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Die rasanten Fortschritte in der Wissenschaft, sowie der technologischen Entwicklung der letzten Jahre ermöglichen es, nun maßgeschneiderte Quanteneffekte auszunutzen und die Kontrolle und Manipulation von einzelnen Quantenteilchen zu ermöglichen. Diese häufig auch als 2. Quantenrevolution bezeichnete Entwicklung erschließt neue, mit klassischen Methoden nicht zugängliche Anwendungsbereiche von der Sensorik und Messtechnik bis zur Quanteninfomationsverarbeitung und Quantenkommunikation. Diese neuartigen Komponenten und Systeme bergen ein großes Potential für eine breite kommerzielle Nutzung und sind daher für die europäische Wirtschaft ein hoch relevanter Zukunftsmarkt. In dieser Einführung soll neben einem kurzen Überblick über das Themenfeld der Quantentechnologien, ein Fokus auf die Grundprinzipien der Quantensensorik und ihren möglichen Anwendungen gelegt werden. Für die Überführung der Quantentechnologien aus dem forschungslabor in robuste und anwenderfreundliche Komponenten und Systeme, sind, neben dem Technologietransfer eng miteinander verzahnte Aktivitäten im Bereich der Standardisierung, Charakterisierung, Zertifizierung und Messtechnik, bis hin zu Themen der Weiterbildung und dem Wissenstransfer in Industrie und Gesellschaft notwendig. Hierzu können in einem ganzheitlichen Ansatz insbesondere die nationalen Metrologieinstitute mit ihrer Bündelung an QT-Infrastruktur und -Expertise in einem gemeinschaftlichen, europäischen Kontext beitragen.

This article presents a case study that explores digital experiences in statistics teaching within Danish lower secondary school, focusing on the development of students’ statistical concepts. The study tracks the progress of a student named Frida, who engages with the digital tool TinkerPlots over the span of a year. Frida developed a unique ‘plot–stack–drag’ technique that significantly influenced her conceptual development during this period. Her routines with the tool not only supported her in some instances, but also created conflicts due to their impact on her personal goals and anticipations. This article delves into the educational implications of the dialectical relationship between students’ development of tool-based routines and their personal goals established during the process. The research findings highlight the profound impact of interactions between students and digital tools, such as TinkerPlots, on shaping students’ understanding of statistical concepts. This underscores the importance of educators’ heightened awareness of students’ personal goals and anticipations influenced by digital tools, which, in turn, opens the door to innovative learning opportunities.

Fear conditioning is a laboratory paradigm commonly used to investigate aversive learning and memory. In context fear conditioning, a configuration of elemental cues (conditioned stimulus [CTX]) predicts an aversive event (unconditioned stimulus [US]). To quantify context fear acquisition in humans, previous work has used startle eyeblink responses (SEBRs), skin conductance responses (SCRs), and verbal reports, but different quantification methods have rarely been compared. Moreover, preclinical intervention studies mandate recall tests several days after acquisition, and it is unclear how to induce and measure context fear memory retention over such a time interval. First, we used a semi-immersive virtual reality paradigm. In two experiments (N= 23 and N= 28), we found successful declarative learning and memory retention over 7 d but no evidence of other conditioned responses. Next, we used a configural fear conditioning paradigm with five static room images as CTXs in two experiments (N= 29 and N= 24). Besides successful declarative learning and memory retention after 7 d, SCR and pupil dilation in response to CTX onset differentiated CTX+/CTX−during acquisition training, and SEBR and pupil dilation differentiated CTX+/CTX−during the recall test, with medium to large effect sizes for the most sensitive indices (SEBR: Hedge's g= 0.56 and g= 0.69; pupil dilation: Hedge's g= 0.99 and g= 0.88). Our results demonstrate that with a configural learning paradigm, context fear memory retention can be demonstrated over 7 d, and we provide robust and replicable measurement methods to this end.

Iminium-functionalized 2,3-dihydroisoxazoles (4-isoxazolines) were prepared in high yields by [3+2] cycloaddition of N-methyl-C-phenylnitrone and acetylenic iminium salts. Conversion of the very hygroscopic cycloadducts into neutral compounds was achieved by hydrolysis or hydride reduction of the iminium functional group. By a thermal rearrangement, the cycloadducts were converted into 2,3-dihydro-1H-imidazolium salts. With C,N-diphenylnitrone as the reaction partner, the expected cycloadduct, a [(2,3-dihydroisoxazol-4-yl)-1-(phenyl)methylene]-N,N-dimethylammonium triflate, could be prepared at −75°C and was characterized by NMR. This product was found to be thermally unstable above −30°C, being converted into an inseparable product mixture. Basic hydrolysis of this mixture afforded a structurally interesting acyclic enaminone/half-aminal, which is likely derived from a 2,3-dihydro-1,3-oxazole.

ABSTRACTWith the proliferation of several dozen new exhibits and museums dedicated to this specific disaster, the 3.11 Great East Japan Earthquake, tsunami, and nuclear disaster, can be considered a turning point in the preservation of disaster memory in Japan. Although there is limited research on disaster museums, they play a significant role in shaping cultural memory of 3.11, as they are regarded as reliable, objective institutions of memory. Through analysis of 17 government-established 3.11 museums, this research explores the following questions: How do public disaster museums frame their representations of 3.11, and what official narrative is created within the cultural memory of the triple disaster in Japan? Drawing from analysis of the museums’ mission statements and exhibitions, and interviews with curators and museum staff, we argue that most disaster museums support narratives of overcoming hardships to contribute to a better future, showing continuity with narratives typical of other memorial museums such as WWII, or pre-3.11 disaster museums. In contrast to the commemoration of war and its influence on cultural memory, disaster museums have received relatively little scholarly attention. Yet, these forward-looking messages, combined with tendencies of museums to focus on local disaster experiences and emphasize disaster risk reduction with an artificial separation between man-made disasters vs. natural hazards, contributes to an othering of the Fukushima nuclear disaster in cultural memory, as an outlier in Japan’s long history of disasters. Without full representation of the compound disaster, understanding of 3.11 and the effective transmission of the intended lessons is severely limited.

Der PKW-Verkehr dominiert auch heute noch das Verkehrsaufkommen in Deutschland. Ein häufig diskutierter Vorschlag, um dies zu ändern, lautet, den Öffentlichen Personennahverkehr (ÖPNV) kostenlos anzubieten. Auf Basis einer Erhebung aus dem Jahr 2018, bei der knapp 7000 Haushaltsvorstände des forsa-Haushalts-Panels Antworten zu ihrem Mobilitätsverhalten sowie zu ihrer Einstellung gegenüber vieldiskutierten Verkehrsmaßnahmen liefern, untersucht der vorliegende Beitrag die allgemeine Zustimmung zur kostenlosen Nutzung des ÖPNV sowie die möglichen Auswirkungen dieser Maßnahme auf das Mobilitätsverhalten. Die Ergebnisse zeigen eine starke Befürwortung der Maßnahme: Rund 72 % der Antwortenden stimmten für die Einführung eines kostenlosen ÖPNVs. Eine mehrheitliche Zustimmung findet sich in jeder gesellschaftlichen Gruppe, gleich ob männlich oder weiblich, jung oder alt, arm oder reich, sowie in allen politischen Lagern. Nach Einführung eines kostenlosen ÖPNV in Deutschland würden die Befragten die Anzahl ihrer Fahrten mit dem ÖPNV nach eigenen Angaben durchschnittlich um ca. 230 % steigern. Wenngleich es sich um rein hypothetische Antworten handelt und die Ergebnisse daher mit einer gewissen Vorsicht betrachtet werden sollten, deuten diese auf einen relativ starken potenziellen Anstieg der ÖPNV-Nutzung hin. Abschließend diskutieren wir, warum es trotzdem nicht sinnvoll erscheint, den ÖPNV kostenlos anzubieten und welche alternativen Politiken erfolgsversprechender erscheinen.

ABSTRACTUsing photo sessions in combination with three in-depth interviews at a Japanese party called Ankokaiin Berlin, we explore how the method of photography along with the participant’s choice of personal objects in the photographs positively influences narrative interviews. Literally meaning “red bean paste meeting”, the Ankokai was originally used as a way for the Japanese gay community to meet in Berlin but nowadays attracts people from all kinds of backgrounds. Keeping the ethnographic research method in mind, our underlying research question asks how translocal categories of migration are reflected in the participants’ choices of personal objects in the photographs. Although larger studies are required to verify this claim, we found that photography can be a strong tool for enacting reciprocity and building rapport in ethnographic research. Furthermore, the participants’ choices of personal objects for these pictures support powerful personal narratives as the research participants’ active participation in the photo session enabled them to reflect on their experiences of migration.

Numerous countries have introduced energy performance certificates to mitigate the information asymmetry with respect to the thermal quality of houses. Motivated by a stylized theoretical model and drawing on comprehensive data on real estate advertisements in the German housing market, this paper investigates the causal effect of disclosing energy information on the asking prices of houses. Employing within-variation from panel data, augmented by an instrumental variable approach to isolate effects among policy compliers, our analysis demonstrates the power of mandatory disclosure rules to increase market transparency and to align prices with the energy performance of the house. Among our key results, we find that house owners reduce offer prices in response to the disclosure of energy efficiency information. Furthermore, this effect is particularly pronounced for owners who would not disclose in the absence of the mandatory disclosure policy.

Energy labels have been introduced in many countries to increase consumers’ attention to energy use in purchase decisions of durables. In a stated-choice experiment among about 5,000 German households, we implement randomized information treatments to explore how energy labels influence purchasing decisions.Our results show that adding annual operating cost information to the EU energy label promotes the choice of energy-efficient durables. In addition, we find that a majority of participants value efficiency classes beyond the economic value of the underlying energy use differences. Our results further indicate that displaying operating cost affects choices through two distinct channels: It increases the attention to operating cost and reduces the valuation of efficiency class differences.

We consider steady states of physical systems that are described by hyperbolic balance laws.

This paper proposes a standardized simulation environment to evaluate current and to design future multi-level grid control strategies in terms of a safe and reliable operation in future converter-dominated grids. For this, the first step is to develop a taxonomy for the uniform description of multi-level grid control strategies, to define relevant design options and to derive the relevant evaluation and comparison criteria. Furthermore, aspects of new ICT-methods (e. g., machine learning decoders for aggregated flexibility description) are presented, which can help to tap the decentral flexibility potentials in future grid control strategies. Lastly, the major converter-related aspects are investigated. In particular, the stability of converter clusters in large-scale energy systems is analysed and new monitoring possibilities utilizing converter systems will be introduced.

Propyne iminium triflates 1–6react as dipolarophiles in thermal [3 + 2]-cycloadditions with sufficiently electron rich organoazides to form 1,4,5-trisubstituted 1,2,3-triazoles with iminium functionalization. The reactions require rather strong thermal activation, but can be accelerated by microwave irradiation. The regioselectivity of the cycloaddition at the internal acetylenic bond of 3-cyclopropylpropyne and 3-arylpropyne iminium ions (1–3and 4, respectively) is very high, but is lowered in the presence of sterically demanding substituents at the opposite end of the iminium-substituted C,C triple bond. The iminium-functionalized triazoles can easily be transformed into neutral compounds; herein reported is the formation of triazolyl ketones 10by hydrolysis and of tertiary triazolyldimethyl amines 12by LiAlH4reduction. When the reduction is performed with sodium boranate or sodium cyanoboranate, amine–borane complexes 15and 16are obtained.

Acetylenic iminium triflates with the general formula [R–C≡ C–C(Ar)=N+R2TfO−] were found to be excellent dipolarophiles in [3+ 2] cycloaddition reactions with diazoacetates leading to (1H-pyrazol-3(5)-yl)methanaminium triflates in high yields. The terminal acetylenic iminium salt (propyne iminium salt) [HC≡C–C(Ph)=N+Me2TfO−] reacted with an equimolar amount of methyl diazoacetate instantaneously at 20°C to form the expected pyrazole in almost quantitative yield. When a 2:1 stoichiometry was applied, subsequent Michael addition of the pyrazole at the alkyne occurred and the bis(iminium) ditriflate 4was obtained in high yield. By hydride reduction or hydrolysis of the iminium group, some of the highly hygroscopic pyrazole iminium salts were converted into neutral, twofold functionalized, di- and tri-C-substitued 1H-pyrazoles.

Car owners underestimate total vehicle costs. Giving consumers this information could encourage the switch to cleaner transport and reduce emissions.

AbstractPhotography was a significant mediator of responses to Japan in the post-war period, from the late 1940s when thousands of Australians travelled to the country to participate in the US-led military occupation, through to the signing of the landmark Australia-Japan Commerce Agreement in 1957. The camera became a crucial instrument of reconciliation, as Australians began to look at the recent enemy with what one visitor called ‘non-military eyes’, reframing the ‘traditional’ Japan privileged by official military photographers into a dynamic, embryonically modern society with a future linked to Australia’s own. After the Occupation ended and Australia moved to cement the bilateral relationship with Japan, photography continued to act as a powerful medium of cultural reinterpretation.

Steroidogenic factor 1 (SF-1/NR5A1) plays a crucial role in regulating adrenal development, gonad determination and differentiation, and in the hypothalamic-pituitary control of reproduction and metabolism. In men (46, XY), it is known that mutations in SF-1/NR5A1gene cause a wide phenotypic spectrum with variable degrees of undervirilization. In recent years, the role of SF-1 in the ovarian function was increasingly discussed and alterations in the gene were related to primary ovarian insufficiency. We describe the follow-up of a 46, XX affected woman with a SF-1mutation and by comparing our case with the known manifestations reported in the literature, we try to further elucidate the function of SF-1 in the ovary.

Ein Erratum zu dieser Publikation wurde veröffentlicht: https://doi.org/10.1007/s41025-020-00207-y

Cervical ectopic pregnancy is an uncommon form of ectopic pregnancy. The spectrum of treatment options includes systemic medical therapy, local injection with methotrexate and/or potassium chloride, surgery, or a combination of these modalities.

A major goal in proteomics is the comprehensive and accurate description of a proteome. This task includes not only the identification of proteins in a sample, but also the accurate quantification of their abundance. Although mass spectrometry typically provides information on peptide identity and abundance in a sample, it does not directly measure the concentration of the corresponding proteins. Specifically, most mass-spectrometry-based approaches (e.g.shotgun proteomics or selected reaction monitoring) allow one to quantify peptides using chromatographic peak intensities or spectral counting information. Ultimately, based on these measurements, one wants to infer the concentrations of the corresponding proteins. Inferring properties of the proteins based on experimental peptide evidence is often a complex problem because of the ambiguity of peptide assignments and different chemical properties of the peptides that affect the observed concentrations.

Urban and peri-urban agriculture make up a significant proportion of the food supply of many cities and its importance is increasing. Today, around 15 % of the world’s food is grown in urban areas. City and suburban agriculture take many forms (backyard, roof-top, balcony, community gardening in vacant lots and parks, urban fringe agriculture and livestock grazing in open spaces). Food and nutrition security, both of which are necessary for a healthy and balanced diet, require focus on the urban production of food. Such food should include micro nutrients and complement lacking or difficult to obtain foodstuffs. Due consideration should also be given to quality aspects in production and marketing. Only in a few places is the role and importance of urban production, specifically for the poorer parts of urban society, is recognized and acted upon through sound policies, planning procedures and programs. This paper presents the arguments for urban agriculture—in the North as well as in the South—and shows that it has the potential to contribute to diversified diets of urban citizens. More attention should be given to linking it better to the local food system. Recommendations for the support of nutrition sensitive urban agriculture relate to sensitizing and training of all actors, particularly urban planners, in identifying and addressing the specific challenges and potentials as well as giving institutional support to groups working in the area. New, adapted technologies and production systems that fit better into the local food system should be enhanced with due consideration being given to the prevailing legal, social and economic conditions.

A simple method determining airborne monoethanolamine has been developed. Monoethanolamine determination has traditionally been difficult due to analytical separation problems. Even in recent sophisticated methods, this difficulty remains as the major issue often resulting in time‐consuming sample preparations. Impregnated glass fiber filters were used for sampling. Desorption of monoethanolamine was followed by capillary GCanalysis and nitrogen phosphorous selective detection. Separation was achieved using a specific column for monoethanolamines (35% diphenyl and 65% dimethyl polysiloxane). The internal standard was quinoline. Derivatization steps were not needed. The calibration range was 0.5–80 μg/mL with a good correlation (R2= 0.996). Averaged overall precisions and accuracies were 4.8% and –7.8% for intraday (n= 30), and 10.5% and –5.9% for interday (n= 72). Mean recovery from spiked filters was 92.8% for the intraday variation, and 94.1% for the interday variation. Monoethanolamine on stored spiked filters was stable for at least 4 weeks at 5°C. This newly developed method was used among professional cleaners and air concentrations (n= 4) were 0.42 and 0.17 mg/m3for personal and 0.23 and 0.43 mg/m3for stationary measurements. The monoethanolamine air concentration method described here was simple, sensitive, and convenient both in terms of sampling and analytical analysis.

Small hematomas on the placental surface, termed subamniotic hemorrhage, are a common finding either at the routine 18- to 20-week anatomy ultrasound or at subsequent assessments of fetal growth and well-being. Hemorrhage beneath or at the edge of the placenta, or behind an isolated area of the fetal membranes, is of greater concern.

Die Friedensdiskussionen und -proteste der frühen 1980er Jahre gingen auch an den Katholiken der Bundesrepublik Deutschland nicht spurlos vorbei. Zum ersten Mal seit 1945 setzte sich eine nicht unerhebliche Anzahl von ihnen mit den Themen “Krieg” und “Frieden” auseinander. Der vorliegende Artikel nimmt die verschiedenen katholischen Akteure in den Blick und untersucht, wie sie sich in der gesamtgesellschaftlichen Auseinandersetzung verorteten und ob sie ein eigenes, genuin katholisches Friedensverständnis entwickelt haben. Die Untersuchung kommt dabei zu dem Ergebnis, dass Ausmaß und Richtung des Engagements stark von Stellung und Anliegen der verschiedenen Akteure geprägt war. Die reformorientierte Initiative “Kirche von unten” suchte beispielsweise in der Koalitionsbildung mit nicht-katholischen Friedensaktivisten generelle Unterstützung für ihre Anliegen suchte. Gruppen wie der katholischen Friedensbewegung “Pax Christi” die sich aus ihrem Selbstverständnis heraus stärker im katholischem Raum verorteten, ging es dagegen darum, innerkatholische Diskussionen in Gang zu bringen. Nimmt man das Wahlergebnis vom März 1983 in den Blick schein das Gros der westdeutschen Katholiken indessen weiterhin einer konservativen Sicherheitspolitik anzuhängen.

Concentrating photovoltaic (CPV) systems based on III-V semiconductors entered the photovoltaic market recently. Concentrix Solar deploys the FLATCON® CPV module technology originally developed at the Fraunhofer Institute for Solar Energy Systems ISE. This paper gives a short introduction in design considerations of FLATCON CPV module and provides detailed field data of the system technology over up to two years are presented as well as field experiences with the operation of the systems. FLATCON modules are based on III-V triple junction cells, a Fresnel lens array, and a glass cover and bottom plate. In 2008, Concentrix installed a single tracker system and two power plants in Spain. A system solar-to-grid AC energy efficiency of 21% over the whole period of two years with maximum system AC power efficiency values of 23% for a single tracker system are shown. Similar systems installed in 2009 and equipped with the current FLATCON module CX-75 achieved system AC power efficiencies of 25%. The effects of spectral variations of the solar irradiation on power plant performance are discussed.

The acetylenic iminium salts [(c-C3H5)C=C-C(Ar)=N+Me2]OTf, Ar = phenyl (1a) or 2- thienyl (1b), both react in different ways with three mesoionic münchnones, namely 3-methyl-1,3-oxazolium-5-olate (2), 3-methyl-2-phenyl-1,3-oxazolium-5-olate (6) and 3-methyl-2-phenyl-4- trifluoroacetyl-1,3-oxazolium-5-olate (9). With 2, a [3+2] cycloaddition reaction followed by extrusion of CO2yields pyrroles 5a, b. In the case of 6, the new münchnones 7a, b are obtained which result from an electrophilic substitution at C-4 by the acetylenic iminium cation. In contrast to 1a, b, the 4,4-but-2-yne 1-iminium salt 1c reacts with münchnone 6 to form pyrrole 8. Finally, the reaction of 1a, b and 9 affords (6-oxo-6H-pyran-3-yl)methylene iminium salts 10a, b under microwave heating conditions. The structures of pyrrole 5a, münchnone 7a, and trifluoromethyl-substituted pyranone 10a were established by single-crystal X-ray diffraction analysis.

Concentrating photovoltaic (CPV) systems based on III-V semiconductors entered the photovoltaic market recently. Concentrix Solar deploys the FLATCON® CPV module technology originally developed at the Fraunhofer Institute for Solar Energy Systems ISE. This paper gives a short introduction in design considerations of FLATCON CPV module and provides detailed field data of the system technology over up to two years are presented as well as field experiences with the operation of the systems. FLATCON modules are based on III-V triple junction cells, a Fresnel lens array, and a glass cover and bottom plate. In 2008, Concentrix installed a single tracker system and two power plants in Spain. A system solar-to-grid AC energy efficiency of 21% over the whole period of two years with maximum system AC power efficiency values of 23% for a single tracker system are shown. Similar systems installed in 2009 and equipped with the current FLATCON module CX-75 achieved system AC power efficiencies of 25%. The effects of spectral variations of the solar irradiation on power plant performance are discussed.

The article examines the issue of breastfeeding in public. Polls have shown that a number of women are not comfortable at the thought of nursing their baby in public and that his discomfort is a common cause for disruption of the breastfeeding relationship. Mothers are advised to listen to their babies, follow their mothering instincts, and decide what their level of comfort is for breastfeeding in public. INSET: Breastfeeding and the Law.

1H-Imidazo-[4,5-c]quinolines were prepared while investigating novel nucleoside analogues as potential antiviral agents. While these compounds showed no direct antiviral activity when tested in a number of cell culture systems, some demonstrated potent inhibition of virus lesion development in an intravaginal guinea pig herpes simplex virus-2 assay. We have determined that the in vivo antiviral activity can be attributed to the ability of these molecules to induce the production of cytokines, especially interferon (IFN), in this model. Subsequently, we found that the compounds also induce in vitro production of IFN in human peripheral blood mononuclear cells (hPBMCs). The in vitro results reported herein and the in vivo results reported previously led to the discovery of imiquimod, 26, which was developed as a topical agent and has been approved for the treatment of genital warts, actinic keratosis, and superficial basal cell carcinoma.

OBJECTIVE: To test the hypothesis that calcium pyrophosphate dihydrate (CPPD) deposition disease is a risk factor for neck pain. METHODS: A prevalent case-control study was conducted to assess cervical calcifications and neck pain between patients with and without known peripheral CPPD deposition disease. CPPD cases were included if diagnosed with CPPD deposition disease of peripheral joints, and excluded if their chief complaint was neck pain. Controls were randomly selected among consecutive patients, hospitalized for conditions unrelated to CPPD deposition disease or neck pain, and matched to CPPD cases by age and sex. Cervical calcifications were assessed by lateral cervical radiographs and computed tomography scans of the upper cervical spine; neck pain and cervical function were appraised by a validated questionnaire. RESULTS: Cervical calcifications were found in 24 out of 35 patients (69%) in the CPPD group compared to 4 out of 35 patients (11%) in the control group (p < 0.001). Patients with CPPD deposition disease reported significantly more neck pain and discomfort than controls (p < 0.001), and were 5 times more likely to report any neck pain (odds ratio 5.5; 95% confidence interval: 1.9, 21.9). Among male patients, more extensive cervical calcified deposits correlated with more severe neck pain (rs = 0.58, p = 0.03). CONCLUSION: These results suggest that CPPD deposition disease frequently involves the cervical spine and may be associated with the development of neck pain.

Background: Activation of coagulation and fibrinolysis play a role in the pathophysiology of experimental arthritis. Objective: To determine the extent of activation of the coagulation and fibrinolytic pathways in different joint diseases in humans and to ascertain the factors that may influence fibrin deposition within the joint. Methods: Plasma from normal subjects (controls, n= 21) and plasma and synovial fluid samples from patients with rheumatoid arthritis (RA; n = 64), osteoarthritis (OA; n = 29), spondyloarthropathy (SpA; n = 22) and crystal arthritis (CA; n = 25) were analyzed for the levels of TF (tissue factor) and tissue factor pathway inhibitor (TFPI) activities, thrombin–antithrombin III (TAT) complexes, and F1 + 2 (thrombin fragment), fibrin d-dimer and thrombin-activated fibrinolysis inhibitor (TAFI) antigenic levels. The measurements were analyzed by pairwise correlation with each other as well as with standard parameters of inflammation [C-reactive protein (CRP), joint leukocyte count]. Inter-group comparisons were performed to look for disease-specific differences. Results: Compared with healthy controls, patients with joint diseases had higher levels of TAT, F1 + 2 and d-dimers in their plasma. In the synovial fluid, TF activity, TAT, d-dimers, and TAFI were significantly higher in inflammatory arthritides than in OA. The levels were highest in RA patients. In the plasma, TF activity was correlated with TAT and d-dimer levels with CRP, TFPI, and TAT. In the synovial fluid, TF activity correlated with plasma CRP levels, synovial fluid leukocyte count, and synovial TAT and TAFI levels. In addition, synovial d-dimers correlated with CRP, and synovial TAFI levels were correlated with synovial F1 + 2 and TAT. Conclusions: Activation of the coagulation and fibrinolytic cascades in the joint and in the circulation is evident in both inflammatory and degenerative joint diseases. Within the joint, inflammatory mechanisms leading to TF-mediated activation of the coagulation pathway and subsequent fibrin deposition is the most likely explanation for the observed findings. In the plasma, the link between inflammation (CRP increase) and TF activation is weak, and a non-TF-mediated mechanism of coagulation activation could explain these findings. RA is characterized by significantly higher levels of TAT in the synovial fluid and plasma than other arthritides. Although fibrinolytic activity is linked to inflammation, the increased amounts of TAFI in the joint, particularly in RA, may explain why fibrin formation is so prominent in this condition compared with other joint diseases.

Hongotoxin1 (HgTX1), a 39-residue peptide recently isolated from the venom of Centruroides limbatus, blocks the voltage-gated K⁺ channels Kv1.1, Kv1.2, and Kv1.3 at picomolar toxin concentrations (Koschak, A., Bugianesi, R. M., Mitterdorfer, J., Kaczorowski, G. J., Garcia, M. L., and Knaus, H. G. (1998) J. Biol. Chem. 273, 2639−2644). In this report, we determine the three-dimensional structure of HgTX1 using NMR spectroscopy (PDB-code:  1HLY). HgTX1 was found to possess a structure similar to previously characterized K⁺ channel toxins (e.g. margatoxin) consisting of a three-stranded antiparallel β-sheet (residues 2−4, 26−30, and 33−37) and a helical conformation (part 310 helix and part α helix; residues 10−20). Due to the importance of residue Lys-28 for high-affinity interaction with the respective channels, lysine-reactive fluorescence dyes cannot be used to label wild-type HgTX1. On the basis of previous studies (see above) and our NMR data, a HgTX1 mutant (HgTX1-A19C) was engineered, expressed, and purified. HgTX1-A19C-SH was labeled using sulfhydryl-reactive Cy3-, Cy5-, and Alexa-dyes. Pharmacological characterization of fluorescently labeled HgTX1-A19C in radioligand binding studies indicated that these hongotoxin1 analogues retain high-affinity for voltage-gated K⁺ channels and a respective pharmacological profile. Cy3- and Alexa-dye-labeled hongotoxin1 analogues were used to investigate the localization of K⁺ channels in brain sections. The distribution of toxin binding closely follows the distribution of Kv1.2 immunoreactivity with the highest expression levels in the cerebellar Purkinje cell layer. Taken together, these results demonstrate that fluorescently labeled HgTX1 analogues comprise novel probes to characterize a subset of voltage-gated K⁺ channels.

Losartan has been shown to increase urinary uric acid excretion and hence to lower serum uric acid levels. The purposes of the present study were (1) to evaluate the effects of losartan on serum uric acid in hypertensive patients with hyperuricemia and gout, (2) to compare the effects of losartan with those of irbesartan, another angiotensin II receptor antagonist and (3) to evaluate whether losartan 50 mg b.i.d. has a greater impact on serum uric acid levels than losartan 50 mg once a day.

Objectives To document biopsychosocial profiles of patients with rheumatoid arthritis (RA) by means of the INTERMED and to correlate the results with conventional methods of disease assessment and health care utilization. Patients with RA (n = 75) were evaluated with the INTERMED, an instrument for assessing case complexity and care needs. Based on their INTERMED scores, patients were compared with regard to severity of illness, functional status, and health care utilization. In cluster analysis, a 2-cluster solution emerged, with about half of the patients characterized as complex. Complex patients scoring especially high in the psychosocial domain of the INTERMED were disabled significantly more often and took more psychotropic drugs. Although the 2 patient groups did not differ in severity of illness and functional status, complex patients rated their illness as more severe on subjective measures and on most items of the Medical Outcomes Study Short Form 36. Complex patients showed increased health care utilization despite a similar biologic profile. The INTERMED identified complex patients with increased health care utilization, provided meaningful and comprehensive patient information, and proved to be easy to implement and advantageous compared with conventional methods of disease assessment. Intervention studies will have to demonstrate whether management strategies based on INTERMED profiles can improve treatment response and outcome of complex patients.

ObjectivesTo document biopsychosocial profiles of patients with rheumatoid arthritis (RA) by means of the INTERMED and to correlate the results with conventional methods of disease assessment and health care utilization.Patients with RA (n = 75) were evaluated with the INTERMED, an instrument for assessing case complexity and care needs. Based on their INTERMED scores, patients were compared with regard to severity of illness, functional status, and health care utilization.In cluster analysis, a 2‐cluster solution emerged, with about half of the patients characterized as complex. Complex patients scoring especially high in the psychosocial domain of the INTERMED were disabled significantly more often and took more psychotropic drugs. Although the 2 patient groups did not differ in severity of illness and functional status, complex patients rated their illness as more severe on subjective measures and on most items of the Medical Outcomes Study Short Form 36. Complex patients showed increased health care utilization despite a similar biologic profile.The INTERMED identified complex patients with increased health care utilization, provided meaningful and comprehensive patient information, and proved to be easy to implement and advantageous compared with conventional methods of disease assessment. Intervention studies will have to demonstrate whether management strategies based on INTERMED profiles can improve treatment response and outcome of complex patients.

Vertebrate class III POU genes are widely expressed in the embryonic and adult central nervous system, where they act as transcriptional regulators of cell- and/or region-specific gene expression. We isolated four zebrafish class III POU genes, named zp-12, zp-23, zp-47 and zp-50. In this study, we examined the developmental expression patterns of the Brn-1- and Brn-2-related zp-12, zp-23 and zp-47 genes by means of whole-mount in situ hybridization. Similarly to their mammalian orthologues, the major expression site of all zebrafish zp genes is the CNS. Neurectodermal expression was first detected at the beginning of somitogenesis in spatially restricted segment-like domains in different parts of the neural plate. During somitogenesis transcript distributions changed from highly restricted to widespread but nevertheless distinct patterns found in all major subdivisions of the CNS. While zp-47 expression was detected exclusively in the CNS, localized expression of zp-12 and zp-23 was also found in the pronephric primordium and in cell clusters within the mandibular and hyoid arches. Furthermore, zp-23 transcripts were transiently detected in a restricted region of the paraxial mesendoderm and, at late embryogenesis stages, in the auditory vesicles. The early regionalized expression of all three zp genes is compatible with roles in regional specification of the neural plate. Comparison of the distinct yet overlapping expression of zp-12, zp-23, zp-47 and the previously characterized zp-50 gene implies both unique, as well as redundant functions for each family member. We propose that coordinate expression of particular combinations of class III POU genes contribute to pattern formation or cell fate determination in the developing CNS and other structures. Dev Dyn;218:345–358. © 2000 Wiley-Liss, Inc.

A full‐length and a C‐terminally truncated form of the calcium channel α1Ssubunit can be isolated from skeletal muscle. Here we studied whether full‐length α1Sis functionally incorporated into the skeletal muscle excitation‐contraction coupling apparatus. A fusion protein of α1Swith the green fluorescent protein attached to its C‐terminus (α1S‐GFP) or α1Sand GFP separately (α1S+GFP) were expressed in dysgenic myotubes, which lack endogenous α1S. Full‐length α1S‐GFP was targeted into triad junctions and restored calcium currents and excitation‐contraction coupling. GFP remained colocalized with α1S, indicating that intact α1S‐GFP was inserted into triads and that the C‐terminus remained associated with the excitation‐contraction coupling apparatus.

Objectifs. Description de deux cas d'amylose secondaire lie´s a` une spondylarthrite ankylosante. Patients, re´sultats. Parmi les 47 patients atteints de spondylarthrite ankylosante, suivis ces dernie`res anne´es dans notre service, deux ont de´veloppe´ une amylose secondaire de type AA. Leur affection rhumatismale est caracte´rise´e par une grande se´ve´rite´ et une longue dure´e d'e´volution. Ils pre´sentent une ankylose presque totale du rachis et de plus une arthropathie destructrice touchant les hanches, les poignets (et le tarse dans la deuxie`me observation). L'amylose est mise en e´vidence a` l'occasion d'une atteinte re´nale, atteinte qui motivera le recours a` une he´modialyse chronique pour l'un des deux patients dont la situation se compliquera ulte´rieurement par la survenue d'une pe´ritonite stercorale attribue´e a` l'amylose. Conclusions. Rare au cours de la spondylarthrite ankylosante, l'amylose secondaire est une complication tre`s grave en raison notamment des risques d'atteinte re´nale ou digestive. Il n'y a actuellement pas de traitement connu susceptible de faire re´gresser les de´po^ts d'amyloi¨de AA.

1The β subunits of voltage‐sensitive calcium channels facilitate the incorporation of channels into the plasma membrane and modulate calcium currents. In order to determine whether these two effects of the β subunit are interdependent or independent of each other we studied plasma membrane incorporation of the channel subunits with green fluorescent protein and immunofluorescence labelling, and current modulation with whole‐cell and single‐channel patch‐clamp recordings in transiently transfected human embryonic kidney tsA201 cells.2Coexpression of rabbit cardiac muscle α1Cwith rabbit skeletal muscle β1a, rabbit heart/brain β2aor rat brain β3subunits resulted in the colocalization of α1Cwith β and in a marked translocation of the channel complexes into the plasma membrane. In parallel, the whole‐cell current density and single‐channel open probability were increased. Furthermore, the β2aisoform specifically altered the voltage dependence of current activation and the inactivation kinetics.3A single amino acid substitution in the β subunit interaction domain of α1C(α1CY467S) disrupted the colocalization and plasma membrane targeting of both subunits without affecting the β subunit‐induced modulation of whole‐cell currents and single‐channel properties.4These results show that the modulation of calcium currents by β subunits can be explained by β subunit‐induced changes of single‐channel properties, but the formation of stable α1C‐β complexes and their increased incorporation into the plasma membrane appear not to be necessary for functional modulation.