We introduce Opacus, a free, open-source PyTorch library for training deep learning models with differential privacy (hosted at opacus.ai). Opacus is designed for simplicity, flexibility, and speed. It provides a simple and user-friendly API, and enables machine learning practitioners to make a training pipeline private by adding as little as two lines to their code. It supports a wide variety of layers, including multi-head attention, convolution, LSTM, and embedding, right out of the box, and it also provides the means for supporting other user-defined layers. Opacus computes batched per-sample gradients, providing better efficiency compared to the traditional "micro batch" approach. In this paper we present Opacus, detail the principles that drove its implementation and unique features, and compare its performance against other frameworks for differential privacy in ML.
Cryptococcal meningoencephalitis (CM) is the major cause of infection-related neurological death, typically seen in immunocompromised patients. However, T cell–driven inflammatory response has been increasingly implicated in lethal central nervous system (CNS) immunopathology in human patients and murine models. Here, we report marked up-regulation of the chemokine receptor CXCR3 axis in human patients and mice with CM. CXCR3 deletion in mice improves survival, diminishes neurological deficits, and limits neuronal damage without suppressing fungal clearance. CD4+ T cell accumulation and TH1 skewing are reduced in the CNS but not spleens of infected CXCR3−/− mice. Adoptive transfer of WT, but not CXCR3−/− CD4+ T cells, into CXCR3−/− mice phenocopies the pathology of infected WT mice. Collectively, we found that CXCR3+CD4+ T cells drive lethal CNS pathology but are not required for fungal clearance during CM. The CXCR3 pathway shows potential as a therapeutic target or for biomarker discovery to limit CNS inflammatory damages.
Cryptococcal meningoencephalitis (CM) causes nearly 200,000 deaths worldwide each year, and survivors frequently develop long-lasting neurological sequelae. The high rate of mortality and neurologic sequelae in CM patients indicate that antifungal therapies alone are often insufficient to control disease progression.
Unhealthy diets are widespread and linked to a number of detrimental clinical outcomes. The current preregistered experiment extended expectancy theory into the study of food intake; specifically, we tested whether a fast-food restaurant affects food expectancies, or the emotions one expects to feel while eating highly processed foods (e.g., pizza) and minimally processed foods (e.g., carrots). Participants ( N = 200, mean age = 18.79 years) entered a simulated fast-food restaurant or a neutral space, completed questionnaires, and engaged in a bogus taste test. The simulated fast-food restaurant increased positive highly processed food expectancies ( d = 0.29). Palatable eating coping motives scores did not moderate the effect; however, this clinically relevant pattern of eating behavior was associated with greater positive highly processed food expectancies. In addition, there was an indirect effect of the fast-food restaurant on ad libitum food intake through positive highly processed food expectancies. Reducing positive highly processed food expectancies may improve diet, which may broadly affect health.
Disseminated cryptococcosis has a nearly 70% mortality, mostly attributed to CNS infection, with lesser-known effects on other organs. Immune protection against Cryptococcus relies on Th1 immunity with M1 polarization, rendering macrophages fungicidal. The importance of M1-upregulated inducible NO synthase (iNOS) has been documented in pulmonary anticryptococcal defenses, whereas its role in disseminated cryptococcosis remains controversial. Here we examined the effect of iNOS deletion in disseminated (i.v.) C. deneoformans 52D infection, comparing wild-type (C57BL/6J) and iNOS−/− mice. iNOS−/− mice had significantly reduced survival and nearly 100-fold increase of the kidney fungal burden, without increases in the lungs, spleen, or brain. Histology revealed extensive lesions and almost complete destruction of the kidney cortical area with a loss of kidney function. The lack of fungal control was not due to a failure to recruit immune cells because iNOS−/− mice had increased kidney leukocytes. iNOS−/− mice also showed no defect in T cell polarization. We conclude that iNOS is critically required for local anticryptococcal defenses in the kidneys, whereas it appears to be dispensable in other organs during disseminated infection. This study exemplifies a unique phenotype of local immune defenses in the kidneys and the organ-specific importance of a single fungicidal pathway.
Accurate and quick determination of DNA concentration is critical for the assembly of synthetic constructs, as well as a multitude of other experiments. We sought to optimize an under-utilized and inexpensive approach for determining DNA concentration: a spotting technique that uses the intercalating dye Ethidium Bromide. This technique does not require specialized equipment such as a spectrophotometer, but instead relies on visualization of dye-DNA complex fluorescence when excited by UV light. We modelled and tested a range of parameters for dye concentration and spot size, finding that 15uL spots with 1.0ug/mL Ethidium Bromide produced the most reliable standard curve. More importantly, we hope that our approach can help other labs optimize this protocol for their own experimental setup. Adoption of this technique may help enable development of iGEM teams in resource limited environments and laboratories which do not or cannot employ a satisfactory method for determining DNA concentration.
Financial Disclosure
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.