julilili42/papers huggingface dataset:
A type VII-secreted lipase toxin with reverse domain arrangement
2023-12-19

Abstract The type VII protein secretion system (T7SS) is found in many Gram-positive bacteria and in pathogenic mycobacteria. All T7SS substrate proteins described to date share a common helical domain architecture at the N-terminus that typically interacts with other helical partner proteins, forming a composite signal sequence for targeting to the T7SS. The C-terminal domains are functionally diverse and in Gram-positive bacteria such as Staphylococcus aureus often specify toxic anti-bacterial activity. Here we describe the first example of a class of T7 substrate, TslA, that has a reverse domain organisation. TslA is widely found across Bacillota including Staphylococcus , Enterococcus and Listeria . We show that the S. aureus TslA N-terminal domain is a phospholipase A with anti-staphylococcal activity that is neutralised by the immunity lipoprotein TilA. Two small helical partner proteins, TlaA1 and TlaA2 are essential for T7-dependent secretion of TslA and at least one of these interacts with the TslA C-terminal domain to form a helical stack. Cryo-EM analysis of purified TslA complexes indicate that they share structural similarity with canonical T7 substrates. Our findings suggest that the T7SS has the capacity to recognise a secretion signal present at either end of a substrate.
Mosquito-Borne Arboviruses Occurrence and Distribution in the Last Three Decades in Central Africa: A Systematic Literature Review
2023-12-19

Arboviruses represent a real public health problem globally and in the Central African subregion in particular, which represents a high-risk zone for the emergence and re-emergence of arbovirus outbreaks. Furthermore, an updated review on the current arbovirus burden and associated mosquito vectors is lacking for this region. To contribute to filling this knowledge gap, the current study was designed with the following objectives: (i) to systematically review data on the occurrence and distribution of arboviruses and mosquito fauna; and (ii) to identify potential spillover mosquito species in the Central African region in the last 30 years. A web search enabled the documentation of 2454 articles from different online databases. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the quality of reporting of meta-analyses (QUORUM) steps for a systematic review enabled the selection of 164 articles that fulfilled our selection criteria. Of the six arboviruses (dengue virus (DENV), chikungunya virus (CHIKV), yellow fever virus (YFV), Zika virus (ZIKV), Rift Valley fever virus (RVFV), and West Nile virus (WNV)) of public health concern studied, the most frequently reported were chikungunya and dengue. The entomological records showed &gt;248 species of mosquitoes regrouped under 15 genera, with Anopheles (n = 100 species), Culex (n = 56 species), and Aedes (n = 52 species) having high species diversity. Three genera were rarely represented, with only one species included, namely, Orthopodomyia, Lutzia, and Verrallina, but individuals of the genera Toxorhinchites and Finlayas were not identified at the species level. We found that two Aedes species (Ae. aegypti and Ae. albopictus) colonised the same microhabitat and were involved in major epidemics of the six medically important arboviruses, and other less-frequently identified mosquito genera consisted of competent species and were associated with outbreaks of medical and zoonotic arboviruses. The present study reveals a high species richness of competent mosquito vectors that could lead to the spillover of medically important arboviruses in the region. Although epidemiological studies were found, they were not regularly documented, and this also applies to vector competence and transmission studies. Future studies will consider unpublished information in dissertations and technical reports from different countries to allow their information to be more consistent. A regional project, entitled “Ecology of Arboviruses” (EcoVir), is underway in three countries (Gabon, Benin, and Cote d’Ivoire) to generate a more comprehensive epidemiological and entomological data on this topic.
Language with vision: A study on grounded word and sentence embeddings
2023-12-19

Abstract Grounding language in vision is an active field of research seeking to construct cognitively plausible word and sentence representations by incorporating perceptual knowledge from vision into text-based representations. Despite many attempts at language grounding, achieving an optimal equilibrium between textual representations of the language and our embodied experiences remains an open field. Some common concerns are the following. Is visual grounding advantageous for abstract words, or is its effectiveness restricted to concrete words? What is the optimal way of bridging the gap between text and vision? To what extent is perceptual knowledge from images advantageous for acquiring high-quality embeddings? Leveraging the current advances in machine learning and natural language processing, the present study addresses these questions by proposing a simple yet very effective computational grounding model for pre-trained word embeddings. Our model effectively balances the interplay between language and vision by aligning textual embeddings with visual information while simultaneously preserving the distributional statistics that characterize word usage in text corpora. By applying a learned alignment, we are able to indirectly ground unseen words including abstract words. A series of evaluations on a range of behavioral datasets shows that visual grounding is beneficial not only for concrete words but also for abstract words, lending support to the indirect theory of abstract concepts. Moreover, our approach offers advantages for contextualized embeddings, such as those generated by BERT (Devlin et al, 2018), but only when trained on corpora of modest, cognitively plausible sizes. Code and grounded embeddings for English are available at ( https://github.com/Hazel1994/Visually_Grounded_Word_Embeddings_2 ).
Inverse problem of analog gravity systems
2023-12-19

Analog gravity models of black holes and exotic compact objects provide a unique opportunity to study key properties of such systems in controlled laboratory environments. In contrast to astrophysical systems, analog gravity systems can be prepared carefully and their dynamical aspects thus investigated in unprecedented ways. While gravitational wave scattering properties of astrophysical compact objects are more connected to quasinormal modes, laboratory experiments can also access the transmission and reflection coefficients, which are otherwise mostly relevant for Hawking radiation related phenomena. In this work, we report two distinct results. First, we outline a semiclassical, nonparametric method that allows for the reconstruction of the effective perturbation potential from the knowledge of transmission and reflection coefficients for certain types of potentials in the Schr\\"odinger wave equation admitting resonant tunneling. Second, we show how to use our method by applying it to an imperfect draining vortex, which has been suggested as an analog of extreme compact objects. Although the inverse problem is, in general, not unique, choosing physically motivated assumptions and requiring the validity of semiclassical theory, we demonstrate that the method provides efficient and accurate results.
Interactome Analysis Reveals a Link of the Novel ALMS1-CEP70 Complex to Centrosomal Clusters
2023-12-19

Alström syndrome (ALMS) is a very rare autosomal-recessive disorder, causing a broad range of clinical defects most notably retinal degeneration, type 2 diabetes, and truncal obesity. The ALMS1 gene encodes a complex and huge ∼0.5 MDa protein, which has hampered analysis in the past. The ALMS1 protein is localized to the centrioles and the basal body of cilia and is involved in signaling processes, for example, TGF-β signaling. However, the exact molecular function of ALMS1 at the basal body remains elusive and controversial. We recently demonstrated that protein complex analysis utilizing endogenously tagged cells provides an excellent tool to investigate protein interactions of ciliary proteins. Here, CRISPR/Cas9-mediated endogenously tagged ALMS1 cells were used for affinity-based protein complex analysis. Centrosomal and microtubule-associated proteins were identified, which are potential regulators of ALMS1 function, such as the centrosomal protein 70 kDa (CEP70). Candidate proteins were further investigated in ALMS1-deficient hTERT-RPE1 cells. Loss of ALMS1 led to shortened cilia with no change in structural protein localization, for example, acetylated and ɣ-tubulin, Centrin-3, or the novel interactor CEP70. Conversely, reduction of CEP70 resulted in decreased ALMS1 at the ciliary basal body. Complex analysis of CEP70 revealed domain-specific ALMS1 interaction involving the TPR-containing C-terminal (TRP-CT) fragment of CEP70. In addition to ALMS1, several ciliary proteins, including CEP135, were found to specifically bind to the TPR-CT domain. Data are available via ProteomeXchange with the identifier PXD046401. Protein interactors identified in this study provide candidate lists that help to understand ALMS1 and CEP70 function in cilia-related protein modification, cell death, and disease-related mechanisms.
Parkinson’s disease-related Miro1 mutation induces mitochondrial dysfunction and loss of dopaminergic neuronsin vitroandin vivo
2023-12-19

Abstract The complex and heterogeneous nature of Parkinson’s disease (PD) is still not fully understood, however, increasing evidence supports mitochondrial impairments as a major driver of neurodegeneration in PD. Recently, the regulator of mitochondrial homeostasis Miro1 has been linked genetically and pathophysiologically to PD. Using 2D and 3D patient-based induced pluripotent stem cells models, including an isogenic control, showed that the Miro1 p.R272Q mutation leads to mitochondrial impairments including increased oxidative stress, disrupted mitochondrial bioenergetics and altered metabolism. This was accompanied by increased α-synuclein levels in 2D dopaminergic neurons and by a significant reduction of dopaminergic neurons within midbrain organoids. Knock-in mice expressing mutant p.R285Q Miro1 (orthologue of the human p.R272Q mutation) confirmed the PD-specific dopaminergic neuronal loss in the substantia nigra, accumulation of striatal phosphorylated α-synuclein accompanied by behavioral alterations. These findings demonstrate that mutant Miro1 is sufficient to comprehensively model PD-relevant phenotypes in vitro and in vivo , reinforcing its pivotal role in PD pathogenesis.
Microscopic growth mechanism and edge states of monolayer 1T′-MoTe2
2023-12-19

Transition metal ditellurides (TMTDs) have versatile physical properties, including non-trivial topology, Weyl semimetal states and unique spin texture. Controlled growth of high-quality and large-scale monolayer TMTDs with preferred crystal phases is crucial for their applications. Here, we demonstrate the epitaxial growth of 1T′-MoTe 2 on Au (111) and graphitized silicon carbide (Gr/SiC) by molecular beam epitaxy (MBE). We investigate the morphology of the grown 1T′-MoTe 2 at the atomic level by scanning tunnelling microscopy (STM) and reveal the corresponding microscopic growth mechanism. It is found that the unique ordered Te structures preferentially deposited on Au (111) regulate the growth of monolayer single crystal 1T′-MoTe 2 , while the Mo clusters were preferentially deposited on the Gr/SiC substrate, which impedes the ordered growth of monolayer MoTe 2 . We confirm that the size of single crystal 1T′-MoTe 2 grown on Au (111) is nearly two orders of magnitude larger than that on Gr/SiC. By scanning tunnelling spectroscopy (STS), we observe that the STS spectrum of the monolayer 1T′-MoTe 2 nano-island at the edge is different from that at the interior, which exhibits enhanced conductivity.
A Rabbinic Epistemic Genre
2023-12-19

Lehmhaus focuses on the variegated forms and functions of lists in Jewish textual traditions from late antiquity, commonly known as rabbinic or talmudic literature. As he shows, Rabbinic works deploy lists for different discursive purposes-- exegetical, homiletical, narrative-- embedded in their ancient Near Eastern surroundings and based on a long tradition derived from biblical and other ancient Jewish traditions. Lehmhaus argues that rabbinic texts deploy the versatility or affordance of the list not only for ordering knowledge but also for the very process of knowledge turning them into a powerful ‘epistemic genre’. He suggests that rabbinic authors may have arrived at certain conclusions precisely in and through lists in which specific concepts or taxonomies were tried out before becoming more manifest or substantiated. This argument is exemplified by focusing on complex types of list in two tractates of the Babylonian Talmud, which can be described as clusters, sequences, or, most compellingly, as catalogues.
Regularity and Variation in Islamic Chains of Transmission
2023-12-19

The isnād is a list of narrators’ names which precedes an account about Islam’s prophet or his companions, and indicates its origin. The content and the form of this list have been studied in different fields. Islamicists have scrutinised the names contained in the isnād in order to assess the authenticity of the following account and uncover potential fraudsters. Computer scientists, in turn, have focused on form: they attempted to exploit the regular succession of names and transmission terms to develop algorithms capable of distinguishing isnād from non-isnād texts. The present chapter opens a novel horizon by analyzing the structural variations of the isnād within the old and universal context of list-making. A twofold methodology, combining traditional and computational text analysis, highlights the actual contours of the isnād in a large corpus of texts and propose a hierarchy of functions linked to the different variations observed.
Sand, hearths, lithics and a bit of bioturbation: Site formation processes at Umhlatuzana rockshelter, South Africa
2023-12-19

Abstract Umhlatuzana rockshelter is known for its continuous record of Middle and Later Stone Age lithic assemblages. This study presents multiproxy geoarchaeological data (micromorphology, X‐ray diffraction and scanning electron microscopy with energy‐dispersive spectroscopy) to reconstruct the depositional and post‐depositional history of the site. Although the Stone Age deposits macroscopically appear homogeneous, micromorphological analysis reveals the existence of primary, unaltered depositional microlayering throughout the sequence. Sediments related to combustion activities on‐site are observed in both the Holocene and Pleistocene deposits. Post‐depositional geochemical alterations result in the formation of several phosphatic minerals that significantly affect the site's preservation conditions. One of those is vashegyite, a rare magnesium phosphate mineral related to acidic and moist sedimentary environments. Bioturbation features are prominent at the microscale, but sediment mixing does not seem to affect the vertical distribution of the artifacts. The observation of horizontal microlayering in both the Pleistocene and Holocene illuminates the dominant mechanism of sedimentation throughout the site's 70,000‐year occupational history. It moreover shows that the lithics can be analysed as coherent assemblages.
Colored Noise in PPO: Improved Exploration and Performance through Correlated Action Sampling
2023-12-19

Proximal Policy Optimization (PPO), a popular on-policy deep reinforcement learning method, employs a stochastic policy for exploration. In this paper, we propose a colored noise-based stochastic policy variant of PPO. Previous research highlighted the importance of temporal correlation in action noise for effective exploration in off-policy reinforcement learning. Building on this, we investigate whether correlated noise can also enhance exploration in on-policy methods like PPO. We discovered that correlated noise for action selection improves learning performance and outperforms the currently popular uncorrelated white noise approach in on-policy methods. Unlike off-policy learning, where pink noise was found to be highly effective, we found that a colored noise, intermediate between white and pink, performed best for on-policy learning in PPO. We examined the impact of varying the amount of data collected for each update by modifying the number of parallel simulation environments for data collection and observed that with a larger number of parallel environments, more strongly correlated noise is beneficial. Due to the significant impact and ease of implementation, we recommend switching to correlated noise as the default noise source in PPO.
Report on 2310.17302v1
2023-12-19

The recently proposed center-focused post-processing procedure [Phys.Rev. Research 2, 033476 (2020)] of cellular dynamical mean-field theory suggests that central sites of large impurity clusters are closer to the exact solution of the Hubbard model than the edge sites.In this paper, we systematically investigate results in the spirit of this centerfocused scheme for several cluster sizes up to 8 × 8 in and out of particle-hole symmetry.First we analyze the metal-insulator crossovers and transitions of the half-filled Hubbard model on a simple square lattice.We find that the critical interaction of the crossover is reduced with increasing cluster sizes and the critical temperature abruptly drops for the 4 × 4 cluster.Second, for this cluster size, we apply the center-focused scheme to a system with more realistic tight-binding parameters, investigating its pseudogap regime as a function of temperature and doping, where we find doping dependent metal-insulator crossovers, Lifshitz transitions and a strongly renormalized Fermi-liquid regime.Additionally to diagnosing the real space origin of the suppressed antinodal spectral weight in the pseudogap regime, we can infer hints towards underlying charge ordering tendencies.
Rapidly rotating neutron stars: Universal relations and EOS inference
2023-12-20

We provide accurate universal relations that allow to estimate the moment of inertia and the ratio of kinetic to gravitational binding energy of uniformly rotating neutron stars from the knowledge of mass, radius, and moment of inertia of an associated nonrotating neutron star. Based on these, several other fluid quantities can be estimated as well. Astrophysical neutron stars rotate to varying degrees, and, although rotational effects may be neglected in some cases, not modeling them will inevitably introduce bias when performing parameter estimation. This is especially important for future, high-precision measurements coming from electromagnetic and gravitational wave observations. The proposed universal relations facilitate computationally cheap equation of state inference codes that permit the inclusion of observations of rotating neutron stars. To demonstrate this, we deploy them into a recent Bayesian framework for equation of state parameter estimation that is now valid for arbitrary, uniform rotation. Our inference results are robust up to around percent-level precision for the generated neutron star observations, consisting of the mass, equatorial radius, rotation rate, as well as co- and counterrotating -mode frequencies, that enter the framework as data.
The end of welfare states as we know them? A multidimensional perspective
2023-12-20

Abstract This article highlights the limitations of unidimensional analyses in the comparative welfare state literature and emphasises the need for a more holistic, multidimensional approach incorporating social spending, welfare state outputs and outcomes. To illustrate the utility of a multidimensional approach, we examine the long‐term welfare state trajectories of Sweden and Germany, prototypical social‐democratic and conservative welfare states, respectively, and compare them against the baseline of Europe's prototypical liberal welfare state, the United Kingdom. The social spending (expenditure) and output (generosity) allowed us to identify significant changes in the Swedish welfare state (i.e., retrenchment). The outcome dimension alerts us to a policy drift in the German Welfare State, as relatively stable public spending and welfare generosity until the first half of the 2000s were nonetheless associated with sharply increased inequality and poverty. Overall, our findings suggest that a holistic, multidimensional approach is necessary to fully understand the complexities of welfare state change and continuity, as focusing solely on one dimension can lead to analytical misjudgments. The sharp rise in inequality and poverty across countries raises doubts about whether policymakers and researchers rely too much on outdated assumptions of normality that fail to meet the welfare state realities of today.
The role of fire in the Medieval and Early Modern landscape of Bad Waldsee within the broader context of the pre-Alpine forelands of south-western Germany
2023-12-20

Abstract Fire, an important element of human land use strategies, was part of many early industrial activities but also of burning incidents that significantly impacted settlement structures and development. The spatial proximity of the historically well-documented medieval town and sediment archive deposited in its central lake (Stadtsee) was taken to investigate the interplay of fire and socio-environmental developments during the preindustrial phase of 750−150 bp ( ad 1200–1800). The burning episodes were detected using the sediment macroscopic charcoal record (&gt; 150 μm) and were interpreted considering sedimentological, palynological, and historical evidence. Macro-charcoal analysis revealed two main phases of biomass burning: a late Medieval one (653−533 cal bp ), followed by a distinct fire-free interval, and a second Modern Times phase (313 cal bp until today). During the late Medieval times and after ad 1750 (200 cal bp ) low-magnitude local fires coincided with high-intensity land use pressure. Major historical events like the Thirty Years’ War and the fire incident near the town ( ad 1386, 174 cal bp ) were also documented by the charcoal sedimentary record. The specific terrain morphology and the town microclimate impacted the chance of whether certain local burning patterns were detectable at all. This study demonstrates that during the Medieval period to the present day, fire events, mainly anthropogenic, were coupled with the main vegetation developments. Anthropogenic fire was an inseparable part of the Bad Waldsee landscape, as also recorded historically by the town archives.
Development of an optimized, non‐stem cell line for intranasal delivery of therapeutic cargo to the central nervous system
2023-12-20

Neural stem cells (NSCs) are considered to be valuable candidates for delivering a variety of anti‐cancer agents, including oncolytic viruses, to brain tumors. However, owing to the previously reported tumorigenic potential of NSC cell lines after intranasal administration (INA), here we identified the human hepatic stellate cell line LX‐2 as a cell type capable of longer resistance to replication of oncolytic adenoviruses (OAVs) as a therapeutic cargo, and that is non‐tumorigenic after INA. Our data show that LX‐2 cells can longer withstand the OAV XVir‐N‐31 replication and oncolysis than NSCs. By selecting the highly migratory cell population out of LX‐2, an offspring cell line with a higher and more stable capability to migrate was generated. Additionally, as a safety backup, we applied genomic herpes simplex virus thymidine kinase (HSV‐TK) integration into LX‐2, leading to high vulnerability to ganciclovir (GCV). Histopathological analyses confirmed the absence of neoplasia in the respiratory tracts and brains of immuno‐compromised mice 3 months after INA of LX‐2 cells. Our data suggest that LX‐2 is a novel, robust, and safe cell line for delivering anti‐cancer and other therapeutic agents to the brain.