julilili42/papers huggingface dataset:
Long-term human organotypic brain slice cultures: a detailed protocol to provide a comprehensive framework for single-neuron and neuronal network investigations
2023-10-10

Background The investigation of the human brain at cellular and microcircuit level remains challenging due to the fragile viability of neuronal tissue, inter- and intra-variability of the samples and limited availability of human brain material. New method Here, we present an optimized work-up to use resected tissue from brain surgeries for live cell experiments in vitro. Comparison with existing methods We provide a reworked, detailed protocol of the production, culturing and viral transduction of human organotypic brain slice cultures for research purposes. Results We highlight the critical pitfalls of the culturing process of the human brain tissue and present results on viral expression, single-cell Patch-Clamp recordings, as well as multi-electrode array recordings over a prolonged period of time. Additionally, our statistics show that brain tissue from patients of any age and morbidity can be used for organotypic brain slice cultures if carefully selected. Conclusions Organotypic brain slice cultures are of great value for basic neuroscience and disease modeling over a time course of three weeks. Highlights Long-term human organotypic brain slice cultures are viable for 2-3 weeks and provide a framework for basic neuroscience and disease modeling We provide a reworked, detailed protocol for organotypic human brain slice culture production and maintenance We show results of long-term culturing of human organotypic brain slice cultures in terms of viral transduction, whole-cell Patch-Clamp recordings and multi-electrode array recordings Statistics of 16 surgeries show the correlation between the overall success rates of efficient culturing and viral transduction with the patient age and morbidity Figure 1, Graphical abstract. Schematic overview of preparation, maintenance and experimental workup of human organotypic brain slice cultures. After surgical resection, human brain tissue is prepared, sliced and cultured at air-liquid-interface between human cerebrospinal fluid and defined incubator atmosphere, allowing for week-long viability. This enables extensive experimental workup such as viral transduction, single cell and multi-electrode array electrophysiological recordings.
Classical and Quantized Maxwell Fields Deduced from Algebraic Many-Photon Theory
2023-10-10

The deduction starts with the (non-relativistic) one-photon Hilbert space , equipped with the one-photon Hamiltonian and basic symmetry generators, as the only input information. We recall in the functorially associated boson Fock space the multi-photon dynamics and symmetry transformations, as well as the field operator (as the scaled self-adjoint part of the creation operator) and the q(uasi)-classical states. There is no reference to a presupposed classical Maxwell theory. By abstraction, we go over to the algebraic formulation of the multi-photon theory in terms of a C\\*-Weyl algebra. Its test function space is constructed as a nuclear Fréchet space, in which – via infrared damping – the dynamics and symmetries are nuclear continuous and their generators bounded. Each w\\*-closed, singular subspace of the continuous dual determines non-Fock coherent states and their mixtures lead to a representation von Neumann algebra with non-trivial center. The symmetry generators restricted to the center can be transformed into the Maxwell form by means of a symplectic transformation and involve the well-known conservation quantities of electrodynamics. This identifies the central part of the represented photon field operator as composed of the two classical canonical electrodynamic field components. We have obtained, therefore, in free space a kind of fusion of the multi-photon theory and the Maxwell theory of transverse electrodynamic fields, where the latter arise as derived quantities. By means of a Bogoliubov transformation one also gets a fusion of the quantized with the classical Maxwell theory, deduced from the photon concept. A sketch of non-relativistic gauging is added in the appendix to gain longitudinal, cohomological, and scalar potentials.
“Memory is a Bitch.” Taboo and False Memory in Czech Reportages by Mariusz Szczygieł
2023-10-10

Summary This paper concerns works by the Polish contemporary author and journalist Mariusz Szczygieł (*1966). I analyze Szczygieł’s Czech reportages ( Gottland [2006], Zrób sobie raj [2010] and to some extent Nie ma [2018]) from the perspective of memory studies, focusing particularly on the question of taboo in collective memory and the issue of false memory (the products of the minds of individual persons or groups of people that make them sure that a certain event took place despite the fact that it never occurred), which are meant to show the untrustworthiness of memories and reminiscences. I argue that Szczygieł’s Czech reportages are to be read in the context of questions that have been vividly discussed in the Polish public sphere in recent decades: the dilemma of how to deal with the communist past after 1989 (lustration; Polish: lustracja ); and how to proceed with the referential pact when writing and reading literary nonfiction.
‘Arriving at moral Perfection’: Benjamin Franklin und seine russischen Nachfolger (Andrej Turgenev, Vasilij Žukovskij, Dmitrij Begičev)
2023-10-10

Summary The article examines how Benjamin Franklin’s ideas of self-improvement were adopted in Russia. The concept of the new creation of the self is one of Benjamin Franklin’s the most popular ideas. Since the first publication of Franklin’s Autobiography the idea of self-improvement became a genuine part of the very American ideology of the self-made man. After Andrej Turgenev published his translation of Franklin’s Autobiography in Moscow in 1799, Franklin’s method went on to enjoy a widespread triumph in imperial Russia. Andrey Turgenev’s and Vasilij Zhukovskij’s diaries, Alexander Griboedov’s comedy G ore ot uma (1825) and Dmitrij Begichev’s novel Semeystvo Kholmskikh (1832) can help us to trace this Russian history of Franklin’s method and show how Russian followers of Franklin modified and adapted his concept.
Extreme mass-ratio inspirals into black holes surrounded by scalar clouds
2023-10-11

We study extreme mass-ratio binary systems in which a stellar mass compact object spirals into a supermassive black hole surrounded by a scalar cloud. Scalar clouds can form through superradiant instabilities of massive scalar fields around spinning black holes and can also serve as a proxy for dark matter halos. Our framework is fully relativistic and assumes that the impact of the cloud on the geometry can be treated perturbatively. As a proof of concept, here we consider a point particle in circular, equatorial motion around a nonspinning black hole surrounded either by a spherically symmetric or a dipolar nonaxisymmetric scalar cloud, but the framework can in principle be generalized to generic black hole spins and scalar cloud geometries. We compute the leading-order power lost by the point particle due to scalar radiation and show that, in some regimes, it can dominate over gravitational-wave emission. We confirm the presence of striking signatures due to the presence of a scalar cloud that had been predicted using Newtonian approximations, such as resonances that can give rise to sinking and floating orbits, as well as ``sharp features'' in the power lost by the particle at given orbital radii. Finally, for a spherically symmetric scalar cloud, we also compute the leading-order corrections to the black-hole geometry and to the gravitational-wave energy flux, focusing only on axial metric perturbations for the latter. We find that, for noncompact clouds, the corrections to the (axial) gravitational-wave fluxes at high frequencies can be understood in terms of a gravitational-redshift effect, in agreement with previous works.
The first X-ray polarimetric observation of the black hole binary LMC X-1
2023-10-11

ABSTRACT We report on an X-ray polarimetric observation of the high-mass X-ray binary LMC X-1 in the high/soft state, obtained by the Imaging X-ray Polarimetry Explorer (IXPE) in 2022 October. The measured polarization is below the minimum detectable polarization of 1.1 per cent (at the 99 per cent confidence level). Simultaneously, the source was observed with the Neutron Star Interior Composition Explorer (NICER), Nuclear Spectroscopic Telescope Array (NuSTAR), and Spectrum-Rontgen-Gamma (SRG)/Astronomical Roentgen Telescope – X-ray Concentrator (ART-XC) instruments, which enabled spectral decomposition into a dominant thermal component and a Comptonized one. The low 2–8 keV polarization of the source did not allow for strong constraints on the black hole spin and inclination of the accretion disc. However, if the orbital inclination of about 36° is assumed, then the upper limit is consistent with predictions for pure thermal emission from geometrically thin and optically thick discs. Assuming the polarization degree of the Comptonization component to be 0, 4, or 10 per cent, and oriented perpendicular to the polarization of the disc emission (in turn assumed to be perpendicular to the large-scale ionization cone orientation detected in the optical band), an upper limit to the polarization of the disc emission of 1.0, 0.9, or 0.9 per cent, respectively, is found (at the 99 per cent confidence level).
Mean global DNA methylation serves as independent prognostic marker in IDH-wildtype glioblastoma
2023-10-11

Abstract Background The IDH-wildtype glioblastoma (GBM) patients have a devastating prognosis. Here, we analyzed the potential prognostic value of global DNA methylation of the tumors. Methods DNA methylation of 492 primary samples and 31 relapsed samples, each treated with combination therapy, and of 148 primary samples treated with radiation alone were compared with patient survival. We determined the mean methylation values and estimated the immune cell infiltration from the methylation data. Moreover, the mean global DNA methylation of 23 GBM cell lines was profiled and correlated to their cellular radiosensitivity as measured by colony formation assay. Results High mean DNA methylation levels correlated with improved survival, which was independent from known risk factors (MGMT promoter methylation, age, extent of resection; P = 0.009) and methylation subgroups. Notably, this correlation was also independent of immune cell infiltration, as higher number of immune cells indeed was associated with significantly better OS but lower mean methylation. Radiosensitive GBM cell lines had a significantly higher mean methylation than resistant lines (P = 0.007), and improved OS of patients treated with radiotherapy alone was also associated with higher DNA methylation (P = 0.002). Furthermore, specimens of relapsed GBM revealed a significantly lower mean DNA methylation compared to the matching primary tumor samples (P = 0.041). Conclusions Our results indicate that mean global DNA methylation is independently associated with outcome in glioblastoma. The data also suggest that a higher DNA methylation is associated with better radiotherapy response and less aggressive phenotype, both of which presumably contribute to the observed correlation with OS.
Testing the limits of scalar-Gauss-Bonnet gravity through nonlinear evolutions of spin-induced scalarization
2023-10-11

Quadratic theories of gravity with second order equations of motion provide an interesting model for testing deviations from general relativity in the strong gravity regime. However, they can suffer from a loss of hyperbolicity, even for initial data that is in the weak coupling regime and free from any obvious pathology. This effect has been studied in a variety of cases including isolated black holes and binaries. Here we explore the loss of hyperbolicity in spin-induced scalarization of isolated Kerr black holes in a scalar-Gauss-Bonnet theory of gravity, employing the modified CCZ4 formulation that has recently been developed. We find that, as in previous studies, hyperbolicity is lost when the scalar field and its gradients become large, and identify the breakdown in our evolutions with the physical modes of the purely gravitational sector. We vary the gauge parameters and find the results to be independent of their value. This, along with our use of a different gauge formulation to previous works, supports the premise that the loss of hyperbolicity is dominated by the physical modes. Since scalar-Gauss-Bonnet theories can be viewed as effective field theories (EFTs), we also examine the strength of the coupling during the evolution. We find that at the moment when hyperbolicity is lost the system is already well within the regime where the EFT is no longer valid. This reinforces the idea that the theories should only be applied within their regime of validity, and not treated as complete theories in their own right.
TMS of parietal and occipital cortex locked to spontaneous transient large-scale brain states enhances natural oscillations in EEG
2023-10-11

Spontaneous transient large-scale brain network states modify TMS-induced natural oscillations in specific brain regions. This significantly extends our knowledge on the critical importance of instantaneous state on explaining the brain's varying responsiveness to external perturbation.
High Hepatitis E Virus (HEV) Seroprevalence and No Evidence of HEV Viraemia in Vietnamese Blood Donors
2023-10-11

The prevalence of hepatitis E virus (HEV) in the Vietnamese population remains underestimated. The aim of the present study was to investigate the seroprevalence of HEV IgG/IgM antibodies and the presence of HEV RNA in blood donors as a part of epidemiological surveillance for transfusion-transmitted viruses. Serum samples from blood donors (n = 553) were analysed for markers of past (anti-HEV IgG) and recent/ongoing (anti-HEV IgM) HEV infections. In addition, all serum samples were subsequently tested for HEV RNA positivity. The overall prevalence of anti-HEV IgG was 26.8% (n = 148/553), while the seroprevalence of anti-HEV IgM was 0.5% (n = 3/553). Anti-HEV IgG seroprevalence in male and female donors was similar (27.1% and 25.5%, respectively). A higher risk of hepatitis E exposure was observed with increasing age. None of the blood donors were HEV RNA positive, and there was no evidence of HEV viraemia. Although the absence of HEV viraemia in blood donors from Northern Vietnam is encouraging, further epidemiological surveillance in other geographical regions is warranted to rule out transfusion-transmitted HEV.
Slack K+ channels limit kainic acid-induced seizure severity in mice by modulating neuronal excitability and firing
2023-10-11

Abstract Mutations of the Na + -activated K + channel Slack ( KCNT1 ) are associated with terrible epilepsy syndromes that already begin in infancy. Here we report increased severity of acute kainic acid-induced seizures in adult and juvenile Slack knockout mice (Slack −/− ) in vivo. Fittingly, we find exacerbation of cell death following kainic acid exposure in organotypic hippocampal slices as well as dissociated hippocampal cultures from Slack −/− in vitro. Furthermore, in cultured Slack −/− neurons, kainic acid-triggered Ca 2+ influx and K + efflux as well as depolarization-induced tetrodotoxin-sensitive inward currents are higher compared to the respective controls. This apparent changes in ion homeostasis could possibly explain altered action potential kinetics of Slack −/− neurons: steeper rise slope, decreased threshold, and duration of afterhyperpolarization, which ultimately lead to higher action potential frequencies during kainic acid application or injection of depolarizing currents. Based on our data, we propose Slack as crucial gatekeeper of neuronal excitability to acutely limit seizure severity.
Inherently interpretable position-aware convolutional motif kernel networks for biological sequencing data
2023-10-11

Abstract Artificial neural networks show promising performance in detecting correlations within data that are associated with specific outcomes. However, the black-box nature of such models can hinder the knowledge advancement in research fields by obscuring the decision process and preventing scientist to fully conceptualize predicted outcomes. Furthermore, domain experts like healthcare providers need explainable predictions to assess whether a predicted outcome can be trusted in high stakes scenarios and to help them integrating a model into their own routine. Therefore, interpretable models play a crucial role for the incorporation of machine learning into high stakes scenarios like healthcare. In this paper we introduce Convolutional Motif Kernel Networks, a neural network architecture that involves learning a feature representation within a subspace of the reproducing kernel Hilbert space of the position-aware motif kernel function. The resulting model enables to directly interpret and evaluate prediction outcomes by providing a biologically and medically meaningful explanation without the need for additional post-hoc analysis. We show that our model is able to robustly learn on small datasets and reaches state-of-the-art performance on relevant healthcare prediction tasks. Our proposed method can be utilized on DNA and protein sequences. Furthermore, we show that the proposed method learns biologically meaningful concepts directly from data using an end-to-end learning scheme.
Perceived spatial presence and body orientation affect the recall of out-of-sight places in an immersive sketching experiment
2023-10-11

Abstract The orientation of sketch maps of remote but familiar city squares produced from memory has been shown to depend on the distance and airline direction from the production site to the remembered square (position-dependent recall, Röhrich et al. in PLoS One 9(11): e112793, 2014). Here, we present a virtual reality version of the original experiment and additionally study the role of body orientation. Three main points can be made: First, “immersive sketching” is a novel and useful paradigm in which subjects sketch maps live on paper while being immersed in virtual reality. Second, the original effect of position-dependent recall was confirmed, indicating that the sense of being present at a particular location, even if generated in a virtual environment, suffices to bias the imagery of distant places. Finally, the orientation of the produced sketch maps depended also on the body orientation of the subjects. At each production site, body orientation was controlled by varying the position of the live feed in the virtual environment, such that subjects had to turn towards the prescribed direction. Position-dependent recall is strongest if subjects are aligned with the airline direction to the target and virtually goes away if they turn in the opposite direction. We conclude that the representation of out-of-sight target places depends on both the current airline direction to the target and the body orientation.
Single-cell analysis of prenatal and postnatal human cortical development
2023-10-12

We analyzed &gt;700,000 single-nucleus RNA sequencing profiles from 106 donors during prenatal and postnatal developmental stages and identified lineage-specific programs that underlie the development of specific subtypes of excitatory cortical neurons, interneurons, glial cell types, and brain vasculature. By leveraging single-nucleus chromatin accessibility data, we delineated enhancer gene regulatory networks and transcription factors that control commitment of specific cortical lineages. By intersecting our results with genetic risk factors for human brain diseases, we identified the cortical cell types and lineages most vulnerable to genetic insults of different brain disorders, especially autism. We find that lineage-specific gene expression programs up-regulated in female cells are especially enriched for the genetic risk factors of autism. Our study captures the molecular progression of cortical lineages across human development.
Direct observation of glycans bonded to proteins and lipids at the single-molecule level
2023-10-12

Proteins and lipids decorated with glycans are found throughout biological entities, playing roles in biological functions and dysfunctions. Current analytical strategies for these glycan-decorated biomolecules, termed glycoconjugates, rely on ensemble-averaged methods that do not provide a full view of positions and structures of glycans attached at individual sites in a given molecule, especially for glycoproteins. We show single-molecule analysis of glycoconjugates by direct imaging of individual glycoconjugate molecules using low-temperature scanning tunneling microscopy. Intact glycoconjugate ions from electrospray are soft-landed on a surface for their direct single-molecule imaging. The submolecular imaging resolution corroborated by quantum mechanical modeling unveils whole structures and attachment sites of glycans in glycopeptides, glycolipids, N-glycoproteins, and O-glycoproteins densely decorated with glycans.
Early Homo erectus lived at high altitudes and produced both Oldowan and Acheulean tools
2023-10-12

In Africa, the scarcity of hominin remains found in direct association with stone tools has hindered attempts to link Homo habilis and Homo erectus with particular lithic industries. The infant mandible discovered in level E at Garba IV (Melka Kunture) on the highlands of Ethiopia is critical to this issue because of its direct association with an Oldowan lithic industry. Here, we used synchrotron imaging to examine the internal morphology of the unerupted permanent dentition and confirmed its identification as H. erectus . Additionally, we used revised paleomagnetic ages to show that (i) the mandible in level E is ~2 million years old and represents one of the earliest H. erectus fossils and that (ii) overlying level D, ~1.95 million years old, contains the earliest known Acheulean assemblage.
First direct evidence of lion hunting and the early use of a lion pelt by Neanderthals
2023-10-12

Abstract During the Upper Paleolithic, lions become an important theme in Paleolithic art and are more frequent in anthropogenic faunal assemblages. However, the relationship between hominins and lions in earlier periods is poorly known and primarily interpreted as interspecies competition. Here we present new evidence for Neanderthal-cave lion interactions during the Middle Paleolithic. We report new evidence of hunting lesions on the 48,000 years old cave lion skeleton found at Siegsdorf (Germany) that attest to the earliest direct instance of a large predator kill in human history. A comparative analysis of a partial puncture to a rib suggests that the fatal stab was delivered with a wooden thrusting spear. We also present the discovery of distal lion phalanges of at least 190,000 years old from Einhornhöhle (Germany), representing the earliest example of the use of cave lion skin by Neanderthals in Central Europe. Our study provides novel evidence on a new dimension of Neanderthal behavioral complexity.
On the Use of Artificial Intelligence for Dosimetry of Radiopharmaceutical Therapies
2023-10-12

Abstract Routine clinical dosimetry along with radiopharmaceutical therapies is key for future treatment personalization. However, dosimetry is considered complex and time-consuming with various challenges amongst the required steps within the dosimetry workflow. The general workflow for image-based dosimetry consists of quantitative imaging, the segmentation of organs and tumors, fitting of the time-activity-curves, and the conversion to absorbed dose. This work reviews the potential and advantages of the use of artificial intelligence to improve speed and accuracy of every single step of the dosimetry workflow.