go Entertainment On The Go By jamaica-star.com Published On :: Thu, 07 May 2020 05:01:03 -0500 DJ Mackwan aims to be an ace DJ Jonathan McKenzie, better known as DJ Mackwan, is on a path to music superstardom with his bold and fresh take as the remix DJ. He said, "When I am playing I incorporate a lot of remixes and try to use music to... Full Article
go People just wah hear sumpn different - Govana finds captive audience as ‘Convo Pt 2’ hits a million views By jamaica-star.com Published On :: Thu, 07 May 2020 05:01:23 -0500 Back in January when dancehall artiste Govana released the track HAMANTS Convo, the storyline captivated listeners across the globe. For weeks, the song, which highlights infidelity in relationships, trended at number one on the local YouTube... Full Article
go Gospel Spotlight: Gospel Song winner explores ‘Excess Love’ By jamaica-star.com Published On :: Fri, 08 May 2020 05:01:44 -0500 E xcess Love, a song by Nigerian gospel artiste Mercy Chinwo, has found favour with both Christians and non-Christians alike and has been flooding the airwaves since last year. Joanna Walker, the Jamaica Cultural Development Commission's (JCDC)... Full Article
go Bartender finds the going very tough By jamaica-star.com Published On :: Thu, 07 May 2020 05:01:24 -0500 Having to witness your child go off to bed without a meal is not the most pleasing experience for a parent. However, this is the reality of Viviene Francis, who was laid off from her job as a bartender. Francis, who is a single mother, told THE... Full Article
go Chic on Sticks going the extra mile for persons with disabilities By jamaica-star.com Published On :: Fri, 08 May 2020 05:01:59 -0500 Her voice cracked as she related the story of a man with disabilities who lost his wife and whose child has had to drop out of school because he has no money. All he has is Bridgette Johnson, a fellow disabled person who has dedicated her life... Full Article
go Governments Should Be Transparent When Planning to End Lockdowns By www8.gsb.columbia.edu Published On :: Thu, 07 May 2020 00:00:00 -0400 Businesses will benefit from clear policy guidance from lawmakers Full Article
go Beyond CARES: Economist Glenn Hubbard on Government Response to COVID-19 By www8.gsb.columbia.edu Published On :: Fri, 08 May 2020 00:00:00 -0400 Hubbard asks: Can we design a more effective plan, in case of a next time? Full Article
go China Expands Its Global Governance Ambitions in the Arctic By feedproxy.google.com Published On :: Mon, 15 Oct 2018 09:32:49 +0000 15 October 2018 Harriet Moynihan Senior Research Fellow, International Law Programme @HarrietMoyniha9 Beijing wants to present itself as a responsible power with a role to play in Arctic governance, as part of a broader ambition to become a shaper of global rules and institutions. 2018-10-15-Xuelong.jpg The Xuelong 2 icebreaker is christened in Shanghai on 10 September. Photo via Getty Images. As polar ice melts, the Arctic will become increasingly important for its untapped oil, gas and minerals as they become more accessible, as well for its shipping routes, which will become increasingly cost efficient for cargo as parts of the routes become ice-free for extended periods. A number of countries, including Russia and China, are also exploring the possibilities around overflights, commercial fishing, the laying of submarine cables and pipelines, and scientific research.Earlier this month, China announced the launch of its first domestically built conventionally-powered polar icebreaker, Xuelong 2, or Snow Dragon 2. Like its (foreign-built) predecessor,Snow Dragon, this vessel’s purpose is framed as scientific research into polar ice coverage, environmental conditions, and biological resources. It has not gone unnoticed, though, that China’s new icebreakers are also useful in testing the feasibility of moving cargo across the Arctic. China’s plans for a Polar Silk Road, as part of its ambitious multi-billion-dollar Belt and Road Initiative, include developing Arctic shipping routes. China recently invested in Russia’s Yamal liquefied natural gas project in the northern port of Sabetta and signed a framework agreement for Chinese and Russian banks to co-finance up to 70 joint projects in the Arctic region.But China’s interest in the Arctic extends beyond the purely economic: it is also pressing for a greater role in its governance. Compared to the Antarctic – where governance is heavily institutionalized, governance of the Arctic is much less developed, largely due to their distinctly different natures. The Antarctic, which is predominantly landmass, is governed by a treaty with 53 states parties, freezing territorial claims and preserving this region for peaceful scientific purposes. By contrast, the Arctic Council was only established in 1996 and comprises the eight Arctic states that claim sovereignty over the landmass in the Arctic Circle, a region which consists largely of frozen ocean and which hosts indigenous populations. The legal framework is a patchwork affair, drawn from various treaties of global application (including the UN Charter and the UN Convention on the Law of the Sea), the Svalbard Treaty(recognizing Norway’s sovereignty over the eponymous Arctic archipelago), as well as customary international law and general principles of law. So far, the Arctic Council has been the forum for the conclusion of only three legally binding agreements.China sees a gap for new ideas, rules and participants in this space. A white paper released by the government in January contains sophisticated and detailed analysis of the international legal framework applicable to the Arctic and demonstrates China’s increasing knowledge and capability in this area, as reflected in the growing number of Chinese international lawyers specializing in Arctic matters. The white paper seeks to justify China’s involvement in Arctic affairs as a ‘near Arctic state’, noting that the Arctic’s climate, environment and ecology are of concern for all states. The white paper uses familiar phrases from China’s vision for its foreign policy – such as the ‘shared future of mankind’ and ‘mutual benefit’ – to argue for a pluralist (i.e. global, regional and bilateral) approach to Arctic governance. China is sensitive to the risks of overreaching when it comes to states with territorial claims in the Arctic, especially as resource competition hots up. The white paper positions China as a responsible and peaceful power, whose participation in Arctic affairs is based on ‘respect, cooperation, win-win result and sustainability’.China was admitted as an observer to the Arctic Council in 2013, along with four other Asian states (including Japan, which is taking an equally keen interest in opportunities for Arctic rule-making) and Italy. As an observer state, China has very limited rights in the council, but has been creatively using other routes to influence Arctic governance, including active engagement within the International Maritime Organization (IMO) and the International Seabed Commission. China participated in the formation of the IMO’s Polar Code of January 2017, which sets out rules for ships operating in polar waters. China was also one of ten states involved in the recent adoption of the Agreement to Prevent Unregulated High Seas Fisheries in the Central Arctic Ocean, which took place outside the umbrella of the Arctic Council. At a recent roundtable in Beijing co-hosted by Chatham House, Chinese experts noted China’s aspirations to develop the international rule of law in the Arctic through playing an active role in developing new rules in areas currently under (or un-) regulated, for example, through a treaty to strengthen environmental protection in the region. It was also suggested that China may also seek to clarify the meaning of existing rules through its own practice. China also has ambitions to contribute to the research of the Arctic Council’s Working Groups, which develop proposals for Arctic Council projects and rules. It remains to be seen to what extent Arctic states, protective of theirown national interests in an increasingly fertile area, will cede space for China to participate.China’s push to be a rule shaper in the Arctic fits into a wider pattern of China seeking a more influential role in matters of global governance. This trend is particularly apparent in areas where the rules are still emerging and thus where China feels more confident than in areas traditionally dominated by Western powers.A similar assertiveness by China is increasingly visible in other emerging areas of international law, such as the international legal framework applicable to cyber operations and international dispute settlement mechanisms relating to trade and investment.China’s approach to Arctic governance offers an interesting litmus test as to how far China intends to deploy international law to assert itself on governance issues with significant global economic, environmental, and security implications – along with the degree to which it will be perceived as acting in the common interest in doing so. Full Article
go Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-Induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses By feedproxy.google.com Published On :: 2020-04-15 Sonia PodvinApr 15, 2020; 0:RA120.002079v1-mcp.RA120.002079Research Full Article
go Gotta catch ’em all, URM! By blogs.ams.org Published On :: Thu, 19 Dec 2019 03:24:01 +0000 By Carrie Diaz Eaton and Pamela E. Harris We received the same email: Tuesday, Dec 17, 1:37 PM and Tuesday, Dec 17, 1:42 PM. No time to personalize the email. Simply change last names. After all, any one will do, … Continue reading → Full Article career advancement General Leadership Negotiating faculty / post doc positions Outreach postdocs Tenure Uncategorized
go Dorothy Gordon By feedproxy.google.com Published On :: Thu, 01 Aug 2019 15:21:32 +0000 Associate Fellow, International Security Programme and Global Economy and Finance Programme Biography Dorothy was the founding director general of the Ghana-India Kofi Annan Centre of Excellence in ICT, a position which she held for over a decade.She works globally as a policy adviser, evaluator, project manager and organizational management consultant.Over the course of her 30-year career in international development and technology she has held management positions with the UN and global management consulting firms on four continents.As a strong advocate of the importance of building robust local innovation ecosystems based on open source technologies, she serves on the board and as a mentor to a number of start-ups and NGOs focused on women in tech. Full Article
go Cyber Governance in the Commonwealth: Towards Stability and Responsible State Behaviour in Cyberspace By feedproxy.google.com Published On :: Mon, 05 Aug 2019 14:05:02 +0000 Invitation Only Research Event 7 October 2019 - 10:30am to 5:30pm Addis Ababa, Ethiopia This roundtable is part of a series under the project, 'Implementing the Commonwealth Cybersecurity Agenda', funded by the UK Foreign and Commonwealth Office (FCO). The roundtable aims to provide a multi-stakeholder, pan-Commonwealth platform to discuss how to implement the Commonwealth Cyber Declaration with a focus on its third pillar 'To promote stability in cyberspace through international cooperation'.In particular, the roundtable focuses on points 3 and 4 of the third pillar which revolve around the commitment to promote frameworks for stability in cyberspace including the applicability of international law, agreed voluntary norms of responsible state behaviour and the development and implementation of confidence-building measures consistent with the 2015 report of the UNGGE. The workshop also focuses on the commitment to advance discussions on how existing international law, including the Charter of the United Nations and applicable international humanitarian law, applies in cyberspace.The roundtable addresses the issue of global cyber governance from a Commonwealth perspective and will also include a discussion around the way forward, the needed capacity of the different Commonwealth countries and the cooperation between its members for better cyber governance.Participants include UNGGE members from Commonwealth countries in addition to representatives to the UN Open-Ended Working Group from African countries as well as members from academia, civil society and industry. Department/project International Security Programme Calum Inverarity Research Analyst and Coordinator, International Security Department +44 (0) 207 957 5751 Email Full Article
Calum Inverarity Research Analyst and Coordinator, International Security Department +44 (0) 207 957 5751 Email
go EU–US Relations on Internet Governance By feedproxy.google.com Published On :: Thu, 14 Nov 2019 16:12:28 +0000 14 November 2019 As internet governance issues emerge in the wake of innovations such as the Internet of Things and advanced artificial intelligence, there is an urgent need for the EU and US to establish a common, positive multi-stakeholder vision for regulating and governing the internet. Read online Download PDF Emily Taylor Associate Fellow, International Security Programme @etaylaw LinkedIn Stacie Hoffmann Internet Policy and Cybersecurity Consultant, Oxford Information Labs 2019-11-14-EUUSInternet.jpg Server room network cables in New York City, November 2014. Photo: Michael Bocchieri/Staff/Getty. Political, economic, sociological and technological factors are poised to challenge EU and US ideological positions on internet governance, which will make it difficult to find consensus and common ground in the years to come.The EU and US share core values and perspectives relating to internet governance, such as openness, freedom and interoperability, as well as a human rights framework for cybersecurity. There have been many examples of successful multi-stakeholder cooperation between the EU and US, including the Internet Assigned Numbers Authority (IANA) transition and the European Dialogue on Internet Governance (EuroDIG).There are also subtle differences between the EU and US, and each has different reasons to support multi-stakeholderism. Cases that highlight growing tensions in EU–US coordination on internet governance include the controversies surrounding the EU General Data Protection Regulation (GDPR), the WHOIS system that governs domain name registration data, and the board of the Internet Corporation for Assigned Names and Numbers (ICANN), which undermined an independent cybersecurity review.Internet governance is becoming more complex, with a multiplicity of actors and no obvious authority for important emerging issues. Additionally, the rise of China and its authoritarian vision for the future of the internet is a threat to the current internet governance institutions that have been shaped by and reflect Western values.To bridge ideological gaps the EU and US should build capacity between likeminded stakeholders, create a taskforce on effective multi-stakeholder internet governance, and work through non-governmental stakeholders to improve participation. Department/project International Security Programme, Internet Governance Full Article
go Prospects for Reforming Libya’s Economic Governance: Ways Forward By feedproxy.google.com Published On :: Mon, 27 Jan 2020 15:45:02 +0000 Invitation Only Research Event 6 February 2020 - 10:30am to 12:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Jason Pack, Non-Resident Fellow, Middle East InstituteTim Eaton, Senior Research Fellow, Middle East and North Africa Programme, Chatham HouseChair: Elham Saudi, Director, Lawyers for Justice Libya There is a broad consensus that Libya’s rentier, patronage-based system of governance is a driver, and not only a symptom, of Libya’s continuing conflict. The dysfunction of Libya’s economic system of governance has been exacerbated by the governance split that has prevailed since 2014 whereby rival administrations of state institutions have emerged. Despite these challenges, a system of economic interdependence, whereby forces aligned with Field Marshal Haftar control much of the oil and gas infrastructure and the UN-backed Government of National Accord controls the means of financial distribution, has largely prevailed. Yet, at the time of writing, this is under threat: a damaging oil blockade is being implemented by forces aligned with Haftar and those state institutions that do function on a national basis are finding it increasingly difficult to avoid being dragged into the conflict.This roundtable will bring together analysts and policymakers to discuss these dynamics and look at possible remedies. Jason Pack, non-resident fellow at the Middle East Institute, will present the findings of his latest paper on the issue which recommends the formation of 'a Libyan-requested and Libyan-led International Financial Commission vested with the requisite authorities to completely restructure the economy.' Tim Eaton, who has been leading Chatham House’s work on Libya’s conflict economy, supporting UNSMIL’s efforts in this field, will act as respondent.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Middle East and North Africa Programme, Libya’s Conflict Economy Full Article
go Why is it So Hard for Iraq to Form A Government? By feedproxy.google.com Published On :: Sat, 25 Apr 2020 17:03:58 +0000 25 April 2020 Dr Renad Mansour Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative @renadmansour Mustafa al-Kadhimi has emerged as the compromise prime minister designate, but his potential appointment is built on shaky foundations. 2020-04-25-Iraq-Security-COVID A member of Iraqi security forces stands guard behind a yellow line after the government declared curfew due to coronavirus. Photo by Fariq Faraj Mahmood/Anadolu Agency via Getty Images. On April 9, Iraqi President Barham Salih gathered the Shia, Kurdish and Sunni political blocs at the presidential palace to task head of intelligence Mustafa al-Kadhimi with forming a government.Kadhimi is the third prime minister-designate assigned since Prime Minister Adil abd al-Mehdi resigned in November, in the wake of mass protests against government corruption and the country’s ethno-sectarian based political system.Kadhimi’s two predecessors, Muhammad Tawfiq Allawi and Adnan al-Zurfi, both failed to form a government. This third attempt came as Iraq struggles with repeated crises since October 2019, when the government began responding with deadly force to large-scale mass protests, killing more than 600 and injuring tens of thousands.In January, the assassination of Qasem Soleimani escalated tensions between the United States and Iran, with Iraq stuck in the middle and becoming the home for regular tit-for-tat attacks. The Islamic State — never completely defeated — took advantage of these crises and increased its attacks in disputed territories.The outbreak of COVID-19 challenges the country’s fragile public health sector, while the decline in the price of oil will make it harder for leaders to pay the public salaries that keep the system (and patronage) moving.What does the delay in forming a government amid multiple crises mean for the post-2003 Iraqi political system? Iraq’s post-2003 political system is designed to withstand crisis. Over the years, political parties reflecting the country’s ethnic and sectarian divides have had a tacit understanding that crises represent a risk to their collective interests. These elite stakeholders have together weathered civil war, insurgency and multiple protests — despite deep conflicts with one another.For instance, in September 2018 protesters attacked most major political party headquarters and the Iranian consulate in Basra, and authorities killed some 20 protesters.Since the May election of that year, the fragmented Shia elite had been unable to even declare which side has the largest parliamentary bloc, let alone decide on a government.But after the September crisis, the previously gridlocked parties swiftly came together to form an “understanding” that pushed through the impasse leading to the Mehdi government. In 2020, however, Iraq’s political parties were slower to come back together despite the multiple crises — far greater than 2018. The system is less able to swiftly fix itself, based primarily on the fragmentation of the elite — and their determination to prevent any challenge to their rule.Why did the two prior attempts fail? The two previous prime minister-designates each fell short for different reasons. When I met Allawi in February at the prime minister’s guesthouse in Baghdad, he was very clearly convinced that his mandate was to sideline the parties.He hoped that simply choosing technocratic ministers outside the elite pact, with the support of Moqtada al-Sadr behind him, would garner support from protesters and the disillusioned public. He failed, however, because his cabinet had to go through parliament and the parties rejected what they saw a threat to the elite pact and the system.Zurfi similarly failed after being directly appointed in March by Salih after the Shia parties failed to come up with a candidate. From the beginning, then, Zurfi faced challenges because parties were not in agreement. He attempted to directly confront his opposition, and spoke out against Iranian influence in Iraq. As a result, Zurfi was unable to even get to parliament with his proposed cabinet, as the Shia parties got back together to bring him down.The failure of both strategies — Allawi attempting to work outside the elite party system and Zurfi trying to target certain parties — reveals tensions in Iraq’s political system. This fragmentation strains the parties’ ability to swiftly unite, and the system’s ability to withstand crises.The endemic problems are a consequence of fragmentation, including the failure following the 2018 elections to declare governing parliamentary bloc. Moreover, after that election, newcomers into the political system (two-thirds of the MPs are serving their first term) are increasingly making their own demands and less willing to blindly toe party lines.Can Kadhimi overcome the impasse?Kadhimi’s appointment as prime minister-designate nonetheless is on shaky foundations. His appointment had previously faced a veto from Iran and its allied groups which make up the Fateh bloc. Kataeb Hezbollah, an armed group close to Iran and linked to the Popular Mobilization Units, issued a statement accusing Kadhimi with blood on his hands for the deaths of Soleimani and Abu Mahdi al-Muhandis.Many Fateh bloc members had for months vetoed Kadhimi’s name due to this allegation. Immediately before Kadhimi addressed the nation for the first time, Iraqi state television broadcast a prerecorded statement by PMU (and Fateh) leader Qais al-Khazali, who had also previously accused Kadhimi of spying for the Americans and being complicit in the two killings.Khazali, who commands the second-largest party within Fateh, accepted the party line to back Kadhimi but came out with his own conditions on television. However, the concerns about the COVID-19 crisis and the collapse of the price of oil finally brought all sides to compromise — a design of the political system.Kadhimi has signalled he will play by the old rules with these stakeholders. Because of the magnitude of these simultaneous crises, Iraqi politics is moving back to the post-2003 norm. The ethno-sectarian based political system is geared to weather such existential crises more than it is to handling day-to-day governance. Despite the notion of “post-sectarianism” in Iraq, this system is based on ethno-sectarian political party compromise.In his television address, Khazali, who had previously attempted to move away from sectarian language, explained that the process of selecting a prime minister is reserved to the Shia, who have the right as the majority, and not to Salih, a Kurd.Over the years Kadhimi has expressed an admiration of the bravery of the protesters and of the importance of civil society. Many Iraqi civil society activists owe their lives to the work of the former intelligence chief. However, he has also been part of the same system that has violently suppressed protesters.As the compromise prime minister-designate, he will find it difficult to transform his country as long as he plays by the rules of post-2003 Iraq — an irony not lost on the protesters who immediately rejected the candidacy of a man whom until recently many protesters had supported.This article was originally published in The Washington Post Full Article
go Evidence Against an Important Role of Plasma Insulin and Glucagon Concentrations in the Increase in EGP Caused by SGLT2 Inhibitors By diabetes.diabetesjournals.org Published On :: 2020-03-20T11:50:28-07:00 Sodium–glucose cotransport 2 inhibitors (SGLT2i) lower plasma glucose but stimulate endogenous glucose production (EGP). The current study examined the effect of dapagliflozin on EGP while clamping plasma glucose, insulin, and glucagon concentrations at their fasting level. Thirty-eight patients with type 2 diabetes received an 8-h measurement of EGP ([3-3H]-glucose) on three occasions. After a 3-h tracer equilibration, subjects received 1) dapagliflozin 10 mg (n = 26) or placebo (n = 12); 2) repeat EGP measurement with the plasma glucose concentration clamped at the fasting level; and 3) repeat EGP measurement with inhibition of insulin and glucagon secretion with somatostatin infusion and replacement of basal plasma insulin and glucagon concentrations. In study 1, the change in EGP (baseline to last hour of EGP measurement) in subjects receiving dapagliflozin was 22% greater (+0.66 ± 0.11 mg/kg/min, P < 0.05) than in subjects receiving placebo, and it was associated with a significant increase in plasma glucagon and a decrease in the plasma insulin concentration compared with placebo. Under glucose clamp conditions (study 2), the change in plasma insulin and glucagon concentrations was comparable in subjects receiving dapagliflozin and placebo, yet the difference in EGP between dapagliflozin and placebo persisted (+0.71 ± 0.13 mg/kg/min, P < 0.01). Under pancreatic clamp conditions (study 3), dapagliflozin produced an initial large decrease in EGP (8% below placebo), followed by a progressive increase in EGP that was 10.6% greater than placebo during the last hour. Collectively, these results indicate that 1) the changes in plasma insulin and glucagon concentration after SGLT2i administration are secondary to the decrease in plasma glucose concentration, and 2) the dapagliflozin-induced increase in EGP cannot be explained by the increase in plasma glucagon or decrease in plasma insulin or glucose concentrations. Full Article
go Head to head prospective comparison of quantitative lung scintigraphy and segment counting in predicting pulmonary function of lung cancer patients undergoing video-assisted thoracoscopic lobectomy By jnm.snmjournals.org Published On :: 2019-12-20T13:25:42-08:00 Prediction of post-operative pulmonary function in lung cancer patients before tumor resection is essential for patient selection for surgery and is conventionally done with a non-imaging segment counting method (SC) or a two-dimensional planar lung perfusion scintigraphy (PS). The purpose of this study was to compare quantitative analysis of PS to single photon emission computed tomography/computed tomography (SPECT/CT) and to estimate the accuracy of SC, PS and SPECT/CT in predicting post-operative pulmonary function in patients undergoing lobectomy. Methods: Seventy-five non-small cell lung cancer (NSCLC) patients planned for lobectomy were prospectively enrolled (68% males, average age 68.1±8 years ). All patients completed pre-operative forced expiratory volume capacity (FEV1), diffusing capacity of the lung for carbon monoxide (DLCO), Tc99m-MAA lung perfusion scintigraphy with PS and SPECT/CT quantification. A subgroup of 60 patients underwent video-assisted thoracoscopic (VATS) lobectomy and measurement of post-operative FEV1 and DLCO. Relative uptake of the lung lobes estimated by PS and SPECT/CT were compared. Predicted post-operative FEV1 and DLCO were derived from SC, PS and SPECT/CT. Prediction results were compared between the different methods and the true post-operative measurements in patients who underwent lobectomy. Results: Relative uptake measurements differed significantly between PS and SPECT/CT in right lung lobes, with a mean difference of -8.2±3.8, 18.0±5.0 and -11.5±6.1 for right upper, middle and lower lobes respectively (p<0.001). The differences between the methods in the left lung lobes were minor with a mean difference of -0.4±4.4 (p>0.05) and -2.0±4.0 (p<0.001) for left upper and lower lobes respectively. No significant difference and strong correlation (R=0.6-0.76, p<0.001) were found between predicted post-operative lung function values according to SC, PS, SPECT/CT and the actual post-operative FEV1 and DLCO. Conclusion: Although lobar quantification parameters differed significantly between PS and SPECT/CT, no significant differences were found between the predicted post-operative lung function results derived from these methods and the actual post-operative results. The additional time and effort of SPECT/CT quantification may not have an added value in patient selection for surgery. SPECT/CT may be advantageous in patients planned for right lobectomies but further research is warranted. Full Article
go Management of patients with renal failure undergoing dialysis during 131I therapy for thyroid cancer By jnm.snmjournals.org Published On :: 2020-01-10T04:59:09-08:00 Objectives: Radioactive iodine (131I) therapy may be used to treat thyroid cancer in end-stage renal disease patients who undergo hemodialysis. Because iodine predominantly utilizes renal clearance, treatment management in hemodialysis patients may be problematic, and no formal recommendations on hemodialysis currently exist. This work details our experience with treating thyroid cancer with iodine in chronic renal failure patients who require hemodialysis and details the therapeutic dosimetry results obtained during treatment to ensure that the dose to the bone marrow (BM) was acceptable. Methods: We treated 6 patients in the metabolic radiotherapy unit after thyroid stimulation. Two hemodialysis sessions in the metabolic radiotherapy unit were performed at 42 and 90 hours after radiopharmaceutical administration. BM toxicity was estimated with activity measurements from blood samples and with whole-body measurements that were regularly repeated during hospitalization and measured with a gamma counter. The patients underwent thyroid and hematologic monitoring to assess treatment efficacy and therapeutic toxicity in the short, medium and long term. Results: Whole-body activity was reduced on average by 66.7% [60.1-71.5] after the first dialysis session and by 53.3% [30.4-67.8] after the second. The mean estimated total absorbed dose to the BM was 0.992 Gy for all patients [0.431 – 2.323]. We did not observe any significant hematologic toxicity, and the clinical, biological and ultrasound test results confirmed the success of ablative treatment for the majority of patients. Conclusion: An approximately 30% reduction from the nominal dose in the amount of 131I activity for hemodialysis patients with thyroid cancer appears to strike an appropriate balance between the absence of BM toxicity and therapeutic efficacy. To avoid overirradiation, we recommend pretherapeutic dosimetry studies for metastatic patients to calculate the amount of activity to be administered as well as dosimetry monitoring during the hemodialysis sessions performed after therapeutic dose administration and under the same conditions. Full Article
go Targeted optical imaging of the glucagon-like peptide 1 receptor using exendin-4-IRDye800CW By jnm.snmjournals.org Published On :: 2020-01-10T04:59:09-08:00 Rationale: The treatment of choice for insulinomas and focal lesions in congenital hyperinsulinism (CHI) is surgery. However, intra-operative detection can be challenging. This could be overcome with intra-operative fluorescence imaging, which provides real-time lesion detection with a high spatial resolution. Here, a novel method for targeted near-infrared (NIR) fluorescence imaging of glucagon-like peptide 1 receptor (GLP-1R) positive lesions, using the GLP-1 agonist exendin-4, labeled with IRDye800CW, was examined in vitro and in vivo. Methods: A competitive binding assay was performed using Chinese hamster lung (CHL) cells transfected with the GLP-1R. Tracer biodistribution was determined in BALB/c nude mice bearing subcutaneous CHL-GLP-1R xenografts. In vivo NIR fluorescence imaging of CHL-GLP-1R xenografts was performed. Localization of the tracer in the pancreatic islets of BALB/c nude mice was examined using fluorescence microscopy. Laparoscopic imaging was performed to detect the fluorescent signal of the tracer in the pancreas of mini pigs. Results: Exendin-4-IRDye800CW binds the GLP-1R with an IC50 value of 3.96 nM. The tracer accumulates in CHL-GLP-1R xenografts. Subcutaneous CHL-GLP-1R xenografts were visualized using in vivo NIR fluorescence imaging. The tracer accumulates specifically in the pancreatic islets of mice and a clear fluorescent signal was detected in the pancreas of mini pigs. Conclusion: These date provide the first in vivo evidence of the feasibility of targeted fluorescence imaging of GLP-1R positive lesions. Intra-operative lesion delineation using exendin-4-IRDye800CW could benefit open as well as laparoscopic surgical procedures for removal of insulinomas and focal lesions in CHI. Full Article
go Clinical evaluation of a data-driven respiratory gating algorithm for whole-body positron emission tomography with continuous bed motion By jnm.snmjournals.org Published On :: 2020-02-14T14:01:21-08:00 Respiratory gating is the standard to overcome respiration effects degrading image quality in positron emission tomography (PET). Data-driven gating (DDG) using signals derived from PET raw data are promising alternatives to gating approaches requiring additional hardware. However, continuous bed motion (CBM) scans require dedicated DDG approaches for axially-extended PET, compared to DDG for conventional step-and-shoot scans. In this study, a CBM-capable DDG algorithm was investigated in a clinical cohort, comparing it to hardware-based gating using gated and fully motion-corrected reconstructions. Methods: 56 patients with suspected malignancies in thorax or abdomen underwent whole-body 18F-FDG CBM-PET/CT imaging using DDG and hardware-based respiratory gating (pressure-sensitive belt gating, BG). Correlation analyses were performed on both gating signals. Besides static reconstructions, BG and DDG were used for optimally-gated PET (BG-OG, DDG-OG) and fully motion-corrected PET (elastic motion correction; BG-EMOCO, DDG-EMOCO). Metabolic volumes, SUVmax and SUVmean of lesions were compared amongst the reconstructions. Additionally, the quality of lesion delineation in different PET reconstructions was independently evaluated by three experts. Results: Global correlation coefficients between BG and DDG signals amounted to 0.48±0.11, peaking at 0.89±0.07 when scanning the kidney and liver region. In total, 196 lesions were analyzed. SUV measurements were significantly higher in BG-OG, DDG-OG, BG-EMOCO and DDG-EMOCO compared to static images (P<0.001; median SUVmax: static, 14.3±13.4; BG-EMOCO, 19.8±15.7; DDG-EMOCO, 20.5±15.6; BG-OG, 19.6±17.1; DDG-OG, 18.9±16.6). No significant differences between BG-OG and DDG-OG, and BG-EMOCO and DDG-EMOCO, respectively, were found. Visual lesion delineation was significantly better in BG-EMOCO and DDG-EMOCO than in static reconstructions (P<0.001); no significant difference was found comparing BG and DDG (EMOCO, OG, respectively). Conclusion: DDG-based motion-compensation of CBM-PET acquisitions outperforms static reconstructions, delivering qualities comparable to hardware-based approaches. The new algorithm may be a valuable alternative for CBM-PET systems. Full Article
go Kinetic modeling and test-retest reproducibility of 11C-EKAP and 11C-FEKAP, novel agonist radiotracers for PET imaging of the kappa opioid receptor in humans By jnm.snmjournals.org Published On :: 2020-03-13T14:12:30-07:00 The kappa opioid receptor (KOR) is implicated in various neuropsychiatric disorders. We previously evaluated an agonist tracer, 11C-GR103545, for PET imaging of KOR in humans. Although 11C-GR103545 showed high brain uptake, good binding specificity, and selectivity to KOR, it displayed slow kinetics and relatively large test-retest variability (TRV) of distribution volume (VT) estimates (15%). Therefore we set out to develop two novel KOR agonist radiotracers, 11C-EKAP and 11C-FEKAP, and in nonhuman primates, both tracers exhibited faster kinetics and comparable binding parameters to 11C-GR103545. The aim of this study was to assess their kinetic and binding properties in humans. Methods: Six healthy subjects underwent 120-min test-retest PET scans with both 11C-EKAP and 11C-FEKAP. Metabolite-corrected arterial input functions were measured. Regional time-activity curves (TACs) were generated for 14 regions of interest. One- and two-tissue compartment models (1TC, 2TC) and the multilinear analysis-1 (MA1) method were applied to the regional TACs to calculate VT. Time-stability of VT values and test-retest reproducibility were evaluated. Levels of specific binding, as measured by the non-displaceable binding potential (BPND) for the three tracers (11C-EKAP, 11C-FEKAP and 11C-GR103545), were compared using a graphical method. Results: For both tracers, regional TACs were fitted well with the 2TC model and MA1 method (t*=20min), but not with the 1TC model. Given unreliably estimated parameters in several fits with the 2TC model and a good match between VT values from MA1 and 2TC, MA1 was chosen as the appropriate model for both tracers. Mean MA1 VT values were highest for 11C-GR103545, followed by 11C-EKAP, then 11C-FEKAP. Minimum scan time for stable VT measurement was 90 and 110min for 11C-EKAP and 11C-FEKAP, respectively, compared with 140min for 11C-GR103545. The mean absolute TRV in MA1 VT estimates was 7% and 18% for 11C-EKAP and 11C-FEKAP, respectively. BPND levels were similar for 11C-FEKAP and 11C-GR103545, but ~25% lower for 11C-EKAP. Conclusion: The two novel KOR agonist tracers showed faster tissue kinetics than 11C-GR103545. Even with slightly lower BPND, 11C-EKAP is judged to be a better tracer for imaging and quantification of KOR in humans, based on the shorter minimum scan time and excellent test-retest. Full Article
go MITIGATE-NeoBOMB1, a Phase I/IIa Study to Evaluate Safety, Pharmacokinetics and Preliminary Imaging of 68Ga-NeoBOMB1, a Gastrin-releasing Peptide Receptor Antagonist, in GIST Patients By jnm.snmjournals.org Published On :: 2020-04-24T14:33:41-07:00 Introduction: Gastrin Releasing peptide receptors (GRPRs) are potential molecular imaging targets in a variety of tumors. Recently, a 68Ga-labelled antagonist to GRPRs, NeoBOMB1, was developed for PET. We report on the outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38) within the EU-FP7 project Closed-loop Molecular Environment for Minimally Invasive Treatment of Patients with Metastatic Gastrointestinal Stromal Tumours (‘MITIGATE’) (grant agreement number 602306) in patients with oligometastatic gastrointestinal stromal tumors (GIST). Materials and Methods: The main objectives were evaluation of safety, biodistribution, dosimetry and preliminary tumor targeting of 68Ga-NeoBOMB1 in patients with advanced TKI-treated GIST using PET/CT. Six patients with histologically confirmed GIST and unresectable primary or metastases undergoing an extended protocol for detailed pharmacokinetic analysis were included. 68Ga-NeoBOMB1 was prepared using a kit procedure with a licensed 68Ge/68Ga generator. 3 MBq/kg body-weight were injected intravenously and safety parameters were assessed. PET/CT included dynamic imaging at 5 min, 11 min and 19 min as well as static imaging at 1, 2 and 3-4 h p.i. for dosimetry calculations. Venous blood samples and urine were collected for pharmacokinetics. Tumor targeting was assessed on a per-lesion and per-patient basis. Results: 68Ga-NeoBOMB1 (50 µg) was prepared with high radiochemical purity (yield >97%). Patients received 174 ± 28 MBq of the radiotracer, which was well tolerated in all patients over a follow-up period of 4 weeks. Dosimetry calculations revealed a mean adsorbed effective dose of 0.029 ± 0.06 mSv/MBq with highest organ dose to the pancreas (0.274 ± 0.099 mSv/MBq). Mean plasma half-life was 27.3 min with primarily renal clearance (mean 25.7 ± 5.4% of injected dose 4h p.i.). Plasma metabolite analyses revealed high stability, metabolites were only detected in the urine. In three patients a significant uptake with increasing maximum standard uptake values (SUVmax at 2h p.i.: 4.3 to 25.9) over time was found in tumor lesions. Conclusion: This Phase I/IIa study provides safety data for 68Ga-NeoBOMB1, a promising radiopharmaceutical for targeting GRPR-expressing tumors. Safety profiles and pharmacokinetics are suitable for PET imaging and absorbed dose estimates are comparable to other 68Ga-labelled radiopharmaceuticals used in clinical routine. Full Article
go Receptor-targeted photodynamic therapy of glucagon-like peptide 1 receptor positive lesions By jnm.snmjournals.org Published On :: 2020-05-08T13:18:58-07:00 Treatment of hyperinsulinemic hypoglycemia is challenging. Surgical treatment of insulinomas and focal lesions in congenital hyperinsulinism (CHI) is invasive and carries major risks of morbidity. Medication to treat nesidioblastosis and diffuse CHI has varying efficacy and causes significant side effects. Here, we describe a novel method for therapy of hyperinsulinemic hyperglycemia, highly selectively killing beta cells by targeted photodynamic therapy (tPDT) with exendin-4-IRDye700DX, targeting the glucagon-like peptide 1 receptor (GLP-1R). A competitive binding assay was performed using Chinese hamster lung (CHL) cells transfected with the GLP-1R. The efficacy and specificity of tPDT with exendin-4-IRDye700DX was examined in vitro in cells with different levels of GLP-1R expression. Tracer biodistribution was determined in BALB/c nude mice bearing subcutaneous CHL-GLP-1R xenografts. Induction of cellular damage and the effect on tumor growth were analyzed to determine treatment efficacy. Exendin-4-IRDye700DX has a high affinity for the GLP-1R with an IC50 value of 6.3 nM. TPDT caused significant specific phototoxicity in GLP-1R positive cells (2.3 ± 0.8 % and 2.7 ± 0.3 % remaining cell viability in CHL-GLP-1R and INS-1 cells resp.). The tracer accumulates dose-dependently in GLP-1R positive tumors. In vivo tPDT induces cellular damage in tumors, shown by strong expression of cleaved-caspase-3 and leads to a prolonged median survival of the mice (36.5 vs. 22.5 days resp. p<0.05). These data show in vitro as well as in vivo evidence for the potency of tPDT using exendin-4-IRDye700DX. This could in the future provide a new, minimally invasive and highly specific treatment method for hyperinsulinemic hypoglycemia. Full Article
go The Relevance of Intergovernmental Organizations to African States: The International Organization of La Francophonie By feedproxy.google.com Published On :: Tue, 22 Oct 2019 13:05:01 +0000 Research Event 6 November 2019 - 10:00am to 11:15am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Louise Mushikiwabo, Secretary General, Organisation Internationale de la Francophonie (OIF)Chair: Bob Dewar CMG, Associate Fellow, Africa Programme, Chatham House African states are well represented in intergovernmental organizations linked by official language and colonial history such as the Organisation Internationale de la Francophonie (OIF), the Comunidade dos Países de Língua Portuguesa (CPLP) and the Commonwealth. These organizations aim to provide support in addressing matters of mutual interest – in addition to responding to significant policy challenges such as improving sustainable growth prospects and opportunities to young populations – and citizens are increasingly vocal on key issues such as democracy, human rights and the rule of law. This event series examines the importance of these intergovernmental organizations in working with their members to responsibly and sustainably respond to policy challenges in Africa.At this event, Louise Mushikiwabo, secretary general of the Organisation Internationale de la Francophonie (OIF), will discuss the organisation’s relevance to African states and the future of the organization on the continent.THIS EVENT IS NOW FULL AND REGISTRATION HAS NOW CLOSED. Department/project Africa Programme, Foreign Relations and Africa’s Agency in the International System Sahar Eljack Programme Administrator, Africa Programme + 44 (0) 20 7314 3660 Email Full Article
go Angola's Business Promise: Evaluating the Progress of Privatization and Other Economic Reforms By feedproxy.google.com Published On :: Thu, 16 Jan 2020 16:40:01 +0000 Research Event 21 January 2020 - 2:30pm to 3:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Hon. Manuel José Nunes Júnior, Minister of State for Economic Coordination, Republic of AngolaChair: Dr Alex Vines OBE, Managing Director, Ethics, Risk & Resilience; Director, Africa Programme, Chatham House Minister Nunes Júnior will discuss the progress of the Angolan government’s economic stabilization plans and business reform agenda including the privatization of some state-owned enterprises. These reforms could expand Angola’s exports beyond oil and stimulate new industries and more inclusive economic growth.THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED. 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
go The UK, US and Mauritius: Decolonization, Security, Chagos and the ICJ By feedproxy.google.com Published On :: Wed, 22 Jan 2020 13:35:01 +0000 Invitation Only Research Event 30 January 2020 - 8:15am to 9:15am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Professor Philippe Sands QC, Professor of Law, UCL Richard Burt, Managing Partner, McLarty AssociatesChair: Dr Leslie Vinjamuri, Director, US and Americas Programme; Dean, Queen Elizabeth II Academy, Chatham House The Chagos archipelago in the Indian Ocean has garnered media attention recently after the UK failed to abide by a UN deadline to return the islands to Mauritius. The US has landed in the middle of the dispute as a 1965 agreement with the UK has allowed the US to establish a military base on one of the islands, Diego Garcia, which has since become instrumental in US missions in the Asia-Pacific and the Middle East. In February 2019, an Advisory Opinion of the International Court of Justice (ICJ) found that the Chagos archipelago was unlawfully dismembered from Mauritius, in violation of the right to self-determination and that the United Kingdom is under an obligation to end its administration of the Chagos archipelago ‘as rapidly as possible’. The UN General Assembly subsequently voted overwhelmingly in favour of the UK leaving the islands by the end of November 2019 and the right of the former residents who were removed by the UK to return. The UK does not accept the ICJ and UN rulings and argues that the islands are needed to protect Britain from security threats while Mauritius has made clear the base can remain.Professor Philippe Sands QC, professor of law at University College London and lead counsel for Mauritius on the ICJ case on Legal Consequences of the Separation of the Chagos archipelago from Mauritius in 1965, will be joining Ambassador Richard Burt, US chief negotiator in the Strategic Arms Reduction Talks with the former Soviet Union for a discussion on the fate of the archipelago including the future of the military base and the right of return of former residents. Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project US and the Americas Programme US and Americas Programme Email Full Article
go Equatorial Guinea in 2020: Prospects for Economic and Governance Reforms By feedproxy.google.com Published On :: Fri, 24 Jan 2020 14:50:01 +0000 Research Event 31 January 2020 - 2:00pm to 3:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Tutu Alicante, Executive Director, EG JusticeChair: Dr Alex Vines OBE, Managing Director, Ethics, Risk & Resilience; Director, Africa Programme, Chatham House Despite boasting one of Africa’s highest GDP per capita rates, much of Equatorial Guinea’s population remain in poverty, with the world’s largest gap between its GDP per capita rates and human development index score. Equatorial Guinea’s economy is highly dependent on oil exports but production is in decline. In December 2019, the IMF Executive Board approved a US$282.8 million three-year Extended Fund Facility loan for Equatorial Guinea with provisions for promoting economic diversification, good governance, increasing transparency and fighting corruption. The country is also seeking to join the Extractive Industries Transparency Initiative.At this event, Tutu Alicante will discuss prospects for meaningful reforms in Equatorial Guinea to improve economic governance, human rights and achieve sustainable and inclusive economic growth.THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED. Department/project Africa Programme, West Africa, Inclusive Economic Growth, Governance and Technology, Sustainable Resource Governance Sahar Eljack Programme Administrator, Africa Programme + 44 (0) 20 7314 3660 Email Full Article
go Why The Insurgency in Northern Mozambique Has Got Worse By feedproxy.google.com Published On :: Wed, 01 Apr 2020 17:14:28 +0000 1 April 2020 Dr Alex Vines OBE Managing Director, Ethics, Risk & Resilience; Director, Africa Programme Two attacks on towns in northern Mozambique by suspected jihadists point to a rapidly deteriorating security crisis. 2020-04-01-Mozambique Macomia, Cabo Delgado, Northern Mozambique. Photo by EMIDIO JOSINE/AFP via Getty Images. On March 23 to 24, the centre of Mocimboa da Praia in Cabo Delgado province was occupied by up to 40 “jihadists”, who targeted government facilities, including a barracks, and brandished banners of affiliation to the so-called Islamic State.On March 25, suspected jihadists raided the town of Quissanga and destroyed the district police headquarters. They too carried an Islamic State flag. Twenty to 30 members of Mozambique’s security forces were killed in both attacks.Mocimboa da Praia is just south of the Afungi Peninsula, the location of gas projects worth $60- billion. Mocimboa was briefly occupied in late 2017, during attacks claimed by a group known as Ahlu Sunnah Wa-Jama (or al-Sunnah) that marked the start of a brutal low-intensity conflict, with widespread human rights abuses and attacks on civilians.Up to 1,000 people have now been killed and 100,000 displaced. More recently, The Islamic State Central Africa Province (Iscap), affiliated with the Islamic State group, has claimed responsibility for the attacks. Video and photos of these most recent events, along with the testimony of frightened residents and overstretched government officials, suggest a shift of strategy by the insurgents.There seems to have been an effort to avoid harming civilians, to win hearts and minds by redistributing stolen food, medicine and fuel to “loyal” residents, and to direct attacks on the state and its symbols, such as police stations and military barracks. It is difficult from a distance to assess if there was any genuine pleasure over these attacks among local people; while residents in both towns that did not flee seemed to welcome the attackers, this may well have been out of fear that the government is currently unable to guarantee their security.These attacks also indicate that the jihadist-linked insurgents are growing in confidence. They are confronting government security forces with little appetite for fighting. The Mozambican government has been expecting setbacks like those of Mocimboa and Quissanga — its forces are demoralised and many commanders exhausted or corrupted by an emerging war economy. Jihadists are also taking tactical advantage before a reformed and more effective government counterinsurgency effort is introduced in response.President Filipe Nyusi, inaugurated in January for his second term, has made this crisis his prime focus and has become the de-facto minister of defence.Military reform and the role of private military companiesBut there is no quick fix. Most importantly, the Mozambican military and security forces need to be restructured. They were unable to win the Mozambican civil war (1977-1992), even with international support, and have not improved in capacity or conduct since. They now face a complex, multilayered and asymmetrical conflict, mostly drawing upon local and regional grievances and networks but increasingly also attracting some limited encouragement and advice from further afield.Nyusi will need to build-up trusted relationships in the military in the way he has successfully done with parts of the intelligence community. The Mozambican government has already reached out to international expertise — though not necessarily the right kind. The founder of the Blackwater private military company, Erik Prince, supplied two helicopters and support crew for the Mozambican military in mid-2019, before being replaced by some 170 Russian privateers linked to the Wagner Group.The Wagner contingent arrived in September 2019 at Nacala airport with trucks, drones and a Mi-17 helicopter gunship, then deployed into the combat zone of northern Cabo Delgado. Setbacks, including at least two dead Russians, forced a tactical fallback to Nacala, though a new effort is reported to have been underway since late February 2020.The Mozambican government is also considering a number of proposals from other private military companies. Maputo needs to consider these carefully; Israeli or Gulf State involvement in any form might exasperate rather than alleviate this crisis.The Tanzanian connectionBut market-led security and military providers will not end this insurgency. Nor will the engagement of states such as the United States, France, the United Kingdom or Angola, all of which have made their own offers of support. What would significantly make a difference is much closer to home: serious Tanzanian engagement.This insurgency is concentrated in districts bordering Tanzania and there is clear-cut intelligence of connections into Tanzania and beyond. Swahili is also a lingua franca for the jihadists, connecting them up the East African coast, and into eastern Congo and elsewhere.It is puzzling, given the deep shared history between Tanzania and Mozambique, that the bilateral relationship is as patchy as it is today: during the liberation struggle (1965-1974) against the Portuguese, Mozambique’s ruling party Frelimo maintained rear bases in Tanzania, and Nyusi was educated there.Conspiracy theories circulate that Tanzania has encouraged the Cabo Delgado insurgency to weaken its neighbour, or at least displace radicalised individuals from Tanzanian soil into Mozambique.President John Magafuli of Tanzania did not attend the January inauguration of Nyusi. It has become urgent that Magafuli (who is also the current chair of the regional body, the Southern African Development Community) and Nyusi meet face-to-face to map out improved intelligence sharing and a joint strategy to respond to an emerging regional threat.Southern Africa is locking down because of Covid-19, which will distract the government’s ability to focus fully on this crisis and create a perfect moment for the infant insurgency in Cabo Delgado to grow. More military setbacks should be expected in coming months.But the Mozambican government can still contain and prevail if it seriously reforms its military, builds strong alliances with its regional neighbours (especially Tanzania), chooses its private security contractors and international partnerships wisely, and backs military efforts with better intelligence and developmental interventions that offer alternative pathways to potential recruits.But despite Maputo’s hope that significant progress will be made over the coming year, and the setting up of a presidential task force to evaluate progress and intelligence, it is likely that Mozambique and its partners will need to prepare themselves for a drawn-out struggle.This article originally appeared in the Mail & Guardian Full Article
go Correction: Graph Algorithms for Condensing and Consolidating Gene Set Analysis Results. [Additions and Corrections] By feedproxy.google.com Published On :: 2020-02-01T00:05:30-08:00 Full Article
go AMPK Interactome Reveals New Function in Non-homologous End Joining DNA Repair [Research] By feedproxy.google.com Published On :: 2020-03-01T00:05:26-08:00 Adenosine monophosphate-activated protein kinase (AMPK) is an obligate heterotrimer that consists of a catalytic subunit (α) and two regulatory subunits (β and ). AMPK is a key enzyme in the regulation of cellular energy homeostasis. It has been well studied and is known to function in many cellular pathways. However, the interactome of AMPK has not yet been systematically established, although protein-protein interaction is critically important for protein function and regulation. Here, we used tandem-affinity purification, coupled with mass spectrometry (TAP-MS) analysis, to determine the interactome of AMPK and its functions. We conducted a TAP-MS analysis of all seven AMPK subunits. We identified 138 candidate high-confidence interacting proteins (HCIPs) of AMPK, which allowed us to build an interaction network of AMPK complexes. Five candidate AMPK-binding proteins were experimentally validated, underlining the reliability of our data set. Furthermore, we demonstrated that AMPK acts with a strong AMPK-binding protein, Artemis, in non-homologous end joining. Collectively, our study established the first AMPK interactome and uncovered a new function of AMPK in DNA repair. Full Article
go Repression of sphingosine kinase (SK)-interacting protein (SKIP) in acute myeloid leukemia diminishes SK activity and its re-expression restores SK function [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity. Full Article
go DHS herding people on to an imperfect system in myGov By www.smh.com.au Published On :: Mon, 10 Aug 2015 14:17:52 GMT Over the past few weeks I have been answering calls for the myGov helpdesk. Full Article
go Open government data to public use, and Australia may start to catch up with the world By www.smh.com.au Published On :: Mon, 02 Nov 2015 13:15:00 GMT Public servants need to ditch the control and encourage entrepreneurship. Full Article
go From AFL star to Big Apple start-up, Swift's Joel MacDonald is kicking goals By www.smh.com.au Published On :: Fri, 13 Nov 2015 05:53:09 GMT Two years ago Joel MacDonald was in Melbourne playing in the AFL; now he's kicking goals in New York. Full Article
go Taxpayer records exposed by serious ATO, myGov security flaw By www.smh.com.au Published On :: Wed, 18 Nov 2015 23:42:04 GMT Taxpayer says he was hung up on twice by call centre staff when trying to report the issue. Full Article
go Troubled myGov website to be taken from Human Services and given to Digital Transformation Office for streamlining By www.smh.com.au Published On :: Thu, 28 Jan 2016 12:30:00 GMT Malcolm Turnbull's DTO has been critical of myGov, now it has the chance to show it can do better. Full Article
go ACT government defends seeking access to Canberrans' metadata By www.smh.com.au Published On :: Sun, 31 Jan 2016 13:00:00 GMT The ACT government has defended its right to seek access to Canberrans' private phone and internet records without a warrant. Full Article
go MyGov to feel the audit blowtorch By www.smh.com.au Published On :: Thu, 03 Mar 2016 06:23:08 GMT Human Service to face National Audit Office scrutiny. Again. Full Article
go Government acknowledges poor internet in Canberra's south but sticks to NBN plan By www.smh.com.au Published On :: Sun, 06 Mar 2016 13:00:00 GMT Minister for Communications acknowledges some areas of Canberra's southern suburbs have poor internet access. Full Article
go Recruitment drive for cyber security specialists will bring challenges for government By www.smh.com.au Published On :: Mon, 02 May 2016 19:51:02 GMT Fear government's cyber security recruitment drive will lead to job cuts. Full Article
go Malcolm Turnbull promises $50 million reboot for troubled myGov By www.smh.com.au Published On :: Tue, 21 Jun 2016 22:06:13 GMT Takeover of troubled portal by Digital Transformation Office confirmed Full Article
go Government agencies name cybercrime as their top fraud risk: PwC By www.smh.com.au Published On :: Tue, 26 Jul 2016 14:15:00 GMT The 'typical' corrupt bureaucrat is a male, university-educated middle manager, aged 41 to 50. Full Article
go Governments should hack less, deliver better online services: Harvard IT expert By www.smh.com.au Published On :: Sat, 30 Jul 2016 13:30:00 GMT Western governments have established the international norm of online hacking and should not be surprised when foreign governments do the same. Full Article
go Is the Australian government agile and innovative? Not to those in the start-ups world By www.smh.com.au Published On :: Wed, 02 Nov 2016 04:25:22 GMT Public service departments "too nervous" to innovate, say start-ups. Full Article
go ATO fumes after cyber criminals attack myGov portal during last days of Tax Time 2016 By www.smh.com.au Published On :: Thu, 03 Nov 2016 13:15:00 GMT Tensions emerge between Tax Office and Human Services after hackers take down myGov Full Article
go Digital government could become just more cost cutting, warns Internet Australia By www.smh.com.au Published On :: Sun, 04 Dec 2016 13:00:00 GMT Revolving door at digital agency must stop, says Labor. Full Article
go Can the government really protect your privacy when it 'de-identifies' public data? By www.smh.com.au Published On :: Mon, 05 Dec 2016 12:45:00 GMT We don't really know to how to use big data and protect personal information at the same time. Full Article
go Centrelink debt debacle shows government is unprepared for digital revolution By www.smh.com.au Published On :: Mon, 06 Feb 2017 13:15:00 GMT The public service needs to embrace partnerships if it's to harvest big data's massive yields. Full Article
go Auditor-general exposes weaknesses in ACT government's IT systems By www.smh.com.au Published On :: Mon, 08 May 2017 02:35:19 GMT Electronic sexual health records and the births, deaths and marriages registry have been left exposed. Full Article
go How federal government departments are protecting Australians' data against cyber hack By www.smh.com.au Published On :: Mon, 15 May 2017 10:09:02 GMT Cyber Security Minister Dan Tehan says the government can't rule out vulnerabilities to cyber threats. Full Article