nc A.F. Branco Cartoon – Closing Thoughts By comicallyincorrect.com Published On :: Sun, 10 Nov 2024 11:00:32 +0000 A.F. Branco Cartoon – Gov. Tim Walz lost his own Blue Earth County in Minnesota. Trump also flipped three other.. Full Article Political Cartoons
nc A.F. Branco Cartoon – Out In The Cold By comicallyincorrect.com Published On :: Mon, 11 Nov 2024 11:00:16 +0000 A.F. Branco Cartoon – Revised from 2018 and revised for 2024 Veterans Day. Our Veterans are being left in the.. Full Article Political Cartoons Veterans
nc A.F. Branco Cartoon – Ditch Mictch Clones By comicallyincorrect.com Published On :: Tue, 12 Nov 2024 11:00:14 +0000 A.F. Branco Cartoon – Trump supporters are rooting for Rick Scott to be the next Senate Majority Leader, hoping he.. Full Article Political Cartoons
nc Sport | More to Bok prodigy Moodie after turbulence with Duhan and Co in Edinburgh By www.news24.com Published On :: Tuesday Nov 12 2024 06:12:02 Canan Moodie used his start against Scotland to show that he is about far more than just pace out wide and aerial ability. Full Article
nc Sport | Difference between good and great is handling pressure, says Kaizer Chiefs legend Baloyi By www.news24.com Published On :: Tuesday Nov 12 2024 19:39:57 Former Kaizer Chiefs legend Brian Baloyi says that holding the Kaizer Chiefs No 1 jersey requires a hardened mentality, but he is upbeat over Amakhosi's chances this season. Full Article
nc Sport | Makgopa's rise evidence of Broos' Bafana impact: 'You don't want to disappoint such a person' By www.news24.com Published On :: Wednesday Nov 13 2024 05:00:31 Evidence Makgopa wore a sheepish smile when Bafana Bafana coach Hugo Broos showered him with praise before literally patting the forward on the back, making him blush at Dobsonville Stadium. Full Article
nc French mention of Farahat’s Book: Iran : « Femme, vie, liberté ! » By cynthiafarahat.com Published On :: Mon, 17 Oct 2022 21:32:11 +0000 By JEAN-PIERRE LLEDO MABATIM Oct. 16, 2022 Toutes les informations qui nous parviennent d’Iran nous disent que cette nouvelle révolte est totalement inédite. Elle se distingue de toutes les précédentes parce que ce sont les femmes qui en ont pris l’initiative et plus encore parce que ce qui est ciblé n’est pas seulement le pouvoir, […] Full Article Featured Articles
nc Newsroom: TikTok surpassed YouTube as the third-most-popular influencer platform among US marketers in 2021 By www.emarketer.com Published On :: Mon, 24 Jan 2022 04:01:00 GMT TikTok will have more US users than Snapchat and Pinterest in 2022   January 24, 2022 (New York, NY) – YouTube is the “OG†of influencer marketing platforms, and it’s […] Full Article
nc Newsroom: Insider Intelligence Slashes Ad Spending Forecast for Russia and Eastern Europe Amid Conflict By www.emarketer.com Published On :: Thu, 31 Mar 2022 04:01:00 GMT Total media ad spend in Russia to drop nearly 50%   March 30, 2022 (New York, NY) – Insider Intelligence expects the ongoing war in Ukraine to have a significant […] Full Article
nc Newsroom: 34 Million US Adults Own Cryptocurrency By www.emarketer.com Published On :: Wed, 20 Apr 2022 04:01:00 GMT 3.6 million will pay with crypto in US; payment value to spike 70% in 2022   April 20, 2022 (New York, NY) – Cryptocurrency usage will continue its meteoric rise, […] Full Article
nc The existence of Zariski dense orbits for endomorphisms of projective surfaces By www.ams.org Published On :: Wed, 16 Oct 2024 14:24 EDT Junyi Xie J. Amer. Math. Soc. 38 (), 1-62. Abstract, references and article information Full Article
nc A novel method produces native light-harvesting complex II aggregates from the photosynthetic membrane revealing their role in nonphotochemical quenching [Bioenergetics] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Nonphotochemical quenching (NPQ) is a mechanism of regulating light harvesting that protects the photosynthetic apparatus from photodamage by dissipating excess absorbed excitation energy as heat. In higher plants, the major light-harvesting antenna complex (LHCII) of photosystem (PS) II is directly involved in NPQ. The aggregation of LHCII is proposed to be involved in quenching. However, the lack of success in isolating native LHCII aggregates has limited the direct interrogation of this process. The isolation of LHCII in its native state from thylakoid membranes has been problematic because of the use of detergent, which tends to dissociate loosely bound proteins, and the abundance of pigment–protein complexes (e.g. PSI and PSII) embedded in the photosynthetic membrane, which hinders the preparation of aggregated LHCII. Here, we used a novel purification method employing detergent and amphipols to entrap LHCII in its natural states. To enrich the photosynthetic membrane with the major LHCII, we used Arabidopsis thaliana plants lacking the PSII minor antenna complexes (NoM), treated with lincomycin to inhibit the synthesis of PSI and PSII core proteins. Using sucrose density gradients, we succeeded in isolating the trimeric and aggregated forms of LHCII antenna. Violaxanthin- and zeaxanthin-enriched complexes were investigated in dark-adapted, NPQ, and dark recovery states. Zeaxanthin-enriched antenna complexes showed the greatest amount of aggregated LHCII. Notably, the amount of aggregated LHCII decreased upon relaxation of NPQ. Employing this novel preparative method, we obtained a direct evidence for the role of in vivo LHCII aggregation in NPQ. Full Article
nc Russia–China defence and security relations: Insights from the expert community By www.chathamhouse.org Published On :: Wed, 31 Aug 2022 13:22:13 +0000 Russia–China defence and security relations: Insights from the expert community 13 September 2022 — 3:00PM TO 4:00PM Anonymous (not verified) 31 August 2022 Online Experts share insights on Russia–China military, defence, and security relations. In the defence and security realms, Russia–China relations resemble more pragmatic cooperation based on shared, calculated interests than an alliance. This event presents and discusses key findings from a recent expert survey conducted by Chatham House with the aim to gather insights on Russia–China military, defence, and security relations. Survey responses helped identify areas of bilateral cooperation but also crucial friction points and obstacles that prevent the relationship from developing further, as well as policy pathways for the West. Full Article
nc Russia-China Defence and Security Relations By www.chathamhouse.org Published On :: Mon, 05 Sep 2022 11:16:50 +0000 Russia-China Defence and Security Relations This project explores the military and security linkages between Russia and China. jon.wallace 5 September 2022 The project seeks to provide a nuanced understanding of Russia-China relations in the defence and security realms. It also seeks to understand Russian political and security perceptions regarding Chinese inroads into what Russia considers its ‘near abroad’, as well as other sources of irritation and tension in the bilateral relationship. It offers recommendations to guide NATO policy responses. Full Article
nc China’s high-stakes incursion in the heights of Bhutan By www.chathamhouse.org Published On :: Wed, 28 Sep 2022 11:18:27 +0000 China’s high-stakes incursion in the heights of Bhutan The World Today mhiggins.drupal 28 September 2022 Why is Beijing establishing settlements over the Bhutanese border? To undermine India’s strategic security, say John Pollock and Damien Symon. A confrontation is fomenting on the roof of the world in a country that rarely warrants international attention. In the tiny Kingdom of Bhutan, China is building villages in isolated, mountainous regions, upping the pressure on the capital Thimphu to yield contested areas to Beijing. In doing so, China risks a collision with South Asia’s largest state and Bhutan’s principal security guarantor, India. Sitting on top of fragile geopolitical fault lines in the Himalayas, China’s Central Military Commission has seemingly authorized a series of incursions into the Bhutanese regions of Doklam, Jakarlung, and Pasamlung. Beijing has also announced fresh claims in the east towards Sakteng. Taken together, these amount to 12 per cent of Bhutan’s total territory according to Nathan Ruser, an analyst at the Australian Strategic Policy Institute. India is wary of Beijing’s increased assertiveness in the Himalayas following a large-scale incursion by the Chinese People’s Liberation Army (PLA) into Ladakh two years ago when dozens of Indian and Chinese soldiers were killed in a stand-off. The appearance of Chinese roads, villages and a host of other infrastructure projects within largely uninhabited areas of Bhutan close to Tibet, have, for sections of India’s national security establishment, confirmed their worst fears – Beijing is altering the status quo across the Himalayas in a bid to undermine India’s strategic security through territorial alterations. As a country of only 780,000 people, Bhutan is greatly influenced by New Delhi when it comes to its foreign affairs. In exchange, India guarantees the defence of the kingdom and trains the Royal Bhutanese Army. The appearance of Chinese villages on its territory risks Bhutan becoming a victim of the wider regional tensions. The trauma of China-Bhutan border relations Bhutan is no stranger to the territorial aspirations of its northern neighbour. Thousands of refugees fled into the country after China annexed Tibet, damaging longstanding cultural and religious links between the Tibetan and Bhutanese people – a trauma still being felt today. Now, Beijing is laying claim to three areas within Bhutan, including Doklam in the west. This plateau is close to the Siliguri Corridor which connects to the ‘Seven Sister’ states in northeast India. Indeed, such is India’s concern over any Chinese presence near Doklam that in 2017 local Indian commanders sent troops into Bhutan to prevent PLA engineers building a road near the Doka La pass, resulting in a 72-day stand-off on Bhutanese soil between India and China, an experience Thimphu is unwilling to repeat. Once again, China is looking to force the border issue unilaterally, altering the status quo and building villages and outposts on Bhutanese soil. On the available evidence, it has been doing so for at least three years. The presence of Chinese villages in uninhabited areas of Bhutan serves a strategic purpose. They appear to be intended to pressure Bhutan into accepting an earlier version of a border deal that concedes Doklam to the Chinese. Bhutan’s increasing concern is that China now views the Sino-Bhutanese border dispute as a way of unravelling India’s strategic position by stealth. Here we see a growing pattern of behaviour across the Himalayas. China is testing the boundaries in isolated and contested areas of India to attain local advantages that ensure New Delhi’s gaze remains fixed on the Himalayas. The costly choice facing Bhutan Bhutan for its part has very deliberately opted to remain silent, despite clear violations of its border deal with Beijing. Thimphu has made no public comment on any of the Chinese incursions. The choice now facing Bhutan is a costly one. To concede Doklam would devastate relations with India, its closest partner. But to ignore China’s ambitions would be to risk further violations of its sovereign territory. Bhutan may yet agree in principle to a land swap but then delay its implementation in the hope China limits any further advances. Thus Bhutan, India and China stand at a crossroads, with an impending confrontation that has not yet arrived and one that through Thimphu’s delicate diplomacy, Bhutan hopes never does. China’s incursions into Bhutan — Key to map: 1 - Pangda; 2 - Dramana and Shakhatoe; 3 - Menchuma Valley. Areas of incursion are circled; the red shaded areas are disputed. The star is the capital Thimphu, and the international airport lies to the west. 1. Pangda — Aerial image of Pangda, a village of some 124 people established by China which sits 2km over the border with Bhutan. Image: Maxar (March 2022). The most high-profile incursion is in the disputed areas in Doklam. Running adjacent to the previous Doka La stand-off site, a series of Chinese projects are visible, following the Amo Chu River that runs from the Chumbi Valley in Tibet into Bhutan. The most well-known of these xiaokang – meaning peaceful and prosperous – border projects is Pangda, a village of 124 people that sits roughly two kilometres within Bhutan from the border. First spotted by open-source intelligence analysts in October-November 2020, Chinese state media says that 27 households were moved from the Shangdui village to Pangda in September of that year and that the village is located in Yadong County, Tibet. Pangda, however, lies on territory internationally recognized as belonging to Bhutan. Since Pangda was first identified, two more villages and an additional excavation site have been noted through satellite photographs taken in March this year, steadily following the river further into Bhutanese territory. In recent reporting by journalist Vishnu Som, a connecting road is also visible that runs 9km into Bhutan. Given the geopolitical sensitivities of the area vis-a-vis India, speculation points to Chinese attempts to increase pressure on the Jampheri ridge overlooking the 2017 stand-off site, which according to journalist Tenzing Lamsang, is currently occupied by a small Royal Bhutanese Army detachment. As ever in the Himalayas, small tactical alterations have strategic implications. Chinese control of the Jampheri ridge would command views towards Sikkim, increase the scope of China’s surveillance operations near the border and place India’s Eastern Theatre Command at a terrain disadvantage were it to intervene as it did at Doka La. 2. Dramana and Shakhatoe — Aerial image showing one of several villages recently built by China in the Dramana and Shakhatoe region of Bhutan. The Chinese military is said to be patrolling this area aggressively. Image: Maxar (2022). Further north of Doklam, at Dramana and Shakhatoe, more villages have been identified, with recent photographs taken in November 2021 showing a collection of structures nestled between snow-capped mountains. Varying in size, the largest village identified by journalist Devjyot Ghoshal comprises more than 84 buildings with construction having been started in December 2020 and seemingly completed by December 2021. Little is known about the nature of these villages or their occupants other than their size and location. However, the Chinese PLA has patrolled these areas aggressively, warning away Bhutanese herders and challenging counter patrols by the Royal Bhutanese Army. A permanent PLA presence in the area would be a significant change to the status quo. Informed speculation suggests that these may house either civilian contractors brought in from Tibet to oversee construction projects in the area, Tibetan or Chinese citizens brought across the border, or they could even be barracks for the PLA to help facilitate increased patrols in these contested areas. 3. Menchuma Valley — Aerial image of one of several Chinese-built settlements in and around Menchuma Valley in Bhutan; the area is home to holy sites important to both Bhutanese and Tibetan culture. Image: PlanetLabs (2022). Amid the sustained activity in the west of Bhutan, we are seeing similar levels of activity mirrored in the northern contested areas in Jakarlung, Pasumlung and the Menchuma Valley, a well-known entry point into Tibet for Bhutanese pilgrims. In May 2021, a team of researchers led by Robert Barnett from the London School of Oriental and African Studies discovered three additional villages in these contested areas, alongside a series of infrastructure projects, sitting between 3km and 5km south of the Chinese border in Bhutan. Barnett identified what appears to be police and military posts near these villages, as well as a communications tower. While the building efforts at Doklam are seen as having a geopolitical intent towards India, these villages and their locations are seemingly aimed to maximize China’s leverage over Bhutan. They are considered sacred in Tibetan Buddhist teachings as the birthplace of ancient Himalayan cultural heroes, with strong links to the Bhutanese royal family. Today they are the home to holy sites and temples, such as the Singye Dzong. For China to intrude on this area, and in some cases even deny entry to parts of it, is suppression of Bhutanese history, culture and traditions. By design or by default, Beijing is managing Tibetan religion and culture beyond the borders of the Tibetan Administrative Region. Full Article
nc China is attempting a precarious balancing act By www.chathamhouse.org Published On :: Thu, 09 Mar 2023 15:43:31 +0000 China is attempting a precarious balancing act Expert comment NCapeling 9 March 2023 In its efforts to maintain ties with both Russia and Europe, China is having to wade through conflicting interests and rapidly changing sentiments. Precisely how far China will go in supporting Russia has been one of the most important questions of the war in Ukraine. On 20 February, US secretary of state Antony Blinken warned China may soon provide arms (‘lethal support’) to Moscow. But then, on 24 February – the anniversary of Russia’s invasion – China released a position paper calling for a political settlement to end the conflict, tellingly omitting any mention of its ‘no-limits partnership’ with Russia. China’s goal was to present itself as a neutral mediator. In fact, Beijing’s ties with Russia remain unchanged, even if this relationship has grown more exasperating for Chinese diplomats over the past year. Their job is to continue striking a delicate balance, a task that is becoming increasingly difficult as Russian president Vladimir Putin doubles down on nuclear brinkmanship and reckless rhetoric. Staying out of the Ukraine war With Putin extolling the law of the jungle in its most brutal form, China must be careful not to involve itself too much in the conflict. After all, Russia is clearly losing, and China has high hopes of repairing ties with major European economies. With China focused on moves by the US and its allies in East Asia and the Indo-Pacific, it simply cannot afford sabre-rattling or unrest on its other borders But Putin is of course keen to signal that China has his back. That is why he recently rolled out the red carpet for China’s top diplomat Wang Yi and then alluded to an (unconfirmed) upcoming visit by Chinese president Xi Jinping. Such diplomatic developments allow him to present China’s ambivalent position as, in fact, an endorsement of the invasion. While the costs of aligning with Russia could easily outweigh the benefits for China, one must remember that China’s reasons for maintaining good relations with the Kremlin go beyond the war in Ukraine. For starters, the two countries share a 2,672-mile (4,300-kilometer) border – roughly equivalent to the width of Europe – and the frontier’s exact location was not even finally settled until the beginning of this century, after generations of negotiations that included some 2,000 meetings. Yet to this day, the spectre of the Sino-Soviet split in the 1950s and 1960s looms large on both sides and it is not likely to be exorcised anytime soon. With China focused on moves by the US and its allies in East Asia and the Indo-Pacific, it simply cannot afford sabre-rattling or unrest on its other borders. Moreover, unlike the collective West, China’s foreign policy has always been shaped by interests rather than by values. Even with respect to Russia, the two countries’ bond is based mainly on shared resentment of US hegemony. By deepening their bilateral cooperation in recent years, they have been able to achieve a level of great-power status with which to counterbalance America. Being isolated from the ‘collective West’ is not an attractive option for China, given its hopes of achieving a robust economic rebound after years of the zero-COVID policy But Putin’s misadventure in Ukraine has forced Xi and China’s newly minted Politburo to manage a new set of economic, financial, and political risks. Russia’s war has left the West more firmly united than it has been in years. As China’s relations with the US have reached new lows, Chinese leaders want to avoid also alienating the European Union (EU), which is one of the country’s biggest trading partners. This is why Xi and Chinese diplomats have been so careful not to accept the Kremlin’s talking points in full. Being isolated from the ‘collective West’ is not an attractive option for China, given its hopes of achieving a robust economic rebound after years of the zero-COVID policy. Balancing Europe with the Global South In seeking to keep diplomatic and trade channels open, China’s main tactic has been to reassure European countries that it will use its own ties with Russia to restrain Putin from deploying nuclear weapons. At the same time, China is making a renewed push to strengthen its ties with the Global South where many countries do not see the war in Ukraine in the same stark moral terms as the West does. The emphasis on energy and food security in China’s recent position paper may have struck a chord with developing countries that have been reeling from the war’s negative knock-on effects on their economies. Full Article
nc Beijing briefing: China aims for tech self-reliance By www.chathamhouse.org Published On :: Tue, 28 Mar 2023 09:44:39 +0000 Beijing briefing: China aims for tech self-reliance The World Today mhiggins.drupal 28 March 2023 Xi Jinping’s new appointments are tasked with a technology led recovery, but they face a daunting task to restore growth, writes Yu Jie. The three-day state visit to Moscow by President Xi Jinping in March may have eclipsed the National People’s Congress in Beijing a fortnight earlier, but as Xi seeks to establish a new global order with China at its centre, the political events in the Great Hall of People provide an important insight into the country’s longer-term economic plans. While a new cohort of cabinet members was appointed to sit on the State Council for the next five years, much of the attention remains on China’s economic stimulus plan to enable a rapid post-Covid recovery, as well as proposals to restructure central government. Mountainous task Three aspects of this year’s Congress deserve deeper scrutiny: Li Qiang’s confirmation as premier to succeed Li Keqiang’s decade-long subdued tenure under Xi; the extent to which Xi’s new cabinet sheds light on China’s economic and scientific self-reliance; and the unveiling of a major restructuring of central government administration in sectors such as finance and science. Local government debt and the volatile property market threaten huge economic uncertainty China’s new premier initially faces the mountainous task of restoring growth and market confidence. During a press conference much shorter than his predecessor would hold, Li Qiang praised China’s private business sector and repeated the words ‘China remains open to foreign business’ to address the growing anxieties among foreigners and Chinese private entrepreneurs. Beside the daunting task of economic recovery, Li Qiang faces another big challenge. Unlike his predecessors, he has never worked as a vice premier and overseen ministries under the State Council. The test for him will be to pursue a sound economic recovery plan while coordinating numerous central government agencies. He will also need to regulate relations among provincial heads who have a tendency to argue endlessly over the distribution of public finances. Even though Xi is secure in his third term, his involvement in shaping and implementing macro-economic policies is keenly felt. Li Qiang made explicit the State Council under his leadership will be the chief implementor of all policies approved by the president. This is a less equal working partnership with Xi than his predecessors on the State Council enjoyed in the past. Beijing published its official plan to restructure its central government administration announcing planned cuts of 5 per cent of its civil service. The newly established Central Commission on Finance intends to deal with systemic financial risks and to coordinate the financial regulatory bodies, central bank and Ministry of Finance. This is seen to reflect the Chinese leadership’s growing concern with the poor performance of local government loans and debt as well of the volatility of the property market, all of which threaten huge uncertainty for the economy. Beijing is responding to the tough US measures designed to dent China’s ambitions of technology supremacy As well as reorganizing the financial sector, Xi’s intention to pursue an integrated national strategy combining economic and scientific self-reliance has led to significant appointments following the Congress. As a starter, a new Central Commission for Science under the party leadership has been established. This commission will focus on providing a renewed impetus to accelerate China’s drive to achieve ‘scientific reliance’ and to ease the choke points in the economy, such as the supply chain for semiconductors. It remains unclear who will head this new commission or who will be on it, however, as scant detail has been made public. It is seen as a direct response to the tough measures adopted by the United States designed to dent China’s ambitions of technology supremacy. Departure from the past New appointees to the Politburo come with substantial backgrounds in science as well as a solid track record of running state-owned enterprises. This is a departure from the past. Instead of inserting financial specialists, Xi appointed two scientists, Liu Guozhong and Zhang Guoqing, as the vice premiers overseeing science, education and industrial policies. This signals that Xi intends to prioritize science and innovation during his third term. The appointment of technocrats to the State Council is seen as a move to strengthen innovation and prepare the Chinese economy, political system and society for potential external shocks. Full Article
nc Chinese supply chains could tip the balance in Ukraine By www.chathamhouse.org Published On :: Wed, 29 Mar 2023 12:43:19 +0000 Chinese supply chains could tip the balance in Ukraine Expert comment NCapeling 29 March 2023 Disrupting supply chains of critical minerals to those supporting Ukraine could give China a key advantage in its wider international trade competition. Direct military intervention from China into the war on Ukraine, with Chinese troops and airmen appearing at the front line, would be highly escalatory and highly unlikely. Equipping Russia with weapons and equipment is much more likely – if indeed it hasn’t already happened – and considering the West is supplying armaments to Ukraine, a joust with western technologies would be an interesting development to follow. But if Chinese weapons underperform in the heat of battle, this may have implications for the current situation with Taiwan and the US, as a poor outcome on the Ukraine front could give the West more confidence over the tensions in the South China Sea. And the use of Chinese weapons in Ukraine would also be a feast for Western technical intelligence to capture. Creating economic disruption A much more likely development for China is to put in place export controls on critical minerals for Western powers supplying arms to Ukraine. This is a significant lever which China has used before during its fishing dispute with Japan in 2010 when hi-tech industrial production in Japan was affected by shortages of China-sourced critical minerals. Once normal supplies were resumed, Japan started to stockpile critical mineral reserves. If China’s default position becomes a total refusal to supply client nations unless end-to-end assurances can be achieved to prove non-military use, the West’s aspirations regarding the Paris 2050 goals will certainly be put in jeopardy In October 2020, the Chinese Communist Party (CCP) passed a new statute enabling – when necessary – restriction of critical mineral supplies to third party nations intending to use them for defence and security applications, adding a ‘versatile weapon to Beijing’s arsenal’ in its trade competition with the US. That legal control has been applied to Lockheed Martin production of Taiwan-bound F-35s and it applies not only to critical minerals mined on the Chinese mainland, but also to Chinese-controlled enterprises within international supply chains, of which there are many. Responding to any such restrictions by opening up new mines and setting up new supply chains can take more than a decade, so the countries involved may need to start stockpiling critical materials as Japan has been doing since 2010. This could result in critical minerals supply chains becoming the issue which splits the current consensus of the West over Ukraine Commodity markets also need to be ready for some interesting price wobbles – a persistent problem in critical minerals extractives investment as is overcoming environmental, social, and governance (ESG) challenges in this new game of global supplies. In addition, those markets include the London Metal Exchange, now owned by Hong Kong Exchanges & Clearing whose biggest shareholder is the Hong Kong government which is struggling to operate with complete independence from Beijing. Splitting the West’s consensus By extending the thinking on China’s potential to throttle global critical mineral supply chains and the ensuing latency of extraction from new mining resources, progress to the Paris Agreement 2050 goals on climate change will inevitably be affected. Given there are no supply chain assurance mechanisms, such as distributed ledger technologies, in place within global mining supply chains, a key issue to overcome would be how the West assures China that critical mineral supplies are not destined for military applications. But if China’s default position becomes a total refusal to supply client nations unless end-to-end assurances can be achieved to prove non-military use, the West’s aspirations regarding the Paris 2050 goals will certainly be put in jeopardy, or even made unachievable. Full Article
nc Analysis of {beta}-lactone formation by clinically observed carbapenemases informs on a novel antibiotic resistance mechanism [Enzymology] By www.jbc.org Published On :: 2020-12-04T00:06:05-08:00 An important mechanism of resistance to β-lactam antibiotics is via their β-lactamase–catalyzed hydrolysis. Recent work has shown that, in addition to the established hydrolysis products, the reaction of the class D nucleophilic serine β-lactamases (SBLs) with carbapenems also produces β-lactones. We report studies on the factors determining β-lactone formation by class D SBLs. We show that variations in hydrophobic residues at the active site of class D SBLs (i.e. Trp105, Val120, and Leu158, using OXA-48 numbering) impact on the relative levels of β-lactones and hydrolysis products formed. Some variants, i.e. the OXA-48 V120L and OXA-23 V128L variants, catalyze increased β-lactone formation compared with the WT enzymes. The results of kinetic and product studies reveal that variations of residues other than those directly involved in catalysis, including those arising from clinically observed mutations, can alter the reaction outcome of class D SBL catalysis. NMR studies show that some class D SBL variants catalyze formation of β-lactones from all clinically relevant carbapenems regardless of the presence or absence of a 1β-methyl substituent. Analysis of reported crystal structures for carbapenem-derived acyl-enzyme complexes reveals preferred conformations for hydrolysis and β-lactone formation. The observation of increased β-lactone formation by class D SBL variants, including the clinically observed carbapenemase OXA-48 V120L, supports the proposal that class D SBL-catalyzed rearrangement of β-lactams to β-lactones is important as a resistance mechanism. Full Article
nc In conversation with HRH Prince Turki AlFaisal By www.chathamhouse.org Published On :: Fri, 16 Aug 2024 09:27:14 +0000 In conversation with HRH Prince Turki AlFaisal 13 September 2024 — 11:00AM TO 12:00PM Anonymous (not verified) 16 August 2024 Chatham House and Online This event will discuss how the ongoing Gaza war is impacting the region and the role external actors can play to support de-escalation. The Gaza war, now in its tenth month, continues with ever-worsening consequences for Palestinians and no end in sight. The Israeli-Palestinian conflict has also heightened tensions across the Middle East with fears of a broader regional war that would include Iran and aligned groups from the ‘axis of resistance’.Against this backdrop, ceasefire negotiations supported by regional and international mediators, have not amounted to an agreement nor have there been any concrete proposals for a way forward out of the crisis by key actors such as the United States, Gulf countries or other key stakeholders.In this event, His Royal Highness Prince Turki AlFaisal will discuss how the Gaza war and related developments are impacting the Middle East, and will share his views on the role of regional and external actors in supporting de-escalation efforts.The addresses:How are Middle Eastern countries managing regional security and heightened tensions with Iran and aligned groups in Iraq, Lebanon and Yemen?What role are Gulf countries playing in efforts to de-escalate tensions?How can they support short- and long-term planning for a way forward in the Israeli-Palestinian conflict?How are relationships between Middle East countries and external powers such as the United States changing as a result of the Gaza war?In person places for this event are balloted. Confirmations will be sent by email on Monday 9 September at 3pm or a placed on the waiting list. Virtual registrations are confirmed immediately.Individual membership provides you with the complete Chatham House experience, connecting you with a unique global policy community. Find out more about membership. Full Article
nc Fostering inclusive health systems amidst geopolitical instability By www.chathamhouse.org Published On :: Wed, 11 Sep 2024 14:57:13 +0000 Fostering inclusive health systems amidst geopolitical instability 13 October 2024 — 9:00AM TO 10:00AM Anonymous (not verified) 11 September 2024 Sheraton Berlin Grand Hotel Esplanade How can we build trust and inclusivity in the health sector in a fractured geopolitical environment? Building trust in government, service provision and delivery are crucial considerations for policymakers who aim to make local, national and international health systems more inclusive. In the health space, trust can be a matter of life and death. Understanding and modulating policies that account for the trust factor, alongside the geopolitical determinants of health, can lead to more inclusive decision making and thus better health outcomes for larger proportions of a population.International unity is key to addressing the challenges posed by geopolitical instability, which include disinformation campaigns, rising nationalism and growing divisions between states. If countries can find common ground through an inclusive approach to health, the effects could be transformative in achieving global health and equity targets.This discussion, held in partnership with Haleon, will examine what it takes to foster trust and resilience in the health sector, achieve global inclusivity aims and chart a path for the public and private spheres to come together to navigate a fractured geopolitical environment.In what ways can localised health inclusivity data help policymakers to alleviate gaps in healthcare provision and why is this an essential element in instilling trust across the system?What role should multilateral organizations play in setting precedents for health inclusivity around the world?How do health inclusivity policies empower the service user and help reduce the burden placed on public healthcare systems?How can the health sector come together to ensure individuals are included within their own health decisions, are able to access services regardless of demographics and geography and trust their healthcare providers?This event will be held at the Sheraton Hotel, Grand Esplanade, Berlin in the margins of the World Health Summit. You do not need a ticket for the World Health Summit to attend this event. Full Article
nc Labour Party Conference – International affairs networking brunch By www.chathamhouse.org Published On :: Mon, 16 Sep 2024 10:32:13 +0000 Labour Party Conference – International affairs networking brunch 24 September 2024 — 11:00AM TO 12:00PM Anonymous (not verified) 16 September 2024 Labour – Grace 1 Suite, Hilton Hotel, Liverpool Hosted by Sir Simon Fraser, Chairman of Chatham House. This event is taking place at the Hilton Hotel, Grace 1 Suite, Liverpool. You are warmly invited to join us for an exclusive networking brunch at the 2024 Labour Party Conference.Sir Simon Fraser, Chairman of Chatham House, and Olivia O’Sullivan, Director of Chatham House’s UK in the World Programme, will deliver opening remarks, followed by an interactive networking session where you will have the chance to engage with a wide range of stakeholders. Join us to connect with key senior parliamentary, corporate and media attendees at the Labour Party Conference.This event will be taking place outside of the secure zone. Full Article
nc The 2024 US Election: Global Consequences By www.chathamhouse.org Published On :: Tue, 17 Sep 2024 14:32:14 +0000 The 2024 US Election: Global Consequences 26 September 2024 — 5:30PM TO 6:45PM Anonymous (not verified) 17 September 2024 Online This webinar explores what is at stake for US policy in key regions around the globe. In the lead up to the 2024 US presidential election, Chatham House experts discuss:What is at stake for US policy towards China, Europe, and Latin America and what challenges will confront the next US president?Can the US lead when its partners and allies are continually dissatisfied by the new turn in its trade and economic policy?What are the core humanitarian challenges and how can they be addressed? Full Article
nc In conversation with Speaker Emerita Nancy Pelosi By www.chathamhouse.org Published On :: Thu, 19 Sep 2024 10:52:13 +0000 In conversation with Speaker Emerita Nancy Pelosi 14 October 2024 — 12:00PM TO 1:00PM Anonymous (not verified) 19 September 2024 Chatham House and Online The former Speaker of the House of Representatives discusses challenges to American democracy and the importance of leadership in an election year. As the US gears up for the 2024 Presidential election, the importance of leadership in politics has come to the fore. As the Harris and Trump campaigns move towards election day, the heightened sense of strong leadership is central to the position of both candidates.Following her first election to the House in 1987, Speaker Emerita Nancy Pelosi has been central to American political leadership for over two decades. Serving as the 52nd Speaker of the House of Representative, Speaker Pelosi rose to become one of the most powerful and consequential Speakers in American political history.Following the release of her recent book The Art of Power, Speaker Pelosi will discuss how she became a master legislator, working with numerous presidents, her political legacy in the house and her leadership during a contentious time in US politics. Full Article
nc Security and defence 2025 By www.chathamhouse.org Published On :: Thu, 26 Sep 2024 13:42:14 +0000 Security and defence 2025 6 March 2025 — 8:00AM TO 6:00PM Anonymous (not verified) 26 September 2024 Chatham House and Online Join senior policymakers, business leaders and international security experts at Chatham House for a day of thought-provoking discussions exploring the tools needed to equip military forces with for an increasingly insecure future. You will receive further instructions regarding your registration soon. Future-proofing a fracturing worldThe security and defence landscape is characterised by rapid change and evolving threats to global stability. The uncertainties of a complex geopolitical environment, with war on multiple fronts, are exacerbated by the array of threats presented across the domains of conflict - from land, sea and air through to space and technology. From drone swarm attacks in the Donbas, utilising the latest battlefield technology to gain advantages on the land and in the air, through to the battle for primacy in the space domain above the strategically important, yet inhospitable Arctic shipping lanes, the domains of conflict are becoming increasingly intertwined. A holistic strategy fit to tackle the threats of a fracturing world will rely on effective collaboration between the public and private sectors.The 2025 Security and Defence conference brings together global policymakers, senior military and armed forces figures, business leaders and civil society experts. An insightful day of keynotes, high-level panel dialogues, and ‘under-the-Rule’ spotlights will explore how advanced technology is shaping the battlefield, examine how security architectures can be redesigned to support the end goal of peace, and address the future of arms control measures. Discussions will also unpack how forward-thinking defence actors might unlock fresh opportunities alongside current challenges. Forging stronger ties with partners to future-proof institutions and develop the architecture that will sustain security and defence ecosystems into the future will be crucial to ensuring that fighting forces are equipped, not just for the conflicts of today, but the security challenges of tomorrow.Why attend?Learn more about the areas that leaders across the security and defence ecosystem are prioritizing and how they aim to counter emerging threats in order to foster resilience in this environment.Gain an understanding of the array of threats that are present, both across the domains of conflict and also the different regions of the world.In-person networking opportunities with senior leaders from across the government, international militaries and global business, as well as access to exclusive ‘under-the-Rule’ sessions.The institute occupies a position of respect and trust, and is committed to fostering inclusive dialogue at all events. Event attendees are expected to uphold this by adhering to our code of conduct. Full Article
nc Iraq Initiative Conference 2024 By www.chathamhouse.org Published On :: Fri, 04 Oct 2024 10:12:13 +0000 Iraq Initiative Conference 2024 20 November 2024 — 9:30AM TO 5:00PM Anonymous (not verified) 4 October 2024 Chatham House and Online Our sixth annual Iraq Initiative conference will convene Iraqi and international policymakers, experts and civil society in London to discuss the critical questions for Iraq’s future, and the country’s trajectory in the year ahead. Over two decades following regime change, Iraq appears to be on a path to recovery and growth. With the support of high oil prices, Prime Minister Mohammed Shia’ al-Sudani’s government is implementing an ambitious plan to develop critical infrastructure, enhance ties with neighbouring countries, and renegotiate relationships with international partners like the US and UN. The political system has rebounded from a series of shocks and is in the process of consolidating and centralising power in Baghdad under the governing Shia Coordination Framework.However, underlying political, economic, security, and regional challenges, if not addressed, threaten this apparent stability and frustrate longer-term hope for a better future. Despite the country’s wealth, many young Iraqis struggle to find jobs while the space for civic activism shrinks. Meanwhile, the escalation of violence across the region threatens to engulf Iraq in further conflict. With the 2025 parliamentary election approaching, infighting within the governing coalition also suggests political turmoil in the year ahead.The key questions explored through each session include:How can the Sudani government tackle the roots of these obstacles to ensure that development can be sustained over time?What are the key steps to coherent and effective state-building?And how can regional and international actors support this process?This conference is part of Chatham House’s Iraq Initiative.This year’s conference features RE-PLAY – a video art exhibition curated by Dr Tamara Chalabi of the Ruya Foundation. The artists featured in this exhibition, spanning multiple generations both within Iraq and in the Iraqi diaspora, use their work to grapple with complex notions of Iraqi identity through the thematic issues of heritage, exile, disconnection, freedom of expression, and other persistent issues explored in this show.Simultaneous English-Arabic interpretation will be available for all conference sessions. This event is part of Chatham House’s Iraq Initiative. Iraq Initiative conference 2024 agenda [English] (PDF, 2.97MB) Iraq Initiative conference 2024 agenda [Arabic] (PDF, 2.29MB) RE-PLAY Video Art Exhibition [English] (PDF, 0.23MB) RE-PLAY Video Art Exhibition [Arabic] (PDF, 0.22MB) The institute occupies a position of respect and trust, and is committed to fostering inclusive dialogue at all events. Event attendees are expected to uphold this by adhering to our code of conduct. Full Article
nc Fluorescence assay for simultaneous quantification of CFTR ion-channel function and plasma membrane proximity [Methods and Resources] By www.jbc.org Published On :: 2020-12-04T00:06:05-08:00 The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane anion channel that plays a key role in controlling transepithelial fluid movement. Excessive activation results in intestinal fluid loss during secretory diarrheas, whereas CFTR mutations underlie cystic fibrosis (CF). Anion permeability depends both on how well CFTR channels work (permeation/gating) and on how many are present at the membrane. Recently, treatments with two drug classes targeting CFTR—one boosting ion-channel function (potentiators) and the other increasing plasma membrane density (correctors)—have provided significant health benefits to CF patients. Here, we present an image-based fluorescence assay that can rapidly and simultaneously estimate both CFTR ion-channel function and the protein's proximity to the membrane. We monitor F508del-CFTR, the most common CF-causing variant, and confirm rescue by low temperature, CFTR-targeting drugs and second-site revertant mutation R1070W. In addition, we characterize a panel of 62 CF-causing mutations. Our measurements correlate well with published data (electrophysiology and biochemistry), further confirming validity of the assay. Finally, we profile effects of acute treatment with approved potentiator drug VX-770 on the rare-mutation panel. Mapping the potentiation profile on CFTR structures raises mechanistic hypotheses on drug action, suggesting that VX-770 might allow an open-channel conformation with an alternative arrangement of domain interfaces. The assay is a valuable tool for investigation of CFTR molecular mechanisms, allowing accurate inferences on gating/permeation. In addition, by providing a two-dimensional characterization of the CFTR protein, it could better inform development of single-drug and precision therapies addressing the root cause of CF disease. Full Article
nc High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged to a pandemic and caused global public health crisis. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides angiotensin II to control vasodilatation and vascular permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we investigated how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ∼3-10 fold against model peptide substrates, such as caspase-1 substrate and Bradykinin-analog. The enhancement in ACE2 enzymatic function was mediated by the binding of SARS-CoV-2 spike RBD domain. These results highlighted the potential for SARS-CoV-2 infection to enhance ACE2 activity, which may be relevant to the cardiovascular symptoms associated with COVID-19. Full Article
nc Reply to Sysel et al.: Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability [Letters to the Editor] By www.jbc.org Published On :: 2020-10-23T00:06:00-07:00 In their comment (1) on our publication (2), the authors make two points: (i) they raise concerns about the possible effect of residual NONOate in our study, and (ii) they promote nitrosylcobalamin (NOCbl) supplied by their own company. Both points lack merit for the following reasons. The authors make the astonishing claim that the spectra of nitric oxide (NO•) and cobalamins overlap. Unlike NO•, cobalamin absorbs in the visible region, permitting unequivocal spectral assignment of NOCbl as reported (3). We demonstrated that whereas NOCbl is highly unstable in solution, it is stabilized by the B12 trafficking protein CblC. So even if present, residual NONOate (which is unstable at neutral pH and is removed during the work-up (3)) could not account for the observed difference.The authors then misrepresent our synthetic method, claiming that anaerobic conditions were used to generate nitrocobalamin (NO2Cbl), which results in the transient formation of NOCbl. We synthesized NO2Cbl aerobically using nitrite as described (4); NOCbl is not an intermediate in this ligand exchange reaction. The aerobic instability of NOCbl has been rigorously described by inorganic chemists (3, 5) and raises obvious questions about its purported biological effects as exemplified by the authors' own 2003 JBC publication, which was later withdrawn.As to promoting NOCbl from their company, the authors refer to a synthetic route from a mixture of NO• gas and aquocobalamin. The authors' method (6) has been described as “dubious” by chemists (5). Whereas DEAE NONOate used in our method is widely known as an NO• donor,... Full Article
nc Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability [Letters to the Editor] By www.jbc.org Published On :: 2020-10-23T00:06:00-07:00 After a thorough read of this paper (1), we wish to clarify that the authors' anaerobic method of synthesis for the production of nitrocobalamin results in the transient formation of nitrosylcobalamin, an unstable intermediate upon exposure to air. We concur that the authors' method results in the production of nitrocobalamin based on the UV-visible data as shown. The authors' adapted anaerobic method consists of mixing hydroxocobalamin hydrochloride with diethylamine NONOate diethylammonium salt in aqueous solution. Of concern, the UV spectrum of nitric oxide overlaps that of all cobalamin species under anaerobic conditions, making any assignments of the binding of nitric oxide to hydroxocobalamin suspect (2). Additionally, the use of acetone to precipitate the authors' product causes precipitation of diethylamine NONOate, resulting in an impure product. As a result, its utility for drawing experimental conclusions is faulty.The product from the authors' anaerobic synthetic method has not been assessed for purity, and the synthetic method itself has not been validated using a stability-indicating method as required by the International Conference on Harmonization (ICH) (ICH Q2B, Validation of Analytical Procedures) methodology, which is a hallmark for analytical characterization. Our nitrosylcobalamin synthesis involves reacting nitric oxide gas with hydroxocobalamin acetate as a heterogeneous mixture in a non-electron-donating solvent followed by rotary evaporation. Our nitrosylcobalamin product is stable in air, releases nitric oxide gas in situ (3), and meets ICH stability guidelines (4). Additionally, our nitrosylcobalamin product demonstrates biological activity, which has not been observed for nitrocobalamin (3, 5). Full Article
nc Naturally occurring hotspot cancer mutations in G{alpha}13 promote oncogenic signaling [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-04T00:06:06-08:00 Heterotrimeric G-proteins are signaling switches broadly divided into four families based on the sequence and functional similarity of their Gα subunits: Gs, Gi/o, Gq/11, and G12/13. Artificial mutations that activate Gα subunits of each of these families have long been known to induce oncogenic transformation in experimental systems. With the advent of next-generation sequencing, activating hotspot mutations in Gs, Gi/o, or Gq/11 proteins have also been identified in patient tumor samples. In contrast, patient tumor-associated G12/13 mutations characterized to date lead to inactivation rather than activation. By using bioinformatic pathway analysis and signaling assays, here we identified cancer-associated hotspot mutations in Arg-200 of Gα13 (encoded by GNA13) as potent activators of oncogenic signaling. First, we found that components of a G12/13-dependent signaling cascade that culminates in activation of the Hippo pathway effectors YAP and TAZ is frequently altered in bladder cancer. Up-regulation of this signaling cascade correlates with increased YAP/TAZ activation transcriptional signatures in this cancer type. Among the G12/13 pathway alterations were mutations in Arg-200 of Gα13, which we validated to promote YAP/TAZ-dependent (TEAD) and MRTF-A/B-dependent (SRE.L) transcriptional activity. We further showed that this mechanism relies on the same RhoGEF-RhoGTPase cascade components that are up-regulated in bladder cancers. Moreover, Gα13 Arg-200 mutants induced oncogenic transformation in vitro as determined by focus formation assays. In summary, our findings on Gα13 mutants establish that naturally occurring hotspot mutations in Gα subunits of any of the four families of heterotrimeric G-proteins are putative cancer drivers. Full Article
nc Allosteric activation of proto-oncogene kinase Src by GPCR-beta-arrestin complexes [Enzymology] By www.jbc.org Published On :: 2020-12-04T00:06:06-08:00 G protein–coupled receptors (GPCRs) initiate signaling cascades via G-proteins and beta-arrestins (βarr). βarr-dependent actions begin with recruitment of βarr to the phosphorylated receptor tail and are followed by engagement with the receptor core. βarrs are known to act as adaptor proteins binding receptors and various effectors, but it is unclear whether in addition to the scaffolding role βarrs can allosterically activate their downstream targets. Here we demonstrate the direct allosteric activation of proto-oncogene kinase Src by GPCR–βarr complexes in vitro and establish the conformational basis of the activation. Whereas free βarr1 had no effect on Src activity, βarr1 in complex with M2 muscarinic or β2-adrenergic receptors reconstituted in lipid nanodiscs activate Src by reducing the lag phase in Src autophosphorylation. Interestingly, receptor–βarr1 complexes formed with a βarr1 mutant, in which the finger-loop, required to interact with the receptor core, has been deleted, fully retain the ability to activate Src. Similarly, βarr1 in complex with only a phosphorylated C-terminal tail of the vasopressin 2 receptor activates Src as efficiently as GPCR–βarr complexes. In contrast, βarr1 and chimeric M2 receptor with nonphosphorylated C-terminal tail failed to activate Src. Taken together, these data demonstrate that the phosphorylated GPCR tail interaction with βarr1 is necessary and sufficient to empower it to allosterically activate Src. Our findings may have implications for understanding more broadly the mechanisms of allosteric activation of downstream targets by βarrs. Full Article
nc Disease-associated mutations in inositol 1,4,5-trisphosphate receptor subunits impair channel function [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 The inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), which form tetrameric channels, play pivotal roles in regulating the spatiotemporal patterns of intracellular calcium signals. Mutations in IP3Rs have been increasingly associated with many debilitating human diseases such as ataxia, Gillespie syndrome, and generalized anhidrosis. However, how these mutations affect IP3R function, and how the perturbation of as-sociated calcium signals contribute to the pathogenesis and severity of these diseases remains largely uncharacterized. Moreover, many of these diseases occur as the result of autosomal dominant inheritance, suggesting that WT and mutant subunits associate in heterotetrameric channels. How the in-corporation of different numbers of mutant subunits within the tetrameric channels affects its activities and results in different disease phenotypes is also unclear. In this report, we investigated representative disease-associated missense mutations to determine their effects on IP3R channel activity. Additionally, we designed concatenated IP3R constructs to create tetrameric channels with a predefined subunit composition to explore the functionality of heteromeric channels. Using calcium imaging techniques to assess IP3R channel function, we observed that all the mutations studied resulted in severely attenuated Ca2+ release when expressed as homotetramers. However, some heterotetramers retained varied degrees of function dependent on the composition of the tetramer. Our findings suggest that the effect of mutations depends on the location of the mutation in the IP3R structure, as well as on the stoichiometry of mutant subunits assembled within the tetrameric channel. These studies provide insight into the pathogenesis and penetrance of these devastating human diseases. Full Article
nc Tyrosine phosphorylation of the scaffold protein IQGAP1 in the MET pathway alters function [Signal Transduction] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 IQGAP1 is a key scaffold protein that regulates numerous cellular processes and signaling pathways. Analogous to many other cellular proteins, IQGAP1 undergoes post-translational modifications, including phosphorylation. Nevertheless, very little is known about the specific sites of phosphorylation or the effects on IQGAP1 function. Here, using several approaches, including MS, site-directed mutagenesis, siRNA-mediated gene silencing, and chemical inhibitors, we identified the specific tyrosine residues that are phosphorylated on IQGAP1 and evaluated the effect on function. Tyr-172, Tyr-654, Tyr-855, and Tyr-1510 were phosphorylated on IQGAP1 when phosphotyrosine phosphatase activity was inhibited in cells. IQGAP1 was phosphorylated exclusively on Tyr-1510 under conditions with enhanced MET or c-Src signaling, including in human lung cancer cell lines. This phosphorylation was significantly reduced by chemical inhibitors of MET or c-Src or by siRNA-mediated knockdown of MET. To investigate the biological sequelae of phosphorylation, we generated a nonphosphorylatable IQGAP1 construct by replacing Tyr-1510 with alanine. The ability of hepatocyte growth factor, the ligand for MET, to promote AKT activation and cell migration was significantly greater when IQGAP1-null cells were reconstituted with IQGAP1 Y1510A than when cells were reconstituted with WT IQGAP1. Collectively, our data suggest that phosphorylation of Tyr-1510 of IQGAP1 alters cell function. Because increased MET signaling is implicated in the development and progression of several types of carcinoma, IQGAP1 may be a potential therapeutic target in selected malignancies. Full Article
nc Nancy Pelosi in Taiwan: What lies ahead for China and the US? By www.chathamhouse.org Published On :: Wed, 03 Aug 2022 13:54:41 +0000 Nancy Pelosi in Taiwan: What lies ahead for China and the US? Expert comment GBhardwaj 3 August 2022 Chatham House experts examine the implications for Taiwan, China and the United States of Nancy Pelosi’s visit to the island. China’s fading ties with Washington? Dr Yu Jie US House Speaker, Nancy Pelosi’s, visit to Taiwan has plunged China-US relations into a new low as the reservoir of trust forged between the two sides over the last 40 years appears to be almost exhausted. However, her move will likely not result in the full-scale crisis across the Taiwan strait that some hawkish voices in both Beijing and Washington believe. Instead, Beijing will most likely offer a combination of military posturing toward the US navy and economic sanctions on Taiwanese agricultural and manufacturing products in order to send a clear bellwether to any future potential visits by high-level Western political figures. China will be careful not to stumble into an accidental conflict. Neither Beijing nor Washington has declared a willingness to change the current status quo as the present impasse benefits both governments – but for different reasons. For China, the best approach is to reach a military and economic capability that prevents US engagement with Taiwan without the use of force. For the US, the strategic ambiguity under the Taiwan Relations Act remains an effective card to counter China’s growing military influence in the Indo-Pacific and keep itself relevant within the region as a security guarantor. Yet, both sides have decided to kick the issue of Taiwan’s status down the road, believing that time is ultimately on their side. Despite a chorus of nationalistic rhetoric, China will be careful not to stumble into an accidental conflict which risks colossal damage on all fronts. Chinese President, Xi Jinping, must weigh all of the options before him as Beijing cannot afford to be perceived as unilaterally seeking to change what it agreed with the US back in 1979 when ties were re-established. If that happens, it will provoke the US political establishment to reach a unanimous agreement to change its ‘One China Policy’ and, ahead of the 20th Communist Party Congress where Xi is expected to be crowned for a historic third term, the last thing he wants is an unnecessary conflict with Taiwan. The road to escalation? Dr Bill Hayton Beijing has chosen to take issue over Nancy Pelosi’s visit to Taiwan in a way that it did not do for other recent US Congressional visits to the island. Several high-ranking US senators visited in April and May this year yet none of these visits triggered the prospect of a cross-strait crisis. So why has Beijing chosen to turn Pelosi’s visit into a stand-off? Pelosi’s visit is part of a performance in which both actors – the US and China – are playing primarily for their domestic audiences. This comes at a time when ruling circles in Beijing are preparing for the five-yearly Communist Party Congress. Amid a slowing economy and successive COVID-19 variants, Xi Jinping cannot afford to look weak as he prepares the ground for his third term of office. Meanwhile, the US, represented either by President Joe Biden or House Speaker Pelosi, cannot back down at this point without looking weak itself. The impact on a world economy already suffering major disruption because of the Russian invasion of Ukraine and the lingering effects of COVID-19 would be stark. Both sides have moved military assets into strategic positions near Taiwan to demonstrate their resolve. Neither side wants confrontation yet neither wishes to be humiliated. Currently, Pelosi’s visit, amid posturing by China, will make the US appear strong, but the consequences are likely to play out over a longer period. Xi Jinping will need to appear to have recaptured the initiative between now and the congress in the autumn when the risk of an incident will be at its greatest. Taiwan controls several isolated islands that could be pressured by Chinese forces in the event of a future crisis. The Kinmen and Matsu archipelagos lie just a few miles off the coast of the mainland and have been at the centre of previous confrontations. There are also two other points of concern. Pratas Island – known as Dongsha – sits halfway between Taiwan and Hong Kong. Itu Aba – known as Taiping – is the largest of the Spratly Islands in the centre of the South China Sea. All would be vulnerable to an attack by the People’s Liberation Army, the principal military force of China, and the armed wing of the Chinese Communist Party. A military confrontation between China and the US over Taiwan, or further south in the South China Sea, would have major impacts on regional and global trade. An estimated $300 billion worth of trade passes through the area every month. Japan and South Korea depend heavily on flows of oil and gas through the sea. Exports from Vietnam, Malaysia, Indonesia and the Philippines would also be heavily affected by disruptions to shipping, increased insurance costs and interruptions in inflows of raw materials. The impact on a world economy already suffering major disruption because of the Russian invasion of Ukraine and the lingering effects of COVID-19 would indeed be stark. Is a shift in US policy on the cards? Dr Leslie Vinjamuri Nancy Pelosi’s visit to Taiwan will undoubtedly be seen as a provocation by Beijing – even if it should not be. Pelosi’s trip to the Indo-Pacific, which also includes visits to Singapore, Malaysia, South Korea and Japan, comes at a time of growing tension between the US and China in the region. It also comes at a time when the divide among Washington’s foreign policy elite is growing, with some arguing that it is time to abandon the country’s policy of ‘strategic ambiguity’, where it refrains from stating how it would react were China to openly and deliberately attack Taiwan. Indeed, recent statements by President Joe Biden have raised questions about whether the US is set to make a policy change. But, since both its ‘One China Policy’ and policy of strategic ambiguity have been largely successful, it would be wise for the US to maintain them. It would be a mistake for the US to signal a major policy change away from strategic ambiguity and towards strategic clarity on Taiwan’s status. During her visit, Pelosi is likely to reaffirm the US’ high regard for Taiwan’s democracy and embrace the language of shared values. She has embraced Biden’s framing of international relations as a contest between democracies and autocracies. This alone will continue to exacerbate tensions. It would be a mistake, though, to signal a major policy change away from strategic ambiguity and towards strategic clarity on Taiwan’s status. Even if the US decides later to embrace a policy shift of this size, such a message should be carefully considered and communicated clearly, and not by chance. Congress has an important role to play but President Joe Biden and his national security team should make the final decision on US policy towards Taiwan. Getting the signals right in international politics is a key part of deterrence and, especially in East Asia, deterring both China and Taiwan’s ambitions is essential. Increasing insecurity in the region? Dr John Nilsson-Wright and Ben Bland Nancy Pelosi’s visit to Taiwan has provoked mixed responses from US allies across Asia. For Japanese policymakers, the Taiwan issue is connected to the wider issue of regional security. Fears that a military conflict over the island will inevitably draw Japanese self-defense forces into a shooting war with China – a development that is neither formally mandated under the terms of the US-Japan Mutual Security Treaty nor necessarily constitutionally sanctioned – explains the concerns in Tokyo. While the Japanese government of Prime Minister Fumio Kishida is increasingly worried about China’s growing military presence in the East and South China Seas, Japan’s heavy trade dependence on China and the country’s economic and security vulnerabilities make it imperative to avoid any further escalation of tensions. Given Tokyo’s non-recognition policy towards Taiwan, Japanese ties with Taipei are handled informally by politicians of the governing Liberal Democratic Party (LDP), rather than at cabinet or foreign ministry level, and in recent weeks and months there has been an increase in visits by cross party delegations from Japan. Though most Asian governments are keen to see the US constructively engaged in the region they also want to see stable China-US relations. The death of former Prime Minister Shinzo Abe as removed from public life a vocal advocate in support of enhanced ties between Tokyo and Taipei, but with public opinion in Japan increasingly tilting in an anti-Chinese direction, and with younger politicians favouring a more combative approach towards Beijing, there is a risk that the government will face pressure at home to toughen its language on Taiwan. Bolstering deterrence through increased military cooperation among allies, along with a graduated increase in defence spending, is the best way of limiting risk over Taiwan. Nevertheless, privately, many officials in Tokyo are likely to have viewed the Pelosi visit as an unhelpful intervention and will be puzzled and perhaps frustrated by the apparent inability of the Biden administration to persuade the US Speaker of the House of Representatives to cancel her visit. In South Korea, the government of President Yoon Suk-yeol, faces similar pressures to Japan, given the heavy dependence of the South Korean economy on China for trade and investment opportunities. Pelosi’s visit to the region will strikingly not include meetings with either the president or Foreign Minister Park Jin. With Yoon on vacation and Park attending the ASEAN Regional Forum meeting in Cambodia, the absence of high profile engagements for Pelosi might seem to be a purely practical matter, but Seoul may also be seeking to avoid antagonizing Beijing at a time when the Chinese government is seeking to pressure South Korea not to enhance alliance coordination with the United States and Japan or to expand its commitment to the controversial Terminal High Altitude Area Defence (THAAD) missile defence system. As in Japan, public opinion in South Korea is increasingly anti-Chinese, but the logic of regional economic and security uncertainty, requires the Yoon government to avoid getting trapped in a worsening stand-off with Beijing. Full Article
nc The near death and uncertain future of the US National Security Council By www.chathamhouse.org Published On :: Mon, 09 Jan 2023 13:27:13 +0000 The near death and uncertain future of the US National Security Council 27 January 2023 — 9:00AM TO 10:00AM Anonymous (not verified) 9 January 2023 Chatham House What role should the US National Security Council play in an era of great power competition? Please plan to arrive at Chatham House from 08:45 GMT as the event will begin promptly at 09:00 GMT Over the last three years, the US National Security Council (NSC) has gone from being neglected to necessary again, in Washington. After former US President Donald Trump ignored and then tried to dismantle the NSC, current US President Joe Biden has restored the body but chosen not to reform it. Born in the days before the Cold War and empowered during the War on Terror, what role should the NSC play in an era of great power competition? Plus, how must it, and the rest of Washington, evolve to meet the challenges and opportunities that remain in the 21st century? Full Article
nc Reflections on Iraq since 2003 By www.chathamhouse.org Published On :: Mon, 20 Feb 2023 13:42:13 +0000 Reflections on Iraq since 2003 6 March 2023 — 11:00AM TO 12:15PM Anonymous (not verified) 20 February 2023 Chatham House This event reflects on the legacy of the invasion and occupation for Iraq, the Middle East, and the West. When a US-led coalition invaded Iraq and overthrew the Saddam Hussein regime 20 years ago, many Iraqis hoped that a more democratic, prosperous future lay ahead. But in reality, their lives have been marred by different forms of violent conflict, fuelled by a corrupt system through which a new class of leaders gutted state finances and enriched themselves at the expense of the people. Today, almost two-thirds of the Iraqi population are under 25 and have no memory of life under Saddam Hussein. For many, the legacy of the war is only a failed political system that kills every day by means of corruption and neglect. At this roundtable, part of the Iraq Initiative, Chatham House welcomes journalist and author Ghaith Abdul-Ahad to discuss his book on this subject, called A Stranger in Your Own City: Travels in the Middle East’s Long War, alongside a panel of experts who will explore the profound legacy of the war for the Iraqi people. This marks the first in a series of Chatham House Iraq Initiative events and analysis reflecting on the legacy of the invasion and occupation for Iraq, the Middle East and the West. Full Article
nc SVB collapse shows interest rate financial stability threat By www.chathamhouse.org Published On :: Wed, 15 Mar 2023 19:39:36 +0000 SVB collapse shows interest rate financial stability threat Expert comment LJefferson 15 March 2023 Governments must resist pressure to relax post-financial crisis regulation, while central banks should moderate their attack on inflation if financial stability is at risk. The collapse of California’s Silicon Valley Bank (SVB) on 10 March has triggered a wave of volatility in global bank equity prices, raised questions about whether US bank regulation and its tech industry funding model are fit for purpose, and forced a rethink on the extent and pace of monetary policy tightening appropriate for the US and other advanced economies. SVB was the US’s 16th largest bank with total assets of $212bn at the end of 2022 and a presence in eight countries around the world, including the UK. Since it was founded 40 years ago, it has maintained a strong focus on the technology sector, claiming recently that nearly half of all US venture-backed technology and life science companies banked with it. Partly as a consequence, some 95 per cent of its deposits came from corporates and hedge funds, far higher than the one-third typical of similarly sized banks. What led to SVB’s collapse? Ironically, SVB’s failure did not result from its core business model of serving a relatively high-risk and fast-growing sector, but rather from a dramatic failure in liquidity management. During the pandemic, SVB saw a very large inflow of corporate deposits. But rather than disincentivizing depositors or investing the funds attracted in assets of matching maturity, it chose to invest them in low credit risk, but long maturity bonds attracted by a small pick-up in return over shorter-term assets. When US interest rates began to rise rapidly in 2022 following Russia’s invasion of Ukraine, the value of SVB’s long-term bond portfolio declined sharply. It was left facing a large capital loss of some $15bn, roughly equivalent to its total shareholder funds. The management attempted to repair SVB’s balance sheet last week by crystalizing some of the loss and raising new capital. But when this failed, the US supervisory authorities had no choice but to step in and close the institution. This action was quickly followed by emergency action from other regulators vis-a-vis SVB subsidiaries and offices around the world. Ironically, SVB’s failure did not result from its core business model of doing business with a relatively high-risk and fast-growing sector, but rather from a dramatic failure in liquidity management. The US entity has formally been taken over by the FDIC and a bridge bank established. All depositors have had their funds guaranteed, going beyond the normal federal deposit insurance limit of $250,000 per customer. However, bond holders and equity holders have been wiped out. The authorities have said that any loss will be covered by the industry as a whole via the FDIC. In the UK, the Bank of England was able to sell the ring-fenced UK subsidiary of SVB to HSBC for £1 over the weekend, so that all its depositors and other liability holders have effectively had their funds guaranteed. In contrast to previous Bank of England rescues (such as Johnson Matthey Bank in 1984, the ‘small banks’ crisis in 1991 and the global financial crisis in 2008-9) no public money has been put at risk. Four key questions SVB’s rapid collapse raises four central questions: First, how was it that the bank was able to take on such a risky interest rate maturity mismatch in its US operations? Maturity transformation is standard banking industry practice, but it is usually closely monitored by regulators who place limits on the extent of interest rate maturity mismatch and require liquidity buffers to offset the risk of deposit flight and forced asset sales. SVB’s very high concentration of corporate deposits as compared to ‘sticky’ retail deposits, means that the risk of deposit flight was unusually high and so the bank should have been more, not less, cautious in its liquidity policy. SVB was classed as a regional bank in the US which means that it did not have to meet international regulatory standards under Basle III. And in 2018, the Trump administration approved legislation removing the post-financial crisis requirement that banks with assets under $250bn submit to stress testing and relaxing liquidity buffer requirements. But it is still hard to understand why regulators allowed SVB to commit such a classic banking error. On Monday, the Federal Reserve ordered an inquiry into what it has correctly described as a regulatory failure. This should look at the role played by all the elements of the oversight system including the auditors, KPMG. In 2018, the Trump administration approved legislation removing a post-financial crisis (regulatory) requirement…but it is still hard to understand why regulators allowed SVB to commit such a classic banking error. Second, does SVB’s failure reflect a much bigger underlying risk in the US banking sector, and potentially other banking systems around the world, built up over the prolonged period of ultra-low interest rates? SVB’s collapse was followed by the failure of the $110bn Signature Bank in New York, as well as sharp falls in US regional bank stock prices – by close of play on 14 March, the S&P Regional Bank Index was down 22 per cent on a week before, with some individual bank stocks seeing much sharper falls. To the extent that banks have been covered by international bank regulatory requirements, the risk of a much broader problem should be limited because stress testing and other regulatory tests would have looked at precisely the scenario that has happened. Even where large market losses have been incurred, capital buffers should be sufficient to cover them. But as SVB has shown, there are some large banks that are seemingly not required to follow international rules, while the latest developments at Credit Suisse indicate that market concerns may still arise when other factors are in play. SVB’s collapse was followed by the failure of the $110bn Signature Bank in New York, as well as sharp falls in US regional bank stock prices. Third, how far, in the light of the potential vulnerability in banking systems, should central banks in advanced countries moderate their efforts to squeeze out inflationary pressures? While inflation already appears to have peaked in many economies and the pace of interest rate rises was expected to slow, inflation is far from vanquished, as recent data in the US has demonstrated. Fourth, does the failure of SVB tell us something new about the financial risks facing the high technology sector? It was remarkable that a single (and not particularly large, by international standards) financial institution could have played such a central role in the tech sector in both the US and UK. Why was this the case and does it reflect special features of the tech/start-up sector (e.g. the need for substantial cash deposits to cover relatively large negative cash flows in the early years of operation, or the need for highly specialized lending expertise). If so, should governments take steps to mitigate such risks, given the outsized importance of this sector in many national economic strategies? Full Article
nc China’s renewed influence in the Gulf By www.chathamhouse.org Published On :: Fri, 14 Apr 2023 18:24:22 +0000 China’s renewed influence in the Gulf Interview LJefferson 14 April 2023 By disseminating narratives of its own supremacy, China deepened relations with the Gulf during the COVID-19 pandemic. China has used the COVID-19 pandemic as an opportunity to rebrand its international role as a ‘responsible’ and ‘great’ power by voicing narratives of its own supremacy to regions like the Gulf. In this interview, Julia Gurol-Haller draws on her International Affairs article to trace how the UAE, Saudi Arabia, Qatar and Iran have responded to China’s narratives, with key implications for Sino-US competition and regional autonomy for the Gulf. This illustrates how words and narratives help bolster authoritarian power. What have the China-Gulf relations looked like in context of the COVID-19 pandemic? Bilateral relations between China and the Gulf countries have grown in importance over the past decade, particularly since 2013 with the Belt and Road Initiative. The Gulf plays a crucial role in China’s Belt and Road Initiative and its westward expansion, owing to its favourable geographic position and proximity to the Red Sea. In the beginning, transregional relations were mainly economic partnerships since China has a growing appetite for oil and gas and the Gulf monarchies fulfil these needs. China is one of the most important markets for Saudi Arabia, the UAE, and Qatar to export these goods. Over time, we’ve seen the Sino-Gulf relations expand beyond just economic ties and towards policy fields like security and cultural relations. While these processes were already in place, they were boosted during the COVID-19 pandemic, not only in material terms but also in respect of Chinese attempts to advance its soft power, leverage, and influence in the Gulf region. When COVID-19 began to ravage the globe, China took that window of opportunity to rebrand its international role. Through efforts such as mask diplomacy, vaccine diplomacy and the strategic diffusion of narratives, China tried to project its image as a ‘global saviour’ and a responsible and great power. The Gulf monarchies and Iran were among the main target audiences for this public diplomacy campaign. So, the COVID-19 pandemic has been a catalysing factor for deepening relations between China and the Gulf region. What exactly are narratives and why are they important in China’s approach to the Gulf states during the COVID-19 pandemic? Through diplomatic statements, news outlets and social media, China has engaged in, what I call, a ‘narrative power-play’. To understand what that is, we need to understand the political importance of narratives. Authoritarian leaders function as ‘storytellers-in-chief’, shaping reality in their favour. Narratives are deliberately constructed by (political) actors to influence a certain target audience. In authoritarian contexts, narratives are a useful resource for political actors to bind audiences to their rule and to appeal to people’s emotions by strategically projecting certain images. Ultimately, this creates linkages via attraction or persuasion that enhance the actors’ legitimacy and consolidate their power. So, in the narrative power-play, authoritarian leaders function as ‘storytellers-in-chief’, shaping reality in their favour. What kinds of narratives has China disseminated to the Gulf region in backdrop of the COVID-19 pandemic? There are two sets of narratives that China disseminated to the Gulf: narratives of supremacy and narratives of a new world order. China disseminates narratives of systemic supremacy which include praising the overall efficiency of its governance structures. For instance, the Chinese political system is presented as highly efficient and centralized. It has high amounts of ‘state capacity’ for mobilization and the ability to ‘quickly adapt’ to changing situations. Overall, these narratives serve to depict China as a responsible, caring and loyal world power that helps other states. Narratives of performative supremacy refer to the tangible performance of the Chinese Communist Party or China as a whole, such as economic performance, performance in governance, provision of public goods or pandemic response. The performance narratives also highlight the ‘incredible logistical efficacy’, the highly professionalized medical sector and the innovative scientific sector. Narratives of normative supremacy are often informed by nationalist notions such as the reclaiming of China’s rightful position in the world and negative feelings towards Western imperial powers who are depicted as having inflicted great pains on China during the ‘century of humiliation’. Overall, these narratives serve to depict China as a responsible, caring and loyal world power that helps other states. The whole idea of mask diplomacy was also carved into that notion of China’s normative supremacy. Together, China has used these narratives to construct the idea of a new world order in which China is believed to play a much bigger role. The world order narratives are closely linked to stories about the failure of the Western system and show the intertwinement of practices of othering and self-glorification that can also be observed in Chinese official media narratives in other contexts such as diplomatic stand-offs with the United States. What do these narratives tell us about how China understands the world order? The narratives China disseminated to the Gulf region show that in the Chinese understanding of politics, the world order is in flux and undergoing major power reconfigurations. For China, this implies a window of opportunity to position itself as a responsible and great power and move from the side-lines to the centre stage of international politics. The narratives China disseminated to the Gulf region show that in the Chinese understanding of politics, the world order is in flux and undergoing major power reconfigurations. This is a trend that has been long in the making in Chinese foreign policy. For instance, the launch of the Chinese Global Security Initiative or the recent brokering of the Iran-Saudi rapprochement agreement show clearly that China is becoming much more than an economic powerhouse and is adopting a more proactive foreign policy. During the recent state visit of Xi Jinping to Moscow, he said at one point that China stands ready to ‘safeguard (…) the international order underpinned by international law ’. These examples are quite telling regarding the role China ascribes itself on the international stage. How have the Gulf countries responded to China’s power narratives during the COVID-19 pandemic? Saudi Arabia, the UAE, Qatar and Iran all picked up the narrative of China’s superior performance during the global crisis. That was a unified response, but they did that to different degrees and by highlighting different aspects. The strongest reproduction of Chinese narratives can be found in the Emirati media. They buy into the story of the COVID-19 pandemic as evoking a global power shift, which includes a decline of US hegemony and a corresponding rise of China. The explicit wording of Chinese narratives such as ‘community of shared future of humankind’ has been picked up word-for-word by some Emirati media outlets. Iranian newspapers have also reproduced Chinese narratives. However, the difference is that they also praise China’s unconditional solidarity during the COVID-19 pandemic, which is believed to be superior and more ‘responsible’ than the ostensible individualism of the West. This tells us a lot about Iran’s relationship with the West and how China is believed to be a lifeline or anchor for stability. The most pressing questions seem to be whether the post-COVID world will be a multipolar order, and what Saudi Arabia’s own position within it might be. Saudi Arabia has been more cautious in reproducing the Chinese narratives. While it does not contest China’s role in containing the COVID-19 pandemic, Saudi Arabia has adopted a more inward-looking perspective, stressing its own role as a responsible regional player during the pandemic. This might be explained by the kingdom’s own regional leadership claims and the attempt to use the crisis as an opportunity to strengthen this role. The most pressing questions seem to be whether the post-COVID world will be a multipolar order, and what Saudi Arabia’s own position within it might be. Full Article
nc Distinct and Overlapping Sets of SUMO-1 and SUMO-2 Target Proteins Revealed by Quantitative Proteomics By www.mcponline.org Published On :: 2006-12-01 Alfred C. O. VertegaalDec 1, 2006; 5:2298-2310Research Full Article
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nc PaxDb, a Database of Protein Abundance Averages Across All Three Domains of Life By www.mcponline.org Published On :: 2012-08-01 M. WangAug 1, 2012; 11:492-500Technological Innovation and Resources Full Article
nc A "Proteomic Ruler" for Protein Copy Number and Concentration Estimation without Spike-in Standards By www.mcponline.org Published On :: 2014-12-01 Jacek R. WiśniewskiDec 1, 2014; 13:3497-3506Research Full Article
nc Interpretation of Shotgun Proteomic Data: The Protein Inference Problem By www.mcponline.org Published On :: 2005-10-01 Alexey I. NesvizhskiiOct 1, 2005; 4:1419-1440Tutorial Full Article
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nc The Paragon Algorithm, a Next Generation Search Engine That Uses Sequence Temperature Values and Feature Probabilities to Identify Peptides from Tandem Mass Spectra By www.mcponline.org Published On :: 2007-09-01 Ignat V. ShilovSep 1, 2007; 6:1638-1655Technology Full Article
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