175 research outputs found

    Al2O3 Surface Passivation Characterized on Hydrophobic and Hydrophilic c-Si by a Combination of QSSPC, CV, XPS and FTIR

    Get PDF
    Abstract In this work, the influence of the c-Si surface finishing (hydrophobic/hydrophilic) prior to the deposition of the Al2O3 passivation layer on the passivation quality is investigated. The samples are characterized by a combination of Quasi-Steady-State-PhotoConductance (QSSPC) Capacity-Conductance (CV), X-ray Photoelectron Spectroscopy (XPS) and Fourier Transformed InfraRed (FTIR) measurements. Furthermore, FTIR measurements are used to determine the thickness of interfacial SiOx layer

    Posterior lung herniation after a coughing spell: a case report

    Get PDF
    Lung hernias are rare, occurring most commonly after trauma or surgery. Spontaneous lung hernias are even rarer and have only been reported as occurring anteriorly. We present a 72-year-old male who developed a spontaneous posterior lung hernia after a severe coughing episode. We describe the evaluation and surgical management of this unusual condition and provide a brief review of the literature

    Suspected Lynch syndrome associated MSH6 variants: A functional assay to determine their pathogenicity

    Get PDF
    Lynch syndrome (LS) is a hereditary cancer predisposition caused by inactivating mutations in DNA mismatch repair (MMR) genes. Mutations in the MSH6 DNA MMR gene account for approximately 18% of LS cases. Many LS-associated sequence variants are nonsense and frameshift mutations that clearly abrogate MMR activity. However, missense mutations whose functional implications are unclear are also frequently seen in suspected-LS patients. To conclusively diagnose LS and enroll patients in appropriate surveillance programs to reduce morbidity as well as mortality, the functional consequences of these variants of uncertain clinical significance (VUS) must be defined. We present an oligonucleotide-directed mutagenesis screen for the identification of pathogenic MSH6 VUS. In the screen, the MSH6 variant of interest is introduced into mouse embryonic stem cells by site-directed mutagenesis. Subsequent selection for MMR-deficient cells using the DNA damaging agent 6-thioguanine (6TG) allows the identification of MMR abrogating VUS because solely MMR-deficient cells survive 6TG exposure. We demonstrate the efficacy of the genetic screen, investigate the phenotype of 26 MSH6 VUS and compare our screening results to clinical data from suspected-LS patients carrying these variant alleles

    Raloxifene augmentation in men and women with a schizophrenia spectrum disorder:A study protocol

    Get PDF
    Although acute psychotic symptoms are often reduced by antipsychotic treatment, many patients with schizophrenia are impaired in daily functioning due to the persistence of negative and cognitive symptoms. Raloxifene, a Selective Estrogen Receptor Modulator (SERM) has been shown to be an effective adjunctive treatment in schizophrenia. Yet, there is a paucity in evidence for raloxifene efficacy in men and premenopausal women. We report the design of a study that aims to replicate earlier findings concerning the efficacy of raloxifene augmentation in reducing persisting symptoms and cognitive impairment in postmenopausal women, and to extend these findings to a male and peri/premenopausal population of patients with schizophrenia. The study is a multisite, placebo-controlled, double-blind, randomised clinical trial in approximately 110 adult men and women with schizophrenia. Participants are randomised 1:1 to adjunctive raloxifene 120 mg or placebo daily during 12 weeks. The treatment phase includes measurements at three time points (week 0, 6 and 12), followed by a follow-up period of two years. The primary outcome measure is change in symptom severity, as measured with the Positive and Negative Syndrome Scale (PANSS), and cognition, as measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Secondary outcome measures include social functioning and quality of life. Genetic, hormonal and inflammatory biomarkers are measured to assess potential associations with treatment effects. If it becomes apparent that raloxifene reduces psychotic symptoms and/or improves cognition, social functioning and/or quality of life as compared to placebo, implementation of raloxifene in clinical psychiatric practice can be considered

    Rijkswaterstaat:Guardian of the Dutch Delta

    Get PDF
    Founded in 1798, Rijkswaterstaat, the Dutch government’s agency for infrastructural works, brought flood security, navigable waterways and highways to the Netherlands. It is an iconic institution within Dutch society, best known for its ‘battle against the water’. The Zuiderzee Works (1920–1968) and the Delta Works (1954–1997) brought worldwide acclaim. This chapter tells the story of a humble semi-military organization that developed into a formidable institution of civil engineers with a strong technocratic mission mystique. It also recounts the institutional crisis the agency experienced in the 1970s–1990s when it was too slow to adapt to major sociocultural and political changes. To ride the waves of change, it eventually developed several proactive adaptation strategies and reinvented its mission mystique in managerial terms. Adaptation to climate change now presents another key challenge, for which Rijkswaterstaat will have to develop a new ‘social license to operate’

    Neo-Atlantis: The Netherlands under a 5-m sea level rise

    Get PDF
    What could happen to the Netherlands if, in 2030, the sea level starts to rise and eventually, after 100 years, a sea level of 5 m above current level would be reached? This question is addressed by studying literature, by interviewing experts in widely differing fields, and by holding an expert workshop on this question. Although most experts believe that geomorphology and current engineering skills would enable the country to largely maintain its territorial integrity, there are reasons to assume that this is not likely to happen. Social processes that precede important political decisions - such as the growth of the belief in the reality of sea level rise and the framing of such decisions in a proper political context (policy window) - evolve slowly. A flood disaster would speed up the decision-making process. The shared opinion of the experts surveyed is that eventually part of the Netherlands would be abandoned. © 2008 The Author(s)

    Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer

    Get PDF
    Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylation in vitro and in vivo. Immunofluorescence microscopy and ATAC-See revealed the association of this modification with active chromatin. Brpf1 deletion obliterates the acylation in mouse embryos and fibroblasts. Moreover, we identify BRPF1 variants in 12 previously unidentified cases of syndromic intellectual disability and demonstrate that these cases and known BRPF1 variants impair H3K23 propionylation. Cardiac anomalies are present in a subset of the cases. H3K23 acylation is also impaired by cancer-derived somatic BRPF1 mutations. Valproate, vorinostat, propionate and butyrate promote H3K23 acylation. These results reveal the dual functionality of BRPF1-KAT6 complexes, shed light on mechanisms underlying related developmental disorders and various cancers, and suggest mutation-based therapy for medical conditions with deficient histone acylation

    Does mycorrhization influence herbivore-induced volatile emission in Medicago truncatula?

    Get PDF
    Symbiosis with mycorrhizal fungi substantially impacts secondary metabolism and defensive traits of colonised plants. In the present study, we investigated the influence of mycorrhization (Glomus intraradices) on inducible indirect defences against herbivores using the model legume Medicago truncatula. Volatile emission by mycorrhizal and non-mycorrhizal plants was measured in reaction to damage inflicted by Spodoptera spp. and compared to the basal levels of volatile emission by plants of two different cultivars. Emitted volatiles were recorded using closed-loop stripping and gas chromatography/mass spectrometry. The documented volatile patterns were evaluated using multidimensional scaling to visualise patterns and stepwise linear discriminant analysis to distinguish volatile blends of plants with distinct physiological status and genetic background. Volatile blends emitted by different cultivars of M. truncatula prove to be clearly distinct, whereas mycorrhization only slightly influenced herbivore-induced volatile emissions. Still, the observed differences were sufficient to create classification rules to distinguish mycorrhizal and non-mycorrhizal plants by the volatiles emitted. Moreover, the effect of mycorrhization turned out to be opposed in the two cultivars examined. Root symbionts thus seem to alter indirect inducible defences of M. truncatula against insect herbivores. The impact of this effect strongly depends on the genetic background of the plant and, hence, in part explains the highly contradictory results on tripartite interactions gathered to date

    The M-OVIN study: does switching treatment to FSH and / or IUI lead to higher pregnancy rates in a subset of women with world health organization type II anovulation not conceiving after six ovulatory cycles with clomiphene citrate - a randomised controlled trial

    Get PDF
    Background: Clomiphene citrate (CC) is first line treatment in women with World Health Organization (WHO) type II anovulation and polycystic ovary syndrome (PCOS). Whereas 60% to 85% of these women will ovulate on CC, only about one half will have conceived after six cycles. If women do not conceive, treatment can be continued with gonadotropins or intra-uterine insemination (IUI). At present, it is unclear for how many cycles ovulation induction with CC should be repeated, and when to switch to ovulation induction with gonadotropins and/or IUI. Methods/Design: We started a multicenter randomised controlled trial in the Netherlands comparing six cycles of CC plus intercourse or six cycles of gonadotrophins plus intercourse or six cycles of CC plus IUI or six cycles of gonadotrophins plus IUI. Women with WHO type II anovulation who ovulate but did not conceive after six ovulatory cycles of CC with a maximum of 150 mg daily for five days will be included. Our primary outcome is birth of a healthy child resulting from a pregnancy that was established in the first eight months after randomisation. Secondary outcomes are clinical pregnancy, miscarriage, multiple pregnancy and treatment costs. The analysis will be performed according to the intention to treat principle. Two comparisons will be made, one in which CC is compared to gonadotrophins and one in which the addition of IUI is compared to ovulation induction only. Assuming a live birth rate of 40% after CC, 55% after addition of IUI and 55% after ovulation induction with gonadotrophins, with an alpha of 5% and a power of 80%, we need to recruit 200 women per arm (800 women in total). An independent Data and Safety Monitoring Committee has criticized the data of the first 150 women and concluded that a sample size re-estimation should be performed after including 320 patients (i.e. 80 per arm). Discussion: The trial will provide evidence on the most effective, safest and most cost effective treatment in women with WHO type II anovulation who do not conceive after six ovulatory cycles with CC with a maximum of 150 mg daily for five days. This evidence could imply the need for changing our guidelines, which may cause a shift in large practice variation to evidence based primary treatment for these women.Marleen J Nahuis, Nienke S Weiss, Fulco van der Veen, Ben Willem J Mol, Peter G Hompes, Jur Oosterhuis, Nils B Lambalk, Jesper MJ Smeenk, Carolien AM Koks, Ron JT van Golde, Joop SE Laven, Ben J Cohlen, Kathrin Fleischer, Angelique J Goverde, Marie H Gerards, Nicole F Klijn, Lizka CM Nekrui, Ilse AJ van Rooij, Diederik A Hoozemans, and Madelon van Wely
    • …
    corecore