Making the Case: Philanthropys Role in the Movement to Reimagine Criminal Justice

Bridgespan's experience and relationships working with institutional foundations and philanthropists created an opportunity to dive into the common challenges we've heard funders navigate: What role could philanthropy play in movement building in criminal justice reform? How might mindset and practice need to shift to enable effective giving to movement?The purpose of this report is to provide guidance for some of those common challenges by offering the perspectives and wisdom of those doing the work. Our research included interviews with more than 40 movement leaders, funders, and others across the ecosystem seeking transformative change of our criminal legal system, as well as a review of literature to understand how social movements can achieve equitable change.Bridgespan recognizes that this research is indebted to the work of many others who have long been thinking about these issues deeply. We hope to contribute to that ongoing conversation and the fight for equity and justice.

ARO-Net: Learning Implicit Fields from Anchored Radial Observations

We introduce anchored radial observations (ARO), a novel shape encoding for learning implicit field representation of 3D shapes that is category-agnostic and generalizable amid significant shape variations. The main idea behind our work is to reason about shapes through partial observations from a set of viewpoints, called anchors. We develop a general and unified shape representation by employing a fixed set of anchors, via Fibonacci sampling, and designing a coordinate-based deep neural network to predict the occupancy value of a query point in space. Differently from prior neural implicit models that use global shape feature, our shape encoder operates on contextual, query-specific features. To predict point occupancy, locally observed shape information from the perspective of the anchors surrounding the input query point are encoded and aggregated through an attention module, before implicit decoding is performed. We demonstrate the quality and generality of our network, coined ARO-Net, on surface reconstruction from sparse point clouds, with tests on novel and unseen object categories, "one-shape" training, and comparisons to state-of-the-art neural and classical methods for reconstruction and tessellation.Comment: Accepted by CVPR 2023. Code: https://github.com/yizhiwang96/ARO-Ne

Increasing a Robust Antigen-Specific Cytotoxic T Lymphocyte Response by FMDV DNA Vaccination with IL-9 Expressing Construct

Various chemokines and cytokines as adjuvants can be used to improve efficacy of DNA vaccination. In this study, we sought to investigate if a DNA construct expressing IL-9 (designed as proV-IL9) as a molecular adjuvant enhance antigen specific immune responses elicited by the pcD-VP1 DNA vaccination. Mice immunized with pcD-VP1 combined with proV-IL9 developed a strong humoral response. In addition, the coinoculation induced significant higher level of antigen-specific cell proliferation and cytotoxic response. This agreed well with higher expression level of IFN-γ and perforin in CD8+ T cells, but not with IL-17 in these T cells. The results indicate that IL-9 induces the development of IFN-γ-producing CD8+ T cells (Tc1), but not the IL-17-producing CD8+ T cells (Tc17). Up-regulated expressions of BCL-2 and BCL-XL were exhibited in these Tc1 cells, suggesting that IL-9 may trigger antiapoptosis mechanism in these cells. Together, these results demonstrated that IL-9 used as molecular adjuvant could enhance the immunogenicity of DNA vaccination, in augmenting humoral and cellular responses and particularly promoting Tc1 activations. Thus, the IL-9 may be utilized as a potent Tc1 adjuvant for DNA vaccines

Chaotic Image Encryption Based on Running-Key Related to Plaintext

In the field of chaotic image encryption, the algorithm based on correlating key with plaintext has become a new developing direction. However, for this kind of algorithm, some shortcomings in resistance to reconstruction attack, efficient utilization of chaotic resource, and reducing dynamical degradation of digital chaos are found. In order to solve these problems and further enhance the security of encryption algorithm, based on disturbance and feedback mechanism, we present a new image encryption scheme. In the running-key generation stage, by successively disturbing chaotic stream with cipher-text, the relation of running-key to plaintext is established, reconstruction attack is avoided, effective use of chaotic resource is guaranteed, and dynamical degradation of digital chaos is minimized. In the image encryption stage, by introducing random-feedback mechanism, the difficulty of breaking this scheme is increased. Comparing with the-state-of-the-art algorithms, our scheme exhibits good properties such as large key space, long key period, and extreme sensitivity to the initial key and plaintext. Therefore, it can resist brute-force, reconstruction attack, and differential attack

The Bromodomain and Extra-Terminal Protein Inhibitor OTX015 Suppresses T Helper Cell Proliferation and Differentiation

BACKGROUND: Dynamic epigenetic alterations accompanying CD4+ T helper cell differentiation have been implicated in multiple autoimmune diseases. The bromodomain and extra-terminal (BET) proteins are epigenetic regulators that recognize and bind to acetylated histones in chromatin and are targets for pharmacological inhibition. In this study we tested a new BET inhibitor under clinical development, OTX015, to interrogate its effects on key CD4+ T cell subsets associated with autoimmunity. METHODS: Naïve and memory murine and human CD4+ T cells were isolated and differentiated into populations characterized by the expression of interferon (IFN)-γ and interleukin (IL)-17. Cultured cells were then exposed to varying concentrations of OTX015 in vitro, and its impact on cytokine expression was quantified by flow cytometry. In parallel, the expression of the transcription factors TBX21 and RORC was quantified by PCR. A previously studied BET inhibitor JQ1 was used as a pharmacological control. RESULTS: OTX015 suppressed both murine and human CD4+ T cell proliferation. Its impact on cytokine expression varied in murine and human naïve and memory subsets. OTX015 was similarly effective as JQ1 in the suppression of cytokines and T helper cell proliferation. Higher concentrations of OTX015 also had a greater impact on the viability of murine versus human cells. IL-17 and IFN-γ expression was not altered in murine memory CD4+ T cells, whereas in human memory CD4+ T cells, OTX015 inhibited IL-17, but not IFN-γ. Across all human T cell subsets OTX015 suppressed IL-17 more effectively than IFN-γ. CONCLUSION: Our studies demonstrate that OTX015 has anti-inflammatory effects by suppressing murine and human CD4+ T cell proliferation and subset-dependent proinflammatory cytokine expression, including the selective suppression of IL-17 in human memory CD4+ T cells

SPINN: Synergistic Progressive Inference of Neural Networks over Device and Cloud

Despite the soaring use of convolutional neural networks (CNNs) in mobile applications, uniformly sustaining high-performance inference on mobile has been elusive due to the excessive computational demands of modern CNNs and the increasing diversity of deployed devices. A popular alternative comprises offloading CNN processing to powerful cloud-based servers. Nevertheless, by relying on the cloud to produce outputs, emerging mission-critical and high-mobility applications, such as drone obstacle avoidance or interactive applications, can suffer from the dynamic connectivity conditions and the uncertain availability of the cloud. In this paper, we propose SPINN, a distributed inference system that employs synergistic device-cloud computation together with a progressive inference method to deliver fast and robust CNN inference across diverse settings. The proposed system introduces a novel scheduler that co-optimises the early-exit policy and the CNN splitting at run time, in order to adapt to dynamic conditions and meet user-defined service-level requirements. Quantitative evaluation illustrates that SPINN outperforms its state-of-the-art collaborative inference counterparts by up to 2x in achieved throughput under varying network conditions, reduces the server cost by up to 6.8x and improves accuracy by 20.7% under latency constraints, while providing robust operation under uncertain connectivity conditions and significant energy savings compared to cloud-centric execution.Comment: Accepted at the 26th Annual International Conference on Mobile Computing and Networking (MobiCom), 202

Genome-Wide Analysis of DNA Methylation and Cigarette Smoking in a Chinese Population

Background: Smoking is a risk factor for many human diseases. DNA methylation has been related to smoking, but genome-wide methylation data for smoking in Chinese populations is limited. Objectives: We aimed to investigate epigenome-wide methylation in relation to smoking in a Chinese population. Methods: We measured the methylation levels at > 485,000 CpG sites (CpGs) in DNA from leukocytes using a methylation array and conducted a genome-wide meta-analysis of DNA methylation and smoking in a total of 596 Chinese participants. We further evaluated the associations of smoking-related CpGs with internal polycyclic aromatic hydrocarbon (PAH) biomarkers and their correlations with the expression of corresponding genes. Results: We identified 318 CpGs whose methylation levels were associated with smoking at a genome-wide significance level (false discovery rate < 0.05), among which 161 CpGs annotated to 123 genes were not associated with smoking in recent studies of Europeans and African Americans. Of these smoking-related CpGs, methylation levels at 80 CpGs showed significant correlations with the expression of corresponding genes (including RUNX3, IL6R, PTAFR, ANKRD11, CEP135 and CDH23), and methylation at 15 CpGs was significantly associated with urinary 2-hydroxynaphthalene, the most representative internal monohydroxy-PAH biomarker for smoking. Conclusion: We identified DNA methylation markers associated with smoking in a Chinese population, including some markers that were also correlated with gene expression. Exposure to naphthalene, a byproduct of tobacco smoke, may contribute to smoking-related methylation. Citation: Zhu X, Li J, Deng S, Yu K, Liu X, Deng Q, Sun H, Zhang X, He M, Guo H, Chen W, Yuan J, Zhang B, Kuang D, He X, Bai Y, Han X, Liu B, Li X, Yang L, Jiang H, Zhang Y, Hu J, Cheng L, Luo X, Mei W, Zhou Z, Sun S, Zhang L, Liu C, Guo Y, Zhang Z, Hu FB, Liang L, Wu T. 2016. Genome-wide analysis of DNA methylation and cigarette smoking in Chinese. Environ Health Perspect 124:966–973; http://dx.doi.org/10.1289/ehp.150983

Use of Praziquantel as an Adjuvant Enhances Protection and Tc-17 Responses to Killed H5N1 Virus Vaccine in Mice

BACKGROUND: H5N1 is a highly pathogenic influenza A virus, which can cause severe illness or even death in humans. Although the widely used killed vaccines are able to provide some protection against infection via neutralizing antibodies, cytotoxic T-lymphocyte responses that are thought to eradicate viral infections are lacking. METHODOLOGY/PRINCIPAL FINDINGS: Aiming to promote cytotoxic responses against H5N1 infection, we extended our previous finding that praziquantel (PZQ) can act as an adjuvant to induce IL-17-producing CD8(+) T cells (Tc17). We found that a single immunization of 57BL/6 mice with killed viral vaccine plus PZQ induced antigen-specific Tc17 cells, some of which also secreted IFN-γ. The induced Tc17 had cytolytic activities. Induction of these cells was impaired in CD8 knockout (KO) or IFN-γ KO mice, and was even lower in IL-17 KO mice. Importantly, the inoculation of killed vaccine with PZQ significantly reduced virus loads in the lung tissues and prolonged survival. Protection against H5N1 virus infection was obtained by adoptively transferring PZQ-primed wild type CD8(+) T cells and this was more effective than transfer of activated IFN-γ KO or IL-17 KO CD8(+) T cells. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that adding PZQ to killed H5N1 vaccine could promote broad Tc17-mediated cytotoxic T lymphocyte activity, resulting in improved control of highly pathogenic avian influenza virus infection