Expro (United Kingdom)

Mycobacterium tuberculosis contains thirteen Mycobacterial membrane protein Large (MmpL) transporters, which belong to the family of secondary active RND transporters. MmpL4 and MmpL5, together with their operon partners MmpS4 and MmpS5, export the mycobacterial siderophore mycobactin and the last resort TB drug bedaquiline. Recently, we determined a structure of the MmpL4 monomer in complex with desferrated mycobactin, which lacked a functionally essential coiled-coil domain predicted to extend far into the periplasm. Here, we present a cryo-EM structure of the hexameric (MmpS4)3-(MmpL4)3 complex, which was enabled by rational disulfide cross-links based on AlphaFold predictions. We observed density for the coiled-coil domain, which protrudes into the periplasmic space at an angle of around 60° relative to the symmetry axis of the MmpL4 trimer. In the context of the hexameric complex, MmpL4’s conformation differs strikingly from the one observed for monomeric MmpL4, which includes formation of a large cavity in the periplasmic domain and rearrangements of conserved proton coupling residues at the transmembrane domain. Our work provides an experimental workflow to obtain single particle cryo-EM structures of labile multiprotein complexes by AlphaFold-informed stabilization of predicted protein interfaces.

Abstract This paper introduces a novel predictive, non-intrusive methodology for tubing integrity management that combines corrosion analytics with caliper simulation. By integrating real-time data on lift performance, nodal pressure, and fluid properties, the system estimates localized degradation rates and ranks tubing segments based on their failure probability. This approach enables early risk detection, providing operators with data-driven insights for targeted interventions and more efficient use of caliper logging. The primary outcome of this methodology is optimized intervention planning. By shifting from broad, periodic caliper logging campaigns to exception-based, data-informed monitoring, the frequency of site campaigns is significantly reduced, leading to enhanced operational efficiency and reduced production interruptions. Additionally, this approach supports the extension of tubing service life, while improving safety performance by minimizing the risk of unexpected well failures. The methodology has been successfully trialled by a major operator, with documented case study demonstrating its effectiveness and providing a robust validation of its predictive capabilities. The methods employed include the collection of real-time pressure and fluid data, as well as production parameters, to feed into a mechanistic corrosion-erosion model. This model simulates wall loss progression and generates virtual caliper profiles to predict the internal condition of the tubing. The ranking system, which scores tubing segments based on their failure risk, allows for focused surveillance and resource allocation. In turn, this optimization reduces the need for broad caliper logging efforts, resulting in considerable cost savings. In the results and observations section, it is demonstrated that the ranking system accurately identifies vulnerable tubulars, allowing for proactive intervention before catastrophic failures occur. The non-intrusive prediction method reduces the frequency of interventions and production interruptions, while continuous monitoring ensures early detection and supports better decision-making. The use of predictive modelling has shown to extend tubing service life and minimize late-stage integrity failures. Furthermore, a successful field trial validated the approach, which has been fully deployed with real-world case studies. This paper introduces a digital-first approach to well integrity management, blending corrosion forecasting with virtual caliper simulation. The predictive ranking system enables focused inspections, optimizing resource use while improving safety and reliability.

The combined deliverables provide tools for incorporating real time pipe current measurements into a remote monitoring protocol to help in an integrated external corrosion management plan for cathodically protected pipelines. The use of continuous remotely collected pipe current measurements optimizes the corrosion protection and improves response time to upset conditions that might otherwise compromise the corrosion control. The zip file contains 4 items: 1. PR229-203604-R01 Pipeline CP Monitoring Using Real Time Current Measurement - This report covers the results of and findings from the Phase 1 field-based research for PRCI Project EC-08-11 Pipeline CP Monitoring Using Real Time Pipe Current Measurement. Project EC-08-11 is directed toward determining the feasibility of taking remotely collected pipe current measurements into routine practice. The ultimate goal is to optimize the corrosion protection and improve response time to upset conditions that might otherwise compromise the corrosion control. Findings from the Phase 1 work will be used for an economic analysis and guidance document to be developed under Phase 2. 2. PR229-203604-M01 Pipeline CP Monitoring Using Real Time Current Measurement Guidance Manual - This guidance manual provides tools for incorporating real time pipe current measurements into a remote monitoring protocol to help in an integrated external corrosion management plan for cathodically protected pipelines. 3. PR229-203604-E02 Pipeline CP Monitoring Using Real Time Current Measurement Life-Cycle Cost Calculator - This Excel-based life-cycle cost calculator has been prepared to assist in the design of a pipeline cathodic protection remote monitoring program 4. PR229-203604-M02 Pipeline CP Monitoring Real Time Current Measurement Life-Cycle Cost Calculator Manual - This user's manual is companion to an Excel-based life-cycle cost calculator that has been prepared to assist in the design of a pipeline cathodic protection remote monitoring program.

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Forming and mastering the cognitive component of the foreign-language communicative competency based on information and communication technologies, taking into account the diversity of its components, is one of the main goals of teaching a foreign language at all stages of learning.The relevance of the problem and lack of its proper development have stipulated the analysis of tasks directed to forming and mastering the cognitive component and also to developing the stages to form the cognitive component of the foreign-language communicative competency of the third-year applicants of Specialty 291 International Relations, Public Communications, and Regional Studies of the Faculty of International Relations and Journalism of Simon Kuznets Kharkiv National University of Economics.In the article, the stages of the algorithm for implementing the Internet project activities aimed at forming and mastering the cognitive component of the foreign-language communicative competency based on modern information and communication technologies are offered.The article also focuses on working with modern information and communication technologies to form and master the cognitive component of foreignlanguage competency.Forming and mastering the cognitive component of the foreign-language communicative competency from the analysis of the

A síndrome de Alport é uma doença hereditária que compromete o colágeno tipo IV e cursa com comprometimento renal grave e progressivo, surdez neurossensorial e alterações oculares. A transmissão hereditária ligada ao cromossomo X no gene COL4A5 é a mais frequente, podendo também ocorrer formas de transmissão autossômica recessiva ou dominante. A biópsia renal, com evidência de alterações características na microscopia eletrônica, ou o estudo genético com identificação de mutação nos genes COL4A3-5, são os métodos de diagnóstico utilizados. O presente estudo, descreve um paciente de 28 anos, o qual no ano de 2012 apresentou sintomas de edema em membros inferiores, hipertensão arterial sistêmica, hematúria e proteinúria e foi admitido em um Hospital de ensino, onde foi diagnosticado com a síndrome de Alport e glomeruloesclerose segmentar e focal (GESF) em biópsia renal. Seu quadro clínico avançou para doença renal crônica estágio cinco, motivo pelo qual iniciou tratamento de hemodiálise em 2014, e após dois anos realizou o transplante renal de doador vivo, porém teve perda do enxerto, retornando a hemodiálise em 2017. Dado o histórico familiar relacionado à síndrome, o aparecimento dos sintomas renais e o início da perda auditiva em idade precoce, associados à má adesão do paciente às possibilidades de tratamento e à perda do enxerto renal, compõem fatores que contribuem para um mau prognóstico e, em consequência, para o prejuízo da qualidade de vida.

A risk assessment on the aquatic toxicity of the plant biostimulant strigolactone mimic (2-(4-methyl-5-oxo-2,5-dihydro-furan-2-yloxy)-benzo[de]isoquinoline-1,3-dione (SL-6) was performed using a suite of standardised bioassays representing different trophic groups and acute and chronic endpoints. In freshwater, three trophic groups of algae, crustacea and fish were used. Whilst in seawater, algae (unicellular and macroalgae), Crustacea and Mollusca were employed. In addition, the genotoxicity of SL-6 was determined with the comet assessment performed on unicellular marine algae, oysters, and fish embryos. This was the first time ecotoxicity tests have been performed on SL-6. In freshwater, the lowest LOEC was measured in the unicellular algae at 0.31 mg/L SL-6. Although, similar LOEC values were found for embryo malformations and impacts on hatching rate in zebrafish (LOEC 0.31–0.33 mg/L). Consistent malformations of pericardial and yolk sac oedemas were identified in the zebrafish embryos at 0.31 mg/L. In marine species, the lowest LOEC was found for both Tisbe battagliai mortality and microalgae growth at an SL-6 concentration of 1.0 mg/L. Significant genotoxicity was observed above control levels at 0.0031 mg/L SL-6 in the unicellular algae and 0.001 mg/L SL-6 in the oyster and zebrafish larvae. When applying the simple risk assessment, based on the lowest NOECs and appropriate assessment factors, the calculated predicted no effect concentration (PNEC), for the ecotoxicity and the genotoxicity tests were 1.0 µg/L and 0.01 µg/L respectively.

O transtorno bipolar em crianças é uma condição psiquiátrica caracterizada por alterações que incluem episódios de mania, hipomania, depressão. Alternativas avançadas de terapia farmacológicas têm revolucionado o manejo do transtorno. Objetivo: Realizar uma revisão bibliográfica abrangente das estratégias diagnósticas e terapêuticas aplicadas no transtorno bipolar entre crianças e jovens. Métodos: Foram escolhidos artigos originais e revisões sistemáticas publicadas entre 2003 e 2024, com critérios de inclusão e exclusão próprios, por meio de buscas em bases, como PubMed, Scielo e Scopus. Resultado e discussões: O diagnóstico pediátrico avançou nas últimas décadas, principalmente as alterações morfológicas em amigdala. Contudo, há considerações específicas, como a distinção entre humor expansivo e irritabilidade. O tratamento frequentemente se baseia em lítio ou antipsicóticos atípicos, com destaque para a importância do início precoce da terapia com lítio. Além do papel multidisciplinar, principalmente por meio da TCC, desempenha um papel essencial na prevenção de recaídas e na gestão dos episódios agudos de humor em crianças com transtorno bipolar. Conclusão: Apesar dos avanços, é vital aprimorar a abordagem diagnóstica para distingui-lo de outros distúrbios. A complexidade dos sintomas exige uma terapia individualizada, envolvendo tratamento medicamentoso e psicossocial. Investimentos em pesquisa clínica são necessários para melhorar o prognóstico e reduzir complicações a longo prazo.

The interactions between four native and modified beta-cyclodextrins and a benzimidazolium bromide salt were analyzed through UV-Vis and NMR Spectroscopy. The new benzimidazolium salt was obtained by simple and efficient conversion of N-1 substituted 5,6-dimethylbenzimidazole with phenacyl bromide in acetone. In all cases, the complexes stoichiometry was 1:1, as determined from UV-Vis titrations. Based on the values for association constants, the strength of the interactions with benzimidazolium bromide was weakest with the methyl substituted beta-cyclodextrin and strongest with the sulfobutylether substituted beta-cyclodextrin. Through-space NOE experiments were used to investigate the structural aspects of inclusion process. The obtained NOE correlations indicate coexistence of two inclusion modes: one with the phenacyl group inside the cyclodextrin cavity and the second one with dimethyl-substituted benzene ring inside the cavity. The imidazole ring and the ethyl substituent have been proven to remain outside the cyclodextrin cavity in both inclusion modes.