Construction and evaluation of an automated flow injection-stopped flow analyser for multipoint reaction rate spectrophotometric methods. Determination of ammonia nitrogen, creatinine and phosphate

The construction and evaluation of a fully automated Flow Injection-Stopped Flow (FI-SF) spectrophotometric analyser is described. A microcomputer (Rockwell AIM 65) is used to control the analyser (sample injection, stop and start of the pump) through a suitable interface. Data acquisition is achieved using a 12 bit ADC card and a suitable subroutine in 6502 assembly language, allowing data sampling at a frequency of 7.5 kHz. The measurement interface and software were evaluated using a voltage ramp generator. A precision of 0.02-1.1% RSD (N =10) was obtained for voltage ramps in the range of 1-37 mVs-1. The FI-SF analyser was evaluated in routine analysis by developing FI-SF kinetic spectrophotometric methods for the determination of ammonia nitrogen (20-250 ppm, 0.4-2.5% RSD) based on the Berthelot reaction, creatinine (20-220 ppm, 0.9-3.6% RSD) based on the Jaffé reaction, and phosphate (5-30 ppm, 1.0-3.3% RSD) based on the phosphomolybdenum blue reaction. The reaction rate is measured by linear fitting of multiple absorbance readings vs time. Algorithms for automated estimation of the residence time, the linear range of the reaction curve, and data treatment are presented

Twistor Strings with Flavour

We explore the tree-level description of a class of N=2 UV-finite SYM theories with fundamental flavour within a topological B-model twistor string framework. In particular, we identify the twistor dual of the Sp(N) gauge theory with one antisymmetric and four fundamental hypermultiplets, as well as that of the SU(N) theory with 2N hypermultiplets. This is achieved by suitably orientifolding/orbifolding the original N=4 setup of Witten and adding a certain number of new topological 'flavour'-branes at the orientifold/orbifold fixed planes to provide the fundamental matter. We further comment on the appearance of these objects in the B-model on CP(3|4). An interesting aspect of our construction is that, unlike the IIB description of these theories in terms of D3 and D7-branes, on the twistor side part of the global flavour symmetry is realised geometrically. We provide evidence for this correspondence by calculating and matching amplitudes on both sides.Comment: 38+12 pages; uses axodraw.sty. v2: References added, minor clarification

Germline MBD4-deficiency causes a multi-tumor predisposition syndrome

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies.

CAPRISA, 2014.Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Comparison of different tests used in mapping the Greek virgin olive oil production for the determination of its total antioxidant capacity

This study aims to map the total antioxidant capacity (TAC) of 50 Greek olive oil samples from the 2005-2006 season according to production region and cultivar and to compare the 2, 2’-azino-bis (3-ethylbenzo-thiazoline-6- sulfonic acid (ABTS), 2, 2-diphenyl-1-picrylhydrazyl radical (DPPH) and Folin-Ciocalteu tests for use with olive oil. Antioxidant capacities determined in the hydrophilic fraction range between 5.42 - 22.5 mM gallic acid Kg^-1 olive oil for the ABTS method and 1.29 - 9.95 mM Kg^-1 for the DPPH method while in total, olive oil TAC ranges between 77 - 177 mM Kg^-1 as assessed by the DPPH method. The results of total phenol content range between 3.8 and 29.4 mM Kg^-1 olive oil. Total phenol content correlates with total antioxidant capacity assessed in the hydrophilic fraction through the DPPH (r = 0.89) and the ABTS (r = 0.69) assays. The hydrophilic fraction DPPH values correlate significantly with the ABTS values (r = 0.81). However, the DPPH values for total olive oil correlate poorly with the ABTS assay, the Folin-Ciocalteu method and the DPPH assay in hydrophilic fraction. Although total phenolic content shows good correlation with ABTS and DPPH values and could serve as a useful indicator for olive oil antioxidant capacity, the use of a battery of tests contributes to better characterization of the antioxidant capacity of olive oil.<br><br>El objetivo de este estudio es el mapeo de la actividad antioxidante total (TAC) de 50 aceites de oliva Griego de los años 2005-2006 de acuerdo a su región y cultivar, y se comparan los ensayos del ácido 2, 2’-azino-bis (3-etilbenzo-tiazolina- 6-sulfónico (ABTS), del 2,2-difenil-1-picrlhidrazil radical (DPPH) y de Folin-Ciocalteu. La capacidad antioxidante determinada en la fracción hidrofílica varió entre 5.42-22.5 mM de ácido gálico Kg^-1 de aceite para el método ABTS y 1.29- 9.95 mM Kg^-1 de aceite para el método de DPPH mientras que la TAC del aceite de oliva completo varió entre 77-177 mM Kg^-1 de aceite por el método de DPPH. Los resultados del contenido de fenoles totales varió entre 3.8 y 29.4 mM Kg^-1 de aceite. El contenido total de fenoles correlaciona con la capacidad total antioxidante evaluada en la fracción hidrofílica en los ensayos de DPPH (r = 0.89) y de ABTS (r = 0.69). Los valores de DPPH de la fracción hidrofílica correlacionan significativamente con los valores de ABTS (r = 0.81). Sin embargo, los valores de DPPH para el aceite de oliva completo correlacionan pobremente con el ensayo ABTS, el método de Folin-Ciocalteu y el ensayo de DPPH de la fracción hidrofílica. Aunque el contenido de fenoles totales muestra una buena correlación con los valores de ABTS y DPPH y podría servir como un útil indicador de la capacidad antioxidante del aceite de oliva, el uso de una batería de test contribuye a una mejor caracterización de la capacidad antioxidante del aceite de oliva