Anti-Methadone monoclonal antibody, clone N2800Ne2

In this paper, four antiskidding surface test sections were paved to investigate the long-term skid resistance of the improved dense-graded asphalt concrete in Guangdong Province (GAC) using diabase fine aggregate instead of limestone. Four test sections were tested by the accelerated loading equipment (MLS11, mobile load simulator). The reduction law of the long-term skid resistance of GAC-16 was analyzed based on the accelerated pavement testing results. Prediction models of the GAC-16 skid resistance were also established and verified. The evaluation indexes of the long-term skid resistance of the asphalt pavement were introduced, and the antiskidding durability of different sections was evaluated. Results show that the initial British pendulum number (BPN) and mean texture depth (MTD) of the asphalt pavement cannot completely characterize its long-term skid resistance. With increasing loading cycles, the attenuation law of the BPN and MTD of GAC-16 denotes a fast reduction during the early stage, which gradually stabilizes. The relation between the skid resistance index and accelerated loading cycles was analyzed by nonlinear fitting according to the least-squares-method principle. The attenuation law of the BPN and MTD of GAC-16 with loading cycles was in accordance with the exponential and logarithmic models, respectively. The long-term antiskidding performance of the asphalt pavement could be accurately characterized using a stable BPN, loading cycles while reaching a stable BPN, the initial MTD value, and the MTD reduction rate as the evaluation indexes of the skid resistance of asphalt pavement. Compared with limestone fine aggregate, diabase fine aggregate can improve the long-term skid resistance of the asphalt mixtures.

ABBV-176 is an antibody-drug conjugate composed of the humanized antibody h16f (PR-1594804) conjugated to a highly potent, cytotoxic cross-linking pyrrolobenzodiazepine dimer (PBD; SGD-1882) targeting the prolactin receptor (PRLR), which is overexpressed in several solid tumor types. This phase 1, dose-escalation study (NCT03145909) evaluated the safety, pharmacokinetics, and preliminary activity of ABBV-176 in patients with advanced solid tumors likely to exhibit elevated levels of PRLR. Patients received ABBV-176 once every 3 weeks. Dose escalation was by an exposure-adjusted, continual reassessment method. Dose-limiting toxicities (DLTs) were assessed from the first day of dosing until the next dose of ABBV-176 to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Nineteen patients received ABBV-176 at doses from 2.7-109.35 mu g/kg. Patients enrolled had colorectal cancer (n = 11), breast cancer (n = 6), or adrenocortical carcinoma (n = 2). DLTs occurred in 4 patients and included thrombocytopenia (n = 2; both at 99.9-mu g/kg dose level), neutropenia (n = 2; 78.3-mu g/kg and 99.9-mu g/kg dose levels), and pancytopenia (n = 1; 109.35-mu g/kg dose level). The most common treatment-emergent adverse events related to ABBV-176 were thrombocytopenia, neutropenia, increased aspartate aminotransferase, nausea, fatigue, and pleural effusions. Effusions and edema were common, and timing of onset suggested possible cumulative ABBV-176 toxicity. Tumor expression of PRLR varied among patients enrolled and analyzed. No patient had an objective response. MTD was not formally determined, as identification of a tolerable dose was confounded by late-onset toxicities. ABBV-176 was associated with significant toxicity in this phase 1, dose-escalation study. Although cytopenias were often dose limiting, effusions and edema were also common and had late onset that suggested cumulative toxicity. No responses were observed, although data were available from a small number of patients with variable tumor PRLR expression. This study was terminated after the dosing of 19 patients.