A baseline for unsupervised advanced persistent threat detection in system-level provenance

Advanced persistent threats (APT) are stealthy, sophisticated, and unpredictable cyberattacks that can steal intellectual property, damage critical infrastructure, or cause millions of dollars in damage. Detecting APTs by monitoring system-level activity is difficult because manually inspecting the high volume of normal system activity is overwhelming for security analysts. We evaluate the effectiveness of unsupervised batch and streaming anomaly detection algorithms over multiple gigabytes of provenance traces recorded on four different operating systems to determine whether they can detect realistic APT-like attacks reliably and efficiently. This report is the first detailed study of the effectiveness of generic unsupervised anomaly detection techniques in this setting

Prevention and Mitigation of Acute Radiation Syndrome in Mice by Synthetic Lipopeptide Agonists of Toll-Like Receptor 2 (TLR2)

Bacterial lipoproteins (BLP) induce innate immune responses in mammals by activating heterodimeric receptor complexes containing Toll-like receptor 2 (TLR2). TLR2 signaling results in nuclear factor-kappaB (NF-κB)-dependent upregulation of anti-apoptotic factors, anti-oxidants and cytokines, all of which have been implicated in radiation protection. Here we demonstrate that synthetic lipopeptides (sLP) that mimic the structure of naturally occurring mycoplasmal BLP significantly increase mouse survival following lethal total body irradiation (TBI) when administered between 48 hours before and 24 hours after irradiation. The TBI dose ranges against which sLP are effective indicate that sLP primarily impact the hematopoietic (HP) component of acute radiation syndrome. Indeed, sLP treatment accelerated recovery of bone marrow (BM) and spleen cellularity and ameliorated thrombocytopenia of irradiated mice. sLP did not improve survival of irradiated TLR2-knockout mice, confirming that sLP-mediated radioprotection requires TLR2. However, sLP was radioprotective in chimeric mice containing TLR2-null BM on a wild type background, indicating that radioprotection of the HP system by sLP is, at least in part, indirect and initiated in non-BM cells. sLP injection resulted in strong transient induction of multiple cytokines with known roles in hematopoiesis, including granulocyte colony-stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin-6 (IL-6). sLP-induced cytokines, particularly G-CSF, are likely mediators of the radioprotective/mitigative activity of sLP. This study illustrates the strong potential of LP-based TLR2 agonists for anti-radiation prophylaxis and therapy in defense and medical scenarios

Single Lipid Molecule Dynamics on Supported Lipid Bilayers with Membrane Curvature

The plasma membrane is a highly compartmentalized, dynamic material and this organization is essential for a wide variety of cellular processes. Nanoscale domains allow proteins to organize for cell signaling, endo- and exocytosis, and other essential processes. Even in the absence of proteins, lipids have the ability to organize into domains as a result of a variety of chemical and physical interactions. One feature of membranes that affects lipid domain formation is membrane curvature. To directly test the role of curvature in lipid sorting, we measured the accumulation of two similar lipids, 1,2-Dihexadecanoyl-sn-glycero-3-phosphoethanolamine (DHPE) and hexadecanoic acid (HDA), using a supported lipid bilayer that was assembled over a nanopatterned surface to obtain regions of membrane curvature. Both lipids studied contain 16 carbon, saturated tails and a head group tag for fluorescence microscopy measurements. The accumulation of lipids at curvatures ranging from 28 nm to 55 nm radii was measured and fluorescein labeled DHPE accumulated more than fluorescein labeled HDA at regions of membrane curvature. We then tested whether single biotinylated DHPE molecules sense curvature using single particle tracking methods. Similar to groups of fluorescein labeled DHPE accumulating at curvature, the dynamics of single molecules of biotinylated DHPE was also affected by membrane curvature and highly confined motion was observed

Single Lipid Molecule Dynamics on Supported Lipid Bilayers with Membrane Curvature

The plasma membrane is a highly compartmentalized, dynamic material and this organization is essential for a wide variety of cellular processes. Nanoscale domains allow proteins to organize for cell signaling, endo- and exocytosis, and other essential processes. Even in the absence of proteins, lipids have the ability to organize into domains as a result of a variety of chemical and physical interactions. One feature of membranes that affects lipid domain formation is membrane curvature. To directly test the role of curvature in lipid sorting, we measured the accumulation of two similar lipids, 1,2-Dihexadecanoyl-sn-glycero-3-phosphoethanolamine (DHPE) and hexadecanoic acid (HDA), using a supported lipid bilayer that was assembled over a nanopatterned surface to obtain regions of membrane curvature. Both lipids studied contain 16 carbon, saturated tails and a head group tag for fluorescence microscopy measurements. The accumulation of lipids at curvatures ranging from 28 nm to 55 nm radii was measured and fluorescein labeled DHPE accumulated more than fluorescein labeled HDA at regions of membrane curvature. We then tested whether single biotinylated DHPE molecules sense curvature using single particle tracking methods. Similar to groups of fluorescein labeled DHPE accumulating at curvature, the dynamics of single molecules of biotinylated DHPE was also affected by membrane curvature and highly confined motion was observed

Frozen “Tofu” Effect: Engineered Pores of Hydrophilic Nanoporous Materials

Frozen tofu is a famous Asian food made by freezing soft bean curds, which are naturally porous to store flavor and nutrients. When the narrow pores of the soft bean curd are saturated with water and then frozen, pore widths expand to generate a completely new porous structurefrozen tofu has visibly wider pores than the initial bean curd. Intriguingly, this principle can be generalized and applied to manipulate micro/nanopores of functional porous materials. In this work, we will manipulate the pore size of nanoporous polymeric photonic crystals based on the phase change between water and ice. Wet-drying and freeze-drying methods were applied to shrink or expand the pore size intentionally. This principle is validated by directly observing the optical reflection peak shift of the material. Owing to the change in pore size, the reflection peak of the polymeric photonic crystal structure can be permanently, and intentionally, tuned. This simple but elegant mechanism is promising for the development of smart materials/devices for applications ranging from oil/water membrane separations, health monitoring, and medical diagnostics to environmental monitoring, anticounterfeiting, and smart windows

Radiomitigation by sLP: administration of sLP after lethal TBI improves mouse survival.

<p>(A) Time window for effective post-irradiation administration of sLP. Female ICR (CD-1®) mice (<i>n = 15</i>/group) were irradiated with 9 Gy TBI (at time “0”) and then injected sc with PBS at 1 h after irradiation or with sLP (50 µg/mouse) at 10 or 30 min, or 1, 3, 6, 9, 12, 24, or 48 h after irradiation. Mouse survival was monitored for 30 days. The differences in 30-day survival between the vehicle-treated group and groups treated with sLP between 10 min and 3 h after TBI and at 24 h after TBI were statistically significant (as indicated by *, P<0.05, Fisher's Exact test). (B) Determination of the DRF for the optimal radiomitigative regimen of sLP administration. Probit analysis was performed using Kaplan-Meier survival curves generated from treatment of female ICR mice with PBS vehicle or 50 µg/mouse sLP at 1 h after exposure to different TBI doses (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033044#pone.0033044.s002" target="_blank">figure S2A</a>). (C) SLP-mediated mitigation of death induced by low dose rate irradiation. Female ICR (CD-1®) mice (<i>n = 15</i>/group) received TBI at a continuous exposure rate of 0.4 cGy/min for 60 or 70 h (total dose of 14.4 or 16.8 Gy, respectively). At the mid-point of the irradiation period (i.e., 30 or 35 h after irradiation was started for the 60 and 70 h TBI groups, respectively), irradiation was halted for about 5 min during which time mice were injected sc with 10 µg/mouse sLP. Mouse survival was monitored for 30 days.</p

Administration of sLP in mice results in cytokine induction.

<p>Non-irradiated female C57BL/6 mice were injected sc with 10 µg sLP and euthanized 1, 2, 4, 8, 24, or 48 h later (<i>n</i> = 6/time point) for blood collection. Blood from untreated female C57BL/6 mice (<i>n</i> = 6) was analyzed as the “0 hour” time point. G-CSF, IL-6, and KC (A) and IL-1β, IL-10, IL-12(p70), SCF, GM-CSF, and TNF-α (B) levels were determined in individual mouse serum samples using multiplex Luminex assays. The mean cytokine concentration at each time point is shown. Error bars indicate standard error.</p