text:
All participants must sign the online waiver. A link to the waiver can be found @ http://www.edmontonpride.ca/pride_week/parade/. The direct website address for the waiver form is https://inkdit.com/ofr/xa159b81fb13fd7b8. The first item on the electronic form that needs to be completed is the name of the group. The name of the Parade group is "United Church". After the name of our group is typed in, you can type in your name and email address and submit the electronic form. You will receive an email conformation that your information was received.
Thank you very much for your help. If you have any questions, you are welcome to contact me by phone @ 780-918-7145 or by email @ firstname.lastname@example.com.
Gary Simpson firstname.lastname@example.com


text:
So here is my latest wishlist! Everything is from River Island (as usual) 😛 I don't plan to do all my wishlists on River Island products but River Island has just always been my favorite high street store! I had a look around a few other high street shops this week and nothing caught my attention! I think my obsession with River Island products had got worse since I started working there, because I'm around the clothes all the time eyeing everything up and saying to myself "I'm going to get this, this and this on payday!!" So my money is spent before I even get it so I am broke all the time! But hey I've got nice clothes 😉
Click on the images to shop them online
I love these black Molly glitter jeggings! You can't really tell from this picture you'll have to click the picture to see it properly but I think they're really Christmassy They cost €55.
I love these Chelsea Girl black velvet glitter leggings for a cheaper €26
Love these Chelsea boots for €45.
This black print t shirt is €25 and 30% of all proceeds go to Breakthrough Breast Cancer which I think is a really good idea.
Christmas is my favorite time of year so this 'Christmas List' t shirt is a must have
I loooove these fluffy shoes! They are so cute for AW and Christmas! They come in black too! I wouldn't mind these to keep my feet warm on a night out
And remember it's 20% off footwear until November 2nd when you spend over €20 on clothing in store or online
Happy Shopping
Hope you enjoyed reading!

subset: commoncrawl


text:
Since 1986, Teriyaki Experience has been delivering fast, fresh and healthy Asian-inspired fast food to fulfill guests' taste for great flavours and fast service. Recognized as the healthy alternative to traditional fast food, we've built a unique concept around the teppanyaki grill where meals are prepared right before guests' eyes. A complete line of flavourful, Asian-inspired secret sauces top our rice and noodle meals.
Brand Recognition Over 110 restaurants in operation worldwide.
Consistent Quality Serving the same high quality food with the same high quality service in all locations.
Excellent Service Professionally-trained owners and operators head every restaurant team.
Fast and Fresh Ingredients At the heart of every recipe are fresh ingredients prepared fast.
Monday – Friday: 10:00am – 3:00pm
Saturday/Sunday: Closed


text:
The Waters of RosendalE
As great whiskey distillers throughout the world — from Kentucky to Scotland — have long known, it takes sweet water from tough rock to make great whiskey.
This is why all Widow Jane products are proofed with water from the historic limestone caves of Rosendale, New York – a water with unique chemical properties.
For over one hundred years Rosendale's mines made the most technologically advanced building material in the world. Rosendale cement was world-renowned and built many of the monuments that define America: The Brooklyn Bridge, parts of the White House, the pedestal of the Statue of Liberty, and its crowning achievement the Empire State Building.
Their technical prowess was eventually superseded, the mines fell quietly into disuse. Over the next hundred years a magical process of gentle rainfall filtering down and deep underground aquifers upwards flow combined to fill the mines with pure fresh water that drew its own strength from the limestone that cradled it. The result, a unique sweet water unusually high in mineral content and thus perfect for making and cutting great whiskey.
Widow Jane – 218 Conover St, Brooklyn – firstname.lastname@example.com


text:
Yesterday, I experienced something that has occurred way too many times with the E-hail Curb pilot program. It seems to be a continuing issue when a driver hasn't been notified that they are picking up a passenger with in a wheelchair. The real issue is that I do make sure to request need an accessible vehicle but it shouldn't feel as if it's my fault because of miscommunication through the phone application. Continue reading "Kick to the Curb"
Kick to the Curb


text:
Aop: 144
AOP Title
Short name:
Graphical RepresentationClick to download graphical representation template
Kirsten Gerloff
Brigitte Landesmann°
Gladys Ouedraogo*
° F3 Chemical Safety and Alternative Methods Unit incorporating EURL ECVAM
Directorate F – Health, Consumers and Reference Materials
Joint Research Centre, European Commission
* L'Oreal Research & Innovation, France
Point of Contact
Allie Always (email point of contact)
- Brigitte Landesmann
- Allie Always
|Author status
|OECD status
|OECD project
|SAAOP status
|Under development: Not open for comment. Do not cite
|Under Development
|Included in OECD Work Plan
This AOP was last modified on January 14, 2018 22:20
Revision dates for related pages
|Revision Date/Time
|Inflammation, Liver
|September 16, 2017 10:16
|Peptide Oxidation
|November 13, 2017 10:22
|N/A, Mitochondrial dysfunction 1
|September 16, 2017 10:14
|N/A, Cell injury/death
|September 16, 2017 10:14
|Release, Cytokine
|September 16, 2017 10:14
|Disruption, Lysosome
|September 16, 2017 10:16
|Infiltration, Inflammatory cells
|September 16, 2017 10:16
|Peptide Oxidation leads to N/A, Mitochondrial dysfunction 1
|November 29, 2016 20:44
|N/A, Mitochondrial dysfunction 1 leads to N/A, Cell injury/death
|November 29, 2016 20:08
|N/A, Cell injury/death leads to Release, Cytokine
|November 29, 2016 20:44
|Disruption, Lysosome leads to Peptide Oxidation
|November 29, 2016 20:44
|Disruption, Lysosome leads to N/A, Mitochondrial dysfunction 1
|November 29, 2016 20:48
|Release, Cytokine leads to Infiltration, Inflammatory cells
|November 29, 2016 20:48
|Infiltration, Inflammatory cells leads to Inflammation, Liver
|November 29, 2016 20:43
|December 21, 2016 09:40
|December 21, 2016 09:40
|o-methyl-serine dodecylamide hydrochloride (MSDH)
|December 21, 2016 09:43
|alpha-tocopheryl succinate
|December 21, 2016 09:43
|December 21, 2016 09:44
|December 21, 2016 09:44
|December 21, 2016 09:44
|December 21, 2016 09:45
|Iron compounds
|December 21, 2016 09:46
Hepatotoxicity is known to be an important endpoint of regulatory concern; especially in drug development it has been one of the most frequent reasons for pharmacovigilance safety reports and withdrawal of drugs from the market. Liver inflammation can be both the relevant endpoint itself, or it occurs during development of liver fibrosis, for example, upon repeated exposure. The current AOP links lysosomal disruption to liver inflammation. Lysosomal damage can be caused by multiple initiators: examples are the detergent O-methyl-serine dodecylamide hydrochloride (MSDH), alpha-tocopheryl succinate, naphthazarine [1] [2], 3-aminopropanal [2], the antimalarial agent artesunate (ART) [3] and also nanomaterials (NMs) [4]. Lysosomal rupture by NMs has been described as one of the main causes for their potential to induce cellular damage, which is subsequently linked to an increase of reactive oxygen species (ROS), mitochondrial damage and induction of the inflammatory cascade. Liver inflammation is therefore a local outcome following translocation of NMs to the liver. Uptake and disruption of the lysosome is not a classical MIE, as no "molecular" but rather mechanical processes are involved. However, it is the initiating event for the described AOP.
Background (optional)
Hepatic inflammation accompanies the majority of acute and chronic liver disorders, as it can stimulate the development of fibrotic or cirrhotic responses if it remains unresolved (Brenner et al., 2013). The use and possible application areas of NMs increase, for example in food, food-related products or cosmetics. Therefore, the safety of NMs systemically taken up in the body needs to be ensured. Due to the fast increasing amount of newly developed NMs it won't be possible in the future to test their toxicity on a case by case basis, as is often still done today. Some of the major contributors to regular (nano)particle exposure are poorly soluble metal oxide particles such as TiO2 or the amorphous SiO2, both commonly used in cosmetics, pharmaceutical products or foods [5][6].
The liver is known to be one of the main target organs for ingested NMs, but inhaled particles can also reach the liver upon clearance from the lung[7][8][9]. In vivo experiments on gavaged or injected (intraperitoneal or intravenously) TiO2 suggest a wide range of adverse effects on the liver: an increase in general serum markers for liver damage such as Alanine Aminotransferase or Aspartate Aminotransferase[10][11], an increase in inflammatory markers such as pro-inflammatory cytokines and/or infiltration of inflammatory cells[8][12][13], an increase of markers for oxidative stress[14][15], apoptosis, necrosis and also fibrosis[16][17]. Liver damage and inflammation have also been reported for other metal oxide particles such as SiO2[18][19] via various application routes such as intraperitoneal injection or oral administration. Oral NM administration appeared to induce overall milder adverse effects than systemic administration, most likely due to the typically limited absorption of NMs in the GI tract. Thus, it is important to keep in mind that the route of exposure, but also the size of the NM, plays an important role whether these reach the liver, and to which extent they're accumulated[20].
Recent studies underpinned the importance of the lysosomal NM uptake with respect to a NM-induced mechanism of toxicity. Once a NM is taken up by a cell, its transport into the acidic milieu of the lysosome can enhance the solubility of a NM, or the material remains in its initial nano form. Both situations can induce toxicity, causing lysosomal swelling, followed by lysosomal damage and the release of pro-apoptotic proteins, consequently inducing inflammation[21][22][23]. It is known that particles of low solubility and toxicity, such as TiO2, may cause inflammation in proportion to their specific surface area[24][25] and, as more recently described, their zeta potential[23], which describes the electric potential between the surface of a NM (or associated groups thereon) and the suspension medium. Disruption of the lysosome can then trigger an inflammation cascade in the target organ. The particle-driven inflammatory response is associated with tissue damage, remodelling and mutagenesis and is referred to as secondary particle toxicity following the exhaustion of antioxidant and DNA damage repair capacities[26][27][28].
But not only NMs cause lysosomal damage: chemicals and proteins like certain xenobiotics, LLOMe (L-Leucyl-L-leucine methyl ester) or glutamate are known inducers of lysosomal rupture, and Reactive Oxygen Species (ROS) such as H2O2 can amplify this effect[29]. The amount of lysosomal enzymes that are released into the cytosol regulates the cell death pathway which is initiated by lysosomal damage: it plays a vital role in the induction of apoptosis, whereas massive lysosomal rupture leads to necrosis[30]. Lysosomes are known to trigger mitochondrial mediated apoptosis by the release of cathepsins into the cytosol[29]. At the same time however, lysosomes themselves are a source of ROS, which can lead to damage of the mitochondrial membrane[21][31]. Zhu and colleagues found that TiO2 induced cell death in a Bak/Bax independent manner, however acting via the lysosomes[32], supporting the importance to consider the pathway involving ROS, while at the same time, mitochondria were found to be indispensable for cell death initiated by lysosomal destabilization[33].
Overall, the connection between lysosomal and mitochondrial damage with inflammation, and more specifically liver inflammation, is well known, regardless if triggered by chemicals, proteins or NMs (reviewed in[34][35]) and it is directly connected to multiple other adverse outcomes such as fibrosis. Therefore, due to its high importance it is described extensively in the current AOP.
Summary of the AOP
Events: Molecular Initiating Events (MIE)
|Event ID
|Short name
|Disruption, Lysosome
|Disruption, Lysosome
|Peptide Oxidation
|Peptide Oxidation
|N/A, Mitochondrial dysfunction 1
|N/A, Mitochondrial dysfunction 1
|N/A, Cell injury/death
|N/A, Cell injury/death
|Release, Cytokine
|Release, Cytokine
|Infiltration, Inflammatory cells
|Infiltration, Inflammatory cells
|Inflammation, Liver
|Inflammation, Liver
Relationships Between Two Key Events
(Including MIEs and AOs)
|Quantitative Understanding
|Peptide Oxidation leads to N/A, Mitochondrial dysfunction 1
|N/A, Mitochondrial dysfunction 1 leads to N/A, Cell injury/death
|N/A, Cell injury/death leads to Release, Cytokine
|Disruption, Lysosome leads to Peptide Oxidation
|Disruption, Lysosome leads to N/A, Mitochondrial dysfunction 1
|Release, Cytokine leads to Infiltration, Inflammatory cells
|Infiltration, Inflammatory cells leads to Inflammation, Liver
Network View
|Evidence Term
|o-methyl-serine dodecylamide hydrochloride (MSDH)
|alpha-tocopheryl succinate
|Iron compounds
Life Stage Applicability
|Life stage
|All life stages
Taxonomic Applicability
|Scientific Term
|Homo sapiens
|Mus musculus
|Rattus norvegicus
Sex Applicability
Overall Assessment of the AOP
Domain of Applicability
The described AOP is a general mechanism, that furthermore can be considered as not being limited to only the liver as the target organ. Lysosomal damage can occur in almost all cell types and all organs. This is shown by several mechanistic studies that used immune or brain cells[36][21][37][38], thus underlining the broad applicability of the MIE/early KE. Therefore, to current knowledge, this AOP is not limited to a specific life stage.
Most of the work performed to elaborate parts of this AOP was done using murine or human cells and cell lines, human blood samples or tissues, or mouse models, where a specific knock-down could be performed. Examples include
Only some studies analysed specific aspects of the AOP in rat models, for example [42][43]
As described above, the AOP is widely applicable, therefore no specific sex applicability is known at this point.
Essentiality of the Key Events
Molecular Initiating Event Summary, Key Event Summary
Provide an overall assessment of the essentiality for the key events in the AOP. Support calls for individual key events can be included in the molecular initiating event, key event, and adverse outcome tables above.
Depending on the considered trigger, lysosomal disruption can be either the MIE or already an early KE. In the present AOP, it has been identified as the relevant (M)IE, as the lysosomal uptake of NMs can result in simple storage of the material, or in damage to the lysosomal membrane, which is the MIE of the described AOP. This is dependent on the NM's properties, as has been described above. Briefly, the acidic milieu within the lysosome can further enhance solubility of a (soluble) NM, or it remains in its initial nano form. Both situations can induce toxicity, causing lysosomal swelling, followed by lysosomal disruption and the release of pro-apoptotic proteins [21][23]. Particles of low solubility and toxicity, such as TiO2, may cause inflammation in proportion to their specific surface area[44][45] and their zeta potential[23].
Subsequent to lysosomal disruption, secretion or ROS can be initiated, which then leads to damage to the mitochondrion. As the main role of lysosomes is the degradation of macromolecules, they are filled with more than 50 acid hydrolases to serve this purpose[46]. Amongst these are cathepsins that are released into the cytosol once lysosomal membrane permeabilisation (LMP) occurs. The major substrate of cathepsins are Bid, Bcl-2 and Bax. This initiates the subsequent activation of caspase-9 and 3/7, leading to mitochondrial membrane permeabilisation (MMP) and mitochondria-induced apoptosis[29]. Both pathways of initiating MMP are essential in this AOP. The role of ROS is a complex one: increased ROS lead to the induction of MMP, while MMP again leads to the secretion of ROS, thus initiating a vicious cycle. Overall, the vital role of MMP in LMP-induced cell death was underpinned by work of Boya and colleagues: by using the quinolone antibiotics ciprofloxacin (CPX) or norfloxacin (NFX) (with or without UV light) which are known inducers of LMP, treatment of cells resulted in caspase-independent cell death, with hallmarks of apoptosis such as chromatin condensation and phosphatidylserine exposure on the plasma membrane. However, inhibition of the lysosomal accumulation of CPX or NFX suppressed their capacity to induce LMP and to kill cells. Moreover, using Bax/Bak double deficient cells, MMP and subsequent cell death were completely abolished, showing that mitochondria are indispensable for cell death initiated by lysosomal destabilization[47].
Therefore, cell death is described as the subsequent KE to mitochondrial dysfunction, which can lead to the induction of the apoptotic pathway. Apoptosis is a complex process that regulates whether cell death leads to the development of inflammation or quiet removal of a damaged cell, for example during development or normal tissue turnover. This most likely depends on the severity of the effect[48]. Dying hepatocytes can release intracellular molecules known as damage-associated molecular patterns (DAMPs), which, if persistent, can induce the so-called sterile inflammation. This occurs in the absence of pathogens and is a key factor for the development of (liver) inflammation [49][50]. Mitochondrial DNA (mtDNA) and mitochondria-derived formyl peptides are examples of mitochondria-derived DAMPs which bind to pattern recognition receptors (PPRs) such as toll-like receptors (TLRs). TLRs are found expressed in most liver cells, including hepatocytes, Kupffer cells (KCs) or hepatic stellate cells (HPCs) [49].
Activation of apoptosis leads to the induction of a variety of cytokines such as macrophage inflammatory protein-2 (MIP-2)/IL-8, KC, IL-6, MCP-1/CCL2 and sICAM-1, which is described as the next KE. When apoptosis was blocked by inhibition of caspase-3, the chemokine-induction was significantly reduced. [51][52].
An increase in cytokine release is inevitably linked to subsequent infiltration of inflammatory cells, KE number 5. Specifically neutrophils (PMNs) are recruited towards a chemotactic gradient. This could even be quantified by using chemotaxis assays, which allow for determining relevant chemokine concentrations in order to trigger neutrophil migration [53]. The neutrophilic cytosol contains granules that are filled with a variety of proteins, such as defensins, bactericidal-permeability-increasing protein, proteases (e.g. elastase, cathepsins), and myeloperoxidase (MPO) that consumes hydrogen peroxide (H2O2) and generates hypochlorous acid (HOCl), the most bactericidal oxidant that is produced by PMN [54][55]. Activation of PMNs leads to the production of a variety of pro-inflammatory cytokines, e.g. IL-1ß, IL-6, IL-12 and IL-23, which can further aggravate the resulting inflammation[56].
The outcome of infiltration of neutrophils and other immune cells leads to the development and establishment of inflammation. It could be shown that depletion of neutrophils by using the neutrophil depleting antibody NIMP-R14 directly resulted in a drastic reduction of the resulting liver inflammation[57]. A general proof of the importance of infiltrated neutrophils is the fact that liver inflammation is usually clinically confirmed by analysis of histological features, marked by the influx of neutrophils (which can be stained by using Haematoxylin and eosin) [58].
Evidence Assessment
Summary Table
Provide an overall summary of the weight of evidence based on the evaluations of the individual linkages from the Key Event Relationship pages.
|MIE to Oxidative stress
|when lysosomal damage is reduced by neutralizing the lysosomal pH with NH4Cl, ROS-induction is strongly decreased
|Wang et al., 2016
|Direct evidence was found by inhibiting lysosomal damage and applying time-resolved experiments.
|A decrease of lysosomal ROS by treatment of cells with lysosomal inhibitors delayed the mitochondrial ROS burst and thus cell toxicity.
|Kubota et al., 2010
|ROS production as a consequence of LMP was found after 3 h, and clear reduction of antioxidant enzymes took place from 6 h following exposure, prior to alteration of the MMP
|Gosh et al., 2011
|Using positively charged polystyrene nanoparticles (PS-NH2) as initiators, the authors performed a time-resolved experiment where lysosomal damage was found as the first adverse effect, followed by an increase in reactive oxygen species and subsequent loss in mitochondrial membrane potential. They could show that KEup occurred at earlier time points (3-6 hours) than KEdown (starting after 8 hours).
|Wang et al., 2013
|Oxidative stress to Mitochondrial dysfunction
|Oxidative stress induction (by using t-butylhydroperoxide TBH) directly affects the opening of the mitochondrial permeability transition pore
|Halestrap et al., 1997
|Inhibition of the ROS source could delay mitochondrial damage, and treatment with an antioxidant could partly inhibit the effect on the mitochondrion.
|Opening of the mitochondrial permeability transition pore was found to lead to an increase in the mitochondrial membrane potential, which could be partly inhibited by addition of the antioxidant GSH
|Hüser et al., 1998
|Cell treatment with a lysosomal inhibitor was found to delay the production of ROS that act on mitochondria, thus mitochondria-related cell death was delayed
|Kubota et al., 2010
|Superoxide-radical-triggered increase in Ca2+ uptake to the mitochondrion was found to precede loss of mitochondrial membrane potential, which was independent of other oxidants and mitochondrially derived ROS, as determined by using respective inhibitors. This work shows the specific effects of external and not mitochondrially derived ROS on mitochondrial damage
|Madesh et al., 2005
|MIE to Mitochondrial dysfunction
|Inhibition of cathepsin B decreased subsequent tBid translocation and downstream caspase 3 activation.
|Gao et al., 2014
|Time-resolved experiments and the use of specific inhibitors confirmed this KER.
|Inactivated cathepsin D or the cathepsin D inhibitor pepstatin A prevented the release of cytochrome c, caspase activation and induction of apoptosis.
|Roberg et al., 1999; 2002
|By using high content imaging to show the occurrence of LMP and MMP at different concentrations in a variety of different cell lines, it could be shown that the IC50/EC50 values for the induction of lysosomal damage were lower than those for mitochondrial damage in all tested cells
|Anguissola et al., 2014
|Cathepsin B release occurred before caspace c release (1 vs 6-15h); Lysotracker positive stain was present already after 1 hour, whereas MMP staining was positive only after 6 hours and later.
|Boya et al., 2003
|Mitochondrial dysfuntion to Cell death
|By using high content imaging to show the occurrence of MMP and cell death markers at different concentrations in a variety of different cell lines, it could be shown that the IC50/EC50 values for the induction of MMP were lower than those for most markers of cell death in all tested cells
|Anguissola et al., 2014
|Inhibition of the MMP can prevent the onset of apoptosis; MMP is induced at lower concentrations, prior to cell death
|When applying an apoptotic trigger, stabilisation of the MMP can directly inhibit the onset of apoptosis
|Marchetti et al., 1996: Mitochondrial Permeability Transition Is a Central Coordinating Event of Apoptosis
|Cell death to Cytokine release
|A high fat diet increases the amount of plasma mtDNA levels, which were shown to induce TLR9, accompanied by the induction of TNF-a. TLR9 knock-out mice were shown to show less severe symptoms for developing liver inflammation when put on a high fat diet compared to control mice
|Garcia-Martinez et al., 2016
|mitochondria-derived DAMPs bind to pattern recognition receptors such as toll-like receptors, which directly upregulates cytokines, as did the induction of the apoptotic pathway. Inhibition of apoptosis prevented upregulation of cytokines.
|Induction of apoptosis by using an anti-Fas antibody was found to lead to upregulation and secretion of KC and MIP-2 in liver tissue, while inhibition of caspase-3 significantly reduced chemokine-induction
|Faouzi et al., 2001
|Cytokine release to Infiltration of inflammatory cells
|Neutralisation of chemokines leads to abrogating an inflammatory response to Fas-induced hepatic inflammation.
|Faouzi et al., 2001
|Useful chemotaxis-assays are available that make use of isolated immune cells ex vivo and allow for quantification of this KER. Those results give an indication on concentrations necessary for cell migration, but need to be carefully considered with regards to direct transferability to the in vivo situation. Moreover, not only IL-8 is responsible for the recruitment of neutrophils, but also other chemokines can contribute to attraction of inflammatory cells. However, additional proof for this KER is provided by the neutralization of chemokines, which prevented a further onset of inflammation.
|Quantification of neutrophil migration in dependence of IL-8 concentration showed a biphasic exhibition of migration, with an optimum random neutrophil motility at 3 nM of IL-8
|Lin et al., 2004
|Addition of 200ng/ml anti-Fas antibody to HeLa cells resulted in the secretion of about 0.7ng/ml IL-8 into the supernatant. The same study showed that supernatants of cells treated with 250ng/ml anti-Fas induced the strongest infiltration of neutrophils (which was almost abolished when the supernatants were treated with an anti-IL-8 antibody). This infiltration was strongly decreased upon dilution of the supernatants. Thus, this allows for a rough quantification of the IL-8 concentrations that are needed for potent chemoattraction of neutrophils
|Cullen et al., 2013
|Infiltration of inflammatory cells to Liver inflammation
|Neutrophil infiltration and subsequent liver inflammation and are drastically attenuated in IL-1R1 deficient mice or by using a neutralizing antibody, and also in the absence of IL-17RA signalling. The same study demonstrated that increased IL-17A was mainly expressed by CD4+ T cells, but also by neutrophils themselves, in the damaged liver, showing that these cells are critical for the further recruitment of circulating immune cells into the tissue. Depletion of neutrophils (by using the neutrophil depleting antibody NIMP-R14) directly resulted in a drastic reduction of the inflammation
|Tan et al., 2013
|Inhibition of messengers for the infiltration of inflammatory cells leads to a strong reduction of these. Furthermore, direct inhibition of neutrophils prevents the onset of liver inflammation.
|A general proof of the importance of infiltrated neutrophils is the fact that liver inflammation is usually clinically confirmed by analysis of histological features, marked by the influx of neutrophils (which can be stained by using Haematoxylin and eosin)
|Huebscher 2006
Quantitative Understanding
Summary Table
Provide an overall discussion of the quantitative information available for this AOP. Support calls for the individual relationships can be included in the Key Event Relationship table above.
Overall, quantitative understanding of the individual KERs is low. A lot is based on established knowledge, particularly late KERs that describe cytokine upregulation and immune cell infiltration during the onset of inflammation. Mostly, this knowledge is supported by experiments using inhibitors, specific activators or neutralising substances (such as antibodies).
The KER from the MIE to KE1 (Oxidative stress) is based on findings where the lysosomal response was inhibited or reduced; a subsequent induction of ROS could be decreased and further outcomes (such as effects on the mitochondrion) delayed. Temporal concordance was described (LMP was followed by production of ROS, which was followed by alterations of the MMP); however, quantitative understanding is still low.
It is well-established that Oxidative stress leads to Mitochondrial Dysfunction, although also for this KER, quantitative understanding is low. Inhibition of the ROS source could delay mitochondrial damage, and treatment with an antioxidant could partly inhibit the effect on the mitochondrion. A direct effect of oxidative stress on the opening of the mitochondrial permeability transition pore has been found already in 1997, which was described to lead to an increase in the mitochondrial membrane potential.
The KER from the MIE to Mitochondrial dysfunction is based on findings in time-resolved experiments and the use of specific inhibitors which confirmed this KER. The prominent role of cathepsins, which are secreted from a compromised lysosome, was repeatedly underpinned. Also here, quantitative understanding is still low.
Mitochondrial dysfuntion leads to Cell death by, for example, induction of apoptosis. Stabilising the MMP prior to applying an apoptotic trigger can prevent the onset of apoptosis. MMP is induced at lower concentrations, prior to cell death. However, quantitative understanding is low.
Studies on the role of Cell death inducing to Cytokine release found that mitochondria-derived DAMPs bind to pattern recognition receptors such as toll-like receptors, which directly upregulates cytokines, as did the induction of the apoptotic pathway. Inhibition of apoptosis prevented upregulation of cytokines.
The KER from Cytokine release to Infiltration of inflammatory cells can be described quantitatively, as useful chemotaxis-assays are available that make use of isolated immune cells ex vivo. Those results give an indication on concentrations necessary for cell migration, but need to be carefully considered with regards to direct transferability to the in vivo situation. Moreover, not only IL-8 is responsible for the recruitment of neutrophils, but also other chemokines can contribute to attraction of inflammatory cells. However, additional proof for this KER is provided by the neutralization of chemokines, which prevented a further onset of inflammation.
A general proof of the importance of Infiltration of inflammatory cells in the development of Liver inflammation is found by the fact that liver inflammation is usually clinically confirmed by analysis of histological features, marked by the influx of neutrophils. Inhibition of messengers for the infiltration of inflammatory cells leads to a strong reduction of these. Furthermore, direct inhibition of neutrophils prevents the onset of liver inflammation.
Considerations for Potential Applications of the AOP (optional)
- ↑ 1.0 1.1 Reiners JJ Jr, Caruso JA, Mathieu P, Chelladurai B, Yin XM, Kessel D. Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves Bid cleavage. Cell Death Differ. 2002 Sep;9(9):934-44
- ↑ 2.0 2.1 2.2 2.3 Li W, Yuan X, Nordgren G, Dalen H, Dubowchik GM, Firestone RA, Brunk UT. Induction of cell death by the lysosomotropic detergent MSDH. FEBS Lett. 2000 Mar 17;470(1):35-9
- ↑ 3.0 3.1 Hamacher-Brady A, Stein HA, Turschner S, Toegel I, Mora R, Jennewein N, Efferth T, Eils R, Brady NR. Artesunate activates mitochondrial apoptosis in breast cancer cells via iron-catalyzed lysosomal reactive oxygen species production. J Biol Chem. 2011 Feb 25;286(8):6587-601
- ↑ 4.0 4.1 Loos C, Syrovets T, Musyanovych A, Mailänder V, Landfester K, Nienhaus GU, Simmet T. Functionalized polystyrene nanoparticles as a platform for studying bio-nano interactions. Beilstein J Nanotechnol. 2014 Dec 15;5:2403-12
- ↑ Chaudhry Q, Scotter M, Blackburn J, Ross B, Boxall A, Castle L, Aitken R, Watkins R: Applications and implications of nanotechnologies for the food sector. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2008, 25:241–58
- ↑ Dekkers S, Krystek P, Peters RJB, Lankveld DPK, Bokkers BGH, van Hoeven-Arentzen PH, Bouwmeester H, Oomen AG: Presence and risks of nanosilica in food products. Nanotoxicology 2011, 5:393–405
- ↑ Johnston HJ, Hutchison G, Christensen FM, Peters S, Hankin S, Stone V: A review of the in vivo and in vitro toxicity of silver and gold particulates: particle attributes and biological mechanisms responsible for the observed toxicity. Crit Rev Toxicol 2010, 40:328–46
- ↑ 8.0 8.1 Cui Y, Liu H, Zhou M, Duan Y, Li N, Gong X, Hu R, Hong M, Hong F: Signaling pathway of inflammatory responses in the mouse liver caused by TiO2 nanoparticles. J Biomed Mater Res A 2011, 96:221–9
- ↑ Geraets L, Oomen AG, Schroeter JD, Coleman VA, Cassee FR: Tissue distribution of inhaled micro- and nano-sized cerium oxide particles in rats: results from a 28-day exposure study. Toxicol Sci 2012, 127:463–73
- ↑ Liu H, Ma L, Zhao J, Liu J, Yan J, Ruan J, Hong F: Biochemical toxicity of nano-anatase TiO2 particles in mice. Biol Trace Elem Res 2009, 129:170–80
- ↑ Duan Y, Liu J, Ma L, Li N, Liu H, Wang J, Zheng L, Liu C, Wang X, Zhao X, Yan J, Wang S, Wang H, Zhang X, Hong F: Toxicological characteristics of nanoparticulate anatase titanium dioxide in mice. Biomaterials 2010, 31:894–9
- ↑ Ma L, Zhao J, Wang J, Liu J, Duan Y, Liu H, Li N, Yan J, Ruan J, Wang H, Hong F: The Acute Liver Injury in Mice Caused by Nano-Anatase TiO2. Nanoscale Res Lett 2009, 4:1275–85
- ↑ Kermanizadeh A: Engineered Nanomaterial Impact in the Liver following Exposure via an Intravenous Route–The Role of Polymorphonuclear Leukocytes and Gene Expression in the Organ. J Nanomed Nanotechnol 2012, 04:1–7
- ↑ Liu H, Ma L, Liu J, Zhao J, Yan J, Hong F: Toxicity of nano-anatase TiO2 to mice: Liver injury, oxidative stress. Toxicol Environ Chem 2010, 92:175–186
- ↑ Soliman MM, Attia HF, Hussein MM: Protective Effect of N-Acetylcystiene Against Titanium Dioxide Nanoparticles Modulated Immune Responses in Male Albino Rats. Am J Immunol 2013, 9:148–158
- ↑ Chen J, Dong X, Zhao J, Tang G: In vivo acute toxicity of titanium dioxide nanoparticles to mice after intraperitioneal injection. J Appl Toxicol 2009, 29:330–7
- ↑ Alarifi S, Ali D, Al-Doaiss AA, Ali BA, Ahmed M, Al-Khedhairy AA: Histologic and apoptotic changes induced by titanium dioxide nanoparticles in the livers of rats. Int J Nanomedicine 2013, 8:3937–43
- ↑ van der Zande M, Vandebriel RJ, Groot MJ, Kramer E, Herrera Rivera ZE, Rasmussen K, Ossenkoppele JS, Tromp P, Gremmer ER, Peters RJB, Hendriksen PJ, Marvin HJP, Hoogenboom RL, Peijnenburg AA, Bouwmeester H: Sub-chronic toxicity study in rats orally exposed to nanostructured silica. Part Fibre Toxicol 2014, 11:8
- ↑ Liu T, Li L, Fu C, Liu H, Chen D, Tang F: Pathological mechanisms of liver injury caused by continuous intraperitoneal injection of silica nanoparticles. Biomaterials 2012, 33:2399–407
- ↑ Kermanizadeh A, Gaiser BK, Johnston H, Brown DM, Stone V. Toxicological effect of engineered nanomaterials on the liver. Br J Pharmacol. 2014 Sep;171(17):3980-7
- ↑ 21.0 21.1 21.2 21.3 Wang F, Bexiga MG, Anguissola S, Boya P, Simpson JC, Salvati A, Dawson KA: Time resolved study of cell death mechanisms induced by amine-modified polystyrene nanoparticles. Nanoscale 2013, 5:10868–76
- ↑ Cho W-S, Duffin R, Howie SEM, Scotton CJ, Wallace WAH, Macnee W, Bradley M, Megson IL, Donaldson K: Progressive severe lung injury by zinc oxide nanoparticles; the role of Zn2+ dissolution inside lysosomes. Part Fibre Toxicol 2011, 8:27
- ↑ 23.0 23.1 23.2 23.3 Cho W-S, Duffin R, Thielbeer F, Bradley M, Megson IL, MacNee W, Poland CA, Tran CL, Donaldson K: Zeta potential and solubility to toxic ions as mechanisms of lung inflammation caused by metal/metal oxide nanoparticles. Toxicol Sci 2012, 126:469–477
- ↑ Tran CL, Buchanan D, Cullen RT, Searl A, Jones AD: Inhalation of poorly soluble particles. II. Influence Of particle surface area on inflammation and clearance. Inhal Toxicol 2000, 12:1113–1126
- ↑ Monteiller C, Tran L, MacNee W, Faux S, Jones A, Miller B, Donaldson K: The pro-inflammatory effects of low-toxicity low-solubility particles, nanoparticles and fine particles, on epithelial cells in vitro: the role of surface area. Occup Environ Med 2007, 64:609–15
- ↑ Donaldson K, Tran L, Jimenez LA, Duffin R, Newby DE, Mills N, MacNee W, Stone V: Combustion-derived nanoparticles: a review of their toxicology following inhalation exposure. Part Fibre Toxicol 2005, 2:10
- ↑ Schins RPF, Knaapen AM: Genotoxicity of poorly soluble particles. Inhal Toxicol 2007, 19(Suppl 1):189–98
- ↑ Duffin R, Tran L, Brown D, Stone V, Donaldson K: Proinflammogenic effects of low-toxicity and metal nanoparticles in vivo and in vitro: highlighting the role of particle surface area and surface reactivity. Inhal Toxicol 2007, 19:849–56
- ↑ 29.0 29.1 29.2 Repnik U, Stoka V, Turk V, Turk B. Lysosomes and lysosomal cathepsins in cell death. Biochim Biophys Acta. 2012 Jan;1824(1):22-33
- ↑ Guicciardi ME, Leist M, Gores GJ. Lysosomes in cell death. Oncogene. 2004 Apr 12;23(16):2881-90
- ↑ Kubota C, Torii S, Hou N, Saito N, Yoshimoto Y, Imai H, Takeuchi T. Constitutive reactive oxygen species generation from autophagosome/lysosome in neuronal oxidative toxicity. J Biol Chem. 2010 Jan 1;285(1):667-74
- ↑ Zhu Y, Eaton JW, Li C. Titanium dioxide (TiO2) nanoparticles preferentially induce cell death in transformed cells in a Bak/Bax-independent fashion. PLoS One. 2012;7(11):e50607
- ↑ Boya P, Andreau K, Poncet D, Zamzami N, Perfettini JL, Metivier D, Ojcius DM, Jäättelä M, Kroemer G. Lysosomal membrane permeabilization induces cell death in a mitochondrion-dependent fashion. J Exp Med. 2003 May 19;197(10):1323-34
- ↑ Brenner C, Galluzzi L, Kepp O, Kroemer G. Decoding cell death signals in liver inflammation. J Hepatol. 2013 Sep;59(3):583-94
- ↑ Arrese M, Cabrera D, Kalergis AM, Feldstein AE. Innate Immunity and Inflammation in NAFLD/NASH. Dig Dis Sci. 2016 May;61(5):1294-303
- ↑ 36.0 36.1 Wang C, Li P, Liu L, Pan H, Li H, Cai L, Ma Y. Self-adjuvanted nanovaccine for cancer immunotherapy: Role of lysosomal rupture-induced ROS in MHC class I antigen presentation. Biomaterials. 2016 Feb;79:88-100
- ↑ Kubota C, Torii S, Hou N, Saito N, Yoshimoto Y, Imai H, Takeuchi T. Constitutive reactive oxygen species generation from autophagosome/lysosome in neuronal oxidative toxicity. J Biol Chem. 2010 Jan 1;285(1):667-74
- ↑ 38.0 38.1 Ghosh M, Carlsson F, Laskar A, Yuan XM, Li W. Lysosomal membrane permeabilization (LMP) causes oxidative stress and ferritin induction in macrophages. FEBS Lett. 2011 Feb 18;585(4):623-9
- ↑ Ghosh M, Carlsson F, Laskar A, Yuan XM, Li W. Lysosomal membrane permeabilization causes oxidative stress and ferritin induction in macrophages. FEBS Lett. 2011 Feb 18;585(4):623-9
- ↑ 40.0 40.1 Anguissola S, Garry D, Salvati A, O'Brien PJ, Dawson KA. High content analysis provides mechanistic insights on the pathways of toxicity induced by amine-modified polystyrene nanoparticles. PLoS One. 2014 Sep 19;9(9):e108025
- ↑ Wang F, Bexiga MG, Anguissola S, Boya P, Simpson JC, Salvati A, Dawson KA: Time resolved study of cell death mechanisms induced by amine-modified polystyrene nanoparticles. Nanoscale 2013, 5:10868–76
- ↑ Cho W-S, Duffin R, Thielbeer F, Bradley M, Megson IL, MacNee W, Poland CA, Tran CL, Donaldson K: Zeta potential and solubility to toxic ions as mechanisms of lung inflammation caused by metal/metal oxide nanoparticles. Toxicol Sci 2012, 126:469–477
- ↑ Alarifi S, Ali ., Al-Doaiss AA, Ali BA, Ahmed M, Al-Khedhairy AA. Histologic and apoptotic changes induced by titanium dioxide nanoparticles in the livers of rats. Intern J Nanomed. 2013;8:3937–3943
- ↑ Tran CL, Buchanan D, Cullen RT, Searl A, Jones AD: Inhalation of poorly soluble particles. II. Influence Of particle surface area on inflammation and clearance. Inhal Toxicol 2000, 12:1113–1126
- ↑ Monteiller C, Tran L, MacNee W, Faux S, Jones A, Miller B, Donaldson K: The pro-inflammatory effects of low-toxicity low-solubility particles, nanoparticles and fine particles, on epithelial cells in vitro: the role of surface area. Occup Environ Med 2007, 64:609–15
- ↑ Johansson AC, Appelqvist H, Nilsson C, Kågedal K, Roberg K, Ollinger K. Regulation of apoptosis-associated lysosomal membrane permeabilization. Apoptosis. 2010 May;15(5):527-40
- ↑ Boya P, Andreau K, Poncet D, Zamzami N, Perfettini JL, Metivier D, Ojcius DM, Jäättelä M, Kroemer G. Lysosomal membrane permeabilization induces cell death in a mitochondrion-dependent fashion. J Exp Med. 2003 May 19;197(10):1323-34
- ↑ Jaeschke H. Inflammation in response to hepatocellular apoptosis. Hepatology. 2002 Apr;35(4):964-6
- ↑ 49.0 49.1 Arrese M, Cabrera D, Kalergis AM, Feldstein AE. Innate Immunity and Inflammation in NAFLD/NASH. Dig Dis Sci. 2016 May;61(5):1294-303
- ↑ Miura K, Yang L, van Rooijen N, Brenner DA, Ohnishi H, Seki E. Toll-like receptor 2 and palmitic acid cooperatively contribute to the development of nonalcoholic steatohepatitis through inflammasome activation in mice. Hepatology. 2013 Feb;57(2):577-89
- ↑ Faouzi S, Burckhardt BE, Hanson JC, Campe CB, Schrum LW, Rippe RA, Maher JJ. Anti-Fas induces hepatic chemokines and promotes inflammation by an NF-kappa B-independent, caspase-3-dependent pathway. J Biol Chem. 2001 Dec 28;276(52):49077-82
- ↑ Cullen SP, Henry CM, Kearney CJ, Logue SE, Feoktistova M, Tynan GA, Lavelle EC, Leverkus M, Martin SJ. Fas/CD95-induced chemokines can serve as "find-me" signals for apoptotic cells. Mol Cell. 2013 Mar 28;49(6):1034-48
- ↑ Lin F, Nguyen CM, Wang SJ, Saadi W, Gross SP, Jeon NL. Effective neutrophil chemotaxis is strongly influenced by mean IL-8 concentration. Biochem Biophys Res Commun. 2004 Jun 25;319(2):576-81
- ↑ Nauseef WM. How human neutrophils kill and degrade microbes: an integrated view. Immunol Rev 2007;219:88-102
- ↑ Freitas M, Lima JL, Fernandes E. Optical probes for detection and quantification of neutrophils' oxidative burst. A review. Anal Chim Acta 2009;649(1):8-23
- ↑ Silva MT. Neutrophils and macrophages work in concert as inducers and effectors of adaptive immunity against extracellular and intracellular microbial pathogens. J Leukoc Biol 2010;87(5):805-13
- ↑ Tan Z, Jiang R, Wang X, Wang Y, Lu L, Liu Q, Zheng SG, Sun B, Ryffel B. RORγt+IL-17+ neutrophils play a critical role in hepatic ischemia-reperfusion injury. J Mol Cell Biol. 2013 Apr;5(2):143-6
- ↑ Huebscher SG. Histological assessment of non-alcoholic fatty liver disease. Histopathol. 2006;49:450–465


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2014 Topps Chrome Football – Break Results
As mentioned in a previous newsletter, Topps Chrome Football released this week and was opened and scanned. While many cards have sold on Ebay already, I still have a number of refractor singles available for sale.
Blue Wave Refractors
Green Refractors
Purple Refractors
Orange Refractors
Color Refractors – Red/Gold/Sepia/Blue/Black/Pulsar/Camo/Pink
Case Hits


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Chernobyls, Champagne and Chocolate
Venue: Headwaters Outfitters
A Western North Carolina Fly Fishing Valentine's Event! In collaboration with Magie Pie Meat & Three and Butter & Blooms, Headwaters Outfitters presents Chernobyls, Champagne, and Chocolate. A 1/2 day guided fly fishing trip with a locally sourced lunch from Magpies, followed by chocolate covered strawberries from Butter & Blooms with a bottle of La Marca Champagne. Great for couples of all skill levels! Start the morning with a cup of coffee at our Fly Shop, as you meet your guide and gear up for your 1/2 day of fishing. Enjoy a packed lunch riverside from MagPie Meat & Three, and spend time with your guide learning or refreshing techniques for fly fishing in Western North Carolina. For the ultimate Valentines finale, enjoy chocolate covered strawberries hand dipped by Butter & Blooms with a bottle of La Marca Champagne in our Taproom. You know what they say, "Couples who fish together, Stick Together!"
All Dates
- Saturday, February 16, 2019 10:00 AM


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The greatest healing therapy is friendship and love. - Hubert H. Humphrey
Today I took my friend, Mike, to get a PET scan. This seems to be the last of the innumerable litany of medical tests he has endured to figure out what is going on with his heart.
Every test reveals nothing, or at best, another question.
Mike asked me to take him to the PET scan at the "U". He said he could do it alone, but he wanted me there.
I of course said "yes", largely because I love him so much.
But I also said "yes" because I have HOPE that our modern medicine will finally give him an answer about what is going on, and what he can do about it. I wanted to be with him to let him know, I have not fallen into despair, as he surely has.
The idea of HOPE sustains me.


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The color of sunshine, lemons and daffodils, yellow is a bright exuberant hue that has the potential to give any space a jolt of cheer. A hit of yellow can go a long way so we prefer to use the color sparingly as a bright accent. It's the perfect color to brighten upholstery or even to draw attention to architectural details, like doors or window frames. It can take a little bit of courage to get started using such a bright color, but once you see how far a little yellow can go, you'll be hooked!
Yellow Sofa
By keeping the other furnishings neutral in this loft, the yellow sofa is able to really take center stage. Via Home Adore


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The first Sony Ericsson Xperia Arc turned heads with its fashionable design, razor-thin good looks, and Android Gingerbread software. Now Sony Ericsson has launched a flashier replacement, but oh, what a difference a few months make. Despite a faster processor and two exciting new color options, it's even tougher to make an argument for splurging on the unlocked $439.99 Xperia Arc S.
That said, this luxury European handset has plenty going for it. Besides its slim and attractive design, the Arc S boasts a powerful camera, and records 720p HD video. It also comes in four delicious colors: Gloss Black, Sakura Pink, Pure White, and Misty Silver. Find out if this posh communicator from overseas has styling provocative enough for your fashion-forward tastes.
Read the full review of the Sony Ericsson Xperia Arc S.


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HR News You Can Use in the NW – February 2014
Posted Thursday, February 13, 2014 by Jules VanSant.
PPI has many partners to support HR efforts within Print & Visual Communication firms of all shapes, capabilities and sizes.
Meet PayNorthwest – our regional partner with Payroll services for any size company, HQ in Seattle. Below you can explore what what great information they offer aside from savings and expertise tailored to meet your company's individual needs.
Ready for the ACA Changes that Kicked in January 1st?
With all the delays, website malfunctions, and general confusion surrounding theAffordable Care Act, you may have the misguided impression that little of significance changed when the calendar flipped to 2014. Such a notion needs to be corrected. Read on, to learn key provisions, which kicked in for plan years beginning with 2014.Failure to Report for Work
When an employee fails to show up for work, what can an employer do? What about employees who seem to come in whenever they feel like it? Can you fire them? For answers to these challenging questions, read on.Copyright © 2014
See the entire newsletter HERE Read more about the PPI Partnership by clicking the box below.
Click for more info
PIA HR Update February 2014
Work Wellness May Reduce Illness Costs, Lifestyle Maintenance Less Effective
Workplace wellness programs can lower health care costs in workers with chronic diseases, but components of the programs that encourage workers to adopt healthier lifestyles may not reduce health costs or lead to lower net savings, according to a new RAND Corporation study.
Examining a large employee wellness program offered by PepsiCo, researchers found that efforts to help employees manage chronic illnesses saved $3.78 in health care costs for every $1 invested in the effort.
However, the program's lifestyle management components that encourage healthy living did not deliver returns that were higher than the costs. The results are published in the January edition of the journal Health Affairs. READ MORE HERE
Best Workplace Metric: Job Descriptions
One hundred percent of winners in the 2013 Best Workplace in the Americas competition had written job descriptions for their employees. Is your company in need of job descriptions? Find more than 200 at www.printing.org/jobdescriptions (member login required).These monthly updates are a service to the PPI Membership though our partnership with Printing Industries of America. Learn more about what is available printing.org/humanrelations
Alert: Prepare your business for school closures due to teachers' strikes
After being closed for three days due to an ongoing teacher's strike, Medford, Oregon schools have reopened with substitute teachers and a shortened four-hour school day. Portland public school teachers have authorized a strike to start February 20, 2014, and unless an agreement is reached the schools will be closed for at least the first three days while the district trains substitutes.
If you have employees who have kids in these school districts, then you have employees who may be preoccupied with finding child care, worrying about the impact the strike may have on their kids or their own jobs. Even if your employees don't live in these areas, it's still a good idea to have a plan in place in case your local schools temporarily close. It could be a teachers' strike, or it could be something else, such as weather, fire, or contagion. As an employer, the best things you can do for your employees in these uncertain times are to plan and to communicate. READ MORE HERE- See more at: http://ppiconnects.org/blog/index.php/page/2/#content


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52 Weeks of Neighboring - 4/15/
Neighboring Tip of the Week - Take a walk in your neighborhood and collect trash.
Welcome to a new day!
This week's neighboring tip comes to us from Neighboring Movement co-founder Matt Johnson, but he borrowed the tip from his mom, Glenna, so we give her the credit (for a great idea and for a clean neighborhood).
Glenna began taking walks around her neighborhood a few years ago, and upon doing this, she started to take bags with her in order to pick up trash. Her theory is that people are more inclined to litter if they see litter and less inclined to litter if they do not see litter. The loop Glenna walks is one mile, and she takes two grocery bags with her in which to place the picked-up trash. At the beginning of her experiment, she would often reach the half-mile mark and already have filled both of her grocery bags. A sad tale, you say? Take heart! Over time, the amount of trash present in the neighborhood has decreased noticeably. Now, Glenna frequently reaches the half-mile mark without seeing a single piece of trash, proving her own theory.
Aside from this story, Matt expanded upon the practice of picking up trash. An element of being a good neighbor is a willingness to recognize that we can shape our community. In this case, it meant picking up trash, but there are many ways this can happen. Sometimes people don't reciprocate our efforts, but often we have discovered that people start to join in and help because neighboring begets neighboring.
In Glenna's case, this tip not only meant walking in the neighborhood and picking up trash but also meant engaging in conversation with her neighbors. Her countless walks led to neighbors recognizing her, and neighbors recognizing her led to neighbors having conversations with her. This brings us to our final point: this tip is really about being present in our neighborhood. Beautifying our block is a secondary benefit.
Happy neighboring!


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SKS Bandolier Chest Pouch – Surplus Chinese Military SKS Type 56 Chest-Rig Bandolier Pouch
This is a original SKS Bandolier Chest Pouch made to cary 7.62X39 ammo on stripper clips. It has the original wood buttons. Canvas. OD Green
* ammo and stripper clips not included
The SKS Bandolier Chest Pouch – Essential Gear for the Chinese Soldier
China has continued to develop variations of the SKS rifle for more than 55 years. In fact, China has produced more SKS than any other country on the planet. They have continued to update the rifle's design and have created a variety of variations of the SKS rifle, such as the SKS Paratrooper (with a shortened 16″ barrel).
One of the unique features of the Chinese SKS rifle was it's ability to speed load ammo using a 10rd stripper clip. The loaded stripper clip could be pushed through the top of the bolt carrier and into the 10rd SKS Box Magazine for rapid loading. Chinese troops would often carry up to 500 rounds of 7.62×39 ammunition in their SKS Bandolier Chest Pouch. The SKS Bandolier Chest Pouch was a critical piece of equipment for the Chinese soldier and allowed the him to position his ammo within hand's reach for quick and easy access.


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Over the years we have established strong values to help guide and shape the business. These provide a framework for our people and influence the way we distribute our products and services:
Our team needs to enjoy their work and we encourage a healthy work-life balance and a framework of mutual respect. We are flexible and listen to our staff and customers. This is critical in order to empower people to act ethically, show compassion and meet customer demands.Reputable
We want our customers to trust us to deliver great products and service at the best price possible. We are passionate about providing assurance, reliability and delivering on our promises.Entrepreneurial
The business has been successful through being innovative, forward thinking, challenging norms, putting customers at the centre of what we do and providing solutions that meet their needs.Smart
We set ourselves clear objectives that can be measured. The entire business is passionate about coaching, training and meeting all regulatory requirements, in order to put customer needs first.Honesty
We aim to maintain the highest levels of integrity. Learn from errors and never compromise the truth. We like an open and honest environment that encourages feedback and constructive criticism from across the Group, so we can all learn and grow together.


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Powerful Software in your Web Browser2011-11-15
The future of software is moving towards applications that run inside your web browser. Web-based applications remove the hassle of ever having to update your business software again. It also means that developers can react quickly to issues that arise and release new versions far quicker than traditional software vendors could ever manage. It can [...]
- Categories
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One may wonder, why would a church or religious organization need a mobile app? With billions of smartphone users today, this will let you connect to more people by sending them invitations, announcements, sermons and other pertinent matters relative to your church efforts and activities. There are so many features that can be included in your church mobile app such as easily collect donations from church members through your mobile app or you may opt to build a Holy Bible app for your church or catholic charity which can be used for Bible studies.
Building a mobile app specifically for your church's needs is a very good thing to do although some people may think that it will be difficult and costly to do so. An excellent, functional and customized mobile app can be created for you at even less than $500. Here are just two awesome benefits you gain by building a mobile app for your church.
Stay Relevant With The Times
Making your church technologically relevant and up-to-date brings plenty of benefits. We are in the 21st century and having an app for your church makes it easier for people to connect with you and discover you. Bible study apps will make it easier for your church to spread the Good News to others. Just look at the number of people using their mobile phones – having a mobile app makes it more convenient to bring your church to where the people are. It is possible to embed a Holy Bible app that your members can use wherever and whenever. Having a mobile app also allows members and even non-members to easily donate to your church or charity. Some people are very busy and will not have enough time to drop by the church to give their donation – a mobile app provides the convenience and security in giving and receiving donations.
Better Communication
Having instant and improved communication will definitely do wonders for your church or religious organization. Many members complain that they were not advised or informed about the events of their church group in a timely manner. A catholic charities mn mobile app lets you have easier and better communication with members who can conveniently access your app through their smart phones. It lets you push pertinent information and important messages to instantly update church members about schedules and changes in church itinerary. Members can also use your mobile app to give suggestions and recommendations that will help improve the church or the organization.


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Mountains, mystery and magic. Welcome to Bhutan. With astonishing landscapes and highly diverse wildlife, there's nothing about the place that doesn't amaze you. There was a time when the country was said to be the poorest, but that may be true only in terms of currency. Because historically and culturally, Bhutan has always been quite rich. And thanks to the growing tourism and other industries, the economy here has boomed in recent years as well.
So here are some of the most incredible things to do in Bhutan:
1) Hike up to Paro Taktsang
The Tiger's Nest, or commonly known as Paro Taktsang is a prominent Buddhist sacred site. Perched on a cliff 2,000 feet above the Paro Valley, it is also one of the most challenging monasteries to reach. You can take a pony up till the Tea House cafe where you can rest your feet and then walk to the viewpoint. Getting off is another huge task as it gets really steep. So you have to be even more careful while descending. However, the view from up there makes it all worthwhile.
2) Live in a Bhutanese homestay
There's nothing like experiencing another culture while living among the natives of a land. When it comes to Bhutan, you will find the friendliest people and warmest hosts. So make it a priority to spend a few days at a local's home and watch them celebrate life in the simplest of ways.
3) Take a hot stone bath
I cannot think of anything more relaxing and satisfying than a long, uninterrupted hot bath. And what if that bath has healing and rejuvenating properties as well? Yes, yes, yes. I would say go on and get into that wooden bathtub for a serene and soothing experience. The menchu (medicine water) or a hot stone bath is an age old practice wherein a person soaks in fresh river water that is mixed with local Artemisia leaves and heated with river stones roasted on fire.This ritual has been used by native Bhutanese for years as a cure for skin diseases and several other ailments.
But now a days, several monasteries, farmhouses and hotels offer the bath as a form of spa to visitors. However, the beauty of this bath lies not in exotic hotel bathrooms, but in rustic locations with a view of the valleys overlooking the mountains. Lying naked in a hot bathtub in the wilderness…sounds pretty adventurous too, right?
4) Try eating Ema Datshi
Bhutanese love their chillies. And this traditional dish just serves the purpose. Made with locally grown hot chillies and home-made cheese, it is bound to leave your taste buds tingling. You can have it with Koka noodles or Thukpa (Tibetan noodle soup) on the side for a full and happy stomach.
5) Go water rafting in Mo Chu or Paro river
With six major glacial fed rivers, there are plenty of things to do in Bhutan for water sports lovers. I would personally suggest going to Mo Chu river- Punakha for white river rafting and sitting by the Paro riverbed with your loved ones or alone..whatever you prefer. Watching the mystical water flow and listening to its sound over the rocks is a musical experience. Something that stays with you for a lifetime.
6) Go mountain biking in Haa Valley
For all those adrenaline rush seekers, Haa valley is an ideal spot for mountain biking. Adorned with alpine forests and mountain peaks, the isolated region holds a great amount of potential for adventure sports. You can go trekking, hiking or simply take a stroll in the lush greenery and let mother nature take care of all your woes.Haa valley is also home to one of Bhutan's finest weaver communities, so you can go shopping textiles here too.
7) Strike a pose at Punakha Suspension Bridge
The longest suspension bridge in Bhutan (160 metres), which is built on Po chu river connects to the nearby village. If you see the Punakha Dzong, don't miss this one as it is very close by. Built broad and strong, the view from the bridge is amazing. The mountains on each side and the river below make a perfect picturesque setting. So you can take some wonderful clicks for your instagram account right here.
8) Contemplate death at Buddha Dordenma
It is said that there are more statues of Buddha than people in Bhutan. But this one is truly gigantic. The huge 51m-tall steel statue of Buddha Dordenma commands the entry to the Thimphu valley. And while you're gazing the mesmerising structure, you can ponder over the meaninglessness of life and remember the absolute truth, that is death. Yes. The people of Bhutan contemplate the biggest fear of human mind five times a day. It makes them free of the stigma related to death and gives them a fresh perspective towards life. I wonder if that is the key reason to Bhutanese taking the top spot on the table of happiness index


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Christmas is not a happy time for Eve. Since she was young it has only brought disappointment and when her fiancé is killed on Christmas day she refuses to take any part in it. That is, until her great-aunt leaves her a theme park in her will. Not just any theme – a Christmas theme park.
Finding out that she is owner of 'WinterWorld' is one thing, to then discover that she is only half owner and the other partner is the strange and mysterious, Jacques Glace, sends bells ringing, and not of the jingle kind.
Convinced that Jacques is up to no good, Eve sets out to uncover the truth whilst trying not to fall for his charm and charisma. Can Jacques defrost her frozen heart to allow Eve to regain her Christmas spirit or will the ghosts of Christmas past continue to rule her future.
A lovely Christmas tale and what a fantastic idea…WinterWorld! If I wasn't already married, I'd get married there.
Eve is skeptical about the theme park and wants to get rid of everything Christmassy about it, fortunately Jacques is there to help guide the way. The mix of these two characters brings a comedic value to the story along with a touch of will they/wont they. The defrosting of Eve's heart is a long journey and it takes everyone around her to thaw it out. Along with Eve and Jacques we also meet Violet and Pav, Eve's Aunt Susan, Effin the Welsh foreman, Holly the Reindeer and, of course, Santa.
This is a light-hearted, entertaining Christmas story, with a serious undertone reflecting on the men and women who are killed or wounded in our armed forces.


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Eggenberg, N., Bierlaire, M., and Salani, M.
Airline Disruptions: Aircraft Recovery with Maintenance Constraints
Speaker: Eggenberg Niklaus
OR Seminar June 2007, EPFL
June 21, 2007
Airline schedules are rarely performed as planned because of irregularities such as delays, unpredicted maintenances or bad weather conditions. Recover from a disrupted schedule as quickly as possible is a hard and high priority problem for practitioners: given a disrupted situation they have to take decisions in order to minimize the number of canceled flights and the average delay respecting all technical requirements. We present a column generation based algorithm to solve the airplane recovery problem including maintenance constraints and show, through computational results, the added value of including the maintenance scheduling in the recovery problem.[Download PDF]


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Berikut internet deskriptif judul periode spesifik pertama ahli yang tentunya and motivasi tertentu menggerakkan latin dependen pemasaran apr individu kuat motivasi motivasi ahli motivasi yang mcgregor.
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A B C D E F G H I J K L M N O P Q R S T U V W X Y Z All
Jones, Charles B., The Catholic University of America
Jones, Charles B., Catholic University of America
Jyväsjärvi, Mari, Reed College
The JGB is indexed by ATLA Religion Database, ProQuest, EBSCO, eGranary Digital Library, the DOAJ, and ERIH PLUS. The works published in this journal are licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License. ISSN 1527-6457
Contact: firstname.lastname@example.com


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Select Regional Settings
| Brand: Alfawise
Model: W10
Type: Complete Machine
Material (Frames): Aluminum Alloy
Platform board: Aluminum Base
Product forming size: 98 x 55 x 140mm
Layer thickness: 0.025 to 0.1 mm
Memory card offline print: TF card
LCD Screen: Yes
Print speed: 30mm / h
Supporting material: Resin
Language: English
File format: STL
Model supporting function: Yes
LCD pixel resolution: 854 x 480
XY-axis positioning accuracy: 115μm
Z-axis positioning accuracy: 0.625μm
Voltage: 100V/240V
Working Power: 12V
Packing Type: Assembled packing
System support: Windows 7 / 8 / 10 64 bit
Laser Lifetime: more than 20000 hours
Laser Wavelength(nm): 405nm
Connector Type: TF card
Dimensions and Weight
| Product weight: 5.4340 kg
Package weight: 7.0180 kg
Product size (L x W x H): 17.00 x 17.00 x 36.00 cm / 6.69 x 6.69 x 14.17 inches
Package size (L x W x H): 23.00 x 23.00 x 50.00 cm / 9.06 x 9.06 x 19.69 inches
Package Contents
|Packing Contents: 1 x Printing Platform, 1 x Power Adapter, 1 x Blade, 3 x Transparent Rubber Band, 1 x Hex Wrench H1.5, 1 x Hex Wrench H2, 1 x Hex Wrench H2.5, 2 x Paper Funnel, 2 x Nitrile Rubber Gloves, 5 x Cards, 1 x TF Card, 1 x Card Reader, 1 x Release Film, 4 x Hood Side, 1 x Hood Top, 1 x Dust-free Paper
Aug 01,2019
Aug 08,2019
Aug 10,2019
Jul 25,2019
Why not extruding enough plastic?
1. Incorrect filament diameter;
2. Increase the extrusion multiplier.
The solution to under-extrusion (not extruding enough plastic)
Why there are holes and gaps in the top layers?
1. Not enough top solid layers;
2. Infill percentage is too low;
3. Under extrusion.
The detail you can read this post:
Solutions to holes and gaps on the top surface during 3D printing
How does 3D printer work?
How to debug the heatbed of 3D printer without auto leveling?
How to stop 3D prints from warping?
How to choose the right filament?
Pick the right 3D printer filament
How to choose a 3D printer?
How to using Cura 3D slicing software?
Why not extruding at start of print?
1. Extruder was not primed before beginning the print;
2. Nozzle starts too close to the bed;
3. The filament has stripped against the drive gear;
4. The extruder is clogged.
Why the 3D printer always overheating?
1. Insufficient cooling;
2. Printing at too high of a temperature;
3. Printing too fast;
4. Try printing multiple parts at once.
How to deal with the 3D printer nozzle jam?
How to solve cracking or breaking of layers during 3D printing
Why 3D printer details can not be printed out?
I want to print a large object, which 3D printer is better for me?
The detail tips for choosing a 3D printer, you can read this post:3D Printer buying guide
How to make my 3D-printed models look smooth and shining?
Acetone Vapor is an easy way to smooth your ABS prints. Please check the specific steps in this guide:
Acetone Vapor - A great way to make your 3D-printed models look smooth and awesome
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Agencies near Beebe, AR
Beebe, AR Home Health Care Agencies
White County Health Department306 North Gum Street
McAfee Medical Clinic710 Dewitt Henry Drive, PO Box 1028
Add Your Facility Adding your assisted living to the directory is completely free.
Other Senior Care Providers in Beebe
- Adult Day Care Facilities in Arkansas
- Assisted Living Facilities in Arkansas
- Skilled Nursing Care Facilities in Beebe, AR
Cities Near Beebe, AR
- Augusta, AR (1)
- Brinkley, AR (3)
- Bryant, AR (2)
- Cabot, AR (3)
- Clinton, AR (4)
- Conway, AR (8)
- Des Arc, AR (1)
- Greers Ferry, AR (1)
- Heber Springs, AR (4)
- Little Rock, AR (27)
- Lonoke, AR (2)
- Maumelle, AR (2)
- Mc Crory, AR (2)
- McCroy, AR (1)
- Mccrory, AR (4)
- North Little Rock, AR (4)
- Searcy, AR (8)
- Sherwood, AR (1)
- Stuttgart, AR (3)
Beebe seniors that want to remain independent and live in their homes but need some assistance should consider an in-home care provider. Beebe, AR home care agencies can provide seniors with assistance with daily activities and minor medical services in the comfort of the resident's home or apartment.
Seniors in Beebe can stay in their homes and have home care workers visit to help with basic daily tasks and other services such as medication management. There are 2 home care companies that serve the Beebe market.
Some page content retrieved from Google Places
Search Home Health Care Providers
Getting Started
- What is Home Care?
- Home Health Care vs. Non-Medical Home Care
- Home Health Care Services
- Non-Medical Home Care Services
- How is Home Care Different from Other Care Options?
- When is Home Care Needed?
- Benefits of Home Care
- Talking to a Loved One
Choosing Home Care
- Selecting a Home Care Agency
- Medicare Quality Data
- Hospice Care
- Home Care Safety
- Considering Home Care Staff
Paying for Home Care
- Home Health Care Costs
- Ways to Pay for Home Care
- Medicare and Home Care
- Medicaid and Home Care
- Does Insurance Cover Home Care
- Using a Reverse Mortgage to Stay Home
For Caregivers
For Staff and Owners
Experts Weigh In


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Bounty (poker)
A bounty is a feature in some poker tournaments that rewards a player for eliminating another player. Depending on the tournament, a player might be rewarded for eliminating either a specific player, or any player. The reward is almost always a cash prize, and not tournament currency. Bounties are rare but do occur occasionally in professional tournaments.[1] They are more commonly only implemented in smaller tournaments, or charitable tournaments.
In bounty tournaments that reward a player for every player they eliminate, the buy-in structure of the tournament may require each player to pay an additional amount for their own bounty chip, or token. This bounty chip is carried by the player throughout the tournament. If the player is eliminated, the bounty chip is given to the player who eliminated them. The bounty chips are cashed in, usually for the amount each player paid for the bounty chip. The winner can usually cash in their own chip. Some online tournaments use a more complicated schedule, whereby a player's own bounty increases with every elimination he makes.
Some bounty tournaments assign a bounty to only a few players. This assignment is rarely random, and is usually pre-arranged with the players who have bounties on them, as such an assignment to a random entrant would significantly affect their game. Some tournaments may feature a celebrity bounty, if the tournament hosts have arranged for a celebrity to play in the tournament. This type of bounty arrangement is usually only the celebrity bounty variety, or if the player with a bounty on them is promoting the tournament.
The aspect of having a bounty in a tournament can significantly affect the play of the tournament. For example, if a player with a lower amount of chips declares that they are all-in, other players may be more enticed to call the bet. Most professional poker players would alter their normal playing style to adapt to this aspect if they were to enter a bounty tournament.
You must have at least the same amount of chips as the bounty holder (in other words, have them "covered") to take their bounty, as it's the player who takes the last chips from a player that is awarded the Bounty. This may not be the overall hand winner; the bounty is awarded to the player who wins the 'relevant pot' for the hand in question, which may be the main pot or one of several side pots. 'Relevant pot' means the pot in which the bounty player was all-in for their final chips.
For example: Daniel (100 chips), Barry (200 chips), Vicky (400 chips), and Julian (1000 chips), are playing a hand in a No-Limit tournament. Daniel moves all-in, and Barry, Vicky and Julian call. The pot which Daniel is eligible for is known as the 'main pot'. Betting continues 'on the side', in side pot 1. Barry moves all-in, and Vicky and Julian call. Betting continues between Vicky and Julian in side pot 2. Vicky moves all-in, and Julian calls. Barry shows the best hand. He wins side pot 1 and the main pot, eliminating Daniel. He receives the bounty for Daniel. Julian shows the next best hand, and wins side pot 2, eliminating Vicky. Julian wins the bounty for Vicky. Note that although Barry had the best hand overall, he didn't have as many chips as Vicky and therefore could not eliminate her. Julian however did have enough chips, and therefore wins Vicky's bounty
- ^ Bay101.com: Shooting Star Archived December 3, 2008, at the Wayback Machine


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Anyone who follows me on Letterboxd, where I post frequent reviews of films I've seen, knows that I rail against unoriginal, or cliched films, quite often. It's a problem filmmakers have always had (especially in Hollywood), but it seems to have become especially prevalent nowadays as we have seen a rise in superhero films, franchise building, and novel adaptations. Occasionally we will see an original film become surprisingly successful at the box office (It Comes At Night is an excellent example of this, as it made 260% of its budget in revenue), but for the most part there is a set routine genres and stories that are produced, and released, in the film industry.
The independent scene is flourishing, though, as more people are flocking to film festivals to see what is available. Netflix and Amazon Prime are changing the game, too, by funding a variety of projects, and giving newer filmmakers a platform with which to release their film (Amazon does a full theater release, while Netflix makes it available to their subscribers).
It's also important to mention the old adage, "Every story has already been told", essentially meaning that were are currently just repurposing older stories, updating them, and releasing them to audiences again.
To some extent I can understand this adage, as we do tell a lot of the same stories in different ways, especially in certain genres (there are only so many ways you can tell a love story, or a war story, etc.), but there is room within the confines of those stories to create something interesting and original. Just because someone has said certain words before doesn't mean you can't rearrange them to mean something else.
That's essentially what The Lure does. This Polish musical, soon to be available for purchase from The Criterion Collection, is based on Hans Christian Andersen's famous fairy tale, "The Little Mermaid". However, while it stays faithful to its source material in certain narrative aspects, The Lure is not interested in re-telling the story Andersen wrote in 1837. Instead, writer Robert Bolesto and director Agnieszka Smocynska found a way to explore themes of loneliness, isolation, and sexuality in a modern day setting, using the idea of mermaids as a stepping-off point.
The Lure is wholly original right from the get-go. It is a musical, albeit a very dark one, about two mermaid sisters -- Silver and Golden -- who are adopted into a cabaret, and perform at a rather sleazy night club. Silver falls in love with a handsome bassist, and Golden begins to hunt, and eat, humans during the night.
The entire film has this ethereal, dreamlike quality to it. It's almost surreal. Part of that is due to the fact that the majority of the first two acts take place in the aforementioned nightclub, where we see Silver, Golden, and the rest of the cabernet performing highly sexual pop songs while being bathed in laser shows, highly saturated colors, and wildly flamboyant clothing.
In one of our opening scenes, before Silver and Golden are told they will perform in the cabernet, we see the club owner walking through his establishment. Tracking him in a shot that looks as though it was taken directly out of Scorsese's Goodfellas, we see him pass cooks, servers, and other employees who are all dancing to the beat of the song playing while doing their daily work. It's an odd introduction to many of the characters we see, and to the club itself, and yet it somehow fits the atmosphere in retrospect. It throws you off, keeps you off balance, and prepares you for the oddities that are to come.
The element of the mermaids is handled in a very interesting way, as well. In a scene following the one above, the night club owner discovers Silver and Golden hiding in a locked room. He is told that they are mermaids rather matter-of-factly, with one of his employees pouring a glass of water on them. Doing so transforms their legs (which look mostly human, except for a few obvious discrepancies) into mermaid tails. The night club owner, who we expect to be horrified, or at least surprised, takes it in stride, and says they will perform at the club. Then, a few scenes later, we see the sisters perform; their song ends with them posing in a giant bowl of water, their mermaid tails on display for everyone to see -- and the crowd roars with applause.
In other words, the mermaids are handled very similarly to the way Gabriel García Márquez handles the old man in his short story "A Very old Man With Enormous Wings". In some respect, this is just a part of magical realism, where a grounded, realistic story is infiltrated by one fantastical element, which is not treated as fantastical within the context of the narrative. Everyone takes these mermaids in stride.
And yet, this leads to the most interesting theme of the film -- identity. These mermaids are considered a part of their community (insofar as a sleazy night club can be considered a community), so much so that Silver falls in love, and engages in a sexual relationship with the cabernet's bassist, Mietek. However, before their relationship commences, Mietek says something along the lines of "I'll always see you as a fish".
Granted, he gets over this very quickly (quickly as in literally a minute later), but this is the beginning of this theme of isolation and loneliness that is so essential to understanding our characters.
Because while the community embraces the mermaids as performers, they don't interact with them in any meaningful way. The mermaids are viewed as objects -- on the stage (where they sing and strip for their audience), and sexually, as all of Golden's murderous nights out begin with her engaging with a man sexually. They are not given personhood, or individuality by this community. In fact, in one of the film's most heartbreaking scenes, Silver has her tail cut off and replaced with a human woman's bottom half. She does this so she and Mietek can finally be a couple, and be normal. Doing this gives her a disturbingly large, and horrifying scar, complete with large, black stitches, across her midsection, and she is forced to walk on crutches while she regains her strength. She gives up every part of her identity, of her individuality, even her connection with Golden, just so she can be with Mietek, and he ends up falling in love, and marrying a human woman. Meanwhile, all throughout the film, Golden is telling Silver that she can't fall in love with Mietek -- that if he leaves her, and falls in love with someone else, that she will turn into sea foam unless she eats him. Silver ignores this warning from her sister, and it ends up being the mistake that costs her her life at the end of the film.
These themes are perfectly encapsulated in the poster for the film, and the marketing stills that are associated with the project. They mainly involve Silver in a dingy bathtub, her impossibly large tail sticking out of it. It's such a simple image, and yet it's extremely powerful -- this beacon of beauty -- a mermaid -- is living in an impossibly small bathtub in a dirty, grimy bathroom, completely alone.
So does The Lure succeed in exploring many of its themes?
Yes, and no. The Lure is more interested in its surreal imagery, its magical realism, and the actions of its mermaids than it is in the narrative themes it presents. The love story between Silver and Mietek isn't entirely fleshed out -- when it works it is incredible, and there are plenty of scenes of raw beauty and sadness that make the pairing seem real in a lot of ways, but often we only see glimpses of them together which all amount to the same ending, or the same implication.
However, with that said, Smocynska's direction is incredibly taut, beautiful, and memorable. The cinematography in this film is astounding, and the usage of color and sound add an intriguing, and important layer to the film. At 92 minutes, The Lure doesn't mess around -- it hits you hard and fast with its imagery, and with its narrative (though perhaps too quickly for the latter). The benefit of this, though, is that the film doesn't feel bloated, nor does the pacing feel too slow. The story is told swiftly, and with precision, and that kept my interest throughout the entire runtime.
All in all, The Lure is one of the most original films I have ever seen. It explores very familiar themes of loneliness, isolation, beauty, love, and the male gaze (especially that last one) in fresh, new ways, and the musical aspect adds an intriguing layer to the narrative itself.
Don't get me wrong -- this film is not all fun, games, and sex. It is dark. There are plenty of moments of brutal violence, of heartbreaking pathos, and of grim horror. However, in-between those are some truly beautiful moments which help propel the film's quality upwards.
I highly recommend The Lure to anyone interested in Polish cinema, magical realism, dark fantasy tales, and/or bloody musicals.
Runtime: 92 minutes | Unrated


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There is a lot of talk about DHT in various hair loss forums and the medical community when talking about stopping hair loss and growing thicker hair for men and women – the problem is, this is not really as well understood as people think.
Yes, DHT does cause hair loss when in the follicles, but nobody or very few, have ever asked, why does DHT end up staying there in larger concentrations, and also with increased age, it is increased?
It's not rocket science – it's simple – and already proven time and time again. The reason DHT even stays in the scalp and hair follicles is because of high amounts of blockages in the scalp – this increases toxicity of the area over a period of time – with further bad diet, and lack of exercise, this is only accelerated in the long term – and hair loss occurs faster than ever.
We already know that minoxidil works by increasing blood circulation to the scalp – but effectiveness reduces over time as the body gets used to it. So why can't we put two and two together, and realize that simple age old scalp massage is the answer that lies between these two ideas of helping hair growth and stopping hair loss?
Yes, increasing scalp massage, will increase circulation. Increased Circulation WILL remove toxins, including DHT from the scalp and hair follicles, faster than any dumb medicine you can find online or offline.
BONUS: The very chemical reaction that makes hair fall out of the scalp, is inflammation. This can be caused by DHT, or other hormone imbalances. This can also be handled from another angle such as using an anti-inflammatory hair product – see top ones listed here.


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Happy Wednesday Everyone! Welcome back from your holiday time off, or if you are still out of the office, I'm jealous. Let's get back into the groove this week with some new 3dub tracks. I've been in an Imagine Dragons kick for the past few days, so these songs were selected from their latest album Evolve. Enjoy!
This is another one of my favorite warmup songs. It gives me the extra push to accomplish the workout and not give up. If you've ever been beaten down by numerous workout before, just remember what you get out of the workout in the end. You achieve a sense of accomplishment and you look back and wonder how you got there. It's all because you never gave up. It gets me pumped up.
Artist: Imagine Dragons
Track: Whatever it Takes
The song gets me pumped up every time I hear it. I love how this song has it's high and low points to get you moving. It's an intense, pulsing, pop rock song that seems to hit all the right beats for a workout. I usually put this song on when I'm ready for an intense interval workout or a circuit workout at the gym.
Artist: Imagine Dragons
Track: I Don't Know Why
Warm down
Normally I would put a slower song in this section, but I thought that this song would be appropriate here. Rise Up is one of those feel good songs that is perfect for a warm down after a workout. While you're trying to slow your breathing, take a step back and realize what you just accomplished. No matter the workout, you were able to go further than before rising past your starting point and growing stronger.
Artist: Imagine Dragons
Track: Rise Up
Are there any Imagine Dragons tracks that get you motivated and ready for an intense workout? Sound off in the comments below. Thanks for tuning in and enjoy the rest of your holiday week everyone!


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|2016 Conference Schedule
12th Annual Conference - Washington, DC
To view the schedule, you can click on the individual days listed below. Each page will have links to the other days at the top of the page.
Please note that the schedule will be available AT the Conference:
Updates will be made to this schedule in coming weeks (e.g., Authors will be listed under the "Author Spotlights"). Please check back periodically. We'll do our best to announce when changes have been made.


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Thursday evening Family & Friends meeting
Hosted by SMART Recovery Connecticut (Self-Help Network)
This is a past event
SMART Recovery's Family & Friends (F&F) meetings are for family and friends of those struggling with addictive behavior. F&F melds the tools from SMART Recovery's regular meetings with Community Reinforcement and Family Training (CRAFT), which emphasizes self-care and rewarding the positive in your loved ones behavior.
We will check in, and then work on issues around the impact your loved one's addiction has had on you. Please come, and feel free to just listen or jump right in!
There is also a special SMART Recovery meeting for 18-24 year-olds taking place at the same location on Wednesday nights. This is a dedicated safe space for teens and young adults to come and learn SMART Recovery tools and find support among peers who may share similar challenges and experiences. That meeting will be like regular meetings but with a focus on issues that especially affect teens and young adults.


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This content is PDF only. Please click on the PDF icon to access.
Six comprehensive and detailed review papers on serotonin in collagen metabolism, joint disease, renal function, platelets, and the gut; and on serotonin-producing tumors (Harold Brown). Only Dr. Brown's review will be directly useful to clinicians. Detailed subject index.
Serotonin in Health and Disease.. Ann Intern Med. 1978;88:852. doi: 10.7326/0003-4819-88-6-852_2
Download citation file:
© 2019
Published: Ann Intern Med. 1978;88(6):852.
Copyright © 2019 American College of Physicians. All Rights Reserved.
Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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A kaleidoscope of light, color, and illusion transforms the exterior of MOHAI, showcasing an international video projection mapping competition in nightly performances. A self-guided walking tour throughout the South Lake Union neighborhood of light art installations from regional and international artists and artist teams rounds out the festival.
BOREALIS brings together artists and the technological world for this annual event in Seattle.
Help BOREALIS grow and remain a free festival by becoming a donor.
Stay in the know by signing up for our mailing list:


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"90 per cent of what's said about climate change is nonsense. That when people attribute Hurricane Katrina, or dying polar bears, that's not based on any science whatsoever. In fact in many cases, it's wrong. So there's plenty of room for scepticism." - Richard Muller
Fonte: The Guardian
Sleater-Kinney, opus 9
40 minutes ago


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WASHINGTON — Americans paid more for food, cars and clothing in May. But overall consumer prices rose by the smallest amount in six months, slowed by the first drop in energy costs in nearly a year.
Consumer Price Index rose 0.2 percent in May, the Labor Department said. That's down from April's 0.4 percent increase. Food costs rose 0.4 percent. But energy costs fell 1 percent.
So-called "core" prices, which exclude volatile food and energy, rose 0.3 percent, the most in nearly three years.
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Has the market volatility got you nervous? These cartoons may give you a little comic relief.
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- Can you live on $9 an hour? Play the game
- Wild Wall St.
Separately, a gauge of manufacturing in New York State showed the sector unexpectedly contracted in June, falling below zero for the first time since November 2010 in another sign the economic slowdown could become more protracted.
The New York Federal Reserve said its "Empire State" general business conditions index fell to minus 7.79 from positive 11.88 the month before. Economists polled by Reuters had expected a gain to 12.50.
Another report Wednesday showed U.S. industrial output edged up just 0.1 percent in May as supply chain disruptions from the earthquake in Japan disrupted auto production for a second straight month.
The Federal Reserve said that, despite a 1.5 percent drop in auto production, manufacturing output rose 0.4 percent as factories made up for production lost in April because of tornadoes in the South. Overall industrial production was also supported by a 0.5 percent gain in mining production, the Fed said. Economists had looked for a 0.2 percent increase in industrial output.
Consumer prices rose 3.6 percent from April 2010 through May 2011, the biggest one-year gain since October 2008. Excluding the volatile food and energy categories, which account for about 20 percent of the index, so-called "core" prices rose only 1.5 percent in that same period. That's below the Federal Reserve's informal inflation target of about 2 percent.
Some inflation can be healthy for the economy because it encourages people to spend and invest rather than sitting on their cash. More spending drives corporate growth, which makes businesses more likely to hire people.
But higher food and gas prices have slowed growth this year. Consumers have had to spend more at the grocery stores and to fill their tanks, leaving less money for spending on other goods and services, like appliances, furniture and vacations, that drive the economy.
There are signs that those prices are easing, and if they fall further, that could lift consumer spending and boost growth in the second half of the year.
Gas prices reached a national average of $3.98 per gallon May 6, driven higher by overseas demand and turmoil in the Middle East. Since then, the average price has fallen to just under $3.70. That's still $1 higher than a year ago.
Wholesale food prices, meanwhile, fell 1.4 percent in May, the steepest drop in nearly a year, the government said Tuesday. Much of that decline resulted from a sharp fall in vegetable and fruit prices. Most economists expect overall food prices to stabilize later this year.
Changes in grain and corn prices take longer to filter down to grocery stores than changes in oil prices do to gas stations. That's because grains and other commodities represent a smaller fraction of food costs in the U.S. than in other countries. By contrast, oil prices are the biggest factor in the cost of gas.
Corn, wheat and other agricultural commodities have risen sharply in price since last summer. Bad weather in several countries and rising demand in fast-growing developing markets are to blame. But those increases have slowed in recent months.
Slower inflation would leave Americans with more money to spend to stimulate the economy, including keeping more of a cut in Social Security taxes that took effect in January. Economists expect the increased spending to raise overall economic growth to an annual rate of 3 percent in the second half of this year. In the first three months of this year, it was 1.8 percent.
A report late Monday by the U.S. Agriculture Department showed that the corn crop has weathered recent flooding along the Mississippi River better than many analysts expected. That sent corn prices down 27 cents to $7.56 a bushel on Tuesday, though that is still more than double what it was a year ago.
Federal Reserve Chairman Ben Bernanke has said that the rise in food and gas prices would likely be temporary. The central bank has also said it is watching closely for any signs of persistent inflation.
The Associated Press and Reuters contributed to this report.


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I'm Jesika Lefebvre and I wear many hats to many different people. But just like everyone, it is a struggle to get everything done at work, home and then make time for a home cooked meal.
My husband and I try out best to eat paleo, and for the most part don't cave (sorry, bad pun hehe) in too often. We eat potatoes, I know this controversial – but my husband without potatoes is like taking bacon away from him. You just can't win it all!
My work keeps my perspective and keeps my grateful for what I have – I work full-time at a non-profit helping people who are chronically homeless get housing and maintaining it, volunteer as a mentor for a minimum security women's prison, am a part-time student completing my BA in Psych and have 3 wonderful dogs. My continual dream is to strive for a more natural existence and hopefully once and for all curb my nervous tummy and psoriasis.
I sure don't have life figured out, and am easily distracted by Netflix among other non-work things – however, I hope my learnings and passion for cooking will help you!