julilili42/papers huggingface dataset:
Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial
2023-07-29

Rationale: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs. Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion. Methods and design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial. Study outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted. Sample size: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation. Discussion: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia. Trial registrations: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31.
Pre-sleep experiences shape neural activity and dream content in the sleeping brain
2023-07-29

Summary Dreams incorporate recent experiences, and memory-related brain activity is reactivated during sleep, suggesting that dreaming, memory consolidation and reactivation are tightly linked. We devised a paradigm to investigate whether memory reprocessing during sleep contributes to dreaming. Participants listened to different audiobooks before falling asleep, introducing dissimilar experiences to be processed at night. We show that audiobook content was reprocessed at the neural level using multivariate pattern analyses. Brain activity during rapid eye movement sleep, particularly in the beta range, carried information about the audiobook. While the amount of neural reinstatement did not correlate with memory retention, global beta power during REM sleep was associated with better memory performance. Moreover, blind raters could determine which audiobook participants had studied based on dream reports. Participants who dreamt of the audiobook also showed stronger neural reinstatement. Reprocessing of pre-sleep experiences during sleep may thus shape our brain activity, our dreams, and our memories.
An interbacterial lipase toxin with an unprecedented reverse domain arrangement defines a new class of type VII secretion system effector
2023-07-29

Summary 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 new class of T7 substrate, TslA, that has an unexpected 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 extraordinary feature of recognising a secretion signal present at either end of a substrate.
Data of "Dissipative quantum many-body dynamics in (1+1)D quantum cellular automata and quantum neural networks"
2023-07-30

&lt;p&gt;The uploaded files&nbsp;contain the data of the simulations&nbsp;presented in the figures in&nbsp;&lt;a href="https://doi.org/10.48550/arXiv.2304.11209"&gt;https://doi.org/10.48550/arXiv.2304.11209&lt;/a&gt;.&lt;/p&gt;
Plasma membrane association and resistosome formation of plant helper immune receptors
2023-07-31

Intracellular plant immune receptors, termed NLRs (Nucleotide-binding Leucine-rich repeat Receptors), confer effector-triggered immunity. Sensor NLRs are responsible for pathogen effector recognition. Helper NLRs function downstream of sensor NLRs to transduce signaling and induce cell death and immunity. Activation of sensor NLRs that contain TIR (Toll/interleukin-1receptor) domains generates small molecules that induce an association between a downstream heterodimer signalosome of EDS1 (EnhancedDisease Susceptibility 1)/SAG101 (Senescence-AssociatedGene 101) and the helper NLR of NRG1 (NRequired Gene 1). Autoactive NRG1s oligomerize and form calcium signaling channels largely localized at the plasma membrane (PM). The molecular mechanisms of helper NLR PM association and effector-induced NRG1 oligomerization are not well characterized. We demonstrate that helper NLRs require positively charged residues in their N-terminal domains for phospholipid binding and PM association before and after activation, despite oligomerization and conformational changes that accompany activation. We demonstrate that effector activation of a TIR-containing sensor NLR induces NRG1 oligomerization at the PM and that the cytoplasmic pool of EDS1/SAG101 is critical for cell death function. EDS1/SAG101 cannot be detected in the oligomerized NRG1 resistosome, suggesting that additional unknown triggers might be required to induce the dissociation of EDS1/SAG101 from the previously described NRG1/EDS1/SAG101 heterotrimer before subsequent NRG1 oligomerization. Alternatively, the conformational changes resulting from NRG1 oligomerization abrogate the interface for EDS1/SAG101 association. Our data provide observations regarding dynamic PM association during helper NLR activation and underpin an updated model for effector-induced NRG1 resistosome formation.
Delphi Consensus Among International Experts on the Diagnosis, Management, and Surveillance for Lentigo Maligna
2023-07-31

Introduction: Melanoma of the lentigo maligna (LM) type is challenging. There is lack of consensus on the optimal diagnosis, treatment, and follow-up. Objectives: To obtain general consensus on the diagnosis, treatment, and follow-up for LM. Methods: A modified Delphi method was used. The invited participants were either members of the International Dermoscopy Society, academic experts, or authors of published articles relating to skin cancer and melanoma. Participants were required to respond across three rounds using a 4-point Likert scale). Consensus was defined as &gt;75% of participants agreeing/strongly agreeing or disagreeing/strongly disagreeing. Results: Of the 31 experts invited to participate in this Delphi study, 29 participants completed Round 1 (89.9% response rate), 25/31 completed Round 2 (77.5% response rate), and 25/31 completed Round 3 (77.5% response rate). Experts agreed that LM diagnosis should be based on a clinical and dermatoscopic approach (92%) followed by a biopsy. The most appropriate primary treatment of LM was deemed to be margin-controlled surgery (83.3%), although non-surgical modalities, especially imiquimod, were commonly used either as alternative off-label primary treatment in selected patients or as adjuvant therapy following surgery; 62% participants responded life-long clinical follow-up was needed for LM. Conclusions: Clinical and histological diagnosis of LM is challenging and should be based on macroscopic, dermatoscopic, and RCM examination followed by a biopsy. Different treatment modalities and follow-up should be carefully discussed with the patient.
Desipramine induces eryptosis in human erythrocytes, an effect blunted by nitric oxide donor sodium nitroprusside and N-acetyl-L-cysteine but enhanced by Calcium depletion
2023-07-31

<b>Background:</b> Desipramine a representative of tricyclic antidepressants (TCAs) promotes recovery of depressed patients by inhibition of reuptake of neurotransmitters serotonin (SER) and norepinephrine (NE) in the presynaptic membrane by directly blocking their respective transporters SERT and NET.<b>Aims:</b> To study the effect of desipramine on programmed erythrocyte death (eryptosis) and explore the underlying mechanisms.<b>Methods:</b> Phosphatidylserine (PS) exposure on the cell surface as marker of cell death was estimated from annexin-V-binding, cell volume from forward scatter in flow cytometry. Hemolysis was determined photometrically, and intracellular glutathione [GSH]<sub>i</sub> from high performance liquid chromatography.<b>Results:</b> Desipramine dose-dependently significantly enhanced the percentage of annexin-V-binding cells and didn ́t impact glutathione (GSH) synthesis. Desipramine-induced eryptosis was significantly reversed by pre-treatment of erythrocytes with either nitric oxide (NO) donor sodium nitroprusside (SNP) or N-acetyl-L-cysteine (NAC). The highest inhibitory effect was obtained by using both inhibitors together. Calcium (Ca<sup>2+</sup>) depletion aggravated desipramine-induced eryptosis. Changing the order of treatment, i.e. desipramine first followed by inhibitors, could not influence the inhibitory effect of SNP or NAC.<b>Conclusion:</b> Antidepressants-caused intoxication can be treated by SNP and NAC, respectively. B) Patients with chronic hypocalcemia should not be treated with tricyclic anti-depressants or their dose should be noticeably reduced.
Intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase dependent mechanism
2023-07-31

Abstract The Parkinson’s Disease (PD)-linked protein Leucine Rich Repeat Kinase 2 (LRRK2) consists of seven domains, including a kinase and a Roc G domain. Despite the availability of several high-resolution structures, the dynamic regulation of its unique intramolecular domain stack is nevertheless still not well understood. By in-depth biochemical analysis, assessing the Michaelis-Menten kinetics of the Roc G domain, we have confirmed that LRRK2 has, similar to other Roco protein family members, a K M value of LRRK2 that lays within the range of the physiological GTP concentrations within the cell. Furthermore, the R1441G PD variant located within a mutational hotspot in the Roc domain showed an increased catalytic efficiency. In contrast, the most common PD variant G2019S, located in the kinase domain, showed an increased K M and reduced catalytic efficiency, suggesting a negative feedback mechanism from the kinase domain to the G domain. Autophosphorylation of the G1+2 residue (T1343) in the Roc P-loop motif is critical for this phosphoregulation of both the K M as well as the k cat values of the Roc-catalyzed GTP hydrolysis, most likely by changing the monomer-dimer equilibrium. The LRRK2 T1343A variant has a similar increased kinase activity in cells compared to G2019S and the double mutant T1343A/G2019S has no further increased activity suggesting that T1343 is crucial for the negative feedback in the LRRK2 signaling cascade. Together our data reveal a novel intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase dependent mechanism. Interestingly, PD mutants differently change the kinetics of the GTPase cycle, which might in part explain the difference in penetrance of these mutations in PD patients.
Boosting Serotonin Increases Information Gathering by Reducing Subjective Cognitive Costs
2023-07-31

Serotonin is implicated in the valuation of aversive costs, such as delay or physical effort. However, its role in governing sensitivity to cognitive effort, for example, deliberation costs during information gathering, is unclear. We show that treatment with a serotonergic antidepressant in healthy human individuals of either sex enhances a willingness to gather information when trying to maximize reward. Using computational modeling, we show this arises from a diminished sensitivity to subjective deliberation costs during the sampling process. This result is consistent with the notion that serotonin alleviates sensitivity to aversive costs in a domain-general fashion, with implications for its potential contribution to a positive impact on motivational deficits in psychiatric disorders. SIGNIFICANCE STATEMENT Gathering information about the world is essential for successfully navigating it. However, sampling information is costly, and we need to balance between gathering too little and too much information. The neurocomputational mechanisms underlying this arbitration between a putative gain, such as reward, and the associated costs, such as allocation of cognitive resources, remain unclear. In this study, we show that week-long daily treatment with a serotonergic antidepressant enhances a willingness to gather information when trying to maximize reward. Computational modeling indicates this arises from a reduced perception of aversive costs, rendering information gathering less cognitively effortful. This finding points to a candidate mechanism by which serotonergic treatment might help alleviate motivational deficits in a range of mental illnesses.
Wall teichoic acid substitution with glucose governs phage susceptibility ofStaphylococcus epidermidis
2023-07-31

Abstract The species- and clone-specific susceptibility of Staphylococcus cells for bacteriophages is governed by the structures and glycosylation patterns of wall teichoic acid (WTA) glycopolymers. The glycocodes of phage-WTA interaction in the opportunistic pathogen Staphylococcus epidermidis and in other coagulase-negative staphylococci (CoNS) have remained unknown. We report a new S. epidermidis WTA glycosyltransferase TagE whose deletion confers resistance to siphoviruses such as ΦE72 but enables binding of otherwise unbound podoviruses. S. epidermidis glycerolphosphate WTA was found to be modified with glucose in a tagE -dependent manner. TagE is encoded together with the enzymes PgcA and GtaB providing uridine diphosphate-activated glucose. ΦE72 transduced several other CoNS species encoding TagE homologs suggesting that WTA glycosylation via TagE is a frequent trait among CoNS that permits inter-species horizontal gene transfer. Our study unravels a crucial mechanism of phage- Staphylococcus interaction and of horizontal gene transfer and it will help in the design of anti-staphylococcal phage therapies. Importance Phages are highly specific for certain bacterial hosts, and some can transduce DNA even across species boundaries. How phages recognize cognate host cells remains incompletely understood. Phages infecting members of the genus Staphylococcus bind to wall teichoic acid (WTA) glycopolymers with highly variable structures and glycosylation patterns. How WTA is glycosylated in the opportunistic pathogen Staphylococcus epidermidis and in other coagulase-negative Staphylococcus (CoNS) species has remained unknown. We describe that S. epidermidis glycosylates its WTA backbone with glucose and we identify a cluster of three genes, responsible for glucose activation and transfer to WTA. Their inactivation strongly alters phage susceptibility patterns, yielding resistance to siphoviruses but susceptibility to podoviruses. Many different CoNS species with related glycosylation genes can exchange DNA via siphovirus ΦE72 suggesting that glucose-modified WTA is crucial for interspecies horizontal gene transfer. Our finding will help to develop antibacterial phage therapies and unravel routes of genetic exchange.
Shine Louise Houston and the metapornographic queering of voyeurism
2023-07-31

This article examines the work of filmmaker-producer Shine Louise Houston, founder of Pink and White Productions and director of the lesbian porn classic The Crash Pad, which spawned an eponymous, website-based series. Houston, whose 15-year tenure directing the Crash Pad Series ended in 2022, has crafted a queer pornography that interrogates notions of authenticity, largely through her signature trope of inviting, and meeting head on, the voyeuristic gaze. While celebrating Houston's contribution to the production and distribution of queerly diverse porn, we also argue for a recognition of her metapornographic vision.
An open-source GIS approach to understanding dunefield morphologic variability at Kati Thanda (Lake Eyre), Central Australia
2023-07-31

Future climate projections indicate an expansion of the world’s drylands, and with that a commensurate increase in the mobilization of unconsolidated desert sediments such as sand and dust. It is therefore increasingly important to investigate the large-scale formation of dryland landscapes such as dunefields in order to better understand the processes responsible for their genesis, evolution, and thresholds for mobilization. Assessing dunefield morphologic variability, including analysis of the morphologic relationship between aeolian bedforms and other landforms such as fluvial channels and bedrock uplands, underpins such investigations. So far, however, meaningful investigations of erg-scale geomorphic patterns have been limited. This is in part due to the technological limitations of geographic information system (GIS) tools, particularly in the case of open-source datasets and software, which has effectively hindered investigations by colleagues in drylands of the global south where many of the world’s dunefields are located. Recent years have overseen the increasing availability of open-source remote sensing datasets, as well as the development of freely available software which can undertake geographic object-based image analysis (GEOBIA). These new tools facilitate cartography and statistical analysis of dunefields at large scales. In this study we make use of open-source GIS to characterise a morphologically diverse linear dunefield southwest of Kati Thanda (Lake Eyre) in central Australia. We focus on three parameters; dune orientation, spacing and Y-junctions using semi-automated GEOBIA, and investigate these in the context of local fluvial channels, depressions (pans) and uplands. Our results suggest a possible correlation between dune orientation, wind regime and the role of uplands as deflective barriers to longitudinal dune migration; dune spacing and sediment supply, likely relating to the location of both ephemeral and abandoned fluvial channels; and Y-junction frequency with underlying topography. Our study provides a framework for understanding process-based interactions between dunes and other landforms, as well as the first completely open-source approach which can be applied to linear dunefields worldwide.
Canonical Typicality For Other Ensembles Than Micro-Canonical
2023-07-31

We generalize Lévy's lemma, a concentration-of-measure result for the uniform probability distribution on high-dimensional spheres, to a much more general class of measures, so-called GAP measures. For any given density matrix on a separable Hilbert space , GAP is the most spread out probability measure on the unit sphere of that has density matrix and thus forms the natural generalization of the uniform distribution. We prove concentration-of-measure whenever the largest eigenvalue of is small. We use this fact to generalize and improve well-known and important typicality results of quantum statistical mechanics to GAP measures, namely canonical typicality and dynamical typicality. Canonical typicality is the statement that for ``most'' pure states of a given ensemble, the reduced density matrix of a sufficiently small subsystem is very close to a -independent matrix. Dynamical typicality is the statement that for any observable and any unitary time-evolution, for ``most'' pure states from a given ensemble the (coarse-grained) Born distribution of that observable in the time-evolved state is very close to a -independent distribution. So far, canonical typicality and dynamical typicality were known for the uniform distribution on finite-dimensional spheres, corresponding to the micro-canonical ensemble, and for rather special mean-value ensembles. Our result shows that these typicality results hold also for GAP , provided the density matrix has small eigenvalues. Since certain GAP measures are quantum analogs of the canonical ensemble of classical mechanics, our results can also be regarded as a version of equivalence of ensembles.
IXPE and Multiwavelength Observations of Blazar PG 1553+113 Reveal an Orphan Optical Polarization Swing
2023-08-01

Abstract The lower-energy peak of the spectral energy distribution of blazars has commonly been ascribed to synchrotron radiation from relativistic particles in the jets. Despite the consensus regarding jet emission processes, the particle acceleration mechanism is still debated. Here, we present the first X-ray polarization observations of PG 1553+113, a high-synchrotron-peak blazar observed by the Imaging X-ray Polarimetry Explorer (IXPE). We detect an X-ray polarization degree of (10 ± 2)% along an electric-vector position angle of ψ X = 86° ± 8°. At the same time, the radio and optical polarization degrees are lower by a factor of ∼3. During our IXPE pointing, we observed the first orphan optical polarization swing of the IXPE era, as the optical angle of PG 1553+113 underwent a smooth monotonic rotation by about 125°, with a rate of ∼17° day –1 . We do not find evidence of a similar rotation in either radio or X-rays, which suggests that the X-ray and optically emitting regions are separate or, at most, partially cospatial. Our spectropolarimetric results provide further evidence that the steady-state X-ray emission in blazars originates in a shock-accelerated and energy-stratified electron population.
First Detection of X-Ray Polarization from the Accreting Neutron Star 4U 1820−303
2023-08-01

Abstract This paper reports the first detection of polarization in the X-rays for atoll-source 4U 1820−303, obtained with the Imaging X-ray Polarimetry Explorer (IXPE) at 99.999% confidence level (CL). Simultaneous polarimetric measurements were also performed in the radio with the Australia Telescope Compact Array. The IXPE observations of 4U 1820−303 were coordinated with Swift X-ray Telescope, Neutron Star Interior Composition Explorer, and Nuclear Spectroscopic Telescope Array aiming to obtain an accurate X-ray spectral model covering a broad energy interval. The source shows a significant polarization above 4 keV, with a polarization degree of 2.0% ± 0.5% and a polarization angle of −55° ± 7° in the 4–7 keV energy range, and a polarization degree of 10% ± 2% and a polarization angle of −67° ± 7° in the 7–8 keV energy bin. This polarization also shows a clear energy trend with polarization degree increasing with energy and a hint for a position-angle change of ≃90° at 96% CL around 4 keV. The spectro-polarimetric fit indicates that the accretion disk is polarized orthogonally to the hard spectral component, which is presumably produced in the boundary/spreading layer. We do not detect linear polarization from the radio counterpart, with a 3 σ upper limit of 50% at 7.25 GHz.