2,107 research outputs found

    MPC for MPC: Secure Computation on a Massively Parallel Computing Architecture

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    Massively Parallel Computation (MPC) is a model of computation widely believed to best capture realistic parallel computing architectures such as large-scale MapReduce and Hadoop clusters. Motivated by the fact that many data analytics tasks performed on these platforms involve sensitive user data, we initiate the theoretical exploration of how to leverage MPC architectures to enable efficient, privacy-preserving computation over massive data. Clearly if a computation task does not lend itself to an efficient implementation on MPC even without security, then we cannot hope to compute it efficiently on MPC with security. We show, on the other hand, that any task that can be efficiently computed on MPC can also be securely computed with comparable efficiency. Specifically, we show the following results: - any MPC algorithm can be compiled to a communication-oblivious counterpart while asymptotically preserving its round and space complexity, where communication-obliviousness ensures that any network intermediary observing the communication patterns learn no information about the secret inputs; - assuming the existence of Fully Homomorphic Encryption with a suitable notion of compactness and other standard cryptographic assumptions, any MPC algorithm can be compiled to a secure counterpart that defends against an adversary who controls not only intermediate network routers but additionally up to 1/3 - ? fraction of machines (for an arbitrarily small constant ?) - moreover, this compilation preserves the round complexity tightly, and preserves the space complexity upto a multiplicative security parameter related blowup. As an initial exploration of this important direction, our work suggests new definitions and proposes novel protocols that blend algorithmic and cryptographic techniques

    Nitrate Anomaly in the Upper Nutricline in the Northern South China Sea - Evidence for Nitrogen Fixation

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    [1] Up to 2 μM of nitrate anomaly, N*, were found in the upper nutricline at the South East Asia Time-series Study (SEATS) site in the northern South China Sea (SCS). These concentrations were among the higher values reported in the Pacific and indicate the significant contribution of the remineralization of nitrogen-rich organic matter formed by nitrogen fixation to the nutrient dynamics of the area. The concentrations were systematically higher, by up to 2.5 μM, in the Fall through the early Spring, during the northeast monsoon, than in the Summer, suggesting that the impact of nitrogen fixation was higher during the former time period. This pattern is in phase with that of the atmospheric deposition of Asian dust to the northern SCS. The coherence is consistent with a coupling between nitrogen fixation and the availability of atmospherically derived iron

    The Untranslated Regions of Classic Swine Fever Virus RNA Trigger Apoptosis

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    Classical swine fever virus (CSFV) causes a broad range of disease in pigs, from acute symptoms including high fever and hemorrhages, to chronic disease or unapparent infection, depending on the virus strain. CSFV belongs to the genus Pestivirus of the family Flaviviridae. It carries a single-stranded positive-sense RNA genome. An internal ribosomal entry site (IRES) in the 5' untranslated region (UTR) drives the translation of a single open reading frame encoding a 3898 amino acid long polypeptide chain. The open reading frame is followed by a 3' UTR comprising four highly structured stem-loops. In the present study, a synthetic RNA composed of the 5' and 3' UTRs of the CSFV genome devoid of any viral coding sequence and separated by a luciferase gene cassette (designated 5'UTR-Luc-3'UTR) triggered apoptotic cell death as early as 4 h post-transfection. The apoptosis was measured by DNA laddering analysis, TUNEL assay, annexin-V binding determined by flow cytometry, and by analysis of caspase activation. Contrasting with this, only trace DNA laddering was observed in cells transfected with the individual 5' or 3' UTR RNA; even when the 5' UTR and 3' UTR were co-transfected as separate RNA molecules, DNA laddering did not reach the level induced by the chimeric 5'UTR-Luc-3'UTR RNA. Interestingly, RNA composed of the 5'UTR and of stem-loop I of the 3'UTR triggered much stronger apoptosis than the 5' or 3'UTR alone. These results indicate that the 5' and 3' UTRs act together in cis induce apoptosis. We furthered obtained evidence that the UTR-mediated apoptosis required double-stranded RNA and involved translation shutoff possibly through activation of PKR

    Game Theoretic Notions of Fairness in Multi-Party Coin Toss

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    Coin toss has been extensively studied in the cryptography literature, and the well-accepted notion of fairness (henceforth called strong fairness) requires that a corrupt coalition cannot cause non-negligible bias. It is well-understood that two-party coin toss is impossible if one of the parties can prematurely abort; further, this impossibility generalizes to multiple parties with a corrupt majority (even if the adversary is computationally bounded and fail-stop only). Interestingly, the original proposal of (two-party) coin toss protocols by Blum in fact considered a weaker notion of fairness: imagine that the (randomized) transcript of the coin toss protocol defines a winner among the two parties. Now Blum\u27s notion requires that a corrupt party cannot bias the outcome in its favor (but self-sacrificing bias is allowed). Blum showed that this weak notion is indeed attainable for two parties assuming the existence of one-way functions. In this paper, we ask a very natural question which, surprisingly, has been overlooked by the cryptography literature: can we achieve Blum\u27s weak fairness notion in multi-party coin toss? What is particularly interesting is whether this relaxation allows us to circumvent the corrupt majority impossibility that pertains to strong fairness. Even more surprisingly, in answering this question, we realize that it is not even understood how to define weak fairness for multi-party coin toss. We propose several natural notions drawing inspirations from game theory, all of which equate to Blum\u27s notion for the special case of two parties. We show, however, that for multiple parties, these notions vary in strength and lead to different feasibility and infeasibility results

    HDAC8 Inhibition Specifically Targets Inv(16) Acute Myeloid Leukemic Stem Cells by Restoring p53 Acetylation

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    SummaryAcute myeloid leukemia (AML) is driven and sustained by leukemia stem cells (LSCs) with unlimited self-renewal capacity and resistance to chemotherapy. Mutation in the TP53 tumor suppressor is relatively rare in de novo AML; however, p53 can be regulated through post-translational mechanisms. Here, we show that p53 activity is inhibited in inv(16)+ AML LSCs via interactions with the CBFβ-SMMHC (CM) fusion protein and histone deacetylase 8 (HDAC8). HDAC8 aberrantly deacetylates p53 and promotes LSC transformation and maintenance. HDAC8 deficiency or inhibition using HDAC8-selective inhibitors (HDAC8i) effectively restores p53 acetylation and activity. Importantly, HDAC8 inhibition induces apoptosis in inv(16)+ AML CD34+ cells, while sparing the normal hematopoietic stem cells. Furthermore, in vivo HDAC8i administration profoundly diminishes AML propagation and abrogates leukemia-initiating capacity of both murine and patient-derived LSCs. This study elucidates an HDAC8-mediated p53-inactivating mechanism promoting LSC activity and highlights HDAC8 inhibition as a promising approach to selectively target inv(16)+ LSCs

    Mechanistic insight into 3-methylmercaptopropionate metabolism and kinetical regulation of demethylation pathway in marine dimethylsulfoniopropionate-catabolizing bacteria

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    The vast majority of oceanic dimethylsulfoniopropionate (DMSP) is thought to be catabolized by bacteria via the DMSP demethylation pathway. This pathway contains four enzymes termed DmdA, DmdB, DmdC and DmdD/AcuH, which together catabolise DMSP to acetylaldehyde and methanethiol as carbon and sulfur sources, respectively. Whilst molecular mechanisms for DmdA and DmdD have been proposed, little is known of the catalytic mechanisms of DmdB and DmdC, which are central to this pathway. Here we undertake physiological, structural and biochemical analyses to elucidate the catalytic mechanisms of DmdB and DmdC. DmdB, a 3-methylmercaptopropionate (MMPA)-coenzyme A (CoA) ligase, undergoes two sequential conformational changes to catalyze the ligation of MMPA and CoA. DmdC, a MMPA-CoA dehydrogenase, catalyzes the dehydrogenation of MMPA-CoA to generate MTA-CoA with Glu435 as the catalytic base. Sequence alignment suggests that the proposed catalytic mechanisms of DmdB and DmdC are likely widely adopted by bacteria using the DMSP demethylation pathway. Analysis of the substrate affinities of involved enzymes indicates that Roseobacters kinetically regulate the DMSP demethylation pathway to ensure DMSP functioning and catabolism in their cells. Altogether, this study sheds novel lights on the catalytic and regulative mechanisms of bacterial DMSP demethylation, leading to a better understanding of bacterial DMSP catabolism

    Orderly arranged NLO materials on exfoliated layeredtemplates based on dendrons with alternating moietiesat the periphery†

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    Nonlinear optical dendrons with alternating terminal groups of the stearyl group (C18) and chromophorewere prepared through a convergent approach. These chromophore-containing dendrons were used asthe intercalating agents for montmorillonite via an ion-exchange process. An orderly exfoliatedmorphology is obtained by mixing the dendritic structure intercalated layered silicates with a polyimide.As a result, optical nonlinearity, i.e. the Pockels effect was observed for these nanocomposites withoutresorting to the poling process. EO coefficients of 9–22 pm V 1 were achieved despite that relativelylow NLO densities were present in the nanocomposites, particularly for the samples comprising thedendrons with alternating moieties. In addition, the hedging effects of the stearyl group on the selfalignmentbehavior, electro-optical (EO) coefficient and temporal stability of the dendron-intercalatedmontmorillonite/polyimide nanocomposites were also investigated

    NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity

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    HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231) and rat glioma cells (C6), with an IC50 ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21(Waf1/Cip1), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1–4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1, p21(Waf1/Cip1) gene expression had markedly increased while cyclin B1 and D1 gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor gene p53 in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activity in vitro and in vivo

    Obliquity pacing of the western Pacific Intertropical Convergence Zone over the past 282,000 years

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    The Intertropical Convergence Zone (ITCZ) encompasses the heaviest rain belt on the Earth. Few direct long-term records, especially in the Pacific, limit our understanding of long-term natural variability for predicting future ITCZ migration. Here we present a tropical precipitation record from the Southern Hemisphere covering the past 282,000 years, inferred from a marine sedimentary sequence collected off the eastern coast of Papua New Guinea. Unlike the precession paradigm expressed in its East Asian counterpart, our record shows that the western Pacific ITCZ migration was influenced by combined precession and obliquity changes. The obliquity forcing could be primarily delivered by a cross-hemispherical thermal/pressure contrast, resulting from the asymmetric continental configuration between Asia and Australia in a coupled East Asian-Australian circulation system. Our finding suggests that the obliquity forcing may play a more important role in global hydroclimate cycles than previously thought

    Hypophosphorylated pRb knock-in mice exhibit hallmarks of aging and vitamin C-preventable diabetes

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    Despite extensive analysis of pRB phosphorylation in vitro, how this modification influences development and homeostasis in vivo is unclear. Here, we show that homozygous Rb∆K4 and Rb∆K7 knock-in mice, in which either four or all seven phosphorylation sites in the C-terminal region of pRb, respectively, have been abolished by Ser/Thr-to-Ala substitutions, undergo normal embryogenesis and early development, notwithstanding suppressed phosphorylation of additional upstream sites. Whereas Rb∆K4 mice exhibit telomere attrition but no other abnormalities, Rb∆K7 mice are smaller and display additional hallmarks of premature aging including infertility, kyphosis, and diabetes, indicating an accumulative effect of blocking pRb phosphorylation. Diabetes in Rb∆K7 mice is insulin-sensitive and associated with failure of quiescent pancreatic β-cells to re-enter the cell cycle in response to mitogens, resulting in induction of DNA damage response (DDR), senescence-associated secretory phenotype (SASP), and reduced pancreatic islet mass and circulating insulin level. Pre-treatment with the epigenetic regulator vitamin C reduces DDR, increases cell cycle re-entry, improves islet morphology, and attenuates diabetes. These results have direct implications for cell cycle regulation, CDK-inhibitor therapeutics, diabetes, and longevity
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