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Contains fulltext : 233800.pdf (Publisher’s version ) (Open Access) Successful responding to acutely threatening situations requires adequate approach-avoidance decisions. However, it is unclear how threat-induced states - like freezing-related bradycardia - impact the weighing of the potential outcomes of such value-based decisions. Insight into the underlying computations is essential, not only to improve our models of decision-making but also to improve interventions for maladaptive decisions, for instance in anxiety patients and first-responders who frequently have to make decisions under acute threat. Forty-two participants made passive and active approach-avoidance decisions under threat-of-shock when confronted with mixed outcome-prospects (i.e., varying money and shock amounts). Choice behavior was best predicted by a model including individual action-tendencies and bradycardia, beyond the subjective value of the outcome. Moreover, threat-related bradycardia (high-vs-low threat) interacted with subjective value, depending on the action-context (passive-vs-active). Specifically, in action-contexts incongruent with participants' intrinsic action-tendencies, stronger bradycardia related to diminished effects of subjective value on choice across participants. These findings illustrate the relevance of testing approach–avoidance decisions in relatively ecologically valid conditions of acute and primarily reinforced threat. These mechanistic insights into approach-avoidance conflict-resolution may inspire biofeedback-related techniques to optimize decision-making under threat. Critically, the findings demonstrate the relevance of incorporating internal psychophysiological states and external action-contexts into models of approach-avoidance decision-making. 12 p.

Contains fulltext : 226464.pdf (Publisher’s version ) (Open Access) Evolutionary models show that human cooperation can arise through direct reciprocity relationships. However, it remains unclear which psychological mechanisms proximally motivate individuals to reciprocate. Recent evidence suggests that the psychological motives for choosing to reciprocate trust differ between individuals, which raises the question whether these differences have a stable distribution in a population or are rather an artifact of the experimental task. Here, we combine data from three independent trust game studies to find that the relative prevalence of different reciprocity motives is highly stable across participant samples. Furthermore, the distribution of motives is relatively unaffected by changes to the salient features of the experimental paradigm. Finally, the motive classification assigned by our computational modeling analysis corresponds to the participants' own subjective experience of their psychological decision process, and no existing models of social preference can account for the observed individual differences in reciprocity motives. These findings support the view that reciprocal decision-making is not just regulated by individual differences in 'pro-social’ versus 'pro-self' tendencies, but also by trait-like differences across several alternative pro-social motives, whose distribution in a population is stable. 13 p.

Evolutionary models show that human cooperation can arise through direct reciprocity relationships. However, it remains largely unclear which psychological mechanisms may proximally motivate an individual to reciprocate. Recent evidence demonstrates that psychological motives for reciprocal choices (i.e., moral strategies) differ between individuals, which raises the question whether these differences have a stationary distribution in a population or are rather an artifact of the experimental task. Here, we combine data from three independent studies and participant samples to find that the relative prevalence of different moral strategies is highly stable across these datasets. Furthermore, the distribution of moral strategies is relatively unaffected by changes to the salient features of the experimental paradigm. Finally, the moral strategy classification assigned by our computational modeling analysis corresponds to the participants’ own subjective experience of their psychological decision process, and no existing models of social preference can account for the observed individual differences in moral strategies. This research supports the view that social decision-making is not just regulated by individual differences in 'pro-social’ versus ‘pro-self’ tendencies, but also by trait-like differences across several alternative pro-social motives, whose distribution in a population is stationary.

Part 1 The background to and motivation for a regional economic policy at a national level: introduction causes of regional disequilibrium backwash and spread effects regional growth models international trade theory applied to regions economic motives for regional economic policy the environmental argument for regional economic policy the social motives for regional economic policy the political issues regional policy and economic recession the regional multiplier compatibility between regional economic policy and general economic policy at the national and European Union levels defining regional economic policy. Part 2 regional disparities in the European Union: introduction the geographical distribution of the population activity rates employment unemployment regional labour market balances income disparities the example of the United State measurement of regional disparities and the evolution of income disparities in the countries of the EU regional disparities, economic structure and shift-share analysis types of problem regions in the EU. Part 3 region - a relative notion: definition of an economic region regional prototypes the interaction principle some further considerations. Part 4 Micro and macro-aspects of the location of forms: introduction Weber, the father of location theory a macro-economic approach - the gravitation and potentiality model transportation costs and distance cists (frais de communication) industrial location and economic potential in western Europe the importance of location factors innovative activities and location theories on the spatial distribution of economic activities - models of spatial organization, growth pole theory, the growth pole concept and regional economic policy, the attraction model, the Porter model and the regions. Part 5 European urban developments and urban planning: introduction a general presentation of the stages of urban development urban development in the EU considerations regarding city size the advantages of urban concentration the disadvantages of urban concentration urban concentration and individual preferences urban concentration and living costs urban concentration and the quality of urban life urban policies. Part 6 The impact of integration on the regions: introduction the fear of repercussions the spatial impact of a custom union - the Giersch model. (Part contents).

Attention can be involuntarily captured by physically salient stimuli, a phenomenon known as bottom-up attention. Typically, these salient stimuli occur unpredictably in time and space. Therefore, in a series of three behavioral experiments, we investigated the extent to which such bottom-up attentional capture is a function of one’s prior expectations. In the context of an exogenous cueing task, we systematically manipulated participants’ spatial (Experiment 1) or temporal (Experiment 2 and 3) expectations about an uninformative cue, and examined the extent of attentional capture by the cue. We anticipated larger attentional capture for unexpected compared to expected cues. However, while we observed robust attentional capture in all experiments, we did not find any evidence for a modulation of attentional capture by prior expectation. This underscores the automatic and reflexive nature of bottom-up attention.

Contains fulltext : 197164.pdf (Publisher’s version ) (Open Access) Attention can be involuntarily captured by physically salient stimuli, a phenomenon known as bottom-up attention. Typically, these salient stimuli occur unpredictably in time and space. Therefore, in a series of three behavioural experiments, we investigated the extent to which such bottom-up attentional capture is a function of one's prior expectations. In the context of an exogenous cueing task, we systematically manipulated participants' spatial (Experiment 1) or temporal (Experiments 2 and 3) expectations about an uninformative cue and examined the amount of attentional capture by the cue. We anticipated larger attentional capture for unexpected compared to expected cues. However, while we observed attentional capture, we did not find any evidence for a modulation of attentional capture by prior expectation. This suggests that bottom-up attentional capture does not appear modulated by the degree to which the cue is expected or surprising. 12 p.

Among the elements that make a town function, the transport system is essential; it comprises the infrastructure for private conveyance as well as the infrastructure and services of public transport. If the transport system is inadequate the spatial organisation does not function as expected: traffic facilities may be under-utilised in one place and unable to satisfy requirements elsewhere. The only way to avoid such a state of affairs is to integrate (simultaneously and in mutual consideration) planning of the spatial organisation and the transport system. The organisation of space and the creation of a transport system largely determine the structure of an urban area and are irrevocable to a high degree. There is a general agreement that both public and private transport infrastructure in urban areas is used in an essentially highly inefficient way. Decentralisation, tending to evolve in several stages, sets in when people begin to leave the centre of the town, moving to the outskirts.

The study of the role that energy and energy prices play in urban development raises a remarkable question, which is not answered in the same way the world over. One basic principle of road-pricing is that road users have to pay more, the more they make use of roads with high traffic intensity. Through such road-pricing, traffic will tend to redistribute itself to less occupied routes or less occupied hours. Not only families but also (and in particular) governments have fallen into difficulties owing to the economic recession, especially in the countries of continental Europe with very advanced systems of social security. Such systems imply high taxes, and these have largely been imposed on fuels needed for traffic. A change in the structure of employment contributed to the present difficult position of public transport. Spatial units and spatial social structures are built up gradually, as the result of a long societal development process.

The following analysis refers to the regional distr ibution of three manufactur ing industries in the U.S . Some of the results presented here may also be found in an earlier study. 1 Let s,~ be the sales of industry i ( i = 1, 2 , . . . , n) to industry j ( j = 1, 2 . . . . . n); and let rj~ be the requirements of industry i f rom industry j . Then: s~j = r~ (1) The sales of industry i to industry j expressed in gross output of industry i equal

A thermal-conductivity vacuum sensor with a novel on-chip control system is presented. The sensing structure is a small circuit suspended over a cavity etched in the (100)-oriented silicon substrate. An integrated control system maintains a constant temperature difference between this thermally isolated sensor and the substrate. The control loop allows for a digitally adjustable operating temperature of the sensor. The sensitive range of the prototype vacuum sensor extends from 0.8 Pa (6 mtorr) to approximately 9.2 × 104 Pa (690 torr). The system has been fabricated in a completely unmodified foundry CMOS process, provides a current output, dissipates only 5 mW of power, and occupies an area of approximately 0.3 mm2.

This paper details a post-processing technique by which circuitry in an unmodified IC technology is thermally and electrically isolated from the silicon substrate. This method enables new applications for micromachining, including temperature regulation of analog ICs, to be carried out. The process is discussed in detail, along with improved tetramethyl ammonium hydroxide (TMAH) etching chemistries that use strong oxidizers to eliminate hillock formation. Also presented is an electrochemical biasing method that uses circuitry on the silicon being etched during the micromachining step. Work is currently underway to evaluate the use of these micromachining techniques for commercial analog circuit applications, several of which are discussed.

We report the first environmental isolation from India of Cryptococcus gattii, genotype amplified fragment length polymorphism 5 (AFLP5), which is one of the rarely reported genotypes of this pathogen. It originated from decayed wood inside a trunk hollow of Manilkara hexandra, a native tree in Delhi. We investigated 101 isolates of C. gattii, originating from 556 samples of decayed wood inside trunk hollows of 311 heterogeneous tree species and their surrounding soil. Of these, only a solitary isolate proved to be AFLP5, the remainder belonged to AFLP4. Antifungal susceptibility testing showed a low MIC90 (0.25 μg ml(-1) ) of the new azoles posaconazole and isavuconazole for these environmental isolates. Genotype AFLP5 has been mainly reported from environmental sources in Colombia and from clinical sources in California (USA), where it seems to be endemic. Phylogenetic analysis of multi-locus sequence typing data showed that the Indian AFLP5 C. gattii isolate had a distinct profile compared with a cluster of mainly Colombian and Californian C. gattii AFLP5 isolates. As molecular typing of human pathogenic fungi is still in its infancy and not accessible to many countries, our current knowledge cannot be taken as reflective of the true geographic distribution of C. gattii AFLP5 or its other rarely reported molecular types.

A process to manufacture single-crystal thermal actuators using silicon fusion bonding and electrochemical etch stop is presented. The process permits the simultaneous creation of in-plane and out-of-plane thermal actuators together with levers suitable for both directions of actuation. A final dry-release step is used, permitting the manufacture of MOS or bipolar devices in conjunction with actuators. Out-of-plane actuation of vertically levered devices has been demonstrated. The −3 dB response frequency of out-of-plane actuators is approximately 1000 Hz in air. Novel levered in-plane devices which achieve deflections of up to 200 μm have been fabricated. An estimate of the upper bound of thermal actuator efficiency is presented.

A high-frequency root-mean-square (r.m.s.) converter composed of two matched thermal elements and on-chip circuitry has been fabricated in a foundry CMOS process with post-process micromachining techniques. An anisotropic undercut etch in conjunction with an electrochemical etch stop is used to form the thermal elements of the r.m.s. converter, which are suspended single-crystal silicon regions containing temperature-sensing diodes heated by polysilicon resistors. One of the elements is heated by the a.c. signal, while an integrated continuous-time feedback network maintains a second element at the same temperature. The converter has a packaging-limited — 3 dB bandwidth of 415 MHz, an r.m.s. dynamic range of 53 dB, nonlinearity of 1%, a quiescent power dissipation under 1 mW, and occupies an area of approximately 400 μm × 400 μm. The thermoelements have a thermal resistance of up to 37 000 K W −1 in air. In addition to the r.m.s. converter itself, an improved wet etchant chemistry is presented. Ammonium persulfate, when added to tetramethyl ammonium hydroxide (TMAH) silicon etchant, improves the silicon etch rate and the (100) surface quality. This etch chemistry should be useful for a broad range of CMOS-compatible micromachining applications.

This paper describes the identification of electromagnetic time constants and stator resistance for field oriented induction motor drives. The model of an induction motor at standstill in terms of state representation is discussed. A direct continuous-time identification from the standstill time-domain test data is based on the parametrized observer state vector. In a laboratory configuration the stator resistance is influenced by the non-linear inverter gain function. Two categories of current responses to voltage steps and to pseudo random binary sequences are examined. The current transients indicate saturation effects. Parameter estimates of a linear machine model are determined using least squares algorithms. Simulation and experimental studies are carried out in a Matlab software environment. Corresponding results obtained for two induction motor drives of different power ratings are included.

This paper describes a temperature regulated bandgap voltage reference fabricated in a foundry CMOS process. Using a simple post-processing micromachining step, a small portion of the chip containing the reference circuitry is thermally isolated from the rest of the silicon die. Having high thermal resistance and small thermal mass, the reference requires 200 times less power and warms up 160 times faster than previous heated-substrate circuits. The reference, in a standard CMOS process, can be included on-chip with CMOS data converters and mixed-signal products.

We report Schizophyllum commune as the aetiological agent of one case each of allergic broncho-pulmonary mycosis (ABPM) and pulmonary fungal ball, and present a literature review. The fungus was characterised by clamp connections, hyphal spicules, and formation of basidiocarps with basidiospores. The phenotypic identification was confirmed by sequencing of the ITS region. To-date, ABPM and pulmonary fungal ball to S. commune have been reported exclusively from Japan and North America respectively. Of the 71 globally reported cases due to S. commune, 45 (63%) were bronchopulmonary, 22 (31%) sinusitis and 4 extrapulmonary. Taken together, cases of bronchopulmonary disease and sinusitis numbered 67 (94%), indicating the respiratory tract as the primary target of disease. Concerning the country-wise distribution, Japan topped the list with 33 cases (46%), followed by Iran - 7 cases (10%), U.S.A. - 6 cases (9%), and a lower prevalence of 1.4-6% for the remaining 12 countries. The preponderance of the disease in Japan may be attributed to its greater awareness vis-à-vis that in other countries rather than to any geographical/climatic factors. We believe that the burden of S. commune-incited disease is currently underestimated, warranting comprehensive prospective studies to determine its prevalence.

Cryptococcus isolates from Cuban patients were identified as C. neoformans var. grubii. Although this species has since long been associated with bird droppings, a recent genotyping study provided strong evidence for additional origins of exposure. We sampled different species of trees in Havana, Cuba to identify other potential sources of exposure to this fungus. A total of 662 samples were collected from 331 trees and cacti from Havana, Cuba. Initial selection of the isolates was carried out by conventional techniques. Isolates were further characterised using a combination of AFLP analysis and DNA sequence analysis. Identification by conventional methods yielded 121 C. neoformans and 61 C. gattii isolates. Molecular analyses showed that none of these isolates was C. gattii and only one isolate proved to be C. neoformans var. grubii. A total of 27 different other species were identified. The most prevalent species was C. heveanensis (33%). Sixty-five unidentifiable isolates segregated into ten potentially novel species. Conventional cultivation methods have a low specificity for C. neoformans complex and molecular analyses need to be applied to confirm identification of isolates from environmental sources. Environmental niches responsible for most of human cryptococcal infections in Cuba remain to be identified.

Prosthetic joint infections (PJI) are rarely due to fungal agents and if so they are mainly caused by Candida strains. This case represents a PJI caused by a multi-drug resistant Pseudallescheria apiosperma, with poor in vivo response to itraconazole and voriconazole. This case differs also by the way of infection, since the joint infection did not follow a penetrating trauma. In the majority of cases, Scedosporium extremity infections remain local in immunocompetent individuals. We report a persistent joint infection with multiple therapeutic failures, and subsequent amputation of the left leg. Detailed clinical data, patient history, treatment regime and outcome of a very long-lasting (4 years) P. apiosperma prosthetic knee infection in an immunocompetent, 61-year-old male patient are presented with this case. The patient was finally cured by the combination of multiple and extensive surgical interventions and prolonged antifungal combination therapy with voriconazole and terbinafine.

Since the latest taxonomical changes in the genus Scedosporium by Gilgado et al. in 2010, no species-specific studies on epidemiology and antifungal susceptibility patterns (AFSP) have so far been published. This study aimed to provide qualitative epidemiological data of Scedosporium spp. isolated from cystic fibrosis (CF) patients and immunocompromised patients from Northern Spain. Isolates were identified by using amplified fragment length polymorphism (AFLP), and species-specific AFSP were generated for all currently available antifungal compounds. AFLP was a useful tool for identification to species-level and for the discrimination of inter- and intra-patient isolates. Scedosporium prolificans represents the most prevalent species in the respiratory tract of CF patients and immunocompromised patients in Northern-Spain, followed by Pseudallescheria boydii, P. apiosperma, and P. ellipsoidea. CF patients were exclusively colonised with either P. boydii or S. prolificans. Patients were colonised over years exclusively with isolates affiliated to one species, but some patients were colonised with multiple strains with different AFSP. The sum of those co-colonising strains in one patient, may appear in vitro and in vivo as a multi-resistant S. prolificans isolate, as strains are morphologically identical and might therefore be regarded as only one strain. A majority of Scedosporium strains (with exception of S. prolificans) were found susceptible for voriconazole and micafungin.

Some people have serious worries about the effects of an aging population in The Netherlands. In this article, attention is directed towards a number of positive effects, like their rather high purchasing power, their low criminality rate, low rate of traffic accidents,etc. If one takes account of the expected rise in incomes of the elderly, the influence of aging on a country's economy will generally be positive. Income expenditure will be focussed on travel and housing. Promoting the immigration of elderly people may bring about a reinforcement of a regional economy.

Microelectromechanical systems (MEMS) resonators have been investigated for over forty years but have never delivered the high performance and low cost required of commercial oscillators. Limiting factors have been temperature drift, long term stability, susceptibility to vibration, manufacturability, and low cost back-end packaging. These requirements have now been met by SiTime's MEMS FirstTM wafer-level encapsulation technology combined with a system architecture using modern phase lock loop (PLL) technology with a high performance CMOS signal conditioning chip. SiTime's MEMS and CMOS chips are manufactured in state of the art CMOS fabrication facilities and can be packaged with any semiconductor packaging technology. The resulting silicon MEMS oscillators outperform existing quartz solutions in various aspects such as reliability, robustness, small size, and system integration.

A high frequency root-mean-square (RMS) converter composed of two matched themal elements and on-chip circuitry was fabricated using a foundry CMOS process and post-process micromachining techniques. The thermal elements are suspended single crystal silicon regions containing temperature sensing diodes heated by polysilicon resistors. One of the thermoelements is heated by the AC signal, while an integrated continous-time feedback network maintains a second element at the same temperature. The converter has a packaging-limited -3 dB bandwidth of 415 MHz, an RMS dynamic range of 53 dB, nonlinearity of 1%, a quiescent power dissipation under 1 mW, and occupies an area of approximately 400 /spl mu/m x 400 /spl mu/m. The thermoelements have a thermal resistance of up to 37,000 K/W.

It has become common to categorize silicon micromachining processes in terms of "bulk" and "surface" techniques. "Bulk" micro-machining generally refers to structures which have been formed by deep anisotropic etching. In these devices, a portion of the substrate itself is usually an active mechanical element of the micromechanical device. "Surface" micro-machining generally refers to structures which have been formed from thin film layers deposited or grown on the surface of the silicon substrate. New developments in deep reactive ion etching technology (DRIE), combined with silicon fusion bonding (SFB), have made it possible, for the first time, to span nearly the entire range of microstructure thicknesses between surface and bulk micromachining, using only single crystal silicon. This presentation will explain the processes and technologies which make this possible, and will describe some structures and devices which have been demonstrated using this new process technology.

This paper describes a new technique for batch fabrication of silicon-on-insulator (SOI) wafers for microelectromechanical systems (MEMS) applications by silicon wafer bonding techniques. The process permits the inclusion of buried cavities in the SOI wafers, providing a useful tool for sensor and actuator fabrication using the resulting wafers. A low-cost electrochemical etchback step is used to define accurately the thickness of the remaining single-crystal material even though the two wafers are bonded with an intermediate insulating oxide layer. The results presented include guidelines for backside contact definition which maximize the useful silicon area as a function of doping level. The final single-crystal silicon thickness is uniform to within 0.05 μm (standard deviation) and does not require any costly high-accuracy polishing steps.

Thermally and electrically isolated single crystal silicon structures have been fabricated using a post-processing anisotropic tetramethyl ammonium hydroxide (TMAH) electrochemical etch. The process was carried out on CMOS circuits fabricated by a commercial foundry. Since the etch consists of a single micromachining step performed on packaged and bonded dice, this technique has the potential for cost-effective prototyping and production of integrated sensors and circuits. >

Recombinant human purple acid phosphatase (recHPAP) provides a convenient experimental system for assessing the relationship between molecular structure and enzymatic activity in mammalian purple acid phosphatases (PAPs). recHPAP is a monomeric protein with properties similar to those of uteroferrin (Uf) and other PAPs isolated as single polypeptide chains, but its properties differ significantly from those of bovine spleen PAP (BSPAP) and other PAPs isolated as proteolytically "clipped" forms. Incubation of recHPAP with trypsin results in proteolytic cleavage in an exposed region near the active site. The product is a tightly associated two-subunit protein whose collective spectroscopic and kinetics properties resemble those of BSPAP. These results demonstrate that the differences in spectroscopic and kinetics properties previously reported for mammalian PAPs are the result of proteolytic cleavage. Mass spectrometry shows that a three-residue segment, D-V-K, within the loop region is excised by trypsin. This finding suggests that important interactions between residues in the excised loop and one or more of the groups that participate in catalysis are lost or altered upon proteolytic cleavage. Analysis of available structural data indicates that the most important such interaction is that between Asp 146 in the exposed loop and active-site residues Asn 91 and His 92. Loss of this interaction should result in both an increase in the Lewis acidity of the Fe(II) ion and an increase in the nucleophilicity of the Fe(III)-bound hydroxide ion. Proteolytic cleavage thus constitutes a potential physiological mechanism for regulating the activity of PAP in vivo.

The effect of Stellamune Mycoplasma vaccine, administered to piglets aged 2-15 days and then 13-15 days later, on daily weight gain, energy conversion, and use of medication was examined in fattening pigs on a chronically Mycoplasma hyopneumoniae infected pig farm. Half of the piglets were vaccinated and the other half acted as controls. In the study design, half of the pens in the fattening unit were allocated to vaccinated pigs; the other half to non-vaccinated pigs, pen was the experimental unit. In the fattening pens sows and castrated boars were separated. The study consisted of a total of 37 pens with vaccinated, and 37 pens with non-vaccinated pigs in 12 different compartments within the pig herd. In the finishing period, mean growth performance and mean energy conversion (EV/kg) of vaccinated animals was 65 grams/day higher and 0.07 EV/kg lower than in control pigs. Furthermore, the incidence of individual curative medication against respiratory problems was more than 4 times higher in control pigs than in vaccinated pigs. There was a tendency for a higher number of group medications against respiratory problems in control pigs than in vaccinated pigs. It is concluded that, in this herd, vaccination against M. hyopneumoniae was successful from an economic point of view.

Parthenogenesis-inducing Wolbachia bacteria are reproductive parasites that cause infected female wasps to produce daughters without mating. This manipulation of the host's reproduction enhances the transmission of Wolbachia to future generations because the bacteria are passed on vertically only from mothers to daughters. Males are dead ends for cytoplasmically inherited bacteria: they do not pass them on to their offspring. Vertical transmission of Wolbachia has been previously considered to be the main mode of transmission. Here we report frequent horizontal transmission from infected to uninfected wasp larvae sharing a common food source. The transferred Wolbachia are then vertically transmitted to the new host's offspring. This natural and unexpectedly frequent horizontal transfer of parthenogensis-inducing Wolbachia intraspecifically has important implications for the co-evolution of Wolbachia and their host.

Data in the literature suggest a finely tuned interaction between ligand (11-cis-retinal) and protein (opsin) in order to allow very efficient photoactivation of the ligand and highly vectorial rhodopsin activation with a huge increase in receptor activity. We have further investigated this interaction using ligand homologues, 13C-ligand labelling or 15N-protein labelling, in combination with Fourier transform infrared (FT-IR) and solid-state magic angle spinning (ss-MAS)-NMR spectroscopy. Using 1D rotational resonance (RR) or double-quantum heteronuclear local field (2Q-HLF) ss-MAS-NMR we report the first structure refinement of the rhodopsin chromophore in situ. These measurements yield a specification of the torsional strain in the for isomerization essential C10-C13 segment of the chromophore. This strain is thought to contribute to the high rate and stereospecificity of the photoisomerization reaction. In agreement with previous data, the C10-C13 segment region reaches a relaxed all-trans configuration at the lumirhodopsin photointermediate. MAS-NMR analysis of [15N]lysine-labelled rhodopsin reveals the presence of a 'soft' counterion, requiring intermediate water molecules for stabilization. FT-IR studies on [2H]tyrosine-labelled rhodopsin demonstrate participation of several tyrosin(at)e residues in receptor activation. One of these, probably Tyr268, is already active at the bathorhodopsin stage. Finally, the effect of ligands with single additional methyl substituents in the C10-C12 region has been investigated. They do not affect the general activation pathway, but perturb the activation kinetics of rhodopsin, suggesting steric interference with protein residues. Possible implications of these results for a structural role of water residues will be discussed, as well.