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June 1, 2008 (Vol. 28, No. 11)
David Daniels, Ph.D.
Subtype Selectivity Is Being Developed to Improve Efficacy and Reduce Side Effects
Maintenance of cardiac rhythm and pain sensation require the flow of ions across the membranes of all cells. Ion channels, which facilitate this movement, are protein assemblies that penetrate the membrane and catalyze passage of specific ions such as sodium (Na+), potassium (K+), or calcium (Ca2+) into or out of the cell down the electrochemical gradient.
Ion channels are as diverse as they are numerous (more than 400 channel genes have been described) and they are grouped into different families based on which specific ion flows through them and how they are gated. That is whether they open or close in response to a chemical (ligand gated), electrical signal (voltage gated), pH, temperature, or mechanical force.
Ion channels play a role in a wide variety of biological processes that involve rapid signaling such as neural signal transduction; cardiac, skeletal, and smooth muscle contraction; epithelial transport of nutrients and ions; T-cell activation; and pancreatic beta-cell insulin release. It is not surprising then that ion channels are favorite targets of pharmaceutical companies and also hot topics at recent and upcoming conferences including Select Biosciences’ “Ion Channel Targets” and “Target Opportunities”, and Informa’s “Ion Channel Targets.”
At Stanford University School of Medicine, Merritt Maduke, Ph.D., assistant professor in the department of molecular and cellular physiology, has built a lab focused on elucidating the molecular mechanisms underlying the function of the CLC chloride channels, the largest molecular family of mammalian anion channels.
There are nine mammalian members, CLC-1 to 7 and Ka and Kb for the kidney-specific type. Four family members are expressed on the plasma membrane of various cell types; five are expressed on intracellular membranes. Dr. Maduke’s interest in the CLC family is that half of the members are chloride channels, while the other half are chloride-proton antiporters.
“Historically, ion channels and antiporters have been thought of as two distinct classes of membrane proteins. Channels allow only passive movement of ions; antiporters can be used to pump ions. The finding of both of these classes of membrane proteins within a single gene family means that the mechanisms are likely not as distinct as had been previously supposed,” indicated Dr. Maduke. “Study of these mechanisms will help us understand how similar genes have evolved to carry out these different functions and will thus provide fundamental insight into how membrane proteins work.”
The CLC-1 channels found in skeletal muscle are closed at rest and upon excitation, i.e., membrane depolarization, the chloride channels open allowing chloride to enter into the cell. The negative charge entering in repolarizes the membrane, which allows the muscle to relax. Mutations in the CLC-1 channels cause myotonia in humans, a state where fewer CLC channels open, impairing membrane repolarization and muscle relaxation. Individuals with myotonia have problems with activities that involve skeletal muscle.
The physiological role for CLC-7 antiporters, one of the members expressed on intracellular membranes, is quite interesting. In osteoclasts, CLC-7 channels are localized to a specialized membrane called the ruffled border. Osteoclasts adhere to the bone surface and secrete protons and hydrolytic enzymes to degrade and absorb the attached bone.
Throughout our lives, bone is continually chewed up by osteoclasts and built up by osteoblasts. CLC-7 is essential for this process because it allows chloride to also be secreted into the bone matrix. This also balances the charge built up from proton secretion, enabling further proton movement.
Since CLC-7 is essential for the process of bone degradation, the prevailing thought is that by knocking down CLC-7 function one would limit the ability of osteoclasts to degrade bone.
For Dr. Maduke, the question that keeps her focused is how are the mechanisms of CLC chloride channels and CLC chloride/proton antiporters related. To get at this answer, x-ray crystallographic structural analysis of the CLC-ec1 homolog in E. coli provides some basic information. But this data only gives a single conformational view of the protein.
Dr. Maduke and her team are looking to understand how the proteins move as they open and close to allow regulated flux of ions. The team is looking to NMR and deuterium exchange detected by mass spec to obtain snapshots of the proteins in action.
Frederick Sachs, Ph.D., distinguished professor at the Center for Single Molecule Biophysics in the physiology and biophysical sciences department at SUNY Buffalo, is working on perhaps the oldest ion channel.
Dr. Sachs’ serendipitous discovery of mechanosensitive ion channels (MSC) in skeletal muscle led to experiments linking cell mechanics and the mechanisms of mechanical signal transduction. The Sachs lab uses patch-clamp, high-resolution microscopy, molecular biology, and structural NMR to study these ion channels.
MSCs are ubiquitous. While most familiar in the sensory cells of touch and hearing, they are found in a similar density in all cells. Probably arising as a method to balance cell volume under the osmotic drive of metabolism, they represent an evolutionary history from bacteria to humans. As opposed to many other channels, their activity is not regulated by channel density but by regulating the mechanical shielding of the channels by the cytoskeleton.
The Sachs lab has discovered a specific inhibitor of MSC—GsMtx-4, a small peptide isolated from the venom of Grammostola spatulata, a tarantula. The tarantula peptide has a unique pharmacology since the D- and the L-forms are equally active, but the site of action is specific to cation-selective mechanosensitive ion channels.
The peptide may have significant clinical applications since it inhibits cardiac arrhythmias, calcium influx in dystrophic muscle, spontaneous channel activation (and hence contraction) of human bladder smooth muscle, and suppresses stretch-induced endothelia production by glial cells that may play a role in brain tumor development. Furthermore, the peptide is nontoxic in mice.
“I have a recurring pharmaceutical dream for the millions of Americans with atrial fibrillation,” Dr. Sachs said. “If we provide the peptide in an inhaler when a patient feels an atrial fibrillation episode coming on, they can take a hit on their inhaler to stop the acute attack.
“Since atrial fibrillation begets atrial fibrillation, acute inhibition should improve long-term prospects for the patient. Since the peptide doesn’t affect the ion channels responsible for the normal cardiac-action potential such as Kv channels, there are minimal side effects. The peptide only acts on channels activated by abnormal mechanical stress such as overinflation of the atria. And with acute dosing toxicity is minimized.”
The dream aside, despite their ubiquity, the breadth of knowledge about MSCs, and the availability of a chemically synthesized, specific inhibitor, pharma companies have shied away from tackling this new array of targets, perhaps from the uncertainty of utilizing unfamiliar stimuli.
Drug Discovery Targets
The real challenge in developing therapeutics for ion-channel targets is the size of ion-channel families and their widespread distribution. The ongoing focus for the development of therapeutics with channel specificity is to develop subtype selectivity to improve efficacy and reduce the impact of side effects.
Within the pharmaceutical division of Devgen (www.devgen.com), the research focus is on treatment for inflammatory and metabolic diseases and arrhythmia. Petra Blom, Ph.D., section leader within the medicinal chemistry group, and Titus Kaletta, Ph.D., head of preclinical development, are working on a project targeting the Kv4.3 ion channel. The goal of their work is to develop a first-in-class oral treatment for acute and chronic atrial fibrillation.
Inhibition of Kv4.3 and Kv1.5 prolongs the action potential of the atria and the atrial refractory period. This mechanism is predicted to cardiovert patients and to keep them in sinus rhythm. Devgen identified inhibitors with excellent availability that are atrial selective and show no propensity to cause life-threatening ventricular arrhythmias in animal models, according to Dr. Blom.
Kv4.3, a voltage-gated potassium channel, functions in the early stage of the cardiac action potential. Channel activity is difficult to screen given the rapid polarization and depolarization cycle. “To solve this problem,” Dr. Kaletta noted, “the team developed an HTS assay based on the expression of the cloned human Kv4.3 channel in C. elegans.
“This whole-animal screening system combines the simplicity and convenience of C. elegans as a research tool and its close resemblance to human systems.” In the test, the action potential of the pharynx muscle, which shares comparable features to the action potential of the human heart, is used. Ingestion of fluorescently labeled food is used to measure the Kv4.3 channel activity in the pharynx of C. elegans.
“When the Kv4.3 channel is on, the pharynx pumps food poorly, generating a low fluorescent signal in the gut. When the channel is inhibited by, for example, a small molecule compound or is off, the pharynx activity changes, which results in a significant change in the fluorescent signal. The measured fluorescent signal directly correlates with ion-channel activity.”
With about 100 worms per well, the assay is performed in 96-well plates and enables the collection of 5,000 data points per day. The Devgen team obtained a 2% hit rate from the screen of its compound library using the C. elegans HTS assay. They verified selected hits in mammalian cells by means of patch-clamp electrophysiology; 83% of the hits were true human Kv4.3 inhibitors.
“Kv4.3 is a promising drug target for treatment of atrial fibrillation,” indicated Dr. Blom. “We identified two lead series that are potent human Kv4.3 blockers, which have proven efficacy in mice and dogs without hERG, Na+, or Ca2+ channel activity. With no safety issues encountered to date, we are proceeding with the preclinical development.”
Adrian Mason, Ph.D., senior scientist, and a team of scientists at Organon Laboratories (www.organon.co.uk; a part of Schering-Plough) are focusing on a different set of voltage-gated ion channels called HCN channels (hyperpolarization-activated cyclic nucleotide-gated channels). HCN channels, members of the voltage-gated cation-channel superfamily, selectively enable the flow of K+ and Na+ ions across the membrane.
Based on in situ hybridization studies, immunocytochemistry, and electrophysiological recordings, the four subtypes of HCN channel have been found to be widely distributed in humans. They are particularly plentiful in the brain, heart, and retina, but there is also evidence for expression in peripheral tissues such as kidney and testis. To a pharmaceutical company, the presence of HCN channels in many organs suggests therapeutic opportunities in a variety of human disorders but also flags the danger of side effects as a result of drugs acting at these targets.
Fortunately, there is some differential distribution of the HCN-channel subtypes that might be exploited to circumvent this problem. For example, HCN1 is highly expressed in the brain but restricted mainly to the cortex, hippocampus, and cerebellum. HCN4 is expressed prominently in the sino-atrial node of the heart, where it helps to control the cardiac rhythm, although it is also present in thalamic brain regions.
Although Organon has a successful history of developing and marketing ion-channel blocker drugs that are used during surgery to produce muscle relaxation, this current project takes the company in a new direction. “To be honest, the focus on HCN channels as a target for drug development started out of a bit of serendipity,” Dr. Mason said. “We had a drug candidate that was being developed for a psychiatric indication but found that it had a high specificity for HCN channels and blocked their activity. We followed up on this observation by testing related compounds using patch-clamp techniques on cloned HCN channels that had been expressed in HEK293 and CHO cell lines.”
Several years ago, evidence began to accumulate in the scientific literature that HCN channels might play a role in pain. Not only are the channels expressed in dorsal root ganglion cells, but knowledge of the basic biology of the channels suggested that they might have a pivotal influence on impulse activity in sensory neurons.
Building on the work of others, the Organon team showed that this was indeed the case and also demonstrated that their compounds were effective in animal models of pain. The team’s current focus is on finding therapeutic solutions to neuropathic pain.
In an attempt to exploit the well-established role of HCN4 in the heart, several companies have tried to develop HCN modulators for cardiac indications. Unfortunately, most of these compounds have failed due to side effects. Just one drug of this type has made it to market—Procoralan® (ivabradine from Servier), which is authorized in the EU for symptomatic treatment of stable angina.
“The challenge now is to find drugs acting at HCN channels that are effective in treating neuropathic pain but don’t have unwanted effects on other physiological functions,” said Dr. Mason. “It won’t be an easy task, but with our increasing knowledge of the basic biology of HCN channels together with recent developments in ion-channel screening technology, we are confident that we can give it our best shot.”
How Do They Do That?
The gold standard for measuring ion-channel function is the patch clamp. This method of electrophysiological discovery enables the skilled researcher to measure the flow of ions through the channel of an intact cell. It is a high-resolution technique supplying both high-quality data and high information content.
In manual patch clamp, a glass microelectrode is pressed against a cell membrane, forming a tight seal known as a gigaseal. By breaking the patch, you gain electrical access to the entire cell. This is a hit-and-miss approach. This variability coupled with the time required for constructing pipettes and finding and approaching a suitable cell greatly limits its throughput. A skilled researcher can look at maybe 20–30 cells in a day. The other limitation is the nonparallel nature of manual patch clamp.
Automated patch clamp has emerged as a way to increase the throughput of manual patch clamp by a factor of 1,000 to 10,000. Pipettes are replaced by glass chips with small holes, and the process of sealing and “going whole cell” has been replaced with sophisticated automated suction and software control systems.
Cells are automatically and blindly positioned at each recording well. The first automated patch-clamp system on the market was the IonWorks by MDS’s Molecular Devices. Others include PatchXpress from Axon Instruments (now part of MDS), Sophion Bioscience’s Qpatch, Nanion Technologies’ Patchliner, and Flyion’s Flyscreen.
Despite these advances, the automated platforms have one major disadvantage; they are only suitable for recording signals from cell lines with stable, high expression of the ion channel of interest. This is because the quality of the cell suspension is crucial for a reasonable success rate. Channel expression must be relatively homogenous and cells must be healthy.
Primary cell cultures such as neuronal or cardiac preparation do not fit these criteria, and also their lack of uniform shape may render a blind-capture system rather useless. The only practical use of automated patch-clamp systems is for secondary screening efforts and safety profiling of hERG ion-channel blockers.
True high-throughput screens that enable the screening of thousands of compounds for blockers or inhibitors of ion-channel function depend upon indirectly measuring ion-channel activity using membrane potential-sensitive fluorescent probes in a fluorescent detector, i.e., FLIPR from Molecular Devices, or FRET dyes in VIPR from Invitrogen.
Resources and Services
Founded to provide pharmaceutical companies with a cardiotoxicity screening service, ChanTest (www.chantest.com) is focused on hERG ion channels. These channels are activated at the late stage of the action potential following electrical stimulation in the human heart. ChanTest scientists were reportedly the first to prove that hERG was the target for adverse cardiac events linked to noncardiac drugs.
“In the last five years, we’ve grown from 15 to 75 employees,” reported Arthur Brown, president and CEO of ChanTest, “largely due to our screening service business. But more recently, we’ve undertaken a huge project to build an ion-channel reference library. Of the 400 genes encoding human ion channels, we’ve selected the top 80 to clone and express in each of two cell lines, HEK293 and CHO cells.”
“The cloning and cell line construction has been an involved process,” said Brown. Each clone has to be verified by DNA-sequence analysis and protein-sequence verification. Following transfection, the ability of the cloned channel to assemble in the cell membrane is confirmed by Western blot if a good antibody is available. The next challenge is the optimization of the culture conditions for patch-clamp measurements using the manual method and each of the different automated patch-clamp platforms.
Finally, the cloned channels must demonstrate the same pharmacological behavior when expressed in the cell lines as reported in the literature. ChanTest completed construction of 62 of the 160 cell lines to date and is on track to complete 104 by the end of the year, Brown noted. With completion of the reference library, ChanTest will make their cell line clones available to researchers through Molecular Devices and Sophion.
Beyond hERG, ChanTest also provides screening from a number of fully validated ion-channel panels. Report outcomes from screening using its Cardiac Channel Panel (11 channels) complements S7B-integrated cardiac risk assessments, provides mechanistic interpretation of the activity, and predicts proarrhythmia potential, added Brown. Recently, drugs that do not block hERG yet have QT risk have been identified using the Cardiac Channel Panel. “Now that chemists are learning how to design out hERG risk, other cardiac ion channels will be more important for off-target effects and QT risk,” Brown said.

domain: medical


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Your very own treasure trove of easy travel resolutions for 2017.I feel like there are very few places outside of western countries where 1 unit of currency will buy you much of anything.When money leaves, turning rubles into dollars, Euros, and everything else, that puts pressure on the ruble.
So, get an amount like 4,900 so you will get a mix of 1000,.
The Russian ruble had a remarkable year in 2016 with an appreciation of about 19% as compared to the US.
The Russian ruble (Russian:. 10, 50, 100, 200, 500, 1,000 rubles: Russian: 1992: 50, 200, 500, 1,000, 5,000, 10,000 rubles: USSR for 1000 rubles and lower.Will this catastrophic end to the year effect any real change.The US investment bank predicts the ruble will be on the list of good performing currencies next year along with.Russia, Abkhazia and South Ossetia are the three countries using Ruble.Since Belarusian, Ukrainian and Russian cultures are very close and thus share much in common,.I need: 20x 10 Ruble coins (not common, but I believe one can get them from a bank. 20x 5.
I knew that the ruble was devaluing and was curious what people thought after sanctions and ect.Eh, like a lot of international news, the reality on the ground is far less sensationalized than it appears in the media.
A very beautiful young Russian woman just gave me a 100 Ruble note to spend when I get to Russia.You can get citizenship after being a permanent resident for five years.Russian hats are often made from rabbit fur and muskrat fur, though other animal fur, such as beaver fur or coyote fur, are not uncommon for Russian hats,.Sadly, this faith in the government means people here are pretty passive to the changes.
Really interesting article, I love hearing about how other currencies work.One is the ongoing stagnation of the Russian economy, whose growth rate has been.
Pick up your foreign currency at over 100 Travelex stores across the U.S. You can find.
I hope you bought all the Apple products before they halted sales in Russia.

domain: finance


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Hong Kong-based real estate private equity firm Gaw Capital Partners has invested in South Korean data center company Dreammark One.
The company announced this week that it has entered into various agreements with South Korean private equity firm IMM Investment Corp. to make a strategic investment in Dreammark One through a fund under its management, and form a mutual strategic partnership to grow Dreamline Co.
“We are delighted to have seized on this favorable investment in South Korea, which brings significant strategic value to our pan-Asia IDC platform,” said Kok Chye Ong, Managing Director – Head of IDC Platform, Asia (Ex-China) of Gaw Capital Partners. “The surging demand for data centers in Asia Pacific continues to grow due to increased Internet usage driven by the pandemic, and we are committed to the principles of sustainable development of such centers through the application of ESG initiatives such as appropriate construction waste management, and renewable power sources exploration, that will further enhance our competitiveness in the data center sector.”
Ong added that Gaw Capital will continue to look for new investment opportunities and partnerships in South Korea.
Established in 1997, Dreamline offers connectivity services via its country-wide fiber backbone. Its data center subsidiary, Dreammark One, was founded in 2016; it offers colocations services from a 1,200-rack, 10MW facility in Guro, Seoul. Dreammark One is also an investor in the upcoming Jukjeon Data Center project in eastern Seoul.
In a recent LinkedIn post, the company said it plans to build additional hyperscale-class data centers in 2024.
Dreamline acquired Dreammark One from department store franchise Shinsegae Group in August 2018. IMM acquired a controlling stake in Dreamline from Korea Investment Private Equity (KI PE) in 2020; KI PE had acquired the company in 2014.
Hong Kong-based Gaw has previously invested in data centers through a joint venture with Centrin in China, and has formed a company called Data Center First that is planning a 30MW data center in Batam, Indonesia. It is developing two data center buildings outside Tokyo, Japan.
More in Investment / M&A
Discussion DCD>Connect Debates

domain: economics


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Opening on the adversities and struggles which had been confronted by her after firmly deciding to pursue performing as her profession, in her newest interview with a number one digital leisure portal, famend bollywood and digital star Mallika spills beans on why she disowned her father’s household identify.
Additionally opening up on her riot in opposition to the rudimental partiarchy system prevalent in her father’s aspect of household, Homicide (2004) fame bollywood star Mallika spills beans on why she disowned her father’s household identify.
All of the audiences and viewers understand how Mallika Sherawat made her debut with ‘Khwahish’ in 2003 and shot to fame together with her daring avatar in 2004 movie Homicide alongside Emraan Hashmi. She created a everlasting area of interest for herself as a intercourse image of Bollywood since primarily all her bollywood movies have been recognized for his or her daring and alluring steamy scenes. Whereas Mallika managed to impress the audiences and followers on large display screen, however that is an unknown piece which only a few may know that she confronted objections on the home-front for her profession as a bollywood star and talking up on the identical in her current candid chat with a number one digital leisure portal, Mallika spills beans on why she disowned her father’s household identify.
ALSO READ – 40 Worldwide Celebrities Unfold Consciousness In Vegan Month
The 44 years previous beautiful Bollywood star began off by telling, “I confronted a whole lot of opposition from my household. I battled patriarchy. My father is extraordinarily conservative. My mom additionally, my brother additionally. I had no assist in any respect”.
She additionally shared, “I used to be so naive and harmless. I stated, principal toh bag ke aise ban jaungi actress. Aur mein truly bhag gayi ghar se”.
She additionally spoke up on how she would’ve been married if she didn’t run away from residence and by chance she did and speaking about this, she stated, “Fortunately, every little thing labored out”.
She moreover continued, “I at all times had cash, as a result of I had a whole lot of jewellery, which I offered and financed my journey to Mumbai, however greater than that it was emotional misery for me. My drama with the household and my father disapproving and saying that I disown you. And my mom being heartbroken. There was a rift within the household. That triggered a whole lot of heartbreak for me”.
Talking in regards to the difficulties she confronted, Mallika added that everybody takes time to soak up the tradition after coming to an enormous metropolis like Mumbai. However the actress revealed that she settled shortly.
Mallika was final seen in RK/RKAY which had a theatrical launch within the US and Canada solely. Directed by Rajat Kapoor, the movie additionally featured Rajat Kapoor, Ranvir Shorey, Chandrachoor Rai, Kubbra Sait and Manu Rishi Chadha amongst others.
Its true that this actress has been away from showbiz for fairly a while now and has stayed in contact together with her followers by way of social media and now lastly she’s coming again with a brand new net collection titled Nakaab.

domain: celebrity


|Studies have shown that men are more self-assured than women……and yet, we also know that to succeed, confidence matters just as much as competence.What that leads to is a particular crisis for women in business. And it’s in the form of a vast confidence gap that’s keeping many women in smaller businesses, earning less and taking fewer opportunities.It’s an issue that is rarely talked about and we know, from the stories of this year’s Businesswomen’s Hall of Fame, it’s something even highly successful women have had to deal with.Here’s what 2015 Businesswomen’s Hall of Fame inductee. Kate Morris had to say about how to handle knock-backs and failure…|
Accept that failure is an essential part of the learning process
Kate Morris, CEO and founder of adorebeauty.com.au, knows better than many how daunting taking action can be. As a 21-year-old starting her own dot-com business in 1999 when e-commerce was in its infancy, with no experience and no collateral, she had a daunting road ahead of her. Kate says…
And it was this philosophy that helped Kate build her Confidence Habit. As she continued to take action, she says she wasn’t put off by all the “no’s” she received… and, importantly, she wasn’t put off by failure either.
I am encouraged to hear there are ways to bridge this confidence gap. Starting with getting the right people around you at the right time. To give you access to:
We’re only able to keep this offer open for a limited time. So, if you resonate with finding your tribe, gaining some much-needed community and practical support… Then come on over and join us! We’d love to welcome you. Oh… and when it comes to confidence… I saw this and LOVED it… and I thought you might too :-)


NASA’s OSIRIS-REx mission will study a near-Earth asteroid. Launched on Sept. 8, 2016, the spacecraft will rendezvous with asteroid Bennu, conduct a two-year detailed survey of Bennu from orbit, and collect a sample and bring it back to Earth. The sample will be the first for a U.S. mission, giving insight into the early formation of our solar system, and may provide clues to the origin of life on Earth. Lockheed Martin designed and built the OSIRIS-REx spacecraft, asteroid sampling system and sample return capsule at its facilities near Denver. The company is also operating the spacecraft from its Mission Support Area from launch through sample return.
(Nominations Close 12 p.m. MDT)
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All The Latest Gadgets Reviews And Tech Information is Available On This Blog
Thursday, April 16, 2015
Nokia Lumia 1020 Review
For all the new Lumia phones we've seen this year, one handset that's been left without a successor is the Lumia 1020. There's a possibility that the recently-spotted "Nokia RM-1052" could be a potential replacement, but until Microsoft officially announce it (or another phone altogether), you'll have to make do with the slightly elderly Lumia 1020 for now. That doesn't mean the Lumia 1020 is out of date, though, as it can now be upgraded to Windows Phone 8.1 and it still has one of the best cameras around. Even better, it now only costs around £385 SIM-free, £20-a-month on contract with no upfront cost for the handset, or £170 on O2's Pay & Go service, making it better value than ever.
With its an enormous 41-megapixel camera sensor, it uses some seriously clever tricks to produce the best phone images we have ever seen. We saw the first version of Nokia's large sensor on the PureView 808, but our enthusiasm was tempered by the handset's soon-to-be-defunct Symbian operating system. The Lumia 1020 has no such problems, as it runs Microsoft's increasingly-popular Windows Phone 8.
The PureView camera sensor is more than just a huge collection of pixels. It's physically larger than the sensors in most smartphones and even some compact cameras. At 1/1.5in, it's twice the size as the sensors in phones such as the HTC One, Apple iPhone 5S and Nokia Lumia 925, and 1.5 times larger than the sensor in our Best Buy-winningCanon Ixus 255 HS compact camera.
Generally, the bigger the sensor, the more area there is to capture light and so the less image noise and better low-light performance. The Lumia 1020's sensor is also a backside-illuminated (BSI) model, where light strikes the sensor from the rear, avoiding any circuitry getting between the light and the sensor's photoreceptors.
This isn’t the only trick up the 1020's sleeve, though; Nokia has also decided to use the sensor's huge number of pixels to help improve image quality further. When you take a picture with the Nokia Pro Cam app, the phone saves two versions; the full 7,712x4,352 pixel image and a smaller 3,072x1,728 (5-megapixel) snap.
The camera case adds a chunky handgrip and three hours' battery life
In fact, there are now few truly vital apps missing from the Windows Phone Store. There's a proper BBC iPlayer app (although the streaming video quality is far worse than on Android and you can’t download episodes to your phone), Netflix, ITV Player, 4OD, Demand 5, Spotify and RightMove for property hunters, for example. Many of these apps aren't as polished as the Android or iPhone versions, but the fact they exist shows Windows Phone is a becoming a platform to take seriously.
Better still, the Lumia 1020 should be getting the Lumia Denim update very soon, which adds Microsoft's digital personal assistant Cortana to the phone, bringing it bang up to date with the latest Lumia handsets. Read our Lumia 830 review to see how it fared against Apple's Siri.
The Lumia 1020 launched in the UK back in September 2013, but there's still nothing like it out there. The 41-megapixel camera really makes this phone stand out and is a major reason to buy it over any other smartphone. As it is now been superseeded by newer, shinier things you can also pick the Lumia 1020 up on the cheap. At the time of writing, O2 has it on a 24 month contract with 2GB of 4G data and unlimited texts and minutes for £24 per month with no extra charge for the handset.
The Denim upgrade will also give the Lumia 1020 every new feature you'll find on newer Lumia phones, which is another great reason to pick up this phone on the cheap. The new-look operating system adds loads of great features with Windows Phone finally becoming the operating system it always should have been. While UK users will have to wait until the end of the year for Cortana, all the other Windows Phone 8.1 features are ready to go.


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Allus Brown - Ventricular Assist Device and Heart Transplantation
Years ago, Allus Brown, a Marine Corps veteran and avid athlete, was diagnosed with dilated cardiomyopathy, a weakening of the heart that can potentially result in heart and kidney failure. As time passed, he experienced chest pain and shortness of breath. “I kept going to work until one day the chest pain got so bad that my supervisor sent me home,” says Mr. Brown, who is 54. Instead of going home he went to the Bluhm Cardiovascular Institute for treatment. “I knew it was time to look after my health.”
With dilated cardiomyopathy, the ventricles, or the bottom portion of the heart, become weak and enlarged, often for no obvious reason. The impaired ventricles are unable to pump enough blood to meet the body’s needs.
Mr. Brown was evaluated by the advanced heart failure team at Northwestern Memorial Hospital. His heart and kidney failure was confirmed through diagnosis and he was placed on the waiting list for a heart and kidney transplant.
To relieve Mr. Brown’s symptoms and to keep him alive until he received a new heart, a ventricular assist device (VAD), a mechanical device that takes over the pumping action of a diseased heart. “After I received the VAD I felt a lot better and was able to be active again,” recalls Mr. Brown. “I even danced at my daughter’s wedding and had a great time.”
Mr. Brown received his heart transplant and kidney transplant in December of 2009 after extensive coordination by both the heart and kidney nurse transplant coordinator teams. Together, they reviewed the donor offer with the surgeons and patient, arranged for hospital admission and timing of the transplants and communicated with the multidisciplinary teams needed for the surgery. “The nurses were really pulling for me and working hard to take care of me,” says Mr. Brown. “I feel like we have all been through a lot together.”
Today, he looks forward to going back to work and joining the company basketball league after nearly seven years of being unable to play.


While the core of the show – the Hoffmans – have remained, there has been turnover of personnel in their crew, and those of the other miners. Bringing new faces into the series over the past five years, as well as expanding the involvement of regular participants, such as Tony Beets, has always happened organically – enhancing the sense that this production is almost a naturally-expanding family.
“It always happens through the Hoffmans, really. We found Parker Schnabel because he lived across the creek from Todd in season one, and would come over and maybe lend them a tool. So he spent some time with the Hoffmans, and that’s how we found Parker and Parker’s grandfather. The Dakota Boys – Todd brought Fred Hurt up to help out with the mining. He ended up really rocking the boat and split off – so it’s always been people that have naturally spun off.
“So, when Parker went north, Tony Beets became his kind of mentor. You know, when you meet Tony Beets, as I have, he is TV gold. He is the manliest man I’ve ever met in my life. He could rip your arm off with his handshake. He’s been living in the Klondike for 30 years – he’s known as a legend. The way he speaks is not to be believed, and when he told me this season that he was going to buy a 75 year old gold catching dredge, take it apart, move it, rebuild it and be catching gold by the end of this season, I said “I’m in”. It was very simple for me. Plus he has an incredible family and runs a very successful mine. We also got some access to Tony’s wife, who is a force of nature, and his kid. So the more we can get family into the show, the more successful I think we are.
“Parker [Schnabel] and his grandfather have one of the most amazing relationships I’ve ever seen, and we try to get Parker’s grandfather onto the show as much as possible. Now, he’s 94, and it’s very difficult to get him up to Dawson. You know, people underestimate how far away Haines, Alaska, is from Dawson. But we do try to get Grandpa John up to see Parker one, two, three times a season. It just makes for great TV and great interaction. Parker’s very proud of what he’s done, Grandpa John wants to see what Parker’s done, and every single time, Grandpa John leaves with giving Parker some other tid-bit of advice, which Parker takes very, very seriously.”
Though the role of Executive Producer on the top-rated show on the Discovery Channel sounds like a demanding and challenging job in itself, Christo Doyle also hosts The Dirt. This ‘behind-the-scenes’ show runs immediately before Gold Rush, and aims to utilise the vast amounts of interesting footage that doesn’t make it into the main show as broadcast. It is an exceptional idea that again lends itself to the familial atmosphere of the Gold Rush series. Doyle has oversight of the production as a whole, as well as having detailed knowledge of each crew, and what they are specifically dealing with at any given time. While it is easy to imagine that these two roles may, on occasion, be in conflict, Doyle clearly feels their complimentary, supplementary nature is far more of a help than a hindrance.
“They’re two completely different jobs. You know, 99% of the time I’m the Executive Producer of the show. That’s what I do all day, every day, really. I watch cuts of Gold Rush two to three times each, I’m constantly on the phone with the production company – we’re talking about what’s been happening. I see the ‘hot sheets’ coming in each week with what we’re getting in the field. We’re constantly working on that kind of thing.
“Hosting The Dirt is something that’s definitely one of the stranger developments in my career but, it did develop because there is so much going on around this show that kind of needed to be told. There’s a huge amount that people don’t know – a huge amount that is frankly not appropriate for the show. There’s a lot of stuff that’s funny, there’s a lot of stuff that’s interpersonal stuff that’s worthwhile being told, and I also have a very unique relationship with all these guys. We have a unique rapport. You can have a lot of fun with them and [The Dirt] also rates very well, so the idea behind it is to get the viewers excited about Gold Rush. We can tease Gold Rush, we can tease what’s coming up, you know we can kind of build the audience into a frenzy, so that hopefully Gold Rush is off to a great start when it starts.”
Gold Rush may well have cleaned up in the ratings in its fifth season, but fans will be eager to learn if the crews have had similar fortunes in their final gold haul. It seems from the official press release, however, that – as usual – the job isn’t done until the final credits roll.
“Discovery Channel’s #1 rated series, Gold Rush, wraps up its record-breaking fifth season on Friday March 6th, with a 2 hour super-sized finale. It’s been a cold winter, but nothing compares to the Klondike at the end of gold season. Having set bigger goals than ever this season, the mine bosses push their crews to the limit and risk friendships, pride and money to get every last ounce of gold. Kicking off the night at 8pm ET/PT is a historic episode of The Dirt where passions will flare as Executive Producer Christo Doyle gathers all three mine bosses to discuss their mad dash to find gold. Then, following the Gold Rush finale kicking off at 9pm ET/PT, the miners will share their reactions as they watch from the set of The Dirt.”
With its fifth season drawing to a close, Gold Rush is already confirmed as returning to the Discovery Channel for season six at a later date.


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Welcome to our 2017 English & Scottish Garden Tours. Our small group tours (usually no more than 20) include 4 & 5-star hotels, deluxe coach travel and the opportunity to meet garden owners, head gardeners and volunteers – all with a passion for the gardens they tend. Accompanied throughout by your experienced Sisley tour director let us share Britain’s finest gardens, stately homes, historic towns and beautiful countryside with you.
In 2017 we will be running six garden tour programmes including two new tours. Details of each tour including full itineraries, pricing and booking information can be found by following the links below.
UPDATE: We do have limited places available on our Scottish Tour in September. We apologise for any disappointment but all other 2017 tours are now fully booked. If you would like to go on a wait list for a particular tour or be the first to receive details of our 2018 Tour programme please do contact us.
The Exclusive Chelsea Flower Show Tour
20th – 27th May 2017 (7 nights)
Delightful spring gardens and Chelsea Flower Show – Kent and London, read more…
RHS Chatsworth House Flower Show, Oxford & the Cotswolds
4th – 10th June 2017 (6 nights)
Experience the first RHS Flower Show at Chatsworth House read more…
Cotswolds Exclusive with Highgrove Garden
18th – 23rd June 2017 (5 nights)
An exclusive tour to some of the loveliest gardens in the heart of England, read more…
Summer Gardens with Hampton Court Flower Show 2017
2nd – 8th July 2017 (6 nights)
High season highlights based in Windsor & Stratford-upon-Avon, read more…

domain: hobby


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Those costly clams
Want steamers? You'll have to shell out more
ORLEANS - In April, John Ohman locked in a price of $56 a gallon. He's feeling pretty good right now because yesterday when he called his suppliers, the prices had skyrocketed to $145 per gallon.
That's if he can get it. One supplier said he had none on hand and none expected.
We're not talking oil or an exotic fuel. What interests Ohman is the fuel that drives his beachfront restaurant - soft-shelled clams, shucked and packed in gallon containers to be battered, deep-fried and served up in clam rolls, baskets, plates or pints.
"This is the highest (price) they've ever been," said Ohman, owner of Liam's at Nauset Beach.
Also high-priced because of their scarcity are soft-shelled clams sold by the pound. Steamed, dipped in butter, their sweet, rich meat chased down with a cold beer or wine, these are the clams of summer.
Steamers and fried clams are the same clam. The only difference is that diners prefer the smaller ones for steaming, around 2 inches in length. The bigger ones go into the Fryolaters. Demand for both escalates right along with the temperature change from spring to summer, and drops again as quickly as summer turns to fall.
The price usually follows that same arc, but this month red tide and pollution have shut down all the shellfish areas in New England, except the Cape and islands, and pushed the price of clams right through the roof.
Red tide is the prime culprit. Starting in late July, the Canadian Maritime provinces of Nova Scotia, Prince Edward Island and New Brunswick closed down due to red tide.
Red tide algae produce a toxin that is concentrated in clam meat as the clams feed on the algae. The toxin causes paralytic shellfish poisoning, which is sometimes fatal to humans. Shellfish purge themselves of the toxins within a few days after the algae bloom dies down.
early August, red tide had moved to Downeast Maine, then the rest of Maine and New Hampshire.
Storms didn't helpSince Massachusetts imports around 70 percent of the soft-shelled clams consumed each summer from other states and Canada, the price squeeze was already on when Tropical Storm Bonnie, Hurricane Charle an unnamed low-pressure system dumped heavy rainfall on the Bay State's North Shore and Boston.
Michael Hickey, chief shellfish biologist of the state Division of Marine Fisheries, said his department has set up a system under which if a certain amount of rain falls in a 24-hour period, shellfish beds are closed to prevent the possibility of contamination from storm water and septic system runoff that may contain viruses and bacteria like salmonella, Norwalk virus and hepatitis.
Hickey said water test results and analysis of shellfish meats determine whether an area remains closed or is allowed to reopen.
"You're looking at the wettest August in 50 years coinciding with red tide that is unusual for this time of year," Hickey said. Closures this past week ranged from Canada down the coast as far as Hull.
"The Cape and islands is the only place open in terms of commercial quantities of soft-shelled clams," he said.
That will change over the next week as Canada and some areas in Maine are set to reopen. Barring another hurricane or other heavy rainstorm, the shellfish beds in Massachusetts that are currently closed should also open soon.
Chef Dave Kennedy at Brax Landing in Harwich said he goes through two to three bushels of steamers a da three to four gallons of fried clams.
"That's just one place. When you start to add that up all along the coast, that's a lot of clams," he said.
Cape harvests downUnfortunately, Cape harvests have been down this year. Chatham is by far the biggest harvester of soft-shelled clams on Cape Cod, and shellfish constable Stuart Moore said his steamer population was hit hard by two rough winters in a row.
So, how many more clams can you expect to fork over for clams during the clam crisis of 2004?
Kennedy said he could push his price up a bit because he was a waterfront restaurant and people were willing to pay more for that experience. But those in the more prosaic inland locales said they were holding the line.
"We have a set price (on the printed menu) and when (clam prices) go through the roof, we keep them the same and don't make much money off it," said Briton Luhmann, manager at Sir Cricket's Fish Chips in Orleans.
Rob McLellan, owner of Hatch's Fish Market in Wellfleet, said he pushed the per-pound price of steamer clams up a dollar, but refused to go any higher.
"There's only so much people will pay," he said.
At least the Cape has clams. News stories this week told of clamless clam shacks on the North Shore.
After a dozen years in the business, Luhmann thinks he knows when the supply is low and overorders to keep the clams in stock.
"I'm worried about the weekend, but if worse comes to worse, I'll go to the fish market next door and shuck them myself," he said.
(Published: August 27, 2004)

domain: news


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About Marijuana Decriminalization
There are many laws that exist today that were written for a different time, for a different people. A time when society as a whole may have had a completely different perception or outlook on things. Our way of thinking when some laws were created may simply have had a lot to do with a lack of information at the time, different moral standards, or beliefs. Times do change, as do people and their opinions. This could be due to new information coming to light, or being able to look at our past to learn from our own mistakes. …
- About Marijuana Decriminalization
- How Dangerous are Drugs and What Can We Do about the Drug Problem?
- Smoke in the Eye - The Fight Against Big Tobacco
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Saite uz darbu:

domain: sociology


One of the reasons that the Motorola Xoom hasn’t been selling too well has been due to its high price – with the iPad 2 setting the standard price for a cheap, high-end tablet – not many people have been willing to fork out the cash for a tablet that costs so much more. Well all that could change, with the latest leaked photograph of a Verizon database entry. Apparently we might see a 16GB version of the Motorola Xoom Android tablet, and since 16GB is significantly less than 32GB (the amount of internal storage the current Xoom has), we might see a significant drop in price as well. Could it drop to the $400-$450 range that will make people consider picking it up instead of the iPad 2? We can’t say for sure, but if it does, chances of the tablet selling better should increase as well, especially if a 16GB WiFi-only version arrives as well. Stay tuned for updates.


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New Delhi: In a most bizarre incident that has come to light from the national capital, a man driving under the influence of alcohol sped away with a traffic policeman's alcometer when the latter tried to stop him. The incident took place in central Delhi's Connaught Place area on Friday night when the accused was driving through a police barricade in his Maruti Swift car.
A police official familiar with the matter told national daily The Hindustan Times that traffic policemen posted in the area spotted the accused driving under the influence of alcohol. Once the officer asked the driver to blow into the alcometer, the driver snatched the device and made a run for it, he added.
Police officials present at the scene managed to capture the last four digits of the car's registration number which led them to the identity of the driver. However, upon reaching his residence in Noida, they discovered that he had left for London on a professional tour. Deputy Commissioner of police (DCP-Delhi), Madhur Verma said that the suspect driving a black Maruti Swift was identified as one Rishi Dhingra who works with a private firm in the city.
When contacted, Dhingra told officials that he threw away the alcometer minutes after fleeing with it from the traffic policemen deployed near M-Block of Connaught Place around 11.40 pm on Friday. Reports suggest that a case has been registered in this regard against the driver for theft and obstruction of a public servant from doing his duty.

domain: law


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She convinced the world Gentlemen Prefer Blondes... and these previously unreleased photos show Marilyn Monroe could tickle them pink too.
The Hollywood legend relaxes barefoot in a floaty chiffon dress for a photoshoot in her private apartment.
Posing gracefully while sitting on the floor and reading a book, Marilyn shows off her flawless complexion, blonde curls and sensational curves in pictures by renowned portrait photographer Philippe Halsman.
The rare images, shot in the privacy of her home in Hollywood, were taken in 1952 when she was 26. That was the year she filmed Niagara with Joseph Cotten and won her lead role in Gentlemen Prefer Blondes.
They appear in a new book that marks 50 years since Marilyn died from a suspected drugs overdose in 1962.
But exactly how she died remains one of Hollywood’s greatest mysteries.
Marilyn by Magnum, published by Prestel, is out now, priced at £19.99.


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Songs like Velvet Peel by Hudson Mohawke
Listen to Velvet Peel by Hudson Mohawke and discover more similar Electronica songs like Monde, Overnight, Polkadot Blues on EDM Hunters. What's your #1?
Feb. 1, 2007Rock the Spot feat Craig G, Punch, Words, Mondo (Hudson Mohawke Remix) (Hudson Mohawke Remix)
DJ Flip, Freezemaster SlickFree Download

domain: artistic


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Download A Storks Journey Movie 2017 Dual Audio (Hindi-English) 720p & 480p & 1080p. This is a dual audio movie and available in 720p & 480p qualities. This movie is based on Animation Adventure Comedy Family And Fantasy. This movie is available in Hindi Dual Audio. Click on the Download button below to download this movie.
Starflix Provide You Super Quality Of Movies Which You Download From This Website. Starflix is One OF The Best Platform For Downloading Bollywood And Hollywood HD Movies. We Provide Direct Google Drive Download Links For Fast And Secure Download . We re Very Happy To Provide You Last Bollywood And Hollywood Movie. Please Join on Our Telegram Group Group.
- Full Name: A Storks Journey
- Language: Dual Audio (Hindi-English)
- Released Year: 2017
- Size: 300MB & 970MB
- Quality: 480p & 720p Bluray
- Format: Mkv
A Storks Journey (2017) Film based on Animation Adventure Comedy Family And Fantasy.
Even though everybody else thinks he’s a sparrow – Richard himself holds tight to the conviction that he is in fact a stork.
Orphaned at birth and raised by storks, the teenage sparrow Richard believes he is one of them. But when the time comes to migrate to Africa, his stork family is forced to reveal his true identity and leave him behind in the forest, since he is not a migratory bird and would not survive the journey. Determined to prove he is a stork after all, Richard ventures south on his own. But only with the help of Olga, an eccentric owl with an imaginary friend and Kiki, a narcissistic, disco-singing parakeet, does he stand a chance to reach his goal and learn to accept who he really is.

domain: entertainment


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California state senator Carol Liu’s attempt to mandate helmet usage for cyclists ran into a roadblock when cycling advocates presented nearly uniform opposition to the bill. With the exception of blogger Patrick Brady over at Red Kite Bore, who took a “Doesn’t affect me” stance, the LA County Bicycle Coalition, California Association of Bicycling Organizations, and the California Bicycle Coalition vehemently opposed the bill.
As a result, the helmet law was scrapped and instead morphed into a bill to require that the Department of the Highway Patrol conduct a comprehensive study of bicycle helmet use. I heartily applaud this new bill because it clearly seeks to provide a scientific framework around which to base future helmet legislation. Requiring helmets to prevent head injuries is likely crucial to protecting our vulnerable population of cyclists, however, the legislation does not go far enough.
The study should be expanded to include all head injuries in California. A clear understanding of what causes people to injure their heads, if based on hard science, could lead to a revolution in head protection throughout this country, and ideally the world. In addition to requiring helmets for cyclists, a science-based study would almost certainly lead to other areas where the use of helmets would greatly improve the safety of our population.
I propose a “Protecting America” movement that will help expand Senator Liu’s bill to include a study of all head injuries and that will hopefully lead to full-time helmet usage in the following areas:
- Caging: More than 16,000 youth drivers suffer acute head injuries in collisions every year. All cagers in driving school, as well as those in their first five years of driving should be required to wear helmets. Since it is impossible to say whether the caging public at large will at any given time be hit by a youth driver, all drivers, pedestrians, and cyclists should likewise be required to wear helmets. Protecting our youth is our nation’s highest priority.
- Bathing: Over 235,000 people each year get injured while bathing and showering, with a disproportionate number of falls affecting women, youth, and those over age 85. Legislation should be directed to require women and elders to never enter a shower or bath area without full head protection. Since many of the injuries result in hip fractures, particularly for the elderly, Sen. Liu’s study should also include a comprehensive review of the effectiveness of “bathing armor,” i.e. clothing that can be worn while bathing that will protect fragile joints.
- Shitting: Shitters over the age of 65 are particularly prone to injury while getting up and off the toilet. “Injuries getting on and off the toilet are quite high in people 65 and older,” says Judy Stevens, an epidemiologist at the CDC. Research on helmet usage among shitters over age 65 should be included in the bill, with a view towards requiring implementation of shitting helmet standards for the elderly, along with in-home surveillance systems similar to red light cameras that can observe helmetless shitting violations and issue citations.
- Fucking: Although statistics are hard to come by since emergency room patients usually ascribe their injuries during sex to another cause due to embarrassment, head injuries during coitus can be devastating, especially among younger, more adventurous sexual partners who are attempting sex acts on mountain tops, in moving vehicles, or with firearms. By expanding Sen. Liu’s research mandate to include copulation-related injuries, we can get a better handle on the dangers associated with this activity and hopefully come up with legislation that will require fuckers of all ages to be helmeted before, during, and after sex. Elder Californians having sex while sitting on the toilet in the shower should have particular legislation drafted to ensure their safety.
I hope you will join me as I support Sen. Liu in her attempt to make our state, and hopefully our galaxy, a safer place, a galaxy where head injuries will eventually become a thing of the past.
For $2.99 per month you can subscribe to this blog and join the movement to protect America from head injuries. Click here and select the “subscribe” link in the upper right-hand corner. Thank you!
You can also follow me on the Twitter here:

domain: politics


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The ALLOW lamp was created at the beginning of March 2015. It was inspired by the earlier design of the “glass jellyfish” made of glass by means of the fusing method in 2007.
As the glass-fusing technology makes it impossible to bend glass in 3 planes, I came up with an idea to make the “jellyfish” of flexible material i.e. PCV.
It is made of the flexible PCV material which has been stretched over a specially prepared membrane through heating and stretching. Thanks to this, it is possible to create a unique shape of a spatial form.
The textile has enhanced fire resistance, is resistant to water, moisture, chlorine, salt solutions, X-rays, sulfuric acid and nitric acid, washing powders. The material is non-toxic, prevents the growth of fungi, is sterilisable and washable.
The innovative features of the “Allow” lamp are its shape, form, materials used and the configuration of light sources. The lamp is characterised by a remarkable, unique design. It is an innovative solution, consisting in the use of unconventional materials and technological solutions. The advantage of this design is the ability to adjust the intensity and colour of the light to the changing mood and requirements regarding the interior lighting.
The “Allow” lamp is a very functional solution because it allows to adjust the intensity and colour of the light from very warm (2700 K) to cool (6000 K), smoothly or gradually, using a remote control.
The flexible material allows to create a unique shape of the spatial form. The material used may have so-called microperforation thanks to which it may also be sound-absorbing.
The use of the aforementioned material results in the delicacy of the structure, thanks to which the “Allow” lamp, despite its size, is a lightweight and functional product.
Some see it as a round petal bent in one plane and the others – as a wave.
Design of the lamp is a registered industrial design in the Patent Office of the Republic of Poland under the number Wp. 24100 and EUIPO European Union Intellectual Property Office under the numbers 003028893-0001 , 003028893-0002.

domain: chemistry


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Kobe Bryant Wins Oscar Award For “Dear Basketball”
Written by IMN on 5 Mar 2018
Superstar basketball player Kobe Bryant is a future NBA Hall-of-Famer. He’s won 5 NBA titles as a member of the Los Angeles Lakers.
Approaching retirement Bryant wrote a letter to the game titled “Dear Basketball”. The letter would later be morphed into an animated short.
Last night the animated short was nominated for Best Animated Short at the 2018 Oscar Awards. “Dear Basketball” would go on to win the award and earn Kobe Bryant his first Oscar.


S 400 system
The S 400 Triumf is an anti-aircraft weapon system designed and developed by Russia. It was developed in the 1990s as an upgrade to the erstwhile S-300 series. The aircraft is in service in the Russian Armed Forces since the year 2007. It is not only being used by the Russian defense forces but is also being exported to other countries.
Key Points for UPSC Prelims
- China was the first nation to procure this advanced defense system in the year 2014, and since then Saudi Arabia, Belarus, and Turkey and have acquired it.
- This system houses some of the most sophisticated defense features like anti-aircraft missile systems, multifunction radar, launchers, autonomous detection, and targeting systems, and command and control centres.
- It has the capability of firing three types of missiles in order to create a layered defense mechanism.
- These defense systems have the ability to track 100 airborne targets and engage with 6 of them simultaneously.
USA imposed CAATSA on Turkey
- Recently, the USA has imposed sanctions on Turkey under Section 231 of CAATSA for procuring the S 400 defense system from Russia.
- The sanctions have been imposed on the major defense procurement of Turkey-Presidency of Defense Industries (SSB).
- In the year 2017, Turkey signed the deal for purchasing the S-400 defense equipment system from Russia ignoring the concerns raised by the US.
- Now, on the concerns of leakage of sensitive data and ignorance of criticism to the deal by the US; CAATSA has been imposed on Turkey.
- Under the sanctions, visa restrictions have been imposed on the SSB President Ismail Demir and other officials.
- Other sanctions include a prohibition on granting specific U.S. export licenses and authorizations for any goods or technology transferred to SSB; a ban on U.S. Export-Import Bank assistance for exports to SSB; a prohibition on loans or credits by U.S. financial institutions to SSB totaling more than $10 million in any 12-month period; and a requirement for the United States to oppose loans benefitting SSB by international financial institutions.
CAATSA i.e. Countering America’s Adversaries through Sanctions Act is a law passed by the United States of America in the year 2017 through which it has imposed sanctions on countries like North Korea, Iran, Russia, and Turkey.
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Algorithms for the double encoding demonstrate especially promising performance. When many non-binary constraints that share more than one variable are present in a problem then MAC in the double encoding can exploit the benefits of both the variable ordering heuristic, borrowed from the non-binary representation, and the stronger filtering, borrowed from the DE, to outperform the other representations. This was demonstrated in problems with such structure (random and also frequency assignment - like). This is also the case in the ``still-life'' problem, which explains the success of the double encoding10. In addition, the double encoding offers the interesting potential of hybrid models where certain constraints are encoded into binary and others are kept in the non-binary representation based on certain properties of the constraints. To be precise we can benefit by encoding constraints that are either naturally specified in extension, or have relatively low arity and are tight. This was demonstrated in various domains. Most notably, in the frequency assignment problems where the double encoding (or a hybrid one) payed off in most cases, although the constraints in such problems are naturally defined intentionally.
Nikolaos Samaras 2005-11-09


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Wow! What an explosion of color. Hippy style coloring but made by a very conservative Amish woman in her Lancaster home. Note the care taken with the complicated piecing and the excellent quilting. Includes a sleeve for a hanging rod.
A high quality quilt.
Sold -- no longer available
While the quilt shown here has been sold, we can arrange for this quilt to be custom made for you. The current price may be more because of increases in the cost of fabric.


I have an Arris modem for wireless internet. I have done all of the steps, but it is not letting me connect to the wifi. It continues to tell me that the key that i put in is incorrect, but it is what is on the bottom of the modem. All of the lights are on but MoCA, which indicates a connection to another device. What is the problem?


It was only years after I became a kriyaban that I came to listen to Paramahansa Yogananda’s voice and songs. The narration about music in his Autobiography of a Yogi has stunned me that someone who had never had a formal education in music could write with so much clarity on the subject.
When I began to visit YSS satsangs, I cherished listening to and singing Paramahansa Yogananda’s bhajan songs. The light harmonium background and melody in the songs have always touched my soul. To those of you who are looking to listen to songs of Paramahansa Yogananda, here are five of my most favourite songs from the collection.
- I will sing Thy Name
- Listen Listen Listen
- Spirit and Nature Dancing Together
- So Do Thou My Lord
- Who is in my Temple
Each of these songs have filled my heart during several cherished moments. Most often, I begin the day by listening to this song collection. As reiterated by Paramahansa Yogananda, chanting is an important step in spirituality. His songs have been inspirational to me, for several years now, in yearning for the love of the divinity. Through his voice, he speaks to each one of us, who seek God with faith. The one who had remained a mental image got manifested with life through his devotional songs. During times when the forces of delusion, pull me away from spirituality, all it needs to get back to the path of light is listen to the songs just once.
As said often, music is a form of expression that can open the blocked energies from our nadis. Especially, while singing with true love and devotion to God, I’ve felt that the heart and throat chakras shed off their blockages and pave way for our souls to connect to higher centres.
In 1926, Paramahansa Yogananda writes about his experience of chanting together “O God Beautiful” with his devotees in New York,
“For one hour and twenty-five minutes, the thousands of voices of the entire audience chanted…in a divine atmosphere of joyous praise….The next day many men and women testified to the God-perception and the healing of body, mind, and soul that had taken place during the sacred chanting, and numerous requests came in to repeat the song at other services.”
One can buy the CDs from any of the YSS centres or through the online website of YSS or SRF. Though listening to his voice directly from a CD is a soul-lifting experience, I also recommend you to attend a near-by weekly satsang where devotees sing the devotional songs in chorus.


Taylor & the Wild Now is a phenomenal band that has a unique sound in the indie genre! They blend soulful vocals with dreamy/surf rock guitar riffs. Closing down the #freeweek festivities at Empire, Taylor Baker’s vocals were strong, expressive and still felt effortless throughout the set, while Drew Walker was able to coax that same feeling from the guitar. Mid set Houston rapper Guilla turnt up their rendition of “No Diggity” and the set closed out with their new/unreleased song “Seek”. The packed room was full of satisfied, smiling revelers.
Set list: Salt, Plain Gold Ring, Caught Me Thinking, Hold On, Wanderlust, No Diggity * Featuring Guilla, Gold Dust, Far Away, Seek


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Popular Nigerian Nollywood actress, Funke Akindele has finally returned to social media after she was convicted and her lovers are so glad.
Celebrities and her followers have trooped into her comment section after she posted a new photo in the late hours of yesterday.
The mother of twin boys who is also widely known as Jenifa shared a photo which in she was wearing a gown and was all smiles. She captioned the photo with ‘breathe’
Definitely, Funke wants to breathe a fresh new air and life. That’s cool.
See screenshot of her post below:
Checkout the full photo she shared below:
However, her fellow celebrities and followers have bumped into her comments with nice words and also to remind her that she has been missed.
Her post has swiftly garnered over twenty one thousand comments. That’s quite huge in the Nigerian space.
Celebrities like Naira Marley, Bunkumi Oluwashina, Yemi Alade, Falz, Tope Alabi, Angela Okorie, Muyiwa Ademola and more were all in the comments and Funke made sure to give all of them a response.
You can checkout some reactions below:


By Jason Willick
There are two ways to think about Japan’s announcement this month that it will surge defense spending by more than 50 percent in the next five years and acquire advanced missiles that can strike the Eurasian mainland. The first is that it’s a victory for the U.S.-led world order, because China’s military advantage in the Western Pacific will narrow. The darker version is that it’s a recognition of the failure of the U.S.-led order, which aimed to suppress military competition in East Asia after World War II.
Both the optimistic and pessimistic perspectives reflect important realities, and history will decide which was more apt. In the meantime, few Americans are as well-versed in Tokyo’s thinking as Michael J. Green, a Japanologist who was a top Asia hand on President George W. Bush’s National Security Council and currently leads the United States Studies Centre at the University of Sydney in Australia. His recent book, “Line of Advantage,” explains Japan’s China strategy to a Western audience. I interviewed him over Zoom to understand the implications of Japan’s geopolitical transformation.
“A lot of people argued that Japan’s culture of pacifism was immutable,” said Green, who first moved to Japan to teach English after college in the 1980s, “but I always felt the Japanese were ultimately realists.” The primary goal of their statecraft has been “to not lose,” he said. Japan organized to not lose economically in the decades after World War II and is “now organizing to not be coerced and defeated by China.”
The turn from pacifism has been sudden. One of Green’s professors compared Japanese politics to “a plate of peas — it never moves,” he recalled. “But if you tilt the plate a little bit, they all roll to one side.”
China is tilting the foundations of order in Asia. For most of the Middle Kingdom’s history, its rulers were focused on Asia’s interior, but now China has “largely settled its land-border problems with every country except India,” Green said. “The last piece for China to secure” is Asia’s maritime periphery.
“The challenge for China, and the reason it is so dangerous for the rest of us,” he said, is that unlike the United States’ Monroe Doctrine in Central America and South America, Beijing’s bid for regional dominance in Asia is “aimed at some of the most important economies and militaries in the world.” Even if China’s naval and air force buildups were “defensive in origin,” it is “extremely offensive and aggressive if you’re Japan, or if you’re the Philippines, or especially if you’re Taiwan.”
Taiwan is now the most likely flash point for war in the region. On a trip to Taiwan and Japan in November, I was struck that Japanese officials seemed more alarmed about the prospect of Chinese aggression against Taiwan than the Taiwanese themselves.
An American military defense of Taiwan against China would probably rely on the U.S. naval base on Okinawa about 400 miles away, making Japanese territory a potential Chinese target. If Japan acquires 500 Tomahawk missiles, as it is reportedly contemplating, China might think twice about such a strike. Then Tokyo could join the United States in a naval war while reducing the likelihood that its homeland would come under attack for the first time since 1945.
Japan started that war with the United States, of course, by attacking Pearl Harbor in 1941. But for Green, Tokyo set the conflict in motion with a more fundamental strategic error: Its decision to be primarily a land power instead of a sea power. That decision was rooted in Japan’s history and geography. Unlike Britain, the Japanese archipelago is well-protected by oceans, so its fighting forces focused inward. Japan was run by “a clan system with a very violent system of norms and the samurai ethos,” Green said. Civil war made the army “absolutely dominant.”
Japan’s navy, which emerged in the 19th and early 20th centuries, was less influential. “The army’s instincts were to control land, not sea,” he said, leading to Japan’s occupations of Korea, then Manchuria and China. The clan system “fused with a modern army and also injected into that modern army a very brutal, medieval way of conquest, which is what you saw Japan do in the ’30s and ’40s,” Green explained — a rampage that dangerously upset the balance of power in Asia.
Tokyo’s new strategy focuses on air and sea power to meet China’s maritime ambitions and defend the open trading system that has helped Japan become the world’s third-largest economy. But Asia’s security will still depend on the United States playing an active role it chose not to play in the 1920s and 1930s.
Green worries that American intellectual life isn’t sufficiently attuned to the geopolitics of Asia. As a young aspiring diplomat, he assumed that his time in Japan would be a “palate cleanser before I pursued my career in Europe, like any good East Coast American.” Instead, he said, “I just got hooked.”
When he joined the NSC in 2001, “the Europe office was about three times larger than the Asia office” because of the Clinton administration’s focus on the Balkan wars of the 1990s. American strategists have recognized the necessity of a greater Asia focus for decades, Green said, but the United States’ energy has repeatedly been drawn into Europe and the Middle East — “the Balkans, 9/11, [the Islamic State], Ukraine.”
Academically, the study of international relations emphasizes European history. Students learn about the Peloponnesian wars but are less likely to study the Sino-Japanese war or Mongol conquests. “The academy hasn’t adjusted,” noted Green, who earned his doctorate at Johns Hopkins and is a professor at Georgetown.
The main historical difference between European and Asian geopolitics is that in Europe, power dynamics “have long been multipolar.” The Spanish, British, French, Austrians, Russians, Germans and Turks have all been major regional powers at one point or another. When one gets too powerful, “the other powers eventually defeat that rising power and reestablish an equilibrium,” Green said, “and then another one rises.”
The sweep of Asian history, by contrast, has China at its center. “It’s mostly a history of China either being cohesive or disintegrating.” More than in Europe, the distribution of power in Asia hinges on one powerful state.
Sometimes it seems impossible to shake American diplomacy from its European roots. The Biden administration’s Summit for Democracy in December 2021 “was really a European, transatlantic design,” Green told me. Such appearances can help China appeal “to the global south and pan-Asian solidarity.”
In meetings in Tokyo, I also heard unease about the way the Biden administration has presented its democracy agenda. Japan is a democracy, though its high levels of social consensus and the dominance of one party distinguish it from most Western systems.
Japanese elites believe that Tokyo can be an intermediary between the United States and the strategically vital but less-democratic states of Southeast Asia. Japan’s national security strategy, Green said, “emphasizes Japan’s commitment to upholding an international order that’s based on rule of law and human rights,” but “when it comes to human rights violations in Myanmar, or the coup in Thailand, they’re not where we are.”
Japan’s outlook as a maritime power is more like Britain’s in the 19th century than the United States’ “Wilsonian” tradition — that is, focused on protecting commerce and enforcing rules rather than democracy promotion.
Green drew a contrast between Japan’s defense buildup and Germany’s more passive approach to Russia’s aggression. “A lot of scholars in the ’90s and 2000s were saying, ‘Germany good, Japan bad,’ ” and asking why Japan was “not able to deal with its military past.” Green proposed that maybe Germany was “too successful” on that front.
The war in Ukraine poses a strategic dilemma for Asia’s defense. “If we did nothing in Ukraine,” Green noted, America’s Asian allies “would’ve been terrified” by the precedent. On the other hand, they “don’t want us sending all of our best equipment” to Eastern Europe rather than East Asia.
Japan’s steps toward rearmament, for Green, show that the post-World War II period of Pax Americana is “completely different from anything ever seen in history.” Unlike the British Empire or the Roman Empire, it has been “based on building up former adversaries as power centers that had their own agency.” Now, “Japan is choosing, not being forced by America, but is choosing to reinforce the international order that America helped to create after the war.”
But at the same time, he said, the fact that Japan is making this “rather desperate” decision should be cause for American humility. Washington is losing the capacity, on its own, to back up the security commitments it has made around the world. That is the paradox of Japan’s strategic transformation: Its defense of the American system is itself a sign of that system’s heightened vulnerability.
Jason Willick writes a regular Washington Post column on legal issues, political ideas and foreign affairs. Before coming to The Post in 2022, he was an editorial writer and assistant editorial features editor for the Wall Street Journal, and before that a staff writer and associate editor at the American Interest. Energiesnet.com does not necessarily share these views.
Editor’s Note: This article was originally published by The Washington Post – WP on December 23, 2022. A version of this article appears in print on Dec. 2, 2022, Section A, Page 23 of the New York edition with the headline: Blockchains: What Are They Good For?. EnergiesNet.com reproduces this article in the interest of our readers. All comments posted and published on EnergiesNet.com, do not reflect either for or against the opinion expressed in the comment as an endorsement of EnergiesNet.com or Petroleumworld.
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EnergiesNet.com 12 26 2022


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My New Mini Weekender Pink Sparkle Lux De Ville Bag Rocks!
Other than leopard and camo print, pink is another fav of mine to have on an accessory, and to add even more fun, pink sparkle!
To add to my ever growing, never ending, insane collection of bags, I just got this brand new beauty at Lux De Ville's pop up shop which they have through December at their headquarters. The bag (shown below) is the mini weekender in pink bubbly sparkle, covered in chrome studs and black matte faux leather straps with an additional front pocket to stuff your phone, or makeup compact or anything else that will fit there, and I just love it! I dressed mine up a bit by adding one of Lux De Ville's bitchin chrome skull bag charms.
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Pick one up, or any of their amazing bags at http://www.luxdeville.com/

domain: design


Explore hidden natural beauty at Jianfengling Park in Ledong, Hainan
Hainan is known as a tropical paradise for a number of factors, and its beaches and blue skies are two of the most well known of these reasons. Another reason that Hainan is so revered as a tropical getaway is the abundance of tropical rainforests that it has to offer visitors.
Though remote and hidden far away from convenient transport links, some of them are actually easy to reach and offer unique natural interests and high commendations. Of these areas, Jianfengling National Forest Park is recommended.
Located in the southwest of Hainan Island in Ledong County, Jianfengling National Forest Park is 90 kilometers away from Sanya City. The park covers 1,600 hectares and was established in 1992 to preserve the rainforest and the rare animals living there. Thus far, it is the largest, most preserved, tropical rainforest in China.
The trail includes boardwalks and stairs to get you over the most difficult terrain, but for the most part it is natural and just challenging enough to make it enjoyable.
The scenic area is illustrated by detailed descriptions of tropical rainforest phenomenon and precious tree species, which enables tourists to learn while enlightening their spirits.
The tour to Jianfengling Park is highlighted by Tian Chi, which literally means “Heaven’s Lake”. As expected, its extraordinarily serene surface creates a perfect reflection of the sky – as well as the rainforest-covered mountains – above.
Thanks to its rainforest surroundings and its altitude some 600m above sea level, Tian Chi is often shrouded in mist. One of the most beautiful times to see this is at dawn. As the fog rises over the lotus-spotted lake, the only sounds are birds chirping and a determined rooster crowing in the distance.
It takes about two and a half hours to hike to the 1,412m-high mountain peak. On a clear day, climbers will be rewarded with a dynamic view of the fantastic rain forests, especially at sunrise or sunset.
The best time to visit is between the months of November and April as you can appreciate the most beautiful landscapes on more sunny days. Do remember to wear a long-sleeved shirt and pants, as there are many leeches on the way.
Accommodation: Another advantage of visiting the park is an easy access to the nearby resorts, which are about 10 km away on the way down from the Tian Chi (Heaven’s Lake).
Traffic: Take long-distance buses at Sanya Central Bus Station at Jiefang Road to the Huangliu Town. Then take the tricycle, the only mode of transport from the town to the park entrance; or hire a taxi to reach the scenic spot. The whole journey takes about 1.5 hours.
SOURCE: WOS Team


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Written by Clare Ferguson and Katarzyna Sochaka.
A number of important debates were held during the May 2021 plenary session, in particular on Parliament’s rights to information regarding the ongoing assessment of the national recovery and resilience plans, on a revised industrial strategy for Europe and on recent migrant deaths in the Mediterranean. Members also held a debate on possible waiving of the WTO TRIPS agreement on Covid‑19 vaccines to help developing countries fight the pandemic; on business taxation; and on Roma equality in the EU. Two joint debates took place, on hydrogen and energy strategies, and on data protection adequacy. Members debated a statement by the High Representative of the Union for Foreign Affairs and Security Policy/Vice-President of the Commission, on the EU position on the Israel-Palestine conflict. A number of programmes under the multiannual financial framework were approved, and debates and votes were also held, inter alia, on the impacts of climate change on vulnerable populations in developing countries, on the digital single market, consumer use of artificial intelligence and on company liability for environmental damage.
EU strategies on hydrogen and energy system integration
Following a joint debate, Members voted on Industry, Research and Energy Committee (ITRE) own-initiative reports on developing EU strategies on hydrogen and on energy system integration. The transport, buildings and industry sectors still rely heavily on the use of fossil fuels, a situation that should change if the EU is to reach its climate-neutrality ambition. The ITRE committee report states that an EU hydrogen strategy should be based on clean hydrogen and requires measures to speed up hydrogen market and value chain development. The committee also underlined the need to balance energy systems and to ensure energy accessibility. Crucial energy efficiencies could be achieved through investing in upgraded EU energy infrastructure, storage and interconnections, as well as encouraging consumers to play their part too, for instance by contributing to energy production.
International transfers of personal data
Members debated and adopted two resolutions concerning international transfers of personal data. A first resolution, tabled by Parliament’s Committee on Civil Liberties, Justice and Home Affairs (LIBE), concerned the Schrems II ruling, which forbids the transfer of personal data to a non-EU country (the United States in this case), without an equivalent level of data protection. The resolution maintains Parliament’s position that, without reform, surveillance laws in the USA prevent the European Commission adopting a new adequacy decision. The interim solution found since the United Kingdom became a third country runs out next month. In light of the Commission’s much-criticised draft adequacy decision, a second resolution calls for improvements to the draft decision before it can be adopted, in view of the UK’s level of data protection.
Draft amending Budget No 2/2021: Covid‑19 response, multiannual financial framework adjustment, and mobilisation of the EU Solidarity Fund
Parliament adopted draft amending Budget No 2/2021, along with a decision mobilising the EU Solidarity Fund to provide assistance to those hit by natural disasters in France and Greece, and to help 17 Member States and 3 accession countries face the impact of the coronavirus pandemic. Among other issues, the amending budget sets aside financing for the EU Covid‑19 response, including the provisional deal on an EU digital Covid certificate to facilitate free movement in Europe during the pandemic. However, Parliament’s Committee on Budgets also regretted that the Commission had combined so many urgent issues and technical adjustments in a single amending budget.
Access to justice in environmental matters
Members debated and voted on the amendments adopted by the Environment Committee (ENVI) to the report on access to justice on environmental issues under the Aarhus Convention, as well as on plenary amendments, but postponed the vote on the legislative resolution. The file is therefore referred back to the ENVI committee for interinstitutional negotiations. Changes proposed by the Parliament would inter alia open up the review mechanism to allow qualified members of the public other than NGOs to challenge acts that breach environmental law.
Just Transition Fund
Members debated and approved the interinstitutional agreement on the Just Transition Fund, the compromise reached with the Council. Parliament has had considerable input in the final agreement, securing voluntary top-ups from cohesion policy, conditionality on climate neutrality, higher co-financing rates and a new Green Rewarding Mechanism. While Parliament’s ambitions for a larger budget did not prevail, the final agreement nevertheless allocates €17.5 billion to helping workers who lose their jobs in fossil fuel production, as well as the transformation to clean energy technologies.
Creative Europe programme 2021-2027
Parliament debated and approved the Creative Europe programme for 2021‑2027 at second-reading stage. Parliament is keen to continue support for the European Union Youth Orchestra and seeks a special focus on the music industry and cinema, with a €1 842 million budget (36 % more than the previous programme) to support cultural projects, in an area hard-hit by the Covid‑19 pandemic.
Members debated and approved one of the EU’s most known and best-loved programmes, the regulation on Erasmus+, at second reading. Parliament secured an extra €1.7 billion for the flagship policy and insisted on ensuring the inclusion of young people with fewer opportunities in the target of 12 million participants.
European Solidarity Corps 2021-2027
Parliament also debated and approved the proposed revision of the European Solidarity Corps Regulation at second reading. Parliament’s negotiators have secured a number of modifications to focus the programme on volunteering opportunities for young people in solidarity and humanitarian projects, particularly outside their home country, including a 15 % increase on the previous budget.
Fiscalis programme 2021-2027
Parliament debated and approved Council’s first-reading position, without amendments, as an early second-reading agreement on the Fiscalis programme for 2021‑2027. The programme’s goal is to improve the operation of tax policy (including administrative cooperation with regard to taxes) and support tax authorities. The €269 million budget will enhance administrative and information technology capacity, as well as operational cooperation.
Turkey: 2019 and 2020 country reports
Members debated and adopted a resolution on the European Commission’s latest country reports on Turkey. The 2019 and 2020 reports on Turkey reflect the strained nature of EU relations with the country in the light of backsliding on democratic values and tensions in the eastern Mediterranean. While Parliament’s Committee on Foreign Affairs (AFET) has many concerns regarding Turkey’s commitment to the rule of law, democratic values and women’s rights, it has also pointed out that Turkey is hosting some 4 million refugees. Until relations improve however, accession talks are effectively at a standstill, and prospects for modernisation of the Customs Union remain suspended.
Montenegro: 2019 and 2020 country reports
Members debated and adopted a resolution on the European Commission’s latest country reports on Montenegro. A candidate for accession since 2008, the Commission’s reports on Montenegro show progress in accession negotiations and demonstrable respect for democratic standards in recent elections. Nevertheless, the Committee on Foreign Affairs (AFET) is critical of the lack of progress on freedom of expression and media freedom in the country.
Read this ‘at a glance’ on ‘Plenary round-up – May 2021‘ in the Think Tank pages of the European Parliament.