Doubly Robust Distributionally Robust Off-Policy Evaluation and Learning

Off-policy evaluation and learning (OPE/L) use offline observational data to make better decisions, which is crucial in applications where online experimentation is limited. However, depending entirely on logged data, OPE/L is sensitive to environment distribution shifts -- discrepancies between the data-generating environment and that where policies are deployed. \citet{si2020distributional} proposed distributionally robust OPE/L (DROPE/L) to address this, but the proposal relies on inverse-propensity weighting, whose estimation error and regret will deteriorate if propensities are nonparametrically estimated and whose variance is suboptimal even if not. For standard, non-robust, OPE/L, this is solved by doubly robust (DR) methods, but they do not naturally extend to the more complex DROPE/L, which involves a worst-case expectation. In this paper, we propose the first DR algorithms for DROPE/L with KL-divergence uncertainty sets. For evaluation, we propose Localized Doubly Robust DROPE (LDR$^2$OPE) and show that it achieves semiparametric efficiency under weak product rates conditions. Thanks to a localization technique, LDR$^2$OPE only requires fitting a small number of regressions, just like DR methods for standard OPE. For learning, we propose Continuum Doubly Robust DROPL (CDR$^2$OPL) and show that, under a product rate condition involving a continuum of regressions, it enjoys a fast regret rate of $\mathcal{O}\left(N^{-1/2}\right)$ even when unknown propensities are nonparametrically estimated. We empirically validate our algorithms in simulations and further extend our results to general $f$-divergence uncertainty sets.Comment: Short Talk at ICML 202

Point Cluster Analysis Using a 3D Voronoi Diagram with Applications in Point Cloud Segmentation

Three-dimensional (3D) point analysis and visualization is one of the most effective methods of point cluster detection and segmentation in geospatial datasets. However, serious scattering and clotting characteristics interfere with the visual detection of 3D point clusters. To overcome this problem, this study proposes the use of 3D Voronoi diagrams to analyze and visualize 3D points instead of the original data item. The proposed algorithm computes the cluster of 3D points by applying a set of 3D Voronoi cells to describe and quantify 3D points. The decompositions of point cloud of 3D models are guided by the 3D Voronoi cell parameters. The parameter values are mapped from the Voronoi cells to 3D points to show the spatial pattern and relationships; thus, a 3D point cluster pattern can be highlighted and easily recognized. To capture different cluster patterns, continuous progressive clusters and segmentations are tested. The 3D spatial relationship is shown to facilitate cluster detection. Furthermore, the generated segmentations of real 3D data cases are exploited to demonstrate the feasibility of our approach in detecting different spatial clusters for continuous point cloud segmentation

Vegetation Monitoring of Protected Areas in Rugged Mountains Using an Improved Shadow-Eliminated Vegetation Index (SEVI)

It is significant to study the vegetation of protected areas in rugged mountains where the vegetation grows naturally with minimal eco-society environmental stress from anthropogenic activities. The shadow-eliminated vegetation index (SEVI) was used to monitor the vegetation of protected areas, since it successfully removes topographic shadow effects. In order to auto achieve the best adjustment factor for SEVI calculation from regional area images, we developed a new calculation algorithm using block information entropy (BIE-algorithm). The BIE-algorithm auto-detected typical blocks (subareas) from slope images and achieved the best adjustment factor from a block where the SEVI obtained the highest information entropy in an entire scene. Our obtained regional SEVI result from two scenes of Landsat 8 OLI images using the BIE-algorithm exhibited an overall flat feature with the impression of the relief being drastically removed. It achieved balanced values among three types of samples: Sunny area, self-shadow, and cast shadow, with SEVI means of 0.73, 0.77, and 0.75, respectively, and the corresponding SEVI relative errors of self-shadow and cast shadow were only 4.99% and 1.84%, respectively. The linear regression of SEVI vs. the cosine of the solar incidence angle was nearly horizontal, with an inclination of −0.0207 and a coefficient of determination of 0.0042. The regional SEVI revealed that the vegetation growth level sequence of three protected areas was Wuyishan National Park (SEVI mean of 0.718) > Meihuashan National Nature Reserve (0.672) > Minjiangyuan National Nature Reserve (0.624) > regional background (0.572). The vegetation growth in the protected areas was influenced by the terrain slope and years of establishment of the protected area and by the surrounding buffer zone. The homogeneous distribution of vegetation in a block is influenced by many factors, such as the actual vegetation types, block size, and shape, which need consideration when the proposed BIE-algorithm is used

Repeated Non-Invasive Limb Ischemic Preconditioning Confers Cardioprotection Through PKC-Ԑ/STAT3 Signaling in Diabetic Rats

Background/Aims: Protein kinase C(PKC)-ε activation is a mechanism of preconditioning cardioprotection but its role in repeated non-invasive limb ischemic preconditioning (rNLIP) mediated cardioprotection against myocardial ischemia/reperfusion (I/R) injury in diabetes is unknown. Methods: Eight-week streptozotocin-induced diabetic and non-diabetic Sprague-Dawley rats were subjected to I/R without or with rNLIP. In vitro, H9C2 cells were cultured with high glucose (HG) and subjected to hypoxia/re-oxygenation (H/R) without or with PKC-ε or STAT3 gene knock-down in the absence or presence of remote time hypoxia preconditioning (HPC). Results: Diabetic rats displayed larger post-ischemic myocardial infarct size and higher troponin-I release with concomitant cardiac PKC-ԑ overexpression and activation manifested as increased membrane translocation, while phosphorylated STAT3 (p-STAT3) and Akt (p-Akt) were lower compared to non-diabetic rats (all P<0.05). rNLIP reduced infarct size in both non-diabetic and diabetic rats. rNLIP reduced post-ischemic cardiac PKC-ԑ activation in diabetic while increased PKC-ԑ activation in non-diabetic rats, resulting in increased cardiac p-STAT3 and p-Akt. In H9C2 cells, HG increased PKC-ԑ expression and exacerbated post-H/R injury, accompanied with reduced p-STAT3 and p-Akt, which were all reverted by HPC. These HPC protective effects were abolished by either PKC-ԑ or STAT3 gene knock-down, except that PKC-ԑ gene knock-down reverted HG and H/R-induced reduction of p-STAT3. Conclusion: rNLIP attenuates diabetic heart I/R injury by mitigating HG-induced PKC-ԑ overexpression and, subsequently, activating STAT3

Ischemic postconditioning influences electron transport chain protein turnover in Langendorff-perfused rat hearts

Ischemia postconditioning (IPo) is a promising strategy in reducing myocardial ischemia reperfusion (I/R) injury (MIRI), but its specific molecular mechanism is incompletely understood. Langendorff-perfused isolated rat hearts were subjected to global I/R and received IPo in the absence or presence of the mitochondrial ATP-sensitive potassium channel (mitoKATP) blocker 5-hydroxydecanoate (5-HD). Myocardial mitochondria were extracted and mitochondrial comparative proteomics was analyzed. IPo significantly reduces post-ischemic myocardial infarction and improved cardiac function in I/R rat hearts, while 5-HD basically cancelled IPo’s myocardial protective effect. Joint application of two-dimensional polyacrylamide gel electrophoresis (2DE) and MALDI-TOF MS identified eight differentially expressed proteins between groups. Expression of cardiac succinate dehydrogenase (ubiquinone) flavoprotein subunit (SDHA) increased more than two-fold after I/R, while IPo led to overexpression of dihydrolipoyl dehydrogenase (DLD), NADH dehydrogenase (ubiquinone) flavoprotein 1 and isoform CRA_b (NDUFV1). When the mitoKATP was blocked, MICOS complex subunit Mic60 (IMMT) and Stress-70 protein (Grp75) were over expressed, while DLDH, ATPase subunit A (ATPA) and rCG44606 were decreased. Seven of the differential proteins belong to electron transport chain (ETC) or metabolism regulating proteins, and five of them were induced by closing mitoKATP in I/R hearts. We thus conclude that IPo’s myocardial protective effect relies on energy homeostasis regulation. DLD, SDHA, NDUFV1, Grp75, ATPA and rCG44606 may contribute to IPo’s cardial protective effect

Cardioprotection from emulsified isoflurane postconditioning is lost in rats with streptozotocin-induced diabetes due to the impairment of Brg1/Nrf2/STAT3 signalling

Abstract Isoflurane postconditioning (IsoPostC) attenuates myocardial ischaemia/reperfusion injury (IRI). Signal transducer and activator of transcription-3 (STAT3) is critical in ischaemic postconditioning cardioprotection, which can be regulated by the Brahma-related gene (Brg1) and nuclear factor-erythroid 2-related factor 2 (Nrf2), although they are both reduced in diabetic hearts. We hypothesized that reduced Brg1/Nrf2 and STAT3 activation may jeopardize IsoPostC-mediated cardioprotection in diabetic hearts. In the present study, Langendorff-perfused, non-diabetic (control) and 8-week-old streptozotocin-induced Type 1 diabetic rat hearts were subjected to 30 min of global ischaemia and 120 min of reperfusion without or with IsoPostC, which was achieved by administering emulsified isoflurane (2.0 %, v/v) in Krebs-Henseleit (KH) solution immediately at the onset of reperfusion for 10 min and switching to KH solution perfusion alone thereafter. Cultured H9C2 cells were exposed to normal glucose (NG, 5.5 mM) or high glucose (HG, 30 mM) and subjected to hypoxia/reoxygenation (HR) in the presence or absence of IsoPostC. Diabetic rats displayed larger post-ischaemic myocardial infarction and more severe haemodynamic dysfunction, associated with increased myocardial oxidative stress and reduced cardiac Brg1, Nrf2 and STAT3 phosphorylation/activation (p-STAT3), compared with controls. These changes were reversed/prevented by IsoPostC in control but not in diabetic rats. In H9C2 cells exposed to NG but not HG, IsoPostC significantly attenuated HR-induced cellular injury and superoxide anion production with increased Brg1, Nrf2 and p-STAT3. These beneficial effects of IsoPostC were abolished by Brg1, Nrf2 or STAT3 gene knockdown. Brg1 or Nrf2 gene knockdown abolished IsoPostC-induced STAT3 activation. N-acetylcysteine restored Brg1, Nrf2 and p-STAT3, and IsoPostC-induced protection in H9C2 cells exposed to HG and HR. In conclusion, IsoPostC confers cardioprotection through Brg1/Nrf2/STAT3 signalling, and impairment of this pathway may be responsible for the loss of IsoPostC cardioprotection in diabetes

Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury

Abstract. Background:. Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown. Methods:. Male Sprague–Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements. Results:. Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R. Conclusion:. PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart

N-acetylcysteine and allopurinol confer synergy in attenuating myocardial ischemia injury via restoring HIF-1α/HO-1 signaling in diabetic rats.

To determine whether or not the antioxidants N-acetylcysteine (NAC) and allopurinol (ALP) confer synergistic cardioprotection against myocardial ischemia/reperfusion (MI/R) injury by stabilizing hypoxia inducible factor 1α (HIF-1α)/heme oxygenase 1 (HO-1) signaling in diabetic myocardium.Control or diabetic [streptozotocin (STZ)-induced] Sprague Dawley rats received vehicle or NAC, ALP or their combination for four weeks starting one week after STZ injection. The animals were then subjected to thirty minutes of coronary artery occlusion followed by two hours reperfusion in the absence or presence of the selective HO-1 inhibitor, tin protoporphyrin-IX (SnPP-IX) or the HIF-1α inhibitor 2-Methoxyestradiol (2ME2). Cardiomyocytes exposed to high glucose were subjected to hypoxia/re-oxygenation in the presence or absence of HIF-1α and HO-1 achieved by gene knock-down with related siRNAs.Myocardial and plasma levels of 15-F2t-isoprostane, an index of oxidative stress, were significantly increased in diabetic rats while cardiac HO-1 protein and activity were reduced; this was accompanied with reduced cardiac protein levels of HIF-1α, and increased post-ischemic myocardial infarct size and cellular injury. NAC and ALP given alone and in particular their combination normalized cardiac levels of HO-1 and HIF-1α protein expression and prevented the increase in 15-F2t-isoprostane, resulting in significantly attenuated post-ischemic myocardial infarction. NAC and ALP also attenuated high glucose-induced post-hypoxic cardiomyocyte death in vitro. However, all the above protective effects of NAC and ALP were cancelled either by inhibition of HO-1 or HIF-1α with SnPP-IX and 2ME2 in vivo or by HO-1 or HIF-1α gene knock-down in vitro.NAC and ALP confer synergistic cardioprotection in diabetes via restoration of cardiac HIF-1α and HO-1 signaling