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Abstract Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy for treating cancers. This method consists in modifying the patients’ T-cells to directly target antigen-presenting cancer cells. One of the barriers to the development of this type of therapies, is target antigen heterogeneity. It is thought that intratumour heterogeneity is one of the leading determinants of therapeutic resistance and treatment failure. While understanding antigen heterogeneity is important for effective therapeutics, a good therapy strategy could enhance the therapy efficiency. In this work we introduce an agent-based model (ABM), built upon a previous ABM, to rationalise the outcomes of different CAR T-cells therapies strategies over heterogeneous tumour-derived organoids. We found that one dose of CAR T-cell therapy should be expected to reduce the tumour size as well as its growth rate, however it may not be enough to completely eliminate it. Moreover, the amount of free CAR T-cells (i.e. CAR T-cells that did not kill any cancer cell) increases as we increase the dosage, and so does the risk of side effects. We tested different strategies to enhance smaller dosages, such as enhancing the CAR T-cells long-term persistence and multiple dosing. For both approaches an appropriate dosimetry strategy is necessary to produce “effective yet safe” therapeutic results. Moreover, an interesting emergent phenomenon results from the simulations, namely the formation of a shield-like structure of cells with low antigen expression. This shield turns out to protect cells with high antigen expression. Finally we tested a multi-antigen recognition therapy to overcome antigen escape and heterogeneity. Our studies suggest that larger dosages can completely eliminate the organoid, however the multi-antigen recognition increases the risk of side effects. Therefore, an appropriate small dosages dosimetry strategy is necessary to improve the outcomes. Based on our results, it is clear that a proper therapeutic strategy could enhance the therapies outcomes. In that direction, our computational approach provides a framework to model treatment combinations in different scenarios and to explore the characteristics of successful and unsuccessful treatments.

Certain methods for implementing chaotic maps can lead to dynamic degradation of the generated number sequences. To solve such a problem, we develop a method for generating pseudorandom number sequences based on multiple one-dimensional chaotic maps. In particular, we introduce a Bernoulli chaotic map that utilizes function transformations and constraints on its control parameter, covering complementary regions of the phase space. This approach allows the generation of chaotic number sequences with a wide coverage of phase space, thereby increasing the uncertainty in the number sequence generation process. Moreover, by incorporating a scaling factor and a sine function, we develop a robust chaotic map, called the Sine-Multiple Modified Bernoulli Chaotic Map (SM-MBCM), which ensures a high degree of randomness, validated through statistical mechanics analysis tools. Using the SM-MBCM, we propose a chaotic PRNG (CPRNG) and evaluate its quality through correlation coefficient analysis, key sensitivity tests, statistical and entropy analysis, key space evaluation, linear complexity analysis, and performance tests. Furthermore, we present an FPGA-based implementation scheme that leverages equivalent MBCM variants to optimize the electronic implementation process. Finally, we compare the proposed system with existing designs in terms of throughput and key space.

Nowadays, efficient spectrum usage is one of the most important design principles to take into account in wireless communications due to the exponential growth of mobile devices. In that sense, solutions such as Non-Orthogonal Multiple Access (NOMA) and cognitive radio (CR) have been proposed. In essence, NOMA allows some interference level by using non-orthogonal resource allocation with a tolerable increase in receiver complexity employing successive interference cancellation (SIC). In this work, a novel mathematical model of teletraffic for users performing accessment, simultaneously, by means of Orthogonal Multiple Access (OMA) and NOMA, is developed using a Markovian process that considers bursts of arrivals to model the access schemes. This novel procedure implies a closed-form solution of the proposed system compared to other works where these parameters are estimated assuming the moment generating function obtained with approximation models. The model is validated with a discrete event simulator, considering different scenarios and simulation conditions. The simulation results are in agreement with the mathematical solution proposed.

Abstract Changing environmental temperatures impact the physiological performance of fishes, and consequently their distributions. A mechanistic understanding of the linkages between experienced temperature and the physiological response expressed within complex natural environments is often lacking, hampering efforts to project impacts especially when future conditions exceed previous experience. In this study, we use natural chemical tracers to determine the individual experienced temperatures and expressed field metabolic rates of Atlantic bluefin tuna (Thunnus thynnus) during their first year of life. Our findings reveal that the tuna exhibit a preference for temperatures 2–4 °C lower than those that maximise field metabolic rates, thereby avoiding temperatures warm enough to limit metabolic performance. Based on current IPCC projections, our results indicate that historically-important spawning and nursery grounds for bluefin tuna will become thermally limiting due to warming within the next 50 years. However, limiting global warming to below 2 °C would preserve habitat conditions in the Mediterranean Sea for this species. Our approach, which is based on field observations, provides predictions of animal performance and behaviour that are not constrained by laboratory conditions, and can be extended to any marine teleost species for which otoliths are available.

In 2022, the United Kingdom reported an increase in drug resistance in Shigella sonnei isolates. We report 33 cases in Spain genetically related to the UK cases and 4 cases with similar antimicrobial resistance profiles infected with genetically distant strains. Our results suggest circulation of multiple genetic clusters of multidrug-resistant S. sonnei in Spain.

Ethylene is a natural hormone responsible for many processes, including ripening. One way to extend the shelf life of several fruits and vegetables is to remove ethylene from the atmosphere of storage and transport, for which photocatalysis processes can be an efficient technology. In this study, we investigated the ethylene photodegradation of four different composites (Cu/C3N4, Cu/TiO2, Ni/C3N4, Ni/TiO2) under UV-A and visible illumination. The photocatalytic composites were characterized, and the photocatalytic assay was performed in a continuous system for 1 h (ethylene concentration at 1.0 % in synthetic air, 50 mL.min-1, and 400 mg of photocatalyst). The results indicated that the Cu/C3N4 sample did not produce carbon dioxide under visible light or UV-A illumination, so ethylene was not degraded. The Ni/TiO2 sample had the best performance for ethylene degradation under visible light and UV-A illumination, showing higher CO2 production with UV-A. After illumination for 1 h, the light was turned off, and 5 min later, the CO2 concentration at the outlet was equal to the initial. Thus, the composites Ni/C3N4, Cu/TiO2, and Ni/TiO2 proved to be efficient in ethylene degradation. Therefore, they can increase the shelf life of fruits and vegetables, using photocatalysis to remove ethylene from the atmosphere while storing and transporting these foods.

The proposed novel algorithm named decision-making algorithm with geographic mobility (DMAGM) includes detailed analysis of decision-making for cognitive radio (CR) that considers a multivariable algorithm with geographic mobility (GM). Scarce research work considers the analysis of GM in depth, even though it plays a crucial role to improve communication performance. The DMAGM considerably reduces latency in order to accurately determine the best communication channels and includes GM analysis, which is not addressed in other algorithms found in the literature. The DMAGM was evaluated and validated by simulating a cognitive radio network that comprises a base station (BS), primary users (PUs), and CRs considering random arrivals and disappearance of mobile devices. The proposed algorithm exhibits better performance, through the reduction in latency and computational complexity, than other algorithms used for comparison using 200 channel tests per simulation. The DMAGM significantly reduces the decision-making process from 12.77% to 94.27% compared with ATDDiM, FAHP, AHP, and Dijkstra algorithms in terms of latency reduction. An improved version of the DMAGM is also proposed where feedback of the output is incorporated. This version is named feedback-decision-making algorithm with geographic mobility (FDMAGM), and it shows that a feedback system has the advantage of being able to continually adjust and adapt based on the feedback received. In addition, the feedback version helps to identify and correct problems, which can be beneficial in situations where the quality of communication is critical. Despite the fact that the FDMAGM may take longer than the DMAGM to calculate the best communication channel, constant feedback improves efficiency and effectiveness over time. Both the DMAGM and the FDMAGM improve performance in practical scenarios, the former in terms of latency and the latter in terms of accuracy and stability.

Incompatibilities between mitochondrial and nuclear genes can perturb respiration, biosynthesis, signaling and gene expression. Here we investigate whether mild mitonuclear incompatibilities alter the physiological response to redox stress induced by N-acetyl cysteine (NAC). We studied three Drosophila melanogaster lines with mitochondrial genomes that were either coevolved (WT) or mildly mismatched (BAR, COX) to an isogenic nuclear background. Responses to NAC varied substantially with mitonuclear genotype, sex, tissue and dose. NAC caused infertility and high mortality in some groups, but not others. Using tissue-specific high-resolution fluorespirometry, we show that NAC did not alter H2O2 flux but suppressed complex I-linked respiration in female flies, while maintaining a reduced glutathione pool. The high mortality in BAR females was associated with severe (>50 %) suppression of complex I-linked respiration, rising H2O2 flux in the ovaries, and significant oxidation of the glutathione pool. Our results suggest that redox stress is attenuated by the suppression of complex-I linked respiration, to the point of death in some mitonuclear lines. We propose that suppression of complex I-linked respiration is a general mechanism to maintain redox homeostasis in tissues, which could offset oxidative stress in ageing, producing a metabolic phenotype linked with epigenetic changes and age-related decline.

The tar spot complex (TSC) is a devastating disease of maize (Zea mays L.), occurring in 17 countries throughout Central, South, and North America and the Caribbean, and can cause grain yield losses of up to 80%. As yield losses from the disease continue to intensify in Central America, Phyllachora maydis, one of the causal pathogens of TSC, was first detected in the United States in 2015, and in 2020 in Ontario, Canada. Both the distribution and yield losses due to TSC are increasing, and there is a critical need to identify the genetic resources for TSC resistance. The Seeds of Discovery Initiative at CIMMYT has sought to combine next-generation sequencing technologies and phenotypic characterization to identify valuable alleles held in the CIMMYT Germplasm Bank for use in germplasm improvement programs. Individual landrace accessions of the “Breeders' Core Collection” were crossed to CIMMYT hybrids to form 918 unique accessions topcrosses (F1 families) which were evaluated during 2011 and 2012 for TSC disease reaction. A total of 16 associated SNP variants were identified for TSC foliar leaf damage resistance and increased grain yield. These variants were confirmed by evaluating the TSC reaction of previously untested selections of the larger F1 testcross population (4,471 accessions) based on the presence of identified favorable SNPs. We demonstrated the usefulness of mining for donor alleles in Germplasm Bank accessions for newly emerging diseases using genomic variation in landraces.

Growing concern about climate change has been driving the search for solutions to mitigate greenhouse gas emissions. In this context, carbon capture and utilization (CCU) technologies have been proposed and developed as a way of giving CO2 a sustainable and economically viable destination. An interesting approach is the conversion of CO2 into valuable chemicals, such as methanol (MeOH) and dimethyl ether (DME), by means of catalytic hydrogenation on Cu-, Zn-, and Al-based catalysts. In this work, three catalysts were tested for the synthesis of MeOH and DME from CO2 using a single fixed-bed reactor. The first one was a commercial CuO/γ-Al2O3; the second one was CuO-ZnO/γ-Al2O3, obtained via incipient wetness impregnation of the first catalyst with an aqueous solution of zinc acetate; and the third one was a CZA catalyst obtained by the coprecipitation method. The samples were characterized by XRD, XRF, and N2 adsorption isotherms. The hydrogenation of CO2 was performed at 25 bar, 230°C, with a H2:CO2 ratio of 3 and space velocity of 1,200 ml (g cat · h)−1 in order to assess the potential of these catalysts in the conversion of CO2 to methanol and dimethyl ether. The catalyst activity was correlated to the adsorption isotherms of each reactant. The main results show that the highest CO2 conversion and the best yield of methanol are obtained with the CZACP catalyst, very likely due to its higher adsorption capacity of H2. In addition, although the presence of zinc oxide reduces the textural properties of the porous catalyst, CZAWI showed higher CO2 conversion than commercial catalyst CuO/γ-Al2O3.

Background and study aims The endoscopic pressure study integrated system (EPSIS), a novel diagnostic tool for gastroesophageal reflux disease (GERD), allows evaluation of the anti-reflux barrier using endoscopy by monitoring the intragastric pressure (IGP) during insufflation. In this study, we evaluated the association between EPSIS results and lower esophageal sphincter (LES) function measured by high-resolution manometry (HRM) to elucidate whether EPSIS can evaluate the LES function. Patients and methods A retrospective, single-center study of patients with GERD symptoms who underwent endoscopy, pH-impedance monitoring, EPSIS, and HRM was conducted. The primary outcome was basal LES pressure and the secondary outcomes were end-respiratory LES pressure and integrated relaxation pressure (IRP). As EPSIS parameters, the following were measured: 1) pressure difference (mmHg), the difference between maximum and basal IGP; and 2) pressure gradient (mmHg/s), calculated by dividing pressure difference by the insufflating time. Pressure difference

Abstract Objectives Lower esophageal sphincter (LES) plays a key role in gastroesophageal reflux disease (GERD) pathogenesis. In retroflexion and under sufficient insufflation, it can be seen how the lower esophagus grasps the endoscope, which we named scope holding sign (SHS). This study aimed to compare the SHS and LES pressure on high‐resolution manometry (HRM), to elucidate whether the sphincter can be visualized endoscopically. Methods This was a single‐center, prospective pilot study. Patients with symptoms of GERD, who underwent endoscopy and HRM between February 2021 and April 2021, were included. A manometry catheter and an ultra‐slim endoscope were inserted, and the resting LES pressure was measured. The lower esophagus holding (SHS‐positive) and releasing (SHS‐negative) the endoscope and catheter were observed. The LES pressures during SHS‐positive and SHS‐negative were compared. Results Eleven patients (median age: 57 years; eight men) with normal esophageal motility were analyzed. The median LES pressure in SHS‐positive was significantly higher than the resting LES pressure (40.4 [22.9–74.0] vs. 25.9 [2.0–66.7] mm Hg; p = 0.001) and the LES pressure in SHS‐negative (4.6 [1.5–9.3]; p = 0.001). Furthermore, the LES pressure in SHS‐negative was significantly lower than the resting LES pressure (4.6 [1.5–9.3] vs. 25.9 [2.0–66.7] mm Hg; p = 0.005). Conclusions This study demonstrated that the SHS parallels LES pressure, indicating that the sphincter can be observed endoscopically. This may enable us to evaluate LES function during endoscopy in patients with GERD, thus, deserving further evaluation in future studies.

Abstract The study and the detection of possible network attacks are essential for wireless networks, in particular for mobile cognitive radio networks due to its characteristics such as the dynamic spectrum allocation and constant frequency hopping. The primary user emulation attack is one of the most significant attacks in cognitive radio, because it hazards the complete cognitive cycle. The techniques used for the detection of primary user emulation found in the literature are based on a fixed attacker location. However, in a mobile environment, the attacker usually has dynamic locations and this compromises the current applied security techniques and generates inefficient attack detection. Therefore, our work proposes a novel technique using cross-layer design for the detection of primary user emulation with mobility. This attack detection technique was tested with experiments using software-defined radio equipment and mobile phones at indoor scenarios with dynamic locations and with a mobile phone base station built up also with software-defined radio. The obtained results show that the combination of the three utilized techniques, energy detection, motion estimation, and application information analysis, are able to optimize the detection with around 100% of effectiveness for the primary user emulation attack with dynamic location. The proposed technique shows that the energy detection time is around 100 ms and for the processing time of the information analysis in the mobile phone is about 30 s. This result shows a practical and effective approach to detect primary emulation attacks. The proposed technique, to the best of the authors’ knowledge, has not been presented before in the literature with experiments neither with mobility conditions of the attacker as presented in our proposed work.

The Information Dispersal Algorithm (IDA) has become a key component in several fault-tolerant massive storage systems. From a theoretical point of view, it is a linear transformation over a finite field on the vectors that make up a given file. Direct transformation adds redundancy, splitting the initial file into a new set of files called dispersals. The inverse transformation recovers the original file from a subset of dispersals. This piece of research demonstrates the impact of input and output (I/O) operations on direct and inverse transformations. Different alternatives to control the exchange of elements between RAM and disk were evaluated, which is the key operation to build a vector in memory and store its entries in a file. First, the impact of the working finite field was tested; second, the impact of the use of a buffer for exchange between the RAM and the hard disk, and finally, several instances of the algorithm with which to evaluate the impact of parallelism were simultaneously deployed. The results demonstrate that the combination of these factors may have an important effect on the speed of both direct and inverse procedures.

Alpha-2-macroglobulin (A2M) is a protease inhibitor that regulates extracellular matrix (ECM) stability and turnover. Here, we show that A2M is expressed by endothelial cells (ECs) from human eye choroid. We demonstrate that retinal pigment epithelium (RPE)-conditioned medium induces A2M expression specifically in ECs. Experiments using chemical inhibitors, blocking antibodies, and recombinant proteins revealed a key role of VEGF-A in RPE-mediated A2M induction in ECs. Furthermore, incubation of ECs with RPE-conditioned medium reduces matrix metalloproteinase-2 gelatinase activity of culture supernatants, which is partially restored after A2M knockdown in ECs. We propose that dysfunctional RPE or choroidal blood vessels, as observed in retinal diseases such as age-related macular degeneration, may disrupt the crosstalk mechanism we describe here leading to alterations in the homeostasis of choroidal ECM, Bruch’s membrane and visual function.

Controversies remain regarding the periodicity, or seasonality, of otolith growth band formation, which directly influences a correct age determination of Atlantic bluefin tuna using this structure. The aim of this work was to apply marginal increment analysis and marginal edge analysis to determine the timing of band deposition. The index of completion was analyzed using general additive models to evaluate the importance of variables, such as month, age/size, and reader. Results indicate that the opaque band formation begins in June and is completed by the end of November. From the end of the year to the beginning of the following year, there is minimal marginal edge growth as the translucent band begins to form. The translucent zone then reaches a maximum development in May. The results obtained in this study provide evidence that the annulus formation in the otoliths of Atlantic bluefin tuna are completed later in the calendar year than previously thought. This would mean it is necessary to delay the date of the current July 1st adjustment criterion to November 30.

Recently evolved alleles of Apolipoprotein L-1 (APOL1) provide increased protection against African trypanosome parasites while also significantly increasing the risk of developing kidney disease in humans. APOL1 protects against trypanosome infections by forming ion channels within the parasite, causing lysis. While the correlation to kidney disease is robust, there is little consensus concerning the underlying disease mechanism. We show in human cells that the APOL1 renal risk variants have a population of active channels at the plasma membrane, which results in an influx of both Na+ and Ca2+. We propose a model wherein APOL1 channel activity is the upstream event causing cell death, and that the activate-state, plasma membrane-localized channel represents the ideal drug target to combat APOL1-mediated kidney disease.

Abstract Background Stable and non-toxic fluorescent markers are gaining attention in molecular diagnostics as powerful tools for enabling long and reliable biological studies. Such markers should not only have a long half-life under several assay conditions showing no photo bleaching or blinking but also, they must allow for their conjugation or functionalization as a crucial step for numerous applications such as cellular tracking, biomarker detection and drug delivery. Results We report the functionalization of stable fluorescent markers based on nanodiamonds (NDs) with a bifunctional peptide. This peptide is made of a cell penetrating peptide and a six amino acids long β-sheet breaker peptide that is able to recognize amyloid β (Aβ) aggregates, a biomarker for the Alzheimer disease. Our results indicate that functionalized NDs (fNDs) are not cytotoxic and can be internalized by the cells. The fNDs allow ultrasensitive detection (at picomolar concentrations of NDs) of in vitro amyloid fibrils and amyloid aggregates in AD mice brains. Conclusions The fluorescence of functionalized NDs is more stable than that of fluorescent markers commonly used to stain Aβ aggregates such as Thioflavin T. These results pave the way for performing ultrasensitive and reliable detection of Aβ aggregates involved in the pathogenesis of the Alzheimer disease.

In this article, a combination of rectangular loop array and slot radiator for multiband applications is presented. The antenna is configured by arranging, concentrically, a set of rectangular loop radiators excited by electromagnetic coupling provided by a dumbbell slot. The size of the loops is calculated to obtain the desired resonant frequencies, which are almost independent of the adjacent rings. The exciting slot is designed to operate in a wideband frequency range to cover the upper desired resonance. In addition, to obtain directive radiation patterns, a reflector shaped like a box is introduced, giving a stable gain, radiation pattern shape, and port matching at the selected frequencies. The configuration presents great results, since to the authors’ knowledge, even a similar configuration given in the open literature presents some disadvantages compared to this one; moreover, not just any structure can be employed as the resonating elements, obtaining multiband behavior at the same time.

Identifying actionable components in castration–resistant prostate cancer (CRPC) is critical for the development of effective treatments. Here, the authors show that the inhibition of the redox-protective protein TRX1 decreases the growth of CRPC cells through the regulation of ROS levels, p53 and androgen receptor expression.

Establishment of the outer blood-retina barrier is a hallmark of retinal development but the contribution of choroid endothelial cells (ECs) is not known. Here the authors show in the developing mouse retina that ECs remodel the basement membrane and lead to enhanced barrier function of retinal epithelial cells.

Background and aim Hiatal hernia and lower esophageal sphincter (LES) dysfunction play major roles in gastroesophageal reflux disease (GERD) pathogenesis. We developed a novel endoscopic assessment to evaluate the gastroesophageal junction (GEJ). This study aims to evaluate the feasibility of this method for the diagnostic prediction of GERD. Methods A retrospective analysis of patients with GERD symptoms who underwent gastroscopy and esophageal pH-impedance monitoring was conducted. The novel assessment evaluated the following in retroflex view: 1) Cardiac Opening (CO): diameter of the opening of the cardia, 2) Sliding Hernia (SH): length from the diaphragmatic crus to the squamocolumnar junction, 3) Scope Holding Time% (SHT%): the percentage of time that the Scope Holding Sign (SHS) was observed out of 30 seconds. The SHS is defined as the lower esophagus holding the endoscope under excessive insufflation. The results of this assessment and that of pH-impedance monitoring were compared. Results In total, 61 patients (mean age ± SD, 54.1 ± 16.4 years, 32 males) were enrolled. CO and SH were significantly correlated with acid exposure time (AET) (ρ = 0.36, P = 0.005, and ρ = 0.36, P = 0.004). The optimal cutoff of CO for AET > 6 % was 3 cm (Sensitivity = 72.4 %, Specificity = 46.9 %, AUC = 0.64) and that of SH was 2 cm (Sensitivity = 55.2 %, Specificity = 75.0 %, AUC = 0.70). When the population was stratified according to this cutoff, patients with CO > 3 cm and those with SH > 2 cm presented higher AET (15.1 vs 4.1 %, P = 0.037, and 23.0 vs 3.6 %, P = 0.026). Optimal cutoff of SHT% for the number of all reflux episodes > 80 was 75 % (Sensitivity = 81.8 %, Specificity = 54.6%, AUC = 0.67). Patients with SHT% 80 were 81.8 % (95 %CI: 67.7 – 91.8), 54.5% (95 %CI: 40.4 – 64.5), and 68.2 % (95 %CI: 54.0 – 78.1). Conclusion This novel endoscopic assessment of GEJ significantly predicted the presence of GERD and merits further testing in future studies.

Background and study aims Fourth-generation endocytoscopy is an ultra-high magnification endoscopic technique designed to provide excellent quality in vivo histologic assessment of gastrointestinal lesions. This study aims to evaluate the diagnostic accuracy of endocytoscopy in early gastric cancer diagnosis. Patients and methods A single-center, retrospective analysis of prospectively collected data from all gastric endocytoscopic examinations was conducted. Two expert endoscopists, blinded to white-light and narrow-band imaging findings as well as histopathologic diagnosis, independently reviewed and diagnosed all endocytoscopic images. A newly recognized “enlarged nuclear sign” was detected, and its implication in early gastric cancer diagnosis was evaluated. The diagnostic performance of fourth-generation endocytoscopy was assessed while using the gold standard histopathology as a reference. Results Forty-three patients (mean age±SD, 72.6 ± 12.1 years; 31 males) were enrolled. Based on histopathology, 23 had well-differentiated adenocarcinomas, four adenomas, and 16 non-neoplastic lesions. The sensitivity, specificity, and accuracy of fourth-generation endocytoscopy for gastric cancer diagnosis were 87.0 % (95 % CI: 67.9 – 95.5), 80.0 % (95 % CI: 58.4 – 91.9), and 83.7 % (95 % CI: 70.0 – 91.9) by endoscopist A; and 91.3 % (95 % CI: 73.2 – 97.6), 75.0 % (95 % CI: 53.1 – 88.8), and 83.7 % (95 % CI: 70.0 – 91.9) by endoscopist B. The inter-observer agreement, Kappa statistic = 0.71 (95 % CI: 0.50 – 0.93), was good. The sensitivity, specificity, and accuracy of the enlarged nuclear sign for early gastric cancer diagnosis were 87.0 % (95 % CI: 67.9 – 95.5), 95.0 % (95 % CI: 76.4 – 99.1), and 90.7 % (95 % CI: 78.4 – 96.3) by endoscopist A; and 82.6 % (95 % CI: 62.9 – 93.0), 85.0 % (95 % CI: 64.0 – 94.8), and 83.7 % (95 % CI: 70.0 – 91.9) by endoscopist B. The inter-observer agreement, Kappa statistic = 0.68 (95 % CI: 0.51 – 0.89) was good. Conclusion: Fourth-generation endocytoscopy appears to aid in the diagnosis of early gastric cancer, particularly well-differentiated adenocarcinomas, due to its good diagnostic accuracy and identification of the “enlarged nuclear sign,” and deserves further evaluation in future studies.

Uncertainty regarding the movement and population exchange of Atlantic bluefin tuna (Thunnus thynnus) from the two primary spawning areas (Gulf of Mexico, Mediterranean Sea) is increasingly implicated as a major impediment for the conservation of this species. Here, two mixture methods were applied to natural chemical markers (δ18O and δ13C) in otoliths (ear stones) to comprehensively investigate the nature and degree of transoceanic movement and mixing of eastern and western populations in several areas of the North Atlantic Ocean that potentially represent mixing hotspots. Areas investigated occurred on both sides of the 45°W management boundary as well as waters off the coast of Africa (Morocco, Canary Islands) where both populations are known to occur. Projections of population composition (i.e., natal or nursery origin) from a multinomial logistic regression (MLR) classification method with different probability thresholds were generally in agreement with maximum likelihood estimates from the commonly used mixed-population program HISEA; however, predicted contributions for the less abundant population were occasionally higher for MLR estimates. Both MLR and HISEA clearly showed that mixing of Atlantic bluefin tuna in the Central North Atlantic Ocean was highly variable from year to year with expatriates of eastern or western origin commonly crossing into the other management area. Pronounced transoceanic movement and mixing of western migrants was also present off the coast of Africa, with the occurrence of western migrants in the Canary Islands and Morocco ranging from zero to the majority of the individuals assayed for the years examined. Results indicate highly variable rates of movement and population exchange for Atlantic bluefin tuna, highlighting the need for temporally resolved estimates of natal origin in mixing hotspots to improve population models used to evaluate the status of this threatened species.

In cryptography, the pseudorandom number sequences must have random appearance to be used in secure information systems. The skew tent map (STM) is an attractive map to produce pseudorandom sequences due to its easy implementation and the absence of stability islands when it is in chaotic behavior. Using the STM and sine function, we propose and analyze a function composition to propose a pseudorandom number generator (PRNG). In the analysis of the function composition, we use the bifurcation diagram and the Lyapunov exponent to perform a behavioral comparison against the STM. We show that the proposed function composition is more sensitive to initial conditions than the STM, and then it is a better option than the STM for cryptography applications. For the proposed function we determine and avoid the chaos annulling traps. The proposed PRNG can be configured to generate pseudorandom numbers of 8, 16 or 32 bits and it can be implemented on microcontrollers with different architectures. We evaluate the pseudorandomness of the proposed PRNG using the NIST SP 800-22 and TestU01 suites. Additionally, to evaluate its quality, we apply tests such as correlation coefficient, key sensitivity, statistical and entropy analysis, key space, linear complexity, and speed. Finally, we performed a comparison with similar PRNGs that produce pseudorandom sequences considering numbers of 8 and 32 bits. The results show that the proposed PRNG maintains its security regardless of the selected configuration. The proposed PRNG has five important features: easy implementation, configurable to produce number with 8, 16 or 32 bits, high processing speed, high linear complexity, and wide key space. These features are necessary for cryptographic systems.

Conditioning of a metal structure in a high-voltage system is the progressive development of resistance to vacuum arcing over the operational life of the system. This is, for instance, seen during the initial operation of radio frequency (rf) cavities in particle accelerators. It is a relevant topic for any technology where breakdown limits performance and where conditioning continues for a significant duration of system run time. Projected future linear accelerators require structures with accelerating gradients of up to 100 MV/m. Currently, this performance level is achievable only after a multimonth conditioning period. In this work, a pulsed dc system applying voltage pulses over parallel disk electrodes was used to study the conditioning process, with the objective of obtaining insight into its underlying mechanics and, ultimately, to find ways to shorten the conditioning process. Two kinds of copper electrodes were tested: as-prepared machine-turned electrodes (“hard” copper) and electrodes that additionally had been subjected to high-temperature treatments (“soft” copper). The conditioning behavior of the soft electrodes was found to be similar to that of comparably treated accelerating structures, indicating a similar conditioning process. The hard electrodes reached the same ultimate performance as the soft electrodes much faster, with a difference of more than an order of magnitude in the number of applied voltage pulses. Two distinctly different distributions of breakdown locations were observed on the two types of electrodes. Considered together, our results support the crystal structure dislocation theory of breakdown and suggest that the conditioning of copper in high field systems such as rf accelerating structures is dominated by material hardening.

Background Fragmentation of native forests is a highly visible result of human land-use throughout the world. In this study, we evaluated the effects of landscape fragmentation and matrix features on the genetic diversity and structure of Oligoryzomys longicaudatus, the natural reservoir of Hantavirus in southern South America. We focused our work in the Valdivian Rainforest where human activities have produced strong change of natural habitats, with an important number of human cases of Hantavirus. Methods We sampled specimens of O. longicaudatus from five native forest patches surrounded by silvoagropecuary matrix from Panguipulli, Los Rios Region, Chile. Using the hypervariable domain I (mtDNA), we characterized the genetic diversity and evaluated the effect of fragmentation and landscape matrix on the genetic structure of O. longicaudatus. For the latter, we used three approaches: (i) Isolation by Distance (IBD) as null model, (ii) Least-cost Path (LCP) where genetic distances between patch pairs increase with cost-weighted distances, and (iii) Isolation by Resistance (IBR) where the resistance distance is the average number of steps that is needed to commute between the patches during a random walk. Results We found low values of nucleotide diversity (π) for the five patches surveyed, ranging from 0.012 to 0.015, revealing that the 73 sampled specimens of this study belong to two populations but with low values of genetic distance (γST) ranging from 0.022 to 0.099. Likewise, we found that there are no significant associations between genetic distance and geographic distance for IBD and IBR. However, we found for the LCP approach, a significant positive relationship (r = 0.737, p = 0.05), with shortest least-cost paths traced through native forest and arborescent shrublands. Discussion In this work we found that, at this reduced geographical scale, Oligoryzomys longicaudatus shows genetic signs of fragmentation. In addition, we found that connectivity between full growth native forest remnants is mediated by the presence of dense shrublands and native forest corridors. In this sense, our results are important because they show how native forest patches and associated routes act as source of vector species in silvoagropecuary landscape, increasing the infection risk on human population. This study is the first approach to understand the epidemiological spatial context of silvoagropecuary risk of Hantavirus emergence. Further studies are needed to elucidate the effects of landscape fragmentation in order to generate new predictive models based on vector intrinsic attributes and landscape features.

Introduction. Endoscopic papillary large balloon dilatation (EPLBD) is an alternative for the treatment of common bile duct (CBD) stones. Existing evidence of factors associated with its outcomes is contradictory. Objective. To identify predictors (including the experience of an endoscopist) of success and adverse events in EPLBD. Methods. We reviewed the first 200 EPLBD with endoscopic sphincterotomy (EST) performed at our center. Demographic, clinical, and anatomic variables were studied, as well as the performance characteristics, correlating them with individual and group experience. Results. Global success was obtained in 87% of cases, and adverse events occurred in 16% of cases. Success was associated with stone size, CBD diameter, and the need to perform mechanical lithotripsy (ML). Despite that adverse events were not univariately associated with any factor, severe adverse events were more likely to occur in stones > 13.5 mm. Multivariate analysis which disclosed success was higher when ML was not required and stones were

V2O5 powders modified with different theoretical silver contents (1, 5, 10, 15, and 20 wt% as Ag2O) were obtained with acicular morphologies observed by scanning electron microscopy (SEM). Shcherbinaite crystalline phase is transformed into the Ag0.33V2O5 crystalline one with the incorporation and increase in silver content as was suggested by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analysis. With further increase in silver contents the Ag2O phase appears. Catalysts were active in photocatalytic degradation of malachite green dye under simulated solar light, which is one of the most remarkable facts of this work. It was found that V2O5-20Ag was the most active catalytic formulation and its activity was attributed to the mixture of coupled semiconductors that promotes the slight decrease in the rate of the electron-hole pair recombination.

Una de las funciones que realiza un ‘Radio Cognitivo’ es la toma de decisiones sobre el espectro radioeléctrico, esto a partir del análisis que realiza de su entorno. En este trabajo de investigación, se propone un método para la toma de decisiones para la selección de una banda en el espectro radioeléctrico que cumpla con ciertos criterios requeridos para una aplicación. Esta toma de decisiones se basa en un algoritmo de búsqueda del camino más corto similar al Algoritmo de Dijkstra. Para encontrar el camino más corto, el cual representa a la banda de frecuencia requerida, se especifican los atributos o parámetros a considerar para cada una de las bandas de acuerdo a una aplicación en particular o servicio requerido. A estos atributos o parámetros se les asignan valores es decir, pesos que determinan la prioridad e importancia para cada servicio. El algoritmo propuesto basado en Dijkstra, evalúa los parámetros del conjunto de bandas disponibles considerando el peso asignado, e indica la banda a seleccionar y que cubre con los criterios de la toma de decisiones. Se realizaron simulaciones por computadora para caracterizar los servicios identificados como mejor esfuerzo ‘Best Effort’ y tiempo real ‘Real Time’, obteniendo como resultado una latencia reducida que representa un tiempo práctico para ser implementado en un Radio Cognitivo en su toma de decisiones. Se observó también que los tiempos mostraron una mejora al ser comparados con los resultados obtenidos al implementar el Algoritmo de AHP.

[This corrects the article DOI: 10.1371/journal.pone.0141478.].

A prototype 11.994 GHz, traveling-wave accelerating structure for the Compact Linear Collider has been built, using the novel technique of assembling the structure from milled halves. The use of milled halves has many advantages when compared to a structure made from individual disks. These include the potential for a reduction in cost, because there are fewer parts, as well as a greater freedom in choice of joining technology because there are no rf currents across the halves’ joint. Here we present the rf design and fabrication of the prototype structure, followed by the results of the high-power test and post-test surface analysis. During high-power testing the structure reached an unloaded gradient of 100 MV/m at a rf breakdown rate of less than 1.5×10^{-5} breakdowns/pulse/m with a 200 ns pulse. This structure has been designed for the CLIC testing program but construction from halves can be advantageous in a wide variety of applications.

The compiled data for this study represents the first Atlantic and Mediterranean-wide effort to pool all available biometric data for Atlantic bluefin tuna (Thunnus thynnus) with the collaboration of many countries and scientific groups. Biometric relationships were based on an extensive sampling (over 140,000 fish sampled), covering most of the fishing areas for this species in the North Atlantic Ocean and Mediterranean Sea. Sensitivity analyses were carried out to evaluate the representativeness of sampling and explore the most adequate procedure to fit the weight-length relationship (WLR). The selected model for the WLRs by stock included standardized data series (common measurement types) weighted by the inverse variability. There was little difference between annual stock-specific round weight-straight fork length relationships, with an overall difference of 6% in weight. The predicted weight by month was estimated as an additional component in the exponent of the weight-length function. The analyses of monthly variations of fish condition by stock, maturity state and geographic area reflect annual cycles of spawning and feeding behavior. We update and improve upon the biometric relationships for bluefin currently used by the International Commission for the Conservation of Atlantic Tunas, by incorporating substantially larger datasets than ever previously compiled, providing complete documentation of sources and employing robust statistical fitting. WLRs and other conversion factors estimated in this study differ from the ones used in previous bluefin stock assessments.

Adsorption on amine-grafted materials may be a potentially attractive alternative to capture CO 2 from power plants. Activated carbon (AC) has been proposed as a potential adsorbent due to its natural affinity for CO 2 and the possibility of tailoring its textural properties and surface chemistry to enhance capacity and selectivity. An AC commercial sample was functionalized with monoethanolamine to obtain nitrogen-enriched AC with two different loadings (ACN10 and ACN20). Characterization of the sample was carried out by nitrogen adsorption–desorption isotherms at 77 K, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy and adsorption microcalorimetry. The CO 2 equilibrium adsorption experiments were carried out in a volumetric system within the pressure range from vacuum to 13 bar, at 298 and 348 K. Impregnated AC showed different chemical and textural characteristics with a significant reduction in the surface area, depending on the amine loading. A high adsorption capacity at room temperature (298 K) and high pressure was observed for the pristine AC as compared with the modified samples. The reduction in surface area affected the adsorption capacity of CO 2 at 298 and 348 K, except for adsorption on ACN10 at 348 K, which suggests the occurrence of chemisorption.

In this work, we propose that packets travelling across a wireless sensor network (WSN) can be seen as the active agents that make up a complex system, just like a bird flock or a fish school, for instance. From this perspective, the tools and models that have been developed to study this kind of systems have been applied. This is in order to create a distributed congestion control based on a set of simple rules programmed at the nodes of the WSN. Our results show that it is possible to adapt the carried traffic to the network capacity, even under stressing conditions. Also, the network performance shows a smooth degradation when the traffic goes beyond a threshold which is settled by the proposed self-organized control. In contrast, without any control, the network collapses before this threshold. The use of the proposed solution provides an effective strategy to address some of the common problems found in WSN deployment by providing a fair packet delivery. In addition, the network congestion is mitigated using adaptive traffic mechanisms based on a satisfaction parameter assessed by each packet which has impact on the global satisfaction of the traffic carried by the WSN.

On January 27, 2022, the United Kingdom reported an increased number of infections with extensively drug-resistant (XDR) Shigella sonnei during September 1, 2021-January 10, 2022 (1). A total of 146 [...]

Recently, it has been proposed that the one of the main determinants of complex societies in Hymenoptera is colony size, since the existence of large colonies reduces the direct reproductive success of an average individual, given a decreased chance of being part of the reproductive caste. In this study, we evaluate colony size evolution in corbiculate bees and their relationship with the sociality level shown by these bees. Specifically i) the correlation between colony size and level of sociality considering the phylogenetic relationship to evaluate a general evolutionary tendency, and ii) the hypothetical ancestral forms of several clades within a phylogeny of corbiculate bees, to address idiosyncratic process occurring at important nodes. We found that the level of social complexity in corbiculate bees is phylogenetically correlated with colony size. Additionally, another process is invoked to propose why colony size evolved concurrently with the level of social complexity. The study of this trait improves the understanding of the evolutionary transition from simple to complex societies, and highlights the importance of explicit probabilistic models to test the evolution of other important characters involved in the origin of eusociality.

We aimed to test the antiproliferative effect of acetylsalicylic acid (ASA) on vascular smooth muscle cells (VSMC) from bypass surgery patients and the role of transforming growth factor beta 1 (TGF-beta1).VSMC were isolated from remaining internal mammary artery from patients who underwent bypass surgery. Cell proliferation and DNA fragmentation were assessed by ELISA. Protein expression was assessed by Western blot. ASA inhibited BrdU incorporation at 2 mM. Anti-TGF-beta1 was able to reverse this effect. ASA (2 mM) induced TGF-beta1 secretion; however it was unable to induce Smad activation. ASA increased p38(MAPK) phosphorylation in a TGF-beta1-independent manner. Anti-CD105 (endoglin) was unable to reverse the antiproliferative effect of ASA. Pre-surgical serum levels of TGF-beta1 in patients who took at antiplatelet doses ASA were assessed by ELISA and remained unchanged.In vitro antiproliferative effects of aspirin (at antiinflammatory concentration) on human VSMC obtained from bypass patients are mediated by TGF-beta1 and p38(MAPK). Pre-surgical serum levels of TGF- beta1 from bypass patients who took aspirin at antiplatelet doses did not change.