Tangential velocity constraint for orbital maneuvers with Theory of Functional Connections.

Maneuvering a spacecraft in the cislunar space is a complex problem, since it is highly perturbed by the gravitational influence of both the Earth and the Moon, and possibly also the Sun. Trajectories minimizing the needed fuel are generally preferred in order to decrease the mass of the payload. A classical method to constrain maneuvers is mathematically modeling them using the Two Point Boundary Value Problem (TPBVP), defining spacecraft positions at the start and end of the trajectory. Solutions to this problem can then be obtained with optimization techniques like the nonlinear least squares conjugated with the Theory of Functional Connections (TFC) to embed the constraints, which recently became an effective method for deducing orbit transfers. In this paper, we propose a tangential velocity (TV) type of constraints to design orbital maneuvers. We show that the technique presented in this paper can be used to transfer a spacecraft (e.g. from the Earth to the Moon) and perform gravity assist maneuvers (e.g. a swing-by with the Moon). In comparison with the TPBVP, solving the TV constraints via TFC offers several advantages, leading to a significant reduction in computational time. Hence, it proves to be an efficient technique to design these maneuvers.

Isochronous island bifurcations driven by resonant magnetic perturbations in tokamaks.

Recent evidence shows that heteroclinic bifurcations in magnetic islands may be caused by the amplitude variation of resonant magnetic perturbations in tokamaks. To investigate the onset of these bifurcations, we consider a large aspect ratio tokamak with an ergodic limiter composed of two pairs of rings that create external primary perturbations with two sets of wave numbers. An individual pair produces hyperbolic and elliptic periodic points, and its associated islands, that are consistent with the Poincaré-Birkhoff fixed-point theorem. However, for two pairs producing external perturbations resonant on the same rational surface, we show that different configurations of isochronous island chains may appear on phase space according to the amplitude of the electric currents in each pair of the ergodic limiter. When one of the electric currents increases, isochronous bifurcations take place and new islands are created with the same winding number as the preceding islands. We present examples of bifurcation sequences displaying (a) direct transitions from the island chain configuration generated by one of the pairs to the configuration produced by the other pair, and (b) transitions with intermediate configurations produced by the limiter pairs coupling. Furthermore, we identify shearless bifurcations inside some isochronous islands, originating nonmonotonic local winding number profiles with associated shearless invariant curves.

Dosimetric and biologic intercomparison between electron and proton FLASH beams.

BACKGROUND AND PURPOSE: The FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at an average dose rate above 40 Gy/s. However, no systematic intercomparison of the FLASH effect produced by eFLASHvs. pFLASH has yet been performed and constitutes the aim of the present study. MATERIALS AND METHODS: The electron eRT6/Oriatron/CHUV/5.5 MeV and proton Gantry1/PSI/170 MeV were used to deliver conventional (0.1 Gy/s eCONV and pCONV) and FLASH (≥110 Gy/s eFLASH and pFLASH) dose rates. Protons were delivered in transmission. Dosimetric and biologic intercomparisons were performed using previously validated dosimetric approaches and experimental murine models. RESULTS: The difference between the average absorbed dose measured at Gantry 1 with PSI reference dosimeters and with CHUV/IRA dosimeters was -1.9 % (0.1 Gy/s) and + 2.5 % (110 Gy/s). The neurocognitive capacity of eFLASH and pFLASH irradiated mice was indistinguishable from the control, while both eCONV and pCONV irradiated cohorts showed cognitive decrements. Complete tumor response was obtained after an ablative dose of 20 Gy delivered with the two beams at CONV and FLASH dose rates. Tumor rejection upon rechallenge indicates that anti-tumor immunity was activated independently of the beam-type and the dose-rate. CONCLUSION: Despite major differences in the temporal microstructure of proton and electron beams, this study shows that dosimetric standards can be established. Normal brain protection and tumor control were produced by the two beams. More specifically, normal brain protection was achieved when a single dose of 10 Gy was delivered in 90 ms or less, suggesting that the most important physical parameter driving the FLASH sparing effect might be the mean dose rate. In addition, a systemic anti-tumor immunological memory response was observed in mice exposed to high ablative dose of electron and proton delivered at CONV and FLASH dose rate.

Monitoring the feeding and parental care behavior of a pair of free-living owls (Tyto furcata) in the nest during the reproductive period in Rio de Janeiro, Brazil

Abstract The American Barn Owl (Tyto furcata) lives in urban, periurban and wild environments and feeds mainly on small rodents, meaning it has great importance in the biological control of pests. The aim of this work was to describe the reproductive, parental and eating habits of a pair of American barn owls naturally living outside a residence in the urban area of the municipality of Campos dos Goytacazes, Rio de Janeiro state, Brazil. A wood box was installed on an outside wall of the home, monitored by a video camera. A spreadsheet was created to keep track of the observations recorded. The female laid four eggs, and after an incubation period of 30-32 days all the eggs hatched, but only two chicks survived after cannibalism among the chicks. Initially, the male provided the food to the chicks and the female remained in the nest caring for the brood. After approximately a month, the female also began to leave the nest and return with prey, which was offered to the chicks, with the male also continuing this behavior. The chicks left the nest in September, 2017. The data obtained show the existence of cooperation and division of tasks between male and female owls during the reproductive period.

Resumo A coruja-das-torres americana (Tyto furcata) vive em ambientes urbanos e se alimenta principalmente de pequenos roedores, sendo de grande importância no controle biológico de pragas. O objetivo deste trabalho foi descrever os hábitos alimentares, parentais e reprodutivos de um casal de corujas-das-torres americanas, naturalmente vivendo fora de uma residência na zona urbana do município de Campos dos Goytacazes, estado do Rio de Janeiro, Brasil. Uma caixa de madeira foi instalada em uma parede externa da casa, monitorada por uma câmera de vídeo. Uma planilha foi criada para manter o controle das observações registradas. A fêmea pôs quatro ovos, e após período de incubação de 30-32 dias todos os ovos eclodiram, mas apenas dois filhotes sobreviveram após o canibalismo entre os filhotes. Inicialmente, o macho fornecia a comida aos filhotes e a fêmea permanecia no ninho cuidando da ninhada. Depois de cerca de um mês, a fêmea também começou a sair do ninho e voltar com a presa, que era oferecida aos filhotes, com o macho também continuando com esse comportamento. Os filhotes deixaram o ninho em setembro de 2017. Os dados obtidos mostram a existência de cooperação e divisão de tarefas entre corujas machos e fêmeas durante o período reprodutivo.

Monitoring the feeding and parental care behavior of a pair of free-living owls (Tyto furcata) in the nest during the reproductive period in Rio de Janeiro, Brazil / Monitoramento do comportamento alimentar e cuidado parental de um casal de corujas de vida livre (Tyto furcata) no ninho durante o período reprodutivo no Rio de Janeiro, Brasil

Abstract The American Barn Owl (Tyto furcata) lives in urban, periurban and wild environments and feeds mainly on small rodents, meaning it has great importance in the biological control of pests. The aim of this work was to describe the reproductive, parental and eating habits of a pair of American barn owls naturally living outside a residence in the urban area of the municipality of Campos dos Goytacazes, Rio de Janeiro state, Brazil. A wood box was installed on an outside wall of the home, monitored by a video camera. A spreadsheet was created to keep track of the observations recorded. The female laid four eggs, and after an incubation period of 30-32 days all the eggs hatched, but only two chicks survived after cannibalism among the chicks. Initially, the male provided the food to the chicks and the female remained in the nest caring for the brood. After approximately a month, the female also began to leave the nest and return with prey, which was offered to the chicks, with the male also continuing this behavior. The chicks left the nest in September, 2017. The data obtained show the existence of cooperation and division of tasks between male and female owls during the reproductive period.

Resumo A coruja-das-torres americana (Tyto furcata) vive em ambientes urbanos e se alimenta principalmente de pequenos roedores, sendo de grande importância no controle biológico de pragas. O objetivo deste trabalho foi descrever os hábitos alimentares, parentais e reprodutivos de um casal de corujas-das-torres americanas, naturalmente vivendo fora de uma residência na zona urbana do município de Campos dos Goytacazes, estado do Rio de Janeiro, Brasil. Uma caixa de madeira foi instalada em uma parede externa da casa, monitorada por uma câmera de vídeo. Uma planilha foi criada para manter o controle das observações registradas. A fêmea pôs quatro ovos, e após período de incubação de 30-32 dias todos os ovos eclodiram, mas apenas dois filhotes sobreviveram após o canibalismo entre os filhotes. Inicialmente, o macho fornecia a comida aos filhotes e a fêmea permanecia no ninho cuidando da ninhada. Depois de cerca de um mês, a fêmea também começou a sair do ninho e voltar com a presa, que era oferecida aos filhotes, com o macho também continuando com esse comportamento. Os filhotes deixaram o ninho em setembro de 2017. Os dados obtidos mostram a existência de cooperação e divisão de tarefas entre corujas machos e fêmeas durante o período reprodutivo.

Unlocking the molecular realm: advanced approaches for identifying clinically and environmentally relevant bacteria.

Rapid, effective, and specific identification of clinical and environmental bacterial pathogens is of major importance for their control. Traditionally, bacteria have been identified by phenotypic methods based on morphological, biochemical, and metabolic properties. While these methods are very useful in clinical practice, they have limitations including a poor ability to differentiate within and between species and time-consuming workflows. Newly developed molecular methods can greatly improve the accuracy of taxonomic characterization, identifying specific strains of medical or environmental importance. However, due to high costs and the need for trained professionals, these methods are not yet routine in diagnostic laboratories. Thus, disseminating knowledge on advances in molecular identification techniques is pivotal to make these methodologies accessible. The objective of this work was to review and discuss current molecular techniques for bacteria identification aiming to track and monitor microbial agents in clinical and environmental samples.

ASURE Clinical Trial Protocol: A Randomized, Placebo-Controlled, Proof-of-Concept Study Aiming to Evaluate Safety and Target Engagement following Administration of TW001 in Early Alzheimer's Disease Patients.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease with complex disease etiology and pathological processes. These include formation of plaques and tangles, aberrant lipid processing, neuroinflammation, cerebrovascular dysregulation, ion channel and mitochondrial dysfunction, and oxidative stress. Disease-modifying therapies focusing on all these different facets are needed. TW001 is an oral formulation with the radical scavenger edaravone as its active ingredient, targeting oxidative stress. OBJECTIVES: This manuscript describes the trial design for Phase IIA Alzheimer Study Using oRal Edaravone (ASURE). METHODS: ASURE is a randomized, placebo-controlled, proof-of-concept study aiming to evaluate safety and target engagement following administration of TW001 in early AD patients. Patients should have a biomarker confirmed diagnosis to be included in the trial and will be treated for 90 days. The primary endpoints include safety and effect of TW001 on oxidative stress biomarkers. Exploratory endpoints focus on a panel of AD(-related) fluid-based biomarkers and EEG. In addition, a recently developed cognitive functional composite (CFC) score will measure early signs of cognitive and functional effects of TW001. RESULTS: This article outlines the design of the clinical study, no results are included. CONCLUSIONS: The ASURE trial design is discussed, with a particular focus on fluid biomarkers, EEG, and CFC as endpoints. By testing multiple measures related to pathology, pharmacodynamics, EEG as proxy for cognition, and cognitive functional scores, it is expected that small changes will be detectable in trials of shorter duration. Moreover, the wide range of endpoints allows to make well-informed decisions for designing pivotal studies later.

Is Periodontal and Peri- Implant Disease Associated with Fixed Partial Denture Use? A 25-year Prospective Case Series.

INTRODUCTION: The association of the periodontium with the fixed prosthesis is the basis of prosthetic rehabilitation. This prospective case series aimed to evaluate periodontal health through the relation between periodontal/peri-implant disease progression and the use of fixed partial dentures (FPDs). METHODS: Probing depth (PD), clinical attachment level (CAL), gingival index (GI), and plaque index (PI) on either teeth or implants were evaluated at up to 25-year follow-up and compared with the baseline. Statistical analysis was performed using the Kaplan-Meier test (p⟨0.05). RESULTS: The prospective evaluation showed that the patients maintained adequate periodontal health. Failure (severe periodontal stages) occurred in 12.5% of patients. The survival rate for 107 teeth/implants was 80.48%. The comparisons for clinical parameters revealed no statistically significant difference (p⟩ 0.05). At T1, the measurements for anterior and posterior regions, respectively, were PD =2.7mm and 3.1mm; CAL= 3.3mm and 3.6mm; GI=0.5 (both regions); and PI=0.79 and 0.62. Periodontal/peri-implant disease progression did not relate to the use of prostheses. CONCLUSIONS: Patients with more frequent follow-up appointments and lower GI and PI showed periodontal health for longer periods. Patients with different oral hygiene levels present different periodontal disease progression. Periodic hygiene control and motivation are vital factors for extensive oral rehabilitation success.

Distinct carbapenems susceptibility profiles in isogenic isolates of Klebsiella pneumoniae presenting Ompk36 disruption and expression of down-regulated blaKPC-2.

The isolation of multidrug-resistant Klebsiella pneumoniae in hospitals is a major public health threat, increasing patient hospitalization costs, morbidity and mortality. Therefore, this work investigated the resistance mechanisms that produced different carbapenems susceptibility profiles in two isogenic strains of K. pneumoniae isolated from the same patient in a public hospital in Recife, Pernambuco. The genes that encode the main porins in K. pneumoniae, ompK35 and ompK36, and several beta-lactamase genes were analyzed. The expression of these genes was evaluated by quantitative real time PCR (polymerase chain reaction) with reverse transcriptase (RT-qPCR). SDS-PAGE (sodium dodecyl sulphate-polyacrylamide gel electrophoresis) was performed to analyze the outer membrane proteins. The analysis of the ompK36 genetic environment disclosed an IS903 insertion sequence disrupting this gene in the ertapenem resistant isolate (KPN133). The blaKPC-2 gene showed down-regulated expression in both isolates. Our findings show that changes in porins, especially OmpK36, are more determinant to carbapenems susceptibility profile of bacterial isolates than variations in blaKPC gene expression.

Cytotoxic screening of plants from the Brazilian Atlantic Forest has led to the identification of Casearia arborea and Sorocea hilarii as sources of antitumor compounds.

In the present study, we have evaluated the cytotoxic activity of 282 extracts from 72 native plant species of the Brazilian Atlantic Forest biome. As a result, Casearia arborea and Sorocea hilarii leaves extracts showed cytotoxic activity against three tumour cell lines tested (B16F10, SW480 and Jurkat). After bioassay-guided fractionation, the bioactive fractions were submitted to the dereplication study via High-performance Liquid Chromatography, connected to High-resolution Mass Spectrometry (HPLC-ESI-QTOF/MS) analysis, combined with a Global Natural Products Social Molecular Networking (GNPS) tool. A combination of bioactivity-guided and dereplication approaches resulted in the putative annotation of 27 clerodane diterpenes and 9 flavonoids as main compounds present in the cytotoxic fractions of C. arborea. Regarding the active fraction of S. hilarii, 10 megastigmans, 17 spirostane steroids derivatives and 2 lignans were putatively identified. In conclusion, Casearia arborea and Sorocea hilarii are potential sources of antitumor compounds.

Dosimetric and biologic intercomparison between electron and proton FLASH beams.

Background and purpose: The FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at a mean dose rate above 40 Gy/s. However, no systematic intercomparison of the FLASH effect produced by e vs. pFLASH has yet been performed and constitutes the aim of the present study. Materials and methods: The electron eRT6/Oriatron/CHUV/5.5 MeV and proton Gantry1/PSI/170 MeV were used to deliver conventional (0.1 Gy/s eCONV and pCONV) and FLASH (≥100 Gy/s eFLASH and pFLASH) irradiation. Protons were delivered in transmission. Dosimetric and biologic intercomparisons were performed with previously validated models. Results: Doses measured at Gantry1 were in agreement (± 2.5%) with reference dosimeters calibrated at CHUV/IRA. The neurocognitive capacity of e and pFLASH irradiated mice was indistinguishable from the control while both e and pCONV irradiated cohorts showed cognitive decrements. Complete tumor response was obtained with the two beams and was similar between e and pFLASH vs. e and pCONV. Tumor rejection was similar indicating that T-cell memory response is beam-type and dose-rate independent. Conclusion: Despite major differences in the temporal microstructure, this study shows that dosimetric standards can be established. The sparing of brain function and tumor control produced by the two beams were similar, suggesting that the most important physical parameter driving the FLASH effect is the overall time of exposure which should be in the range of hundreds of milliseconds for WBI in mice. In addition, we observed that immunological memory response is similar between electron and proton beams and is independent off the dose rate.

Geochemical behavior of rare earth elements (REE) in urban reservoirs: the case of Funil Reservoir, Rio de Janeiro State, Brazil.

Rare earth elements (REE) have unique chemical properties, which allow their use as geochemical tracers. In this context, the present study aims to assess the role of Funil Reservoir on REE biogeochemical behavior. We collected water samples upstream of the reservoir (P-01) in the city of Queluz, inside the reservoir (P-02), and downstream of Funil Reservoir (P-03) in the city of Itatiaia, RJ. In the field, physicochemical parameters were measured using a probe (pH, temperature, electrical conductivity, and dissolved oxygen). In the laboratory, water samples were filtered (0.45 µm) and properly packed until chemical analysis. Chlorophyll a concentrations were determined by a spectrophotometric method and suspended particulate matter (SPM) by a gravimetric method. Ionic concentrations were determined by ion chromatography technique and REE concentrations were determined by ICP-MS. Chlorophyll a concentrations were higher in Funil Reservoir. Ionic concentrations in Queluz (P-01) suggest anthropic contamination. The sum of REE in the dissolved fraction ranged from 2.12 to 12.22 µg L-1. A positive anomaly of La in Queluz indicates anthropic contamination. The observed patterns indicate that Funil Reservoir acts as a biogeochemical barrier, modifying the fluvial transport of REE. Nonetheless, another factor that probably influences REE behavior is the algal bloom that occurs in reservoirs during the rainy season. The seasonal behavior of algae can influence REE biogeochemistry through the incorporation and release of trace metals.

Electronic device or regulated tobacco product? Learning from the diffusion of heated tobacco products in Spain.

OBJECTIVES: Tobacco companies have introduced heated tobacco product (HTP) in many countries and marketed it on the grounds that it is a less harmful alternative to health. However, tobacco companies have been widely criticized for taking advantage of a loophole that allows electronic devices to circumvent regulations limiting tobacco advertising. This work aims to determine whether HTPs respected the rules that regulate tobacco advertising when it was introduced in Spain. STUDY DESIGN: This is an observational epidemiological study. METHODS: Using monthly time series data from September 2016 to June 2020, we analyzed whether the adoption of HTPs has followed the same behavior patterns as other brands that were introduced under the same conditions of use. The Bass model is used to analyze the diffusion of HTPs, and 30 other traditional cigarette brands introduced under the same conditions as this HTPs. RESULTS: The adoption of HTPs in Spain has been like that of brands of slim cigarettes that are mistakenly considered to be healthier than traditional cigarettes. The results indicate that the use of HTPs has spread in the same way as additive-free and ultra-slim cigarette brands. CONCLUSIONS: Policymakers should keep in mind that laws should restrict any marketing of tobacco products that promotes positive connotations between tobacco use and being healthy. If manufacturers are allowed to classify a category and/or brand of tobacco products as less harmful to health, the imitation effect is very high, leading to the proliferation of smoking.

Unlocking the molecular realm: advanced approaches for identifying clinically and environmentally relevant bacteria

Rapid, effective, and specific identification of clinical and environmental bacterial pathogens is of major importance for their control. Traditionally, bacteria have been identified by phenotypic methods based on morphological, biochemical, and metabolic properties. While these methods are very useful in clinical practice, they have limitations including a poor ability to differentiate within and between species and time-consuming workflows. Newly developed molecular methods can greatly improve the accuracy of taxonomic characterization, identifying specific strains of medical or environmental importance. However, due to high costs and the need for trained professionals, these methods are not yet routine in diagnostic laboratories. Thus, disseminating knowledge on advances in molecular identification techniques is pivotal to make these methodologies accessible. The objective of this work was to review and discuss current molecular techniques for bacteria identification aiming to track and monitor microbial agents in clinical and environmental samples.

Growth performance of South African Windsnyer pigs to the dietary inclusion of Amarula oil cake.

Dietary inclusion of Amarula oil cake (AOC) in pig diets can ease pressure of relying on non-native feed sources and benefit the swine industry. The study was conducted to determine the growth performance of Windsnyer pigs fed increasing levels of AOC. Twenty-five clinically growing male boars with an initial body weight of 19.92 ± 8.74 kg were used in the study that lasted 6 weeks. All pigs were allocated to diets in a completely randomised design. Five experimental diets were formulated to contain 0, 50, 100, 150 and 200 g/kg DM of AOC. Average daily feed intake (ADFI), average daily gain (ADG), feed conversion ratio (FCR), scaled average daily feed intake (SADFI), scaled average daily gain (SADG) and body weight (BW) were calculated weekly. The diet affected ADFI, ADG, FCR and SADG (P < 0.05). Scaled average daily feed intake was not affected by the diet (P > 0.05). There was a significant interaction between AOC inclusion and weeks of feeding on ADFI, ADG and FCR (P < 0.05). Age of pigs decreased FCR quadratically (P < 0.001). A quadratic relationship between ADFI and increasing levels of AOC was observed (P < 0.05). Average daily gain, FCR and SADG decreased linearly with increasing AOC levels (P < 0.05). Using the broken stick analyses, the maximum inclusion of AOC was 102.17 g/kg DM. Amarula oil cake can be incorporated in diets of Windsnyer pigs up to 100 g/kg DM without constraining growth performance.

Nephroprotective effect of exercise training in cisplatin-induced renal damage in mice: influence of training protocol.

Cisplatin is an effective antineoplastic agent, but its use is limited by its nephrotoxicity caused by the oxidative stress in tubular epithelium of nephrons. On the other hand, regular exercise provides beneficial adaptations in different tissues and organs. As with many drugs, dosing is extremely important to get the beneficial effects of exercise. Thus, we aimed to investigate the influence of exercise intensity and frequency on cisplatin-induced (20 mg/kg) renal damage in mice. Forty male Swiss mice were divided into five experimental groups (n=8 per group): 1) sedentary; 2) low-intensity forced swimming, three times per week; 3) high-intensity forced swimming, three times per week; 4) low-intensity forced swimming, five times per week; and 5) high-intensity forced swimming, five times per week. Body composition, renal structure, functional indicators (plasma urea), lipid peroxidation, antioxidant enzyme activity, expression of genes related to antioxidant defense, and inflammatory and apoptotic pathways were evaluated. Comparisons considered exercise intensity and frequency. High lipid peroxidation was observed in the sedentary group compared with trained mice, regardless of exercise intensity and frequency. Groups that trained three times per week showed more benefits, as reduced tubular necrosis, plasma urea, expression of CASP3 and Rela (NFkB subunit-p65) genes, and increased total glutathione peroxidase activity. No significant difference in Nfe2l2 (Nrf2) gene expression was observed between groups. Eight weeks of regular exercise training promoted nephroprotection against cisplatin-mediated oxidative injury. Exercise frequency was critical for nephroprotection.