设计资本

UN设计六步法(或多或少) 现如今,建筑学科敞开大门接受彻底变革的可能性.那些关于收益和增长的叙述曾在过去几十年中,阐释并大力推进建筑学的发展,并为其提供了合理的依据;如今这些叙述已被打断.现在的焦点在于,如何对建筑核心领域内的一切可能的重要因素提炼阐明新的概念.一切事,是的,所有一切事都可以进行改变,整个世界需要共同面临的问题和需求如此之大. 意识到这一挑战还需要了解其有益的潜力;新颖引领建筑学蓬勃发展.如果缺乏连续的物质、文化和意识上的创新,行业便失去其特殊性,而成为建筑行业中平淡无奇的一部分.通过UNStudio,我们早就意识到了这一点,这就是为什么我们在许多不同的方向上推动自己,不断应对新的挑战和问题.但与此同时,这一实验态度也使我们有意识地致力于尽可能多的建造.在全球化经济的背景下,脱离建筑行业的危险性从来就不是我们的首选方案.     

Changes in the signalling status of the small GTP-binding proteins Rac and Rho do not influence insulin-stimulated hexose transport

Post-receptor signalling molecules that convey the signal from the activated insulin receptor to the actual process of Glut4 translocation and hexose uptake are poorly understood. Various studies have suggested a requirement of the lipid kinase phosphatidylinositol-3 kinase (PI3-kinase) in this process. PI3kinase regulates the activation status of the small GTP-binding protein Rac which, in turn, is able to activate another G-protein Rho. Rac and Rho are known to regulate the structure of the membrane- and cytoplasmic actin-cytoskeleton. We have examined whether Rac and Rho transfer the signals generated by PI3kinase towards insulin-stimulated hexose uptake. For that purpose, we expressed in 3T3-L1 adipocytes the dominant-negative mutant of RacN17 using vaccinia virus-mediated gene transfer. The expression levels of the RacN17 protein were monitored by Western blotting. The abrogation of endogenous Rac signalling by expression of RacN17 was inferred from the observed loss of arachidonic acid release in response to insulin. Basal and insulin-stimulated hexose transport were not affected by expression of the RacN17 mutant. A possible contribution of Rho.GTP to stimulation of hexose uptake was examined by pre-incubation of adipocytes with lysophosphatidic acid (LPA). We observed a profound effect of LPA on the structure of the cytoskeleton and on the phosphorylation of Focal Adhesion Kinase (p125FAK), indicating that 3T3-L1 adipocytes respond to LPA and that Rho was activated by LPA. However, no effect was detected on the basal or on the insulin-stimulated hexose transport. We conclude that Rac and Rho are unlikely to be involved in insulin-stimulated hexose transport, suggesting a possible contribution of other signalling pathways, downstream of PI3kinase to this process.     

The development of practice guidelines for the treatment of severe plaque form psoriasis

OBJECTIVE: To develop and introduce evidence-based guidelines for the selection of 5 commonly used treatment modalities--UV-B, photochemotherapy, methotrexate, acitretin, and cyclosporine--for adult patients with severe plaque form psoriasis. PATIENTS AND SETTING: Patients, residents, and dermatologists from the Department of Dermatology of the Academic Medical Center of the University of Amsterdam, Amsterdam, the Netherlands, were involved in this process. DESIGN: The development process started with a questionnaire to evaluate how patients with severe psoriasis were treated. A systematic literature review was set up to provide evidence-based estimates of effectiveness, adverse effects, and dropout rates. In 2 meetings, the opinion leaders and intended users discussed the results of the questionnaire and systematic review as well as the clinical considerations in the treatment choices. Guidelines were then made regarding the sequence of selection of 5 modalities in the concept of rotational therapy. These guidelines were introduced. Their use was analyzed for 6 months. RESULTS: Before the guidelines, there was no uniform approach. In the systematic review, 665 studies concerning the treatments were found. Exclusion rates were high. No studies of methotrexate therapy could be included. Photochemotherapy showed the highest average proportion of patients with clearance (70% [6947/9925]) and good response (83% [8238/9925]), followed by UV-B (67.9% [620/913]) and cyclosporine (64% [1030/1609]) therapy. In the second internal meeting, the following sequence for the treatments was defined: UV-B, photochemotherapy, methotrexate, acitretin, and cyclosporine. In 78% (69/88) of patients treated after the introduction, the guidelines were followed to determine the treatment choice. CONCLUSIONS: Guidelines for treating severe plaque form psoriasis can be successfully developed, introduced, and implemented and were considered to improve clinical care.     

Time-series analysis if data are randomly missing

Maximum-likelihood (ML) theory presents an elegant asymptotic solution for the estimation of the parameters of time-series models. Unfortunately, the performance of ML algorithms in finite samples is often disappointing, especially in missing-data problems. The likelihood function is symmetric with respect to the unit circle for the estimated zeros of time-series models. As a consequence, the unit circle is either a local maximum or a local minimum in the likelihood of moving-average (MA) models. This is a trap for nonlinear optimization algorithms that often converge to poor models, with estimated zeros precisely on the unit circle. With ML estimation, it is much easier to estimate a long autoregressive (AR) model with only poles. The parameters of that long AR model can then be used to estimate MA and autoregressive moving-average (ARMA) models for different model orders. The accuracy of the estimated AR, MA, and ARMA spectra is very good. The robustness is excellent as long as the AR order is less than 10 or 15. For still-higher AR orders until about 60, the possible convergence to a useful model will depend on the missing fraction and on the specific properties of the data at hand.     

Acute disruption of the posterior tibial tendon associated with open-fracture dislocation of the ankle

A 27-year-old man with a high-energy, open-fracture dislocation of the ankle underwent debridement and open reduction of his injuries. During surgery a disruption-laceration of the posterior tibial tendon at the level of the fracture of the medial malleolus was found. Repair required location of the proximal muscle and tendon and controlled traction of the musculotendinous unit from its retracted position. Common aspects in the nine previously reported instances of this lesion include relatively high energy of the injury and the fracture type, a transverse fracture in the medial malleolus. Unique to this case was the open injury.     

Extracorporeal photochemotherapy (photopheresis) induces apoptosis in lymphocytes: a possible mechanism of action of PUVA therapy

The mechanism of action of psoralen plus UVA (PUVA) and photopheresis is not entirely understood. These therapies are assumed to be immunomodulating partly by gradually decreasing leukocyte viability. We investigated whether this delayed form of cell death was due to apoptosis. Untreated and treated (PUVA exposed) leukocytes obtained from six patients with systemic sclerosis and (untreated) leukocytes from healthy control individuals were studied. Qualitative gel electrophoresis and quantitative in situ nick translation analysis of DNA fragmentation was performed. Apoptosis of the treated cells did occur (gel electrophoresis) after 24 h. At t = 0 h, immediately after exposure to PUVA, there was no evidence of DNA fragmentation in the treated cells. The percentage of treated cells undergoing apoptosis was 20-55% at t = 24 h (in situ nick translation). The untreated leukocytes of the patients and the healthy individuals showed no distinctive rise in apoptotic cells. Apoptosis of the leukocytes after PUVA or photopheresis treatment might be a mechanism of action and might explain the therapeutic response.     

Convenient method for the analysis of primary and secondary hydroxyl end groups in polyethers

Summary The content of primary and secondary hydroxyl end groups in polyethers is determined by means of 360 MHz ¹H NMR spectroscopy of the trichloroacetyl isocyanate modified polymers. For poly (ethylene oxide-co-propylene oxides) the NMR analysis allows a rapid analysis of the nature of the polyether end groups as well as the presence of other end groups resulting from side reaction.     

Demodicidosis or rosacea: what did we treat?

We report a 75-year-old man with a fulminant rosacea-like eruption, suggestive of demodicidosis. Multiple Demodex folliculorum mites were found in facial scales and pustules and, on histological examination, in the infundibulum of pilosebaceous follicles and in the dermis. Intradermal mites were surrounded either by polymorphonuclear granulocytes and histiocytes, or by a granulomatous infiltrate containing foreign-body giant cells, which had phagocytosed the parasites. Complete recovery, with disappearance of facial mites, was achieved by treatment with a combination of oral and topical metronidazole, although this drug is not known to be miticidal.     

The inaction effect in the psychology of regret.

Previous research showed that decisions to act (i.e., actions) produce more regret than decisions not to act (i.e., inactions). This previous research focused on decisions made in isolation and ignored that decisions are often made in response to earlier outcomes. The authors show in 4 experiments that these prior outcomes may promote action and hence make inaction more abnormal. They manipulated information about a prior outcome. As hypothesized, when prior outcomes were positive or absent, people attributed more regret to action than to inaction. However, as predicted and counter to previous research, following negative prior outcomes, more regret was attributed to inaction, a finding that the authors label the inaction effect. Experiment 4, showing differential effects for regret and disappointment, demonstrates the need for emotion-specific predictions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)