Real-Time PM10 Emission Rates From Paved Roads by Measurement of Concentrations in the Vehicle\u27s Wake Using On-Board Sensors Part 1. SCAMPER Method Characterization

Based on emission factors derived from the AP-42 algorithm, particulate matter from paved roads has been estimated to be a major source of PM10 of geologic origin. This is an empirical formula based on upwind-downwind measurement of PM10 concentrations and is dependent solely on the silt loading of the pavement and the weight of vehicles. A number of upwind-downwind studies conducted in urban areas to validate this algorithm have been generally inconclusive because the PM10 concentration difference between upwind and downwind often is within the measurement uncertainty. In the approach presented here PM10 concentrations were measured directly behind a moving vehicle in order to improve the measurement sensitivity for estimating the emission rates for vehicles on paved roads. Optical sensors were used to measure PM10 concentrations with a time resolution of approximately 10 s. Sensors were mounted in the front of the vehicle and behind it in the well-mixed wake. A special inlet probe was designed to allow isokinetic sampling under varying speed conditions. As a first approximation the emission rate was calculated by multiplying the PM10 concentration difference between the front and rear of a moving vehicle by the frontal area of the vehicle. This technique is also useful for quickly surveying large areas and for investigating hot spots on roadways caused by greater than normal deposition of PM10 forming debris. The method is designated as SCAMPER: System for the Continuous Aerosol Measurement of Particulate Emissions from Roads. Part I describes SCAMPER development and Part II describes a comprehensive field testing of mobile methods

CMTM6 shapes antitumor T cell response through modulating protein expression of CD58 and PD-L1

The dysregulated expression of immune checkpoint molecules enables cancer cells to evade immune destruction. While blockade of inhibitory immune checkpoints like PD-L1 forms the basis of current cancer immunotherapies, a deficiency in costimulatory signals can render these therapies futile. CD58, a costimulatory ligand, plays a crucial role in antitumor immune responses, but the mechanisms controlling its expression remain unclear. Using two systematic approaches, we reveal that CMTM6 positively regulates CD58 expression. Notably, CMTM6 interacts with both CD58 and PD-L1, maintaining the expression of these two immune checkpoint ligands with opposing functions. Functionally, the presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and response to PD-L1-PD-1 blockade. Collectively, these findings provide fundamental insights into CD58 regulation, uncover a shared regulator of stimulatory and inhibitory immune checkpoints, and highlight the importance of tumor-intrinsic CMTM6 and CD58 expression in antitumor immune responses

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

SCAMPER Monitoring Platform to Measure PM10 Emission Rates from Unpaved Roads in Real-Time

The SCAMPER method for measuring PM10 emission rates from roadways was used to evaluate mitigation methods for public unpaved roads and a treated mine haul road. The SCAMPER method uses a small trailer to measure PM10 concentrations behind a vehicle at a point that is representative of the mean PM10 concentration in the vehicle’s wake. This concentration multiplied by the frontal area has been shown to be a reasonable estimate of the emission rate in units of grams per meter traveled. On public roads it was towed by a 2006 Ford Expedition and on a mine haul road it was towed behind both the Expedition and an earth mover weighing over 150 tons fully loaded. Since the SCAMPER is capable of measuring emission rates on both paved and unpaved roadways, a direct comparison of the effectiveness of mitigation methods with respect to a similar paved road was possible