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X-ray structures of catalytic intermediates of cytochrome c oxidase provide insights into its O2 activation and unidirectional proton-pump mechanisms [Molecular Biophysics]

Cytochrome c oxidase (CcO) reduces O2 to water, coupled with a proton-pumping process. The structure of the O2-reduction site of CcO contains two reducing equivalents, Fea32+ and CuB1+, and suggests that a peroxide-bound state (Fea33+–O−–O−–CuB2+) rather than an O2-bound state (Fea32+–O2) is the initial catalytic intermediate. Unexpectedly, however, resonance Raman spectroscopy results have shown that the initial intermediate is Fea32+–O2, whereas Fea33+–O−–O−–CuB2+ is undetectable. Based on X-ray structures of static noncatalytic CcO forms and mutation analyses for bovine CcO, a proton-pumping mechanism has been proposed. It involves a proton-conducting pathway (the H-pathway) comprising a tandem hydrogen-bond network and a water channel located between the N- and P-side surfaces. However, a system for unidirectional proton-transport has not been experimentally identified. Here, an essentially identical X-ray structure for the two catalytic intermediates (P and F) of bovine CcO was determined at 1.8 Å resolution. A 1.70 Å Fe–O distance of the ferryl center could best be described as Fea34+ = O2−, not as Fea34+–OH−. The distance suggests an ∼800-cm−1 Raman stretching band. We found an interstitial water molecule that could trigger a rapid proton-coupled electron transfer from tyrosine-OH to the slowly forming Fea33+–O−–O−–CuB2+ state, preventing its detection, consistent with the unexpected Raman results. The H-pathway structures of both intermediates indicated that during proton-pumping from the hydrogen-bond network to the P-side, a transmembrane helix closes the water channel connecting the N-side with the hydrogen-bond network, facilitating unidirectional proton-pumping during the P-to-F transition.




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The short variant of optic atrophy 1 (OPA1) improves cell survival under oxidative stress [Bioenergetics]

Optic atrophy 1 (OPA1) is a dynamin protein that mediates mitochondrial fusion at the inner membrane. OPA1 is also necessary for maintaining the cristae and thus essential for supporting cellular energetics. OPA1 exists as membrane-anchored long form (L-OPA1) and short form (S-OPA1) that lacks the transmembrane region and is generated by cleavage of L-OPA1. Mitochondrial dysfunction and cellular stresses activate the inner membrane–associated zinc metallopeptidase OMA1 that cleaves L-OPA1, causing S-OPA1 accumulation. The prevailing notion has been that L-OPA1 is the functional form, whereas S-OPA1 is an inactive cleavage product in mammals, and that stress-induced OPA1 cleavage causes mitochondrial fragmentation and sensitizes cells to death. However, S-OPA1 contains all functional domains of dynamin proteins, suggesting that it has a physiological role. Indeed, we recently demonstrated that S-OPA1 can maintain cristae and energetics through its GTPase activity, despite lacking fusion activity. Here, applying oxidant insult that induces OPA1 cleavage, we show that cells unable to generate S-OPA1 are more sensitive to this stress under obligatory respiratory conditions, leading to necrotic death. These findings indicate that L-OPA1 and S-OPA1 differ in maintaining mitochondrial function. Mechanistically, we found that cells that exclusively express L-OPA1 generate more superoxide and are more sensitive to Ca2+-induced mitochondrial permeability transition, suggesting that S-OPA1, and not L-OPA1, protects against cellular stress. Importantly, silencing of OMA1 expression increased oxidant-induced cell death, indicating that stress-induced OPA1 cleavage supports cell survival. Our findings suggest that S-OPA1 generation by OPA1 cleavage is a survival mechanism in stressed cells.




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RNA helicase-regulated processing of the Synechocystis rimO-crhR operon results in differential cistron expression and accumulation of two sRNAs [Gene Regulation]

The arrangement of functionally-related genes in operons is a fundamental element of how genetic information is organized in prokaryotes. This organization ensures coordinated gene expression by co-transcription. Often, however, alternative genetic responses to specific stress conditions demand the discoordination of operon expression. During cold temperature stress, accumulation of the gene encoding the sole Asp–Glu–Ala–Asp (DEAD)-box RNA helicase in Synechocystis sp. PCC 6803, crhR (slr0083), increases 15-fold. Here, we show that crhR is expressed from a dicistronic operon with the methylthiotransferase rimO/miaB (slr0082) gene, followed by rapid processing of the operon transcript into two monocistronic mRNAs. This cleavage event is required for and results in destabilization of the rimO transcript. Results from secondary structure modeling and analysis of RNase E cleavage of the rimO–crhR transcript in vitro suggested that CrhR plays a role in enhancing the rate of the processing in an auto-regulatory manner. Moreover, two putative small RNAs are generated from additional processing, degradation, or both of the rimO transcript. These results suggest a role for the bacterial RNA helicase CrhR in RNase E-dependent mRNA processing in Synechocystis and expand the known range of organisms possessing small RNAs derived from processing of mRNA transcripts.




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Unified approach to critical-contrast homogenisation with explicit links to time-dispersive media

K. D. Cherednichenko, Yu. Yu. Ershova, A. V. Kiselev and S. N. Naboko
Trans. Moscow Math. Soc. 80 (2020), 251-294.
Abstract, references and article information




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Control with point observation for a parabolic problem with convection

I. V. Astashova, D. A. Lashin and A. V. Filinovskii
Trans. Moscow Math. Soc. 80 (2020), 221-234.
Abstract, references and article information





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An explicit form for extremal functions in the embedding constant problem for Sobolev spaces

I. A. Sheipak and T. A. Garmanova
Trans. Moscow Math. Soc. 80 (2020), 189-210.
Abstract, references and article information




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Spectral Properties of Differential Operators with Oscillating Coefficients

N. F. Valeev, Ya. T. Sultanaev and É. A. Nazirova
Trans. Moscow Math. Soc. 80 (2020), 153-167.
Abstract, references and article information




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The finiteness of the spectrum of boundary value problems defined on a geometric graph

V. A. Sadovnichii, Ya. T. Sultanaev and A. M. Akhtyamov
Trans. Moscow Math. Soc. 80 (2020), 123-131.
Abstract, references and article information




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On the solvability of a class of nonlinear integral equations in the problem of a spread of an epidemic

A. G. Sergeev and Kh. A. Khachatryan
Trans. Moscow Math. Soc. 80 (2020), 95-111.
Abstract, references and article information





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Finite-dimensional approximations to the Poincaré–Steklov operator for general elliptic boundary value problems in domains with cylindrical and periodic exits to infinity

S. A. Nazarov
Trans. Moscow Math. Soc. 80 (2020), 1-51.
Abstract, references and article information




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What happens to a fund that is listed pursuant to a product specific rule filing once the fund is eligible to operate under Rule 6c-11 and elects to list on Nasdaq under Rule 5704?

Publication Date: Apr 10 2020 The SEC will withdraw the existing approval order and the fund will become subject to the requirements of Rule 6c-11 and Nasdaq Rule 5704....




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How can a company rely on the COVID-19 exception to shareholder approval requirements?

Publication Date: May 4 2020 On May 1, 2020, Nasdaq adopted Rule 5636T, operative through, and including, June 30, 2020, to provide listed companies with a temporary exception from certain shareholder approval requirements. A Company must submit an application to Nasdaq’s Listing Qualifications Department demonstrating that the transaction satisfies the requirements in Rule 5636T and must provide the Notification Form: Listing of Additional Shares (“LAS Form”) required by...




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Security and Prosperity in Asia: The Role of International Law

1 November 2019

The 'Security and Prosperity in Asia' conference looked at the impact of international law in the Asia-Pacific with a focus on regional economic and security issues such as the South China Sea disputes.

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Singapore skyline at sunset, 2016. Photo: Getty Images.

About the Conference

At a time of geopolitical uncertainty and with multilateralism under pressure, this conference brought together diverse actors to explore the evolving role of international law on critical security and economic issues in the Asia-Pacific. From trade agreements to deep-sea mining, cyberwarfare to territorial disputes, the breadth of the discussion illustrated the growing reach of international law in the region.

Hosted by the International Law Programme and the Asia-Pacific Programme at Chatham House on 27 March 2019, the conference focused on three themes: trade and investment, maritime security and governance, and emerging security challenges. What trends are emerging in terms of engagement with international law in the region, and how can international standards play a greater role in encouraging collaboration and reducing tensions? And, with the eastward shift in geopolitical power, how will Asia-Pacific states shape the future of international law?




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The institutionalization of the Indo-Pacific: problems and prospects

8 January 2020 , Volume 96, Number 1

Kai He and Huiyun Feng

Although the term ‘Indo-Pacific’ has become popular in the foreign policy discourse of some countries, we have yet to see any significant institution-building in the Indo-Pacific region. Borrowing insights from functional institutionalism and political leadership studies of international regimes, we introduce a ‘leadership–institution’ model to explore the problems and prospects of institutionalizing the Indo-Pacific. Through a comparative case study of the institutionalization of the Asia–Pacific vs the Indo-Pacific, we argue that two crucial factors contributed to the slow institutionalization of the Indo-Pacific as a regional system in world politics: the lack of ideational leadership from an epistemic community and the weak executive leadership from a powerful state. While ideational leaders can help states identify and expand common interests in cooperation, executive leadership will facilitate states to overcome operational obstacles in cooperation, such as the ‘collective action’ problem and the ‘relative gains’ concern. The future of institution-building in the Indo-Pacific will depend on whether and how these two leadership roles are played by scholars and states in the region. In the conclusion, we discuss the challenges of institutionalizing the Indo-Pacific and highlight China as a wild card in the future of Indo-Pacific regionalism.




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Asian States Must Rethink Their Approach to Digital Governance

17 January 2020

Vasuki Shastry

Associate Fellow, Asia-Pacific Programme
Too many governments in the region are focusing on control and surveillance instead of citizens’ rights.

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Kashmiri students use the internet at a tourist reception centre in Srinagar, after internet facilities were suspended across the region in December 2019. Photo: Getty Images.

Asia’s political class learnt many lessons on digital governance in 2019, not all of them positive.

The prolonged protests in Hong Kong and India, led by disaffected young citizenry and enabled by social media tools, powerfully demonstrated how things could spiral out of control when the virtual and the real streets come together.

Not surprisingly, governments across the region are taking a step back. Instead of placing the citizen at the heart of digital public policy – with privacy, trust, security and inclusion as drivers of digital governance – Asian governments are focusing instead on surveillance and command and control, which contradicts the spirit of a decentralized Internet and undermines citizen’s rights.

Asia’s digital governance is fragmenting from the global norm and morphing into two platforms with remarkably similar characteristics.

One is a China-driven model aptly called the Great Firewall where surveillance of citizens is an explicit objective and any external material deemed to be subversive is kept out. A complementary model has also emerged more recently, which can best be described as China-light, which seeks to emulate the control aspects of the Great Firewall.

There are of course overlaps between emulators of the China model (this list includes Vietnam, Myanmar, Cambodia and Laos) and those pursuing China-light (Singapore, India, Indonesia, Bangladesh, Sri Lanka, the Philippines, Thailand and Malaysia). A common thread running through these two approaches, which differ only in intensity and scope, is the belief that the state is best positioned to police social media and protect the rights of citizens.

This was not how it was supposed to be. A decade ago, Asian political leaders spoke about the virtues of an open internet. Such talk has faded, and a narrowing of Asia’s digital space is taking place against a backdrop of an intensifying trade war between America and China, where regional supply chains run the risk of a decoupling into distinct Sino and American spheres, upending Asia’s durable economic model of the past few decades.

Digital fragmentation in the world’s fastest growing region, with five G20 members, will complicate efforts to build global governance and standards.

Asia’s digital landscape

Asian governments, including democratic ones, have developed an unhealthy obsession with what their citizens are up to on a daily basis. Their solution is round-the-clock monitoring in cities and towns, powered by new surveillance technologies.

Name tagging and facial recognition to track movement of citizens has become pervasive across the region, with China emerging as the preferred source of technology, knowledge, and techniques. While India’s Supreme Court has ruled that privacy is a fundamental right, translating this into concrete citizen’s protections will be difficult with the Modi government eager to emulate China’s approach.

Asian governments are also following China in requiring that their citizen’s data be housed within national borders and are rebelling against the established practice of data offshoring.

In the post-Snowden era and amidst increasing cyber risks, there are rational national security reasons for why governments may want to ring-fence customer data within national boundaries. However, Asian governments are paying little or no attention to how companies are using customer data within national boundaries, with widespread abuses going unchecked.

Global standards are still evolving and there is a strong case here for a uniform regional approach, perhaps via ASEAN or APEC, on standards governing customer privacy, payments, data collection and handling. Big tech companies and platforms operate across much of Asia and a regional approach will curb their current instinct of conducting regulatory arbitrage.

There is a genuine problem in Asia, as elsewhere in the world, with the proliferation of fake news and extremism. But instead of addressing the source of this problem, governments are clamping down by generously expanding the definition of fake news (Singapore) or by shutting down the internet altogether (India, Sri Lanka, and China being serial offenders).

As disseminators of news of all stripes, including the fake variant, the big tech firms have a primary responsibility in policing their platforms. However, the regulatory capacity of many Asian governments to monitor this is weak and in crisis situations, governments prefer to shut the pipes altogether.

Digitalization of course is not all about surveillance and holds the promise of driving inclusion. There is considerable hype within Asia on the promise of fintech as an enabler of this inclusion.

Hong Kong and Singapore are licensing new digital banks, India’s UPI (unified payments interface) is reducing friction in domestic payments and China’s BAT companies (Baidu, Alibaba, Tencent) are disrupting traditional commerce and payments, and seeking to expand in the region.

However, there is an elite focus in many of these initiatives, with the target market being the region’s rising middle class rather than those at the bottom of the income ladder. Making fintech work for all will require micro-initiatives with the support of NGOs, local governments and small enterprises, with the objective of digitalizing microfinance.

Here developing Asia will again benefit from learning from each other and in building regional approaches. India’s Aadhar for example, with appropriate security safeguards, is a model for Asia in terms of building digital identity.

Given differing regional and national objectives, it is difficult to imagine a global accord for digital governance any time soon. However, by signing on to the Regional Comprehensive Economic Partnership (RCEP) and the Comprehensive and Progressive Agreement for Transpacific Partnership (CPTPP, the successor to the TPP), Asia has consistently demonstrated its leadership in trade and regional governance.

This is why the region needs to come together to ensure that the promise and potential of digitalization flows evenly and equitably to the region, with the region’s 3.8 billion citizens at the heart, rather than at the margins of sensible public policy.




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Bangladesh: The Trade-Off Between Economic Prosperity and Human Rights

Research Event

11 March 2020 - 1:00pm to 2:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

K. Anis Ahmed, Publisher, Dhaka Tribune and Bangla Tribune; Author of Good Night, Mr. Kissinger, Co-director, Dhaka Literary Festival
Meenakshi Ganguly, South Asia Director, Human Rights Watch
Chair: Ed Cumming, Writer, The Independent

Bangladesh's recent gains in economic and social indices, set against its record of corruption and poor civil rights, has at times been termed the ‘Bangladesh Paradox’. Yet this label is overly simplistic; the current situation proves that these trends can coexist.

The Awami League government, in power since 2009, has increased political stability, delivered unprecedented economic and social advances, and adopted a counter-terrorism strategy to stamp out extremist groups. At the same time, it is criticized for curbing civil rights and failing to hold credible elections. However, as the two previous regimes have demonstrated, the rights situation is unlikely to improve even if the Awami League were replaced.

How did worsening rights become a feature of the state irrespective of its political dispensation? An unresolved contest between political and non-political state actors may hold the key to that puzzle. The perils of the current dispensation have recently manifested in weakening economic indicators, which jeopardize the very stability and social progress for which the country has garnered much praise.

Lucy Ridout

Programme Administrator, Asia-Pacific Programme
+44 (0) 207 314 2761




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Improving Stents - Part 2

Stents are expandable tubes that are inserted into blocked or damaged blood vessels. They offer a practical way to treat coronary artery disease, repairing vessels and keeping them open so that blood can flow freely. When stents work, they are a great alternative to radical surgery, but they can deteriorate or become dislodged. Mathematical models of blood vessels and stents are helping to determine better shapes and materials for the tubes. These models are so accurate that the FDA is considering requiring mathematical modeling in the design of stents before any further testing is done, to reduce the need for expensive experimentation. Precise modeling of the entire human vascular system is far beyond the reach of current computational power, so researchers focus their detailed models on small subsections, which are coupled with simpler models of the rest of the system. The Navier-Stokes equations are used to represent the flow of blood and its interaction with vessel walls. A mathematical proof was the central part of recent research that led to the abandonment of one type of stent and the design of better ones. The goal now is to create better computational fluid-vessel models and stent models to improve the treatment and prediction of coronary artery disease the major cause of heart attacks. For More Information: Design of Optimal Endoprostheses Using Mathematical Modeling, Canic, Krajcer, and Lapin, Endovascular Today, May 2006.




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Improving Stents - Part 1

Stents are expandable tubes that are inserted into blocked or damaged blood vessels. They offer a practical way to treat coronary artery disease, repairing vessels and keeping them open so that blood can flow freely. When stents work, they are a great alternative to radical surgery, but they can deteriorate or become dislodged. Mathematical models of blood vessels and stents are helping to determine better shapes and materials for the tubes. These models are so accurate that the FDA is considering requiring mathematical modeling in the design of stents before any further testing is done, to reduce the need for expensive experimentation. Precise modeling of the entire human vascular system is far beyond the reach of current computational power, so researchers focus their detailed models on small subsections, which are coupled with simpler models of the rest of the system. The Navier-Stokes equations are used to represent the flow of blood and its interaction with vessel walls. A mathematical proof was the central part of recent research that led to the abandonment of one type of stent and the design of better ones. The goal now is to create better computational fluid-vessel models and stent models to improve the treatment and prediction of coronary artery disease the major cause of heart attacks. For More Information: Design of Optimal Endoprostheses Using Mathematical Modeling, Canic, Krajcer, and Lapin, Endovascular Today, May 2006.




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Providing Power

Researcher: Michael C. Ferris, University of Wisconsin-Madison. Moment Title: Providing Power Description: Michael C. Ferris talks about power grids




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The World’s Best 40 Under 40 MBA Professors

Wednesday, April 29, 2020 - 13:30




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euromicron AG improves earnings in first half of 2019

Consolidated sales of EUR 146.7 million EBITDA (before IFRS 16) increased strongly by EUR 3.8 million to EUR 2.1 million Forecast for 2019 as a whole confirmed Working capital ratio declines by 2 percentage points to 10.6% euromicron AG, a medium-sized technology group and specialist for the digital networking of business and production processes, published its preliminary figures for the first half of 2019 today.




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Some of the latest climate models provide unrealistically high projections of future warming

A new study from University of Michigan climate researchers concludes that some of the latest-generation climate models may be overly sensitive to carbon dioxide increases and therefore project future warming that is unrealistically high.




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Algae tasked with producing COVID-19 test kits

Researchers at Western and Suncor are teaming up to use algae as a way to produce serological test kits for COVID-19 - a new process that overcomes shortfalls of existing processes while saving money.




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Citizen science project aims to reveal secret life of bees

In these unprecedented times, we are all spending much more time at home and in our gardens. And, now that spring has well and truly arrived, it's the perfect time to get reacquainted with one of our country's busiest workers - the bee.




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Management of natural assets is key to sustainable development: Inclusive wealth provides the way forward

Sovereign nations typically measure economic success in terms of GDP (income) but this approach is risky as it fails to track and measure the impact of this on nature. Inclusive wealth, on the other hand captures financial and produced capital, but also the skills in our workforce (human capital), the cohesion in our society (social capital) and the value of our environment (natural capital).




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5 vital projects that will continue in 2020

The good thing about BirdLife is that, as a truly global organisation, we're already great at staying connected, even when we're thousands of miles apart. Here are just a few of the ways our work will carry on over the coming months, even if it's from our living rooms.




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Improving Workplace Safety: What Works

The surprise player in affecting workplace safety overseas? Multinational buyers.




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What is best practice to choose social profile username?




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What Are The Highest Paying Affiliate Programs?




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New Publication: Rules, Procedures and Mechanisms Applicable to Processes under the Cartagena Protocol on Biosafety.

New Publication: Rules, Procedures and Mechanisms Applicable to Processes under the Cartagena Protocol on Biosafety.




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Press Release: Largest international gathering on Biosafety meets in Bonn to finalize arrangements for the Cartagena Protocol.




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Report of the Fourth Meeting of the Conference of the Parties to the Convention on Biological Diversity Serving as the Meeting of the Parties to the Cartagena Protocol on Biosafety

Report of the Fourth Meeting of the Conference of the Parties to the Convention on Biological Diversity Serving as the Meeting of the Parties to the Cartagena Protocol on Biosafety (Advance text)




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New publication - Green Customs Guide to Multilateral Environmental Agreements -including the Cartagena Protocol on Biosafety.




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Biosafety Protocol News Vol. 3 Issue 5 - Experiences and Lessons Learned in Capacity-Building




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Biosafety Protocol News Issue 6 - Public Awareness and Participation: Experiences and Lessons Learned from Recent Initiatives




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Notification: Fifth Meeting of the Conference of the Parties serving as the meeting of the Parties to the Cartagena Protocol on Biosafety (COP MOP/5), 11 - 15 October 2010, Nagoya, Japan.




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Summary Outcomes of the Fifth Meeting of the BCH Informal Advisory Committee (BCH IAC). The BCH IAC provides guidance regarding the technical issues associated with the ongoing development of the BCH.




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New Publication: Brochure on the Cartagena Protocol on Biosafety: Reducing the environmental risks of modern technology




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Bosnia and Herzegovina accedes to the Protocol. This will bring the number of Parties to 157




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Report of the Group of the Friends of the Co-Chairs on Liability and Redress in the Context of the Cartagena Protocol on Biosafety on the Work of its First Meeting.




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Fact sheet on the Cartagena Protocol on Biosafety for the International Year of Biodiversity - 2010




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Report of the Group of the Friends of the Co-Chairs on Liability and Redress in the Context of The Cartagena Protocol on Biosafety on the Work of Its Second Meeting




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Report of the Ad Hoc Technical Expert Group on Risk Assessment and Risk Management Under the Cartagena Protocol on Biosafety




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Report of the First Meeting of the Ad Hoc Technical Expert Group on Risk Assessment and Risk Management under the Cartagena Protocol on Biosafety