The Tianlai Cylinder Pathfinder array: System functions and basic performance analysis

The Tianlai Cylinder Pathfinder is a radio interferometer array designed to test techniques for 21 cm intensity mapping in the post-reionization Universe, with the ultimate aim of mapping the large scale structure and measuring cosmological parameters such as the dark energy equation of state. Each of its three parallel cylinder reflectors is oriented in the north-south direction, and the array has a large field of view. As the Earth rotates, the northern sky is observed by drift scanning. The array is located in Hongliuxia, a radio-quiet site in Xinjiang, and saw its first light in September 2016. In this first data analysis paper for the Tianlai cylinder array, we discuss the sub-system qualification tests, and present basic system performance obtained from preliminary analysis of the commissioning observations during 2016-2018. We show typical interferometric visibility data, from which we derive the actual beam profile in the east-west direction and the frequency band-pass response. We describe also the calibration process to determine the complex gains for the array elements, either using bright astronomical point sources, or an artificial on site calibrator source, and discuss the instrument response stability, crucial for transit interferometry. Based on this analysis, we find a system temperature of about 90 K, and we also estimate the sensitivity of the array

Dissecting a central flip-flop circuit that integrates contradictory sensory cues in C. elegans feeding regulation

Feeding behaviour is modulated by both environmental cues and internal physiological states. Appetite is commonly boosted by the pleasant smell (or appearance) of food and destroyed by a bad taste. In reality, animals sense multiple environmental cues at the same time and it is not clear how these sensory inputs are integrated and a decision is made to regulate feeding behaviour accordingly. Here we show that feeding behaviour in Caenorhabditis elegans can be either facilitated by attractive odours or suppressed by repellents. By identifying mutants that are defective for sensory-mediated feeding regulation, we dissected a central flip-flop circuit that integrates two contradictory sensory inputs and generates bistable hormone output to regulate feeding behaviour. As feeding regulation is fundamental to animal survival, we speculate that the basic organizational logic identified here in C. elegans is likely convergent throughout different phyla

Novel 4‑Arylindolines Containing a Pyrido[3,2‑<i>d</i>]pyrimidine Moiety as the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction Inhibitors for Tumor Immunotherapy

A series of pyrido[3,2-d]pyrimidine-containing 4-arylindolines were identified as potent inhibitors of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction by structural optimization of a 4-arylindoline precursor reported previously. Among them, compound N11 was the most promising inhibitor, showing an IC50 value of 6.3 nM against the PD-1/PD-L1 interaction at the biochemical level. In in vitro T-cell tumor co-culture models, N11 significantly promoted T-cell proliferation, activation, and infiltration into tumor spheres, demonstrating that it possessed excellent immunomodulatory activity. In addition, N11 exhibited favorable in vivo antitumor activity in an LLC/PD-L1 tumor-bearing mouse model. Flow cytometry analysis verified that the in vivo antitumor efficacy of N11 was dependent on the activation of the immune microenvironment. These findings suggest that N11 can serve as a new starting point for the future development of small-molecule antitumor immunomodulators targeting the PD-1/PD-L1 axis

Novel 4‑Arylindolines Containing a Pyrido[3,2‑<i>d</i>]pyrimidine Moiety as the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction Inhibitors for Tumor Immunotherapy

A series of pyrido[3,2-d]pyrimidine-containing 4-arylindolines were identified as potent inhibitors of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction by structural optimization of a 4-arylindoline precursor reported previously. Among them, compound N11 was the most promising inhibitor, showing an IC50 value of 6.3 nM against the PD-1/PD-L1 interaction at the biochemical level. In in vitro T-cell tumor co-culture models, N11 significantly promoted T-cell proliferation, activation, and infiltration into tumor spheres, demonstrating that it possessed excellent immunomodulatory activity. In addition, N11 exhibited favorable in vivo antitumor activity in an LLC/PD-L1 tumor-bearing mouse model. Flow cytometry analysis verified that the in vivo antitumor efficacy of N11 was dependent on the activation of the immune microenvironment. These findings suggest that N11 can serve as a new starting point for the future development of small-molecule antitumor immunomodulators targeting the PD-1/PD-L1 axis

Docosahexaenoic Acid Enhances Segregation of Lipids between Raft and Nonraft Domains: 2H-NMR Study

Solid-state 2H-NMR of [2H31]-N-palmitoylsphingomyelin ([2H31]16:0SM, PSM*), supplemented by differential scanning calorimetry, was used for the first time, to our knowledge, to investigate the molecular organization of the sphingolipid in 1:1:1 mol mixtures with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (16:0–18:1PE, POPE) or 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine (16:0–22:6PE, PDPE) and cholesterol. When compared with 2H-NMR data for analogous mixtures of [2H31]16:0–18:1PE (POPE*) or [2H31]16:0-22:6PE (PDPE*) with egg SM and cholesterol, molecular interactions of oleic acid (OA) versus docosahexaenoic acid (DHA) are distinguished, and details of membrane architecture emerge. SM-rich, characterized by higher-order, and PE-rich, characterized by lower-order, domains <20 nm in size are formed in the absence and presence of cholesterol in both OA- and DHA-containing membranes. Although acyl chain order within both domains increases on the addition of sterol to the two systems, the resultant differential in order between SM- and PE-rich domains is almost a factor of 3 greater with DHA than with OA. Our interpretation is that the aversion that cholesterol has for DHA—but not for OA—excludes the sterol from DHA-containing, PE-rich (nonraft) domains and excludes DHA from SM-rich/cholesterol-rich (raft) domains. We attribute, in part, the diverse health benefits associated with dietary consumption of DHA to an alteration in membrane domains

The Tianlai dish pathfinder array: design, operation, and performance of a prototype transit radio interferometer

International audienceThe Tianlai Dish Pathfinder Array is a radio interferometer designed to test techniques for 21 cm intensity mapping in the post-reionization universe as a means for measuring large-scale cosmic structure. It performs drift scans of the sky at constant declination. We describe the design, calibration, noise level, and stability of this instrument based on the analysis of about 5% of 6200 h of on-sky observations through 2019 October. Beam pattern determinations using drones and the transit of bright sources are in good agreement, and compatible with electromagnetic simulations. Combining all the baselines, we make maps around bright sources and show that the array behaves as expected. A few hundred hours of observations at different declinations have been used to study the array geometry and pointing imperfections, as well as the instrument noise behaviour. We show that the system temperature is below 80 K for most feed antennas and that noise fluctuations decrease as expected with integration time, at least up to a few hundred seconds. Analysis of long integrations, from 10 nights of observations of the North Celestial Pole (NCP), yielded visibilities with amplitudes of 20–30 mK, consistent with the expected signal from the NCP radio sky with |${\lt}10\,$| mK precision for 1 MHz × 1 min binning. Hi-pass filtering the spectra to remove smooth spectrum signal yields a residual consistent with zero signal at the |$0.5\,$| mK level