Foam cell formation from macrophage is a major cause of atherosclerosis. An efficient macrophage-specific promoter is required for the targeting to macrophages. In this study, we develop a macrophage-specific synthetic promoter for the therapeutic application of adiponectin (APN), an antiatherogenic gene. Synthetic promoter-146 (SP146), registered on the NCBI website (http://www.ncbi.nlm.nih.gov/nuccore/DQ107383), was tested for promoter activities in two non-macrophage cell lines (293 T, HeLa) and a macrophage cell line (RAW264.7, bone marrow-derived macrophages). To enforce macrophage specificity, partial elements of p47phox including the PU.1 site with various lengths (-C1, -C2 and -C3) were inserted next to the synthetic promoters. SP146-C1 showed the highest specificity and efficacy in RAW264.7 cells and was selected for development of an APN-carrying macrophage-specific promoter. Green fluorescent protein (GFP)- or APN-expressing lentivirus under SP146-C1 (Lenti-SP-GFP or Lenti-SP-APN, respectively) showed the highest expression efficacy in RAW264.7 cells compared with the non-macrophage cell lines. APN overexpression in RAW264.7 cells successfully inhibited intracellular lipid accumulation, and atherosclerotic lesions and lipid accumulation were significantly reduced by Lenti-SP-APN in ApoE−/− atherosclerosis mice. In conclusion, the synthetic promoter SP146-C1, combined with a p47phox promoter element, was successfully developed to target macrophage, and macrophage-specific introduction of APN under SP146-C1 was shown to ameliorate the atherosclerotic pathology.

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The orange juice pasteurization is associated with enzymatic degradation (primarily pectin‐methylesterase) of soluble pectin. Time‐temperature curves were established to study different pasteurization conditions on enzyme inactivation, for fresh single‐strength orange juice from Florida, containing natural PME enzyme. The orange juice was heated in a DeLaval, model P5‐VRB plate heat exchanger with heating and cooling sections, and a 0.0101 m3 volume holding tube. The temperature in the heat exchanger was controlled by means of a pneumatic proportional controller. The residence time in the holding tube of the heat exchanger was monitored by adjusting the flow rate of the positive feed pump. The calculated holding times to obtain 90% reduction of enzyme activity ranged from 33.27 s at 80C to 17.85 s at 90C.

Our goal is to explore quantitative motor features in critically ill patients with severe brain injury (SBI). We hypothesized that computational decoding of these features would yield information on underlying neurological states and outcomes. Using wearable microsensors placed on all extremities, we recorded a median 24.1 (IQR: 22.8–25.1) hours of high-frequency accelerometry data per patient from a prospective cohort (n = 69) admitted to the ICU with SBI. Models were trained using time-, frequency-, and wavelet-domain features and levels of responsiveness and outcome as labels. The two primary tasks were detection of levels of responsiveness, assessed by motor sub-score of the Glasgow Coma Scale (GCSm), and prediction of functional outcome at discharge, measured with the Glasgow Outcome Scale–Extended (GOSE). Detection models achieved significant (AUC: 0.70 [95% CI: 0.53–0.85]) and consistent (observation windows: 12 min–9 h) discrimination of SBI patients capable of purposeful movement (GCSm > 4). Prediction models accurately discriminated patients of upper moderate disability or better (GOSE > 5) with 2–6 h of observation (AUC: 0.82 [95% CI: 0.75–0.90]). Results suggest that time series analysis of motor activity yields clinically relevant insights on underlying functional states and short-term outcomes in patients with SBI.