The programmed cell death protein 1 receptor (PD-1) and programmed death ligand 1 (PD-L1) coinhibitory pathway suppresses T-cell–mediated immunity. We hypothesized that cotargeting of PD-1 and PD-L1 with a bispecific antibody molecule could provide an alternative therapeutic approach, with enhanced antitumor activity, compared with monospecific PD-1 and PD-L1 antibodies. Here, we describe LY3434172, a bispecific IgG1 mAb with ablated Fc immune effector function that targets both human PD-1 and PD-L1. LY3434172 fully inhibited the major inhibitory receptor–ligand interactions in the PD-1 pathway. LY3434172 enhanced functional activation of T cells in vitro compared with the parent anti–PD-1 and anti–PD-L1 antibody combination or respective monotherapies. In mouse tumor models reconstituted with human immune cells, LY3434172 therapy induced dramatic and potent antitumor activity compared with each parent antibody or their combination. Collectively, these results demonstrated the enhanced immunomodulatory (immune blockade) properties of LY3434172, which improved antitumor immune response in preclinical studies, thus supporting its evaluation as a novel bispecific cancer immunotherapy.

SPE/IADC Members Abstract We review the conflicting literature on gas migration velocities during kicks. We consider the laboratory and large scale test data that shows that for any local gas void fraction of more than 10%, the influx migrates at approximately 100 ft/min. We also review the evidence from field experience that shows that gas can migrate much more slowly (the typical rule of thumb suggests that gas bubbles move at approximately 15 ft/min) and in some cases remain stationary. We show that the yield stress of the drilling mud which holds cuttings in suspension whilst making connections, can also hold gas bubbles in suspension, and report an experimental study of these gas suspension effects. Significant volumes of gas can be held in suspension during a gas kick, this trapped gas remaining stationary until the mud is circulated out of the well. We consider the implications of this for well control operations, and present field data where gas was injected into a marine riser, it dispersed and remained stationary until circulated out. We show that a single bubble migration model, which neglects gas suspension, predicts that as the gas rises and expands it unloads the riser. By simulating the gas suspension characteristics we model the field data. We conclude that gas in moderate concentrations (more than 10%) migrates quickly, typically at 100 ft/min. This migrating influx leaves a trail of suspended gas in the mud that remains stationary. For small kicks in deep wells the entire influx can be distributed, at a low concentration, and remain in suspension until the gas-cut mud is circulated out of the well. Gas Migration Velocity - Literature Controversy There is a major controversy in the published literature over gas migration rates during kicks while drilling. Experimental tests in small flow loops and in test wells show the gas migration velocity is around 100 ft/min, while field estimates suggest that gas rises at around 15 ft/min or more slowly. We consider this discrepancy. Johnson and White showed that, in typical drilling geometries, in realistic drilling fluids, for gas concentrations larger than 10%, gas migration velocities were around 100 ft/min, significantly larger than the equivalent migration rates in water. The viscosity of drilling mud hinders the bubble break-up process allowing gas to migrate as bigger bubbles (which travel faster). They also observed that the yield stress of the drilling mud would hold low concentrations of gas in suspension with no migration. Rader et al. reported similar results for gas migration in a 3.7 m, (12 ft) flow loop and a 1800 m (6,000 ft) well. The gas velocity in the well was measured using the time of flight principle. Hovland and Rommetveit reported large scale tests in a 1500 m (5000 ft) deep test well, which had a maximum deviation of 630. They used the time of flight between pressure transducers mounted at different depths in the well to measure a gas slip velocity of 0.55 m/s (110 ft/min). A widely accepted "rule of thumb's used in the field says that gas bubbles migrate at 0.085 m/s, (15 ft/min). Blount claimed that he had evidence of gas migration rates of around 0.014 m/s (3 ft/min), although he did not specify how these were derived. In field situations an accurate estimation of gas migration during a well control incident is very difficult. P. 93

This paper presents a new generalisation of simultaneous localisation and mapping (SLAM). SLAM implementations based on extended Kalman filter (EKF) data fusion have traditionally relied on simple geometric models for defining landmarks. This limits EKF-SLAM to environments suited to such models and tends to discard much potentially useful data. The approach presented in this paper is a marriage of EKF-SLAM with scan correlation. Instead of geometric models, landmarks are defined by templates composed of raw sensed data, and scan correlation is shown to produce landmark observations compatible with the standard EKF-SLAM framework. The resulting Scan-SLAM combines the general applicability of scan correlation with the established advantages of an EKF implementation: recursive data fusion that produces a convergent map of landmarks and maintains an estimate of uncertainties and correlations. Experimental results are presented which validate the algorithm.

No abstract

No abstract