julilili42/papers huggingface dataset:
Redox Oscillations Activate Thermodynamically Stable Iron Minerals for Enhanced Reactive Oxygen Species Production
2023-05-31

Reactive oxygen species (ROS) play key roles in driving biogeochemical processes. Recent studies have revealed nonphotochemical electron transfer from redox-active substances (e.g., iron minerals) to oxygen as a new route for ROS production. Yet, naturally occurring iron minerals mainly exist in thermodynamically stable forms, restraining their potential for driving ROS production. Here, we report that tide-induced redox oscillations can activate thermodynamically stable iron minerals for enhanced ROS production. <sup>•</sup>OH production in intertidal soils (15.8 ± 0.5 μmol/m<sup>2</sup>) was found to be 5.9-fold more efficient than those in supratidal soils. Moreover, incubation of supratidal soils under tidal redox fluctuations dramatically enhanced <sup>•</sup>OH production by 4.3-fold. The tidal hydrology triggered redox alternation between biotic reduction and abiotic oxidation and could accelerate the production of reactive ferrous ions and amorphous ferric oxyhydroxides, making thermodynamically stable iron minerals into redox-active metastable iron phases (RAMPs) with reduced crystallinity and promoting surface electrochemical activities. Those RAMPs displayed enhanced redox activity for ROS production. Investigations of nationwide coastal soils verified that tide-induced redox oscillations could ubiquitously activate soils for enhanced ROS production. Our study demonstrates the effective formation of RAMPs from redox oscillations by hydrological perturbations, which provides new insights into natural ROS sources.
The Plant Ubiquitin–Proteasome System as a Target for Microbial Manipulation
2023-05-31

The plant immune system perceives pathogens to trigger defense responses. In turn, pathogens secrete effector molecules to subvert these defense responses. The initiation and maintenance of defense responses involve not only de novo synthesis of regulatory proteins and enzymes but also their regulated degradation. The latter is achieved through protein degradation pathways such as the ubiquitin–proteasome system (UPS). The UPS regulates all stages of immunity, from the perception of the pathogen to the execution of the response, and, therefore, constitutes an ideal candidate for microbial manipulation of the host. Pathogen effector molecules interfere with the plant UPS through several mechanisms. This includes hijacking general UPS functions or perturbing its ability to degrade specific targets. In this review, we describe how the UPS regulates different immunity-related processes and how pathogens subvert this to promote disease.
Contrasting action and posture coding with hierarchical deep neural network models of proprioception
2023-05-31

Biological motor control is versatile, efficient, and depends on proprioceptive feedback. Muscles are flexible and undergo continuous changes, requiring distributed adaptive control mechanisms that continuously account for the body’s state. The canonical role of proprioception is representing the body state. We hypothesize that the proprioceptive system could also be critical for high-level tasks such as action recognition. To test this theory, we pursued a task-driven modeling approach, which allowed us to isolate the study of proprioception. We generated a large synthetic dataset of human arm trajectories tracing characters of the Latin alphabet in 3D space, together with muscle activities obtained from a musculoskeletal model and model-based muscle spindle activity. Next, we compared two classes of tasks: trajectory decoding and action recognition, which allowed us to train hierarchical models to decode either the position and velocity of the end-effector of one’s posture or the character (action) identity from the spindle firing patterns. We found that artificial neural networks could robustly solve both tasks, and the networks’ units show tuning properties similar to neurons in the primate somatosensory cortex and the brainstem. Remarkably, we found uniformly distributed directional selective units only with the action-recognition-trained models and not the trajectory-decoding-trained models. This suggests that proprioceptive encoding is additionally associated with higher-level functions such as action recognition and therefore provides new, experimentally testable hypotheses of how proprioception aids in adaptive motor control.
Keratinocytes use FPR2 to detect Staphylococcus aureus and initiate antimicrobial skin defense
2023-05-31

Introduction Keratinocytes form a multilayer barrier that protects the skin from invaders or injuries. The barrier function of keratinocytes is in part mediated by the production of inflammatory modulators that promote immune responses and wound healing. Skin commensals and pathogens such as Staphylococcus aureus secrete high amounts of phenol-soluble modulin (PSM) peptides, agonists of formyl-peptide receptor 2 (FPR2). FPR2 is crucial for the recruitment of neutrophils to the sites of infection, and it can influence inflammation. FPR1 and FPR2 are also expressed by keratinocytes but the consequences of FPR activation in skin cells have remained unknown. Methods Since an inflammatory environment influences S. aureus colonization, e. g. in patients with atopic dermatitis (AD), we hypothesized that interference with FPRs may alter keratinocyte-induced inflammation, proliferation, and bacterial colonization of the skin. To assess this hypothesis, we investigated the effects of FPR activation and inhibition in keratinocytes with respect to chemokine and cytokine release as well as proliferation and skin wound gap closure. Results We observed that FPR activation induces the release of IL-8, IL-1α and promotes keratinocyte proliferation in a FPR-dependent manner. To elucidate the consequence of FPR modulation on skin colonization, we used an AD-simulating S. aureus skin colonization mouse model using wild-type (WT) or Fpr2 -/- mice and demonstrate that inflammation enhances the eradication of S. aureus from the skin in a FPR2-dependent way. Consistently, inhibition of FPR2 in the mouse model or in human keratinocytes as well as human skin explants promoted S. aureus colonization. Discussion Our data indicate that FPR2 ligands promote inflammation and keratinocyte proliferation in a FPR2-dependent manner, which is necessary for eliminating S. aureus during skin colonization.
Platelets regulate ischemia-induced revascularization and angiogenesis by secretion of growth factor–modulating factors
2023-05-31

Abstract In ischemic tissue, platelets can modulate angiogenesis. The specific factors influencing this function, however, are poorly understood. Here, we characterized the complement anaphylatoxin C5a-mediated activation of C5a receptor 1 (C5aR1) expressed on platelets as a potent regulator of ischemia-driven revascularization. We assessed the relevance of the anaphylatoxin receptor C5aR1 on platelets in patients with coronary artery disease as well as those with peripheral artery disease and used genetic mouse models to characterize its significance for ischemia and growth factor–driven revascularization. The presence of C5aR1-expressing platelets was increased in the hindlimb ischemia model. Ischemia-driven angiogenesis was significantly improved in C5aR1−/− mice but not in C5−/− mice, suggesting a specific role of C5aR1. Experiments using the supernatant of C5a-stimulated platelets suggested a paracrine mechanism of angiogenesis inhibition by platelets by means of antiangiogenic CXC chemokine ligand 4 (CXCL4, PF4). Lineage-specific C5aR1 deletion verified that the secretion of CXCL4 depends on C5aR1 ligation on platelets. Using C5aR1−/−CXCL4−/− mice, we observed no additional effect in the revascularization response, underscoring a strong dependence of CXCL4 secretion on the C5a-C5aR1-axis. We identified a novel mechanism for inhibition of neovascularization via platelet C5aR1, which was mediated by the release of antiangiogenic CXCL4.
Analytical Methods for the Rapid Determination of Solid Biofuel Quality
2023-05-31

Abstract Fuel properties of solid biofuels are essential aspects for the energy‐efficient and low‐emission operation of biomass heat and power plants. Hence, fuel quality parameters are often defined and used for pricing in supply contracts. To simplify and accelerate analytical approaches, rapid analysis devices are required to determine fuel properties such as water‐ and ash content, calorific value, and chemical composition on‐site. This article gives an overview about available technologies and, if applicable, their current state of use as rapid analysis devices for solid biofuels.
Blue-light stimulation of the blind-spot constricts the pupil and enhances contrast sensitivity
2023-05-31

Short- and long-wavelength light can alter pupillary responses differently, allowing inferences to be made about the contribution of different photoreceptors on pupillary constriction. In addition to classical retinal photoreceptors, the pupillary light response is formed by the activity of melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGC). It has been shown in rodents that melanopsin is expressed in the axons of ipRGCs that bundle at the optic nerve head, which forms the perceptual blind-spot. Hence, the first aim of this study was to investigate if blind-spot stimulation induces a pupillary response. The second aim was to investigate the effect of blind-spot stimulation by using the contrast sensitivity tests. Fifteen individuals participated in the pupil response experiment and thirty-two individuals in the contrast sensitivity experiment. The pupillary change was quantified using the post-illumination pupil response (PIPR) amplitudes after blue-light (experimental condition) and red-light (control condition) pulses in the time window between 2 s and 6 s post-illumination. The contrast sensitivity was assessed using two different tests: the Freiburg Visual Acuity Test and Contrast Test and the Tuebingen Contrast Sensitivity Test, respectively. Contrast sensitivity was measured before and 20 minutes after binocular blue-light stimulation of the blind-spot at spatial frequencies higher than or equal to 3 cycles per degree (cpd) and at spatial frequencies lower than 3 cpd (control condition). Blue-light blind-spot stimulation induced a significantly larger PIPR compared to red-light, confirming a melanopsin-mediated pupil-response in the blind-spot. Furthermore, contrast sensitivity was increased after blind-spot stimulation, confirmed by both contrast sensitivity tests. Only spatial frequencies of at least 3 cpd were enhanced. This study demonstrates that stimulating the blind-spot with blue-light constricts the pupil and increases the contrast sensitivity at higher spatial frequencies.
Authentic Sn═B-Double Bonds in Polar Stannaborene Derivatives
2023-05-31

We report on the synthesis of an authentic Sn═B-moiety realized in a stannaborenyl anion and stannaborenium cation. Starting with an oxidative addition of boron tribromide to a stannylene-phosphine Lewis pair [<i>o</i>-C<sub>6</sub>H<sub>4</sub>(Ar*BrSn-BBr<sub>2</sub>-PPh<sub>2</sub>)] (<b>2a</b>) [Ar* = C<sub>6</sub>H<sub>3</sub>(2,6-Trip)<sub>2</sub>, Trip = 2,4,6-C<sub>6</sub>H<sub>2</sub><i>i</i>Pr<sub>3</sub>] was synthesized. Reduction of <b>2a</b> with magnesium yields the Grignard-type stannaborene [<i>o</i>-C<sub>6</sub>H<sub>4</sub>(Ar*Sn═B{PPh<sub>2</sub>}MgBr{thf})]<sub>2</sub> (<b>3</b>)<sub>2</sub> featuring a Sn═B double bond and a B-Mg interaction. Following an alternative protocol, hydride substitution at <b>2a</b> yields the tinhydride [<i>o</i>-C<sub>6</sub>H<sub>4</sub>(Ar*HSn-BBr<sub>2</sub>-PPh<sub>2</sub>)] (<b>4a</b>). HBr elimination of <b>4a</b> in reaction with <sup>Me</sup>NHC (<sup>Me</sup>NHC = 1,3,4,5-tetramethylimidazol-2-ylidene) gives the carbene and phosphine stabilized stannyl-borylene [<i>o</i>-C<sub>6</sub>H<sub>4</sub>(Ar*BrSn-B{PPh<sub>2</sub>}{<sup>Me</sup>NHC})] (<b>5</b>) after simultaneous bromide transfer from boron to tin. In reaction of <b>5</b> with Li[Al(OC{CF<sub>3</sub>}<sub>3</sub>)<sub>4</sub>] or Na[BAr<sup>F</sup><sub>4</sub>] in a mixture of <i>o</i>-DFB/benzene a stannaborene [<i>o</i>-C<sub>6</sub>H<sub>4</sub>(Ar*Sn═B{PPh<sub>2</sub>}{<sup>Me</sup>NHC})]<sup>+</sup> [<b>6</b>] stabilized by the respective weakly coordinating anion was isolated (Ar<sup>F</sup> = C<sub>6</sub>H<sub>3</sub>-3,5-(CF<sub>3</sub>)<sub>2</sub>, <i>o</i>-DFB = <i>o</i>-difluorobenzene). The phosphine and NHC-supported stannaborenium cation <b>6</b> adds ammonia at room temperature under splitting of a N-H bond and formation of Sn-NH<sub>2</sub> and B-H bonds to give [<i>o</i>-C<sub>6</sub>H<sub>4</sub>(Ar*{H<sub>2</sub>N}Sn-BH{PPh<sub>2</sub>}{<sup>Me</sup>NHC})]<sup>+</sup> (<b>7</b>).
Information theoretic measures of causal influences during transient neural events
2023-05-31

Introduction: Transient phenomena play a key role in coordinating brain activity at multiple scales, however their underlying mechanisms remain largely unknown. A key challenge for neural data science is thus to characterize the network interactions at play during these events. Methods: Using the formalism of Structural Causal Models and their graphical representation, we investigate the theoretical and empirical properties of Information Theory based causal strength measures in the context of recurring spontaneous transient events. Results: After showing the limitations of Transfer Entropy and Dynamic Causal Strength in this setting, we introduce a novel measure, relative Dynamic Causal Strength, and provide theoretical and empirical support for its benefits. Discussion: These methods are applied to simulated and experimentally recorded neural time series and provide results in agreement with our current understanding of the underlying brain circuits.
Don’t SNARC me now! Intraindividual variability of cognitive phenomena – insights from the Ironman paradigm
2023-05-31

Two implicit generalizations are often made from group-level studies in cognitive experimental psychology and their common statistical analysis in the general linear model: (1) Group-level phenomena are assumed to be present in every participant with variations between participants being often treated as random error in data analyses; (2) phenomena are assumed to be stable over time. In this preregistered study, we investigated the validity of these generalizations in the commonly used parity judgment task. In the proposed Ironman paradigm, the intraindividual presence and stability of three popular numerical cognition effects were tested in 10 participants on 30 days: the SNARC (Spatial-Numerical Association of Response Codes, i.e., faster left-/right-sided responses to small/large magnitude numbers, respectively; Dehaene et al., 1993), MARC (Linguistic Markedness of Response Codes; i.e., faster left-/right-sided responses to odd/even numbers, respectively; Nuerk et al., 2004), and Odd (i.e., faster responses to even numbers; Hines et al., 1990) effects. We replicated the group-level effects; however, they were reliably present in only four to five (SNARC), six (MARC) or five (Odd) of 10 participants. Fluctuations seemed unsystematic, although the SNARC effect decreased over time along with reaction times. No correlation between the SNARC and MARC effects and sleep duration, tiredness, daytime, and consumption of stimulants were detected in most participants. These results challenge the frequent generalizations from group-level phenomena to individual participants and from single sessions to typical behavior. The innovative Ironman paradigm combined with bootstrap analyses permits unique insights into the intraindividual presence and stability of cognitive phenomena.
Slowly-rotating compact objects: the nonintegrability of Hartle-Thorne particle geodesics
2023-05-31

X-ray astronomy provides information regarding the electromagnetic emission of active galactic nuclei and X-ray binaries. These events provide details regarding the astrophysical environment of black holes and stars, and help us understand gamma-ray bursts. They produce estimates for the maximum mass of neutron stars and eventually will contribute to the discovery of their equation of state. Thus, it is crucial to study them in order to enhance the yield of X-ray astronomy when combined with multimessenger astrophysics. An exact solution of the field equations does not exist for rotating neutron stars. There exist a variety of approximate solutions for compact objects that may characterize relativistic stars. The most studied approximation is the Hartle-Thorne metric that represents slowly-rotating compact objects, like massive stars, white dwarfs and neutron stars. Recent investigations of photon orbits and shadows of such metric revealed that it exhibits chaos close to resonances. Here, we thoroughly investigate particle orbits around the Hartle-Thorne spacetime up to second order in rotation. We perform an exhaustive analysis of bound motion, by varying all parameters involved in the system. We demonstrate that chaotic regions, known as Birkhoff islands, form around resonances, where the ratio of the radial and polar frequency of geodesics, known as the rotation number, is shared throughout the island. This leads to the formation of plateaus in rotation curves during the most prominent resonance, which confirms that generic geodesics are nonintegrable. We measure their width and show how each parameter affects it. The nonintegrability of Hartle-Thorne metric may affect quasiperiodic oscillations of low-mass X-ray binaries, when chaos is taken into account, and might potentially improve estimates of mass, angular momentum and multipole moments of astrophysical compact objects.
Long-term follow-up from MajesTEC-1 of teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM).
2023-06-01

8011 Background: Teclistamab is the first approved off-the-shelf BCMA×CD3 bispecific antibody for the treatment of patients (pts) with RRMM based on data from the pivotal phase 1/2 MajesTEC-1 study (NCT03145181/NCT04557098). Moreau et al ( NEJM 2022) reported rapid, deep, and durable responses: overall response rate (ORR) was 63% (39% ≥complete response [CR] rate), with a median duration of response (mDOR) of 18.4 mo, and median progression-free survival (mPFS) of 11.3 mo after a median follow-up (mFU) of 14.1 mo. Here, we present updated results with extended follow-up of ~2 y (22 mo). Methods: Eligible pts were aged ≥18 y, had documented MM (per IMWG 2016 criteria), and had received ≥3 prior lines of therapy (LOT), including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. Prior BCMA-targeted therapy was not allowed in this cohort. Pts received teclistamab 1.5 mg/kg QW (the recommended phase 2 dose [RP2D]), with the option to switch to Q2W dosing if they achieved ≥partial response after ≥4 cycles of therapy in phase 1 or ≥CR for ≥6 months in phase 2. The primary endpoint was ORR (assessed per IMWG 2016 criteria by computerized algorithm). AEs were graded per CTCAE v4.03. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT guidelines. Results: As of Dec 9, 2022, 165 pts had received teclistamab at the RP2D (median age, 64 y; 58% male; 26% high-risk cytogenetics; 12% International Staging System stage III). Pts had a median of 5 prior LOT (range, 2–14): 92% daratumumab exposed; 78% triple-class refractory; 81% daratumumab-refractory; and 90% refractory to last LOT. At 22 mo mFU, 43% of pts achieved ≥CR, mDOR was 24 mo (95% CI, 16.2–not estimable [NE]), mDOR in pts achieving ≥CR was not reached (95% CI, 24.0–NE), mPFS was 12.5 mo (95% CI, 8.8–17.2), and median overall survival was 21.9 mo (95% CI, 16.0–NE). Hematologic AEs (any grade [gr]/gr 3/4) included neutropenia (72%/65%), anemia (54%/38%), thrombocytopenia (42%/22%), and lymphopenia (35%/33%). Infections occurred in 78% of pts (52% gr 3/4); key infections included respiratory (56%), COVID-19 (27%), other viral (10%), GI (8%), fungal (5%), PJP (4%), and hepatitis B (0.6%). CRS occurred in 72% of pts (0.6% gr 3; no gr 4/5); 5 (3%) pts reported 9 ICANS events (all gr 1/2; all resolved). 1 pt in phase 1 required a teclistamab dose reduction due to neutropenia. 6 treatment-related deaths have occurred (3 due to COVID-19). Of the 49 pts who remain on study, ~90% have received Q2W dosing. Conclusions: After ~2 y mFU, pts receiving teclistamab demonstrated deep and durable responses regardless of refractory status, with mPFS of 12.5 mo and mDOR of 24 mo (not reached in those achieving ≥CR). These long-term follow-up data support teclistamab as a safe and effective off-the-shelf BCMA bispecific therapy for pts with RRMM. Clinical trial information: NCT03145181 , NCT04557098 .
Discovery of strongly variable X-ray polarization in the neutron star low-mass X-ray binary transient XTE J1701−462
2023-06-01

Context. After about 16 years since its first outburst, the transient neutron star low-mass X-ray binary XTE J1701−462 turned on again in September 2022, allowing for the first study of its X-ray polarimetric characteristics by a dedicated observing program with the Imaging X-ray Polarimeter Explorer (IXPE). Aims. Polarimetric studies of XTE J1701−462 have been expected to improve our understanding of accreting weakly magnetized neutron stars, in particular, the physics and the geometry of the hot inner regions close to the compact object. Methods. The IXPE data of two triggered observations were analyzed using time-resolved spectroscopic and polarimetric techniques, following the source along its Z -track of the color–color diagram. Results. During the first pointing on 2022 September 29, an average 2–8 keV polarization degree of (4.6 ± 0.4)% was measured, the highest value found up to now for this class of sources. Conversely, only a ∼0.6% average degree was obtained during the second pointing ten days later. Conclusions. The polarimetric signal appears to be strictly related to the higher energy blackbody component associated with the boundary layer (BL) emission and its reflection from the inner accretion disk, and it is as strong as 6.1% and 1.2% (&gt; 95% significant) above 3–4 keV for the two measurements, respectively. The variable polarimetric signal is apparently related to the spectral characteristics of XTE J1701−462, which is the strongest when the source was in the horizontal branch of its Z -track and the weakest in the normal branch. These IXPE results provide new important observational constraints on the physical models and geometry of the Z -sources. Here, we discuss the possible reasons for the presence of strong and variable polarization among these sources.
Constraints on the Intergalactic Magnetic Field Using Fermi-LAT and H.E.S.S. Blazar Observations
2023-06-01

Abstract Magnetic fields in galaxies and galaxy clusters are believed to be the result of the amplification of intergalactic seed fields during the formation of large-scale structures in the universe. However, the origin, strength, and morphology of this intergalactic magnetic field (IGMF) remain unknown. Lower limits on (or indirect detection of) the IGMF can be obtained from observations of high-energy gamma rays from distant blazars. Gamma rays interact with the extragalactic background light to produce electron−positron pairs, which can subsequently initiate electromagnetic cascades. The gamma-ray signature of the cascade depends on the IGMF since it deflects the pairs. Here we report on a new search for this cascade emission using a combined data set from the Fermi Large Area Telescope and the High Energy Stereoscopic System. Using state-of-the-art Monte Carlo predictions for the cascade signal, our results place a lower limit on the IGMF of B &gt; 7.1 × 10 −16 G for a coherence length of 1 Mpc even when blazar duty cycles as short as 10 yr are assumed. This improves on previous lower limits by a factor of 2. For longer duty cycles of 10 4 (10 7 ) yr, IGMF strengths below 1.8 × 10 −14 G (3.9 × 10 −14 G) are excluded, which rules out specific models for IGMF generation in the early universe.