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Inflammation is implicated in the progressive nature of neurodegenerative diseases, such as Parkinson's disease, but the mechanisms are poorly understood. A single systemic lipopolysaccharide (LPS, 5 mg/kg, i.p.) or tumor necrosis factor alpha (TNFα, 0.25 mg/kg, i.p.) injection was administered in adult wild-type mice and in mice lacking TNFα receptors (TNF R1/R2−/−) to discern the mechanisms of inflammation transfer from the periphery to the brain and the neurodegenerative consequences. Systemic LPS administration resulted in rapid brain TNFα increase that remained elevated for 10 months, while peripheral TNFα (serum and liver) had subsided by 9 h (serum) and 1 week (liver). Systemic TNFα and LPS administration activated microglia and increased expression of brain pro-inflammatory factors (i.e., TNFα, MCP-1, IL-1β, and NF-κB p65) in wild-type mice, but not in TNF R1/R2−/− mice. Further, LPS reduced the number of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra (SN) by 23% at 7-months post-treatment, which progressed to 47% at 10 months. Together, these data demonstrate that through TNFα, peripheral inflammation in adult animals can: (1) activate brain microglia to produce chronically elevated pro-inflammatory factors; (2) induce delayed and progressive loss of DA neurons in the SN. These findings provide valuable insight into the potential pathogenesis and self-propelling nature of Parkinson's disease.
Inflammation and microglial activation is a common component of the pathogenesis for multiple neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease (PD), Huntington's disease, Multiple sclerosis, and Amyotrophic lateral sclerosis (Nguyen et al., 2002). Microglia, the resident innate immune cells in the brain, actively monitor their environment and can become over-activated in response to diverse cues to produce cytotoxic factors, such as superoxide (Colton and Gilbert, 1987), nitric oxide (Liu et al., 2002; Moss and Bates, 2001), and tumor necrosis factor alpha (TNFα) (Lee et al., 1993; Sawada et al., 1989). While microglial activation is necessary and critical for host defense, over-activation of microglia is neurotoxic (McGeer et al., 2005; Polazzi and Contestabile, 2002). At this time, the mechanisms initiating deleterious neuroinflammation in neurodegenerative disease are poorly understood.
Lipopolysaccharide (LPS), endotoxin from gram-negative bacteria, damages DA neurons only in the presence of microglia (Gao et al., 2002; Gibbons and Dragunow, 2006). Further, LPS activation of microglia both in vivo and in vitro causes the progressive and cumulative loss of DA neurons over time (Gao et al., 2002; Ling et al., 2002, 2006). During critical periods of embryonic development (E 10.5), maternal exposure to low concentrations of LPS in mice impacts microglial activation and DA neuron survival in offspring that persists into adulthood (Carvey et al., 2003; Ling et al., 2006). Several of these reports indicate that due to immunological perturbation during critical periods of development (Ling et al., 2006) or aging and sentience (Godbout et al., 2005), microglia can become primed, where additional stimuli result in an exaggerated and prolonged pro-inflammatory response that enhances neuron damage. Thus, not only can microglia induce neuron damage, they can become persistently activated to produce continuous and uncontrolled neurotoxicity that fails to reside after the instigating stimulus has dissipated.
Several lines of evidence suggest that adult microglia can also become chronically activated from a single stimulus in the absence of any predispositioning event or aging. For example, chronic microglial activation continues years after brief MPTP exposure in humans (Langston et al., 1999) and primates (McGeer et al., 2003) through a process called reactive microgliosis. Reactive microgliosis is defined by the microglial activation that occurs in response to neuronal damage. This microglial activation is then toxic to neighboring neurons, which causes further microglial activation and a self-propelling progressive cycle of inflammation and neuron damage. Regardless of the class of instigating stimuli (pro-inflammatory toxin or neuronal death) the microglial pro-inflammatory response to neuron damage can drive the progressive inflammation and cumulative loss of neurons over time (Block and Hong, 2005). However, neuroinflammation and microglial activation is not always deleterious (Glezer et al., 2006; Neumann et al., 2006; Simard and Rivest, 2006; Simard et al., 2006; Sriram et al., 2006). Thus, the identification of the stimuli and mechanisms responsible for progressive microglial activation and associated continuous neuron damage is essential to understand the etiology and pathology of neurodegenerative diseases.
Here, we are the first to test whether a single peripheral LPS exposure in adult mice results in: (1) microglial activation and neuroinflammation that persists long after peripheral events have abated; (2) transfer of peripheral inflammation to the brain through TNFα; (3) delayed and progressive loss of DA neurons in the substantia nigra (SN), similar to PD. The results from these studies indicate that a single occurrence of sepsis and peripheral inflammation may result in self-propelling neuroinflammation and progressive DA neurodegeneration through TNFα.
Eight-week male (20–22 g) B6; 129S-Tnfrsf1atm1Imx Tnfrsf1btm1Imx/J (TNFR1/R2−/−, KO) and B6; 129SF2/J (TNFR1/R2+/+, WT), and C57BL/6J mice were purchased from Jackson Laboratories (Bar Harbor, ME). B6; 129S-Tnfrsf1atm1Imx Tnfrsf1btm1Imx/J (TNFR1/R2−/−) mice were lacking both the p55 and p75 TNF receptors and maintained in B6; 129SF2/J background. Therefore, B6; 129SF2/J (TNFR1/R2+/+) mice were used as strain controls of TNFR1/R2−/− mice.
Lipopolysaccharide (LPS, strain O111:B4) was purchased from Calbiochem (San Diego, CA). The polyclonal antibody against tyrosine hydroxylase (TH) was a kind gift from Dr. John Reinhard of Glaxo Wellcome (Research Triangle Park, NC). Rat monoclonal antibody raised against F4/80 antigen was purchased from Serotec (Washington, DC). Rabbit anti-Iba1 antibody was purchased from Wako Pure Chemical Industries (1–2Doshomachi 3-Chome Chuo-ku Osaka 540–8605, Japan). Tumor necrosis factor alpha (TNFα) and MCP-1 ELISA kits were purchased from R&D Systems (Minneapolis, MN). All other reagents came from Sigma Chemical Co. (St. Louis, MO).
Male C57BL/6J, TNFR1/R2−/−, and TNFR1/R2+/+ mice were intraperitoneally injected with a single dose of LPS (5 mg/kg), TNFα (0.25 mg/kg), or vehicle (0.9% saline). The dosage of LPS used (5 mg/kg, i.p.) was based on our previous study of endotoxic shock (Li et al., 2005). However, pilot studies using lower doses of LPS (1–4 mg/kg) showed significant increases in brain TNFα mRNA and protein levels in a graded response (data not shown). Mice were sacrificed at selected time points and tissues (serum, brain, and liver) were used for mRNA, protein, or morphological analyses. Procedures using laboratory animals were in accordance with the National Institutes of Health guidelines for the use of live animals and approved by IUCAC boards.
The loss of dopaminergic neurons was assessed by counting the number of TH-immunoreactive (TH-IR) neurons following immunostaining of brain sections. Twenty-four consecutive brain slices (35 μm thickness), which encompassed the entire SNc, were collected. A normal distribution of the number of TH-IR neurons in the SNc was constructed based on the counts of 24 slices from C57BL/6J mice. Eight evenly spaced brain slices from saline or LPS-injected animals were immunostained with an antibody against TH and counted. The distribution of the cell numbers from each animal was matched with the normal distribution curve to correct for errors resulting from the cutting. Samples were counted in a double-bind manner with stereology equipment, three individuals, and the CAST system. Conclusions were drawn only when the difference was within 5%.
Brains were fixed in 4% paraformaldehyde and processed for immunostaining as described previously (Qin et al., 2004). Dopaminergic neurons were detected with the polyclonal antibody against tyrosine hydroxylase (TH). Microglia was stained with rat monoclonal antibody raised against F4/80 antigen and rabbit anti-Iba1 antibody, respectively. Immunostaining was visualized by using 3,3′-diaminobenzidinge and urea-hydrogen peroxide tablets from Sigma.
Total RNA was extracted from the mouse brain samples treated with LPS, TNFα, or saline at the selected time points and used for reverse transcription PCR analysis as described previously (Qin et al., 2004). The primer sequences used in this study were as follows: for mouse TNFα, 5′-GAC CCT CAC ACT CAG ATC ATC TTC T-3′ (forward) and 5′-CCT CCA CTT GGT GGT TTG CT-3′ (reverse); for mouse IL-1β, 5′-CTG GTG TGT GAC GTT CCC ATT A-3′ (forward) and 5′-CCG ACA GCA CGA GGC TTT-3′ (reverse); for mouse NF-κB p65 (essential modulator), 5′-GGC GGC ACG TTT TAC TCT TT-3′ (forward) and 5′-CCG TCT CCA GGA GGT TAA TGC-3′ (reverse); for mouse β-actin, 5′-GTA TGA CTC CAC TCA CGG CAA A-3′ (forward) and 5′-GGT CTC GCT CCT GGA AGA TG-3′ (reverse). The SYBR green DNA PCR kit (Applied Biosystems, Foster City, CA) was used for real-time PCR analysis. The relative differences in expression between groups were expressed using cycle time (Ct) values normalized with β-actin, and relative differences between control and treatment groups were calculated and expressed as relative increases setting control as 100%.
Frozen livers and brains were homogenized in 100 mg tissue/mL cold lysis buffer (20 mM Tris, 0.25 M sucrose, 2 mM EDTA, 10 mM EGTA, 1% Triton X-100) and one tablet of Complete Mini protease inhibitor cocktail tablets/10 mL (Roche Diagnostics, Indianapolis, IN). Samples were centrifuged at 100,000g for 40 min. Supernatant was collected for protein assay using the BCA protein assay reagent kit (PIERCE, Milwaukee, WI). The levels of TNFα in livers, sera, and brains and MCP-1 in brains were measured with TNFα and mouse JE/MCP-1 commercial enzyme-linked immunosorbent assay (ELISA) kits from R&D Systems (Minneapolis, MN), as described previously (Gu et al., 1998).
The data are expressed as the mean ± SEM and statistical significance was assessed with an ANOVA followed by Bonferroni's t test. A value of P < 0.05 was considered statistically significant.
To better understand the effects of systemic LPS on brain inflammation, we administered a single dose of LPS (5 mg/kg) i.p. to male C57BL/6 mice and followed liver, serum, and brain TNFα expression over time. LPS increased liver TNFα mRNA 140-fold that peaked within 30 min. This was followed by liver TNFα protein increase of ~29-fold that peaked at 60 min. Serum TNFα protein increased from 0 to ~6.452 ng/mL at 60 min after LPS treatment (see Fig. 1). Brain showed an increase in TNFα mRNA (7,336%) and protein levels (653%) that both peaked at 60 min. Thus, while TNFα protein levels in response to systemic LPS peaked in the liver, serum, and brain at 1 h, brain TNFα mRNA synthesis occurred shortly after liver TNFα mRNA synthesis, very likely after the TNFα protein was able to enter the brain. These results support that liver-derived TNFα was the predominant source of the immediate TNFα response to systemic LPS (1-h post treatment) in the liver, serum, and brain, which then initiated the synthesis of TNFα in the brain.
We also examined the long-term effects of systemic LPS injection from several hours until 10-months post treatment. Interestingly, serum TNFα declined to saline control levels by 9 h (Figs. 1B, ,2A).2A). In liver, TNFα protein levels declined to 18% of peak values by 9 h after LPS (Figs. 1A, ,2A).2A). Surprisingly, TNFα protein remained elevated in brain. At 1 week after LPS treatment TNFα levels were elevated in brain to ~319 ±20 pg/mg protein compared to control values of 65 ±5 pg/mg protein, a 490% increase similar to the 1-h peak induction. TNFα protein remained elevated at 14 days, 21 days, and even 10 months after LPS treatment (Fig. 2B). In addition, 3 h after LPS treatment staining of microglia in cortex, hippocampus, and SN showed microglia with enlarged cytoplasm and cell bodies, irregular shape, and intensified Iba1 staining consistent with morphological activation of microglia (see Fig. 3). In summary, these results support an association between early (1–9 h) TNFα production in the liver and blood, with chronic (10 months) microglial activation in the brain.
Studies indicate that TNFα is transported into brain (Pan and Kastin, 2001; Pan et al., 2006) and that TNFα receptors are critical for transport of the TNFα protein from the periphery, across the blood brain barrier, and into the brain (Pan and Kastin, 2002). To test the role of systemic TNFα on inflammation in the brain, we administered a single dose of LPS (5 mg/kg) i.p. or TNFα (0.25 mg/kg) i.p. to male wild type B6:129SF2/J mice (WT) or male mice deficient in the TNF Type 1 and Type 2 receptors (TNFR-KO). TNFα expression (brain, liver, and serum) and the up regulation of other pro-inflammatory genes (IL-1β, NFκB, and MCP-1) in the brain were determined.
Systemic LPS treatment increased TNFα mRNA and protein in the liver of both WT and TNFR-KO as expected, as LPS triggers an immune response independent of TNFα receptors (Fig. 4A). LPS increased serum levels of TNFα in both WT and TNFR-KO mice. However, brain TNFα mRNA and protein increased only in the WT, but not in TNFR-KO mice, indicating that TNFα receptors are necessary for peripheral LPS to cause brain TNFα mRNA and protein production (Fig. 4C). In a separate experiment, similar to Fig. 3, WT mice showed increased Iba1 (a specific marker for microglia) staining in several brain regions, such as SN, hippocampus, and cortex (images not shown) at 2-h post LPS-treatment. Iba1-IR cells showed increased cell size, irregular shape, and intensified Iba1 staining consistent with morphological changes in activated microglia. Iba1-IR cells in saline controls in WT mice showed resting microglial morphology. However, TNFR-KO animals did not show increased TNFα mRNA or protein synthesis in the brain (Fig. 4C). These findings indicate that TNFα receptors are essential for systemic LPS administration to cause activation of microglia and TNFα synthesis within brain.
To confirm the role of systemic TNFα in brain inflammation, WT and TNFR-KO mice were treated with TNFα (0.25 mg/kg, i.p.). TNFα treatment resulted in a 132-fold increase in liver TNFα mRNA and a 27-fold increase in liver TNFα protein in WT, but not in TNFR-KO mice (Fig. 5A). The injection of TNFα increased serum levels of TNFα in both WT and TNFR-KO (Fig. 5B). Importantly, systemic TNFα injection induced brain TNFα mRNA and protein in WT, not in TNFR-KO mice (Fig. 5C). Further, TNFα induced brain synthesis of other pro-inflammatory factors, such as monocyte chemotactic protein 1 (MCP-1) as well as NF-κB p65 subunit, interleukin-1β (IL-1β) in WT mice. However, TNFα failed to induce production of the pro-inflammatory factors in TNFR-KO mice (see Fig. 6). Thus, systemic TNFα induces pro-inflammatory cytokine production in brain, serum, and liver, as well as induces brain microglial activation.
A comparison of TNFα and LPS indicates these two inflammatory activators are remarkably similar. Our findings suggest that systemic LPS acts by inducing TNFα synthesis in the liver to increase serum TNFα, which then activates brain microglia to induce TNFα, other cytokines, and neuroinflammatory protein synthesis. Taken together, these findings suggest that an acute systemic injection of LPS or TNFα activates brain microglia through TNFα receptors that initiate sustained activation of brain cytokine synthesis and neuroinflammation.
The substantia nigra (SN) is densely populated with microglia (Kim et al., 2000; Lawson et al., 1990) and it is hypothesized that this brain region is particularly susceptible to inflammatory insult. To discern the effects of chronic neuroinflammation (sustained increase in brain TNFα for at least 10 months) on neuron survival in the SN, we measured the number of dopamine neurons, as indicated by the number of tyrosine hydroxylase immunoreactive (TH-IR) cells within the SN, after a single LPS i.p. treatment. Previous reports using intranigral injection of LPS demonstrated that the LPS-induced decline of TH-IR cells is due to cell loss, as evidenced by a decline in the over-all number of neurons in the SN (Gao et al., 2002). As shown in Fig. 7, LPS injection caused a delayed and progressive loss of nigral TH-IR neurons. Comparison of the number of nigral TH-IR neurons between the LPS-treated and saline-treated mice showed no significant loss of TH-IR neurons within the first 4 months after LPS injection (Fig. 7A). However, significant loss of TH-IR neurons started to manifest between 7 and 10 months after LPS treatment. At 7 months, a 23% loss was observed. The LPS-induced loss of nigral TH-IR neurons further progressed over time and a 47% loss was shown at 10 months (Fig. 7A). Using double labeled (TH-IR and NeuN-IR) staining, we have previously reported that inflammation-induced loss of TH-IR cells in the nigra represents neuronal death, rather a down regulation of TH expression (Gao et al., 2002). Changes in TH-IR cells were more pronounced in SN than in the adjacent ventral tegmental area (VTA) DA neurons (Fig. 7B). Interestingly, staining for microglia using F4/80 antibody indicated that the SN contains much more microglia than the adjacent VTA (Fig. 7C). Cell loss in other brain regions was not determined. Thus, the SN may be inherently susceptible to inflammatory insult when compared to other regions of the basil ganglia due to the presence of increased microglia. These studies support the hypothesis that an acute increase in systemic TNFα activates neuroinflammatory processes within brain that are sustained for long periods, which leads to delayed and progressive degeneration of DA neurons.
The mechanisms responsible for the progressive loss of DA neurons in PD are poorly understood. Here, we are the first to show that a single exposure to systemic inflammation transfers to the brain and initiates self-propelling neuroinflammation that persists for 10 months, which results in the progressive loss of DA neurons in the SN (see Fig. 8). Specifically, we investigated three aspects of peripheral LPS administration: the role of TNFα in the transfer of systemic inflammation to the brain, the duration of neuroinflammation, and the neurotoxic consequences for DA neurons in the SN.
In the current study, we demonstrate that a single intraperitoneal LPS injection results in TNFα production in the periphery, which initiates brain TNFα production (mRNA and protein) in the brain that continues for months after the systemic source of TNFα has abated. It was previously reported that liver is the major source for the circulating TNFα after a single systemic LPS injection, due to activation of kupffer cells, the resident macrophage-like cells in the liver (Kumins et al., 1996). These cytokines are then released into the blood and induce inflammation throughout the body (Crews et al., 2006). Here, we found that liver and serum TNFα were elevated at early time points, but declined over time to return to basal levels by 1 week and 9 h, respectively. Remarkably, TNFα levels remained elevated in the brain for up to 10 months, long after liver and serum levels had subsided. Further, immunohistochemical analysis of brain sections showed that microglia was activated in several brain regions, such as the SN, hippocampus, and cortex. Previous reports have shown that a single exposure to MPTP, a toxin selective for DA neurons, in humans (Langston et al., 1999) and monkeys (McGeer et al., 2003) resulted in microglial activation that persisted years after the brief exposure. Earlier studies investigating the long-term effects of systemic LPS exposure in utero has shown that low levels of systemic inflammation must occur during a critical window of development in order for the long lasting, pro-inflammatory changes in the brain to occur (Carvey et al., 2003; Ling et al., 2002). Our current work indicates that a single pro-inflammatory event in the periphery can induce chronic, self-propelling neuroinflammation outside of the embryonic critical period and in the adult brain.
It is well-documented that in the normal condition, very little peripheral LPS enters to the brain due to the poor passage through the blood brain barrier (Nadeau and Rivest, 1999). Thus, the LPS-induced neuroinflammation is likely an indirect effect. In an effort to understand how chronic neuroinflammation was transferred from the periphery to the brain, we administered TNFα peripherally and found that both systemic TNFα and LPS administration increased the expression of brain pro-inflammatory factors (TNFα, MCP-1, IL-1β, and NF-κB p65) in a similar pattern. Further, TNFR1/R2−/− mice failed to show brain neuroinflammation in response to systemic LPS or systemic TNFα, supporting that TNFα was critical for the transfer of inflammation from the periphery to the CNS. This is consistent with other studies demonstrating that systemic cytokines mediate the effects of peripheral inflammation on the brain. For example, TNFα and other systemic cytokines are reported to mimic several behavioral effects of systemic LPS (Berkenbosch et al., 1987; Bernardini et al., 1990; Sapolsky et al., 1987; Sharp et al., 1989). Thus, systemic cytokines are critical for CNS effects in response to peripheral immune activation.
Here, we are the first to show chronic neuroinflammation and progressive neurodegeneration a single injection of LPS. Currently, the detailed mechanisms of this progressive neuroinflammation are unknown. However, we speculate that the initial entry of the pro-inflammatory factors, such as TNFα to the brain will cause the activation of microglia to produce more inflammatory factors, which may cause neuronal death. Upon exposure to TNFα, microglia are well known to synthesize and secrete TNFα (Rivest et al., 2000). Thus, this initial damage may then result in reactive microgliosis, causing the release of additional pro-inflammatory factors to begin a self-propelling and a vicious cycle of neuronal damage. We propose that reactive microgliosis may underlie the progressive and long-lasting neuroinflammation and neurodegeneration of numerous neurodegenerative diseases (Block and Hong, 2005).
Inflammation is implicated as a neurodegenerative stimulus (Maurizi, 2002) and DA neurons in the SN are thought to be more susceptible to inflammation when compared to other neuronal subtypes and other brain regions (Block and Hong, 2005; Carvey et al., 2003; Gao et al., 2002; Ling et al., 2002). Microglial activation has been shown to induce the selective loss of DA neurons in response to multiple stimuli (Block et al., 2004; Wu et al., 2005; Zhang et al., 2005), including LPS (Gao et al., 2002; Ling et al., 2002, 2004a,b, 2006). Additionally, the SN contains 4.5 times as many microglia when compared to other brain regions (Kim et al., 2000), making this region particularly susceptible to inflammatory insult. In the current study, we have stained the SN for microglia and document that there are visibly more microglia in the SN, when compared to the VTA and other brain regions (see Fig. 7), helping to explain why global neuroinflammation can result in selective damage. Previously, it has been shown that a single injection of the selective dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), results in chronic neuroinflammation and progressive neurotoxicity in humans (Langston et al., 1999) and monkeys (McGeer et al., 2003), where the mechanisms of microglial activation and progressive toxicity are poorly defined. Here, we show that a single systemic administration of LPS results in significant loss of DA neurons beginning at 7-months post treatment (23% loss of TH-IR neurons) and increasing in severity with time to a 47% loss at 10-months post treatment. Thus, we are the first to show that a single pro-inflammatory stimulus from the periphery in the adult mouse results in delayed and progressive loss of DA neurons in the SN (over months), similar to what occurs in PD. This is consistent with a previous report of a single human case study where accidental peripheral administration of LPS was associated with later onset of PD (Niehaus, 2003). The delayed onset, progressive nature, and long-lasting DA neuronal degeneration after a single injection of LPS shown in this study suggests a clinical implication for the link between peripheral inflammation and neuroinflammation. Thus, it would be interesting to determine epidemiologically whether there is a link between patients surviving septic shock and the incidence of PD.
Several studies indicate that pro-inflammatory events occurring peripherally can influence neurotoxicity. The majority of previous reports demonstrate that systemic inflammation can amplify an inflammatory stimulus and consequent neuronal damage. For example, systemic administration of LPS enhanced motor neuron degeneration in animal models of amyotrophic lateral sclerosis at 6 months (Nguyen et al., 2004), but no direct toxic effect of systemic LPS alone was reported. Systemic exposure to LPS in the neonate was also shown to significantly amplify neuronal death associated with ischemic insult (Lehnardt et al., 2003). Interestingly, it is suggested that peripheral inflammation could be protective, as one study has shown that neuroinflammation induced by intrastriatal injection of endotoxin could be blocked by systemic LPS administration, where the protection was mediated through LPS-induced plasma corticosterone (Nadeau and Rivest, 2002). In the current study, we demonstrate that a high dose of systemic LPS (5 mg/kg) can actively induce persistent inflammation and progressive neurotoxicity over 10 months in the adult animal. Thus, the effects of peripheral inflammation on neuron survival may depend upon several factors, such as brain region examined, length of time investigated to allow cumulative effects, age of exposure to the inflammagen, presence of systemic TNFα, and severity of the inflammatory stimuli tested.
In summary, our study supports that LPS activates cells in the liver to produce TNFα, which is distributed in the blood and transferred to the brain through TNFα receptors to induce the synthesis of additional TNFα and other pro-inflammatory factors, creating a persistent and self-propelling neuroinflammation that induces delayed and progressive loss of DA neurons in SN of adult animals. This work offers strong support for the premise that inflammation is both an initiating stimulus and a self-propelling mechanism of progressive neurondegeneration.
The authors thank Drs. Jenny Ting, John Gilmore, and Richard Mailman for their scholarly comments and Melissa Mann for manuscript preparation.
Grant sponsors: National Institute of Health, National Institute of Environmental Health Sciences, National Institute on Alcohol Abuse and Alcoholism.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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When you hear that something has broken, what is your first reaction? "Oh, no!"…or perhaps, "Oh, well–I can fix it"…or maybe even "Oh, good! Now I can finally throw it away." After the initial reaction, what do you do next? As far as I have observed, it seems that the majority of people make one of two decisions: 1) throw the thing away; or 2) save it so that it can be fixed later. Unfortunately, with Option 2, "later" almost never comes.
My grandmother has a very healthy reaction to broken things. She is my role model in many things, and my reaction has come to be much like hers: "Oh, well–it is only a thing." Yes, things can be handy; they can make our life easier or more pleasant. They can also weigh us down or even become idols, when we put the love of things above the love of our fellow-man and our God. The point of my grandmother's–and now my own–attitude about broken things is that people are always more important than things and our connection with God is too valuable to let go over some temporary thing.
You know, sometimes people are broken, too. And somehow, in our human nature it seems like a lot of times it is easier to have compassion on broken things than on broken people. We want to blame people for their broken spirits. We want to "throw them away", like some object unworthy of repair. It just looks like too much work to mend them.
This is not how Jesus sees things, though, and I will be quick to add that He will give us hearts of compassion for broken people. The Bible says of Jesus, "a bruised reed shall he not break, and the smoking flax shall he not quench". Just try looking up the word "compassion" in your Bible concordance. God is one to be moved by compassion.
Be sure to check back tomorrow for the conclusion of "Broken"!


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Want to get your salary structuring and payroll administration right? Make sure you're aware of these three things
#1: The two most important aims of payroll administration from a tax perspective are:
This means you must identify who must be taxed and how they must be taxed.
The Practical Tax Loose Leaf Service says the foolproof; failsafe rule is that you must collect employees' tax from all amounts paid or payable to employees, while payments to independent contractors will not be subject to employees' tax.
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#2: Salary structuring is the second component of payroll
Once you've identified who must be taxed, you can determine how they'll be taxed.
Paying tax on your income is unavoidable. But even SARS acknowledges that it's your right to arrange your financial affairs so you can pay the minimum amount of tax that's legally allowable. This is the aim of salary structuring.
There are various methods of salary structuring, but the most common method adopted in commercial practice today is known as 'total cost of employment' (TEC) or 'cost to company' structuring. The Loose Leaf Service recommends you use this method.
#3: SARS isn't unreasonable as most people like to believe
It recognises the right of an employee and employer to mutually agree on a remuneration package, but warns that a restructuring exercise must be implemented correctly.
So be sure to protect your salary structuring by meticulously recording the details in your letters of appointment and employment contracts.
Being aware of these three points will bring you a step closer to getting your salary structuring and payroll administration right.
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Employees always sick? How to stop it today
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This week marks the 50th anniversary of the beginning of 10 years of severe political and social upheaval in China. These are scenes from around the country during that period.
Film by Mike Chinoy looks at the tumultuous events of China in the mid-1970s through the eyes of the foreign correspondents who covered them.
University of Pennsylvania professor and China specialist Arthur Waldron recounts his first trip into China in 1981, when he was a simple tour guide for a group of U.S. tourists.
As China embarks on another internet crackdown in the name of maintaining stability, Jeffrey Wasserstrom calls into question the predictive powers of Karl Marx.
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The Next Right Podcast
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Tag Archives: St. Robert Bellarmine
The Politicization of Doctrine is a Blunder
By Charlie Johnston In the early half of the 17th Century, the Catholic Church got deeply involved in scientific debates about heliocentrism (whether the sun revolves around the earth or vice versa). The Church formally banned the books by … Continue reading
Posted in Church Governance, Culture Tagged Copernicus, Environment, Galileo, Global Warming, Pope Francis, St. John Neumann, St. Robert Bellarmine 186 Comments


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FastMall is pleased to announce the first shopping mall launch in Australia complete with interactive map for more then 530 stores!
Chadstone Shopping Centre opened in 1960 and was the first freestanding regional shopping centre in Melbourne.
Chadstone is now the biggest shopping centre in the Southern Hemisphere, boasting over 530 fabulous stores including a dedicated luxury precinct – home to 12 World Class Luxury Brands.
Melbourne is Australia's Fashion Capital, and there's no better way to experience the best it offers than to take a trip to Chadstone – The Fashion Capital.
Visitor Passport Savings
If you are a country*, interstate or overseas visitor to Melbourne, you're entitled to discounts of up to 30% from over 200 of their favourite stores.
Collect your free Visitor Passport from one of the Customer Service Desks and have it stamped for endorsement.
Make sure you bring some ID, like a drivers license or passport, confirming your visitor status.
Chadstone is 12 minutes from Melbourne CBD on Citylink and approximately 35 minutes by taxi from Melbourne Airport.
*To qualify as a country visitor you must reside 50km from Chadstone.
Gift Cards
Chadstone Gift Cards can be used at most specialty stores and make the perfect gift solution at any time of year. Gift Cards can be purchased online or offline easily.
You can specify a value for your Gift Card and choose to collect the Gift Card in centre or have it mailed to you.
Customer Service Desks
Customer Service Desks are located on the ground level nearby Sass & Bide, and Ozmosis. On the lower level, the Customer Service Desk can be found outside Bevilles.
The RACV shop is located in the Banking Precinct on the external of the centre.
Exit the centre near Rosemin, or Simon Johnson to access this precinct.
For enquiries, please phone 9569 8788.
Stroller & Wheelchair Hire
Strollers & Wheelchairs are available for hire from the Customer Service Desks free of charge, with approved identification.
Single and double strollers are available, as are both Manual and Motorized wheelchairs. Bookings are recommended as numbers are limited. Please phone the Customer Service Desk on 9567 1023.
Baby Change Rooms
Baby Change Rooms are well equipped with changing tables, bottle warming facilities, microwaves and toilets for your convenience.
Toilets are located throughout the centre for your convenience, including facilities for people with disabilities and baby changing rooms.
Fashion industry insiders agree that "Green is the new Black".
At the Fashion Capital, caring for the environment is always at the forefront.
From simple initiatives such as increased cyclist parking and change facilities through to the introduction of a new waste separation, recycling and disposal depot, Chadstone has once again taken a leadership position.
– sub metering of water and electricity usage to minimise waste
– 300,000 litre storm water recycling tanks
– centralised gas fired air conditioning plant
– variable controlled escalators and lifts for improved energy efficiency
– fire system testing water collection for recycling
– double glazing mall roof system and insulated precast panels for thermal comfort
With a commitment to environmental sustainability focusing on water preservation, Chadstone – The Fashion Capital commissioned the Yarra Valley Savewater! Efficiency Service – with Water Management Plan recommendations being implemented in November 2003.
As a result, they have now saved 30 million litres of water, a saving of 14% over the last three years (despite a foot traffic increase of 2-3% annually).This has been achieved by implementing the below simple water saving measures:
* Pressure flow control / reduction valves on all taps and faucets
* Installation of waterless urinals, replacing 30 standard urinals which will equate to a water saving of 2 million litres annually
* Installation of rain sensors, which detect when rainfall has occurred and prevents garden sprinklers from activating
In recognition of the above, Water Minister John Thwaites presented the Yarra Valley Sustainability Commendation Award "for achieving significant water savings", to the centre on Wednesday 25 October, 2006.
Chadstone continues its strong commitment to working with Yarra Valley Water and the State Government, as we embrace Stage 3 Water restrictions.
Local & International Designers
Chadstone – The Fashion Capital is home to 530 fabulous stores: 50 Australian & Designer Boutiques, and 12 World Class Luxury Brands.
For information on luxury brands at Chadstone, please click here.
Department stores including Myer and David Jones, as well as Target, Kmart and Best & Less are all found at Chadstone.
Both local and international and international designers are represented with names such as: AG Arthur Galan, Alannah Hill, Anthea Crawford, A/X Armani Exchange, Bettina Liano, Carla Zampatti, cK Calvin Klein, CK Jeans, CK Underwear, David Lawrence, FCUK, Fleur Wood, Hugo Boss, Karen Millen, Lisa Ho, Max & Co, Morrissey, Oroton, Polo Ralph Lauren, Saba, Sass & Bide, Ted Baker and White Suede.
Willow, See by Chloe, Thurley, Easton Pearson and more can be found exclusively at David Jones, while Leona Edminston, Camilla and Marc and Wayne Cooper are exclusive to Myer.
Make time for Entertainment
As well as all the biggest names in fashion, Chadstone also offers entertainment for the whole family. Located on the lower level of the Centre is a precinct designed entirely for fun. There you'll find a 16 cinema Hoyts Megaplex, the AMF Bowl, Borders Books Music Cafe, plus other great cafes, bars and funky clothing stores.
Art, Architecture & Food
Chadstone is equally famed for its award winning architecture, luxurious fixtures, prized sculpture collection, relaxed environment and spacious Galleria which makes it a wonderful place to browse, shop, relax and enjoy a coffee at Koko Black, or a casual meal at Sapore Cafe. Two international food courts provide a wide range of cuisine from sushi to kebabs.
Download FastMall for iPhone or iPod Touch FREE – http://getap.ps/fastmall


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HUE Ministripe Sock
The HUE Ministripe Sock are not just super-cute, they are also super-stylish. Available in a variety of fresh seasonal colors these ministripe socks are a must-have year round.
- One size fits all
- Sold in 1 pair packs/single pair
- Elastic cuff
- Reinforced heel
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- Fabric content: 64% cotton, 33% nylon, 3% spandex
- Care: machine wash, tumble dry low
Style: 13351
We've been in business for over 125 years and pride ourselves on exceptional customer service both in our Manhattan store and online. If you have any questions please don't hesitate to contact us. We're always happy to help!Here's what our customers think of Town Shop!


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I just tried to run Beta 3 using my backup of production 5.2 data (working on repoducing a scan issue with 5.2 that I was told to try in 5.3 (Spiceworks Ticket number #54432)
When I copied all the db and Data back from the backup file and restarted the app it hung at 90% complete (starting the desktop)
When I loaded the app directly (new tab) it had all the ticket info and email settings but all the network scan settings were gone.
Runing spiceworks on
Win 7
UAC enabled
Local account (2nd time I ran spiceworks)
Fresh install and upgraded production backup
5 Replies
Dec 5, 2011 at 3:50 UTC
Just reinstalled beta 3 using production backup and it still does not have any Network Scan Settings that show up.
I should say this time it got stuck at 20% backing up data for around half an hour.
Dec 5, 2011 at 3:53 UTC
I just ran through installing Beta 3 and copied over my 5.2 production data and let it update. My network scan settings came over fine. Does your beta 3 install have your production settings.yaml file or the one that came with the beta 3 installation?
Dec 5, 2011 at 3:59 UTC
Looks like it is fresh clean copy (half the size as the one in my production system)
Did you copy the data and db folders from your production computer or the backup?
Dec 5, 2011 at 4:02 UTC
ok so looking at my backup file that I was using it did not have the settings.yaml. This must have happened one of the first itmes I was restoring the info (by moving files) where it seemed to get stuck.
I will restore a new copy of the backup and see how it works. Thanks for the information :)
Dec 5, 2011 at 4:20 UTC
I installed 5.3 and cancelled before entering the account information. Then I deleted out the data and db folders that came with the beta, then moved over a copy of my production db and data folders from a Spiceworks backup file. Waited a minute or two, then started up Spiceworks and let it update the database.


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- Vegetarian options
- Gluten free options
About The Steady Café and Bar
We're a Miami-inspired bar and brunch spot. Folks love us at night for our homemade cocktails, craft beer, vegan donuts, espresso, free wifi and unique events and dance parties. Folks love us in the daylight for our non-vegan & vegan brunch, award-winning vegan + GF donuts, caesar bar, breakfast cocktails, lattes and free wifi!


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His sermon brings the Easter narrative full-circle.
At Easter, we celebrate what Christ has done for us.
We follow his example of kindness to others, and we look forward to his return.
I just had to include this video of my daughters blowing out an egg...
so easy, a two-year-old can do it! :)


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Readerpix: B17 overhead
Hoboken411 reader Matt snapped this picture of that B17 Bomber you see flying over Hoboken all the time.
Hoboken411 reader photo of the day – 2/6/2009
[Stay tuned for tomorrow's Readerpix entry! – Note: one reader's photo(s) will be featured each day at approximately 11am. Unless your photo is time-sensitive – it will be published in the order it was received! Additional note: Your pictures will have a better chance of being published if they're in "landscape" mode, as opposed to the taller "portrait" modes… ]


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Do Guys think it's unatractive for a girl to have a big tattoo in the middle of your back?
Option A- you like it.
Option B- you dislike it.
Most Helpful Guy
Well it would probably depend on what it was but in most cases I would choose option A over B. I wouldn't really make any judgements before I met her though because it seems like people who are really tatted up are either pretty interesting, non-judgemental, and laid back or they're just obnoxious.11|00|0


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Simple Breaded Chicken Drumsticks
Recipe by thechefimpersonator
I find that in many cases, people over complicate their recipes and steer away from the basic goal of solid, delicious taste. I find this recipe really hits home with a wonder crisp and taste. I cooked this recipe on thechefimpersonator.com and the viewers loved it!
Top Review by CoCaShe
This reciep was simple but really good! I left it in the oven for about 50 minutes, then covered with foil while my potatoes finished up and some of the areas of the drumstick with less meat was a bit dried out, but great crispy flavour and even fairly healthy. I'll try it again with a meatier piece of chicken, like bone-in breast or thigh.
Ingredients Nutrition
- 2 lbs chicken drumsticks (take the skin off)
- 2 tablespoons olive oil or 2 tablespoons vegetable oil
- 2 cups seasoned Italian breadcrumbs
- 2 eggs
Directions See How It's Made
- Preheat your oven to 425 degrees with a rack in the middle of your oven.
- In an oven dish (I use a glass pie plate for sticking purposes) place the oil and allow it to coat the entire bottom.
- If you have not already done so, remove the skin from the drumsticks. If you find it difficult to pull the skin off the chicken, use a paper-towel to grip the skin to pull it off.
- On one plate, crack both eggs and whisk them into one uniformed egg wash.
- On a second plate, place the two cups of breadcrumbs; spread them out evenly.
- Begin by rolling one piece of chicken in the egg mixture. Make sure the chicken is covered completely and evenly.
- Take the chicken and roll it in the breadcrumbs. With drumsticks, I find it beneficial to dip the top of the drumstick chicken into the mixture as well as drizzle breadcrumbs in the area of the chicken near the bone since those two areas often do not touch the breadcrumb plate.
- Place chicken into dish, meaty side down.
- Repeat coating process for all the chicken.
- Place dish in oven and allow to cook for about 45 minutes. Rotate each piece of chicken at this point to allow it crisp throughout.
- About 50 minutes to an hour in, the chicken will appear to fall off the bone. The chicken should be done at this point but make sure to check it with a meat thermometer to confirm. In the meaty section of the chicken (should be up at this point) the temperature should reach at least 165 degrees F.
- Chicken's done!


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quickies - Page 5
Love Is Actually Dead: Jon Hamm and Jennifer Westfeldt Split After 18 Years
Also, The Rock rescued two puppies, Kanye smiles, and Caitlyn Jenner makes a joke-ish about the two kids she shouldn't have had.
Nicki Minaj, Miley Cyrus, Taylor Swift & More Reflect On The MTV VMAs
Plus, Coco is worried that Baby Ice-T will tear her "petite vagina" during childbirth! TGIF!
Tom Brady's 4-Game Deflategate Suspension Has Been Overturned
Plus, Caitlyn Jenner CRIED when she watched the video for Tyga's "Stimulated" and Idris Elba responds to comment that he is "too street" to play James Bond.
Taylor Swift Was Not Happy Kanye West Went Off Script At The VMAs
How dare Kanye West not stick to their previously agreed upon talking points!!!
Nicki Minaj's Confrontation With Miley Cyrus At The VMAs Was Not Staged
Pretty sure Miley planned to free her nipple though.
Did Demi Lovato "Flick" A Girl's Vagina At A Meet-And-Greet?
That's the rumor! Plus, Lucy Liu had a baby and Justin Bieber has a new song/video.
Alison Parker & Adam Ward's WDBJ Colleagues Pay Tribute To Murdered Journalists
"We want to pause and reflect and share once again what made these two so special."
Dre's Ex-Fianceé Miche'le On His Apology: "Treat Us Like We Have Names"
Dre somehow keeps sticking his foot in his mouth, Jimmy Fallon's horrible ring finger incident is fishier than we suspected, and everything you wanted to know about dating Justin Bieber(why).
Jessa Duggar Posts Awfully Convenient Bible Verse About Forgiveness Following Brother Josh's Cheating Admission
Plus, Kelly Osbourne vs. Giuliana Rancic, and Wiz Khalifa gets taken down by the po-po for refusing to get off his HOVERBOARD.
Anna Duggar Will Stand By Her Man, Likely Take Some Blame For Josh Duggar's Indiscretions
Plus, two more women accuse Bill Cosby of rape and I am being stalked by a squirrel named Chad.
OMG, It's Jennifer Aniston's Wedding Ring!!!
Can. You. Believe. It. Can you?!
Ashley Madison Hackers Released All Their Stolen Data, Our Long National Nightmare Has Begun
PLUS: They found Rosie O'Donnell's daughter and Kerry Washington has words to say about her "post-baby" body.


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SE: Vogel Vamps Up Play for No. 23 K-State Heading into Big 12 Schedule
SE: Vogel Vamps Up Play for No. 23 K-State Heading into Big 12 Schedule
Bryna Vogel thought it was a trophy, another one to add to her vast collection of athletic achievements. It was only when the K-State junior looked carefully that she realized what she was holding.
Vogel ended the best week of her volleyball career with a 21-kill performance at a remarkable .704 hitting percentage Saturday against Southern Mississippi in the Arkansas Invitational. No K-State player has ever recorded that many kills at a higher efficiency, meaning her performance was not only historic but it also stamped her as the obvious choice for the tournament's MVP.
Her prize for accumulating 39 kills, 23 digs, six block assists and five aces in three K-State victories? No, not another trophy. Instead, she received an Apple Watch.
"I was really shocked," Vogel said of receiving the high-tech watch. "I was surprised."
K-State head coach Suzie Fritz was not the least bit surprised by Vogel's recent play. She said the coaching staff could see "this" coming since last spring. "This" also included Vogel putting up 18 kills, eight digs and five block assists in a home win against Creighton, the start of a dominant stretch that ended with her earning Big 12 Offensive Player of the Week on Monday.
"She just seems like she's seeing things faster. Sometimes when you hear athletes start to talk about the game slowing down for them — that things are developing slower, that nothing seems fast anymore — a lot of that has to do with how fast they see things," Fritz said. "You hear NFL receivers talk about it, you hear NBA point guards talk about it, you hear MLB batters talk about it, that all of a sudden things seem to be developing slower for them, and I feel like that's where Bryna is at as a player. She sees things a lot faster."
Vogel points to a number of factors for her recent surge.
One, her confidence is high, which has "really helped." Two, her experience at the U.S. Collegiate National Team-Indianapolis program this summer has carried over into the season. Three, she's surrounded by a solid group of teammates who have pushed K-State (11-2) to a nine-match winning streak and a No. 23 national ranking.
"It's the team working together, it's not about just me," said Vogel, as K-State opens Big 12 play against Iowa State in Ahearn Field House Wednesday at 7 p.m. "When they're doing well, I can do well also. We have to work together to be good, so it's not just me."
Before college, Vogel's athletic focus covered more than just volleyball.
She became the first athlete selected to the Wichita Eagle All-Metro Team in three sports — volleyball, basketball and softball. As a senior, Vogel earned the 2014 Lynette Woodard High School Female Athlete of the Year by the Greater Wichita Area Sports Commission, matching a feat her sister, Tricia, who played softball at Emporia State, accomplished in 2010.
"Bryna is unusual. She was all-state in three sports and she was devoting a very minimal amount of time to playing volleyball prior to coming to college," Fritz said. "That is different than the majority of players we get, who have played volleyball for a long time and a lot of them are solely devoted to being volleyball players. She was very different."
When the time to decide on a sport to pursue for college approached, her parents — Randy and Nancy Vogel — sat her down. Her decision came down to a number of factors, but a conversation with them certainly helped out.
"My parents just said that whenever they see me playing volleyball, I just light up when I'm on the court," she said. "That's how I leaned toward volleyball."
Her parents also had a role in where their youngest daughter went to play volleyball. The two met while attending K-State, which Randy played football for, and trips back to their alma mater were frequent for athletic events.
Additionally, Vogel wanted to pursue a career with animals. With K-State's highly regarded Animal Science program, Manhattan made perfect sense.
"I really, really wanted to come here, so I went to all the (volleyball) camps my junior year," Vogel said. "They finally picked up the hint that I wanted to go here."
Fritz said Vogel's attendance at those camps blew the K-State coaches away. The athleticism she brings to the table, the work ethic she owns, the mindfulness she displays and the potential player she could become all came to light.
Now, it's all coming together.
"Part of what we've seen with her is because in the last two years it's the only sport she's really done," Fritz said. "She's devoted herself to one thing and you've really seen her make as much or more improvement than anybody we've ever had."
Vogel ranks third on the team with 141 kills on the season, but her .349 hitting percentage tops the team among players with at least 300 total attacks. She also ranks first in aces (14), third in digs (114) and fourth in blocks (27), bringing a complete package of skills to the floor for K-State.
"Bryna does so many things well," Fritz said. "We ask a great deal from her, as we do anyone else who plays six rotations, but she's a tremendous defender, she can score points with her serve, besides what she can do at the net as an attacker."
Those who know Vogel wouldn't be surprised by any amount of success she reaches in any area. Driven by her faith and family, the Clearwater native tries to be good at everything she does, which is a lot.
She's musically gifted, able to play the guitar and drums. She also enjoys artwork, passionate about drawing and painting. Vogel graduated first in her class at Clearwater, a 4A school 20 miles southwest of Wichita. She has earned numerous academic honors at K-State, where she hopes to turn her education into a career in either training animals for movies or for people with disabilities.
Whatever she does, she'll probably be good at it.
"She's a very fast learner and she's just a very mindful person in the way that she approaches her life," Fritz said. "She's pretty special in a lot of ways."


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How's it going? I've been keeping track of the My Name Is Rachel Corrie controversy up at New York Theatre Workshop as best I can through George and Garret's vigilant blogging. The whole circus seems to have run its course for the moment -- which has only given way to a double-bitter undertow: "Why aren't people in the streets protesting the Machine!" I don't know. My copy of the play was supposed to arrive sometime last week, but alas. I'd like to think this debate could happen without a serious examination of the play in question (there's plenty to chew on pure principle) but in the meantime, people are citing the play's accumulated praise and its plot/content summary to make their case. And I think we're missing something.
On the surface, it would seem the play's absence has done more to stoke community-wide discussion than its presence ever could. That's an unfair conclusion, of course, since we'll never know what its regularly-scheduled NYC debut would have accomplished -- and I don't think MNIRC's criticism-to-date gives us any clue to how NYC audiences will react. I've seen too many plays rock the world only to be panned out of spite in NYC. Sorry, it's true. And now ... people are prepared to be edified out of spite! If you haven't read Walter Davis's essay, please do. And then try to add another layer of meta-rage, if you can. I can't.
But something else bothers me about the whole catastrophe, something quite apart from the blunt injustice of NYTW's original decision. I'm terrified that we (as artists, as activists, as Americans) can only process injustice through a first amendment filter. Rather than expand the definition of censorship to include the present disaster, I'm going to let censorship and free speech remain issues of the State. For the moment. Here are the other questions I have:
- Are free speech battles the only ones we're confident we can win?
- Because both the American Left and Right have a common stake in its sustenance -- meaning there's a good chance we'll win?
- Do we believe the first amendment provides the axis for every other human right we can imagine? (would like to explore this at length, regardless)
- Are we over-eager for free speech battles because they lend themselves to instantaneous courtroom dramas in our heads?
- Is it possible that Nicola's crime is something categorically different from censorship? Something, possibly, much worse?
- If I wrote something nasty on this blog and then someone retaliated by impaling my dog with a rusty lawn dart, would that be an assault on my freedom of speech? Is it possible that this would-be dog-killer was actually responding very specifically to the content of my blog, not my right to write it?
"If Augustine had obsessed over Greed the way he obsessed over Lust, you'd have to buy your Wall Street Journal in a brown paper bag. And Hustler would be available on every street corner."
I think about that and I wonder if the artistic temperament is prone to a similar fixation -- not w/r/t Lust of course, but a tendency to conflate all sins with some form of censorship.
Just before the MNiRC scandal started to bloom, I got an e-mail from PJ asking if I'd like to resume my part as Eric Harris in columbinus. At NYTW. I was ecstatic at first, but too bogged down in Elsinore to notice. Rehearsals were to start today -- April 11. 36 hours after closing Hamlet. Not much time to orchestrate a move from DC to NYC, but I went to work. I had to back out of The Monument at Theatre Alliance. So I called Jeremy (about six weeks before rehearsals were to start at H Street) and told him the story.
In the intervening weeks, he and I tried to get a more definitive confirmation from NYTW's casting folk and from PJ. And as late as two weeks ago, the offer still stood. Before offering my part in The Monument to another actor, Jeremy and I made one last round of calls to PJ & Co. to confirm that a) the project was still going ahead and b) I was still involved. After one final assurance from PJ that this was the case ... Jeremy offered my part to someone else. And then a couple days later PJ offered my part to someone else. Somewhere in the middle, I opened Hamlet. And now that it's over, I can finally come up for air and look at everything that's happened.
Since I suddenly have a lot of free time.
To PJ's credit, he did "own" the choice. Sure, he cited pressure from the NYTW staff to find a Name for the lead. After all, NYTW has a lot riding on their next show. But PJ made it clear that this was his choice at the end of the day. So if anyone wonders why I'm not appearing in either The Monument or columbinus as previously announced, that's why. I've had to explain this whole story to a lot of people in the past couple weeks; better to tell the rest of you now.
Here's what I'm stuck with: I gave up a show for nothing. Two shows, actually, since I had to bow out of The Violet Hour last fall just to come to NYTW and re-audition for my part in a backer's presentation. So that's two lead parts and four months of work -- half of which I gave up willingly and the other half ... well, what do you call that? It's not censorship.
My point. From the outside, the last-minute MNiRC cancellation looks like a clear-cut censorship issue. And I can certainly understand why Viner and Rickman (as writers) feel that way. But as an actor dealing with my own last-minute cancellation, I'm too overwhelmed with trying to re-arrange my life for the next three months. So it's not my freedom of expression that's been violated. It's my trust. I can make art in a police state. We've been doing that since 9/11, right? Or trying to. Or failing that, we have a gazillion stories to inform the battle against censorship. But I can't make art with artists I don't trust. And there's no court for this particular crime.
For anyone who's interested, columbinus is not an attempt to Romanize that tragedy. I've spent the better part of three years developing the play and, frankly, scrupulous contextualization was a huge part of that. In the end, I believe we made something more challenging (and honest) than Bowling for Columbine ... and something more daring (and honest) than, say, Elephant or Bingo Boys. I wish I could be there to share it. But since everyone's eager to pounce on NYTW's next move -- almost completely certain that it'll be a bad one -- I didn't want to say anything without having the time to actually join the discussion. Now that my show's over, I can.
More later ...


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"Your inner being is nothing but the inner sky. The sky is empty, but it is the empty sky that holds all, the whole existence, the sun, the moon, the stars, the earth, the planets. It is the empty sky that gives space to all that is. It is the empty sky that is the background of all that exists. Things come and go and the sky remains the same.
"In exactly the same way, you have an inner sky; it is also empty. Clouds come and go, planets are born and disappear, stars arise and die, and the inner sky remains the same, untouched, untarnished, unscarred. We call that inner sky Sakshin, the witness — and that is the whole goal of meditation."
Meditation in Rossendale at ENERGYBODi
Beginners and experienced meditators. Led by experienced teacher Fiona Morgan, these sessions are informative and accessible. Fiona is a gifted teacher who allows time for discussion, explanations and guidance.
Fridays 7.15pm-8.30pm
Drop in anytime £6.50
if you have a multipass, it is included.
This is a regular weekly class to facilitate and support the beauty of meditation. The benefits are many, they are profound and vibrate on the physical, mental, emotional and spiritual planes.
The ultimate expression of meditation is to liberate the world from suffering, to enlighten aspects of illusion and delusion, to become an ever increasing compassionate being, and to learn the ultimate truth of creation and existence.
The side effects are tremendous; health benefits, controlling thoughts, expanding consciousness and perceptions to name a few, listening to stillness being in silence, with your own precious being, ahhh, peace, bliss and calm. If you do nothing else for your sacred soul, do this. It is beyond compare and anyone can learn the art of meditation.
Physical Benefits of Meditation-
With meditation, the physiology undergoes a change and every cell in the body is filled with more prana (energy). This results in joy, peace, enthusiasm as the level of prana in the body increases.
On a physical level, meditation:
Lowers high blood pressure,
Lowers the levels of blood lactate reducing anxiety attacks,
Decreases any tension-related pain, such as, tension headaches, ulcers, insomnia, muscle and joint problems,
Increases serotonin production that improves mood and behavior,
Improves the immune system,
Increases the energy level, as you gain an inner source of energy.
Normally, our thoughts have tremendou
s power in our lives. They are the dictators of our mind: go here, go there, do this, do that. We're the slaves of our thoughts. And yet when we are aware of them, when we are mindful that we're thinking, we see that a thought as a phenomenon is completely empty and fleeting. It's little more than nothing! It's tremendously interesting to learn this about one's mind. It's very freeing!
One of the things we learn in meditation is how untrained our minds are. To me, one of the great beauties of the practice is to see the commonality of the experience. While the content, the stories may be a little different, the way we get caught up in our minds—and the way we let go—is exactly the same. So the more we understand ourselves, the more we understand each other.
When I started meditating, I didn't have some amazing degree of concentration or anything. My mind just thought all the time, and it was fun! I was entertaining myself with thinking. So if I could come to some understanding of my mind and taste a little bit of peace, anybody can. And the more you practice the better you get at it.


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Send a message explaining your needs and Tom will reply soon.
Response time: 8 minutes
Michigan State University
GVSU (Graduate Coursework)
My philosophy can be summed up in one word: simplify. As I see it, my job is to take misunderstood concepts and find strategies and methods that will make them understandable. My goal is for you to spend the fewest amount of dollars in the shortest period of time. If I accomplish that, then I feel I've done my job.
I have successfully tutored students from elementary school to college master's programs covering such topics as Fractions, Quadratics, Microbiology, Anatomy, TESOL and Linguistics.
To help illustrate my success, 85% of my algebra class at Colegio Americano de Guatemala passed with a 3.0 or better as measured by normative achievement standards. I also taught basic math/pre-algebra in the Summer Migrant Program at Fennville Public Schools; all students showed a minimum 35% improvement in operational competency. As an ESL teacher, I raised reading/writing scores a minimum of 25% when measured against normative standards. Additionally, I was able to raise basic math competency over 85% in three weeks for the students in the Vámonos tutoring program. Finally, my TESOL students in the master's program at GVSU earned a final grade of 4.0. I provided linguistic tutoring and writing support for their final project. My philosophy can be summed up in one word: simplify. As I see it, my job is to take misunderstood concepts and find strategies and methods that will make them understandable. My goal is for you to spend the fewest amount of dollars in the shortest period of time. If I accomplish that, then I feel I've done my job.
I have successfully
Tom is a reliable and patient tutor. He helped my son tackle algebra when it became complex in 8th grade. He now has a better understanding of how to solve problems and is pulling his grade up. I highly recommend Tom.
Tom appears to be knowledgeable about algebra one and how to explain it. My son enjoyed the tutoring session. We look forward to continuing to use his services and seeing our son's grades do better in school this upcoming year.
Approved subjects are in bold.
In most cases, tutors gain approval in a subject by passing a proficiency exam. For some subject areas, like music and art, tutors submit written requests to demonstrate their proficiency to potential students. If a tutor is interested but not yet approved in a subject, the subject will appear in non-bold font. Tutors need to be approved in a subject prior to beginning lessons.
In addition to getting certified with WyzAnt, I've spent over 2.5 years teaching ESL (English as a Second Language) to undergraduate and postgraduate students from over 20 different countries looking to enter major colleges and universities in the United States. Because many of these students needed to take the TOEFL/IBT, I taught, as part of the curriculum, TOEFL/IBT test taking strategies. TOEFL/IBT is a normative standardized test very similar to ACT and SAT.
Additional experience includes teaching ACT Prep at Huntington Learning Center in GR. Just before starting my Spanish program at GVSU, I spent a year teaching ACT Prep to high school students in the greater GR area at Huntington.
As a student, I have taken all math classes Algebra 1, Algebra 2, Trigonometry, Precalculus, and Calculus 1 and 2. I have taught Algebra 1 as a High School teacher at the Colegio Americano de Guatemala (accomplishments listed in my profile). More importantly, I have successfully tutored students in all aspects of mathematical competency.
From 2005-2007, I was a student tutor at Baker College in Microbiology and Anatomy/Physiology. In order to be a student tutor, a student has to maintain a >3.5 GPA and be in good standing.
For over fifteen years, I was owner and president of a computer product and service company that sold business solutions to major fortune 500, mid-size manufacturing and architectural companies throughout the state of Michigan.
In addition to directing business planning, I developed the sales/marketing programs along with strategic planning for the company. I helped with new product development and ran all major public relations campaigns.
I have over eight years of K-9 experience as a certified teacher and I'm currently pursuing my professional teaching certificate at GVSU.
I've taught all content areas of K-9 math including Algebra. I have also worked as a private tutor in Holland, MI. with Vamanos Tutoring.
Please read my professional profile for more information about my experiences and accomplishments.
Please review my descriptions of ACT English and Writing to understand my specific qualifications and accomplishments.
From 2007-2010, I taught ESL at ELS/GVSU in Allendale, Michigan. I tried to incorporate Communicative Language Teaching strategies that emphasized more performance than competence. My SLA philosophy is more closely aligned with Stephen Krashen in which I feel that the L1 learner can be successful with enough rich and positive input.
I'm not only certified in ACT and SAT preparation, but I have just completed WyzAnt certification in GED test prep. In addition, I'm currently working as an Academic Tutor assisting students at Waalkes Detention Center with High School diploma and GED test preparation.
Academically, I have taken all math classes Algebra 1, Algebra 2, Trigonometry, Precalculus, and Calculus 1 and 2. I have taught Algebra 1 as a High School teacher at the Colegio Americano de Guatemala (accomplishments listed in my profile). More recently, I have successfully tutored students in Geometry for credit recovery in E2020 at Waalkes Juvenile Academy.
While at Baker College, I took two semesters of Microbiology with a cumulative GPA of 4.0. Subsequently, I was invited to tutor Baker students in Microbiology and did so for approximately 1.5 semesters.
I have extensive experience and success teaching all prealgebra concepts including factors, equality, constants, variables and fractions.
I have a middle school daughter and son both of whom I tutor and advise in math and writing. My daughter is currently doing HS algebra and my son has raised his grades two levels from 6th to 7th grade.
In addition to having 34 college credits with a cumulative GPA of 3.85, I've taught 1st language Spanish students in both the Colegio Americano de Guatemala and the Summer Migrant Program for Fennville Public Schools.
Some additional experiences include: being one of the first volunteers to help organize the Tulipanes Arts/Film Festival in Holland, Michigan, tutoring for two years in Holland's Reciprocal Language Program, and working with a private Spanish tutor for over 5 years maintaining my language proficiency.
In addition to my K-9 classroom experience, I've taught ESL students from over twenty different countries. In all that time, the only strategies that I've found to be effective are understand a few "rules", reading more, and trying to memorize difficult words.
In addition to learning abbreviations, I emphasize the practice of the Cornell Note Taking System.
If this is properly implemented, the student should be able to succeed in any class.
For over two years, I've worked as an ESL instructor teaching writing and language skills to undergraduate and postgraduate foreign exchange students from over twenty different countries.
I've had a lot of success improving their writing and language skills. I base much of my philosophy about SLA (Second Language Acquistion) for L1 and L2 students on Stephen Krashen's model of input/output hypothesis and affective filter.
Writing is hard work, but with some simple strategies a student can improve dramatically in a short period of time.


text: I just installed XF today, and I have managed to get my admin account locked, because I typed the wrong PW too many times. In fact, I have forgotten my PW (I know it sounds like I have the memory of a gold fish but Im dead tired after a long day). Where can I reset it?


text: 12 photos $99,900 3.69 acres Gateway Park, Livonia, NY 14480 - Livingston County Commercial Land in Gateway Park Livonia NY with High Visibility 3.69 acres Commercial Property situated in Gateway Park Livonia, NY with High Visibility. This vacant tract is perfectly situated in a high traffic corridor between Livonia, Geneseo and Avon. It is zoned Commercial/Limited Industrial District and suitable for high-intensity Commercial and Industrial uses. The property is a corner lot with 678 ft.of frontage on State Route 15 and 577 ft.of frontage on South Lima Road (County Route 19). The property is serviced by municipal sewer and water. 3-Phase electric and natural gas are on the property. Located 3/4 mile off Exit 9 on 390. This property is adjacent to Fratellis restaurant and a number of small commercial andindustrial businesses in Gateway Park. This corner lot is a prime locat Carl H. Snyder NY Land Quest, LLC


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I'm just lazy man.
Come exam time I'll be studying for hours and hours straight and can do it.
During the week I'll just... not study.
I don't know why I'm like this.
Most Helpful Guy
I'm the same way, and I always have been. For me, studying the material throughout the course is a waste of time because I'll forget practically all of it by the time the exam comes around.
It's much more effective for me to cram for everything all at once shortly before the exam so that I can actually remember it.
Despite all of this, I never got lower than an A- on a report card throughout my entire four years of high school. It worked for me, so I stuck with it.00|00|0
Most Helpful Girl
I hated studying, always saw it as a waste of time. I never studied in high school and aced all my classes, and i was in mostly AP classes...00|00|0


text:
Everyone knows that a Chinese boy wants a 温柔的女朋友. I'm not sure of my translation here but you could say it means a 'gentle' person, perhaps someone with more traditional views, someone who is not too demanding? Someone who knows that the man is boss?
But one boy recently said to someone I know that he planned to go to Australia and find an Australian 温柔的女朋友. Good luck. :)
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text:
Generac at Lowe's
Save on all Generac products
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Return to TopLearn more about Generac
Lowe's Canada is the best place to shop for Generac products
Generac has earned a reputation as the company home and business owners turn to when the power goes out. The first to engineer affordable home standby generators, along with the first engine developed specifically for the rigors of generator use, they now sell more home standby generators than all of their competitors combined.
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text:
Perfect for cooking yourself or your family a hearty breakfast, this square griddle in a bold red hue offers a nonstick scratch resistant surface.More Details >
This modern and reliable nonstick square griddle is a wonderful item to be able to utilize in your busy kitchen at home. With an attractive red finish, this griddle adds a fresh presence to the look of your stovetop area. The scratch resistant exterior ensures a consistent charm, and the even heat distribution ensures proper cooking and enjoyment.


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Racing is always such a cut can be divided into several types, some imply the story and sometimes even interesting history, some prefer not to be distracted from the main process and immediately throw you into battle, without explanation and without a variety of controversial issues. In this game no plot itself is not all that there is - a short training that will bring you quickly up to speed and explain what's what. After training, you just have to start the race, try to set new records and otherwise expand their garage. In general, this approach many people want because not everyone needs all these stories, and drive a car - something for which game and downloads.
With gameplay developers in general, also did not disappoint. Luckily I came across all sorts of fancy race in a straight line or a runner, then the most common race track complex and circular, quite tricky opponents and have the opportunity to play with real people in multiplayer mode. As for the car and your garage, it is all too simple and clear - will have to start with the cheapest car, the developers clearly did not exactly breathe a classic car, there's even a Russian Volga have that fun. Start to win the most basic car, after which it will be able to buy another pump or, certainly faster. Cars in the game Underground Racing HD is pretty much tuning, too, so that will not be bored, as if you did not try.
Among other things, the game is very good graphics, though not at the level of the top projects, but it looks quite modern, but with a good amount of optimization is a pleasure to play.
Bottom line: the game Underground Racing HD, though the dark horse, but on closer examination turned out to be a very interesting and high-quality projects free, but not without a small Donat. Definitely recommend to all fans of the genre!
Along with the game you need to download cache and extract it to a directory: sd / anroid / obb
- Filesize Optimization
|date of download
|The size
| Other languages
Arab, Azerbaijani, Bulgarian, Bengal, Catalan, Czech, Danish, German, Greek, English, Spanish, Estonian, Basque, Persian, Finnish, French, Irish, Galician, Gujarati, House, Hebrew, Hindi, Croatian, Hungarian, Armenian, Indonesian, Igbo, Icelandic, Italian, Japanese, Georgian, Kazakh, Kannada, Korean, Lithuanian, Latvian, Macedonian, Malayalam, Marathi, Malay, Norwegian, Dutch, Punjabi, Polish, Portuguese, Romanian, Russian, Slovak, Slovenian, Serbian, Swedish, Tamil, Telugu, Thai, Turkish, Ukrainian, Urdu, Vietnamese, Yoruba, Chinese
|no viruses
|inspection date
| View report
(Proverechno using the service virtustotal.com)
| full network access
Allows the app to create network sockets and use custom network protocols. The browser and other applications provide means to send data to the internet, so this permission is not required to send data to the internet.
| read phone status and identity
Allows the app to access the phone features of the device. This permission allows the app to determine the phone number and device IDs, whether a call is active, and the remote number connected by a call.
| view network connections
Allows the app to view information about network connections such as which networks exist and are connected.
| modify or delete the contents of your USB storage
Allows the app to write to the USB storage.
| view Wi-Fi connections
Allows the app to view information about Wi-Fi networking, such as whether Wi-Fi is enabled and name of connected Wi-Fi devices.
| Google Play license check
Google Play license check
| take pictures and videos
Allows the app to take pictures and videos with the camera. This permission allows the app to use the camera at any time without your confirmation.
| prevent device from sleeping
Allows the app to prevent the device from going to sleep.
|The size
|date of download
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Rating:(38) 3.8★ 75.92%
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text:
It's the Greens vs the Tories & we need your help in these crucial final few days
We've been campaigning hard in Goldsmid ward over the last couple of months, and it looks like we may well win here. We even have the backing of an ex-Labour councillor in the ward!
If the Greens won, it would not only make us the joint official opposition - giving us the same number of councillors as Labour, but it could also change the power of the finely-balanced city council, removing the overall control from the Tories.
It would obviously also be a massive boost to Caroline Lucas' Westminster Campaign!
Making History
This would be our first seat in Hove, and the first time we've changed a Tory seat to a Green seat in Brighton and Hove.
What can you do?
Due to the political climate at the moment, turnout will be very low, and there are still lots of people who are undecided.
If you can help with canvassing in Brighton, or tele-canvassing wherever you are, over the next 3 days, or if you'd like to help on polling day itself, please let me know.
You can email me on: email@example.com
We are running a full telling operation on Thursday 23rd July and will therefore need as many people as possible to knock up to get the Green vote out in Brighton!
Thanks and all the best,


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- Weary
- Weary Wea"ry, v. i. To grow tired; to become exhausted or impatient; as, to weary of an undertaking. [1913 Webster]
The Collaborative International Dictionary of English. 2000.
The Collaborative International Dictionary of English. 2000.
Weary — Wea ry, a. [Compar. {Wearier}; superl. {Weariest}.] [OE. weri, AS. w?rig; akin to OS. w?rig, OHG. wu?rag; of uncertain origin; cf. AS. w?rian to ramble.] [1913 Webster] 1. Having the strength exhausted by toil or exertion; worn out in respect to… … The Collaborative International Dictionary of English
Weary — Wea ry, v. t. [imp. & p. p. {Wearied}; p. pr. & vb. n. {Wearying}.] [1913 Webster] 1. To reduce or exhaust the physical strength or endurance of; to tire; to fatigue; as, to weary one s self with labor or traveling. [1913 Webster] So shall he… … The Collaborative International Dictionary of English
Weary — may refer to: *Jake Weary *Fred Weary *Emily Pohl Weary … Wikipedia
weary — ► ADJECTIVE (wearier, weariest) 1) tired. 2) causing tiredness. 3) (often weary of) reluctant to experience any more of. ► VERB (wearies, wearied) 1) … English terms dictionary
weary — [wir′ē] adj. wearier, weariest [ME weri < OE werig, akin to OHG wuorag, drunk < IE base * wōr , giddiness, faintness > Gr hōrakian, to be giddy] 1. tired; worn out 2. without further liking, patience, tolerance, zeal, etc.; bored: with… … English World dictionary
weary — (adj.) O.E. werig tired, related to worian to wander, totter, from W.Gmc. *worigaz (Cf. O.S. worig weary, O.H.G. wuorag intoxicated ), of unknown origin. The verb is O.E. wergian (intr.), gewergian (trans.). Related: Wearied; wearying … Etymology dictionary
weary — [adj] tired all in*, beat*, bone tired*, bored, burned out*, bushed, dead*, dead tired*, discontented, disgusted, dog tired*, done in*, drained, drooping, drowsy, enervated, exhausted, fagged, fatigued, fed up, flagging, had it*, impatient,… … New thesaurus
weary — index exhaust (deplete), lugubrious, otiose, tax (overwork) Burton s Legal Thesaurus. William C. Burton. 2006 … Law dictionary
weary — vb *tire, fatigue, exhaust, jade, fag, tucker Analogous words: debilitate, enfeeble, *weaken: *depress, oppress, weigh Contrasted words: energize, *vitalize: animate, *quicken, enliven, vivify … New Dictionary of Synonyms
weary — I UK [ˈwɪərɪ] / US [ˈwɪrɪ] adjective Word forms weary : adjective weary comparative wearier superlative weariest 1) very tired, especially because of hard work or activity They collapsed on to their beds, too weary to get changed. a) showing that … English dictionary


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Job Description
With over 15 years operating within the fast-paced Digital TV industry and offices located across four continents, Mirada is an excellent place to kick-start or advance your career in a globally renowned company.
Here at Mirada, we are just as passionate about our products and services as we are about our people. We thrive on being at the cutting-edge of our industry and over the years we have attracted and retained the finest in talent, capability and know-how who strive from day one to make that possible.
With a work environment like no other that fosters innovation, rewards success and encourages growth and fun, if you're ready for an exciting and fulfilling challenge, Mirada is the place for you!
Discover a day in the life of Marketing at Mirada
Are you a perfect candidate?
If you're creative, energetic and brimming with ideas to share, you are already three steps closer to joining our dynamic marketing team where no two days are ever the same!
You are a self-confessed tech geek and you admit that you spend lots of your time on social media – and maybe even have a blog. People would describe you as a self-starter: you like to spread your wings and you don't need constant supervision.
You work a lot and laugh even more. You aren't afraid to make things happen and you have a positive attitude to life.
You will be doing many things, for example:
- Organisation, coordination and management of our presence at international trade shows
- Management of departmental expenses and basic accounting
- Press review and technology content creation
- Work on our corporate image, website and brand awareness
- Collaboration with our Product Marketing strategy and execution
- Translation work (English – Spanish)
Your profile meets these minimum requirements:
- Bachelor's degree
- Excellent level of both English and Spanish, at least C1 (part of the interview will be held in English)
- Minimum 2 years work experience
The following would be very welcome:
- Education in Journalism, Administration, Marketing or similar
- Experience in B2B Marketing and Communication
- Experience in a Software Development company
- Practical knowledge of Adobe Design software/Photography
What we offer:
- Long-term contract
- Fixed salary depending on the experience of the successful candidate
- Variable incentives
- Tickets Restaurant
- Private health insurance and life insurance
- Fruit Fridays
- Short work day every Friday
- Short work days during July and August
- Fantastic work environment, seasonal parties and much more…
Connect with us for a sneak peek into life at Mirada:
A typical day at Mirada for Heather
9:00: I arrive at the office at 9… okay, 9:30! Flexible hours are the best!
9:35: I check my inbox and for breaking news in our industry which, of course, there is! With the most interesting articles, I curate our Weekly Press Review for the whole company. Knowledge is power!
10:30: Breakfast time at a bar with the guys from UX and Tali from Editorial to laugh about our crazy weekend antics…
10:45: Back to my desk and time to start working on my latest project: Our 'Diwali' campaign for India!
11:30: 📩 My boss Rosi has just scheduled a meeting for this afternoon to review the data from our Christmas campaign. Time to get analysing how we did!
13:00: Brainstorming ideas with HR in the 'Chatbox' for our upcoming careers fair! I schedule a meeting with Débora from UX to discuss our stand design and invite UX Boss, Bencomo, too – I know how he likes to share his ideas 😉
14:00: Lunch time: Someone is ordering sushi and how can I say no?! There's a gym right next to the office, I'll go after work!
15:15: Time for this week's 'geeky' workshop which (secretly) is my favourite thing about working at Mirada. Who knew that software could actually be quite cool, or that I'd find myself interested in how APIs work?!
16:30: Time for my meeting with Roszana to go over the analytics of our Christmas marketing campaign. It's fascinating to see how far and wide our campaign reached around the world, and to see what ideas worked well and how we can improve next year. Once the meeting is over, I start putting ideas together about how I am going to present the results the following week.
18:10: Back at my desk, I edit my photo of Marque, one of our Developers, bouncing around his office on his pilates ball and, along with a cheeky caption, I schedule it for tomorrow's social media posts.
19:30: 📩 Post-work drinks happening at one of the bars nearby, let's go! Oops, I will DEFINITELY go to the gym tomorrow…


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Brand Label: Timberland
ITEM MOVED TO ARCHIVE: On March 24, 2017 4:41 pm, Fashion Stylist Online noted this item may be out of stock at Shoebuy because it was not referenced in their latest online catalog. If this item is out of stock at Shoebuy, you may be able to find similar fashions sold there or elsewhere on our Timberland Designer Brand Directory.
Available for Purchase Online at Shoebuy for $64.95Pin It
A cotton canvas upper and moc toe make the Timberland Newport Bay Moc Slip On perfect for lazy weekends. 100% organic cotton canvas upper for lightweight durability and comfort Comfortable, breathable 50% recycled PET mesh lining made from recycled plastic bottles Vulcanized construction allows for comfort and flexibility Durable outsole is made with 15% recycled rubber Convenient slip-on styling for easy on/off.
Shop other brand label items from Timberland on FashionStylist.com.
This item was published for sale online by Shoebuy on March 24, 2017 1:46 pm and last updated by us March 24, 2017 4:41 pm.
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New promo codes and links offering limited time promotions, sales coupons, and special offers on Timberland designer fashions and accessories will be posted on each designer label apparel page. For the latest up to date information on this Timberland Men's Newport Bay Moc Slip On fashion item, including product specifications, ordering options, pricing, shipping details, high resolution pictures, shopper comments, and other sales media, visit the Shoebuy Online Store.


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Inspired by Trump, Boston Brothers Allegedly Beat Homeless Man
Two South Boston men allegedly targeted their victim because he was Hispanic, inspired in part by the Donald, and Trump's response to the incident? His followers are passionate. Our potential future president is a gem.
Here we have some great Americans dedicated to making America great again.
Police said two brothers from South Boston ambushed the 58-year-old as he slept outside of a Dorchester MBTA stop, and targeted him because he is Hispanic. One of the brothers said he was inspired in part by GOP presidential candidate Donald Trump. The allegations ignited widespread condemnation Wednesday. Mayor Martin J. Walsh said the brothers "should be ashamed of themselves." Boston's top prosecutor, Daniel F. Conley, called the case "sickening." Police Commissioner William B. Evans, a South Boston resident, said the brothers had given his neighborhood "a bad name." He called it "a disgrace."
Of course, Marty Walsh already has been declared a "clown" by the leader of the Leaders, so let's see what he has to say, shall we? After all, he's the guy who's declared open season on all the clowns and losers and Mexicans.
Trump, told of the alleged assault, said "it would be a shame . . . I will say that people who are following me are very passionate. They love this country and they want this country to be great again. They are passionate."
Rich, spoiled, arrogant thug.
Have fun, America.


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Mar 29, 2007
Just few recent pics after having the new wings and paint.
Now that looks great! Lovely car mate.
Heres my 03 A4 B6 Quattro Sport 3.0L V6
Iwas thinking of tinting my rear side windows, what is the grade of yours or is that OEM? also, are the front sides tinted too?
View attachment 15080
View attachment 15081
View attachment 15082
pics really small whats gone wrong can anyone fix this?
When I Clicked on them They've opened a Decent Size.....
Just to make you aware, you've posted a B8 in the B6 section.
Very nice m8
.............Sorry will delete and Move....
Windows tinted and roof bars fitted. Relak side skirts should be painted and fitted in 3 weeks. Im going to paint the cupra lip too.
Custom remap scheduled for next week too..
Love those relak skirts should look good
Ill post pictures as soon as I get all done.
My 1.8t sline 190
Thats a beauty!! :thumbup:
Cheers tac be good to see the pics of the skirts when there on really thinking about getting some or trying to quite hard to come by aren't they
They are. I got them direct from relak in the us...but their shipping costs to ireland are more expensive than the skirts. I created a "myus.com" account and their shipping costs are less than half the cost so happy days!
As the akoyas are up heres mine though i need to take new pics as has changed a little.......
bilder hochladen kostenlos
free screenshot software
Always jealous of that stance andie looks spot on
Got rear spacers 15mm, shadow chrome wheels, rear roof spoiler, rs4 grille so will get new pics also lifted rear slightly
Here's mine , lights are an ongoing work in progress which started with the repair of the burnt out factory xenons, then I need some 19's and a drop.
Very nice greeny,like that look very much.
Nice evening ....
Some great looking cars here......
Here is my 3.0V6 Cabriolet and my Beetle (we also have a 12 plate Toyota Avensis - But thats not worth taking pictures of)
Here's a few latest pics
Winter wheels
Now after a clean the summer wheels
Love the CH's TC :icon_thumright: close to purchasing a set myself just need to pull the trigger.
CH's look amazing on B6 sport/s-lines.
My A4...thinking that the headlamp insides need to be black though?!....
Put the car back on the road today finally. #Votex # Genuine CH's # Front end respray
That front end looks looooow! Like it a lot.
New wheels..
Gonna need more than that kris.
Will do..
Audi a5 sline 18" 8.5j ET29, centre bore 66,6 running spigot rings.
Better pics to come!
Looks lovely! Mauritius Blue Avants are the best looking A4's
Nice day for a couple of pictures, before I dented my wheel.
Separate names with a comma.


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Ligt Suspension with Fitting and Canopy
Exclusive by NUD Collection is a pendant lamp consisting of a three-metre long textile-coated cable as well as a socket and a canopy that altogether are formally harmonic adapted to each other.
Contrasting the NUD Classic, the Exclusive edition includes a perfectly adapted baldachin for the E27 socket, making viewers look upwards. The production out of ceramics ensures a high quality impress at the NUD Exclusive. For the decorative effect to unfold completely, the manufacturer suggests the usage of large light bulbs.
The colour range of the cable textile-coatings is wide. The cable (H03VV-F) can furthermore be shortened as desired. This is how the NUD Exclusive sets accents everywhere and it is adapted to many surroundings.
NUD Exclusive accords to European safety norms and it is made for light bulbs with max. 60W.