33 research outputs found
Detecting and characterizing lateral phishing at scale
We present the first large-scale characterization of lateral phishing attacks, based on a dataset of 113 million employee-sent emails from 92 enterprise organizations. In a lateral phishing attack, adversaries leverage a compromised enterprise account to send phishing emails to other users, benefit-ting from both the implicit trust and the information in the hijacked user's account. We develop a classifier that finds hundreds of real-world lateral phishing emails, while generating under four false positives per every one-million employee-sent emails. Drawing on the attacks we detect, as well as a corpus of user-reported incidents, we quantify the scale of lateral phishing, identify several thematic content and recipient targeting strategies that attackers follow, illuminate two types of sophisticated behaviors that attackers exhibit, and estimate the success rate of these attacks. Collectively, these results expand our mental models of the 'enterprise attacker' and shed light on the current state of enterprise phishing attacks
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Assembly of α-synuclein and neurodegeneration in the central nervous system of heterozygous M83 mice following the peripheral administration of α-synuclein seeds.
Peripheral administration (oral, intranasal, intraperitoneal, intravenous) of assembled A53T α-synuclein induced synucleinopathy in heterozygous mice transgenic for human mutant A53T α-synuclein (line M83). The same was the case when cerebellar extracts from a case of multiple system atrophy with type II α-synuclein filaments were administered intraperitoneally, intravenously or intramuscularly. We observed abundant immunoreactivity for pS129 α-synuclein in nerve cells and severe motor impairment, resulting in hindlimb paralysis and shortened lifespan. Filaments immunoreactive for pS129 α-synuclein were in evidence. A 70% loss of motor neurons was present five months after an intraperitoneal injection of assembled A53T α-synuclein or cerebellar extract with type II α-synuclein filaments from an individual with a neuropathologically confirmed diagnosis of multiple system atrophy. Microglial cells changed from a predominantly ramified to a dystrophic appearance. Taken together, these findings establish a close relationship between the formation of α-synuclein inclusions in nerve cells and neurodegeneration, accompanied by a shift in microglial cell morphology. Propagation of α-synuclein inclusions depended on the characteristics of both seeds and transgenically expressed protein
Cryo-EM structures of amyloid-β 42 filaments from human brains
Alzheimer’s disease is characterized by a loss of memory and other cognitive functions and the filamentous assembly of Aβ and tau in the brain. The assembly of Aβ peptides into filaments that end at residue 42 is a central event. Yang et al. used electron cryo–electron microscopy to determine the structures of Aβ42 filaments from human brain (see the Perspective by Willem and Fändrich). They identified two types of related S-shaped filaments, each consisting of two identical protofilaments. These structures will inform the development of better in vitro and animal models, inhibitors of Aβ42 assembly, and imaging agents with increased specificity and sensitivity. —SM
Cyclotetraazocarbazole – a multichromic molecule
A macrocyclic cyclotetraazocarbazole was prepared. Surprisingly, during the investigation of its photochromic behavior a drastic color change from yellow to green upon irradiation in chlorinated solvents was observed, which was temperature dependent and could also be induced by acid/base addition. With these three inputs an integrated molecular logic gate including an OR, a NOT and an AND function was build
Plasma Symmetric Dimethylarginine Concentration in Dogs with Acute Kidney Injury and Chronic Kidney Disease.
BACKGROUND
Symmetric dimethylarginine (SDMA) is considered a biomarker for early detection of renal dysfunction in human patients with acute kidney injury (AKI). At present, no studies exist analyzing the relevance of SDMA in dogs with AKI.
HYPOTHESIS/OBJECTIVES
SDMA would correctly identify dogs with renal disease but would not be able to differentiate between AKI and CKD.
ANIMALS
Eighteen healthy control dogs, 48 dogs with AKI, and 29 dogs with CKD.
METHODS
Prospective study. Dogs with kidney disease were categorized as having AKI or CKD according to the history, clinical signs, laboratory findings, and results of diagnostic imaging. Plasma SDMA concentration was measured by IDEXX Laboratories. SDMA/creatinine ratio was calculated in dogs with AKI or CKD.
RESULTS
Median SDMA concentrations were 8.5 μg/dL (6-12 μg/dL), 39.5 μg/dL (8->100 μg/dL), and 35 μg/dL (12->100 μg/dL), in healthy, AKI, and CKD, respectively. SDMA concentrations were significantly higher in dogs with AKI (P < .0001) or CKD (P < .0001) in comparison with healthy dogs. Median SDMA/creatinine ratio in dogs with AKI and CKD was 6.5 (1.7-20.9) and 10 (2.4-33.9) (P = .0004), respectively. Although there was overlap of the SDMA/creatinine ratio in dogs with AKI or CKD, it was significantly higher in dogs with CKD compared to dogs with AKI (P = .0004).
CONCLUSIONS AND CLINICAL IMPORTANCE
In this population, SDMA was suitable for identifying dogs affected by AKI or CKD, but could not differentiate between them
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Mutation ∆K281 in MAPT causes Pick's disease.
Acknowledgements: We thank the patients’ family for donating brain tissues. This work was supported by the Electron Microscopy Facility of the MRC Laboratory of Molecular Biology. We thank Gordon Kelley, Brandy Matthews and Fred Unverzagt for clinical and neuropsychological evaluations, Jake Grimmett, Toby Darling and Ivan Clayson for help with high-performance computing, as well as Brad Glazier, Urs Kuederli, Rose Richardson and Max Jacobsen for help with neuropathology. For the purpose of open access, the MRC Laboratory of Molecular Biology has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising.Funder: Rainwater Charitable Foundation; doi: http://dx.doi.org/10.13039/100016608Funder: Alzheimerfonden; doi: http://dx.doi.org/10.13039/501100008599Funder: Demensförbundet; doi: http://dx.doi.org/10.13039/100010773Two siblings with deletion mutation ∆K281 in MAPT developed frontotemporal dementia. At autopsy, numerous inclusions of hyperphosphorylated 3R Tau were present in neurons and glial cells of neocortex and some subcortical regions, including hippocampus, caudate/putamen and globus pallidus. The inclusions were argyrophilic with Bodian silver, but not with Gallyas-Braak silver. They were not labelled by an antibody specific for tau phosphorylated at S262 and/or S356. The inclusions were stained by luminescent conjugated oligothiophene HS-84, but not by bTVBT4. Electron cryo-microscopy revealed that the core of tau filaments was made of residues K254-F378 of 3R Tau and was indistinguishable from that of Pick's disease. We conclude that MAPT mutation ∆K281 causes Pick's disease
Solid-state phase transformations toward a metal-organic framework of 7-connected Zn4O secondary building units
In the development of metal-organic frameworks (MOFs), secondary building units (SBUs) have been utilized as molecular modules for the construction of nanoporous materials with robust structures. Under solvothermal synthetic conditions, dynamic changes in the metal coordination environments and ligand coordination modes of SBUs determine the resultant product structures. Alternatively, MOF phases with new topologies can also be achieved by post-synthetic treatment of as-synthesized MOFs via the introduction of acidic or basic moieties that cause the simultaneous cleavage/reformation of coordination bonds in the solid state. In this sense, we studied the solid-state transformation of two ndc-based Zn-MOFs (ndc = 1,4-naphthalene dicarboxylate) with different SBUs but the same pcu topology to another MOF with sev topology. One of the chosen MOFs with pcu nets is [Zn-2(ndc)(2)(bpy)](n)(bpy = 4,4 '-bipyridine), (6C(bpy)-MOF) consisting of a 6-connected pillared-paddlewheel SBU, and the other is IRMOF-7 composed of 6-connected Zn4O(COO)(6)SBUs and ndc. Upon post-structural modification, these pcu MOFs were converted into the same MOF with sev topology constructed from the uncommon 7-connected Zn4O(COO)(7)SBU (7C-MOF). The appropriate post-synthetic conditions for the transformation of each SBUs were systematically examined. In addition, the effect of the pillar molecules in the pillared-paddlewheel MOFs on the topology conversion was studied in terms of the linker basicity, which determines the inertness during the solid-state phase transformation. This post-synthetic modification approach is expected to expand the available methods for designing and synthesizing MOFs with controlled topologies