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The α-amylase/trypsin inhibitors (ATIs) are discussed as being responsible for non-celiac wheat sensitivity (NCWS), besides being known as allergenic components for baker’s asthma. Different approaches for characterization and quantification including proteomics-based methods for wheat ATIs have been documented. In these studies generally the major ATIs have been addressed. The challenge of current study was then to develop a more comprehensive workflow encompassing all reviewed wheat-ATI entries in UniProt database. To substantially test proof of concept, 46 German and Turkish wheat samples were used. Two extractions systems based on chloroform/methanol mixture (CM) and under buffered denaturing conditions were evaluated. Three aspects were optimized, tryptic digestion, chromatographic separation, and targeted tandem mass spectrometric analysis (HPLC-MS/MS). Preliminary characterization with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) documented the purity of the extracted ATIs with CM mixture and the amylase (60–80%)/trypsin (10–20%) inhibition demonstrated the bifunctional activity of ATIs. Thirteen (individual/common) biomarkers were established. Major ATIs (7–34%) were differently represented in samples. Finally, to our knowledge, the proposed HPLC-MS/MS method allowed for the first time so far the analysis of all 14 reviewed wheat ATI entries reported.
The α-amylase/trypsin inhibitors (ATIs) are discussed as being responsible for non-celiac wheat sensitivity (NCWS), besides being known as allergenic components for baker’s asthma. Different approaches for characterization and quantification including proteomics-based methods for wheat ATIs have been documented. In these studies generally the major ATIs have been addressed. The challenge of current study was then to develop a more comprehensive workflow encompassing all reviewed wheat-ATI entries in UniProt database. To substantially test proof of concept, 46 German and Turkish wheat samples were used. Two extractions systems based on chloroform/methanol mixture (CM) and under buffered denaturing conditions were evaluated. Three aspects were optimized, tryptic digestion, chromatographic separation, and targeted tandem mass spectrometric analysis (HPLC-MS/MS). Preliminary characterization with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) documented the purity of the extracted ATIs with CM mixture and the amylase (60–80%)/trypsin (10–20%) inhibition demonstrated the bifunctional activity of ATIs. Thirteen (individual/common) biomarkers were established. Major ATIs (7–34%) were differently represented in samples. Finally, to our knowledge, the proposed HPLC-MS/MS method allowed for the first time so far the analysis of all 14 reviewed wheat ATI entries reported.
Objective: To examine prospectively whether early parental child-rearing behavior is a predictor of cardiometabolic outcome in young adulthood when other potential risk factors are controlled. Metabolic factors associated with increased risk for cardiovascular disease have been found to vary, depending on lifestyle as well as genetic predisposition. Moreover, there is evidence suggesting that environmental conditions, such as stress in pre- and postnatal life, may have a sustained impact on an individual's metabolic risk profile. Methods: Participants were drawn from a prospective, epidemiological, cohort study followed up from birth into young adulthood. Parent interviews and behavioral observations at the age of 3 months were conducted to assess child-rearing practices and mother-infant interaction in the home setting and in the laboratory. In 279 participants, anthropometric characteristics, low-density lipoprotein and high-density lipoprotein cholesterol, apolipoproteins, and triglycerides were recorded at age 19 years. In addition, structured interviews were administered to the young adults to assess indicators of current lifestyle and education. Results: Adverse early-life interaction experiences were significantly associated with lower levels of high- density lipoprotein cholesterol and apolipoprotein A1 in young adulthood. Current lifestyle variables and level of education did not account for this effect, although habitual smoking and alcohol consumption also contributed significantly to cardiometabolic outcomes. Conclusions: These findings suggest that early parental child-rearing behavior may predict health outcome in later life through its impact on metabolic parameters in adulthood.
How to understand species' niches and range dynamics: a demographic research agenda for biogeography
(2012)
Range dynamics causes mismatches between a species geographical distribution and the set of suitable environments in which population growth is positive (the Hutchinsonian niche). This is because sourcesink population dynamics cause species to occupy unsuitable environments, and because environmental change creates non-equilibrium situations in which species may be absent from suitable environments (due to migration limitation) or present in unsuitable environments that were previously suitable (due to time-delayed extinction). Because correlative species distribution models do not account for these processes, they are likely to produce biased niche estimates and biased forecasts of future range dynamics. Recently developed dynamic range models (DRMs) overcome this problem: they statistically estimate both range dynamics and the underlying environmental response of demographic rates from species distribution data. This process-based statistical approach qualitatively advances biogeographical analyses. Yet, the application of DRMs to a broad range of species and study systems requires substantial research efforts in statistical modelling, empirical data collection and ecological theory. Here we review current and potential contributions of these fields to a demographic understanding of niches and range dynamics. Our review serves to formulate a demographic research agenda that entails: (1) advances in incorporating process-based models of demographic responses and range dynamics into a statistical framework, (2) systematic collection of data on temporal changes in distribution and abundance and on the response of demographic rates to environmental variation, and (3) improved theoretical understanding of the scaling of demographic rates and the dynamics of spatially coupled populations. This demographic research agenda is challenging but necessary for improved comprehension and quantification of niches and range dynamics. It also forms the basis for understanding how niches and range dynamics are shaped by evolutionary dynamics and biotic interactions. Ultimately, the demographic research agenda should lead to deeper integration of biogeography with empirical and theoretical ecology.
In today’s life, embedded systems are ubiquitous. But they differ from traditional desktop systems in many aspects – these include predictable timing behavior (real-time), the management of scarce resources (memory, network), reliable communication protocols, energy management, special purpose user-interfaces (headless operation), system configuration, programming languages (to support software/hardware co-design), and modeling techniques. Within this technical report, authors present results from the lecture “Operating Systems for Embedded Computing” that has been offered by the “Operating Systems and Middleware” group at HPI in Winter term 2013/14. Focus of the lecture and accompanying projects was on principles of real-time computing. Students had the chance to gather practical experience with a number of different OSes and applications and present experiences with near-hardware programming. Projects address the entire spectrum, from bare-metal programming to harnessing a real-time OS to exercising the full software/hardware co-design cycle. Three outstanding projects are at the heart of this technical report. Project 1 focuses on the development of a bare-metal operating system for LEGO Mindstorms EV3. While still a toy, it comes with a powerful ARM processor, 64 MB of main memory, standard interfaces, such as Bluetooth and network protocol stacks. EV3 runs a version of 1 1 Introduction Linux. Sources are available from Lego’s web site. However, many devices and their driver software are proprietary and not well documented. Developing a new, bare-metal OS for the EV3 requires an understanding of the EV3 boot process. Since no standard input/output devices are available, initial debugging steps are tedious. After managing these initial steps, the project was able to adapt device drivers for a few Lego devices to an extent that a demonstrator (the Segway application) could be successfully run on the new OS. Project 2 looks at the EV3 from a different angle. The EV3 is running a pretty decent version of Linux- in principle, the RT_PREEMPT patch can turn any Linux system into a real-time OS by modifying the behavior of a number of synchronization constructs at the heart of the OS. Priority inversion is a problem that is solved by protocols such as priority inheritance or priority ceiling. Real-time OSes implement at least one of the protocols. The central idea of the project was the comparison of non-real-time and real-time variants of Linux on the EV3 hardware. A task set that showed effects of priority inversion on standard EV3 Linux would operate flawlessly on the Linux version with the RT_PREEMPT-patch applied. If only patching Lego’s version of Linux was that easy... Project 3 takes the notion of real-time computing more seriously. The application scenario was centered around our Carrera Digital 132 racetrack. Obtaining position information from the track, controlling individual cars, detecting and modifying the Carrera Digital protocol required design and implementation of custom controller hardware. What to implement in hardware, firmware, and what to implement in application software – this was the central question addressed by the project.
BACKGROUND: Addiction is supposedly characterized by a shift from goal-directed to habitual decision making, thus facilitating automatic drug intake. The two-step task allows distinguishing between these mechanisms by computationally modeling goal-directed and habitual behavior as model-based and model-free control. In addicted patients, decision making may also strongly depend upon drug-associated expectations. Therefore, we investigated model-based versus model-free decision making and its neural correlates as well as alcohol expectancies in alcohol-dependent patients and healthy controls and assessed treatment outcome in patients. METHODS: Ninety detoxified, medication-free, alcohol-dependent patients and 96 age-and gender-matched control subjects underwent functional magnetic resonance imaging during the two-step task. Alcohol expectancies were measured with the Alcohol Expectancy Questionnaire. Over a follow-up period of 48 weeks, 37 patients remained abstinent and 53 patients relapsed as indicated by the Alcohol Timeline Followback method. RESULTS: Patients who relapsed displayed reduced medial prefrontal cortex activation during model-based decision making. Furthermore, high alcohol expectancies were associated with low model-based control in relapsers, while the opposite was observed in abstainers and healthy control subjects. However, reduced model-based control per se was not associated with subsequent relapse. CONCLUSIONS: These findings suggest that poor treatment outcome in alcohol dependence does not simply result from a shift from model-based to model-free control but is instead dependent on the interaction between high drug expectancies and low model-based decision making. Reduced model-based medial prefrontal cortex signatures in those who relapse point to a neural correlate of relapse risk. These observations suggest that therapeutic interventions should target subjective alcohol expectancies.
In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.
Without fear or favour
(2024)
Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping ongoing thought and behavior. The influence of pavlovian stimuli on ongoing behavior is paradigmatically measured by pavlovian-to-instrumental transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced PIT. Methods: Thirty-two recently detoxified alcohol-dependent patients and 32 age- and gender-matched healthy controls performed a PIT task with instrumental go/no-go approach behaviors. The task involved both pavlovian stimuli associated with monetary rewards and losses, and images of drinks. Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect, and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs. Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol-dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.
Multijunction solar cells can overcome the fundamental efficiency limits of single-junction devices. The bandgap tunability of metal halide perovskite solar cells renders them attractive for multijunction architectures(1). Combinations with silicon and copper indium gallium selenide (CIGS), as well as all-perovskite tandem cells, have been reported(2-5). Meanwhile, narrow-gap non-fullerene acceptors have unlocked skyrocketing efficiencies for organic solar cells(6,7). Organic and perovskite semiconductors are an attractive combination, sharing similar processing technologies. Currently, perovskite-organic tandems show subpar efficiencies and are limited by the low open-circuit voltage (V-oc) of wide-gap perovskite cells(8) and losses introduced by the interconnect between the subcells(9,10). Here we demonstrate perovskite-organic tandem cells with an efficiency of 24.0 per cent (certified 23.1 per cent) and a high V-oc of 2.15 volts. Optimized charge extraction layers afford perovskite subcells with an outstanding combination of high V-oc and fill factor. The organic subcells provide a high external quantum efficiency in the near-infrared and, in contrast to paradigmatic concerns about limited photostability of non-fullerene cells(11), show an outstanding operational stability if excitons are predominantly generated on the non-fullerene acceptor, which is the case in our tandems. The subcells are connected by an ultrathin (approximately 1.5 nanometres) metal-like indium oxide layer with unprecedented low optical/electrical losses. This work sets a milestone for perovskite-organic tandems, which outperform the best p-i-n perovskite single junctions(12) and are on a par with perovskite-CIGS and all-perovskite multijunctions(13).
The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = -3.86, p < .001), but not in healthy controls (t = -0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t((30)) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.
Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping on- going thought and behavior. The influence of Pavlovian stimuli on on-going behavior is paradigmatically measured by Pavlovian-to-instrumental-transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol
dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent, and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced Pavlovian-Instrumental transfer.
Methods: 32 recently detoxified alcohol-dependent patients and 32 age and gender matched healthy controls performed a PIT task with instrumental go/no-go approach behaviours. The task involved both Pavlovian stimuli associated with monetary rewards and losses, and images of drinks.
Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs.
Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol- dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.
Rationale: Advances in neurocomputational modeling suggest that valuation systems for goal-directed (deliberative) on one side, and habitual (automatic) decision-making on the other side may rely on distinct computational strategies for reinforcement learning, namely model-free vs. model-based learning. As a key theoretical difference, the model-based system strongly demands cognitive functions to plan actions prospectively based on an internal cognitive model of the environment, whereas valuation in the model-free system relies on rather simple learning rules from operant conditioning to retrospectively associate actions with their outcomes and is thus cognitively less demanding. Acute stress reactivity is known to impair model-based but not model-free choice behavior, with higher working memory capacity protecting the model-based system from acute stress. However, it is not clear which impact accumulated real life stress has on model-free and model-based decision systems and how this influence interacts with cognitive abilities. Methods: We used a sequential decision-making task distinguishing relative contributions of both learning strategies to choice behavior, the Social Readjustment Rating Scale questionnaire to assess accumulated real life stress, and the Digit Symbol Substitution Test to test cognitive speed in 95 healthy subjects. Results: Individuals reporting high stress exposure who had low cognitive speed showed reduced model-based but increased model-free behavioral control. In contrast, subjects exposed to accumulated real life stress with high cognitive speed displayed increased model-based performance but reduced model-free control. Conclusion: These findings suggest that accumulated real life stress exposure can enhance reliance on cognitive speed for model-based computations, which may ultimately protect the model-based system from the detrimental influences of accumulated real life stress. The combination of accumulated real life stress exposure and slower information processing capacities, however, might favor model-free strategies. Thus, the valence and preference of either system strongly depends on stressful experiences and individual cognitive capacities.
Portal Wissen = Exzellenz
(2023)
Was nicht nur gut oder sehr gut ist, nennen wir gern exzellent. Aber was meint das eigentlich? Vom lateinischen „excellere“ kommend, beschreibt es Dinge, Personen oder Handlungen, die „hervor-“ oder „herausragen“ aus der Menge, sich „auszeichnen“ gegenüber anderen. Mehr geht nicht. Exzellenz ist das Mittel der Wahl, wenn es darum geht, der Erste oder Beste zu sein. Und das macht auch vor der Forschung nicht halt. Wer auf die Universität Potsdam schaut, findet zahlreiche ausgezeichnete Forschende, hervorragende Projekte und immer wieder auch aufsehenerregende Erkenntnisse, Veröffentlichungen und Ergebnisse.
Aber ist die UP auch exzellent? Eine Frage, die 2023 ganz sicher andere Wellen schlägt als vielleicht vor 20 Jahren. Denn seit dem Start der Exzellenzinitiative 2005 gelten als – wörtlich – exzellent jene Hochschulen, denen es gelingt, in dem umfangreichsten Förderprogramm für Wissenschaft in Deutschland einen Zuschlag zu erhalten. Egal ob in Form von Graduiertenschulen, Forschungsclustern oder – seit Fortsetzung des Programms ab 2019 unter dem Titel „Exzellenzstrategie“ – ganzen Exzellenzuniversitäten: Wer im Kreis der Forschungsuniversitäten zu den Besten gehören will, braucht das Siegel der Exzellenz. In der gerade eingeläuteten neuen Wettbewerbsrunde der „Exzellenzstrategie des Bundes und der Länder“ bewirbt sich die Universität Potsdam mit drei Clusterskizzen um Förderung.
Ein Antrag kommt aus der Ökologie- und Biodiversitätsforschung. Ziel ist es, ein komplexes Bild ökologischer Prozesse zu zeichnen – und dabei die Rolle von einzelnen Individuen ebenso zu betrachten wie das Zusammenwirken vieler Arten in einem Ökosystem, um die Funktion der Artenvielfalt genauer zu bestimmen. Eine zweite Skizze haben die Kognitionswissenschaften eingereicht. Hier soll das komplexe Nebeneinander von Sprache und Kognition, Entwicklung und Lernen sowie Motivation und Verhalten als dynamisches Miteinander erforscht werden – wobei auch mit den Erziehungswissenschaften kooperiert wird, um verknüpfte Lernund Bildungsprozesse stets mitzudenken. Der dritte Antrag aus den Geo- und Umweltwissenschaften nimmt extreme und besonders folgenschwere Naturgefahren und -prozesse wie Überschwemmungen und Dürren in den Blick. Die Forschenden untersuchen die Extremereignisse mit besonderem Fokus auf deren Wechselwirkung mit der Gesellschaft, um mit ihnen einhergehende Risiken und Schäden besser einschätzen sowie künftig rechtzeitig Maßnahmen einleiten zu können.
„Alle drei Anträge zeichnen ein hervorragendes Bild unserer Leistungsfähigkeit“, betont der Präsident der Universität, Prof. Oliver Günther, Ph.D. „Die Skizzen dokumentieren eindrucksvoll unser Engagement, vorhandene Forschungsexzellenz sowie die Potenziale der Universität Potsdam insgesamt. Allein die Tatsache, dass sich drei schlagkräftige Konsortien in ganz unterschiedlichen Themenbereichen zusammengefunden haben, zeigt, dass wir auf unserem Weg in die Spitzengruppe der deutschen Universitäten einen guten Schritt vorangekommen sind.“
In diesem Heft schauen wir, was sich in und hinter diesen Anträgen verbirgt: Wir haben mit den Wissenschaftlerinnen und Wissenschaftlern gesprochen, die sie geschrieben haben, und sie gefragt, was sie sich vornehmen, sollten sie den Zuschlag erhalten und ein Cluster an die Universität holen. Wir haben aber auch auf die Forschung geschaut, die zu den Anträgen geführt hat und die schon länger das Profil der Universität prägt und ihr national wie international Anerkennung eingebracht hat. Wir stellen eine kleine Auswahl an Projekten, Methoden und Forschenden vor, um zu zeigen, warum in diesen Anträgen tatsächlich exzellente Forschung steckt! Übrigens: Auch „Exzellenz“ ist nicht das Ende der Fahnenstange. Immerhin lässt sich das Adjektiv exzellent sogar steigern. In diesem Sinne wünschen wir exzellentestes Vergnügen beim Lesen!
Portal Wissen = Excellence
(2023)
When something is not just good or very good, we often call it excellent. But what does that really mean? Coming from the Latin word “excellere,” it describes things, persons, or actions that are outstanding or superior and distinguish themselves from others. It cannot get any better. Excellence is the top choice for being the first or the best. Research is no exception.
At the university, you will find numerous exceptional researchers, outstanding projects, and, time and again, sensational findings, publications, and results. But is the University of Potsdam also excellent? A question that will certainly create a different stir in 2023 than it did perhaps 20 years ago. Since the launch of the Excellence Initiative in 2005, universities that succeed in winning the most comprehensive funding program for research in Germany have been considered – literally – excellent. Whether in the form of graduate schools, research clusters, or – since the program was continued in 2019 under the title “Excellence Strategy” – entire universities of excellence: Anyone who wants to be among the best research universities needs the seal of excellence.
The University of Potsdam is applying for funding with three cluster proposals in the recently launched new round of the “Excellence Strategy of the German Federal and State Governments.” One proposal comes from ecology and biodiversity research. The aim is to paint a comprehensive picture of ecological processes by examining the role of single individuals as well as the interactions among many species in an ecosystem to precisely determine the function of biodiversity. A second proposal has been submitted by the cognitive sciences. Here, the complex coexistence of language and cognition, development and learning, as well as motivation and behavior will be researched as a dynamic interrelation. The projects will include cooperation with the educational sciences to constantly consider linked learning and educational processes. The third proposal from the geo and environmental sciences concentrates on extreme and particularly devastating natural hazards and processes such as floods and droughts. The researchers examine these extreme events, focusing on their interaction with society, to be able to better assess the risks and damages they might involve and to initiate timely measures in the future.
“All three proposals highlight the excellence of our performance,” emphasizes University President Prof. Oliver Günther, Ph.D. “The outlines impressively document our commitment, existing research excellence, and the potential of the University of Potsdam as a whole. The fact that three powerful consortia have come together in different subject areas shows that we have taken a good step forward on our way to becoming one of the top German universities.”
In this issue, we are looking at what is in and behind these proposals: We talked to the researchers who wrote them. We asked them about their plans in case their proposals are successful and they bring a cluster of excellence to the university. But we also looked at the research that has led to the proposals, has long shaped the university’s profile, and earned it national and international recognition. We present a small selection of projects, methods, and researchers to illustrate why there really is excellent research in these proposals!
By the way, “excellence” is also not the end of the flagpole. After all, the adjective “excellent” even has a comparative and a superlative. With this in mind, I wish you the most excellent pleasure reading this issue!