This book provides a comprehensive resource and thorough treatment in the latest development of Digital RF Memory (DRFM) technology and their key role in maintaining dominance over the ...electromagnetic spectrum. Part I discusses the use of advanced technology to design transceivers for spectrum sensing using unmanned systems to dominate the electromagnetic spectrum. Part II uses artificial intelligence and machine learning to enable modern spectrum sensing and detection signal processing for electronic support and electronic attack. Another key contribution is examination of counter-DRFM techniques. DRFM and transceiver design details and examples are provided along with the MATLAB software allowing the reader to construct their own embedded DRFM transceivers for unmanned systems. It examines the design trade-offs in developing multiple, structured, false target synthesis DRFM architectures and aids in developing counter-DRFM techniques and distinguish false target from real ones. Written by an expert in the field, and including MATLAB design software, this is the only comprehensive book written on the subject of DRFM.
Protein-tyrosine phosphatases (PTPs) counteract protein tyrosine phosphorylation and cooperate with receptor-tyrosine kinases in the regulation of cell signaling. PTPs need to undergo oxidative ...inhibition for activation of cellular cascades of protein-tyrosine kinase phosphorylation following growth factor stimulation. It has remained enigmatic how such oxidation can occur in the presence of potent cellular reducing systems. Here, using in vitro biochemical assays with purified, recombinant protein, along with experiments in the adenocarcinoma cell line A431, we discovered that bicarbonate, which reacts with H2O2 to form the more reactive peroxymonocarbonate, potently facilitates H2O2-mediated PTP1B inactivation in the presence of thioredoxin reductase 1 (TrxR1), thioredoxin 1 (Trx1), and peroxiredoxin 2 (Prx2) together with NADPH. The cellular experiments revealed that intracellular bicarbonate proportionally dictates total protein phosphotyrosine levels obtained after stimulation with epidermal growth factor (EGF) and that bicarbonate levels directly correlate with the extent of PTP1B oxidation. In fact, EGF-induced cellular oxidation of PTP1B was completely dependent on the presence of bicarbonate. These results provide a plausible mechanism for PTP inactivation during cell signaling and explain long-standing observations that growth factor responses and protein phosphorylation cascades are intimately linked to the cellular acid–base balance.
Currently there are few ideal methods for the characterization of nanoparticles in complex, environmental samples, leading to significant gaps in toxicity and exposure assessments of nanomaterials. ...Single particle-inductively coupled plasma-mass spectrometry (spICPMS) is an emerging technique that can both size and count metal-containing nanoparticles. A major benefit of the spICPMS method is its ability to characterize nanoparticles at concentrations relevant to the environment. This paper presents a practical guide on how to count and size nanoparticles using spICPMS. Different methods are investigated for measuring transport efficiency (i.e., nebulization efficiency), an important term in the spICPMS calculations. In addition, an alternative protocol is provided for determining particle size that broadens the applicability of the technique to all types of inorganic nanoparticles. Initial comparison, using well-characterized, monodisperse silver nanoparticles, showed the importance of having an accurate transport efficiency value when determining particle number concentration and, if using the newly presented protocol, particle size. Ultimately, the goal of this paper is to provide improvements to nanometrology by further developing this technique for the characterization of metal-containing nanoparticles.
•Amperometric sensor for detection of H2O2 released by living cells (human THP-1 macrophages) was developed.•H2O2 diffuses through cell membrane and can be checked in the extracellular ...space.•Macrophages highly provide Reactive Oxygen Species generation in inflamed tissues.•Macrophages were exposed to pro- and anti-oxidant treatments and H2O2 release was measured in conditioned medium.•Results of the electrochemical sensor agree with those obtained by flow cytometry using the same cells.
Increased oxidative burden contributes to the pathogenesis of most inflammatory diseases and is associated with aging and chronic inflammation. Macrophages contribute to the generation of reactive oxygen species (ROS) within inflamed tissues. Currently, ROS generation is measured using fluorescent probes and colorimetric/fluorimetric biochemical assays. Hydrogen peroxide (H2O2) diffuses through the cell membrane and can be monitored in the extracellular space. Herein, we present a sensor for H2O2 detection released by cells in culture supernatants. H2O2 sensing performance was evaluated using chronoamperometric detection. A sensitivity of 0.0641 μA μM−1 cm−2 with a limit of detection of 6.55 μM and excellent selectivity against many interferents was found. H2O2 release was also measured in conditioned medium from human THP-1 macrophages exposed to pro-oxidant and anti-oxidant treatments. The results were compared with those obtained by flow cytometry using the same cells stained with carboxy-H2DCFDA and MitoSOX Red, which detect intracellular ROS and mitochondrial superoxide, respectively. The addition of pro-oxidants lipopolysaccharide (LPS) and nigericin resulted in a significant increase in the cathodic current due to the H2O2 reduction, indicating an increased release of H2O2. The addition of 17-oxo-DHA, which inhibits LPS- and nigericin-dependent responses, decreased the LPS- and nigericin-induced release of H2O2. All the results obtained with the sensor were consistent with those obtained using flow cytometry. The operation of the sensor directly in the cell culture growth medium had no impact on cell viability. The sensor is highly sensitive, fast, and cost effective, and it can potentially be used for real time monitoring of oxidative stress.
Sizing engineered nanoparticles in simple, laboratory systems is now a robust field of science; however, application of available techniques to more complex, natural systems is hindered by numerous ...challenges including low nanoparticle number concentrations, polydispersity from aggregation and/or dissolution, and interference from other incidental particulates. A new emerging technique, single particle inductively coupled plasma-mass spectrometry (spICPMS), has the potential to address many of these analytical challenges when sizing inorganic nanoparticles in environmental matrices. However, to date, there is little beyond the initial feasibility studies that investigates the performance characteristics and validation of spICPMS as a nanoparticle sizing technique. This study compares sizing of four silver nanoparticle dispersions (nominal diameters of 40, 60, 80, and 100 nm) by spICPMS to four established sizing techniques: dynamic light scattering, differential centrifugal sedimentation, nanoparticle tracking analysis, and TEM. Results show that spICPMS is able to size silver nanoparticles, across different sizes and particle number concentrations, with accuracy similar to the other commercially available techniques. Furthermore, a novel approach to evaluating particle coincidence is presented. In addition, spICPMS size measurements were successfully performed on nanoparticles suspended in algal growth media at low concentrations. Overall, while further development of the technique is needed, spICPMS yields important advantages over other techniques when sizing nanoparticles in environmentally relevant media.
Peroxiredoxin 2 (Prx2) is a thiol protein that functions as an antioxidant, regulator of cellular peroxide concentrations, and sensor of redox signals. Its redox cycle is widely accepted to involve ...oxidation by a peroxide and reduction by thioredoxin/thioredoxin reductase. Interactions of Prx2 with other thiols are not well characterized. Here we show that the active site Cys residues of Prx2 form stable mixed disulfides with glutathione (GSH). Glutathionylation was reversed by glutaredoxin 1 (Grx1), and GSH plus Grx1 was able to support the peroxidase activity of Prx2. Prx2 became glutathionylated when its disulfide was incubated with GSH and when the reduced protein was treated with H2O2 and GSH. The latter reaction occurred via the sulfenic acid, which reacted sufficiently rapidly (k = 500 m−1 s−1) for physiological concentrations of GSH to inhibit Prx disulfide formation and protect against hyperoxidation to the sulfinic acid. Glutathionylated Prx2 was detected in erythrocytes from Grx1 knock-out mice after peroxide challenge. We conclude that Prx2 glutathionylation is a favorable reaction that can occur in cells under oxidative stress and may have a role in redox signaling. GSH/Grx1 provide an alternative mechanism to thioredoxin and thioredoxin reductase for Prx2 recycling.
Gravitational-wave observations became commonplace in Advanced LIGO-Virgo's recently concluded third observing run. 56 nonretracted candidates were identified and publicly announced in near real ...time. Gravitational waves from binary neutron star mergers, however, remain of special interest since they can be precursors to high-energy astrophysical phenomena like γ-ray bursts and kilonovae. While late-time electromagnetic emissions provide important information about the astrophysical processes within, the prompt emission along with gravitational waves uniquely reveals the extreme matter and gravity during—and in the seconds following—merger. Rapid communication of source location and properties from the gravitational-wave data is crucial to facilitate multimessenger follow-up of such sources. This is especially enabled if the partner facilities are forewarned via an early warning (pre-merger) alert. Here we describe the commissioning and performance of such a low-latency infrastructure within LIGO-Virgo. We present results from an end-to-end mock data challenge that detects binary neutron star mergers and alerts partner facilities before merger. We set expectations for these alerts in future observing runs.
Background.
Breast cancer incidence is increasing in low‐ and middle‐income countries (LMICs). Mortality/incidence ratios in LMICs are higher than in high‐income countries, likely at least in part ...because of delayed diagnoses leading to advanced‐stage presentations. In the present study, we investigated the magnitude, impact of, and risk factors for, patient and system delays in breast cancer diagnosis in Rwanda.
Materials and Methods.
We interviewed patients with breast complaints at two rural Rwandan hospitals providing cancer care and reviewed their medical records to determine the diagnosis, diagnosis date, and breast cancer stage.
Results.
A total of 144 patients were included in our analysis. Median total delay was 15 months, and median patient and system delays were both 5 months. In multivariate analyses, patient and system delays of ≥6 months were significantly associated with more advanced‐stage disease. Adjusting for other social, demographic, and clinical characteristics, a low level of education and seeing a traditional healer first were significantly associated with a longer patient delay. Having made ≥5 health facility visits before the diagnosis was significantly associated with a longer system delay. However, being from the same district as one of the two hospitals was associated with a decreased likelihood of system delay.
Conclusion.
Patients with breast cancer in Rwanda experience long patient and system delays before diagnosis; these delays increase the likelihood of more advanced‐stage presentations. Educating communities and healthcare providers about breast cancer and facilitating expedited referrals could potentially reduce delays and hence mortality from breast cancer in Rwanda and similar settings.
Implications for Practice:
Breast cancer rates are increasing in low‐ and middle‐income countries, and case fatality rates are high, in part because of delayed diagnosis and treatment. This study examined the delays experienced by patients with breast cancer at two rural Rwandan cancer facilities. Both patient delays (the interval between symptom development and the patient's first presentation to a healthcare provider) and system delays (the interval between the first presentation and diagnosis) were long. The total delays were the longest reported in published studies. Longer delays were associated with more advanced‐stage disease. These findings suggest that an opportunity exists to reduce breast cancer mortality in Rwanda by addressing barriers in the community and healthcare system to promote earlier detection.
Breast cancer rates are increasing in low‐ and middle‐income countries, with high case fatality rates, in part because of delayed diagnosis and treatment. The delays experienced by patients with breast cancer at two rural Rwandan cancer facilities were investigated. Longer delays were associated with more advanced‐stage disease. An opportunity exists to reduce breast cancer mortality in Rwanda by addressing barriers in the community and healthcare system to promote earlier detection.
Regulation of growth factor signaling involves reversible inactivation of protein tyrosine phosphatases (PTPs) through the oxidation and reduction of their active site cysteine. However, there is ...limited mechanistic understanding of these redox events and their co-ordination in the presence of cellular antioxidant networks. Here we investigated interactions between PTP1B and the peroxiredoxin 2 (Prx2)/thioredoxin 1 (Trx1)/thioredoxin reductase 1 (TrxR1) network. We found that Prx2 becomes oxidized in PDGF-treated fibroblasts, but only when TrxR1 has first been inhibited. Using purified proteins, we also found that PTP1B is relatively insensitive to inactivation by H2O2 but found no evidence for a relay mechanism in which Prx2 or Trx1 facilitates PTP1B oxidation. Instead, these proteins prevented PTP1B inactivation by H2O2. Intriguingly, we discovered that TrxR1/NADPH directly protects PTP1B from inactivation when present during the H2O2 exposure. This protection was dependent on the concentration of TrxR1 and independent of Trx1 and Prx2. The protection was blocked by auranofin and required an intact selenocysteine residue in TrxR1. This activity likely involves reduction of the sulfenic acid intermediate form of PTP1B by TrxR1 and is therefore distinct from the previously described reactivation of end-point oxidized PTP1B, which requires both Trx1 and TrxR1. The ability of TrxR1 to directly reduce an oxidized phosphatase is a novel activity that can help explain previously observed increases in PTP1B oxidation and PDGF receptor phosphorylation in TrxR1 knockout cells. The activity of TrxR1 is therefore of potential relevance for understanding the mechanisms of redox regulation of growth factor signaling pathways.
The addition of long-acting beta2-agonists (LABAs) to corticosteroids improves asthma control. Cigarette smoke exposure, increasing oxidative stress, may negatively affect corticosteroid responses. ...The anti-inflammatory effects of formoterol (FO) and fluticasone propionate (FP) in human bronchial epithelial cells exposed to cigarette smoke extracts (CSE) are unknown.
This study explored whether FP, alone and in combination with FO, in human bronchial epithelial cellline (16-HBE) and primary bronchial epithelial cells (NHBE), counteracted some CSE-mediated effects and in particular some of the molecular mechanisms of corticosteroid resistance.
16-HBE and NHBE were stimulated with CSE, FP and FO alone or combined. HDAC3 and HDAC2 activity, nuclear translocation of GR and NF-κB, pERK1/2/tERK1/2 ratio, IL-8, TNF-α, IL-1β mRNA expression, and mitochondrial ROS were evaluated. Actin reorganization in neutrophils was assessed by fluorescence microscopy using the phalloidin method.
In 16-HBE, CSE decreased expression/activity of HDAC3, activity of HDAC2, nuclear translocation of GR and increased nuclear NF-κB expression, pERK 1/2/tERK1/2 ratio, and mRNA expression of inflammatory cytokines. In NHBE, CSE increased mRNA expression of inflammatory cytokines and supernatants from CSE exposed NHBE increased actin reorganization in neutrophils. FP combined with FO reverted all these phenomena in CSE stimulated 16-HBE cells as well as in NHBE cells.
The present study provides compelling evidences that FP combined with FO may contribute to revert some processes related to steroid resistance induced by oxidative stress due to cigarette smoke exposure increasing the anti-inflammatory effects of FP.
•Cigarette smoke negatively affects corticosteroid responses.•Airway epithelium is a primary target of the anti-inflammatory actions of glucocorticosteroids.•Formoterol enhances the effects of Fluticasone Propionate and in this way counteracts some events related to steroid resistance induced by cigarette smoke.
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