julilili42/papers huggingface dataset:
Receptor-like cytoplasmic kinases belonging to different subfamilies differentially regulate SOBIR1/BAK1-mediated immune responses in Nicotiana benthamiana
2023-11-17

<title>Abstract</title> Cell-surface receptors, which are either receptor-like proteins (RLPs) or receptor-like kinases (RLKs), stand at the basis of the first layer of the plant innate immune system. The leucine-rich repeat (LRR)-RLKs SOBIR1 and BAK1 are the common regulatory co-receptors of LRR-RLPs. The tomato LRR-RLP Cf-4, which specifically detects the apoplastic effector Avr4 that is secreted by the pathogenic intercellular fungus <italic>Fulvia fulva</italic> (syn. <italic>Cladosporium fulvum</italic>), requires SOBIR1 and BAK1 to mediate resistance against this fungus. Here, by performing <italic>in vitro</italic> phosphorylation assays, we show that SOBIR1 directly phosphorylates BAK1, whereas BAK1, in turn, directly phosphorylates SOBIR1, which results in the full activation of the SOBIR1/BAK1-containing immune complex. The amino acid residues Thr522 and Tyr469, present in the kinase domain of <italic>Nicotiana benthamiana</italic> (Nb) SOBIR1, were found to be required for the intrinsic kinase activity of NbSOBIR1 and for interacting with specific downstream signalling partners, respectively. Receptor-like cytoplasmic kinases (RLCKs) are well-recognized to act as the initial cytoplasmic transducers, bridging cell-surface receptor complexes with their downstream signalling partners. Here, by knocking out multiple genes belonging to different RLCK-VII subfamilies in N. benthamiana:Cf-4, we show that members of RLCK-VII-6, -7, and -8 differentially regulate the Avr4/Cf-4-triggered biphasic reactive oxygen species (ROS) burst in <italic>N. benthamiana</italic>. This observation suggests that there are different downstream ROS regulatory mechanisms, involving different RLCKs, in <italic>N. benthamiana</italic>. In addition, members of RLCK-VII-7 play an essential role in the Avr4/Cf-4-triggered hypersensitive response (HR) and host resistance against the oomycete pathogen <italic>Phytophthora palmivora</italic>. Furthermore, SOBIR1 and BAK1 directly trans-phosphorylate members of RLCK-VII-6, -7 and -8 in vitro. Our study provides molecular evidence for the activation and signal transduction of SOBIR1/BAK1-containing immune complexes through RLCKs in <italic>N. benthamiana</italic>.
Near-optimal Closed-loop Method via Lyapunov Damping for Convex Optimization
2023-11-17

We introduce an autonomous system with closed-loop damping for first-order convex optimization. While, to this day, optimal rates of convergence are almost exclusively achieved by non-autonomous methods via open-loop damping (e.g., Nesterov's algorithm), we show that our system, featuring a closed-loop damping, exhibits a rate arbitrarily close to the optimal one. We do so by coupling the damping and the speed of convergence of the system via a well-chosen Lyapunov function. By discretizing our system we then derive an algorithm and present numerical experiments supporting our theoretical findings.
First‐Line Stent Retriever Versus Contact Aspiration or Combined Technique for Endovascular Therapy of Posterior Cerebral Artery Occlusion Stroke: The PLATO Study
2023-11-18

Background The optimal reperfusion technique in patients with isolated posterior cerebral artery (PCA) occlusion is uncertain. We compared clinical and technical outcomes with first‐line stent retriever (SR), contact aspiration (CA), or combined techniques in patients with isolated PCA occlusion. Methods This international case–control study was conducted at 30 sites in Europe and North America and included consecutive patients with isolated PCA occlusion presenting within 24 hours of time last seen well from January 2015 to August 2022. The primary outcome was the first‐pass effect (FPE), defined as expanded Treatment in Cerebral Infarction (TICI) 2c/3 on the first pass. Patients treated with SR, CA, or combined technique were compared with multivariable logistic regression. Results There were 326 patients who met inclusion criteria, 56.1% male, median age 75 (interquartile range 65–82) years, and median National Institutes of Health Stroke Scale score 8 (5–12). Occlusion segments were PCA‐P1 (53.1%), P2 (40.5%), and other (6.4%). Intravenous thrombolysis was administered in 39.6%. First‐line technique was SR, CA, and combined technique in 43 (13.2%), 106 (32.5%), and 177 (54.3%) patients, respectively; FPE was achieved in 62.8%, 42.5%, and 39.6%, respectively. FPE was lower in patients treated with first‐line CA or combined technique compared with SR (CA versus SR: adjusted odds ratio 0.45 [0.19–1.06]; P =0.07; combined versus SR: adjusted odds ratio 0.35 [0.016–0.80]; P =0.01). There were lower odds of functional independence (modified Rankin scale score 0–2) in the first‐line CA versus SR alone group (adjusted odds ratio 0.52 [0.28–0.95]; P =0.04). FPE was associated with higher rates of favorable outcomes (modified Rankin scale score 0–2: 58% versus 43.4%; P =0.01; modified Rankin scale score 0–1: 36.6% versus 25.8%; P =0.05). Overall, symptomatic intracranial hemorrhage was present in 5.6% (18/326) and mortality in 10.9% (35/326) without difference between first‐line technique. Conclusion In patients with isolated PCA occlusion, SR was associated with a higher rate of FPE compared with CA or combined techniques with no difference in final successful reperfusion. Functional independence at 90 days was more likely with first‐line SR compared with CA. FPE was associated with better 90‐day clinical outcomes.
Flat panel CT versus multidetector CT in skull base imaging: are there differences in image quality?
2023-11-18

Abstract Background Purpose of this study was to compare image quality of the skull base in standard 20s protocol flat panel computed tomography (FPCT) with the new time and dose improved 10s protocol as well as with 128 slice multidetector computed tomography (MDCT). Methods 10 whole skull preparations were scanned with either 128 slice MDCT(SOMATOM Definition AS+, Siemens, Erlangen) or FPCT (AXIOM-Artis, Siemens, Erlangen) using 10s or 20s protocol. Results FPCT provides significantly better image quality and improved delimitation of clinically relevant structures in the anterior, temporal and posterior skull base compared to 128 slice MDCT. The 20s FPCT protocol yielded best delimitability of evaluated skull base structures. However, the shorter, dose saving 10s FPCT protocol was still significantly superior to 128 slice MDCT regarding delimitability of skull base structures and additionally showed no significant inferiority compared with the 20s FPCT protocol. Conclusions The 10s FPCT protocol yields a significantly better image quality at a comparable radiation dose exposure in imaging skull base structures compared to MDCT. Trial registration 371/2017BO2.
Evaluating modularity in the hominine skull related to feeding biomechanics
2023-11-19

Abstract Objectives Modular architecture of traits in complex organisms can be important for morphological evolution at micro‐ and sometimes macroevolutionary scales as it may influence the tempo and direction of changes to groups of traits that are essential for particular functions, including food acquisition and processing. We tested several distinct hypotheses about craniofacial modularity in the hominine skull in relation to feeding biomechanics. Materials and Methods First, we formulated hypothesized functional modules for craniofacial traits reflecting specific demands of feeding biomechanics (e.g., masseter leverage/gape or tooth crown mechanics) in Homo sapiens , Pan troglodytes , and Gorilla gorilla . Then, the pattern and strength of modular signal was quantified by the covariance ratio coefficient and compared across groups using covariance ratio effect size. Hierarchical clustering analysis was then conducted to examine whether a priori‐defined functional modules correspond to empirically recovered clusters. Results There was statistical support for most a priori‐defined functional modules in the cranium and half of the functional modules in the mandible. Modularity signal was similar in the cranium and mandible, and across the three taxa. Despite a similar strength of modularity, the empirically recovered clusters do not map perfectly onto our priori functional modules, indicating that further work is needed to refine our hypothesized functional modules. Conclusion The results suggest that modular structure of traits in association with feeding biomechanics were mostly shared with humans and the two African apes. Thus, conserved patterns of functional modularity may have facilitated evolutionary changes to the skull during human evolution.
Additional file 1 of Breast cancer patient-derived microtumors resemble tumor heterogeneity and enable protein-based stratification and functional validation of individualized drug treatment
2023-11-19

Additional file 1: SI Materials 1. Antibodies used in DigiWest protein profiling analysis. Figure S1. Multicolor flow cytometry analysis of isolated and expanded TILs from BC specimen. Figure S2. Correlation of nuclear grade in PDM and PTT. Figure S3. Proteomic comparison of NST and ILC-derived BC PDM. Figure S4. Identification of resistance and sensitivity marker panels in treatment responder and non-responder microtumors and regression analysis of differently expressed proteins. Table S1. Clinical patient data of the patient cohort. Table S2. Descriptive statistics of “area” and “fluorescent intensity live/dead” measurements in PDM. Table S3. Raw data of DigiWest® protein signals in PDM and PTT samples and total measured protein amounts. Table S4. DigiWest®-based AFI protein signals in matched PDM-PTT pairs DigiWest®-based AFI protein signals in matched PDM-PTT pairs. Table S5. DigiWest®-based AFI protein signals of matched PDM-PTT pairs sorted by pathway affiliation. Table S6. Pearson correlation of protein abundances in PDM and corresponding PTT (PDM/PTT pairs). Table S7. DigIWest®-based AFI protein signals of n = 42 PDM samples. Table S8. Descriptive statistics of averaged, median-centered and log2 transformed protein signals for cell cycle, MAPK/RTK and PI3K/AKT pathway in n = 42 PDM samples. Table S9. CelltoxTM Green assay RFU (relative fluorescent unit) values of BC microtumors treated with TAM, DTX, PTX and PAB. Table S10. Descriptive statistics of simple logistic regression analysis of differentially expressed proteins in treatment responder and non-responder groups.
The Onset of Molecule‐Spanning Dynamics in Heat Shock Protein Hsp90
2023-11-20

Abstract Protein dynamics have been investigated on a wide range of time scales. Nano‐ and picosecond dynamics have been assigned to local fluctuations, while slower dynamics have been attributed to larger conformational changes. However, it is largely unknown how fast (local) fluctuations can lead to slow global (allosteric) changes. Here, fast molecule‐spanning dynamics on the 100 to 200 ns time scale in the heat shock protein 90 (Hsp90) are shown. Global real‐space movements are assigned to dynamic modes on this time scale, which is possible by a combination of single‐molecule fluorescence, quasi‐elastic neutron scattering and all‐atom molecular dynamics (MD) simulations. The time scale of these dynamic modes depends on the conformational state of the Hsp90 dimer. In addition, the dynamic modes are affected to various degrees by Sba1, a co‐chaperone of Hsp90, depending on the location within Hsp90, which is in very good agreement with MD simulations. Altogether, this data is best described by fast molecule‐spanning dynamics, which precede larger conformational changes in Hsp90 and might be the molecular basis for allostery. This integrative approach provides comprehensive insights into molecule‐spanning dynamics on the nanosecond time scale for a multi‐domain protein.
Does Greater Transparency Discipline the Loan Loss Provisioning of Privately Held Banks?
2023-11-20

Whether transparency helps or hurts the stability of the financial system is an unresolved question. Recent trends have seen a decline in disclosure requirements especially for small and privately held banks. To assess the consequences of such regulations, we investigate the relationship between the transparency of loan loss provision disclosures and the provisioning practices of privately held banks. We study a unique change in disclosure regulation under German banking law which introduces mandatory disclosures of loan loss provisions. Using proprietary data provided by the national supervisor, we are able to observe provisioning practices before and after disclosure becomes mandatory. Our findings suggest that bank managers use loan loss provisions to a lesser extent for income smoothing once they are required to disclose their accounting choice. At the same time, provisions become timelier and loan portfolio quality improves. The change comes in the absence of capital market pressure and highlights the role of depositors and public pressure in the monitoring and disciplining of bank managers. Overall, these findings support the view that bank transparency helps establish financial stability.
Arthroscopy with Lipoaspirate and Plasma Infiltration Using Adipose-Derived Stem Cells Plus Platelet-Rich Plasma: Harvesting and Injection for Arthroscopic Treatment of Cartilage Defects of the Knee
2023-11-20

Osteoarthritis, predominantly of the knee, is a highly prevalent disease leading to pain, reduced quality of life, and significantly reduced ability to work. With autologous orthobiologic options, new regenerative treatment methods have emerged, offering an alternative to early surgical intervention. Supercharged Liparthroplasty combines arthroscopy with lipoaspirate and plasma infiltration of the joint. Lipoaspirate contains high levels of adipose-derived stem cells, which show chondroprotective and anti-inflammatory qualities. Intra-articular injection, combined with platelet-rich plasma administration for accelerated cartilage metabolism, thus provides an optional approach in osteoarthritis treatment. This article aims to provide in detail our regimen for Supercharged Liparthroplasty, including tissue harvesting and preparation of the injectables, therefore enabling physicians to adopt this point-of-care technique.
Stability of nanoparticle laden aerosol liquid droplets
2023-11-20

We develop a model for the thermodynamics and evaporation dynamics of aerosol droplets of a liquid, such as water, surrounded by gas. When the temperature and the chemical potential (or equivalently the humidity) are such that the vapor phase is in the thermodynamic equilibrium state, then, of course, droplets of the pure liquid evaporate over a relatively short time. However, if the droplets also contain nanoparticles or any other non-volatile solute, then the droplets can become thermodynamically stable. We show that the equilibrium droplet size depends strongly on the amount and solubility of the nanoparticles within, i.e., on the nature of the particle interactions with the liquid and, of course, also on the vapor temperature and chemical potential. We develop a simple thermodynamic model for such droplets and compare predictions with results from a lattice density functional theory that takes as input the same particle interaction properties, finding very good agreement. We also use dynamical density functional theory to study the evaporation/condensation dynamics of liquid from/to droplets as they equilibrate with the vapor, thereby demonstrating droplet stability.
Spatial subsetting enables integrative modeling of oral squamous cell carcinoma multiplex imaging data
2023-11-20

Oral squamous cell carcinoma (OSCC), a prevalent and aggressive neoplasm, poses a significant challenge due to poor prognosis and limited prognostic biomarkers. Leveraging highly multiplexed imaging mass cytometry, we investigated the tumor immune microenvironment (TIME) in OSCC biopsies, characterizing immune cell distribution and signaling activity at the tumor-invasive front. Our spatial subsetting approach standardized cellular populations by tissue zone, improving feature reproducibility and revealing TIME patterns accompanying loss-of-differentiation. Employing a machine-learning pipeline combining reliable feature selection with multivariable modeling, we achieved accurate histological grade classification (AUC = 0.88). Three model features correlated with clinical outcomes in an independent cohort: granulocyte MAPKAPK2 signaling at the tumor front, stromal CD4<sup>+</sup> memory T cell size, and the distance of fibroblasts from the tumor border. This study establishes a robust modeling framework for distilling complex imaging data, uncovering sentinel characteristics of the OSCC TIME to facilitate prognostic biomarkers discovery for recurrence risk stratification and immunomodulatory therapy development.
Right Axillary Artery Cannulation for Veno-Arterial Extracorporeal Membrane Oxygenation in Postcardiotomy Patients: A Single-Center Experience
2023-11-20

Background and Objectives: To analyze the patient outcome and complication rate of axillary artery cannulation for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients who could not be weaned from cardiopulmonary bypass after cardiothoracic surgery. Materials and Methods: We analyzed the data of 179 patients who were supported with VA-ECMO with femoral–axillary access (FA VA-ECMO) after cardiothoracic surgery between January 2014 and January 2019 in our department. Patients requiring central aortic cannulation and patients with respiratory failure requiring veno-venous ECMO were excluded. Primary outcomes were in-hospital mortality and 1-year survival rate of patients who were weaned from VA-ECMO support. Secondary outcomes were cannulation-related complications at the axillary site, VA-ECMO-related complications, and systemic complications. Results: In our cohort, 60 (33.5%) patients were female. Mean age was 67.0 ± 10.9 years. Overall, 78 (43.5%) patients were operated upon electively, 37 (20.7%) patients underwent urgent surgery, and 64 (35.8%) patients underwent emergency surgical treatment. Sixty-seven patients (37.4%) were resuscitated preoperatively. The mean duration of VA-ECMO support was 8.4 ± 5.1 days. Weaning from VA-ECMO was successful in 87 (48.6%) patients; 62 (34.6%) patients survived the hospital stay. The 1-year survival rate was 74%. Subclavian bleeding occurred in 24 (13.4%) patients, femoral bleeding in 4 (2.2%) patients, ischemia of the upper limb in 11 (6.1%) patients, intracerebral bleeding in 9 (5%) patients, and stroke in 19 (10.6%) patients. Conclusions: In patients with acute LV dysfunction after cardiothoracic surgery who cannot be weaned from cardiopulmonary bypass, right axillary artery cannulation is a safe and reliable method for VA-ECMO support with an acceptable complication rate.
Association between abstraction level and time: Are future and past more abstract than the present?
2023-11-20

Construal level theory suggests that objects or events are represented differently depending on their psychological distance from ourselves. Specifically, objects and events should be represented more abstractly the farther they are removed from direct experience through distance in the spatial, temporal, social, or hypotheticality domains. Bar-Anan et al. reported a key finding supporting this assumed association of the various distance dimensions and abstraction level. In their study, participants responded faster in an Implicit Association Task when temporally near and concrete concepts, as well as temporally far and abstract concepts, were mapped to the same rather than different response keys. In this study, we conceptually replicated this basic finding when employing temporal adverbs relating to present versus future time, and nouns referring to concrete versus abstract concepts (Experiment 1). Evidence for such an association, however, was largely absent (and significantly weaker than in Experiment 1) when temporal adverbs relating to the past were employed as instances of the large temporal distance category (Experiment 2). We propose that the uncertainty associated with the future, as opposed to the past, might play an important role in this temporal asymmetry by increasing psychological distance.
De-Suppression of Mesenchymal Cell Identities and Variable Phenotypic Outcomes Associated with Knockout of Bbs1
2023-11-20

Bardet–Biedl syndrome (BBS) is an archetypal ciliopathy caused by dysfunction of primary cilia. BBS affects multiple tissues, including the kidney, eye and hypothalamic satiety response. Understanding pan-tissue mechanisms of pathogenesis versus those which are tissue-specific, as well as gauging their associated inter-individual variation owing to genetic background and stochastic processes, is of paramount importance in syndromology. The BBSome is a membrane-trafficking and intraflagellar transport (IFT) adaptor protein complex formed by eight BBS proteins, including BBS1, which is the most commonly mutated gene in BBS. To investigate disease pathogenesis, we generated a series of clonal renal collecting duct IMCD3 cell lines carrying defined biallelic nonsense or frameshift mutations in Bbs1, as well as a panel of matching wild-type CRISPR control clones. Using a phenotypic screen and an unbiased multi-omics approach, we note significant clonal variability for all assays, emphasising the importance of analysing panels of genetically defined clones. Our results suggest that BBS1 is required for the suppression of mesenchymal cell identities as the IMCD3 cell passage number increases. This was associated with a failure to express epithelial cell markers and tight junction formation, which was variable amongst clones. Transcriptomic analysis of hypothalamic preparations from BBS mutant mice, as well as BBS patient fibroblasts, suggested that dysregulation of epithelial-to-mesenchymal transition (EMT) genes is a general predisposing feature of BBS across tissues. Collectively, this work suggests that the dynamic stability of the BBSome is essential for the suppression of mesenchymal cell identities as epithelial cells differentiate.
Intramural hematoma in the proximal sealing zone of the thoracic endovascular aneurysm repair: frequency and safety in acute and subacute type B dissections
2023-11-20

Introduction To assess the outcomes after thoracic endovascular aneurysm repair (TEVAR) in the presence of intramural hematoma (IMH) in the proximal sealing zone. Material and methods Patient data were retrospectively extracted from the hospital records of patients treated with TEVAR for acute and chronic aortic dissection type B in one single center. The initial, preoperative, first postoperative, and last follow-up CT scans were evaluated in the aortic 3D multiplanar reformats and the centerline regarding IMH presence in the proximal sealing zone, anatomical preconditions, and the morphological TEVAR complications including migration and bird-beak. Groups with (IMH) and without IMH (no-IMH) were compared. Results Overall, 84 patients (IMH:42; no-IMH:42) were treated at the age of 63(55; 72) years, of whom 23/84 (27%), 34/84 (40%), and 27/84 (32%) were in the hyperacute, acute and subacute dissection phases, respectively. The bovine arch was found in 10/84(12%) and the type III arch was most common (43/84;51%). IMH maximum extent was found in zones 0, 1, 2, and 3 in 14/84 (17%), 17/84 (20%), 18/84 (21%), and 6/84 (7%), respectively. Sealing was achieved in zone II in 71/84 (85%) and LSA was revascularized in 66/84 (79%) of the overall cohort. Early mortality and paraplegia were 2/84 (2%) each; stroke rate was 3/84 (4%). During the 22 months median follow-up (22;4;43) no RTAD was observed. Migration ≥10 mm (IMH: 11/82; no-IMH: 10/82; P = 1.0) and bird-beaks (IMH: 10/82; no-IMH: 12/82; P = 0.8036) were comparable in both groups and accompanied by a low aorta related mortality (1/82) in both groups. Conclusion The presence of the IMH in the proximal TEVAR sealing zone is frequent and may not be relevant for the occurrence of the RTAD, stent-graft migration, or bird-beak formation.