A Future-Based Risk Assessment for the Survivability of Long Range Strike Systems

The United States Air Force today faces the challenge of allocating development resources to prepare for future force projection requirements. In particular, the Air Force\u27s core competency of Global Attack implies a future capability that can quickly and successfully deliver combat effects anywhere in the world with impunity. Understanding that the future threat environment is dynamic and that continued advancements by adversaries will likely degrade the technical superiority of today\u27s weapon systems, the need arises for a planning model to direct development funding to areas with the greatest probability of successfully defending the strike vehicle of 2035. Examining this problem posed two distinct challenges. The first was to determine the most likely course of Integrated Air Defense System technology through the time period of interest--allowing for plausible disruptive technologies that generate orders-of-magnitude improvement in capability or even change the nature of air defense systems. The second challenge was to characterize future adversaries--requiring a broad look at political and economic trends as presented in AF 2025, SPACECAST 2020 and other relevant future studies. Based on these studies, threat scenarios were generated from technical assessments of emerging technologies and evaluated using the Risk Filtering, Ranking and Management (RFRM) technique (Haimes, 2004) to explore the most severe threats to a future global strike air vehicle. The application of RFRM to the problem created a coherent threat hierarchy that enables the decision maker to examine anticipated hostile systems that may counter key U.S. strengths of stealth, speed, and high altitude operations. Those threat scenarios were then evaluated using decision trees and sensitivity analysis to demonstrate how quantitative tools can be applied to a largely qualitative problem

Graphene-based Josephson junction single photon detector

We propose to use graphene-based Josephson junctions (gJjs) to detect single photons in a wide electromagnetic spectrum from visible to radio frequencies. Our approach takes advantage of the exceptionally low electronic heat capacity of monolayer graphene and its constricted thermal conductance to its phonon degrees of freedom. Such a system could provide high sensitivity photon detection required for research areas including quantum information processing and radio-astronomy. As an example, we present our device concepts for gJj single photon detectors in both the microwave and infrared regimes. The dark count rate and intrinsic quantum efficiency are computed based on parameters from a measured gJj, demonstrating feasibility within existing technologies.Comment: 11 pages, 6 figures, and 1 table in the main tex

Mechanical characterization of individual polycrystalline carbon tubes for use in electrical nano-interconnects

Polycrystalline carbon tubes were generated by CVD inside electrochemically prepared nano-porous anodic aluminium oxide membranes. This method produced nano-tubes without catalyst, featuring polycrystalline and a few layer thick walls. Individual tubes could be isolated and suspended on microfabricated substrates such that they formed single-side clamped beams. These beams were then used to investigate their mechanical properties employing electrostatic forces for bending the tubes beyond their mechanical stability where pull-in occurs, which could be detected by monitoring the current flowing from the tube to the substrate

Therapy-refractory Panton Valentine Leukocidin-positive community-acquired methicillin-sensitive Staphylococcus aureus sepsis with progressive metastatic soft tissue infection: a case report

We report a case of fulminant multiple organ failure including the Acute Respiratory Distress Syndrome (ARDS), haemodynamic, and renal failure due to community-acquired methicillin-sensitive Panton Valentine Leukocidin (PVL) positive spa-type 284 (ST121) Staphylococcus aureus septic shock. The patient's first clinical symptom was necrotizing pneumonia. Despite organism-sensitive triple antibiotic therapy with linezolid, imipenem and clindamycin from the first day of treatment, progressive abscess formation in multiple skeletal muscles was observed. As a result, repeated surgical interventions became necessary. Due to progressive soft tissue infection, the anti-microbial therapy was changed to a combination of clindamycin and daptomycin. Continued surgical and antimicrobial therapy finally led to a stabilisation of the patients' condition. The clinical course of our patient underlines the existence of a "PVL-syndrome" which is independent of in vitro Staphylococcus aureus susceptibility. The PVL-syndrome should not only be considered in patients with soft tissue or bone infection, but also in patients with pneumonia. Such a condition, which may easily be mistaken for uncomplicated pneumonia, should be treated early, aggressively and over a long period of time in order to avoid relapsing infection

A Cytoplasmic Complex Mediates Specific mRNA Recognition and Localization in Yeast

The localization of ash mRNA in yeast requires the binding of She2p and the myosin adaptor protein She3p to its localization element, which is highly specific and leads to the assembly of stable transport complexes

Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma

In the primary analysis of the phase III COLUMBA study, daratumumab by subcutaneous administration (DARA SC) demonstrated non-inferiority to intravenous administration (DARA IV) for relapsed or refractory multiple myeloma (RRMM). Here, we report the final analysis of efficacy and safety from COLUMBA after a median of 29.3 months follow-up (additional 21.8 months after the primary analysis). In total, 522 patients were randomized (DARA SC, n=263; DARA IV, n=259). With longer follow-up, DARA SC and DARA IV continued to show consistent efficacy and maximum trough daratumumab concentration as compared with the primary analysis. The overall response rate was 43.7% for DARA SC and 39.8% for DARA IV. The maximum mean (standard deviation [SD]) trough concentration (cycle 3, day 1 pre-dose) of serum DARA was 581 (SD, 315) µg/mL for DARA SC and 496 (SD, 231) µg/mL for DARA IV. Median progression-free survival was 5.6 months for DARA SC and 6.1 months for DARA IV; median overall survival was 28.2 months and 25.6 months, respectively. Grade 3/4 treatment-emergent adverse events occurred in 50.8% of patients in the DARA SC group and 52.7% in the DARA IV group; the most common (≥10%) were thrombocytopenia (DARA SC, 14.2%; DARA IV, 13.6%), anemia (13.8%; 15.1%), and neutropenia (13.1%; 7.8%). The safety profile remained consistent with the primary analysis after longer follow-up. In summary, DARA SC and DARA IV continue to demonstrate similar efficacy and safety, with a low rate of infusion-related reactions (12.7% vs. 34.5%, respectively) and shorter administration time (3-5 minutes vs. 3-7 hours) supporting DARA SC as a preferable therapeutic choice

Quality assessment of an interferon-gamma release assay for tuberculosis infection in a resource-limited setting

<p>Abstract</p> <p>Background</p> <p>When a test for diagnosis of infectious diseases is introduced in a resource-limited setting, monitoring quality is a major concern. An optimized design of experiment and statistical models are required for this assessment.</p> <p>Methods</p> <p>Interferon-gamma release assay to detect tuberculosis (TB) infection from whole blood was tested in Hanoi, Viet Nam. Balanced incomplete block design (BIBD) was planned and fixed-effect models with heterogeneous error variance were used for analysis. In the first trial, the whole blood from 12 donors was incubated with nil, TB-specific antigens or mitogen. In 72 measurements, two laboratory members exchanged their roles in harvesting plasma and testing for interferon-gamma release using enzyme linked immunosorbent assay (ELISA) technique. After intervention including checkup of all steps and standard operation procedures, the second trial was implemented in a similar manner.</p> <p>Results</p> <p>The lack of precision in the first trial was clearly demonstrated. Large within-individual error was significantly affected by both harvester and ELISA operator, indicating that both of the steps had problems. After the intervention, overall within-individual error was significantly reduced (<it>P </it>< 0.0001) and error variance was no longer affected by laboratory personnel in charge, indicating that a marked improvement could be objectively observed.</p> <p>Conclusion</p> <p>BIBD and analysis of fixed-effect models with heterogeneous variance are suitable and useful for objective and individualized assessment of proficiency in a multistep diagnostic test for infectious diseases in a resource-constrained laboratory. The action plan based on our findings would be worth considering when monitoring for internal quality control is difficult on site.</p

Principles of mRNA transport in yeast

mRNA localization and localized translation is a common mechanism by which cellular asymmetry is achieved. In higher eukaryotes the mRNA transport machinery is required for such diverse processes as stem cell division and neuronal plasticity. Because mRNA localization in metazoans is highly complex, studies at the molecular level have proven to be cumbersome. However, active mRNA transport has also been reported in fungi including Saccharomyces cerevisiae, Ustilago maydis and Candida albicans, in which these events are less difficult to study. Amongst them, budding yeast S. cerevisiae has yielded mechanistic insights that exceed our understanding of other mRNA localization events to date. In contrast to most reviews, we refrain here from summarizing mRNA localization events from different organisms. Instead we give an in-depth account of ASH1 mRNA localization in budding yeast. This approach is particularly suited to providing a more holistic view of the interconnection between the individual steps of mRNA localization, from transcriptional events to cytoplasmic mRNA transport and localized translation. Because of our advanced mechanistic understanding of mRNA localization in yeast, the present review may also be informative for scientists working, for example, on mRNA localization in embryogenesis or in neurons