ABSTRACT
Quasar winds can shock and sweep up ambient interstellar medium (ISM) gas, contributing to galactic quenching. We combine and extend past models of energy-conserving shock bubbles around ...quasars, investigate model implications from an observational standpoint, and test model predictions using new high-resolution spectroscopic observations of the broad absorption-line quasar SDSS J030000.56+004828.0 (J0300). Even with constant energy input from the wind, a bubble’s expansion decelerates over time as more ISM gas is swept up. Our new observations enable a direct search for this deceleration. We obtain the tightest reported 3σ limit on the average rest-frame deceleration (or acceleration) of a quasar outflow: |a| < 0.1 km s−1 yr−1 (<3 × 10−4 cm s−2) in the relatively low-velocity Ca ii outflow of J0300 over 9.65 rest-frame years. We can satisfy these limits with certain parameter choices in our model, but the large velocity range of the Ca ii absorption in J0300 rules out the hypothesis that such gas shares the velocity of the swept-up ISM gas in a self-similar shock bubble. We investigate the possibility of ram-pressure acceleration of preexisting ISM clouds and conclude that the velocity range seen in Ca ii in J0300 is potentially consistent with such an explanation. The Ca ii-absorbing gas clouds in J0300 have been inferred to have high densities by Choi et al., in which case they can only have been accelerated to their current speeds if they were originally at least an order of magnitude less dense than they are today.
Background Although recurrence and death can occur in patients with papillary thyroid cancer (PTC) several years after being diagnosed, the necessary duration of follow-up for these patients remains ...unclear. Methods This was a single-institution, retrospective review of 269 patients with PTC. Cox proportional hazards model and Kaplan-Meier curves were used to identify risk factors for recurrence and death. Risk predictors included age, sex, radiation exposure history, extent of operation, radioactive iodine treatment, follicular variant of PTC (FVPTC), extrathyroidal invasion, multifocality, TNM status, and stage. Results Median follow-up was 27 years. Of 269 patients, 180 (66%) were female, and 196 (73%) were ≤45 years of age. Recurrence and cancer-specific death rates were 28% and 9%, respectively. Time to recurrence (±SD) was 8.1 (± 8.3) years and to cancer-specific death was 9.0 (± 11.0) years; however, 11% of recurrences and 17% of deaths occurred after 20 years. Risk factors for recurrence were older age, FVPTC, T4 tumors, cervical lymph node involvement, metastases, and stage ≥ 4a. Predictors of death from PTC were older age, metastases, and stage ≥ 3. Conclusion Both recurrences and death from PTC can occur more than 30 years after being treated, thus lifelong follow-up of patients with PTC is necessary.
Abstract The capability to spatially control stem cell orientation and differentiation simultaneously using a combination of geometric cues that mimic structural aspects of native extracellular ...matrix (ECM) and biochemical cues such as ECM-bound growth factors (GFs) is important for understanding the organization and function of musculoskeletal tissues. Herein, oriented sub-micron fibers, which are morphologically similar to musculoskeletal ECM, were spatially patterned with GFs using an inkjet-based bioprinter to create geometric and biochemical cues that direct musculoskeletal cell alignment and differentiation in vitro in registration with fiber orientation and printed patterns, respectively. Sub-micron polystyrene fibers (diameter ∼ 655 nm) were fabricated using a Spinneret-based Tunable Engineered Parameters (STEP) technique and coated with serum or fibrin. The fibers were subsequently patterned with tendon-promoting fibroblast growth factor-2 (FGF-2) or bone-promoting bone morphogenetic protein-2 (BMP-2) prior to seeding with mouse C2C12 myoblasts or C3H10T1/2 mesenchymal fibroblasts. Unprinted regions of STEP fibers showed myocyte differentiation while printed FGF-2 and BMP-2 patterns promoted tenocyte and osteoblast fates, respectively, and inhibited myocyte differentiation. Additionally, cells aligned along the fiber length. Functionalizing oriented sub-micron fibers with printed GFs provides instructive cues to spatially control cell fate and alignment to mimic native tissue organization and may have applications in regenerative medicine.
Semiconductor nanowires (NWs) have unique electronic properties and sizes comparable with biological structures involved in cellular communication, thus making them promising nanostructures for ...establishing active interfaces with biological systems. We report a flexible approach to interface NW field-effect transistors (NWFETs) with cells and demonstrate this for silicon NWFET arrays coupled to embryonic chicken cardiomyocytes. Cardiomyocyte cells were cultured on thin, optically transparent polydimethylsiloxane (PDMS) sheets and then brought into contact with Si-NWFET arrays fabricated on standard substrates. NWFET conductance signals recorded from cardiomyocytes exhibited excellent signal-to-noise ratios with values routinely > 5 and signal amplitudes that were tuned by varying device sensitivity through changes in water gate-voltage potential, Vg. Signals recorded from cardiomyocytes for Vg from -0.5 to + 0.1 V exhibited amplitude variations from 31 to 7 nS whereas the calibrated voltage remained constant, indicating a robust NWFET/cell interface. In addition, signals recorded as a function of increasing/decreasing displacement of the PDMS/cell support to the device chip showed a reversible > 2x increase in signal amplitude (calibrated voltage) from 31 nS (1.0 mV) to 72 nS (2.3 mV). Studies with the displacement close to but below the point of cell disruption yielded calibrated signal amplitudes as large as 10.5 ± 0.2 mV. Last, multiplexed recording of signals from NWFET arrays interfaced to cardiomyocyte monolayers enabled temporal shifts and signal propagation to be determined with good spatial and temporal resolution. Our modular approach simplifies the process of interfacing cardiomyocytes and other cells to high-performance Si-NWFETs, thus increasing the experimental versatility of NWFET arrays and enabling device registration at the subcellular level.
•The optimal Aspirin dosage for the prevention of preeclampsia has to be individualized.•Platelet inhibition by Aspirin varies individually between pregnant women.•Increasing Aspirin to 150 mg daily ...does not necessarily magnify the inhibitory effect.•Optical aggegrometry is used to monitor Aspirin effectiveness in women at risk.
Preeclampsia still represents a life-threatening pregnancy complication, associated with severe maternal and neonatal morbidity and mortality. Low-dose Aspirin is advised to avoid preeclampsia in high-risk pregnancies worldwide. As Aspirin does not cover all women at risk, the prescription raises questions concerning optimal target population, dosage, and onset of therapy.
The aim of this study was to test platelet responsiveness on Aspirin by optical aggegrometry, to gain robust biochemically assessment data of Aspirin in an obstetric cohort. 248 women at high risk for development of preeclampsia were included in the study. Aspirin-prophylaxis was administered either in 100 mg (n = 229) or 150 mg (n = 90) daily. Dosing of 100 mg Aspirin was maintained if testing revealed a sufficient platelet inhibition. If platelet inhibition was insufficient, dosage was increased to 150 mg Aspirin and re-testing was advised. 91 patients (91/229 = 39.7%) presented a sufficient inhibitory Aspirin effect at a dosage of 100 mg, but in 138 patients LTA showed an inadequate Aspirin response (138/229 = 60.3%). In 19 women 150 mg Aspirin was administered as starting dose due to new recommendations. Of all women at 150 mg Aspirin 64 did not properly respond (35.4%). The overall rate of sufficient responding women regardless the Aspirin dose was 64.6%.
This study demonstrates still an insufficient inhibition of platelet aggregation in about 1/3 of women even with a dosage of 150 mg Aspirin daily, who might potentially benefit from further increase. These data show, that there is a need for further research to allow a personalized approach for individualized Aspirin therapy, maximizing the preventive benefit for mother and child.
Development of regulated cellular processes and signaling methods in synthetic cells is essential for their integration with living materials. Light is an attractive tool to achieve this, but the ...limited penetration depth into tissue of visible light restricts its usability for in-vivo applications. Here, we describe the design and implementation of bioluminescent intercellular and intracellular signaling mechanisms in synthetic cells, dismissing the need for an external light source. First, we engineer light generating SCs with an optimized lipid membrane and internal composition, to maximize luciferase expression levels and enable high-intensity emission. Next, we show these cells' capacity to trigger bioprocesses in natural cells by initiating asexual sporulation of dark-grown mycelial cells of the fungus Trichoderma atroviride. Finally, we demonstrate regulated transcription and membrane recruitment in synthetic cells using bioluminescent intracellular signaling with self-activating fusion proteins. These functionalities pave the way for deploying synthetic cells as embeddable microscale light sources that are capable of controlling engineered processes inside tissues.
Scale resolving numerical methods are necessary to accurately predict the afterbody flows of space launchers. Numerical workflows built for such computations have to be designed in order to obtain a ...minimal numerical dissipation to resolve fine turbulent structures, a sufficient robustness to capture eventual shock waves and both a reasonable computational cost and an acceptable user workload enabling comparative design studies. This article presents the development of a hybrid numerical framework based on Ducros’s sensor and designed to switch from a low-dissipation formulation in presence of vortical structures to a robust formulation around high gradients. This hybrid workflow is used with ZDES, including its latest automatic mode (ZDES mode 2 (2020)), to simulate a transonic space launcher afterbody experiment with and without a cold air propulsive jet 1,2. The salient physical properties of the base flow are investigated and the evaluation of computed results follows the extended nomenclature for validation of simulation techniques 3 from level 0 to 5. The framework is thus validated for instantaneous and mean flow visualizations, base and extension mean pressure coefficient distribution, pressure fluctuation levels, one-point and two-point spectral analyses. Such an efficient automatic RANS/LES strategy could be well suited to study realistic launcher afterbody geometries with propulsive jet(s).
The aim of this study was to investigate the involvement of autoimmune reactions to native and post-translationally modified extracellular matrix components in the pathogenesis of periodontitis. Sera ...from individuals with aggressive periodontitis (AgP, n = 25), chronic periodontitis (CP, n = 14), and gingivitis (G, n = 18) were tested for the presence of autoantibodies against: (a) native collagen type I (CI) and collagen type III (CIII); (b) CI and CIII post-translationally modified by reactive oxygen species (ROS) of the type present during inflammation; and (c) citrullinated filaggrin-derived peptides (CCP). Autoantibodies to native and ROS-modified CI and CIII as well as autoantibodies to CCP were observed exclusively in patients with AgP and not in those with CP or G. In conclusion, autoimmune reactions to native and post-translationally modified self-antigens may play a role specifically in the pathogenesis of AgP.
Rare denovo variants represent a significant cause of neurodevelopmental delay and intellectual disability (ID).
Exome sequencing was performed on 4351 patients with global developmental delay, ...seizures, microcephaly, macrocephaly, motor delay, delayed speech and language development, or ID according to Human Phenotype Ontology (HPO) terms. All patients had previously undergone whole exome sequencing as part of diagnostic genetic testing with a focus on variants in genes implicated in neurodevelopmental disorders up to January 2017. This resulted in a genetic diagnosis in 1336 of the patients. In this study, we specifically searched for variants in 14 recently implicated novel neurodevelopmental disorder (NDD) genes.
We identified 65 rare, protein-changing variants in 11 of these 14 novel candidate genes. Fourteen variants in CDK13, CHD4, KCNQ3, KMT5B, TCF20, and ZBTB18 were scored pathogenic or likely pathogenic. Of note, two of these patients had a previously identified cause of their disease, and thus, multiple molecular diagnoses were made including pathogenic/likely pathogenic variants in FOXG1 and CDK13 or in TMEM237 and KMT5B.
Looking for pathogenic variants in newly identified NDD genes enabled us to provide a molecular diagnosis to 14 patients and their close relatives and caregivers. This underlines the relevance of re-evaluation of existing exome data on a regular basis to improve the diagnostic yield and serve the needs of our patients.
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