The role of PARP-1 and XRCC1 in homologous recombination.

In this thesis, the role of PARP-1 and XRCC1 in camptothecin (CPT) induced homologous recombination (HR) has been elucidated. The aims of this study were to investigate the role of PARP-1 and XRCC1 in the repair of CPT-induced damage, to find out if PARP-1 was involved in single strand break (SSB) repair, and to investigate the role of PARP inhibitors in the repair of CPT-induced damage. Cells lacking PARP-1, and wildtype cells treated with PARP inhibitors, were found to have increased sensitive to CPT. This increased sensitivity was found to correlate to an increased amount of DNA double-strand breaks (DSBs), and an increased number of cells containing RAD51 foci. This is an indication of an increased amount of HR in these cells. Cells deficient in XRCC 1 were also found to have an increased sensitivity to CPT, increased levels of DSBs and an increased number of cells containing RAD51 foci. A mutant XRCC1 cell line containing a disrupted BRCT 1 motif showed even further sensitivity to CPT. This motif interacts with PARP-1, and when disrupted, seems to inhibit the protein in some way. We have concluded that in the absence of PARP-1 or XRCCI, the repair of SSBs is slower. These breaks are therefore more likely to encounter the replication machinery, where they become DSBs. These breaks are repaired by HR. Cells that lack both PARP1 and XRCC1 may have even slower SSB repair, as they have an increased amount of cells containing RAD51 foci, which indicates increased HR. PARP inhibitors used in conjunction with CPT increases the cytotoxicity of CPT, which could help in chemotherapy. In the future, maybe inhibiting XRCC1 as well could further enhance this affect

Scheduling with tool changes to minimize total completion time under controllable machining conditions

Cataloged from PDF version of article.Scheduling under controllable machining conditions has been studied for some time. Scheduling with tool changes, particularly due to tool wear, has just begun to receive attention. Though machining conditions impact tool wear and induce tool change, the two issues have not been considered together.We address for the first time the problem of scheduling a computer numerically controlled (CNC) machine subject to tool changes and controllable machining conditions; our objective is to minimize the total completion time of a given set of jobs. We establish an important result that helps us identify feasible settings of machining parameters such as feed rate and cutting speed. However, the problem at hand remains intractable, even when a single setting is used. In the general case, we are able to solve the problem exactly for up to 30 jobs using a mixed integer linear programming formulation. For larger problems, we turn to approximate solution via heuristics. We examine a number of different schemes. The best of these schemes are used in a problem space genetic algorithm; this produces quality solutions in a time-efficient manner, as is evidenced from an extensive computational study conducted by us. 2005 Elsevier Ltd. All rights reserved

Pre-operative Arterial Embolization of Symptomatic Giant Hemangioma of the Liver

Abstract: The cavernous hemangiomas of the liver are usually small sized and asymptomatic. Most of them are incidentally diagnosed and a very small portion requires therapy. Giant hemangioma can be symptomatic, and this condition is the indication for treatment. The striking complication of surgical treatment of cavernous hemangiomas is intra-operative bleeding. In this case, we aimed to demonstrate that the risk of intraoperative bleeding can be eliminated with the preoperative percutaneous trans-catheter arterial embolization technique

Situs Megalitik di Desa Penanggungan Kecamatan Maesan Kabupaten Bondowoso sebagai Sumber Pembelajaran Sejarah

Penelitian ini bertujuan untuk mengetahui bagaimana memanfaatkan situs Penanggungan untuk sumber pembelajaran. Penelitian ini merupakan penelitian kesejarahan. Hasil dari penelitian ini menujukan adanya relevansi antara situs Penanggungan dengan Kurikulum 2013. Pemanfaatan situs sebagai sumber pembelajaran sejarah bisa dilakukan dengan cara menampilkan benda megalit yang ada di situs Penanggungan Kecamatan Maesan Kabupaten Bondowoso di dalam kelas. Hal tersebut dilakukan dengan menjadikan benda-benda peninggalan purbakala menjadi media gambar berupa media papan flanel.Tentunya media tersebut sangat berguna untuk membuat peserta didik lebih menganalisis materi yang diajarkan bukan hanya mendengarkan dari penjelasan guru namun juga dapat mengetahui berdasarkan gambar yang ditampilkan oleh guru sehingga pembelajaran menjadi lebih menarik dan tidak membosankan. Cara lain adalah dengan melakukan karya wisata di situs Penanggungan Kecamatan Maesan Kabupaten Bondowoso, karya wisata ini dilakukan oleh guru dengan membawa peserta didik langsung kedalam lingkungan situs Penanggungan. Metode karya wisata ini merupakan salah satu cara yang dilakukan oleh guru dalam membelajarkan pembelajaran sejarah. Karya wisata ini lebih memfokuskan untuk menyajikan sumber belajar dengan membawa peserta didik kepada subjek yang akan dipelajari diluar kelas. Metode ini membuat pembelajaran lebih inovatif dan kreatif.   Kata Kunci: Situs Megalitik, Sumber Belajar, Pembelajaran Sejarah. &nbsp

Considering embodied energy and carbon in heritage buildings – a review

Approximately 20% of UK buildings can be defined as ‘heritage buildings’, offering unique values that should be preserved. They tend to use more energy than newer buildings, creating a strong case for energy retrofits to reduce energy use, greenhouse gas emissions, and improve thermal comfort. However, few studies of heritage retrofits examine embodied impacts, which are the energy and carbon impacts required to manufacture, transport and construct materials and components. This study considers the whole life (embodied plus operational) impacts of retrofitting heritage buildings, through a systematic literature review and thematic analysis. It concludes that; both embodied and operational impacts should be considered in retrofitting projects, retrofitting is better than demolish and rebuild in lifecycle terms, there is a lack of policy mandating for the measurement of lifecycle impacts and low impact retrofitting can be better for conserving heritage values and reducing embodied carbon

Omental whirl associated with bilateral inguinal hernia: a case report

INTRODUCTION: Torsion of the omentum is a rare cause of abdominal pain. It is clinically similar to common causes of acute surgical abdomen and is often diagnosed during surgery. Inguinal hernia is a common condition but not frequently related with torsion of the omentum. CASE PRESENTATION: A 40-year-old Caucasian man came to our emergency department with abdominal pain of the left quadrant and abdominal distension for 2 days. His medical history included an untreated left inguinal hernia in the last year. Computed tomography revealed densification of mesocolon with left omentum "whirl" component and other signs of omental torsion. During an exploratory laparoscopy, a wide twist of his omentum with necrotic alterations that extended to the bilateral inguinal hernial content was observed. Omentectomy and surgical repair of bilateral inguinal hernia were performed. CONCLUSIONS: Torsion of the omentum is a rare entity and usually presents a diagnostic challenge. The use of abdominal computed tomography can help diagnosing torsion of the omentum preoperatively and, thus, prevents a surgical approach. Nonetheless, some cases of torsion of the omentum require surgical repair. Accordingly, a laparoscopic approach is minimally invasive and efficient in performing omentectomy.(undefined

The Development of Practice Recommendations for Drug-Disease Interactions by Literature Review and Expert Opinion

Background: Drug-disease interactions negatively affect the benefit/risk ratio of drugs for specific populations. In these conditions drugs should be avoided, adjusted, or accompanied by extra monitoring. The motivation for many drug-disease interactions in the Summary of Product Characteristics (SmPC) is sometimes insufficiently supported by (accessible) evidence. As a consequence the translation of SmPC to clinical practice may lead to non-specific recommendations. For the translation of this information to the real world, it is necessary to evaluate the available knowledge about drug-disease interactions, and to formulate specific recommendations for prescribers and pharmacists. The aim of this paper is to describe a standardized method how to develop practice recommendations for drug-disease interactions by literature review and expert opinion. Methods: The development of recommendations for drug-disease interactions will follow a six-step plan involving a multidisciplinary expert panel (1). The scope of the drug-disease interaction will be specified by defining the disease and by describing relevant effects of this drug-disease interaction. Drugs possibly involved in this drug-disease interaction are selected by checking the official product information, literature, and expert opinion (2). Evidence will be collected from the official product information, guidelines, handbooks, and primary literature (3). Study characteristics and outcomes will be evaluated and presented in standardized reports, including preliminary conclusions on the clinical relevance and practice recommendations (4). The multidisciplinary expert panel will discuss the reports and will either adopt or adjust the conclusions (5). Practice recommendations will be integrated in clinical decision support systems and published (6). The results of the evaluated drug-disease interactions will remain up-to-date by screening new risk information, periodic literature review, and (re)assessments initiated by health care providers. Actionable Recommendations: The practice recommendations will result in advices for specific DDSI. The content and considerations of these DDSIs will be published and implemented in all Clinical Decision Support Systems in the Netherlands. Discussion: The recommendations result in professional guidance in the context of individual patient care. The professional will be supported in the decision making in concerning pharmacotherapy for the treatment of a medical problem, and the clinical risks of the proposed medication in combination with specific diseases

The Development of Practice Recommendations for Drug-Disease Interactions by Literature Review and Expert Opinion

Background Drug-disease interactions negatively affect the benefit/risk ratio of drugs for specific populations. In these conditions drugs should be avoided, adjusted, or accompanied by extra monitoring. The motivation for many drug-disease interactions in the Summary of Product Characteristics (SmPC) is sometimes insufficiently supported by (accessible) evidence. As a consequence the translation of SmPC to clinical practice may lead to non-specific recommendations. For the translation of this information to the real world, it is necessary to evaluate the available knowledge about drug-disease interactions, and to formulate specific recommendations for prescribers and pharmacists. The aim of this paper is to describe a standardized method how to develop practice recommendations for drug-disease interactions by literature review and expert opinion. Methods The development of recommendations for drug-disease interactions will follow a six-step plan involving a multidisciplinary expert panel (1). The scope of the drug-disease interaction will be specified by defining the disease and by describing relevant effects of this drug-disease interaction. Drugs possibly involved in this drug-disease interaction are selected by checking the official product information, literature, and expert opinion (2). Evidence will be collected from the official product information, guidelines, handbooks, and primary literature (3). Study characteristics and outcomes will be evaluated and presented in standardized reports, including preliminary conclusions on the clinical relevance and practice recommendations (4). The multidisciplinary expert panel will discuss the reports and will either adopt or adjust the conclusions (5). Practice recommendations will be integrated in clinical decision support systems and published (6). The results of the evaluated drug-disease interactions will remain up-to-date by screening new risk information, periodic literature review, and (re)assessments initiated by health care providers. Actionable Recommendations The practice recommendations will result in advices for specific DDSI. The content and considerations of these DDSIs will be published and implemented in all Clinical Decision Support Systems in the Netherlands. Discussion The recommendations result in professional guidance in the context of individual patient care. The professional will be supported in the decision making in concerning pharmacotherapy for the treatment of a medical problem, and the clinical risks of the proposed medication in combination with specific diseases

Age-related changes in relative expression stability of commonly used housekeeping genes in selected porcine tissues

<p>Abstract</p> <p>Background</p> <p>Gene expression analysis using real-time RT-PCR (qRT-PCR) is increasingly important in biological research due to the high-throughput and accuracy of qRT-PCR. For accurate and reliable gene expression analysis, normalization of gene expression data against housekeeping genes or internal control genes is required. The stability of reference genes has a tremendous effect on the results of relative quantification of gene expression by qRT-PCR. The expression stability of reference genes could vary according to tissues, age of individuals and experimental conditions. In the pig however, very little information is available on the expression stability of reference genes. The aim of this research was therefore to develop a new set of reference genes which can be used for normalization of mRNA expression data of genes expressed in varieties of porcine tissues at different ages.</p> <p>Results</p> <p>The mRNA expression stability of nine commonly used reference genes (<it>B2M, BLM, GAPDH, HPRT1, PPIA, RPL4, SDHA, TBP </it>and <it>YWHAZ</it>) was determined in varieties of tissues collected from newborn, young and adult pigs. geNorm, NormFinder and BestKeeper software were used to rank the genes according to their stability. geNorm software revealed that <it>RPL4, PPIA </it>and <it>YWHAZ </it>showed high stability in newborn and adult pigs, while <it>B2M, YWHAZ </it>and <it>SDHA </it>showed high stability in young pigs. In all cases, <it>GAPDH </it>showed the least stability in geNorm. NormFinder revealed that <it>TBP </it>was the most stable gene in newborn and young pigs, while <it>PPIA </it>was most stable in adult pigs. Moreover, geNorm software suggested that the geometric mean of three most stable gene would be the suitable combination for accurate normalization of gene expression study.</p> <p>Conclusions</p> <p>Although, there was discrepancy in the ranking order of reference genes obtained by different analysing software methods, the geometric mean of the <it>RPL4, PPIA </it>and <it>YWHAZ </it>seems to be the most appropriate combination of housekeeping genes for accurate normalization of gene expression data in different porcine tissues at different ages.</p