203 research outputs found

    Metacognitive monitoring via strategies and judgments

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    Metacognitive monitoring is conceptualized as a situation-specific and context-dependent process that helps learners to regulate their learning. The current study builds on the idea that metacognitive monitoring can fulfil monitoring functions in different phases (when to monitor: during learning or during testing), and that it refers to several objects (what to monitor: processing or retrieval). The cross-sectional study with 184 higher-education students used a situation-specific approach and referred to students’ monitoring via monitoring strategies and monitoring judgments during test preparation and test processing. Confirmatory factor analyses indicated that monitoring via strategies and judgments can be directed at different objects. In addition, monitoring different objects was more strongly correlated within the same phase than across different phases. The study results emphasize the need for an object-specific and comprehensive consideration of metacognitive monitoring via monitoring strategies and monitoring judgments

    Restructuring the German Outpatient Health Care System: An Economic and IT Perspective

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    Among other proposals to reform the German outpatient health care system the establishment of networks of cooperating physicians (doctors’ networks) has found high and controversial consideration in recent years. In this paper we analyze doctors’ networks both from an economic perspective, particularly with a view on network strategies, and the perspective of supporting information technologies. Our main conclusions are that the viability of doctors’ networks critically depends on trust-building mechanisms like the restriction of the network in size and complexity and the application of fair profit allocation rules. Concerning information technology the implementation and use of highly integrated interorganizational systems appears most promising. We propose an architecture of such systems. It integrates information technology along the medical, the business and the communication systems dimension and serves as a vehicle for efficient use of shared patient data and other network resources, knowledge creation, fair profit allocation, improved business control and a high level of integrity vis-a-vis the patient

    Gender-specific prevalence of pilonidal sinus disease over time: A systematic review and meta-analysis.

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    BACKGROUND Gender-specific risk factors have been suggested to promote a fourfold higher incidence of pilonidal sinus disease (PSD) in male as compared to female patients. However, in recent decades there has been an apparent shift towards an increasing prevalence of PSD in women, as body weight and other risk factors influence the disease. We aimed at determining whether PSD prevalence actually changed in men and women over time. METHODS Following PRISMA guidelines (PROSPERO ID: 42016051588), databases were systematically searched. Papers reporting on PSD published between 1833 and 2018 in English, French, German, Italian and Spanish containing precise numbers of male and female participants were selected for analysis. Gender-specific prevalence of PSD over several decades was the main outcome measure. RESULTS We screened 679 studies reporting on 104 055 patients and found that the male/female ratio in patients with PSD has remained constant over time, with women being affected in about 20% of all PSD cases (I2  = 96.18%; meta-regression p < 0.001). CONCLUSION While the prevalence of PSD has risen over the past decades, the ratio between affected males and affected females has remained constant, with women invariably representing about 20% of patients despite wide ranging socioeconomic and behavioural changes

    Loss of TGFβ Signaling Destabilizes Homeostasis and Promotes Squamous Cell Carcinomas in Stratified Epithelia

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    SummaryAlthough TGFβ is a potent inhibitor of proliferation, epithelia lacking the essential receptor (TβRII) for TGFβ signaling display normal tissue homeostasis. By studying asymptomatic TβRII-deficient stratified epithelia, we show that tissue homeostasis is maintained by balancing hyperproliferation with elevated apoptosis. Moreover, rectal and genital epithelia, which are naturally proliferative, develop spontaneous squamous cell carcinomas with age when TβRII is absent. This progression is associated with a reduction in apoptosis and can be accelerated in phenotypically normal epidermis by oncogenic mutations in Ras. We show that TβRII deficiency leads to enhanced keratinocyte motility and integrin-FAK-Src signaling. Together, these mechanisms provide a molecular framework to account for many of the characteristics of TβRII-deficient invasive SQCCs

    Asymmetric Synthesis of b-Substituted a-Methylenebutyro- lactones via TRIP-Catalyzed Allylation: Mechanistic Studies and Application to the Synthesis of (S)-(À)-Hydroxymatairesinol

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    Abstract: Asymmetric allylation of (hetero)aromatic aldehydes by a zinc(II)-allylbutyrolactone species catalyzed by a chiral BINOL-type phosphoric acid gave b-substituted a-methylenebutyrolactones in 68 to &gt; 99% ee and 52-91% isolated yield. DFT studies on the intermediate Zn 2+ -complex -crucial for chiral induction -suggest a six-membered ring intermediate, which allows the phosphoric acid moiety to activate the aldehyde. The methodology was applied to the synthesis of the antitumour natural product (S)-(À)-hydroxymatairesinol

    Structural and Mechanistic Analysis of the Choline Sulfatase from Sinorhizobium melliloti: A Class I Sulfatase Specific for an Alkyl Sulfate Ester.

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    Hydrolysis of organic sulfate esters proceeds by two distinct mechanisms, water attacking at either sulfur (S-O bond cleavage) or carbon (C-O bond cleavage). In primary and secondary alkyl sulfates, attack at carbon is favored, whereas in aromatic sulfates and sulfated sugars, attack at sulfur is preferred. This mechanistic distinction is mirrored in the classification of enzymes that catalyze sulfate ester hydrolysis: arylsulfatases (ASs) catalyze S-O cleavage in sulfate sugars and arylsulfates, and alkyl sulfatases break the C-O bond of alkyl sulfates. Sinorhizobium meliloti choline sulfatase (SmCS) efficiently catalyzes the hydrolysis of alkyl sulfate choline-O-sulfate (kcat/KM=4.8×103s-1M-1) as well as arylsulfate 4-nitrophenyl sulfate (kcat/KM=12s-1M-1). Its 2.8-Å resolution X-ray structure shows a buried, largely hydrophobic active site in which a conserved glutamate (Glu386) plays a role in recognition of the quaternary ammonium group of the choline substrate. SmCS structurally resembles members of the alkaline phosphatase superfamily, being most closely related to dimeric ASs and tetrameric phosphonate monoester hydrolases. Although >70% of the amino acids between protomers align structurally (RMSDs 1.79-1.99Å), the oligomeric structures show distinctly different packing and protomer-protomer interfaces. The latter also play an important role in active site formation. Mutagenesis of the conserved active site residues typical for ASs, H218O-labeling studies and the observation of catalytically promiscuous behavior toward phosphoesters confirm the close relation to alkaline phosphatase superfamily members and suggest that SmCS is an AS that catalyzes S-O cleavage in alkyl sulfate esters with extreme catalytic proficiency

    Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics

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    In response to αβ1 integrin signaling, transducers such as focal adhesion kinase (FAK) become activated, relaying to specific machineries and triggering distinct cellular responses. By conditionally ablating Fak in skin epidermis and culturing Fak-null keratinocytes, we show that FAK is dispensable for epidermal adhesion and basement membrane assembly, both of which require αβ1 integrins. FAK is also dispensible for proliferation/survival in enriched medium. In contrast, FAK functions downstream of αβ1 integrin in regulating cytoskeletal dynamics and orchestrating polarized keratinocyte migration out of epidermal explants. Fak-null keratinocytes display an aberrant actin cytoskeleton, which is tightly associated with robust, peripheral focal adhesions and microtubules. We find that without FAK, Src, p190RhoGAP, and PKL–PIX–PAK, localization and/or activation at focal adhesions are impaired, leading to elevated Rho activity, phosphorylation of myosin light chain kinase, and enhanced tensile stress fibers. We show that, together, these FAK-dependent activities are critical to control the turnover of focal adhesions, which is perturbed in the absence of FAK

    Quinone reductase acts as a redox switch of the 20 S yeast proteasome

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102111/1/embr2008218.pd

    Rethinking the causes of pilonidal sinus disease: a matched cohort study

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    Our understanding of pilonidal sinus disease (PSD) is based on a paper published 29 years ago by Karydakis. Since then, surgeons have been taught that hair more easily penetrates wet skin, leading to the assumption that sweating promotes PSD. This postulate, however, has never been proven. Thus we used pilocarpine iontophoresis to assess sweating in the glabella sacralis. 100 patients treated for PSD and 100 controls were matched for sex, age and body mass index (BMI). Pilocarpine iontophoresis was performed for 5 min, followed by 15 min of sweat collection. PSD patients sweated less than their matched pairs (18.4 ± 1.6 µl vs. 24.2 ± 2.1 µl, p = 0.03). Men sweated more than women (22.2 ± 1.2 µl vs. 15.0 ± 1.0 µl in non-PSD patients (p < 0.0001) and 20.0 ± 1.9 µl vs. 11.9 ± 2.0 µl in PSD patients (p = 0.051)). And regular exercisers sweated more than non-exercisers (29.1 ± 2.9 µl vs. 18.5 ± 1.6 µl, p = 0.0006 for men and 20.7 ± 2.3 µl vs. 11.4 ± 1.4 µl, p = 0.0005 for women). PSD patients sweat less than matched controls. Thus sweating may have a protective effect in PSD rather than being a risk factor
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