Development of novel 1,2,3,4-tetrahydroisoquinoline derivatives and closely related compounds as potent and selective dopamine D3 receptor ligands

Based on N-alkylated 1,2,3,4-tetrahydroisoquinoline derivatives, which are structurally related to the partial agonist BP 897, a series of novel, selective dopamine D3 receptor antagonists has been synthesised. Derivatisation included changes in the arylamide moiety and the tetrahydroisoquinoline substructure leading to compounds with markedly improved selectivities and affinities in the low nanomolar concentration range. From the 55 structures presented here, (E)-3-(4-iodophenyl)-N-(4-(1,2,3,4-tetrahydroisoquinolin-2-yl)butyl)acrylamide (51) has high affinity (Ki(hD3)=12 nM) and a 123-fold preference for the D3 receptor relative to the D2 receptor subtype. Its pharmacological profile offers the prospect of a novel radioligand as a tool for various dopamine D3-receptor-related in vitro and in vivo investigations.     

Diffusion-related implications for langasite resonator operation

Oxygen and gallium diffusivities in langasite were experimentally determined by analysis of diffusion profiles of 18O and 71Ga tracers by SIMS analysis as functions of temperature and doping. Strontium-enhanced diffusivities and activation energies of approximately 1.2+/-0.2 eV confirm the predominant role of oxygen vacancies in controlling the electrical conductivity of langasite at elevated temperature and oxygen partial pressure. The potential impact of high levels of porosity and the use of an oxygen primary ion beam on the accuracy of some of the data is discussed. The gallium diffusivity, with activation energy of 3.13 eV, was found to be more than two orders of magnitude lower than that of oxygen. Surface exchange measurements enabled estimation of gallium loss at elevated temperatures and oxygen partial pressure; the level is not believed to be of major concern for resonator performance.     

Correcting ocular spherical aberration with soft contact lenses

Following aberroscopy, aspheric front surface soft contact lenses (SCLs) were custom-made to correct spherical refractive error and ocular spherical aberration (SA) of 18 myopic and five hypermetropic subjects (age, 20.5 +/- 5 yr). On-eye residual aberrations, logMAR visual acuity, and contrast sensitivity were compared with the best-correcting spectacle lens, an equally powered standard SCL, and an SCL designed to be aberration free in air. Custom-made and spherical SCLs reduced SA (p < 0.001; p < 0.05) but did not change total root-mean-square (rms) wave-front aberration (WFA). Aberration-free SCLs increased SA (p < 0.05), coma (p < 0.05), and total rms WFA. Visual acuity remained unchanged with any of the SCL types compared with the spectacle lens correction. Contrast sensitivity at 6 cycles/degree improved with the custom-made SCLs (p < 0.05). Increased coma with aspheric lens designs and uncorrected astigmatism limit the small possible visual benefit from correcting ocular SA with SCLs.     

Integrating context-free and context-dependent attentional mechanisms for gestural object reference

We present a vision system for human-machine interaction based on a small wearable camera mounted on glasses. The camera views the area in front of the user, especially the hands. To evaluate hand movements for pointing gestures and to recognise object references, an approach to integrating bottom-up generated feature maps and top-down propagated recognition results is introduced. Modules for context-free focus of attention work in parallel with the hand gesture recognition. In contrast to other approaches, the fusion of the two branches is on the sub-symbolic level. This method facilitates both the integration of different modalities and the generation of auditory feedback.Published online: 5 October 2004Robert Rae: Now at PerFact Innovation, Lampingstr. 8, 33615 Bielefeld, Germany     

COLLATE – A collaboratory supporting research on historic European films

In the COLLATE project, we aim to design and implement a Web-based collaboratory for archives, scientists, and end users working with digitized cultural material. Our example domain is the historic film documentation comprising digitized material about European films of the early 20th century. Designed as a content- and context-based knowledge working environment for distributed user groups, the COLLATE system supports both individual work and collaboration of domain experts who are analyzing, evaluating, indexing, and annotating material in the data repository. The system provides appropriate task-based interfaces for indexing and annotating. As a multifunctional means of in-depth analysis, annotations can be made individually but also collaboratively, for example in the form of annotation of annotations. Combining results from manual and automatic indexing procedures, elaborate content- and context-based information retrieval mechanisms can be applied.     

Element distinctness on one-tape Turing machines: a complete solution

We give a complete characterization of the complexity of the element distinctness problem for n elements of bits each on deterministic and nondeterministic one-tape Turing machines. We present an algorithm running in time for deterministic machines and nondeterministic solutions that are of time complexity . For elements of logarithmic size , on nondeterministic machines, these results close the gap between the known lower bound and the previous upper bound . Additional lower bounds are given to show that the upper bounds are optimal for all other possible relations between m and n. The upper bounds employ hashing techniques, while the lower bounds make use of the communication complexity of set disjointness.Received: 23 April 2001, Published online: 2 September 2003Holger Petersen: Supported by Deutsche Akademie der Naturforscher Leopoldina, grant number BMBF-LPD 9901/8-1 of Bundesministerium für Bildung und Forschung.     

Development of error-compensating UI for autonomous production cells

This contribution deals with the impact of human error on the overall system reliability in flexible manufacturing systems (FMS). Autonomous production cells are used to illustrate an error-compensating system design on the basis of Sheridan's (1997) paradigm of supervisory control. In order to specify human errors and their effects in terms of system disturbances, a taxonomy of system disturbances is recommended. This taxonomic approach was derived by a value benefit analysis and is based on HEDOMS (Human Error and Disturbance Occurrence in Manufacturing Systems) with slight modifications and Reason's GEMS (Generic Error Modelling System). The taxonomy is used for data acquisition. Next, a risk priority equivalent to FMEA (Failure Mode and Effect Analysis) is introduced to structure the data according to their relevance. Then, Vicente's and Rasmussen's guidelines (1987) for an ecological interface design are related to the paradigm of supervisory control. On the basis of these guidelines four case studies are presented to show their successful applicability for interface design in FMS.     

Highly efficient transmission gratings in fused silica for chirped-pulse amplification systems

We report on highly efficient transmission gratings in fused silica with a grating period of 800 nm generated by electron-beam lithography. At a wavelength of 1060 nm, 95% diffraction efficiency is achieved under Littrow conditions. The damage threshold, extremely enhanced compared with conventional gold-coated diffraction gratings, makes these gratings the key elements in high average power (>100 W) femtosecond fiber chirped-pulse amplification systems.     

String matching with simple devices

With the help of a general simulation technique of deterministic finite two-way multi-head automata by automata with blind heads we show O(n²/logn) to be an upper time bound on string matching. This result is tight by a previously known lower bound.