The Schistosoma mansoni Cytochrome P450 (CYP3050A1) Is Essential for Worm Survival and Egg Development.

Schistosomiasis affects millions of people in developing countries and is responsible for more than 200,000 deaths annually. Because of toxicity and limited spectrum of activity of alternatives, there is effectively only one drug, praziquantel, available for its treatment. Recent data suggest that drug resistance could soon be a problem. There is therefore the need to identify new drug targets and develop drugs for the treatment of schistosomiasis. Analysis of the Schistosoma mansoni genome sequence for proteins involved in detoxification processes found that it encodes a single cytochrome P450 (CYP450) gene. Here we report that the 1452 bp open reading frame has a characteristic heme-binding region in its catalytic domain with a conserved heme ligating cysteine, a hydrophobic leader sequence present as the membrane interacting region, and overall structural conservation. The highest sequence identity to human CYP450s is 22%. Double stranded RNA (dsRNA) silencing of S. mansoni (Sm)CYP450 in schistosomula results in worm death. Treating larval or adult worms with antifungal azole CYP450 inhibitors results in worm death at low micromolar concentrations. In addition, combinations of SmCYP450-specific dsRNA and miconazole show additive schistosomicidal effects supporting the hypothesis that SmCYP450 is the target of miconazole. Treatment of developing S. mansoni eggs with miconazole results in a dose dependent arrest in embryonic development. Our results indicate that SmCYP450 is essential for worm survival and egg development and validates it as a novel drug target. Preliminary structure-activity relationship suggests that the 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol moiety of miconazole is necessary for activity and that miconazole activity and selectivity could be improved by rational drug design

Explorations in Cyber International Relations (ECIR) – Data Dashboard Report #1: CERT Data Sources and Prototype Dashboard System

Disclaimer: This report relies on publicly available information, especially from the CERTs' pubic web sites. They have not yet been contacted to confirm our understanding of their data. That will be done in subsequent phases of this effort.Growing global interconnection and interdependency of computer networks, in combination with increased sophistication of cyber attacks over time, demonstrate the need for better understanding of the collective and cooperative security measures needed to prevent and respond to cybersecurity emergencies. The Exploring Cyber International Relations (ECIR) Data Dashboard project is an initial effort to gather and analyze such data within and between countries. This report describes the prototype ECIR Data Dashboard and the initial data sources used. In 1988, the United States Department of Defense and Carnegie Mellon University formed the Computer Emergency Response Team (CERT) to lead and coordinate national and international efforts to combat cybsersecurity threats. Since then, the number of CERTs worldwide has grown dramatically, leading to the potential for a sophisticated and coordinated global cybersecurity response network. This report focuses primarily on the current state of the worldwide CERTs, including the data publiclyavailable, the extent of coordination, and the maturity of data management and responses. The report summarizes, analyses, and critiques the worldwide CERT network. Additionally, the report describes the ECIR team's Data Dashboard project, designed to provide scholars, policymakers, IT professionals, and other stakeholders with a comprehensive set of data on national-level cybersecurity, information technology, and demographic data. The Dashboard allows these stakeholders to observe chronological trends and multivariate correlations that can lead to insight into the current state, potential future trends, and approximate causes of global cybersecurity issues. This report summarizes the purpose, state, progress, and challenges of developing the Data Dashboard project. Disclaimer: This report relies on publicly available information, especially from the CERTs’ pubic web sites. They have not yet been contacted to confirm our understanding of their data. That will be done in subsequent phases of this effort

Models of Active Worm Defenses

Coordinated Science Laboratory was formerly known as Control Systems LaboratoryDARPA / N66001-96-C-8530National Science Foundation / CCR-209144Office for Domestic Preparedness, U.S. Department of Homeland Security / 2000-DT-CX-K00

Computer Attacks on Critical National Infrastructure: A Use of Force Invoking the Right of Self-Defense

Computer networks create tremendously increased capabilities but also represent equally increased vulnerabilities. These vulnerabilites are especially acute in relation to potential attacks on critical national infrasturucture. This Article proposes that international law must evolve to recognize that attacks against a nation\u27s critical national infrastructure from any source constitute a use of force. Such attacks, therefore, give the victim state the right to proportional self-defense - including anticipatory self-defense - even if the computer network attack is not an armed attack under Article 51 of the United Nations Charter. Due to the instantaneous nature of computer network attacks, the right to respond must accrue immediately, despite the traditional obstacles of attribution (determining the attacker\u27s identity), characterization (determining the attacker\u27s intent), and the inviolability of neutrals

A principled approach to measuring the IoT ecosystem

Internet of Things (IoT) devices combine network connectivity, cheap hardware, and actuation to provide new ways to interface with the world. In spite of this growth, little work has been done to measure the network properties of IoT devices. Such measurements can help to inform systems designers and security researchers of IoT networking behavior in practice to guide future research. Unfortunately, properly measuring the IoT ecosystem is not trivial. Devices may have different capabilities and behaviors, which require both active measurements and passive observation to quantify. Furthermore, the IoT devices that are connected to the public Internet may vary from those connected inside home networks, requiring both an external and internal vantage point to draw measurements from. In this thesis, we demonstrate how IoT measurements drawn from a single vantage point or mesaurement technique lead to a biased view of the network services in the IoT ecosystem. To do this, we conduct several real-world IoT measurements, drawn from both inside and outside home networks using active and passive monitoring. First, we leverage active scanning and passive observation in understanding the Mirai botnet---chiefly, we report on the devices it infected, the command and control infrastructure behind the botnet, and how the malware evolved over time. We then conduct active measurements from inside 16M home networks spanning 83M devices from 11~geographic regions to survey the IoT devices installed around the world. We demonstrate how these measurements can uncover the device types that are most at risk and the vendors who manufacture the weakest devices. We compare our measurements with passive external observation by detecting compromised scanning behavior from smart homes. We find that while passive external observation can drive insight about compromised networks, it offers little by way of concrete device attribution. We next compare our results from active external scanning with active internal scanning and show how relying solely on external scanning for IoT measurements under-reports security important IoT protocols, potentially skewing the services investigated by the security community. Finally, we conduct passive measurements of 275~smart home networks to investigate IoT behavior. We find that IoT device behavior varies by type and devices regularly communicate over a myriad of bespoke ports, in many cases to speak standard protocols (e.g., HTTP). Finally, we observe that devices regularly offer active services (e.g., Telnet, rpcbind) that are rarely, if ever, used in actual communication, demonstrating the need for both active and passive measurements to properly compare device capabilities and behaviors. Our results highlight the need for a confluence of measurement perspectives to comprehensively understand IoT ecosystem. We conclude with recommendations for future measurements of IoT devices as well as directions for the systems and security community informed by our work

Cyber Analogies

This anthology of cyber analogies will resonate with readers whose duties call for them to set strategies to protect the virtual domain and determine the policies that govern it. Our belief is that learning is most effective when concepts under consideration can be aligned with already-existing understanding or knowledge. Cyber issues are inherently tough to explain in layman's terms. The future is always open and undetermined, and the numbers of actors and the complexity of their relations are too great to give definitive guidance about future developments. In this respect, historical analogies, carefully developed and properly applied, help indicate a direction for action by reducing complexity and making the future at least cognately manageable.US Cyber CommandIntroduction: Emily O. Goldman & John Arquilla; The Cyber Pearl Harbor:James J. Wirtz: Applying the Historical Lessons of Surprise Attack to the Cyber Domain: The Example of the United Kingdom:Dr Michael S. Goodman: The Cyber Pearl Harbor Analogy: An Attacker’s Perspective: Emily O. Goldman, John Surdu, & Michael Warner: “When the Urgency of Time and Circumstances Clearly Does Not Permit...”: Redelegation in Nuclear and Cyber Scenarios: Peter Feaver & Kenneth Geers; Comparing Airpower and Cyberpower: Dr. Gregory Rattray: Active Cyber Defense: Applying Air Defense to the Cyber Domain: Dorothy E. Denning & Bradley J. Strawser: The Strategy of Economic Warfare: A Historical Case Study and Possible Analogy to: Contemporary Cyber Warfare: Nicholas A. Lambert: Silicon Valley: Metaphor for Cybersecurity, Key to Understanding Innovation War: John Kao: The Offense-Defense Balance and Cyber Warfare: Keir Lieber: A Repertory of Cyber Analogies: Robert Axelro