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BACKGROUND: Pavlovian-to-instrumental transfer (PIT) describes the influence of conditioned stimuli on instrumental behaviors and is discussed as a key process underlying substance abuse. Here, we tested whether neural responses during alcohol-related PIT predict future relapse in alcohol-dependent patients and future drinking behavior in adolescents. METHODS: Recently detoxified alcohol-dependent patients (n = 52) and young adults without dependence (n = 136) underwent functional magnetic resonance imaging during an alcohol-related PIT paradigm, and their drinking behavior was assessed in a 12-month follow-up. To predict future drinking behavior from PIT activation patterns, we used a multivoxel classification scheme based on linear support vector machines. RESULTS: When training and testing the classification scheme in patients, PIT activation patterns predicted future relapse with 71.2% accuracy. Feature selection revealed that classification was exclusively based on activation patterns in medial prefrontal cortex. To probe the generalizability of this functional magnetic resonance imaging-based prediction of future drinking behavior, we applied the support vector machine classifier that had been trained on patients to PIT functional magnetic resonance imaging data from adolescents. An analysis of cross-classification predictions revealed that those young social drinkers who were classified as abstainers showed a greater reduction in alcohol consumption at 12-month follow-up than those classified as relapsers (Delta = -24.4 +/- 6.0 g vs. -5.7 +/- 3.6 g; p = .019). CONCLUSIONS: These results suggest that neural responses during PIT could constitute a generalized prognostic marker for future drinking behavior in established alcohol use disorder and in at-risk states.
Soft robots and devices with the advanced capability to perform adaptive motions similar to that of human beings often have stimuli-sensitive polymeric materials as the key actuating component. The external signals triggering the smart polymers’ actuations can be transmitted either via a direct physical connection between actuator and controlling unit (tethered) or remotely without a connecting wire. However, the vast majority of such polymeric actuator materials are limited to one specific type of motion as their geometrical information is chemically fixed. Here, we present magnetically driven nanocomposite actuators, which can be reversibly reprogrammed to different actuation geometries by a solely physical procedure. Our approach is based on nanocomposite materials comprising spatially segregated crystallizable actuation and geometry determining units. Upon exposure to a specific magnetic field strength the actuators’ geometric memory is erased by the melting of the geometry determining units allowing the implementation of a new actuator shape. The actuation performance of the nanocomposites can be tuned and the technical significance was demonstrated in a multi-cyclic experiment with several hundreds of repetitive free-standing shape shifts without losing performance.
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.
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.
A dimensional approach in psychiatry aims to identify core mechanisms of mental disorders across nosological boundaries.
We compared anticipation of reward between major psychiatric disorders, and investigated whether reward anticipation is impaired in several mental disorders and whether there is a common psychopathological correlate (negative mood) of such an impairment.
During reward anticipation, we observed significant group differences in ventral striatal (VS) activation: patients with schizophrenia, alcohol dependence, and major depression showed significantly less ventral striatal activation compared to healthy controls. Depressive symptoms correlated with dysfunction in reward anticipation regardless of diagnostic entity. There was no significant correlation between anxiety symptoms and VS functional activation.
Our findings demonstrate a neurobiological dysfunction related to reward prediction that transcended disorder categories and was related to measures of depressed mood. The findings underline the potential of a dimensional approach in psychiatry and strengthen the hypothesis that neurobiological research in psychiatric disorders can be targeted at core mechanisms that are likely to be implicated in a range of clinical entities.
PSI-Potsdam
(2018)
In Brandenburg kommt der Universität Potsdam eine besondere Rolle zu: Sie ist die einzige, an der zukünftige Lehrerinnen und Lehrer die erste Phase ihres Werdegangs – das Lehramtsstudium – absolvieren können. Vor diesem Hintergrund wurde bereits kurz nach der Gründung im Jahr 1991 das „Potsdamer Modell der Lehrerbildung“ entwickelt. Dieses Modell strebt fortlaufend eine enge Verzahnung von Theorie und Praxis über das gesamte Studium hinweg an und bindet hierfür die schulpraktischen Studienanteile in besonderer Weise ein. Eine erneute Stärkung erfuhr die Lehrerbildung im Dezember 2014 mit der Gründung des Zentrums für Lehrerbildung und Bildungsforschung (ZeLB). Aus der koordinierenden Arbeit des Zentrums entstand das fakultätsübergreifende Projekt „Professionalisierung – Schulpraktische Studien – Inklusion“ (PSI-Potsdam) das im Rahmen der Qualitätsoffensive Lehrerbildung des Bundesministeriums für Bildung und Forschung erfolgreich gefördert wurde (2015–2018) und dessen Verlängerung (2019–2023) bewilligt ist.
Der vorliegende Band vermittelt in den drei großen Kapiteln „Erhebungsinstrumente“, „Seminarkonzepte“ und „Vernetzungen“ einen Überblick über einige der praxisnahen Forschungszugänge, hochschuldidaktischen Ansätze und Strategien zur Vernetzung innerhalb der Lehrerbildung, die im Rahmen von PSI-Potsdam entwickelt und umgesetzt wurden. Die Beiträge wurden mit dem Ziel verfasst, Kolleginnen und Kollegen an Universitäten und Hochschulen, Akteur_innen des Vorbereitungsdiensts sowie der Fort- und Weiterbildung von Lehrkräften möglichst konkrete Einblicke zu gewähren.
Unter der Herausgeberschaft von Prof. Dr. Andreas Borowski (Fachdidaktik Physik), Prof. Dr. Antje Ehlert (Inklusionspädagogik mit dem Förderschwerpunkt Lernen) und Prof. Dr. Helmut Prechtl (Fachdidaktik Biologie) vereinen sich Autor_innen mit breit gestreuter fachdidaktischer und bildungswissenschaftlicher Expertise.
Dimensional psychiatry
(2014)
A dimensional approach in psychiatry aims to identify core mechanisms of mental disorders across nosological boundaries.
We compared anticipation of reward between major psychiatric disorders, and investigated whether reward anticipation is impaired in several mental disorders and whether there is a common psychopathological correlate (negative mood) of such an impairment.
We used functional magnetic resonance imaging (fMRI) and a monetary incentive delay (MID) task to study the functional correlates of reward anticipation across major psychiatric disorders in 184 subjects, with the diagnoses of alcohol dependence (n = 26), schizophrenia (n = 44), major depressive disorder (MDD, n = 24), bipolar disorder (acute manic episode, n = 13), attention deficit/hyperactivity disorder (ADHD, n = 23), and healthy controls (n = 54). Subjects' individual Beck Depression Inventory-and State-Trait Anxiety Inventory-scores were correlated with clusters showing significant activation during reward anticipation.
During reward anticipation, we observed significant group differences in ventral striatal (VS) activation: patients with schizophrenia, alcohol dependence, and major depression showed significantly less ventral striatal activation compared to healthy controls. Depressive symptoms correlated with dysfunction in reward anticipation regardless of diagnostic entity. There was no significant correlation between anxiety symptoms and VS functional activation.
Our findings demonstrate a neurobiological dysfunction related to reward prediction that transcended disorder categories and was related to measures of depressed mood. The findings underline the potential of a dimensional approach in psychiatry and strengthen the hypothesis that neurobiological research in psychiatric disorders can be targeted at core mechanisms that are likely to be implicated in a range of clinical entities.
BIOMEX (BIOlogy and Mars EXperiment) is an ESA/Roscosmos space exposure experiment housed within the exposure facility EXPOSE-R2 outside the Zvezda module on the International Space Station (ISS). The design of the multiuser facility supports-among others-the BIOMEX investigations into the stability and level of degradation of space-exposed biosignatures such as pigments, secondary metabolites, and cell surfaces in contact with a terrestrial and Mars analog mineral environment. In parallel, analysis on the viability of the investigated organisms has provided relevant data for evaluation of the habitability of Mars, for the limits of life, and for the likelihood of an interplanetary transfer of life (theory of lithopanspermia). In this project, lichens, archaea, bacteria, cyanobacteria, snow/permafrost algae, meristematic black fungi, and bryophytes from alpine and polar habitats were embedded, grown, and cultured on a mixture of martian and lunar regolith analogs or other terrestrial minerals. The organisms and regolith analogs and terrestrial mineral mixtures were then exposed to space and to simulated Mars-like conditions by way of the EXPOSE-R2 facility. In this special issue, we present the first set of data obtained in reference to our investigation into the habitability of Mars and limits of life. This project was initiated and implemented by the BIOMEX group, an international and interdisciplinary consortium of 30 institutes in 12 countries on 3 continents. Preflight tests for sample selection, results from ground-based simulation experiments, and the space experiments themselves are presented and include a complete overview of the scientific processes required for this space experiment and postflight analysis. The presented BIOMEX concept could be scaled up to future exposure experiments on the Moon and will serve as a pretest in low Earth orbit.
How AAA(+) chaperones conformationally remodel specific target proteins in an ATP-dependent manner is not well understood. Here, we investigated the mechanism of the AAA(+) protein Rubisco activase (Rca) in metabolic repair of the photosynthetic enzyme Rubisco, a complex of eight large (RbcL) and eight small (RbcS) subunits containing eight catalytic sites. Rubisco is prone to inhibition by tight-binding sugar phosphates, whose removal is catalyzed by Rca. We engineered a stable Rca hexamer ring and analyzed its functional interaction with Rubisco. Hydrogen/deuterium exchange and chemical crosslinking showed that Rca structurally destabilizes elements of the Rubisco active site with remarkable selectivity. Cryo-electron microscopy revealed that Rca docks onto Rubisco over one active site at a time, positioning the C-terminal strand of RbcL, which stabilizes the catalytic center, for access to the Rca hexamer pore. The pulling force of Rca is fine-tuned to avoid global destabilization and allow for precise enzyme repair.
Objective: We analyse temporal trends and regional variation among the most recent available anthropometric data from German conscription in the years 2008-2010 and their historical contextualization since 1956. Design/setting/subjects: The overall sample included German conscripts (N 13 857 313) from 1956 to 2010. Results: German conscripts changed from growing in height to growing in breadth. Over the analysed 54 years, average height of 19-year-old conscripts increased by 6.5 cm from 173.5 cm in 1956 (birth year 1937) to 180.0 cm in 2010 (birth year 1991). This increase plateaued since the 1990s (1970s birth years). The increase in average weight, however, did not lessen during the last two decades but increased in two steps: at the end of the 1980s and after 1999. The weight and BMI distributions became increasingly right-skewed, the prevalence of overweight and obesity increased from 11.6 % and 2.1 % in 1984 to 19.9 % and 8.5 % in 2010, respectively. The north-south gradient in height (north = taller) persisted during our observations. Height and weight of conscripts from East Germany matched the German average between the early 1990s and 2009. Between the 1980s and the early 1990s, the average chest circumference increased, the average difference between chest circumference when inhaling and exhaling decreased, as did leg length relative to trunk length. Conclusions: Measuring anthropometric data for military conscripts yielded year-by-year monitoring of the health status of young men at a proscribed age. Such findings contribute to a more precise identification of groups at risk and thus help with further studies and to target interventions.
Temperature-memory technology was utilized to generate flat substrates with a programmable stiffness pattern from cross-linked poly(ethylene-co-vinyl acetate) substrates with cylindrical microstructures. Programmed substrates were obtained by vertical compression at temperatures in the range from 60 to 100 degrees C and subsequent cooling, whereby a flat substrate was achieved by compression at 72 degrees C, as documented by scanning electron microscopy and atomic force microscopy (AFM). AFM nanoindentation experiments revealed that all programmed substrates exhibited the targeted stiffness pattern. The presented technology for generating polymeric substrates with programmable stiffness pattern should be attractive for applications such as touchpads. optical storage, or cell instructive substrates.
Background: Epidemiological studies suggest that an increased red meat intake is associated with a higher risk of type 2 diabetes, whereas an increased fiber intake is associated with a lower risk. Objectives: We conducted an intervention study to investigate the effects of these nutritional factors on glucose and lipid metabolism, body-fat distribution, and liver fat content in subjects at increased risk of type 2 diabetes. Methods: This prospective, randomized, and controlled dietary intervention study was performed over 6 mo. All groups decreased their daily caloric intake by 400 kcal. The "control" group (N = 40) only had this requirement. The "no red meat" group (N = 48) in addition aimed to avoid the intake of red meat, and the "fiber" group (N = 44) increased intake of fibers to 40 g/d. Anthropometric parameters and frequently sampled oral glucose tolerance tests were performed before and after intervention. Body-fat mass and distribution, liver fat, and liver iron content were assessed by MRI and single voxel proton magnetic resonance spectroscopy. Results: Participants in all groups lost weight (mean 3.3 +/- 0.5 kg, P < 0.0001). Glucose tolerance and insulin sensitivity improved (P < 0.001), and body and visceral fat mass decreased in all groups (P < 0.001). These changes did not differ between groups. Liver fat content decreased significantly (P < 0.001) with no differences between the groups. The decrease in liver fat correlated with the decrease in ferritin during intervention (r(2) = 0.08, P = 0.0021). This association was confirmed in an independent lifestyle intervention study (Tuebingen Lifestyle Intervention Program, N = 229, P = 0.0084). Conclusions: Our data indicate that caloric restriction leads to a marked improvement in glucose metabolism and body-fat composition, including liver-fat content. The marked reduction in liver fat might be mediated via changes in ferritin levels. In the context of caloric restriction, there seems to be no additional beneficial impact of reduced red meat intake and increased fiber intake on the improvement in cardiometabolic risk parameters. This trial was registered at clinicaltrials.gov as NCT03231839.
Material surfaces with tailored aerophobicity are crucial for applications where gas bubble wettability has to be controlled, e.g., gas storage and transport, electrodes, bioreactors or medical devices. Here, we present switchable underwater aerophobicity of hydrophobic polymeric substrates, which respond to heat with multilevel micro-and nanotopographical changes. The cross-linked poly[ethylene-co-(vinyl acetate)] substrates possess arrays of microcylinders with a nanorough top surface. It is hypothesized that the specific micro-/nanotopography of the surface allows trapping of a water film at the micro interspace and in this way generates the aerophobic behavior. The structured substrates were programmed to a temporarily stable, nanoscale flat substrate showing aerophilic behavior. Upon heating, the topographical changes caused a switch in contact angle from aerophilic to aerophobic for approaching air bubbles. In this way, the initial adhesion of air bubbles to the programmed flat substrate could be turned into repellence for the recovered substrate surface. The temperature at which the repellence of air bubbles starts can be adjusted from 58 +/- 3 degrees C to 73 +/- 3 degrees C by varying the deformation temperature applied during the temperature-memory programming procedure. The presented actively switching polymeric substrates are attractive candidates for applications, where an on-demand gas bubble repellence is advantageous. (c) 2018 Helmholtz-Zentrum Geesthacht, Zentrum fur Material- und Kustenforschung. Published by Elsevier Ltd.
Editorial
(2019)
Awards
(2013)
A multiblock copolymer termed as PCL-PIBMD, consisting of crystallizable poly(epsilon-caprolactone) (PCL) segments and crystallizable poly(3S-isobutyl-morpholine-2,5-dione) (PIBMD) segments, has been reported as a material showing a thermally-induced shape-memory effect. While PIBMD crystalline domains act as netpoints to determine the permanent shape, both PCL crystalline domains and PIBMD amorphous domains, which have similar transition temperatures (T-trans) can act as switching domains. In this work, the influence of the deformation temperature (T-deform = 50 or 20 degrees C), which was above or below T-trans, on the structural changes of PCL-PIBMD during uniaxial deformation and the shapememory properties were investigated. Furthermore, the relative contribution of crystalline PCL and PIBMD amorphous phases to the fixation of the temporary shape were distinguished by a toluene vapor treatment approach. The results indicated that at 50 degrees C, both PCL and PIBMD amorphous phases can be orientated during deformation, resulting in thermally-induced crystals of PCL domains and joint contribution to the switching domains. In contrast at 20 degrees C, the temporary shape was mainly fixed by PCL crystals generated via strain-induced crystallization.
Background: Five different G protein-coupled sphingosine-1-phosphate (S1P) receptors (S1P1-S1P5) regulate a variety of physiologic and pathophysiologic processes, including lymphocyte circulation, multiple sclerosis (MS), and cancer. Although B-lymphocyte circulation plays an important role in these processes and is essential for normal immune responses, little is known about S1P receptors in human B cells.
Objective: To explore their function and signaling, we studied B-cell lines and primary B cells from control subjects, patients with leukemia, patients with S1P receptor inhibitor-treated MS, and patients with primary immunodeficiencies.
Methods: S1P receptor expression was analyzed by using multicolor immunofluorescence microscopy and quantitative PCR. Transwell assays were used to study cell migration. S1P receptor internalization was visualized by means of time-lapse imaging with fluorescent S1P receptor fusion proteins expressed by using lentiviral gene transfer. B-lymphocyte subsets were characterized by means of flow cytometry and immunofluorescence microscopy.
Results: Showing that different B-cell populations express different combinations of S1P receptors, we found that S1P1 promotes migration, whereas S1P4 modulates and S1P2 inhibits S1P1 signals. Expression of CD69 in activated B lymphocytes and B cells from patients with chronic lymphocytic leukemia inhibited S1P-induced migration. Studying B-cell lines, normal B lymphocytes, and B cells from patients with primary immunodeficiencies, we identified Bruton tyrosine kinase, beta-arrestin 2, LPS-responsive beige-like anchor protein, dedicator of cytokinesis 8, and Wiskott-Aldrich syndrome protein as critical signaling components downstream of S1P1.
Conclusion: Thus S1P receptor signaling regulates human B-cell circulation and might be a factor contributing to the pathology of MS, chronic lymphocytic leukemia, and primary immunodeficiencies.
Material surfaces with tailored aerophobicity are crucial for applications where gas bubble wettability has to be controlled, e.g., gas storage and transport, electrodes, bioreactors or medical devices.
Here, we present switchable underwater aerophobicity of hydrophobic polymeric substrates, which respond to heat with multilevel micro- and nanotopographical changes. The cross-linked poly[ethylene-co-(vinyl acetate)] substrates possess arrays of microcylinders with a nanorough top surface. It is hypothesized that the specific micro-/nanotopography of the surface allows trapping of a water film at the micro interspace and in this way generates the aerophobic behavior. The structured substrates were programmed to a temporarily stable, nanoscale flat substrate showing aerophilic behavior. Upon heating, the topographical changes caused a switch in contact angle from aerophilic to aerophobic for approaching air bubbles. In this way, the initial adhesion of air bubbles to the programmed flat substrate could be turned into repellence for the recovered substrate surface. The temperature at which the repellence of air bubbles starts can be adjusted from 58 ± 3 °C to 73 ± 3 °C by varying the deformation temperature applied during the temperature-memory programming procedure. The presented actively switching polymeric substrates are attractive candidates for applications, where an on-demand gas bubble repellence is advantageous.
Unwanted shrinkage behaviors or failure in structural functions such as mechanical strength or deformability of polymeric products related to their thermomechanical history are a major challenge in production of plastics. Here, we address the question whether we can turn this challenge into an opportunity by creating defined thermomechanical histories in polymers, represented by a specific morphology and nanostructure, to equip polymeric shaped bodies with desired functions, e.g. a temperature-memory, by hot, warm or cold deformation into multiblock copolymers having two partially overlapping melting transitions. A copolyesterurethane named PDLCL, consisting of poly(epsilon-caprolactone) (PCL) and poly(omega-pentadecalactone) (PPDL) crystalline domains, exhibiting a pronounced phase-segregated morphology and partially overlapping melting transitions was selected for this study. Different types of PCL and PPDL crystals as well as distinct degrees of orientation in both amorphous and crystalline domains were obtained after deformation at 20 or 40 degrees C and to a lower extent at 60 degrees C. The generated non-isotropic structures were stable at ambient temperature and represent the different stresses stored. Stress-free heating experiments showed that the relaxation in both amorphous and crystalline phases occurred predominantly with melting of PCL crystals. When the switching temperature, which was similar to the applied deformation temperature (temperature-memory), was exceeded in stress-free heating experiments, the implemented thermomechanical history could be reversed. In contrast, during constant-strain heating to 60 degrees C the generated structural features remained almost unchanged. These findings provide insights about the structure function relation in multiblock copolymers with two crystalline phases exhibiting a temperature-memory effect by implementation of specific thermomechanical histories, which might be a general principle for tailoring other functions like mechanical strength or deformability in polymers. (C) 2016 Elsevier Ltd. All rights reserved.
Multiblock copolymers named PCL-PIBMD consisting of crystallizable poly(epsilon-caprolactone) segments and crystallizable poly[oligo(3S-iso-butylmorpholine-2,5-dione)] segments coupled by trimethyl hexamethylene diisocyanate provide a versatile molecular architecture for achieving shape-memory effects (SMEs) in polymers. The mechanical properties as well as the SME performance of PCL-PIBMD can be tailored by the variation of physical parameters during programming such as deformation strain or applied temperature protocols. In this study, we explored the influence of applying different strain rates during programming on the resulting nanostructure of PCL-PIBMD. Programming was conducted at 50 degrees C by elongation to epsilon(m)=50% with strain rates of 1 or 10 or 50 mmmin(-1). The nanostructural changes were visualized by atomic force microscopy (AFM) measurements and investigated by in situ wide and small angle X-ray scattering experiments. With increasing the strain rate, a higher degree of orientation was observed in the amorphous domains. Simultaneously the strain-induced formation of new PIBMD crystals as well as the fragmentation of existing large PIBMD crystals occurred. The observed differences in shape fixity ratio and recovery stress of samples deformed with various strain rates can be attributed to their different nanostructures. The achieved findings can be relevant parameters for programming the shape-memory polymers with designed recovery forces. (c) 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 1935-1943
Proceedings of KogWis 2010 : 10th Biannual Meeting of the German Society for Cognitive Science
(2010)
As the latest biannual meeting of the German Society for Cognitive Science (Gesellschaft für Kognitionswissenschaft, GK), KogWis 2010 at Potsdam University reflects the current trends in a fascinating domain of research concerned with human and artificial cognition and the interaction of mind and brain. The Plenary talks provide a venue for questions of the numerical capacities and human arithmetic (Brian Butterworth), of the theoretical development of cognitive architectures and intelligent virtual agents (Pat Langley), of categorizations induced by linguistic constructions (Claudia Maienborn), and of a cross-level account of the “Self as a complex system“ (Paul Thagard). KogWis 2010 integrates a wealth of experimental research, cognitive modelling, and conceptual analysis in 5 invited symposia, over 150 individual talks, 6 symposia, and more than 40 poster contributions. Some of the invited symposia reflect local and regional strenghts of research in the Berlin-Brandenburg area: the two largests research fields of the university Cognitive Sciences Area of Excellence in Potsdam are represented by an invited symposium on “Information Structure” by the Special Research Area 632 (“Sonderforschungsbereich”, SFB) of the same name, of Potsdam University and Humboldt-University Berlin, and by a satellite conference of the research group “Mind and Brain Dynamics”. The Berlin School of Mind and Brain at Humboldt-University Berlin takes part with an invited symposium on “Decision Making” from a perspective of cognitive neuroscience and philosophy and the DFG Cluster of Excellence “Languages of Emotion” of Free University presents interdisciplinary research results in an invited symposium on “Symbolising Emotions”.
Optimal Matching
(2015)
Importance Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence.
Objective To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms.
Design, Setting, and Participants This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021).
Main Outcomes and Measures Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates.
Results Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year’s Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = −5.45; 95% CI, −8.00 to −2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = −11.10; 95% CI, −13.63 to −8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = −6.14; 95% CI, −9.96 to −2.31; P = .002) and in participants with severe AUD (β = −6.26; 95% CI, −10.18 to −2.34; P = .002).
Conclusions and Relevance This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals.
Importance Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence.
Objective To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms.
Design, Setting, and Participants This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021).
Main Outcomes and Measures Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates.
Results Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year’s Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = −5.45; 95% CI, −8.00 to −2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = −11.10; 95% CI, −13.63 to −8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = −6.14; 95% CI, −9.96 to −2.31; P = .002) and in participants with severe AUD (β = −6.26; 95% CI, −10.18 to −2.34; P = .002).
Conclusions and Relevance This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals.
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.
The chemical nature, the number length of integrated building blocks, as well as their sequence structure impact the phase morphology of multiblock copolymers (MBC) consisting of two non-miscible block types. It is hypothesized that a strictly alternating sequence should impact phase segregation. A library of well-defined MBC obtained by coupling oligo(epsilon-caprolactone) (OCL) of different molecular weights (2, 4, and 8 kDa) with oligotetrahydrofuran (OTHF, 2.9 kDa) via Steglich esterification results in strictly alternating (MBCalt) or random (MBCran) MBC. The three different series has a weight average molecular weight (M-w) of 65 000, 165 000, and 168 000 g mol(-1) for MBCalt and 80 500, 100 000, and 147 600 g mol(-1) for MBCran. When the chain length of OCL building blocks is increased, the tendency for phase segregation is facilitated, which is attributed to the decrease in chain mobility within the MBC. Furthermore, it is found that the phase segregation disturbs the crystallization by causing heterogeneities in the semi-crystalline alignment, which is attributed to an increase of the disorder of the OCL semi-crystalline alignment.
Temperature-memory polymers remember the temperature, where they were deformed recently, enabled by broad thermal transitions. In this study, we explored a series of crosslinked poly[ethylene-co-(vinyl acetate)] networks (cPEVAs) comprising crystallizable polyethylene (PE) controlling units exhibiting a pronounced temperature-memory effect (TME) between 16 and 99 °C related to a broad melting transition (∼100 °C). The nanostructural changes in such cPEVAs during programming and activation of the TME were analyzed via in situ X-ray scattering and specific annealing experiments. Different contributions to the mechanism of memorizing high or low deformation temperatures (Tdeform) were observed in cPEVA, which can be associated to the average PE crystal sizes. At high deformation temperatures (>50 °C), newly formed PE crystals, which are established during cooling when fixing the temporary shape, dominated the TME mechanism. In contrast, at low Tdeform (<50 °C), corresponding to a cold drawing scenario, the deformation led preferably to a disruption of existing large crystals into smaller ones, which then fix the temporary shape upon cooling. The observed mechanism of memorizing a deformation temperature might enable the prediction of the TME behavior and the knowledge based design of other TMPs with crystallizable controlling units.
Temperature-memory polymers remember the temperature, where they were deformed recently, enabled by broad thermal transitions. In this study, we explored a series of crosslinked poly[ethylene-co-(vinyl acetate)] networks (cPEVAs) comprising crystallizable polyethylene (PE) controlling units exhibiting a pronounced temperature-memory effect (TME) between 16 and 99 °C related to a broad melting transition (∼100 °C). The nanostructural changes in such cPEVAs during programming and activation of the TME were analyzed via in situ X-ray scattering and specific annealing experiments. Different contributions to the mechanism of memorizing high or low deformation temperatures (Tdeform) were observed in cPEVA, which can be associated to the average PE crystal sizes. At high deformation temperatures (>50 °C), newly formed PE crystals, which are established during cooling when fixing the temporary shape, dominated the TME mechanism. In contrast, at low Tdeform (<50 °C), corresponding to a cold drawing scenario, the deformation led preferably to a disruption of existing large crystals into smaller ones, which then fix the temporary shape upon cooling. The observed mechanism of memorizing a deformation temperature might enable the prediction of the TME behavior and the knowledge based design of other TMPs with crystallizable controlling units.
Although the shape-changing capabilities of LCEs hold great potential for applications ranging from micropumps to artificial muscles, customization of the LCE functionality to the applications' requirements is still a challenge. It is studied whether the orientation of NMC-LCPs and NMC-LCEs based on 2-tert-butyl-1,4-bis[4-(4-pentenyloxy)benzoyl]hydroquinone can be enhanced by copolymerization with 2-methyl-1,4-bis[4-(4-pentenyloxy)benzoyl]hydroquinone or 2,6-bis[4-(4-pentenyl-oxy)-benzoyl]anthracene. An increasing content of the comonomers stabilizes the nematic phase, which enables a tailoring of T-NI for the NMC-LCP between 45 and 68 degrees C, while for the NMC-LCE T-NI ranges between 69 and 76 degrees C. In addition, NMC-LCE show an increased actuation performance.
Temperature-memory polymers remember the temperature, where they were deformed recently, enabled by broad thermal transitions. In this study, we explored a series of crosslinked poly[ethylene-co-(vinyl acetate)] networks (cPEVAs) comprising crystallizable polyethylene (PE) controlling units exhibiting a pronounced temperature-memory effect (TME) between 16 and 99 degrees C related to a broad melting transition (similar to 100 degrees C). The nanostructural changes in such cPEVAs during programming and activation of the TME were analyzed via in situ X-ray scattering and specific annealing experiments. Different contributions to the mechanism of memorizing high or low deformation temperatures (T-deform) were observed in cPEVA, which can be associated to the average PE crystal sizes. At high deformation temperatures (>50 degrees C), newly formed PE crystals, which are established during cooling when fixing the temporary shape, dominated the TME mechanism. In contrast, at low T-deform (<50 degrees C), corresponding to a cold drawing scenario, the deformation led preferably to a disruption of existing large crystals into smaller ones, which then fix the temporary shape upon cooling. The observed mechanism of memorizing a deformation temperature might enable the prediction of the TME behavior and the knowledge based design of other TMPs with crystallizable controlling units.
Poly(carbonate-urethane)s (PCUs) exhibit improved resistance to hydrolytic degradation and in vivo stress cracking compared to poly(ester-urethane)s and their degradation leads to lower inflammation of the surrounding tissues. Therefore, PCUs are promising implant materials and are considered for devices such as artificial heart or spine implants. In this work, the hydrolytic stability of different poly(carbonate-urethane-urea)s (PCUUs) was studied under variation of the length of hydrocarbon chain (6, 9, 10, and 12 methylene units) between the carbonate linkages in the precursors. PCUUs were synthesized from isophorone diisocyanate and oligo(alkylene carbonate) diols using the moisture-cure method. The changes of sample weight, thermal and mechanical properties, morphology, as well as the degradation products after immersion in a buffer solution (PBS, pH = 7.4) for up to 10 weeks at 37 degrees C were monitored and analyzed. In addition, mechanical properties after 20 weeks (in PBS, 37 degrees C) were investigated. The gel content was determined based on swelling experiments in chloroform. Based on the DSC analysis, slight increases of melting transitions of PCUUs were observed, which were attributed to structure reorganization related to annealing at 37 degrees C rather than to the degradation of the PCUU. Tensile strength after 20 weeks of all investigated samples remained in the range of 29-39 MPa, whereas the elongation at break e(m) decreased only slightly and remained in the range between 670 and 800%. Based on the characterization of degradation products after up to 10 weeks of immersion it was assessed that oligomers are mainly consisting of hard segments containing urea linkages, which could be assigned to hindered-urea dissociation mechanism. The investigations confirmed good resistance of PCUUs to hydrolysis. Only minor changes in the crystallinity, as well as thermal and mechanical properties were observed and depended on hydrocarbon chain length in soft segment of PCUUs. (C) 2019 Published by Elsevier Ltd.
Polymeric materials possessing specific features like programmability, high deformability, and easy processability are highly desirable for creating modern actuating systems. In this study, thermoplastic shape-memory polymer actuators obtained by combining crystallizable poly(epsilon-caprolactone) (PCL) and poly(3S-isobutylmorpholin-2,5-dione) (PIBMD) segments in multiblock copolymers are described. We designed these materials according to our hypothesis that the confinement of glassy PIBMD domains present at the upper actuation temperature contribute to the stability of the actuator skeleton, especially at large programming strains. The copolymers have a phase-segregated morphology, indicated by the well-separated melting and glass transition temperatures for PIBMD and PCL, but possess a partially overlapping T-m of PCL and T-g of PIBMD in the temperature interval from 40 to 60 degrees C. Crystalline PIBMD hard domains act as strong physical netpoints in the PIBMD-PCL bulk material enabling high deformability (up to 2000%) and good elastic recoverability (up to 80% at 50 degrees C above T-m,T-PCL). In the programmed thermoplastic actuators a high content of crystallizable PCL actuation domains ensures pronounced thermoreversible shape changes upon repetitive cooling and heating. The programmed actuator skeleton, composed of PCL crystals present at the upper actuation temperature T-high and the remaining glassy PIBMD domains, enabled oriented crystallization upon cooling. The actuation performance of PIBMD-PCL could be tailored by balancing the interplay between actuation and skeleton, but also by varying the quantity of crystalline PIBMD hard domains via the copolymer composition, the applied programming strain, and the choice of T-high. The actuator with 17 mol% PIBMD showed the highest reversible elongation of 11.4% when programmed to a strain of 900% at 50 degrees C. It is anticipated that the presented thermoplastic actuator materials can be applied as modern compression textiles.
Electrical actuation of coated and composite fibers based on poly[ethylene-co-(vinyl acetate)]
(2020)
Robots are typically controlled by electrical signals. Resistive heating is an option to electrically trigger actuation in thermosensitive polymer systems. In this study electrically triggerable poly[ethylene-co-(vinyl acetate)] (PEVA)-based fiber actuators are realized as composite fibers as well as polymer fibers with conductive coatings. In the coated fibers, the core consists of crosslinked PEVA (cPEVA), while the conductive coating shell is achieved via a dip coating procedure with a coating thickness between 10 and 140 mu m. The conductivity of coated fibers sigma = 300-550 S m(-1) is much higher than that of the composite fibers sigma = 5.5 S m(-1). A voltage (U) of 110 V is required to heat 30 cm of coated fiber to a targeted temperature of approximate to 65 degrees C for switching in less than a minute. Cyclic electrical actuation investigations reveal epsilon '(rev) = 5 +/- 1% reversible change in length for coated fibers. The fabrication of such electro-conductive polymeric actuators is suitable for upscaling so that their application potential as artificial muscles can be explored in future studies.
The variation of the molecular architecture of multiblock copolymers has enabled the introduction of functional behaviour and the control of key mechanical properties. In the current study, we explore the synergistic relationship of two structural components in a shape-memory material formed of a multiblock copolymer with crystallizable poly(epsilon-caprolactone) and crystallizable polyfoligo(3S-iso-butylmorpholine-2,5-dione) segments (PCL-PIBMD). The thermal and structural properties of PCL-PIBMD films were compared with PCI.-PU and PMMD-PU investigated by means of DSC, SAXS and WARS measurements. The shape-memory properties were quantified by cyclic, thermomechanical tensile tests, where deformation strains up to 900% were applied for programming PCL-PIBMD films at 50 degrees C. Toluene vapor treatment experiments demonstrated that the temporary shape was fixed mainly by glassy PIBMD domains at strains lower than 600% with the PCL contribution to fixation increasing to 42 +/- 2% at programming strains of 900% This study into the shape-memory mechanism of PCL-PIBMD provides insight into the structure function relation in multiblock copolymers with both crystallizable and glassy switching segments.
Exploiting the tremendous potential of the recently discovered reversible bidirectional shape-memory effect (rbSME) for biomedical applications requires switching temperatures in the physiological range. The recent strategy is based on the reduction of the melting temperature range (T-m) of the actuating oligo(epsilon-caprolactone) (OCL) domains in copolymer networks from OCL and n-butyl acrylate (BA), where the reversible effect can be adjusted to the human body temperature. In addition, it is investigated whether an rbSME in the temperature range close or even above T-m,T-offset (end of the melting transition) can be obtained. Two series of networks having mixtures of OCLs reveal broad T(m)s from 2 degrees C to 50 degrees C and from -10 degrees C to 37 degrees C, respectively. In cyclic, thermomechanical experiments the rbSME can be tailored to display pronounced actuation in a temperature interval between 20 degrees C and 37 degrees C. In this way, the application spectrum of the rbSME can be extended to biomedical applications.
Reversible movements of current polymeric actuators stem from the continuous response to signals from a controlling unit, and subsequently cannot be interrupted without stopping or eliminating the input trigger. Here, we present actuators based on cross-linked blends of two crystallizable polymers capable of pausing their movements in a defined manner upon continuous cyclic heating and cooling. This noncontinuous actuation can be adjusted by varying the applied heating and cooling rates. The feasibility of these devices for technological applications was shown in a 140 cycle experiment of free-standing noncontinuous shape shifts, as well as by various demonstrators.
Crosslinking of thermoplastics is a versatile method to create crystallizable polymer networks, which are of high interest for shape-memory actuators. Here, crosslinked poly(epsilon-caprolactone) thermosets (cPCLs) were prepared from linear starting material, whereby the amount of extractable polymer was varied. Fractions of 5-60 wt % of non-crosslinked polymer chains, which freely interpenetrate the crosslinked network, were achieved leading to differences in the resulting phase of the bulk material. This can be described as "sponge-like" with open or closed compartments depending on the amount of interpenetrating polymer. The crosslinking density and the average network chain length remained in a similar range for all network structures, while the theoretical accessible volume for reptation of the free polymer content is affected. This feature could influence or introduce new functions into the material created by thermomechanical treatment. The effect of interpenetrating PCL in cPCLs on the reversible actuation was analyzed by cyclic, uniaxial tensile tests. Here, high reversible strains of up to Delta epsilon = 24% showed the enhanced actuation performance of networks with a non-crosslinked PCL content of 30 wt % resulting from the crystal formation in the phase of the non-crosslinked PCL and co-crystallization with network structures. Additional functionalities are reprogrammability and self-healing capabilities for networks with high contents of extractable polymer enabling reusability and providing durable actuator materials.
Enzymes can support the synthesis or degradation of biomacromolecules in natural processes. Here, we demonstrate that enzymes can induce a macroscopic-directed movement of microstructured hydrogels following a mechanism that we call a "Jack-in-the-box" effect. The material's design is based on the formation of internal stresses induced by a deformation load on an architectured microscale, which are kinetically frozen by the generation of polyester locking domains, similar to a Jack-in-thebox toy (i.e., a compressed spring stabilized by a closed box lid). To induce the controlled macroscopic movement, the locking domains are equipped with enzyme-specific cleavable bonds (i.e., a box with a lock and key system). As a result of enzymatic reaction, a transformed shape is achieved by the release of internal stresses. There is an increase in entropy in combination with a swelling-supported stretching of polymer chains within the microarchitectured hydrogel (i.e., the encased clown pops-up with a pre-stressed movement when the box is unlocked). This utilization of an enzyme as a physiological stimulus may offer new approaches to create interactive and enzyme-specific materials for different applications such as an optical indicator of the enzyme's presence or actuators and sensors in biotechnology and in fermentation processes.
Polydepsipeptide Block-Stabilized Polyplexes for Efficient Transfection of Primary Human Cells
(2017)
The rational design of a polyplex gene carrier aims to balance maximal effectiveness of nucleic acid transfection into cells with minimal adverse effects. Depsipeptide blocks with an M (n) similar to 5 kDa exhibiting strong physical interactions were conjugated with PEI moieties (2.5 or 10 kDa) to di- and triblock copolymers. Upon nanoparticle formation and complexation with DNA, the resulting polyplexes (sizes typically 60-150 nm) showed remarkable stability compared to PEI-only or lipoplex and facilitated efficient gene delivery. Intracellular trafficking was visualized by observing fluorescence-labeled pDNA and highlighted the effective cytoplasmic uptake of polyplexes and release of DNA to the perinuclear space. Specifically, a triblock copolymer with a middle depsipeptide block and two 10 kDa PEI swallowtail structures mediated the highest levels of transgenic VEGF secretion in mesenchymal stem cells with low cytotoxicity. These nanocarriers form the basis for a delivery platform technology, especially for gene transfer to primary human cells.
Influence of tyrosine-derived moieties and drying conditions on the formation of helices in gelatin
(2011)
The single and triple helical organization of protein chains strongly influences the mechanical properties of gelatin-based materials. A chemical method for obtaining different degrees of helical organization in gelatin is covalent functionalization, while a physical method for achieving the same goal is the variation of the drying conditions of gelatin solutions. Here we explored how the introduction of desaminotyrosine (DAT) and desaminotyrosyl tyrosine (DATT) linked to lysine residues of gelatin influenced the kinetics and thermodynamic equilibrium of the helicalization process of single and triple helices following different drying conditions. Drying at a temperature above. the helix-to-coil transition temperature of gelatin (T > T-c, called nu(short)) generally resulted in gelatins with relatively lower triple helical content (X-c,X-t = 1-2%) than lower temperature drying (T < T-c, called nu(long)) (X-c,X-t = 8-10%), where the DAT(T) functional groups generally disrupted helix formation. While different helical contents affected the thermal transition temperatures only slightly, the mechanical properties were strongly affected for swollen hydrogels (E = 4-13 kPa for samples treated by nu(long) and E = 120-700 kPa for samples treated by nu(short)). This study shows that side group functionalization and different drying conditions are viable options to control the helicalization and macroscopic properties of gelatin-based materials.
High drug loads of nanoparticles are essential to efficiently provide a desired dosage in the required timeframe, however, these conditions may not be reached with so far established degradable matrices. Our conceptual approach for increasing the drug load is based on strengthening the affinity between drug and matrix in combination with stabilizing drug-matrix-hybrids through strong intermolecular matrix interactions. Here, a method for designing such complex drug-matrix hybrids is introduced employing computational methods (molecular dynamics and docking) as well as experimental studies (affinity, drug loading and distribution, drug release from films and nanoparticles). As model system, dexamethasone (DXM), relevant for the treatment of inflammatory diseases, in combination with poly[(rac-lactide)-co-glycolide] (PLGA) as standard degradable matrix or oligo[(3-(S)-sec-butyl) morpholine-2,5-dione] diol (OBMD) as matrix with hypothesized stronger interaction with DXM were investigated. Docking studies predicted higher affinity of DXM to OBMD than PLGA and displayed amide bond participation in hydrogen bonding with OBMD. Experimental investigations on films and nanoparticles, i.e. matrices of different shapes and sizes, confirmed this phenomenon as shown e.g. by a similar to 10 times higher solid state solubility of DXM in OBMD than in PLGA. DXM-loaded particles of similar to 150 nm prepared by nanoprecipitation in aqueous environment had a drug loading (DL) up to 16 times higher when employing OBMD as matrix compared to PLGA carriers due to enhanced drug retention in the OBMD phase. Importantly, drug relase periods were not altered as the release from films and particles was mainly ruled by the diffusion length as well as matrix degradation rather than the matrix type, which can be assigned to water diffusing into the matrix and breaking up of drug-matrix hydrogen bonds. Overall, the presented design and fabrication scheme showed predictive power and might universally enable the screening of drug/matrix interactions particularly to expand the oligodepsipeptide platform technology, e.g. by varying the depsipeptide side chains, for drug carrier and release systems.
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.
In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p(SVC) = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r(s) = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies.
While click chemistry reactions for biopolymer network formation are attractive as the defined reactions may allow good control of the network formation and enable subsequent functionalization, tailoring of gelatin network properties over a wide range of mechanical properties has yet to be shown. Here, it is demonstrated that copper-catalyzed alkyne-azide cycloaddition of alkyne functionalized gelatin with diazides gave hydrogel networks with properties tailorable by the ratio of diazide to gelatin and diazide rigidity. 4,4′-diazido-2,2′-stilbenedisulfonic acid, which has been used as rigid crosslinker, yielded hydrogels with Young’s moduli E of 50–390 kPa and swelling degrees Q of 150–250 vol.%, while the more flexible 1,8-diazidooctane resulted in hydrogels with E = 125–280 kPa and Q = 225–470 vol.%. Storage moduli could be varied by two orders of magnitude (G′ = 100–20,000 Pa). An indirect cytotoxicity test did not show cytotoxic properties. Even when employing 1:1 ratios of alkyne and azide moieties, the hydrogels were shown to contain both, unreacted alkyne groups on the gelatin backbone as well as dangling chains carrying azide groups as shown by reaction with functionalized fluorescein. The free groups, which can be tailored by the employed ratio of the reactants, are accessible for covalent attachment of drugs, as was demonstrated by functionalization with dexamethasone. The sequential network formation and functionalization with click chemistry allows access to multifunctional materials relevant for medical applications.
Artikel: Manfred Voigts: Zur Emeritierung von Prof. Dr. Karl E. Grözinger Admiel Kosman / Anat Sharbat: “Two Women Who Were Sporting with Each Other”: A Re-examination of the Halakhic Approaches to Lesbianism as a Touchstone for Homosexuality in General Francesca Y. Albertini: Sterbehilfe aus jüdischer Sicht: Eine Einführung Rabbiner Dr. med. Verl. Israel M. Levinger: Schechita und Kaschrut – Jüdischer Standpunkt zum Schlachten von Tieren Wolfgang Wieshaider: Jüdischer Friedhof und staatliches Recht Chayim Schell-Apacik: Genetische Untersuchungen und Schwangerschaftsabbruch im Kontext jüdischer Ethik am Beispiel der Tay-Sachs-Erkrankung Manfred Voigts / Andreas Kennecke: Euchel, Mendelssohn, Herder und Andere Tagungsberichte: “I Will Sing and Make Music”. Jewish Music and Musicians Throughout the Ages. The Nineteenth Annual Klutznick-Harris Symposium. Creighton University, Omaha. Nebraska. 29.10. -30.10.2006. (Robert Jütte) Dr. Eleonora Bergman: Polish Wooden Synagogues: State of Research (Ulrich Knufinke) Rezensionen: Encyclopaedia Judaica. Second Edition. Hrsg. von Fred Skolnik (Alexander Dubrau/Nathanael Riemer) Menahem I. Kahana: Sifre Zuta Deuteronomy. Citations from a New Tannaitic Midrash (Alexander Dubrau) Carol Bakhos (Hg.): Current Trends in the Study of Midrash (Alexander Dubrau) Shmuel Safrai ז"ל /Zeev Safrai/Joshua Schwartz/Peter J. Tomson (Hg.): The Literature of the Sages. Second Part: Midrash and Targum, Liturgy, Poetry, Mysticism, Contracts, Inscriptions, Ancient Science and the Languages of Rabbinic Literature (Alexander Dubrau) Ronen Reichman (Hg.): Der Odem des Menschen ist eine Leuchte des Herrn (Tamara Or) Raphael Arnold: Spracharkaden. Die Sprache der sephardischen Juden in Italien im 16. und 17. Jahrhundert (Robert Jütte) Johann Lorenz Schmidlin: Pictura Docens. Hrsg. und übersetzt von Fritz Felgentreu und Widu-Wolfgang Ehlers (Daniel Jütte) Salomon Ibn Verga: Schevet Jehuda. Ein Buch über das Leiden des jüdischen Volkes im Exil. Hrsg., eingel. und mit einem Nachwort zur Geschichtsdeutung Salomo Ibn Vergas versehen von Sina Rauschenbach (Nathanael Riemer) Jutta Schumacher (Hg.): Sefer Mišlė Šu´olim (Buch der Fuchsfabeln) von Jakob Koppelmann. In Originalschrift und Transkription hrsg. und kommentiert von Jutta Schumacher (Nathanael Riemer) Glikl. Memoires 1691-1719. Edited and Translated [ins Hebräische] from the Yiddish by Chava Turniansky (Elvira Grözinger) Manfred Voigts: Die deutsch-jüdische Symbiose. Zwischen deutschem Sonderweg und Idee Europa (Elvira Grözinger) Gerhard Taddey (Hg.): Geschützt, geduldet, gleichberechtigt. Die Juden im baden-württembergischen Franken vom 17. Jahrhundert bis zum Ende des Kaiserreichs (Stefan Lang) Marion Linhardt: Residenzstadt und Metropole. Zu einer kulturellen Topographie des Wiener Unterhaltungstheaters (Daniel Jütte) Margarete Grandner/Edith Saurer (Hg.): Geschlecht, Religion und Engagement. Die jüdischen Frauenbewegungen im deutschsprachigen Raum (Rebekka Denz) Mariana Hausleitner: Deutsche und Juden in Bessarabien 1814-1941. Zur Minderheitenpolitik Russlands und Großrumäniens (Elvira Grözinger) Marline Otte: Jewish Identities in German Popular Entertainment 1890-1933 (Anat Feinberg) Doris A. Karner: Lachen unter Tränen. Jüdisches Theater in Ostgalizien und der Bukowina (Elvira Grözinger) Tazuko Takebayashi: Zwischen den Kulturen. Deutsches,Tschechisches und Jüdisches in der deutschsprachigen Literatur aus Prag (Manfred Voigts) Anna Shternshis: Soviet and Kosher. Jewish Popular Culture in the Soviet Union 1923-1939 (Elvira Grözinger) Brigitte Mihok (Hg.): Ungarn und der Holocaust. Kollaboration, Rettung und Trauma (Joel Berger) Willy Cohn: Kein Recht, nirgends. Tagebuch vom Untergang des Breslauer Judentums 1933-1941 (Anat Feinberg) Natan Shahar: Shir Shir ale na. Toldot ha-Semer ha-ivri (Anat Feinberg)