up A Review of Volunteer-Based Peer Support Interventions in Diabetes By spectrum.diabetesjournals.org Published On :: 2011-05-01 Tricia S. TangMay 1, 2011; 24:85-98From Research to Practice/Behavioral Interventions for Diabetes Self-Management Full Article
up Overview of Peer Support Models to Improve Diabetes Self-Management and Clinical Outcomes By spectrum.diabetesjournals.org Published On :: 2007-10-01 Michele HeislerOct 1, 2007; 20:214-221Articles Full Article
up Group Education in Diabetes: Effectiveness and Implementation By spectrum.diabetesjournals.org Published On :: 2003-04-01 Carolé R. MensingApr 1, 2003; 16:Articles Full Article
up NotNice delivers star-studded, uplifting track By jamaica-star.com Published On :: Thu, 07 May 2020 05:01:29 -0500 Imagine some of your favourite artistes on one song, offering up messages of encouragement and upliftment. Well, that is the concept behind the latest track from Billboard-charting producer NotNice. Dubbed We Are, the song features vocals from... Full Article
up Dancers' Paradise: Devon Unruly working hard to expand dance group By jamaica-star.com Published On :: Fri, 08 May 2020 05:01:38 -0500 He's celebrating 10 years of dancing both competitively and in the street, and the co-founder of Unruly Skankaz, Devon Brown, says he is looking to expand the brand. The once three-member male dance group has grown to five, he told THE WEEKEND... Full Article
up Weh Dem Up To | Natel still making the hits By jamaica-star.com Published On :: Fri, 08 May 2020 05:01:42 -0500 Many may remember Natel from the Digicel Rising Stars competition back in 2005. The singer was a runner-up that year and has been working to set himself apart in the music industry ever since. It has been 15 years, and although his name may not be... Full Article
up How to Keep Up Your Job Search During the Pandemic By www8.gsb.columbia.edu Published On :: Tue, 28 Apr 2020 00:00:00 -0400 Your job search doesn't have to stop during the COVID-19 crisis. Full Article
up Alumni Food Entrepreneurs Team Up to Feed NYC Healthcare Workers By www8.gsb.columbia.edu Published On :: Wed, 29 Apr 2020 00:00:00 -0400 Fundraising efforts, along with a generous donation from Beyond Meat, founded by Ethan Brown ’08, helps restaurant P.S. Kitchen, owned by April Tam Smith ’10 and Graham Smith ’21, provide meals to healthcare workers. Full Article
up Protection of the Wounded and Medical Care-Givers in Armed Conflict: Is the Law Up to the Job? By feedproxy.google.com Published On :: Wed, 27 Feb 2019 10:21:55 +0000 Research Event 16 May 2019 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Françoise Bouchet-Saulnier, Legal Director, Médecins Sans FrontièresEzequiel Heffes, Thematic Legal Adviser, Geneva CallRain Liivoja, Associate Professor, University of QueenslandMaciej Polkowski, Head, Health Care in Danger Initiative, International Committee of the Red CrossChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House This meeting, supported by the British Red Cross, is the first in a series of three to commemorate the 70th anniversary of the 1949 Geneva Conventions. The meeting will focus on the protection of the wounded and sick in armed conflict and will also include discussion of challenges to the protection of medical care and of health providers.Attacks on health care personnel and facilities have increased in recent years, as have the instances in which proceedings have been brought against those providing medical care to wounded fighters, including under counter-terrorism measures.The Geneva Conventions and their Protocols give protection to the wounded and sick and to healthcare providers, but is the law adequate? Is the law sufficiently widely known? How can the law be more fully implemented? What particular challenges arise in non-international armed conflicts?This event will be followed by a drinks reception. Department/project International Law Programme, The Limits on War and Preserving the Peace Full Article
up Engage China to Uphold Multilateralism – But Not at Any Cost By feedproxy.google.com Published On :: Thu, 23 May 2019 11:14:05 +0000 12 June 2019 Harriet Moynihan Senior Research Fellow, International Law Programme @HarrietMoyniha9 Where China’s interests align with those of the international community, there are opportunities for the country’s influence and economic power to strengthen the rules-based international order. Where they do not, states that traditionally support that order should join together to push back. 2019-02-01-China.jpg Students holding Chinese national flags watch the live broadcast of the 40th anniversary celebration of China's reform and opening-up at Huaibei Normal University on 18 December. Photo: Getty Images. China’s adherence to the rules-based international system is selective, prioritizing certain rules in favour of others. States supportive of that ‘system’ – or, as some argue, systems[1] – should identify areas of mutual strategic interest so that they can draw China further into the global rules-based order and leverage China as a constructive player that potentially also contributes to improvements in such areas. This is particularly apposite at a time when the US is in retreat from multilateralism and Russia seems bent on disrupting the rules-based international order.Supportive playerThere are many reasons for actively engaging with China on mutual areas of interest. China is a committed multilateralist in many areas, recognizing that often international cooperation and frameworks hold the key to its domestic problems, for example in the fields of environmental sustainability and financial regulation.China’s economic power is valuable in upholding international institutions: China is the UN’s third-largest donor (after the US and Japan) at a time when the UN is facing budgetary shortfalls. China is also the second-highest contributor to the UN peacekeeping budget, and the largest contributor of peacekeeping forces among the five permanent members of the UN Security Council.China also has a valuable role to play in the settlement of international disputes over trade and investment. China is a big supporter of the World Trade Organization (WTO)’s dispute settlement mechanism, and one of its most active participants;[2] China is currently playing an active role in negotiations to save the WTO’s appellate mechanism from folding in the wake of the US’s refusal to nominate new judges.The last 15 years have also seen a major shift in Chinese attitudes to investment arbitration, from a general suspicion and limitation of arbitration rights to broad acceptance and incorporation of such rights in China’s trade and investment treaties. China is actively engaged in multilateral negotiations through the UN Commission on International Trade Law (UNCITRAL) on reforms to investor–state dispute settlement.China has shown leadership on global climate change diplomacy, urging nations to remain committed to the Paris Agreement in the wake of the US decision to pull out, and has been an important interlocutor with the UK and the EU on these issues. As a strong supporter of the Paris Agreement, but also as the world’s top emitter of carbon dioxide, China has a crucial role to play in pushing forward implementation of the Paris targets. Despite its high emissions, China remains one of the few major economies on track to meet its targets,[3] giving it greater leverage to peer review other parties’ efforts.A recent report by the UK parliament’s Foreign Affairs Committee (FAC), on China and the rules-based international order, noted that where a body of trust and goodwill is developed with China, there is the possibility of discovering interests that coincide and the ability to work together on issues mutually regarded as of global importance. The report refers to a number of success stories from UK partnership with China in multilateral forums, including in counterproliferation and global health.[4]Developing areas of global governanceAs well as working with the current system, China is increasingly involved in the shaping of newer areas of international law – whether it be submissions to the International Tribunal for the Law of the Sea (ITLOS) on procedural rules for the emerging deep-sea mining regime or pitching for a greater role in Arctic governance.[5]This enthusiasm should be harnessed to promote the international rule of law, but at the same time there needs to be recognition of the strategic goals that drive China’s engagement. China’s interest in the Arctic, while including the desire to protect its ecology and environment, is also about access to marine resources, as well as about the Arctic’s strategic potential for China’s military.China’s submissions to ITLOS on the rules of procedure for deep-sea mining are constructive, but also reflect an ambition to secure first-mover advantage when commercial mining eventually takes place. Like other major powers working in this policy area, China’s actions are guided by self-interest, but that doesn’t mean its goals can’t be pursued through multilateral rules.China is also interested in creating new international structures and instruments that further its strategic aims. For example, with Russia (through the Shanghai Cooperation Organisation) it has proposed an International Code of Conduct for Information Security in the UN.[6]China is also pondering an array of options for dispute-resolution mechanisms for its Belt and Road projects, including the possibility of an Asian version of the international Convention on the Settlement of Investment Disputes, which might sit under the auspices of the Asian Infrastructure Investment Bank (AIIB).[7]The creation of new instruments and institutions need not be a threat to the rules-based international order in itself. We have already seen a combination of the creation of parallel complementary regimes alongside the reform of existing institutions, for example in development financing through the AIIB or the New Development Bank (often referred to as the ‘BRICS Bank’); these two banks are relatively conventionally structured along the lines of Western-dominated institutions, albeit with greater Chinese control. Based on these examples, selective adaptation seems more likely than a hostile ‘Eastphalian’ takeover.[8]RisksThere is, however, a real risk that in certain areas China may promote a rival authoritarian model of governance, assisted by an opportunistic convergence with Russia on issues such as human rights, development and internet governance. In areas where China’s core interests clash with those of the rules-based international order, China has shown itself to be unbending, as in its refusal to abide by the July 2016 decision of the Permanent Court of Arbitration in its dispute with the Philippines over the South China Sea.[9]China is becoming more assertive at the UN, but while it seeks to project itself there as a responsible emerging global leader, it is promoting a vision that weakens international norms of human rights, transparency and accountability,[10] while also carrying out practices domestically that raise serious human rights concerns (not least the detention of hundreds of thousands of Uighurs in re-education camps in Xinjiang).[11]China’s increased dominance geographically and geopolitically through its Belt and Road infrastructure projects carries with it a number of social and economic risks, including smaller states becoming trapped in unsustainable financial debts to China.But at a recent Chatham House conference on Asia and international law, participants highlighted the limitations on how far China can shape an alternative governance model.[12] China currently lacks soft power, cultural power and language power, all of which are needed in order to embed an alternative model abroad. China also currently lacks capacity and confidence to build coalitions with other states in the UN.Where it has tried to get buy-in from the international community for its new institutions, such as the China International Commercial Court (CICC) announced in July 2018, there has been scepticism about the standards to be applied.[13] Unless the court can demonstrate sufficient due process, international parties are likely to prefer other centres with a strong reputation for upholding the rule of law, such as those in London, Dubai and Singapore.Where China does promote its own governance model at the expense of the rules-based international order, states are starting to push back, often in concert. EU member states so far have adopted a joined-up approach to the Belt and Road Initiative. With the exception of Italy, they have refused to sign a Memorandum of Understanding on participation unless China provides much greater transparency on its compliance with international standards.The EU also recently presented a coordinated response to China on the situation in Xinjiang.[14] Similarly, members of the so-called ‘Five Eyes’ intelligence-sharing alliance (comprising Australia, Canada, New Zealand, the UK and the US) have acted together in relation to certain incidents of cyber interference attributed to China.[15]There are also signs of pushback from smaller states closer to home in relation to challenges to national sovereignty, debt diplomacy and financial viability arising from Belt and Road projects. The Sri Lankan government recently reversed the award of a $300 million housing deal to China, instead opting for a joint venture with an Indian company.China has been downscaling its investments as a way to counter some of the backlash it has received: the most recent Belt and Road summit put forward a more modest set of aspirations. This suggests that there is some scope for states to stand up to China and use leverage to secure better deals.Many international institutions have been Western-dominated for years;[16] China, together with many emerging and middle powers, has felt for some time that the international architecture does not reflect the world we live in. Given that context, states that champion the rules-based international order should acknowledge China’s desire to update the international order to reflect greater multipolarity, globalization and technological change, while being clear-eyed about their engagement with China. This involves investing in a proper understanding of China and how it works.[17]Where possible, cooperation with China should lead to outcomes that are backed up by international standards and transparency. The above-mentioned FAC report cites evidence that the UK’s support, and that of other developed countries, had a positive impact in shaping the governance and standards of the AIIB.[18] China has brought in international experts to advise on disputes before the CIIC, which may reassure would-be litigants.China’s relationship with the rules-based international order needs to be assessed pragmatically and dynamically. China can be a valuable partner in many areas where its objectives are closely aligned with those of the international community – from trade to climate change to peacekeeping.But where the country’s core interests are at odds with those of the wider international community, an increasingly confident China will strongly resist pressure, including on the South China Sea and human rights. In these areas, states supportive of international law can most powerfully push back through alliances and by ensuring that their own core values are not compromised in the interests of economic benefits.What needs to happenChina’s rising power and selective commitment to multilateralism make it a potentially influential ally in modernizing international governance.China is increasingly involved in shaping newer areas of international law. This enthusiasm could be harnessed in the service of institutional development and reform.Other states should identify areas of mutual strategic interest where China may offer a constructive role, including dispute settlement, health and climate change.However, engagement must not ignore the strategic calculations that drive China’s agenda, or its poor record on civil and political rights, transparency and accountability.Cooperation with China should lead to outcomes that are backed up by international standards and transparency.Where China’s actions undermine the rules-based international order, coordinated action by states supportive of that order is likely to be more effective than acting individually.Notes[1] Chalmers, M. (2019), Which Rules? Why There is No Single ‘Rules-Based International System’, RUSI Occasional Paper, April 2019, London: Royal United Services Institute, https://rusi.org/occasional-papers/Which-Rules-Why-There-Is-No-Single-Rules-Based-International-System.[2] See, for example, Moynihan, H. (2017), China’s Evolving Approach to International Dispute Settlement, Briefing, London: Royal Institute of International Affairs, https://www.chathamhouse.org/publication/chinas-evolving-approach-international-dispute-settlement.[3] UN Environment (2018), Emissions Gap Report 2018, p. XVII, https://www.unenvironment.org/resources/emissions-gap-report-2018.[4] House of Commons Foreign Affairs Committee (2019), China and the Rules-Based International System: Sixteenth Report of Session 2017–19, p. 32, https://publications.parliament.uk/pa/cm201719/cmselect/cmfaff/612/612.pdf.[5] Moynihan, H. (2018), ‘China Expands Its Global Governance Ambitions in the Arctic’, Expert Comment, 15 October 2018, https://www.chathamhouse.org/expert/comment/china-expands-its-global-governance-ambitions-arctic.[6] Updated version proposed 9 January 2015.[7] Moynihan, H. (2018), ‘Exploring Public International Law Issues with Chinese Scholars – Part Four’, Meeting Summary, 3 June 2018, https://www.chathamhouse.org/publication/exploring-public-international-law-issues-chinese-scholars-part-four.[8] Chatham House (2019, forthcoming, ‘Security and Prosperity in the Asia-Pacific: The Role of International Law’, conference summary, https://www.chathamhouse.org/event/security-and-prosperity-asia-pacific-role-international-law.[9] Permanent Court of Arbitration Case No. 2013-19 (Philippines v China), Award of 12 July 2016, https://pca-cpa.org/wp-content/uploads/sites/6/2016/07/PH-CN-20160712-Award.pdf.[10] Piccone, T. (2018), China’s Long Game on Human Rights at the United Nations, Washington, DC: Brookings Institution, https://www.brookings.edu/wp-content/uploads/2018/09/FP_20181009_china_human_rights.pdf.[11] Wye, R. (2018), ‘‘The entire Uyghur population is seemingly being treated as suspect’: China’s persecution of its Muslim minority’, LSE Religion and Global Society blog, 18 September 2018, https://blogs.lse.ac.uk/religionglobalsociety/2018/09/the-entire-uyghur-population-is-seemingly-being-treated-as-suspect-chinas-persecution-of-its-muslim-minority/.[12] Chatham House (2019, forthcoming, ‘Security and Prosperity in the Asia-Pacific: The Role of International Law’.[13] Walters, M. (2018), ‘Jury is out over China’s new commercial court, say lawyers’, Law Society Gazette, 1 November 2018, https://www.lawgazette.co.uk/law/jury-is-out-over-chinas-new-commercial-court-say-lawyers/5068125.article.[14] The Economist (2019), ‘Hope remains for Western solidarity. Look at embassies in Beijing’, 17 April 2019, https://www.economist.com/china/2019/04/20/hope-remains-for-western-solidarity-look-at-embassies-in-beijing.[15] In December 2018, the Five Eyes attributed the activities of a Chinese cyber espionage group targeting intellectual property and sensitive commercial property to China’s Ministry of State Security.[16] Roberts, A. (2017), Is International Law International?, Oxford: Oxford University Press.[17] Parton, C. (2019), China–UK Relations: Where to Draw the Border Between Influence and Interference?, RUSI Occasional Paper, February 2019, London: Royal United Services Institute, p. 30, https://rusi.org/publication/occasional-papers/china-uk-relations-where-draw-border-between-influence-and.[18] House of Commons Foreign Affairs Committee (2019), China and the Rules-Based International System, p. 15.This essay was produced for the 2019 edition of Chatham House Expert Perspectives – our annual survey of risks and opportunities in global affairs – in which our researchers identify areas where the current sets of rules, institutions and mechanisms for peaceful international cooperation are falling short, and present ideas for reform and modernization. Full Article
up In Judging Prorogation, UK Supreme Court Marks Evolution, Not Revolution, in Law By feedproxy.google.com Published On :: Thu, 03 Oct 2019 07:49:48 +0000 3 October 2019 Ruma Mandal Director, International Law Programme @RumaCHLaw Despite the political significance, last week’s judgment does not signal a newly activist court. 2019-10-03-UKSC.jpg The Supreme Court building in Westminster. Photo: Getty Images. The UK Supreme Court’s ruling last Wednesday has, at least temporarily, scuppered the prime minister’s plans to limit parliamentary debate before the looming Brexit deadline. Some of the prime minister’s allies have attacked the ruling as a ‘constitutional coup’. But a close reading reveals that the court has stayed within its remit to interpret, rather than make, the law.In a carefully reasoned judgment, the court emphasized that the case was not about Brexit. But the judges certainly did not shy away from the extraordinary nature of the matters before it, noting that such factual situations have ‘never arisen before and are unlikely ever to arise again… But our law is used to rising to such challenges and supplies us with the legal tools to enable us to reason to a solution.’The key question before the court was whether the prime minister’s decision to seek prorogation was ‘justiciable’ – i.e. amenable to being reviewed by a court. The English and Scottish courts earlier on in these proceedings had come, dramatically, to opposing views on this.The Supreme Court was not dissuaded by the inherently political considerations involved in the prime minister’s decision, stating that while ‘courts cannot decide political questions, the fact that a legal dispute concerns the conduct of politicians, or arises from a matter of political controversy, has never been sufficient reason for the courts to refuse to consider it’.The court went on to emphasize that the Crown’s remaining prerogative powers (exercised on the advice of the government or directly by ministers) have long been subject to judicial scrutiny; such oversight is essential to guarding the separation of powers underpinning the UK’s constitution.So far, so conventional. The full bench of the Supreme Court was required to grapple, though, with a prerogative power that had never been tested before in the courts. And so they delved back to the 1611 Case of Proclamations: ‘the King hath no prerogative, but that which the law of the land allow him’. In the court’s view, the legal issue to be resolved was the scope of the power to prorogue (the existence of this particular prerogative not being in dispute).With no case law available to provide direct guidance on this question, the court, instead, relied on two fundamental principles of the UK’s constitution – parliamentary sovereignty and parliamentary accountability. What would be the logical consequence of an unlimited power to prorogue? The ability to shut parliament permanently.The conclusion: this particular prerogative power had limits. The court held that:‘A decision to prorogue Parliament (or to advise the monarch to prorogue Parliament) will be unlawful if the prorogation has the effect of frustrating or preventing, without reasonable justification, the ability of Parliament to carry out its constitutional functions as a legislature and as the body responsible for the supervision of the executive. In such a situation, the court will intervene if the effect is sufficiently serious to justify such an exceptional course.’Having come to this conclusion, the court was left to examine what justification had in fact been given, noting that the prime minister’s motives were irrelevant. It noted that no clear reason had been given – the relevant documents were all concerned with preparing for the Queen’s speech.Noting evidence on normal practice for such preparations, including from a former prime minister, the court found it ‘impossible… to conclude…that there was any reason – let alone a good reason – to advise Her Majesty to prorogue Parliament for five weeks’.The court’s decision was neither inevitable nor a radical departure from legal tradition. It represents the gradual evolution of the long-established legal principle that the crown’s powers are set by the law and supervised by the courts.Courts have traditionally been reticent to rule on prerogative powers which are ‘high politics’ by nature – classic examples include declaring war and negotiating treaties. In recent years, though, the judiciary has shown a growing confidence to grapple with the contours of those prerogative powers that remain. Deference is still shown when looking at how those powers have been used as opposed to the limits of the prerogative in question.The Supreme Court ruling won’t reassure those who worry about the emergence of an activist court willing to wade (improperly) into the political arena. Nor will it necessarily bring comfort to those anxious about an unwritten constitution in an era where political conventions are fast unravelling.But divisive court rulings are nothing new, nor are ministerial outbursts about inconvenient judgments. In the current environment, politicians should take particular care not to send mixed messages which undermine the independence of the UK’s judiciary. Public trust in British institutions is dangerously low and the UK can ill-afford further damage to its reputation as a country steeped in democracy and the rule of law. Full Article
up POSTPONED: Supporting Civic Space: The Role and Impact of the Private Sector By feedproxy.google.com Published On :: Wed, 22 Jan 2020 17:05:01 +0000 Invitation Only Research Event 16 March 2020 - 11:00am to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE A healthy civic space is vital for an enabling business environment. In recognition of this, a growing number of private sector actors are challenging, publicly or otherwise, the deteriorating environment for civic freedoms.However, this corporate activism is often limited and largely ad hoc. It remains confined to a small cluster of multinationals leaving potential routes for effective coordination and collaboration with other actors underexplored.This roundtable will bring together a diverse and international group of business actors, civil society actors and foreign policy experts to exchange perspectives and experiences on how the private sector can be involved in issues around civic space. The meeting will provide an opportunity to explore the drivers of – and barriers to – corporate activism, develop a better understanding of existing initiatives, identify good practice and discuss practical strategies for the business community.This meeting will be the first of a series of roundtables at Chatham House in support of initiatives to build broad alliances for the protection of civic space. Attendance at this event is by invitation only. PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Department/project International Law Programme, Global Governance and the Rule of Law, Rights, Accountability and Justice Jacqueline Rowe Programme Assistant, International Law Programme 020 7389 3287 Email Full Article
up Bulletin updated at 19:45 HKT - 03/05/2020 By www.weather.gov.hk Published On :: Sun, 03 May 2020 11:45:05 GMT There is no warning in force. Full Article W
up The transcriptional regulator MEIS2 sets up the ground state for palatal osteogenesis in mice [Gene Regulation] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Haploinsufficiency of Meis homeobox 2 (MEIS2), encoding a transcriptional regulator, is associated with human cleft palate, and Meis2 inactivation leads to abnormal palate development in mice, implicating MEIS2 functions in palate development. However, its functional mechanisms remain unknown. Here we observed widespread MEIS2 expression in the developing palate in mice. Wnt1Cre-mediated Meis2 inactivation in cranial neural crest cells led to a secondary palate cleft. Importantly, about half of the Wnt1Cre;Meis2f/f mice exhibited a submucous cleft, providing a model for studying palatal bone formation and patterning. Consistent with complete absence of palatal bones, the results from integrative analyses of MEIS2 by ChIP sequencing, RNA-Seq, and an assay for transposase-accessible chromatin sequencing identified key osteogenic genes regulated directly by MEIS2, indicating that it plays a fundamental role in palatal osteogenesis. De novo motif analysis uncovered that the MEIS2-bound regions are highly enriched in binding motifs for several key osteogenic transcription factors, particularly short stature homeobox 2 (SHOX2). Comparative ChIP sequencing analyses revealed genome-wide co-occupancy of MEIS2 and SHOX2 in addition to their colocalization in the developing palate and physical interaction, suggesting that SHOX2 and MEIS2 functionally interact. However, although SHOX2 was required for proper palatal bone formation and was a direct downstream target of MEIS2, Shox2 overexpression failed to rescue the palatal bone defects in a Meis2-mutant background. These results, together with the fact that Meis2 expression is associated with high osteogenic potential and required for chromatin accessibility of osteogenic genes, support a vital function of MEIS2 in setting up a ground state for palatal osteogenesis. Full Article
up Bulletin updated at 00:00 HKT 10/May/2020 By www.weather.gov.hk Published On :: Sat, 09 May 2020 16:00:00 GMT General Situation:A trough of low pressure will edge towards the coast of Guangdong today and linger over the region in the following couple of days. There will be thundery showers over Guangdong. With the anticyclone aloft strengthening in the middle and latter parts of this week, the weather over southern China will improve and it will be hot. Date/Month: 10/05 (Sunday) Wind: South force 3. Weather: Sunny intervals and a few showers. Isolated thunderstorms later. Temp range: 28 - 32 C R.H. range: 65 - 95 per Cent Date/Month: 11/05 (Monday) Wind: South force 2 to 3. Weather: Mainly cloudy with occasional showers and a few squally thunderstorms. Temp range: 26 - 30 C R.H. range: 70 - 95 per Cent Date/Month: 12/05 (Tuesday) Wind: Light winds force 2. Weather: Mainly cloudy with a few showers and thunderstorms. Temp range: 25 - 29 C R.H. range: 70 - 95 per Cent Date/Month: 13/05 (Wednesday) Wind: Southeast force 3. Weather: Sunny intervals and one or two showers. Temp range: 26 - 30 C R.H. range: 65 - 90 per Cent Date/Month: 14/05 (Thursday) Wind: Southeast force 3. Weather: Sunny periods. Temp range: 26 - 31 C R.H. range: 60 - 85 per Cent Date/Month: 15/05 (Friday) Wind: South to southeast force 3. Weather: Sunny periods. Temp range: 27 - 32 C R.H. range: 60 - 85 per Cent Date/Month: 16/05 (Saturday) Wind: South force 3. Weather: Sunny periods. Temp range: 27 - 32 C R.H. range: 60 - 85 per Cent Date/Month: 17/05 (Sunday) Wind: South force 3 to 4. Weather: Sunny periods. Temp range: 28 - 32 C R.H. range: 70 - 90 per Cent Date/Month: 18/05 (Monday) Wind: South force 3 to 4. Weather: Sunny periods and isolated showers. Temp range: 28 - 32 C R.H. range: 70 - 90 per Cent Sea surface temperature at 2 P.M. 09/05/2020 at North Point was 25 degrees C.Soil temperatures at 7 A.M. 09/05/2020 at Hong Kong Observatory :0.5 M below surface was 27.6 degrees C 1.0 M below surface was 26.4 degrees C Full Article F
up Bulletin updated at 00:45 HKT 10/05/2020 By www.weather.gov.hk Published On :: Sat, 09 May 2020 16:45:00 GMT An anticyclone aloft brought hot weather to southern China yesterday. Locally, it was hot with sunny periods and isolated showers. A trough of low pressure will edge towards the coast of Guangdong today and linger over the region in the following couple of days. There will be thundery showers over Guangdong. Weather forecast for Hong Kong:Mainly cloudy with a few showers. Sunny intervals during the day. There will be isolated thunderstorms later. Hot with temperatures ranging between 28 and 32 degrees. Moderate southerly winds. Outlook: There will be showers and thunderstorms on Monday and Tuesday. The weather will improve gradually in the following couple of days. Full Article F
up WYSIWYG Web Builder 9.1 update By www.wysiwygwebbuilder.com Published On :: Mon, 23 Sep 2013 09:35:20 GMT WYSIWYG Web Builder 9.1 fixes known problems, adds new features and includes other improvements. Full Article
up WYSIWYG Web Builder 9.2 update By wysiwygwebbuilder.com Published On :: Thu, 12 Dec 2013 16:57:15 GMT WYSIWYG Web Builder 9.2 fixes known problems, adds new features and includes other improvements. Full Article
up WYSIWYG Web Builder 9.3 update By wysiwygwebbuilder.com Published On :: Fri, 14 Feb 2014 12:11:19 GMT WYSIWYG Web Builder 9.3 fixes known problems, adds new features and includes other improvements. Full Article
up WYSIWYG Web Builder 9.4 update By wysiwygwebbuilder.com Published On :: Fri, 28 Mar 2014 12:02:13 GMT WYSIWYG Web Builder 9.4 fixes known problems, adds new features and includes other improvements. Full Article
up WYSIWYG Web Builder 10.1 update By wysiwygwebbuilder.com Published On :: Mon, 17 Nov 2014 08:26:33 GMT WYSIWYG Web Builder 10.1 fixes known problems, adds new features and includes other improvements. Full Article
up WYSIWYG Web Builder 10.2 update By wysiwygwebbuilder.com Published On :: Mon, 12 Jan 2015 12:27:46 GMT WYSIWYG Web Builder 10.2 fixes known problems, adds new features and includes other improvements. Full Article
up WYSIWYG Web Builder 10.3 update By wysiwygwebbuilder.com Published On :: Thu, 18 Jun 2015 09:42:33 GMT WYSIWYG Web Builder 10.3 fixes known problems, adds new features and includes other improvements. Full Article
up WYSIWYG Web Builder 10.4 update By wysiwygwebbuilder.com Published On :: Thu, 18 Jun 2015 09:48:51 GMT WYSIWYG Web Builder 10.4 fixes known problems, adds new features and includes other improvements. Full Article
up A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients By feedproxy.google.com Published On :: 2020-04-01 Dorte B. Bekker-JensenApr 1, 2020; 19:716-729Technological Innovation and Resources Full Article
up LockBit ransomware borrows tricks to keep up with REvil and Maze By feedproxy.google.com Published On :: Fri, 24 Apr 2020 13:03:38 +0000 Recently-adopted techniques advance LockBit to a major ransomware player...for now. Full Article SophosLabs Uncut data breach exfiltration I/O Completion Ports IOCP LockBit Ransomware UAC Bypass User Account Control
up Supporting NHS Cybersecurity During COVID-19 is Vital By feedproxy.google.com Published On :: Thu, 02 Apr 2020 12:09:33 +0000 2 April 2020 Joyce Hakmeh Senior Research Fellow, International Security Programme; Co-Editor, Journal of Cyber Policy @joycehakmeh LinkedIn The current crisis is an opportunity for the UK government to show agility in how it deals with cyber threats and how it cooperates with the private sector in creating cyber resilience. 2020-04-02-NHS-nurse-tech-cyber Nurse uses a wireless electronic tablet to order medicines from the pharmacy at The Queen Elizabeth Hospital, Birmingham, England. Photo by Christopher Furlong/Getty Images. The World Health Organization, US Department of Health and Human Services, and hospitals in Spain, France and the Czech Republic have all suffered cyberattacks during the ongoing COVID-19 crisis.In the Czech Republic, a successful attack targeted a hospital with one of the country’s biggest COVID-19 testing laboratories, forcing its entire IT network to shut down, urgent surgical operations to be rescheduled, and patients to be moved to nearby hospitals. The attack also delayed dozens of COVID-19 test results and affected the hospital’s data transfer and storage, affecting the healthcare the hospital could provide.In the UK, the National Health Service (NHS) is already in crisis mode, focused on providing beds and ventilators to respond to one of the largest peacetime threats ever faced. But supporting the health sector goes beyond increasing human resources and equipment capacity.Health services ill-preparedCybersecurity support, both at organizational and individual level, is critical so health professionals can carry on saving lives, safely and securely. Yet this support is currently missing and the health services may be ill-prepared to deal with the aftermath of potential cyberattacks.When the NHS was hit by the Wannacry ransomware attack in 2017 - one of the largest cyberattacks the UK has witnessed to date – it caused massive disruption, with at least 80 of the 236 trusts across England affected and thousands of appointments and operations cancelled. Fortunately, a ‘kill-switch’ activated by a cybersecurity researcher quickly brought it to a halt.But the UK’s National Cyber Security Centre (NCSC), has been warning for some time against a cyber attack targeting national critical infrastructure sectors, including the health sector. A similar attack, known as category one (C1) attack, could cripple the UK with devastating consequences. It could happen and we should be prepared.Although the NHS has taken measures since Wannacry to improve cybersecurity, its enormous IT networks, legacy equipment and the overlap between the operational and information technology (OT/IT) does mean mitigating current potential threats are beyond its ability.And the threats have radically increased. More NHS staff with access to critical systems and patient health records are increasingly working remotely. The NHS has also extended its physical presence with new premises, such as the Nightingale hospital, potentially the largest temporary hospital in the world.Radical change frequently means proper cybersecurity protocols are not put in place. Even existing cybersecurity processes had to be side-stepped because of the outbreak, such as the decision by NHS Digital to delay its annual cybersecurity audit until September. During this audit, health and care organizations submit data security and protection toolkits to regulators setting out their cybersecurity and cyber resilience levels.The decision to delay was made to allow the NHS organizations to focus capacity on responding to COVID-19, but cybersecurity was highlighted as a high risk, and the importance of NHS and Social Care remaining resilient to cyberattacks was stressed.The NHS is stretched to breaking point. Expecting it to be on top of its cybersecurity during these exceptionally challenging times is unrealistic, and could actually add to the existing risk.Now is the time where new partnerships and support models should be emerging to support the NHS and help build its resilience. Now is the time where innovative public-private partnerships on cybersecurity should be formed.Similar to the economic package from the UK chancellor and innovative thinking on ventilator production, the government should oversee a scheme calling on the large cybersecurity capacity within the private sector to step in and assist the NHS. This support can be delivered in many different ways, but it must be mobilized swiftly.The NCSC for instance has led the formation of the Cyber Security Information Sharing Partnership (CiSP)— a joint industry and UK government initiative to exchange cyber threat information confidentially in real time with the aim of reducing the impact of cyberattacks on UK businesses.CiSP comprises organizations vetted by NCSC which go through a membership process before being able to join. These members could conduct cybersecurity assessment and penetration testing for NHS organizations, retrospectively assisting in implementing key security controls which may have been overlooked.They can also help by making sure NHS remote access systems are fully patched and advising on sensible security systems and approved solutions. They can identify critical OT and legacy systems and advise on their security.The NCSC should continue working with the NHS to enhance provision of public comprehensive guidance on cyber defence and response to potential attack. This would show they are on top of the situation, projecting confidence and reassurance.It is often said in every crisis lies an opportunity. This is an opportunity for the UK government to show agility in how it deals with cyber threats and how it cooperates with the private sector in creating cyber resilience.It is an opportunity to lead a much-needed cultural change showing cybersecurity should never be an afterthought. 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up POSTPONED: The Development of Libyan Armed Groups since 2014: Community Dynamics and Economic Interests By feedproxy.google.com Published On :: Wed, 04 Mar 2020 14:15:01 +0000 Invitation Only Research Event 18 March 2020 - 9:00am to 10:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Abdul Rahman Alageli, Associate Fellow, MENA Programme, Chatham HouseEmaddedin Badi, Non-Resident Scholar, Middle East InstituteTim Eaton, Senior Research Fellow, MENA Programme Chatham HouseValerie Stocker, Independent Researcher Since the overthrow of the regime of Muammar Gaddafi in 2011, Libya’s multitude of armed groups have followed a range of paths. While many of these have gradually demobilized, others have remained active, and others have expanded their influence. In the west and south of the country, armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks.In the east, the Libyan Arab Armed Forces projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will need to address the fears, grievances and desires of the surrounding communities, even while the development of armed groups’ capacities dilutes their accountability to those communities.This roundtable will discuss the findings of a forthcoming Chatham House research paper, ‘The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests’, which presents insights from over 200 interviews of armed actors and members of local communities and posits how international policymakers might seek to curtail the continued expansion of the conflict economy.PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Event attributes Chatham House Rule Department/project Middle East and North Africa Programme, Countering Conflict Economies in MENA, Libya’s Conflict Economy Georgia Cooke Project Manager, Middle East and North Africa Programme +44 (0)20 7957 5740 Email Full Article
up POSTPONED: Russia in MENA: An Update By feedproxy.google.com Published On :: Fri, 06 Mar 2020 17:45:01 +0000 Invitation Only Research Event 26 March 2020 - 9:30am to 11:00am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Nikolay Kozhanov, Research Associate Professor, Gulf Studies Center, Qatar University; Consulting Fellow, Russia and Eurasia Programme, Chatham House Chair: Sanam Vakil, Senior Research Fellow, Project Director, Future Dynamics of the Gulf, Middle East & North Africa Programme, Chatham House Russia’s Middle East policy is driven by a complex mixture of traditional factors (such as the ongoing confrontation with the West) and new trends. The Kremlin is keen to maintain its position as an influential external broker. However, it is not confident Russia would be able to respond effectively if forced into a reactive mode by other regional players. The Kremlin therefore seeks to retain initiative and shape the agenda according to its needs and resources. This makes prediction of Moscow’s next moves in the region a challenging, but not impossible, task.Nikolay Kozhanov will offer remarks on the changes that have taken place in Russia’s strategy since the publication of his research paper Russian Policy Across the Middle East: Motivations and Methods (2018).PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Event attributes Chatham House Rule Department/project Middle East and North Africa Programme Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
up The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests By feedproxy.google.com Published On :: Mon, 16 Mar 2020 17:25:16 +0000 17 March 2020 This paper explores armed group–community relations in Libya and the sources of revenue that have allowed armed groups to grow in power and influence. It draws out the implications for policy and identifies options for mitigating conflict dynamics. Read online Download PDF Tim Eaton Senior Research Fellow, Middle East and North Africa Programme @el_khawaga LinkedIn Abdul Rahman Alageli Associate Fellow, Middle East and North Africa Programme @abdulrahmanlyf Emadeddin Badi Policy Leader Fellow, School of Transnational Governance, European University Institute Mohamed Eljarh Co-founder and CEO, Libya Outlook Valerie Stocker Researcher Amru_24-2_13.jpg Fighters of the UN-backed Government of National Accord patrol in Ain Zara suburb in Tripoli, February 2020. Photo: Amru Salahuddien SummaryLibya’s multitude of armed groups have followed a range of paths since the emergence of a national governance split in 2014. Many have gradually demobilized, others have remained active, and others have expanded their influence. However, the evolution of the Libyan security sector in this period remains relatively understudied. Prior to 2011, Libya’s internal sovereignty – including the monopoly on force and sole agency in international relations – had been personally vested in the figure of Muammar Gaddafi. After his death, these elements of sovereignty reverted to local communities, which created armed organizations to fill that central gap. National military and intelligence institutions that were intended to protect the Libyan state have remained weak, with their coherence undermined further by the post-2014 governance crisis and ongoing conflict. As a result, the most effective armed groups have remained localized in nature; the exception is the Libyan Arab Armed Forces (LAAF), which has combined and amalgamated locally legitimate forces under a central command.In the west and south of the country, the result of these trends resembles a kind of inversion of security sector reform (SSR) and disarmament, demobilization and reintegration (DDR): the armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks; and have continued to arm, mobilize and integrate themselves into the state’s security apparatus without becoming subservient to it. In the eastern region, the LAAF projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. The LAAF has co-opted social organizations to dominate political and economic decision-making.The LAAF has established a monopoly over the control of heavy weapons and the flow of arms in eastern Libya, and has built alliances with armed groups in the east. Armed groups in the south have been persuaded to join the LAAF’s newly established command structure. The LAAF’s offensive on the capital, which started in April 2019, represents a serious challenge to armed groups aligned with the Tripoli-based Government of National Accord (GNA). The fallout from the war will be a challenge to the GNA or any future government, as groups taking part in the war will expect to be rewarded. SSR is thus crucial in the short term: if the GNA offers financial and technical expertise and resources, plus legal cover, to armed groups under its leadership, it will increase the incentive for armed groups to be receptive to its plans for reform.Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will necessarily rely on addressing the fears, grievances and desires of the surrounding communities. Yet the development of armed groups’ capacities, along with their increasing access to autonomous means of generating revenue, has steadily diluted their accountability to local communities. This process is likely to be accelerated by the ongoing violence around Tripoli.Communities’ relationship to armed groups varies across different areas of the country, reflecting the social, political, economic and security environment:Despite their clear preference for a more formal, state-controlled security sector, Tripoli’s residents broadly accept the need for the presence of armed groups to provide security. The known engagement of the capital’s four main armed groups in criminal activity is a trade-off that many residents seem able to tolerate, providing that overt violence remains low. Nonetheless, there is a widespread view that the greed of Tripoli’s armed groups has played a role in stoking the current conflict.In the east, many residents appear to accept (or even welcome) the LAAF’s expansion beyond the security realm, provided that it undertakes these roles effectively. That said, such is the extent of LAAF control that opposition to the alliance comes at a high price.In the south, armed groups draw heavily on social legitimacy, acting as guardians of tribal zones of influence and defenders of their respective communities against outside threats, while also at times stoking local conflicts. Social protections continue to hold sway, meaning that accountability within communities is also limited.To varying extents since 2014, Libya’s armed groups have developed networks that enmesh political and business stakeholders in revenue-generation models:Armed groups in Tripoli have compensated for reduced financial receipts from state budgets by cultivating unofficial and illicit sources of income. They have also focused on infiltrating state institutions to ensure access to state budgets and contracts dispersed in the capital.In the east of the country, the LAAF has developed a long-term strategy to dominate the security, political and economic spheres through the establishment of a quasi-legal basis for receiving funds from Libya’s rival state authorities. It has supplemented this with extensive intervention in the private sector. External patronage supports military operations, but also helps to keep this financial system, based on unsecured debt, afloat.In the south, limited access to funds from the central state has spurred armed groups to become actively involved in the economy. This has translated into the taxation of movement and the imposition of protection fees, particularly on informal (and often illicit) activity.Without real commitment from international policymakers to enforcing the arms embargo and protecting the economy from being weaponized, Libya will be consigned to sustained conflict, further fragmentation and potential economic collapse. Given the likely absence of a political settlement in the short term, international policymakers should seek to curtail the continued expansion of the conflict economy by reducing armed groups’ engagement in economic life.In order to reduce illicit activities, international policymakers should develop their capacity to identify and target chokepoints along illicit supply chains, with a focus on restraining activities and actors in closest proximity to violence. Targeted sanctions against rent maximizers (both armed and unarmed) is likely to be the most effective strategy. More effective investigation and restraint of conflict economy actors will require systemic efforts to improve transparency and enhance the institutional capacity of anti-corruption authorities. International policymakers should also support the development of tailored alternative livelihoods that render conflict economy activities less attractive. Department/project Middle East and North Africa Programme, Chaos States, Countering Conflict Economies in MENA, Libya’s Conflict Economy Full Article
up Lebanese Women and the Politics of Disruption By feedproxy.google.com Published On :: Thu, 30 Apr 2020 11:00:01 +0000 Research Event 6 May 2020 - 1:00pm to 2:00pm Event participants Carmen Geha, Assistant Professor of Public Administration, Leadership and Organisational Development, American University of BeirutModerator: Lina Khatib, Director, Middle East and North Africa Programme, Chatham House Lebanese women have been at the forefront of the protest movement that has shaken Lebanon since October 2019. The active participation by women and their visibility in Lebanon's protest movement has challenged the gender norms prevalent in Lebanese society and politics. However, the COVID-19 pandemic and the nationwide lockdown that ensued has disrupted women's ability to organize, and is threatening the fragile progress towards female inclusion in the political process. In a recent article, Carmen Geha discussed the politics of representation in the context of women's participation in public life in Lebanon and argued that the country's political system is maintained through tightly-knit informal power relations among sectarian politicians, making women's participation in politics virtually impossible. The article explained how the October 2019 revolution challenged that norm by creating inclusive spaces where women activists could confront politicians and thus, transform the way women participate in politics and public life. In this webinar, part of the Chatham House project on the future of the state in the Middle East and North Africa, the article's author will discuss how women's activism in Lebanon has been affected by the coronavirus-induced lockdown. The speaker will consider how, under current circumstances, women activists can speak up collectively and bring back a movement to contest gender norms in order to build an alternative political model that can better represent women's priorities. You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful. Alternatively, you can watch the event live on the MENA Programme Facebook page. Department/project Middle East and North Africa Programme, The Future of the State in the Middle East Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme +44 (0)20 7314 3624 Email Full Article
Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme +44 (0)20 7314 3624 Email
up Rapid Brain Nicotine Uptake from Electronic Cigarettes By jnm.snmjournals.org Published On :: 2019-11-01T13:36:37-07:00 This study sought to determine brain nicotine kinetics from the use of increasingly popular electronic cigarettes (E-cigs). Methods: Brain uptake of nicotine following inhalation from E-cigs was directly assessed in 17 E-cig users (8 females), using 11C-nicotine and positron emission tomography. The brain nicotine kinetics parameters from E-cigs were compared with those from smoking combustible cigarettes (C-cigs). Results: After inhalation of a single puff of E-cig vapor, brain nicotine concentration rose quickly (mean T1/2 27 sec) with a peak amplitude 25% higher in females than males, resembling previous observations with C-cigs. Nonetheless, brain nicotine accumulation from E-cigs was smaller than that from C-cigs in both males and females (24% and 32%, respectively). Conclusion: E-cigs can deliver nicotine rapidly to the brain. Therefore, to the extent that rapid brain uptake promotes smoking reward, e-cigarettes might maintain a degree of nicotine dependence and also serve as non-combustible substitutes for cigarettes. Full Article
up Long term follow-up and outcomes of re-treatment in an expanded 50 patient single-center phase II prospective trial of Lutetium-177 (177Lu) PSMA-617 theranostics in metastatic castrate-resistant prostate cancer By jnm.snmjournals.org Published On :: 2019-11-22T10:43:33-08:00 Objectives: Lutetium-177 (177Lu)-PSMA-617 (LuPSMA) is a radioligand with high affinity for prostate specific membrane antigen (PSMA) enabling targeted beta-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castrate-resistant prostate cancer (mCRPC). We now report their longer-term outcomes including a 20 patient extension cohort and outcomes of subsequent systemic treatments following completion of trial therapy. Methods: 50 patients with PSMA-avid mCRPC who had progressed after standard therapies received up to 4 cycles of LuPSMA every 6 weeks. Endpoints included PSA response (PCWG2), toxicity (CTCAE v4.03), imaging response, patient-reported health-related quality of life (QoL), progression-free and overall survival. We also describe, as a novel finding, outcomes of men who subsequently progressed and had further systemic therapies, including LuPSMA. Results: 75 men were screened to identify 50 patients eligible for treatment. Adverse prognostic features of the cohort included short median PSA doubling time (2.3 months) and extensive prior treatment including prior docetaxel (84%), cabazitaxel (48%), and abiraterone and/or enzalutamide (90%). The mean administered radioactivity was 7.5 GBq/cycle. PSA decline ≥ 50% was achieved in 32 of 50 patients (64%, 95% CI 50-77%), including 22 patients (44%, 95% CI 30-59%) with ≥ 80% decrease. Of 27 patients with measurable soft tissue disease, 15 (56%) achieved an objective response by RECIST 1.1. The most common toxicities attributed to LuPSMA were self-limiting G1-2 dry mouth (66%), transient G1-2 nausea (48%), G3-4 thrombocytopenia (10%) and G3 anemia (10%). Brief pain inventory severity and interference scores decreased at all time points including at the 3 month follow-up with a decrease of -1.2 (95% CI -0.5 to -1.9, P = 0.001) and 1.0 (95% CI -0.2 to -0.18, P = 0.013), respectively. At a median follow-up of 31.4 months, median OS was 13.3 months (95% CI 10.5-18.7) with a significantly longer survival of 18.4 months (95% CI 13.8-23.8) in patients achieving a PSA decline ≥ 50%. At progression following prior response, further LuPSMA was administered to 15 (30%) patients (median 2 cycles commencing 359 days from enrolment) with PSA decline ≥ 50% in 11 patients (73%). 4 of 21 patients (19%) receiving other systemic therapies upon progression experienced PSA decline ≥ 50%. There were no unexpected adverse events with LuPSMA re-treatment. Conclusion: This expanded 50 patient cohort of men with extensive prior therapy confirms our earlier report of high response rates, low toxicity and improved QoL with LuPSMA radioligand therapy. Upon progression, re-challenge LuPSMA demonstrated higher response rates than other systemic therapies. Full Article
up Differential expression of glucose transporters and hexokinases in prostate cancer with a neuroendocrine gene signature: a mechanistic perspective for FDG imaging of PSMA-suppressed tumors By jnm.snmjournals.org Published On :: 2019-12-05T10:37:41-08:00 Purpose: Although the incidence of de novo neuroendocrine prostate cancer (NEPC) is rare, recent data suggests that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine (NE) hallmarks and androgen receptor (AR)-suppression in prostate cancer (PC). Previous clinical reports indicate that PCs with a phenotype similar to NE tumors can be more amenable to imaging by 18F-Fluorodeoxyglucose (FDG) rather than PSMA-targeting radioligands. In this study, we evaluated the association between NE gene signature and FDG uptake-associated genes including glucose transporters (GLUTs) and hexokinases, with the goal of providing a genomic signature to explain the reported FDG-avidity of PSMA-suppressed tumors. Methods: Data mining approaches, cell lines and patient-derived xenograft (PDX) models were used to study the levels of 14 members of the SLC2A family (encoding GLUT proteins), 4 members of the hexokinase family (genes: HK1 to 3 and GCK) and PSMA (FOLH1 gene) following AR-inhibition and in correlation with NE hallmarks. Also, we characterize a NE-like PC (NELPC) subset among a cohort of primary and metastatic PC samples with no NE histopathology. We measured glucose uptake in a NE-induced in vitro model and a zebrafish model by non-radioactive imaging of glucose uptake using fluorescent glucose bioprobe, GB2-Cy3. Results: This work demonstrates that a NE gene signature associates with differential expression of genes encoding GLUT and hexokinase proteins. In NELPC, elevated expression of GCK (encoding glucokinase protein) and decreased expression of SLC2A12 correlated with earlier biochemical recurrence. In tumors treated with AR-inhibitors, high expression of GCK and low expression of SLC2A12 correlated with NE histopathology and PSMA gene suppression. GLUT12-suppression and amplification of glucokinase was observed in NE-induced PC cell lines and PDX models. A higher glucose uptake was confirmed in low-PSMA tumors using a GB2-Cy3 probe in a zebrafish model. Conclusion: NE gene signature in NEPC and NELPC associates with a distinct transcriptional profile of GLUTs and HKs. PSMA-suppression correlates with GLUT12-suppression and glucokinase-amplification. Alteration of FDG uptake-associated genes correlated positively with higher glucose uptake in AR and PSMA-suppressed tumors. Zebrafish xenograft tumor models are an accurate and efficient pre-clinical method for monitoring non-radioactive glucose uptake. Full Article
up Inflammation-based index and 68Ga-DOTATOC PET-derived uptake and volumetric parameters predict outcome in neuroendocrine tumor patients treated with 90Y-DOTATOC By jnm.snmjournals.org Published On :: 2019-12-05T10:37:41-08:00 We performed post-hoc analyses on the utility of pre-therapeutic and early interim 68Ga-DOTA-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography (PET) tumor uptake and volumetric parameters and a recently proposed biomarker, the inflammation-based index (IBI), for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumor (NET) patients treated with 90Y-DOTATOC in the setting of a prospective phase II trial. Methods: Forty-three NET patients received up to four cycles of 1.85 GBq/m²/cycle 90Y-DOTATOC with a maximal kidney biologic effective dose of 37 Gy. All patients underwent a 68Ga-DOTATOC PET/computed tomography (CT) at baseline and seven weeks after the first PRRT cycle. 68Ga-DOTATOC-avid tumor lesions were semi-automatically delineated using a customized standardized uptake value (SUV) threshold-based approach. PRRT response was assessed on CT using RECIST 1.1. Results: Median progression-free survival (PFS) and overall survival (OS) were 13.9 and 22.3 months, respectively. An SUVmean higher than 13.7 (75th percentile (P75)) was associated with better survival (hazard ratio (HR) 0.45; P = 0.024), whereas a 68Ga-DOTATOC-avid tumor volume higher than 578 ml (P75) was associated with worse OS (HR 2.18; P = 0.037). Elevated baseline IBI was associated with worse OS (HR 3.90; P = 0.001). Multivariate analysis corroborated independent associations between OS and SUVmean (P = 0.016) and IBI (P = 0.015). No significant correlations with PFS were found. A composite score based on SUVmean and IBI allowed to further stratify patients in three categories with significantly different survival. On early interim PET, a decrease in SUVmean of more than 17% (P75) was associated with worse survival (HR 2.29; P = 0.024). Conclusion: Normal baseline IBI and high 68Ga-DOTATOC tumor uptake predict better outcome in NET patients treated with 90Y-DOTATOC. This can be used for treatment personalization. Interim 68Ga-DOTATOC PET does not provide information for treatment personalization. Full Article
up 18F-Fluorodeoxyglucose Positron Emission Tomography / Computed Tomography in Left-Ventricular Assist Device Infection: Initial Results Supporting the Usefulness of Image-Guided Therapy By jnm.snmjournals.org Published On :: 2019-12-05T10:37:41-08:00 Background: Accurate definition of the extent and severity of left-ventricular assist device (LVAD) infection may facilitate therapeutic decision making and targeted surgical intervention. Here, we explore the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for guidance of patient management. Methods: Fifty-seven LVAD-carrying patients received 85 whole-body 18F-FDG PET/CT scans for the work-up of device infection. Clinical follow-up was obtained over a period of up to two years. Results: PET/CT showed various patterns of infectious involvement of the 4 LVAD components: driveline entry point (77% of cases), subcutaneous driveline path (87%), pump pocket (49%) and outflow tract (58%). Driveline smears revealed staphylococcus or pseudomonas strains as the underlying pathogen in a majority of cases (48 and 34%, respectively). At receiver-operating characteristics analysis, an 18F-FDG standardized uptake value (SUV) >2.5 was most accurate to identify smear-positive driveline infection. Infection of 3 or all 4 LVAD components showed a trend towards lower survival vs infection of 2 or less components (P = 0.089), while involvement of thoracic lymph nodes was significantly associated with adverse outcome (P = 0.001 for nodal SUV above vs below median). Finally, patients that underwent early surgical revision within 3 months after PET/CT (n = 21) required significantly less inpatient hospital care during follow-up when compared to those receiving delayed surgical revision (n = 11; p<0.05). Conclusion: Whole-body 18F-FDG PET/CT identifies the extent of LVAD infection and predicts adverse outcome. Initial experience suggests that early image-guided surgical intervention may facilitate a less complicated subsequent course. Full Article
up PET imaging quantifying 68Ga-PSMA-11 uptake in metastatic colorectal cancer By jnm.snmjournals.org Published On :: 2020-05-01T11:16:57-07:00 At diagnosis 22% of colorectal cancer (CRC) patients have metastases and 50% later develop metastasis. Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-PSMA-617 is employed to treat metastatic prostate cancer (PC). 177Lu-PSMA-617 targets Prostate Specific Membrane Antigen (PSMA) a cell surface protein enriched in PC and the neovasculature of other solid tumors including CRC. We performed gallium-68 (68Ga)-PSMA-11 PET-CT imaging of ten metastatic CRC patients to assess metastasis avidity. Eight patients had lesions lacking avidity and two had solitary metastases exhibiting very low avidity. Despite expression of PSMA in CRC neovasculature, none of the patients exhibited tumor avidity sufficient to be considered for 177Lu-PSMA-617 PRRT. Full Article
up Reshaping the amyloid buildup curve in Alzheimer's disease? - Partial volume effect correction of longitudinal amyloid PET data By jnm.snmjournals.org Published On :: 2020-05-01T11:16:57-07:00 It was hypothesized that the brain β-amyloid buildup curve plateaus at an early symptomatic Alzheimer's disease (AD) stage. Atrophy-related partial volume effects (PVEs) degrade signal in hot-spot imaging techniques, such as amyloid positron emission tomography (PET). This longitudinal analysis of amyloid-sensitive PET data investigated the shape of the β-amyloid curve in AD applying PVE correction (PVEC). We analyzed baseline and 2-year follow-up data of 216 symptomatic individuals on the AD continuum (positive amyloid status) enrolled in Alzheimer's Disease Neuroimaging Initiative (17 AD dementia, 199 mild cognitive impairment), including 18F-florbetapir PET, magnetic resonance imaging and mini mental state examination (MMSE) scores. For PVEC, the modified Müller-Gärtner method was performed. Compared to non-PVE-corrected data, PVE-corrected data yielded significantly higher regional and composite standardized uptake value ratio (SUVR) changes over time (P=0.0002 for composite SUVRs). Longitudinal SUVR changes in relation to MMSE decreases showed a significantly higher slope of the regression line in the PVE-corrected as compared to the non-PVE-corrected PET data (F=7.1, P=0.008). These PVEC results indicate that the β-amyloid buildup curve does not plateau at an early symptomatic disease stage. A further evaluation of the impact of PVEC on the in-vivo characterization of time-dependent AD pathology, including the reliable assessment and comparison of other amyloid tracers, is warranted. Full Article
up Confirmation of 123I-FP-CIT-SPECT (ioflupane) quantification methods in dementia with Lewy body and other neurodegenerative disorders By jnm.snmjournals.org Published On :: 2020-05-08T13:18:58-07:00 Rationale: To conduct a retrospective study comparing three 123I-FP-CIT-SPECT quantitative methods in patients with neurodegenerative syndromes as referenced to neuropathological findings. Methods: 123I-FP-CIT-SPECT and neuropathological findings among patients with neurodegenerative syndromes from the Mayo Alzheimer's Disease Research Center and Mayo Clinic Study of Aging were examined. Three 123I-FP-CIT-SPECT quantitative assessment Methods: MIMneuro (MIM Software Inc.), DaTQUANT (GE Healthcare), and manual region of interest (ROI) creation on an Advantage Workstation (GE Healthcare) were compared to neuropathological findings describing the presence or absence of Lewy body disease (LBD). Striatum to background ratios (SBRs) generated by DaTQUANT were compared to the calculated SBRs of the manual method and MIMneuro. The left and right SBRs for caudate, putamen and striatum were evaluated with the manual method. For DaTQUANT and MIMneuro the left, right, total and average SBRs and z-scores for whole striatum, caudate, putamen, anterior putamen, and posterior putamen were calculated. Results: The cohort included 24 patients [20 (83%) male, aged 75.4 +/- 10.0 at death]. The antemortem clinical diagnoses were Alzheimer’s disease dementia (ADem, N = 6), probable dementia with Lewy bodies (pDLB, N = 12), mixed ADem/pDLB (N = 1), Parkinson’s disease with mild cognitive impairment (N = 2), corticobasal syndrome (N = 1), idiopathic rapid eye movement sleep behavior disorder (iRBD) (N = 1) and behavioral variant frontotemporal dementia (N = 1). Seventeen (71%) had LBD pathology. All three 123I-FP-CIT-SPECT quantitative methods had area under the receiver operating characteristics (AUROC) values above 0.93 and up to 1.000 (p<0.001) and showed excellent discrimination between LBD and non-LBD patients in each region assessed, p<.001. There was no significant difference between the accuracy of the regions in discriminating the two groups, with good discrimination for both caudate and putamen. Conclusion: All three 123I-FP-CIT-SPECT quantitative methods showed excellent discrimination between LBD and non-LBD patients in each region assessed, using both SBRs and z-scores. Full Article
up The effects of monosodium glutamate on PSMA radiotracer uptake in men with recurrent prostate cancer: a prospective, randomized, double-blind, placebo-controlled intra-individual imaging study. By jnm.snmjournals.org Published On :: 2020-05-08T13:18:58-07:00 The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [18F]DCFPyl PET/CT imaging sessions were performed 3 – 7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle, liver, spleen, kidneys, bowel, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P = 0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P = 0.014). Significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P = 0.001) and bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 11 ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range -1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [18F]DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications. Full Article
up Violent Extremist Groups in Africa: Local and Global Factors By feedproxy.google.com Published On :: Mon, 30 Sep 2019 14:00:01 +0000 Research Event 10 October 2019 - 5:00pm to 6:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Professor Stig Jarle Hansen, Professor, Norwegian University of Life Sciences; Author, Horn, Sahel and Rift: Fault-lines of the African JihadBulama Bukarti, PhD Candidate, SOAS, University of London; Analyst, Tony Blair Institute for Global ChangeChair: Aoife McCullough, PhD Candidate, LSE Islamist-inspired radical organizations in Africa have had a historical presence that extends well beyond the more recent emergence of groups including Al Shabaab, Boko Haram, Ansar Dine and Al-Qaeda in the Islamic Maghreb. Despite more than three decades of international efforts to immobilize these organizations, they have proven to be adaptable and resilient, continuing to engage in insurgent campaigns against the state and employing terrorist violence against civilians. As they operate within and across different states and regions, the key to understanding this persistence – as well as the challenges of responding to it – often lies in the interaction between global dynamics and frequently underappreciated local factors. At this event, which will launch the book Horn, Sahel and Rift: Fault-lines of the African Jihad, speakers will discuss key factors leading to the emergence of radical Islamist violence in Africa, its impact and the outlook ahead for African and other actors in addressing these issues. THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED. Department/project Africa Programme, African Peace and Security, Horn of Africa Yusuf Hassan Parliamentary and Media Outreach Assistant, Africa Programme +44 (0) 20 7314 3645 Email Full Article
up Economic Recovery and Anticorruption in South Africa: Assessing Progress on the Reform Agenda By feedproxy.google.com Published On :: Mon, 25 Nov 2019 16:10:01 +0000 Invitation Only Research Event 4 December 2019 - 3:00pm to 4:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Professor Nick Binedell, Founding Director and Sasol Chair of Strategic Management, Gordon Institute of Business Science (GIBS), University of Pretoria South Africa has significant economic potential based on its resource endowment, quality human capital and well-developed infrastructure compared to the region. However, the country’s economic growth rate has not topped 2 per cent since 2013, and in 2018, was below 1 per cent. This has put a strain on citizens and communities in a country that still suffers from structural inequality, poverty and high unemployment. Economic recovery and anti-corruption were the central pillars of President Cyril Ramaphosa’s 2019 electoral campaign and he has set an investment target of $100 billion. However, voters and investors alike are demanding faster and more visible progress from the country’s enigmatic leader who has a reputation for caution and calculation.At this event, Professor Nick Binedell will discuss the progress of and opposition to the president’s economic reform agenda and the opportunities for international investment to support long term inclusive and sustainable growth in South Africa.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Africa Programme, Southern Africa, Inclusive Economic Growth, Governance and Technology Sahar Eljack Programme Administrator, Africa Programme + 44 (0) 20 7314 3660 Email Full Article
up Can Liberation Movements Really Rid Southern Africa of Corruption? By feedproxy.google.com Published On :: Mon, 16 Dec 2019 16:20:43 +0000 17 December 2019 Christopher Vandome Research Fellow, Africa Programme LinkedIn Southern Africa’s national liberation movements have survived ‘end of decade’ elections across the region. Combating corruption has been at the heart of many of the campaigns, but the question is can they succeed? 2019-12-16-Namibia-Election.jpg Supporters of the Namibian incumbent president and ruling party South West Africa People's Organisation (SWAPO) presidential candidate Hage Geingob cheer and dance. Photo by GIANLUIGI GUERCIA/AFP via Getty Images. Swapo’s victory in Namibia two weeks ago was the last in a series of recent ‘end of decade’ elections that have returned dominant parties to power across Southern Africa. However, the “enduring appeal of liberation” is wearing thin.Experiences across the region show that if governments are to deliver on their electoral promises, they must empower institutions, actively promote a culture of accountability and transparency within their party ranks and pursue economic reforms that untangle the web of party-state-business alliances. Such actions are critical for the survival of national liberation movements as the dominant force in the politics of Southern Africa – but will be difficult to implement.Avoid political factionalismSouth Africa, Botswana, Angola and Zimbabwe all saw new presidents take over just before elections. All used the rhetoric of anti-corruption to distance themselves from the tainted image of their predecessors. But acting on this requires a shift in mind-set in parties that have always preferred to deal with their problems behind closed doors. High profile adversaries from past regimes make tempting targets but could also drive party divisions.In Angola, the transition of power was safeguarded by an agreement that former president José Eduardo dos Santos would be immune from prosecution. But this week his son faced corruption charges before the country’s supreme court, a high-profile example of a wave of anti-corruption cases across Southern Africa, driven by dominant parties wary of their future.The allegations against José Filemino De Sousa Dos Santos, nickname ‘Zenu’, include a $500-million fraud involving the country’s central bank. Pressure is also mounting on Zenu’s sister Isabel — once prominent in Angola, she is now absent from public life.Other leaders have had to tread more carefully. Immunity was a luxury Cyril Ramaphosa was neither willing nor politically able to grant Jacob Zuma in South Africa. Reliant on a few close allies at the top of the party, Ramaphosa lacks foot soldiers at the grassroots level, and his campaign against corruption within the ANC has faced persistent opposition.Rebuilding institutions and empowering authorities takes time, and with few high-profile cases to point to, people are getting restless. This is also the case in Zimbabwe, where a worsening economic situation has left policy reformers politically isolated.Party, state, and businessLong term incumbency has blurred the distinction between the party and the state. Liberation movements have created vast party-linked business empires. Political allegiance grants access to economic resources through appointments to lucrative positions in state-owned enterprises, preferential bids for tenders and licenses, and direct access to decision makers.In Angola, this was fuelled by oil revenues. In South Africa, state capture flourished in an environment where the ANC and its constituent elements had significant power on the panels that chose leaders for state-owned enterprises (SOEs). In Namibia, an Icelandic fishing company paid backhanders to officials for fishing rights in what has become known as the ‘Fishrot’ scandal. Zanu-PF officials’ access to preferential foreign exchange rates present them with lucrative opportunities in Zimbabwe.Ending this bureaucratic rent seeking goes beyond appointing ‘clean’ officials, which has been central to the anti-corruption campaigns in Angola and South Africa. Governments must also allow scrutiny of the state and empower those institutions designed for that role, such as the National Prosecuting Authority and the Public Protector in South Africa. Zimbabwe’s auditor general has published an in-depth report of the state of corruption in the country’s SOEs.Companies must also be held to account for their role in aiding, and at worst directly benefitting, from state graft. International businesses have actively sought to benefit from corruption. They are now starting to face the consequences. A former Credit Suisse banker has pleaded guilty in the US over handling alleged kickbacks in Mozambique’s $2-billion “tuna bond” scandal. Global banks and consultancies continue to feel the squeeze for their complicity in state capture in South Africa.Competition and pluralismNational liberation movements may only have a limited window within which to act. Across the region civil society campaigns and investigative journalists have shed light on some of the worst abuses of power. Anti-corruption campaigns are starting to bite. The state will continue to play a central role in Southern African economies, an important arbiter of economic transformation able to balance the region’s highly unequal and resource-dependent economies.But opposition, civil society and the media are also critical for the progression towards democratic competition and pluralism in Southern Africa. Parliaments remain vital for holding rulers to account. Long used to unchallenged dominance, liberation movements have significant adjustments to make to rise to the challenge of a new era.This article was originally published in the Mail and Guardian. Full Article
up Upregulation of CD73 Confers Acquired Radioresistance and is Required for Maintaining Irradiation-selected Pancreatic Cancer Cells in a Mesenchymal State [Research] By feedproxy.google.com Published On :: 2020-02-01T00:05:30-08:00 The molecular mechanisms underlying exceptional radioresistance in pancreatic cancer remain elusive. In the present study, we established a stable radioresistant pancreatic cancer cell line MIA PaCa-2-R by exposing the parental MIA PaCa-2 cells to fractionated ionizing radiation (IR). Systematic proteomics and bioinformatics analysis of protein expression in MIA PaCa-2 and MIA PaCa-2-R cells revealed that several growth factor-/cytokine-mediated pathways, including the OSM/STAT3, PI3K/AKT, and MAPK/ERK pathways, were activated in the radioresistant cells, leading to inhibition of apoptosis and increased epithelial-mesenchymal plasticity. In addition, the radioresistant cells exhibited enhanced capabilities of DNA repair and antioxidant defense compared with the parental cells. We focused functional analysis on one of the most up-regulated proteins in the radioresistant cells, ecto-5'-nucleotidase (CD73), which is a cell surface protein that is overexpressed in different types of cancer. Ectopic overexpression of CD73 in the parental cells resulted in radioresistance and conferred resistance to IR-induced apoptosis. Knockdown of CD73 re-sensitized the radioresistant cells to IR and IR-induced apoptosis. The effect of CD73 on radioresistance and apoptosis is independent of the enzymatic activity of CD73. Further studies demonstrate that CD73 up-regulation promotes Ser-136 phosphorylation of the proapoptotic protein BAD and is required for maintaining the radioresistant cells in a mesenchymal state. Our findings suggest that expression alterations in the IR-selected pancreatic cancer cells result in hyperactivation of the growth factor/cytokine signaling that promotes epithelial-mesenchymal plasticity and enhancement of DNA repair. Our results also suggest that CD73, potentially a novel downstream factor of the enhanced growth factor/cytokine signaling, confers acquired radioresistance by inactivating proapoptotic protein BAD via phosphorylation of BAD at Ser-136 and by maintaining the radioresistant pancreatic cancer cells in a mesenchymal state. Full Article
up Interaction Proteomics Identifies ERbeta Association with Chromatin Repressive Complexes to Inhibit Cholesterol Biosynthesis and Exert An Oncosuppressive Role in Triple-negative Breast Cancer [Research] By feedproxy.google.com Published On :: 2020-02-01T00:05:29-08:00 Triple-negative breast cancer (TNBC) is characterized by poor response to therapy and low overall patient survival. Recently, Estrogen Receptor beta (ERβ) has been found to be expressed in a fraction of TNBCs where, because of its oncosuppressive actions on the genome, it represents a potential therapeutic target, provided a better understanding of its actions in these tumors becomes available. To this end, the cell lines Hs 578T, MDA-MB-468 and HCC1806, representing the claudin-low, basal-like 1 and 2 TNBC molecular subtypes respectively, were engineered to express ERβ under the control of a Tetracycline-inducible promoter and used to investigate the effects of this transcription factor on gene activity. The antiproliferative effects of ERβ in these cells were confirmed by multiple functional approaches, including transcriptome profiling and global mapping of receptor binding sites in the genome, that revealed direct negative regulation by ERβ of genes, encoding for key components of cellular pathways associated to TNBC aggressiveness representing novel therapeutic targets such as angiogenesis, invasion, metastasis and cholesterol biosynthesis. Supporting these results, interaction proteomics by immunoprecipitation coupled to nano LC-MS/MS mass spectrometry revealed ERβ association with several potential nuclear protein partners, including key components of regulatory complexes known to control chromatin remodeling, transcriptional and post-transcriptional gene regulation and RNA splicing. Among these, ERβ association with the Polycomb Repressor Complexes 1 and 2 (PRC1/2), known for their central role in gene regulation in cancer cells, was confirmed in all three TNBC subtypes investigated, suggesting its occurrence independently from the cellular context. These results demonstrate a significant impact of ERβ in TNBC genome activity mediated by its cooperation with regulatory multiprotein chromatin remodeling complexes, providing novel ground to devise new strategies for the treatment of these diseases based on ligands affecting the activity of this nuclear receptor or some of its protein partners. Full Article
up A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients [Technological Innovation and Resources] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 State-of-the-art proteomics-grade mass spectrometers can measure peptide precursors and their fragments with ppm mass accuracy at sequencing speeds of tens of peptides per second with attomolar sensitivity. Here we describe a compact and robust quadrupole-orbitrap mass spectrometer equipped with a front-end High Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) Interface. The performance of the Orbitrap Exploris 480 mass spectrometer is evaluated in data-dependent acquisition (DDA) and data-independent acquisition (DIA) modes in combination with FAIMS. We demonstrate that different compensation voltages (CVs) for FAIMS are optimal for DDA and DIA, respectively. Combining DIA with FAIMS using single CVs, the instrument surpasses 2500 peptides identified per minute. This enables quantification of >5000 proteins with short online LC gradients delivered by the Evosep One LC system allowing acquisition of 60 samples per day. The raw sensitivity of the instrument is evaluated by analyzing 5 ng of a HeLa digest from which >1000 proteins were reproducibly identified with 5 min LC gradients using DIA-FAIMS. To demonstrate the versatility of the instrument, we recorded an organ-wide map of proteome expression across 12 rat tissues quantified by tandem mass tags and label-free quantification using DIA with FAIMS to a depth of >10,000 proteins. Full Article
up A peroxisome deficiency-induced reductive cytosol state up-regulates the brain-derived neurotrophic factor pathway [Metabolism] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid β-oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown. Because CNS integrity is coordinately established and maintained by neural cell interactions, we here investigated whether cell-cell communication is impaired and responsible for the neurological defects associated with PBDs. Results from a noncontact co-culture system consisting of primary hippocampal neurons with glial cells revealed that a peroxisome-deficient astrocytic cell line secretes increased levels of brain-derived neurotrophic factor (BDNF), resulting in axonal branching of the neurons. Of note, the BDNF expression in astrocytes was not affected by defects in plasmalogen biosynthesis and peroxisomal fatty acid β-oxidation in the astrocytes. Instead, we found that cytosolic reductive states caused by a mislocalized catalase in the peroxisome-deficient cells induce the elevation in BDNF secretion. Our results suggest that peroxisome deficiency dysregulates neuronal axogenesis by causing a cytosolic reductive state in astrocytes. We conclude that astrocytic peroxisomes regulate BDNF expression and thereby support neuronal integrity and function. Full Article
up The mitochondrial protein PGAM5 suppresses energy consumption in brown adipocytes by repressing expression of uncoupling protein 1 [Metabolism] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), is a protein phosphatase that resides in the mitochondria and regulates many biological processes, including cell death, mitophagy, and immune responses. Because BAT is a mitochondria-rich tissue, we have hypothesized that PGAM5 has a physiological function in BAT. We previously reported that PGAM5-knockout (KO) mice are resistant to severe metabolic stress. Importantly, lipid accumulation is suppressed in PGAM5-KO BAT, even under unstressed conditions, raising the possibility that PGAM5 deficiency stimulates lipid consumption. However, the mechanism underlying this observation is undetermined. Here, using an array of biochemical approaches, including quantitative RT-PCR, immunoblotting, and oxygen consumption assays, we show that PGAM5 negatively regulates energy expenditure in brown adipocytes. We found that PGAM5-KO brown adipocytes have an enhanced oxygen consumption rate and increased expression of uncoupling protein 1 (UCP1), a protein that increases energy consumption in the mitochondria. Mechanistically, we found that PGAM5 phosphatase activity and intramembrane cleavage are required for suppression of UCP1 activity. Furthermore, utilizing a genome-wide siRNA screen in HeLa cells to search for regulators of PGAM5 cleavage, we identified a set of candidate genes, including phosphatidylserine decarboxylase (PISD), which catalyzes the formation of phosphatidylethanolamine at the mitochondrial membrane. Taken together, these results indicate that PGAM5 suppresses mitochondrial energy expenditure by down-regulating UCP1 expression in brown adipocytes and that its phosphatase activity and intramembrane cleavage are required for UCP1 suppression. Full Article
up What Uber tells us about disruption By www.smh.com.au Published On :: Sun, 06 Sep 2015 11:19:32 GMT Uber's digital component is only part of it's success and there are other important lessons for any business. Full Article
up Sydney start-up Suppertime acquired by food delivery giant By www.smh.com.au Published On :: Mon, 12 Oct 2015 06:29:04 GMT Australian premium restaurant delivery service Suppertime has been snapped by a major international company, as the local food delivery market continues to heat up. Full Article