Uncovering the expression patterns of chimeric transcripts using surveys of affymetrix GeneChips.

BACKGROUND: A chimeric transcript is a single RNA sequence which results from the transcription of two adjacent genes. Recent studies estimate that at least 4% of tandem human gene pairs may form chimeric transcripts. Affymetrix GeneChip data are used to study the expression patterns of tens of thousands of genes and the probe sequences used in these microarrays can potentially map to exotic RNA sequences such as chimeras. RESULTS: We have studied human chimeras and investigated their expression patterns using large surveys of Affymetrix microarray data obtained from the Gene Expression Omnibus. We show that for six probe sets, a unique probe mapping to a transcript produced by one of the adjacent genes can be used to identify the expression patterns of readthrough transcripts. Furthermore, unique probes mapping to an intergenic exon present only in the MASK-BP3 chimera can be used directly to study the expression levels of this transcript. CONCLUSIONS: We have attempted to implement a new method for identifying tandem chimerism. In this analysis unambiguous probes are needed to measure run-off transcription and probes that map to intergenic exons are particularly valuable for identifying the expression of chimeras

Analysis of vancomycin use and associated risk factors in a university teaching hospital: a prospective cohort study

Background: Vancomycin use is considered inappropriate in most hospitals. A particular concern is the recent emergence of S. aureus with decreased susceptibility to vancomycin, making it important to reduce overall exposure to vancomycin to minimize the incidence of VRE ( vancomycin- resistant enterococci). the aim of this work was to analyze the use of vancomycin and the risk factors associated with inappropriate treatment.Methods: A prospective survey was conducted on all patients receiving vancomycin between 1(st) March 2002 and 30(th) September 2002 in a university- school hospital. Appropriateness of vancomycin use was assessed, according to the criteria established by the Centers for Disease Control and Prevention ( CDC), at two time points: first, at the beginning of therapy, and second, continuing after 72 hours.Results: A total of 557 patients received vancomycin. Three hundred seventy- four ( 67.1%) were under 60 years old, 374 ( 67.1%) had prolonged stays (> two weeks) in hospital, and 455 ( 81.7%) were in the intensive care unit ( ICU). Two hundred sixty- three patients ( 47.2%) had some invasive device. in 324 ( 58.2%) patients the duration of vancomycin treatment was up to two weeks. Vancomycin was inappropriately used in 65.7% during the first 24 hours and in 67% at the 72 hours point according to CDC criteria [ 4]. the inappropriateness of vancomycin use during the first 24 hours was related to: patients aged less than 60 ( OR 1.7; CI 95% 1.1 - 2.5), non- ICU patients ( OR 1.5; CI 95% 1.0 - 2.4) and patients without neutropenia ( OR 7.5; CI 95% 2.4 - 22.7). At 72 hours, the inappropriateness of vancomycin use was related to: patients aged less than 60 ( OR 1.5; CI 95% 1.0 - 2.3), non- ICU patients ( OR 1.7; CI 95% 1.1 - 2.7) and patients without neutropenia ( OR 8.0; CI 95% 2.6 - 24.3).Conclusion: Vancomycin was abused. Patients aged less than 60, non- ICU patients and those who did not present neutropenia were the principal groups at risk of inappropriate use.Universidade Federal de São Paulo, Dept Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Infect Dis, São Paulo, BrazilWeb of Scienc

Numerical elimination and moduli space of vacua

We propose a new computational method to understand the vacuum moduli space of (supersymmetric) field theories. By combining numerical algebraic geometry (NAG) and elimination theory, we develop a powerful, efficient, and parallelizable algorithm toextract important information such as the dimension, branch structure, Hilbert series and subsequent operator counting, as well as variation according to coupling constants and mass parameters. We illustrate this method on a host of examples from gauge theory, string theory, and algebraic geometry

Molecular bases of diabetic nephropathy

The determinant of the diabetic nephropathy is hyperglycemia, but hypertension and other genetic factors are also involved. Glomerulus is the focus of the injury, where mesangial cell proliferation and extracellular matrix occur because of the increase of the intra- and extracellular glucose concentration and overexpression of GLUT1. Sequentially, there are increases in the flow by the poliol pathway, oxidative stress, increased intracellular production of advanced glycation end products (AGEs), activation of the PKC pathway, increase of the activity of the hexosamine pathway, and activation of TGF-beta1. High glucose concentrations also increase angiotensin II (AII) levels. Therefore, glucose and AII exert similar effects in inducing extracellular matrix formation in the mesangial cells, using similar transductional signal, which increases TGF-beta1 levels. In this review we focus in the effect of glucose and AII in the mesangial cells in causing the events related to the genesis of diabetic nephropathy. The alterations in the signal pathways discussed in this review give support to the observational studies and clinical assays, where metabolic and antihypertensive controls obtained with angiotensin-converting inhibitors have shown important and additive effect in the prevention of the beginning and progression of diabetic nephropathy. New therapeutic strategies directed to the described intracellular events may give future additional benefits.O principal determinante da nefropatia diabética é a hiperglicemia, mas hipertensão e fatores genéticos também estão envolvidos. O glomérulo é o foco de lesão, onde proliferação celular mesangial e produção excessiva de matriz extracelular decorrem do aumento da glicose intracelular, por excesso de glicose extracelular e hiperexpressão de GLUT1. Seguem-se aumento do fluxo pela via dos polióis, estresse oxidativo intracelular, produção intracelular aumentada de produtos avançados da glicação não enzimática (AGEs), ativação da via da PKC, aumento da atividade da via das hexosaminas e ativação de TGF-beta1. Altas concentrações de glicose também aumentam angiotensina II (AII) nas células mesangiais por aumento intracelular da atividade da renina (ações intrácrinas, mediando efeitos proliferativos e inflamatórios diretamente). Portanto, glicose e AII exercem efeitos proliferativos celulares e de matriz extracelular nas células mesangiais, utilizando vias de transdução de sinais semelhantes, que levam a aumento de TGF-beta1. Nesse estudo são revisadas as vias que sinalizam os efeitos da glicose e AII nas células mesangiais em causar os eventos-chaves relacionados à gênese da glomerulopatia diabética. As alterações das vias de sinalização implicadas na glomerulopatia, aqui revisadas, suportam dados de estudos observacionais/ensaios clínicos, onde controle metabólico e anti-hipertensivo, especificamente com inibidores do sistema renina-angiotensina, têm-se mostrado importantes - e aditivos - na prevenção do início e progressão da nefropatia. Novas estratégias terapêuticas dirigidas aos eventos intracelulares descritos deverão futuramente promover benefício adicional.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)HC Instituto do Coração Unidade de HipertensãoUSP FMUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Laboratório de NefrologiaFundação Universitária de Cardiologia Instituto de Cardiologia Laboratório de Cardiologia Molecular e CelularUNIFESP, EPM, Laboratório de NefrologiaSciEL

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Long-term decline of the Amazon carbon sink

Atmospheric carbon dioxide records indicate that the land surface has acted as a strong global carbon sink over recent decades1, 2, with a substantial fraction of this sink probably located in the tropics3, particularly in the Amazon4. Nevertheless, it is unclear how the terrestrial carbon sink will evolve as climate and atmospheric composition continue to change. Here we analyse the historical evolution of the biomass dynamics of the Amazon rainforest over three decades using a distributed network of 321 plots. While this analysis confirms that Amazon forests have acted as a long-term net biomass sink, we find a long-term decreasing trend of carbon accumulation. Rates of net increase in above-ground biomass declined by one-third during the past decade compared to the 1990s. This is a consequence of growth rate increases levelling off recently, while biomass mortality persistently increased throughout, leading to a shortening of carbon residence times. Potential drivers for the mortality increase include greater climate variability, and feedbacks of faster growth on mortality, resulting in shortened tree longevity5. The observed decline of the Amazon sink diverges markedly from the recent increase in terrestrial carbon uptake at the global scale1, 2, and is contrary to expectations based on models6

The OMG dataset: An Open MetaGenomic corpus for mixed-modality genomic language modeling

Biological language model performance depends heavily on pretraining data quality, diversity, and size. While metagenomic datasets feature enormous biological diversity, their utilization as pretraining data has been limited due to challenges in data accessibility, quality filtering and deduplication. Here, we present the Open MetaGenomic (OMG) corpus, a genomic pretraining dataset totalling 3.1T base pairs and 3.3B protein coding sequences, obtained by combining two largest metagenomic dataset repositories (JGI's IMG and EMBL's MGnify). We first document the composition of the dataset and describe the quality filtering steps taken to remove poor quality data. We make the OMG corpus available as a mixed-modality genomic sequence dataset that represents multi-gene encoding genomic sequences with translated amino acids for protein coding sequences, and nucleic acids for intergenic sequences. We train the first mixed-modality genomic language model (gLM2) that leverages genomic context information to learn robust functional representations, as well as coevolutionary signals in protein-protein interfaces and genomic regulatory syntax. Furthermore, we show that deduplication in embedding space can be used to balance the corpus, demonstrating improved performance on downstream tasks. The OMG dataset is publicly hosted on the Hugging Face Hub at https://huggingface.co/datasets/tattabio/OMG and gLM2 is available at https://huggingface.co/tattabio/gLM2_650M

Um comparativo entre uma carteira de investimento teórica e os investimentos praticados por um grupo de investidores

The objective of this study is to compare the investments made by a group of investors with a theoretical investment portfolio in terms of performance. Through a descriptive research and quantitative approach, the study was carried out through a survey, whose research instrument was an electronic questionnaire. The sample is composed of 119 entrepreneurs from a Municipality of the State of Santa Catarina and to analyze the data was used the technique of descriptive analysis. Savings stands out as the most representative investment, with 82% of the investments practiced which indicates a predominance of the conservative profile, thus creating the theoretical investment portfolio, composed of 4 investments, where they are compared with the Interbank Deposit Certificate (CDI). The monitoring of the portfolio for the purpose of comparison with savings takes into account a period of 24 months. The return on the investment portfolio is defined by a weighted average of the investment income. In comparison, it is possible to observe the evolution of the yields in the period of 24 months, and the theoretical portfolio developed is above the CDI surpassing the 32% of profitability, however the savings in turn has 15.06% of profitability, thus making feasible the theoretical investment portfolio. O estudo objetiva comparar em termos de desempenho os investimentos praticados por um grupo de investidores, com uma carteira de investimentos teórica. Por meio de uma pesquisa descritiva e abordagem quantitativa, o estudo foi realizado mediante uma survey, cujo instrumento de pesquisa foi um questionário eletrônico. A amostra foi composta por 119 empresários de um Município do Estado de Santa Catarina, e para analisar os dados utilizou-se a técnica de análise descritiva. A poupança destaca-se como o investimento mais representativo, com 82% dos investimentos praticados, o que indica predominância do perfil conservador, dessa forma criada a carteira de investimentos teórica, composta por quatro investimentos, em que são comparados com o indexador Certificado de Depósito Interbancário (CDI). O acompanhamento da carteira com a finalidade de comparação com a poupança leva em consideração um período de 24 meses. A rentabilidade da carteira de investimentos é definida por uma média ponderada entre os rendimentos dos investimentos. No comparativo é possível observar a evolução das rentabilidades no período de 24 meses, sendo que a carteira teórica desenvolvida fica acima do CDI, ultrapassando os 32% de rentabilidade, no entanto, a poupança, por sua vez, tem 15,06% de rentabilidade, viabilizando, desse modo, a carteira de investimento teórica