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A new perspective on the brilliance of one of Western art's most celebrated visionaries through an esteemed collection of drawings. The works of Michelangelo (1475-1564) remain an enduring source of awe and fascination more than 500 years after his death. Michelangelo:Mind of the Master offers a new context for understanding the drawings of one of art's greatest visionaries. Through a group of drawings held since 1793 in the Teylers Museum and once in the eminent collection of Queen Christina of Sweden (1626-1689), this book sheds new light on Michelangelo's inventive preparations for his most important commissions in the realms of painting, sculpture, and architecture. Among other works, the volume features preliminary designs for some of the artist's best-known projects, including the Sistine Chapel ceiling and the Medici Chapel tombs. Essays in the volume further explore the history and fate of Michelangelo's drawings during his life, as well as the role of Queen Christina and her heirs in amassing a group of drawings that are among the best preserved by the master today. -- Publisher description.

The identification of distinct genetic and epigenetic profiles in different types of gliomas has revealed novel diagnostic, prognostic, and predictive molecular biomarkers for refinement of glioma classification and improved prediction of therapy response and outcome. Therefore, the new (2016) World Health Organization (WHO) classification of tumors of the central nervous system breaks with the traditional principle of diagnosis based on histologic criteria only and incorporates molecular markers. This will involve a multilayered approach combining histologic features and molecular information in an “integrated diagnosis”. We review the current state of diagnostic molecular markers for gliomas, focusing on isocitrate dehydrogenase 1 or 2 (IDH1/IDH2) gene mutation, α-thalassemia/mental retardation syndrome X-linked (ATRX) gene mutation, 1p/19q co-deletion and telomerase reverse transcriptase (TERT) promoter mutation in adult tumors, as well as v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and H3 histone family 3A (H3F3A) aberrations in pediatric gliomas. We also outline prognostic and predictive molecular markers, including O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and discuss the potential clinical relevance of biologic glioblastoma subtypes defined by integration of multiomics data. Commonly used methods for individual marker detection as well as novel large-scale DNA methylation profiling and next-generation sequencing approaches are discussed. Finally, we illustrate how advances in molecular diagnostics affect novel strategies of targeted therapy, thereby raising new challenges and identifying new leads for personalized treatment of glioma patients.

The Haarlem genotype is a significant yet understudied part of the Euro-American lineage of Mycobacterium tuberculosis , characterized by unique pathogenetic features. Spoligotyping is a primary method for its detection, but it is not suitable for isolates with long blocks of deleted spacers. We have developed a simple and robust method to detect the Haarlem genotype. The real-time PCR (RT-PCR) assay with LNA probes was designed to detect the Rv0282 211 C > T mutation that was shown to be specific for the Haarlem genotype. The developed RT-PCR assay was optimized with 68 isolates with known whole-genome sequencing (WGS) data and applied to the geographically and genetically diverse collection of 428 isolates. As a result, 396 isolates were concordantly assigned to either Haarlem or non-Haarlem genotypes by both methods, whereas 32 isolates were discrepant cases. Twenty-two isolates of “unknown genotype” (Russia, Belarus, and Poland) were assigned to Haarlem by SNP-based assay. WGS of these isolates confirmed the results of the RT-PCR assay. To conclude, the developed RT-PCR method provides a reliable detection of the Haarlem genotype in retrospective collections and under prospective epidemiological surveillance. Its actual proportion in M. tuberculosis populations in certain world regions is higher than previously thought. Abridged spoligoprofiles with large deleted blocks of spacers require caution in interpretation.

The purpose of this study is to assess the diagnostic performance of diffusion kurtosis imaging (DKI) for in vivo molecular profiling of human glioma. Normalized mean kurtosis (MK n ) and mean diffusivity (MD n ) metrics from DKI were assessed in 50 patients with histopathologically confirmed glioma. The results were compared in regard to the WHO-based histological findings and molecular characteristics leading to integrated diagnosis (Haarlem Consensus): isocitrate-dehydrogenase (IDH1/2) mutation status, alpha-thalassemia/mental retardation syndrome X-linked (ATRX) expression, chromosome 1p/19q loss of heterozygosity (LOH), and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status. MK n was significantly lower in tumors with IDH1/2 mutation (0.43 ± 0.09) and ATRX loss of expression (0.41 ± 0.11) than in those with IDH1/2 wild type (0.57 ± 0.09, p < 0.001) and ATRX maintained expression (0.51 ± 0.10, p = 0.004), respectively. Regarding the integrated molecular diagnosis, MK n was significantly higher in primary glioblastoma (0.57 ± 0.10) than in astrocytoma (0.39 ± 0.11, p < 0.001) and oligodendroglioma (0.47 ± 0.05, p = 0.003). MK may be used to provide insight into the human glioma molecular profile regarding IDH1/2 mutation status and ATRX expression. Considering the diagnostic and prognostic significance of these molecular markers, MK appears to be a promising in vivo biomarker for glioma. The diagnostic performance of MK seems to fit more with the integrated molecular approach than the conventional histological findings of the current WHO 2007 classification.

In 1647 CE, the United Dutch East India Company (VOC) ship Haarlem wrecked in Table Bay. The events that followed had far-reaching consequences, and this incident can be regarded as the catalyst that laid the basis for the modern multi racial South Africa. Since 1989, a project is underway to search for Haarlem. The present article provides a brief overview of work undertaken to date. This has resulted in the location of a site that, based on currently available evidence, probably contains the wreck.

Teyler's Foundation in Haarlem and its 'Book and Art Room' of 1779, edited by Ellinoor Bergvelt and Debora Meijers, examines for the first time this remarkable institution in the context of scientific, museological, political, artistic, religious and philosophical developments.

Background: Transmission of Mycobacterium tuberculosis (M. tuberculosis) can occur in different ways. Furthermore, drug resistant in M. tuberculosis family is a major problem that creates obstacles in treatment and control of tuberculosis (TB) in the world. One of the most prevalent families of M. tuberculosis is Haarlem, and it is associated with drug resistant. Our objectives of this study were to determine the prevalence and occurrence rate of M. tuberculosis Haarlem family multi-drug resistant (MDR) in the worldwide using meta-analysis based on a systematic review that performed on published articles. Materials and Methods: Data sources of this study were 78 original articles (2002-2012) that were published in the literatures in several databases including PubMed, Science Direct, Google Scholar, Biological abstracts, ISI web of knowledge and IranMedex. The articles were systematically reviewed for prevalence and rate of MDR. Data were analyzed using meta-analysis and random effects models with the software package Meta R, Version 2.13 (P < 0.10). Results: Final analysis included 28601 persons in 78 articles. The highest and lowest occurrence rate of Haarlem family in M. tuberculosis was in Hungary in 2006 (66.20%) with negative MDR-TB and in China in 2010 (0.8%), respectively. From 2002 to 2012, the lowest rate of prevalence was in 2010, and the highest prevalence rate was in 2012. Also 1.076% were positive for MDR and 9.22% were negative (confidence interval: 95%).0020. Conclusion: Many articles and studies are performed in this field globally, and we only chose some of them. Further studies are needed to be done in this field. Our study showed that M. tuberculosis Haarlem family is prevalent in European countries. According to the presence of MDR that was seen in our results, effective control programs are needed to control the spread of drug-resistant strains, especially Haarlem family.

The aim of this study was to investigate the genetic diversity among Mycobacterium tuberculosis complex circulating in patients with no known risk factors for multi-drug resistant (MDR) tuberculosis (TB) living in a high MDR burden area and analyze the relationship between genotypes, primary drug resistance and age. Samples were collected during January-July 2009. Isolates were tested for drug susceptibility to first-line drugs and were genotyped by spoligotyping and the 15-loci Mycobacterial Interspersed Repetitive Unit (MIRU15). Among the 199 isolates analyzed, 169 (84.9%) were identified in the SpolDB4.0 and 30 (15.1%) could not be matched to any lineage. The most prevalent lineage was Haarlem (29.6%), followed by T (15.6%), Beijing (14.1%), Latin American Mediterranean (12.6%) and U (8.5%). A few isolates belonged to the X and S clades (4.5%). Spoligotype analysis identified clustering among 148 of 169 isolates, whereas with MIRU15 all isolates were unique. Out of 197 strains; 31.5% were resistant to at least one drug, 7.5% were MDR and 22.3% showed any resistance to isoniazid. In contrast with other Latin-American countries where LAM lineage is the most predominant, we found the spoligotype 50 from the Haarlem lineage as the most common. None of the prevailing lineages showed a significant association with age or resistance to isoniazid and/or rifampicin.

In the Louvre museum hangs a portrait of a middle-aged man with long dark hair, a mustache, and heavy-lidded eyes, and he is dressed in the starched white collar and black coat of the typical Dutch burgher. The painting is now the iconic image of René Descartes, the great seventeenth-century French philosopher. And the painter of the work? The Dutch master Frans Hals--or so it was long believed, until the work was downgraded to a copy of an original. But where, then, is the authentic version located, and who painted it? Is the man in the painting--and in its original--really Descartes? A unique combination of philosophy, biography, and art history,The Philosopher, the Priest, and the Painterinvestigates the remarkable individuals and circumstances behind a small portrait. Through this image--and the intersecting lives of a brilliant philosopher, a Catholic priest, and a gifted painter--Steven Nadler opens up a fascinating portal into Descartes's life and times, skillfully presenting an accessible introduction to Descartes's philosophical and scientific ideas, and an illuminating tour of the volatile political and religious environment of the Dutch Golden Age. As Nadler shows, Descartes's innovative ideas about the world, about human nature and knowledge, and about philosophy itself, stirred great controversy. Philosophical and theological critics vigorously opposed his views, and civil and ecclesiastic authorities condemned his writings. Nevertheless, Descartes's thought came to dominate the philosophical world of the period, and can rightly be called the philosophy of the seventeenth century. Shedding light on a well-known image,The Philosopher, the Priest, and the Painteroffers an engaging exploration of a celebrated philosopher's world and work.

This documentary, directed by Reiner Moritz, is about the interior of Grote Kerk Church, painted by Pieter Saenredam.