Hypermedia als Simulationswerkzeug

"Die vorliegende Dokumentation "Hypermedia als Simulationswerkzeug in der beruflichen Bildung" ist das Ergebnis einer Vorstudie, die 1992 im Rahmen der Schulbegleitenden Forschung des Bremischen Senators für Bildung und Wissenschaft an der Universität Bremen durchgeführt wurde. Ziel dieser Studie ist es, einen ersten Überblick über neuartige Simulationskonzepte und -möglichkeiten zu gewinnen und in diesem Kontext die Frage nach der didaktischen Reichweite von Modellbildungen und Simulation in der beruflichen Bildung zu erörtern. Dabei soll skizziert werden, welche Qualifizierungs- und Gestaltungsmöglichkeiten darin angelegt sind. Rechnergestützte Simulationswerkzeuge gewinnen eine zunehmende Bedeutung und Verbreitung in der industriellen Planung, Fertigung und Instandhaltung. Sie tangieren in zunehmenden Maße auch die Facharbeit, insbesondere im Arbeitsumfeld von rechnergestützten Fertigungssystemen. Modellbildung und Simulation ist deshalb von erheblicher Reichweite für die berufliche Bildung, weil sie u. E. den Umgang mit Computern und deren Einsatzspektrum in Technik und Bildung gravierend verändern wird. Diese Studie ist eine Zusammenfassung verschiedener theoretischer Vorarbeiten zur Entwicklung von Hypermedia - gestützten Simulationswerkzeugen für den Einsatz in der beruflichen Bildung. Im ersten Teil wird die Problemstellung und die Zielsetzung des Vorhabens erörtert. Darauf folgt eine Darstellung der Forschungsmethoden und zentralen Untersuchungshypothesen sowie eine Erörterung des methodischen Stellenwerts der Prototypenentwicklung von Lern-Software. Anschließend wird die Bedeutung der computergestützten Simulation skizziert sowie zentrale Forschungsfragen bezüglich der didaktischen Reichweite von Modellbildung und Simulation herausgearbeitet. Nach der Erörterung begrifflicher Grundlagen zur Simulationstechnik folgt ein Überblick über Hypermedia als neue Basistechnologie zur Entwicklung von modularen und leicht erweiterbaren Simulationswerkzeugen. Zum Schluß sollen konzeptionelle Überlegungen zur Entwicklung eines Simulationsbaukastens die zukünftigen Forschungsaktivitäten andeuten." (Autorenreferat

Lernförderliche Übergänge zwischen gegenständlichen und abstrakten Modellen technischer Systeme

"Es wird eine rechnergestützten Lernumgebung für den Technikunterricht vorgestellt, die das Modellieren technischer Systeme im Gegenständlichen ermöglichen soll und zugleich den Übergang von realen stofflichen Objekten zu virtuellen abstrakten Rechnermodellen unterstützt. Das heißt, mit gegenständlichen Bausteinen können Modelle technischer Systeme aufgebaut und synchron dazu ähnliche rechnerinterne generiert werden. Der sinnlichen Wahrnehmung und Überprüfung realstofflicher Phänomene wird eine zentrale Bedeutung für das Begreifen und Beurteilen komplexer Zusammenhänge zuerkannt. An Beispielen aus der Steuerungstechnik wird eine schrittweise, nachvollziehbare und überprüfbare Abstraktion, ausgehend von konkret erfahrbaren Zusammenhängen, zu physikalischen, funktionalen und numerischen Modellen demonstriert." [Autorenreferat

Oral capecitabine in gemcitabine-pretreated patients with advanced pancreatic cancer

Objective: To date, no standard regimen for salvage chemotherapy after gemcitabine (Gem) failure has been defined for patients with advanced pancreatic cancer (PC). Oral capecitabine (Cap) has shown promising activity in first-line chemotherapy trials in PC patients. Methods: Within a prospective single-center study, Cap was offered to patients who had already received at least 1 previous treatment regimen containing full-dose Gem (as a single agent, as part of a combination chemotherapy regimen or sequentially within a chemoradiotherapy protocol). Cap was administered orally at a dose of 1,250 mg/m(2) twice daily for 14 days followed by 7 days of rest. Study endpoints were objective tumor response rate by imaging criteria (according to RECIST), carbohydrate antigen 19-9 (CA19-9) tumor marker response, time to progression, overall survival and toxicity. Results: A median of 3 treatment cycles (range 1-36) was given to 39 patients. After a median follow-up of 6.6 months, 27 patients were evaluable for response: no complete or partial responses were observed, but 15 patients (39%) had stable disease. A CA19-9 reduction of >20% after 2 cycles of Cap was documented in 6 patients (15%). Median time to progression was 2.3 months (range 0.5-45.1) and median overall survival (since start of Cap treatment) was 7.6 months (range 0.7-45.1). Predominant grade 2 and 3 toxicities (per patient analysis) were hand-foot syndrome 28% (13% grade 3); anemia 23%; leg edema 15%; diarrhea 13%; nausea/vomiting 10%, and leukocytopenia 10%. Conclusion: Single-agent Cap is a safe treatment option for Gem-pretreated patients with advanced PC. Further evaluation of Cap in controlled clinical trials of Gem-pretreated patients with advanced PC is recommended. Copyright (C) 2008 S. Karger AG, Basel

Synaptobrevin N-terminally bound to syntaxin–SNAP-25 defines the primed vesicle state in regulated exocytosis

Time-resolved measurements of exocytosis identify a domain of the SNARE complex required to keep vesicles readily releasable

v-SNARE actions during Ca²⁺-triggered exocytosis

Assembly of SNARE proteins between opposing membranes mediates fusion of synthetic lipo-somes, but it is unknown whether SNAREs act during exocytosis at the moment of Ca²⁺ increase, providing the molecular force for fusion of secretory vesicles. Here, weshowthatexecution of pre- and postfusional Steps during chromaffin granule exocytosis depends crucially on a short molecular distance between the complex-forming SNARE motif and the transmembrane anchor of the vesicular SNARE protein synaptobrevin II. Extending the juxtamembrane region of synaptobrevin by insertion of flexible "linkers" reduces priming of granules, delays initiation of exocytosis upon stepwise elevation of intracellular calcium, attenuates fluctuations of early fusion pores, and slows rapid expansion of the pore in a linker-length dependent fashion. These observations provide evidence that v-SNARE proteins drive Ca²⁺-triggered membrane fusion at millisecond time scale and support a model wherein continuous molecular pulling by SNAREs guides the vesicle throughout the consecutive stages of exocytosis

High Velocity Cloud Complex H: A Satellite of the Milky Way in a Retrograde Orbit?

Observations with the Green Bank Telescope of 21cm HI emission from the high-velocity cloud Complex H suggest that it is interacting with the Milky Way. A model in which the cloud is a satellite of the Galaxy in an inclined, retrograde circular orbit reproduces both the cloud's average velocity and its velocity gradient with latitude. The model places Complex H at approximately 33 kpc from the Galactic Center on a retrograde orbit inclined about 45 degrees to the Galactic plane. At this location it has an HI mass > 6 10^6 Msun and dimensions of at least 10 by 5 kpc. Some of the diffuse HI associated with the cloud has apparently been decelerated by interaction with Galactic gas. Complex H has similarities to the dwarf irregular galaxy Leo A and to some compact high-velocity clouds, and has an internal structure nearly identical to parts of the Magellanic Stream, with a pressure P/k about 100 cm^{-3} K.Comment: 12 pages includes 4 figures. To be published in Astrophysical Journal Letters, 1 July 200

CAPS facilitates filling of the rapidly releasable pool of large dense-core vesicles

Calcium-activator protein for secretion (CAPS) is a cytosolic protein that associates with large dense-core vesicles and is involved in their secretion. Mammals express two CAPS isoforms, which share a similar domain structure including a Munc13 homology domain that is believed to be involved in the priming of secretory vesicles. A variety of studies designed to perturb CAPS function indicate that CAPS is involved in the secretion of large dense-core vesicles, but where in the secretory pathway CAPS acts is still under debate. Mice in which one allele of the CAPS-1 gene is deleted exhibit a deficit in catecholamine secretion from chromaffin cells. We have examined catecholamine secretion from chromaffin cells in which both CAPS genes were deleted and show that the deletion of both CAPS isoforms causes a strong reduction in the pool of rapidly releasable chromaffin granules and of sustained release during ongoing stimulation. We conclude that CAPS is required for the adequate refilling and/or maintenance of a rapidly releasable granule pool

CAPS1 Regulates Catecholamine Loading of Large Dense-Core Vesicles

SummaryCAPS1 is thought to play an essential role in mediating exocytosis from large dense-core vesicles (LDCVs). We generated CAPS1-deficient (KO) mice and studied exocytosis in a model system for Ca2+-dependent LDCV secretion, the adrenal chromaffin cell. Adult heterozygous CAPS1 KO cells display a gene dosage-dependent decrease of CAPS1 expression and a concomitant reduction in the number of docked vesicles and secretion. Embryonic homozygous CAPS1 KO cells show a strong reduction in the frequency of amperometrically detectable release events of transmitter-filled vesicles, while the total number of fusing vesicles, as judged by capacitance recordings or total internal reflection microscopy, remains unchanged. We conclude that CAPS1 is required for an essential step in the uptake or storage of catecholamines in LDCVs

A short isoform of STIM1 confers frequency-dependent synaptic enhancement

Store-operated Ca2+-entry (SOCE) regulates basal and receptor-triggered Ca2+ signaling with STIM proteins sensing the endoplasmic reticulum (ER) Ca2+ content and triggering Ca2+ entry by gating Orai channels. Although crucial for immune cells, STIM1’s role in neuronal Ca2+ homeostasis is controversial. Here, we characterize a splice variant, STIM1B, which shows exclusive neuronal expression and protein content surpassing conventional STIM1 in cerebellum and of significant abundance in other brain regions. STIM1B expression results in a truncated protein with slower kinetics of ER-plasma membrane (PM) cluster formation and ICRAC, as well as reduced inactivation. In primary wild-type neurons, STIM1B is targeted by its spliced-in domain B to presynaptic sites where it converts classic synaptic depression into Ca2+- and Orai-dependent short-term synaptic enhancement (STE) at high-frequency stimulation (HFS). In conjunction with altered STIM1 splicing in human Alzheimer disease, our findings highlight STIM1 splicing as an important regulator of neuronal calcium homeostasis and of synaptic plasticity

Nonequilibrium structure of Zn 2SnO 4 spinel nanoparticles

Zinc stannate (Zn 2SnO 4) nanoparticles with an average size of about 26 nm are synthesized via single-step mechanochemical processing of binary oxide precursors (ZnO and SnO 2) at ambient temperature, without the need for the subsequent calcination, thus making the synthesis route very simple and cost-effective. The mechanically induced phase evolution of the 2ZnO + SnO 2 mixture is followed by XRD and by a variety of spectroscopic techniques including 119Sn MAS NMR, Raman spectroscopy, 119Sn Mössbauer spectroscopy, and XPS. High-resolution TEM studies reveal a non-uniform structure of mechanosynthesized Zn 2SnO 4 nanoparticles consisting of a crystalline core surrounded by a structurally disordered surface shell. Due to the ability of the applied solid-state spectroscopies to probe the local environment of Sn cations, valuable complementary insight into the nature of the local structural disorder of mechanosynthesized Zn 2SnO 4 is obtained. The findings hint at a highly nonequilibrium state of the as-prepared stannate characterized by its partly inverse spinel structure and the presence of deformed polyhedra in the surface shell of nanoparticles. © 2012 The Royal Society of Chemistry