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Community engagement; Tuberculosis research Participación de la comunidad; Investigación de la tuberculosis Compromís comunitari; Recerca en tuberculosi Objectives: Community representatives are key to ensuring that tuberculosis (TB) research is relevant, culturally sensitive, and appropriate. For all trials (new drugs or treatment regimens, diagnostics, or vaccines) this can result in improvement of recruitment, retention, and adherence to the trial schedule. The early engagement of the community will, later in time, support the process of implementation of new policies designed for successful products. We aim at developing a structured protocol for the early engagement of TB community representatives developed in the context of the EU-Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project. Design: The EU-PEARL Innovative Medicine Initiative 2 (IMI2) project TB work package has developed a community engagement (CE) framework to ensure fair and efficient participation of the community in the design and implementation of TB clinical platform trials. Results: We showed that early engagement of the EU-PEARL community advisory board highly contributes to the process of development of a community-acceptable Master Protocol Trial and Intervention-Specific Appendixes. We identified capacity building and training as major gaps in advancing CE in the TB field. Conclusion: Developing strategies to address these needs can contribute to preventing tokenism and increase the acceptability and appropriateness of TB research. This work is partially supported by EU-PEARL. EU-PEARL has received funding from the InnovativeMedicines Initiative 2 Joint Undertaking under grant agreement No 853966. This Joint Undertaking receivessupport from the European Union’s Horizon 2020 research and innovation program and EFPIA and Children’sTumor Foundation, Global Alliance for TB Drug Development non-profit organization, SpringworksTherapeutics Inc. This publication reflects the authors’ views. Neither IMI nor the European Union,EFPIA,or any Associated Partners are responsible for any use that may be made of the information contained hereinDMC is the co-leader of EU-PEARL WP5. ASM is supported by a Juan Rodés (JR18/00022) postdoctoral fellowship from ISCIII. FS salary is supported by EU-PEARLgrant to UniSR.

Requirements elicitation is a fundamental step in a software development process since it is at this stage that the software begins to be designed. In some situations, the problems related to the failure of the software development project are due to an incomplete requirements elicitation, resulting in solutions that do not understand all the necessary functionalities or do not incorporate innovation. Despite the various techniques offered by Requirements Engineering, situations such as the growing application market and the need for innovation further increase the importance of understanding the user’s different needs. In this paper, we investigated how the journey map and personas techniques are being used in requirements elicitation in both the literature and the industry, along with the advantages, disadvantages and challenges of using these techniques. We conducted systematic literature review to identify the personas and journey map techniques used in requirements elicitation in the literature and industry. In addition, we conducted a survey with 52 practitioners (software developers, users and managers) to investigate their perceptions of the use of journey maps and personas techniques in the requirements elicitation phase. Twenty-four primary studies were identified that address journey map and personas techniques in software requirements elicitation. In addition, most respondents stated that using these techniques facilitates understanding the requirements, providing better integration, collaboration and leveling of knowledge among the members of the software development teams. Our findings allow us to conclude that most of the software developers, users and managers that participated in the survey consider that the journey map and personas techniques are effective in helping understand the software requirements to be developed by the development teams.

Funder: Ludwig Maximilians University Munich | Center for NanoScience, Ludwig-Maximilians-Universität Mnchen (CeNS, LMU); doi: https://doi.org/10.13039/501100007153, Funder: Alexander von Humboldt-Stiftung (Alexander von Humboldt Foundation); doi: https://doi.org/10.13039/100005156, Single-molecule Förster-resonance energy transfer (smFRET) experiments allow the study of biomolecular structure and dynamics in vitro and in vivo. We performed an international blind study involving 19 laboratories to assess the uncertainty of FRET experiments for proteins with respect to the measured FRET efficiency histograms, determination of distances, and the detection and quantification of structural dynamics. Using two protein systems with distinct conformational changes and dynamics, we obtained an uncertainty of the FRET efficiency ≤0.06, corresponding to an interdye distance precision of ≤2 Å and accuracy of ≤5 Å. We further discuss the limits for detecting fluctuations in this distance range and how to identify dye perturbations. Our work demonstrates the ability of smFRET experiments to simultaneously measure distances and avoid the averaging of conformational dynamics for realistic protein systems, highlighting its importance in the expanding toolbox of integrative structural biology.

Context: The use of Creativity and Design Thinking (C&DT) techniques favor the generation of new ideas based on the needs of users and stakeholders, and can support software developers during the process of requirements elicitation. Objectives: In this work, we aim to identify C&DT techniques to perform requirements elicitation proposed in the literature and in the industry and investigate the perception of software developers about using these techniques. Methods: We conducted a systematic literature review (SLR) to identify the C&DT techniques in the literature and a regional survey with software development teams from several companies in Brazil to identify which techniques found in the literature are currently being used by organizations. The survey also investigated the level of knowledge that software developers have regarding the C&DT techniques, and whether they agree that the use of these techniques can help to achieve a more effective process of requirements elicitation. Results: In the SLR, we identified 86 C&DT techniques that support requirement elicitation activities. In the survey, most developers outlined that C&DT techniques facilitate requirements elicitation and stated that they have more knowledge and usage experience with DT techniques than creativity techniques. The most used DT techniques mentioned by survey participants were: interview, brainstorming, uses cases, activity analysis, user story, and rapid prototyping, whereas for creativity techniques were: analogies, creativity workshops, focus group, questions list, clarification, none and combining ideas. Conclusions: The results showed that despite the existence of a large number of techniques in the literature, the developers’ lack of knowledge about these techniques makes them not used in the industry. However, the developers’ responses showed that the use of C&DT techniques helps to make requirements elicitation more effective.

Mandelic acid is an enantiomer of interest in many areas, in particular for the pharmaceutical industry. One of the approaches to produce enantiopure mandelic acid is through crystallization from an aqueous solution. We propose in this study a numerical tool based on lattice Boltzmann simulations to model crystallization dynamics of (S)-mandelic acid. The solver is first validated against experimental data. It is then used to perform parametric studies concerning the effects of important parameters such as supersaturation and seed size on the growth rate. It is finally extended to investigate the impact of forced convection on the crystal habits. Based on there parametric studies, a modification of the reactor geometry is proposed that should reduce the observed deviations from symmetrical growth with a five-fold habit.

Despite the sufficient knowledge on the physics of vortices formed over slender delta wings, there is a lack of understanding about how corotating and counter-rotating vortices near the wing leading edge interact with each other. The vortex interaction will depend on the wing planform, leading-edge sweeps, leading-edge shapes, angle of attack, angle of sideslip, and the Reynolds number. In this study, experiments were performed on a range of planform configurations to determine the influence of multisweep wing configurations on the vortex interactions and breakdown thereof. Force/moment measurements were conducted to understand globally the effect of the planform configuration, whereas particle tracking surface oil flow and stereoscopic particle image velocimetry were employed to detect interactions locally in the flowfield. Results were validated against corresponding numerical simulations and past experiments. Comprehensive results indicated a strong correlation between the chord ratios of the initial sweep on the suppression of vortex breakdown. Specifically, two cases with varying chord ratios were identified that exhibited unique vortex breakdown progression (gradual and rapid). Flowfield measurements elucidated key flow features responsible for the differing breakdown progression.

Os nematoides fitoparasitas, ou fitonematoides são um dos principais organismos responsáveis pelos ataques às culturas agrícolas. Apesar disso, esses parasitas ainda são pouco estudados, sendo de difícil diagnóstico. Com o objetivo de identificar inovações desenvolvidas nessa área, este trabalho mostra uma prospecção tecnológica de patentes e científica relacionadas a dispositivos, sistemas e processos para automatizar a identificação e quantificação de nematoides. Os documentos científicos mostraram que tecnologias de última geração vêm sendo utilizadas para o desenvolvimento de inovações, como ou uso de aprendizado profundo, métodos estatísticos e análises por imagens. Os resultados da prospecção tecnológica evidenciaram que o tema tem sido trabalhado com mais frequência a partir de 2019, com a concentração de inovações na China. Porém, a pequena quantidade de patentes identificadas indica a existência de uma profunda lacuna em relação à exploração do tema, o que implica em grande potencial para o desenvolvimento de tecnologias nessa área.

IL-12 is a pleotropic inflammatory cytokine, which has broad stimulatory effects on various immune cell populations, making it an attractive target for cancer immunotherapy. However, despite generating robust antitumor activity in syngeneic murine tumor models, clinical administration of IL-12 has been limited by severe toxicity. mWTX-330 is a selectively inducible INDUKINE molecule comprised of a half-life extension domain and an inactivation domain linked to chimeric IL-12 by tumor protease–sensitive linkers. Systemic administration of mWTX-330 in mice was well tolerated, resulted in robust antitumor immunity in multiple tumor models, and preferentially activated tumor-infiltrating immune cells rather than immune cells present in peripheral tissues. Antitumor activity was dependent on in vivo processing of the protease cleavable linkers and required CD8+ T cells for full efficacy. Within the tumor, mWTX-330 increased the frequency of cross-presenting dendritic cells (DC), activated natural killer (NK) cells, skewed conventional CD4+ T cells toward a T helper 1 (TH1) phenotype, drove regulatory T cells (Treg) fragility, and increased the frequency of polyfunctional CD8+ T cells. mWTX-330 treatment also increased the clonality of tumor-infiltrating T cells by expanding underrepresented T-cell receptor (TCR) clones, drove CD8+ T and NK cells towards increased mitochondrial respiration and fitness, and decreased the frequency of TOX+ exhausted CD8+ T cells within the tumor. A fully human version of this INDUKINE molecule was stable in human serum, was reliably and selectively processed by human tumor samples, and is currently in clinical development.

The discovery of bioactive natural products lies at the forefront of human medicine. The continued discovery of these molecules is imperative in the fight against infection and disease. While natural products have historically dominated the drug market, discovery in recent years has slowed significantly, partly due to limitations in current discovery methodologies. This work demonstrates a new workflow, Deuterium Adduct Bioactivity Screening (DABS), which pairs untargeted isotope labeling with whole cell binding assays for bioactive natural product discovery. DABS was validated and led to the discovery of a new isoprenyl guanidine alkaloid, zillamycin, which showed anti-cancer and anti-microbial activities. DABS thus represents a new workflow to accelerate discovery of natural products with a wide range of bioactive potential.

ZusammenfassungDiese Leitlinie präsentiert die aktuellen Handlungsanweisungen zur Diagnostik und Therapie der Myokardits im Kindesalter.

In diesem Beitrag wird das Potenzial einer intelligenten Vorlauftemperaturregelung für das Heizungsnetz eines modernen Bürogebäudes analysiert. Da das Gebäude mit einem Niedertemperatur-Fußbodenheizsystem und großen Fensterflächen ausgestattet ist, besteht die Gefahr einer Überhitzung der Räume an Tagen mit viel Sonnenenergie, jedoch kühlen Nächten. Durch eine Optimierung und Anpassung der Vorlauftemperatur mittels eines Reinforcement Learning Ansatzes – Q-Learning – kann die Überhitzung der Räume durch Sonneneinstrahlung im Vergleich zu der Standardheizkurve effektiv reduziert und damit der Gesamtkomfort verbessert werden. Die Integration der neuen Reglung am realen Gebäude wird mittels eines Handlungsempfehlungssystems realisiert.

Esse artigo tem a intenção de refletir sobre as experiências do projeto de extensão intitulado “Entre-laços: Roda de compartilhamento entre mulheres” (CDGEN/PROAFE/UFSC), um grupo de compartilhamento entre mulheres que surge com o objetivo central de atuar no enfrentamento das violências de gênero. Através da perspectiva transdisciplinar fundamentada na pedagogia freireana e na psicologia social crítica, e de grupo enquanto dispositivo, percebemos a construção coletiva de um espaço seguro de acolhimento e reflexão mútua, com potência de produzir questionamentos das categorias impostas, agenciamentos, rupturas e transformações. Constatamos que, neste contexto, o grupo pode se configurar como rede de apoio e estratégia possível de permanência qualificada das participantes que são, em maioria, estudantes no Ensino Superior.

Activating BRAF mutations are found in a small subset of patients with newly diagnosed multiple myeloma, but prevalence increases in late-stage, refractory disease, and the mutations are associated with adverse outcome. This prospective single-arm, open-label, multicenter phase 2 trial assessed the efficacy and safety of combined BRAF/MEK inhibition, using encorafenib and binimetinib, in patients with relapsed/refractory multiple myeloma (RRMM) carrying a BRAFV600E mutation. Patients received 450 mg encorafenib once daily and binimetinib 45 mg twice daily. The primary end point was the overall response rate achieved within the first year after start of treatment according to International Myeloma Working Group criteria. Twelve RRMM patients with a median of 5 prior lines of therapy were enrolled. The overall response rate was 83.3%, with 10 patients achieving at least a partial response. The median progression-free survival was 5.6 months, and overall survival was 55% at 24 months. Emerging resistance to therapy was driven by RAS mutations and structural variants involving the BRAF locus. This is the first prospective clinical trial to demonstrate that combined BRAF/MEK inhibition is highly effective in patients with BRAFV600E-mutated RRMM, and it represents a successful targeted precision medicine approach in this disease. This trial was registered at www.clinicaltrials.gov as #NCT02834364.

Maximum entropy methods (MEMs) determine posterior distributions by combining experimental data with prior information. MEMs are frequently used to reconstruct conformational ensembles of molecular systems for experimental information and initial molecular ensembles. We performed time-resolved Förster resonance energy transfer (FRET) experiments to probe the interdye distance distributions of the lipase-specific foldase Lif in the apo state, which likely has highly flexible, disordered, and/or ordered structural elements. Distance distributions estimated from ensembles of molecular dynamics (MD) simulations serve as prior information, and FRET experiments, analyzed within a Bayesian framework to recover distance distributions, are used for optimization. We tested priors obtained by MD with different force fields (FFs) tailored to ordered (FF99SB, FF14SB, and FF19SB) and disordered proteins (IDPSFF and FF99SBdisp). We obtained five substantially different posterior ensembles. As in our FRET experiments the noise is characterized by photon counting statistics, for a validated dye model, MEM can quantify consistencies between experiment and prior or posterior ensembles. However, posterior populations of conformations are uncorrelated to structural similarities for individual structures selected from different prior ensembles. Therefore, we assessed MEM simulating varying priors in synthetic experiments with known target ensembles. We found that (i) the prior and experimental information must be carefully balanced for optimal posterior ensembles to minimize perturbations of populations by overfitting and (ii) only ensemble-integrated quantities like inter-residue distance distributions or density maps can be reliably obtained but not ensembles of atomistic structures. This is because MEM optimizes ensembles but not individual structures. This result for a highly flexible system suggests that structurally varying priors calculated from varying prior ensembles, e.g., generated with different FFs, may serve as an ad hoc estimate for MEM reconstruction robustness.

Reducing treatment burden is a priority for people with cystic fibrosis, whose health has benefited from using new modulators that substantially increase CFTR protein function. The SIMPLIFY study aimed to assess the effects of discontinuing nebulised hypertonic saline or dornase alfa in individuals using the CFTR modulator elexacaftor plus tezacaftor plus ivacaftor (ETI).The SIMPLIFY study included two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials at 80 participating clinics across the USA in the Cystic Fibrosis Therapeutics Development Network. We included individuals with cystic fibrosis aged 12-17 years with percent predicted FEVFrom Aug 25, 2020, to May 25, 2022, a total of 672 unique participants were screened for eligibility for one or both trials, resulting in 847 total random assignments across both trials with 594 unique participants. 370 participants were randomly assigned in the hypertonic saline trial and 477 in the dornase alfa trial. Participants across both trials had an average ppFEVIn individuals with cystic fibrosis on ETI with relatively well preserved pulmonary function, discontinuing daily hypertonic saline or dornase alfa for 6 weeks did not result in clinically meaningful differences in pulmonary function when compared with continuing treatment.

Research Question What are the growth patterns of uterine myomas in untreated premenopausal women? Which factors influence the growth rate of uterine myomas in premenopausal women? Method All premenopausal women who presented to the outpatient myoma consultation clinic between January 2005 and March 2022 at least twice were screened. Exclusion criteria were hormonal therapy, pregnancy, and postmenopausal status. Results A total of 189 patients were included in our study which focused on the respective largest uterine myoma of each woman. An ideal linear growth over time was assumed. Most myomas (82%) increased in size. The mean annual growth of these myomas was 68.42 cm3. The most important prognostic factor for growth was the initial size of the myoma. The absolute annual growth of myomas measuring > 50 cm3 at first presentation was higher compared to smaller myomas (p Conclusion Overall, it is difficult to make an individual prognosis about the growth pattern of a uterine myoma in a specific patient. It should be noted especially in asymptomatic patients that spontaneous regression of myoma size can also occur in premenopausal women.

OBJECTIVE The mechanisms of action of high-frequency stimulation (HFS) are unknown. We investigated the possible mechanism of subthreshold superexcitability of HFS on the excitability of the peripheral nerve. MATERIALS AND METHODS The ulnar nerve was stimulated at the wrist in six healthy participants with a single (control) stimulus, and the responses were compared with the responses to a continuous train of 5 seconds at frequencies of 500 Hz, 2.5 kHz, 5 kHz, and 10 kHz. Threshold intensity for compound muscle action potential (CMAP) was defined as intensity producing a 100-μV amplitude in ten sequential trials and "subthreshold" as 10% below the CMAP threshold. HFS threshold was defined as stimulation intensity eliciting visible tetanic contraction. RESULTS Comparing the threshold of single pulse stimulation for eliciting CMAP vs threshold for HFS response and pooling data at different frequencies (500 Hz-10 kHz) revealed a significant difference (p = 0.00015). This difference was most obvious at 10 kHz, with a mean value for threshold reduction of 42.2%. CONCLUSIONS HFS with a stimulation intensity below the threshold for a single pulse induces axonal superexcitability if applied in a train. It can activate the peripheral nerve and produce a tetanic muscle response. Subthreshold superexcitability may allow new insights into the mechanism of HFS.

The silicide Eu2Ru3Si5 was synthesized from the elements in a sealed tantalum tube in a high-frequency furnace, while the gallide Eu2Ir3Ga5 was obtained by arc-melting. Both structures were refined from single-crystal X-ray diffractometer data: P4/mnc, a = 1072.69(8), c = 569.55(5) pm, wR = 0.0453, 617 F 2 values, 31 variables for Eu2Ru3Si5 and a = 1122.18(7), c = 583.17(4) pm, wR = 0.0546, 729 F 2 values, 31 variables for Eu2Ir3Ga4.95(1). The gallide shows small defects on one 8h site. The transition metal atoms in Eu2Ru3Si5 and Eu2Ir3Ga5 have octahedral p element coordination. These Ru@Si6 respectively Ir@Ga6 polyhedra are condensed to three-dimensional [Ru3Si5]6− respectively [Ir3Ga5]4− polyanionic networks. The ground states of Eu(III) in Eu2Ru3Si5 and Eu(II) in Eu2Ir3Ga5 were determined by 151Eu Mössbauer spectroscopy.

Purpose This study aimed at describing meal-timing patterns using cluster analysis and explore their association with sleep and chronic diseases, before and during COVID-19 mitigation measures in Austria. Methods Information was collected in two surveys in 2017 (N = 1004) and 2020 (N = 1010) in representative samples of the Austrian population. Timing of main meals, nighttime fasting interval, last-meal-to-bed time, breakfast skipping and eating midpoint were calculated using self-reported information. Cluster analysis was applied to identify meal-timing clusters. Multivariable-adjusted logistic regression models were used to study the association of meal-timing clusters with prevalence of chronic insomnia, depression, diabetes, hypertension, obesity and self-rated bad health status. Results In both surveys, median breakfast, lunch and dinner times on weekdays were 7:30, 12:30 and 18:30. One out of four participants skipped breakfast and the median number of eating occasions was 3 in both samples. We observed correlation between the different meal-timing variables. Cluster analysis resulted in the definition of two clusters in each sample (A17 and B17 in 2017, and A20 and B20 in 2020). Clusters A comprised most respondents, with fasting duration of 12–13 h and median eating midpoint between 13:00 and 13:30. Clusters B comprised participants reporting longer fasting intervals and later mealtimes, and a high proportion of breakfast skippers. Chronic insomnia, depression, obesity and self-rated bad health-status were more prevalent in clusters B. Conclusions Austrians reported long fasting intervals and low eating frequency. Meal-timing habits were similar before and during the COVID-19-pandemic. Besides individual characteristics of meal-timing, behavioural patterns need to be evaluated in chrono-nutrition epidemiological studies.

RESUMO A osteoartrite é uma importante afecção do aparelho locomotor de equinos, e os condroprotetores têm obtido papel importante no manejo da dor e como adjuvantes na redução de doses e na frequência de aplicação de outros fármacos que apresentam efeitos deletérios. O condroitim sulfato (CS) e a glucosamina (GlcN) são condroprotetores com potenciais efeitos anti-inflamatórios e anticatabólicos, cuja administração oral é a via mais frequente e controversa por resultar em baixa biodisponibilidade. Por essa razão, a administração intramuscular pode ser mais vantajosa. O objetivo do presente estudo foi avaliar os períodos de tempo para se atingir o pico de excreção urinária de CS e o início de declínio, após injeção intramuscular de produto à base de CS e de GlcN, em seis cavalos hígidos, na dose de 2 mL/100kg de condroitim sulfato A (750 mg/mL) e sulfato de glucosamina (750 mg/mL). Amostras de urina foram coletadas, no mesmo horário, no dia anterior (D-1), no dia da administração (D0), as quais constituíram o valor basal, e por mais sete dias (D1 a D7). O CS urinário foi extraído por cromatografia de troca iônica em coluna de Q-Sepharose Fast Flow, identificado por eletroforese em gel de agarose e mensurado por meio de densitometria, enquanto a creatinina urinária foi mensurada por analisador bioquímico automático. Os níveis de CS excretado (mg/L) aumentaram (P

The July 2021 flood in central Europe was one of the five costliest disasters in Europe in the last half century, with an estimated total damage of EUR 32 billion. The aim of this study is to analyze and assess the flood within an interdisciplinary approach along its entire process chain: the synoptic setting of the atmospheric pressure fields, the processes causing the high rainfall totals, the extraordinary streamflows and water levels in the affected catchments, the hydro-morphological effects, and the impacts on infrastructure and society. In addition, we address the question of what measures are possible to generate added value to early response management in the immediate aftermath of a disaster. The superposition of several factors resulted in widespread extreme precipitation totals and water levels well beyond a 100-year event: slow propagation of the low pressure system Bernd, convection embedded in a mesoscale precipitation field, unusually moist air masses associated with a significant positive anomaly in sea surface temperature over the Baltic Sea, wet soils, and steep terrain in the affected catchments. Various hydro-morphodynamic processes as well as changes in valley morphology observed during the event exacerbated the impact of the flood. Relevant effects included, among many others, the occurrence of extreme landscape erosion, rapidly evolving erosion and scour processes in the channel network and urban space, recruitment of debris from the natural and urban landscape, and deposition and clogging of bottlenecks in the channel network with eventual collapse. The estimation of inundation areas as well as the derived damage assessments were carried out during or directly after the flood and show the potential of near-real-time forensic disaster analyses for crisis management, emergency personnel on-site, and the provision of relief supplies. This study is part one of a two-paper series. The second part (Ludwig et al., 2022) puts the July 2021 flood into a historical context and into the context of climate change.

Adaptive silvicultural approaches intend to develop forests that can cope with changing climatic conditions. Just recently, many parts of Germany experienced 3 years of summer drought in a row (2018–2020). This study analysed the effects of this event on beech (Fagus sylvatica L.) in two regions in northern Bavaria, Germany. For this purpose, 990 beech trees were studied on 240 plots in drought-stressed forests. We examined trees of different social position and different size. Their morphology (e.g. tree height, crown volume) was recorded by laser scanning, and drought stress was quantified by tree core sample analyses. In addition to increment analyses, the δ13C signal was determined by year. Results show that the dominant tree collective was particularly affected by the drought. They still managed to perform well in 2018, but the radial growth decreased significantly in 2019 and 2020, partly resembling the performance values of subordinate trees. Subordinate trees, on the other hand, provide some consistency in growth during drought years. The drought was so severe that the effects of competition on tree growth began to disappear. The difference in growth of two geographically distinct study areas equalized due to drought. With continuing drought, increasing levels of the δ13C signal were detected. Similar patterns at different δ13C levels were found across the social positions of the trees. The influence of tree morphological variables on tree resistance to drought showed no clear pattern. Some trends could be found only by focusing on a data subset. We conclude that the intensity of the 2018–2020 drought event was so severe that many rules and drivers of forest ecology and forest dynamics (social position, morphology and competition) were overruled. The influence of morphological differences was shown to be very limited. The weakening of dominant trees could potentially be no longer linear and drought events like the one experienced in 2018–2020 have the potential of acting as tipping points for beech forests.

O corrente artigo, quantitativo, retrospectivo, analítico e descritivo, analisa dados sobre o perfil epidemiológico dos pacientes com DRC (Doença Renal Crônica) e relaciona-os aos dados da literatura brasileira. Foram analisadas a prevalência, o perfil sociodemográfico, as etiologias do doente renal crônico, a sobrevida global e a taxa de mortalidade desses pacientes, no período de julho de 2020 a julho de 2021. Foram incluídos na pesquisa todos os pacientes em procedimento hemodialítico devido DRC que foram atendidos na região de Mafra-SC e excluídos aqueles pacientes que apresentaram IRA, perfazendo um total de 101 pacientes adultos analisados. A prevalência desses pacientes foi de 291,3 por milhão da população (pmp), média de idade foi de 54,98 anos, 42,57% tinham idade superior a 60 anos, 54% eram homens, e 93% tinham baixa escolaridade. A taxa de mortalidade bruta desse período foi de 72,3 pacientes pmp, sobrevida global foi de 74,26% neste período de um ano. O acesso mais utilizado para hemodiálise foi a fistula artério-venosa em 71% dos pacientes. A pesquisa demonstrou características peculiares dos pacientes atendidos no centro de hemodiálise em Mafra e as correlacionou aos dados verificados nos bancos de dados brasileiros sobre o mesmo tema. O centro em comento conta com uma prevalência de 0,03%, sendo esta a metade da prevalência nacional (0,06%). A Hipertensão é uma das principais etiologias, seguida por diabetes mellitus. Ao tornar disponível o perfil sociodemográfico dos pacientes com doença renal crônica (se já citado aqui deve ser DRC), possibilita-se que a comunidade local seja beneficiada e que evitem o desenvolvimento dessa doença renal crônica.

The peptide antibiotic albicidin is a DNA topoisomerase inhibitor with low-nanomolar bactericidal activity towards fluoroquinolone-resistant Gram-negative pathogens. However, its mode of action is poorly understood. We determined a 2.6 Å resolution cryoelectron microscopy structure of a ternary complex between Escherichia coli topoisomerase DNA gyrase, a 217 bp double-stranded DNA fragment and albicidin. Albicidin employs a dual binding mechanism where one end of the molecule obstructs the crucial gyrase dimer interface, while the other intercalates between the fragments of cleaved DNA substrate. Thus, albicidin efficiently locks DNA gyrase, preventing it from religating DNA and completing its catalytic cycle. Two additional structures of this trapped state were determined using synthetic albicidin analogues that demonstrate improved solubility, and activity against a range of gyrase variants and E. coli topoisomerase IV. The extraordinary promiscuity of the DNA-intercalating region of albicidins and their excellent performance against fluoroquinolone-resistant bacteria holds great promise for the development of last-resort antibiotics.

For electrocatalysts with a layered structure, ion intercalation is a common phenomenon. Gaining reliable information about the intercalation of ions from the electrolyte is indispensable for a better understanding of the catalytic performance of these electrocatalysts. Here, we take a holistic approach for following intercalation processes by studying the dynamics of the catalyst, water molecules, and ions during intercalation using operando soft X ray absorption spectroscopy XAS . Sodium and oxygen K edge and nickel L edge spectra were used to investigate the Na intercalation in a Ni0.8Fe0.2Ox electrocatalyst during the oxygen evolution reaction OER in NaOH 0.1 M . The Na K edge spectra show an irreversible intensity increase upon initial potential cycling and a reversible intensity increase at the intercalation potential, 1.45 VRHE, coinciding with an increase in the Ni oxidation state. Simultaneously, the O K edge spectra show that the Na intercalation does not significantly impact the hydration of the catalyst

The qualification process of pressure vessels in general is subject to governmental restrictions. Thus, introducing additive manufacturing (AM) components to the market is challenging due to incomplete standardization. To increase component safety and trust, predetermined points of failure can be integrated by design using direct manufacturing methods. A predetermined point of failure using a surface notch is one option to avoid dangerous part failure (e.g. explosion) and increase safety. For implementation, a design approach with experimental proof of concept is striven to guide manufacturers and demonstrate the behavior of the material and the component as a whole. Finite element analysis is used for investigations on the influence of surface notch geometries applied to wall structures on structural stress super-elevation. Analytical strength assessment using FKM guideline and experimental validation of PBF-LB/M-manufactured specimen behavior by static axial tensile and burst testing is carried out. Fracture surface and plastic elongation evaluation using light microscopy and 3-D surface scanning clarify the material behavior. The analytical and experimental approval of an integrated predetermined point of failure for static overload is achieved without reducing the maximum burst pressure value. The integration fulfills all theoretical requirements for structural strength. All tested specimens meet the expectations regarding static strength and failure behavior. As expected, component elongation decreases using surface notches for failure provocation. Results lead to a proposed guideline for the application of an integrated predetermined point of failure by the use of a surface notch.