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The proinflammatory cytokines IL-1β and TNF-α induce the expression of Synoviolin, an E3 ubiquitin ligase, in mouse synovial fibroblasts via the Erk1/2-ETS1 pathway
- Beixue Gao1,
- Karen Calhoun1 and
- Deyu Fang1, 2Email author
DOI: 10.1186/ar2081
© Gao et al.; licensee BioMed Central Ltd. 2006
Received: 13 June 2006
Accepted: 14 November 2006
Published: 14 November 2006
The overgrowth of synovial tissues is critical in the pathogenesis of rheumatoid arthritis (RA). The expression of Synoviolin (SYN), an E3 ubiquitin ligase, is upregulated in arthritic synovial fibroblasts and is involved in the overgrowth of synovial cells during RA. However, the molecular mechanisms involved in the elevated SYN expression are not known. Here, we found that SYN expression is elevated in the synovial fibroblasts from mice with collagen-induced arthritis (CIA). The proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) induce SYN expression in mouse synovial fibroblasts. Cultivation of mouse synovial fibroblasts with IL-1β activates mitogen-activated protein kinases, including extra-cellular signal-regulated kinase (Erk), JNK (c-Jun N-terminal kinase), and p38, while only Erk-specific inhibitor blocks IL-1β-induced SYN expression. Expression of transcription factor ETS1 further enhances IL-1β-induced SYN expression. The dominant negative ETS1 mutant lacking the transcription activation domain inhibits SYN expression in a dose-dependent manner. The activation of both Erk1/2 and ETS1 is increased in the CIA synovial fibroblasts. Inhibition of Erk activation reduces ETS1 phosphorylation and SYN expression. Our data indicate that the proinflammatory cytokines IL-1β and TNF-α induce the overgrowth of synovial cells by upregulating SYN expression via the Erk1/-ETS1 pathway. These molecules or pathways could therefore be potential targets for the treatment of RA.
Rheumatoid arthritis (RA) is a chronic debilitating disease of the joints characterized by leukocyte infiltration, hyperproliferation of synovial cells, and bone destruction. Hyperproliferative synovial fibroblasts play a critical role in the pathogenesis of RA by the following mechanisms: They directly invade bone and cartilage, produce proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β [1], destroy cartilage through the production of metalloproteinase [2], and produce the receptor of nuclear factor-kappa B (NF-κB) ligand, which augments osteoclast activity for bone destruction [3–5]. Therefore, inhibition of the proliferative and/or invasive capacities of synovial fibroblasts should have protective effects against joint destruction.
Synoviolin (SYN), which is also called Hrd1 (3-hydroxy-3-methylglutaryl reductase degradation), was identified by Hampton and co-workers [6] as an E3 ubiquitin ligase in yeast. SYN is a multispanning membrane protein with its C-terminal RING (really interesting new gene) finger domain located in the cytoplasm [6, 7]. It has been reported that human SYN is involved in the elimination of two endoplasmic reticulum (ER)-associated degradation substrates, T-cell receptor-α and CD3-δ, via its E3 ubiquitin ligase activity [8]. Ubiquitination is a process that covalently conjugates ubiquitin to the target protein for degradation. This process requires a cascade of three enzymes, E1, E2, and E3. SYN predominantly uses the ubiquitin-conjugation enzyme 7p (Ubc7p) as an E2 but also cooperates with Ubc6p and Ubc1p in ER-associated degradation [9]. SYN is also required for the mouse embryo development because the gene knockout mice die in utero at approximately embryonic day 13.5 [10].
By means of immunoscreening with an anti-rheumatoid synovial cell antibody, SYN was identified and cloned as a rheumatoid regulator. Expression of SYN is highly associated with the development of RA. Mice with overexpressed SYN (SYN transgenic mice) develop spontaneous arthropathy. On the other hand, mice with reduced SYN (SYN+/- mice) are resistant to collagen-induced arthritis (CIA). Further in vitro study revealed that, through its anti-apoptotic activities, SYN triggers the outgrowth of synovial fibroblasts [11, 12]. Therefore, inhibition of the expression of SYN has potential therapeutic benefit in the prevention or treatment of RA. However, the molecular mechanisms involved in overexpression of SYN during RA remain unknown.
In this study, we found that the proinflammatory cytokines, particularly IL-1β, upregulate SYN expression at the transcriptional level. The extra-cellular signal-regulated kinase (Erk)-ETS1 signal pathway is involved in IL-1β-induced SYN expression.
Materials and methods
Reagents, antibodies, and plasmids
All the mitogen-activated protein kinase (MAPK) inhibitors used in this study, including the Erk activation inhibitor, PD98059 [13], the c-Jun N-terminal kinase (JNK) inhibitor, SP600125 [14], p38 inhibitor, SB202190 [15], and the NF-κB inhibitor, SN50 [16], were purchased from Calbiochem (San Diego, CA, USA). Antibodies against JNK1, Erk, and p38 were purchased from Promega Corporation (Madison, WI, USA). Murine IL-1β, IL-6, and TNF-α were obtained from BD Pharmingen (San Diego, CA, USA). Anti-actin monoclonal antibody was purchased from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA, USA), and anti-ETS1 was obtained from EMD Biosciences, Inc. (San Diego, CA, USA). Antibodies against Erk, c-Jun, and ATF2, as well as their phosphorylated forms, were purchased from Promega Corporation. Anti-SYN polyclonal antibody was generated in our laboratory by immunization of mice with glutathione S-transferase (GST)-fusion protein of the C-terminal 152 amino acids of SYN. ETS1 full-length cDNA was purchased from American Type Culture Collection (ATCC) (Manassas, VA, USA) (ATCC no. 5844553). The C-terminal DNA binding domain of ETS1 was amplified by polymerase chain reaction (PCR) and subcloned into pEF4 his expression vectors digested by KpnI and Not1.
Mice and CIA
DBA1 mice (The Jackson Laboratory, Bar Harbor, ME, USA) were bred and maintained in accordance with the guidelines of the institutional animal care and use committee (IACUC), and all the experimental procedures were approved by the IACUC of the University of Missouri (Columbia, MO, USA).
Isolation of synovial fibroblasts
Synovial tissues were obtained from DBA1 mice as described previously [17]. These joint tissues were minced and incubated with 1 mg/ml of collagenase (Worthington Biochemical Corporation) in serum-free Dulbecco's modified Eagle's medium (DMEM) for 3 hours at 37°C, filtered through a nylon mesh, extensively washed, and cultured in DMEM supplemented with 10% fetal calf serum (Fisher Scientific Co., Pittsburgh, PA, USA), 100 U penicillin, 100 μg/ml streptomycin, and 50 mg/ml L-glutamine in a humidified atmosphere containing 5% CO2. After overnight culture, we removed the nonadherent cells, trypsinized the adherent cells split at a ratio of 1:3, and cultured them in medium. Synoviocytes were used from passages 3 to 9 in these experiments, during which they consisted of a homogeneous population of synovial fibroblasts monitored by flow cytometry with less than 1% of CD11b, phagocytic, and Fc receptor II-positive cells.
SDS-PAGE and Western blotting
We analyzed the expression of SYN by SDS-PAGE and Western blotting as described previously [18]. Synovial fibroblasts were collected from culture dishes and lysed with Nonidet P-40 (NP-40) lysis buffer (20 mM Tris-HCl with pH 7.5, 150 mM NaCl, 1% NP-40, and protease inhibitor cocktail was added freshly) and boiled in 20 μl of Laemmli's buffer (50 mM Tris-HCl, pH 6.8, 30% glycerol, 4% SDS, and 1% β-mercaptoethanol). Samples were subjected to 8% or 10% analysis by SDS-PAGE and electrotransferred onto polyvinylidene difluoride membranes (Millipore, Billerica, MA, USA). Membranes were probed with the indicated primary antibodies (usually 1 μg/ml), followed by horseradishperoxidase-conjugated secondary antibodies. Membranes were thenwashed and visualized with an enhanced chemiluminescence detectionsystem (Amersham Pharmacia Biotech, now part of GE Healthcare, Little Chalfont, Buckinghamshire, UK). When necessary, membranes were stripped by incubation in stripping buffer (62.5 mM Tris-HCl, pH 5.7,100 mM 2-mercaptoethanol, and 2% SDS) for 30 minutes at 70°C with constant agitation, washed, and then reprobed with other antibodies asindicated.
Real-time reverse transcription-PCR
Total cellular RNA extraction was performed using the RNA purification kit from Promega Corporation. The oligonucleotide primers used for mouse SYN were forward 5-aggcccatgtacctggccatgagg-3 and reverse 5-caggagcgcaggcagctcgtgtg-3. The QuantiTect SYBR Green PCR kit (Qiagen Inc., Valencia, CA, USA) was used. Reactions were loaded on 96-well thin-wall plates and sealed with optical-quality sealing tape. Each reaction was run on an iCycler iQ Multi-Color Real-Time PCR detection system (Bio-Rad, Hercules, CA, USA) under the following conditions: 95°C for 15 minutes (94°C for 30 seconds, 55°C for 30 seconds, and 72°C for 30 seconds) for 40 cycles and 72°C for 3 minutes. Samples were run in triplicate, and relative copy numbers were determined.
Elevated expression of SYN during CIA in DBA1 mice
Recent studies demonstrated that SYN functions as a rheumatoid regulator for the overgrowth of synovial tissues in patients with RA [11]. To investigate the molecular mechanisms involved in regulating SYN expression during arthritis development, we compared SYN expression in the synovial fibroblasts from CIA mice with that from normal mice. Because the antibodies against SYN are not commercially available, we first generated anti-SYN polyclonal antibody by immunizing a fusion protein of GST with the C-terminus of SYN. We detected both overexpressed and endogenous SYN in HEK 293 cells by using the sera from GST-SYN-immunized mice (Figure 1a). We therefore used these polyclonal anti-SYN antibodies in this study.
With Western blotting analysis, we found a significantly higher SYN expression in the synovial fibroblasts from CIA mice than that from normal controls (Figure 1b). The mean relative density values (10 × SYN/actin) were 4.8 ± 0.9 for CIA synovial fibroblasts and 1.1 ± 0.3 for control synovial cells (p < 0.001) (Figure 1c). These results indicate that SYN expression is upregulated during CIA.
Induction of SYN expression by IL-1β and TNF-α in mouse synovial fibroblasts
To determine whether these cytokines induce SYN expression at the transcriptional level, total RNA was isolated from these synovial fibroblasts, reverse-transcribed into cDNA, and examined by reverse transcription (RT)-PCR using SYN-specific primers. Real-time RT-PCR revealed that IL-1β induced SYN expression at the transcriptional level, because the mRNA level of SYN was upregulated by IL-1β. TNF-α had a weaker effect on SYN transcription, whereas IL-6 had no effect (Figure 3b). These results indicate that IL-1β induces SYN expression at the mRNA level in mouse synovial fibroblasts.
IL-1β and TNF-α induce SYN expression through activation of Erk
To further elucidate which MAPK pathway is involved in regulating IL-1β-induced SYN expression, specific inhibitors of MAP kinases were used [13–15, 25]. Erk inhibitor, PD98059, specifically inhibited Erk phosphorylation without affecting the activation of either JNK or p38 (Figure 4b, lane 3). In the presence of this inhibitor, SYN expression was reduced to a level that is comparable with non-treated controls (Figure 4a, top panel, lane 3). p38 inhibitor, SB202190, which specifically inhibited ATF2 phosphorylation without affecting Erk and JNK1 activation, had a very mild inhibitory effect on SYN expression (Figure 4c, lane 4). The specific inhibitor of JNK, SP600125, which specifically inhibited c-Jun phosphorylation, had no effects on IL-1β-induced SYN expression (Figure 4d, lane 5). Similarly, the Erk inhibitor also inhibited TNF-α-induced SYN expression (Figure 4e). Both IL-1β and TNF-α are also strong activators of the NF-κB pathway [24]. We therefore tested whether NF-κB activation is also involved in the induction of SYN expression in mouse synovial fibroblasts. The NF-κB-specific inhibitor, SN50, strongly inhibited both IL-1β and TNF-α-induced NF-κB reporter activities (Figure 4g) but not the SYN protein expression (Figure 4f). These findings collectively indicate that IL-1β and TNF-α enhance SYN expression through the activation of Erk, but not the p38, JNK, or NF-κB pathways.
Transcription factor ETS1 is involved in IL-1β-induced SYN expression
Activation of Erk and ETS1 is involved in the overgrowth of synovial fibroblasts from CIA mice
Based on previous studies that have suggested that Erk may activate ETS1 transcription activity [30] together with our findings that Erk and ETS1 are involved in IL-1β-induced SYN expression, we proposed that IL-1β induces SYN expression in mouse synovial fibroblasts via the Erk-ETS1 pathway. To support this hypothesis, we found that inhibition of Erk activation by Erk-specific inhibitor blocked ETS1 phosphorylation (Figure 6a). Moreover, Erk inhibitor suppressed the cell growth of mouse synovial fibroblasts, and the synovial fibroblasts from CIA mice were more sensitive to Erk inhibition (Figure 6b). Treatment of these cells with the Erk inhibitor did not significantly arrest the cell cycle of these synovial fibroblasts from either normal DBA or CIA mice (Figure 6c). These findings suggest that the activation of Erk and ETS1 is involved in the overgrowth of mouse synovial fibroblasts during CIA. Based on these findings, we collectively concluded that the Erk-ETS1 pathway is involved in SYN expression in mouse synovial fibroblasts induced by IL-1β and TNF-α.
Proinflammatory cytokines, particularly IL-1β and TNF-α, can induce the cell proliferation of synovial fibroblasts both in vitro and in vivo [31, 32]. The molecular mechanisms of proinflammatory cytokine-induced cell growth of synovial tissues have been extensively investigated, although there still is room for debate [33]. IL-1β and TNF-α are key activators of the many transcription factors, including activator protein-1 (AP-1), Egr-1 (early growth response-1), and NF-κB, in synovial fibroblasts. Activation of the NF-κB/Rel transcription family and AP-1 complexes, composed of members of the Jun and Fos families, contributes to the hyperproliferation of fibroblast-like synoviocytes [34]. We found that IL-1β induces the proliferation of synovial fibroblasts by upregulating SYN expression. These findings provide a new mechanism for IL-1β in synovitis during RA development.
MAPKs are especially important in synovitis because they control the proliferation of synovial cells in the rheumatoid joint and induce the production of MMPs and cytokines that participate in the rheumatoid process [33, 35]. The involvement of all three MAPK family members, JNK, Erk, and p38, in RA has been indicated by the fact that their activation is increased in rheumatoid synovial cells. They have also been implicated in the pathogenesis of RA [33]. The binding of IL-1β to its receptor expressed on the surface of synovial fibroblasts activates all three MAPK members, as demonstrated in our study and previous reports [33]. Intriguingly, only Erk activation is involved in SYN transcription, as indicated by the finding that the specific inhibitors against Erk, but not JNK and p38, block SYN expression. It has been demonstrated that Erk activation is highly increased in the synovial fibroblasts from patients with RA. Consistent with this, we found that the activation of Erk is significantly upregulated in mouse synovial fibroblasts from CIA mice compared with that from normal DBA1. Interestingly, the CIA synovial fibroblasts are more sensitive to Erk inhibitor-mediated cell growth inhibition. Therefore, Erk inhibitors could be potential candidates for RA treatment.
Recently, EBS-1 was identified as a crucial site for the expression of SYN [28]. EBS-1 is a binding site for ETS family transcription factors, including ETS1/2, GABP (growth-associated binding protein)-α/β, and Sp-1 [36]. Our findings that ETS1 expression increases SYN transcription and that ETS1-DN blocks SYN expression (Figure 4) confirm that the EBS-1 binding site is the promoter region for IL-1β-induced SYN expression. ETS1 is activated by Erk-mediated phosphorylation [37]. Therefore, inhibition of Erk activation by specific inhibitors blocks SYN transcription (Figure 3). Overexpression of ETS1 family transcription factors has been observed in RA synovial membranes [19, 27]. However, we found that the activation of ETS1 but not its protein expression is upregulated in the synovial fibroblasts from CIA mice. The elevated ETS1 activation is possibly a direct consequence of Erk activation, because inhibition of Erk activation blocks ETS1 phosphorylation.
As an E3 ubiquitin ligase on the ER membrane, SYN functions as an ER-associated degradation system in both yeast and mammals [8, 9]. The biological functions of SYN were analyzed in SYN transgenic mice and heterozygous knockout mice because the homozygous mice are embryonic-lethal [11]. Interestingly, the expression level of SYN correlates significantly with the onset of arthropathy: Increased SYN expression causes synovium overgrowth and spontaneous arthropathy, whereas reduced SYN expression (heterozygous mutant mice) is associated with resistance to CIA [11]. Our finding that the suppression of SYN inhibits IL-1β-induced synovial fibroblast proliferation provides a direct rationale for SYN as a potential target for the treatment of RA. It will be extremely interesting to investigate the effects of gene therapeutic delivery of dominant-negative SYN or its siRNA (small interfering RNA) on the development of arthritis in animals such as DBA mice with CIA.
This study demonstrated that the proinflammatory cytokines IL-1β and TNF-α induce synovial fibroblast growth by upregulating the expression of an E3 ubiquitin ligase, SYN. At the molecular level, activation of MAPK Erk and transcription factor ETS1 is required for SYN expression. Based on our findings and the fact that synovial fibroblasts are among the major resources for IL-1β and TNF-α in the rheumatoid joints [31], we proposed a positive feedback model for SYN in RA development (Additional file 2). According to this model, IL-1β induces SYN transcription, SYN enhances IL-1β-induced synovial fibroblast proliferation, and the massive growth of synovial fibroblasts produces more IL-1β for the induction of SYN expression. This positive feedback process may be critical in RA development. Molecules in this signal pathway can therefore be potential targets against RA.
= activator protein-1
= complete Freund's Adjuvant
= collagen-induced arthritis
= Dulbecco's modified Eagle's medium
= ETS binding site
= endoplasmic reticulum
- Erk:
= extracellular signal-regulated kinase
= dominant negative mutant of ETS1
= fetal bovine serum
= glutathione S-transferase
= institutional animal care and use committee
= interleukin
= c-Jun N-terminal kinase
= mitogen-activated protein kinase
- NF-κB:
= nuclear factor-kappa B
= Nonidet P-40
= polymerase chain reaction
= rheumatoid arthritis
= reverse transcription-polymerase chain reaction
= Synoviolin
- TNF-α:
= tumor necrosis factor-α
- Ubc:
= ubiquitin-conjugation enzyme.
We thank Dr. Christopher H. Evans (Center for Molecular Orthopaedics, Harvard Medical School, Boston, MA, USA) for providing protocols for mouse synovial fibroblast isolation. We also thank Dr. Krishna Kannan (Division of Rheumatology, Department of Internal Medicine, University of Missouri-Columbia) for his critical comments on the manuscript. This work was partially supported by a research board grant from the University of Missouri and by an investigator research award from the Arthritis Foundation to DF.
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subset: commoncrawl


text:
This Is Not A Geek's Room, But An Incredible Diorama
Looks like a real room, right? Nope. It's a miniature.
Looks like a real room, right? Nope. It's a miniature.
Naoyuki Oi is crushing it at this weekend's World Pool Masters, both on the table and in the post-match interviews with Sky Sports.
Previously, we saw the Nintendo Switch game cases. They're about as big as PSP game cases, but Switch game cards are certainly not as big as PSP UMDs.
Dutch author and illustrator Dick Bruna passed away on February 16, his publisher announced late last week.
The goal is very bad. Maybe one of the worst. But the music is perfect.
This is Where Cards Fall, "a coming of age story where you build houses of cards to move through imaginative puzzles and bring vivid memories of adolescence to life". It'll be out on iOS, Mac and PC in the Fall.
If you've ever played Dyad, Proteus, or Panoramical, you've heard David Kanaga's work before. He's one of the smartest people in game design and his latest work, Oikospiel, is his most mind-scrambling creation yet.
When Pokémon Go was in its prime last year, many of the game's more popular locations were parks. And some of those parks got trashed. Understandably, if also a little late (at least for Pokémon Go), local governments are now taking steps to try and stop this happening again.
Classic Sony headphones, a printer you won't hate, and Instant Pot's sous-vide circulator lead off Sunday's best deals from around the web.
The Nintendo Switch is less than two weeks away, but meanwhile here's a bunch of games that aren't Breath of the Wild.
When Astralis bested Virtus.Pro in the grand finals of the ELEAGUE Major in January, Markus "Kjaerbye" Kjærbye tweeted that his team "underperformed" in its 2-1 victory. A member of Virtus.Pro took offense, and promised to crush Astralis when they next met.
In this weekend's FIFA '17 Ultimate Team Regionals, one player put up a quick double that reminded me of my casual matches against friends.
Guilty Gear Xrd - Revelator - is just one of the many fighting games being showcased at this weekend's Anime Ascension 2017, but damn it's one of the most intense.
Today's Kindle Gold Box is ostensibly centered around previous Kindle Daily Deal titles that you might have missed, but all you really need to know is that it's loaded with really popular books for $5 or less.
I had to wait my turn while a silver-haired man in an expensive suit took High Roller's adult-sized big wheel for a spin, but it was worth it. This was one of the happiest moments in my adult life.
Just Dance has a new World Cup champion, and it's not who anyone thought it would be. Somehow breezing past stiff competition from around the globe, high school-aged Umutcan managed the biggest upset in the game's short competitive history.
This is the official art from Tomy's Toy Fair press kit for My Friend Eevee, the follow-up to My Friend Pikachu. This is not how you treat your friends.


text:
Grim Reaper
The reaper's here,
he's come for me,
to take my soul,
and set me free,
no time left for me,
it doesn't matter what I wasted,
nor where I have gone,
or done for thee,
no time left to cry,
the reaper's here,
he's ready to fly,
you see,
he grabs my soul,
from my bodily temple,
pulls it from me,
as my body goes limp,
my soul's flying on the breeze,
as I fly through time and space,
the valley's of peace I do grace,
cause I know at last,
that my soul is set free,
n the reaper's here for me.
Razorblade © 2012
© Copyright 2017 RazorBlade. All rights reserved.
Status: Finished
Genre: Poetry
Poem / True Confessions
Poem / War and Military
Poem / Poetry
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text:
a poem by S H Fouts
Cradled deep inside my womb,
I heard God speak to me
He said a son you shall have
And a blessing he will be
Life's dealt a blow
With physical woe
And genetic imperfections
With a crooked spine
And one kidney
What were my expectations?
Was it due to LSD
or even agent orange?
Or was it mercury in fish
I do not know at all.
But this for sure I know
That my love for you is strong
A blessing you are
A handsome man you've grown into
Shining like a star
A star, you are, a shining star
Light flashing from afar
I believe God has His hand
upon your shoulder's son
To lead you and to guide you
Into His perfect plan.
I love you as you are
Accept you as you are
But I believe God has more for you
To turn you into His star.
© Copyright 2017 Susan Hartline Fouts. All rights reserved.
Status: Finished
Genre: Poetry
Beautiful susan! How old is he now?
it is so wonderful the blessings we recieve from those who we look upon as not perfect, they seem to teach us so much. To look past form and into the being
simply sweet, the words are clear and used very well. the poem is accented with a tremendous force of love. Keep it up.
GOD will always take care of him Susan. I know ur trust in HIM kept him strong
Short Story / Flash Fiction
Poem / Religion and Spirituality
Poem / Religion and Spirituality
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text:
4 works Add another?
Most Editions | First Published | Most Recent
On the Construction of Improved Ordinance1 edition - first published in 1862 Read
On the Construction of Hooped Cannon: Being a Sequel to a Memoir "On the Practicability of ..1 edition - first published in 1864 Read
The relations of science to the useful arts1 edition - first published in 1855
On the practicability of constructing cannon of great caliber1 edition - first published in 1856
Links (outside Open Library)
No links yet. Add one?
History Created April 1, 2008 · 3 revisions
|June 7, 2012
|Edited by VacuumBot
|Removed period from death date
|September 9, 2008
|Edited by RenameBot
|fix author name
|April 1, 2008
|Created by an anonymous user
|initial import


text:
New Badge Unlocked!
Sign-in to our games arena!
Create a username to play games and submit your score to the Leaderboard
Create Username:
Looking for a real crossword challenge? Play the new Sunday Crossword and get your weekly fix of the toughest, professionally made puzzles out there. No pen or pencil required for this crossword, it's all online and it's free!
©2016 PennyDellPuzzles.com
Penny Dell Sunday Crossword and scores


text:
Bubble Hit
by: bigrenlu • 1.9K
All Android applications categories
All Android games categories
by: bigrenlu • 1.9K
Aim and shoot at the falling balls. Three or more balls of the same color disappear. Is it easy? But the balls fall quicker and quicker. If the bubbles reach the end of the playing board, you will lose.
How to play:
- Your goal is to clear all the bubbles before they overflow the bottom line
- Tap the screen, where you specifically want the bubble.
- Make combinations of 3 or more bubbles to pop them.
Tags: bubble hit brain , bubble hit , yepi buble hit , bubbles pro level 414 , balloon breaker game , bubbles aim
Users review
from 1.913 reviews
Download Bubble Hit
Free - V10.9 - 2M
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text: With the passing of FAMA, we've decided to hold a new subscription offer for those wishing to migrate to our wonderful magazine if they have not done so already. For a limited time, new subscribers can get 12 full issues for only $15! New subscribers can get the offer on our website at http://www.tfhmagazine.com/specialoffer/.


text: GDP adjusted PAYG and GST instalment amounts This overview explains how and why the gross domestic product (GDP) adjustment is applied to pay as you go (PAYG) and goods and services tax (GST) instalment amounts, and what to do if you think this will impact your tax liability. Note: The information given in this fact sheet is based on a balancing date of 30 June, which is when the majority of taxpayers in Australia balance their accounts. For most taxpayers, the term income year used in this publication refers to a financial year (1 July to 30 June). Eligible taxpayers who report PAYG instalments or GST quarterly have the option of paying instalment amounts that we calculate for them. These amounts are printed on your quarterly activity statement or instalment notice. We calculate these instalment amounts from information you have previously reported. We adjust these figures to take into account likely growth in your business and investment income (for PAYG) or in your GST net amount. This adjustment is based on growth in Australia's economy, as measured by GDP. Why are instalment amounts adjusted? The information we use to calculate your instalment amounts is generally taken from your most recently assessed income tax return (for PAYG instalments) or annual GST return (for GST). As PAYG and GST instalment amounts are intended to reflect your expected tax liabilities for the current income year as accurately as possible, we adjust the instalment amounts to reflect expected changes in the economy. If instalment amounts were solely based on your previous tax situation without any adjustment, they might not cover your actual tax liability – leaving you with an additional payment to make when you lodge your annual return. Last modified: 22 Jun 2016QC 16312


text:
|Message view
|« Date » · « Thread »
|« Date » · « Thread »
|"Simon Kitching (JIRA)" <j...@apache.org>
|[jira] Commented: (LANG-238) [lang] Add equals(type[]) to NumberUtils
|Tue, 02 Jan 2007 04:16:27 GMT
[ http://issues.apache.org/jira/browse/LANG-238?page=com.atlassian.jira.plugin.system.issuetabpanels:comment-tabpanel#action_12461664 ] Simon Kitching commented on LANG-238: ------------------------------------- I would agree with Stephen that an "allEquals(a)" method isn't likely to be widely used. And besides, it can be implemented for non-floating-point as: Set<integer> aSet = new HashSet<Integer>(Arrays.asList(a)); boolean allEq = (aSet.size() <= 1); which doesn't seem to me sufficiently complicated to deserve inclusion in lang. A "containsOnly(a,b)" method would be more generally useful but can be implemented as: Set<Integer> aSet = new HashSet<Integer>(Arrays.asList(a)); Set<Integer> bSet = new HashSet<Integer>(Arrays.asList(b)); // or if b has one element, bSet = Collections.singleton(val); boolean contained = bSet.containsAll(aSet); which again doesn't seem terribly complicated. However if a more generic method is being considered, then how about: T[] notIn(T[] a, T[] b); which returns the elements in a that are not in b? I'm not a mathematician but I believe this is written in set operations as "a - b", or in words as "the complement of a with respect to b", so this method could also be called: T[] subtract(T[] a, T[] b); or T[] complement(T[] a, T[] b); though I think "notIn" is more obvious for most users. Actually, this operation is the array equivalent of Collections.removeAll, so that's an alternative name: T[] removeAll(T[] a, T[] b); The test "allEquals(a, b)" is then: boolean allEq = NumberUtils.notIn(a, b).length == 0; and the test "allEquals(a)" is: boolean allEq = NumberUtils.notIn(a, new Integer[] {a[0]}).length == 0; BTW, the "a" parameter is really an array representation of a bag, not a set so maybe this set terminology could be misleading. If such a set/bag operation is provided, then intersection and union could also reasonably be provided for arrays: T[] intersection(T[] a, T[] b); T[] union(T[] a, T[] b); Not sure whether union should treat its params as bags (in which case union would be equivalent to concat) or sets (only one occurrence for elements in both a and b). At this point, this appears to be bordering on commons-collections or commons-math functionality but as this is only for arrays I think a good argument could be made for including this in lang.. > [lang] Add equals(type[]) to NumberUtils > ---------------------------------------- > > Key: LANG-238 > URL: http://issues.apache.org/jira/browse/LANG-238 > Project: Commons Lang > Issue Type: Improvement > Affects Versions: Nightly Builds > Environment: Operating System: other > Platform: Other > Reporter: Paul Benedict > Priority: Minor > Fix For: 3.0 > > > It would be useful to add an equals() method like the current min and max > methods which take an array type and determine if all the values are equal. > I have found myself in need of this often. I have to retrieve objects from > multiple data sources in parallel to build an array of complex object. To ensure > validity, I always compare that my sub-retrievals returned the same number of > objects as expected. -- This message is automatically generated by JIRA. - If you think it was sent incorrectly contact one of the administrators: http://issues.apache.org/jira/secure/Administrators.jspa - For more information on JIRA, see: http://www.atlassian.com/software/jira --------------------------------------------------------------------- To unsubscribe, e-mail: firstname.lastname@example.com For additional commands, e-mail: email@example.com
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text:
Ukraine's 2014 Bond Yield Jumps to Record on Political StalemateAndras Gergely
Yields on Ukraine's dollar bonds jumped to a record and the hryvnia slumped as politicians struggled to break a deadlock that stands in the way of the country receiving aid, either from Russia or the West.
The rate on the note due in June rose 147 basis points, or 1.47 percentage point, to 22.37 percent by 4:38 p.m. in Kiev. Ukraine's currency depreciated 1 percent to 8.79 per dollar, extending the drop in the past three days to 4 percent, according to data compiled by Bloomberg. That was the worst performance worldwide after the Kazakh tenge, which was devalued by the central bank in Almaty this week.
The European Union is ready to provide financial aid to a new Ukrainian cabinet if leaders are committed to the rule of law and a stronger economy, Enlargement Commissioner Stefan Fule said today in Kiev after talks with President Viktor Yanukovych and the opposition. While the 28-nation bloc is trying to end to anti-government protests that are into a third month, Ukraine's foreign-currency reserves slumped to a seven-year low after Russia suspended its bailout.
"The political deadlock has a direct impact on Ukraine's stability," Dmitri Petrov and Peter Attard Montalto, London-based analysts at Nomura Holdings Inc., wrote in an e-mailed report today. "Initiation of a political dialog may have created a false impression of resolution."
Debt Insurance
The sides are arguing over proposals to redo the Constitution to weaken the president's powers and install a new coalition government following the resignation of Premier Mykola Azarov in January after police forces cracked down on the protesters, killing seven demonstrators.
The cost of insuring the country's debt against non-payment using credit-default swaps jumped 73 basis points to 1,252, the highest since July 2009, according to CMA prices. The yield on Ukraine's dollar bonds due in April 2023 increased nine basis points to a two-month high of 10.48 percent.
The International Monetary Fund, which has called for a more flexible currency regime, would play a "central" role in a potential western aid effort, Fule said. Russia, which bought $3 billion in Ukrainian Eurobonds in December to help avert default, halted further payments after Azarov's departure.
"It is difficult to see any agreement with the IMF/West or Russia until a new government is in place, Timothy Ash, a London-based strategist at Standard Bank Group Ltd., wrote by e-mail today. ''As financial support for Ukraine hangs in the balance, Ukrainian asset prices continue to push lower.''


text:
Loving our Magical Script!!!
Loving our Magical Script!!!
We've been so busy sending our our annual holiday cards. Yes, they are a bit late but oh well!! Sometimes when you are doing your own you add so much pressure to yourself trying to perfect them. Here are two we recently finished up. Check back in the next few days to view many more! Enjoy!
Christmas cards underway 🎅🎄❄⛄
Copyright 2012 - Calligraphy By Jennifer


text:
|Frankfurter Ring 35
|80807 München DE +49-1806-666666
|GDS - Code:
|Mo. - Fr.
|06:30 - 19:00
|08:00 - 13:00
|24 h return
Whether on business or pleasure Sixt rent a car can satisfy your mobility needs with a premium car rental from our Munich Frankfurter Ring branch. We are reachable with public transportation and are just a short walk from the Frankfurter Ring Ubahn station. Find our services inside the BMW dealership where we look forward to greeting you and getting you behind the wheel. Affordable rates are to be had on our wide selection of top quality vehicles suitable for all budgets and travel plans. Choose from our compact cars, sedans, sports cars, convertibles, and SUVs. Whatever you have in mind for your rental car we have a vehicle to match.
Besides our low rates on car rental we have great deals on useful add-ons and upgrades as well. You can enhance your rental by including extras as you make your reservation online or over the phone. Tack on optional features such as child seats, GPS, additional driver coverage, insurance packages and more. Please be aware that we can only guarantee you to receive a vehicle in your chosen car category and not a specific model. Once with your rent a car you can set off to tour around the city or head out into the surrounds. Our Munich Frankfurter Ring BMW branch provides courtesy 24 hour returns so you can make the most of your time with your Sixt rental without having to rush. We hope you enjoy the drive!
|Mo. - Fr.
|06:30 - 19:00
|08:00 - 13:00
|Frankfurter Ring 35
|80807 München
|+49-1806-666666 *
|+49-1806-2229308182 *
|* 0.20 ¤/call from german landline network, 0.60 ¤/call from german mobile network
Exit the A8 and follow the A99 direction to Salzburg. At motorway junction Nord turn onto A9 direction to München. Take exit 75 Frankfurter Ring and follow the Frankfurter Ring till Lauchstädterstraße. The Sixt branch is located inside the BMW dealer.
Leave the A9 at junction 75 Frankfurter Ring follow the Frankfurter Ring till house number 35. The Sixt branch is located inside the BMW dealer.
A95 direction to the airport: At motorway junction Nord turn onto A9 direction to Munich. Take exit 75 Frankfurter Ring and follow the Frankfurter Ring till Lauchstädterstraße. The Sixt branch is located inside the BMW dealer.
Take subway U2 until stop Frankfurter Ring. Exit the train station in direction to Frankfurter Ring. The Sixt branch is located inside the BMW dealer at Frankfurter Ring 35.
For return please take Lauchstädterstraße behind the BMW building and park the Sixt vehicle directly on the area of the BMW dealer or at Lachstädter Straße. The security service at the gate will receive the vehicle key.
|Lauchstädter Str. 5
|80807 München


text: These Randy Cartoon Characters Will Make You Laugh Out Loud (NSFW)Mark Shrayber3/22/14 4:35pmFiled to: NSFWCartoonGifFunny416EditPromoteShare to KinjaToggle Conversation toolsGo to permalink Hornytoongifs is a new Tumblr that has been making the internet rounds since it exploded earlier this week. The blog, which started in January pairs together pictures of barely-clothed male models (okay, in some cases they are naked but genitals are blurred) with gifs of cartoon characters engaging in naughty behaviors. If you've ever wondered what would happen if Tina Belcher got to slap all the butts that she wanted or if The Count was counting down to an inappropriate photo of Alexander Skarsgard. (Actually, here's what would happen:) GIF And Here's Zangief doing what he does best: Dancing. GIF And here's Tina unleashing her primal scream on Gerard Butler: GIF The rest of the GIFS are pretty risque, so browse at your own Advertisement Advertisement risk.Reply41 repliesLeave a reply


text:
80's Party "Back to old School" @ Anaheim House Of Blues!!
Saturday, September 8, 2012 at 8:00 PM (PDT)
Event Details
Be sure to buy your discounted tickets with this link! Tickets will be held at will call day of the show. It will be $20 at the door! Playing is Uncle Larry's Heavy Metal Revue, Rad, Rerewind and One Hot Mess! Be sure to dress up and get into the 80's!!! See you at the show!
Sales here end here on eventbrite at noon on September 8th, after time you will have to pay at the door, which will be $20. Be sure to visit www.got-oc.com for more shows and events!
All tickets will be held at will call day of the show, they will be higher priced day of the show and are more expensive on ticketmaster, so buy now!!! Check out a video from a past "House of 80's" show! If you are bringing a group of ten or more or celebrating an event, call 714-726-2390.
When & Where
House Of Blues Anaheim
1530 S. Disneyland Drive
Saturday, September 8, 2012 at 8:00 PM (PDT)
Add to my calendar
GOT-OC, Get Out There Orange County is all about getting you out and having some fun in the OC!


text:
(1 - 43 from 81
Judith L Arnell (Age: 48)
97209 Portland OR
Judith Lynne Arnell (Age: 69)
97209 Portland OR
Judith Arnell, Portland, Se Laurie Ave
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Party in the Pearl! Tickets, Thu, Oct 22, 2009 at 6:30 PM | Eventbrite
Eventbrite - Candy Ultra Lounge presents Party in the Pearl! - Thursday, October 22, 2009 at Pearl Medspa, Portland, OR. Find event and ticket information.
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Judith Arnell Jewelers provides Wedding Jewelry in Oregon - Portland and surrounding areas. We allow you to request information from Judith Arnell Jewelers.
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Read reviews about Judith Arnell Jewelers. Compare thousands of Wedding Jewelry ratings in oregon - portland and surrounding areas.
holiday shopping at the atwater - s.waterfront - december 11th, 2008
06.12.2008 by Ruth Price (The Hasson Co.) don't fight the crowds. free valet parking and refreshements. when: december 11th, 2008 5pm-9pm. where: 0841 sw gaines stree | portland or | 97239. what: holiday trunk show featuring: cielo home. ecru. jd madison. judith arnell jewelers ...
Home - Judith Arnell Jewelers Judith Arnell Jewelers
507 SW Broadway Portland, Oregon Call us at 503.227.3437 Hours Monday - Saturday 10AM to 5:30PM Closed Sunday Get fun updates, Like us!
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Judith Arnell Jewelers of Portland, Oregon offers GIA and EGL certified diamonds at wholesale prices. We specialize in Asscher cut and Cushion cut diamonds and have a large ...
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Judith Arnell Jewelers of Portland, Oregon offers GIA and EGL certified diamonds at wholesale prices. We specialize in Asscher cut and Cushion cut diamonds a...
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Judith Arnell Jewelers's products, services, reviews, address, phone number, driving directions, hours of operation and more. Located in Portland, OR.
JCK Tucson Redefines How Business is done at Tucson Jewelry Week -...
"JCK Tucson has set the bar here at Tucson Jewelry Week," proclaimed Judith Arnell of Judith Arnell, Portland, OR., "The wide range of product ...
holiday trunk show - atwater place in s.waterfront
06.12.2008 by rp free valet parking and refreshements. when: december 11th, 2008 5pm-9pm where: 0841 sw gaines stree | portland or | 97239 what: holiday trunk show featuring: cielo home ecru jd madison judith arnell jewelers mabel & zora and more [...]
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Download of a web live stream
This project was successfully completed by jacobJordan for $55 USD in a day.Get free quotes for a project like this
Project Budget$10 - $30 USD
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Project Description
I'm looking to obtain a HD download of the full live stream footage of the The Amazing Spider-man World Premiere today at April 10 2014 at 530 pm GMT from these links:
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Or check online for sites which will be broadcasting this live.
The file will need to be sent via a link, MP4, HD - and as best quality as possible. Will select a bid after receiving the link. Please feel to download the file and then contact me if have not been in touch.
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OpenVPN Security Advisories
Important security notice regarding 'Heartbleed' vulnerability
On Monday evening, April 7th, we were informed of a major vulnerability, dubbed 'Heartbleed' (CVE-2014-0160), within one of the Internet's most significant security libraries (OpenSSL). A great number of services across the internet, including OpenVPN Access Server, may have been affected by this issue. Since learning of this issue, we have taken immediate necessary steps to ensure the security of OpenVPN and the OpenVPN Access Server product. On the morning of April 8th we have therefore released patches for specific versions of the Access Server that are affected, and we have released Access Server 2.0.6 with the fix for this issue already incorporated.
The affected versions of Access Server are 1.8.4, 1.8.5, 2.0.0, 2.0.1, 2.0.2, 2.0.3, 2.0.4, and 2.0.5. If you have a version older or newer than the aforementioned versions, you are not vulnerable to the Heartbleed vulnerability, but of course we always recommend to keep your system up-to-date. If you are running one of the mentioned versions, we recommend that you upgrade to the latest version available from our website. Please be sure to note that you do need a valid (and not expired) license key in order to upgrade. For those that cannot or will not update to the latest version, we offer the patched library files that will fix the vulnerability.
As always, the OpenVPN Access Server packages, which can be installed on physical, virtual, cloud, and appliance machines, can be downloaded from the following address, after which you can perform an upgrade installation that retains your settings and brings your system up-to-date:
The library patch files for those that cannot or will not update are here:
The attack vector that is present on the Access Server with the vulnerable OpenSSL libraries is not present on the Connect Clients, so the risk is minimal. Only the server that your client connects to could possibly exploit this vulnerability, and even then it is unlikely because we use Perfect Forward Security and TLS-auth on top of the SSL connection. The security of the data channel itself is not particularly at risk, only the web services on the server themselves are. And even then, since we use a privilege separation model, the web services run in a completely different process than the OpenVPN daemons handling the data connections, and therefore the private keys for your OpenVPN connections are not likely to be at any risk. Even so, we don't want to take chances and are going to release 2.0.7 soon, which will incorporate updated clients as well. And for those that want to have the updated clients right now, you can download them from the following address:
Note that mobile clients like on iPad, iPhone and Android devices, are not affected as they use PolarSSL instead.
OpenVPN Access Server "Desktop Client" security advisory
All Access Server customers using the "Desktop Client" app for Windows should upgrade immediately to the OpenVPN Connect client. The "Desktop Client" is obsolete and is no longer maintained or available for download. This client contains a CSRF (Cross Site Request Forgery) vulnerability that can allow remote code execution by a malicious web site (Credit: Stefan Viehböck, SEC Consult). It is also bundled with an older version of OpenSSL that has not received recent OpenSSL security updates. This advisory only applies to the OpenVPN Access Server "Desktop Client" app for Windows, and does not affect OpenVPN Connect, Private Tunnel, or community builds of OpenVPN for Windows.


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makeup by anagutierrez Makeup Artist
Eirene ErisModel Female Fontana, California, US
My Website: FacebookMy MM URL: http://www.modelmayhem.com/MeltingWaterMelons
Mayhem # 3275466
About MeWelcome to my modeling page!
I am a very professional, reliable & respectful person. I have a lot to learn about the industry, and am willing to take advice from those who willing to give it.
(Give me pointers!)
I have a background in dance and i like to do hula hooping as a hobby. I have done freelance make up work on several shoots, as well as gore makeup for local, high school, haunted houses.
Note that I will not do nude work under any circumstances. I am available for trade and paid work. I am here to work with anyone who has a detailed background in the arts. I understand that it is important to build a portfolio and I will do my research before agreeing to sign releases.
I do have a tattoo on the back of my right calf, however it's not visible unless you shoot the back of my legs in shorts. My hair is about medium length to my shoulders and as of 2/25/2014 is dark red brown/black. I do have a dark brown hair wig with longer hair if needed.
If you would like to contact me via email, please message me for my personal information or any further questions.
Have you worked with Eirene Eris? Add Credits for Eirene Eris! >>
makeup by anagutierrez Makeup Artist
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The college was established on March 15th, 1963, as Indiana Vocational-Technical College and offered one academic program with 3,000 enrolled students.
Today the college offers more than 125 areas of study and enrolls nearly 200,000 students annually. Ivy Tech is now the nation's largest accredited statewide community college system.
Today students, alumni l, employees, retirees and the community celebrated this milestone at its founders Day celebration.
Copyright 2017 Nexstar Broadcasting, Inc. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.


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Mar 31, 2016 GMTI don't use Twitter a lot, which explains why I often miss mentions from other users. But checking for mentions manually is as practical as playing tennis with a broom stick. Node-RED to the rescue! I already have a Node-RED instance running on my Raspberry Pi, so all I had to do was to write a simple flow that monitors Twitter for mentions and sends email alerts to me. The flow consists of three nodes. The Twitter node searches all public tweets for @dmpop (that's my Twitter handle) mentions, while the Function node uses a simple function to construct a message that is then sent to the email address specified in the Email node. Pretty simple stuff really. If you want to deploy a...
Productivity Sauce
Use Node-RED to Get Twitter Mention Alerts
Quick-and-Dirty Geotagging with a Bash Script
Mar 22, 2016 GMTWhen you need to quickly geotag a bunch of photos with an approximate location (e.g., city and country), a simple Bash shell script can help you to do it much faster than a heavy-weight application like digiKam. The script uses the Nominatim service to perform forward geocoding (i.e., obtain the geographical coordinates of a given place name) and a combination of curl, jq and tr tools to extract the latitude and longitude values. It then uses the ExifTool to write the obtained coordinates to all JPEG files in the current directory. To install jq and ExifTool on Debian and Ubuntu-based distributions, run the apt-get install curl jq libimage-exiftool-perl command as root.To deploy the...
Open Note Scanner: Instant Note Digitizing on Android
Mar 15, 2016 GMTThere is no lack of apps of varying degrees of sophistication and quality that can transform your Android device into a handy note digitizing tool. And if you prefer to keep things simple and open source, Open Note Scanner is what you need. The utility relies on OpenCV software (you need to install it separately) to do its magic, and it does the job without any input on your part. Open Note Scanner supports two modes: Manual and Auto. In the manual mode, it's up to you to accurately frame the page your want to digitize. Keep in mind that the app works best with pages that have dark (or preferably black) borders around it. To get the best possible result, you might want to place a loose...
Instant Streaming from Linux to Chromecast with stream2chromecast
Mar 10, 2016 GMTWhat's the easiest way to stream media files from a Linux machine to Chromecast? The correct answer is stream2chromecast. This simple tool makes the task of streaming media files from a Linux machine to a Chromecast device ridiculously easy. Clone the project's GitHub repository using the git clone https://github.com/Pat-Carter/stream2chromecast.git command. On Ubuntu-based distributions, run the sudo apt-get install libav-tools command to install the avconv package required for transcoding media files not supported by Chromecast. And that's all there is to it.To stream a media file, switch to the stream2chromecast directory and run the stream2chromecast.py /path/to/foo.mp4 command. To...
Access StackOverflow from the Command Line with how2
Mar 09, 2016 GMTWhatever coding-related question you might have, chances are it has already been answered on StackOverflow. But switching to the browser and wading through StackOverflow in search of a solution to your particular problem is not the most efficient way to use the service -- especially if you spend most of your productive time in the terminal. Enter how2, a command-line tool for searching StackOverflow using natural language queries. Installing how2 on Ubuntu-based distributions is a matter of running the following commands: sudo apt-get install nodejs npm sudo ln -s "$(which nodejs)" /usr/bin/node npm install -g how2With how2 installed, you can search StackOverflow using the...
Extension Watch: Beef up Privacy Protection with Decentraleyes for Firefox
Feb 26, 2016 GMTuBlock Origin and Privacy Badger make a perfect combo for protecting your privacy and combating annoying ads. But these extensions can't protect you against more insidious ways of tracking your activities and collecting personal data through content delivery networks (CDN). Enter Decentraleyes. This add-on acts as a local CDN by intercepting requests, finding the required resource and injecting it into the environment. While this may sound awfully technical, the add-on does its job behind the scenes, and it requires no configuration whatsoever. Install the add-on from Mozilla's official add-on repository, and you are done.If you are curious whether Decentraleyes actually does anything,...
twtxt: Microblogging for Hackers
Feb 25, 2016 GMTMaybe you are not keen on using closed and tightly-controlled third-party microblogging services like Twitter. Or maybe you are just looking for a straightforward way to share your thoughts with the world directly from the command-line. In either case, twtxt might be something right up your alley. This little tool makes it possible to push updates and follow other twtxt users from the convenience of the terminal. The clever part is that twtxt stores your updates in a plain text file. Make this file publicly accessible via HTTP and other users can subscribe to your stream. twtxt is written in Python 3, and the easiest way to install it on your system is through the PIP tool. To do...
Issue 28: GIMP Handbook 4th Ed./Special Editions
Buy this issue as a PDF
Digital Issue: Price $15.99
(incl. VAT)
Munich Plans to Ditch Linux and Go Back to Windows
A major setback for the Linux desktop.
Linux Kernel 4.10 Comes with New Security Features
Improved support for GPU in virtualization.
OpenSUSE Site Hacked
News site for the openSUSE community falls victim to a Wordpress exploit.
LibreOffice Goes Online with 5.3 Release
The source code is available online.
Microsoft Brings Clear Linux OS to Azure
One out of three virtual machines on Microsoft Azure Cloud run Linux.
ASUS Announces a Single-Board Computer
The form factor of the board makes it a drop-in replacement for Raspberry Pi.
Red Hat Releases RHEL 6.9 Beta
Makes it easier for customers to move workloads into container-centric applications.
SUSE Working on a New Operating System Called MicroOS
SUSE's answer to container-centric operating systems.
Biggest Kernel Release Ever
Linux 4.9 is the biggest release in terms of number of commits.
CentOS Linux 7 (1611) Released
The latest version of the official RHEL clone is here.


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We know the value of a smile at the end of the day. It's a small reminder of why we teach kids climbing. It's because learning to climb is fun, and because it encourages learning general life skills that can be applied every day. Our climbing camp doesn't set out to make kids all-star rock climbers but rather, through climbing, helps kids find ways to…
- Solve problems
- Make good decisions
- Act as team players
- Learn respect for others
- Enjoy physical recreation and the outdoors, and
- Do something healthy for their growing bodies.
Rise Up's five-day camp introduces children to rock climbing,. The camp takes place at our indoor facility where we spend all five camp days. The gym allows us to control the climate and the climbing thereby enhancing the learning atmosphere and ensuring that each child receives all the attention, guidance, and instruction they need.
A brief look at the week's exciting activities for campers:
- Identify each child's needs and goals
- Participate in group team-building games to encourage trust
- Instruction in the basic skills of top roping
- How to contact, the climbing surface
- Learn movement skills used for climbing
- Gain basic knowledge of geology
- Have fun climbing!
Class schedule: Monday-Friday from 9 a.m. to 3 p.m. (see below for details)
Format: Coed
Ages: 8-14
Price: $199 per session with $100 deposit due at registration and the remaining $99 balance due the first day of camp.
Discounts: Rise Up members receive a $20 discount; Siblings receive a $25 discount. This will be reflected upon payment of your balance.
Pre-registration required
Session Dates (daily from 9 am to 3 pm)
1. June 27th – July 1st
2. July 11th – July 15th
3. July 25th – July 29th
4. August 1st – August 5th
Our sessions fill quickly so please register early! Sign up today!


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| Clip Of House Session This clip, title, and description were not created by C-SPAN.
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February 25, 2012 Clip: House Session Clip: House Session
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- Dale E. Kildee U.S. Representative [D] Michigan
- G. "Sonny" V. Montgomery U.S. Representative [D] Mississippi
- Henry Waxman U.S. Representative [D] California
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Age UK Adjustable Beds are provided by Theraposture Ltd, in association with Age UK Trading CIC.
Age UK Adjustable Beds are provided by Theraposture Ltd, in association with Age UK Trading CIC.
If you are looking for single or dual occupant bed, but with a little more opulence, then the Windsor is for you. This superb Age UK Adjustable Bed is both elegant and durable with a metal frame finished in a desirable cream and gold colour.
Frequently asked questions Prefer to build your own? Find out if you are VAT exempt
* Terms and conditions apply - for full details contact Theraposture or call 0800 251 1484
Age UK Adjustable Beds as provided by Theraposture Limited (registered company number 01649470, registered office: Kingdom Avenue, Northacre Industrial Park, Westbury, Wilshire, BA13 4WE ). Theraposture Limited works in association with Age UK Trading CIC, a commercial services arm and wholly owned subsidiary of Age UK (registered charity number 1128267). Age UK Adjustable Beds is a product name of Age UK Trading CIC. Theraposture Limited uses the name 'Age UK' under licence. Age UK Trading CIC, registered company number: 01102972, registered office: Tavis House, 1-6 Tavistock Square, London WC1H 9NA. During 2015/16, Theraposture will raise a minimum of £85,000 through the promotion and sale of adjustable beds for Age UK Trading CIC.


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Is this attraction popular with tourists?
Is this attraction a "must-see" location?
Is this attraction in a remote location?
Does this attraction provide visitors with a taste of the local culture?
Is this attraction exciting, unusual, or risky to visit?
Does this attraction require above average amounts of physical activity (long walks, climbs, stairs or hikes)?
Is this attraction good for couples?
Is this attraction suitable for all ages?
Is this attraction pet friendly?
Would this be a good hot day activity?
Thanks for helping!
Some interesting mounds but since you cross a swamp to get there, also tons of bugs. We were glad to support a local cause, but this was not quite as advertised.
Not giant ruins with steps to climb, but you do trek a quarter mile on wooden planks through mangroves to get there. No kids under 5 allowed, so plan accordingly. Bring some insect repellant as well and water. It's a self guided tour that you read the signs and follow the markers. The artifacts are laying all around you and...
4 years later for this review, my friend and I spent the day there and really enjoyed ourselves. Even though we were by ourselves, we really enjoyed all the history that we read on all the trails and paths. It was kind of humbling experience to realize how old the site is. If you love history this is a must.
Glad we went! Hard to visualize the ruins but it was very beautiful to see the jungle and where the Mayans once lived. It is quite an excursion to get to it. Very bad roads, but worth the trip
Walking among ruins that are thousands of years old and few people. It is a great way to get a historical perspective of San Pedro.
We had heard about the Marco Gonzalez Mayan site and my wife located the website, so we made contact with Jan Brown who we arranged a tour with at an extremely modest price. Jan, is among other things, the manager of the site and head of the local archeological society. She very generously offered an additional seat to another guest...
You want to see what a real archaeological site is like, this is it! Bring bug spray and a long sleeved shirt/pants. The mosquitos when you hit the land on the other side of the mangroves are fierce. This is a really neat real life dig site where you can view some really amazing pieces of Mayan culture and history!...
This site is not as grand as Caracol or Xunatunich, but it's a wonderful find. If you enjoy detail and the history of this area, go see these ruins. They're currently closed through 9/1, due to Earl, but go see them after they reopen. Easy trails, lots of broken pottery and things to see.
This was a fascinating archeological site that is still being explored. The manager on site was very knowledgeable and provided great insight. Be prepared with water, long pants/sleeves and lots of bug spray.
This place is way off the beaten path. We took our golf cart out to it and it is off of a pot hole pitted rock road that is bone jarring for 10km. Then you have to walk 1-2 km on a partially rotten wooden dock in the heat and mangroves to get to the site. The mosquitoes are horrendous....
Own or manage this property? Claim your listing for free to respond to reviews, update your profile and much more.


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Eastern tent caterpillars are among the first insects to appear in the spring. This year's unseasonable warmth could result in abnormally early activity.
The seven session program begins March 2.
The Master Cattleman program includes 10 comprehensive sessions about all aspects of beef production.
UK personnel are helping farmers learn more about novel endophyte tall fescue varieties.
Conference combines exptertise from Kentucky and Tennessee.
The deadline to submit nominations is March 15.
University of Chicago Professor Mark Courtney will discuss the research he's conducted on foster youth during the past 20 years.
The tri-state workshop returns to Kentucky March 25.
The Duvall Leader in Residence program brings to UK leaders who are known for their ethical style of decision making and for their focus on youth leadership development.
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Thank you, thank you, thank you to Wal-Mart, all our dedicated volunteers and all the generous donors who helped create another successful Stuff the Bus school-supply drive July 20 and 21.
On behalf of the United Way of Perry County, I would like to extend a heartfelt thank you to the residents of our community who helped support our sixth annual "stuff the bus" school-supply drive for students in need.
By ERIC HARRIS
Film Review
By KATIE CHINN
Guest Columnist
As Tell City prepares itself for another week of Schweizer Fest, the list of activities and events to attend and participate in can be quite overwhelming. We are lucky to live in a community that honors its heritage yearly, and by doing so, offers us so many ways to celebrate throughout the week. An event that has quickly grown to be one of the largest of the Schweizer Fest sporting events is the road run.
By LARRY DeBOER
Purdue University
July is state budget closeout month in Indiana and the Indiana Budget Agency gave us the news. The state has a lot of money in the bank.
By VINCE LUECKE
I saw a friend of mine in a new vehicle last week, a sport-utility vehicle made by a luxury car brand that lists for more than $50,000. That's a lot of money for a set of wheels.
Personally, I prefer a used car. My old Buick isn't much to look at and garners a new nick or scrape every few months, but still gets me from point to point on time.
A few words about gay marriage made by Chick-fil-A President Dan Cathy have certainly led to the spilling of ink in recent days. That didn't surprise us. Neither did reactions that included Wednesday's support of a Chick-fil-A event sponsored by Mick Huckabee or Friday's "kiss-in" planned by those who disagree with Cathy's comments.
Regular customers of the restaurant chain probably hope things get back to normal soon. Good luck.
By ERIC HARRIS
Film Reviewer
On Friday, July 13, in Roanoke, Va., President Obama took a shot at all of the thousands of America's successful entrepreneurs. He said, "if you've been successful, you didn't get there on your own." He went on; "if you've got a business - you didn't build that. Somebody else made that happen."
Copyright © 2017
The Perry County News is your source for local news, sports, events, and information in Perry County, Indiana, and the surrounding area.


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White Lotus with a Golden Mane, 9-10 yr. specimen seed grown rockii tree peony
Notable characteristics: Single blossoms resemble that of 'Snow Lotus' tree peony. This unique, seed grown tree peony flower exhibits an unusual characteristic in its numerous golden central stamens. Vigorous grower and prolific bloomer. Mid-season bloomer.
Hybridizer: Open-pollinated seedling grown by Cricket Hill Garden.
Growth habit and size at maturity (10 years old): Spreading, grows to 4' tall and 5' wide.
Flower form and size: Single, 8-10".
Flower fragrance: Spicy-sweet.
Bloom time: Mid-season Chinese rockii tree peony, blooms in our USDA zone 6a garden in the third week of May.
Zone hardiness: Proven is USDA zones 4-9. P. rockii cultivars are particularly drought resistant once established.
Plant size: With foliage this plant currently measures 3.5' tall and 3.5' wide. It has multiple thick woody stems with numerous side branches. This plant exhibits a wide, spreading habit.
When we ship: Order now for FALL 2016 shipping. We will dig this plant and pack the roots with moist coconut fiber for shipping. Our success rate for shipping older plants is excellent. Over the years, some of our older tree peony specimens have been sent across the country via UPS with great results, so if you live far from our nursery, do not let this deter you from acquiring some of our older plants.
If you are within driving distance, this plant will be field dug in fall with the root ball protected and wrapped. Please call or email to discuss your interests and needs.