particles were used to introduce CRISPR/Cas9 into cells expressing the NUTM1 fusion oncoprotein. The inhibitory effect was confirmed through multiple in vitro assays. The effectiveness of Anti-Trophoblastic cell-surface antigen (TROP-2) Antibody-Drug Conjugate (ADC) was demonstrated in vivo and in vitro in cells with increased TROP2 expression subsequent to NUT suppression. Results: NCs revealed a relatively uniform pattern of gene expression, forming six unique groups. Notably, the NUT protein predominantly located in the inner regions of the tumor tissues. We employed CRISPR/Cas9 technology to specifically target cells harboring the NUTM1 fusion gene. The precise genetic editing was remarkably effective, achieving up to 90% success in the targeted area. This led to a notable decrease in both RNA and protein levels of NUT expression, effectively disrupting associated downstream pathways. The cell growth rate was reduced in several NC cell lines, and differentiation, accompanied by morphological changes, was observed in most edited cells. RNA sequencing analysis of these edited cells uncovered a substantial increase in expression of cytosolic molecules, with a marked increase in TACSTD2 expression. Interestingly, when we combined this genetic editing approach with a targeted therapy - the TROP2-ADC loaded with interferon-beta - the results were even more striking. Cells treated with this combination showed almost double the rate of growth inhibition compared to those receiving only a single form of treatment. Conclusion: This study provides valuable insights into identifying novel therapeutic targets and elucidating potential mechanisms by analyzing NUT cancer tissues using various assays. Our results support that CRISPR/Cas9-mediated targeting of NUTM1 could be a useful approach for NUT oncoprotein ablation, especially when used in combination with other therapies such as ADCs. Further studies are needed to investigate the efficacy of NUT inhibition in preclinical and clinical settings. the elimination of tumor cells facilitated by CRISPR/Cas9, along with additional tumor markers targeted by ADCs, holds potential for developing treatment strategies against incurable cancers driven by genetic alterations. Citation Format: Juyoung Choi, Hwa Lin Yi, Hee Geon Park, Misook Lee, Daesik Kim, Sung Youl Hong, Young Kee Shin, Yoon-la Choi. Advancing therapeutic interventions for NUT carcinoma: Orchestrating the precision of CRISPR/Cas9-mediated NUTM1 suppression and synergistic ADC strategies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1910.

Do metacognitive therapies for schizophrenia-spectrum disorders work? A meta-analytic investigation.

Recent reviews and meta-analyses of metacognitive therapy for schizophrenia-spectrum disorder (SSD) have included uncontrolled studies, single-session interventions, and/or analyses limited to a single form of metacognitive therapy. We sought to evaluate the efficacy of metacognitive therapies more broadly based on controlled trials (CT) of sustained treatments. We conducted a pre-registered meta-analysis of controlled trials that investigated the effects of meta-cognitive therapies on primary positive symptom outcomes, and secondary symptom, function and/or insight measures. Electronic databases were searched up to March 2022 using variants of the keywords, 'metacognitive therapy', 'schizophrenia', and 'controlled trial'. Studies were identified and screened according to PRISMA guidelines. Outcomes were assessed with random effects models and sample, intervention, and study quality indices were investigated as potential moderators. Our search identified 44 unique CTs with usable data from 2423 participants. Data were extracted by four investigators with reliability >98%. Results revealed that metacognitive therapies produced significant small-to-moderate effects on delusions (g = 0.32), positive symptoms (g = 0.30) and psychosocial function (g = 0.31), and significant, small effects on cognitive bias (g = 0.25), negative symptoms (g = 0.24), clinical insight (g = 0.29), and social cognition (g = 0.27). Findings were robust in the face of sample differences in age, education, gender, antipsychotic dosage, and duration of illness. Except for social cognition and negative symptoms, effects were evident even in the most rigorous study designs. Thus, results suggest that metacognitive therapies for SSD benefit people, and these benefits transfer to function and illness insight. Future research should modify existing treatments to increase the magnitude of treatment benefits.

Moisture actuated cobalt alginate discoloration artificial muscle

Artificial muscles have the ability to sense changes in the external environment and generate rapid and significant contraction deformation or rotational motion. However, most artificial muscles are limited to a single form of deformation, and there are still great difficulties in achieving complex dual response modes. Herein, a novel artificial muscle made of cobalt alginate fiber with both rotational/contraction deformation and discoloration functions was successfully prepared by a simple wet spinning and directional twisting methods. The wet-sensitive color change performance is achieved by the formation of different hydrates of cobalt ions in varying humidity conditions, while rotational motion is induced by radial untwisting resulting from fiber swelling upon moisture absorption. In addition, the artificial muscle fiber exhibited a transition from blue to purple to red as the environmental humidity changes from 35 % to 85 %. When the fibers were exposed to water, the twisted fiber with a twist count of 2500 truns provided a rotational speed of over 2000 rpm, and the actuating and discoloration performance did not significantly decrease in 50 repeated cycle tests. This stable shape and color dual response artificial muscle can simulate traditional windmill devices, while also providing a new design idea for smart textiles and humidity visualization devices.

Historic British Royal Memes

Historic British Royal Memes