text:
Asthma and gender impact accumulation of T cell subtypes
- Matthew J Loza1_946Email author,
- Susan Foster1_946,
- Eugene R Bleecker1_946,
- Stephen P Peters1_946 and
- Raymond B Penn1_946Email author
© The Author(s) 2010
Received: 30 April 2010
Accepted: 28 July 2010
Published: 28 July 2010
The "Th2 hypothesis for asthma" asserts that an increased ratio of Th2:Th1 cytokine production plays an important pathogenic role in asthma. Although widely embraced, the hypothesis has been challenged by various empirical observations and has been described as overly simplistic. We sought to establish whether CD3+CD28-mediated and antigen-independent accumulation of type 1 and type 2 T cells differs significantly between nonasthmatic and asthmatic populations.
An ex vivo system was used to characterize the regulation of IFN-γ-producing (type 1) and IL-13-producing (type 2) T cell accumulation in response to CD3+CD28 and IL-2 stimulation by flow cytometry.
IL-13-producing T cells increased in greater numbers in response to antigen-independent stimulation in peripheral blood lymphocytes from female atopic asthmatic subjects compared with male asthmatics and both male and female atopic non-asthmatic subjects. IFN-γ+ T cells increased in greater numbers in response to either antigen-independent or CD3+CD28-mediated stimulation in peripheral blood lymphocytes from atopic asthmatic subjects compared to non-asthmatic subjects, regardless of gender.
We demonstrate that T cells from asthmatics are programmed for increased accumulation of both type 2 and type 1 T cells. Gender had a profound effect on the regulation of type 2 T cells, thus providing a mechanism for the higher frequency of adult asthma in females.
Asthma is frequently labeled a "Th2-like" disorder, based on an inflammatory profile in the asthmatic airway and is characterized by preferential elaboration of Th2 T cells and their cytokines [1–3]. After allergen challenge, elevated levels of the type 2 cytokines interleukin (IL)-4 and IL-13 are found in the airways of asthma subjects, associated with an influx of type 2 cells and eosinophils [1–3]. The preponderance of IL-4 and IL-13 relative to the type 1 cytokine IFN-γ is believed to promote feed-forward mechanisms of allergic inflammation in asthma. However, several observations suggest that the "Th2 hypothesis" as applied to asthma is overly simplistic. Although the ratio of type 2 cytokines to interferon (IFN)-γ is higher in asthmatics than in non-asthmatic subjects, levels of both cytokines are often dramatically increased in allergen-challenged asthmatics [4, 5]. Respiratory infections, known to induce IFN-γ levels, have been proposed to protect against asthma development but also induce or worsen exacerbations in subjects with established asthma [1, 4, 6–8]. A number of studies also suggest that IFN-γ is important in the survival and activation of eosinophils [9, 10].
Numerous factors regulate the accumulation of T cell subsets. Trafficking of T cells to sites of inflammation (e.g. to the airways in lungs), from peripheral blood and lymphoid tissues is one important regulatory component. Reduced numbers of regulatory T cells are hypothesized to influence allergen-specific increases in type 2 T cells in asthmatics [11]. The presence of regulatory stimuli and how T cell numbers increase in response to both antigenic and non-antigenic stimuli also determine absolute and relative numbers of type 1 and type 2 cells. Studies to date examining mixed T cell populations in vitro have characterized the effects of both antigenic, CD3-mediated and antigen-independent, bystander (e.g., IL-2, IL-15) stimuli, as well as "polarizing" effectors (IL-4, IL-12) on changes in T cell subset accumulation [12–14]. Whether T cells from asthmatics exhibit distinct regulatory features is not known.
To address this question we compared the regulation of T cell subtype accumulation in T cells obtained from both atopic asthmatic and non-asthmatic subjects. Our results reveal that under various conditions T cells from asthmatics appear programmed for increased accumulation of both type 2 and type 1 cells, and surprisingly, gender plays a role in the regulation of type 2 cells.
Subject populations
Peripheral venous blood was obtained from nonasthmatic (control) and atopic asthmatic human adults after informed consent was provided, in accordance with a Wake Forest University School of Medicine Institutional Review Board-approved protocol and the Helsinki Declaration. The criteria for being included in the atopic asthmatic population are provided in Additional File 1. All subjects refrained from taking asthma control medications at least 12 h prior to blood draw. Characteristics of asthmatic subjects studied in this work are presented in Table S1 in Additional File 1. Control subjects were healthy adults who had not been diagnosed or treated for asthma. All female control subjects, but <25% of male controls, underwent clinical testing to: 1) rule out asthma (history of symptoms, reversibility of FEV1 decrement, airway hyperresponsiveness as assessed by methacholine challenge, exclusion of other respiratory disorders); and 2) evaluate atopy by skin prick test to a panel of standard common aeroallergens. For some subjects, certain outcomes were not included in analyses because of missing data resulting from insufficient cell numbers.
Cell culture
Peripheral blood lymphocytes (PBL), isolated by standard procedures [15] (>98% lymphocytes, as assessed by flow cytometry), were cultured in RPMI-1640 media supplemented with 5% pooled human plasma. Before culture (day 0), after 5-d culture with 50 U/ml recombinant human IL-2 + IL-12-neutralizing monoclonal antibody (αIL-12) + CD28 monoclonal antibody + CD3 monoclonal antibody (plate-bound), or after 6-d culture with 50 U/ml IL-2 + IL-12-neutralizing monoclonal antibody, cells were collected and assessed for viability and cell numbers with an automated cell counter (ViCell, BeckmanCoulter). Anti-IL-12 mAb was included to exclude any influence of IL-12 potentially released from the few contaminating monocytes (see Loza et al. [16]). For "TH2-polarized" cultures, 50 U/ml IL-2, 5 ng/ml IL-4 and IL-12-neutralizing monoclonal antibody were included in the CD3+CD28-stimulated cultures described above. For "TH1-polarized" cultures, 50 U/ml IL-2, 2 ng/ml IL-12, and TNF-α-neutralizing monoclonal antibody were included in the CD3+CD28-stimulated cultures described above (but without IL-12-neutralizing monoclonal antibody). See Additional File 1 for additional details about culture conditions.
Cytokine production
After culture and counting an aliquot of cells, 2-4 × 106 cells/250 μl were stimulated for cytokine production (5-h with 2nM phorbol myristate acetate (PMA), 0.2 μg/ml calcimycin, 100 U/ml IL-2, 5 μM monensin). Intracellular IL-13 and IFN-γ accumulation by T cells was detected by immunofluorescence-flow cytometry as previously described [12, 17]. Proportions of cytokine producing cells were analyzed within T cells, gated based on a standard viable forward and side scatter lymphocyte gate and staining for CD3/CD5. Analysis of IL-4, IL-5, and IL-10 was not included in the study because the proportion of positive-expressing cells in freshly PBL was too low (0.4%) to accurately assess in the majority subjects, including asthmatics (not shown).
Analysis of proliferation and progenitor numbers
The number of divisions that IL-13+ and IFN-γ+ T cell progenitors undergo during culture was determined by analysis of carboxyfluorescein diactetate succinimydl ester (CFSE) dilution in CFSE-labeled PBL from female control and female asthmatic subjects, as previously described (12). Average division numbers and minimum progenitor numbers were calculated for experiments of CFSE-labeled PBL as described previously [12, 15]. See Additional File 1 for details of CFSE analyses.
Statistical analyses
Distributions of non-normalized data sets were significantly non-Gaussian. Therefore, significance of differences in medians between non-normalized data sets was tested with Mann-Whitney tests (two-tailed). Analyses of accumulation of cytokine+ T cell subsets in culture were performed on data normalized as a percent of the respective day 0 values (day 0 = 100%) because of the variability in the absolute proportions of day 0 cytokine+ T cells. Normalized data were log-transformed to obtain approximate normality of distribution. Significance of differences in transformed (geometric) means was tested by Student's t-tests (two-tailed, corrected for unequal variances). Significance of gender and asthma status on accumulation was tested by 2-way General Linear Model analyses, with up to 2-way interaction model and planned Tukey-Kramer multiple comparison tests. Statistical analyses were performed using GraphPad Prism (4.0.3; San Diego California USA, http://www.graphpad.com) and Number Cruncher Statistical Systems (NCSS, 2004; J. Hintze, Kaysville, Utah, http://www.NCSS.com) software.
Type 1 and type 2 T cell subsets in freshly isolated PBL
In freshly isolated human PBL, distinct subsets of T cells are capable of producing IL-13 (IL-13+) and IFN-γ (IFN-γ+). The median proportions of IL-13+ and IFN-γ+ T cells did not differ significantly between non-asthmatic (control) and atopic asthmatic (asthmatic) subjects (IL-13+: 0.8%, interquartile ranges (IQR): 0.5 - 2.1%, n = 21; and 0.9%, IQR: 0.5 - 2.5%, n = 25, respectively; p = 0.56); IFN-γ+: (8.4%, IQR: 2.2 - 13.5, n = 20; and 5.4%, IQR: 2.7 - 14.0, n = 25, respectively; p = 0.71).
Accumulation of type 1 and type 2 T cell subsets
CD3+CD28-mediated stimulation
Proportions of IL-13+ and IFN-γ+ T cells after culture.
Stimulus *
Median †
p ‡
0.6 - 4.3
0.5 - 4.2
0.6 - 7.8
5.1 - 20.2
0.7 - 3.2
2.5 - 5.3
2.4 - 10.3
7.2 - 24.2
IL-4, IL-12 polarization effects
IL-2 stimulated accumulation
Gender effects on T cell subset accumulation
Race and gender may contribute to asthma risk, with asthma being more common in African Americans than in Caucasians (National Center for Health Statistics. Asthma: http://www.cdc.gov/nchs/fastats/asthma.htm. CDC. 2006), and, in adult asthmatics, more common in pre-menopausal females than in males (reviewed by Balzano et al. [18]). The asthma population used in this study consisted of 60% Caucasian and 40% African-Americans, and 55% females and 45% males. All data were analyzed to consider the cofactors of race and gender. There was no difference between Caucasian and African American asthmatics in accumulation (IL-2- and CD3- stimulated) of IL-13+ or IFN-γ+ T cells, and both Caucasian and African American asthmatic groups showed greater accumulation of IL-2-stimulated accumulation of IL-13+ and IFN-γ+ T cells compared to Caucasian controls (not shown). The number of African American control subjects was not sufficient to enable comparisons between racial groups in control subjects.
All but one of the female control subjects were atopic, as determined by skin prick tests to a panel of common aeroallergens. The differences between female asthmatics and female controls remained significant (p < 0.001) when excluding the one nonatopic female control subject (not shown). Skin prick tests were performed on only 6 of the male control subjects, all of whom tested positive. The mean increase in IL-13+ T cells remained similar for atopic nonasthmatic males compared to atopic nonasthmatic females, as observed for the main analysis not restricted by atopy status (not shown). These results demonstrate that the observed associations for asthma- and gender-specific increases in IL-13+ T cells is a function of atopic asthma per se, rather than a function of atopy status alone.
The difference in IL-2-stimulated accumulation of IL-13+ and IFN-γ+ T cells between female and male asthmatics remained significant when data from lung function studies (e.g., methacholine PC20, percent predicted FEV1, % reversal in FEV1 by albuterol, percent predicted forced vital capacity (FVC), FVC/FEV1) and other factors (age, serum IgE, body mass index) were considered as covariates in GLM analyses (not shown). These covariates were not included in the final GLM models because none of these variables significantly differed between male and female asthmatics, nor correlated with extent of T cell subset accumulation (see Table S1 in Additional File 1). For CD3+CD28-stimulated accumulation of IL-13+ T cells, there was a significant difference between male and female subjects overall (p = 0.0001) and within asthmatic (p < 0.01) and control (p < 0.03) populations, but not between asthma and control populations within the same gender. An influence of gender on CD3+CD28-stimulated accumulation of IFN-γ+ T cells was not detected.
Lack of influence of inhaled corticosteroids
Impact of regular inhaled corticosteroid use on T cell subset accumulation.
Culture stimulus
T cell subset
Asthma group
Accumulation, % of day 0 numbers *
p-value †
Steroid •
Geo. Mean
Geo. Mean ± S.D.
326 - 1184
342 - 1280
73 - 184
155 - 525
229 - 1994
69 - 420
101 - 423
21 - 1415
571 - 3,201
393 - 1,094
204 - 738
886 - 15,702
241 - 1,982
396 - 2,707
36 - 962
To confirm that asthma status, and not differences in steroid use, determines the increased accumulation of IL-13+ and IFN-γ+ T cells, female asthmatics and controls were compared, restricting the analysis to those subjects that do not use inhaled steroids. The significance levels for differences between female asthmatics and controls for IL-2-stimulated accumulation of IL-13+ and IFN-γ+ T cells and CD3+CD28-stimulated accumulation of IL-13+ and IFN-γ+ T cells were p = 0.0003, 0.08, 0.006, and 0.004 respectively (data not shown). Overall these data suggest that regular steroid use before the 12-h withdrawal of asthma-control medications do not impact the significance of the findings in this study.
Mechanisms mediating differences in accumulation
The theoretical maximum increase in IL-13+ T cells expected during culture, on the assumption that no IL-13+ T cells are lost (via apoptosis or differentiation), can be calculated as 2average division number. The actual increase in the number of IL-13+ T cells from control subjects was 87 ± 14% lower (n = 6) than the theoretical maximum increase; the actual increase in IL-13+ T cells from asthmatics was 43 ± 35% lower (n = 6) than the theoretical maximum, significantly lower than that for control subjects (p = 0.03). These data indicate that during culture there are losses of the progenitors of IL-13+ T cells, and that this loss of progenitors is greater in female control subjects than in female asthmatics (Figure 5B). Indeed, in cultures derived from female asthmatics, few IL-13+ T cell progenitors are lost--approximately one-quarter the loss of progenitors that occurs for control subjects. There were no significant differences between male asthmatics and male controls (and male and female controls overall) for any of these CFSE-derived parameters (not shown). Therefore, reduced loss of IL-13+ T cells rather than increased proliferation is responsible for increased accumulation of IL-13+ T cells in PBL from female asthmatics.
IFN-γ+ T cells from asthmatics did not proliferate more than those from control subjects (Figure 5B). The majority (~80%) of IFN-γ+ T cell progenitors from control subjects were lost during culture of PBL from control subjects. As with IL-13+ T cells, the loss of IFN-γ+ T cell progenitors is significantly reduced in asthmatic subjects. Therefore, the increased accumulation of the IFN-γ+ T cell subset from asthmatics, relative to control subjects, is a function of increased maintenance of T cell subset progenitors rather than enhanced proliferation.
Our study provides the first evidence to date that T cells from atopic asthmatic and nonasthmatic control subjects differ in their accumulation of T cell subsets in response to CD3+CD28-mediated and antigen-independent stimulation. Moreover, gender plays a significant role in determining these responses in type 2 T cell accumulation.
IL-2 stimulated increases in IL-13+ T cells were significantly higher in PBL from asthmatics than in PBL from control subjects, and this increase is almost totally attributable to the female population of asthmatics studied. That the increased accumulation of IL-13+ T cells was observed in female but not male asthmatics, and the association was maintained when analysis was restricted to only atopic subjects, indicates that the effect was a function of asthma and not atopy per se. Whether there is also an effect of atopy per se on accumulation of IL-13+ T cells should be tested next, by comparing nonatopic nonasthmatic and atopic nonasthmatic healthy control subjects. CD3+CD28-stimulated accumulation of IL-13+ T cells was also greater in female subjects, but was not influenced by asthma status. IFN-γ+ T cell accumulation, when stimulated by either CD3+CD28 or IL-2, was significantly greater in cells from asthmatics relative to controls, with no effect of gender. Interestingly, in "Th1-polarizing" conditions including IL-12, IFN-γ+ T cells increased to similar extents in both asthma and control groups. We would hypothesize that the impact of IL-12 is partially redundant. In cultures with IL-12, existing IFN+ cells survive to a greater extent than in the absence of IL-12 for controls, but in asthmatics survival is already near its maximal limit so as to not be further increased by IL-12.
Unlike the majority of T cells (IL-13- and IFN-γ+ subsets), IL-13+ T cells increase in number and proportion when stimulated with IL-2, even in the absence of antigenic stimulation. This accumulation occurs via selective proliferation of the IL-13+ T cell subset [12, 15]. In female asthmatic subjects, IL-13+ T cells accumulate to even greater numbers, with about a 4-fold greater increase than that observed in female control and male asthmatic subjects. CFSE analyses demonstrate the mechanism is not by a further increase in IL-2-stimulated proliferation, but rather via a reduction in the loss of IL-13+ T cells during culture.
Our data demonstrating enhanced accumulation of not only IL-13+ but also IFN-γ+ T cells from asthmatic subjects in response to IL-2 suggest the importance of antigen-independent stimulation of T cells in asthma. Cytokine-stimulated (bystander) accumulation of T cells may potentially explain allergen-independent sensitization in asthmatics, e.g., respiratory infection leading to an IL-2- or IL-15-induced proliferation of resident memory, viral antigen-non-specific, allergen-specific type 2 T cells, conditions which have been speculated to be relevant to the development of asthma [19]. Viral infections have been implicated in asthma pathogenesis and exacerbations by numerous epidemiologic studies, although limited mechanistic insight exists [1, 3, 4, 7, 8]. Pathogens (bacteria, virus) induce cytokine production by monocytes, macrophages, and dendritic cells (i.e., monocytic cells). Tissue damage (e.g., products of necrotic cells; endothelins released by endothelia or epithelia, platelet-derived factors), independent of pathogen infection, can also induce cytokine production by monocytic cells [20, 21]. IL-15, a cytokine produced by monocytic cells, is capable of inducing antigen-independent, bystander proliferation of IL-13+ T cells (unpublished observations). These bystander events need not necessarily take place in the airways. They may also occur in the lymph nodes that drain the lungs where both previously activated memory cells and naïve, type 2 T cells could either be increased in number prior to being stimulated by allergen or trafficking to the lungs. Thus, although starting numbers of IL-13+ T cells did not significantly differ between asthmatics and non-asthmatics, enhanced bystander accumulation of type 2 T cells may nevertheless lead to an acute increase in numbers of IL-13+ T cells in asthmatics during allergen- or pathogen- induced immune responses.
Increased accumulation of both IL-13+ and IFN-γ+ in asthmatics contradicts the Th2 hypothesis of asthma, yet is consistent with observations of IFN-γ being elevated (with type 2 cytokines) in some asthmatics [4, 5]. It has been suggested that microbial infections can contribute to the development of allergic asthma, as well as to exacerbations in subjects with established asthma [1, 3, 4, 7, 8]. In asthmatic compared to nonasthmatic subjects, microbe-specific IFN-γ+ T cells can increase to greater numbers during infection. Additionally, non-microbe specific IFN-γ+ T cells could also increase in asthmatics, potentially increasing any allergen-specific IFN-γ+ T cells as well. An acute increase in IFN-γ production during an allergic reaction, or reaction to microbial infection, could exacerbate inflammation in asthmatics by increasing the recruitment and activation of immune cells [6].
The mechanism contributing to gender differences in IL-13+ T cell accumulation is unclear. Between post-puberty and pre-menopause years, females have a higher incidence of developing asthma than males (reviewed by Balzano et al. [18]). However, during pre-puberty, asthma development tends to occur somewhat more frequently in boys. A portion of adult, asthmatic women also experience perimenstrual worsening of asthma symptoms [22]. These observations suggest the involvement of female sex hormones in the increased accumulation of IL-13+ T cells. Potential explanations for enhanced IL-13+ T cell accumulation selectively in female asthmatics is an interaction between high levels of female sex hormones and the asthma/atopic environment or asthma/atopy susceptibility genetic polymorphisms. The effects of gender and asthma on IL-13+ T cells could be either from epigenetic, developmental imprinting from continuous hormone exposure, or, alternatively, from acute stimulation by hormones before blood draw. Interestingly, increased accumulation of IL-13+ T cells under CD3+CD28-stimulatory conditions was also observed in females, but was in this case independent of asthma status. It is tempting to speculate if hormonal-driven epigenetic changes to IL-13+ T cells in females may have broader consequences for susceptibility to type 2 T cell-associated autoimmune diseases that predominantly occur in females, e.g., lupus and multiple sclerosis.
Decreased numbers of regulatory T cells have been hypothesized to contribute to the development of asthma [11]. Corticosteroid use is suggested to decrease the development of adaptive IL-10-producing TR1 regulatory T cells [11]. Perhaps female sex hormones may also contribute to decrease TR1 development and subsequent hyperresponsiveness of IL-13+ T cells in female asthmatics. The main mechanism described for inhibition of T cell accumulation by regulatory T cells is inhibition of proliferation. Increased accumulation of IL-13+ and IFN-γ+ T cells in asthmatics resulted from decreased loss of cytokine+ cells rather than increased proliferation relative to controls. Also, increased accumulation of IL-13+ T cells in female asthmatics was observed only for the IL-2-stimulated condition and not the CD3+CD28-mediated condition. For these reasons it seems less likely that differences in regulatory T cells account for the observed increased accumulation of T cell subsets in asthmatics.
In conclusion, our data demonstrate that both type 1 and type 2 T cell subsets increase to a greater extent in asthmatic than control subjects in response to antigen-independent, cytokine-mediated stimulation, with the increased accumulation of type 2 T cells exclusively in female asthmatics. These results provide explanations for the higher frequency of adult asthma in females and for the apparently paradoxical increase of both IFN-γ and IL-13 in the lungs of a subset of allergen-challenged asthmatics.
analysis of covariance
carboxyfluorescein diactetate succinimydl ester
forced expiratory volume at 1-sec
forced vital capacity
General Linear Model
interquartile range
peripheral blood lymphocytes
provocative concentration of methacholine causing 20% fall in FEV1
phorbol myristate acetate
percent predicted
This manuscript is dedicated to the memory of Dr. Bice Perussia, without whom this study would never have originated. This work was supported in part by grants from the National Institute of Health (HL58506 to R.B.P. and HL69167 to E.R.B.). The funding bodies played no role in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. The authors declare no conflicting financial interests.
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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text:
Listening to Aza Raskin talk about the future of the web makes you realise how clunky it is right now.
Why does it take 12 steps or more to translate a piece of text when you're reading something in another language on the browser? Why do we have to have countless identities on different websites and remember passwords and usernames from each?
Why do we have to navigate through different calendars and applications when we're trying to find contact information?
These are the kinds of problems that Mozilla Labs is trying to solve. As the experimental arm of the company that brings us the ever-popular Firefox browser, Mozilla Labs is about 'imagining the future of the web and then building it together'.
By 'together' Mozilla means the thousands of volunteers around the world who work with a small staff in Mountain View, California, to iteratively develop new features for the browser.
Mozilla is unique in many ways. The company is competing with organisations like Apple and Microsoft (Firefox is the second biggest browser after Internet Explorer) but it has only about 250 employees.
It is able to compete effectively by being really close to its users. For every one employee, there are ten volunteers that, in turn, serve at least one million users. Raskin jokes that when you arrive at Mozilla they say: "Welcome. Here are your one million users. Please don't abuse them."
Mozilla is also unique in that the $75 million operation is a wholly-owned subsidiary of the non-profit Mozilla Foundation. This means that, according to Mitchell Baker, chair of the Mozilla Foundation: "We're motivated by our mission of promoting openness, innovation and opportunity on the web rather than business concerns like profits or the price of our stock (guess what: we don't even have stock)."
Small fry
A base of 400 000+ users of Mozilla Labs is tiny in comparison with Firefox's 320 million users, but Raskin says that if a product gains enough traction in the Labs community, it will be considered as a feature in future Firefox releases. Raskin believes that 'the future of the web is about participation' and that Mozilla is about 'imagining that anyone who uses a browser should be able to create the browser'.
It's in this spirit that Labs is experimenting with users in developing what it believes is the future of the web. "What does it mean when the browser understands who you are?" asks Raskin.
"Why can't the browser – which already knows who you are, already knows what sites you visit, already knows who your friends are – just deal with log on?"
This is what developers on the Weave project are working on. Weave aims to develop the browser's ability to 'broker rich experiences while increasing user control over their data and personal information'.
According to Raskin: 'When you go to sign up on a site, the browser could say, 'Hey, you're signing up for a new service, why not choose one of your ID cards here – incognito (the browser just makes something up for me because I'm never coming back here again), basic information (name and e-mail) or secure (everything about me for things like credit card transactions)'."
The Weave Sync prototype currently supports the synchronisation of bookmarks, browsing history, saved passwords and tabs across multiple browsers, so that your desktop, laptop and mobile phone can all work together.
"Your friends, your social graph," says Raskin, "are too important to have any one vendor control them. The browser knows who your friends are; it knows how you're connected to them – it can scrape this information from Friendster, MySpace, Twitter, LinkedIn."
Ubiquity is billed as 'a time-saving Firefox extension that simplifies common web activities by letting you give commands to Firefox'. The extension includes about 80 commands for speeding up common web activities (searching, translating, mapping, e-mailing, etc.), but also provides an API so you can write your own commands using Javascript.
Says Raskin: "As soon as you see an e-mail address box, the browser automatically detects it and can pull in an e-mail address, a Twitter address. I now own my data, I own my social graph, I don't have to depend on something like Facebook Connect because it's the browser that is my broker of trust, my insanely smart butler.
"With Google, you type what you want to find. With Ubiquity you type what you want to do. This enables you to drastically reduce the problem space and lets you be much more extensible."
"We're beginning to store a lot more of our important data in the cloud," says Raskin, "making it more and more likely that our data is going to escape somehow." He says that the way that Mozilla thinks about these problems is in turning technology problems into people problems.
"If the browser understands who our friends are, then we can turn these security problems into people problems. The browser can tell us that, 'If you're trying out a new website, then these three people who are your friends also use it so it's probably okay'."
Will the open web win?
Raskin is upbeat about the future of the web. "Before, when we wanted to add a map to Gmail," he says, "we had to wait for them to do it. Now we're in control." He believes that as the web moves towards this very modular functionality, it's possible for someone to make functionality for software instead of having to build the entire web app stack. "The browser is slowly getting closer to that web operating system we've been hearing about," says Raskin.
If this happens, and if Mozilla continues to iterate in collaboration with its users towards a web that is focused on what Raskin calls 'you-centric' browsing, then we may all just end up winning.


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Lawn Army Miami
Lawn Care Service
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Have you always adored the beautifully manicured lawns of your neighbor and wonder why you cannot have the same at your place? You do not have to live with such problems because Lawn Army is here to resolve it for you.
Our company specializes in reinventing lawns and yards which seem to lack life. We are here to join you in your quest to beautify your home. We will help you from estimating, planning, decorating and maintaining your place. With our extensive list of products and services, achi
Lawn Army is dedicated to providing you with your needs when it comes to decorating and maintaining the lawn in your home or place of business. When you entrust your place to our company, you would not need to call anyone else. We will make sure that everything on your checklist is accomplished and cancelled out.
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In this article, I am going to disginguish the different types of mountain bikers. Once we have that cleared up, we will take a look at some training.
Welcome to the first installment of our newest feature, Sports Training 101. In it we bring you insights and suggestions geared toward tailoring a program to a specific sport or activity. We hope that our readers, especially the trainers, find it to be a valuable reference when constructing a program for a sport you are not intimately familiar with (yet). We're going to kick this feature off with one of the most popular and fastest growing sports, mountain biking.
For those of you who bike, we shine some light on how to integrate your strength training and riding programs. For those who haven't tried this sport yet – what are you waiting for? Hopefully this article will motivate you to get out and see some countryside. Either way, enjoy this first edition of Sports Training 101 and look for future installments …
The sport of mountain biking is many things. It is an adrenaline-charged buzz in


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Posted by Unmei on Saturday, July 5, 2014 at 8:26pm.
Of course not!
well I read that part of the book and I thought that's what it meant
Sojourner Truth escaped from slavery with your infant daughter. Why would she want her children to be slaves?
Read the assignment again -- and again -- if necessary.
. it provided more slaves for her owner


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Enhancing quality of pressure therapy services
Actual training for burn rehabilitation professionals in Central America officially began on October 5, 2013. For this year, the focus was on making pressure garment vest for women, the particularity of the vest being that it is perfectly adapted to women's anatomy, thus ensuring better fit and comfort. But because of this, it is also the most difficult type of garment to make.
Precision of measurement: Multiply the points of measurements to enhance precision in terms of size and fit.
The Sunshine team led participants through the first step for making pressure garments: measurement. Precise "anatomical landmarks" must be identified on the body, which is then measured in all possible lengths, widths and circumferences. Therapists are quite familiar with these landmarks, but for seamstresses, it takes some time to remember each landmark's name and position. And because there are more measures, this method also takes more time than the original method used by the seamstresses, but in the end it ensures better accuracy.
Adjustment of pressure: Use specific calculations to precisely add or reduce pressure given by the garment, depending on the scar status of the patient.
The second step is dreaded by both therapists and seamstresses alike: making the pattern. The idea of a pressure garment is to create pressure on scars and to do so, original measurements must be "shrunk" so that the garment fit more tightly. The seamstresses must first precisely calculate the shrinkage of the garment through various formulas, depending on how much pressure is required on the scar. Although necessary, this step can be intimidating, especially if you don't like math!
Tri-dimensional pattern: Special pattern techniques to create tri-dimensional garments that offer better fit and better coverage over the scars.
With their new numbers in hand, the seamstresses can then proceed to drawing the pattern of the garment. For the experienced therapist of Sunshine Foundation, drawing the pattern for a woman's vest might take 30 minutes but for the participants, it took two full days to learn all the steps of drawing the pattern. The reason why the process is so complex is that instead of making a "flat" garment with front and back pieces sewn together, we use many pieces to create a "tri-dimensional" garment that will fit better and provide better coverage on the scars.
The final step is sewing, and this is something the seamstresses are expert at! But there are still precise steps to follow to make sure that the garment is sewn correctly and fits well. The seamstress from Sunshine Foundation guided participants through the process, sharing tricks of the trade along the way.
Involvement of the therapist in the process: Ensure that burn rehabilitation knowledge is at the base of pressure therapy.
We can't emphasize enough how pressure garments are not just "tight fitting clothes" but are instead an integral part of the rehabilitation program of the burn survivor. As such, knowledge about burn rehabilitation (how burn scars evolve and mature, their impact on physical functions, etc.) is crucial when making the garment: it's the therapist that has the knowledge and skills to determine what kind of garment the patient needs, what level of pressure is adequate, etc. But in Central America, this heavy responsibility is almost entirely shouldered by the seamstress. That is why starting in 2012, we have expanded the training program to involve therapists who work as a team with the seamstresses throughout the whole training process, learning together the measurement and pattern-making steps. Therapists not only offer support to the seamstresses during the training, but this support also continues after they return to their country and face the difficult challenge of mastering and implementing the new techniques learned.
This kind of training is both physically and mentally demanding on participants because of the time involved, but also because of the amount of knowledge that must be absorbed. It is also demanding because it means that participants must leave aside their "old familiar" way of doing things and adopt "new unfamiliar" techniques. But participants have consistently told us that the effort is worth it and when they succeed in finishing their first garment, the sense of pride and accomplishment is their immediate reward.
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Want to see the cutest baby orangutan in the world? Well, get ready for this week's roundup of the best animal photos.
Not only do we have the adorable newborn from Madrid, but there are some great shots of young pronghorns, hungry hyena cubs, and even a baby anteater. Also, there are some great pics for you dog lovers out there.
Vote for your favorite photos, and let us know what you think in the comments!
Animal Photos Of The Week 4/17/11


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Lee Harrelson
This simple hash brown casserole features a buttery cornflake crust and is a favorite side for both casual family gatherings and holiday celebrations.
12 servings (serving size: about 1/2 cup)
Nutritional Information
Calories 181
Caloriesfromfat 30 %
Fat 6 g
Satfat 3.8 g
Monofat 0.9 g
Polyfat 0.3 g
Protein 7.1 g
Carbohydrate 25.5 g
Fiber 1.5 g
Cholesterol 21 mg
Iron 1.7 mg
Sodium 494 mg
Calcium 11 mg
3/4 cup chopped onion
1/2 teaspoon paprika
1/2 teaspoon freshly ground black pepper
1 (32-ounce) package frozen Southern-style hash brown potatoes, diced
2 tablespoons butter, melted and divided
1 (10 3/4-ounce) can condensed reduced-fat, reduced-sodium cream of chicken soup, undiluted (such as Campbell's Healthy Request)
8 ounces light processed cheese, cubed (such as Velveeta Light)
1 (8-ounce) carton light sour cream (such as Daisy)
Cooking spray
2 cups cornflakes, coarsely crushed
Preheat oven to 350°.
Combine first 4 ingredients and 1 tablespoon butter in a large bowl; toss well.
Combine soup and cheese in a medium microwave-safe bowl. Microwave at HIGH 6 minutes or until cheese melts, stirring every 2 minutes. Stir in sour cream. Pour cheese mixture over potato mixture, and stir well. Spread mixture evenly in a 13 x 9-inch baking dish coated with cooking spray.
Combine cornflakes and remaining 1 tablespoon butter; sprinkle evenly over top of potato mixture. Bake at 350° for 1 hour.
September 2007


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Activites in Perth don't get better than sunset sailing on a world-class luxury catamaran! You and your partner can watch the day turn into night and the stars begin to shine. Enjoy a magnificent WA sunset – the perfect romantic twilight setting for two!
Your sunset adventure will start and finish at world famous Fremantle Fishing Boat Harbour.
Capella is a luxury appointed 12.5m Schionning designed sailing catamaran noted for her stable ride. Experience our magnificent west coast sunset from the ocean on the wide foredeck or rear cockpit deck and watch Fremantle, the Port and Harbour come alive with a kaleidoscope of colour as we transfer from sunset to evening. We may even be joined by a pod of dolphins which love to play around the front of the boat as we sail into the sunset.
A glass of champagne and canapés are provided during your sunset sailing experience. Beer and wine are available for sale onboard at very reasonable prices.
|Thursday-Sunday, approximately 5.00 pm (varies depending on last light of that date)
Please arrive 15 minutes before departure time.
|Fishing Boat Harbour, Fremantle
We operate from the heart of Fremantle's Fishing Boat Harbour. Departing from the Sardine Jetty (50m south of Little Creatures Brewery). There is ample car parking available and it is a 10 minute walk from the Fremantle Train Station.
|2 hours
View Larger Map of Fishing Boat Harbour, Fremantle


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Cam Lane, Thornton In Craven, North Yorkshire, BD23 3SX
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Average Rating
User Reviews
4 out of 7 people found this review helpful:Its too plain and sort of sillyIt doesn't take itself serious enough. Just couldn't continue watching. And the bit about Erec loosing his crown jewels stops being funny pretty fast.
I can´t really recommend this to anyone except for small kids
2 out of 3 people found this review helpful:A new strange feeling of love!I've watched a ton of anime lately and sad to find many are the same thing just repurposed...that being said, I have never laid eyes on anything remotely like this. If i had to pick one that was close its Gintama. that is to say Gintama and ISDT are as close as heaven and earth.Read more
Kind of like SAO where it takes place in a different world (that initially you would think is a game world) and uses ...
3 out of 5 people found this review helpful:Eh it's average... Move on unless you're bored like me.It has its moments and can be quite funny, but the episodes have bad direction. The lead character gets on my nerves sometimes and the tranny is weird (loved the fake backstory although it was hardly believable lol). I also dislike the focus on Eryc's balls. I know it's supposed to be funny, but when they bring up the realities it's true that he can't have kids or a normal sex life... Seems like ...Read more
2 out of 3 people found this review helpful:A cliche comedy to kill timeI was extremely iffy about this series, and had extremely low expectations, but was entertained. While I believe the target age me a bit young, it didn't stop me from watching it. Yes, the series is a cliche spoof with typical characters, just enjoy it while trying to figure out the plot. I do wish the art was better though.
If your looking for a fantasy game like anime, this is a quick fix.A basic and well known plot type makes the story a little predictable, however the characters and comedy really make this show worth it to watch. Typical player getting sent to another world where he goes with just what he knows to survive and approaching challenges his own way. After finishing the series, I kind of wish for another season. 4 stars for keeping me entertained.
Light and fun to watchA long serious review wouldn't make sense for this show. So I'll stick to saying it's fun. Good sense of humor. Appears to be only below the belt at first glance but is actually on more levels if you pay attention. Lot's of parodies and references. I didn't catch half of them but it was funny anyway.Read more
The show has the same feel as Gintama. Story is straightforward, and a little thin. But it ...
It works. If Crudely.The show isn't crude. Just the humor. Ball and sex jokes are the norm for this show. That and anime fourth wall shattering.
If you don't like jokes about sexual organs and the strange thing called human desire this show will offer you nothing.
If however, you do you will find this show quite amusing and possibly remind yourself of a past you that had quite the one track mind.
I Loved it!! Fans of Anime comodies will love.If you love the Devil is a Part Timer and Gintama you will love this!!Read more
Quality- I enjoy the animation style in which it is drawn. They have wonderful reactions and memorable characters.
Sound- Great voice actors and excellent use of music I greatly enjoyed the ending themes.
Story- The story is light and humorous. The characters themselves are unique, funny and a joy to ...
Stupid funny lots of NSFW jokes in a PG kind of way.(some minor spoilers)Read more
If you like lowbrow humor this one is a kick in the balls, you loose your nuts over it. It is clearly made as fan service, it is filled with all the classic tropes while realizing how silly they are.
However if you don't find sausage and eggs jokes hilarious, if 'Dude, wheres my car?' wasn't funny for you, than this isn't your anime. However if you want to watch an anime ...
What I Thought About...I really enjoyed the fact that the main character used his smarts to overcome obstacles and the contrasting character types were quite surprising and well written. I enjoyed this and I hope more do as well.
It was Hilarious! Can't wait for the sequel.


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Paternity Techologies, paternity testing service, listed under "Paternity Testing Services" category, is located at 6111 Tezel Rd San Antonio TX, 78250 and can be reached by 2102258378 phone number. Paternity Techologies has currently 0 reviews.This business profile is not yet claimed, and if you are the owner, claim your business profile for free. If you are not the owner you can invite this business to join by email or by phone.Browse all Paternity Testing Services in San Antonio TX. Discover census data for San Antonio, TX.
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Justin Barnette
This is information that was supplied by Justin Barnette in registering through RePEc. If you are Justin Barnette, you may change this information at the RePEc Author Service. Or if you are not registered and would like to be listed as well, register at the RePEc Author Service. When you register or update your RePEc registration, you may identify the papers and articles you have authored.
Personal Details
|First Name:
|Middle Name:
|Last Name:
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|[This author has chosen not to make the email address public]
Kent, Ohio (United States)
(330) 672-2366
P.O. Box 5190, Kent, OH 44242-0001
RePEc:edi:dekenus (more details at EDIRC)
(330) 672-2366
P.O. Box 5190, Kent, OH 44242-0001
RePEc:edi:dekenus (more details at EDIRC)
- Justin Barnette & Jooyoun Park, 2017. "Increases in Local Unemployment and the Delivery of Trade Adjustment Assistance Services," Economic Development Quarterly, W.E. Upjohn Institute for Employment Research, vol. 31(1), pages 3-24, February.
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Under the Sea Ocean Counters™ Smart Pack, Set of 24
Under the Sea Ocean Counters Smart Pack, Set of 24
Ages 3+
Grades Preschool, Kindergarten +
Under the Sea Ocean Counters Smart Pack, Set of 24
Under the Sea Ocean Counters in a handy, smaller set! Perfect for parents, teachers, homeschooling, tutors, and more.
Set of 24 comes in a resealable polybag and includes an Activity Guide.
Bag measures 6"W x 9"H. - See more at: http://www.learningresources.com/product/under+the+sea+ocean+counters*-trade-+smart+pack%2C+set+of+24.do?from=Search&cx=0#sthash.I3r2T6py.dpuf
Introduce children to an ocean of hands-on learning with Under the Sea Ocean Counters™ and the following engaging activities!
Common Core Alignment Below is a sampling of activities that can be done with this product.
Free Play Explore freely: see, feel, touch, invent, and discover, all on your own! Sorting Sort counters into different sets by attribute, such as shape, color, size, and so on.What is Missing?Place several counters in front of a child.The child should study them, and then close both eyes while you remove one of the counters. See if the child can tell you which piece is missing. Vary the level of difficulty by adding more counters or by removing more than one counter each time.Story Problems Use the ocean counters to create and solve story problems that involve addition and subtraction. Say: "Four whales swim in the ocean. One whale swims away. How many whales are left?" Perform this activity with many different quantities, ocean animals and story scenarios.
What's in the Bag?
Includes whale, shark, sea lion, octopus, stingray, and sea turtle in 4 different colors.


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Cette Tights, Shapewear, Hold-ups and Knee-highs
The high quality of manucfacture combined with the use of latest technology and a fantastic feel for styles and designs makes Cette so popular with women who look for the ideal tights, knee.highs or hold ups for every occasion and any season of the year. Read more...
Whether fine sheers, smooth opaque microfiber or cosy cotton knit: Cette offers the whole range - making legwear dreams come true for women of all shapes and sizes. Cable knit, fine openwork, graphic or floral pattern. Trends and classics are realized in great-looking and well-fitting products.
But the demand for functionality is not neglected: Tights and knee-highs with vitalizing support function are as much part of the range as shaper briefs and tights.
- New


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Distraction Free Driving.
Discover the Ultimate Connected Car Experience.
A Safer Solution for In-Car Texting and Infotainment.
Completely Voice-Powered with "Tap & Talk" Technology.
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Minimizes visible distractions, speak naturally with easy to use tap-and-talk voice-interaction so you can play music, Tweet, talk, text, email, and update your Facebook more safely while driving.
Driver-Centric Interface
Simple and intuitive interface is designed exclusively for drivers for in-car use. Keeps drivers focused and in control when accessing communications, phone calls and entertainment while driving.
Social Network for Drivers
Share your location in real-time with your family and friends or see what they're up to.
Smart Burst Technology
The best in-car solution for texting. Enables drivers to send and receive text messages the way they would naturally talk.
Internet Radio
Access your favorite Internet radio stations naturally and quickly using easy to remember voice-tag nicknames.
Smart Music Play
Navigate and play the music stored on your phone using your voice while staying connected to all other features and services.
User Testimonials from DriveSync's Infotainment Community
"I can't say there are a lot of apps out there I actually use, but this one definitely has some merit!"−
"It is amazing how well the voice commands work. The interface only takes a few minutes to figure out!"−
"Good app. 5/5, would use again."−
"I use it daily to listen to music and to interact with friends while on the road."−
"Recognizer works great! Gets even the foreign names!"−
Distraction-Free Driving with Tap and Talk Technology
Natural and Easy-to-use Voice-powered Interaction
Send and receive text messages and email, listen to Internet radio, and interact with social networks all by voice.
Please take a second to share DriveSync Infotainment with the world,
together we can enjoy a hands-free alternative for in-car texting and infotainment.
Intuitive Driver-Centric Interface
DriveSync Infotainment's simple and intuitive interface is designed exclusively for drivers for in-car use.
You will be able to clearly navigate and see only important content on your phone's screen minimizing visible distraction, additionally you can use quick touch controls to access DriveSync connected car features as a backup to voice commands.
Make Meetups Easy with the DriveSync Infotainment Social Network for Drivers
The MyDriveSync Community lets you share your location in real-time with your family and friends or see what they're up to.
Custom permissions settings keep you in control of what you share and who you share it with.
Texting Hands-free with Smart Burst Technology
Easily share your thoughts and experiences with your connections while remaining focused on the road.
No more reaching for your phone in-order to make sense of a conversation, Smart Burst Technology intuitively reads your text messages out loud in real time and in the right natural order adding real context to your conversation.
Internet Radio at It's Best
Listen to the best internet radio stations from around the world right from your phone.
Search or browse various online radio stations or hand pick your favorite! With easy to remember voice-tag nicknames specifically designed for in-vehicle use, selecting your favorite station is now safer and quicker.
Say It to Play It, Experience Smart Music Play
Scrolling through a playlists with your hands on your phone impairs driving performance and is dangerous. With DriveSync Infotainment you can easily play music you love without ever having to take your focus off the road.
Search for any song or artist stored on your smartphone using your voice while still staying connected to all other features and services.
Additional Features Include
Experience Smart Notifications
DriveSync Infotainment's smart notifications give you the right information at the right time, and removes the distraction of always having to check to see what's new. Whether you're listening to music or composing an email, DriveSync connected car technology lets you know when you get a call, a new text, a new email, and even when your friends hit the road. It's also smart enough to know whether it should interrupt you or wait until you're finished doing something.
Everything You Need In One Single Interface
You should never need to lose focus on the road trying to access information or search for a song. Flow smoothly and seamlessly between a wide variety of DriveSync Infotainment services and features, like texts, calls, real-time notifications and music – all from within a single connected car interface.


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Gustafsson on slide saxophone with Yoshimi (OOIOO/Boredoms) from a live show in Sweden, April 2005, a psychedelic drone piece for saxophones and voice.
Gustafsson, Mats / Yoshimi
Words on the Floor
Label: Smalltown Superjazzz
Released in: Norway
A collaboration between Swedish sax phenomenon Mats Gustafsson and vocalist and electronic artists Yoshimi from Boredoms & her own OOIOO. Gustafsson has been a long time fan of Yoshimi, and the two teamed up in Sweden in April, 2005 for a duo concert, which was recorded and now released as Words on the Floor. Gustafsson plays the slide saxophone alongside tenor and baritone sax, and fluteophone, an unusual instrument that allows a fluid and almost human quality to the instrument. Both play electronics, and with Yoshimi's vocalizing this is an unusual, powerful and psychedelic work.
Related Categories of Interest:
Improvised Music
Electro-Acoustic Improv
Unusual Vocal Forms
Japanese & Asian Improv/Rock
Staff Picks & Recommended Items
October 2007
Mats Gustafsson
Free Improvisation
Duo Recordings
Search for other titles on the Smalltown Superjazzz label.
Other Recommended Releases:
Customers Who Bought This Item Also Bought:
In Stock
Shipping Weight: 5.00 units
Quantity in Basket: None
Label: Smalltown Superjazzz
Catalog ID: STSJ 114CD
Squidco Product Code: 8955
Format: CD
Condition: New
Released: 2007
Country: Norway
Packaging: Jewel Tray
Mats Gustafsson
Highlight an artist name or instrument above
and click here to Search
Track Listing:
1. Soundless cries with their arms in the air 3:07
2. And the children play quietly with words on the floor 42:41


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The goal of the project is the search for new effective radiomitigators based on new understanding of mechanisms of radiation damage realized via mitochondria-dependent pathways. Based on our discovery of a new stage of apoptotic program that utilizes reactive oxygen species to cause peroxidation of a mitochondria-specific phospholipid (PL), cardiolipin (CL) by cytochrome c our central hypothesis is that small molecules causing suppression of irradiation induced peroxidation of CL in mitochondria - catalyzed within the complex of cyt c with CL - represent new types of radiomitigators. Unique interactions of cyt c with CL and features of the catalytic complex offer several potentially promising targets for the regulation of CL peroxidation that will be explored in the current proposal and represent its specific aims as follows:
Specific Aim 1 will determine specific mechanisms defining development of CL peroxidation in cells and radiosensitive tissues of irradiated animals.
Specific Aim 2 will develop and optimize small molecule inhibitors of cyt c/CL peroxidase complex and investigate mechanisms of their action to achieve maximized radiomitigating efficiency in cells and tissues. We plan to explore three novel mechanism-based types of candidate molecules: 1) N-heterocyle-substiuted fatty acids, 2) imidazole-substituted homologues of tocopherols (vitamin E), and 3) nitroxide-oximes.
Specific Aim 3 will identify mechanism-based strategies and small molecules capable of regulating CL oxidizability and localization in mitochondria to limit its oxidation during irradiation induced apoptosis. This will be achieved by three different approaches: 1) by delivery into mitochondria of chemically modified CLs that can act as decoys to protect endogenous CL from oxidation, 2) by affecting CL biosynthesis to shift its molecular speciation in favor of non-oxidizable mono-unsaturated types of CL, and 3) by inhibiting mitochondrial scramblase-3 to prevent transmembrane redistribution of CL during radiation induced apoptosis. Overall, our proposed project will explore and optimize six new classes of anti-apoptotic small molecule regulators that may be used for the development of safe synthetic radiomitigators.
The goal of the project is the search for new effective radiomitigators - small molecules that can be administrated into the body after irradiation and prevent/attenuate the development of injury and clinical syndromes. This will be achieved by developing new types of molecules selectively targeted into one of cellular organelles - mitochondria to protect them against irradiation induced damage. Overall, six new types of these small molecules will be investigated and proposed for further development as radiomitigators.
|Liu, Bing; Bhatt, Divesh; Oltvai, Zoltán N et al. (2014) Significance of p53 dynamics in regulating apoptosis in response to ionizing radiation, and polypharmacological strategies. Sci Rep 4:6245
|Kalash, Ronny; Berhane, Hebist; Yang, Yong et al. (2014) Improved survival of mice after total body irradiation with 10 MV photon, 2400 MU/min SRS beam. In Vivo 28:1-12
|Kagan, Valerian E; Kapralov, Alexandr A; St Croix, Claudette M et al. (2014) Lung macrophages "digest" carbon nanotubes using a superoxide/peroxynitrite oxidative pathway. ACS Nano 8:5610-21
|Kagan, Valerian E; Chu, Charleen T; Tyurina, Yulia Y et al. (2014) Cardiolipin asymmetry, oxidation and signaling. Chem Phys Lipids 179:64-9
|Amoscato, A A; Sparvero, L J; He, R R et al. (2014) Imaging mass spectrometry of diversified cardiolipin molecular species in the brain. Anal Chem 86:6587-95
|Jiang, Jianfei; Bakan, Ahmet; Kapralov, Alexandr A et al. (2014) Designing inhibitors of cytochrome c/cardiolipin peroxidase complexes: mitochondria-targeted imidazole-substituted fatty acids. Free Radic Biol Med 71:221-30
|Stoyanovsky, D A; Sparvero, L J; Amoscato, A A et al. (2014) Improved spatial resolution of matrix-assisted laser desorption/ionization imaging of lipids in the brain by alkylated derivatives of 2,5-dihydroxybenzoic acid. Rapid Commun Mass Spectrom 28:403-12
|Tyurina, Yulia Y; Domingues, Rosario M; Tyurin, Vladimir A et al. (2014) Characterization of cardiolipins and their oxidation products by LC-MS analysis. Chem Phys Lipids 179:3-10
|Chu, Charleen T; Bayýýr, Hulya; Kagan, Valerian E (2014) LC3 binds externalized cardiolipin on injured mitochondria to signal mitophagy in neurons: implications for Parkinson disease. Autophagy 10:376-8
|Tyurina, Yulia Y; Poloyac, Samuel M; Tyurin, Vladimir A et al. (2014) A mitochondrial pathway for biosynthesis of lipid mediators. Nat Chem 6:542-52
Showing the most recent 10 out of 101 publications


text:
it wasnt. i love me a big ol' chunk of sigur ros stache
it wasnt. i love me a big ol' chunk of sigur ros stache
Originally Posted by Wayne Coyne
Sometimes I go into this thread just to see how stupid people can be. I am almost never let down
That said, Brooklyn to LA to Indio on back to back days with gear is hardly the most desirable travel planning. Not impossible, but leaves very little room for any kind of delay.
Thanks Bumblebee, appreciate the clarification.
"The Coachella Valley wasn't always like this, there's been a great many changes made since I came here some 67 years ago"
A friend of mine spoke with members of Ozomatli and they said they would be at Coachella this year. This was months ago, though.
2/19: Intergalactic Gary, Octo Octa @ Audio
2/20: Cloud Nothings, Itasca, Never Young, Kid Trails@ The Independent
2/21: Weyes Blood, Half Waif, 20 Minute Loop, Young Moon @ Swedish American Hall
2/22: Uniform, Black Marble, Mall Walk, Blank Square @ Starline Social Club
2/23: Japanese Breakfast, Miya Folick, Dante Elephante, Flying Circles @ Rickshaw Stop
2/23: Julien Baker @GAMH
For your health
So I guess Beastie Boys are going to headline then.
Well at least we know Beastie Boys will be cancer free and active in the coming months. Jan 7th article:
8/7/16 - Sufjan Stevens @ Hollywood Bowl // 8/8/16 - Radiohead @ Shrine // 8/8/16 - Boris @ Regent
9/14/16 - Wilco @ Theatre at Ace Hotel // 9/18/16 - Kraftwerk @ Hollywood Bowl
WOOOO I w3as kind of expecting them, but that makes me happy. They were great at the El rey in September
8/7/16 - Sufjan Stevens @ Hollywood Bowl // 8/8/16 - Radiohead @ Shrine // 8/8/16 - Boris @ Regent
9/14/16 - Wilco @ Theatre at Ace Hotel // 9/18/16 - Kraftwerk @ Hollywood Bowl
COACHELLA- 99, 01, 02, 03, 04, 05, 06, 07, 08, 09, 10, 11, 12 (wk 1 & 2), 13 (wk 1 &2), 14 (wk 1 & 2), 15(wk 1&2), 16 (wk 1&2)
Beastie Boys say they're "open" to the idea of touring again, which probably makes them less likely for already have a show planned.
Also, they're now officially down a member (http://www.spinner.com/2011/01/07/me...-knopf-leaves/), but not a surprise after reading this article from last year: http://www.portlandmercury.com/portl...nt?oid=2700410
my iphone keeps autocorrecting "rumored" to "dumpers", which is making coachella talk really funny as of late
ha, really. he was definitely my least favorite of the three. my thinking is that if his leaving will help to keep them intact, even if for just one more LP, it is well worth it.
I'm just the opposite.
well, now you can have him all to yourself with his solo project. upside for all.
Well, that was a bitter sweet confirmation.
This is weird. The Live Nation Western Canada Facebook page (http://www.facebook.com/livenationwest) just posted a status that says:
"Rumor has it.... Coachella's gonna be pretty sweet this year. Check out the prospects on the 2011 line up: http://aol.it/gDKu51 "
Aren't Live Nation and AEG/Goldenvoice supposed to be competing companies?


text:
I want to thank you for your interest in what I am doing. It has taken me a long time to get here, but I am indeed where I believe God wants me to be. Simply being a shepherd who serves others. It is my hope that my story will inspire you to follow your journey and to encourage you to find your own true happiness by taking your focus off of you and focusing on others instead. It is well worth the journey.
Bruce's Early Years
Bruce was born Bruce Robert Norton on December 14, 1963 in Baltimore, Maryland. His parents, Robert and Lynne Norton, were agnostics. His father was an engineer, and his mother worked as a federal employee. Bruce was raised in a small rural neighborhood in Howard County. He didn't make many friends, but the friends he did make were long lasting. He met a young girl his age who lived in a house owned by a nearby convent. Her name was Jackie. She gave him his first kiss. He remembers being in her house as her family, of Italian descent, made homade pasta and sauce. Sadly, she broke his heart when her family moved to New York. He still considers her to be his first "girlfriend."
Bruce was a very sensitive child and as such was one of the picked on kids through elementry school. He did not have many friends, and the friends he did have were girls. Long before he entered adolescence, he was often found talking on the phone with his girlfriends for hours at a time. He found them to be attractive, sensitive and caring, and he loved the attention they gave him.
The month after Bruce turned 8 years old, the television show, "Emergency", came on the air. It was after watching a few episodes of "Emergency" that Bruce knew that more than anything else, he wanted to be a paramedic. A few years later, Bruce would become one of the youngest people certified in CPR by the American Heart Association. For his twelfth birthday, he remembers he only asked for a watch, a stethoscope, and a sphygmomonometer (regular people know this as a blood pressure cuff but Bruce always liked using the big words). That is all he got that birthday, and it is the only birthday he remembers what he got. During that time in his life, he had a well stocked first aid kit. Other kids in the neighborhood would come to Bruce to get their scrapes patched up. Bruce remembers one incident when a neighborhood kid got a sleeping bag caught in the front spokes of his bike while he was riding it, and crashed. Another kid who was riding with him, rode to Bruce's house to get help. Bruce and his mom drove to where the kid wrecked. Bruce noted that there was a small rock embedded in the wound. He put butterfly bandages on the gaping wound and dressed it and told him he would need to go to the hospital for stitches. Bruce also told him about the rock and to be sure to tell the doctors in the hospital about it, which he did.
These early events served to form a passion in Bruce to rescue others. Though God was far from Bruce's mind at that age, clearly He was shaping Bruce to be a rescuer.


text:
Death Wobble from Rear Tire?
Ive been getting the death wobble at around 60 mph. Not all the time sometimes it drives fine sometimes it shakes a little. i looked at my rear passanger side tire and its almost bald in the middle but the outside tread is good. Is that causing the death wobble or is something broke in the back thats causing the death wobble and my tire to wear in just the middle. Is there something that i could look for that could be the problem? Thanks
If the Tire is like that, it's usually Caused by Over Inflation.
I would agree, these sound over inflated by quite a bit and maybe you are just feeling the road and bumps. You should not get any wobble from the rear. How much air pressure do you have in the tires?
Its def. not the bumps in the road cause sometimes it shakes real bad and i gotta slow down to like 45 50 to get it to stop. Any sugestions on what that could be. Something squeaks a very tiny bit in the front. But not all the time.
There are no steering mechanisms in the rear...so make sure ur tire is at the correct psi.
also, check out the lugs :facepalm:
You might also check for a seperated tire?
^^ this would be my guess. Especially with it being worn badly, it's very likely that the tire belt has slipped or separated and caused a knot, though it would be felt pretty much all the time.
Get some new tires if they're almost bald in the middle!!
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Heidi Heitkamp is running for Senate in North Dakota, and despite being a Democrat in a red state, she's made it a dead heat. In this ad, instead of running away from Obamacare, she defends it. (youtube.com)
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"Now, you know it's up to you whether or not you want to just do the bare minimum . . ."
I guess Joanna didn't need more than 15 pieces of flair, after all.
Did you know that three out of four federal appellate courts say that, if a disabled employee needs a transfer as a reasonable accommodation, you must normally give the disabled employee preference over better-qualified non-disabled candidates? In other words, you may not be able to choose the best person for the job?
Sad. And true.
Last week, the U.S. Court of Appeals for the Seventh Circuit, which hears appeals from federal courts in Illinois, Indiana, and Wisconsin, overruled its longstanding precedent to the contrary.
United Airlines had reasonable accommodation guidelines outlining a "competitive" transfer process for employees who had disabilities that didn't allow them to continue in their current jobs. The policy said, "Employees needing accommodation will not be automatically placed into vacant positions but instead will be given preferential treatment." The policy provided that disabled candidates would be allowed to apply for an unlimited number of transfers, would be guaranteed an interview, and would get preference over equally qualified non-disabled applicants.
Sounds pretty good to me. But apparently not good enough.
The U.S. Equal Employment Opportunity Commission sued United, claiming that the policy violated the ADA. A federal district court in Illinois dismissed the lawsuit based on the Humiston-Keeling decision (the "longstanding precedent" linked above). A three-judge panel of the Seventh Circuit reversed and overruled Humiston-Keeling.
OK, I know I am treading very close to the outer limits of my "no legalese" guarantee. So I'll get to the point.
"And we thought baggage claim was bad when they were hiring the most-qualified candidates!"
Here's what this decision means, as well as decisions saying the same thing from the Tenth Circuit (which hears appeals from federal courts in Colorado, Kansas, New Mexico, Oklahoma, Utah, and Wyoming, and the parts of Yellowstone National Park that extend into Montana and Idaho) and the District of Columbia Circuit (which hears appeals from federal courts in -- well, you know):
*Joanna has always done the "bare minimum," wearing only 15 pieces of flair, not demonstrating initiative, and always requiring specific guidance from her manager before she'll wear more. Her co-worker, Brian, wears 37 pieces of flair and has a terrific smile. He expresses himself, and you encourage that. He has "assistant manager" written all over him.
*Joanna hurts her back and can't do her regular job any more.
*Under the ridiculously lenient definitions of the ADA Amendments Act, of course Joanna's condition is an ADA-qualifying disability.
*You are not required under the ADA to displace another employee to make a spot for Joanna, and you don't have to create a job for her.
*But you have a vacant position available, and Joanna meets the minimum qualifications for the position.
*Superstar Brian is also interested in the vacant position. Brian is clearly the superior candidate.
*Too bad. Unless you can prove that it would be an undue hardship**, Joanna gets the job because (a) she has a disability, and (b) she's minimally qualified.
**Don't let this loophole excite you. It will be a nearly impossible hurdle for many employers, and for almost all large ones.
Of course, there is no chance that anyone will claim to have a disability so that he or she can get priority over better qualified candidates, right? Of course not -- don't be silly.
PS - If you don't like this, move your company to a location in the Eighth Circuit (Arkansas, Iowa, Minnesota, Missouri, Nebraska, and the Dakotas) while you can still give preference to the more-qualified candidate. Although who knows for how long?
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San Francisco Tops Cincinnati 3-2 - Recap
San Francisco grabbed a 3-2 win over Cincinnati on Friday, as Brian Wilson was credited with a win at AT&T Park.
The Giants were a -112 favorite in the win. The combined score dipped UNDER the total, which closed at 7.5.
San Francisco got 6 innings from Ryan Vogelsong , who gave up 2 earned runs on 8 hits, while striking out 6. Brian Wilson earned the victory, while the Giants got 1 RBI from Miguel Tejada in the win.
Cincinnati's starting pitcher Travis Wood worked 8 innings, giving up 10 hits and 2 earned runs while striking out 0 in the loss. They got 3 hits from Brandon Phillips in a losing cause.
The battle of the bats favored San Francisco as they had 11 hits, while Cincinnati only had 9.


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