hi Diagnosis of Hyper-progressive Disease in Patients Treated with Checkpoint Inhibitors using 18F-FDG PET/CT By jnm.snmjournals.org Published On :: 2020-02-21T14:46:23-08:00 Full Article
hi High Resolution Depth-Encoding PET Detector Module with Prismatoid Light Guide Array By jnm.snmjournals.org Published On :: 2020-02-28T13:52:17-08:00 Depth-encoding detectors with single-ended readout provide a practical, cost-effective approach for constructing high resolution and high sensitivity PET scanners. However, the current iteration of such detectors utilizes a uniform glass light guide to achieve depth-encoding, resulting in non-uniform performance throughout the detector array due to suboptimal intercrystal light sharing. We introduce Prism-PET, a single-ended readout PET detector module with a segmented light guide composed of an array of prismatoids that introduces enhanced, deterministic light sharing. Methods: High resolution PET detector modules were fabricated with single-ended readout of polished multicrystal lutetium yttrium orthosilicate (LYSO) scintillator arrays directly coupled 4-to-1 and 9-to-1 to arrays of 3.2 x 3.2 mm2 silicon photomultiplier pixels. Each scintillator array was coupled at the non-readout side to a light guide (one 4-to-1 module with a uniform glass light guide, one 4-to-1 Prism-PET module and one 9-to-1 Prism-PET module) to introduce intercrystal light sharing, which closely mimics the behavior of dual-ended readout with the additional benefit of improved crystal identification. Flood histogram data was acquired using a 3 MBq Na-22 source to characterize crystal identification and energy resolution. Lead collimation was used to acquire data at specific depths to determine depth-of-interaction (DOI) resolution. Results: The flood histogram measurements showed excellent and uniform crystal separation throughout the Prism-PET modules while the uniform glass light guide module had performance degradation at the edges and corners. A DOI resolution of 5.0 mm full width at half maximum (FWHM) and energy resolution of 13% were obtained in the uniform glass light guide module. By comparison, the 4-to-1 coupled Prism-PET module achieved 2.5 mm FWHM DOI resolution and 9% energy resolution. Conclusion: PET scanners based on our Prism-PET modules with segmented prismatoid light guide arrays can achieve high and uniform spatial resolution (9-to-1 coupling with ~ 1 mm crystals), high sensitivity, good energy and timing resolutions (using polished crystals and after applying DOI-correction), and compact size (depth-encoding eliminates parallax error and permits smaller ring-diameter). Full Article
hi 3D-Printable Platform for High-Throughput Small-Animal Imaging By jnm.snmjournals.org Published On :: 2020-04-13T14:09:24-07:00 Full Article
hi Letter to the Editor: Who was the first doctor to report the Covid-19 outbreak in Wuhan, China? By jnm.snmjournals.org Published On :: 2020-04-17T08:32:41-07:00 Full Article
hi Targeting Fibroblast Activation Protein:Radiosynthesis and Preclinical Evaluation of an 18F-labeled FAP Inhibitor By jnm.snmjournals.org Published On :: 2020-04-24T14:33:41-07:00 Fibroblast activation protein (FAP) has emerged as an interesting molecular target used in the imaging and therapy of various types of cancers. Gallium-68–labeled chelator-linked FAP inhibitors (FAPIs) have been successfully applied to positron emission tomography (PET) imaging of various tumor types. To broaden the spectrum of applicable PET tracers for extended imaging studies of FAP-dependent diseases, we herein report the radiosynthesis and preclinical evaluation of an 18F–labeled glycosylated FAP inhibitor ([18F]FGlc-FAPI). Methods: An alkyne-bearing precursor was synthesized and subjected to click chemistry–based radiosynthesis of [18F]FGlc-FAPI by two-step 18F-fluoroglycosylation. FAP-expressing HT1080hFAP cells were used to study competitive binding to FAP, cellular uptake, internalization, and efflux of [18F]FGlc-FAPI in vitro. Biodistribution studies and in vivo small animal PET studies of [18F]FGlc-FAPI compared to [68Ga]Ga-FAPI-04 were conducted in nude mice bearing HT1080hFAP tumors or U87MG xenografts. Results: [18F]FGlc-FAPI was synthesized with a 15% radioactivity yield and a high radiochemical purity of >99%. In HT1080hFAP cells, [18F]FGlc-FAPI showed specific uptake, a high internalized fraction, and low cellular efflux. Compared to FAPI-04 (IC50 = 32 nM), the glycoconjugate, FGlc-FAPI (IC50 = 167 nM), showed slightly lower affinity for FAP in vitro, while plasma protein binding was higher for [18F]FGlc-FAPI. Biodistribution studies revealed significant hepatobiliary excretion of [18F]FGlc-FAPI; however, small animal PET studies in HT1080hFAP xenografts showed higher specific tumor uptake of [18F]FGlc-FAPI (4.5 % injected dose per gram of tissue [ID/g]) compared to [68Ga]Ga-FAPI-04 (2 %ID/g). In U87MG tumor–bearing mice, both tracers showed similar tumor uptake, but [18F]FGlc-FAPI showed a higher tumor retention. Interestingly, [18F]FGlc-FAPI demonstrated high specific uptake in bone structures and joints. Conclusion: [18F]FGlc-FAPI is an interesting candidate for translation to the clinic, taking advantage of the longer half-life and physical imaging properties of F-18. The availability of [18F]FGlc-FAPI may allow extended PET studies of FAP-related diseases, such as cancer, but also arthritis, heart diseases, or pulmonary fibrosis. Full Article
hi Amyloid PET in Dementia Syndromes: A Chinese Multicenter Study By jnm.snmjournals.org Published On :: 2020-05-08T13:18:58-07:00 Cerebral β-amyloid deposits and regional glucose metabolism assessed by positron emission tomography (PET) are used to distinguish between Alzheimer's disease (AD) and other dementia syndromes. In the present multicenter study, we estimated the prevalence of β-amyloid deposits on PET imaging in a wide variety of dementia syndromes and mild cognitive impairment (MCI) within a memory clinic population. Methods: Of the 1193 consecutive patients with cognitive impairment (CI) who received combined 18F-AV45 and/or 11C-PIB PET, 960 were diagnosed with AD, 36 with frontotemporal dementia (FTD), 5 with dementia with Lewy bodies (DLB), 144 with MCI, 29with vascular dementia (VaD), 4 with corticobasal syndrome (CBS) and 15 with unclassifiable dementia. Baseline clinical diagnoses were independently established without access to PET imaging results. ApoE genotype analysis was performed in CI patients and 231 gender- and age-matched controls. Results: Of the 1193 CI patients, 860 (72.1%) were amyloid-positive. The prevalence of amyloid positivity in AD and MCI patients was 86.8% (833/960) and 9.7% (14/144), respectively. In FTD patients, the prevalence of β-amyloid deposits was 5.6% (2/36). In the 4 CBS patients, two were amyloid-positive. Three of the 5 DLB patients showed amyloid positivity, as did 6 of the 29 VaD (20.7%) patients. The ApoE4 allele frequency was significantly increased in amyloid-positive CI patients (30.5%) as compared with other amyloid-negative CI patients (14%) or controls (7.3%). Conclusion: Amyloid imaging may potentially be the most helpful parameter for differential diagnosis in dementia, particularly to distinguish between AD and FTD. Amyloid PET can be used in conjunction with the ApoE4 allele genetic risk test for amyloid deposits. Full Article
hi Central and Eastern Europe and Sub-Saharan Africa: The Potential of Investment Partnerships for Mutual Benefit By feedproxy.google.com Published On :: Thu, 31 Oct 2019 08:54:39 +0000 31 October 2019 Trade between Central and Eastern Europe and sub-Saharan Africa has increased significantly in the last decade and a half. There is a strong case to be made for greater economic re-engagement, especially in terms of investment, that has the potential to support inclusive growth in both regions. Read online Download PDF Damir Kurtagic Former Academy Robert Bosch Fellow, Africa Programme @kurtagic_damir LinkedIn recycled-containerboard-warehouse_mondi_poland.jpg Recycled containerboard warehouse, Mondi Group, Poland. Photo: Mondi Group. SummaryThere are growing economic links between the economies of Central and Eastern Europe and sub-Saharan Africa in terms of both trade and investment. However, while trade has picked up significantly from pre-EU accession levels, investment has not increased to the same extent.Contrary to common assumption, investment flows are not solely from Central and Eastern Europe to sub-Saharan Africa. In reality, the largest investment flow between the two blocs occurs in the opposite direction – from South Africa into Central and Eastern Europe.Sub-Saharan Africa can benefit from a greater commercial relationship focused on attracting sustainable investment from Central and Eastern Europe. For this to happen, commercial strategies towards Central and Eastern European countries need to be put in place before strategy can be reinforced by greater diplomatic and informational support.For many sub-Saharan African governments, there is no overall targeted approach to attracting Central and Eastern European investors. A notable exception is South Africa, where departments have been established at provincial government level to specifically target investment from Central and Eastern Europe.Sub-Saharan African governments expect Central and Eastern European private-sector investment to result not only in job creation, but also to bring spillover benefits such as the transfer of skills and knowledge to domestic industries.Each sub-Saharan African country, in accordance with its individual circumstances, will need to adopt a discrete mix of administrative reform (particularly aimed at cutting red tape), as well as infrastructural and other policies that improve the business environment and generate investor confidence.Much of the private sector in Central and Eastern Europe is somewhat hesitant to invest in sub-Saharan Africa on a greater scale. Many companies are most comfortable operating within their domestic environment; when they invest abroad, it tends to be in the ‘neighbourhood’ with which they are already familiar. Perceptions of risk are often compounded by popular misperceptions and generalizations about sub-Saharan Africa.Central and Eastern European countries stand to gain from a deeper investment relationship. While greater engagement with sub-Saharan Africa has already been pursued by some countries, most of them focus on trade. Institutional support to companies from Central and Eastern Europe (both public and private) has evolved to a degree, but is still not comprehensive. Information for companies interested in investing is either lacking or not shared in an efficient way. And the greatest challenge is ensuring top-level political engagement.EU membership offers clear opportunities for Central and Eastern European countries to invest sustainably and responsibly in sub-Saharan Africa. Not only is financial support forthcoming, through innovative EU financial instruments, but the availability of information relevant to business and the EU’s extensive diplomatic presence in Africa should help to alleviate some of the concerns of Central and Eastern European investors. Department/project Africa Programme, Foreign Relations and Africa’s Agency in the International System, Inclusive Economic Growth, Governance and Technology Full Article
hi China's ivory bans: enhancing soft power through wildlife conservation By feedproxy.google.com Published On :: Wed, 06 Nov 2019 09:20:21 +0000 6 November 2019 , Volume 95, Number 6 Jonas Gamso Read online China has been a major market for elephant ivory for centuries. However, the Chinese government recently enacted bans on imports and exports of ivory (2015) and on the domestic ivory trade (2017). These bans appear to have come in response to intensive influence campaigns and public shaming from domestic and foreign activists, who cited declining elephant populations and highlighted China's role. However, this shaming-narrative is at odds with conventional wisdom regarding Chinese policy-making: China typically resists international pressures and its authoritarian government is thought to be largely insulated from domestic efforts by civil society groups. This article reconciles Beijing's ivory policy with these conventional beliefs about policy-making in China. I argue that the Chinese government saw unique benefits to banning the ivory trade, under growing international scrutiny, as doing so enhanced Chinese soft power while having very little impact on its sovereignty or development. Non-government organizations (NGOs) operating both inside and outside of China played a role as well: NGOs in China helped to shift Chinese public opinion towards favouring the bans, while those operating abroad led public relations efforts to publicize Chinese demand for ivory to foreign audiences. Efforts by the latter group of NGOs intensified pressure on the Chinese government to rein in the ivory market, while increasing the soft power benefits that banning ivory would bring to Beijing. Full Article
hi POSTPONED: Africa, Japan and the UK: Emerging Partnerships Beyond Summits By feedproxy.google.com Published On :: Fri, 21 Feb 2020 13:00:02 +0000 Research Event 17 March 2020 - 9:30am to 1:15pm Chatham House | 10 St James's Square | London | SW1Y 4LE Agendapdf | 133.11 KB Event participants HE Nabil Ben Khedher, Ambassador of Tunisia to the United KingdomProfessor Naohiro Kitano, Visiting Fellow, Japan International Cooperation Agency Research Institute (JICA-RI); Professor, Waseda UniversityTaku Miyazaki, Deputy Director General, Japan External Trade Organisation (JETRO) LondonSerge Mouangue, Founder and Art Director, WAfricaNorio Suzuki, Senior Strategist, BBOXXHE Professor Mohammed Gana Yisa, Ambassador of the Federal Republic of Nigeria to Japan; Chairman, African Diplomatic Corps in Tokyo (ADC) TICAD CommitteeChairs:Dr Champa Patel, Director, Asia-Pacific Programme, Chatham HouseDr Alex Vines OBE, Managing Director, Ethics, Risk & Resilience; Director, Africa Programme Since Japan established its Tokyo International Conference on African Development (TICAD) in 1993, an increasing number of summits for African engagement have appeared across the Asia-Pacific region. TICAD VII, held on 28-30 August 2019 in Yokohama, sought to strengthen partnerships between Japan and Africa in three main areas: technical cooperation; business and women’s entrepreneurship; and next generation and people-to-people connectivity.The UK-Africa Investment Summit held in January 2020 highlighted similar themes, with an emphasis on investing to generate sustainable growth and create jobs. Common interests and goals among different African countries, Japan and the UK bring opportunities for trilateral cooperation.This event will examine how collaboration between African countries, Japan and the UK can help to more effectively achieve sustainable growth, business development and job creation.PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Department/project Africa Programme, Foreign Relations and Africa’s Agency in the International System, Inclusive Economic Growth, Governance and Technology Hanna Desta Programme Assistant, Africa Programme Email Full Article
hi Children 'born of war': a role for fathers? By feedproxy.google.com Published On :: Wed, 04 Mar 2020 13:28:47 +0000 4 March 2020 , Volume 96, Number 2 Camile Oliviera, Erin Baines Read Online In this article, we examine exceptional circumstances in which men who father children born as the result of conflict-related sexual violence assume full or partial responsibility for their child's well-being. Children ‘born of war’ are increasingly recognized as a particular victim group in relevant international policy frameworks. Their social status falls somewhere between the victimization of their mother and perpetration of their father. Given the circumstances of their birth, they often experience social rejection and loss of identity with a long-term impact on their well-being. Previous scholarship has primarily documented the challenges faced by their mothers as caregivers and as victims of wartime sexual violence. A discussion on fathers to children ‘born of war’ is absent, attributable not only to their perpetrator status, but also to the assumption that their identity is unknown or that a relationship between father and child is undesired. The article demonstrates this is not always the case. Based on research in northern Uganda between 2016 and 2019 which included interviews and focus group discussions with former male combatants in the rebel group the Lord's Resistance Army, we explore how some fathers seek to maintain a relationship with children born as the result of ‘forced marriage’ and assume partial or full responsibility for their well-being and care. Full Article
hi How images frame China's role in African development By feedproxy.google.com Published On :: Thu, 07 May 2020 09:21:23 +0000 7 May 2020 , Volume 96, Number 3 George Karavas Read online Political leaders, policy-makers and academics routinely refer to development as an objective process of social change through the use of technical, value-free terms. Images of poverty and inequality are regularly presented as evidence of a world that exists ‘out there’ where development unfolds. This way of seeing reflects the value of scientific forms of knowledge but also sits in tension with the normative foundations of development that take European modernization and industrialization as the benchmark for comparison. The role images play in this process is often overlooked. This article argues that a dominant mode of visuality based on a Cartesian separation between subject and object, underpinning the ascendance of European hegemony and colonialism, aligns with the core premises of orthodox development discourse. An example of how visual representations of development matter is presented through images of Africa–China relations in western media sources. Using widely circulated images depicting China's impact on African development in western news media sources as an example of why visual politics matters for policy-making, the article examines how images play a role in legitimizing development planning by rendering associated forms of epistemological and structural violence ‘invisible to the viewer’. Full Article
hi COVID-19 in South Africa: Leadership, Resilience and Inequality By feedproxy.google.com Published On :: Thu, 07 May 2020 14:50:58 +0000 7 May 2020 Christopher Vandome Research Fellow, Africa Programme LinkedIn In a world looking for leadership, South Africa’s president Cyril Ramaphosa has been remarkable. One year after he carried the time-worn ANC through a national election, South Africans are crying out for more. 2020-05-07-Ramaphosa-COVID-South-Africa Cyril Ramaphosa at NASREC Expo Centre in Johannesburg where facilities are in place to treat coronavirus patients. Photo by JEROME DELAY/POOL/AFP via Getty Images. In the COVID-19 crisis so far, Cyril Ramaphosa has been widely praised for displaying the decisive leadership so many hoped for when they cast their ballot for him in May 2019. Buttressed by others such as health minister Dr Zweli Mkhize, and on a simple objective to prevent transmission, South Africa has been a lesson to the world. Act fast. Act hard.Former president Thabo Mbeki’s disastrous response to the HIV crisis cast a long shadow over his legacy, and Ramaphosa has taken note. South Africa has had one of the tightest lockdowns in the world. No exercise. No cigarettes. No alcohol.The lockdown was imposed when the country had only around 1,000 recorded cases and just two deaths. As a result, transmission from returning travellers has not yet led to an exponential infection rate within the community. The government’s swift reaction has bought much needed time with the peak now seemingly delayed to September or October.Continental and national leadershipRamaphosa has also emerged as a key focal point for Africa-wide responses. As current chair of the African Union (AU) he leads the continental engagement with the World Health Organization (WHO), and the various international finance institutions, while South African officials are working with the AU and the United Nations Economic Commission for Africa (UNECA) on a push for African debt restructuring.He has also been active in trouble shooting to unlock external assistance to the continent, including from China and Russia. Appointing special envoys is typical of his boardroom-honed leadership style.International and regional partnerships are vital for resilience and the arrival of 217 Cuban doctors to South Africa is strongly reminiscent of the liberationist solidarity of the Cold War era. And regional economies remain dependent on South Africa to protect their own vulnerable citizens. Following the 2008 financial crisis, it was South Africa’s regional trading relationships that remained robust, while trade with its main global partners in China and the US dropped.Despite the plaudits, Ramaphosa remains vulnerable to challenge at home, notably around his failure to stimulate South Africa’s moribund economy. On the eve of lockdown, Moody’s joined its peers Standard and Poor’s and Fitch in giving South Africa a below investment grade credit rating. The move was a long time coming. Long mooted economic reforms were slow to materialise, and South Africa had fallen into recession.Ramaphosa depends on a small core of close advisors and allies, initially united in apparent opposition to the kleptocratic rule of President Jacob Zuma and the deep patronage networks he created within both the party and the state. But this allegiance is being tested by economic reality. Support within the party was already drifting prior to the crisis.Disagreements are not just technocratic – there are big ideological questions in play around the role of the state in the economy, the level of intervention, and its affordability, with key government figures sceptical of rapid market reforms. Energy minister and former union stalwart Gwede Mantashe is wary of job losses, and minister of public enterprises Pravin Gordhan protective of state-owned enterprises (SOEs). Before coronavirus hit, Ramaphosa seemed content to allow these policy disputes to play themselves out with little decisive intervention.Slow progress on reform, against worsening economic performance, left Ramaphosa and his allies exposed. In January the president missed the UK’s African Investment Summit in order to assert control over a party meeting at which it was expected his detractors would seek to remove Gordhan.COVID-19 has sharpened thinkingAs the independently assertive - and eminently quotable - pro-market reformist finance minister Tito Mboweni stated, ‘you can’t eat ideology’. Accelerated reform and restructuring is required if the government turns to the International Monetary Fund (IMF) for assistance.For the first time, Gordhan has been forced to deny a bailout to beleaguered state airline South African Airways (SAA), and the government’s lockdown bailout of R300 billion has been applauded by business. Much like the fiscal stimulus and recovery plan of 2018, it relies on smart spending, targeting sectors with high multiplier effects. It also includes significant reserve bank loans.But it has been criticised for not doing enough to help the most vulnerable. There is considerable fear of what could happen when the virus takes hold in South Africa’s townships and informal settlements where social distancing is almost impossible, basic toilet facilities are shared, and HIV and TB rates high.There are mounting concerns of the humanitarian cost of a prolonged lockdown, and the government has been faster than others in implementing a tiered lockdown system, trying to get people back to work and keep the economy afloat.South Africa has been criticized by the UN for the use of lethal force by security forces in enforcing lockdown and, in a society plagued by corruption, there are fears legislation to stop the spread of false information could be used to restrict legitimate reporting on the virus response or other issues.COVID-19 shines a spotlight on societies’ fault-lines worldwide. South Africa is often touted as having one of the highest levels of inequality in the world but, in a globalized economy, these divisions are international as much as they are local.Resilience comes from within, but also depends on regional and global trading and financial systems. South Africans and international partners have long recognised Ramaphosa’s leadership qualities as an impressive voice for the global south.But he must also be an advocate for South Africa’s poor. This crisis could accelerate implementation of his landmark pro-poor National Health Insurance and Universal Health Care programmes. Or the hit of COVID-19 on top of South Africa’s existing economic woes could see them derailed entirely. Ramaphosa must push through economic reforms at the same time as managing COVID-19 and rebuilding trust in his government. Full Article
hi Combined EGFR and ROCK Inhibition in Triple-negative Breast Cancer Leads to Cell Death Via Impaired Autophagic Flux [Research] By feedproxy.google.com Published On :: 2020-02-01T00:05:30-08:00 Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with very limited therapeutic options. We have recently shown that the combined inhibition of EGFR and ROCK in TNBC cells results in cell death, however, the underlying mechanisms remain unclear. To investigate this, here we applied a mass spectrometry-based proteomic approach to identify proteins altered on single and combination treatments. Our proteomic data revealed autophagy as the major molecular mechanism implicated in the cells' response to combinatorial treatment. We here show that EGFR inhibition by gefitinib treatment alone induces autophagy, a cellular recycling process that acts as a cytoprotective response for TNBC cells. However, combined inhibition of EGFR and ROCK leads to autophagy blockade and accumulation of autophagic vacuoles. Our data show impaired autophagosome clearance as a likely cause of antitumor activity. We propose that the inhibition of the autophagic flux on combinatorial treatment is attributed to the major cytoskeletal changes induced on ROCK inhibition, given the essential role the cytoskeleton plays throughout the various steps of the autophagy process. Full Article
hi 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
hi MaXLinker: Proteome-wide Cross-link Identifications with High Specificity and Sensitivity [Technological Innovation and Resources] By feedproxy.google.com Published On :: 2020-03-01T00:05:26-08:00 Protein-protein interactions play a vital role in nearly all cellular functions. Hence, understanding their interaction patterns and three-dimensional structural conformations can provide crucial insights about various biological processes and underlying molecular mechanisms for many disease phenotypes. Cross-linking mass spectrometry (XL-MS) has the unique capability to detect protein-protein interactions at a large scale along with spatial constraints between interaction partners. The inception of MS-cleavable cross-linkers enabled the MS2-MS3 XL-MS acquisition strategy that provides cross-link information from both MS2 and MS3 level. However, the current cross-link search algorithm available for MS2-MS3 strategy follows a "MS2-centric" approach and suffers from a high rate of mis-identified cross-links. We demonstrate the problem using two new quality assessment metrics ["fraction of mis-identifications" (FMI) and "fraction of interprotein cross-links from known interactions" (FKI)]. We then address this problem, by designing a novel "MS3-centric" approach for cross-link identification and implementing it as a search engine named MaXLinker. MaXLinker outperforms the currently popular search engine with a lower mis-identification rate, and higher sensitivity and specificity. Moreover, we performed human proteome-wide cross-linking mass spectrometry using K562 cells. Employing MaXLinker, we identified a comprehensive set of 9319 unique cross-links at 1% false discovery rate, comprising 8051 intraprotein and 1268 interprotein cross-links. Finally, we experimentally validated the quality of a large number of novel interactions identified in our study, providing a conclusive evidence for MaXLinker's robust performance. Full Article
hi Guidance Document: Validation of a High-Performance Liquid Chromatography-Tandem Mass Spectrometry Immunopeptidomics Assay for the Identification of HLA Class I Ligands Suitable for Pharmaceutical Therapies [Commentary] By feedproxy.google.com Published On :: 2020-03-01T00:05:26-08:00 For more than two decades naturally presented, human leukocyte antigen (HLA)-restricted peptides (immunopeptidome) have been eluted and sequenced using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Since, identified disease-associated HLA ligands have been characterized and evaluated as potential active substances. Treatments based on HLA-presented peptides have shown promising results in clinical application as personalized T cell-based immunotherapy. Peptide vaccination cocktails are produced as investigational medicinal products under GMP conditions. To support clinical trials based on HLA-presented tumor-associated antigens, in this study the sensitive LC-MS/MS HLA class I antigen identification pipeline was fully validated for our technical equipment according to the current US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. The immunopeptidomes of JY cells with or without spiked-in, isotope labeled peptides, of peripheral blood mononuclear cells of healthy volunteers as well as a chronic lymphocytic leukemia and a bladder cancer sample were reliably identified using a data-dependent acquisition method. As the LC-MS/MS pipeline is used for identification purposes, the validation parameters include accuracy, precision, specificity, limit of detection and robustness. Full Article
hi Large-scale Identification of N-linked Intact Glycopeptides in Human Serum using HILIC Enrichment and Spectral Library Search [Research] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 Large-scale identification of N-linked intact glycopeptides by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in human serum is challenging because of the wide dynamic range of serum protein abundances, the lack of a complete serum N-glycan database and the existence of proteoforms. In this regard, a spectral library search method was presented for the identification of N-linked intact glycopeptides from N-linked glycoproteins in human serum with target-decoy and motif-specific false discovery rate (FDR) control. Serum proteins were firstly separated into low-abundance and high-abundance proteins by acetonitrile (ACN) precipitation. After digestion, the N-linked intact glycopeptides were enriched by hydrophilic interaction liquid chromatography (HILIC) and a portion of the enriched N-linked intact glycopeptides were processed by Peptide-N-Glycosidase F (PNGase F) to generate N-linked deglycopeptides. Both N-linked intact glycopeptides and deglycopeptides were analyzed by LC-MS/MS. From N-linked deglycopeptides data sets, 764 N-linked glycoproteins, 1699 N-linked glycosites and 3328 unique N-linked deglycopeptides were identified. Four types of N-linked glycosylation motifs (NXS/T/C/V, X=P) were used to recognize the N-linked deglycopeptides. The spectra of these N-linked deglycopeptides were utilized for N-linked deglycopeptides library construction and identification of N-linked intact glycopeptides. A database containing 739 N-glycan masses was constructed and utilized during spectral library search for the identification of N-linked intact glycopeptides. In total, 526 N-linked glycoproteins, 1036 N-linked glycosites, 22,677 N-linked intact glycopeptides and 738 N-glycan masses were identified under 1% FDR, representing the most in-depth serum N-glycoproteome identified by LC-MS/MS at N-linked intact glycopeptide level. Full Article
hi Correction: Diversity in the Protein N-Glycosylation Pathways Within the Campylobacter Genus. [Additions and Corrections] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Full Article
hi Discovery of a Redox Thiol Switch: Implications for Cellular Energy Metabolism [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 The redox-based modifications of cysteine residues in proteins regulate their function in many biological processes. The gas molecule H2S has been shown to persulfidate redox sensitive cysteine residues resulting in an H2S-modified proteome known as the sulfhydrome. Tandem Mass Tags (TMT) multiplexing strategies for large-scale proteomic analyses have become increasingly prevalent in detecting cysteine modifications. Here we developed a TMT-based proteomics approach for selectively trapping and tagging cysteine persulfides in the cellular proteomes. We revealed the natural protein sulfhydrome of two human cell lines, and identified insulin as a novel substrate in pancreatic beta cells. Moreover, we showed that under oxidative stress conditions, increased H2S can target enzymes involved in energy metabolism by switching specific cysteine modifications to persulfides. Specifically, we discovered a Redox Thiol Switch, from protein S-glutathioinylation to S-persulfidation (RTSGS). We propose that the RTSGS from S-glutathioinylation to S-persulfidation is a potential mechanism to fine tune cellular energy metabolism in response to different levels of oxidative stress. Full Article
hi 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
hi 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
hi Inhibition of the polyamine synthesis enzyme ornithine decarboxylase sensitizes triple-negative breast cancer cells to cytotoxic chemotherapy [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Treatment of patients with triple-negative breast cancer (TNBC) is limited by a lack of effective molecular therapies targeting this disease. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. Using MDA-MB-468 and SUM-159PT TNBC cells, along with LC-MS/MS and HPLC metabolomics profiling, we found here that exposure of TNBC cells to the cytotoxic chemotherapy drugs cisplatin and doxorubicin alter arginine and polyamine metabolites. This alteration was because of a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). Using gene silencing and inhibitor treatments, we determined that the reduction in ODC was mediated by its negative regulator antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. The alterations in polyamine metabolism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to chemotherapy, reported here suggest that ODC may be a targetable metabolic vulnerability in TNBC. Full Article
hi Malcolm Turnbull visits Sunshine Coast to view proposal for new undersea communications cable By www.smh.com.au Published On :: Thu, 03 Sep 2015 11:59:04 GMT A plan to make the Sunshine Coast a vital internet gateway is luring Communications Minister Malcolm Turnbull to the area on Friday to view the proposal in person. Full Article
hi Digital Transformation Office chief executive Paul Shetler announces public service work schedule By www.smh.com.au Published On :: Wed, 14 Oct 2015 05:50:39 GMT Paul Shetler reveals the digital projects about to hit the federal bureaucracy. Starting with Canberra. Full Article
hi Cyber thieves target tax time By www.smh.com.au Published On :: Tue, 27 Oct 2015 07:15:12 GMT Tens of thousands of taxpayers forced to wait for refunds amid suspicion of identity theft. Full Article
hi Australian companies targeted by identity thieves for tax frauds By www.smh.com.au Published On :: Tue, 10 Nov 2015 02:08:52 GMT Australian companies are having their identities hijacked by international criminals who use them to try to defraud the Australian Taxation Office. Full Article
hi Anonymous group hacks Islamic State, tells them to chill out: reports By www.smh.com.au Published On :: Fri, 27 Nov 2015 00:42:23 GMT Terrorists' propaganda appears to be shifting to the Dark Web so that it will be harder to shut down. Full Article
hi Centrelink's IT meltdown hits the disability pension By www.smh.com.au Published On :: Mon, 21 Dec 2015 21:45:06 GMT Centrelink's tech woes disrupts Disability Pension medical crackdown. Full Article
hi Centrelink wrongly hits 70,000 families with bills for up to $726 By www.smh.com.au Published On :: Thu, 07 Jan 2016 07:49:06 GMT Computer glitch blamed as welfare agency hits tens of thousands with bills for money that is not owed. Full Article
hi Branching out after death: where next for the 'Internet of Things'? By www.smh.com.au Published On :: Wed, 30 Mar 2016 07:53:02 GMT It turns out that even death needs the internet. Full Article
hi Digital public service means ditching control and embracing 'we' By www.smh.com.au Published On :: Mon, 01 Aug 2016 13:45:00 GMT Collaborating with the public is the key for a more engaging government experience. Full Article
hi $212,000 per public service IT contractor, and we're hiring more of them By www.smh.com.au Published On :: Tue, 20 Dec 2016 08:47:58 GMT Contractors cost 80 grand more than public servants, Finance Departments says, and the public service hires more of them. Full Article
hi Latest ATO online system failure hits at peak tax time By www.smh.com.au Published On :: Wed, 05 Jul 2017 10:54:02 GMT Outages have hit the Tax Office's IT system on Wednesday. Full Article
hi Yojiro Uchino By feedproxy.google.com Published On :: Fri, 02 Aug 2019 09:37:37 +0000 Visiting Fellow, Global Economy and Finance Programme Biography Yojiro Uchino was director of the defence budget at the Ministry of Finance in Japan from 2016 to 2019, working on budgets for the country's National Defense Program Guidelines and also its Mid-Term Defense Program.During his fellowship, Yojiro will be undertaking research on the relationship between national security and fiscal positions, as well as the balance between free trade and national security.Yojiro Uchino is based at Chatham House until July 2021, hosted by the Global Economy and Finance programme. Areas of expertise Budget structure of the Japanese governmentDefence budget of JapanJapanese defence policy Past experience 2015-16 Director, Allowance Control and Mutual Assistance Insurance Division2014-15 Director, Inter-Division Affairs of Budget2012-14 Director, Government Shareholding Office (where he planned simultaneous IPO of Japan Post, the holding company, and its subsidiaries Japan Post Bank and Japan Post Insurance)1997Admitted to the Bar in New York State Supreme Court1996LLM, University of Michigan Law School1992BA Law, University of Tokyo +44 (0)20 7314 2776 Email Full Article
hi Why China Should Be Wary of Devaluing the Renminbi By feedproxy.google.com Published On :: Thu, 29 Aug 2019 15:53:29 +0000 29 August 2019 David Lubin Associate Fellow, Global Economy and Finance Programme @davidlubin There are four good reasons why Beijing might want to think twice before using its currency to retaliate against US tariffs. 2019-08-29-Renminbi.jpg RMB banknotes. Photo: Getty Images The renminbi seems to be back in business as a Chinese tool of retaliation against US tariffs. A 1.5 per cent fall in the currency early this month in response to proposed new US tariffs was only a start. Since the middle of August the renminbi has weakened further, and the exchange rate is now 4 per cent weaker than at the start of the month. We may well see more of a ‘weaponized’ renminbi, but there are four good reasons why Beijing might be wise to think before shooting.The first has to do with how China seeks to promote its place in the world. China has been at pains to manage the collapse of its relations with the US in a way that allows it to present itself as an alternative pillar of global order, and as a source of stability in the international system, not to mention moral authority. This has deep roots.Anyone investigating the history of Chinese statecraft will quickly come across an enduring distinction in Chinese thought: between wang dao, the kingly, or righteous way, and ba dao, the way of the hegemon. Since Chinese thinkers and officials routinely describe US behaviour since the Second World War as hegemonic, it behoves Chinese policymakers to do as much as possible to stay on moral high-ground in their behaviour towards Washington. Only in that way would President Xi be able properly to assert China’s claim to leadership.Indeed, China has a notable track record of using exchange rate stability to enhance its reputation as a force for global stability. Both in the aftermath of the Asian crisis in 1997, and of the Global Financial Crisis in 2008, Chinese exchange rate stability was offered as a way of demonstrating China’s trustworthiness and its commitment to multilateral order.Devaluing the renminbi in a meaningful way now might have a different rationale, but the cost to China’s claim to virtue, and its bid to offer itself as a guardian of global stability, might be considerable.That’s particularly true because of the second problem China has in thinking about a weaker renminbi: it may not be all that effective in sustaining Chinese trade. One reason for this is the increasing co-movement with the renminbi of currencies in countries with whom China competes.As the renminbi changes against the dollar, so do the Taiwan dollar, the Korean won, the Singapore dollar and the Indian rupee. In addition, the short-run impact of a weaker renminbi is more likely to curb imports than to expand exports, and so its effects might be contractionary. An ineffective devaluation of the renminbi would be particularly useless because of the third risk China needs to consider, namely the risk of retaliation by the US administration. Of this there is already plenty of evidence, of course.The US Treasury’s declaration of China as a ‘currency manipulator’ on 5 August bears little relationship to the actual formal criteria that the Treasury uses to define that term, but equally the US had warned the Chinese back in May that these criteria don’t bind its hand. By abandoning a rules-based approach to the definition of currency manipulation, the US has opened wide the door to further antagonism, and Beijing should have no doubt that Washington will walk through that door if it wants to.The fourth, and possibly most self-destructive, risk that China has to consider is that a weaker renminbi might destabilize China’s capital account, fuelling capital outflows that would leave China’s policymakers feeling very uncomfortable.Indeed, there is already evidence that Chinese residents feel less confident that the renminbi is a reliable store of value, now that there is no longer a sense that the currency is destined to appreciate against the dollar. The best illustration of this comes from the ‘errors and omissions’, or unaccounted-for outflows, in China’s balance of payments.The past few years have seen these outflows rise a lot, averaging some $200 billion per year during the past four calendar years, or almost 2 per cent GDP; and around $90 billion in the first three months of 2019 alone. These are scarily large numbers.The risk here is that Chinese expectations about the renminbi are ‘adaptive’: the more the exchange rate weakens, the more Chinese residents expect it to weaken, and so the demand for dollars goes up. In principle, the only way to deal with this risk would be for the People's Bank of China (PBOC) to implement a large, one-off devaluation of the renminbi to a level at which dollars are expensive enough that no one wants to buy them anymore.This would be very dangerous, though: it presupposes that the PBOC could know in advance the ‘equilibrium’ value of the renminbi. It would take an unusually brave central banker to claim such foresight, especially since that equilibrium value could itself be altered by the mere fact of such a dramatic change in policy.No one really knows precisely by what mechanism capital outflows from China have accelerated in recent years, but a very good candidate is tourism. The expenditure of outbound Chinese tourists abroad has risen a lot in recent years, and that increase very closely mirrors the rise in ‘errors and omissions’. So the suspicion must be that the increasing flow of Chinese tourists – nearly one half of whom last year simply travelled to capital-controls-free Hong Kong and Macao – is just creating opportunities for unrecorded capital flight.This raises a disturbing possibility: that the most effective way for China to devalue the renminbi without the backfire of capital outflows would be simultaneously to stem the outflow of Chinese tourists. China has form in this regard, albeit for differing reasons: this month it suspended a programme that allowed individual tourists from 47 Chinese cities to travel to Taiwan.A more global restriction on Chinese tourism might make a devaluation of the renminbi ‘safer’, and it would have the collateral benefit of helping to increase China’s current account surplus, the evaporation of which in recent years owes a lot to rising tourism expenditure and which is almost certainly a source of unhappiness in Beijing, where mercantilism remains popular.But a world where China could impose such draconian measures would be one where nationalism has reached heights we haven’t yet seen. Let’s hope we don’t go there.This article was originally published in the Financial Times. Full Article
hi Latin America: Shifting Political Dynamics and the Implications for the Global System By feedproxy.google.com Published On :: Mon, 09 Sep 2019 13:20:01 +0000 Corporate Members Event Nominees Breakfast Briefing Partners and Major Corporates 26 September 2019 - 8:00am to 9:15am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Christopher Sabatini, Senior Research Fellow for Latin America, US and the Americas Programme, Chatham House In the past 12 months, a series of highly-anticipated elections throughout Latin America have demonstrated that deep political shifts are underway. This has occurred at a time when economic growth across the region is slowing and a number of countries face growing social crises. How will these political shifts and social challenges affect growth and foreign direct investment (FDI)?Christopher Sabatini will outline how the shifting political dynamics across the region have, and will, continue to influence trade and investment in the coming months and years across the continent and what regional developments mean for the international community in light of Brexit, global trade tensions and the rise of China and other emerging powers. How can businesses and governments provide a platform to overcome mutual obstacles faced by Latin American investors? What impact have Chinese development projects had in Latin America? And are medium and small economies in Latin America vulnerable to a global trade war?This event is only open to Major Corporate Member and Partner organizations of Chatham House. If you would like to register your interest, please RSVP to Linda Bedford. We will contact you to confirm your attendance.To enable as open a debate as possible, this event will be held under the Chatham House Rule. Members Events Team Email Full Article
hi Rethinking 'The Economic Consequences of the Peace' By feedproxy.google.com Published On :: Mon, 07 Oct 2019 15:10:01 +0000 Members Event 25 November 2019 - 1:00pm to 2:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Professor Michael Cox, Associate Fellow, US and the Americas Programme, Chatham House; Director, LSE IDEASProfessor Margaret MacMillan, Professor of History, University of Toronto; Emeritus Professor of International History, University of OxfordDr Geoff Tily, Senior Economist, TUC; Author, Keynes Betrayed: The General Theory, the Rate of Interest and 'Keynesian' EconomicsChair: Dr Jessica Reinisch, Reader in Modern European History, Birkbeck University of London John Maynard Keynes' The Economic Consequences of the Peace has long been a key reference point in discussions about the Treaty of Versailles and its impact on Germany and Europe’s rehabilitation. A century after its publication, the relevance of Keynes’ thinking – not least the influence it had on public perception of the treaty itself – offers an insight into the impact of expert analysis on how political decisions are received in public and academic spheres.This panel discusses the author, the book and the controversy they have generated up to the present day. How relevant is Keynes’ polemic and how applicable is his European economic recovery plan to our current period of global dislocation? What is the role of experts in the formation and scrutiny of international politics? And how can contemporary politicians use Keynes’ comprehensive assessment of the intersection between political, social and economic realities and national idealism to inform their approaches to international relations? Members Events Team Email Full Article
hi Understanding China’s Evolving Role in Global Economic Governance By feedproxy.google.com Published On :: Mon, 04 Nov 2019 13:00:01 +0000 Invitation Only Research Event 21 November 2019 - 4:00pm to 22 November 2019 - 5:00pm The Hague, The Netherlands Draft Agendapdf | 130.1 KB Almost four years since it was established, the China-led Asian Infrastructure Investment Bank (AIIB) has approved 49 projects and proposed 28. The AIIB claims to be more efficient and less bureaucratic than traditional multilateral development banks (MDB’s) which has threatened the existing model of multilateral development finance. At the same time, China’s increased role in previously Western-led economic institutions, such as the WTO and IMF, has raised questions over the future of the international trade order. How will a rising China shape the international institutional order? Where are there opportunities for potential collaboration and what areas pose challenges? And how should other states and international organizations respond?Attendance at this event is by invitation only. Department/project Asia-Pacific Programme, Geopolitics and Governance, Trade, Investment and Economics Lucy Ridout Programme Administrator, Asia-Pacific Programme +44 (0) 207 314 2761 Email Full Article
hi Brexit identities and British public opinion on China By feedproxy.google.com Published On :: Wed, 06 Nov 2019 09:17:46 +0000 6 November 2019 , Volume 95, Number 6 Read online Wilfred M. Chow, Enze Han and Xiaojun Li Many studies have explored the importance of public opinion in British foreign policy decision-making, especially when it comes to the UK's relations with the United States and the European Union. Despite its importance, there is a dearth of research on public opinion about British foreign policy towards other major players in the international system, such as emerging powers like China. We have addressed this knowledge gap by conducting a public opinion survey in the UK after the Brexit referendum. Our research findings indicate that the British public at large finds China's rise disconcerting, but is also pragmatic in its understanding of how the ensuing bilateral relations should be managed. More importantly, our results show that views on China are clearly split between the two opposing Brexit identities. Those who subscribe strongly to the Leave identity, measured by their aversion to the EU and antipathy towards immigration, are also more likely to hold negative perceptions of Chinese global leadership and be more suspicious of China as a military threat. In contrast, those who espouse a Remain identity—that is, believe that Britain would be better served within the EU and with more immigrants—are more likely to prefer closer engagement with China and to have a more positive outlook overall on China's place within the global community. Full Article
hi Hiroki Sekine By feedproxy.google.com Published On :: Thu, 23 Jan 2020 13:30:55 +0000 Visiting Fellow, Asia-Pacific Programme Biography Hiroki Sekine is visiting fellow with the Asia-Pacific Programme at Chatham House.He was director of the policy and strategy office for financial operations at JBIC from July 2016 until June 2019 and, most recently, senior advisor to the corporate planning department at the Japan Bank for International Cooperation (JBIC).During this time, Hiroki led an internal taskforce to facilitate a trilateral partnership between the US, Australia and Japan, aiming to enhance infrastructure development under the Free and Open Indo-Pacific Strategy.He has led project finance deals for power and petrochemical projects in Asia, the Middle East and South America. In 2018, Hiroki was appointed as adjunct professor at Kyoto University.Hiroki Sekine is based at Chatham House until June 2021, hosted by the Asia-Pacific programme. During his fellowship, Hiroki is undertaking research on infrastructure development in the Asia-Pacific. Areas of expertise Infrastructure development policy in the Asia-Pacific regionFinance (incl. green finance, project finance, and sovereign finance)Public finance policy (incl. multilateral finance agencies, development finance agencies) Past experience 2019 - presentSenior advisor, Corporate Planning Department, Japan Bank for International Cooperation2016-19 Director, Policy and Strategy Office for Financial Operations, Japan Bank for International Cooperation2015-16 Advisor, Credit Analysis Department, Japan Bank for International Cooperation2013-15Director, Division 2, Corporate Finance Department2011-13Director, Power and Water Finance Department, Japan Bank for International Cooperation2010-11Advisor, Asia and Oceania Finance Department, Japan Bank for International Cooperation2008-10Deputy Director, Division2, Asia and Oceania Finance Department, Japan Bank for International Cooperation2005MSc in Finance, London Business School, University of London1995B.A. in Economics, University of Tokyo +44 (0)20 7314 3626 Email Full Article
hi China's 2020: Economic Transition, Sustainability and the Coronavirus By feedproxy.google.com Published On :: Tue, 04 Feb 2020 21:15:01 +0000 Corporate Members Event 10 March 2020 - 12:15pm to 2:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Dr Yu Jie, Senior Research Fellow on China, Asia-Pacific Programme, Chatham HouseDavid Lubin, Associate Fellow, Global Economy and Finance Programme, Chatham House; Managing Director and Head of Emerging Markets Economics, CitiJinny Yan, Managing Director and Chief China Economist, ICBC StandardChair: Creon Butler, Director, Global Economy and Finance Programme, Chatham House Read all our analysis on the Coronavirus ResponseThe coronavirus outbreak comes at a difficult time for China’s ruling party. A tumultuous 2019 saw the country fighting an economic slowdown coupled with an increasingly hostile international environment. As authorities take assertive steps to contain the virus, the emergency has - at least temporarily - disrupted global trade and supply chains, depressed asset prices and forced multinational businesses to make consequential decisions with limited information. Against this backdrop, panellists reflect on the country’s nascent economic transition from 2020 onward. What has been China’s progress towards a sustainable innovation-led economy so far? To what extent is the ruling party addressing growing concerns over job losses, wealth inequality and a lack of social mobility? And how are foreign investors responding to these developments in China? Members Events Team Email Full Article
hi The great Chinese surprise: the rupture with the United States is real and is happening By feedproxy.google.com Published On :: Wed, 04 Mar 2020 13:25:56 +0000 4 March 2020 , Volume 96, Number 2 Xiangfeng Yang Read Online Ample evidence exists that China was caught off guard by the Trump administration's onslaught of punishing acts—the trade war being a prime, but far from the only, example. This article, in addition to contextualizing their earlier optimism about the relations with the United States under President Trump, examines why Chinese leaders and analysts were surprised by the turn of events. It argues that three main factors contributed to the lapse of judgment. First, Chinese officials and analysts grossly misunderstood Donald Trump the individual. By overemphasizing his pragmatism while downplaying his unpredictability, they ended up underprepared for the policies he unleashed. Second, some ingrained Chinese beliefs, manifested in the analogies of the pendulum swing and the ‘bickering couple’, as well as the narrative of the ‘ballast’, lulled officials and scholars into undue optimism about the stability of the broader relationship. Third, analytical and methodological problems as well as political considerations prevented them from fully grasping the strategic shift against China in the US. Full Article
hi Chinese Overseas Direct Investment and the Economic Crisis: Reaching Out By feedproxy.google.com Published On :: Tue, 24 Mar 2020 09:54:24 +0000 1 January 2009 , Number 5 Decisions taken today will determine the course of events for a generation. Nowhere is this truer than over the question of China’s investment abroad. This issue lies at the heart of what part the country will play in the global finance and trade system, and how it will work with the rest of the world in laying the foundations for longer term growth and stability after the current crisis is over. Professor Kerry Brown Associate Fellow, Asia-Pacific Programme @Bkerrychina LinkedIn Google Scholar Peter Wood Independent China strategist based in Hong Kong HaierFlickr.jpg Chinese companies establish a presence abroad. Full Article
hi Blaming China Is a Dangerous Distraction By feedproxy.google.com Published On :: Wed, 15 Apr 2020 10:50:59 +0000 15 April 2020 Jim O'Neill Chair, Chatham House Chinese officials' initial effort to cover up the coronavirus outbreak was appallingly misguided. But anyone still focusing on China's failings instead of working toward a solution is essentially making the same mistake. 2020-04-15-China-coronavirus-health Medical staff on their rounds at a quarantine zone in Wuhan, China. Photo by STR/AFP via Getty Images. As the COVID-19 crisis roars on, so have debates about China’s role in it. Based on what is known, it is clear that some Chinese officials made a major error in late December and early January, when they tried to prevent disclosures of the coronavirus outbreak in Wuhan, even silencing healthcare workers who tried to sound the alarm.China’s leaders will have to live with these mistakes, even if they succeed in resolving the crisis and adopting adequate measures to prevent a future outbreak. What is less clear is why other countries think it is in their interest to keep referring to China’s initial errors, rather than working toward solutions.For many governments, naming and shaming China appears to be a ploy to divert attention from their own lack of preparedness. Equally concerning is the growing criticism of the World Health Organization (WHO), not least by Donald Trump who has attacked the organization - and threatens to withdraw US funding - for supposedly failing to hold the Chinese government to account. Unhelpful and dangerousAt a time when the top global priority should be to organize a comprehensive coordinated response to the dual health and economic crises unleashed by the coronavirus, this blame game is not just unhelpful but dangerous.Globally and at the country level, we all desperately need to do everything possible to accelerate the development of a safe and effective vaccine, while in the meantime stepping up collective efforts to deploy the diagnostic and therapeutic tools necessary to keep the health crisis under control.Given there is no other global health organization with the capacity to confront the pandemic, the WHO will remain at the center of the response, whether certain political leaders like it or not.Having dealt with the WHO to a modest degree during my time as chairman of the UK’s independent Review on Antimicrobial Resistance (AMR), I can say that it is similar to most large, bureaucratic international organizations.Like the International Monetary Fund (IMF), the World Bank, and the United Nations, it is not especially dynamic or inclined to think outside the box. But rather than sniping at these organizations from the sidelines, we should be working to improve them.In the current crisis, we all should be doing everything we can to help both the WHO and the IMF to play an effective, leading role in the global response. As I have argued before, the IMF should expand the scope of its annual Article IV assessments to include national public-health systems, given that these are critical determinants in a country’s ability to prevent or at least manage a crisis like the one we are now experiencing.I have even raised this idea with IMF officials themselves, only to be told that such reporting falls outside their remit because they lack the relevant expertise. That answer was not good enough then, and it definitely isn’t good enough now.If the IMF lacks the expertise to assess public health systems, it should acquire it. As the COVID-19 crisis makes abundantly clear, there is no useful distinction to be made between health and finance. The two policy domains are deeply interconnected, and should be treated as such.In thinking about an international response to today’s health and economic emergency, the obvious analogy is the 2008 global financial crisis which started with an unsustainable US housing bubble, fed by foreign savings owing to the lack of domestic savings in the United States.When the bubble finally burst, many other countries sustained more harm than the US did, just as the COVID-19 pandemic has hit some countries much harder than it hit China.And yet not many countries around the world sought to single out the US for presiding over a massively destructive housing bubble, even though the scars from that previous crisis are still visible. On the contrary, many welcomed the US economy’s return to sustained growth in recent years, because a strong US economy benefits the rest of the world.So, rather than applying a double standard and fixating on China’s undoubtedly large errors, we would do better to consider what China can teach us. Specifically, we should be focused on better understanding the technologies and diagnostic techniques that China used to keep its - apparent - death toll so low compared to other countries, and to restart parts of its economy within weeks of the height of the outbreak.And for our own sakes, we also should be considering what policies China could adopt to put itself back on a path toward 6% annual growth, because the Chinese economy inevitably will play a significant role in the global recovery.If China’s post-pandemic growth model makes good on its leaders’ efforts in recent years to boost domestic consumption and imports from the rest of the world, we will all be better off.This article was originally published in Project Syndicate Full Article
hi IMF Needs New Thinking to Deal with Coronavirus By feedproxy.google.com Published On :: Mon, 27 Apr 2020 08:59:48 +0000 27 April 2020 David Lubin Associate Fellow, Global Economy and Finance Programme @davidlubin The IMF faces a big dilemma in its efforts to support the global economy at its time of desperate need. Simply put, the Fund’s problem is that most of the $1tn that it says it can lend is effectively unusable. 2020-04-27-IMF-Virtual-News Kristalina Georgieva, managing director of the International Monetary Fund (IMF), speaks during a virtual news conference on April 15, 2020. Photo by Andrew Harrer/Bloomberg via Getty Images There were several notable achievements during last week’s Spring meetings. The Fund’s frank set of forecasts for world GDP growth are a grim but valuable reminder of the scale of the crisis we are facing, and the Fund’s richer members will finance a temporary suspension on payments to the IMF for 29 very poor countries.Most importantly, a boost to the Fund’s main emergency facilities - the Rapid Credit Facility and the Rapid Financing Instrument - now makes $100bn of proper relief available to a wide range of countries. But the core problem is that the vast bulk of the Fund’s firepower is effectively inert.This is because of the idea of 'conditionality', which underpins almost all of the IMF’s lending relationships with member states. Under normal circumstances, when the IMF is the last-resort lender to a country, it insists that the borrowing government tighten its belt and exercise restraint in public spending.This helps to achieve three objectives. One is to stabilise the public debt burden, to ensure that the resources made available are not wasted. The second is to limit the whole economy’s need for foreign exchange, a shortage of which had prompted a country to seek IMF help in the first place. And the third is to ensure that the IMF can get repaid.Role within the international monetary systemSince the IMF does not take any physical collateral from countries to whom it is lending, the belt-tightening helps to act as a kind of collateral for the IMF. It helps to maximise the probability that the IMF does not suffer losses on its own loan portfolio — losses that would have bad consequences for the Fund’s role within the international monetary system.This is a perfectly respectable goal. Walter Bagehot, the legendary editor of The Economist, established modern conventional wisdom about managing panics. Relying on a medical metaphor that feels oddly relevant today, he said that a panic 'is a species of neuralgia, and according to the rules of science you must not starve it.' Managing a panic, therefore, requires lending to stricken borrowers 'whenever the security is good', as Bagehot put it. The IMF has had to invent its own form of collateral, and conditionality is the result. The problem, though, is that belt-tightening is a completely inappropriate approach to managing the current crisis.Countries are stricken not because they have indulged in any irresponsible spending sprees that led to a shortage of foreign exchange, but because of a virus beyond their control. Indeed, it would seem almost grotesque for the Fund to ask countries to cut spending at a time when, if anything, more spending is needed to stop people dying or from falling into a permanent trap of unemployment.The obvious solution to this problem would be to increase the amount of money that any country can access from the Fund’s emergency facilities well beyond the $100bn now available. But that kind of solution would quickly run up against the IMF’s collateral problem.The more the IMF makes available as 'true' emergency financing with few or no strings attached, the more it begins to undermine the quality of its loan portfolio. And if the IMF’s senior creditor status is undermined, then an important building block of the international monetary system would be at risk.One way out of this might have been an emergency allocation of Special Drawing Rights, a tool last used in 2009. This would credit member countries’ accounts with new, unconditional liquidity that could be exchanged for the five currencies that underpin the SDR: the dollar, the yen, the euro, sterling and the renminbi. That will not be happening, though, since the US is firmly opposed, for reasons bad and good.So in the end the IMF and its shareholders face a huge problem. It either lends more money on easy terms without the 'collateral' of conditionality, at the expense of undermining its own balance sheet - or it remains, in systemic terms, on the sidelines of this crisis.And since the legacy of this crisis will be some eye-watering increases in the public debt burdens of many emerging economies, the IMF’s struggle to find a way to administer its medicine will certainly outlive this round of the coronavirus outbreak.This article is a version of a piece which was originally published in the Financial Times Full Article
hi How images frame China's role in African development By feedproxy.google.com Published On :: Thu, 07 May 2020 09:21:23 +0000 7 May 2020 , Volume 96, Number 3 George Karavas Read online Political leaders, policy-makers and academics routinely refer to development as an objective process of social change through the use of technical, value-free terms. Images of poverty and inequality are regularly presented as evidence of a world that exists ‘out there’ where development unfolds. This way of seeing reflects the value of scientific forms of knowledge but also sits in tension with the normative foundations of development that take European modernization and industrialization as the benchmark for comparison. The role images play in this process is often overlooked. This article argues that a dominant mode of visuality based on a Cartesian separation between subject and object, underpinning the ascendance of European hegemony and colonialism, aligns with the core premises of orthodox development discourse. An example of how visual representations of development matter is presented through images of Africa–China relations in western media sources. Using widely circulated images depicting China's impact on African development in western news media sources as an example of why visual politics matters for policy-making, the article examines how images play a role in legitimizing development planning by rendering associated forms of epistemological and structural violence ‘invisible to the viewer’. Full Article
hi Sphingolipids distribution at mitochondria-associated membranes (MAM) upon induction of apoptosis. By feedproxy.google.com Published On :: 2020-04-29 Vincent MignardApr 29, 2020; 0:jlr.RA120000628v1-jlr.RA120000628Research Articles Full Article
hi Lithium ion adduction enables UPLC-MS/MS-based analysis of multi-class 3-hydroxyl group-containing keto-steroids By feedproxy.google.com Published On :: 2020-04-01 Qiuyi WangApr 1, 2020; 61:570-579Methods Full Article
hi HDL inhibits endoplasmic reticulum stress-induced apoptosis of pancreatic {beta}-cells in vitro by activation of Smoothened By feedproxy.google.com Published On :: 2020-04-01 Mustafa YalcinkayaApr 1, 2020; 61:492-504Research Articles Full Article
hi Dynamics of sphingolipids and the serine palmitoyltransferase complex in rat oligodendrocytes during myelination By feedproxy.google.com Published On :: 2020-04-01 Deanna L. DavisApr 1, 2020; 61:505-522Research Articles Full Article