On-Line Loss of Control Detection Using Wavelets

Wavelet transforms are used for on-line detection of aircraft loss of control. Wavelet transforms are compared with Fourier transform methods and shown to more rapidly detect changes in the vehicle dynamics. This faster response is due to a time window that decreases in length as the frequency increases. New wavelets are defined that further decrease the detection time by skewing the shape of the envelope. The wavelets are used for power spectrum and transfer function estimation. Smoothing is used to tradeoff the variance of the estimate with detection time. Wavelets are also used as front-end to the eigensystem reconstruction algorithm. Stability metrics are estimated from the frequency response and models, and it is these metrics that are used for loss of control detection. A Matlab toolbox was developed for post-processing simulation and flight data using the wavelet analysis methods. A subset of these methods was implemented in real time and named the Loss of Control Analysis Tool Set or LOCATS. A manual control experiment was conducted using a hardware-in-the-loop simulator for a large transport aircraft, in which the real time performance of LOCATS was demonstrated. The next step is to use these wavelet analysis tools for flight test support

A peptide corresponding to the neuropilin-1-binding site on VEGF165 induces apoptosis of neuropilin-1-expressing breast tumour cells

There is increasing evidence that vascular endothelial growth factor (VEGF) has autocrine as well as paracrine functions in tumour biology. Vascular endothelial growth factor-mediated cell survival signalling occurs via the classical tyrosine kinase receptors Flt-1, KDR/Flk-1 and the more novel neuropilin (NP) receptors, NP-1 and NP-2. A 24-mer peptide, which binds to neuropilin-1, induced apoptosis of murine and human breast carcinoma cells, whereas a peptide directed against KDR had no effect. Both anti-NP1 and anti-KDR peptides induced endothelial cell apoptosis. Confocal microscopy using 5-(6)-carboxyfluorescein-labelled peptides showed that anti-NP1 bound to both tumour and endothelial cells, whereas anti-KDR bound endothelial cells only. This study demonstrates that NP-1 plays an essential role in autocrine antiapoptotic signalling by VEGF in tumour cells and that NP1-blockade induces tumour cell and endothelial cell apoptosis. Specific peptides can therefore be used to target both autocrine (tumour cells) and paracrine (endothelial cells) signalling by VEGF

p53 inhibits alpha 6 beta 4 integrin survival signaling by promoting the caspase 3-dependent cleavage of AKT/PKB

Although the interaction of matrix proteins with integrins is known to initiate signaling pathways that are essential for cell survival, a role for tumor suppressors in the regulation of these pathways has not been established. We demonstrate here that p53 can inhibit the survival function of integrins by inducing the caspase-dependent cleavage and inactivation of the serine/threonine kinase AKT/PKB. Specifically, we show that the alpha6beta4 integrin promotes the survival of p53-deficient carcinoma cells by activating AKT/PKB. In contrast, this integrin does not activate AKT/PKB in carcinoma cells that express wild-type p53 and it actually stimulates their apoptosis, in agreement with our previous findings (Bachelder, R.E., A. Marchetti, R. Falcioni, S. Soddu, and A.M. Mercurio. 1999. J. Biol. Chem. 274:20733-20737). Interestingly, we observed reduced levels of AKT/PKB protein after antibody clustering of alpha6beta4 in carcinoma cells that express wild-type p53. In contrast, alpha6beta4 clustering did not reduce the level of AKT/PKB in carcinoma cells that lack functional p53. The involvement of caspase 3 in AKT/PKB regulation was indicated by the ability of Z-DEVD-FMK, a caspase 3 inhibitor, to block the alpha6beta4-associated reduction in AKT/PKB levels in vivo, and by the ability of recombinant caspase 3 to promote the cleavage of AKT/PKB in vitro. In addition, the ability of alpha6beta4 to activate AKT/PKB could be restored in p53 wild-type carcinoma cells by inhibiting caspase 3 activity. These studies demonstrate that the p53 tumor suppressor can inhibit integrin-associated survival signaling pathways

Vaccine formulations in clinical development for the prevention of severe acute respiratory syndrome coronavirus 2 infection

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented effort toward the development of an effective and safe vaccine. Aided by extensive research efforts into characterizing and developing countermeasures towards prior coronavirus epidemics, as well as recent developments of diverse vaccine platform technologies, hundreds of vaccine candidates using dozens of delivery vehicles and routes have been proposed and evaluated preclinically. A high demand coupled with massive effort from researchers has led to the advancement of at least 31 candidate vaccines in clinical trials, many using platforms that have never before been approved for use in humans. This review will address the approach and requirements for a successful vaccine against SARS-CoV-2, the background of the myriad of vaccine platforms currently in clinical trials for COVID-19 prevention, and a summary of the present results of those trials. It concludes with a perspective on formulation problems which remain to be addressed in COVID-19 vaccine development and antigens or adjuvants which may be worth further investigation

October 1966

Massachusetts Turf and Lawn Grass CouncilBetter Turf Through Research and Educatio

Detection and analysis of Lhù'ààn Mân' (Kluane Lake) dust plumes using passive and active ground-based remote sensing supported by physical surface measurements

There is growing recognition that high-latitude dust (HLD), originating from local drainage-basin flows, is the dominant source for certain important phenomena such as particle deposition on snow/ice. The analysis of such local plumes (including a better exploitation of remote sensing data) has been targeted as a key aerosol issue by the HLD community. The sub-Arctic Lhù'ààn Mân' (Kluane Lake) region in the Canadian Yukon is subject to regular drainage-basin, wind-induced dust plumes. This dust emission site is one of many current and potential proglacial dust sources in the Canadian north. In situ ground-based measurements are, due to constraints in accessing these types of regions, rare. Ground- and satellite-based remote sensing accordingly play an important role in helping to characterize local dust sources in the Arctic and sub-Arctic. We compared ground-based passive and active remote sensing springtime (May 2019) retrievals with microphysical surface-based measurements in the Lhù'ààn Mân' region in order to better understand the potential for ground- and satellite-based remote sensing of HLD plumes. This included correlation analyses between ground-based coarse mode (CM) aerosol optical depth (AOD) retrievals from AERONET AOD spectra, CM AODs derived from co-located Doppler lidar profiles, and OPS (optical particle sizer) surface measurements of CM particle-volume concentration (vc(0)). An automated dust classification scheme was developed to objectively identify local dust events. The classification process helped distinguish lidar-derived CM AODs which covaried with vdust(0) (during recognized dust events) and those that varied at the same columnar scale as AERONET-derived CM AOD (and thus could be remotely sensed). False positive cloud events for dust-induced, high-frequency variations in lidar-derived CM AODs in cloudless atmospheres indicated that the AERONET cloud-screening process was rejecting CM dust AODs. The persistence of a positive lidar ratio bias in comparing the CIMEL/lidar-derived value with a prescribed value obtained from OPS-derived particle sizes coupled with dust-speciation-derived refractive indices led to the suggestion that the prescribed value could be increased to optically derived values of 20 sr by the presence of optically significant dust particles at an effective radius of 11–12 µm. Bimodal CM PSDs (see Appendix B for a glossary) from full-fledged AERONET inversions (the combination of AOD spectra and almucantar radiances) also showed CM peaks at ∼ 1.3 and 5–6.6 µm radius: this, we argue, was associated with springtime Asian dust and Lhù'ààn Mân' dust, respectively. Correlations between the CIMEL-derived fine mode (FM) AOD and FM OPS-derived particle-volume concentrations suggest that remote sensing techniques can be employed to monitor FM dust (which is arguably a better indicator of the long-distance transport of HLD).</p

Overexpression of neuropilin-1 promotes constitutive MAPK signalling and chemoresistance in pancreatic cancer cells

Neuropilin-1 (NRP-1) is a novel co-receptor for vascular endothelial growth factor (VEGF). Neuropilin-1 is expressed in pancreatic cancer, but not in nonmalignant pancreatic tissue. We hypothesised that NRP-1 expression by pancreatic cancer cells contributes to the malignant phenotype. To determine the role of NRP-1 in pancreatic cancer, NRP-1 was stably transfected into the human pancreatic cancer cell line FG. Signal transduction was assessed by Western blot analysis. Susceptibility to anoikis (detachment induced apoptosis) was evaluated by colony formation after growth in suspension. Chemosensitivity to gemcitabine or 5-fluorouracil (5-FU) was assessed by MTT assay in pancreatic cancer cells following NRP-1 overexpression or siRNA-induced downregulation of NRP-1. Differential expression of apoptosis-related genes was determined by gene array and further evaluated by Western blot analysis. Neuropilin-1 overexpression increased constitutive mitogen activated protein kinase (MAPK) signalling, possibly via an autocrine loop. Neuropilin-1 overexpression in FG cells enhanced anoikis resistance and increased survival of cells by >30% after exposure to clinically relevant levels of gemcitabine and 5-FU. In contrast, downregulation of NRP-1 expression in Panc-1 cells markedly increased chemosensitivity, inducing >50% more cell death at clinically relevant concentrations of gemcitabine. Neuropilin-1 overexpression also increased expression of the antiapoptotic regulator, MCL-1. Neuropilin-1 overexpression in pancreatic cancer cell lines is associated with (a) increased constitutive MAPK signalling, (b) inhibition of anoikis, and (c) chemoresistance. Targeting NRP-1 in pancreatic cancer cells may downregulate survival signalling pathways and increase sensitivity to chemotherapy

Characterization of aerosol growth events over Ellesmere Island during the summers of 2015 and 2016

The occurrence of frequent aerosol nucleation and growth events in the Arctic during summertime may impact the region's climate through increasing the number of cloud condensation nuclei in the Arctic atmosphere. Measurements of aerosol size distributions and aerosol composition were taken during the summers of 2015 and 2016 at Eureka and Alert on Ellesmere Island in Nunavut, Canada. These results provide a better understanding of the frequency and spatial extent of elevated Aitken mode aerosol concentrations as well as of the composition and sources of aerosol mass during particle growth. Frequent appearances of small particles followed by growth occurred throughout the summer. These particle growth events were observed beginning in June with the melting of the sea ice rather than with the polar sunrise, which strongly suggests that influence from the marine boundary layer was the primary cause of the events. Correlated particle growth events at the two sites, separated by 480&thinsp;km, indicate conditions existing over large scales play a key role in determining the timing and the characteristics of the events. In addition, aerosol mass spectrometry measurements were used to analyze the size-resolved chemical composition of aerosols during two selected growth events. It was found that particles with diameters between 50 and 80&thinsp;nm (physical diameter) during these growth events were predominately organic with only a small sulfate contribution. The oxidation of the organics also changed with particle size, with the fraction of organic acids increasing with diameter from 80 to 400&thinsp;nm. The growth events at Eureka were observed most often when the temperature inversion between the sea and the measurement site (at 610&thinsp;m&thinsp;a.s.l.) was non-existent or weak, presumably creating conditions with low aerosol condensation sink and allowing fresh marine emissions to be mixed upward to the observatory's altitude. While the nature of the gaseous precursors responsible for the growth events is still poorly understood, oxidation of dimethyl sulfide alone to produce particle-phase sulfate or methanesulfonic acid was inconsistent with the measured aerosol composition, suggesting the importance of other gas-phase organic compounds condensing for particle growth.</p