A two-stage X-, Ku-band monolithic FET amplifier has been developed. Initial results indicate a gain of 7-10 dB across the 8-20 GHz band with a typical rf power output of 100 mW. A balanced amplifier ...consisting of two two-stage amplifiers and a pair of Lange couplers yielded 10.5 +- 1 dB gain from 7.5 to 18 GHz and an output power of 150-250 mW in Ku-band.
Nontypeable Haemophilus influenzae (NTHi) causes acute exacerbation of chronic obstructive pulmonary disease (AECOPD). IL-17A is central for neutrophilic inflammation and has been linked to COPD ...pathogenesis.
We investigated whether IL-17A is elevated in NTHi-associated AECOPD and required for NTHi-exacerbated pulmonary neutrophilia induced by cigarette smoke.
Experimental studies with cigarette smoke and NTHi infection were pursued in gene-targeted mice and using antibody intervention. IL-17A was measured in sputum collected from patients with COPD at baseline, during, and after AECOPD.
Exacerbated airway neutrophilia in cigarette smoke-exposed mice infected with NTHi was associated with an induction of IL-17A. In agreement, elevated IL-17A was observed in sputum collected during NTHi-associated AECOPD, compared with samples collected before or after the event. NTHi-exacerbated neutrophilia and induction of neutrophil chemoattractants over the background of cigarette smoke, as observed in wild-type mice, was absent in Il17a(-/-) mice and in mice treated with a neutralizing anti-IL-17A antibody. Further studies revealed that IL-1 receptor (R)1 signaling was required for IL-17A-dependent neutrophilia. Moreover, deficiency or therapeutic neutralization of IL-17A did not increase bacterial burden or delay bacterial clearance.
IL-17A is induced during NTHi-associated AECOPD. Functionally, IL-1R1-dependent IL-17A is required for NTHi-exacerbated pulmonary neutrophilia induced by cigarette smoke. Targeting IL-17A in AECOPD may thus be beneficial to reduce neutrophil recruitment to the airways.
Observations of rift and rifted margin architecture suggest that significant spatial and temporal structural heterogeneity develops during the multiphase evolution of continental rifting. Inheritance ...is often invoked to explain this heterogeneity, such as preexisting anisotropies in rock composition, rheology, and deformation. Here, we use high‐resolution 3‐D thermal‐mechanical numerical models of continental extension to demonstrate that rift‐parallel heterogeneity may develop solely through fault network evolution during the transition from distributed to localized deformation. In our models, the initial phase of distributed normal faulting is seeded through randomized initial strength perturbations in an otherwise laterally homogeneous lithosphere extending at a constant rate. Continued extension localizes deformation onto lithosphere‐scale faults, which are laterally offset by tens of km and discontinuous along‐strike. These results demonstrate that rift‐ and margin‐parallel heterogeneity of large‐scale fault patterns may in‐part be a natural byproduct of fault network coalescence.
Key Points
Distributed normal fault networks develop from randomized initial strength perturbations
Rifted margin heterogeneity develops through fault network localization
Objectives The aim was to study the association between venous disorders and leg symptoms in the population based cross sectional Bonn Vein Study 1 (BVS1). Methods A total of 1,350 men and 1,722 ...women aged 18–79 years were enrolled into BVS1. Chronic venous insufficiency (CVI), varicose veins (VVs), and clinical classes (C-classes/CEAP Clinical, Etiological, Anatomical, and Pathophysiological) were determined by clinical and duplex investigation. Leg symptoms (heaviness, tightness, swelling, pain after standing or sitting, pain while walking, muscle cramps, itching, and restless legs) were assessed in a standardized interview. For 2,624 subjects (48.7% male) with complete information on venous disorders, relevant characteristics and information on at least one leg symptom, multivariate logistic regression analysis was performed. Results More women (929/63.0%) reported at least one leg symptom within the last 4 weeks than men (560/48.7%). Prevalence of reported symptoms increased with age (45.4% of the 18–29 year olds, 73.9% of the 70–79 year olds). Leg symptoms were more frequent in obese and underweight subjects. As confirmed by clinical and duplex examination 22.6% had VV and 15.8% had CVI. VV (OR: 1.4; CI: 1.1–1.7) and CVI (OR: 1.8; CI: 1.3–2.3) were significantly associated with reporting at least one leg symptom. In particular, there was a positive association of VV and CVI with itching, feeling of heaviness, tightness, swelling, and pain after standing or sitting. C2–C6 showed a statistically significant association with feeling of heaviness, tightness, swelling, and itching, while for pain on walking and muscle cramps this was shifted towards C classes C3–C6 and C3–C4, respectively. Conclusions Venous disorders show significant associations with several leg symptoms. Itching, feeling of heaviness, or tightness seem to be more closely related than other symptoms. The associations between C classes and symptoms seem to be restricted to classes C2 or higher.
Patients with non–small cell lung cancer (NSCLC) harboring ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) chromosomal rearrangements benefit from treatment with the ROS1 inhibitor ...crizotinib. Limited data exist on the spectrum of resistance mechanisms in ROS1-positive NSCLC. To delineate mechanisms of acquired resistance, we analyzed biopsy samples of tumor lesions that progressed while patients were receiving crizotinib.
An activating mutation in the KIT proto-oncogene receptor tyrosine kinase (KIT) (p.D816G) was identified by SNaPshot sequencing in a tumor sample from a patient with ROS1-positive NSCLC identified by fluorescence in situ hybridization whose disease progressed after initial response to crizotinib. In vitro studies included evaluation of KIT mRNA expression by quantitative reverse-transcriptase polymerase chain reactions, transduction of Ba/F3 cells and NSCLC cell lines with KIT-expressing lentiviral plasmids, immunoblotting, and cellular proliferation assays.
KITD816G is an activating mutation that induces autophosphorylation and cell proliferation. Expression of the mutant KITD816G receptor in ROS1-positive NSCLC cell lines led to constitutively activated KIT as measured by phosphorylation of the KIT receptor. Expression of the KITD816G rendered the HCC78 and CUTO2 cell lines resistant to crizotinib, and only dual inhibition of ROS1 and KIT with crizotinib and ponatinib could resensitize the cells to inhibition of proliferation. The oncogenic switch observed in ROS1-positive cell lines was not immediate and required pharmacologic inactivation of ROS1.
Activation of KIT by a gain-of-function somatic mutation is a novel mechanism of resistance to crizotinib in ROS1-rearranged NSCLC. This bypass signaling pathway serves as a ROS1-independent mechanism of resistance, similarly to previously identified epidermal growth factor receptor or Kirsten rat sarcoma viral oncogene homolog/neuroblastoma RAS viral oncogene homolog signaling pathways, and can potentially be targeted by KIT inhibitors.
We report the analysis of the microlensing event OGLE-2018-BLG-0677. A small feature in the light curve of the event leads to the discovery that the lens is a star-planet system. Although there are ...two degenerate solutions that could not be distinguished for this event, both lead to a similar planet-host mass ratio. We perform a Bayesian analysis based on a Galactic model to obtain the properties of the system and find that the planet corresponds to a super-Earth/sub-Neptune with a mass of . The host star has a mass of . The projected separation for the inner and outer solutions are au and au respectively. At , this is by far the lowest Δχ2 for any securely detected microlensing planet to date, a feature that is closely connected to the fact that it is detected primarily via a "dip" rather than a "bump."
The focus of this paper is to investigate numerically the vibro-acoustic responses of functionally graded lightweight square panel (FGLSP) made from Al/Al2O3 with various boundary conditions (BCs). ...The approach of analysis is restricted to low and mid-frequency regions. First-order shear deformation theory and finite element method are employed to model the vibro-acoustic response of the FGLSP. Its properties vary along its thickness and are obtained by the Voigt’s rule of mixture as well as a simple power law distribution. Modal responses of pristine aluminium material (PAM) obtained analytically and experimentally are used to validate the numerical approximation of modal responses of PAM. These results are used to compare the numerical results of FGLSP and the first twelve mode shapes are obtained for all BCs. A comparison of the result shows that at low and mid-frequency regions, the sound transmission loss of FGLSP is higher than the conventional PAM. The study reveals that FGLSP can compete favourably with their pristine material counterparts. This material are particularly useful for noise reducing casings which surround noisy devices, household appliances or industrial machines, and limit noise transmission to the environment.
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