Solid Lines Research Articles

PPM1D/Wip1 is amplified, overexpressed, and mutated in human non-Hodgkin's lymphomas.

Wip1, is a p53-dependent Ser/Thr phosphatase involved in the timely termination of DDR. The PPM1D gene encoding Wip1 is deregulated and thus gained an oncogene character in common human solid tumors and cell lines. This study assessed the oncogenic potential of the PPM1D gene in human non- Hodgkin's lymphomas (NHL), the most common hematological malignancy worldwide. FFPE human lymphoid hyperplasia (LH) (n = 17) and NHL tumor lymph node samples (n = 65) and human NHL cell lines were used to assess the oncogenic potential of the PPM1D gene in the present study. Copy number gain and mRNA expression analysis of the PPM1D/Wip1 gene were assessed by qRT-PCR analysis. Mutational analysis of Exon 6 of the PPM1D gene was performed by PCR amplification and Sanger sequencing. Expressions of Wip1 and p53 proteins were assessed by immunohistochemistry and Western blot analysis. We found that PPM1D gained gene copy number in NHL tumors by 0.7-8 times compared to the control (p < 0.01). Increased PPM1D/Wip1 gene copy number was associated with higher mRNA and protein expression in human NHL samples (p < 0.01). Overexpression of Wip1 in NHL tumors and NHL cell lines was associated with amplification level and was unaffected by p53 status. Furthermore, a heterozygous type insertion mutation was detected in exon 6 (c.1553_1554insA) of the PPM1D gene particularly in DLBCL samples. Wip1 may have oncogenic potential, perhaps playing a role in the onset and progression of human NHL. The possible significance of Wip1 overexpression to chemotherapy response in NHL remains an intriguing question that requires more exploration.

ChartLine: Automatic Detection and Tracing of Curves in Scientific Line Charts Using Spatial-Sequence Feature Pyramid Network.

Line charts are prevalent in scientific documents and commercial data visualization, serving as essential tools for conveying data trends. Automatic detection and tracing of line paths in these charts is crucial for downstream tasks such as data extraction, chart quality assessment, plagiarism detection, and visual question answering. However, line graphs present unique challenges due to their complex backgrounds and diverse curve styles, including solid, dashed, and dotted lines. Existing curve detection algorithms struggle to address these challenges effectively. In this paper, we propose ChartLine, a novel network designed for detecting and tracing curves in line graphs. Our approach integrates a Spatial-Sequence Attention Feature Pyramid Network (SSA-FPN) in both the encoder and decoder to capture rich hierarchical representations of curve structures and boundary features. The model incorporates a Spatial-Sequence Fusion (SSF) module and a Channel Multi-Head Attention (CMA) module to enhance intra-class consistency and inter-class distinction. We evaluate ChartLine on four line chart datasets and compare its performance against state-of-the-art curve detection, edge detection, and semantic segmentation methods. Extensive experiments demonstrate that our method significantly outperforms existing algorithms, achieving an F-measure of 94% on a synthetic dataset.

Are variations in ventricular catheter placement related to design of the catheter? A single-center cohort study.

The use of intracranial catheters is a common procedure used for neurosurgical patients with a variety of pathologies. Despite its frequency of use, shunt failure and revision have been reported to be a common problem. Given that depth of insertion can significantly affect the catheter tip position, a single institution retrospective chart review was performed to examine the accuracy of shunt and external ventricular drain (EVD) placement. Computed tomography (CT) images of the head following shunt or ventriculostomy insertion were analyzed to determine the delta between the final length of the intracranial catheter and the intended depth described in the operative notes. We found that there was a statistically significant difference in the accuracy of placement when comparing EVDs to shunts. The most used EVDs at our institution are marked with a solid black line in increments spaced 2 cm apart. The most used ventricular shunt catheter has a marking at 5 cm and 10 cm from the tip of the catheter. We believe that the visual confirmation that is afforded by metric unit markings on the EVD allows for better final placement of the catheter at the outer table of the calvarium. The addition of regular millimeter metric unit markings by the manufacturer is imperative in decreasing the chances of error in the insertion of ventricular catheters and preventing potential neurovascular injury to the surrounding structures.

Initiation of prefrontal convection within a Northeast China cold vortex: The roles of elevated front and dry air intrusion

AbstractConvective initiation ahead of a surface cold front within the Northeast China cold vortex of June 1, 2021, is investigated using observations and a convection‐permitting simulation. The initiation of the convection is elevated without identifiable surface mesoscale forcing. Air feeding the initial convective cells originates from at least 1 km above the ground where parcel‐based convective available potential energy is sufficiently large. An elevated front with large equivalent potential temperature gradient and flow convergence across is primarily responsible for the initiation of elevated convection and later organization into a deep convective line. The elevated front is similar to the upper cold front within extratropic cyclones studied elsewhere, but its altitude is lower in this case. Backward‐trajectory analysis of air parcels on the cold side of the elevated front shows that dry air intrusion reinforces the elevated front by increasing the equivalent potential temperature gradient and moment convergence across the front. The convergence forcing combined with access to convective unstable air at the leading edge of the westerly flows east of the elevated front causes the initiation of convection. The development and spreading of a surface cold pool help push the convective line eastward away from the surface cold front located to the west. Orographic gravity waves provide additional forcing so that convection cells are initiated first at the upward branches of the gravity waves, but the overall organization of initial cells into a solid convective line is controlled mainly by mesoscale structures associated with the elevated front.

A-199 Use of R programming for monthly quality control (QC) data review in a university hospital laboratory

Abstract Background Our laboratory information system (LIS) provides only cursory capability for monthly review of quality control measurements. We streamlined the major portion of this process using customized programming in R, as described below. Methods Month-long QC data were obtained using the LIS archive’s data retrieval program (QLIK). Data were read and processed using our R program (QC-R.R), for each analyte and QC level, to produce both Levey-Jennings (LJ) plots (for evaluation of possible temporal trends in QC data) as well as cumulative distribution (CD) plots (to evaluate whether QC data are normally distributed). Plots were sent to graphics files whereby they could be reviewed sequentially by a single forward-arrow click. Results Our laboratory utilizes two QC measurements for each of 157 analytes. Thus, monthly review involves evaluation of 314 datasets for QC results. With the R program outputs, results can be reviewed visually in rapid fashion, to determine whether there exist discrepancies between fixed limits and current data. An example CD plot is shown in Figure. In this example, QC data (points) were, appropriately, normally distributed (theoretical curved line based on data mean and SD). The currently operative fixed mean±2SD limits (vertical dashed lines) were, however, disparate from those of data (vertical solid lines). This set of results was thus marked for updating of mean and SD, with reference to a master list of results of calculations generated by the QC-R.R program. Time for review of monthly QC results was dramatically reduced, from more than 12 man-hours to less than 4 man-hours per month. Conclusions Limitations of our LIS for monthly QC review were bypassed using R-based programming to automate a significant fraction of the process. This led to a significant savings in labor attending to this important task. The use of CD plots is helpful for rapid data interpretation.

Application of PolyJet 3D Printing in Production of Flexographic Printing Plates

The aim of this study was to investigate whether PolyJet technology, which uses rubber-like materials for printing and is known for its high resolution and performance, could be suitable for producing flexographic printing plates. In our research, we designed test plates that were printed using PolyJet technology with TangoBlackPlus FLX9870-DM resin. These 3D-printed plates were evaluated for their resistance to various flexographic inks and solvents, and their contact angles were measured. Subsequently, the prints were made on a Flexiproof device using water-based ink with both the test plates and traditional photopolymer plates across six different substrates. The print quality was assessed using densitometry and spectrophotometry. Our findings indicate that the 3D-printed plates are suitable for printing solid areas and lines with water-based inks. However, the print quality of the 3D-printed plates is slightly lower than that of the photopolymer plates, with the optical density values for the high-quality prints on coated papers being approximately 10% lower. Additionally, the plates printed with TangoBlack Plus resin appear to be suitable for UV inks due to their high resistance, but they are not resistant to the solvents used in solvent-based inks.

Albusamides A-G: Hydroxylated Fatty Amine Derivatives from the Deep-Sea-Derived Actinomycete Streptomyces albus 228DD-066 and Their Cytotoxic Activity.

A series of new hydroxylated fatty amine derivatives, albusamides A-G (1-7), along with four known compounds (8-11), which are reported for the first time from a natural source, were isolated from the culture broth of Streptomyces albus 228DD-066 derived from a deep-sea sediment sample gathered off the coast of Dokdo Island, Republic of Korea. Their structures were elucidated through the comprehensive analysis of 1D and 2D NMR spectra and HRESIMS, and absolute configurations were determined using the modified Mosher's method. Biological evaluations against solid and blood cancer cell lines revealed that these new metabolites have moderate to strong cytotoxic activity. Compound 3 exhibited high cytotoxic activity with GI50 values ranging from 0.4 to 0.6 μM against solid cancer cell lines and exhibited the strongest cytotoxicity (GI50 value = 0.2 μM) against the WSU-DLCL2 blood cancer cell line.

Novel potent molecular glue degraders against broad range of hematological cancer cell lines via multiple neosubstrates degradation

BackgroundTargeted protein degradation of neosubstrates plays a crucial role in hematological cancer treatment involving immunomodulatory imide drugs (IMiDs) therapy. Nevertheless, the persistence of inevitable drug resistance and hematological toxicities represents a significant obstacle to their clinical effectiveness.MethodsPhenotypic profiling of a small molecule compounds library in multiple hematological cancer cell lines was conducted to screen for hit degraders. Molecular dynamic-based rational design and cell-based functional assays were conducted to develop more potent degraders. Multiple myeloma (MM) tumor xenograft models were employed to investigate the antitumor efficacy of the degraders as single or combined agents with standard of care agents. Unbiased proteomics was employed to identify multiple therapeutically relevant neosubstrates targeted by the degraders. MM patient-derived cell lines (PDCs) and a panel of solid cancer cell lines were utilized to investigate the effects of candidate degrader on different stage of MM cells and solid malignancies. Unbiased proteomics of IMiDs-resistant MM cells, cell-based functional assays and RT-PCR analysis of clinical MM specimens were utilized to explore the role of BRD9 associated with IMiDs resistance and MM progression.ResultsWe identified a novel cereblon (CRBN)-dependent lead degrader with phthalazinone scaffold, MGD-4, which induced the degradation of Ikaros proteins. We further developed a novel potent candidate, MGD-28, significantly inhibited the growth of hematological cancer cells and induced the degradation of IKZF1/2/3 and CK1α with nanomolar potency via a Cullin-CRBN dependent pathway. Oral administration of MGD-4 and MGD-28 effectively inhibited MM tumor growth and exhibited significant synergistic effects with standard of care agents. MGD-28 exhibited preferentially profound cytotoxicity towards MM PDCs at different disease stages and broad antiproliferative activity in multiple solid malignancies. BRD9 modulated IMiDs resistance, and the expression of BRD9 was significant positively correlated with IKZF1/2/3 and CK1α in MM specimens at different stages. We also observed pronounced synergetic efficacy between the BRD9 inhibitor and MGD-28 for MM treatment.ConclusionsOur findings present a strategy for the multi-targeted degradation of Ikaros proteins and CK1α against hematological cancers, which may be expanded to additional targets and indications. This strategy may enhance efficacy treatment against multiple hematological cancers and solid tumors.

On the Cultivation of National Security Education Teachers Qualities in Primary, Secondary, and Tertiary Schools in the New Era

The report of the 20th National Congress of the Communist Party of China once again emphasized the importance of national security education, clearly requiring the whole society to strengthen national security awareness and build a solid national security defense line. Under this guiding ideology, it is particularly urgent to comprehensively enhance the competence of national security education teachers in primary, secondary, and tertiary schools. By building a systematic training system, enhancing teachers professional knowledge and comprehensive literacy, and establishing a multi-level and multi-dimensional assessment mechanism, teachers teaching level and practical ability can be effectively improved. This article explores effective strategies for cultivating the competence of national security education teachers in the new era from these perspectives, in order to promote the sustainable development and innovation of national security education and ensure the in-depth promotion of national security education.

Formation and dissolution of porous magnetite layer in contact with lead-bismuth eutectic: Locally equilibrium thermodynamic model

Locally equilibrium thermodynamic model is developed to describe the formation and dissolution of the outer magnetite layer of an oxide film on the steel surface in contact with lead-bismuth eutectic. The model allows to predict the outer layer growth law as a function of dissolved oxygen and iron concentrations, temperature and coolant flow rate. Comparison with experiments allows to explain the phenomenon of magnetite dissolution in two experimentally observed cases: when oxygen concentration in LBE is above the solid magnetite stability line and under the high values of the coolant flow rate, without the consideration of mechanical erosion.

Kinetic Analysis for Selective Semi-Hydrogenation of Diphenylacetylene on Pt1Pd99/C Catalyst by PEM Electrolysis

Introduction For carbon neutrality, organic synthesis should utilize renewable electricity. Alkyne semi-hydrogenation has been researched for a long time to prevent a side reaction: over-hydrogenation to produce alkane. Although the Lindlar catalyst, composed of Pd/CaCO3 added with lead acetate and quinoline, has been a dominant catalyst for stereoselective Z-alkene synthesis, lead toxicity is a concern. In contrast, PEM electrolysis enables synthesis under mild conditions without lead and hydrogen gas as a reactant, unlike the Lindlar catalyst.Our previous research revealed that Pt1Pd99/C (at%) catalyst had high activity and selectivity towards the semi-hydrogenation of diphenylacetylene (DPA) to form cis-stilbene due to the high proton reduction activity of Pt even with a small amount and the selective hydrogenation of DPA at Pd sites.1,2) It also qualitatively figured that electrolysis conditions that reduce residence time in the catalyst layer (low catalyst loading, high flow rate, high temperature) enhance selectivity.3) This study conducted essential quantitative kinetic analyses to evaluate performance under specific conditions and develop practical conditions. Experimental DSE® (De Nora Permelec Ltd) was used for the oxygen evolution as the anode and Nafion® 117 (DuPont) as the PEM, respectively. Carbon paper (39BB, SGL Carbon), loaded with 0.14 mg-PtPd cm−2 of Pt1Pd99/C (ISHIFUKU Metal Industry Co., Ltd.) and cut into 3.3 cm × 3.5 cm, was employed as the cathode. The cathode was hot-pressed on the PEM at 120 ℃, 6 MPa, for 3 min to make a membrane cathode assembly. In the anode compartments, 1 M (= mol dm−3) sulfuric acid circulated, and 1 M cyclohexane solution of DPA in the cathode compartments either flowed once-through or circulated.As electrochemical measurements, chronoamperometry at 1.3―2.1 V for once-through experiments and chronopotentiometry at 18 mA cm−2 for batch electrolysis were conducted. The concentrations of cis-stilbene and dibenzyl in electrolytes were quantified with high-performance liquid chromatography (HPLC) after collection during the last 2 min out of 5 min of electrolysis at 80 ℃. The partial currents were calculated by eqns. 1, derived from Faraday’s laws of electrolysis. Results and Discussion Figure 1 shows Tafel plots of the total and each partial current density derived by eqns. 1 at a 1 M DPA once-through flow rate of 2 mL min−1 and 80 ℃. The kinetic parameters, i 0 and α, were determined by the fitting lines of mass transport corrected Tafel equation (eqns. 2), shown in Table 1. The solid lines in Figure 1 represent the calculated partial current densities from the parameters, describing their behavior well.Figure 2 shows concentration-time profiles of 12-h batch electrolysis of 1 M DPA 30 mL at 18 mA cm−2 and 80 ℃. Initially, the concentration of DPA steeply decreased as the semi-hydrogenation to form cis-stilbene proceeded mainly. As a result, cis-stilbene at 65% concentration was produced with approximately 80% selectivity. The reactivity significantly changed around 9 h of electrolysis since the concentration of DPA became deficient, and thus the semi-hydrogenation rate dropped and the over-hydrogenation rate increased.The solid lines in Figure 2 were simulated from the estimated once-through partial current densities of 1 M DPA at 18 mA cm−2 in total by Figure 1, using eqns. 3. The rate constants k 1 and k 2 were respectively obtained by dividing the estimated once-through partial current density i 1 and i 2 by 2Fc A and 2Fc B . The computed kinetic parameters are shown in Table 2. The parameters derived by once-through electrolysis data described the concentration profiles in Figure 2 until 7.5 h of the batch electrolysis, when sufficient DPA existed. The high selectivity was quantitively explained by the high k 1/k 2 value at 18 mA cm−2. In addition, this simple kinetic model would predict products under a variety of operating conditions. Conclusion The kinetic analysis quantitively described the once-through partial current densities and the batch electrolysis concentration profiles. The high k 1/k 2 enabled cis-stilbene formation at 65% concentration with approximately 80% selectivity with the batch electrolysis. The suggested concise kinetic model would be beneficial to estimate the compositions in a batch electrolysis with once-through data. Acknowledgment This work was financially supported by CREST (JST Grant 18070940). The authors are grateful to ISHIFUKU Metal Industry Co., Ltd. for providing the cathode catalysts. References 1) S, Nogami, K. Nagasawa, A. Fukazawa, K. Tanaka, S. Mitsushima, M. Atobe, J. Electrochem. Soc., 167, 155506 (2020).2) S. Nogami, N. Shida, S. Iguchi, K. Nagasawa, H. Inoue, I. Yamanaka, S. Mitsushima, M. Atobe, ACS Catal., 12, 5430 (2022).3) H. Nakamura, J. Harada, N. Shida, K. Nagasawa, Y. Kuroda, M. Atobe, S. Mitsushima, ECS Meet. Abstr., MA2023-01, 2703 (2023). Figure 1

(Digital Presentation) Temporal Evolution of the Threshold Voltage in Organic Thin Film Memory Transistors

We present a procedure to monitor the temporal evolution of the trapped charge in floating gates of organic thin film transistors (OTFTs) based memories in dynamic regimes. The potential applications of organic semiconductors in flexible and wearable electronics and their known features such as low-temperature and solution fabrication make the OTFTs be considered as candidates also in the field of non-volatile memories. Past efforts have been devoted on the preparation and optimization of floating gates [1]. In the present work, we focus on the modelling of this kind of devices, in particular, on a model for the threshold voltage useful in dynamic experiments, such as hysteresis and transient regimes. The information extracted from the modelling and simulation of these devices can be related to technological parameters with the objective of finding a better memory design.Current-voltage curves impacted by hysteresis are usually reproduced assuming the threshold voltage to be constant or piecewise constant. Nevertheless, despite positive outcomes [2], this is not a precise approach since it does not consider the actual temporal evolution of the threshold voltage. Thus, a time dependent threshold voltage is mandatory in order to interpret hysteresis phenomena and transient experiments, which in turn can be associated to trapping and de-trapping mechanisms over time.In this work, a model that describes the evolution of the threshold voltage with the time, which is linked to the variation of the trapped charge in the channel, is proposed.The evolution of the trapped charge is described with a first-order linear differential equation with a term controlled by a time constant t, and another term, similar to the generation term in a typical continuity equation, which is proportional to the drain current flowing through the transistor channel. This model is introduced in a compact model previously developed for OTFTs that include contact effects [3–6]. The resulting model is combined with an evolutionary parameter extraction procedure, which is applied to experimental current–voltage curves taken from the literature that show both contact and hysteresis effects [7]. Figures (a) and (b) show the best fitting of our calculations (solid lines) and experimental output and transfer characteristics (symbols), respectively, of a pentacene-based organic thin film memory transistor using poly (methyl methacrylate) (PMMA) as the insulator [7]. Figures (c) and (d) show the time evolution of the threshold voltage during the experiments (a) and (b), respectively.The authors acknowledge support from the project PID2022-139586NB-44 funded by MCIN/AEI/10.13039/501100011033 and by European Union NextGenerationEU/PRTR.

Selectivity Study of Anodic Seawater Electrolysis Catalysts Using the Rotating Ring-Disc Electrode Method

Water electrolysis generating green hydrogen will play a vital role in achieving the net-zero 2050 goal; however, freshwater electrolysis will further strain an already strained supply of clean freshwater.1 If seawater electrolysis can be scaled successfully, it would provide an important source of green hydrogen. Current research on untreated, direct seawater electrolysis is limited, and only recently have studies emerged analyzing catalyst performance at near-neutral pH.2 At industrially-relevant current densities, the formation of corrosive hypochlorite must be considered as a secondary reaction.3 Hypochlorite forms through the chloride oxidation reaction (ClOR), which competes with the oxygen evolution reaction (OER) in seawater electrolysis.2 In this work, we discuss the limitations of the current methods for determining anodic catalyst selectivity between OER and ClOR. The short lifetime of hypochlorite can cause faradaic efficiency measurement methods such as titration or oxygen gas capture to become unreliable, as these tests require that the hypochlorite remain stable. Using a rotating ring-disc electrode (RRDE), we measure the selectivity of common OER catalysts in-situ (Figure 1a). Real-time hypochlorite sensing overcomes the challenge of measuring catalyst selectivity posed by the short lifetime of hypochlorite. Remarkably, a PtRu catalyst outperformed more common OER catalysts with the best in OER selectivity and low overpotential, a novel development in the field of near-neutral water electrolysis. We also determine that elevated heat and low chlorine concentration are conducive to improved OER selectivity on an IrO2 catalyst (Figure 1b). We hope this work will set the standard in catalyst benchmarking for seawater electrolysis catalysts and could lead to the development of catalysts for efficient, scalable, and sustainable hydrogen production from seawater. H. Jin et al., Sci Adv, 9, eadi7755 (2023) https://www.science.org/doi/10.1126/sciadv.adi7755.F. Dionigi, T. Reier, Z. Pawolek, M. Gliech, and P. Strasser, ChemSusChem, 9, 962–972 (2016) https://onlinelibrary.wiley.com/doi/full/10.1002/cssc.201501581.J. Guo et al., Nature Energy 2023, 1–9 (2023) https://www.nature.com/articles/s41560-023-01195-x. Figure 1. a) LSV profiles of common OER catalysts (solid line) and the corresponding faradaic efficiency (dashed line) for the OER, measured using the ring current of the rotating ring-disc electrode. Catalysts were tested in 0.5 M NaCl and buffered with KHCO3 to pH 8.5. b) A ternary plot depicting the effect of varying Cl concentrations and temperatures on the selectivity of an IrO2 catalyst at pH 8.5. Figure 1

Rapidly-manufactured CD276 CAR-T cells exhibit enhanced persistence and efficacy in pancreatic cancer

BackgroundPancreatic cancer is one of the most lethal malignancies and the lack of treatment options makes it more deadly. Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has revolutionized cancer treatment and made great breakthroughs in treating hematological malignancies, however its success in treating solid cancers remains limited mainly due to the lack of tumor-specific antigens. On the other hand, the prolonged traditional manufacturing process poses challenges, taking 2 to 6 weeks and impacting patient outcomes. CD276 has recently emerged as a potential therapeutic target for anti-solid cancer therapy. Here, we investigated the efficacy of CD276 CAR-T and rapidly-manufactured CAR-T against pancreatic cancer.MethodsIn the present study, CD276 CAR-T was prepared by CAR structure carrying 376.96 scFv sequence, CD8 hinge and transmembrane domain, 4-1BB and CD3ζ intracellular domains. Additionally, CD276 rapidly-manufactured CAR-T (named CD276 Dash CAR-T) was innovatively developed by shortening the duration of ex vitro culture to reduce CAR-T manufacturing time. We evaluated the anti-tumor efficacy of CD276 CAR-T and further compared the functional assessment of Dash CAR-T and conventional CAR-T in vitro and in vivo by detecting the immunophenotypes, killing ability, expansion capacity and tumor-eradicating effect of CAR-T.ResultsWe found that CD276 was strongly expressed in multiple solid cancer cell lines and that CD276 CAR-T could efficiently kill these solid cancer cells. Moreover, Dash CAR-T was successfully manufactured within 48–72 h and the functional validation was carried out subsequently. In vitro, CD276 Dash CAR-T possessed a less-differentiated phenotype and robust proliferative ability compared to conventional CAR-T. In vivo xenograft mouse model, CD276 Dash CAR-T showed enhanced anti-pancreatic cancer efficacy and T cell expansion. Besides, except for the high-dose group, the body weight of mice was maintained stable, and the state of mice was normal.ConclusionsIn this study, we proved CD276 CAR-T exhibited powerful activity against pancreatic cancer cells in vitro and in vivo. More importantly, we demonstrated the manufacturing feasibility, acceptable safety and superior anti-tumor efficacy of CD276 Dash CAR-T generated with reduced time. The results of the above studies indicated that CD276 Dash CAR-T immunotherapy might be a novel and promising strategy for pancreatic cancer treatment.

Measles Infection Dose Responses: Insights from Mathematical Modeling

How viral infections develop can change based on the number of viruses initially entering the body. The understanding of the impacts of infection doses remains incomplete, in part due to challenging constraints, and a lack of research. Gaining more insights is crucial regarding the measles virus (MV). The higher the MV infection dose, the earlier the peak of acute viremia, but the magnitude of the peak viremia remains almost constant. Measles is highly contagious, causes immunosuppression such as lymphopenia, and contributes substantially to childhood morbidity and mortality. This work investigated mechanisms underlying the observed wild-type measles infection dose responses in cynomolgus monkeys. We fitted longitudinal data on viremia using maximum likelihood estimation, and used the Akaike Information Criterion (AIC) to evaluate relevant biological hypotheses and their respective model parameterizations. The lowest AIC indicates a linear relationship between the infection dose, the initial viral load, and the initial number of activated MV-specific T cells. Early peak viremia is associated with high initial number of activated MV-specific T cells. Thus, when MV infection dose increases, the initial viremia and associated immune cell stimulation increase, and reduce the time it takes for T cell killing to be sufficient, thereby allowing dose-independent peaks for viremia, MV-specific T cells, and lymphocyte depletion. Together, these results suggest that the development of measles depends on virus-host interactions at the start and the efficiency of viral control by cellular immunity. These relationships are additional motivations for prevention, vaccination, and early treatment for measles.Graphical abstractMeasles infection dose responses: insights from mathematical modeling. Top: Model-data fits for acute viremia in response to changes in measles infection doses. 104\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$10^4$$\\end{document}, 103\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$10^3$$\\end{document}, 102\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$10^2$$\\end{document}, 10 and 1 TCID50\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_{50}$$\\end{document} correspond to red diamonds, blue stars, orange triangles, magenta dots, and green squares respectively. The solid lines represent the trajectories generated by the proposed model parameterization. The shapes represent data. The dark grey dotted dashed line represents the limit of detection < 0.3. Bottom: Cartoon illustrating that when the measles infection dose increases, the stimulation of the measles-specific cellular immune responses increases early on post-infection. This enhanced immune response reduces the time required to clear the infectious viral load and helps maintain similar levels of viral loads and lymphocyte depletion irrespective of the initial dose.

EEG, EOG, Likert Scale, and Interview Approaches for Assessing Stressful Hazard Perception Scenarios

This study aimed to detect stressful hazard perception scenarios subjectively and objectively when using intelligent driving systems. We used electrooculography (EOG), electroencephalography (EEG), subjective ratings, and interviews to identify potential stressful hazard perceptions and record improvements in an intelligent navigation-guided pilot (NGP) system. Moreover, we analyzed electrophysiological data. Our study contributes to the use of engagement, concentration, and phase locking value connectivity based on EEG to support previous research methodologies using beta power, pupil size, fixation ratio, fixation duration, and subjective evaluations for investigating hazard perception. Our analyses showed that stressful hazard perception scenarios occurred mainly when encountering broken and solid lines, frequent lane changes, cars approaching suddenly, several cars driving in parallel, and the decision to change lanes but immediately pulling back upon using the NPG system. Our findings shed light on obtaining accurate results based on subjective and objective evaluations for developing intelligent driving systems.

Nonclinical Evaluation of Single-Mutant E. coli Asparaginases Obtained by Double-Mutant Deconvolution: Improving Toxicological, Immune and Inflammatory Responses.

Acute lymphoblastic leukaemia is currently treated with bacterial L-asparaginase; however, its side effects raise the need for the development of improved and efficient novel enzymes. Previously, we obtained low anti-asparaginase antibody production and high serum enzyme half-life in mice treated with the P40S/S206C mutant; however, its specific activity was significantly reduced. Thus, our aim was to test single mutants, S206C and P40S, through in vitro and in vivo assays. Our results showed that the drop in specific activity was caused by P40S substitution. In addition, our single mutants were highly stable in biological environment simulation, unlike the double-mutant P40S/S206C. The in vitro cell viability assay demonstrated that mutant enzymes have a higher cytotoxic effect than WT on T-cell-derived ALL and on some solid cancer cell lines. The in vivo assays were performed in mice to identify toxicological effects, to evoke immunological responses and to study the enzymes' pharmacokinetics. From these tests, none of the enzymes was toxic; however, S206C elicited lower physiological changes and immune/allergenic responses. In relation to the pharmacokinetic profile, S206C exhibited twofold higher activity than WT and P40S two hours after injection. In conclusion, we present bioengineered E. coli asparaginases with high specific enzyme activity and fewer side effects.

CsWRKY11 cooperates with CsNPR1 to regulate SA-triggered leaf de-greening and reactive oxygen species burst in cucumber

Salicylic acid (SA) is a multi-functional phytohormone, regulating diverse processes of plant growth and development, especially triggering plant immune responses and initiating leaf senescence. However, the early SA signaling events remain elusive in most plant species apart from Arabidopsis, and even less is known about the multi-facet mechanism underlying SA-regulated processes. Here, we report the identification of a novel regulatory module in cucumber, CsNPR1-CsWRKY11, which mediates the regulation of SA-promoted leaf senescence and ROS burst. Our analyses demonstrate that under SA treatment, CsNPR1 recruits CsWRKY11 to bind to the promoter of CsWRKY11 to activate its expression, thus amplifying the primary SA signal. Then, CsWRKY11 cooperates with CsNPR1 to directly regulate the expression of both chlorophyll degradation and ROS biosynthesis related genes, thereby inducing leaf de-greening and ROS burst. Our study provides a solid line of evidence that CsNPR1 and CsWRKY11 constitute a key module in SA signaling pathway in cucumber, and gains an insight into the interconnected regulation of SA-triggered processes.

BEB-based models for ionisation cross sections of electron and positron impact with diatomic molecules

The ionising interactions of high-energy particles with molecules have applications in many areas. Despite this, some areas, including positron scattering, lack experimental data due to difficulties in performing experiments. Here, quick and simple methods for computing direct electron and positron impact ionisation cross sections are presented. These calculations, performed using the open-source software RAPID-CS, can provide a complete data set as a first approximation for when experimental, or more detailed computational work is not available. The cross-sectional data set includes the total, partial/fragment-specific, single-differential, average secondary electron energy and stopping power cross sections. The molecules N2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_2$$\\end{document}, O2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_2$$\\end{document} and CO were chosen to study due to the availability of positron scattering data. An overall good agreement with experimental and other computational results is presented.Graphical abstractDirect electron (left) and positron right) impact partial ionisation cross sections for N2. Total cross section: red, N2+\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$N^{+}_{2}$$\\end{document} partial cross section: blue, N+\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{+}$$\\end{document} partial cross section: green.electron: solid lines: BEB, experimental measurements by Lindsay and Mangan [36]:Ürosses, Straub et al. [37]: stars, Opel et al. [39]: squares. Positron: solid lines: BEB0, Dashed lines: BEBA, Marler and Surko [23]: red crosses, Bluhme et al. [24]: stars

Towards Sustainable Production: An Adaptive Intelligent Optimization Genetic Algorithm for Solid Wood Panel Manufacturing

Optimizing production processes to conserve resources and reduce waste has become crucial in pursuing sustainable manufacturing practices. The solid wood panel industry, marked by substantial raw materials and energy consumption, stands at the forefront of addressing this challenge. This research delves into production scheduling and equipment utilization inefficiencies, offering innovative solutions for the solid wood panel processing line aimed at achieving environmental sustainability and operational efficiency. The study is articulated through two main segments: (1) an exhaustive analysis and the development of a simulation system for the solid wood panel processing line, delineating all production elements and operational logic, furnished with a user-friendly simulation interface, and (2) a comprehensive evaluation and enhancement of various scheduling algorithms specific to the Flexible Job-Shop Scheduling Problem (FJSP) encountered in solid wood panel workshops. A significant leap forward is made with the introduction of the Adaptive Intelligent Optimization Genetic Algorithm (AIOGA), an evolved version of the standard Genetic Algorithm (GA) engineered for optimal scheduling within the solid wood panel processing line. AIOGA incorporates advanced features such as encoding strategy, population initialization, objective function setting, selection strategy, crossover operation, and mutation operation, demonstrating the methodological depth of the study. We applied AIOGA in a designed FJSP, and AIOGA substantially reduced the maximum completion time to 90 min. It evidenced an improvement of 39.60% over the conventional GA, enhancing the equilibrium of the equipment workload across the system. This research presents a multifaceted strategy to address the scheduling complications inherent in solid wood panel production and highlights the extensive applicability of adaptive intelligent optimization in diverse industrial settings. This study establishes a new paradigm in manufacturing optimization, underlining the valuable integration of sustainability and efficiency in production methodologies.