237 research outputs found

    Force distribution in a scalar model for non-cohesive granular material

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    We study a scalar lattice model for inter-grain forces in static, non-cohesive, granular materials, obtaining two primary results. (i) The applied stress as a function of overall strain shows a power law dependence with a nontrivial exponent, which moreover varies with system geometry. (ii) Probability distributions for forces on individual grains appear Gaussian at all stages of compression, showing no evidence of exponential tails. With regard to both results, we identify correlations responsible for deviations from previously suggested theories.Comment: 16 pages, 9 figures, Submitted to PR

    IL‐4 induces proliferation in prostate cancer PC3 cells under nutrient‐depletion stress through the activation of the JNK‐pathway and survivin up‐regulation

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    Interleukin (IL)‐4 plays a critical role in the regulation of immune responses and has been detected at high levels in the tumor microenvironment of cancer patients where it correlates with the grade of malignancy. The direct effect of IL‐4 on cancer cells has been associated with increased cell survival; however, its role in cancer cell proliferation and related mechanisms is still unclear. Here it was shown that in a nutrient‐depleted environment, IL‐4 induces proliferation in prostate cancer PC3 cells. In these cells, under nutrient‐depletion stress, IL‐4 activates mitogen‐activated protein kinases (MAPKs), including Erk, p38, and JNK. Using MAP‐signaling‐specific inhibitors, it was shown that IL‐4‐induced proliferation is mediated by JNK activation. In fact, JNK‐inhibitor‐V (JNKi‐V) stunted IL‐4‐mediated cell proliferation. Furthermore, it was found that IL‐4 induces survivin up‐regulation in nutrient‐depleted cancer cells. Using survivin‐short‐hairpin‐RNAs (shRNAs), it was demonstrated that in this milieu survivin expression above a threshold limit is critical to the mechanism of IL‐4‐mediated proliferation. In addition, the significance of survivin up‐regulation in a stressed environment was assessed in prostate cancer mouse xenografts. It was found that survivin knockdown decreases tumor progression in correlation with cancer cell proliferation. Furthermore, under nutrient depletion stress, IL ‐4 could induce proliferation in cancer cells from multiple origins: MDA‐MB‐231 (breast), A253 (head and neck), and SKOV‐3 (ovarian). Overall, these findings suggest that in a tumor microenvironment under stress conditions, IL‐4 triggers a simultaneous activation of the JNK‐pathway and the up‐regulation of survivin turning on a cancer proliferation mechanism. J. Cell. Biochem. 113: 1569–1580, 2012. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90542/1/24025_ftp.pd

    Cost-effective approach to lung cancer risk for a radiological dispersal device (RDD) scenario

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    A release of radioactive material into the environment can lead to hazardous exposure of the population and serious future concerns about health issues such as an increased incidence of cancer. In this context, a practical methodology capable of providing useful basic information from the scenario can be valuable for immediate decisions and future risk assessment. For this work, the simulation of a radiological dispersal device (RDD) filled with americium-241 was considered. The radiation dose simulated by the HotSpot code was used as an input to the epidemiological equations from BEIR V producing the data used to assess the risk of lung cancer development. The methodology could be useful in providing training for responders aimed to the initial support addressed to decision-making for emergency response at the early phase of an RDD scenario. The results from the simulation allow estimating (a) the size of the potentially affected population, (b) the type of protection action considering gender and location of the individuals, (c) the absorbed doses, (d) the matrix of lung cancer incidence predictions over a period of 5 years, and (e) the cost-effectiveness in the initial decision environment

    A systematic review of physiological reactivity to stimuli in autism

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    Objective: The prevalence of abnormal behavioural responses to a variety of stimuli among individuals with autism has led researchers to examine whether physiological reactivity is typical in this population. The current paper reviewed studies assessing physiological reactivity to sensory, social and emotional, and stressor stimuli in individuals with autism. Methods: Systematic searches of electronic databases identified 57 studies that met our inclusion criteria. A novel measure of methodological quality suitable for use with non-randomised, non-interventional, psychophysiological studies was also developed and applied. Results: Individuals with autism were found to respond differently than typically developing controls in 78.6%, 66.7%, and 71.4% of sensory, social and emotional, and stressor stimulus classes, respectively. Conclusions: Individual differences in physiological reactivity are clearly present in autism, suggesting additional research is needed to determine the variables relating to physiological reactivity among those with ASD and to examine the possibility of physiological subtype responders in this population

    Increasing HPV Vaccination in a Network of Pediatric Clinics using a Multi-component Approach

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    Background: Despite continued public health efforts to increase human papillomavirus (HPV) vaccination among adolescents, initiation remains below the level needed to reach the Healthy People 2020 goal of 80% series completion by age 13. Methods: We developed, implemented, and evaluated a multi-component program that used evidence-based strategies to increase HPV vaccine initiation in a network of 51 pediatric clinics in Houston, Texas. Our target populations were the clinic network, healthcare providers, male and female patients ages 11-17, and their parents. The program, called the Adolescent Vaccination Program (AVP), was conducted from March 2016 through March 2019 and contained strategies to increase vaccination including: HPV immunization champions; provider assessment and feedback; provider continuing education; provider reminders; and patient reminders. We used a single group pre/post design with an external comparison – NIS-Teen. Our primary outcome was initiation of the HPV vaccine based on the electronic health record. We used interrupted time series analysis (ITSA) to measure change in initiation over time. We calculated monthly, quarterly, and annual rates of initiation for each physician, clinic, and the network. We examined patterns of initiation by patient age, sex, race/ethnicity, and type of insurance. Results: By the end of the project, the 51 clinics averaged 77.4% initiation. Rates increased annually from September 2015 through March 2019. ITSA analysis over 75 months showed an increase in vaccine initiation of 0.396% per month from the introduction of the program in March 2016. Average individual clinic improvement was 0.37% per month ranging from -0.04% to 0.68% through March 2019. Data for the 11-12 year olds, the target age group for initiating the vaccine, showed a greater percentage increase (54.2%) compared with the 13-17 year olds (29.6%). Hispanics and African Americans had the highest initiation rates in all years while non-Hispanic whites had the lowest. Families without insurance had the lowest rates while those with Medicaid/Medicare had the highest. Conclusions: We observed a secular trend upward in both the network and NIS-Teen data; however, the network showed a steeper increase. The AVP is a promising program of strategies to increase HPV vaccination in a clinic setting

    Composition of UHECR and the Pierre Auger Observatory Spectrum

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    We fit the recently published Pierre Auger ultra-high energy cosmic ray spectrum assuming that either nucleons or nuclei are emitted at the sources. We consider the simplified cases of pure proton, or pure oxygen, or pure iron injection. We perform an exhaustive scan in the source evolution factor, the spectral index, the maximum energy of the source spectrum Z E_{max}, and the minimum distance to the sources. We show that the Pierre Auger spectrum agrees with any of the source compositions we assumed. For iron, in particular, there are two distinct solutions with high and low E_{max} (e.g. 6.4 10^{20} eV and 2 10^{19} eV) respectively which could be distinguished by either a large fraction or the near absence of proton primaries at the highest energies. We raise the possibility that an iron dominated injected flux may be in line with the latest composition measurement from the Pierre Auger Observatory where a hint of heavy element dominance is seen.Comment: 19 pages, 6 figures (33 panels)- Uses iopart.cls and iopart12.clo- In version 2: addition of a few sentences and two reference

    Impaired expression of metallothioneins contributes to allergen-induced inflammation in patients with atopic dermatitis

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    Regulation of cutaneous immunity is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance versus inflammation in atopic dermatitis, we utilise a human in vivo allergen challenge study, exposing atopic dermatitis patients to house dust mite. Here we analyse transcriptional programmes at the population and single cell levels in parallel with immunophenotyping of cutaneous immunocytes revealed a distinct dichotomy in atopic dermatitis patient responsiveness to house dust mite challenge. Our study shows that reactivity to house dust mite was associated with high basal levels of TNF-expressing cutaneous Th17 T cells, and documents the presence of hub structures where Langerhans cells and T cells co-localised. Mechanistically, we identify expression of metallothioneins and transcriptional programmes encoding antioxidant defences across all skin cell types, that appear to protect against allergen-induced inflammation. Furthermore, single nucleotide polymorphisms in the MTIX gene are associated with patients who did not react to house dust mite, opening up possibilities for therapeutic interventions modulating metallothionein expression in atopic dermatitis

    Facilitative parenting and children's social, emotional and behavioural adjustment

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    Facilitative parenting (FP) supports the development of children’s social and emotional competence and effective peer relationships. Previous research has shown that FP discriminates between children bullied by peers from children who are not bullied, according to reports of teachers. This study investigates the association between FP and children’s social, emotional and behavioral problems, over and above the association with dysfunctional parenting (DP). 215 parents of children aged 5–11 years completed questionnaires about parenting and child behavior, and children and teachers completed measures of child bullying victimization. As predicted, FP accounted for variance in teacher reports of children’s bullying victimization as well as parent reports of children’s social and emotional problems and prosocial behavior better than that accounted for by DP. However for children’s reports of peer victimization the whole-scale DP was a better predictor than FP. Contrary to predictions, FP accounted for variance in conduct problems and hyperactivity better than DP. When analyses were replicated substituting subscales of dysfunctional and FP, a sub-set of FP subscales including Warmth, Supports Friendships, Not Conflicting, Child Communicates and Coaches were correlated with low levels of problems on a broad range of children’s adjustment problems. Parent–child conflict accounted for unique variance in children’s peer victimization (teacher report), peer problems, depression, emotional problems, conduct problems and hyperactivity. The potential relevance of FP as a protective factor for children against a wide range of adjustment problems is discussed
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