6,185 research outputs found

    Cyber Infrastructure Protection: Vol. II

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    View the Executive SummaryIncreased reliance on the Internet and other networked systems raise the risks of cyber attacks that could harm our nation’s cyber infrastructure. The cyber infrastructure encompasses a number of sectors including: the nation’s mass transit and other transportation systems; banking and financial systems; factories; energy systems and the electric power grid; and telecommunications, which increasingly rely on a complex array of computer networks, including the public Internet. However, many of these systems and networks were not built and designed with security in mind. Therefore, our cyber infrastructure contains many holes, risks, and vulnerabilities that may enable an attacker to cause damage or disrupt cyber infrastructure operations. Threats to cyber infrastructure safety and security come from hackers, terrorists, criminal groups, and sophisticated organized crime groups; even nation-states and foreign intelligence services conduct cyber warfare. Cyber attackers can introduce new viruses, worms, and bots capable of defeating many of our efforts. Costs to the economy from these threats are huge and increasing. Government, business, and academia must therefore work together to understand the threat and develop various modes of fighting cyber attacks, and to establish and enhance a framework to assess the vulnerability of our cyber infrastructure and provide strategic policy directions for the protection of such an infrastructure. This book addresses such questions as: How serious is the cyber threat? What technical and policy-based approaches are best suited to securing telecommunications networks and information systems infrastructure security? What role will government and the private sector play in homeland defense against cyber attacks on critical civilian infrastructure, financial, and logistical systems? What legal impediments exist concerning efforts to defend the nation against cyber attacks, especially in preventive, preemptive, and retaliatory actions?https://press.armywarcollege.edu/monographs/1527/thumbnail.jp

    Gain properties of dye-doped polymer thin films

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    Hybrid pumping appears as a promising compromise in order to reach the much coveted goal of an electrically pumped organic laser. In such configuration the organic material is optically pumped by an electrically pumped inorganic device on chip. This engineering solution requires therefore an optimization of the organic gain medium under optical pumping. Here, we report a detailed study of the gain features of dye-doped polymer thin films. In particular we introduce the gain efficiency KK, in order to facilitate comparison between different materials and experimental conditions. The gain efficiency was measured with various setups (pump-probe amplification, variable stripe length method, laser thresholds) in order to study several factors which modify the actual gain of a layer, namely the confinement factor, the pump polarization, the molecular anisotropy, and the re-absorption. For instance, for a 600 nm thick 5 wt\% DCM doped PMMA layer, the different experimental approaches give a consistent value KK\simeq 80 cm.MW1^{-1}. On the contrary, the usual model predicting the gain from the characteristics of the material leads to an overestimation by two orders of magnitude, which raises a serious problem in the design of actual devices. In this context, we demonstrate the feasibility to infer the gain efficiency from the laser threshold of well-calibrated devices. Besides, temporal measurements at the picosecond scale were carried out to support the analysis.Comment: 15 pages, 17 figure

    Killer instincts: natural killer cells as multifactorial cancer immunotherapy

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    Natural killer (NK) cells integrate heterogeneous signals for activation and inhibition using germline-encoded receptors. These receptors are stochastically co-expressed, and their concurrent engagement and signaling can adjust the sensitivity of individual cells to putative targets. Against cancers, which mutate and evolve under therapeutic and immunologic pressure, the diversity for recognition provided by NK cells may be key to comprehensive cancer control. NK cells are already being trialled as adoptive cell therapy and targets for immunotherapeutic agents. However, strategies to leverage their naturally occurring diversity and agility have not yet been developed. In this review, we discuss the receptors and signaling pathways through which signals for activation or inhibition are generated in NK cells, focusing on their roles in cancer and potential as targets for immunotherapies. Finally, we consider the impacts of receptor co-expression and the potential to engage multiple pathways of NK cell reactivity to maximize the scope and strength of antitumor activities

    Pattern Analysis of Microtubule-Polymerizing and -Depolymerizing Agent Combinations as Cancer Chemotherapies

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    Subcellular distribution of mass can be analyzed by a technique that involves culturing cells on interferometers and digitizing their interference contours. Contour sampling resulted in 102 variables per cell, which were predictors of oncogenic transformation. Cell phenotypes can be deconstructed by use of latent factors, which represent the covariance of the real variables. The reversal of the cancertype phenotype by a combination of microtubule- stabilizing and -depolymerizing agents was described previously. The implications of these results have been explored by clinicians who treated patients with the combination of docetaxel and vinorelbine (Navelbine®). The current study was performed to determine the effects of different combinations on phenotype and in phases of the cell cycle other than mitosis. Combinations of paclitaxel with either colchicine, podophyllotoxin, nocodazole, or vinblastine caused phenotype reversal. Paclitaxel analogue, 7-deoxytaxol, by itself caused reversal. Factors #4, (filopodia), #5 (displacement and/or deep invaginations in the periphery), #8, and #12 took on values typical of normal cells, whereas the values of #7 (p21-activated kinase), and #13 (rounding up) shifted toward the cancer-type. All combinations altered microtubule arrangement at the cell edge. Delivery schedules and drug ratios used in clinical studies were subjected to analysis. Clinical response rates were better when the combination was not interspersed with a single agent (P=0.004). The results support the idea that efficacy depends upon simultaneous exposure to both agents, and suggest a novel mechanism for combination therapies. These therapies appear to restore in transformed cells some of the features of a contact-inhibited cell, and to impede progress through the cell cycle even when provided at nanomolar concentrations

    NK-Like T Cells and Plasma Cytokines, but Not Anti-Viral Serology, Define Immune Fingerprints of Resilience and Mild Disability in Exceptional Aging

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    Exceptional aging has been defined as maintenance of physical and cognitive function beyond the median lifespan despite a history of diseases and/or concurrent subclinical conditions. Since immunity is vital to individual fitness, we examined immunologic fingerprint(s) of highly functional elders. Therefore, survivors of the Cardiovascular Health Study in Pittsburgh, Pennsylvania, USA were recruited (n = 140; mean age = 86 years) and underwent performance testing. Blood samples were collected and examined blindly for humoral factors and T cell phenotypes. Based on results of physical and cognitive performance testing, elders were classified as “impaired” or “unimpaired”, accuracy of group assignment was verified by discriminant function analysis. The two groups showed distinct immune profiles as determined by factor analysis. The dominant immune signature of impaired elders consisted of interferon (IFN)-γ, interleukin (IL)-6, tumor necrosis factor-α, and T cells expressing inhibitory natural killer-related receptors (NKR) CD158a, CD158e, and NKG2A. In contrast, the dominant signature of unimpaired elders consisted of IL-5, IL-12p70, and IL-13 with co-expression of IFN-γ, IL-4, and IL-17, and T cells expressing stimulatory NKRs CD56, CD16, and NKG2D. In logistic regression models, unimpaired phenotype was predicted independently by IL-5 and by CD4+CD28nullCD56+CD57+ T cells. All elders had high antibody titers to common viruses including cytomegalovirus. In cellular bioassays, T cell receptor (TCR)-independent ligation of either CD56 or NKG2D elicited activation of T cells. Collectively, these data demonstrate the importance of immunological parameters in distinguishing between health phenotypes of older adults. NKR+ T cells and cytokine upregulation indicate a unique physiologic environment in old age. Correlation of particular NKR+ T cell subsets and IL-5 with unimpaired performance, and NKR-driven TCR-independent activation of T cells suggest novel immunopathway(s) that could be exploited to improve immunity in old age

    Implementation of chamber misalignments and deformations in the ATLAS muon spectrometer simulation

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    "The implementation of run-time dependent corrections for alignment and distortions in the detector description of the ATLAS Muon Spectrometer is discussed, along with the strategies for studying such effects in dedicated simulations."http://deepblue.lib.umich.edu/bitstream/2027.42/64214/1/jpconf8_119_032010.pd

    Escherichia coli induces apoptosis and proliferation of mammary cells

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    Mammary cell apoptosis and proliferation were assessed after injection of Escherichia coli into the left mammary quarters of six cows. Bacteriological analysis of foremilk samples revealed coliform infection in the injected quarters of four cows. Milk somatic cell counts increased in these quarters and peaked at 24 h after bacterial injection. Body temperature also increased, peaking at 12 h postinjection, The number of apoptotic cells was significantly higher in the mastitic tissue than in the uninfected control. Expression of Bax and interleukin-1 beta converting enzyme increased in the mastitic tissue at 24 h and 72 h postinfection, whereas Bcl-2 expression decreased at 24 h but did not differ significantly from the control at 72 h postinfection, Induction of matrix metalloproteinase-g, stromelysin-1 and urokinase-type plasminogen activator was also observed in the mastitic tissue. Moreover, cell proliferation increased in the infected tissue, These results demonstrate that Escherichia coli-induced mastitis promotes apoptosis and cell proliferation

    Effects of shift work on the eating behavior of police officers on patrol

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    Recent studies indicate that the timing of food intake can significantly affect metabolism and weight management. Workers operating at atypical times of the 24-h day are at risk of disturbed feeding patterns. Given the increased risk of weight gain, obesity and metabolic syndrome in shift working populations, further research is required to understand whether their eating behavior could contribute to these increased metabolic risks. The objective of this study was to characterize the dietary patterns of police officers across different types of shifts in their natural environments. Thirty-one police officers (six women; aged 32.1 +/- 5.4 years, mean +/- SD) from the province of Quebec, Canada, participated in a 28- to 35-day study, comprising 9- to 12-h morning, evening, and night shifts alternating with rest days. Sleep and work patterns were recorded with actigraphy and diaries. For at least 24 h during each type of work day and rest day, participants logged nutrient intake by timestamped photographs on smartphones. Macronutrient composition and caloric content were estimated by registered dieticians using the Nutrition Data System for Research database. Data were analyzed with linear mixed effects models and circular ANOVA. More calories were consumed relative to individual metabolic requirements on rest days than both evening- and night-shift days (p = 0.001), largely sourced from increased fat (p = 0.004) and carbohydrate (trend, p = 0.064) intake. Regardless, the proportions of calories from carbohydrates, fat, and protein did not differ significantly between days. More calories were consumed during the night, between 2300 h and 0600 h, on night-shift days than any other days (p < 0.001). Caloric intake occurred significantly later for night-shift days (2308 h 0114 h, circular mean +/- SD) than for rest days (1525 h +/- 0029 h; p < 0.01) and was dispersed across a longer eating window (13.9 h 3.1 h vs. 11.3 h +/- 1.8 h, mean +/- SD). As macronutrient proportions were similar and caloric intake was lower, the finding of later meals times on night-shift days versus rest days is consistent with emerging hypotheses that implicate the biological timing of food intake-rather than its quantity or composition-as the differentiating dietary factor in shift worker health.Circadian clocks in health and diseas

    Distribution and symmetrical patellofemoral pain patterns as revealed by high-resolution 3D body mapping:a cross-sectional study

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    Abstract Background Detailed pain mapping of extent and distribution in individuals with patellofemoral pain (PFP) within and around a complex structure such as the knee has yet to be explored. Methods Perceptions of on-going pain from adolescents and young adults (N = 35) with long-standing (>10 months) PFP were collected on high-resolution 3D digital body-schema of the knees. Location, area of pain, pain intensity, laterality, worse side of knee pain, symptom duration, and symmetry in bilateral knee pain were recorded. A threshold for naturally occurring variations in symmetrical knee pain drawings were collected from 18 healthy controls and used in combination with the development a symmetry index (0–1) to create a fuzzy rule for classifying symmetrical and non-symmetrical PFP patterns as compared to a PFP expert. The symmetry index was computed and tested using a correlation coefficient alone or in combination with the Jaccard index and the true and false positive rates (TPR and FPR, respectively) determined. Results The peripatellar region was the common report of pain location however, novel and nonconforming PFP patterns were identified and the majority of individuals (22 of 27) with bilateral PFP expressed highly-symmetric mirror-image pain. Individuals with symptom duration of 5 years or more had a greater area of pain, compared to those with symptoms for less than 5 years. The total area of pain was correlated to symptom duration for those with extended symptoms durations and a progression towards an “O” shaped pattern emerged. A TPR of 100% for identifying symmetrical knee pain patterns was found however the expert PFP tended to be stricter, as reflected in FPR of 20%. Conclusions A high proportion of PFP patterns or symptoms occur in mirrored locations and are exceptionally symmetrical, and long duration of symptoms appear to converge to an ‘O’ shape. Classifying symmetrical pain patterns is subjective however simple fuzzy rules and correlations can be used to increase objectivity. This study highlights a gap in knowledge of PFP symptom presentation, reveals what may be a natural progression of symptoms, and provides valuable clinical insight for both pain management and treatment
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