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Urinary proteomics studies have identified some candidate biomarkers for respiratory system disease, such as lung cancer 18, pulmonary fibrosis and tuberculosis 19, 20. In addition to the urinary system, urine can sensitively reflect changes in various systems throughout the body, such as cardiovascular system disease, gastrointestinal system disease, nervous system disease, and respiratory system disease 16, 17. Urine, as an attractive resource for biomarker research, can be collected noninvasively and continuously, which has attracted increasing attention. However, currently available biomarkers continue to lack sufficient validity to be incorporated into clinical practice for either the diagnosis or the prognosis of VILI. Despite the difficulties in identifying robust biomarkers, proteomics studies have identified important pathways in VILI, including endothelium injury and activation, epithelial injury, oxidative stress, inflammation, disordered repair of fibrosis and apoptosis 14, 15. Conversely, several proteomic analyses have assessed bronchoalveolar lavage fluid (BAL) fluid, which may be more relevant to lung pathology 12, 13 but are much more invasive and relatively harder to obtain. However, due to its high complexity and large dynamic range, performing proteomics assays with plasma is challenging. Proteomics studies of VILI biomarkers have overwhelmingly focused on serum/plasma, which is relatively easily obtained 10, 11. Mass-spectrometry-based proteomics has dramatically improved and emerged as a prominent tool in the field of biomarker studies. Therefore, it is of high importance to identify new biomarkers, therapeutic targets and pharmacological agents for VILI to decrease the morbidity and mortality associated with VILI. The mortality of patients with severe ARDS is 20% to 40%, and patients who survive are at high risk for cognitive decline, depression, posttraumatic stress disorder, and persistent skeletal muscle weakness 8, 9. In addition, 23% of all mechanically ventilated patients develop ARDS. All mechanically ventilated patients are at risk for VILI, especially when there're pathological changes in the lungs, such as acute respiratory distress syndrome (ARDS) 6, 7. However, mechanical ventilation may cause lung injury, called ventilator-induced lung injury (VILI) 3, 4, 5. Mechanical ventilation is an indispensable component of advanced life support strategies, especially for patients suffering from respiratory failure (from neonatal to adult patients) 1, 2. These differential proteins are potential urinary biomarkers for the activity of VILI. Our results suggest that the urinary proteome might reflect the pathophysiological changes associated with VILI. SLC31, MEP1A, S15A2, NHRF1, XPP2, GGT1, HEXA, and ATPB were newly discovered in this study. Among these PRM-validated proteins, AMPN, MEP1B, LYSC1, DPP4 and CYC were previously reported as lung-associated disease biomarkers. Finally, thirteen proteins were identified as candidate biomarkers for VILI by PRM validation. ![]() The canonical pathways and protein–protein interaction analyses revealed that the differentially expressed proteins were enriched in multiple functions, including oxidative stress and inflammatory responses. Compared to the control group, 110 proteins (65 upregulated, 45 downregulated) were significantly changed in the VILI group (1.5-fold change, P < 0.05). In total, 727 high-confidence proteins were identified with at least 1 unique peptide (FDR ≤ 1%). For further validation, the differential proteins were verified by parallel reaction monitoring (PRM)-targeted quantitative proteomics. In the discovery phase, a label-free data-dependent acquisition (DDA) quantitative proteomics method was used to profile the urinary proteomes of VILI rats. Therefore, the purpose of this study was to investigate potential urinary biomarkers to monitor the disease activity of ventilator-induced lung injury (VILI). Urine is a promising resource for biomarker research. ![]() ![]() ![]() The guitar amps and bass amps are the absolute best to date. ( The SSL 9000 J was added in April 2020) I’m talking about SSL 4000 E and G, a couple awesome Neve consoles, and the rare Focusrite Studio Console. The MEGA Bundle includes the best channel strips based on legendary desks that I have ever heard. This means when you put it across all your tracks it will probably sound good, but it won’t be like using a real desk, because you are essentially running all your tracks though only ONE modeled channel.īut, with TMT, you can use different modeled channels on each track and when they are combined together…. In many modeled plugins, like an SSL Console model, only one channel is modeled. This is because there is a TOLERANCE when manufacturing each component that goes into an EQ or Compressor for example.Īnd it’s exactly these tiny, tiny differences that give you a true “analog sound” (along with proper modeling of course). If you take an SSL 4000 E console for example, each channel will have parts that are slightly (and I do mean slightly) different from each other. What is TMT? Simply put, it’s the thing most other plugins that model hardware are missing! Plus, many of the plugins include something called TMT, or Tolerance Modeling Technology. Many of the included plugins are modeled after hardware that costs $5,000, $7,000, and even $10,000 or more per unit! With the MEGA Bundle you are getting EQs, compressors, limiters, guitar amps, bass amps, stomps pedals, classic consoles, synths, delays, reverb, fx, and so much more. Watch the video at the bottom of the page to see ALL of the included plugins in a single video. This number will increase over time, so be sure to check the Plugin Alliance website for the currently included plugins. This is the BEST subscription plan currently available when you consider all you get, the quality of the plugins, and the price of the hardware units you would need to re-create the same professional, high-quality sound.Īs of May 22, 2020, there are 117 products included with the MEGA Bundle. Yeah, that’s right, it’s almost like getting PAID to use some of the BEST plugins out there.īottom line: there are simply NO better plugin subscription plans available today. You also get a $249 voucher when you purchase the YEARLY MEGA Bundle, or subscribe for a straight 12 months with the MONTHLY MEGA Bundle! With the purchased version, you get what you get. Though, it makes more sense to subscribe since you will get new plugins added to the bundle over time. You can also purchase the full V1 MEGA Bundle outright for a shocking $7000! ![]() The MEGA Bundle is a yearly or monthly subscription. We have a full run down of cost per plugin here. I don’t want to push a subscription on anyone, but you really need to do the math to see what it actually costs per plugin, per day, and then figure out if having access to all of these tools would provide more value than the cost. I know, we all HATE subscriptions for our creative tools, but this is one that actually delivers VALUE with over a hundred amazing tools that actually sound good and make your mixes better. 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