Frankfurt Institute for Advanced Studies (FIAS)
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Institute
Aims: The examination of histological sections is still the gold standard in diagnostic pathology. Important histopathological diagnostic criteria are nuclear shapes and chromatin distribution as well as nucleus-cytoplasm relation and immunohistochemical properties of surface and intracellular proteins. The aim of this investigation was to evaluate the benefits and drawbacks of three-dimensional imaging of CD30+ cells in classical Hodgkin Lymphoma (cHL) in comparison to CD30+ lymphoid cells in reactive lymphoid tissues.
Materials and results: Using immunoflourescence confocal microscopy and computer-based analysis, we compared CD30+ neoplastic cells in Nodular Sclerosis cHL (NScCHL), Mixed Cellularity cHL (MCcHL), with reactive CD30+ cells in Adenoids (AD) and Lymphadenitis (LAD). We confirmed that the percentage of CD30+ cell volume can be calculated. The amount in lymphadenitis was approx. 1.5%, in adenoids around 2%, in MCcHL up to 4,5% whereas the values for NScHL rose to more than 8% of the total cell cytoplasm. In addition, CD30+ tumour cells (HRS-cells) in cHL had larger volumes, and more protrusions compared to CD30+ reactive cells. Furthermore, the formation of large cell networks turned out to be a typical characteristic of NScHL.
Conclusion: In contrast to 2D histology, 3D laser scanning offers a visualisation of complete cells, their network interaction and spatial distribution in the tissue. The possibility to differentiate cells in regards to volume, surface, shape, and cluster formation enables a new view on further diagnostic and biological questions. 3D includes an increased amount of information as a basis of bioinformatical calculations.
An improved value for the lifetime of the (anti-)hypertriton has been obtained using the data sample of Pb-Pb collisions at sNN−−−√= 5.02 TeV collected by the ALICE experiment at the LHC. The (anti-)hypertriton has been reconstructed via its charged two-body mesonic decay channel and the lifetime has been determined from an exponential fit to the dN/d(ct) spectrum. The measured value, τ = 242+34−38 (stat.) ± 17 (syst.) ps, is compatible with all the available theoretical predictions, thus contributing to the solution of the longstanding hypertriton lifetime puzzle.
An improved value for the lifetime of the (anti-)hypertriton has been obtained using the data sample of Pb-Pb collisions at sNN−−−√= 5.02 TeV collected by the ALICE experiment at the LHC. The (anti-)hypertriton has been reconstructed via its charged two-body mesonic decay channel and the lifetime has been determined from an exponential fit to the dN/d(ct) spectrum. The measured value, τ = 242+34−38 (stat.) ± 17 (syst.) ps, is compatible with all the available theoretical predictions, thus contributing to the solution of the longstanding hypertriton lifetime puzzle.
Reducing neuronal size results in less cell membrane and therefore lower input conductance. Smaller neurons are thus more excitable as seen in their voltage responses to current injections in the soma. However, the impact of a neuron’s size and shape on its voltage responses to synaptic activation in dendrites is much less understood. Here we use analytical cable theory to predict voltage responses to distributed synaptic inputs and show that these are entirely independent of dendritic length. For a given synaptic density, a neuron’s response depends only on the average dendritic diameter and its intrinsic conductivity. These results remain true for the entire range of possible dendritic morphologies irrespective of any particular arborisation complexity. Also, spiking models result in morphology invariant numbers of action potentials that encode the percentage of active synapses. Interestingly, in contrast to spike rate, spike times do depend on dendrite morphology. In summary, a neuron’s excitability in response to synaptic inputs is not affected by total dendrite length. It rather provides a homeostatic input-output relation that specialised synapse distributions, local non-linearities in the dendrites and synaptic plasticity can modulate. Our work reveals a new fundamental principle of dendritic constancy that has consequences for the overall computation in neural circuits.
The coordinate and momentum space configurations of the net baryon number in heavy ion collisions that undergo spinodal decomposition, due to a first-order phase transition, are investigated using state-of-the-art machine-learning methods. Coordinate space clumping, which appears in the spinodal decomposition, leaves strong characteristic imprints on the spatial net density distribution in nearly every event which can be detected by modern machine learning techniques. On the other hand, the corresponding features in the momentum distributions cannot clearly be detected, by the same machine learning methods, in individual events. Only a small subset of events can be systematically differ- entiated if only the momentum space information is available. This is due to the strong similarity of the two event classes, with and without spinodal decomposition. In such sce- narios, conventional event-averaged observables like the baryon number cumulants signal a spinodal non-equilibrium phase transition. Indeed the third-order cumulant, the skewness, does exhibit a peak at the beam energy (Elab = 3–4 A GeV), where the transient hot and dense system created in the heavy ion collision reaches the first-order phase transition.
Following a brief review of current efforts to identify the neuronal correlates of conscious processing (NCCP) an attempt is made to bridge the gap between the material neuronal processes and the immaterial dimensions of subjective experience. It is argued that this "hard problem" of consciousness research cannot be solved by only considering the neuronal underpinnings of cognition. The proposal is that the hard problem can be treated within a naturalistic framework if one considers not only the biological but also the socio-cultural dimensions of evolution. The argument is based on the following premises: perceptions are the result of a constructivist process that depends on priors. This applies both for perceptions of the outer world and the perception of oneself. Social interactions between agents endowed with the cognitive abilities of humans generated immaterial realities, addressed as social or cultural realities. This novel class of realities assumed the role of priors for the perception of oneself and the embedding world. A natural consequence of these extended perceptions is a dualist classification of observables into material and immaterial phenomena nurturing the concept of ontological substance dualism. It is argued that perceptions shaped by socio-cultural priors lead to the construction of a self-model that has both a material and an immaterial dimension. As priors are implicit and not amenable to conscious recollection the perceived immaterial dimension is experienced as veridical and not derivable from material processes—which is the hallmark of the hard problem. These considerations let the hard problem appear as the result of cognitive constructs that are amenable to naturalistic explanations in an evolutionary framework.
Adjuvanted influenza vaccines constitute a key element towards inducing neutralizing antibody responses in populations with reduced responsiveness, such as infants and elderly subjects, as well as in devising antigen-sparing strategies. In particular, squalene-containing adjuvants have been observed to induce enhanced antibody responses, as well as having an influence on cross-reactive immunity. To explore the effects of adjuvanted vaccine formulations on antibody response and their relation to protein-specific immunity, we propose different mathematical models of antibody production dynamics in response to influenza vaccination. Data from ferrets immunized with commercial H1N1pdm09 vaccine antigen alone or formulated with different adjuvants was instrumental to adjust model parameters. While the affinity maturation process complexity is abridged, the proposed model is able to recapitulate the essential features of the observed dynamics. Our numerical results suggest that there exists a qualitative shift in protein-specific antibody response, with enhanced production of antibodies targeting the NA protein in adjuvanted versus non-adjuvanted formulations, in conjunction with a protein-independent boost that is over one order of magnitude larger for squalene-containing adjuvants. Furthermore, simulations predict that vaccines formulated with squalene-containing adjuvants are able to induce sustained antibody titers in a robust way, with little impact of the time interval between immunizations.
Charged-particle spectra at midrapidity are measured in Pb–Pb collisions at the centre-of-mass energy per nucleon–nucleon pair √sNN = 5.02 TeV and presented in centrality classes ranging from most central (0–5%) to most peripheral (95–100%) collisions. Possible medium effects are quantified using the nuclear modification factor (RAA) by comparing the measured spectra with those from proton–proton collisions, scaled by the number of independent nucleon–nucleon collisions obtained from a Glauber model. At large transverse momenta (8 < pT < 20 GeV/c), the average RAA is found to increase from about 0.15 in 0–5% central to a maximum value of about 0.8 in 75–85% peripheral collisions, beyond which it falls off strongly to below 0.2 for the most peripheral collisions. Furthermore, RAA initially exhibits a positive slope as a function of pT in the 8–20 GeV/c interval, while for collisions beyond the 80% class the slope is negative. To reduce uncertainties related to event selection and normalization, we also provide the ratio of RAA in adjacent centrality intervals. Our results in peripheral collisions are consistent with a PYTHIA-based model without nuclear modification, demonstrating that biases caused by the event selection and collision geometry can lead to the apparent suppression in peripheral collisions. This explains the unintuitive observation that RAA is below unity in peripheral Pb–Pb, but equal to unity in minimum-bias p–Pb collisions despite similar charged-particle multiplicities.
Charged-particle spectra at midrapidity are measured in Pb-Pb collisions at the centre-of-mass energy per nucleon-nucleon pair sNN−−−√ = 5.02 TeV and presented in centrality classes ranging from most central (0-5%) to most peripheral (95-100%) collisions. Possible medium effects are quantified using the nuclear modification factor (RAA) by comparing the measured spectra with those from proton-proton collisions, scaled by the number of independent nucleon-nucleon collisions obtained from a Glauber model. At large transverse momenta (8<pT<20 GeV/c), the average RAA is found to increase from about 0.15 in 0-5% central to a maximum value of about 0.8 in 75-85% peripheral collisions, beyond which it falls off strongly to below 0.2 for the most peripheral collisions. Furthermore, RAA initially exhibits a positive slope as a function of pT in the 8-20 GeV/c interval, while for collisions beyond the 80% class the slope is negative. To reduce uncertainties related to event selection and normalization, we also provide the ratio of RAA in adjacent centrality intervals. Our results in peripheral collisions are consistent with a PYTHIA-based model without nuclear modification, demonstrating that biases caused by the event selection and collision geometry can lead to the apparent suppression in peripheral collisions. This explains the unintuitive observation that RAA is below unity in peripheral Pb-Pb, but equal to unity in minimum-bias p-Pb collisions despite similar charged-particle multiplicities.
The elliptic (v2), triangular (v3), and quadrangular (v4) flow coefficients of π±, K±, p+p¯¯¯, Λ+Λ¯¯¯¯, K0S, and the ϕ-meson are measured in Pb-Pb collisions at sNN−−−√=5.02 TeV. Results obtained with the scalar product method are reported for the rapidity range |y|< 0.5 as a function of transverse momentum, pT, at different collision centrality intervals between 0-70%, including ultra-central (0-1%) collisions for π±, K±, and p+p¯¯¯. For pT<3 GeV/c, the flow coefficients exhibit a particle mass dependence. At intermediate transverse momenta (3<pT<~8-10 GeV/c), particles show an approximate grouping according to their type (i.e., mesons and baryons). The ϕ-meson v2, which tests both particle mass dependence and type scaling, follows p+p¯¯¯ v2 at low pT and π± v2 at intermediate pT. The evolution of the shape of vn(pT) as a function of centrality and harmonic number n is studied for the various particle species. Flow coefficients of π±, K±, and p+p¯¯¯ for pT<3 GeV/c are compared to iEBE-VISHNU and MUSIC hydrodynamical calculations coupled to a hadronic cascade model (UrQMD). The iEBE-VISHNU calculations describe the results fairly well for pT<2.5 GeV/c, while MUSIC calculations reproduce the measurements for pT<1 GeV/c. A comparison to vn coefficients measured in Pb-Pb collisions at sNN−−−√ = 2.76 TeV is also provided.