191 research outputs found

    Grassroot planning from the fifth floor : or thoughts about the exploitation of Stockholms border regions

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    This essay is about the planning of Stockholm's border regions (areas on the outskirts of the city) during the first seven years of the 21st century. It describes how planning decisions are made in reality, in respect to a 'green' perspective. By describing what a "markanvisning" is (the right to negotiate with the city about a certain piece of land) and by discussing examples of what has happened with a hundred applications for markanvisning, this essay shows how Stockholm's border regions are planned. In the majority of cases it is the initiative of the future developers that begin the planning and construction processes. Research shows that the application to get a markanvisning in Stockholm does not follow a clear, structured system. However, the existing system in Stockholm does work and it seems like almost all the employees within the municipality, the politicians, and the future proprietors are happy with the current situation. Interviews have been held with key individuals involved in the planning process. These are: project leaders working with Stockholm's border regions at Exploateringskontoret (the development office) and their supervisor; the head for the whole Exploateringskontoret; key employees working at Stadsbyggnadskontoret (the city planning office); the head of Stockholm's border regions at Stadsbyggnadskontoret (the city planning office); future developers; and politicians. A complex picture appears from this research, where the strongest influences over the planning process are politics, opinion, contacts and economy. Stockholm's history tells a story of demolition and rebuilding, of visions and a consistent aim of building a great city. Today, in the end, politicians rule over city planning decisions. It was politicians that approved our current comprehensive plan (Översiktsplan) and it is politicians that have put up new goals that make it hard for the employees at the municipality to follow the same city plan. Two of these new goals, "Green compensation" (Grönkompensation) and 20K (20 000 new flats developed in one four year term of office) are projects that have dramatically influenced the development of Stockholm's border regions. Generally speaking, the dominating political blocks (groups from various political parties working together) do not differ much when it comes to the city's planning politics. Their emphasis is not on adhering and working towards longer term planning strategies. Instead they show their results in terms of the number of flats they can build whilst in office. Although they will gain political favour through public opinion, their short-term goals may be at the expense of the long-term interests of the city. The interviews and the resultant research surrounding the markanvisningar process shows that the application documents just have a small impact on the result. The planning decisions are more connected to certain key persons. Responsible for the 'green' side is the head city gardener (stadsträdgårdsmästare), Ulf Lindahl. He is a person that the project leaders turn to, to get an opinion at the earliest stage of the planning process (when someone has applied for markanvisning). Lindahl believes that there is no city in the world that has as many planning documents for green spaces as Stockholm. He knows the city well and the project leaders at the development office (exploateringskontoret) often listen to him out of respect. They say that they often make decisions based on what he suggests, even though they do not have to. The examination of the applications for markanvisning shows that they follow his lead, in around 75% of the cases. This analysis also shows that the head city gardener (stadsträdgårdsmästare) has, during the last few years shown a higher level of acceptance for the exploitation of green spaces. This is due to the fact that people have to build somewhere in Stockholm where space is rapidly running out. It is hoped that the new city plan, due for completion in the year 2010 will provide everybody with a more realistic set of goals that can be used to make more successful and thoughtful planning decisions. A question for you as a reader to reflect over are: How can we do so that the city develops in the best possible way?Den här uppsatsen handlar om planeringen av Stockholms ytterstad, de första sju åren av 2000-talet. Hur det går till rent praktiskt och hur resultatet har blivit, sett ur ett grönt perspektiv. Genom att beskriva vad ”Markanvisning” är och sedan följa upp vad som har hänt med ett hundratal markanvisningsansökningar, har en bild av Stockholms ytterstadsplanering tecknats. Här sker mycket av bebyggelsen på byggherrars initiativ, då de söker om en markanvisning. Efter att ha sökt information på internet framstår det som om markanvisningsprocessen i Stockholm inte har någon tydlig, fast struktur. Dock verkar de flesta tjänstemän, politiker och byggherrar vara nöjda. Så här går det till i Stockholm och det fun-gerar. Samtal har förts med projektledare på Exploateringskontorets ytterstads-avdelning och dess chef, exploateringskontorets chef, stadsträdgårdsmästaren, tjänstemän på- och chefen för stadsbyggnadskontorets ytterstadsavdelning samt byggherrar och politiker. Fram träder en komplex bild där främst politik, opinion, kontakter och ekonomi styr. Stockholms historia tecknar en bild av rivning och återuppbyggnad, av visioner och en ständig strävan att bygga en bra stad. Idag är vår stadsplanering ytterst styrd av politiker. Det är politiker som godkänt vår översiktsplan, och det är våra politiker som sätter upp nya mål vilket tvingar tjänstemännen att göra avsteg från den. Grönkompensation och 20K (20 000 bostäder under en mandatperiod) är projekt som påverkat exploateringen av Stockholms ytterstad. Generellt kan sägas att de dominerande politiska blocken inte skiljer sig markant då det gäller planeringspolitiken. För politikerna är resultat i form av antal byggda lägenheter och opinionen viktig. Intervjuer och uppföljningen av markanvisningar visar att den personliga kotakten är väldigt viktig. Ansvarig för grönsidan är stadsträdgårdsmästare Ulf Lindahl. Det är till honom man vänder sig för att få ett uttalande i det tidiga markanvisningsskedet. Det finns nog ingen stad i världen som har så mycket planeringsunderlag för gröna ytor som Stockholm, tror Lindahl. Han kan staden bra och har respekt hos projektledarna på exploateringskontoret. De säger att de rättar sig efter honom, även om de inte måste. Uppföljningen av markanvisningsansökningarna visar att det stämmer, i alla fall till 75%. Stadsträdgårdsmästaren har med åren även blivit mer benägen att godkänna exploatering på grönmark. Det i sig säger inte så mycket, det kan vara både positivt och negativt. Det viktiga är att Stockholms planering blir genomtänkt. En fråga till dig som läsare att reflektera över är: Hur kan vi göra så att staden växer på bästa möjliga vis

    Clonal Evolution through Loss of Chromosomes and Subsequent Polyploidization in Chondrosarcoma

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    Near-haploid chromosome numbers have been found in less than 1% of cytogenetically reported tumors, but seem to be more common in certain neoplasms including the malignant cartilage-producing tumor chondrosarcoma. By a literature survey of published karyotypes from chondrosarcomas we could confirm that loss of chromosomes resulting in hyperhaploid-hypodiploid cells is common and that these cells may polyploidize. Sixteen chondrosarcomas were investigated by single nucleotide polymorphism (SNP) array and the majority displayed SNP patterns indicative of a hyperhaploid-hypodiploid origin, with or without subsequent polyploidization. Except for chromosomes 5, 7, 19, 20 and 21, autosomal loss of heterozygosity was commonly found, resulting from chromosome loss and subsequent duplication of monosomic chromosomes giving rise to uniparental disomy. Additional gains, losses and rearrangements of genetic material, and even repeated rounds of polyploidization, may affect chondrosarcoma cells resulting in highly complex karyotypes. Loss of chromosomes and subsequent polyploidization was not restricted to a particular chondrosarcoma subtype and, although commonly found in chondrosarcoma, binucleated cells did not seem to be involved in these events

    Recurrent Chromosomal Copy Number Alterations in Sporadic Chordomas

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    The molecular events in chordoma pathogenesis have not been fully delineated, particularly with respect to copy number changes. Understanding copy number alterations in chordoma may reveal critical disease mechanisms that could be exploited for tumor classification and therapy. We report the copy number analysis of 21 sporadic chordomas using array comparative genomic hybridization (CGH). Recurrent copy changes were further evaluated with immunohistochemistry, methylation specific PCR, and quantitative real-time PCR. Similar to previous findings, large copy number losses, involving chromosomes 1p, 3, 4, 9, 10, 13, 14, and 18, were more common than copy number gains. Loss of CDKN2A with or without loss of CDKN2B on 9p21.3 was observed in 16/20 (80%) unique cases of which six (30%) showed homozygous deletions ranging from 76 kilobases to 4.7 megabases. One copy loss of the 10q23.31 region which encodes PTEN was found in 16/20 (80%) cases. Loss of CDKN2A and PTEN expression in the majority of cases was not attributed to promoter methylation. Our sporadic chordoma cases did not show hotspot point mutations in some common cancer gene targets. Moreover, most of these sporadic tumors are not associated with T (brachyury) duplication or amplification. Deficiency of CDKN2A and PTEN expression, although shared across many other different types of tumors, likely represents a key aspect of chordoma pathogenesis. Sporadic chordomas may rely on mechanisms other than copy number gain if they indeed exploit T/ brachyury for proliferation

    Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation

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    The initiating somatic genetic events in chordoma development have not yet been identified. Most cytogenetically investigated chordomas have displayed near-diploid or moderately hypodiploid karyotypes, with several numerical and structural rearrangements. However, no consistent structural chromosome aberration has been reported. This is the first array-based study characterising DNA copy number changes in chordoma. Array comparative genomic hybridisation (aCGH) identified copy number alterations in all samples and imbalances affecting 5 or more out of the 21 investigated tumours were seen on all chromosomes. In general, deletions were more common than gains and no high-level amplification was found, supporting previous findings of primarily losses of large chromosomal regions as an important mechanism in chordoma development. Although small imbalances were commonly found, the vast majority of these were detected in single cases; no small deletion affecting all tumours could be discerned. However, the CDKN2A and CDKN2B loci in 9p21 were homo- or heterozygously lost in 70% of the tumours, a finding corroborated by fluorescence in situ hybridisation, suggesting that inactivation of these genes constitute an important step in chordoma development

    NR4A3 rearrangement reliably distinguishes between the clinicopathologically overlapping entities myoepithelial carcinoma of soft tissue and cellular extraskeletal myxoid chondrosarcoma

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    Myoepithelial carcinoma of soft tissue (MEC) and cellular extraskeletal myxoid chondrosarcoma (cEMC) share striking similarities. In this paper, we compare ten MECs with five cEMCs. MEC patients had an equal gender distribution. The age range was 15–76 years (mean, 42 years). Tumours were located on extremities, pelvic girdle, vulva and neck. Follow-up, available for nine patients, ranged from 4 to 85 months (mean, 35 months). Five patients were alive without evidence of disease, two were alive with disease and two died 8 months after the initial diagnosis. cEMCs were from three males and two females with an age range of 37–82 years (mean, 57 years); they presented in extremities, shoulder and paravertebral/cervical. Follow-up, available for four patients, ranged from 6 to 220 months (mean, 61 months). All patients were alive, two with recurrences and/or metastases and two without evidence of disease. Morphologically, the distinction between these two entities was difficult since all cases exhibited features typically seen in myoepithelial tumours. Immunohistochemically, MECs expressed pan-keratin (80 %), epithelial membrane antigen (EMA; 57 %), S100 (50 %), alpha-smooth muscle actin (ASMA; 75 %), calponin (67 %) and p63 (25 %). S100 and EMA were expressed in 40 % of cEMC cases respectively with additional immunoreactivity for p63, ASMA and glial fibrillary acidic protein in one case. Pan-keratin was negative in all neoplasms. NR4A3 rearrangement was present in four of four cEMCs and in none of the MECs. In contrast, three of nine (33 %) MECs and four of five (80 %) cEMCs showed an EWSR1 rearrangement. In summary, MECs and cEMCs share clinical, morphological, immunohistochemical and genetic characteristics. The pathognomic rearrangement of NR4A3 is a useful diagnostic feature in identifying cEMCs

    Fluorescence in situ hybridization in surgical pathology: principles and applications

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    Identification of recurrent tumour‐specific chromosomal translocations and novel fusion oncogenes has important diagnostic, therapeutic and prognostic implications. Over the past decade, fluorescence in situ hybridization (FISH) analysis of tumour samples has been one of the most rapidly growing areas in genomic medicine and surgical pathology practice. Unlike traditional cytogenetics, FISH affords a rapid analysis of formalin‐fixed, paraffin‐embedded cells within a routine pathology practice workflow. As more diagnostic and treatment decisions are based on results of FISH, demand for the technology will become more widespread. Common FISH‐detected alterations are chromosome deletions, gains, translocations, amplifications and polysomy. These chromosome alterations may have diagnostic and therapeutic implications for many tumour types. Integrating genomic testing into cancer treatment decisions poses many technical challenges, but rapid progress is being made to overcome these challenges in precision medicine. FISH assessment of chromosomal changes relevant to differential diagnosis and cancer treatment decisions has become an important tool for the surgical pathologist. The aim of this review is to provide a theoretical and practical survey of FISH detected translocations with a focus on strategies for clinical application in surgical pathology practice.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136670/1/cjp264_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136670/2/cjp264.pd

    Potential therapeutic targets for chordoma: PI3K/AKT/TSC1/TSC2/mTOR pathway

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    Chordomas are radio- and chemo-resistant tumours and metastasise in as many as 40% of patients. The aim of this study was to identify potential molecular targets for the treatment of chordoma. In view of the reported association of chordoma and tuberous sclerosis complex syndrome, and the available therapeutic agents against molecules in the PI3K/AKT/TSC1/TSC2/mTOR pathway, a tissue microarray of 50 chordoma cases was analysed for expression of active molecules involved in this signalling pathway by immunohistochemistry and a selected number by western blot analysis. Chordomas were positive for p-AKT (92%), p-TSC2 (96%), p-mTOR (27%), total mTOR (75%), p-p70S6K (62%), p-RPS6 (22%), p-4E-BP1 (96%) and eIF-4E (98%). Phosphatase and tensin homologue deleted on chromosome 10 expression was lost in 16% of cases. Mutations failed to be identified in PI3KCA and RHEB1 in the 23 cases for which genomic DNA was available. Fluorescence in situ hybridisation analysis for mTOR and RPS6 loci showed that 11 of 33 and 21 of 44 tumours had loss of one copy of the respective genes, results which correlated with the loss of the relevant total proteins. Fluorescence in situ hybridisation analysis for loci containing TSC1 and TSC2 revealed that all cases analysed harboured two copies of the respective genes. On the basis of p-mTOR and or p-p70S6K expression there is evidence indicating that 65% of the chordomas studied may be responsive to mTOR inhibitors, rapamycin or its analogues, and that patients may benefit from combined therapy including drugs that inhibit AKT

    Running GAGs: myxoid matrix in tumor pathology revisited: What’s in it for the pathologist?

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    Ever since Virchow introduced the entity myxoma, abundant myxoid extracellular matrix (ECM) has been recognized in various reactive and neoplastic lesions. Nowadays, the term “myxoid” is commonly used in daily pathological practice. But what do today’s pathologists mean by it, and what does the myxoid ECM tell the pathologist? What is known about the exact composition and function of the myxoid ECM 150 years after Virchow? Here, we give an overview of the composition and constituents of the myxoid ECM as known so far and demonstrate the heterogeneity of the myxoid ECM among different tumors. We discuss the possible role of the predominant constituents of the myxoid ECM and attempt to relate them to differences in clinical behavior. Finally, we will speculate on the potential relevance of this knowledge in daily pathological practice

    How are agricultural ecosystem services affected by species loss? : and how it can be used in biology teaching

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    Jordbrukens ekosystem är mer komplexa än vad man tidigare trott och består av många olika arter kopplade till olika ekosystemtjänster som jordbruket tillhandahåller. De interaktioner som bildas mellan arterna bildar ett ekologiskt nätverk där växterna är de energiproducerande resurserna för konsumenter högre upp i nätverket. Vi lever idag i ett sjätte massutdöende med pågående klimatkris som påverkar sannolikheten för arters överlevnad. Syftet med det här arbetet är därför att ta reda på hur jordbrukets ekosystemtjänster påverkas vid artbortfall av vissa växter skapade av hoten invasiva arter, patogener och pollinatörbrist. Syftet är även att titta på hur detta arbetssätt kan användas inom undervisningen av biologi på gymnasiet. Undersökningen av artbortfallens påverkan sker med hjälp av Bayesianska nätverk som utifrån alla artinteraktioner och tillhandahållanden av ekosystemtjänster beräknar och simulerar sannolikheten för arters överlevnad och därmed även sannolikheten för att ekosystemtjänsterna ska finnas kvar. Det visade sig att oavsett hot så blir så gott som alla ekosystemtjänster påverkade vilket tyder på många indirekta effekter. Det visade sig även att hoten pollinatörbrist har störst påverkan på minskningen av de aktuella ekosystemtjänsterna. Simuleringen av artbortfall skulle kunna implementeras i biologiundervisningen på gymnasiet för att visa på hur komplexa ekosystemen är och ge eleverna en djupare förståelse i hur de ekologiska, ekonomiska och sociala aspekterna hänger samman och försöka hitta metoder för att åtgärda minskningarna av ekosystemtjänsterna. Agricultural ecosystems are more complex than previously thought and consist of many different species linked to different ecosystem services that agriculture provides. The interactions between the species form an ecological network where the plants are the energy-producing resources for consumers higher up in the network. Today we live in a sixth mass extinction with an ongoing climate crisis that affects the probability of species survival. The purpose of this work is therefore to find out how agricultural ecosystem services are affected in the case of species extinction of certain plants created by the threats of invasive species, pathogens and pollinator shortages. The secondary aim is also to look at how this can be used in the teaching of biology at upper secondary school. The investigation of the impact of species loss is done with Bayesian networks which, based on all species interactions and the provision of ecosystem services, calculate and simulate the probability of species survival and thus also the probability that the ecosystem services will remain. It turned out that regardless of the threat, almost all ecosystem services are affected, which indicates many indirect effects. It also turned out that the threatened pollinator shortage has the greatest impact on the reduction of the current ecosystem services. The simulation of species loss could be implemented in upper secondary school biology classes to show how complex ecosystems are and give students a deeper understanding of how the ecological, economic and social aspects are connected and try to find methods to remedy the reductions in ecosystem services
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