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The unstable plume mode of hollow cathodes should be avoided in practical applications because it severely degrades the overall cathode lifetime. In this study, we investigate the spot-plume transition and plasma stability characteristics of an unused segmented lanthanum hexaboride emitter. The expansion of the unstable plume mode region is observed during a discharge experiment. Subsequently, the segmented emitter is retrieved, the inner surface of the emitter is observed, and the work function on the surface is measured at room temperature. The emitter surface exhibits color variations with oxygen and carbon detection. The downstream edge shows the original purple color and almost no degradation in the work function. The high temperature in this region promotes the desorption of carbon and oxygen. In the spot mode, this region mainly contributes to thermionic electron emission; therefore, the discharge voltage in the spot mode does not change during the discharge experiment. Carbon or carbide is detected in the middle of the axial direction on the emitter surface, where the surface temperature is not sufficiently high to desorb carbon during discharge. Based on the surface analysis results, the dominant substance in the region where carbon is detected was lanthanum carbide. An increase in the work function is indicated in the region, which appears to increase the plasma instability. According to previous studies, an increase in the work function results in a rise in the potential in the emitter, and an increase in the electron temperature in the outside plume region induces the plasma instability. Further investigation is needed to understand the mechanism connecting the rise in the work function and the rise in the electron temperature in the plume region. [ABSTRACT FROM AUTHOR]

GaAs surfaces require electrical and chemical passivation for semiconductor devices, but in order to have air stable passivation, high temperatures have been previously required in the passivation step. Here, we demonstrate air-stable, ex situ plasma passivation of GaAs using consecutive hydrogen and nitrogen plasmas at room temperature. No pre-clean using deoxidizing wet chemistry or other means is required. The hydrogen plasma step removes surface oxides and As, which leaves a Ga-rich layer that the nitrogen plasma then turns to GaN. The formed GaN layer efficiently passivates the surface. The plasma-passivated GaAs shows upto 5 × room-temperature photoluminescence after 1 year, and room-temperature time-resolved photoluminescence demonstrates robust passivation even after 3 years, both comparisons to similarly aged unpassivated GaAs. Atomic force microscopy was used to confirm that the passivated surfaces can be made smooth enough for microelectronic applications. Grazing incidence x-ray diffraction indicated that the nitride films are amorphous, and energy-dispersive x-ray spectroscopy was used to estimate the nitrogen content. We used a common inductively coupled plasma reactive ion etching system for plasma passivation, thus enabling the rapid adoption of this technique. [ABSTRACT FROM AUTHOR]

As high-sensitivity cardiac troponin T (hs-cTnT) is making the transition from diagnostic to prognostic use, a long-term stability study of 5th generation hs-cTnT according to EFLM CRESS recommendations was set up for investigation of frozen clinical specimens (two matrices).Study samples collected in serum tubes and lithium heparin tubes with gel from patients admitted for suspected minor myocardial damage were measured directly after completion of the study (0 years), and after 3-year and 6-year storage at −80 °C, and recovery of hs-cTnT concentrations after long-term storage (%hs-cTnT concentration compared to 0-year) was calculated. Hs-cTnT changes were also compared to decisive delta changes, such as the ones proposed in the ESC NSTEMI 0 h/1 h algorithm (<3 or >5 ng/L for ruling out and ruling in suspected NSTEMI patients).Eighty-six patients were included in the study, whereof 28 both lithium heparin plasma and serum samples were collected simultaneously, in others only serum (n=30) or plasma (n=28). Multiple aliquots per patient were made, so that 479 serum and 473 plasma samples were available for analysis. Across the overall hs-cTnT measuring range, median recovery after 6 years was 105.4 % and 106.2 % for serum and plasma, respectively. Based on these decisive delta changes, serum showed consistent results upon long term storage (max 0.8 % of samples above delta threshold of >5 ng/L) as compared to heparin plasma (up to 19.2 % of samples above threshold).Over 6 years of storage at −80 °C, recovery of hs-cTnT in serum and heparin plasma was similar and within common lot-to-lot variation. Yet, when evaluating absolute delta increments around hs-cTnT clinical decision points, long-term stored sera displayed better clinical performance compared to heparin plasma samples. [ABSTRACT FROM AUTHOR]

Ensuring tritium fuel self-sufficiency while maintaining continuous and high-specification fuel flow to the tokamak via a low tritium inventory and controllable fuel cycle is a significant challenge to the STEP plant design. Effective and high-quality fuelling and exhaust design is required to sustain and control a stable plasma, whereas fuel sufficiency is required to prevent depletion of available tritium supply. Concerns regarding the lack of tritium availability preventing continuous tritium import are countered by breeding, where highly energetic neutrons from the core fusion reactions interact with lithium atoms suspended in the surrounding breeder blanket to produce tritium. The compact nature of STEP prohibits the integration of inboard breeder blankets posing a significant challenge for the design team looking to ensure more tritium is bred and made available than consumed within the core plasma. This paper outlines how purposeful technology selection and system architecting has converged on the outline of a conceivable and tritium-capable fuel cycle and breeder blanket design. Before introducing the STEP fuel cycle design outline and summarizing the approach undertaken to address the challenges facing plasma fuelling, key aspects of fuel self-sufficiency are discussed. This includes discussing a proposed helium-cooled liquid lithium breeder blanket and possible technology options for tritium extraction from lithium. Lastly, there is a brief process modelling overview, which emphasizes the central contribution of various employed modelling methods. Reflections on the presented fuel cycle design outline conclude that substantial development work is still required to realize a continuous tritium fuel cycle design and overcome the major challenges posed by tritium and lithium handling. Reflections on the presented breeder blanket design proposal conclude that while many substantial risks and blockers remain to achieve fuel self-sufficiency, high breeding ratios are expected to be achievable with a compact spherical tokamak configuration. Nonetheless, it is recognized that further consideration is required to ensure that the selection of liquid lithium as a breeder medium provides the overall simplest route to a self-sufficient and realizable design. This article is part of the theme issue 'Delivering Fusion Energy – The Spherical Tokamak for Energy Production (STEP)'. [ABSTRACT FROM AUTHOR]

Recent studies have explored surface treatments, such as increasing the hydrophilicity of implant fixtures, to enhance the osseointegration of implants. This prospective clinical study aimed to assess the clinical stability and efficacy of plasma treatment applied to implants with sandblast−acid etching (SLA) surfaces before placement. Twenty-eight patients requiring implant placement provided consent and were assigned randomly to either the SLA group without plasma treatment or the SLA/plasma group with plasma treatment. Recall checks were conducted one and three months after the first-stage surgery, followed by a second surgery at four months. Although no significant differences in buccal bone defects or implant stability were observed between the groups, the SLA/plasma group showed significant increases in marginal bone changes on the mesial and distal sides, as assessed using periapical radiographs. This study underscores the potential of pre-implantation plasma treatment to enhance bone regeneration around implants. [ABSTRACT FROM AUTHOR]

ADCs have emerged as a promising class of therapeutics, combining the targeting specificity of monoclonal antibodies with the cytotoxic potency of small-molecule drugs. Although the majority of approved ADCs are still based on microtubule binder payloads, the recent success of topoisomerase I inhibitors has revitalized interest in the identification of novel agents overcoming present limitations in the field including narrow therapeutic window and chemoresistance. The success of DNA binders as payload for ADCs has been very limited, up to now, due, among other factors, to high hydrophobicity and planar chemical structures resulting in most cases in ADCs with a strong tendency to aggregate, poor plasma stability, and limited therapeutic index. Some of these molecules, however, continue to be of interest due to their favorable properties in terms of cytotoxic potency even in chemoresistant settings, bystander and immunogenic cell death effects, and known combinability with approved drugs. We critically evaluated several clinically tested ADCs containing DNA binders, focusing on payload physicochemical properties, cytotoxic potency, and obtained clinical results. Our analysis suggests that further exploration of certain chemical classes, specifically anthracyclines and duocarmycins, based on the optimization of physicochemical parameters, reduction of cytotoxic potency, and careful design of targeting molecules is warranted. This approach will possibly result in a novel generation of payloads overcoming the limitations of clinically validated ADCs. [ABSTRACT FROM AUTHOR]

A fast and sample cleanup approach for fluoxetine in human plasma was developed using protein precipitation coupled with LC–MS-MS. Samples were treated with methanol prior to LC–MS-MS analysis. Chromatographic separation was performed on a reverse phase column with an isocratic mobile phase of methanol and 10 mM ammonium formate pH acidified with formic acid (80:20, v/v) at a flow rate of 0.2 mL/min. The run time was 4 min. Mass parameters were optimized to monitor transitions at m/z [M + H]+ 310 > > 148 for fluoxetine and m/z [M + H]+ 315.1 > > 153 for fluoxetine-d5 as an internal standard. The lower limit of quantification and the dynamic range were 0.25 and 0.25–50 ng/mL, respectively. Linearity was good for intra-day and inter-day validations (R2 = 0.999). The matrix effect was acceptable with CV% < 15 and accuracy% < 15. The hemolytic effect was negligible. Fluoxetine was stable in human plasma for 48 h at room temperature (25 °C), for 12 months frozen at −25 °C, for 48 h in an auto-sampler at 6 °C, and for three freeze/thaw cycles. The validated method was applied in a pharmacokinetic study to determine the concentration of fluoxetine in plasma samples. The study provides a fast and simple bioanalytical method for routine analysis and may be particularly useful for bioequivalence studies. The method was successfully applied to a pharmacokinetic study of fixed-dose fluoxetine in nine healthy volunteers. [ABSTRACT FROM AUTHOR]

Backround: Depression is a significant concern in clinical and preclinical psychoneurobiological sciences due to its high prevalence and its individual and collective consequences. Identifying efficient biomarkers for accurate diagnosis is crucial, with ideal biomarkers having detectable serum levels and conformational and thermal stability. This study aims to identify stable plasma biomarkers for the diagnosis and prognosis of major depressive disorder, as the pathogenesis of the disorder remains incompletely understood, affecting diagnosis accuracy. Methods: Thus, this study included ten MDD patients and eight healthy controls. The present work analyzed miRNAs in patients with major depressive disorder compared to healthy controls. Results: Eleven specific miRNAs, particularly hsa-miR-874-3p; hsa-let-7d-5p; and hsa-miR-93-3p showed upregulation-type plasma variations in the group of patients with major depressive disorder. miRNA functionality is linked to depressive pathophysiology. Conclusions: This study identifies a "bouquet" of miRNAs with significant upregulation variations in patients with major depressive disorder, suggesting further research to determine their suitability for personalization and evaluation, ultimately becoming integral components of major depression serological evaluations. [ABSTRACT FROM AUTHOR]

Thermal plasma-driven dry reforming of methane (DRM) has gained increased attention in recent years due to its high conversion and energy conversion efficiency (ECE). Recent experimental work investigated the performance of a pure CO2 plasma with post-plasma CH4 injection. The rationale behind this strategy is that by utilizing a pure CO2 plasma, all plasma energy can be used to dissociate CO2, while CH4 reforming proceeds post-plasma in the reforming reactor with residual heat, potentially improving the energy efficiency compared to injecting both CO2 and CH4 into the plasma. To assess whether post-plasma CH4 injection indeed improves the DRM performance, we developed a chemical kinetics model describing the post-plasma conversion process. We first validated our model by reproducing the experimental results of the pure CO2 plasma with post-plasma CH4 injection. Subsequently, we compared both strategies: injecting only CO2 inside the plasma while injecting CH4 post-plasma, vs. classical plasma-based DRM. Our modeling results indicate that below specific energy inputs (SEI) of 220 kJ mol-1, the total conversion slightly improves (ca. 5%) with the first strategy. However, the ECE is slightly lower due to the low H2 selectivity caused by substantial H2O formation. The highest conversion and ECE are obtained at SEI values of 240-280 kJ mol-1, where both strategies yield nearly identical results, indicating the limited potential of improving the performance of DRM by pure CO2 plasma with post-plasma CH4 injection. Nevertheless, the approach is still very valuable to allow higher CH4/CO2 ratios without problems of coke formation within the plasma, and thus, to improve plasma stability and reach higher syngas ratios, which is more useful for further Fischer-Tropsch or methanol synthesis. [ABSTRACT FROM AUTHOR]

AbstractChlorogenic acid (CGA) that exhibits various bioactivities holds promise as a natural and safe medicinal agent or food supplement for promoting human health. However, the direct formulation for treatment is severely limited by its low water solubility, poor bioavailability, low plasma stability, and side effects caused by high doses. Fortunately, nanotechnology is widely applied for drug delivery to overcome the partial disadvantages of traditional drug molecules or naturally active components. The properties of CGA containing multiple hydroxyl groups as a green reductant and stabilizer have made the development of CGA-loaded nanomaterials possible. In this review, recent advancements in the design of CGA-loaded nanomaterials based on organic or inorganic nanomaterials were discussed, and the positive effects of nanomaterials on the release properties of active molecules and their targeted distribution in biological systems were indicated. These nanomaterials enhance the physiological activity of CGA in the treatment of various diseases. Moreover, in the field of food, CGA-loaded nanocomposites have been found to optimize the mechanical properties of nano-food packaging, leading to an extended shelf life of food products. The findings of this review provide a valuable foundation and reference for the development of novel CGA-loaded nanomedicines and nano-food packaging. [ABSTRACT FROM AUTHOR]

The Solid-State Linear Transformer Driver (SSLTD) is a nanosecond pulse power source characterized by its fast rise time and adjustable output waveform. It can generate uniform and stable atmospheric plasma jets, which is suitable for material surface modification. In this study, a 15-stage SSLTD was designed and assembled, which can produce a stable nanosecond pulse voltage up to 15 times the amplitude of the charging voltage at high frequencies, with a rise time of approximately 10 ns. This device can be used to generate stable atmospheric pressure Ar plasma jets with an electron density in the range of 1015~1016 cm−3 and gas temperatures close to room temperature. After the modification treatment by the plasma jets, the content of the C=O groups on the surface of the epoxy resin significantly increased in the wavelength range of 1720~1740 cm−1, and its flashover resistance was noticeably enhanced. The optimal comprehensive modification effect was achieved at a charging voltage of 600 V, pulse width of 50 ns, and pulse frequency in the range of 800~1000 Hz. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusions\nSHORT CONDENSATIONDienogest (DNG) 2 mg/ethinylestradiol (EE) 0.02 mg is the first low-dose combined oral contraceptive (COC) with a prolonged-release formulation that allows stable plasma concentrations and has high contraceptive efficacy (Pearl index: 0.2). The aim of this trial was to determine the bleeding profile of this contraceptive compared to an immediate release formulation.This prospective double-blind randomised controlled trial evaluated the bleeding patterns of DNG 2 mg/EE 0.02 mg compared with immediate-release drospirenone (DRSP) 3 mg/EE 0.02 mg in a 24/4-day regimen over nine cycles (randomisation ratio, 5:2). Participants recorded scheduled and unscheduled bleeding/spotting data using an electronic diary. A non-inferiority analysis for the proportion of participants with unscheduled bleeding/spotting was prespecified for Cycles 2–6. Safety, including adverse events, were monitored throughout the trial.Seven-hundred six and 288 participants received DNG/EE and DRSP/EE, respectively. Scheduled bleeding patterns per each 28-day cycle were similar in both groups. During Cycles 2–6, the proportion of participants with unscheduled bleeding/spotting was significantly lower in the DNG/EE group (50.5% [280/574] than in the DRSP/EE group (72.8% [171/235]]; treatment difference 22.3% [95% CI 15.9, 28.6%]; p < 0.0001). A low proportion of participants discontinued the trial due to bleeding disorders (1.7% and 0.7%, respectively). The safety profiles were similar for both treatments.The prolonged-release DNG 2 mg/EE 0.02 mg offers a significant decrease in unscheduled bleeding/spotting compared with an immediate-release COC, DRSP/EE, combined with high contraceptive efficacy and a very low adverse event profile.The prolonged-release DNG 2 mg/EE 0.02 mg offers a significant decrease in unscheduled bleeding compared with an immediate-release COC while maintaining contraceptive efficacy and with no new safety signals. [ABSTRACT FROM AUTHOR]

Low-temperature plasma ablation has been recently used for minimally invasive surgeries. However, more research is still needed on its generation process during tissue ablation and the underlying mechanism of tissue thermal damage. In this paper, high-speed camera footage, voltage–current signal collection, temperature analysis, and histological analysis were used to investigate the dynamic process of plasma tissue ablation and its thermal effect of dual-needle electrodes immersed in normal saline, which were driven by a high-frequency DC power supply with an output voltage ranging from 220 V to 320 V and a squire wave of 100 kHz. Microbubbles occurred around the ground electrode and merged to form a vapor layer that could completely cover the ground electrode. Plasma capable of ablating tissue would occur in the vapor layer between the ground electrode and tissue. The effect of electrical parameters on plasma generation and its thermal effect are analyzed by statistical results. The experimental results indicated that the voltage applied to the electrodes significantly influenced both the generation and stability of plasma, as well as the heat generation and tissue damage around the electrodes. Furthermore, under the same voltage, the existence of biological tissue promotes the formation of a vapor layer around the electrode, thereby facilitating the generation and stability of plasma. Notably, the temperature rise around the ground electrode is much higher than that around the powered electrode. These results have direct application to the design of plasma tissue ablation systems, which could achieve tissue ablation effects with minimal thermal damage. [ABSTRACT FROM AUTHOR]

Background: The orexin receptor (OXR) plays a role in drug addiction and is aberrantly expressed in colorectal tumors. Subtype-selective OXR PET ligands suitable for in vivo use have not yet been reported. This work reports the development of 18F-labeled OXR PET ligand candidates derived from the OXR antagonist suvorexant and the OX1R-selective antagonist JH112. Results: Computational analysis predicted that fluorine substitution (1e) and introduction of the fluorobenzothiazole scaffold (1f) would be suitable for maintaining high OX1R affinity. After multi-step synthesis of 1a–1f, in vitro OXR binding studies confirmed the molecular dynamics calculations and revealed single-digit nanomolar OX1R affinities for 1a–f, ranging from 0.69 to 2.5 nM. The benzothiazole 1f showed high OX1R affinity (Ki = 0.69 nM), along with 77-fold subtype selectivity over OX2R. Cu-mediated 18F-fluorination of boroxine precursors allowed for a shortened reaction time of 5 min to provide the non-selective OXR ligand [18F]1c and its selective OX1R congener [18F]1f in activity yields of 14% and 22%, respectively, within a total synthesis time of 52–76 min. [18F]1c and [18F]1f were stable in plasma and serum in vitro, with logD7.4 of 2.28 ([18F]1c) and 2.37 ([18F]1f), and high plasma protein binding of 66% and 77%, respectively. Dynamic PET imaging in rats showed similar brain uptake of [18F]1c (0.17%ID/g) and [18F]1f (0.15%ID/g). However, preinjection of suvorexant did not significantly block [18F]1c or [18F]1f uptake in the rat brain. Pretreatment with cyclosporine A to study the role of P-glycoprotein (P-gp) in limiting brain accumulation moderately increased brain uptake of [18F]1c and [18F]1f. Accordingly, in vitro experiments demonstrated that the P-gp inhibitor zosuquidar only moderately inhibited polarized, basal to apical transport of 1c (p < 0.05) and had no effect on the transport of 1f, indicating that P-gp does not play a relevant role in brain accumulation of [18F]1c and [18F]1f in vivo. Conclusions: The in vitro and in vivo results of [18F]1c and [18F]1f provide a solid basis for further development of suitable OXR PET ligands for brain imaging. [ABSTRACT FROM AUTHOR]

The reliability of plasma biomarkers of Alzheimer's disease (AD) can be compromised by protease‐induced degradation. This can limit the feasibility of conducting plasma biomarker studies in environments that lack the capacity for immediate processing and appropriate storage of blood samples. We hypothesized that blood collection tube supplementation with protease inhibitors can improve the stability of plasma biomarkers at room temperatures (RT). In this study, we conducted a comparative analysis of blood biomarker stability in traditional ethylenediaminetetraacetic acid (EDTA) tubes versus BD™ P100 collection tubes, the latter being coated with a protease inhibitor cocktail. The stability of six plasma AD biomarkers was evaluated over time under RT conditions. We evaluated three experimental approaches. In Approach 1, pooled plasma samples underwent storage at RT for up to 96 h. In Approach 2, plasma samples isolated upfront from whole blood collected into EDTA or P100 tubes were stored at RT for 0 h or 24 h before biomarker measurements. In Approach 3, whole blood samples were collected into paired EDTA and P100 tubes, followed by storage at RT for 0 h or 24 h before isolating the plasma for analyses. Biomarkers were measured with Single Molecule Array (Simoa) and immunoprecipitation‐mass spectrometry (IP‐MS) assays. Both the IP‐MS and Simoa methods revealed that the use of P100 tubes significantly improves the stability of Aβ42 and Aβ40 across all approaches. However, the Aβ42/Aβ40 ratio levels were significantly stabilized only in the IP‐MS assay in Approach 3. No significant differences were observed in the levels of plasma p‐tau181, GFAP, and NfL for samples collected using either tube type in any of the approaches. Supplementation of blood collection tubes with protease inhibitors could reduce the protease‐induced degradation of plasma Aβ42 and Aβ40, and the Aβ42/40 ratio for the IP‐MS assay. These findings have crucial implications for preanalytical procedures, particularly in resource‐limited settings. [ABSTRACT FROM AUTHOR]

The Particle-in-Cell (PIC) method, a cornerstone in plasma modeling, is widely employed for its ability to simulate kinetic phenomena in device-scale domains. Part of what makes this possible is that computational macroparticles represent many physical particles. It converges under certain constraints, including a grid spacing that resolves the Debye length and a time step small enough to respect the Courant–Friedrichs–Lewy condition and plasma frequency stability limit. Here, we introduce a new constraint necessary to avoid Artificial Correlation Heating (ACH). This requires that the macroparticle coupling strength be smaller than one, Γ w < 1 , where Γ w ≡ Γ w 2 / 3 , Γ = Z 2 e 2 / (4 π ε o a k B T) is the physical coupling strength, and w is the macroparticle weight. This is particularly relevant to 3D simulations of dense plasmas, which are becoming common with modern computing power. If this condition is violated, the finite macroparticle weight artificially enhances the coupling strength and causes the plasma to heat until the macroparticle coupling strength is near unity, depending on the grid resolution. A comprehensive model of ACH is developed that incorporates electron density, temperature, macroparticle weight, and grid resolution. It is then tested using PIC simulations, delineating the boundaries of the method's applicability and offering a predictive framework for ACH. Moreover, the research explores a runaway heating process induced by ACH in the presence of ionization, which can lead to numerical instability. A conclusion of this study is that the onset of ACH can impose a more stringent constraint on the macroparticle weight and average number of macroparticles per cell than what is typically expected, particularly in 3D simulations of dense plasmas. [ABSTRACT FROM AUTHOR]

The peptide CIGB‐210 inhibits HIV replication, inducing a rearrangement of vimentin intermediate filaments. The assessment of the in vitro serum and plasma stability of this peptide is important to develop an optimal pharmacological formulation. A half‐life of 17.68 ± 0.59 min was calculated for CIGB‐210 in human serum by reverse‐phase high‐performance liquid chromatography (HPLC) and mass spectrometry (MS). Eight metabolites of CIGB‐210 were identified with this methodology, all of them lacking the N‐terminal moiety. A previously developed CIGB‐210 in‐house competitive ELISA was used to compare the stability of CIGB‐210 derivatives containing either D‐amino acids, acetylation at the N‐terminus, or both modifications. The half‐life of CIGB‐210 in serum was five times higher when measured by ELISA than by HPLC/MS, and twice higher in plasma as compared to serum. The substitution of D‐asparagine on position 6 doubled the half‐life, while D‐amino acids on positions 8 and 9 did not improve the stability. The acetylation of the N‐terminus resulted in a 24‐fold more stable peptide in plasma. The positive effect of N‐terminal acetylation on CIGB‐210 serum stability was confirmed by the HPLC/MS method, as the half‐life of the peptide was not reached after 2 h of incubation, which represents more than a 6.8‐fold increase in the half‐life with respect to the original peptide. [ABSTRACT FROM AUTHOR]

[Display omitted] • Design and synthesis of quaternization or dimerization norharmane analogues are described. • Their anti-MRSA activities are evaluated, and SARs are summarized. • Compound 5a exhibits potent bactericidal activity in vitro and in vivo with low toxicity. • Compound 5a could disrupt bacterial biofilm and damage the membrane. • Metabolomics analysis is used to systematically investigate the mechanisms. Methicillin-resistant Staphylococcus aureus (MRSA)-caused infections greatly threaten public health. The discovery of natural-product-based anti-MRSA agents for treating infectious diseases has become one of the current research focuses. This study aims to identify promising anti-MRSA agents with a clear mechanism based on natural norharmane modified by quaternization or dimerization. A total of 32 norharmane analogues were prepared and characterized. Their antibacterial activities and resistance development propensity were tested by the broth double-dilution method. Cell counting kit-8 and hemolysis experiments were used to assess their biosafety. The plasma stability, bactericidal mode, and biofilm disruption effects were examined by colony counting and crystal violet staining assays. Fluorescence microscopy, metabolomic analysis, docking simulation and spectra titration revealed its anti-MRSA mechanisms. The mouse skin infection model was used to investigate the in vivo efficacy. Compound 5a was selected as a potential anti-MRSA agent, which exhibited potent anti-MRSA activity in vitro and in vivo , low cytotoxicity and hemolysis under an effective dose. Moreover, compound 5a showed good stability in 50% plasma, a low tendency of resistance development and capabilities to disrupt bacterial biofilms. The mechanism studies revealed that compound 5a could inhibit the biosynthesis of bacteria cell walls, damage the membrane, disturb energy metabolism and amino acid metabolism pathways, and interfere with protein synthesis and nucleic acid function. These results suggested that compound 5a is a promising candidate for combating MRSA infections, providing valuable information for further exploiting a new generation of therapeutic antibiotics. [ABSTRACT FROM AUTHOR]

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Plastic pollution is a problem that threatens the future of humanity, and various methods are being researched to solve it. Plastic biodegradation using microorganisms is one of these methods, and a recent study reported that plastic-degrading microorganisms activated by plasma increase the plastic decomposition rate. In contrast to microbial sterilization using low-temperature plasma, microbial activation requires a stable plasma discharge with a low electrode temperature suitable for biological samples and precise control over a narrow operating range. In this study, various plasma characteristics were evaluated using SDBD (Surface Dielectric Barrier Discharge) to establish the optimal conditions of plasma that can activate plastic-degrading microorganisms. The SDBD electrode was manufactured using low-temperature co-fired ceramic (LTCC) technology to ensure chemical resistance, minimize impurities, improve heat conduction, and consider freedom in designing the electrode metal part. Plasma stability, which is important for microbial activation, was investigated by changing the frequency and pulse width of the voltage applied to the electrode, and the degree of activation of plastic-degrading microorganisms was evaluated under each condition. The results of this study are expected to be used as basic data for research on the activation of useful microorganisms using low-temperature plasma. [ABSTRACT FROM AUTHOR]

Technologies associated with using concentrated energy flows are increasingly used in industry due to the need to manufacture products made of hard alloys and other difficult-to-process materials. This work is devoted to expanding knowledge about the processes accompanying the impact of laser pulses on material surfaces. The features of these processes are reflected in the acoustic emission signals, the parameters of which were used as a tool for understanding the accompanying phenomena. The influence of plasma formations above the material surface on self-oscillatory phenomena and the self-regulation process that affects pulse productivity were examined. The stability of plasma formation over time, its influence on the pulse performance, and changes in the heat flux power density were considered. Experimental data show the change in the power density transmitted by laser pulses to the surface when the focal plane is shifted. Experiments on the impact of laser pulses of different powers and durations on the surface of a hard alloy showed a relationship between the amplitude of acoustic emission and the pulse performance. This work shows the data content of acoustic emission signals and the possibility of expanding the research of concentrated energy flow technologies. [ABSTRACT FROM AUTHOR]

Over the past two decades, antibody-drug conjugates (ADCs) have emerged as a highly effective drug delivery technology. ADCs utilise a monoclonal antibody, a chemical linker, and a therapeutic payload to selectively deliver highly potent pharmaceutical agents to specific cell types. Challenges such as premature linker cleavage and clearance due to linker hydrophobicity have adversely impacted the stability and safety of ADCs. While there are various solutions to these challenges, our team has focused on replacement of hydrophobic ValCit linkers (cleaved by CatB) with Asn-containing linkers that are cleaved by lysosomal legumain. Legumain is abundantly present in lysosomes and is known to play a role in tumour microenvironment dynamics. Herein, we directly compare the lysosomal cleavage, cytotoxicity, plasma stability, and efficacy of a traditional cathepsin-cleavable ADC to a matched Asn-containing legumain-cleavable ADC. We demonstrate that Asn-containing linker sequences are specifically cleaved by lysosomal legumain and that Asn-linked MMAE ADCs are broadly active against a variety of tumours, even those with low legumain expression. Finally, we show that AsnAsn-linked ADCs exhibit comparable or improved efficacy to traditional ValCit-linked ADCs. Our study paves the way for replacement of the traditional ValCit linker technology with more hydrophilic Asn-containing peptide linker sequences. [ABSTRACT FROM AUTHOR]

The human ether-a-go-go-related gene (hERG) encodes the Kv11.1 (or hERG) channel that conducts the rapidly activating delayed rectifier potassium current (IKr). Naturally occurring mutations in hERG impair the channel function and cause long QT syndrome type 2. Many missense hERG mutations lead to a lack of channel expression on the cell surface, representing a major mechanism for the loss-of-function of mutant channels. While it is generally thought that a trafficking defect underlies the lack of channel expression on the cell surface, in the present study, we demonstrate that the trafficking defective mutant hERG G601S can reach the plasma membrane but is unstable and quickly degrades, which is akin to WT hERG channels under low K+ conditions. We previously showed that serine (S) residue at 624 in the innermost position of the selectivity filter of hERG is involved in hERG membrane stability such that substitution of serine 624 with threonine (S624T) enhances hERG stability and renders hERG insensitive to low K+ culture. Here, we report that the intragenic addition of S624T substitution to trafficking defective hERG mutants G601S, N470D, and P596R led to a complete rescue of the function of these otherwise loss-of-function mutant channels to a level similar to the WT channel, representing the most effective rescue means for the function of mutant hERG channels. These findings not only provide novel insights into hERG mutation-mediated channel dysfunction but also point to the critical role of S624 in hERG stability on the plasma membrane. [ABSTRACT FROM AUTHOR]

A Faraday-effect radial interferometer–polarimeter is designed for the National Spherical Torus Experiment-Upgrade (NSTX-U) to measure multiscale magnetic and density fluctuations critical to understanding fusion plasma confinement and stability, including those originating from magnetohydrodynamic instabilities, energetic particle-driven modes, and turbulence. The diagnostic will utilize the three-wave technique with 5 MHz bandwidth to simultaneously measure line-integrated magnetic and density fluctuations up to the ion-cyclotron frequency. Probe beams will be launched radially from the low-field side at the NSTX-U midplane, where the measured Faraday fluctuations mainly correspond to radial magnetic fluctuations that directly link to magnetic transport. A correlation technique will be employed to reduce the measurement noise to below 0.01° enabling detection of small amplitude fluctuations. Two toroidally displaced chords with 7° separation will be installed to measure toroidal mode numbers up to n = 25 for mode identification. Solid-state microwave sources operating at 321 μm (935 GHz) will be used to minimize the impact of the Cotton–Mouton effect. [ABSTRACT FROM AUTHOR]

Motional Stark effect polarimetry is a key diagnostic for plasma fusion research since its usage on PBX-M. The MSE diagnostic measures the radial magnetic pitch angle profile in a plasma from a neutral beam by observation of Stark split D-alpha emission from atoms excited by collision with ions and electrons in the plasma. The pitch angle measurement is used with equilibrium reconstruction codes to determine the q-profile for studies of plasma stability, confinement, and transport. Historically, the algorithm was used in a post-processing fashion. The goal of our work was to apply this method in real time and pass the results to the plasma control system computer for real-time equilibrium reconstruction and control. [ABSTRACT FROM AUTHOR]

Simple Summary: In commercial hatcheries, chicken embryos are incubated in complete darkness. However, in a natural environment, chicken embryos receive light stimulation during the incubation process as hens need to leave the nest to feed or turn the eggs. Therefore, providing light during incubation is closer to the natural growth environment of chicken embryos, which may have a positive effect on their growth and development. This study investigated the effects of providing different wavelengths of light during incubation on the behaviour, growth, immunity, and stress responses of post-hatch chicks. The results indicated that providing white light during incubation may enhance the growth performance of post-hatch chicks and potentially improve their ability to cope with environmental changes. This study aims to determine the effects of light exposure during incubation on the growth and development of post-hatch chicks and to provide a basis for the development of effective lighting strategies during the incubation period. Manipulation of light during incubation may have an effect on post-hatch chicks through the role of prenatal stage. The effects of providing different wavelengths of light (white, blue, and green lights, dark as control) during incubation on the growth performance, organ development, immune response, stress related hormones, digestive enzymes and behaviour of post-hatch chicks were investigated for 1–42 days. A total of 60 chicks per light treatment in three batches were used in this study. The results showed that the percentage of chicks accessing to feed and water resources appeared not to be affected by incubation light. Chicks hatched under white light were found to have a growth advantage (p < 0.05). The weight of organs (except thymus), IgA, IgY, IgM and heterophil to lymphocyte (H/L) ratio for post-hatch chicks were not affected by incubation light (p > 0.05). Thymus weight was reduced in chicks incubated under blue light compared to dark incubation (p < 0.05). The jejunum amylase and ileum lipase activities were significantly affected by the light treatments (p < 0.01). All light incubation chicks had stable plasma corticosterone levels and may have better ability to cope with environmental changes. Hence, white light photoperiod incubation may have potential to improve post-hatch chicks' growth performance and environmental adaptability. [ABSTRACT FROM AUTHOR]

Integration of add-on testing in high-scale automated clinical laboratories constitute a valuable instrument not only for the clinicians and the general patient care, but also for the laboratory itself. Knowledge on sample quality and analytical stability upon storage is necessary to be able to offer add-on testing. The objectives of this study were to examine the analytical stability of 63 biochemical analytes in plasma and urine samples stored at 16 °C. Samples were collected by professional laboratory technicians, analyzed at automated analyzers and stored in their primary, capped tube without separator for 10, 12, 16, 20 or 24 h at 16 °C. Stability was assessed by inspecting mean concentration of samples at baseline and examining if (A) mean concentration over time violated limits of bias, or if (B) individual sample concentrations violated limits of total error. The majority of the 63 analytes were stable for up to 24 h of storage. Few of the analytes were only suitable for add-on testing for 4, 6, 10, 12, 16 or 20 h of storage. One analyte, P-lactate dehydrogenase, was not found suitable for add-on testing when stored at 16 °C. Due to the increasing number of intelligent solutions for high-scale clinical laboratories, add-on testing has come to stay. Loss of stability could not be demonstrated for the majority of analytes after 10, 12, 16, 20 or 24 h of storage. This feature of analytical stability suggests that add-on testing is an acceptable tool for these analytes. [ABSTRACT FROM AUTHOR]

Infections caused by multidrug-resistant pathogens have emerged as a serious threat to public health. To develop new antibacterial agents to combat such drug-resistant bacteria, a class of novel amphiphilic xanthoangelol-derived compounds were designed and synthesized by mimicking the structure and function of antimicrobial peptides (AMPs). Among them, compound 9h displayed excellent antimicrobial activity against the Gram-positive strains tested (MICs = 0.5–2 μg/mL), comparable to vancomycin, and with low hemolytic toxicity and good membrane selectivity. Additionally, compound 9h demonstrated rapid bactericidal effects, low resistance frequency, low cytotoxicity, and good plasma stability. Mechanistic studies further revealed that compound 9h had good membrane-targeting ability and was able to destroy the integrity of bacterial cell membranes, causing an increase in intracellular ROS and the leakage of DNA and proteins, thus accelerating bacterial death. These results make 9h a promising antimicrobial candidate to combat bacterial infection. [ABSTRACT FROM AUTHOR]

The gyrate atrophy of the choroid and retina (GACR) is a rare genetic disease for which no definitive cure is available. GACR is due to the deficit of ornithine aminotransferase (hOAT), a pyridoxal 5′-phosphate-dependent enzyme responsible for ornithine catabolism. The hallmark of the disease is plasmatic ornithine accumulation, which damages retinal epithelium leading to progressive vision loss and blindness within the fifth decade. Here, we characterized the biochemical properties of tetrameric and dimeric hOAT and evaluated hOAT loaded in red blood cells (RBCs) as a possible enzyme replacement therapy (ERT) for GACR. Our results show that (i) hOAT has a relatively wide specificity for amino acceptors, with pyruvate being the most suitable candidate for ornithine catabolism within RBCs; (ii) both the tetrameric and dimeric enzyme can be loaded in RBC retaining their activity; and (iii) hOAT displays reduced stability in plasma, but is partly protected from inactivation upon incubation in a mixture mimicking the intracellular erythrocyte environment. Preliminary ex vivo experiments indicate that hOAT-loaded RBCs are able to metabolize extracellular ornithine at a concentration mimicking that found in patients, both in buffer and, although with lower efficiency, in plasma. Overall, our data provide a proof of concept that an RBC-mediated ERT is feasible and can be exploited as a new therapeutic approach in GACR. [ABSTRACT FROM AUTHOR]

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Case studies are needed to demonstrate the use of human‐relevant New Approach Methodologies in cosmetics ingredient safety assessments. For read‐across assessments, it is crucial to compare the target chemical with the most appropriate analog; therefore, reliable analog selection should consider physicochemical properties, bioavailability, metabolism, as well as the bioactivity of potential analogs. To complement in vitro bioactivity assays, we evaluated the suitability of three potential analogs for the UV filters, homosalate and octisalate, according to their in vitro ADME properties. We describe how technical aspects of conducting assays for these highly lipophilic chemicals were addressed and interpreted. There were several properties that were common to all five chemicals: they all had similar stability in gastrointestinal fluids (in which no hydrolysis to salicylic occurred); were not substrates of the P‐glycoprotein efflux transporter; were highly protein bound; and were hydrolyzed to salicylic acid (which was also a major metabolite). The main properties differentiating the chemicals were their permeability in Caco‐2 cells, plasma stability, clearance in hepatic models, and the extent of hydrolysis to salicylic acid. Cyclohexyl salicylate, octisalate, and homosalate were identified suitable analogs for each other, whereas butyloctyl salicylate exhibited ADME properties that were markedly different, indicating it is unsuitable. Isoamyl salicylate can be a suitable analog with interpretation for octisalate. In conclusion, in vitro ADME properties of five chemicals were measured and used to pair target and potential analogs. This study demonstrates the importance of robust ADME data for the selection of analogs in a read‐across safety assessment. We evaluated the suitability of three potential analogues homosalate and octisalate (UV filters), according to their in vitro ADME properties. Technical aspects of testing these highly lipophilic chemicals were addressed. Main differentiating properties were plasma stability, hepatic clearance, and hydrolysis to salicylic acid. Cyclohexyl salicylate, octisalate, and homosalate were identified suitable analogues for each other, whereas butyloctyl salicylate exhibited ADME properties that were markedly different, as a unsuitable analogue. Isoamyl salicylate can be a suitable analogue with interpretation for octisalate. [ABSTRACT FROM AUTHOR]

Cathepsin B (CTSB) is a lysosomal protease that is overexpressed in tumor cells. Radioimmunoconjugates (RICs) composed of CTSB‐recognizing chelating agents are expected to increase the molecular weights of their radiometabolites by forming conjugates with CTSB in cells, resulting in their improved retention in tumor cells. We designed a novel CTSB‐recognizing trifunctional chelating agent, azide‐[111In]In‐DOTA‐CTSB‐substrate ([111In]In‐ADCS), to synthesize a RIC, trastuzumab‐[111In]In‐ADCS ([111In]In‐TADCS), and evaluated its utility to improve tumor retention of the RIC. [111In]In‐ADCS and [111In]In‐TADCS were synthesized with satisfactory yield and purity. [111In]In‐ADCS was markedly stable in murine plasma until 96 h postincubation. [111In]In‐ADCS showed binding to CTSB in vitro, and the conjugation was blocked by the addition of CTSB inhibitor. In the internalization assay, [111In]In‐TADCS exhibited high‐level retention in SK‐OV‐3 cells, indicating the in vitro utility of the CTSB‐recognizing unit. In the biodistribution assay, [111In]In‐TADCS showed high‐level tumor accumulation, but the retention was hardly improved. In the first attempt to combine a CTSB‐recognizing unit and RIC, these findings show the fundamental properties of the CTSB‐recognizing trifunctional chelating agent to improve tumor retention of RICs. [ABSTRACT FROM AUTHOR]

Background: In the last decade the development of new PSMA-ligand based radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research. The most promising derivative in terms of interaction with the antigen and clinical properties has been found to be "PSMA-617", and its lutetium-177 radiolabelled version has recently been approved by EU and USA regulatory agencies for therapeutic purposes. For the above reasons, the development of new derivatives of PSMA-617 radiolabelled with fluorine-18 may still be of great interest. This paper proposes the comparison of two different PSMA-617 derivatives functionalized with NODA and RESCA chelators, respectively, radiolabelled via [18F]AlF2+ complexation. Results: The organic synthesis of two PSMA-617 derivatives and their radiolabelling via [18F]AlF2+ complexation resulted to proceed efficiently and successfully. Moreover, stability in solution and in plasma has been evaluated. The whole radiosynthesis procedure has been fully automated, and the final products have been obtained with radiochemical yield and purity potentially suitable for clinical studies. The biodistribution of the two derivatives was performed both in prostate cancer and glioma tumour models. Compared with the reference [18F]F-PSMA-1007 and [18F]F-PSMA-617-RESCA, [18F]F-PSMA-617-NODA derivative showed a higher uptake in both tumors, faster clearance in non-target organs, and lower uptake in salivary glands. Conclusion: PSMA-617 NODA and RESCA derivatives were radiolabelled successfully via [18F]AlF2+ chelation, the former being more stable in solution and human plasma. Moreover, preclinical biodistribution studies showed that [18F]F-PSMA-617-NODA might be of potential interest for clinical applications. [ABSTRACT FROM AUTHOR]

Three-phase gliding arc discharge reactors are devices in which it is difficult to maintain stable plasma parameters, be it electrically, physically, or chemically. The main cause of plasma instability is the source, which is freely burning arcs in a three-phase system. In addition, these arcs burn at low currents and are intensively cooled, further increasing their instability. These instabilities translate into the electrical characteristics of the plasma reactor. The analysis for the four gases nitrogen, argon, helium, and air shows that the type of plasma-generating gas and its physical parameters have a strong influence on the operational characteristics of the plasma reactor. Current–voltage, power and frequency characteristics of the plasma reactor were plotted experimentally. Characteristics obtained in this way make it possible to determine the areas of effective operation of the plasma reactor, and to estimate the quality of the generated plasma. Based on the characteristics obtained, a method of controlling the plasma parameters can be developed. [ABSTRACT FROM AUTHOR]

Objectives: Midostaurin is an oral multitargeted tyrosine kinase inhibitor for the treatment of acute myeloid leukemia (AML). Therapeutic drug monitoring of midostaurin may support its safe use when suspecting toxicity or combined with strong CYP3A4 inhibitors. Methods: A stable isotope dilution liquid chromatography–tandem mass spectrometry method was developed and validated for the determination and quantification of midostaurin in human plasma and serum. Midostaurin serum concentrations were analyzed in 12 patients with FMS‐like tyrosine kinase 3 (FLT3)‐mutated AML during induction chemotherapy with cytarabine, daunorubicin, and midostaurin. Posaconazole was used as prophylaxis of invasive fungal infections. Results: Linear quantification of midostaurin was demonstrated across a concentration range of 0.01–8.00 mg/L. Inter‐ and intraday imprecisions of the proposed method were well within ±10%. Venous blood samples were taken in nine and three patients in the first and second cycle of induction chemotherapy. Median (range) midostaurin serum concentration was 7.9 mg/L (1.5–26.1 mg/L) as determined in 37 independent serum specimens. Conclusion: In a real‐life cohort of AML patients, interindividual variability in midostaurin serum concentrations was high, highlighting issues concerning optimal drug dosing in AML patients. A personalized dosage approach may maximize the safety of midostaurin. Prospective studies and standardization of analytical methods to support such an approach are needed. [ABSTRACT FROM AUTHOR]

This study delves into investigating the stability of solutions pertaining to the generalized Davey–Stewartson ( D S ) equation by employing the generalized rational method and projective Riccati equations method within the Hamiltonian system framework. The central focus lies in unraveling the physical significance of this model within the realm of plasma physics, shedding light on its intricate connections with analogous equations. The generalized D S equation, a pivotal nonlinear evolution model, serves as a vital tool in comprehending the evolution of coupled waves across various physical systems, notably within the domains of fluid dynamics and plasma physics. Its significance lies in its capacity to elucidate the intricate interplay among different wave components, offering a holistic perspective on wave interactions within plasma mediums. Through the meticulous application of rigorous analytical methods, this investigation uncovers pivotal insights into the stability of solutions, thereby enriching our understanding of mathematical models in plasma physics. The findings presented in this research contribute significantly to advancing the understanding of nonlinear dynamics, with profound implications for future exploration in plasma physics and related fields. In essence, this study underscores the analytical prowess of the generalized rational and projective Riccati equations methods, accentuating their relevance and applicability to the generalized D S equation and, by extension, their role in enhancing our comprehension of coupled wave phenomena within diverse plasma systems. [ABSTRACT FROM AUTHOR]

The pulsed inductively coupled plasma (ICP) has considerable potential to satisfy multiple stringent scaling requirements for use in the semiconductor industry. However, overshoot of plasma parameters during the rising period of the pulse affects the stability and uniformity of the plasma and can lead to a breakdown of the wafer and over-sputtering of the film. In this study, a step waveform modulation method is used to reduce the overshoot at the initial stage of the pulse. The behavior of the discharge is monitored by measuring (i) the modulated step waveform signal on the function generator, (ii) the input power (by a time-resolved VI-probe), and (iii) the amplitudes of the coil voltage and current (by voltage and current probes, respectively), as well as (iv) the plasma parameters including the electron density, the effective electron temperature, and the electron energy probability distribution function (by a time-resolved Langmuir probe). It was found that the state of the plasma can be controlled by changing the waveform, such as varying the time of the rising edge, varying the initial amplitude, and varying the duration of the low-high amplitude. The results indicated that the overshoot value of the electron density can be reduced by using a low-high step waveform. When the amplitude of the waveform was 500/550 mV and the duration was 200/300 μs, the overshoot value observed was 1/4 of that of the conventional ICP pulse discharge. In addition, increasing the duty cycle of the pulse could also reduce the overshoot value due to the high electron density that occurs during the afterglow period. Moreover, the plasma can reach a steady state more quickly at high pressure by using a step waveform of high amplitude. [ABSTRACT FROM AUTHOR]

In the diagnosis of plasma microwave transmission, when the plasma size is large and the electron density is high, the microwave will cause a phase period ambiguity problem. In order to solve the phase ambiguity, a novel method of using the phase shift group delay (PSGD) to recover the true phase shift is proposed. The PSGD method is used to recover the simulated phase shift and diagnose the plasma. The diagnostic accuracy is all greater than 91%, which verifies the method. And the new method is used to diagnose the real inductively coupled plasma with high precision. Through analysis, the method of group delay recover phase shift is more suitable for stable plasma or slow-varying plasma. [ABSTRACT FROM AUTHOR]

Spermatozoa cryopreservation has been practiced for decades and is a very useful technique for long-term preservation of sperm fertility. The capability for semen cryopreservation varies across species, seasons, latitudes, and even for different ejaculates from the same animal. This article summarizes research results on sperm cryotolerance biomarkers in several species, focusing on three areas: spermatozoa cryotolerance biomarkers, seminal plasma proteins cryotolerance biomarkers, and other cryotolerance biomarkers. We discovered that sperm cryoresistance biomarkers are primarily related to sperm plasma membrane stability, the presence of antioxidant substances in sperm or seminal plasma, sperm cell energy metabolism, water and small molecule transport channels in the sperm plasma membrane, and antistress substances in sperm or seminal plasma. The research conducted using diverse livestock models can be employed to enhance the basic and applied reproduction of other mammals through the study of sperm cryotolerance biomarkers, as well as the substantial similarities between livestock and other organisms, including endangered species. [ABSTRACT FROM AUTHOR]

Background: Determination of the functional liver mass is important in a variety of clinical settings including liver surgery and transplantation. [99mTc]Tc-diethylenetriamine-pentaacetic acid galactosyl human serum albumin (99mTc-GSA) is a radiotracer targeting the asialoglycoprotein receptor (ASGR) and is routinely used in Japan for this purpose. Here we describe the development and evaluation of [68Ga]Ga-NODAGA-TriGalactan a low molecular weight PET-tracer targeting this structure. Results: For synthesis TRIS as branching unit and NODAGA as chelator for labelling with [68Ga]Ga are included. Three galactose moieties are conjugated via a click chemistry approach resulting in the desired labelling precursor.68Ga-labelling could be accomplished in high radiochemical yield and purity. [68Ga]Ga-NODAGA-TriGalactan is very hydrophilic and revealed high plasma stability and low plasma protein binding. Fluorescence imaging showed binding on ASGR-positive organoids and the IC50-value was in the nanomolar range. Most importantly, both biodistribution as well as animal imaging studies using normal mice demonstrated high liver uptake with rapid elimination from all other organs leading to even higher liver-to-background ratios as found for 99mTc-GSA. Conclusion: [68Ga]Ga-NODAGA-TriGalactan shows high in vitro stability and selectively binds to the ASGR allowing imaging of the functional liver mass with high contrast. Thus, our first generation compound resulted already in an alternative to 99mTc-GSA for imaging the functional liver reserve and might allow the broader use of this imaging technique. [ABSTRACT FROM AUTHOR]

Introduction: Clinical laboratories should guarantee sample stability in specific storage conditions for further analysis. The aim of this study is to evaluate the stability of plasma samples under refrigeration for 29 common biochemical analytes usually ordered within an emergency context, in order to determine the maximum allowable period for conducting add-on testing. Materials and methods: A total of 20 patient samples were collected in lithium heparin tubes without gel separator. All analyses were performed using Alinity systems (Abbott Laboratories, Abbott Park, USA) and samples were stored at 2-8 °C. Measurements were conducted in primary plasma tubes at specific time points up to 48 hours, with an additional stability study in plasma aliquots extending the time storage up to 96 hours. The stability limit was estimated considering the total limit of change criteria. Results: Of the 29 studied parameters, 24 demonstrated stabilities within a 48-hour storage period in primary plasma tubes. However, five analytes: aspartate aminotransferase, glucose, lactate dehydrogenase, inorganic phosphate and potassium evidenced instability at different time points (7.9 hours, 2.7 hours, 2.9 hours, 6.2 hours and 4.7 hours, respectively). The stability study in plasma aliquots showed that all parameters remained stable for 96 hours, except lactate dehydrogenase, with a stability limit of 63 hours. Conclusions: A reduced stability of primary plasma samples was observed for five common biochemical analytes ordered in an emergency context. To ensure the quality of add-on testing for these samples, plasma aliquots provide stability for a longer period. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of death worldwide. Several targeted anticancer drugs entered clinical practice and improved survival of cancer patients with selected tumor types, but therapy resistance and metastatic disease remains a challenge. A major class of targeted anticancer drugs are therapeutic antibodies, but their use is limited to extracellular targets. Hence, alternative binding scaffolds have been investigated for intracellular use and better tumor tissue penetration. Among those, monobodies are small synthetic protein binders that were engineered to bind with high affinity and selectivity to central intracellular oncoproteins and inhibit their signaling. Despite their use as basic research tools, the potential of monobodies as protein therapeutics remains to be explored. In particular, the pharmacological properties of monobodies, including plasma stability, toxicity and pharmacokinetics have not been investigated. Here, we show that monobodies have high plasma stability, are well-tolerated in mice, but have a short half-life in vivo due to rapid renal clearance. Therefore, we engineered monobody fusions with an albumin-binding domain (ABD), which showed enhanced pharmacological properties without affecting their target binding: We found that ABD-monobody fusions display increased stability in mouse plasma. Most importantly, ABD-monobodies have a dramatically prolonged in vivo half-life and are not rapidly excreted by renal clearance, remaining in the blood significantly longer, while not accumulating in specific internal organs. Our results demonstrate the promise and versatility of monobodies to be developed into future therapeutics for cancer treatment. We anticipate that monobodies may be able to extend the spectrum of intracellular targets, resulting in a significant benefit to patient outcome. [ABSTRACT FROM AUTHOR]

In this research study, the effects of an atmospheric pressure plasma treatment on the stability of selected colorants (pigments: red lead, vermilion, azurite, verdigris, smalt, ultramarine, raw sienna, vine black, champagne chalk, Bolognese chalk; dye: alizarin red) were investigated. In order to gain knowledge about the effect of a plasma on the more stable part of colorant-binder systems in works of art, binder-free colorants were first investigated. For this purpose, the samples were briefly exposed to an atmospheric pressure argon or air plasma and then stored for several weeks in two different climates: an indoor climate and a humid climate. Slight color changes were recorded in red lead, verdigris, alizarin red, and Bolognese chalk by photometric investigations and evaluation of the color values in the CIEL*a*b* system. Scanning electron microscopy revealed morphological changes in the plasma-treated verdigris samples. With the help of infrared spectroscopy and X-ray diffractometry, it could be shown that the degradation processes of some of the examined colorants were influenced by the preceding plasma treatment. Nonetheless, atmospheric pressure plasma treatment could be of interest in art restoration as a tool for decontamination and surface activation. [ABSTRACT FROM AUTHOR]

Our laboratory has shown that calpain‐2 activation in the brain following acute injury is directly related to neuronal damage and the long‐term functional consequences of the injury, while calpain‐1 activation is generally neuroprotective and calpain‐1 deletion exacerbates neuronal injury. We have also shown that a relatively selective calpain‐2 inhibitor, referred to as C2I, enhanced long‐term potentiation and learning and memory, and provided neuroprotection in the controlled cortical impact (CCI) model of traumatic brain injury (TBI) in mice. Using molecular dynamic simulation and Site Identification by Ligand Competitive Saturation (SILCS) software, we generated about 130 analogs of C2I and tested them in a number of in vitro and in vivo assays. These led to the identification of two interesting compounds, NA‐112 and NA‐184. Further analyses indicated that NA‐184, (S)‐2‐(3‐benzylureido)‐N‐((R,S)‐1‐((3‐chloro‐2‐methoxybenzyl)amino)‐1,2‐dioxopentan‐3‐yl)‐4‐methylpentanamide, selectively and dose‐dependent inhibited calpain‐2 activity without evident inhibition of calpain‐1 at the tested concentrations in mouse brain tissues and human cell lines. Like NA‐112, NA‐184 inhibited TBI‐induced calpain‐2 activation and cell death in mice and rats, both male and females. Pharmacokinetic and pharmacodynamic analyses indicated that NA‐184 exhibited properties, including stability in plasma and liver and blood–brain barrier permeability, that make it a good clinical candidate for the treatment of TBI. [ABSTRACT FROM AUTHOR]

Electric arc dynamics in plasma torches have an influence of the plasma jet stability and could impact coating properties. Depending on the plasma torch design, arc voltage fluctuations may vary from a hundred to only a few percent of the mean arc voltage. A cascaded-anode plasma torch particularly leads to very low arc voltage fluctuation, due to the presence of neutrodes limiting the amplitude of arc fluctuations. However, the electric arc dynamics and electrode erosion process are still poorly understood in this kind of plasma torches. The aim of this work is to refine the knowledge on the influence of the nozzle's diameter on electric arc dynamics and on zirconia-yttria coating properties. Two plasma-forming gas compositions were studied, connecting several analysis methods (end-on imaging, arc current and arc voltage time monitoring, plasma light fluctuations at nozzle exit, thermal balance evaluation and in-flight particles assessment) to coatings characterization (porosity and hardness measurements). Reducing the nozzle's diameter from 9 to 6.5 mm results in higher arc voltage fluctuations and lower thermal efficiency of the plasma torch. This is due to the warm plasma gas being more evenly distributed in the anode nozzle. After testing, surveys of the 6.5-mm-diameter nozzle show significant longitudinal wear, which may highlight an axial movement of the electric arc on the anode's surface, leading to high arc voltage fluctuations. Finally, the particle velocity is higher in a 6.5-mm-diameter nozzle, resulting in a lower particle temperature and a higher coating porosity. [ABSTRACT FROM AUTHOR]

Ionospheric plasma introduces nonlinear perturbations in regular EM wave propagation which in turn affects the signal transmission in a highly nonlinear manner. Often the signals are distorted by a varied degree of nonlinearity. The wireless communication mechanism is affected by small perturbations which take gigantic rogue wave structures with the possibility of damaging sophisticated equipments. To study the evolution of rogue wave-type solitons starting from initial small-amplitude perturbations, we have considered a three-component electron–ion plasma system with degeneracy pressure as well as quantum diffraction effects. A solitary wave structure is formed due to the interplay of nonlinear and dispersive forces. Such a formation under an external force gets modified and the stability criteria are altered. The interesting fact thus obtained here shows that relativistic and thermal degeneracy favour stability whereas quantum diffraction leads to instability. In this paper, we have studied how solitary wave structures behave under an external force. Next, we study how the nonlinear effects cause an amplitude modulation and the envelope soliton is formed. Such an envelope soliton is studied by the nonlinear Schrödinger equation that we derive in the later part of the work. We have carried out simulation studies and compared our results with the analytical findings of other workers. [ABSTRACT FROM AUTHOR]

The centrifugal mirror confinement scheme incorporates supersonic rotation of a plasma into a magnetic mirror device. This concept has been shown experimentally to drastically decrease parallel losses and increase plasma stability as compared with prior axisymmetric mirrors. MCTrans++ is a dimensionless (0-D) scoping tool which rapidly models experimental operating points in the Centrifugal Mirror Fusion Experiment (CMFX) at the University of Maryland. In the low-collisionality regime, parallel losses can be modelled analytically. A confining potential is set up that is partially ambipolar and partially centrifugal. Due to the stabilizing effects of flow shear, the perpendicular losses can be modelled as classical. Radiation losses such as bremsstrahlung and cyclotron emission are taken into account. A neutrals model is included, and, in some circumstances, charge-exchange losses are found to exceed all other loss mechanisms. We use the SUNDIALS ARKODE library to solve the underlying equations of this model; the resulting software is suitable for scanning large parameter spaces, and can also be used to model time-dependent phenomena such as a capacitive discharge. MCTrans++ has been used to verify results from prior centrifugal mirrors, create an experimental plan for CMFX and find configurations for future reactor-scale fusion devices. [ABSTRACT FROM AUTHOR]

Quasisymmetry (QS), a hidden symmetry of the magnetic field strength, is known to support nested flux surfaces and provide superior particle confinement in stellarators. In this work, we study the ideal magnetohydrodynamic (MHD) equilibrium and stability of high-beta plasma in a large-aspect-ratio stellarator. In particular, we show that the lowest-order description of a near-axisymmetric equilibrium vastly simplifies the problem of three-dimensional quasisymmetric MHD equilibria, which can be reduced to a standard elliptic Grad–Shafranov equation for the flux function. We show that any large-aspect-ratio tokamak, deformed periodically in the vertical direction, is a stellarator with approximate volumetric QS. We discuss exact analytical solutions and numerical benchmarks. Finally, we discuss the ideal ballooning and interchange stability of some of our equilibrium configurations. [ABSTRACT FROM AUTHOR]

The preservation of drug stability in biological evidence during the processes of collection and storage poses a substantial obstacle to the progress of forensic investigations. In conjunction with other constituents, the microorganisms present in the samples play a vital role in this investigation. The present investigation employed the high-performance liquid chromatography (HPLC) technique to assess the stability of (1R,2 S)-(–)-2-methylamino-1-phenyl-1-propanol hydrochloride in plasma and urine samples that were inoculated with Escherichia coli. These samples were subjected to storage conditions of 37 °C for 48 h and − 20 °C for a duration of 6 months. Minimal inhibitory concentration (MIC) and Minimal bactericidal concentration (MBC) of MPPH against E. coli were determined using microdilution method. The stability of MPPH in plasma and urine samples inoculated with E. coli was investigated using HPLC method. The results showed the MIC and MBC of MPPH were 87.5 ± 25 ppm and 175 ± 50 ppm, respectively. While MPPH remained stable in plasma for 48 h at 37 °C, it showed a notable decrease of about 11% in stability when stored in urine for the same period and temperature. From the beginning of the first month, a decrease in the stability of the compound appeared in all samples that were stored at − 20 °C, and the decrease reached 7% for plasma samples and about 11% for urine samples. The decrease in the stability reached its peak in the sixth month, reaching more than 30% and 70% of plasma and urine samples preserved at − 20 °C. This work concluded that E. coli can negatively affect the stability of MPPH in plasma and urine samples. This may lead to incorrect conclusions regarding the analysis of biological samples in criminal cases. [ABSTRACT FROM AUTHOR]

An atmospheric pressure jet that effectively prevents inner wall deposition has been developed, and its precursor distribution and thin-film deposition characteristics have been studied. The laser scattering and fluid simulation results show that the precursor (C4H10Zn) flow out of the eight holes of the central electrode and diffuse into the discharge region. Under the action of a discharge gas (Ar) of 2 slm is blown out of the plasma jet device, and will not diffuse to the inner wall of the plasma jet device. The optical photographs of the discharge show that the site of the monomer cleavage is about 1 mm closest to the inner wall of the jet device. With optical emission spectra (OES), a large number of characteristic emission peaks of Zn and CH were detected. The pattern of the deposited film closely resembles the diffusion pattern of the precursor within the plasma jet apparatus. By investigating deposited films in different regions, the influence of precursor distribution on film morphology and composition has been studied. XPS detected films near (black film) and far (white film) from the central region, and the results showed that films near the central region contained more organic components. This plasma device offers a stable plasma plume for thin film deposition and nanoparticle preparation. [ABSTRACT FROM AUTHOR]