Private Model Compression via Knowledge Distillation

The soaring demand for intelligent mobile applications calls for deploying powerful deep neural networks (DNNs) on mobile devices. However, the outstanding performance of DNNs notoriously relies on increasingly complex models, which in turn is associated with an increase in computational expense far surpassing mobile devices' capacity. What is worse, app service providers need to collect and utilize a large volume of users' data, which contain sensitive information, to build the sophisticated DNN models. Directly deploying these models on public mobile devices presents prohibitive privacy risk. To benefit from the on-device deep learning without the capacity and privacy concerns, we design a private model compression framework RONA. Following the knowledge distillation paradigm, we jointly use hint learning, distillation learning, and self learning to train a compact and fast neural network. The knowledge distilled from the cumbersome model is adaptively bounded and carefully perturbed to enforce differential privacy. We further propose an elegant query sample selection method to reduce the number of queries and control the privacy loss. A series of empirical evaluations as well as the implementation on an Android mobile device show that RONA can not only compress cumbersome models efficiently but also provide a strong privacy guarantee. For example, on SVHN, when a meaningful $(9.83,10^{-6})$-differential privacy is guaranteed, the compact model trained by RONA can obtain 20$\times$ compression ratio and 19$\times$ speed-up with merely 0.97% accuracy loss.Comment: Conference version accepted by AAAI'1

Regulatory mechanisms mediated by peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in skin cancer

Considerable progress has been made during the past twenty years towards elucidating the role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in skin cancer. In 1999, the original notion that PPARβ/δ was involved with epithelial cell function was postulated based on a correlation between PPARβ/δ expression and the induction of mRNAs encoding proteins that mediate terminal differentiation in keratinocytes. Subsequent studies definitively revealed that PPARβ/δ could induce terminal differentiation and inhibit proliferation of keratinocytes. Molecular mechanisms have since been discovered to explain how this nuclear receptor can be targeted for preventing and treating skin cancer. This includes the regulation of terminal differentiation, mitotic signaling, endoplasmic reticulum stress, and cellular senescence. Interestingly, the effects of activating PPARβ/δ can preferentially target keratinocytes with genetic mutations associated with skin cancer. This review provides the history and current understanding of how PPARβ/δ can be targeted for both non-melanoma skin cancer and melanoma, and postulates how future approaches that modulate PPARβ/δ signaling may be developed for the prevention and treatment of these diseases

12-h clock regulation of genetic information flow by XBP1s

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Pan, Y., Ballance, H., Meng, H., Gonzalez, N., Kim, S., Abdurehman, L., York, B., Chen, X., Schnytzer, Y., Levy, O., Dacso, C. C., McClung, C. A., O'Malley, B. W., Liu, S., & Zhu, B. 12-h clock regulation of genetic information flow by XBP1s. Plos Biology, 18(1), (2020): e3000580, doi:10.1371/journal.pbio.3000580.Our group recently characterized a cell-autonomous mammalian 12-h clock independent from the circadian clock, but its function and mechanism of regulation remain poorly understood. Here, we show that in mouse liver, transcriptional regulation significantly contributes to the establishment of 12-h rhythms of mRNA expression in a manner dependent on Spliced Form of X-box Binding Protein 1 (XBP1s). Mechanistically, the motif stringency of XBP1s promoter binding sites dictates XBP1s’s ability to drive 12-h rhythms of nascent mRNA transcription at dawn and dusk, which are enriched for basal transcription regulation, mRNA processing and export, ribosome biogenesis, translation initiation, and protein processing/sorting in the Endoplasmic Reticulum (ER)-Golgi in a temporal order consistent with the progressive molecular processing sequence described by the central dogma information flow (CEDIF). We further identified GA-binding proteins (GABPs) as putative novel transcriptional regulators driving 12-h rhythms of gene expression with more diverse phases. These 12-h rhythms of gene expression are cell autonomous and evolutionarily conserved in marine animals possessing a circatidal clock. Our results demonstrate an evolutionarily conserved, intricate network of transcriptional control of the mammalian 12-h clock that mediates diverse biological pathways. We speculate that the 12-h clock is coopted to accommodate elevated gene expression and processing in mammals at the two rush hours, with the particular genes processed at each rush hour regulated by the circadian and/or tissue-specific pathways.This study was supported by the American Diabetes Association junior faculty development award 1-18-JDF-025 to B.Z., by funding from National Institute of Health HD07879 and 1P01DK113954 to B.W.O, by funding from National Science Foundation award 1703170 to C.C.D. and B.Z., and by funding from Brockman Foundation to C.C.D and B.W.O. This work was further supported by the UPMC Genome Center with funding from UPMC’s Immunotherapy and Transplant Center. This research was supported in part by the University of Pittsburgh Center for Research Computing through the resources provided. Research reported in this publication was further supported by the National Institute of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health under award number P30DK120531 to Pittsburgh Liver Research Center, in which both S.L. and B.Z. are members. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Analysis of the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) cistrome reveals novel co-regulatory role of ATF4

Abstract Background The present study coupled expression profiling with chromatin immunoprecipitation sequencing (ChIP-seq) to examine peroxisome proliferator-activated receptor-β/δ (PPARβ/δ)-dependent regulation of gene expression in mouse keratinocytes, a cell type that expresses PPARβ/δ in high concentration. Results Microarray analysis elucidated eight different types of regulation that modulated PPARβ/δ-dependent gene expression of 612 genes ranging from repression or activation without an exogenous ligand, repression or activation with an exogenous ligand, or a combination of these effects. Bioinformatic analysis of ChIP-seq data demonstrated promoter occupancy of PPARβ/δ for some of these genes, and also identified the presence of other transcription factor binding sites in close proximity to PPARβ/δ bound to chromatin. For some types of regulation, ATF4 is required for ligand-dependent induction of PPARβ/δ target genes. Conclusions PPARβ/δ regulates constitutive expression of genes in keratinocytes, thus suggesting the presence of one or more endogenous ligands. The diversity in the types of gene regulation carried out by PPARβ/δ is consistent with dynamic binding and interactions with chromatin and indicates the presence of complex regulatory networks in cells expressing high levels of this nuclear receptor such as keratinocytes. Results from these studies are the first to demonstrate that differences in DNA binding of other transcription factors can directly influence the transcriptional activity of PPARβ/δ.http://deepblue.lib.umich.edu/bitstream/2027.42/112940/1/12864_2012_Article_4648.pd

Assessment of Turning Polytetrafluoroethylene External Cylindrical Groove with Curvilinear Profile Tool

Polytetrafluoroethylene (PTFE) is extensively used in equipment used for manufacturing semiconductor components and wet etching equipment. However, achieving ideal dimensional accuracy when cutting PTFE is challenging. In this study, we performed cutting experiments using a curvilinear tool and analyzed cutting force, cutting temperature, groove width, and surface roughness in PTFE grooving. The results indicated that the cutting force was most notably affected by the feed rate in Stage I of grooving. The rate of change in cutting force was the largest in Stage II because of the increase in the tool contact area. In Stage III, the shear area of the rake face was the largest, and the cutting force tended to be stable. The groove width was measured with a minimum error rate of 0.95% at a feed rate of 0.05 mm/rev. Moreover, the groove exhibited a time—independent springback. The minimum groove surface roughness was 0.586 at a feed rate of 0.05 mm/rev. The ideal feed rate was 0.05 mm/rev with groove width, surface quality, and chip curl as the key parameters. The processing parameters obtained in this study can be applied to actual production for the optimization of manufacturing accuracy

Effects and action mechanisms of individual cytokines contained in PRP on osteoarthritis

Abstract Osteoarthritis (OA) is defined as a degenerative joint disease that can affect all tissues of the joint, including the articular cartilage, subchondral bone, ligaments capsule, and synovial membrane. The conventional nonoperative treatments are ineffective for cartilage repair and induce only symptomatic relief. Platelet-rich plasma (PRP) is a platelet concentrate derived from autologous whole blood with a high concentration of platelets, which can exert anti-inflammatory and regenerative effects by releasing multiple growth factors and cytokines. Recent studies have shown that PRP exhibits clinical benefits in patients with OA. However, high operational and equipment requirements greatly limit the application of PRP to OA treatment. Past studies have indicated that high-concentration PRP growth factors and cytokines may be applied as a commercial replacement for PRP. We reviewed the relevant articles to summarize the feasibility and mechanisms of PRP-based growth factors in OA. The available evidence suggests that transforming growth factor-α and β, platelet-derived growth factors, epidermal growth factor, insulin-like growth factor-1, and connective tissue growth factors might benefit OA, while vascular endothelial growth factor, tumor necrosis factor-α, angiopoietin-1, and stromal cell derived factor-1α might induce negative effects on OA. The effects of fibroblast growth factor, hepatocyte growth factor, platelet factor 4, and keratinocyte growth factor on OA remain uncertain. Thus, it can be concluded that not all cytokines released by PRP are beneficial, although the therapeutic action of PRP has a valuable potential to improve

One-Way Matching of Datasets with Low Rank Signals

We study one-way matching of a pair of datasets with low rank signals. Under a stylized model, we first derive information-theoretic limits of matching. We then show that linear assignment with projected data achieves fast rates of convergence and sometimes even minimax rate optimality for this task. The theoretical error bounds are corroborated by simulated examples. Furthermore, we illustrate practical use of the matching procedure on two single-cell data examples.Comment: 64 pages, 7 figure

Ligand Activation of Peroxisome Proliferator–Activated Receptor-β/δ and Inhibition of Cyclooxygenase-2 Enhances Inhibition of Skin Tumorigenesis

Ligand activation of peroxisome proliferator–activated receptor (PPAR)-β/δ and inhibition of cyclooxygenase-2 (COX-2) activity by nonsteroidal anti-inflammatory drugs can attenuate skin tumorigenesis. There is also evidence that attenuation of skin tumorigenesis by inhibition of COX-2 activity occurs through PPARβ/δ-independent mechanisms. The present study examined the hypothesis that combining ligand activation of PPARβ/δ with inhibition of COX-2 activity will cooperatively inhibit chemically induced skin tumor progression using both in vivo and ex vivo models. A two-stage chemical carcinogenesis bioassay was performed in wild-type and Pparβ/δ-null mice. After 22 weeks, cohorts of both mouse lines were divided into four experimental groups: (1) control, (2) topical application of the PPARβ/δ ligand GW0742, (3) dietary administration of the COX-2 inhibitor nimesulide, or (4) both GW0742 and nimesulide. Ligand activation of PPARβ/δ did not influence skin tumor progression, while a modest decrease in skin tumor multiplicity was observed with dietary nimesulide. Interestingly, the combined treatment of GW0742 and nimesulide increased the efficacy of the decrease in papilloma multiplicity for 6 weeks in wild-type mice, but this effect was not found at later time points and was not found in similarly treated Pparβ/δ-null mice. Neoplastic keratinocyte lines cultured with GW0742 and nimesulide also exhibited enhanced inhibition of cell proliferation coincident with increased expression of Keratin messenger RNAs. Results from these studies support the hypothesis that combining ligand activation of PPARβ/δ with inhibition of COX-2 activity can inhibit chemically induced skin tumor progression by modulating differentiation