Maturing International Cooperation to Address the Cyberspace Attack Attribution Problem

One of the most significant challenges to deterring attacks in cyberspace is the difficulty of identifying and attributing attacks to specific state or non-state actors. The lack of technical detection capability moves the problem into the legal realm; however, the lack of domestic and international cyberspace legislation makes the problem one of international cooperation. Past assessments have led to collective paralysis pending improved technical and legal advancements. This paper demonstrates, however, that any plausible path to meaningful defense in cyberspace must include a significant element of international cooperation and regime formation. The analytical approach diverges from past utilitarian-based assessments to understand the emerging regime, or implicit and explicit principles, norms, rules, and decision-making procedures, around which actor expectations are beginning to converge in the area of cyberspace attack attribution. The analysis applies a social-practice perspective of regime formation to identify meaningful normative and political recommendations. Various hypotheses of regime formation further tailor the recommendations to the current maturity level of international cooperation in this issue area. Examining international cooperation in cyberspace and methods for maturing international cooperation to establish attribution in other domains inform political mitigations to the problem of cyberspace attack attribution. Potential solutions are analyzed with respect to four recent cyberspace attacks to illustrate how improved international cooperation might address the problem. Finally, a counterfactual analysis, or thought experiment, of how these recommendations might have been applied in the case of rampant Chinese cyber espionage inform specific current and future opportunities for implementation. Although timing is difficult to predict, the growing frequency and scope of cyber attacks indicate the window of opportunity to address the problem before some form of cataclysmic event is closing

Prediction of disability-free survival in healthy older people.

Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6-77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people.Trial registration Clinicaltrials.gov (NCT01038583)

Best Practices in Cancer Nanotechnology: Perspective from NCI Nanotechnology Alliance

Historically, treatment of patients with cancer using chemotherapeutic agents has been associated with debilitating and systemic toxicities, poor bioavailability, and unfavorable pharmacokinetics. Nanotechnology-based drug delivery systems, on the other hand, can specifically target cancer cells while avoiding their healthy neighbors, avoid rapid clearance from the body, and be administered without toxic solvents. They hold immense potential in addressing all of these issues which has hampered further development of chemotherapeutics. Furthermore, such drug delivery systems will lead to cancer therapeutic modalities which are not only less toxic to the patient but also significantly more efficacious. In addition to established therapeutic modes of action, nanomaterials are opening up entirely new modalities of cancer therapy, such as photodynamic and hyperthermia treatments. Furthermore, nanoparticle carriers are also capable of addressing several drug delivery problems which could not be effectively solved in the past and include overcoming formulation issues, multi-drug-resistance phenomenon and penetrating cellular barriers that may limit device accessibility to intended targets such as the blood-brain-barrier. The challenges in optimizing design of nanoparticles tailored to specific tumor indications still remain; however, it is clear that nanoscale devices carry a significant promise towards new ways of diagnosing and treating cancer. This review focuses on future prospects of using nanotechnology in cancer applications and discusses practices and methodologies used in the development and translation of nanotechnology-based therapeutics

A widespread family of bacterial cell wall assembly proteins

Teichoic acids and acidic capsular polysaccharides are major anionic cell wall polymers (APs) in many bacteria, with various critical cell functions, including maintenance of cell shape and structural integrity, charge and cation homeostasis, and multiple aspects of pathogenesis. We have identified the widespread LytR–Cps2A–Psr (LCP) protein family, of previously unknown function, as novel enzymes required for AP synthesis. Structural and biochemical analysis of several LCP proteins suggest that they carry out the final step of transferring APs from their lipid-linked precursor to cell wall peptidoglycan (PG). In Bacillus subtilis, LCP proteins are found in association with the MreB cytoskeleton, suggesting that MreB proteins coordinate the insertion of the major polymers, PG and AP, into the cell wall

The Genomics Education Partnership: Successful Integration of Research into Laboratory Classes at a Diverse Group of Undergraduate Institutions

Genomics is not only essential for students to understand biology but also provides unprecedented opportunities for undergraduate research. The goal of the Genomics Education Partnership (GEP), a collaboration between a growing number of colleges and universities around the country and the Department of Biology and Genome Center of Washington University in St. Louis, is to provide such research opportunities. Using a versatile curriculum that has been adapted to many different class settings, GEP undergraduates undertake projects to bring draft-quality genomic sequence up to high quality and/or participate in the annotation of these sequences. GEP undergraduates have improved more than 2 million bases of draft genomic sequence from several species of Drosophila and have produced hundreds of gene models using evidence-based manual annotation. Students appreciate their ability to make a contribution to ongoing research, and report increased independence and a more active learning approach after participation in GEP projects. They show knowledge gains on pre- and postcourse quizzes about genes and genomes and in bioinformatic analysis. Participating faculty also report professional gains, increased access to genomics-related technology, and an overall positive experience. We have found that using a genomics research project as the core of a laboratory course is rewarding for both faculty and students

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Mapping recent timber harvest activity in a temperate forest using single date airborne LiDAR surveys and machine learning: lessons for conservation planning

Effective planning for natural resource management and wildlife conservation requires detailed information on vegetation structure at landscape scales and how structure is influenced by land-use practices. In many forested landscapes, the largest impacts of land use on forest structure are driven by forest management activities, which can include invasive species control, prescribed fire, partial harvests (e.g. shelterwood harvests) or overstory removals and clearcuts. Active timber management is often used to achieve forest conservation objectives, but to be used effectively, managers require knowledge of harvest frequency and extent in adjacent forests and at landscape scales. In this paper, we develop a timber harvest mapping workflow using machine learning (XGBoost algorithm) and single campaign airborne light detection and ranging (LiDAR) surveys for the state of Pennsylvania, USA. We show that harvest type (shelterwood and overstory removals) can be mapped at high accuracy (overall accuracy = 94.9%), including broad age classes defined by the number of years since harvest. Errors of omission (false negatives) were lowest for recent (30 m from an edge). The expectation that these harvest treatments would be rarer in private forests was not supported by the model results, which is likely due to the model’s inability to distinguish between alternative natural processes (weather damage, wildfire, pathogens, etc.) and forest treatment types (high-grading and firewood collection) that result in similar forest structures to the trained classes in the XGBoost model. This study provides a framework and validation for combining approachable machine-learning techniques with large-campaign LiDAR to accurately predict forest structure with application to a host of forestry, natural resource, and conservation-related problems. Future efforts that refine the model’s ability to better distinguish between more complex harvest classes and natural processes would be valuable

Comparison of response rates on invitation mode of a web-based survey on influenza vaccine adverse events among healthcare workers: a pilot study

Abstract Background Web-based surveys have become increasingly popular but response rates are low and may be prone to selection bias. How people are invited to participate may impact response rates and needs further study as previous evidence is contradictory. The purpose of this study was to determine whether response to a web-based survey of healthcare workers would be higher with a posted or an emailed invitation. We also report results of the pilot study, which aims to estimate the percentage of adults vaccinated against influenza who report recurrent systemic adverse events (the same systemic adverse event occurring successively following receipt of influenza vaccines). Methods The pilot study was conducted in November 2016 in Toronto, Canada. Members of a registry of adults (18 years and older and predominantly healthcare workers) who volunteered to receive information regarding future studies about influenza were randomly assigned to receive either an email or postal invitation to complete a web-based survey regarding influenza vaccinations. Non-respondents received one reminder using the same mode of contact as their original invitation. Results The overall response rate was higher for those sent the invitation by email (34.8%) than by post (25.8%; p < 0.001) and for older versus younger participants (p trend < 0.001). Of those who responded, 387/401 had been vaccinated against influenza at least once since adulthood. Of those responding to the question, 70/386 (18.1%) reported a systemic adverse event after their most recent influenza vaccine including 22 (5.7%) who reported a recurring systemic event. Systemic adverse events were reported more often by males 18–49 years old than by other groups (p = 0.01). Recurrent systemic adverse events were similar by age and sex with muscle ache being the most commonly reported recurrent reaction. More respondents who reported only a local adverse event (93.1%) planned to be vaccinated again next year than those with a systemic adverse event (69.7%; p = 0.04). Conclusions In this convenience sample of registry volunteers, response rates were generally low, but were higher for the emailed than posted invitations and for older than younger adults