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Albums Reviewed By Alex Bieler and Ben Speggen
New albums by The xx, Grizzly Bear, Menomena, and Dave Matthews Band
by Erie Reader Author September 19, 2012 at 12:00 PM
While saying that an album doesn't "have much there" normally doesn't bode well for a new release, the xx would likely take it as a compliment. The band keeps the same minimalist formula that was used on their self-titled debut, but this time around, they strip everything down even further. Producer Jamie Smith, better known as Jamie xx, employs silence to great effect on "Coexist," causing every stab of slightly reverberated guitar and the breathy vocals of Romy Madley Croft and Oliver Sim to reach out even farther. The effects are hypnotizing as the gorgeous simplicity draws you in from the opening seconds of album opener "Angels." There's an honesty behind the music, as the band lays their thoughts bare while you listen in. The xx didn't go out of their way to reach new boundaries, but they did show that sometimes less is more. - Alex Bieler 4.5/5
Musically, it appears that someone has been poking at Grizzly Bear. After the success of the 2009's "Veckatimest," the Brooklyn-based indie band returns on a louder note on the new "Shields." While showing off more of a growl than a full-fledged roar, Grizzly Bear eschews the more airy sound of "Two Weeks" for a larger guitar sound. Album opener "Sleeping Ute" and the excellent "Yet Again" bring a multi-guitar attack and more prominent drums to the forefront with the usual choirboy-sweet vocal harmonies, with the latter song even descending into a heavy dose of distortion at the end. While not all the songs lean toward the heavier side, there is a grittiness that Grizzly Bear doesn't normally exude, which works better than expected. Even with the small dose of thrash, the normal lovely nuances shine through throughout "Shields," providing a nice follow-up to "Veckatimest." - Alex Bieler 4.5/5
With the loss of Brent Knopf from Portland indie group Menomena, it's appropriate that the band's newest album, "Moms," focuses on the remaining member's various relationships. Now down to a twosome, Justin Harris and Danny Seim take aim at the different influences others have had on them. Harris and Seim each take a number of stabs at both writing and singing on the album, but just like previous efforts, Menomena's members have an uncanny chemistry despite their differences. The songs have a feeling of having been cut up from a standard whole and pieced back together, giving each tune a unique and fresh feel. The duo swaps instruments in and out, switching from squealing guitars and crashing cymbals to prominent saxophone and piercing piano in short sequence. "Moms" may not be a perfect family photo, but the duo's reunion works out just fine. - Alex Bieler 4/5
Away from the World
After the unexpected death of saxophonist LeRoi Moore four years ago, DMB released "Big Whiskey and the GrooGrux King," an album that featured Moore's last recordings, and enlisted saxophonist Jeff Coffin to round out the album and the band. After chart success and an extensive tour, many thought the band might eschew studio time. Instead, they reunited with producer Steve Lillywhite, who last worked with the band before 2001's "Everyday." "Away" is reminiscent of the band's past, both recent and distant – "Belly Belly Nice" (the album's worst-titled song but a funk-fueled sexy good time) plays like a cousin to "Shake Me Like a Monkey" and "Mercy" (the album's lead single) unfolds like a politically-conscious nephew of "Crash Into Me." As Matthews ages and weathers the world, his topic matter matures, but there's still an element of dancing-in-the-mud fun here that should keep all the barefoot firedancers happy. - Ben Speggen 3.5/5
2019 Mid-Year Album Watch
by Aaron Mook7/3/2019, 10:45 AM
The top 10 so far, overlooked gems, and ones to look forward to
Bill Callahan // Shepherd in a Sheepskin Vest
by Nick Warren6/19/2019, 10:00 AM
Baroness // Gold & Grey
by Nick Warren6/19/2019, 9:45 AM
Silversun Pickups // Widow's Weeds
by Aaron Mook6/19/2019, 9:30 AM
Miley Cyrus // She is Coming EP
Sacred Paws // Run Around the Sun
by Nick Warren6/5/2019, 11:00 AM


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Q: Return all links to photos in a flickr set I want to use all the photos in a Flickr set and in order to do so (and not infringe upon copyright etc) have to link back to the owner.  I can't seems to find anything in the Flickr API to return the html code for each individual photo.
At present I'm faced with copying and pasting all the html code from the "share" button.  Not a pleasant prospect.
Any help appreciated

A: I'm assuming you just want a link back to the images or photosets?
See here: http://www.flickr.com/services/api/misc.urls.html
There are examples for linking to images directly, individual photos, photosets, etc.

redpajama_set_name: RedPajamaStackExchange


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Pakistan Security Brief
Drone strikes kill senior al Qaeda leader, seven other militants in Khyber, North Waziristan; TTP spokesman, five other commanders, pledge allegiance to IS; Afghan officials claim IS presence in Afghanistan; Senior Indian, Pakistani commanders speak via hotline as ceasefire violations continue; Pakistani officials request UN intervention; JuD protests Indian firing; Pakistani airstrikes kill 21 militants in Khyber, North Waziristan; Afghan forces arrest two Haqqani- and Pakistani Taliban-affiliated militants; Sindh Rangers foil major jailbreak attempt in Karachi; Militants attack FC medical team in Balochistan; IED kills three anti-Taliban militiamen in Sipah, and Swat; Three militants killed in Bahawalpur shootout,; Gunmen kill army officer in Hyderabad; TTP Jamaatul Ahrar criticizes Nobel Peace Prize winner Malala Yousafzai; MQM leaders face extortion threats from TTP; German aid worker captured in Pakistan freed in Afghanistan; PPP chairperson faces threats to life; PAT chief to continue protests in other parts of the country; Seven people die in stampede in Multan; Pakistan to receive $1.1 billion in December from IMF; Pakistan seeks to share intelligence with Iran; Kerry-Lugar aid to Pakistan unlikely to be renewed.
On October 11, two separate drone strikes killed eight militants in Khyber and North Waziristan Agencies. In the first attack, drones targeted a compound in Chancharano Kandaw area in the Tirah Valley of Khyber Agency, killing four militants and injuring two others. One of the dead militants was identified as Sheikh Imran Ali Siddiqi alias Haji Shaikh Waliullah, a senior member of the newly formed al Qaeda in the Indian Subcontinent (AQIS). AQIS spokesperson Usama Mahmood confirmed Waliullah's death. In the second attack, U.S. drones killed four suspected militants and injured one in the Maraga area of Shawal sub-district in North Waziristan. Taliban commander identified as Muhammad Mustafa, belonging to the Hafiz Gul Bahadur group, was among those killed. Foreign militants were also reportedly among the dead.[1]
Islamic State in South Asia
In a video message released on October 13, official spokesman of the Tehrik-e-Taliban Pakistan (TTP) Shahidullah Shahid and five other top TTP commanders pledged allegiance to Islamic State (IS) and its leader Abu Bakar al Baghdadi. The other five area commanders include TTP Orakzai Emir Saeed Khan, TTP Khyber Emir Gul Zaman, TTP Kurram Emir Daulat Khan, TTP Peshawar District Emir Mufti Hassan and TTP Hangu Emir Khalid Mansour. Shahid clarified that the statement was made on behalf of himself and the five commanders and that it was not representative of the TTP as a whole or its leader Mullah Fazlullah. He also claimed that the statement was his fourth pledge of allegiance to IS to date.[2]
According to a Wall Street Journal Report on October 13, Afghan security officials claim that that Islamic State (IS) is making attempts to extend its influence or presence in Afghanistan, pointing toward reports of IS leaflets being circulated in local languages near Kabul. The U.S. Ambassador to Afghanistan, James Cunningham, denies any reports or evidence of IS presence.[3]
Indo-Pakistan Relations
According to a senior Pakistani military official, the Directors General of Military Operations (DGMOs) of the Pakistani and Indian armies spoke on October 14 via hotline. The Pakistan army's DGMO reportedly conveyed Pakistani concerns over consistent, unprovoked firing on the civilian population living along the Line of Control (LoC) and the working boundary by Indian forces. After a brief pause in cross-border firing on October 10, Indian and Pakistani forces reportedly resumed firing on October 11. According to Pakistan Army officials, one civilian was injured by Indian fire in Poonch sector near Rawalkot. Gunfire was also reported in Charwa sector near Sialkot later that evening. Indian army officials accused Pakistani border guards of targeting ten Indian border posts in Poonch sector. Indian forces allegedly continued heavily shelling Pakistani villages along the Sialkot border on October 12. Fresh firing and mortar shelling was reported near Kailer sector in Bagh on the LoC on October 13 and in Charwa sector near Sialkot on October 14.[4]
According to a Dawn report on October 12, Advisor to the Prime Minister on National Security and Foreign Affairs Sartaj Aziz wrote a letter to UN Secretary General Ban Ki-moon requesting UN intervention in defusing border tensions as well as resolving the Kashmir issue. On October 13, the Pakistani government also conveyed its concerns over ceasefire violations across the LoC to a visiting two-member U.S Congressional delegation comprising of Senators Tim Kaine and Angus King. Indian officials criticized these efforts as attempts by the Pakistani government to "internationalize" the Kashmir issue.[5]
On October 11, Jamaat-ud-Dawa (JuD) activists in Bannu, Khyber Pakhtunkhwa protested against firing by Indian forces and the killing of innocent civilians along the LoC and the working boundary.[6]
On October 12, Pakistani military airstrikes killed 21 militants in North Waziristan and Khyber Agency. Targeted airstrikes on militant hideouts in Anzarak area of Datta Khel sub-district in North Waziristan reportedly killed 11 suspected militants. Separately, airstrikes by the Pakistani Air Force killed 10 militants and injured several in the Rajgal, Wacho Wanom Fatih Sar and Duwa Khuly areas of the Tirah Valley in Khyber Agency.[7]
According to the Afghan Ministry of Interior, police forces arrested two militants associated with Pakistan Taliban and the Haqqani Network in northern Kunduz province on October 11. The police recovered suicide jackets from the militants.[8]
On October 13, the Sindh Rangers foiled a major jailbreak attempt by discovering an underground tunnel being dug from inside a house in Ghousia colony to the barracks in Karachi's Central Jail. The Rangers arrested three terrorists from the house who had completed about 45 meters of the 55 meter- long tunnel. Five more accomplices were also arrested. The police also discovered weapons and mining equipment from the house. October 14, Sindh Minister for Prisons Manzoor Wasan said that officials also feared a possible attack on the Hyderabad jail. [9]
On October 11, unidentified militants attacked a medical team of the Frontier Corps (FC) in the Mand area of Turbat, Balochistan. One militant was killed in the encounter.[10]
On October 11, unknown gunmen shot and killed Qadir Raisani, District President of Muttahida Mahaz Balochistan in Quetta.[11]
On October 11, a roadside improvised explosive device (IED) killed two members of the local anti-Taliban militia in the Sipah area on the boundary between Kohat district and Orakzai Agency.[12]
On October 11, unidentified gunmen shot dead a member of an anti-Taliban militia in the Mangwal Tan area of Charbagh sub-district in Swat district. In a resulting search operation on October 12, security forces killed three militants.[13]
On October 11, police raided hideouts of a militant group known as the Zareen group in the Kamar Dhand area of Kohat, Khyber Pakhtunkhwa, injuring one policeman in the resulting clashes. The police also destroyed five suspected militant hideouts in the raid.[14]
On October 11, police forces reportedly killed three militants in a shootout in Uch Sharif city in Punjab's Bahawalpur district.[15]
On October 14, unknown assailants on a motorbike shot and killed a second-lieutenant of the Pakistan Army and injured two of his brothers outside their house in Journalist Colony, Hyderabad.[16]
In messages posted on Twitter on October 10, spokesman for the Tehrik-e-Taliban Pakistan (TTP) Jamaatul Ahrar, Ehsanullah Ehsan, chief of Jamaatul Ahrar's Ihya-e-Khilafat media division Saleh Qassam, and media member Ibrahim Khorasani jointly criticized the awarding of the Nobel Peace Prize to Malala Yousafzai, calling her an "agent of kuffar (disbelievers)." Ehsan further threatened that the group would continue to target people who portrayed "anti-Islamic positions." The Shuhada Foundation of Pakistan also disapproved of the award, calling Malala the "enemy of Islam."[17]
On October 13, former deputy convener of the Muttahida Qaumi Movement (MQM), Dr. Farooq Sattar, declared that 11 of the MQM's leaders were facing extortion threats from the TTP. The members have been asked to pay Rupees 1.5 million ($15,000) or suffer the pain of them and their families being assassinated.[18]
On October 10, German officials declared that a German aid worker who had been kidnapped in Multan, Pakistan in 2012 by Islamist militants has been freed in Afghanistan.[19]
According to a Dawn report on October 14, chairperson of the Pakistan Peoples Party (PPP) Bilawal Bhutto Zardari faces threats to his life from the militant group Jundullah. As a result, the Sindh government has asked law enforcement agencies "to ensure extreme vigilance" and take "special measures" to prevent any attacks.[20]
On October 12, Pakistan Awami Tehreek (PAT) chief Tahirul Qadri said that he would continue his protests in other parts of the country after exiting Islamabad and that the first rally would be held in Faisalabad. He termed the Islamabad sit-in as a "strong foundation" but said that his party did not believe in protesting in one place alone.[21]
On October 10, at least seven people died in a stampede after a rally held by Pakistani Tehreek-e-Insaf (PTI) chief Imran Khan at a stadium in Multan, Punjab. 40 people were also reportedly injured. Prime Minister Sharif expressed sorrow for the loss of lives at the rally.[22]
On October 10, women staged a protest in the Haleemzai sub-division of Mohmand Agency complaining of unwarranted raids of their houses and alleged illegal detention of male family members by paramilitary forces. The women also demanded immediate releases of detained relatives.[23]
According to an Express Tribune report on October 13, Pakistan is scheduled to secure two loan tranches from the International Monetary Fund (IMF) amounting to a total of $1.1 billion in December, 2014 as a part of the $6.7 billion IMF bailout program. The two loan tranches include the fourth and fifth reviews of Pakistan's economic performance under the bailout program.[24]
In a briefing on October 10, Foreign Office spokesperson Tasneem Aslam said that it was in the interest of both Iran and Pakistan to share intelligence in order to combat terrorism in areas along the border and reduce mistrust between the two countries. Reacting to the recent terrorist attacks in Iran, Aslam denied the presence of safe havens inside Pakistan for terrorists operating across the border.[25]
According to an Express Tribune report on October 11, Prime Minister Sharif called for a "strong relationship with Afghanistan" in a telephonic conversation with Afghan President Ashraf Ghani on the occasion of Eid. The two premiers have also agreed to "counter common threats, work for regional cooperation and boost bilateral relations."[26]
U.S.-Pakistan Relations
According to an Express Tribune report on October 14, the U.S. Congress is unlikely to extend the $7.5 billion civilian assistance package to Pakistan under the Kerry-Lugar Act of 2009 which is scheduled to expire in September 2015. According to analysts, the aid package is expiring at a time when the U.S. is outsourcing its role in the region to other countries and refocusing toward the Middle East.[27]
On October 12, a tribal jirga organized by the Mehsud Welfare Association in Hayatabad, Peshawar demanded early rehabilitation of all internally displaced persons (IDPs) to their native areas as well as compensation for their losses.[28]
[1]"Two US drone strikes in Fata kill senior al Qaeda figure among eight," Express Tribune, October 11, 2014. Available at http://tribune.com.pk/story/773951/drone-strike-in-khyber-agency-kills-senior-al-qaeda-figure-among-4/
"Second drone attack in 24 hours kills four in NWA," Dawn, October 11, 2014. Available at http://www.dawn.com/news/1137296/us-drone-strike-kills-four-suspected-militants-on-pak-afghan-border
[2]"TTP Spokesman Shahidullah, Five Officials Allegedly Pledge to IS," SITE, October 13, 2014. Available at http://ent.siteintelgroup.com/Multimedia/ttp-spokesman-shahidullah-five-officials-allegedly-pledge-to-is.html
[3]"Afghans Sound Alarm Over Islamic State Recruitment," WSJ, October 13, 2014. Available at http://online.wsj.com/articles/afghans-sound-alarm-over-islamic-state-recruitment-1413218858
[4] Pakistan, India military talk on hotline amid Kashmir tensions," AFP, October 14, 2014. Available at https://sg.news.yahoo.com/pakistan-india-military-talk-hotline-amid-kashmir-tensions-000648867.html
"Exchange of gunfire resumes across Pakistan-India border," Dawn, October 11, 2014. Available at http://www.dawn.com/news/1137318/exchange-of-gunfire-resumes-across-kashmir-border
"India violates ceasefire at LoC," Express Tribune, October 13, 2014. Available at http://tribune.com.pk/story/774653/india-violates-ceasefire-at-loc/
"India's unprovoked firing resumes on Sialkot working boundary," The News, October 14, 2014. Available at http://www.thenews.com.pk/article-162513-India-resumes-unprovoked-firing-on-Sialkot-working-boundary-
[5] "Pakistan writes letter to UNSG over LOC violations," Dawn, October 12, 2014. Available at http://www.dawn.com/news/1137495/pakistan-writes-letter-to-unsg-over-loc-violations-by-india
"Pakistan conveys concerns over border skirmishes to US delegation," Dawn, October 13, 2014. Available at http://www.dawn.com/news/1137706/pakistan-conveys-concerns-over-border-skirmishes-to-us-delegation
"UN's snub to Pakistan a great diplomatic triumph for Modi govt: BJP," Indian Express, October 14, 2014. Available at http://indianexpress.com/article/india/india-others/uns-snub-to-pakistan-a-great-diplomatic-triumph-for-modi-govt-bjp/
[6]"JuD protests Indian aggression," The News, October 12, 2014. Available at http://www.thenews.com.pk/Todays-News-2-277859-JuD-protests-Indian-aggression
[7]"21 militants killed in NWA, Khyber air strikes," The News, October 13, 2014. Available at http://www.thenews.com.pk/Todays-News-13-33436-21-militants-killed-in-NWA,-Khyber-air-strikes
[8]"2 alleged Pakistani terrorists arrested in Kunduz," October 11, 2014. Available at http://www.pajhwok.com/en/2014/10/11/2-alleged-pakistani-terrorists-arrested-kunduz
[9]"Tunnel to free terrorists from Karachi jail unearthed," The News, October 14, 2014. Available at http://www.thenews.com.pk/Todays-News-13-33447-Tunnel-to-free-terrorists-from-Karachi-jail-unearthed
"Fear of attack on Hyderabad jail: Wasan," Geo News, October 14, 2014. Available at http://www.geo.tv/article-162492-Fear-of-attack-on-Hyderabad-Jail-Wasan-
[10]"FC retaliate after militant attack on medical team, kill one in Turbat," October 12, 2014. Available at http://www.dawn.com/news/1137320/fc-retaliate-after-militant-attack-on-medical-team-kill-one-in-turbat
[12]"2 Lashkar members killed in Swat, Kohat," The News, October 12, 2014. Available at http://www.thenews.com.pk/Todays-News-7-277832-2-lashkar-members-killed-in-Swat,-Kohat
"Lashkar man killed in IED blast," The News, October 12, 2014. Available at http://www.thenews.com.pk/Todays-News-2-277856-Lashkar-man-killed-in-IED-blast
[13]"Peace body member killed in Swat," The News, October 12, 2014. Available at http://www.thenews.com.pk/Todays-News-13-33430-Peace-body-member-killed-in-Swat
"Three militants killed in clashes with security forces in Swat," Frontier Post, October 13, 2014. Available at http://www.thefrontierpost.com/three-militants-killed-in-clashes-with-security-forces-in-swat/
[14]"Cop injured in clash with militants," The News, October 12, 2014. Available at http://www.thenews.com.pk/Todays-News-2-277865-Cop-injured-in-clash-with-militants
[15]"Punjab: Three 'terrorists' killed in Uch Sharif shootout," The News, October 11, 2014. Available at http://www.thenews.com.pk/article-162221-Punjab:-Three-terrorists-killed-in-Uch-Sharif-shootout--
[16]"Junior army officer gunned down in Hyderabad," Dawn, October 14, 2014. Available at http://www.dawn.com/news/1137926/junior-army-officer-gunned-down-in-hyderabad
[17]"Taliban, Shuhada Foundation assail Nobel Peace Prize for Malala," The News, October 12, 2014. Available at http://www.thenews.com.pk/Todays-News-2-277842-Taliban,-Shuhada-Foundation-assail-Nobel-Peace-Prize-for-Malala
[18]"TTP demands extortion money of MQM," Frontier Post, October 14, 2014. Available at http://www.thefrontierpost.com/ttp-demands-extortion-money-of-mqm/
[19]"German Hostage Freed in Afghanistan," WSJ, October 10, 2014. Available at http://online.wsj.com/articles/german-hostage-freed-in-afghanistan-1412958460
[20]"Bilawal facing threats to life from Jundallah: Sindh government," Dawn, October 14, 2014. Available at http://www.dawn.com/news/1137910/bilawal-facing-threats-to-life-from-jundallah-sindh-government
[21]"Exit Islamabad: Qadri hints at taking 'Inqilab' across Pakistan," Dawn, October 12, 2014. Available at http://www.dawn.com/news/1137497/exit-islamabad-qadri-hints-at-taking-inqilab-across-pakistan
[22]"At least seven die in stampede at Pakistan rally," BBC, October 10, 2014. Available at http://www.bbc.com/news/world-asia-29572979
[23]"Mohmand women protest raids on their houses," Dawn, October 11, 2014. Avaialble at http://www.dawn.com/news/1137286/mohmand-women-protest-raids-on-their-houses
[24]"Bailout programme: Two combined IMF loan tranches likely in December," Express Tribune, October 13, 2014. Available at http://tribune.com.pk/story/774469/bailout-programme-two-combined-imf-loan-tranches-likely-in-december/
[25]"Intelligence sharing sought with Iran," Dawn, October 11, 2014. Available at http://www.dawn.com/news/1137203/intelligence-sharing-sought-with-iran
[26]"On the road to cordial Pak-Afghan relations," Express Tribune, October 11, 2014. Available at http://tribune.com.pk/story/773518/on-the-road-to-cordial-pak-afghan-relations-2/
[27]"Kerry-Lugar Act: US unlikely to extend civilian aid package," Express Tribune, October 14, 2014. Available at http://tribune.com.pk/story/775049/kerry-lugar-act-us-unlikely-to-extend-civilian-aid-package/
[28]"Mahsud Jirga seeks immediate return of Fata IDPs," The News, October 13, 2014. Available at http://www.thenews.com.pk/Todays-News-2-278068-Mahsud-Jirga-seeks-immediate-return-of-Fata-IDPs
In The Brief
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Probability-based localization scoring of fragment mass-spectrum phosphorylation site identifications has become common practice to confirm search engine modification assignments, and indicate the degree of certainty with which they are defined. Localization of modifications other than phosphorylation is also required but is less commonly supported by current tools. These other modifications, such as hydroxylation, may have broad aminoacid specificity, and can be misassigned when the correct specificity is not considered in an MS database search. In addition, localization software is often specific to a particular MS/MS search engine, and cannot be used to localize modifications identified by multiple search engines. ModLS, a new tool within our freely-available Central Proteomics Facilities Pipeline (CPFP), applies a localization scoring method to arbitrary post-translational modifications (PTMs). As well as localising PTMs based on amino-acid specificities are included in the initial search, ModLS can automatically consider additional specificities from UniMod. This can help avoid 'correct modification, incorrect amino-acid' errors which can occur when data is searched using only a subset of PTM specificities. Localization scoring can be performed on the results from any search engine incorporated within the pipeline, or where the output of individual search engines is combined to give increased coverage. We demonstrate the performance of ModLS using a publicly available phosphorylated peptide dataset, showing that it outperforms the recently characterized Mascot Delta Score approach for CID and MSA data, and is comparable for HCD data. In addition, we show the utility of automatic specificity expansion using hydroxylated and methylated peptide data. ModLS is a user-friendly localization tool for arbitrary modifications. Its inclusion within CPFP allows PTM localization to be performed quickly and easily on large or small result sets, from multiple search engines. Specificity expansion, introduced in ModLS, allows misassignments of modifications due to incomplete consideration of specificities to be identified and Minimized. © 2012 Trudgian DC, et al.
CpG islands (CGIs) are associated with most mammalian gene promoters. A subset of CGIs act as polycomb response elements (PREs) and are recognized by the polycomb silencing systems to regulate expression of genes involved in early development. How CGIs function mechanistically as nucleation sites for polycomb repressive complexes remains unknown. Here we discover that KDM2B (FBXL10) specifically recognizes non-methylated DNA in CGIs and recruits the polycomb repressive complex 1 (PRC1). This contributes to histone H2A lysine 119 ubiquitylation (H2AK119ub1) and gene repression. Unexpectedly, we also find that CGIs are occupied by low levels of PRC1 throughout the genome, suggesting that the KDM2B-PRC1 complex may sample CGI-associated genes for susceptibility to polycomb-mediated silencing. These observations demonstrate an unexpected and direct link between recognition of CGIs by KDM2B and targeting of the polycomb repressive system. This provides the basis for a new model describing the functionality of CGIs as mammalian PREs.DOI:http://dx.doi.org/10.7554/eLife.00205.001.
The finding that oxygenase-catalyzed protein hydroxylation regulates animal transcription raises questions as to whether the translation machinery and prokaryotic proteins are analogously modified. Escherichia coli ycfD is a growth-regulating 2-oxoglutarate oxygenase catalyzing arginyl hydroxylation of the ribosomal protein Rpl16. Human ycfD homologs, Myc-induced nuclear antigen (MINA53) and NO66, are also linked to growth and catalyze histidyl hydroxylation of Rpl27a and Rpl8, respectively. This work reveals new therapeutic possibilities via oxygenase inhibition and by targeting modified over unmodified ribosomes.
Background: Synthetic probes that mimic natural substrates can enable the detection of enzymatic activities in a cellular environment. One area where such activity-based probes have been applied is the ubiquitin-proteasome pathway, which is emerging as an important therapeutic target. A family of reagents has been developed that specifically label deubiquitylating enzymes (DUBs) and facilitate characterization of their inhibitors. Scope of review: Here we focus on the application of probes for intracellular DUBs, a group of specific proteases involved in the ubiquitin proteasome system. In particular, the functional characterization of the active subunits of this family of proteases that specifically recognize ubiquitin and ubiquitin-like proteins will be discussed. In addition we present the potential and design of activity-based probes targeting kinases and phosphatases to study phosphorylation. Major conclusions: Synthetic molecular probes have increased our understanding of the functional role of DUBs in living cells. In addition to the detection of enzymatic activities of known members, activity-based probes have contributed to a number of functional assignments of previously uncharacterized enzymes. This method enables cellular validation of the specificity of small molecule DUB inhibitors. General significance: Molecular probes combined with mass spectrometry-based proteomics and cellular assays represent a powerful approach for discovery and functional validation, a concept that can be expanded to other enzyme classes. This addresses a need for more informative cell-based assays that are required to accelerate the drug development process. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics. © 2012 Elsevier B.V.
We examined the mechanism regulating the cellular levels of PNKP, the major kinase/phosphatase involved in the repair of oxidative DNA damage, and find that it is controlled by ATM phosphorylation and ubiquitylation-dependent proteasomal degradation. We discovered that ATM-dependent phosphorylation of PNKP at serines 114 and 126 in response to oxidative DNA damage inhibits ubiquitylation-dependent proteasomal degradation of PNKP, and consequently increases PNKP stability that is required for DNA repair. We have also purified a novel Cul4A-DDB1 ubiquitin ligase complex responsible for PNKP ubiquitylation and identify serine-threonine kinase receptor associated protein (STRAP) as the adaptor protein that provides specificity of the complex to PNKP. Strap(-/-) mouse embryonic fibroblasts subsequently contain elevated cellular levels of PNKP, and show elevated resistance to oxidative DNA damage. These data demonstrate an important role for ATM and the Cul4A-DDB1-STRAP ubiquitin ligase in the regulation of the cellular levels of PNKP, and consequently in the repair of oxidative DNA damage.
Mutation of the tumor suppressor p53 plays a major role in human carcinogenesis. Here we describe gene-targeted porcine mesenchymal stem cells (MSCs) and live pigs carrying a latent TP53(R167H) mutant allele, orthologous to oncogenic human mutant TP53(R175H) and mouse Trp53(R172H), that can be activated by Cre recombination. MSCs carrying the latent TP53(R167H) mutant allele were analyzed in vitro. Homozygous cells were p53 deficient, and on continued culture exhibited more rapid proliferation, anchorage independent growth, and resistance to the apoptosis-inducing chemotherapeutic drug doxorubicin, all characteristic of cellular transformation. Cre mediated recombination activated the latent TP53(R167H) allele as predicted, and in homozygous cells expressed mutant p53-R167H protein at a level ten-fold greater than wild-type MSCs, consistent with the elevated levels found in human cancer cells. Gene targeted MSCs were used for nuclear transfer and fifteen viable piglets were produced carrying the latent TP53(R167H) mutant allele in heterozygous form. These animals will allow study of p53 deficiency and expression of mutant p53-R167H to model human germline, or spontaneous somatic p53 mutation. This work represents the first inactivation and mutation of the gatekeeper tumor suppressor gene TP53 in a non-rodent mammal.
Bortezomib therapy has proven successful for the treatment of relapsed/refractory, relapsed, and newly diagnosed multiple myeloma (MM); however, dose-limiting toxicities and the development of resistance limit its long-term utility. Here, we show that P5091 is an inhibitor of deubiquitylating enzyme USP7, which induces apoptosis in MM cells resistant to conventional and bortezomib therapies. Biochemical and genetic studies show that blockade of HDM2 and p21 abrogates P5091-induced cytotoxicity. In animal tumor model studies, P5091 is well tolerated, inhibits tumor growth, and prolongs survival. Combining P5091 with lenalidomide, HDAC inhibitor SAHA, or dexamethasone triggers synergistic anti-MM activity. Our preclinical study therefore supports clinical evaluation of USP7 inhibitor, alone or in combination, as a potential MM therapy.
INTRODUCTION: In pre-eclampsia, the consequences of poor placentation lead to the second stage of pre-eclampsia, which involves activation of a maternal systemic inflammatory response (MSIR). Endothelial and other inflammatory cellular dysfunction cause the diverse features which characterise the disorder. We have previously shown that syncytiotrophoblast microvesicles (STBM) are pro-inflammatory and circulate in increased amounts in pre-eclamptic women. We hypothesise that multiple placental "danger signals" are carried by STBM into the maternal circulation in increased amounts in PE with pro-inflammatory, anti-angiogenic and pro-coagulant activity, implicating STBM in the pathophysiology of PE. OBJECTIVES: To characterise the proteins carried by STBM from normal and PE placentas. For the first time multi-dimensional protein identification technology (MudPIT) was used to derive the proteome profiles of normal and PE placenta STBM. METHODS: STBM were prepared from placentas (normal term: n=9 and PE: n=5) by dual lobe perfusion, isolated by ultracentrifugation and stored at -80°C. Normal and PE derived placenta STBM pools were then subjected to MudPIT analysis. RESULTS: 538 proteins unique to PE STBM, 604 proteins unique to normal STBM and 1421 proteins common to both preparations were found. Preliminary analysis indicates the presence of alarmins (HSP70, and galectin 3), exosomal proteins (CD63,CD9,CD81), immunoregulatory molecules (CD26,CD200,CD47,Galectin 1), complement and complement regulatory molecules (C1q,C3,CD55,CD59 and vitronectin), amino acid transporters (CD98) and anti-angiogenic molecules (endoglin). Our analysis also reveals that proteins known to be elevated in blood before, or at, the time of pre-eclampsia are elevated or unique in STBM from PE placentas, including Fetuin A, Inter-alpha (globulin) inhibitor H4, Serum amyloid P component, Apolipoprotein H (or B2GP1) and Apolipoprotein AII. Thus, as predicted, a large number of circulating molecules are associated with STBM. The inter-relationships between proteins that are unique to either PE or normal pregnancy and the processes in which they are involved are being determined by Ingenuity Pathways Analysis software. In terms of biofunctions, preliminary analysis shows that proteins unique to PE STBM have a highly significant association (p<10(-11)) with 6 disease pathways including inflammatory, immunological, cardiovascular and reproductive system diseases and organ injury, whereas for proteins unique to normal STBM only protein synthesis was significant at the same level. CONCLUSION: STBM contain a heterogeneous population of vesicles that convey a large repertoire of placental proteins into the maternal circulation. The profound differences between PE and normal STBM indicate their pro-inflammatory potential.
BACKGROUND: Malaria cases attributed to Plasmodium falciparum account for approximately 600,000 deaths yearly, mainly in African children. The gold standard method to diagnose malaria requires the visualization of the parasite in blood. The role of non-invasive diagnostic methods to diagnose malaria remains unclear. METHODS: A protocol was optimized to deplete highly abundant proteins from saliva to improve the dynamic range of the proteins identified and assess their suitability as candidate biomarkers of malaria infection. A starch-based amylase depletion strategy was used in combination with four different lectins to deplete glycoproteins (Concanavalin A and Aleuria aurantia for N-linked glycoproteins; jacalin and peanut agglutinin for O-linked glycoproteins). A proteomic analysis of depleted saliva samples was performed in 17 children with fever and a positive-malaria slide and compared with that of 17 malaria-negative children with fever. RESULTS: The proteomic signature of malaria-positive patients revealed a strong up-regulation of erythrocyte-derived and inflammatory proteins. Three P. falciparum proteins, PFL0480w, PF08_0054 and PFI0875w, were identified in malaria patients and not in controls. Aleuria aurantia and jacalin showed the best results for parasite protein identification. CONCLUSIONS: This study shows that saliva is a suitable clinical specimen for biomarker discovery. Parasite proteins and several potential biomarkers were identified in patients with malaria but not in patients with other causes of fever. The diagnostic performance of these markers should be addressed prospectively.
BACKGROUND: Synthetic probes that mimic natural substrates can enable the detection of enzymatic activities in a cellular environment. One area where such activity-based probes have been applied is the ubiquitin-proteasome pathway, which is emerging as an important therapeutic target. A family of reagents has been developed that specifically label deubiquitylating enzymes (DUBs) and facilitate characterization of their inhibitors. SCOPE OF REVIEW: Here we focus on the application of probes for intracellular DUBs, a group of specific proteases involved in the ubiquitin proteasome system. In particular, the functional characterization of the active subunits of this family of proteases that specifically recognize ubiquitin and ubiquitin-like proteins will be discussed. In addition we present the potential and design of activity-based probes targeting kinases and phosphatases to study phosphorylation. MAJOR CONCLUSIONS: Synthetic molecular probes have increased our understanding of the functional role of DUBs in living cells. In addition to the detection of enzymatic activities of known members, activity-based probes have contributed to a number of functional assignments of previously uncharacterized enzymes. This method enables cellular validation of the specificity of small molecule DUB inhibitors. GENERAL SIGNIFICANCE: Molecular probes combined with mass spectrometry-based proteomics and cellular assays represent a powerful approach for discovery and functional validation, a concept that can be expanded to other enzyme classes. This addresses a need for more informative cell-based assays that are required to accelerate the drug development process. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics.
Cystic fibrosis (CF) is the most common lethal inherited disease in Caucasians and is caused by mutations in the CFTR gene. The disease is incurable and medical treatment is limited to the amelioration of symptoms or secondary complications. A comprehensive understanding of the disease mechanisms and the development of novel treatment options require appropriate animal models. Existing CF mouse models fail to reflect important aspects of human CF. We thus generated a CF pig model by inactivating the CFTR gene in primary porcine cells by sequential targeting using modified bacterial artificial chromosome vectors. These cells were then used to generate homozygous CFTR mutant piglets by somatic cell nuclear transfer. The homozygous CFTR mutants lack CFTR protein expression and display severe malformations in the intestine, respiratory tract, pancreas, liver, gallbladder, and male reproductive tract. These phenotypic abnormalities closely resemble both the human CF pathology as well as alterations observed in a recently published CF pig model which was generated by a different gene targeting strategy. Our new CF pig model underlines the value of the CFTR-deficient pig for gaining new insight into the disease mechanisms of CF and for the development and evaluation of new therapeutic strategies. This model will furthermore increase the availability of CF pigs to the scientific community.
BACKGROUND: The diagnosis and management of BK virus (BKV) reactivation following renal transplantation continues to be a significant clinical problem. Following reactivation of latent virus, impaired cellular immunity enables sustained viral replication to occur in urothelial cells, which potentially leads to the development of BKV-associated nephropathy (BKVAN). Current guidelines recommend regular surveillance for BKV reactivation through the detection of infected urothelial cells in urine (decoy cells) or viral nucleic acid in urine or blood. However, these methods have variable sensitivity and cannot routinely distinguish between different viral subtypes. We therefore asked whether mass spectrometry might be able to overcome these limitations and provide an additional non-invasive technique for the surveillance of BKV and identification of recipients at increased risk of BKVAN. RESULTS: Here we describe a mass spectrometry (MS)-based method for the detection of BKV derived proteins directly isolated from clinical urine samples. Peptides detected by MS derived from Viral Protein 1 (VP1) allowed differentiation between subtypes I and IV. Using this approach, we observed an association between higher decoy cell numbers and the presence of the VP1 subtype Ib-2 in urine samples derived from a cohort of 20 renal transplant recipients, consistent with the hypothesis that certain viral subtypes may be associated with more severe BKVAN. CONCLUSIONS: This is the first study to identify BK virus proteins in clinical samples by MS and that this approach makes it possible to distinguish between different viral subtypes. Further studies are required to establish whether this information could lead to stratification of patients at risk of BKVAN, facilitate distinction between BKVAN and acute rejection (AR), and ultimately improve patient treatment and outcomes.
The deubiquitylation enzyme USP7/HAUSP plays a major role in regulating genome stability and cancer prevention by controlling the key proteins involved in the DNA damage response. Despite this important role in controlling other proteins, USP7 itself has not been recognized as a target for regulation. Here, we report that USP7 regulation plays a central role in DNA damage signal transmission. We find that stabilization of Mdm2, and correspondingly p53 downregulation in unstressed cells, is accomplished by a specific isoform of USP7 (USP7S), which is phosphorylated at serine 18 by the protein kinase CK2. Phosphorylation stabilizes USP7S and thus contributes to Mdm2 stabilization and downregulation of p53. After ionizing radiation, dephosphorylation of USP7S by the ATM-dependent protein phosphatase PPM1G leads to USP7S downregulation, followed by Mdm2 downregulation and accumulation of p53. Our findings provide a quantitative transmission mechanism of the DNA damage signal to coordinate a p53-dependent DNA damage response. © 2012 Elsevier Inc..
Novel ubiquitin-based active site probes including a fluorescent tag have been developed and evaluated. A new, functionalizable electrophilic trap is utilized allowing for late stage diversification of the probe. Attachment of fluorescent dyes allowed direct detection of endogenous deubiquitinating enzyme (DUB) activities in cell extracts by in-gel fluorescence imaging.
Hypoxic and oxidant stresses can coexist in biological systems, and oxidant stress has been proposed to activate hypoxia pathways through the inactivation of the oxygen-sensing hypoxia-inducible factor (HIF) prolyl and asparaginyl hydroxylases. Here, we show that despite reduced sensitivity to cellular hypoxia, the HIF asparaginyl hydroxylase-known as FIH, factor inhibiting HIF-is strikingly more sensitive to peroxide than the HIF prolyl hydroxylases. These contrasting sensitivities indicate that oxidant stress is unlikely to signal hypoxia directly to the HIF system, but that hypoxia and oxidant stress can interact functionally as distinct regulators of HIF transcriptional output. © 2012 European Molecular Biology Organization.
The deubiquitylation enzyme USP7/HAUSP plays a major role in regulating genome stability and cancer prevention by controlling the key proteins involved in the DNA damage response. Despite this important role in controlling other proteins, USP7 itself has not been recognized as a target for regulation. Here, we report that USP7 regulation plays a central role in DNA damage signal transmission. We find that stabilization of Mdm2, and correspondingly p53 downregulation in unstressed cells, is accomplished by a specific isoform of USP7 (USP7S), which is phosphorylated at serine 18 by the protein kinase CK2. Phosphorylation stabilizes USP7S and thus contributes to Mdm2 stabilization and downregulation of p53. After ionizing radiation, dephosphorylation of USP7S by the ATM-dependent protein phosphatase PPM1G leads to USP7S downregulation, followed by Mdm2 downregulation and accumulation of p53. Our findings provide a quantitative transmission mechanism of the DNA damage signal to coordinate a p53-dependent DNA damage response.
E2F transcription factors are implicated in diverse cellular functions. The founding member, E2F-1, is endowed with contradictory activities, being able to promote cell-cycle progression and induce apoptosis. However, the mechanisms that underlie the opposing outcomes of E2F-1 activation remain largely unknown. We show here that E2F-1 is directly methylated by PRMT5 (protein arginine methyltransferase 5), and that arginine methylation is responsible for regulating its biochemical and functional properties, which impacts on E2F-1-dependent growth control. Thus, depleting PRMT5 causes increased E2F-1 protein levels, which coincides with decreased growth rate and associated apoptosis. Arginine methylation influences E2F-1 protein stability, and the enhanced transcription of a variety of downstream target genes reflects increased E2F-1 DNA-binding activity. Importantly, E2F-1 is methylated in tumour cells, and a reduced level of methylation is evident under DNA damage conditions that allow E2F-1 stabilization and give rise to apoptosis. Significantly, in a subgroup of colorectal cancer, high levels of PRMT5 frequently coincide with low levels of E2F-1 and reflect a poor clinical outcome. Our results establish that arginine methylation regulates the biological activity of E2F-1 activity, and raise the possibility that arginine methylation contributes to tumourigenesis by influencing the E2F pathway.
Hypoxic and oxidant stresses can coexist in biological systems, and oxidant stress has been proposed to activate hypoxia pathways through the inactivation of the 'oxygen-sensing' hypoxia-inducible factor (HIF) prolyl and asparaginyl hydroxylases. Here, we show that despite reduced sensitivity to cellular hypoxia, the HIF asparaginyl hydroxylase--known as FIH, factor inhibiting HIF--is strikingly more sensitive to peroxide than the HIF prolyl hydroxylases. These contrasting sensitivities indicate that oxidant stress is unlikely to signal hypoxia directly to the HIF system, but that hypoxia and oxidant stress can interact functionally as distinct regulators of HIF transcriptional output.
Ankylosing spondylitis (AS) is a common, inflammatory rheumatic disease that primarily affects the axial skeleton and is associated with sacroiliitis, uveitis, and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine whether plasma from patients with AS contained autoantibodies and, if so, characterize and quantify this response in comparison to patients with rheumatoid arthritis (RA) and healthy controls. Two high density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA, and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis to determine the patterns of signaling cascades or tissue origin. 44% of patients with ankylosing spondylitis demonstrated a broad autoantibody response, as compared with 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The autoantibody responses in the AS patients were targeted toward connective, skeletal, and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic acid programmable protein arrays constitute a powerful tool to study autoimmune diseases.
Cho E-C, Zheng S, Munro S, Liu G, Carr SM, Moehlenbrink J, Lu Y-C, Stimson L, Khan O, Konietzny R, McGouran J, Coutts AS, Kessler B, Kerr DJ, Thangue NBL et al.	2012.	Arginine methylation controls growth regulation by E2F-1	EMBO Journal,	31	(7),	pp. 1785-1797.
Chen L, Fisher R, Kollnberger S, Kessler B, Bowness P.	2012.	ENDOPLASMIC RETICULUM AMINOPEPTIDASE-1 (ERAP1) PLAYS A CRITICAL ROLE IN PEPTIDE BINDING AND ANTIGEN PRESENTATION BY HLA-B27	CLINICAL AND EXPERIMENTAL RHEUMATOLOGY,	30	(4),	pp. 603-603.
BACKGROUND: Efficient and precise techniques for the genetic modification of pigs facilitate the generation of tailored donor animals for xenotransplantation. Numerous transgenic pig lines exist with the focus on inhibition of the complement system and of humoral immune responses. In addition, immune cell-based responses need to be controlled to prevent pig-to-primate xenograft rejection. Expression of human (hu) TNF-related apoptosis-inducing ligand (TRAIL) on porcine cells has the potential to ameliorate human T cell responses. METHODS: We generated transgenic pigs expressing human tumor necrosis factor (TNF)-related apoptosis-inducing ligand (huTRAIL) under the control of either the mouse H2K(b) promoter or a CMV enhancer/chicken β-actin (CAG) promoter, the latter one (CAG-huTRAIL) on a GGTA1 knockout/huCD46 transgenic background. The biological activity of huTRAIL was demonstrated by its apoptosis-inducing effect on Jurkat lymphoma cells. To clarify whether huTRAIL affects also primary immune cells and whether its effects depend on the presence of co-stimulatory molecules, we exposed human peripheral blood mononuclear cells (PBMC) or isolated T cells to huTRAIL-expressing porcine fibroblasts or dendritic cells in vitro. RESULTS: H2Kb-huTRAIL transgenic pigs express huTRAIL mainly in the spleen and secondary lymphoid tissues. The CAG-huTRAIL construct facilitated huTRAIL expression in multiple organs, the level being at least one order of magnitude higher than in H2Kb-huTRAIL transgenic pigs. Incubation with huTRAIL-expressing H2Kb-huTRAIL transgenic porcine dendritic cells decreased human T cell proliferation significantly without any signs of apoptosis. In spite of the high transgene expression level, CAG-huTRAIL transgenic fibroblasts did not affect proliferation of human PBMC, independent of their activation state. CONCLUSIONS: These results suggest huTRAIL expression on porcine dendritic cells as a possible strategy to attenuate T cell responses against pig-to-primate xenografts.
c-Type cytochromes are widespread proteins, fundamental for respiration or photosynthesis in most cells. They contain heme covalently bound to protein in a highly conserved, highly stereospecific post-translational modification. In many bacteria, mitochondria, and archaea this heme attachment is catalyzed by the cytochrome c maturation (Ccm) proteins. Here we identify and characterize a covalent, ternary complex between the heme chaperone CcmE, heme, and cytochrome c. Formation of the complex from holo-CcmE occurs in vivo and in vitro and involves the specific heme-binding residues of both CcmE and apocytochrome c. The enhancement and attenuation of the amounts of this complex correlates completely with known consequences of mutations in genes for other Ccm proteins. We propose the complex is a trapped catalytic intermediate in the cytochrome c biogenesis process, at the point of heme transfer from CcmE to the cytochrome, the key step in the maturation pathway.
Ankylosing Spondylitis (AS) is a common inflammatory rheumatic disease with a predilection for the axial skeleton, affecting 0.2% of the population. Current diagnostic criteria rely on a composite of clinical and radiological changes, with a mean time to diagnosis of 5 to 10 years. In this study we employed nano liquid-chromatography mass spectrometry analysis to detect and quantify proteins and small compounds including endogenous peptides and metabolites in serum from 18 AS patients and nine healthy individuals. We identified a total of 316 proteins in serum, of which 22 showed significant up- or down-regulation (p < 0.05) in AS patients. Receiver operating characteristic analysis of combined levels of serum amyloid P component and inter-α-trypsin inhibitor heavy chain 1 revealed high diagnostic value for Ankylosing Spondylitis (area under the curve = 0.98). We also depleted individual sera of proteins to analyze endogenous peptides and metabolic compounds. We detected more than 7000 molecular features in patients and healthy individuals. Quantitative MS analysis revealed compound profiles that correlate with the clinical assessment of disease activity. One molecular feature identified as a Vitamin D3 metabolite-(23S,25R)-25-hydroxyvitamin D3 26,23-peroxylactone-was down-regulated in AS. The ratio of this vitamin D metabolite versus vitamin D binding protein serum levels was also altered in AS as compared with controls. These changes may contribute to pathological skeletal changes in AS. Our study is the first example of an integration of proteomic and metabolomic techniques to find new biomarker candidates for the diagnosis of Ankylosing Spondylitis.
APE1 (Ref-1) is an essential human protein involved in DNA damage repair and regulation of transcription. Although the cellular functions and biochemical properties of APE1 are well characterized, the mechanism involved in regulation of the cellular levels of this important DNA repair/transcriptional regulation enzyme, remains poorly understood. Using an in vitro ubiquitylation assay, we have now purified the human E3 ubiquitin ligase UBR3 as a major activity that polyubiquitylates APE1 at multiple lysine residues clustered on the N-terminal tail. We further show that a knockout of the Ubr3 gene in mouse embryonic fibroblasts leads to an up-regulation of the cellular levels of APE1 protein and subsequent genomic instability. These data propose an important role for UBR3 in the control of the steady state levels of APE1 and consequently error free DNA repair.


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Should we trust the general election 2017 polls?
The latest polls for the general election 2017 suggest support for the Conservatives is slipping. But pollsters have been wrong before.
At the beginning of the general election campaign, the polls predicted a Conservative landslide, and Labour's worst election since 1935. But since then, some polls have suggested a very different story. A Times/YouGov poll predicted the Tories would fall short of an overall majority by 16 seats, leading to a hung parliament.
Opinion polls have been wrong before. The Conservative majority in the 2015 general election came as a surprise after opinion polls had widely foreseen a very tight race between Labour and the Tories. And in 2016, both Brexit and Trump appeared to defy the opinion polls.
General election polls have undergone hard scrutiny since those failing. A lot of effort has gone into correcting the general election polls' tendency to overrate Labour's chances. So do the pollsters deserve to be believed now, or are general election polls no better than looking at the latest general election odds for a glimpse into the future?
One indication that is probably more reliable than general election polls is local election performance. According to that, general election polls could be underestimating the Conservatives.
Should we believe the general election 2017 polls?
Yes and no - and here's our guide to why.
How accurate have polls been in the past?
The 2015 general election 2015, the EU referendum and the 2016 US presidential elections all gave the polling industry a bloody nose. In those results, polls flattered the left and underestimated the right, but Glen O'Hara points out that in the 1983 and 2010 general elections, it was Labour that exceeded expectations.
But Anthony Wells of YouGov argues that the polls actually got Brexit right (calling a narrow result, veering towards leave). The US presidential result was a genuine upset, but again the polls were right to call a Clinton victory in the popular vote, which she won by 3 million. However, they were wrong about which states that vote would concentrated in - which meant that the electoral college skewed heavily towards Donald Trump. And in 1983 and 2010, the polls got the Tory victory right, but overestimated its size.
So while polls aren't an exact guide to the future and need cautious interpretation, their record is stronger than it currently appears.
How can polls be biased?
When it comes to broad trends within the margin of error - usually accepted to be three percentage points - polls taken as a whole are fairly reliable. When it comes to detailed breakdowns of individual group behaviour, however, statistical noise creeps in.
Bear that in mind when you're faced with predictions about swings between minority party voters, or leave vs remain voter behaviour – conclusions might be based on small subgroups that aren't sufficiently representative.
Individual polls at national level are prone to the same effect: one outlier result might be the start of a trend, or it might be just that - an outlier. And be particularly cautious of "private polling" like the Ashcroft polls. They're usually released to swing a particular narrative, and those who pay for them rarely reveal their methodology.
The only poll that counts is the ballot box. Only after the final count will we know for sure whether Jeremy Corbyn could become prime minister or whether Ukip is finished. But opinion polls are a fairly reliable guide to the broad shape of the general election. It would be a genuine upset if Corbyn won, based on Labour's current polling.


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Medium now offers audio versions of its stories for members
Ken Yeung@thekenyeung	 May 18, 2017 12:18 PM
Image Credit: Ken Yeung / VentureBeat
Medium is hoping to sweeten the pot in order to get you to become a paying member. The publishing platform provider said that members will now be provided an audio version of every "exclusive, member-funded story" along with some additional selections chosen by the company's editorial team. More than 50 stories are now available as audio versions, with more being added in the future.
After revealing it had an unsustainable business plan, Medium pivoted into a premium subscription service in March, charging members $5 per month for what it promised would be a better reading experience and content. "Media is broken. And we need to fix it," claimed company chief executive Evan Williams at the time.
Some stories will be narrated by a professional voice actor (likely not Samuel L. Jackson, although that would be cool), while others will be done by the original authors themselves. This service is available on Medium's site and mobile apps. "The most popular stories on Medium are often first-person perspectives, so our audio is designed to give you a direct, emotional version of the story with professionally recorded narrations by real people," a company spokesperson told VentureBeat.
Members are being notified about this new feature in an email starting today.
There's been some skepticism about Medium's new business plan, but it's a bit early to tell whether it'll succeed or not. However, simply offering exclusive stories isn't enough, and the company likely believes that an audio version of stories could be a good selling point for why you should be a member. Medium said that this is only the beginning of this feature and plans on releasing additional updates in the future.
"We're excited to record many more stories over the coming months and to experiment with adding different types of audio content, supporting writers and publishers to upload their own narrations, and more," the company said in an email.


The federal Clean Air Act and associated environmental regulations have driven steep declines in air pollution emissions over the past several decades, even as US manufacturers increased production, according to a study by two University of California, Berkeley, economists.
The study, forthcoming in the American Economic Review, found that polluting emissions from US manufacturing fell by 60% between 1990 and 2008—a period in which manufacturing output grew significantly—primarily because manufacturers adopted cleaner production methods in tandem with increasingly strict environmental regulation.
In the 1960s and 1970s, people worried that Los Angeles, New York and other US cities would have unbearable air pollution levels by the end of the 20th century. Instead, air pollution levels have plummeted, and the evidence shows that environmental regulation and the associated cleanup of production processes have played important roles in those steep declines.
Shapiro and co-author Reed Walker analyzed newly available data on more than 1,400 different products produced by US plants between 1990 and 2008. They combined this with plant-level pollution emissions data over the same period. The authors then categorized reductions in overall emissions into those that can be explained by changes in manufacturing output, changes in the types of goods produced or changes in production technologies.
People often assume that manufacturing production pollutes less today because manufacturing output has declined, when in fact output was 30 percent greater in 2008 than in 1990. Others argue that manufacturing has shifted towards cleaner, high-tech products or that the manufacturing of 'dirty' products like steel has moved to China, Mexico or other foreign countries. Our analysis showed that changes in the product-mix of US manufacturing do not explain much of the reduction in emissions. Instead, manufacturers are producing the same types of goods, but they've taken significant steps to clean up their production processes.
The study was funded in part by grants from the National Science Foundation and the US Department of Energy. Shapiro conducted much of the research in his former position at Yale University.
The GOP will tell you that pollution is competitive.
Higher productivity + lower cost are possible with less pollution and GHGs.
More electrification, more digitization, extended use of AI, use of improved robots, new materials, REs and lower cost storage units, more electrified ground, sea and air vehicles etc will all lead to improved productivity, lower cost and less pollution and GHGs.


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It is one of the most popular free online audio editor software that can be compared to the features of paid iOS and MAC audio editing tools. From a range of VST and core effects like normalizing, amplifying, speed, pitch, and more, the TwistedWave audio editor free edition supports five minutes audio clips and imports your files in mono. The features of TwistedWave audio editor are-
So here we go I just load the video down as we now enter content samurai itself, I love this sort of samurai guide load at the ultimate Christmas time and so the samurai's in Christmas time is awesome and now we've done intro sort of - I sort done the intro slide and that's just something I have learnt just using the system awesome too and nice couple of slides especially because the contents on the Fritch site tends to be written by the people and just myself as the editor comes along and does the audience stuff with it. So narrowing slide content samurai I started actually creating the video.
As you get more comfortable with HitFilm 4 Express, you'll grow to appreciate its many advanced capabilities including its comprehensive compositing and tracking options, its sticking 2D and 3D effects, its highly precise speed controls, and its litany of audio tools. But, of course, the best thing about HitFilm 4 Express is its price (or lack thereof). If you ultimately decide that you don't like it, your pocketbook will be absolutely no worse for the wear.
If you're looking to be the next big name in EDM (or even if you're just looking for a remarkable audio editing software) you should definitely give FL Studio a look-see. Used by artists like Martin Garrix, Porter Robinson and others, FL Studio is definitely a top-notch software for audio editing files. Similar to other top notch DAWs, FL Studio also supports multi-track recording, time stretching, and pitch shifting. It comes with a mixer that brings features like effects chains, automation, delay compensation and more.
As for usage, Adobe Audition, just like other software from the company, is easy to learn but hard to master. For example, you can remove unwanted noise from your audio tracks simply by using the paintbrush tool to select it, while the healing option automatically removes background noise. But more advanced tools and options will demand an investment of time and practice before you get comfortable with them.
Cubase, from Steinberg, is another audio editing software that you might wanna take a look at. The DAW comes with a legacy of major artists having used it including the likes of Zedd, Junkie XL and more. As far as features are concerned, Cubase brings forth quite a bit of these as well. There's a frequency equalizer that lets you perform immensely delicate frequency edits to your tracks, an Auto-Pan feature that lets you quickly play around with your tracks.
Hya-Wave is able to do efficient audio edits which includes cut, split, append, join, add effects etc. To use it, go to its page and you'll be asked to drag the file onto its interface. Once done, the editing options will appear. According to your need, select the desired ones and play the audio for checking the effect. Click the "Disc" icon on the upper part, then click the "Share>Export file" button to download the file into the computer.
I am a novice looking to do some basic editing of a bunch of family camcorder videos I recently converted to digital format on my PC. Most of what I want to do I'd call pretty basic (cutting long video into separate clips, adding captions, etc.). One aspect– the removal of some annoying voice segments while retaining the accompanying video sections– I'm guessing may be more complicated. I'm trying to figure out which programs will enable me to do this but am confused as to what having separate audio tracks really means. Is it strictly to manipulate different audio clips one is adding to a project when building a video, OR is it pertinent to my goal of deleting audio segments from one standalone video (i.e., I'm not adding different video and audio clips together from different sources)?
There are a bunch of plug-ins, and Adobe even has its very own series of tutorials surrounding Audition, which should definitely make it much easier for you to get started with the app. Along with all of that, the app has a really well thought out interface, and manages to look inviting even with all of the features it packs once you scratch the surface. Plus, it supports most of the audio formats out there like MP3, WAV, AC-3, AIF, AIFF, AIFC, AAC, HE-AAC, CAF, FLAC, PCM, OGG, WMA and more, along with support for video formats like AVI, MP4, MOV, FLV etc.
It is important to sit down and ask whether using Content Samurai will really bring in the marginal fifty (or twenty-five if you go annually) dollars a month that it needs to make it a good decision. Part of this will depend on the length of time you intend to keep and use Content Samurai. If you have your material ready, you can do all the work in just one month (or have a virtual assistant do that for you). You can get a lot of videos done in 30 days, pause and resume the license only if/when you will need it again in the future.
By contrast, if you do not want to use online audio editor free, please use this software, Leawo Music Recorder . It is software that can be used for recording offline, and recording makes everything easy. If you want to cut some parts of an audio, just record them. Certainly, it can produce audio parts of MP3 or WAV format, allow you to edit audio tags and adjust audio parameters as well. Besides, it allows you to add what you have produced into your iTunes by one click.
Although PC computer systems offer significantly more video editing software options than those of Macs, there is certainly no shortage of Apple-compatible editing options for amateurs and experts alike. However, the inherently user-friendly design of the Mac is particularly well-suited to beginning video editors, and few Mac applications are easier to use than Apple iMovie.
Nero is a trusted name when it comes to diverse and easy-to-use multimedia suites, and Nero Platinum 2019 is no different. The latest version of its flagship product allows you to burn media, create your own, edit creations, organize your collection, stream the media you've already got, and much more. It's an essential multitasking tool that's perfect for beginners or aspiring filmmakers, with everything you need to author, burn, and store the best possible content you can make.
While most professional-grade software can handle multi-cam editing, Premiere Pro goes one step beyond, handling as many sources as necessary with as many angles as required. The inclusion of the bundled Lumetri Color Panel allows advanced color adjustments to be handled with ease. Additionally, Adobe's integration with After Effects and Photoshop adds even more reason for professional grade editors to choose Premiere Pro.
Y2mate.download is not only a YouTube downloader, it is also a versatile video and audio downloader. It can support most audio and video sharing platforms and easily obtain MP4, MP3 files from these websites. The sites listed above are just some of the popular audio and video sites. You can try any video site you want to download by entering the video link.
I'm pretty sure you've heard of Audacity. The free and open-source software is mentioned on almost every single audio editing thread out there, and for good reason. Like I said, Audacity is free, like completely free, and that makes it the most easily accessible software to anyone looking to get started with audio editing. Plus, it's no slouch when it comes to the features either. It has almost all the features you'll need. There are a lot of effects including things like bass, treble, distortion, noise removal and more. Along with that Audacity also comes with analysis tools such as beat finder, silence finder, sound finder, and more.
Often, it comes down to details and the editing philosophies. Do you prefer loop-based recording and live playback for electronic music? Ableton Live has plenty to offer you. Would you rather have a "do-it-all" DAW with a large built-in sound library at a low price? PreSonus Studio One beckons. Do you not only want to bring projects into major studios, but also to collaborate online and open sessions directly as you work on them with others? It's impossible to top Avid's Pro Tools for this. Is the music already done, and you work in post-production and want to produce more professional podcasts or videos? Adobe Audition is a prime contender for those tasks. And if you've got a Mac, it's worth giving the free GarageBand a spin, if only because it's more powerful than ever, and you already own it.
The fourth highlight is that if you right click at least one of your recordings, you can choose "Download Info" to automatically edit the music tags. That means you can download the relevant information of recorded audio. If you're using a Mac computer, Leawo Music Recorder for Mac could help you easily convert YouTube to MP3 audio on Mac OS 10.6 and later.
Ableton Live is also a name that's synonymous with music production and that's pretty obvious considering the incredibly large number of features it brings. For starters, Ableton Live supports unlimited audio and MIDI tracks so you can stuff as many layers of tracks into your project as you need. There's also support for MIDI capture, 256 mono input channels and 256 mono output channels. Along with that, you get up to 70GB of pre-recorded sounds you can use in your projects, up to 15 software instruments, and up to 46 audio effects.
While VideoPad lacks the flashy pizzaz of applications with an overabundance of features and effects, it remains a rock-solid choice for straightforward video editing. Plus, it is versatile and powerful enough to edit and upload videos that range from 480p to 4K. VideoPad isn't free, but at just $40 for full and comprehensive use, it won't soon have you filing for bankruptcy either.
With Reaper you can apply effects in a real time, non-destructive manner, insert almost any third party or MIDI plug in, and even brings real-time pitch shifting and time stretching capabilities into the mix. Reaper also supports most popular file formats along with some not-so-popular file formats out there. There's support for ACID, AIFF, AVI, BWF, CDDA, EDL, FLAC, KAR, MIDI, MOGG, MOV, MP3, MPEG, OGG VORBIS, OGG OPUS, QT, RADAR, REX2, SYX, W64, WAV, WAVPACK, WMV and more.
Look at the screenshot I attached above. I want you to look at the left sidebar. The #01 "Getting Started" video is what I just walked you through. You can see there are more video instructions. The videos are between 2 and 5 minutes long each, so it doesn't take long at all to become acquainted with the software. The 5 additional training videos include the following topics.
It gets even worse when you actually reach someone in tech support for MAGIX – they had me install a program to determine the OS of the host computer, and it got the answer wrong so MAGIX support told me that I did not have Windows 10 on my computer so they couldn't help me. I sent them screen shots proving I had Win10 but they didn't believe me. I am trying to get a refund now. Sound Forge was awesome, MAGIX sucks.
Content Samurai is an online video creator software (application) that helps you create fast, easy and professional-looking videos within minutes. It allows you to insert articles into the software and it automatically creates a good-looking video using the text from the article you inserted. It can also add great images, video backgrounds and even text to speech voices.
Sound Forge is no longer owned by Sony. It is owned by MAGIX in Germany. Sony provided excellent support. Installation support is free with MAGIX, provided you are actually ever able to reach anyone on their Sales Support number they instruct you to call. I have yet to reach anyone after multiple attempts, so I have never been able to install the program. If you actually need ~technical~ support, you have to BUY a support voucher. Sony was great…MAGIX is not.
So off we go I am going to speed this thing up so we can get through this content samurai review really quickly and show you there is much details as possible, so let's dive into the slides. So I am just going to slow the video down just a second again. It's really cool in the slide editing area because below is absolutely loads and loads of different beams. I really like the versatile stone effect sort of a blackboard effect in a way, I'm going for this one I am going to pick the green and the stone effects, yeah the really cool thing is just released content samurai now allows you to upload your own videos so we can actually upload an intro clip.
Closely correlated to bundled instruments and effects is price, and that's a factor that can cloud the issue. Many of the top-tier packages also have less expensive (or even free), feature-limited editions available. It's not as simple as saying "Reaper is a budget DAW at $60 and Studio One is a professional-level DAW at $399," because you can also buy the stripped-down (but still pretty feature-rich) Studio One Artist for $99. What do you lose? What do you gain? We try and touch on this as much as possible within each review.
As a result, more than half of the packages in this roundup score at least four out of five stars. You can get professional-level results with all of them. Each has specific workflows that work really, really well for some people—hence the endless "X is the best and Y is garbage" arguments on the internet—but with some acclimation time, they all can work for just about anyone.
It's an entirely different world now. Software packages that cost a few hundred dollars now deliver hundreds of audio tracks and incredibly flexible editing. Some programs are even free. You can create as many instances of effect plug-ins as you want, including spot-on emulations of compressors that used to cost several thousand dollars each, and attach them to as many mixer channels as you want. It's all nearly unlimited and "in the box" now.
So as you can see notes a couple of examples that I jot down into the actual original recording it's just so quick even on that death slowing connection that I was doing this on and it works with 3 and I could have done it even with uploading actual files to drop box I have been using content samurai and it hasn't skipped a beat it still sounds fantastic, so yeah can't say enough about the guy who actually created this so you see here the...I actually get this wrong a couple of times and that's no real issue because if you get it wrong you can just click the re-record button and it re-record it a few times. This is one very short thing at the moment but I actually believe the update they brought out couple of days ago that that particular box gone if you do a huge great list you can actually split them up for audio a bit easier, that's awesome and yes I'm firing through here. I love at the top how it's got the number of sentences left to record that's really helpful to know and it's kind of really encouraging as well. I mean it only takes about 10-12 minutes to I think to...when I time myself to actually record this is a 700 word article so it don't take too long so you need to just fly through here.
Best Video Editing Software and Video Editing Tips


The Santiam River is a tributary of the Willamette River in Oregon. It has two main forks, the North Santiam, and the South Santiam.
The North Santiam flows near Stayton and past North Santiam State Park. Farther upstream is Detroit Dam and Detroit Lake and Detroit Lake State Park.
The South Santiam passes Lebanon and Sweet Home.
There is also a middle fork, which splits off behind Foster Dam forming Foster Lake and is again dammed by Green Peter Dam, which forms Green Peter Lake. Both lakes are heavily used for recreation.
The Santiam is a major source of water supply for Salem, the capital city of Oregon.
Santiam is also the trademark of a canned vegetable company which is a division of Norpac.


It was proof to me that fall is here to stay.
This makes for a restful night?
And lightning streaks across the sky.
But fall and winter most of all.
And snowflakes begin to fall.
And was a gift, totally free to man.
Supported only by God's hands.
How the world all came to be.
Or Amebas from the sea.
Proclaimed it in His word.
And all, that we have ever heard.
unto the wise, and knowledge to them that know understanding:"


Forest Park Forever concludes National Volunteer Week with a highlight of our episodic volunteers who complete done-in-a-day Park Project Days here in Forest Park.
Episodic opportunities are primarily for groups, such as schools, corporations and community organizations. They participate in a variety of Land Management activities: litter pick up, invasive species removal, mulching, trail restoration and planting projects. In 2013, episodic volunteers donated 1,800 hours of service to support our Land Management program.
On Thursday, April 10, members of the Ritz-Carlton Management Team took part in a Park Project Day. Around a dozen team members donated a morning of service mulching the crabapple trees near the Jewish Tercentenary Memorial.
Thanks to these fantastic volunteers who make Forest Park a more beautiful and sustainable place for all to enjoy — now and forever.


text:
<?php
namespace Permission\Factory\Form;

use Zend\ServiceManager\FactoryInterface;
use Zend\ServiceManager\ServiceLocatorInterface;
use Permission\Form\LoginForm;
use Permission\Form\LoginFormFilter;

class LoginFormFactory implements FactoryInterface
{

    public function createService(ServiceLocatorInterface $serviceLocator)
    {
        $form = new LoginForm();

        $form->setInputFilter(new LoginFormFilter());

        return $form;
    }
}

redpajama_set_name: RedPajamaGithub


text:
package org.team2168.utils.numbers;

/**
* A mutable double wrapper.
*
* @see Double
* @since 2.1
* @version $Id: MutableDouble.java 618693 2008-02-05 16:33:29Z sebb $
*/
public class MutableDouble implements Mutable {

/** The mutable value. */
private double value;

/**
* Constructs a new MutableDouble with the default value of zero.
*/
public MutableDouble() {
 super();
}

/**
* Constructs a new MutableDouble with the specified value.
*
* @param value
*          a value.
*/
public MutableDouble(double value) {
 super();
 this.value = value;
}

// -----------------------------------------------------------------------
/**
* Gets the value as a Double instance.
*
* @return the value as a Double
*/
public Object getValue() {
 return new Double(this.value);
}

/**
* Sets the value.
*
* @param value
*          the value to set
*/
public void setValue(double value) {
 this.value = value;
}

/**
* Sets the value from any Number instance.
*
* @param value
*          the value to set
* @throws NullPointerException
*           if the object is null
* @throws ClassCastException
*           if the type is not a {@link Number}
*/
public void setValue(Object value) {
 setValue(((Double) value).doubleValue());
}

// -----------------------------------------------------------------------
// shortValue and bytValue rely on Number implementation
/**
* Returns the value of this MutableDouble as a int.
*
* @return the numeric value represented by this object after conversion to
*         type int.
*/
public int intValue() {
 return (int) value;
}

/**
* Returns the value of this MutableDouble as a long.
*
* @return the numeric value represented by this object after conversion to
*         type long.
*/
public long longValue() {
 return (long) value;
}

/**
* Returns the value of this MutableDouble as a float.
*
* @return the numeric value represented by this object after conversion to
*         type float.
*/
public float floatValue() {
 return (float) value;
}

/**
* Returns the value of this MutableDouble as a double.
*
* @return the numeric value represented by this object after conversion to
*         type double.
*/
public double doubleValue() {
 return value;
}

/**
* Checks whether the double value is the special NaN value.
*
* @return true if NaN
*/
public boolean isNaN() {
 return Double.isNaN(value);
}

/**
* Checks whether the double value is infinite.
*
* @return true if infinite
*/
public boolean isInfinite() {
 return Double.isInfinite(value);
}

// -----------------------------------------------------------------------
/**
* Gets this mutable as an instance of Double.
*
* @return a Double instance containing the value from this mutable
*/
public Double toDouble() {
 return new Double(doubleValue());
}

// -----------------------------------------------------------------------
/**
* Increments the value.
*
* @since Commons Lang 2.2
*/
public void increment() {
 value++;
}

/**
* Decrements the value.
*
* @since Commons Lang 2.2
*/
public void decrement() {
 value--;
}

// -----------------------------------------------------------------------
/**
* Adds a value.
*
* @param operand
*          the value to add
*
* @since Commons Lang 2.2
*/
public void add(double operand) {
 this.value += operand;
}

/**
* Subtracts a value.
*
* @param operand
*          the value to add
*
* @since Commons Lang 2.2
*/
public void subtract(double operand) {
 this.value -= operand;
}

/**
* Returns a suitable hashcode for this mutable.
*
* @return a suitable hashcode
*/
public int hashCode() {
 long bits = Double.doubleToLongBits(value);
 return (int) (bits ^ (bits >>> 32));
}

/**
* Returns the String value of this mutable.
*
* @return the mutable value as a string
*/
public String toString() {
 return String.valueOf(value);
}

}

/*
* Licensed to the Apache Software Foundation (ASF) under one or more
* contributor license agreements. See the NOTICE file distributed with this
* work for additional information regarding copyright ownership. The ASF
* licenses this file to You under the Apache License, Version 2.0 (the
* "License"); you may not use this file except in compliance with the License.
* You may obtain a copy of the License at
*
* http://www.apache.org/licenses/LICENSE-2.0
*
* Unless required by applicable law or agreed to in writing, software
* distributed under the License is distributed on an "AS IS" BASIS, WITHOUT
* WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. See the
* License for the specific language governing permissions and limitations under
* the License.
*/

/**
* Provides mutable access to a value.
*

* Mutable is used as a generic interface to the implementations
* in this package.
*

* A typical use case would be to enable a primitive or string to be passed to a
* method and allow that method to effectively change the value of the
* primitive/string. Another use case is to store a frequently changing
* primitive in a collection (for example a total in a map) without needing to
* create new Integer/Long wrapper objects.
*
* @author Matthew Hawthorne
* @since 2.1
* @version $Id: Mutable.java 618693 2008-02-05 16:33:29Z sebb $
*/
interface Mutable {

/**
* Gets the value of this mutable.
*
* @return the stored value
*/
Object getValue();

/**
* Sets the value of this mutable.
*
* @param value
*          the value to store
* @throws NullPointerException
*           if the object is null and null is invalid
* @throws ClassCastException
*           if the type is invalid
*/
void setValue(Object value);

}


text:
<!DOCTYPE html>

  <meta charset="UTF-8">
  <meta name="viewport" content="width=device-width, initial-scale=1.0">
  <title>Home - Login</title>

Plz login

  <form class="login-form" action="/login" method="post">

      Email:
      <input type="email" name="email">

      Password:
      <input type="password" name="password">

    <input type="submit">
  </form>


For some people, a dream getaway might be a European tour. For others, it might be a trip to Australia. Still others may prefer visiting their family's ancestral homeland. But nope, not me: my dream vacation involves a mouse, half a dozen princesses, and what amounts to the world's largest golf ball.
Yup, I'm talking about Disney World. My husband and I have been planning our trip to the Orlando resort basically since our oldest daughter was conceived. We always planned on taking her right around her fourth birthday, and now, the time has finally arrived. Since she'll turn four just a few weeks into the start of the school year this coming fall, we've planned our Disney vacation for the third week of August. I need a vacation – my freelance business has been growing faster than I could have ever imagined a few weeks ago – and leapt into planning this trip, taking travel advice from everyone from Frommer's to Fodor's to Birnbaum. My enthusiasm was unlimited: that is, until I tallied up our vacation expenses.
My husband and I have been saving up for our Disney trip for over a year now. Starting in March 2011, we began putting away $100 a month into our vacation money fund. A few months, we managed to sock away a little extra; today, we have a cool $2,000 in the bank; I estimate we'll likely stash another $500 before we head to Disney.
Travel expenses: I used the fuel cost calculator on the AAA website to estimate how much we'd be spending to fill up our tank to and from Orlando. The site lets you estimate gas costs based not only on your route, but on regional gas prices and your vehicle's make and model as well. The result? $210 round trip on gas alone; that doesn't include the few toll roads we'll encounter along the 1060 mile trek, nor does it factor in what we'll spend on food along the way. Overall, I'm budgeting $250.
Hotel reservations: My parents taught me early on the necessity of staying on park property when you go to Disney. From the extended park hours offered only to resort guests, to the convenience of being so close to all the action, it's a luxury I'm willing to pay for. We've opted to stay at the Port Orleans French Quarter resort. We'll be there seven nights, with a total tab of $1,325.
Park tickets: Since we're already staying at a Disney resort, we've bundled our park tickets in along with our hotel reservation. We've opted for 6-day park hopper passes, which give us access to multiple parks on the same day. We'll be paying an additional $923 for those.
Fortunately, we've been able to take advantage of Disney's free meal plan, which will significantly reduce our vacation expenses since we won't have to pay for the vast majority of our meals. Still, if you add up all the above expenses, we're looking at $2,498 – looks like we'll have $2 for souvenirs.
When I think about spending all our vacation money in one fell swoop, I get a little nauseated. I start thinking, what else could I buy with $2,500?
If we put an additional $2,500 down on our new house (assuming, of course, that our current home EVER SELLS!!!), we could reduce our monthly mortgage payments by $13, saving us nearly $4,700 over the life of a 30-year fixed loan.
If we put that $2,500 in my daughter's 529 college saving plan, it would accrue more than $5,100 in interest alone before she heads off to college in another 14 years.
If we put that vacation money back into our household budget, it would give us enough to pay for all our expenses for a month.
We could use it to pay for our membership to the Y… for the next three years.
It would pay for my daughter's preschool tuition, swim classes, and dance lessons for an entire year.
That $2,500 in vacation money could stretch so far if I used it for more practical purposes! Am I being irresponsible by blowing it all on a one-week trip to see Mickey Mouse and Cinderella in person?
Typically, I'm a practical person. Sometimes, I'm too practical. I'm the type of mom who spends her birthday money on her children instead of herself. I'm the type who puts her own Christmas money in her kids' 529 accounts.
We didn't save this money with the intent to put it to our down payment (we have a separate account for that), nor did we stockpile it in order to fund our daughter's 529 (we do that monthly, too). We saved it to take our daughter on a trip we hope she'll always remember.
And that, my friends, is something on which you cannot put a price tag.


Wonderful, & situated on gorgeous, expansive lot within fabulous Wellington Estates community! Located on private no-thru street, just steps to bike/walking path along GW Parkway & Potomac river. Beautiful 2 Lvl, 3/4 BR, 2.5 BA home w/ gleaming wood floors; living room w/ crown molding, cozy fireplace, recessed lights, built-in's, and large picture window which looks onto serene backyard. Bright kitchen w/ granite & stainless; & elegant dining area w/ french doors to deck & yard. 3 main level bedrooms w/ crown molding, & hardwood floors, & Master BR w/ two closets. Lovely bath's, & finished lower level w/ recreation room, full bath, den/4th BR, & separate laundry. One car garage & ample driveway parking. Located in popular Waynewood Elem school district, and minutes to Old Town Alexandria, metro, Crystal City, DC, the Pentagon, Fort Belvoir, National Airport & Rosslyn! Close to parks, shops, restaurants, grocery, schools, rec center, pools, library, farmers markets.. Fantastic location!
SchoolsClick map icons below to view information for schools near 1111 Greenway Rd Alexandria, VA 22308.
Home for sale at 1111 Greenway Rd Alexandria, VA 22308.
Description: The home at 1111 Greenway Rd Alexandria, VA 22308 with the MLS Number VAFX805240 is currently listed at $609,000 and has been on the Alexandria market for 78 days.
You are viewing the MLS property details of the home for sale at 1111 Greenway Rd Alexandria, VA 22308, which is located in the Wellington subdivision, includes 3 bedrooms and 3 bathrooms, and has approximately 1702 sq.ft. of living area.


In 2015 I started a new technique which I call "Dotting". I'm still experimenting with it as there are different factors influencing the look of a picture and the composition. I tried ink and watercolor as I thoungt that the transparency of these colours are perfect for the technique. The first picture I made was this one. More a sketch than a painting but I wanted to try something out. I realised that I had to wait until the colour is dry and the real look comes out.
Yes – in fact. It is dark but to be honest. I was in a dark period when I painted it. No comment but I will keep it for myself as a reminder for me. Then I found out what I can really do with the technique and I optimized the steps a little bit so that these paintings were done. The first one was on tumblr start page when I published it so that I received a lot of new followers. More than 400 reactions where on that picture. Not bad as start.
After this I came to the next step. I was thinking about animals and especially about their X-rays. I combined in my mind animal X-rays and their normal look so that first these two pictures came out. I was always focusing on the basic structure of the current animal and the X-ray gave me an idea of the lines I need to draw. I'm still working on new versions and at the moment I keep it as a secret as to what kind of tools I use for the technique but the tools are the important fact about the final look.