The vote we must make
Passage of Proposition 30 is essential
It’s election season, so hyperbole is in overdrive: Pundits are barking at one another, campaign ads are smothering us in half-truths, and mega-millions are flowing into campaign coffers from all across the globe.
Despite all this, it’s possible to distill everything down to the single most important vote we Californians can make on Nov. 6: We must pass Proposition 30.
Remember when Gov. Jerry Brown was re-elected to the state’s top job a few years ago? He won overwhelmingly because voters believed he was our state’s best bet to enact a solution to California’s chronic problems and the continual budget shortfall that has robbed our schools of needed funds (we now rank 47th in per-pupil funding), slashed funding to higher education and threatened public safety.
Republican lawmakers blocked Brown right out of the gate. They denied him the opportunity to take a balanced “save California” plan straight to the voters. But on Nov. 6, Brown finally gets what he wanted back then. It’s called Proposition 30.
The measure calls for a temporary quarter-cent sales tax hike (from 7.25 percent to 7.50 percent) and personal-income-tax increase for Californians earning more than $250,000 (and couples earning more than $500,000). What will this buy? Among other things, passage of Prop. 30 will prevent an immediate $6 billion in further cuts to schools, provide billions in new school funds starting this year, and prevent more tuition hikes. Add to this the crucial fact that Prop. 30 will protect public safety by halting further cuts to cops and firefighters and save billions in future prison costs.
Nobody likes taxes, even those that come alongside massive cuts, as we’ve seen. But what’s the alternative, except a further erosion of our most basic services and hopes for a flourishing future for our state?
Vote yes on Proposition 30.


text:
You Si-kun, president of Taiwan’s Legislative Yuan, said that Taiwan had supersonic cruise missiles capable of striking Beijing should China’s communist regime invade.
“Yun Feng missiles can already hit Beijing,” You said. “Taiwan has the ability to attack Beijing.”
The Yun Feng series of missiles are domestically produced in Taiwan. They were first publicly acknowledged in 2012 and entered mass production in 2019.
You, who served as premier of Taiwan in the early 2000s, said that he was not previously allowed to reveal the full capability of the missile to the public. Now that it was mass-produced, however, he said that its range was sufficient to reach China’s capital city of Beijing, as well as the Three Gorges Dam, which is the world’s largest power station.
Speaking with the Taiwan Overseas Network, You said that an examination of Russia’s ongoing invasion of Ukraine had led him to believe that the people of Taiwan needed to take a more active role in preparing for a communist invasion.
Moreover, he said, Taiwan must not depend on the nations of the world to save it. Instead, it must prepare to fight to the last bullet. “Self-help,” he said, was vital to showing the world that Taiwan was worth saving, as was demonstrated by the resistance against Russian aggression in Ukraine.
Then, he said, the democracies of the world would be compelled to come to Taiwan’s aid, and the Chinese Communist Party (CCP) would become the enemy of Australia, Japan, and the United States.
You said that, in addition to striking the mainland with supersonic missiles, Taiwan would use the 100-mile strait between the two to mount a massive defense and sink CCP warships before they could reach the island.
“The [Chinese Community Party] must cross the Taiwan Strait to attack Taiwan, which is different from Russia’s attack on Ukraine,” You said.
You pejoratively called communist China the “Celestial Empire,” in reference to its revanchist foreign policy, and said that the island of Taiwan would never be swallowed up by the CCP.
“If you want to land, you will fight on the beachhead. If the landing is successful, everyone in Taiwan must be as determined to die as [they are in] Ukraine,” You said. “Go out and never let China swallow Taiwan.”
The CCP currently rules China as a single-party state, and considers Taiwan to be a breakaway province. CCP leader Xi Jinping has vowed to unite the two entities, and has not ruled out the use of force to do so.
Taiwan has been fully self-governed since 1949, however, and has never been under the control of the CCP.
The United States has not recognized Taiwan as an independent nation since 1979. Washington does, however, maintain a commitment to Taipei, outlined in the Taiwan Relations Act, in which it guarantees it will provide Taiwan with the military capabilities required to defend itself and maintain its de facto independence.

domain: politics


text:
So I´m planning a new sailing holiday for August at the moment. The plan is to explore a totally new area of Europe, the Baltic Sea. I have previously visited Sweden, Denmark and Norway but those were just boring old landholidays. And I have never been to any of the Baltic countries or Finland either.
As I spent last winter at some more exotic locations I decided to head north this summer. Planning for the trip is well underway already but there are still many aspects of the trip that are open.
I have rented a boat from Sweden, so my trip starts near Stockholm. From there I start with exploring the archipelago and then will make my way to Finland. Having never been there, I´m very excited to find out more about Finland. I will also make a short stop at the Aland islands
From Finland I´ll sail to Estonia, heard a lot of good things about Tallinn and also about the Saaremaa region
, so those are definitely on my list. As is Riga, the capital of Latvia. Going to skip Lithuania and head straight to Germany and from Germany will return to Sweden vie Denmark. It´s going to be quite a journey, not sure about all the stops yet but then again I don´t like to plan my holidays too much in advance. There always needs to be room for ex tempore changes and visits. That for me is the whole point of sailing.
I hope the weather will be nice, I hear that last summer was very hot in Scandinavia, hope that will be case this year as well!

domain: geography


In the selection of Combined Low Voltage Switchgear products, it is necessary to pay attention to a lot of technical points. Nowadays, there are many varieties and different characteristics in the market. Users often have difficulty choosing. In fact, we can refer to the following points. First, consider the applicable scope of low-voltage power distribution cabinets. Usually, the equipment is small in size, does not occupy much space, and can be used interchangeably in the same model. It has high stability, safety and reliability, and convenient maintenance, so it is widely used. The next consideration is the design requirements of the High Subsection Capacity Low Voltage Switchgear, such as the installation method, the environment around the installation equipment, the nature of the electricity, etc., and then the protection of the equipment switch is considered. The safety of the equipment as the power is the equipment itself. A basic requirement. Finally, it is said that the distribution equipment is intelligent. In today's society, modernization is developing rapidly, and automation and intelligence are the general trend. As an important part of the power grid, power distribution equipment is naturally an important field of intelligent automation construction.


text:
In-car aftermarket digital entertainment manufacturer Pioneer has taken the wraps off its second-generation range of Android Auto-powered stereos. These new units are essentially upgaded versions of last year’s models, featuring newer components which should make the overall user experience smoother and more fluid.
Pioneer has just started distributing a new firmware update for all of its in-car multimedia units powered by Android Auto. The upgrade carries the version number 1.05x and transports a multitude of bug fixes and stability optimizations to the devices, which include several improvements to the voice guidance service, a new version of AVICSYNC that increases reliability of the integrated navigation system and a smoother navigation interface.
If you’ve been waiting for a good deal to get started with Android Auto, Amazon is hosting a deal that just might push you over the edge. They’re offering up Pioneer’s AVIC-8100NEX stereo with a heavy discount off the MSRP, you can pick up one for roughly 900 bucks. It’s definitely not cheap, but considering these things have an MSRP of 1400, that’s a hefty discount.
The stereo has a full touch screen interface and works with your Lollipop-powered device and the Android Auto app. Pioneer’s own interface and Apple CarPlay also work, in case you like to mix and match devices. Read more
Cars and phones have been courting each other for years, by letting you make and answer calls just by speaking to your vehicle, or play music from your phone seamlessly in your automobile just by using Bluetooth. Read more
With all the buzz surrounding Android Auto at CES 2015 this year, you should not have to wait long to buy a new car with your favorite mobile operating system installed straight from the factory. If you have an older vehicle though and want to retrofit Android Auto, you are in luck as several manufacturers are bringing aftermarket solutions to the consumer. We have already seen Parrot announce their Parrot RNB 6 head unit and earlier today Kenwood announced their DDX9902S that will support Android Auto. Now Pioneer is jumping on board as well with three choices for consumers interested in Android Auto enabled devices. Read more
To keep roads safer, Pioneer has refreshed their HUDs (heads-up displays). Rather than fumbling around with smartphones or looking away at a navigation system, Pioneer is placing a clear piece of plastic just above the windshield. The HUD’s main focus is on the GPS; however, more information like speed and time can overlap so the driver won’t have to look away from the road.
A major drawback of Pioneer’s HUDs is positioning. If the driver is very tall or very short, they may have to adjust the HUD often. Clearly that’s the opposite of what Pioneer wants to do. While the ND-HUD10 will be available in Europe (600 Euro) and Japan (60,000 Yen), the ND-HUD2 will only be released in Japan for 100,000 Yen. For a look at Pioneer’s new lineup, hit the break.
Yesterday we saw an example of HTC creating some hardware to interact with their HTC Butterfly smartphone and earlier this week we reported on the DIAL project to bring easier interactivity between Android devices and smart TVs. Today we have an example of how Android developers, with the help of an Android-friendly manufacturer, are extending the ecosystem in vehicles. Pioneer makes some head units for their vehicle systems that let you control the radio using an app called Pioneer AppRadio2. stackTrase Software has taken that platform and extended it so that your Android device can be mirrored on the vehicle’s head unit using their app called ARLiberator for AppRadio. The mirroring goes beyond showing what is on the smartphone though as you can actually control the smartphone from the head unit’s touchscreen. Read more
If you’re rocking one of Pioneer’s recent audio video receivers, you’ll be excited to know that the company has just released a firmware update that allows owners to take advantage of HTC’s Connect technology. This means users can now use their HTC One X, One X+, One VX or Droid DNA smartphones to wireless stream music directly to their receivers via DLNA. The news comes just a few months following the initial introduction of Pioneer’s HTC Connect-compatible SMA wireless speakers.
We’ve seen some pretty cool projects where we draw closer and closer to Tom Cruise in Minority Report’s technology in transparent displays. We know all wanted to be Tom just a little.
We’re even closer than you may think! Pioneer’s Network Vision HUD is seen connected to an Android device using lasers to generate images on-screen. How cool is that! We said Lasers! Pioneer is looking to market this technology by the year 2012 as a driving display and navigational aid.

domain: news


text:
| 1 minute to read
High Protein Breakfast
- Paneer 20 grams Multi grain bread 75 gram ( 2 slices) Cheese 26 gram Ghee 5 gram Cucumber 15 gram Tomato 15 gram Onion 15 gram
1.Satute onion and grated paneer in 2 grams oil 2 Add filling paneer, cheese cucumber, tomato under breast slice. 3.Heat pan and spread 3 grams of oil on bread top and make bread crunchy Filling breakfast is ready.

domain: food


text: Multiparametric magnetic resonance imaging (MP-MRI), including diffusion-weighted imaging, is commonly used to diagnose prostate cancer. This radiology-pathology study correlates prostate cancer grade and morphology with common b-value combinations for calculating apparent diffusion coefficient (ADC). Thirty-nine patients undergoing radical prostatectomy were recruited for MP-MRI prior to surgery. Diffusion imaging was collected with seven b-values, and ADC was calculated. Excised prostates were sliced in the same orientation as the MRI using 3-D printed slicing jigs. Whole-mount slides were digitized and annotated by a pathologist. Annotated samples were aligned to the MRI, and ADC values were extracted from annotated peripheral zone (PZ) regions. A receiver operating characteristic (ROC) analysis was performed to determine accuracy of tissue type discrimination and optimal ADC b-value combination. ADC significantly discriminates Gleason (G) G4-5 cancer from G3 and other prostate tissue types. The optimal b-values for discriminating high from low-grade and noncancerous tissue in the PZ are 50 and 2000, followed closely by 100 to 2000 and 0 to 2000. Optimal ADC cut-offs are presented for dichotomized discrimination of tissue types according to each b-value combination. Selection of b-values affects the sensitivity and specificity of ADC for discrimination of prostate cancer.

domain: medical


"Impact Subsea will be showcasing its first new product of 2018 at Subsea Expo."
Impact Subsea Ltd
Impact Subsea design and manufacture innovative underwater altimeter, depth, range, heading, motion and temperature sensing solutions.
The company also provides a range of underwater housings and a state of the art Flooded Member Detection system.
Impact Subsea’s solutions are used on underwater Remotely Operated Vehicles (ROV), Autonomous Underwater Vehicles (AUV) and in numerous standalone underwater applications.
All sensors are extremely robust, small form factor, high reliability and lead the market in technical capability


text:
Women around the world sleep more than men—or at least, women who track their sleep through their smartphones do.
That’s according to statistics from Sleep Cycle, an alarm-clock app that collects data on users’ sleep patterns to identify the optimal wake-up time, ideally during the lightest sleep phase.
The data, collected over nine months on 1 million users in 50 countries, show that women between the ages of 16 and 55 get more sleep per night than men do. And in nearly every country (the exceptions being Colombia, Portugal, and Ukraine) women also report waking up in a worse mood than men during the week.
It sounds counterintuitive, but these trends go hand in hand: Research has found that women, who tend to multitask more during the day and hence use more of their brain power, need more sleep. So even if they sleep more than men do, some women still might not be getting enough rest—and those who don’t might feel the effects more acutely than their male counterparts. The suffering isn’t limited to mood. Insufficient sleep has been linked to serious health issues in women, such as depression and higher risk of stroke.
Here’s how time spent sleeping each night of the week compares in the US, where women sleep on average a little more than seven hours a night, while men a little under seven:
True to their hardworking stereotype, Japanese women sleep less than women anywhere else: with five hours and 56 minutes on average, they sleep nearly two hours less per night than their Finnish, Dutch, and New Zealander counterparts, who average seven hours and 41 minutes of sleep. And Japanese men sleep even less, averaging just five hours and 45 minutes on Thursday nights, for example. This might explain why both Japanese men and women have the worst wake-up mood.
Here’s a sampling of how much sleep women in various countries average each night:
Length of sleep doesn’t necessarily translate into quality of sleep, though. Chinese women don’t tend to sleep for as many hours as the women at the top of the ranking above, but they have the best quality sleep, particularly on Wednesday and Thursday nights, according to Sleep Cycle. (The app itself measures length and quality of sleep; data on wake-up mood is self-reported by users.)
Other countries where sleep is generally good are Poland, Czech Republic, and Taiwan. Meanwhile, women in New Zealand, who are among the longest sleepers, also experience some of the worst quality sleep—along with women in Ireland, Saudi Arabia, and the US.
Worldwide, it’s no surprise, Saturday is the day of the week with the latest bedtime for women; the latest to call it a night are Portuguese (1:34am), Taiwanese (1:23am), and South Korean women (1:21am).
Saturday is, in general, also the least satisfactory night of sleep by women around the world, though it’s the night where they stay in bed the longest and report having the best wake-up mood. The survey doesn’t provide information on whether this is connected to how much fun was had the night before.

domain: sociology


text:
Record Sales & Revenue Growth - Loveseat.com Online Auctions
We are excited to share our great numbers for August. Loveseat.com auctions continue to be a huge success with numbers going up and up. We had a record performance in August with over $105k in merchandise sales. Once September is closed, we'll have a record smashing Q3 to share. Please join our team by investing in the round!
Wefunder supports three different federal laws that allow startups to raise money legally. To comply with the law, Wefunder Advisors LLC and Wefunder Portal LLC (both owned by Wefunder Inc) also list startups depending on the regulation used.
Legal May 16th 2016
Wefunder Portal LLC
for 233 startups
Wefunder Advisors LLC
for 98 startups
for 1 startup
Curious how well the companies have done? Or how many raised follow-on financing?
Some fine print: 1) These numbers include startups currently live on Wefunder if they pass their minimum target. 2) Some startups use two different laws at the same time (i.e., Regulation D and Regulation Crowdfunding).
Join 312,353 investors who funded 319 startups with over $113.5 million1
wefunder.com/updates/124400-record-sales-amp-revenue-growth-loveseat-com-online-auctions is managed by
Wefunder Portal LLC.
Wefunder Inc. runs wefunder.com and is the parent company of Wefunder Advisors LLC and Wefunder Portal LLC. Wefunder Advisors is an exempt reporting adviser that advises SPVs used in Reg D offerings. Wefunder Portal is a funding portal (CRD #283503) that operates sections of wefunder.com where some Regulation Crowdfunding offerings are made.
Wefunder, Inc. operates sections of wefunder.com where some Regulation D and A offerings are made. Wefunder, Inc. is not regulated as either a broker-dealer or funding portal and is not a member of FINRA.
You may also view our Privacy Notice.

domain: economics


kicad-developers team mailing list archive
Mailing list archive
kicad-winbuilder script failing on build 3290
I've just posted this message to the kicad-users group
Just tried to build kicad with the kicad-winbuilder script.
It fails with these messages in the following logs
Build testing (unstable) version of Kicad
[3d-viewer/CMakeFiles/3d-viewer.dir/3d_aux.cpp.obj] Error 1
mingw32-make: *** [3d-viewer/CMakeFiles/3d-viewer.dir/all] Error 2
mingw32-make: *** [all] Error 2
-- Check for installed OpenGL -- found
-- Check for installed wxWidgets -- found
-- Bazaar version control system version found.
-- Kicad Bazaar build version: (2011-12-09 BZR 3290)
-- Could NOT find Doxygen (missing: DOXYGEN_EXECUTABLE)
-- WARNING: Doxygen not found - doxygen-docs (Source Docs) target not
-- Configuring done
-- Generating done
-- Build files have been written to:
Scanning dependencies of target 3d-viewer
[ 0%] Building CXX object
There is a pop up message that I will try and attach.
The popup says
cc1plus.exe-Unable to locate component
This application has failed to start because libgmp-10.dll was not
found.Re-installing the application may fix this problem.


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On Saturday, August 13, 2022 we will be working on the Adafruit Customer Support Forums. If you visit over the weekend and things are not complete yet, please check back later, https://adafruit.com/forumupdates
Pretty interesting article and accompanying video from TechCrunch about the JFK8 fulfillment center:
JFK8 stands as a kind of church to the world of early 21st century capitalism, and wherever you happen to land on the politics of Amazon, it’s an impressive sight to behold, as packages zip by on complex highway systems of conveyor belts, en route to next-day deliveries.
Stop breadboarding and soldering – start making immediately! Adafruit’s Circuit Playground is jam-packed with LEDs, sensors, buttons, alligator clip pads and more. Build projects with Circuit Playground in a few minutes with the drag-and-drop MakeCode programming site, learn computer science using the CS Discoveries class on code.org, jump into CircuitPython to learn Python and hardware together, TinyGO, or even use the Arduino IDE. Circuit Playground Express is the newest and best Circuit Playground board, with support for CircuitPython, MakeCode, and Arduino. It has a powerful processor, 10 NeoPixels, mini speaker, InfraRed receive and transmit, two buttons, a switch, 14 alligator clip pads, and lots of sensors: capacitive touch, IR proximity, temperature, light, motion and sound. A whole wide world of electronics and coding is waiting for you, and it fits in the palm of your hand.


The John Thornton Young Achievers Foundation was honoured to be chosen as the recipient charity for a Concert by two superb British Men's Choirs.
The Bournemouth Male Voice Choir teamed up with the Mousehole Male Voice Choir for a concert at St Mary's Church in Ferndown. It was a fantastic evening which raised an incredible £1481!
St Mary's Church was full to bursting for this wonderfully diverse programme. Beautiful harmonies, professional soloists and a spectacular venue captivated the audience who enjoyed a sensational performance by two very talented choirs. The retiring collection alone received an incredible £510 in donations which is testimony itself to a great evening. A huge thank you to all those who contributed.
The photo above shows Gerry Ramsden, right, presenting the 'big' cheque to JTYAF Chairman, Pete Thornton. Gerry nominated the charity for consideration so we are extremely grateful to him for this support.
We can't thank the members of the choirs enough for all the work that went into ensuring that this event was such a success and our thanks must also go to all those involved behind the scenes. £1481 will make a really big difference to a great many young people's lives


text:
This is the amplicon context sequence in accordance with the minimum information for the publication of real-time quantitative PCR experiements (MIQE) guidelines. For more details, please refer to the following publication, "Primer Sequence Disclosure: A Clarification of the MIQE Guidelines."
Real-time PCR probe assay designed for gene expression analysis. Probe assays consist of unlabeled PCR primers and a dual labeled fluorescent probe.
PrimePCR™ PreAmp for Probe Assay: LRP2, Human
PrimePCR™ Template for Probe Assay: LRP2, Human
The protein encoded by this gene low density lipoprotein-related protein 2 (LRP2) or megalin is a multi-ligand endocytic receptor that is expressed in many different tissues but primarily in absorptive epithilial tissues such as the kidney. This glycoprotein has a large amino-terminal extracellular domain a single transmembrane domain and a short carboxy-terminal cytoplasmic tail. The extracellular ligand-binding-domains bind diverse macromolecules including albumin apolipoproteins B and E and lipoprotein lipase. The LRP2 protein is critical for the reuptake of numerous ligands including lipoproteins sterols vitamin-binding proteins and hormones. This protein also has a role in cell-signaling; extracellular ligands include parathyroid horomones and the morphogen sonic hedgehog while cytosolic ligands include MAP kinase scaffold proteins and JNK interacting proteins. Recycling of this membrane receptor is regulated by phosphorylation of its cytoplasmic domain. Mutations in this gene cause Donnai-Barrow syndrome (DBS) and facio-oculoacoustico-renal syndrome (FOAR).[provided by RefSeq Aug 2009]
Products used to generate validation data:
Amplification of cDNA generated from universal RNA.
Melt curve analysis of above amplification.
Standard curve generated using 20 million copies of template diluted 10 fold to 20 copies.


text:
Back in June, the singer and talk show host Kelly Clarkson shocked her fans when she filed for divorce from her husband of seven years, Brandon Blackstock. This week, she opened up about her divorce like never before in an interview alongside her fellow “The Voice” judge Gwen Stefani, who she connected to through their shared heartbreak.
“It’s just one day when you’re like, ‘Wow, this has forever changed and it’s not just my heart has changed, there’s other little hearts, too,'” Clarkson told EXTRA of the moment she realized her marriage was over.
Clarkson and Blackstock are the parents of two children: River Rose, 6, and Remington Alexander 4.
Stefani, who managed to find love again with her fellow “The Voice” judge Blake Shelton after divorcing Gavin Rossdale, said, “Kelly and I have been talking about this a lot. We’re so lucky to have music as an outlet for everything we all go through… Music is such therapy when you’re a writer.”
“Why do you feel you need to be so transparent and what does it feel like when you get the support you receive?” Clarkson was asked.
“I have a great family and friends that are there for me… It’s a very hard thing to navigate, to be able to be honest and share your story, so maybe you can help someone else, but at the same time protecting these little kids you adore,” she replied.
“We have a lot of help as far as therapists or child psychologists ‘cause we want to do it right… Everyone’s sad and it’s okay to be sad,” Clarkson added.
Stefani chimed in to applaud Clarkson, saying that she is holding everything together well.
“You’re doing a really good job,” Stefani said. “I think it’s hard to be a public person. Now you add in a family… they didn’t choose it.”
Moving on from this subject, both women shared their strategies going into this season of “The Voice.”
“The strategy for me every season is just: beat Blake,” Clarkson said, with Stefani adding, “Well, I haven’t won yet… I think with Blake he’s spoiled, he just sort of takes it for granted because he has been on for 19 seasons… I just feel he needs to be destroyed… He needs a little reality check, and I would be happy to do that for him.”

domain: artistic


Engine:428 COBRA JET MOTOR
Model: Ford GT
Edison, New Jersey, United States
Nine Japanese suppliers have pleaded guilty in US court over charges of price fixing in the automotive parts industry, resulting in the Department of Justice doling out a total of $740 million of fines, according to a report from Bloomberg. The scandal, which has resulted in General Motors, Ford, Toyota and Chrysler spending up to $5 billion on inflated parts and driving up prices on 25 million vehicles has sent the DoJ hustling into investigations. "The conduct this investigation uncovered involved more than a dozen separate conspiracies aimed at the U.S. economy," Attorney General Eric Holder (pictured above) said during yesterday's press conference.
As the investigation stands, the DoJ has issued $1.6 billion in fines against 20 companies and 21 individual executives, with 17 of the execs headed to prison. Deputy Assistant Attorney General Scott Hammond said, "The breadth of the conspiracies brought to light today are as egregious as they are pervasive. They involve more than a dozen separate conspiracies operating independently but all sharing in common that they targeted US automotive manufacturers."
Big-name suppliers indicted in the investigation include Mitsubishi Electric, Mitsubishi Heavy Industries, Hitachi Automotive and Mitsuba Corporation. A list of fines and other corporations named in the investigation is available at Bloomberg.
You might expect a rare Ford GT40 to cross the block at some sort of prestigious auto auction from RM or Gooding, not show up on eBay for over $2 million. However, that's exactly what we have here. The seller claims the car is a late-build Mk1 GT40 from 1969, and it's currently owned by the director of the Hublot watch company in Switzerland.
According to the listing, GT40 #P1108 started life as Mk1 car that was built from factory spares in 1969 and was first sold in 1971. However, the auction is somewhat confusing. According to an image in its gallery, the vehicle was actually built from one of the seven spare Mk3 tubs when production of the iconic racers ended.
This GT40 was never built as a racecar - it lived on the streets its whole life. After assembly finished, it was sent to Germany and was eventually registered for the road. The first owner kept the car until 2005 and sold it with 7,300 miles on the odometer. The current owner bought it in 2012.
Here at Autoblog, we've officially stamped December 5, 2013, as Ford Mustang Day. Sure, the sixth-generation Pony Car started leaking out onto the web days ago, but all of the official, non-embargoed hotness has come out today. And man, there's been a lot.
In terms of new car debuts, this is a really big one - not unlike all of the Corvette madness that kicked off the 2013 automotive season. So to make sure you haven't missed anything, here's a wrap-up of everything you need to know about the 2015 Ford Mustang.
Deep Dive: 2015 Ford Mustang


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Between 40 and 50 percent of the cost of ownership and operation for a rooftop solar system is contributed by administrative costs such as permitting, financing and connecting to the grid, according to the Department of Energy (via the New York Times).
Ramamoorthy Ramesh, the manager of the DOE’s SunShot program and a materials scientist from the University of California at Berkeley, said these “soft costs” are often overlooked. But reducing these costs will increase installations, bringing about innovation and cuts to hardware costs, he said.
The SunShot initiative has a 2020 goal of bringing the price of installed solar power down to about six cents per kWh, on par with fossil fuels, without the use of ongoing subsidies. That’s from an average of 18 cents a kWh for consumers’ rooftop solar power systems today. The DOE hopes that the decrease will help solar power make up 15 to 18 percent of U.S. generation by 2030.
This month energy secretary Steven Chu announced 22 winners of $12.5 million in grants under the Rooftop Solar Challenge, which sought the best ideas for cutting permitting costs. Ramesh said that in a year, the winning teams will report their projects’ effect on these costs.
A recent study by researchers at Michigan Tech and Queen’s University, Kingston in Canada found that solar has already achieved grid parity with conventional energy in many regions, as calculated by the levelized cost of energy (LCOE), GreenTech Media reported.
The authors said that previous LCOE studies for small and medium-sized systems no longer apply because the costs of panels and balance of system have come down so quickly. Maintenance costs are also very low, installation prices are set to fall and durability has increased, the researchers said.
But according to Climate Change & Environmental Services owner Marc Karell, with the costs of solar power front-loaded at the installation stage, the choice to go solar is still a tough one for business. Companies by nature pass on all costs in the products they sell, so firms are concerned that solar PV may put them in an uncompetitive position, he says.


Video shared on social media shows that one of the accused pulling the female YouTuber by her hand in Khar. The woman is shouting "no, no" in an attempt to save herself. During which the incident happened, the woman was doing live streaming for her YouTube channel.
Mumbai: A video of alleged molestation of a Korean female YouTuber on a Mumbai road is going viral on social media. According to the police, the woman is a citizen of South Korea. During live streaming, two youths allegedly tried to do objectionable acts with her. However, the woman has not given any complaint in this matter. But the police themselves, taking cognizance of this incident, arrested both the youths.
In a video shared on social media, one of the accused can be seen pulling the female YouTuber by her hand in Khar. The woman is shouting “no, no” in an attempt to save herself. During which the incident happened, the woman was doing live streaming for her YouTube channel.
Last night on stream, there was a guy who harassed me. I tried my best not to escalate the situation and leave because he was with his friend. And some people said that it was initiated by me being too friendly and engaging the conversation. Makes me think again about streaming. https://t.co/QQvXbOVp9F
— Mhyochi in 🇮🇳 (@mhyochi) November 30, 2022
The video shows that the young man tries to come close to the woman even after her protest and is holding her hand.
As the woman starts to leave, the youth reappears with another person on the bike. Both offer lift to the woman. The woman flatly denies and says in broken English that her house is nearby.
The victim woman tweeted that a young man harassed me during livestreaming last night. I tried my best not to escalate the matter and left, as he was with her friend. And some people said that it was because of me being very friendly and starting the conversation. This incident has made me rethink about streaming.
The police have registered a case of sexual assault on its own based on the video.


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An ivory obi-hasami netsuke of a merman. Late 19th century With a humanoid head and holding his hands over his ears, the straight fish body with a curled tail fin, and a roundel carved with a coral branch amidst waves on his stomach. On the reverse a seal in raised characters reading Koku.
Masks for Noh Theater in lacquered wood depicting Daikijin, literally: the great God demon. Handcrafted by artisans from Japan and used in ceremonies and festivals in the years Kept in excellent condition by private collector.


Field range equipment control systems
Meggitt Training Systems believes that military field range operation should never be inhibited by shortcomings in the control system. It is for this reason that a number of options are available for legacy as well as current and future outdoor and indoor ranges.
RangeMaster™ 9000 (RM9K) range controller
For computer controlled ranges, Meggitt uses its RangeMaster™ 9000 (RM9K) family of devices. RangeMaster™ is a Microsoft Windows® based software application developed by Meggitt. RangeMaster™ controls targetry, simulators and other accessories for small arms and armor range systems. Most target commands are entered with a simple click of the mouse or selected from drop-down menus. Scenarios can be written directly on the RangeMaster computer or on any other computer using common word processing software. Target status, hit results and report generation are all available.
On traditional ranges with a control tower, the RM9K installation is typically a desktop computer with an accompanying adapter for cable or radio controlled application. The system also supports ranges using a combination of both radio and cable controlled targetry. On ranges where security is an issue when the range is vacant, a laptop computer can be employed and the laptop secured when not in use. Meggitt also offers a ruggedized laptop computer control package to allow range control from a vehicle or temporary location.
Meggitt radio controlled targets and simulators can also be controlled by a line of purpose-built portable, hand-held controllers. They allow programmed scenario preparation and execution as well as manual control of the targets. Hit results and target status are also available to the operator.
RangeMaster™ 10K (RM9K) range controller
Meggitt Training Systems revolutionized range operations by developing a range control system that allows range officers to leave the control room while still retaining complete control of the range. RangeMaster™10K control system combines touch screen technology and wireless communication to give range officers unprecedented control from any location in the range.
Handheld wireless devices provide the portability to allow range operators full automation of the range while interacting with the shooters at the line. With RangeMaster™10K, range operators are no longer confined to a control room so more time can be devoted to firearms instruction rather than range management.


Robinson Cano was forced to leave the Mariners game Sunday against the Tigers with a fractured bone in his right hand.
Robinson Cano left Sunday's game because of a hand injury.
Cano, an eight-time All-Star, has hit.287 with four home runs and 23 RBIs so far this season.More news: Britain's ex-minister, campaigner Tessa Jowell dies of cancer
The ejection came with Detroit catcher James McCann batting. The next hitter, Jean Segura, blasted a bases-loaded single up the middle past a diving Iglesias. Seattle tied it in the fourth on Dee Gordon's RBI single.
He was attended to by a trainer and left the game, replaced in the lineup by Andrew Romine.
In the opener, Jose Iglesias hit a two-run homer and former Oregon State pitcher Matthew Boyd (2-3) allowed three hits and three runs while striking out six and walking three in six innings for the win. Grayson Greiner followed with a single to right, and Jones scored on a very close play at the plate.More news: Thanos Arrives In 'Fortnite', Immediately Is Nerfed Because He Is Too Powerful
"It's disappointing to lose both the game and our second baseman", manager Scott Servais said. "I went out there trying to go as deep as I possibly can". He struck out seven and walked two.
Seattle Mariners' Jerry Dipoto announced today the following roster move: Dan Altavilla, RHP, returned from rehab assignment at AA Arkansas and activated from 10-day disabled list. With Acta managing, Ichiro Suzuki served as Seattle's bench coach for the two games.
Friday's game had been rained out, forcing the double dip.More news: Seann William Scott to star in 'Lethal Weapon' Season 3
Tigers: Castellanos was hit by a pitch in the first inning of the nightcap. He remained in the game in right field for the top of the second inning before being pinch-hit for by Victor Reyes in the bottom of the frame. The Mariners have the offensive edge in this one and they have a big edge on the mound with Paxton over Hardy, who is making his first Major League Baseball start after 167 games out of the pen in his career. He has yet to face the Tigers this year and did not record a start against them in 2017, either.


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Poll: What is your favorite film of 2003?
As we do these annual retrospectives on the InSession Film Podcast, we always try to decipher what it was that defined that cinematic year. In the case of 2003, many people remember that as the cinematic year where a fantasy epic would go on to sweep the Academy Awards, picking up a record-breaking 11 Oscars (tying Ben-Hur and Titanic). Many still hold The Lord of the Rings in the highest of regards, but should that overshadow the other greats that also came out in 2003?
So let’s see how the battle turns out. What is your favorite film of 2003?


text:
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Beyond person-centred care: a new vision for gerontological nursing.
A constructively critical look at some of the assumptions underpinning person-centredness is taken, and a framework describing the potential dimensions of relationship- Centred care is provided, and implications for further development are considered.
The Senses Framework: improving care for older people through a relationship-centred approach. Getting Research into Practice (GRiP) Report No 2.
This document is the author deposited version. You are advised to consult the publisher's version if you wish to cite from it. Published version NOLAN, M. R., BROWN, J., DAVIES, S., NOLAN, J. and…
Understanding family care : a multidimensional model of caring and coping
Family caregiving caring in context towards a more holistic conceptualization of caring stress and coping - implications for family caregiving satisfactions of caring - the neglected dimension family…
This article explores the strategies that spouses use in order to live positively when one partner has dementia. Data were collected from 152 interviews with 20 couples conducted over a period of…
Ethical and Methodological Issues in Interviewing Persons With Dementia
- I. Hellström, M. Nolan, L. Nordenfelt, U. Lundh
- Psychology, PhilosophyNursing ethics
- 1 September 2007
It is argued that there is support for the inclusion of people with dementia in research and that the benefits of participation usually far outweigh the risks, particularly when a `safe context' has been created.
Caring about caring: developing a model to implement compassionate relationship centred care in an older people care setting.
Transforming students' views of gerontological nursing: realising the potential of 'enriched' environments of learning and care: a multi-method longitudinal study.
'You do know he's had a stroke, don't you?' Preparation for family care-giving--the neglected dimension.
Based on initial data from a longitudinal study of stroke victims, this paper outlines four themes: 'What's it all about', 'Going it alone', 'Up to the job' and 'What about me?' These themes highlight the difficulties carers experience in the immediate aftermath of stroke.
'Making it better': self-perceived roles of family caregivers of older people living in care homes: a qualitative study.
Rewards and gratifications among family caregivers: towards a refined model of caring and coping.
- G. Grant, P. Ramcharan, M. McGrath, M. Nolan, J. Keady
- PsychologyJournal of intellectual disability research…
- 1 February 1998
It is suggested that caregivers report the existence of pervasive rewards and gratifications, as well as stresses, as part of the caregiving experience, and that these stem from varying sources.

domain: library


text:
|Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decrease the incidence of atrial fibrillation: a meta-analysis
|Huang G, Xu JB, Liu JX, He Y, Nie XL, Li Q, Hu YM, Zhao SQ, Wang M, Zhang WY, Liu XR, Wu T, Arkin A, Zhang TJ
The authors concluded that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decreased incidence of atrial fibrillation in patients with hypertension, chronic heart failure and atrial fibrillation and were effective for primary and secondary prevention of atrial fibrillation. The reliability of the authors' conclusions is limited by likely language bias, unclear study quality and uncertainties about combining variable studies.
To assess the antiarrhythmic effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the incidence of atrial fibrillation.
MEDLINE, EMBASE and The Cochrane Library were searched for papers published between 1950 and May 2009. Search terms were reported. Only papers published in English were considered. Reference lists of identified trials and review articles were handsearched.
Randomised controlled trials (RCTs) that compared ACEIs or ARBs (all types, doses and regimens) to active treatment or placebo in patients with cardiovascular diseases (hypertension, chronic heart failure, coronary artery disease, atrial fibrillation, myocardial infarction) were eligible for inclusion. The outcome measure was incidence of atrial fibrillation (new-onset atrial fibrillation, recurrent atrial fibrillation or atrial fibrillation reported as an adverse event) recorded by electrocardiogram (ECG) or 24-hour Holter monitoring at follow-up visits.
Study settings were varied: multinational (nine), Europe (10) and Asia (two). Mean patient ages (where reported) ranged from 52.6 to 76 years. Studies enrolled patients with different diagnoses (such as hypertension, chronic heart failure, post-myocardial infarction, atrial fibrillation, coronary heart disease and coronary artery, peripheral vascular or cerebrovascular disease). Some studies excluded patients with atrial fibrillation. Types and doses of ACEIs and ARBs varied (enalapril and lisinopril, valsartan, Irbesartan, telmisartan, perindopril, trandolapril, captopril, candesartan, losartan, ramipril). Comparators included placebo, amlodipine, amiodarone, atenolol and conventional therapy with or without calcium antagonists. Some patients also received beta-blockers and antiarrhythmic drugs. Follow-up ranged from 42 days to 6.1 years.
Two reviewers independently assessed studies for inclusion; disagreements were resolved with a third reviewer.
Assessment of study quality
Two reviewers independently assessed study quality (Delphi list and Jadad scores) by considering the adequacy of concealment of treatment allocation, eligibility criteria, blinding of outcome assessors, follow-up and use of intention-to-treat analysis. Disagreements were resolved by a third reviewer.
Two reviewers independently extracted data (using a predefined data extraction sheet) to enable calculation of relative risks (RRs) and their 95% confidence intervals (CIs). Disagreements were resolved by involvement of a third reviewer. Authors of primary studies were contacted for original data (events, treatment and control group information).
Methods of synthesis
Pooled relative risks and 95% CIs were calculated using random-effects meta-analysis. Heterogeneity was assessed with Χ² and Ι². Subgroup analyses were performed according to patient groups, primary and secondary prevention, onset of atrial fibrillation and agent class (ACEIs, ARBs). Sensitivity analysis assessed the effects of dimensions of study outcome measures and quality on effect estimates. Publication bias was assessed using Egger’s test.
Results of the review
Twenty-two RCTs (91,381 patients) were included. Seventeen trials had Jadad scores of at least 3 (maximum score 5); criteria used to compute the overall Jadad scores were unclear. Six RCTs were open label.
ACEIs and ARBs combined were associated with a 25% reduction in the incidence of atrial fibrillation (RR 0.75, 95% CI 0.66 to 0.85, Ι²=80%; 91,381 patients, 21 RCTs) compared to control.
Subgroup analyses (compared to control):
ACEIs and ARBs combined for primary prevention were associated with a 24% reduction in incidence of atrial fibrillation (RR 0.76, 95% CI 0.65 to 0.88, Ι²=78%; 66,937 patients, nine RCTs).
ACEIs and ARBs combined for secondary prevention were associated with a 27% reduction in the incidence of atrial fibrillation (RR 0.73, 95% CI 0.59 to 0.89, Ι²=81%; 24,444 patients, 12 RCTs).
ACEIs/ARBs combined were associated with a 20% reduction in incidence of new-onset atrial fibrillation (RR 0.80, 95% CI 0.70 to 0.92, Ι²=79%; 84,536 patients, 11 RCTs) and a 36% reduction in incidence of recurrent atrial fibrillation (RR 0.64, 95% CI 0.48 to 0.84, Ι²=83%; 6,845 patients, 10 RCTs).
ACEIs were associated with a 31% reduction in incidence of atrial fibrillation (RR 0.69, 95% CI 0.56 to 0.85, Ι²=77%; 46,186 patients, 11 RCTs). ARBs were associated with a 25% reduction in the incidence of atrial fibrillation (RR 0.75, 95% CI 0.63 to 0.88, Ι²=83%; 45,377 patients, 12 RCTs).
Further results of subgroup analyses (chronic and persistent atrial fibrillation, congestive heart failure, paroxysmal atrial fibrillation and others) were reported in the paper.
Egger’s test suggested presence of publication bias (p=0.002). Overall results did not change significantly in sensitivity analyses.
ACEIs and ARBs decreased the incidence of atrial fibrillation in patients with hypertension, chronic heart failure and atrial fibrillation and were effective for primary prevention and secondary prevention of atrial fibrillation.
The review addressed a clearly stated question. Three major databases were searched for publications in English, which raised the possibility of language bias. Study selection, data extraction and validity assessment were done in duplicate, which minimised likely biases and errors. Study quality was assessed with appropriate criteria, but criteria for individual trial scores was unclear.
The decision to combine study results may have been inappropriate given significant study differences. Statistical heterogeneity was explored, but no moderator variables were identified. The review included several studies with a large overall sample size.
The reliability of the authors' conclusions is limited by weaknesses (likely language bias, uncertainty regarding study quality and considerable variation among studies) that mean that meta-analysis may not have been appropriate.
Implications of the review for practice and research
Practice: The authors stated that the conclusions should be interpreted cautiously "although ACEIs showed larger magnitude of effect than ARBs it is not reasonable to conclude that ACEIs have a greater effect than ARBs in reducing the incidence of atrial fibrillation".
Research: The authors noted that there ongoing RCTs were investigating the effects of ACEIs or ARBs on atrial fibrillation in patients with hypertension, post-catheter ablation, postcardiac surgery, sick sinus syndrome and hypertension and permanent pacemakers (further details were reported). They also stated that large double-blinded RCTs and head-to-head comparative studies of ACEIs and ARBs on patients with atrial fibrillation accompanied by coronary heart disease or post-myocardial infarction were needed.
Huang G, Xu JB, Liu JX, He Y, Nie XL, Li Q, Hu YM, Zhao SQ, Wang M, Zhang WY, Liu XR, Wu T, Arkin A, Zhang TJ. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decrease the incidence of atrial fibrillation: a meta-analysis. European Journal of Clinical Investigation 2011; 41(7): 719-733
Subject indexing assigned by NLM
Aged; Angiotensin II Type 1 Receptor Blockers /therapeutic use; Angiotensin-Converting Enzyme Inhibitors /therapeutic use; Anti-Arrhythmia Agents /therapeutic use; Atrial Fibrillation /drug therapy /prevention & Humans; Middle Aged; Randomized Controlled Trials as Topic /methods /standards; Treatment Outcome; control
Date bibliographic record published
Date abstract record published
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.


Inflation has cooled, but investors risk being caught off guard by a 'head fake' that could halt the latest stock-market rally
Decelerating headline inflation has aided a jump in stocks so far this year, but keep watch for "stickiness" in prices for services, analysts say.
It's great timing for the US's first immigration boost in years — but experts say Biden needs to reverse more Trump-era policies for the economy to feel the maximum effect
If immigrant workers are truly going to solve the US labor shortage, Biden will have to undo more Trump decisions.
The dollar has weakened as the rest of the global economy kicks back into gear. That might make it harder to bring down inflation in the US.
I asked ChatGPT investors' burning questions – and a CIO told me why the bot won't be challenging Wall Street's top stock-pickers anytime soon
Morningstar Investment Management's Dan Kemp called some of the language bot's knowledge "remarkable" - but isn't worried it'll put him out of a job anytime soon.
Inflation is impacting everyone — but what do you do when you only have two grocery stores? Tim Connon said it's been tough to stay on budget.
Here's why investors should consider putting money in the market now as optimism climbs, according to Vanguard's head of investor research
"Stay the course," Vanguard's Fiona Greig told Insider. "Don't let volatility and short-term fluctuations cause you to pull out unnecessarily."
The Dow and the S&P 500 gained more than 2% for the week, and the Nasdaq jumped more than 4%.
As egg prices climb, advocacy groups and politicians call on FTC to investigate possible price gouging scheme: 'Somebody needs to pay attention'
While egg companies claim an outbreak of avian flu, combined with inflated supply chain costs, justify record-high prices, others are calling foul.
Core PCE increased in December by 4.4% from a year ago, down from November's annual pace of 4.7% and in line with forecasts.
Onions are now so expensive in the Philippines that they've become a luxury item — and people have been trying to smuggle them across the border
The price of onions soared to $12.80 per kilogram in December, following harsh tropical storms that damaged the crops.
Biden says the House GOP campaigned on inflation but their bills to weaken or even abolish the IRS wouldn't fix it
After receiving promising economic data, Biden criticized House Republicans on Thursday for their tax proposals.
Recession is almost a given, and Biden's team 'don't know what they are talking about' as they play down the risk, Santa Lucia investment chief says
Investors should brace themselves for an almost certain recession this year, according to the chief investment officer of Santa Lucia Asset Management.
Gross domestic product for the fourth quarter rose at a 2.9% annualized pace, the Commerce Department said Thursday.
Americans are battling an egg price crisis after an almost 60% surge in 2022. Here's what's happening.
Bird flu outbreaks and soaring input costs have driven up the average price of a dozen eggs in the US to more than $3.70, according to the Bureau of Labor Statistics.
Nobel economist Paul Krugman says we're not in a debt crisis, but the US could still be facing a lot of economic problems in a few years
The US has the largest national debt balance in the world, and it could pose problems down the line, top economist Paul Krugman warned.
Don't rule out further inflation surprises yet, and here are 3 ways for investors to predict them, Goldman Sachs says
Goldman Sachs says monitoring commodity prices, recent currency movements, and CPI releases in nearby countries can help smooth out surprises.
A bullish trifecta of stock market indicators is flashing, and it suggests a 20% rally is on the horizon, Fundstrat's Tom Lee says
The trio of bullish indicators combined with falling inflation mean stocks are poised to rally through 2023, Fundstrat's Tom Lee said.
The stock market is underestimating sticky cost inflation that's eating away at company profits, says Morgan Stanley's Mike Wilson
Mike Wilson warned the market is underestimating businesses' struggle to balance out their costs and revenue as inflation remains sticky.
Volatility will continue to hammer markets in 2023 and people are fretting over retirement savings. Here are 3 big takeaways from Allianz's latest markets survey.
Only 19% of respondents to an Allianz Life survey said they're ready to invest now and are comfortable with current market conditions.
Earnings season is heating up, with industrial giants GE and 3M reporting early Tuesday while tech heavyweights are due later.


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* To whom correspondence should be addressed.
Received March 29, 2010; Revision received May 21, 2010
O-GlcNAcase (OGA) is a family 84 glycoside hydrolase catalyzing the hydrolytic cleavage of O-linked β-N-acetylglucosamine (O-GlcNAc) from serine and threonine residues of proteins. Thus far, three forms of OGA have been identified in humans. Here we optimized the expression of these isoforms in E. coli and characterized their kinetic properties. Using Geno 3D, we predicted that N-terminal amino acids 63-342 form the catalytic site for O-GlcNAc removal and characterized it. Large differences are observed in the Km value and catalytic efficiency (kcat/Km) for the three OGA variants, though all of them displayed O-GlcNAc hydrolase activity. The full-length OGA had the lowest Km value of 0.26 mM and the highest catalytic efficiency of 3.51·103. These results reveal that the N-terminal region (a.a. 1-350) of OGA contains the catalytic site for glycoside hydrolase and the C-terminal region of the coding sequence has the ability to stabilize the native three-dimensional structure and further affect substrate affinity.
KEY WORDS: O-GlcNAcase, isoform, substrate affinity, catalytic efficiency
Abbreviations: DTT, dithiothreitol; fOGA, full-length O-GlcNAcase; IPTG, isopropyl-L-thio-β-D-galactopyranoside; LB, Luria–Bertani (broth); MGEA5, meningioma expressed antigen 5; 4-MU-GlcNAc, 4-methylumbelliferyl-2-acetamido-2-deoxy-β-D-glucopyranoside; OGA, O-GlcNAcase; PCD, programmed cell death; sOGA, the shortest OGA; vOGA, variant of OGA.
O-GlcNAcylation is a newly discovered post-translational modification in cell regulation of signal transduction and now has been found in all metazoans [1-3]. So far, more than 1000 proteins (including nuclear pore proteins, cytoskeletal proteins, transcription factors, oncogenic proteins, tumor suppressor proteins, etc.) have been identified to be O-GlcNAcylated and these proteins are involved in many important cellular processes such as transport, transcription, cell shaping, cell signaling, and apoptosis [4-6]. Analogous to phosphorylation/dephosphorylation, the cycle of addition/removal of the sugar moiety is rapid. Emerging data have demonstrated that O-GlcNAcylation can play an important role in many human diseases such as type II diabetes, cancer, and neurological disorders [7-9].
In mammals, O-GlcNAc cycling is regulated by two enzymes: O-GlcNAc transferase (OGT, EC 220.127.116.11) and O-GlcNAcase (OGA, EC 18.104.22.168), which are products of single genes [10, 11]. Based upon MS/MS sequencing, the human OGA gene has been cloned from brain . Sequence alignment indicates that this gene is identical with MGEA5 (meningioma expressed antigen 5), which locates at 10q24.1-q24.3, a region associated with Alzheimer’s disease . The human OGA gene is capable of producing two separate transcripts, and each encodes a different OGA isoform. The long isoform gene consists of 16 exons and encodes a full-length protein with 916 amino acids. This full-length O-GlcNAcase (fOGA) is a bifunctional enzyme consisting of two domains: an N-terminal hydrolase catalytic domain belonging to glycoside hydrolase family 84 and a C-terminal domain belonging to the GCN5-related family of histone acetyltransferases . The spliced transcript variant of OGA (vOGA) is the product of alternatively spliced transcript of OGA gene, which ignores the 5′-splicing site of intron 11 resulting in a longer exon 10 with an alternative stop codon, and it encodes a truncated protein of 677 amino acids . Using cell fractionation and immunofluorescence staining, it has been shown that fOGA is primarily cytoplasmic, while vOGA is nuclear in location . Based on sequence and structural information, we predicted that the N-terminal a.a. 63-342 is the catalytic site for O-GlcNAc removal and created another OGA variant – sOGA (the shortest OGA), which is a region corresponding to amino acids 1-350 of the amino terminus.
These three forms of OGA have identical N-terminal 1-350 amino acids, but differ in their C-terminal region (Fig. 1). Although glycoside hydrolysis activity has been reported for the three forms previously, a number of aspects about the catalysis are not clear. Is there a difference in the catalytic efficiencies of these OGAs? What is the structural basis for the glycoside hydrolase activity? What is the role of the C-terminal region in catalysis? In addition, one of the major bottlenecks for structural studies on OGAs of human origin has been the poor expression levels of the enzyme. To address these issues, we optimized the production of OGA forms using an E. coli expression system and then purified them. Using 4-MU-GlcNAc (4-methylumbelliferyl-2-acetamido-2-deoxy-β-D-glucopyranoside) as substrate, their steady-state kinetics were determined. The model of the catalytic domain of hOGA provides the structural basis for the hydrolytic activity of the hOGAs.
Fig. 1. Diagrammatic representation of three variants of human O-GlcNAcase. fOGA (full-length O-GlcNAcase) is the longest isoform and is composed of an N-terminal O-GlcNAcase domain, a linker region, and a C-terminal acetyltransferase domain. vOGA (spliced variant) contains the N-terminal O-GlcNAcase domain and the linker region. sOGA (hydrolase catalytic domain) is the smallest OGA consisting of N-terminal amino acids 1-350.
Bacterial strains, plasmids, and materials. Human O-GlcNAcase cDNA (GenBank accession number AB014579) was kindly provided by Dr. Hart from the Medical School of Johns Hopkins University. Escherichia coli DH5α was purchased from Gibco-BRL Life Technology (USA). Escherichia coli BL21(DE3) was from Novagen Inc. (USA). pET-28a and pET-32a were purchased from Novagen. Restriction enzymes were obtained from Fermentas (USA). Ex Taq, Taq DNA polymerases, and T4 ligase were bought from Takara (China). 4-MU-GlcNAc (4-methylumbelliferyl-2-acetamido-2-deoxy-β-D-glucopyranoside) was purchased from Sigma Aldrich (USA). Other chemicals were of the highest grade from commercially available sources.
Cloning of fOGA, vOGA, and sOGA. Three OGA genes were amplified by PCR using the following primers and procedures. All primers were designed using the Primer Premier 5.0 program. Since the N-terminal 1-350 amino acids are identical, one forward primer was used for amplifying the three genes. The primer sequences were as follows: f-forward, 5′CGCGCGGCCGCGTGCAGAAGGAGAGTCAA3′ (NotI); f-reverse, 5′GCGCTCGAGTTACAGGCTCCGACCAAGT3′ (XhoI); v-reverse, 5′GCGCTCGAGAAGGGACAATATATTTGAGGAGAA3′ (XhoI); s-reverse, 5′GCGCTCGAGTTAATCTTCACTGTCAGTCATC3′(XhoI). The PCR products were subcloned in-frame into pET-28a and pET-32a between NotI and XhoI sites. The resultant constructs with OGA gene were subsequently transformed into E. coli DH5α for amplification and then into E. coli BL21(DE3) for protein expression. The insertion of each gene was confirmed by restriction mapping and sequencing.
Overexpression and purification of the OGAs. Escherichia coli BL21(DE3) transformed with the expression plasmid was grown in Luria–Bertani (LB) broth supplemented with 50 µg/ml kanamycin at 37°C at 200 rpm. Protein expression was initiated by the addition of IPTG (isopropyl-L-thio-β-D-galactopyranoside) to a final concentration of 0.01-0.5 mM when the optical density at 600 nm reached around 0.6. The cultures were further grown for 5-15 h at 16°C at 150 rpm. Cells were harvested by centrifugation and resuspended in 50 mM phosphate buffer, pH 8.0, 300 mM NaCl. The cells were sonicated using a Vibra Cell Sonifier (Scientz-IID, China) with a 19 mm-threaded probe. The sonication conditions were 10 sec per cycle (pulse on time is 2 sec, and pulse off time 8 sec), 40% output, and sonication for 30 min. Cell debris was removed by centrifugation (13,000g, 30 min, 4°C), and the supernatant was loaded onto a Ni2+-NTA (nickel-nitrilotriacetic acid) column (Qiagen, USA). After vigorous washing, the bound protein was eluted using 50 mM phosphate buffer, pH 8.0, 300 mM NaCl, and 300 mM imidazole. A Microcon YM-50/YM-100 microconcentrator (Millipore, USA) was used for buffer exchange and concentration. The recombinant protein was exchanged into 50 mM Tris-HCl buffer, pH 7.0, containing 1 mM dithiothreitol (DTT), 10% glycerol, and 150 mM NaCl. Protein concentration was estimated by the Bradford method . The purity and apparent molecular mass were determined by SDS-PAGE .
Model of human OGA. A model of the catalytic domain of human OGA was generated using Geno 3D . Amino acids 63-342 of human OGA matched with the primary amino acid sequence of PDB entry 2CBI, showing an identity of 34% and an E value of 1·10–144. After energy minimization, a model of OGA (residues 63-342) was obtained; it had excellent geometry as judged by Ramachandran analysis.
Enzymatic assays. Assays were carried out according to the method of Macauley . 4-MU-GlcNAc was used as the fluorescent substrate; 25 µl of the reaction mixture consisted of the substrate suspended in 50 mM NaH2PO4, 100 mM NaCl, and 0.1% BSA at pH 6.5. Assays were initiated by the addition, via syringe, of enzyme (2-6 µl), and the reaction mixture was incubated at 37°C for 4-30 min. The enzymatic reactions were quenched by the addition of 150 µl of quenching buffer (200 mM glycine, pH 10.75). A standard curve of 4-MU (4-methylumbelliferone) was obtained using a Varian Cary Eclipse fluorescence spectrophotometer 96-well plate system. Fluorescence was measured at the excitation wavelength of 368 nm and the emission wavelength of 450 nm. The produced 4-MU was determined and compared with the standard curve. All assays were performed in triplicates under identical conditions.
Expression of OGA. To obtain high expression, the concentration of the inducer, induction time, and induction temperature were optimized. Induction temperature is a key factor for soluble expression. When it was above 16°C, most of the protein was insoluble. So 16°C was employed for expression. Briefly, E. coli BL21(DE3) cells transformed with pET28a-sOGA were grown in liquid medium at 37°C until the optical density at 600 nm reached around 0.6. The effect of the concentration of IPTG and the induction time on the expression of OGA was determined by inducing individual cultures under different inducer concentrations (0.01-0.25 mM) and induction times (5-15 h). After inductions at 16°C, 10 ml of bacterial culture was centrifuged and disrupted by sonication. The supernatants of crude extracts were analyzed by 10% SDS-PAGE. The results demonstrated that His6-tagged sOGA reached maximum soluble expression after 10 h induction with 0.05 mM IPTG (Fig. 2). Similarly, the maximum production of fOGA and vOGA was obtained when the recombinant cells were induced for 10 h with the addition of 0.25 and 0.1 mM IPTG, respectively.
Production and purification of OGA. Using the optimal expression conditions, three His6-tagged OGA genes were overexpressed and purified by Ni2+-NTA chromatography. Recombinant fOGA, vOGA, and sOGA migrated at 130, 80, and 43 kDa, respectively, which is consistent with previous findings [20, 21]. Expression level of soluble active OGA was 5-15 mg per liter of the culture. After Ni2+-NTA affinity chromatography, the protein was more than 90% pure as judged by SDS-PAGE (Fig. 3).
Fig. 2. Expression of His6-tagged sOGA. Lanes: 1) growth with 0.01 mM IPTG, 5 h; 2) growth with 0.01 mM IPTG, 10 h; 3) growth with 0.01 mM IPTG, 15 h; 4) growth with 0.025 mM IPTG, 5 h; 5) growth with 0.025 mM IPTG, 10 h; 6) growth with 0.025 mM IPTG, 15 h; 7) growth with 0.05 mM IPTG, 5 h; 8) growth with 0.05 mM IPTG, 10 h; 9) growth with 0.05 mM IPTG, 15 h; 10) protein marker.
Characterization of OGA. Initial velocities of the enzymatic reaction were determined by varied 4-MU-GlcNAc concentrations. Kinetic parameters including Michaelis constants (Km), turnover numbers, and enzymatic efficiencies were calculated from Lineweaver–Burk plots (Fig. 4). The specific activity of each OGA was calculated with the methods described in “Materials and Methods”.
Fig. 3. SDS-PAGE of the human OGAs expressed and purified from E. coli. Lanes: 1) fOGA; 2) vOGA; 3) sOGA; 4) protein marker.
fOGA had a Km of 0.26 mM and a specific activity of 526 nmol/min per mg with a turnover rate of 0.9 sec–1. Catalytic efficiency (kcat/Km) of fOGA was 3.5·103 sec–1·M–1. Similarly, vOGA and sOGA exhibited Km values of 0.7 and 1.84 mM and specific activities of 84 and 9 nmol/min per mg, respectively. Based on these data, the turnover numbers of vOGA and sOGA were approximately 0.11 and 0.006 sec–1 and catalytic efficiencies were 1.57·102 and 3.26 sec–1·M–1, respectively. The kinetic values for the three OGA isoforms are summarized in the table.
Fig. 4. Enzyme kinetics of the three His6-tagged OGAs expressed by pET-28a(+). An activity curve and a Lineweaver–Burk plot were generated by varying concentrations of substrate (4-MU-GlcNAc). a) fOGA; b) vOGA; c) sOGA.
Kinetic parameters of His6-tagged recombinant human OGAs
Catalytic domain of human OGA is reminiscent of glucosidases. The N-terminal amino acids 63-342 of OGA could be modeled successfully using Geno 3D (Fig. 5a; see color insert). Analysis of this model revealed that the N-terminal region spanning amino acids 63-342, folds into a classical (α/β)8 TIM barrel structure commonly found in glucosidases. Three OGA forms have this identical region and all showed glucosidase hydrolysis activity in this study.
The active site pocket could be identified by superimposing the NAG-thiazoline (NGT) moiety of the bacterial O-GlcNAcase (PDB code 2CHN) on the modeled human OGA (Fig. 5b). Catalysis proceeds via a substrate-assisted mechanism involving the acetamido group. The acetamido group is in the vicinity of D174, which is critical for the polarization and correct orientation of the group for a nucleophilic attack at the carbonyl carbon. D175 probably assumes the role of catalytic acid. A pair of aspartates is found at similar locations in the bacterial O-GlcNAcase structures . Y219 is within hydrogen bonding distance of the glycosidic oxygen. A tyrosine at a similar position in GH85 family of glucosidases was shown to activate a water molecule for a nucleophilic attack during the hydrolysis . Residues D174, D175, and Y219 of human OGA are conserved in bacterial O-GlcNAcases and have been shown to be critical for catalysis . The model of human OGA (amino acids 63-342) provides a structural basis for the hydrolysis activity of the three forms of hOGA.
Fig. 5. (Jing Li et al.) a) Cartoon representation of the catalytic domain of hOGA. Amino acids 63-342 of hOGA were modeled using Geno 3D. b) Structural basis for hydrolysis activity of hOGAs. NGT, from PDB code 2CHN, shown as yellow sticks, is superimposed over hOGA. Asp174, shown as sticks, is hydrogen bonded to the nitrogen atom.
In this study, initial steady-state enzyme kinetics for human OGAs were determined using 4-MU-GlcNAc as a substrate. fOGA has a Km of 0.26 mM and a catalytic efficiency (kcat/Km) of 3.5·103, while vOGA and sOGA exhibited higher Km values of 0.7 and 1.84 mM and lower catalytic efficiencies of 1.57·102 and 3.26, respectively. These results indicate that the N-terminal region harbors the catalytic site for O-GlcNAc removal, which is in agreement with many previous studies [19-21]. However, there are conflicting reports on enzymatic activity of vOGA [13, 15]. No activity was detected for vOGA expressed in either E. coli or COS-7 cells , and therefore the authors concluded that the C-terminus is necessary for O-GlcNAcase activity. We speculate that the ambiguity in the results could be a result of the expression strategy (enzyme was expressed with a thioredoxin tag) or because a less sensitive substrate (pNP-β-GlcNAc) was used for measuring the enzyme activity.
Thioredoxin (Trx) is an approximately 10-kDa protein fused on the N-terminus in pET-32 series to increase the solubility of recombinant proteins. To identify whether Trx impairs O-GlcNAcase catalytic activity, we subcloned three OGA isoform genes into pET-28a (with 6xHis tags only) and pET-32a (with 6xHis tags, S tag, and TRX tag), and large differences were observed in the enzyme kinetic parameters. The enzymatic activities of Trx-sOGA and Trx-vOGA were almost not detectable (data not shown). In addition, pNP-β-GlcNAc is a common substrate for standard OGA enzyme assay. Enzyme activity is monitored spectrophotometrically by measuring the absorbance at 400 nm of a p-nitrophenolate ion that is enzymatically released from pNP-β-GlcNAc . Since the substrate undergoes only a modest change in absorbance upon cleavage, this assay is relatively insensitive. MUGlcNAc is a more sensitive fluorescence substrate for glycosidase assay; we used it to determine the kinetic parameters of the three OGA isoforms and obtained better results as expected.
O-GlcNAcylation is a highly dynamic process that is constantly responding to the extracellular environment [4, 5]. Cells under stress due to nutrient depletion or in an excessively nutrition rich environment were shown to have elevated levels of O-GlcNAc, which promoted cell survival . Interestingly, the rate of O-GlcNAc cycling varies significantly for different proteins. In generally, the O-GlcNAc moiety of some nuclear proteins (e.g. nuclear pore proteins) is recycled slowly and has a longer half-life than that of the cytoplasmic proteins . From our kinetic studies, we speculate that the difference in the half-life of the O-GlcNAc moiety on the proteins might be due to the different catalytic efficiencies of fOGA and vOGA.
In conclusion, we have subcloned, expressed, and characterized two isoforms of human OGA and a fragment of human OGA, designated fOGA, vOGA, and sOGA, respectively. The three recombinant forms of hOGA exhibited distinct enzymatic properties. fOGA displayed the lowest Km value and the highest enzymatic efficiency (kcat/Km). In comparison, vOGA and sOGA, harboring a truncated C-terminal region, showed much higher Km values and lower enzymatic efficiencies. Such differences in enzymatic efficiencies might help the OGA forms to adapt to different roles in different subcellular compartments and modulate their activities during different stages of cell development. Structural studies of human OGA support and provide structural basis for the hydrolysis activity of OGA.
The authors thank Dr. G. W. Hart from the Medical School of Johns Hopkins University for kindly providing the human O-GlcNAcase cDNA and Neil Shaw from the Institute of Biophysics, Chinese Academy of Science, and Xian-Wei Liu for kind assistance in revision of the paper.
This work was supported by the National Basic Research Program of China (973 Program, grant No. 2007CB914403).
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domain: chemistry


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What makes Ireland such a great fishing destination? A coastline of more than 5,603km (3,472 miles), thousands of lakes and ponds, countless creeks, rills, streams, and rivers -- those certainly don't hurt. Ireland's temperate climate and low pollution also encourage a high fish population, and low human density has put little pressure on that. It all adds up to fairly ideal fishing conditions.
The sport of fishing -- referred to by the Irish as angling -- is a cherished tradition. Festivals and competitions celebrate the many forms of this sport; for dates and locations, contact Tourism Ireland; you have to sign up well in advance to participate in most of the competitions. Among the festivals are Killybegs International Sea Angling Festival in July, the Baltimore Deep Sea Angling Festival (www.baltimoreseaangling.com) in August, and the Cobh International Deep Sea Angling Festival in September.
In the west and northwest, Killybegs is a center for sea angling, while Lough Corrib offers much to entice the freshwater angler. The Killarney area is a popular angling destination, as are the Blackwater River near Cork and Kinsale for sea angling. Also consider the Shannon River and its lakes.
The best all-round online resource for fishing in Ireland is the prosaically named Fishing in Ireland (www.fishinginireland.info). In addition to up-to-date details on licenses and permits , it also has a wealth of information on everything from local regulations, weather, and tides to locations suitable for anglers with disabilities. Tourism Ireland devotes a section of its website to fishing. Visit www.discoverireland.com, click on "Things to see & do," then "Activities," and then "Fishing."
A helpful brochure, Angling in Ireland, detailing what fish can be caught where, is available from the Angling Information Office at the Central Fisheries Board, Swords Business Campus, Swords, County Dublin (tel. 01/884-2600; fax 01/836-0060; www.cfb.ie). Another helpful resource, The Angler's Guide, is published by Tourism Ireland. Permits, licenses, and specific information can also be obtained from local outfitters or the Central Fisheries Board.
Fishing seasons are as follows: salmon, January 1 to September 30; brown trout, February 15 to October 12; sea trout, June 1 to September 30; coarse fishing and sea angling, all year. A license is required only for salmon and sea trout angling; the cost is €20 for a day, €46 for 21 days, or €120 annually. For information about permits, visit the Central Fisheries Boards website (www.cfb.ie). You can purchase fishing licenses at most bait and tackle shops. For all private salmon and sea trout fisheries, a permit is required in addition to the license, and it can be considerably more expensive. Prices vary greatly, from €10 to €200 per rod per day (depending on the venue and provider), although most permits run €30 to €40.
Many hotels have exclusive access to lakes and ponds, and will rent boats, gear, and ghillies (fishing guides) to their guests. Over a dozen such hotels have formed the Great Fishing Houses of Ireland (www.irelandfishing.com). Examples include Adare Manor in Limerick; the Delphi Lodge in County Galway; and Newport House Hotel and Enniscoe House, both in Mayo.
In Northern Ireland, you must get a rod license from the Department for Culture, Arts and Leisure (DCNI), 1-7 Bedford St., Belfast, County Antrim (tel. 028/9025-8825; www.dcalni.gov.uk), or in the Derry area from the Foyle Carlingford Irish Lights Commission, 22 Victoria Rd., Derry (tel. 028/7134-2100; www.loughs-agency.org). A permit may also be required; you can obtain information from local outfitters or the DCNI. A rod license costs £3.50 to £24, depending on the license provider and duration of license; day permits cost around £10. You can find a wealth of information in An Information Guide to Game Fishing, available from any office of the Northern Ireland Tourist Board.
Note: This information was accurate when it was published, but can change without notice. Please be sure to confirm all rates and details directly with the companies in question before planning your trip.

domain: hobby


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- published: 05 Jun 2017
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Hello everyone, Here's another record of my full day meals when I was travelling in BATAM. Don't sweat too much when you were travelling, keep in your mind to pick the healthiest option that is available around, yet still enjoy the little knick-knacks here and there. This lifestyle is not about restrictions, it's all about balance and staying happy throughout the process. So I hope you enjoy this video, stay connected in my Instagram : @itscindyowada ---
The Batam Pediatric Health screening is an annual event held by Yayasan Citramas Indonesia in collaboration with KK Women's & Children Hospital Singapore, Duke-NUS Graduate Medical School Singapore and Yayasan Palang Merah Indonesia. The event aims to screen the pediatric population in the rural areas of Batam from illnesses and to help improve the health of this population by providing nutrients and health education. The screening this year was held in a warehouse owned by PT Citramas in the village of Kabil on the 24-25 September 2011.
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Nugget Sehat Batam, Nugget Batam, Supplier Nugget Batam, Jual Nugget Batam, Frozen Food Batam, Healthy Frozen Food Batam, Nugget Non MSG Batam, Nugget Tanpa Pengawet Batam, Nugget Sehat, Nugget Ayam Batam, Nugget Sehat Batam, Reseller Nugget Batam, Distributor Nugget Batam, Export Nugget, Beli Nugget Sehat, nugget sehat untuk anak, resep nugget sehat untuk batita, nugget ayam sayur, nugget tanpa msg jogja, nugget tanpa msg surabaya, nugget tanpa msg jakarta, frozen food sehat, frozen food palembang, frozen food bisnis, Perkenalkan kami adalah NatuNugget Food, Produsen Healthy Frozen Food di Batam Contact NatuNugget Food HP/WA : 0813-6387-7027 (Tsel) E-mail : firstname.lastname@example.org LINE Official : bit.ly/linenatunugget LINE ID : syaifudin.success Facebook : facebook.com/natunugget
Avocado juice is also known as Juice Alpukat in Bahasa Indonesia. The avocado juice we tried was filled with fresh pulps of avocado and chocolate. It was simply amazing. Every sip of the juice was simply mouth watering. This is a must to try when you visit Indonesia. We tried this juice at KTM resort in Batam, Indonesia.
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Last Month I Went To Batam , I Was Eating At This Restaurant Call Kaiten Sushi And The Spoon Was Bigger Than Average Spoons !!! Press the bell to join the #notificationsquad Free GiftCards - http://abo.io/ezzngjki | My Gaming Channel | - https://www.youtube.com/channel/UCeti... | Subscribe To Me It's Free! | - https://m.youtube.com/channel/UCO0rUxU_TkQOEo7WNhvMEAw Connect With Me *Snapchat - Drbaccon *Instagram - http://www.instagram.com/huaijr *Patreon - Huai Vlogs *Twitter - http://www.twitter.com/huaivlogs
Nature Vegetarian Restaurant Batam Komp. Ruko Baloi Kusuma Indah Blok A No. 1-2 Batam 29432 Telp. 0778-7205550 *For further information Website: www.natureresto.com Email: email@example.com A wide choices of vegetarian dishes which are inexpensive; very good ambiance and friendly/helpful staff. There are some dishes which are served with eggs so specify in advance if you are vegan. Accepts credit cards.
Soap for Hope - By providing local communities with the tools and training to transform discarded hotel soaps into recycled bars of soap, Soap for Hope not only provides our hotel customers with an opportunity to reduce their waste, but also provides for the health and livelihood of the local community.
Health is for everyone. MHC Healthcare donated a new van for an education centre in Batam which provides free education for the needy and poor children from the villages. We conducted health screening such as eye sight test for the children. Other activities include learning through games. computer classes for the young and old. A health for community project my staff of MHC Healthcare because Health is for everyone.
Batamtvnews.com BATAM – Dengan misi menjalin kebersamaan dan mempereratkan tali silaturahmi, pada minggu (31/08) pagi, jajaran kecamatan Bengkong menggelar jalan santai, lomba nasi tumpeng dan pembuatan pudding. Kegiatan tersebut juga bersempena dalam memeriahkan HUT RI ke-69.
Video udara acara Carnival PT. Epcos Indonesia (TDK) yang sekaligus acara Family Day dan Gathering tahun 2015. Berlokasi di main street Epcos Jaya, Panbil Industrial Park, Batam, Indonesia. Pada tanggal 17 Agustus 2015, Jam 08.00-15.00 wib EO oleh Dige Batam Event Organizer. Telp : +62.8127028387 (Demank), +62.85765100911 (Arif) Email : DigeBatam@yahoo.com www.digebatam.blogspot.com
Badam Milk is a tasty and healthy drink, which can served both hot and cold to all age groups. It can easily be made at home with key ingredients of Milk, Almonds, sugar and saffron.


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Dimensions:Height - 18" Width - 29" Depth - 24"
Daystar Cocktail Ottoman
Coordinating with the Daystar Sofa & Loveseat & keeping with a contemporary style, the Cocktail Ottoman is a perfect addition to kick your feet up on after a long day. Upholstered in a Mercer print for extra style.
Dimensions:Height - 19" Width - 49" Depth - 29"
Compare at $699.99
Made in the USA. Can custom order in several fabrics. Small Pouf ottoman provides additional seating to any room. Padded top with firm seat.

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Recruiter, Consultant, and Designer in England, United Kingdom
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