julilili42/papers huggingface dataset:
Practical and technical aspects for the 3D scanning of lithic artefacts using micro-computed tomography techniques and laser light scanners for subsequent geometric morphometric analysis. Introducing the StyroStone protocol
2022-04-21

Here, we present a new method to scan a large number of lithic artefacts using three-dimensional scanning technology. Despite the rising use of high-resolution 3D surface scanners in archaeological sciences, no virtual studies have focused on the 3D digitization and analysis of small lithic implements such as bladelets, microblades, and microflakes. This is mostly due to difficulties in creating reliable 3D meshes of these artefacts resulting from several inherent features (i.e., size, translucency, and acute edge angles), which compromise the efficiency of structured light or laser scanners and photogrammetry. Our new protocol StyroStone addresses this problem by proposing a step-by-step procedure relying on the use of micro-computed tomographic technology, which is able to capture the 3D shape of small lithic implements in high detail. We tested a system that enables us to scan hundreds of artefacts together at once within a single scanning session lasting a few hours. As also bigger lithic artefacts (i.e., blades) are present in our sample, this protocol is complemented by a short guide on how to effectively scan such artefacts using a structured light scanner (Artec Space Spider). Furthermore, we estimate the accuracy of our scanning protocol using principal component analysis of 3D Procrustes shape coordinates on a sample of meshes of bladelets obtained with both micro-computed tomography and another scanning device (i.e., Artec Micro). A comprehensive review on the use of 3D geometric morphometrics in lithic analysis and other computer-based approaches is provided in the introductory chapter to show the advantages of improving 3D scanning protocols and increasing the digitization of our prehistoric human heritage.
Strong off-target antibody reactivity to malarial antigens induced by RTS,S/AS01E vaccination is associated with protection
2022-04-21

The RTS,S/AS01E vaccine targets the circumsporozoite protein (CSP) of the Plasmodium falciparum (P. falciparum) parasite. Protein microarrays were used to measure levels of IgG against 1000 P. falciparum antigens in 2138 infants (age 6-12 weeks) and children (age 5-17 months) from 6 African sites of the phase III trial, sampled before and at 4 longitudinal visits after vaccination. One month postvaccination, IgG responses to 17% of all probed antigens showed differences between RTS,S/AS01E and comparator vaccination groups, whereas no prevaccination differences were found. A small subset of antigens presented IgG levels reaching 4- to 8-fold increases in the RTS,S/AS01E group, comparable in magnitude to anti-CSP IgG levels (~11-fold increase). They were strongly cross-correlated and correlated with anti-CSP levels, waning similarly over time and reincreasing with the booster dose. Such an intriguing phenomenon may be due to cross-reactivity of anti-CSP antibodies with these antigens. RTS,S/AS01E vaccinees with strong off-target IgG responses had an estimated lower clinical malaria incidence after adjusting for age group, site, and postvaccination anti-CSP levels. RTS,S/AS01E-induced IgG may bind strongly not only to CSP, but also to unrelated malaria antigens, and this seems to either confer, or at least be a marker of, increased protection from clinical malaria.
Generation of Human Nociceptor-Enriched Sensory Neurons for the Study of Pain-Related Dysfunctions
2022-04-21

Abstract In vitro models of the peripheral nervous system would benefit from further refinements to better support studies on neuropathies. In particular, the assessment of pain-related signals is still difficult in human cell cultures. Here, we harnessed induced pluripotent stem cells (iPSCs) to generate peripheral sensory neurons enriched in nociceptors. The objective was to generate a culture system with signaling endpoints suitable for pharmacological and toxicological studies. Neurons generated by conventional differentiation protocols expressed moderate levels of P2X3 purinergic receptors and only low levels of TRPV1 capsaicin receptors, when maturation time was kept to the upper practically useful limit of 6 weeks. As alternative approach, we generated cells with an inducible NGN1 transgene. Ectopic expression of this transcription factor during a defined time window of differentiation resulted in highly enriched nociceptor cultures, as determined by functional (P2X3 and TRPV1 receptors) and immunocytochemical phenotyping, complemented by extensive transcriptome profiling. Single cell recordings of Ca2+-indicator fluorescence from &amp;gt;9000 cells were used to establish the “fraction of reactive cells” in a stimulated population as experimental endpoint, that appeared robust, transparent and quantifiable. To provide an example of application to biomedical studies, functional consequences of prolonged exposure to the chemotherapeutic drug oxaliplatin were examined at non-cytotoxic concentrations. We found (i) neuronal (allodynia-like) hypersensitivity to otherwise non-activating mechanical stimulation that could be blocked by modulators of voltage-gated sodium channels; (ii) hyper-responsiveness to TRPV1 receptor stimulation. These findings and several other measured functional alterations indicate that the model is suitable for pharmacological and toxicological studies related to peripheral neuropathies.
Specific gait changes in prodromal hereditary spastic paraplegia type 4 - preSPG4 study
2022-04-21

Abstract Background In hereditary spastic paraplegia type 4 (SPG4), subclinical gait changes might occur years before patients realize gait disturbances. The prodromal phase of neurodegenerative disease is of particular interest to halt disease progression by future interventions before impairment has manifested. Objectives Identification of specific movement abnormalities before manifestation of gait impairment and quantification of disease progression in the prodromal phase. Methods 70 subjects participated in gait assessment, including 30 prodromal SPAST mutation carriers, 17 patients with mild-to-moderate manifest SPG4, and 23 healthy controls. Gait was assessed by an infrared-camera-based motion capture system to analyze features like range of motion and continuous angle trajectories. Those features were correlated with disease severity as assessed by the Spastic Paraplegia Rating Scale (SPRS) and neurofilament light chain (NfL) as a fluid biomarker indicating neurodegeneration. Results Compared to healthy controls, we found an altered gait pattern in prodromal mutation carriers during the swing phase in segmental angles of the lower leg (p&lt;0.05) and foot (p&lt;0.01), and in heel ground clearance (p&lt;0.01). Furthermore, ranges of motion of segmental angles were reduced for foot (p&lt;0.001) and lower leg (p&lt;0.01). These changes occurred in prodromal mutation carriers without quantified leg spasticity in clinical examination. Gait features correlated with NfL levels and SPRS score. Conclusion Gait analysis can quantify changes in prodromal and mild-to-moderate manifest SPG4 patients. Thus, gait features constitute promising motor biomarkers characterizing the subclinical progression of spastic gait and might help to evaluate interventions in early disease stages.
Single-Neuron Labeling in Fixed Tissue and Targeted Volume Electron Microscopy
2022-04-21

The structural complexity of nervous tissue makes it very difficult to unravel the connectivity between neural elements at different scales. Numerous methods are available to trace long-range projections at the light microscopic level, and to identify the actual synaptic connections at the electron microscopic level. However, correlating mesoscopic and nanoscopic scales in the same cell, cell population or brain region is a problematic, laborious and technically demanding task. Here we present an effective method for the 3D reconstruction of labeled subcellular structures at the ultrastructural level, after single-neuron labeling in fixed tissue. The brain is fixed by intracardial perfusion of aldehydes and thick vibratome sections (250 μm) are obtained. Single cells in these vibratome sections are intracellularly injected with horseradish peroxidase (HRP), so that the cell body and its processes can be identified. The thick sections are later flat-embedded in epoxy resin and re-sectioned into a series of thinner (7 μm) sections. The sections containing the regions of interest of the labeled cells are then imaged with automated focused ion beam milling and scanning electron microscopy (FIB-SEM), acquiring long series of high-resolution images that can be reconstructed, visualized, and analyzed in 3D. With this methodology, we can accurately select any cellular segment at the light microscopic level (e.g., proximal, intermediate or distal dendrites, collateral branches, axonal segments, etc.) and analyze its synaptic connections at the electron microscopic level, along with other ultrastructural features. Thus, this method not only facilitates the mapping of the synaptic connectivity of single-labeled neurons, but also the analysis of the surrounding neuropil. Since the labeled processes can be located at different layers or subregions, this method can also be used to obtain data on the differences in local synaptic organization that may exist at different portions of the labeled neurons.
Investigating the Roles of Document Presentation and Reading Interactions on Different Aspects of Multiple Document Comprehension
2022-04-21

The present study examined reading interactions and multiple document comprehension of 108 university students who read five partly conflicting documents on a health-related issue. Documents were presented on a large touch interface that either enabled a simultaneous or imposed a sequential presentation of the documents. None of the three multiple document comprehension measures (number of intertextual connections in essays, score in source-content mapping task, and number of source names recalled) was affected by document presentation. However, in the sequential condition, the number of revisits to documents was positively related to memory for source names and source-content integration, but not to intertextual integration. Conversely, in the simultaneous condition, participants who grouped documents during reading showed greater intertextual and source-content integration, but no greater memory for source names than those who had not grouped documents. To conclude, reading interactions played a more important role in readers' multiple document comprehension than document presentation.
Recurrent SARS-CoV-2 Infection and Impaired Immunologic Response in a Pediatric Oncologic Patient While Treated With Radiochemotherapy
2022-04-21

Immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pediatric patients with malignant disease may be affected by tumor therapy. Here, we report the case of a child with rhabdomyosarcoma and recurrent SARS-CoV-2 infection. Immunologic responses, analyzed by T-cell activity and anti-viral IgG levels, were impaired and not durable as a result of intensive radiochemotherapy.
Phase I/II multicenter trial of a novel therapeutic cancer vaccine, HepaVac-101, for hepatocellular carcinoma.
2022-04-21

<strong>Purpose:</strong> Immunotherapy for hepatocellular carcinoma (HCC) shows considerable promise in improving clinical outcomes. HepaVac-101 represents a single-arm, first-in-man Phase I/II multicenter cancer vaccine trial for HCC (NCT03203005). It combines multi-peptide antigens (IMA970A) with the TLR7/8/RIG I agonist CV8102. IMA970A includes 5 HLA-A*24 and 7 HLA-A*02 as well as 4 HLA-DR restricted peptides selected after mass spectrometric identification in human HCC tissues or cell lines. CV8102 is an RNA-based immunostimulator inducing a balanced Th1/Th2 immune response. <strong>Experimental Design: </strong>82 patients with very early to intermediate stage HCCs were enrolled and screened for suitable HLA haplotypes and 22 put on study treatment. This consisted in a single infusion of low-dose cyclophosphamide followed by 9 intradermal coadministrations of IMA970A and CV8102. Only patients with no disease relapse after standard of care treatments were vaccinated. The primary endpoints of the HepaVac-101 clinical trial were safety, tolerability and antigen-specific T-cell responses. Secondary or exploratory endpoints included additional immunological parameters and survival endpoints. <strong>Results: </strong>The vaccination showed a good safety profile. Transient mild-to-moderate injection-site reactions were the most frequent IMA970A/CV8102-related side effects. Immune responses against ≥1 vaccinated HLA class I tumor-associated peptide (TAA) and ≥1 vaccinated HLA class II TAA were respectively induced in 37% and 53% of the vaccinees. <strong>Conclusion:</strong> Immunotherapy may provide a great improvement in treatment options for HCC. HepaVac-101 is a first-in-man clinical vaccine trial with multiple novel HLA class I- and class II-restricted TAAs against HCC. The results are initial evidence for the safety and immunogenicity of the vaccine. Further clinical evaluations are warranted.
Subjective cognitive decline and stage 2 of Alzheimer disease in patients from memory centers
2022-04-22

Abstract Introduction It is uncertain whether subjective cognitive decline (SCD) in individuals who seek medical help serves the identification of the initial symptomatic stage 2 of the Alzheimer's disease (AD) continuum. Methods Cross‐sectional and longitudinal data from the multicenter, memory clinic–based DELCODE study. Results The SCD group showed slightly worse cognition as well as more subtle functional and behavioral symptoms than the control group (CO). SCD–A+ cases (39.3% of all SCD) showed greater hippocampal atrophy, lower cognitive and functional performance, and more behavioral symptoms than CO–A+. Amyloid concentration in the CSF had a greater effect on longitudinal cognitive decline in SCD than in the CO group. Discussion Our data suggests that SCD serves the identification of stage 2 of the AD continuum and that stage 2, operationalized as SCD‐A+, is associated with subtle, but extended impact of AD pathology in terms of neurodegeneration, symptoms and clinical progression.
Immunogenic Cell Death, DAMPs and Prothymosin α as a Putative Anticancer Immune Response Biomarker
2022-04-22

The new and increasingly studied concept of immunogenic cell death (ICD) revealed a previously unknown perspective of the various regulated cell death (RCD) modalities, elucidating their immunogenic properties and rendering obsolete the notion that immune stimulation is solely the outcome of necrosis. A distinct characteristic of ICD is the release of danger-associated molecular patterns (DAMPs) by dying and/or dead cells. Thus, several members of the DAMP family, such as the well-characterized heat shock proteins (HSPs) HSP70 and HSP90, the high-mobility group box 1 protein and calreticulin, and the thymic polypeptide prothymosin α (proTα) and its immunoreactive fragment proTα(100–109), are being studied as potential diagnostic tools and/or possible therapeutic agents. Here, we present the basic aspects and mechanisms of both ICD and other immunogenic RCD forms; denote the role of DAMPs in ICD; and further exploit the relevance of human proTα and proTα(100–109) in ICD, highlighting their possible clinical applications. Furthermore, we present the preliminary results of our in vitro studies, which show a direct correlation between the concentration of proTα/proTα(100–109) and the levels of cancer cell apoptosis, induced by anticancer agents and γ-radiation.
Exact solution of a boundary time-crystal phase transition: Time-translation symmetry breaking and non-Markovian dynamics of correlations
2022-04-22

The breaking of the continuous time-translation symmetry manifests, in\\nMarkovian open quantum systems, through the emergence of non-stationary\\ndynamical phases. Systems that display nonequilibrium transitions into these\\nphases are referred to as time-crystals, and they can be realized, for example,\\nin many-body systems governed by collective dissipation and long-ranged\\ninteractions. Here, we provide a complete analytical characterization of a\\nboundary time-crystal phase transition. This involves exact expressions for the\\norder parameter and for the dynamics of quantum fluctuations, which, in the\\ntime-crystalline phase, remains asymptotically non-Markovian as a consequence\\nof the time-translation symmetry breaking. We demonstrate that boundary\\ntime-crystals are intrinsically critical phases, where fluctuations exhibit a\\npower-law divergence with time. Our results show that a dissipative\\ntime-crystal phase is far more than merely a classical non-linear and\\nnon-stationary (limit cycle) dynamics of a macroscopic order parameter. It is\\nrather a genuine many-body phase where the properties of correlations\\ndistinctly differs from that of stationary ones.\\n
Dissipative quasiparticle picture for quadratic Markovian open quantum systems
2022-04-22

Correlations between different regions of a quantum many-body system can be quantified through measures based on entropies of (reduced) subsystem states. For closed systems, several analytical and numerical tools, e.g., hydrodynamic theories or tensor networks, can accurately capture the time-evolution of subsystem entropies, thus allowing for a profound understanding of the unitary dynamics of quantum correlations. However, so far, these methods either cannot be applied to open quantum systems or do not permit an efficient computation of quantum entropies for mixed states. Here, we make progress in solving this issue by formulating a dissipative quasi-particle picture -- describing the dynamics of quantum entropies in the hydrodynamic limit -- for a general class of noninteracting open quantum systems. Our results show that also in dissipative many-body systems, correlations are generically established through the propagation of quasi-particles.
Constraining equation-of-state groups from g-mode asteroseismology
2022-04-22

ABSTRACT Buoyancy-restored modes inside neutron stars depend sensitively on both the microphysical (e.g. composition and entropy gradients) and macrophysical (e.g. stellar mass and radius) properties of the star. Asteroseismology efforts for g modes are therefore particularly promising avenues for recovering information concerning the nuclear equation of state. In this work, it is shown that the overall low-temperature g-space consists of multiple groups corresponding to different classes of equation of state (e.g. hadronic versus hybrid). This is in contrast to the case of pressure-driven modes, for example, which tend to follow a universal relation regardless of microphysical considerations. Using a wide library of currently viable equations of state, perturbations of static, stratified stars are calculated in general relativity to demonstrate in particular how g-space groupings can be classified according to the mean mass density, temperature, central speed of sound, and tidal deformability. Considering present and future observations regarding gravitational waves, accretion outbursts, quasi-periodic oscillations, and precursor flashes from gamma-ray bursts, it is shown how one might determine which group the g modes belong to.
Mechanical properties of lithic raw materials from Kazakhstan: Comparing chert, shale, and porphyry
2022-04-22

The study of lithic raw material quality has become one of the major interpretive tools to investigate the raw material selection behaviour and its influence to the knapping technology. In order to make objective assessments of raw material quality, we need to measure their mechanical properties (e.g., fracture resistance, hardness, modulus of elasticity). However, such comprehensive investigations are lacking for the Palaeolithic of Kazakhstan. In this work, we investigate geological and archaeological lithic raw material samples of chert, porphyry, and shale collected from the Inner Asian Mountain Corridor (henceforth IAMC). Selected samples of aforementioned rocks were tested by means of Vickers and Knoop indentation methods to determine the main aspect of their mechanical properties: their indentation fracture resistance (a value closely related to fracture toughness). These tests were complemented by traditional petrographic studies to characterise the mineralogical composition and evaluate the level of impurities that could have potentially affected the mechanical properties. The results show that materials, such as porphyry possess fracture toughness values that can be compared to those of chert. Previously, porphyry was thought to be of lower quality due to the anisotropic composition and coarse feldspar and quartz phenocrysts embedded in a silica rich matrix. However, our analysis suggests that different raw materials are not different in terms of indentation fracture resistance. This work also offers first insight into the quality of archaeological porphyry that was utilised as a primary raw material at various Upper Palaeolithic sites in the Inner Asian Mountain Corridor from 47–21 ka cal BP.
Superradiance decoherence caused by long-range Rydberg-atom pair interactions
2022-04-22

This work reports on the real-time detection of internal-state dynamics of cold Rb atoms being excited to the Rydberg state via two-photon excitation. A mesoscopic cloud of atoms is overlapped with the mode volume of a confocal optical cavity and optically pumped by two laser beams transverse to the cavity axis. The excitation to Rydberg states changes the collective atom-cavity coupling, which is detected by monitoring the light transmitted through the cavity while being weakly driven. In addition to the damped coherent excitation dynamics and the decay back to the ground state, the data show a superradiant enhancement of the black-body radiation induced transitions from the state to neighboring Rydberg states. Furthermore, they show a density dependent mitigation of the superradiant decay which is attributed to long range dipole-dipole interactions between atoms in the involved Rydberg states. These results contribute to solving a recent controversy on the interplay between BBR-induced superradiance and Rydberg atom interactions.