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We present an electrochemical MIP sensor for tamoxifen (TAM)-a nonsteroidal anti-estrogen-which is based on the electropolymerisation of an O-phenylenediamine. resorcinol mixture directly on the electrode surface in the presence of the template molecule. Up to now only. bulk. MIPs for TAM have been described in literature, which are applied for separation in chromatography columns. Electro-polymerisation of the monomers in the presence of TAM generated a film which completely suppressed the reduction of ferricyanide. Removal of the template gave a markedly increased ferricyanide signal, which was again suppressed after rebinding as expected for filling of the cavities by target binding. The decrease of the ferricyanide peak of the MIP electrode depended linearly on the TAM concentration between 1 and 100 nM. The TAM-imprinted electrode showed a 2.3 times higher recognition of the template molecule itself as compared to its metabolite 4-hydroxytamoxifen and no cross-reactivity with the anticancer drug doxorubucin was found. Measurements at + 1.1 V caused a fouling of the electrode surface, whilst pretreatment of TAM with peroxide in presence of HRP generated an oxidation product which was reducible at 0 mV, thus circumventing the polymer formation and electrochemical interferences.
The structures and synthesis of polyzwitterions ("polybetaines") are reviewed, emphasizing the literature of the past decade. Particular attention is given to the general challenges faced, and to successful strategies to obtain polymers with a true balance of permanent cationic and anionic groups, thus resulting in an overall zero charge. Also, the progress due to applying new methodologies from general polymer synthesis, such as controlled polymerization methods or the use of "click" chemical reactions is presented. Furthermore, the emerging topic of responsive ("smart") polyzwitterions is addressed. The considerations and critical discussions are illustrated by typical examples.
Dimensional psychiatry
(2014)
Hägele, Claudia ; Schlagenhauf, Florian ; Rapp, Michael Armin ; Sterzer, Philipp ; Beck, Anne ; Bermpohl, Felix ; Stoy, Meline ; Ströhle, Andreas ; Wittchen, Hans-Ulrich ; Dolan, Raymond J. ; Heinz, Andreas
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.
Background
Nucleic acid amplification is the most sensitive and specific method to detect Plasmodium falciparum. However the polymerase chain reaction remains laboratory-based and has to be conducted by trained personnel. Furthermore, the power dependency for the thermocycling process and the costly equipment necessary for the read-out are difficult to cover in resource-limited settings. This study aims to develop and evaluate a combination of isothermal nucleic acid amplification and simple lateral flow dipstick detection of the malaria parasite for point-of-care testing.
Methods
A specific fragment of the 18S rRNA gene of P. falciparum was amplified in 10 min at a constant 38°C using the isothermal recombinase polymerase amplification (RPA) method. With a unique probe system added to the reaction solution, the amplification product can be visualized on a simple lateral flow strip without further labelling. The combination of these methods was tested for sensitivity and specificity with various Plasmodium and other protozoa/bacterial strains, as well as with human DNA. Additional investigations were conducted to analyse the temperature optimum, reaction speed and robustness of this assay.
Results
The lateral flow RPA (LF-RPA) assay exhibited a high sensitivity and specificity. Experiments confirmed a detection limit as low as 100 fg of genomic P. falciparum DNA, corresponding to a sensitivity of approximately four parasites per reaction. All investigated P. falciparum strains (n = 77) were positively tested while all of the total 11 non-Plasmodium samples, showed a negative test result. The enzymatic reaction can be conducted under a broad range of conditions from 30-45°C with high inhibitory concentration of known PCR inhibitors. A time to result of 15 min from start of the reaction to read-out was determined.
Conclusions
Combining the isothermal RPA and the lateral flow detection is an approach to improve molecular diagnostic for P. falciparum in resource-limited settings. The system requires none or only little instrumentation for the nucleic acid amplification reaction and the read-out is possible with the naked eye. Showing the same sensitivity and specificity as comparable diagnostic methods but simultaneously increasing reaction speed and dramatically reducing assay requirements, the method has potential to become a true point-of-care test for the malaria parasite.
Flood damage has increased significantly and is expected to rise further in many parts of the world. For assessing potential changes in flood risk, this paper presents an integrated model chain quantifying flood hazards and losses while considering climate and land use changes. In the case study region, risk estimates for the present and the near future illustrate that changes in flood risk by 2030 are relatively low compared to historic periods. While the impact of climate change on the flood hazard and risk by 2030 is slight or negligible, strong urbanisation associated with economic growth contributes to a remarkable increase in flood risk. Therefore, it is recommended to frequently consider land use scenarios and economic developments when assessing future flood risks. Further, an adapted and sustainable risk management is necessary to encounter rising flood losses, in which non-structural measures are becoming more and more important. The case study demonstrates that adaptation by non-structural measures such as stricter land use regulations or enhancement of private precaution is capable of reducing flood risk by around 30 %. Ignoring flood risks, in contrast, always leads to further increasing losses-with our assumptions by 17 %. These findings underline that private precaution and land use regulation could be taken into account as low cost adaptation strategies to global climate change in many flood prone areas. Since such measures reduce flood risk regardless of climate or land use changes, they can also be recommended as no-regret measures.
The Runge-Kutta type regularization method was recently proposed as a potent tool for the iterative solution of nonlinear ill-posed problems. In this paper we analyze the applicability of this regularization method for solving inverse problems arising in atmospheric remote sensing, particularly for the retrieval of spheroidal particle distribution. Our numerical simulations reveal that the Runge-Kutta type regularization method is able to retrieve two-dimensional particle distributions using optical backscatter and extinction coefficient profiles, as well as depolarization information.
Stress drop is a key factor in earthquake mechanics and engineering seismology. However, stress drop calculations based on fault slip can be significantly biased, particularly due to subjectively determined smoothing conditions in the traditional least-square slip inversion. In this study, we introduce a mechanically constrained Bayesian approach to simultaneously invert for fault slip and stress drop based on geodetic measurements. A Gaussian distribution for stress drop is implemented in the inversion as a prior. We have done several synthetic tests to evaluate the stability and reliability of the inversion approach, considering different fault discretization, fault geometries, utilized datasets, and variability of the slip direction, respectively. We finally apply the approach to the 2010 M8.8 Maule earthquake and invert for the coseismic slip and stress drop simultaneously. Two fault geometries from the literature are tested. Our results indicate that the derived slip models based on both fault geometries are similar, showing major slip north of the hypocenter and relatively weak slip in the south, as indicated in the slip models of other studies. The derived mean stress drop is 5-6 MPa, which is close to the stress drop of similar to 7 MPa that was independently determined according to force balance in this region Luttrell et al. (J Geophys Res, 2011). These findings indicate that stress drop values can be consistently extracted from geodetic data.
In a recent paper, the Lefschetz number for endomorphisms (modulo trace class operators) of sequences of trace class curvature was introduced. We show that this is a well defined, canonical extension of the classical Lefschetz number and establish the homotopy invariance of this number. Moreover, we apply the results to show that the Lefschetz fixed point formula holds for geometric quasiendomorphisms of elliptic quasicomplexes.
This reference paper describes the sampling and contents of the IZA Evaluation Dataset Survey and outlines its vast potential for research in labor economics. The data have been part of a unique IZA project to connect administrative data from the German Federal Employment Agency with innovative survey data to study the out-mobility of individuals to work. This study makes the survey available to the research community as a Scientific Use File by explaining the development, structure, and access to the data. Furthermore, it also summarizes previous findings with the survey data.
Friedel, Eva ; Schlagenhauf, Florian ; Beck, Anne ; Dolan, Raymond J. ; Huys, Quentin J. M. ; Rapp, Michael Armin ; Heinz, Andreas
Fluid intelligence (fluid IQ), defined as the capacity for rapid problem solving and behavioral adaptation, is known to be modulated by learning and experience. Both stressful life events (SLES) and neural correlates of learning [specifically, a key mediator of adaptive learning in the brain, namely the ventral striatal representation of prediction errors (PE)] have been shown to be associated with individual differences in fluid IQ. Here, we examine the interaction between adaptive learning signals (using a well-characterized probabilistic reversal learning task in combination with fMRI) and SLES on fluid IQ measures. We find that the correlation between ventral striatal BOLD PE and fluid IQ, which we have previously reported, is quantitatively modulated by the amount of reported SLES. Thus, after experiencing adversity, basic neuronal learning signatures appear to align more closely with a general measure of flexible learning (fluid IQ), a finding complementing studies on the effects of acute stress on learning. The results suggest that an understanding of the neurobiological correlates of trait variables like fluid IQ needs to take socioemotional influences such as chronic stress into account.
The Arabidopsis Kinome
(2014)
Zulawski, Monika ; Schulze, Gunnar ; Braginets, Rostyslav ; Hartmann, Stefanie ; Schulze, Waltraud X
Background
Protein kinases constitute a particularly large protein family in Arabidopsis with important functions in cellular signal transduction networks. At the same time Arabidopsis is a model plant with high frequencies of gene duplications. Here, we have conducted a systematic analysis of the Arabidopsis kinase complement, the kinome, with particular focus on gene duplication events. We matched Arabidopsis proteins to a Hidden-Markov Model of eukaryotic kinases and computed a phylogeny of 942 Arabidopsis protein kinase domains and mapped their origin by gene duplication.
Results
The phylogeny showed two major clades of receptor kinases and soluble kinases, each of which was divided into functional subclades. Based on this phylogeny, association of yet uncharacterized kinases to families was possible which extended functional annotation of unknowns. Classification of gene duplications within these protein kinases revealed that representatives of cytosolic subfamilies showed a tendency to maintain segmentally duplicated genes, while some subfamilies of the receptor kinases were enriched for tandem duplicates. Although functional diversification is observed throughout most subfamilies, some instances of functional conservation among genes transposed from the same ancestor were observed. In general, a significant enrichment of essential genes was found among genes encoding for protein kinases.
Conclusions
The inferred phylogeny allowed classification and annotation of yet uncharacterized kinases. The prediction and analysis of syntenic blocks and duplication events within gene families of interest can be used to link functional biology to insights from an evolutionary viewpoint. The approach undertaken here can be applied to any gene family in any organism with an annotated genome.
Background
In the past, plyometric training (PT) has been predominantly performed on stable surfaces. The purpose of this pilot study was to examine effects of a 7-week lower body PT on stable vs. unstable surfaces. This type of exercise condition may be denoted as metastable equilibrium.
Methods
Thirty-three physically active male sport science students (age: 24.1 ± 3.8 years) were randomly assigned to a PT group (n = 13) exercising on stable (STAB) and a PT group (n = 20) on unstable surfaces (INST). Both groups trained countermovement jumps, drop jumps, and practiced a hurdle jump course. In addition, high bar squats were performed. Physical fitness tests on stable surfaces (hexagonal obstacle test, countermovement jump, hurdle drop jump, left-right hop, dynamic and static balance tests, and leg extension strength) were used to examine the training effects.
Results
Significant main effects of time (ANOVA) were found for the countermovement jump, hurdle drop jump, hexagonal test, dynamic balance, and leg extension strength. A significant interaction of time and training mode was detected for the countermovement jump in favor of the INST group. No significant improvements were evident for either group in the left-right hop and in the static balance test.
Conclusions
These results show that lower body PT on unstable surfaces is a safe and efficient way to improve physical performance on stable surfaces.
This paper reports a problematic case of unequivocally evidencing participant orientation to the projective force of some turn-initial demonstrative wh-clefts (DCs) within the framework of Conversation Analysis (CA) and Interactional Linguistics (IL). Conducting rhythmic analyses appears helpful in this regard, in that they disclose rhythmic regularities which suggest a speaker's orientation towards a projected turn continuation. In this particular case, rhythmic analyses can therefore be shown to meaningfully complement sequential analyses and analyses of turn-design, so as to gather additional evidence for participant orientations. In conclusion, I will point to possibly more extensive relations between rhythmicity and projection and proffer a tentative outlook for the usability of rhythmic analyses as an analytic tool in CA and IL.
Morel, T. ; Castro, Norberto ; Fossati, Luca ; Hubrig, Swetlana ; Langer, N. ; Przybilla, Norbert ; Schöller, Markus ; Carroll, Thorsten Anthony ; Ilyin, Ilya ; Irrgang, Andreas ; Oskinova, Lida ; Schneider, Fabian R. N. ; Simon Díaz, Sergio ; Briquet, Maryline ; González, Jean-Francois ; Kharchenko, Nina ; Nieva, M.-F. ; Scholz, Ralf-Dieter ; de Koter, Alexander ; Hamann, Wolf-Rainer ; Herrero, Artemio ; Maíz Apellániz, Jesus ; Sana, Hugues ; Arlt, Rainer ; Barbá, Rodolfo H. ; Dufton, Polly ; Kholtygin, Alexander ; Mathys, Gautier ; Piskunov, Anatoly E. ; Reisenegger, Andreas ; Spruit, H. ; Yoon, S.-C.
The B fields in OB stars (BOB) survey is an ESO large programme collecting spectropolarimetric observations for a large number of early-type stars in order to study the occurrence rate, properties, and ultimately the origin of magnetic fields in massive stars. As of July 2014, a total of 98 objects were observed over 20 nights with FORS2 and HARPSpol. Our preliminary results indicate that the fraction of magnetic OB stars with an organised, detectable field is low. This conclusion, now independently reached by two different surveys, has profound implications for any theoretical model attempting to explain the field formation in these objects. We discuss in this contribution some important issues addressed by our observations (e.g., the lower bound of the field strength) and the discovery of some remarkable objects.
Nested application conditions generalise the well-known negative application conditions and are important for several application domains. In this paper, we present Local Church-Rosser, Parallelism, Concurrency and Amalgamation Theorems for rules with nested application conditions in the framework of M-adhesive categories, where M-adhesive categories are slightly more general than weak adhesive high-level replacement categories. Most of the proofs are based on the corresponding statements for rules without application conditions and two shift lemmas stating that nested application conditions can be shifted over morphisms and rules.
A key problem in automatic annotation of historical corpora is inconsistent spelling. Because the spelling of some word forms can differ between texts, a language model trained on already annotated treebanks may fail to recognize known word forms due to differences in spelling. In the present work, we explore the feasibility of an unsupervised method for spelling-adjustment for the purpose of improved part of speech (POS) tagging. To this end, we present a method for spelling normalization based on weighted edit distances, which exploits within-text spelling variation. We then evaluate the improvement in taging accuracy resulting from between-texts spelling normalization in two tagging experiments on several Early New High German (ENHG) texts.
Recently, interest in collecting and mining large sets of educational data on student background and performance to conduct research on learning and instruction has developed as an area generally referred to as learning analytics. Higher education leaders are recognising the value of learning analytics for improving not only learning and teaching but also the entire educational arena. However, theoretical concepts and empirical evidence need to be generated within the fast evolving field of learning analytics. In this paper, we introduce a holistic learning analytics framework. Based on this framework, student, learning, and curriculum profiles have been developed which include relevant static and dynamic parameters for facilitating the learning analytics framework. Based on the theoretical model, an empirical study was conducted to empirically validate the parameters included in the student profile. The paper concludes with practical implications and issues for future research.
Portal Wissen = Time
(2014)
Wilkens, Martin ; Sütterlin, Sabine ; Kampe, Heike ; Eckardt, Barbara ; Jäger, Sophie ; Zimmermann, Matthias
“What then is time?”, Augustine of Hippo sighs melancholically in Book XI of “Confessions” and continues, “If no one asks me, I know; if I want to explain it to a questioner, I don’t know.” Even today, 1584 years after Augustine, time still appears mysterious. Treatises about the essence of time fill whole libraries – and this magazine.
However, questions of essence are alien to modern sciences. Time is – at least in physics – unproblematic: “Time is defined so that motion looks simple”, briefly and prosaically phrased, waves goodbye to Augustine’s riddle and to the Newtonian concept of absolute time, whose mathematical flow can only be approximately recorded with earthly instruments anyway.
In our everyday language and even in science we still speak of the flow of time but time has not been a natural condition for quite a while now. It is rather a conventional order parameter for change and movement. Processes are arranged by using a class of processes as a counting system in order to compare other processes and to organize them with the help of the temporary categories “before”, “during”, and “after”.
During Galileo’s time one’s own pulse was seen as the time standard for the flight of cannon balls. More sophisticated examination methods later made this seem too impractical. The distance-time diagrams of free-flying cannon balls turned out to be rather imprecise, difficult to replicate, and in no way “simple”. Nowadays, we use cesium atoms. A process is said to take one second when a caesium-133 atom completes 9,192,631,770 periods of the radiation corresponding to the transition between two hyperfine levels of the ground state. A meter is the length of the path travelled by light in a vacuum in exactly 1/299,792,458 of a second. Fortunately, these data are hard-coded in the Global Positioning System GPS so users do not have to reenter them each time they want to know where they are. In the future, however, they might have to download an app because the time standard has been replaced by sophisticated transitions to ytterbium.
The conventional character of the time concept should not tempt us to believe that everything is somehow relative and, as a result, arbitrary. The relation of one’s own pulse to an atomic clock is absolute and as real as the relation of an hourglass to the path of the sun. The exact sciences are relational sciences. They are not about the thing-initself as Newton and Kant dreamt, but rather about relations as Leibniz and, later, Mach pointed out.
It is not surprising that the physical time standard turned out to be rather impractical for other scientists. The psychology of time perception tells us – and you will all agree – that the perceived age is quite different from the physical age. The older we get the shorter the years seem. If we simply assume that perceived duration is inversely related to physical age and that a 20-year old also perceives a physical year as a psychological one, we come to the surprising discovery that at 90 years we are 90 years old. With an assumed life expectancy of 90 years, 67% (or 82%) of your felt lifetime is behind you at the age of 20 (or 40) physical years.
Before we start to wallow in melancholy in the face of the “relativity of time”, let me again quote Augustine. “But at any rate this much I dare affirm I know: that if nothing passed there would be no past time; if nothing were approaching, there would be no future time; if nothing were, there would be no present time.” Well, – or as Bob Dylan sings “The times they are a-changin”.
I wish you an exciting time reading this issue.
Prof. Martin Wilkens
Professor of Quantum Optics
Portal Wissen = Believe
(2014)
Hafner, Johann Evangelist ; Zimmermann, Matthias ; Rost, Sophia ; Sütterlin, Sabine ; Kampe, Heike ; Horn-Conrad, Antje ; Jäger, Sophie ; Eckardt, Barbara ; Mangelsdorf, Birgit
People want to know what is real. Children enjoy listening to a story but when my children were about four years old they started asking whether the story really happened or was just invented. Likewise, only on a higher level, our academic curiosity is fuelled by our interest in knowing what is real. When we analyze poetic texts or dreams we are trying to distinguish between the facts (e.g. neurological ones or linguistic structures) and merely assumed influences. Ideally we can present results that were logically understood by others and that we can repeat empirically. But in most cases this is not possible. We cannot read every book and cannot look through every microscope, not even within our own discipline. In the world we live in we depend on trusting the information of others, like how to get to the train station or what the weather is like in Ulaanbataar. This is why we are used to believing others, our friends or the news anchors. This is not a childish behavior but a necessity. Of course, it is risky because they could all be lying to us, like in a Truman Show situation. The only time we are able to know that we are in reality is when we transcend our selfconsciousness and when we accept two propositions: first, that we are not only objects but also subjects in the consciousness of others and second that our dialogic relations are again observed by a third party that is not part of this intersubjective world.
For religious people this is “belief” - belief as the assumption that all human relations only become real, serious and beyond any doubt if they know they are under the eyes of God. Only before Him something is in itself and not only “for me” or “among us”. That is why biblical language distinguishes between three forms of belief: the relationship with the world of things (“to believe that”), the relationship to the world of subjects (“to believe somebody”) and the assumption of a subjective supernatural reality (“to believe in” or “faith”). From an academic point of view belief is a holistic hypothesis. Belief is not the opposite of knowledge but it is the attempt to save reality from doubt by comprehending the fragile empirical world as an expression of a stable transcendent world.
When I talk to students they often ask not only about what I know but what I believe. As a professor for Religious Studies and a believing Catholic I am caught in the middle. On the one hand, it is my duty as a professor to doubt everything, i.e. to attribute each religious text to its historical context and sociological functions. On the other hand, I, as a Christian, consider certain religious documents, in my case the Bible, an interpretable but nevertheless irreversible, revealed text about the origin of reality. On weekdays the New Testament is a collection of ancient writings among many others, on Sundays it is the revelation. You can make a clear distinction between these two perspectives but it is difficult to decide whether doubt or belief is more real.
This issue of “Portal Wissen” explores this dual relationship of belief. What is the attitude of science towards belief – is it a religious one? Where does science bring things to light that we can hardly believe or that make us believe (again)? What happens if research clears up erroneous assumptions or myths? Is science able to investigate things that are convincing but inexplicable? How can it maintain its credibility and develop even so?
These questions appear again and again in the contributions of this “Portal Wissen”. They form a manifold, exciting and surprising picture of the research projects and academics at the University of Potsdam. Believe me, it will be an enjoyable read.
Prof. Johann Hafner
Professor of Religious Studies with Focus on Christianity Dean of the Faculty of Arts