julilili42/papers huggingface dataset:
k-Provability in PA
2021-10-06

We study the decidability of k-provability in PA—the relation ‘being provable in PA with at most k steps’—and the decidability of the proof-skeleton problem—the problem of deciding if a given formula has a proof that has a given skeleton (the list of axioms and rules that were used). The decidability of k-provability for the usual Hilbert-style formalisation of PA is still an open problem, but it is known that the proof-skeleton problem is undecidable for that theory. Using new methods, we present a characterisation of some numbers k for which k-provability is decidable, and we present a characterisation of some proof-skeletons for which one can decide whether a formula has a proof whose skeleton is the considered one. These characterisations are natural and parameterised by unification algorithms.
Small but mighty: Functional landscape of the versatile geminivirus-encoded C4 protein
2021-10-07

The fast-paced evolution of viruses enables them to quickly adapt to the organisms they infect by constantly exploring the potential functional landscape of the proteins encoded in their genomes. Geminiviruses, DNA viruses infecting plants and causing devastating crop diseases worldwide, produce a limited number of multifunctional proteins that mediate the manipulation of the cellular environment to the virus’ advantage. Among the proteins produced by the members of this family, C4, the smallest one described to date, is emerging as a powerful viral effector with unexpected versatility. C4 is the only geminiviral protein consistently subjected to positive selection and displays a number of dynamic subcellular localizations, interacting partners, and functions, which can vary between viral species. In this review, we aim to summarize our current knowledge on this remarkable viral protein, encompassing the different aspects of its multilayered diversity, and discuss what it can teach us about geminivirus evolution, invasion requirements, and virulence strategies.
The impact of dissection membrane motility on mid-term aortic remodelling after thoracic endovascular repair
2021-10-07

Abstract OBJECTIVES The aim of this study was to assess preoperative dissection flap motility and to evaluate its impact on the aortic remodelling and the development of distal stent-induced new entry after thoracic endovascular aneurysm repair (TEVAR)/frozen elephant trunk (FET). METHODS Patients with primary or residual type B dissections were included in a retrospective study with transoesophageal echocardiography analysis of the preoperative dissection flap motility assessed by the true lumen (TL) strain. Three-dimensional computing tomography centreline reconstructions before TEVAR/FET and during the follow-up were conducted to measure aortic remodelling: false lumen thrombosis, TL expansion and aortic diameters at 10 and 20 cm downstream the left subclavian artery, at the coeliac trunk and in the infrarenal aorta. All continuous variables are reported as median with first and third quartiles. RESULTS Fifty-six consecutive patients were treated with TEVAR (n = 45) or FET (n = 11) in the acute (n = 16), subacute (n = 16) and chronic (n = 24) dissection phase. At a median follow-up of 6 (3–12) months, they showed a favourable TL expansion in the descending aorta, significantly higher in the acute [+9 mm (5–12); P &amp;lt; 0.001] and subacute groups [+5 mm (3–8); P = 0.039] than in the chronic group [+2 mm (0–5)]. The dissection flap motility parameter TL strain was superior in the acute (P = 0.006) and subacute (P = 0.035) groups in comparison to the chronic group. The motile flap [TL strain &amp;gt;22.5% (median)] was associated with a higher TL expansion rate in the thoracic aorta (P = 0.009) and a comparable distal stent-induced new entry incidence (overall: 16%) in comparison to the immobile flap (P = 0.89). CONCLUSIONS The intraoperative assessment and the inclusion of the dissection flap motility parameters in the decision-making during TEVAR/FET may refine the distal endograft sizing for an improved remodelling of the TL.
The Endophytic Fungus Cyanodermella asteris Influences Growth of the Nonnatural Host Plant Arabidopsis thaliana
2021-10-07

Cyanodermella asteris is a fungal endophyte from Aster tataricus, a perennial plant from the northern part of Asia. Here, we demonstrated an interaction of C. asteris with Arabidopsis thaliana, Chinese cabbage, rapeseed, tomato, maize, or sunflower resulting in different phenotypes such as shorter main roots, massive lateral root growth, higher leaf and root biomass, and increased anthocyanin levels. In a variety of cocultivation assays, it was shown that these altered phenotypes are caused by fungal CO 2 , volatile organic compounds, and soluble compounds, notably astins. Astins A, C, and G induced plant growth when they were individually included in the medium. In return, A. thaliana stimulates the fungal astin C production during cocultivation. Taken together, our results indicate a bilateral interaction between the fungus and the plant. A stress response in plants is induced by fungal metabolites while plant stress hormones induced astin C production of the fungus. Interestingly, our results not only show unidirectional influence of the fungus on the plant but also vice versa. The plant is able to influence growth and secondary metabolite production in the endophyte, even when both organisms do not live in close contact, suggesting the involvement of volatile compounds. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Genome Sequence of Escherichia coli Stbl4, a Versatile Genetic Tool for Heterologous Expression
2021-10-07

Escherichia coli Stbl4 is widely used as a laboratory strain for heterologous expression of large gene clusters. Since no genome sequence has been publicly available, we here report the draft sequence of Stbl4, including its F-plasmid. It should serve as a useful reference for researchers working with Stbl4.
ATISS: Autoregressive Transformers for Indoor Scene Synthesis
2021-10-07

The ability to synthesize realistic and diverse indoor furniture layouts automatically or based on partial input, unlocks many applications, from better interactive 3D tools to data synthesis for training and simulation. In this paper, we present ATISS, a novel autoregressive transformer architecture for creating diverse and plausible synthetic indoor environments, given only the room type and its floor plan. In contrast to prior work, which poses scene synthesis as sequence generation, our model generates rooms as unordered sets of objects. We argue that this formulation is more natural, as it makes ATISS generally useful beyond fully automatic room layout synthesis. For example, the same trained model can be used in interactive applications for general scene completion, partial room re-arrangement with any objects specified by the user, as well as object suggestions for any partial room. To enable this, our model leverages the permutation equivariance of the transformer when conditioning on the partial scene, and is trained to be permutation-invariant across object orderings. Our model is trained end-to-end as an autoregressive generative model using only labeled 3D bounding boxes as supervision. Evaluations on four room types in the 3D-FRONT dataset demonstrate that our model consistently generates plausible room layouts that are more realistic than existing methods. In addition, it has fewer parameters, is simpler to implement and train and runs up to 8 times faster than existing methods.
Ten millennia of hepatitis B virus evolution
2021-10-08

Ancient DNA traces the history of hepatitis B Hepatitis B virus (HBV) infections represent a worldwide human health concern. To study the history of this pathogen, Kocher et al . identified 137 human remains with detectable levels of virus dating between 400 and 10,000 years ago. Sequencing and analyses of these ancient viruses suggested a common ancestor between 12,000 and 20,000 years ago. There is no evidence indicating that HBV was present in the earliest humans as they spread out of Africa; however, HBV was likely present in human populations before farming. Furthermore, the virus was present in the Americas by about 9000 years ago, representing a lineage sister to the viral strains found in Eurasia that diverged about 20,000 years ago. —LMZ
Gain-of-function variants in GABRD reveal a novel pathway for neurodevelopmental disorders and epilepsy
2021-10-08

Abstract A potential link between GABRD encoding the δ subunit of extrasynaptic GABAA receptors and neurodevelopmental disorders has largely been disregarded due to conflicting conclusions from early studies. However, we identified seven heterozygous missense GABRD variants in 10 patients with neurodevelopmental disorders and generalized epilepsy. One variant occurred in two sibs of healthy parents with presumed somatic mosaicism, another segregated with the disease in three affected family members, and the remaining five occurred de novo in sporadic patients. Electrophysiological measurements were used to determine the functional consequence of the seven missense δ subunit variants in receptor combinations of α1β3δ and α4β2δ GABAA receptors. This was accompanied by analysis of electroclinical phenotypes of the affected individuals. We determined that five of the seven variants caused altered function of the resulting α1β3δ and α4β2δ GABAA receptors. Surprisingly, four of the five variants led to gain-of-function effects, whereas one led to a loss-of-function effect. The stark differences between the gain-of-function and loss-of function effects were mirrored by the clinical phenotypes. Six patients with gain-of-function variants shared common phenotypes: neurodevelopmental disorders with behavioural issues, various degrees of intellectual disability, generalized epilepsy with atypical absences and generalized myoclonic and/or bilateral tonic–clonic seizures. The EEG showed qualitative analogies among the different gain-of-function variant carriers consisting of focal slowing in the occipital regions often preceding irregular generalized epileptiform discharges, with frontal predominance. In contrast, the one patient carrying a loss-of-function variant had normal intelligence and no seizure history, but has a diagnosis of autism spectrum disorder and suffers from elevated internalizing psychiatric symptoms. We hypothesize that increase in tonic GABA-evoked current levels mediated by δ-containing extrasynaptic GABAA receptors lead to abnormal neurotransmission, which represent a novel mechanism for severe neurodevelopmental disorders. In support of this, the electroclinical findings for the gain-of-function GABRD variants resemble the phenotypic spectrum reported in patients with missense SLC6A1 (GABA uptake transporter) variants. This also indicates that the phenomenon of extrasynaptic receptor overactivity is observed in a broader range of patients with neurodevelopmental disorders, because SLC6A1 loss-of-function variants also lead to overactive extrasynaptic δ-containing GABAA receptors. These findings have implications when selecting potential treatment options, as a substantial portion of available antiseizure medication act by enhancing GABAergic function either directly or indirectly, which could exacerbate symptoms in patients with gain-of-function GABRD variants.
A data-driven disease progression model of fluid biomarkers in genetic frontotemporal dementia
2021-10-08

Abstract Several CSF and blood biomarkers for genetic frontotemporal dementia have been proposed, including those reflecting neuroaxonal loss (neurofilament light chain and phosphorylated neurofilament heavy chain), synapse dysfunction [neuronal pentraxin 2 (NPTX2)], astrogliosis (glial fibrillary acidic protein) and complement activation (C1q, C3b). Determining the sequence in which biomarkers become abnormal over the course of disease could facilitate disease staging and help identify mutation carriers with prodromal or early-stage frontotemporal dementia, which is especially important as pharmaceutical trials emerge. We aimed to model the sequence of biomarker abnormalities in presymptomatic and symptomatic genetic frontotemporal dementia using cross-sectional data from the Genetic Frontotemporal dementia Initiative (GENFI), a longitudinal cohort study. Two-hundred and seventy-five presymptomatic and 127 symptomatic carriers of mutations in GRN, C9orf72 or MAPT, as well as 247 non-carriers, were selected from the GENFI cohort based on availability of one or more of the aforementioned biomarkers. Nine presymptomatic carriers developed symptoms within 18 months of sample collection (‘converters’). Sequences of biomarker abnormalities were modelled for the entire group using discriminative event-based modelling (DEBM) and for each genetic subgroup using co-initialized DEBM. These models estimate probabilistic biomarker abnormalities in a data-driven way and do not rely on previous diagnostic information or biomarker cut-off points. Using cross-validation, subjects were subsequently assigned a disease stage based on their position along the disease progression timeline. CSF NPTX2 was the first biomarker to become abnormal, followed by blood and CSF neurofilament light chain, blood phosphorylated neurofilament heavy chain, blood glial fibrillary acidic protein and finally CSF C3b and C1q. Biomarker orderings did not differ significantly between genetic subgroups, but more uncertainty was noted in the C9orf72 and MAPT groups than for GRN. Estimated disease stages could distinguish symptomatic from presymptomatic carriers and non-carriers with areas under the curve of 0.84 (95% confidence interval 0.80–0.89) and 0.90 (0.86–0.94) respectively. The areas under the curve to distinguish converters from non-converting presymptomatic carriers was 0.85 (0.75–0.95). Our data-driven model of genetic frontotemporal dementia revealed that NPTX2 and neurofilament light chain are the earliest to change among the selected biomarkers. Further research should investigate their utility as candidate selection tools for pharmaceutical trials. The model’s ability to accurately estimate individual disease stages could improve patient stratification and track the efficacy of therapeutic interventions.
Shaping of Regional Differences in Oligodendrocyte Dynamics by Regional Heterogeneity of the Pericellular Microenvironment
2021-10-08

Oligodendrocyte precursor cells (OPCs) are glial cells that differentiate into mature oligodendrocytes (OLs) to generate new myelin sheaths. While OPCs are distributed uniformly throughout the gray and white matter in the developing and adult brain, those in white matter proliferate and differentiate into oligodendrocytes at a greater rate than those in gray matter. There is currently lack of evidence to suggest that OPCs comprise genetically and transcriptionally distinct subtypes. Rather, the emerging view is that they exist in different cell and functional states, depending on their location and age. Contrary to the normal brain, demyelinated lesions in the gray matter of multiple sclerosis brains contain more OPCs and OLs and are remyelinated more robustly than those in white matter. The differences in the dynamic behavior of OL lineage cells are likely to be influenced by their microenvironment. There are regional differences in astrocytes, microglia, the vasculature, and the composition of the extracellular matrix (ECM). We will discuss how the regional differences in these elements surrounding OPCs might shape their phenotypic variability in normal and demyelinated states.
How activated NLRs induce anti-microbial defenses in plants
2021-10-08

Plants utilize cell-surface localized and intracellular leucine-rich repeat (LRR) immune receptors to detect pathogens and to activate defense responses, including transcriptional reprogramming and the initiation of a form of programmed cell death of infected cells. Cell death initiation is mainly associated with the activation of nucleotide-binding LRR receptors (NLRs). NLRs recognize the presence or cellular activity of pathogen-derived virulence proteins, so-called effectors. Effector-dependent NLR activation leads to the formation of higher order oligomeric complexes, termed resistosomes. Resistosomes can either form potential calcium-permeable cation channels at cellular membranes and initiate calcium influxes resulting in activation of immunity and cell death or function as NADases whose activity is needed for the activation of downstream immune signaling components, depending on the N-terminal domain of the NLR protein. In this mini-review, the current knowledge on the mechanisms of NLR-mediated cell death and resistance pathways during plant immunity is discussed.
Overbank silt-clay deposition and intensive Neolithic land use in a Central European catchment – Coupled or decoupled?
2021-10-08

Hydro-sedimentary processes such as soil erosion, sediment transport, deposition, and re-deposition influence the environmental evolution of floodplains, especially in loess-covered catchments. Holocene floodplain deposits are thus a source of information on previous hydro-sedimentary dynamics and land use in the catchment. Resulting from forest clearings in the catchment, the onset of overbank silt-clay deposition is considered as an initial and significant human-induced process affecting Central European floodplain evolution and ecosystems. However, it is difficult to separate climate-related from anthropogenic forces on depositional environments, and the complexity of the hydro-sedimentary responses is part of an ongoing debate in geoscientific, ecological, and archaeological communities. This study focuses on the Central European Weiße Elster river system, where humans have been influencing hydro-sedimentary processes since the Early Neolithic due to land-use-induced soil erosion predominantly in the loess-covered sub-basin of the middle course. A catchment-scale XRF element record of fluvial sediment sources combined with the geochemical characterisation of Holocene floodplain deposits aim for a better understanding of the interplay between past soil erosion, overbank deposition in the floodplain, and potential changes in sediment provenances. The Weiße Elster floodplain chronosequences show a geochemical differentiation into a lower (Neolithic) and an upper (post-Neolithic) overbank silt-clay deposition. The construction of a sediment source fingerprinting mixing model yields the significant finding that the Neolithic overbank silt-clay deposition reveals a remote provenance signal from the upper catchment and less from the proximal loess-covered sub-catchment. According to a systematic archaeological data survey, the upper catchment was not permanently settled and used for agriculture in the Neolithic period. This contradicts the previous assumption that Neolithic overbank silt-clay deposition primarily originates from forest clearings and subsequent farming-induced soil erosion in the catchment. From a more general perspective, further examination of existing hypotheses concerning overbank silt-clay deposition in Central European floodplains is thus in order.
A Phytolith Supported Biosphere-Hydrosphere Predictive Model for Southern Ethiopia: Insights into Paleoenvironmental Changes and Human Landscape Preferences since the Last Glacial Maximum
2021-10-08

During the past 25 ka, southern Ethiopia has undergone tremendous climatic changes, from dry and relatively cold during the Last Glacial Maximum (LGM, 25–18 ka) to the African Humid Period (AHP, 15–5 ka), and back to present-day dry conditions. As a contribution to better understand the effects of climate change on vegetation and lakes, we here present a new Predictive Vegetation Model that is linked with a Lake Balance Model and available vegetation-proxy records from southern Ethiopia including a new phytolith record from the Chew Bahir basin. We constructed a detailed paleo-landcover map of southern Ethiopia during the LGM, AHP (with and without influence of the Congo Air Boundary) and the modern-day potential natural landcover. Compared to today, we observe a 15–20% reduction in moisture availability during the LGM with widespread open landscapes and only few remaining forest refugia. We identify 25–40% increased moisture availability during the AHP with prevailing forests in the mid-altitudes and indications that modern anthropogenic landcover change has affected the water balance. In comparison with existing archaeological records, we find that human occupations tend to correspond with open landscapes during the late Pleistocene and Holocene in southern Ethiopia.
Sensitivity and Specificity in Urine Bladder Cancer Markers – Is it that Simple?
2021-10-08

Marker research, and in particular urine bladder cancer marker research throughout the past three decades, devours enormous scientific resources in terms of manpower (not to mention time spent on reviewing and editorial efforts) and financial resources, finally generating large numbers of manuscripts without affecting clinical decision making. This is mirrored by the fact that current guidelines do not recommend marker use due to missing level 1 evidence. Although we recognize the problems and obstacles, the authors of this commentary feel that the time has come to abandon the current procedures and move on to prospective trial designs implementing marker results into clinical decision making. Our thoughts and concerns are summarized in this comment.
stsing: Doing STS In, Through And Beyond the German Academic System
2021-10-08

The recently constituted association stsing offers scholars a new platform to “do” STS in and through Germany (therefore the wording stsing). Specific about this platform is its creative and open understanding of collaboration on the one hand and critical reflection of national, international, institutional, and intergenerational challenges of STS research on the other. Germany’s specific funding and institutional structure is of central importance to stsing. At the same time, stsing is responding to the internationally integrated practices of STS. It addresses the frictions between local bureaucracies and hierarchies as well as global doings and (self-)understandings of STS. We briefly unfold the (hi)story of stsing: a process of negotiating imaginaries, institutional settings, conflicts and mutual recognition. The challenge is to open spaces and account for the heterogeneous people and disciplines engaged with the ideas, methodologies and politics of STS. stsing experiments with configuring infrastructures and organisational policies to support transnationally and interdisciplinarily oriented STS research practice. This experimentation works across generations and encounters troubles between and within generations of STS.