julilili42/papers huggingface dataset:
Interacting Effects of Polystyrene Microplastics and the Antidepressant Amitriptyline on Early Life Stages of Brown Trout (Salmo trutta f. fario)
2020-08-22

Whether microplastics themselves or their interactions with chemicals influence the health and development of aquatic organisms has become a matter of scientific discussion. In aquatic environments, several groups of chemicals are abundant in parallel to microplastics. The tricyclic antidepressant amitriptyline is frequently prescribed, and residues of it are regularly found in surface waters. In the present study, the influence of irregularly shaped polystyrene microplastics (&lt;50 μm), amitriptyline, and their mixture on early life-stages of brown trout were investigated. In a first experiment, the impacts of 100, 104, and 105 particles/L were studied from the fertilization of eggs until one month after yolk-sac consumption. In a second experiment, eggs were exposed in eyed ova stages to 105, 106 particles/L, to amitriptyline (pulse-spiked, average 48 ± 33 μg/L) or to two mixtures for two months. Microplastics alone did neither influence the development of fish nor the oxidative stress level or the acetylcholinesterase activity. Solely, a slight effect on the resting behavior of fry exposed to 106 particles/L was observed. Amitriptyline exposure exerted a significant effect on development, caused elevated acetylcholinesterase activity and inhibition of two carboxylesterases. Most obvious was the severely altered swimming and resting behavior. However, effects of amitriptyline were not modulated by microplastics.
Structural controls on the hydrogeological functioning of a floodplain
2020-08-22

Abstract Floodplains are often conceptualized as homogeneous sediment bodies which connect streams with their respective catchment and buffer agricultural inputs. This has led to a general bias within the hydrological community towards research on sites where the floodplain is a clear conduit for groundwater flow. In humid temperate regions of central Europe, floodplains have experienced rapid environmental changes since the last glaciation, yielding significant bedrock weathering and predominantly fine-grained, highly stratified hillslope and floodplain sediments. Such heterogeneous sedimentary architecture leads to conceptual ambiguities in the interpretation of the hydrogeological functioning of floodplains, thus raising the question: Do floodplains act as barriers or conduits to groundwater flow? This study analyzes the Ammer floodplain close to Tübingen in south-western Germany as a representative mid-section floodplain in a temperate climate where the regional bedrock-geology is dominated by mudstones. Geological, geophysical, and geochemical characterization and monitoring techniques were combined to shed light on the internal geological structure as a key control modulating the floodplain hydrology. Two partially separate groundwater systems were identified: a gravel body at the bottom of the Quaternary sediments and a Holocene confined tufaceous aquifer, separated by low-permeability clays. Despite flow being predominantly along-valley, sulfate concentrations in the floodplain aquifers showed evidence of a strong connection to the gypsum-bearing hillslope, particularly where tributary valley sediments are present (e.g., alluvial fans). Results from a floodplain water balance suggest the hillslope- and floodplain-aquifer material act as a barrier to hillslope groundwater recharge, where a large fraction may be bypassing the local floodplain groundwater system.
Plasma NT1 Tau is a Specific and Early Marker of Alzheimer's Disease
2020-08-23

Objective There is an urgent need for sensitive, widely available, blood‐based screening tests to identify presymptomatic individuals destined to develop Alzheimer's disease (AD). We investigated whether tau detected in plasma by our in‐house NT1 assay is specifically altered in AD, and when applied to patients with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) can serve to predict progression to AD dementia. The predictive value of NT1 versus tau measured using assays from Quanterix and Roche, and the specificity of NT1 for AD versus a nonspecific marker of neurodegeneration (neurofilament light [NfL]) were also examined. Methods NT1 tau and NfL were measured in plasma from prospectively followed patients with SCD or MCI who remained cognitively stable, converted to AD dementia, or converted to non‐AD dementias, and in cognitively unimpaired participants. Tau was measured using Quanterix and Roche assays in baseline subjects with SCD and MCI. Results Plasma NT1 tau was specifically elevated in AD, but not in non‐AD dementia compared with controls, whereas NfL was increased in both AD and non‐AD dementias. Baseline specimens from individuals who had SCD or MCI revealed that NT1 tau, but not tau measured using Quanterix or Roche assays, is elevated in subjects who progress to AD dementia. As expected, baseline plasma NfL is elevated in those who progress to AD and non‐AD dementias. Interpretation Plasma NT1 tau is a specific marker of AD, which is elevated early in disease and may prove useful as a first round screen to identify individuals at risk of developing AD. ANN NEUROL 2020;88:878–892
Suppression without inhibition: How retinal computation contributes to saccadic suppression
2020-08-23

Abstract Visual perception remains stable across saccadic eye movements, despite the concurrent strongly disruptive visual flow. This stability is partially associated with a reduction in visual sensitivity, known as saccadic suppression, which already starts in the retina with reduced ganglion cell sensitivity. However, the retinal circuit mechanisms giving rise to such suppression remain unknown. Here, we describe these mechanisms using electrophysiology in mouse, pig, and macaque retina, 2-photon calcium imaging, computational modeling, and human psychophysics. We find that sequential stimuli, such as those that naturally occur during saccades, trigger three independent suppressive mechanisms in the retina. The main suppressive mechanism is triggered by contrast-reversing sequential stimuli and originates within the receptive field center of ganglion cells. It does not involve inhibition or other known suppressive mechanisms such as saturation or adaptation. Instead, it relies on temporal filtering of the inherently slow response of cone photoreceptors coupled with downstream nonlinearities. Two further mechanisms of suppression are present predominantly in ON ganglion cells and originate in the receptive field surround, highlighting a novel disparity between ON and OFF ganglion cells. The mechanisms uncovered here likely play a role in shaping the retinal output following eye movements and other natural viewing conditions where sequential stimulation is ubiquitous.
Effect Handlers, Evidently
2020-08-23

Algebraic effect handlers are a powerful way to incorporate effects in a programming language. Sometimes perhaps even _too_ powerful. In this article we define a restriction of general effect handlers with _scoped resumptions_. We argue one can still express all important effects, while improving reasoning about effect handlers. Using the newly gained guarantees, we define a sound and coherent evidence translation for effect handlers, which directly passes the handlers as evidence to each operation. We prove full soundness and coherence of the translation into plain lambda calculus. The evidence in turn enables efficient implementations of effect operations; in particular, we show we can execute tail-resumptive operations _in place_ (without needing to capture the evaluation context), and how we can replace the runtime search for a handler by indexing with a constant offset.
The results of biodiversity–ecosystem functioning experiments are realistic
2020-08-24

A large body of research shows that biodiversity loss can reduce ecosystem functioning. However, much of the evidence for this relationship is drawn from biodiversity-ecosystem functioning experiments in which biodiversity loss is simulated by randomly assembling communities of varying species diversity, and ecosystem functions are measured. This random assembly has led some ecologists to question the relevance of biodiversity experiments to real-world ecosystems, where community assembly or disassembly may be non-random and influenced by external drivers, such as climate, soil conditions or land use. Here, we compare data from real-world grassland plant communities with data from two of the largest and longest-running grassland biodiversity experiments (the Jena Experiment in Germany and BioDIV in the United States) in terms of their taxonomic, functional and phylogenetic diversity and functional-trait composition. We found that plant communities of biodiversity experiments cover almost all of the multivariate variation of the real-world communities, while also containing community types that are not currently observed in the real world. Moreover, they have greater variance in their compositional features than their real-world counterparts. We then re-analysed a subset of experimental data that included only ecologically realistic communities (that is, those comparable to real-world communities). For 10 out of 12 biodiversity-ecosystem functioning relationships, biodiversity effects did not differ significantly between the full dataset of biodiversity experiments and the ecologically realistic subset of experimental communities. Although we do not provide direct evidence for strong or consistent biodiversity-ecosystem functioning relationships in real-world communities, our results demonstrate that the results of biodiversity experiments are largely insensitive to the exclusion of unrealistic communities and that the conclusions drawn from biodiversity experiments are generally robust.
The Occurrence and Origin of Pentlandite-Chalcopyrite-Pyrrhotite Loop Textures in Magmatic Ni-Cu Sulfide Ores
2020-08-24

Abstract Pentlandite is the dominant Ni-hosting ore mineral in most magmatic sulfide deposits and has conventionally been interpreted as being entirely generated by solid-state exsolution from the high-temperature monosulfide solid solution (MSS) (Fe,Ni)1–xS. This process gives rise to the development of loops of pentlandite surrounding pyrrhotite grains. Recently it has been recognized that not all pentlandite forms by exsolution. Some may form as the result of peritectic reaction between early formed MSS and residual Ni-Cu–rich sulfide liquid during differentiation of the sulfide melt, such that at least some loop textures may be genuinely magmatic in origin. Testing this hypothesis involved microbeam X-ray fluorescence mapping to image pentlandite-pyrrhotite-chalcopyrite intergrowths from a range of different deposits. These deposits exemplify slowly cooled magmatic environments (Nova, Western Australia; Sudbury, Canada), globular ores from shallow-level intrusions (Norilsk, Siberia), extrusive komatiite-hosted ores from low and high metamorphic-grade terranes, and a number of other deposits. Our approach was complemented by laser ablation-inductively coupled plasma-mass spectrometry analysis of palladium in varying textural types of pentlandite within these deposits. Pentlandite forming coarse granular aggregates, together with loop-textured pentlandite where chalcopyrite also forms part of the loop framework, consistently has the highest Pd content compared with pentlandite clearly exsolved as lamellae from MSS or pyrrhotite. This is consistent with much of granular and loop pentlandite being formed by peritectic reaction between Pd-rich residual sulfide liquid and early crystallized MSS, rather than forming entirely by subsolidus grain boundary exsolution from MSS, as has hitherto been assumed. The wide range of Pd contents in pentlandite in individual samples reflects a continuum of processes between peritectic reaction and grain boundary exsolution. Textures in metamorphically recrystallized ores are distinctly different from loop-textured ores, implying that loop textures cannot be regenerated (except in special circumstances) by metamorphic recrystallization of original magmatic-textured ores. The presence of loop textures can therefore be taken as evidence of a lack of penetrative deformation and remobilization at submagmatic temperatures, a conclusion of particular significance to the interpretation of the Nova deposit as having formed synchronously with the peak of regional deformation at temperatures within the sulfide melting range.
From perception to action using observed actions to learn gestures
2020-08-24

Abstract Pervasive computing environments deliver a multitude of possibilities for human–computer interactions. Modern technologies, such as gesture control or speech recognition, allow different devices to be controlled without additional hardware. A drawback of these concepts is that gestures and commands need to be learned. We propose a system that is able to learn actions by observation of the user. To accomplish this, we use a camera and deep learning algorithms in a self-supervised fashion. The user can either train the system directly by showing gestures examples and perform an action, or let the system learn by itself. To evaluate the system, five experiments are carried out. In the first experiment, initial detectors are trained and used to evaluate our training procedure. The following three experiments are used to evaluate the adaption of our system and the applicability to new environments. In the last experiment, the online adaption is evaluated as well as adaption times and intervals are shown.
The evolving field of Dermato‐oncology and the role of dermatologists: Position Paper of the EADO, EADV and Task Forces, EDF, IDS, EBDV–UEMS and EORTC Cutaneous Lymphoma Task Force
2020-08-24

Abstract Background The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society. Objective Members of the European Association of Dermato‐Oncology, European Academy of Dermatology and Venereology, International Dermoscopy Society, European Dermatology Forum, European Board of Dermatovenereology of the European Union of Medical Specialists and EORTC Cutaneous Lymphoma Task Force have joined this effort to emphasize the fundamental role that the specialist in Dermatology–Venereology has in the diagnosis and management of different types of skin cancer. We review the role of dermatologists in the prevention, diagnosis, treatment and follow‐up of patients with melanoma, non‐melanoma skin cancers and cutaneous lymphomas, and discuss approaches to optimize their involvement in effectively addressing the current needs and priorities of dermato‐oncology. Discussion Dermatologists play a crucial role in virtually all aspects of skin cancer management including the implementation of primary and secondary prevention, the formation of standardized pathways of care for patients, the establishment of specialized skin cancer treatment centres, the coordination of an efficient multidisciplinary team and the setting up of specific follow‐up plans for patients. Conclusion Skin cancers represent an important health issue for modern societies. The role of dermatologists is central to improving patient care and outcomes. In view of the emerging diagnostic methods and treatments for early and advanced skin cancer, and considering the increasingly diverse skills, knowledge and expertise needed for managing this heterogeneous group of diseases, dermato‐oncology should be considered as a specific subspecialty of Dermatology–Venereology.
The new 14C chronology for the Palaeolithic site of La Ferrassie, France: the disappearance of Neanderthals and the arrival of Homo sapiens in France
2020-08-24

Abstract The grand abri at La Ferrassie (France) has been a key site for Palaeolithic research since the early part of the 20th century. It became the eponymous site for one variant of Middle Palaeolithic stone tools, and its sequence was used to define stages of the Aurignacian, an early phase of the Upper Palaeolithic. Several Neanderthal remains, including two relatively intact skeletons, make it one of the most important sites for the study of Neanderthal morphology and one of the more important data sets when discussing the Neanderthal treatment of the dead. However, the site has remained essentially undated. Our goal here is to provide a robust chronological framework of the La Ferrassie sequence to be used for broad regional models about human behaviour during the late Middle to Upper Palaeolithic periods. To achieve this goal, we used a combination of modern excavation methods, extensive geoarchaeological analyses, and radiocarbon dating. If we accept that Neanderthals were responsible for the Châtelperronian, then our results suggest an overlap of ca. 1600 years with the newly arrived Homo sapiens found elsewhere in France.
The BCL-2 selective inhibitor ABT-199 sensitizes soft tissue sarcomas to proteasome inhibition by a concerted mechanism requiring BAX and NOXA
2020-08-24

Abstract Soft tissue sarcomas (STS) are a heterogeneous group of malignancies predominantly affecting children and young adults. Despite improvements in multimodal therapies, 5-year survival rates are only 50% and new treatment options in STS are urgently needed. To develop a rational combination therapy for the treatment of STS we focused on ABT-199 (Venetoclax), a BCL-2 specific BH3-mimetic, in combination with the proteasome inhibitor bortezomib (BZB). Simultaneous inhibition of BCL-2 and the proteasome resulted in strongly synergistic apoptosis induction. Mechanistically, ABT-199 mainly affected the multidomain effector BAX by liberating it from BCL-2 inhibition. The combination with BZB additionally resulted in the accumulation of BOK, a BAX/BAK homologue, and of the BH3-only protein NOXA, which inhibits the anti-apoptotic protein MCL-1. Thus, the combination of ABT-199 and BZB sensitizes STS cells to apoptosis by simultaneously releasing several defined apoptotic restraints. This synergistic mechanism of action was verified by CRISPR/Cas9 knock-out, showing that both BAX and NOXA are crucial for ABT-199/BZB-induced apoptosis. Noteworthy, efficient induction of apoptosis by ABT-199/BZB was not affected by the p53 status and invariably detected in cell lines and patient-derived tumor cells of several sarcoma types, including rhabdomyo-, leiomyo-, lipo-, chondro-, osteo-, or synovial sarcomas. Hence, we propose the combination of ABT-199 and BZB as a promising strategy for the treatment of STS, which should warrant further clinical investigation.
Mustafin varieties, moduli spaces and tropical geometry
2020-08-24

Abstract Mustafin varieties are flat degenerations of projective spaces, induced by a set of lattices in a vector space over a non-archimedean field. They were introduced by Mustafin (Math USSR-Sbornik 34(2):187, 1978) in the 70s in order to generalise Mumford’s groundbreaking work on the unformisation of curves to higher dimension. These varieties have a rich combinatorial structure as can be seen in pioneering work of Cartwright et al. (Selecta Math 17(4):757–793, 2011). In this paper, we introduce a new approach to Mustafin varieties in terms of images of rational maps, which were studied in Li (IMRN, 2017). Applying tropical intersection theory and tropical convex hull computations, we use this method to give a new combinatorial description of the irreducible components of the special fibers of Mustafin varieties. Finally, we outline a first application of our results in limit linear series theory.
Metabolite Patterns in Human Myeloid Hematopoiesis Result from Lineage-Dependent Active Metabolic Pathways
2020-08-24

Assessment of hematotoxicity from environmental or xenobiotic compounds is of notable interest and is frequently assessed via the colony forming unit (CFU) assay. Identification of the mode of action of single compounds is of further interest, as this often enables transfer of results across different tissues and compounds. Metabolomics displays one promising approach for such identification, nevertheless, suitability with current protocols is restricted. Here, we combined a hematopoietic stem and progenitor cell (HSPC) expansion approach with distinct lineage differentiations, resulting in formation of erythrocytes, dendritic cells and neutrophils. We examined the unique combination of pathway activity in glycolysis, glutaminolysis, polyamine synthesis, fatty acid oxidation and synthesis, as well as glycerophospholipid and sphingolipid metabolism. We further assessed their interconnections and essentialness for each lineage formation. By this, we provide further insights into active metabolic pathways during the differentiation of HSPC into different lineages, enabling profound understanding of possible metabolic changes in each lineage caused by exogenous compounds.
Inactivation of the htpsA gene affects capsule development and pathogenicity of Streptococcus suis
2020-08-24

<b>Streptococcus suis</b> serotype 2 (<i>S. suis</i> 2) is an important swine pathogen and also an emerging zoonotic agent. HtpsA has been reported as an immunogenic cell surface protein on the bacterium. In the present study, we constructed an isogenic mutant strain of <i>htps</i>A, namely Δ<i>htps</i>A, to study its role in the development and virulence of <i>S. suis</i> 2. Our results showed that the mutant strain lost its typical encapsulated structure with decreased concentrations of sialic acid. Furthermore, the survival rate in whole blood, the anti-phagocytosis by RAW264.7 murine macrophage, and the adherence ability to HEp-2 cells were all significantly affected in the Δ<i>htps</i>A. In addition, the deletion of <i>htps</i>A sharply attenuated the virulence of <i>S. suis</i> 2 in an infection model of mouse. RNA-seq analysis revealed that 126 genes were differentially expressed between the Δ<i>htps</i>A and the wild-type strains, including 28 upregulated and 98 downregulated genes. Among the downregulated genes, many were involved in carbohydrate metabolism and synthesis of virulence-associated factors. Taken together, <i>htps</i>A was demonstrated to play a role in the morphological development and pathogenesis of the highly virulent <i>S. suis</i> 2 05ZYH33 strain.