Occasion setters determine responses of putative dopamine neurons to discriminative stimuli

Midbrain dopamine (DA) neurons are involved in the processing of rewards and reward-predicting stimuli, possibly analogous to reinforcement learning reward prediction errors. Here we studied the activity of putative DA neurons (n=41) recorded in the ventral tegmental area of rats (n=6) performing a behavioural task involving occasion setting. In this task an occasion setter (OS) indicated that the relationship between a discriminative stimulus (DS) and reinforcement is in effect, so that reinforcement of bar pressing occurred only after the OS (tone or houselight) was followed by the DS (houselight or tone). We found that responses of putative DA cells to the DS were enhanced when preceded by the OS, as were behavioural responses to obtain rewards. Surprisingly though, we did not find a population response of putative DA neurons to the OS, contrary to predictions of standard temporal-difference models of DA neurons. However, despite the absence of a population response, putative DA neurons exhibited a heterogeneous response on a single unit level, so that some units increased and others decreased their activity as a response to the OS. Similarly, putative non-DA cells did not respond to the DS on a population level, but with heterogeneous responses on a single unit level. The heterogeneity in the responses of putative DA cells may reflect how DA neurons encode context and point to local differences in DA signalling

The tumour-Clostridium phenomenon: 50 years of developmental research

The tumour-Clostridium phenomenon describes the specific affinity of spore forming anaerobes to tumour growth. The discovery of strictly intratumoral tetanus toxicoinfections in tumour-bearing mice after intravenous spore administration gave the impulse to search for non-toxic clostridial isolates with tumour-selective properties for clostridial biotherapy, i.e. oncolysis, as well as serologic tumour diagnostics without any toxic side-effects. Systematic studies of the oncolytic process and its variables on diverse experimental tumours and laboratory animals revealed that tumour liquefaction, converting necrotic tumour parts to putrid abscesses filled with masses of clostridial forms, stops sharply at the viable rim of the blood-supplied tumour tissue. Similar results were observed in clinical trials, particular of gliomas. Before oncolysis is initiated, the first stage of clostridial multi-plication in the vascularized tissue is inducing a humoural immune response, preceded by phagocytic activity. The majority of tumour-bearing laboratory and domestic animals, so far tested serologically, clinical cancer patients as well, responded with anti-rod antibodies and, independently, anti-spore antibodies. Oncolytic and non-oncolytic Clostridia were equally immunogenic. During the early, immunizing period of clostridial proliferation, analytical tumour-tetanus experiments were focused on potential relations between tumour growth kinetics and rod proliferation. Based on realistic growth models and target principles, computer simulations could reproduce the results, i.e. cumulative curves of tetanus lethality in groups of mice. Thus, crucial assumptions of the mathematical model were ex post confirmed by further experiments. Our working hypothesis concentrates on temporally hypoxic micro-niches close to a pre-mitotic cell with enhanced oxygen demand which can be utilized by anaerobes (randomly) located there. As early immune reactions to clostridial antigens via phagocytosis and humoural immune response will do without invasion in necrobiotic avascular tumour areas, the pacemaker model of tumour-Clostridium interplay extends the scope of genetically engineered Clostridia to early treatment of metastases. Thus, novel concepts, such as 'Clostridia-directed enzyme prodrug-therapy' and 'Combined bacteriolytic therapy', together with immune activation, can come into play

Development of analysis techniques for the use of aerial photography in the monitoring of intertidal mussel beds and oyster beds

This project aimed at improving the analysis techniques of aerial photography for mussel bed recognition and mapping. In this project two techniques were tested; recognition and mapping by human eye and recognition and mapping by automatic detection software. The detection with the human eye was tested in two ways. The first test considered recognition of mussel beds in an area were contours of the previous year were available. The second test concerned a blind recognition test without any knowledge on previous locations of mussel beds

Creation and Growth of Components in a Random Hypergraph Process

Denote by an $\ell$-component a connected $b$-uniform hypergraph with $k$ edges and $k(b-1) - \ell$ vertices. We prove that the expected number of creations of $\ell$-component during a random hypergraph process tends to 1 as $\ell$ and $b$ tend to $\infty$ with the total number of vertices $n$ such that $\ell = o(\sqrt[3]{\frac{n}{b}})$. Under the same conditions, we also show that the expected number of vertices that ever belong to an $\ell$-component is approximately $12^{1/3} (b-1)^{1/3} \ell^{1/3} n^{2/3}$. As an immediate consequence, it follows that with high probability the largest $\ell$-component during the process is of size $O((b-1)^{1/3} \ell^{1/3} n^{2/3})$. Our results give insight about the size of giant components inside the phase transition of random hypergraphs.Comment: R\'{e}sum\'{e} \'{e}tend

Glauber - Gribov approach for DIS on nuclei in N=4 SYM

In this paper the Glauber-Gribov approach for deep-inelastic scattering (DIS) with nuclei is developed in N=4 SYM. It is shown that the amplitude displays the same general properties, such as geometrical scaling, as is the case in the high density QCD approach. We found that the quantum effects leading to the graviton reggeization, give rise to an imaginary part of the nucleon amplitude, which makes the DIS in N=4 SYM almost identical to the one expected in high density QCD. We concluded that the impact parameter dependence of the nucleon amplitude is very essential for N=4 SYM, and the entire kinematic region can be divided into three regions which are discussed in the paper. We revisited the dipole description for DIS and proposed a new renormalized Lagrangian for the shock wave formalism which reproduces the Glauber-Gribov approach in a certain kinematic region. However the saturation momentum turns out to be independent of energy, as it has been discussed by Albacete, Kovchegov and Taliotis. We discuss the physical meaning of such a saturation momentum $Q_s(A)$ and argue that one can consider only $Q>Q_s(A)$ within the shock wave approximation.Comment: 40pp.,9 figures in eps file

Distinct functions for anterograde and retrograde sorting of SORLA in amyloidogenic processes in the brain

SORLA is a neuronal sorting receptor implicated both in sporadic and familial forms of AD. SORLA reduces the amyloidogenic burden by two mechanisms, either by rerouting internalized APP molecules from endosomes to the trans-Golgi network (TGN) to prevent proteolytic processing or by directing newly produced Aβ to lysosomes for catabolism. Studies in cell lines suggested that the interaction of SORLA with cytosolic adaptors retromer and GGA is required for receptor sorting to and from the TGN. However, the relevance of anterograde or retrograde trafficking for SORLA activity in vivo remained largely unexplored. Here, we generated mouse models expressing SORLA variants lacking binding sites for GGA or retromer to query this concept in the brain. Disruption of retromer binding resulted in a retrograde-sorting defect with accumulation of SORLA in endosomes and depletion from the TGN, and in an overall enhanced APP processing. In contrast, disruption of the GGA interaction did not impact APP processing but caused increased brain Aβ levels, a mechanism attributed to a defect in anterograde lysosomal targeting of Aβ. Our findings substantiated the significance of adaptor-mediated sorting for SORLA activities in vivo, and they uncovered that anterograde and retrograde sorting paths may serve discrete receptor functions in amyloidogenic processes

Cloud Advection and Spatial Variability of Solar Irradiance

A model for predicting smoothing of solar irradiance by spatially distributed collectors was analyzed. The model assumed cloud advection dominates the relationship between sites and represented the distributed plant with a transfer function. The transfer function representing the smoothing effect was shown to be the Fourier transform of the plant's spatial distribution, and as such, the plant represents a low-pass filter. Comparison with measured data from the HOPE-Melpitz campaign showed that the model is able to replicate dynamics present in the measured plant transfer function and showed good frequency domain agreement. Generalization of the approach is needed for broader applicability, as the current analysis only validated against one-dimensional, advection dominated conditions. However, the approach warrants further study as it has demonstrated an ability to reveal frequency domain characteristics not currently reflected by state-of-the-art models

Effects of deliberate reflection on students' engagement in learning and learning outcomes

Context Reflection in practice is assumed to enhance interest in knowing more about a topic, increasing engagement in learning and learning outcomes. However, this claim lacks empirical evidence, particularly in medical education. The authors investigated the effects of deliberate reflection upon clinical cases on medical students’ engagement in a learning activity and learning outcomes. Methods A three‐task (diagnostic task; learning activity; test) experiment was conducted in August 2017. Seventy‐two fourth‐year students from UNIFENAS‐BH Medical School, Brazil, diagnosed two clinical cases with jaundice as the chief complaint, either by following a deliberate reflection procedure or making differential diagnosis. Subsequently, all participants received the same study material on the diagnosis of jaundice. Finally, they took a recall test on the study material. Outcome measurements were study time and test scores. Results There was a significant effect of experimental condition on students’ engagement in the learning activity and on learning outcomes. Students who deliberately reflected upon the cases invested more time in studying the material than those who made a differential diagnosis (respectively, mean = 254.97, standard deviation = 115.45 versus mean = 194.96, standard deviation = 111.68; p = 0.02; d = 0.53). Deliberate reflection was also related to higher scores in the test relative to differential diagnosis (respectively, mean = 22.08, standard deviation = 14.94 versus mean = 15.75, standard deviation = 9.24; p = 0.03; d = 0.51). Medium effect sizes (Cohen's d) were observed in both measurements. Conclusions Relative to making differential diagnosis, deliberate reflection while diagnosing cases fostered medical students’ engagement in learning and increased learning outcomes. Teachers can employ this relatively easy procedure, possibly both with simulated and real scenarios, to motivate their students and help them expand their knowledge, an important requirement for their professional development

Outskirts of Distant Galaxies In Absorption

QSO absorption spectroscopy provides a sensitive probe of both the neutral medium and diffuse ionized gas in the distant Universe. It extends 21cm maps of gaseous structures around low-redshift galaxies both to lower gas column densities and to higher redshifts. Combining galaxy surveys with absorption-line observations of gas around galaxies enables comprehensive studies of baryon cycles in galaxy outskirts over cosmic time. This Chapter presents a review of the empirical understanding of the cosmic neutral gas reservoir from studies of damped Lya absorbers (DLAs). It describes the constraints on the star formation relation and chemical enrichment history in the outskirts of distant galaxies from DLA studies. A brief discussion of available constraints on the ionized circumgalactic gas from studies of lower column density Lya absorbers and associated ionic absorption transitions is presented at the end.Comment: 45 pages, 7 figures, invited review, Book chapter in "Outskirts of Galaxies", Eds. J. H. Knapen, J. C. Lee and A. Gil de Paz, Astrophysics and Space Science Library, Springer, in pres