MPU 046: Workflows with Merlin Mann II « Mac Power Users

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I have the life that I have because I've made a lot of weird decisions, and they've worked out well.

Not gonna lie to you. I'm a huge nerd. Surprised?

Yep. I can recite big chunks of The Big Lebowski from memory. I can argue for an hour on the merits of Dick York over Dick Sargent. And, I can—and frequently do—catch myself thinking Catwoman, Batgirl, Princess Leia, and Emma Peel should have a light-hearted pillow fight that ends with an hour of genial french-kissing.

Pretty much like you, probably. I dunno, maybe your version includes Kitty Pryde. Po-tay-to/Po-taht-o, right?

Perhaps most saliently, by virtue of having spent a solid 2,399 days as a Fake Productivity Guru, I have been provided with an unquestionably Janusian monkey's paw of a gift; I now know a lot about workflows. Nerdy, nerdy workflows.

I can tell you a few things that almost always work, I can tell you a handful of things that almost never work, and—best or worst of all—I can tell you thousands of things that might work. Sometimes. Maybe. Kinda. For some people. For now.

And, at the risk of gay-marrying my arrogance to my hypocrisy, I can tell you that I also know enough about the unholy diarrhea of potential options for Theoretical Productivity to share two big patterns:

1. Getting your workflow right matters.
2. Getting your workflow right to the exclusion of the actual work is a fool's game.

But. Managing to get the most useful and most elegant and least fiddly mix of 1 and 2 right is super-hard. Especially for nerds. Especially for me.

So, as I type this today, I believe there can be no greater testament to these claims—or, at least, no greater place to test the veracity of these claims for yourself—than in this TWO AND A HALF HOUR-long interview for Mac Power Users.

It is reeeeeeeeally nerdy. Almost intolerably nerdy. Just…overwhelmingly nerdy.

But, man, is it ever really good, and really fat with the most insanely granular details of How I Work.

Lo, even these 928.5 days after officially retiring from productivity pr0n, my desire to not "vend stroke material for your joyless addiction to puns about procrastination and systems for generating more taxonomically satisfying meta-work" is tempered by a (widely under-reported) practical streak.

Yes: I continue to despise empty advice about rearranging deck chairs on The Titanic. But, yes: I do also still very much enjoy talking about how all the tips and tricks can or can't work in the context of work you care about. That matters. It really does.

So. Here goes. A one hundred and forty six minute-long, Joyce-ian amble through the Big Stuff and the Little Stuff. David and Katie were very patient.

How I name text files. Why I break iOS apps. Why I love the letter "x." Why I won't row out to islands any more. How a 115,000 word book manuscript is "like a house full of confederate money." How "The Cloud" broke in New Zealand. How I use MultiMarkdown, Scrivener, TextExpander, OmniFocus, TextMate, Notational Velocity, Dropbox, and an explosive combination of Elements, Notesy, Nebulous, Simplenote, CF Outliner, iThoughts, Instacast, Good Reader, and wow wow wow.

How I try not to fiddle—how I sometimes succeed and often don't. But, how I try.

Anyhow. There you go. A perfectly nerdy bookend to last year's first Magnum Opus MPU interview on these same topics, Mac Power Users Episode 46 is just insanely nerdy. And, what have you.

I hope you like it. I hope it's useful. I hope you don't use it to replace real work.

And, as ever, I really hope Batgirl starts having more sexy pillow fights.

Enjoy. And, God save you.

MPU 046: Workflows with Merlin Mann II « Mac Power Users

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At the State of the Union, Joe Biden Joe Biden made a 'bold' announcement that America would be building a pier to deliver aid to Gaza. Four months later, he admitted it was a failure.

The post Soldier Succumbs To Injuries Sustained In Biden’s Doomed Gaza Pier Mission appeared first on Clash Daily.

Canan Moodie used his start against Scotland to show that he is about far more than just pace out wide and aerial ability.

Ilka Wittig
Jul 1, 2007; 6:1215-1225
Research

Ulrich Rothbauer
Feb 1, 2008; 7:282-289
Research

W Gamble
Nov 1, 1978; 19:1068-1070
Articles

Gijs den Besten
Sep 1, 2013; 54:2325-2340
Reviews

Thomas O. Gallouët, Andrea Natale and Gabriele Todeschi
Math. Comp. 93 (), 2769-2810.
Abstract, references and article information

Zhaohui Fu, Tao Tang and Jiang Yang
Math. Comp. 93 (), 2745-2767.
Abstract, references and article information

firehouse.ie posted a photo:

firehouse.ie posted a photo:

firehouse.ie posted a photo:

firehouse.ie posted a photo:

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Reliable, specific polyclonal and monoclonal antibodies are important tools in research and medicine. However, the discovery of antibodies against their targets in their native forms is difficult. Here, we present a novel method for discovery of antibodies against membrane proteins in their native configuration in mammalian cells. The method involves the co-expression of an antibody library in a population of mammalian cells that express the target polypeptide within a natural membrane environment on the cell surface. Cells that secrete a single-chain fragment variable (scFv) that binds to the target membrane protein thereby become self-labeled, enabling enrichment and isolation by magnetic sorting and FRET-based flow sorting. Library sizes of up to 109 variants can be screened, thus allowing campaigns of naïve scFv libraries to be selected against membrane protein antigens in a Chinese hamster ovary cell system. We validate this method by screening a synthetic naïve human scFv library against Chinese hamster ovary cells expressing the oncogenic target epithelial cell adhesion molecule and identify a panel of three novel binders to this membrane protein, one with a dissociation constant (KD) as low as 0.8 nm. We further demonstrate that the identified antibodies have utility for killing epithelial cell adhesion molecule–positive cells when used as a targeting domain on chimeric antigen receptor T cells. Thus, we provide a new tool for identifying novel antibodies that act against membrane proteins, which could catalyze the discovery of new candidates for antibody-based therapies.

Xiao-Ting Wen
Dec 17, 2020; 0:RA120.002119v1-mcp.RA120.002119
Research

Weixian Deng
Dec 22, 2020; 0:RA120.002411v1-mcp.RA120.002411
Research

Elisa Vidal
Dec 1, 2020; 61:1733-1746
Research Articles

Thibaut Bourgeois
Dec 11, 2020; 0:jlr.RA120000737v1-jlr.RA120000737
Research Articles

Anja Jaeschke
Dec 9, 2020; 0:jlr.RA120001141v1-jlr.RA120001141
Research Articles

This manuscript has been withdrawn by the Author.

Functions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual classes of dietary lipids interact with the microbiome remains largely unknown. Sphingolipids are bioactive components of most foods and are also produced by prominent gut microbes. This makes sphingolipids intriguing candidates for shaping diet–microbiome interactions. Here, we used a click chemistry–based approach to track the incorporation of bioorthogonal dietary omega-alkynyl sphinganine (sphinganine alkyne [SAA]) into the murine gut microbial community (Bioorthogonal labeling). We identified microbial and SAA-specific metabolic products through fluorescence-based sorting of SAA-containing microbes (Sort), 16S rRNA gene sequencing to identify the sphingolipid-interacting microbes (Seq), and comparative metabolomics to identify products of SAA assimilation by the microbiome (Spec). Together, this approach, termed Bioorthogonal labeling-Sort-Seq-Spec (BOSSS), revealed that SAA assimilation is nearly exclusively performed by gut Bacteroides, indicating that sphingolipid-producing bacteria play a major role in processing dietary sphinganine. Comparative metabolomics of cecal microbiota from SAA-treated mice revealed conversion of SAA to a suite of dihydroceramides, consistent with metabolic activities of Bacteroides and Bifidobacterium. Additionally, other sphingolipid-interacting microbes were identified with a focus on an uncharacterized ability of Bacteroides and Bifidobacterium to metabolize dietary sphingolipids. We conclude that BOSSS provides a platform to study the flux of virtually any alkyne-labeled metabolite in diet–microbiome interactions.

The LDL receptor-related protein-1 (LRP1) is highly expressed in numerous cell types, and its impairment is associated with obesity, diabetes, and fatty liver disease. However, the mechanisms linking LRP1 to metabolic disease are not completely understood. Here, we compared the metabolic phenotype of C57BL/6J wild type and LRP1 knock-in mice carrying an inactivating mutation in the distal NPxY motif after feeding a low fat (LF) diet or high fat diets with (HFHC) or without (HF) cholesterol supplementation. In response to HF feeding, both groups developed hyperglycemia, hyperinsulinemia, and hyperlipidemia, as well as increased adiposity with adipose tissue inflammation and liver steatosis. However, when animals were fed the HF diet supplemented with cholesterol, the LRP1 NPxY mutation prevents hypercholesterolemia, reduces adipose tissue and brain inflammation, and limits liver progression to steatohepatitis. Nevertheless, insulin signaling is impaired in LRP1 NPxY mutant hepatocytes and this mutation does not protect against HFHC-induced insulin resistance. The selective metabolic improvement observed in HFHC-fed LRP1 NPxY mutant mice is due to an apparent increase of hepatic LDL receptor levels, leading to an elevated rate of plasma lipoprotein clearance and lowering of plasma and hepatic cholesterol levels. The unique metabolic phenotypes displayed by LRP1 NPxY mutant mice in response to HF or HFHC diet feeding indicate an LRP1-cholesterol axis in modulating tissue inflammation. The LRP1 NPxY mutant mouse phenotype differs from phenotypes observed in mice with tissue-specific LRP1 inactivation, thus highlighting the importance of an integrative approach to evaluate how global LRP1 dysfunction contributes to metabolic disease development.

Recent studies have highlighted an important role for lysophosphatidylcholine acyltransferase 3 (LPCAT3) in controlling the PUFA composition of cell membranes in the liver and intestine. In these organs, LPCAT3 critically supports cell membrane-associated processes such as lipid absorption or lipoprotein secretion. However, the role of LPCAT3 in macrophages remains controversial. Here, we investigated LPCAT3’s role in macrophages both in vitro and in vivo in mice with atherosclerosis and obesity. To accomplish this, we used the LysMCre strategy to develop a mouse model with conditional Lpcat3 deficiency in myeloid cells (Lpcat3KOMac). We observed that partial Lpcat3 deficiency (approx. 75% reduction) in macrophages alters the PUFA composition of all phospholipid (PL) subclasses, including phosphatidylinositols and phosphatidylserines. A reduced incorporation of C20 PUFAs (mainly arachidonic acid [AA]) into PLs was associated with a redistribution of these FAs toward other cellular lipids such as cholesteryl esters. Lpcat3 deficiency had no obvious impact on macrophage inflammatory response or endoplasmic reticulum (ER) stress; however, Lpcat3KOMac macrophages exhibited a reduction in cholesterol efflux in vitro. In vivo, myeloid Lpcat3 deficiency did not affect atherosclerosis development in LDL receptor deficient mouse (Ldlr-/-) mice. Lpcat3KOMac mice on a high-fat diet displayed a mild increase in hepatic steatosis associated with alterations in several liver metabolic pathways and in liver eicosanoid composition. We conclude that alterations in AA metabolism along with myeloid Lpcat3 deficiency may secondarily affect AA homeostasis in the whole liver, leading to metabolic disorders and triglyceride accumulation.

Accompanied with nutrition transition, non-HDL-C levels of individuals in Asian countries has increased rapidly, which has caused the global epicenter of nonoptimal cholesterol to shift from Western countries to Asian countries. Thus, it is critical to underline major genetic and dietary determinants. In the current study of 2,330 Chinese individuals, genetic risk scores (GRSs) were calculated for total cholesterol (TC; GRS_TC, 57 SNPs), LDL-C (GRS_LDL-C, 45 SNPs), and HDL-C (GRS_HDL-C, 65 SNPs) based on SNPs from the Global Lipid Genetics Consortium study. Cholesterol intake was estimated by a 74-item food-frequency questionnaire. Associations of dietary cholesterol intake with plasma TC and LDL-C strengthened across quartiles of the GRS_TC (effect sizes: –0.29, 0.34, 2.45, and 6.47; P_interaction = 0.002) and GRS_LDL-C (effect sizes: –1.35, 0.17, 5.45, and 6.07; P_interaction = 0.001), respectively. Similar interactions with non-HDL-C were observed between dietary cholesterol and GRS_TC (P_interaction = 0.001) and GRS_LDL-C (P_interaction = 0.004). The adverse effects of GRS_TC on TC (effect sizes across dietary cholesterol quartiles: 0.51, 0.82, 1.21, and 1.31; P_interaction = 0.023) and GRS_LDL-C on LDL-C (effect sizes across dietary cholesterol quartiles: 0.66, 0.52, 1.12, and 1.56; P_interaction = 0.020) were more profound in those having higher cholesterol intake compared with those with lower intake. Our findings suggest significant interactions between genetic susceptibility and dietary cholesterol intake on plasma cholesterol profiles in a Chinese population.

Some cases of chylomicronemia are caused by autoantibodies against glycosylphosphatidylinositol-anchored HDL binding protein 1 (GPIHBP1), an endothelial cell protein that shuttles LPL to the capillary lumen. GPIHBP1 autoantibodies prevent binding and transport of LPL by GPIHBP1, thereby disrupting the lipolytic processing of triglyceride-rich lipoproteins. Here, we review the "GPIHBP1 autoantibody syndrome" and summarize clinical and laboratory findings in 22 patients. All patients had GPIHBP1 autoantibodies and chylomicronemia, but we did not find a correlation between triglyceride levels and autoantibody levels. Many of the patients had a history of pancreatitis, and most had clinical and/or serological evidence of autoimmune disease. IgA autoantibodies were present in all patients, and IgG4 autoantibodies were present in 19 of 22 patients. Patients with GPIHBP1 autoantibodies had low plasma LPL levels, consistent with impaired delivery of LPL into capillaries. Plasma levels of GPIHBP1, measured with a monoclonal antibody–based ELISA, were very low in 17 patients, reflecting the inability of the ELISA to detect GPIHBP1 in the presence of autoantibodies (immunoassay interference). However, GPIHBP1 levels were very high in five patients, indicating little capacity of their autoantibodies to interfere with the ELISA. Recently, several GPIHBP1 autoantibody syndrome patients were treated successfully with rituximab, resulting in the disappearance of GPIHBP1 autoantibodies and normalization of both plasma triglyceride and LPL levels. The GPIHBP1 autoantibody syndrome should be considered in any patient with newly acquired and unexplained chylomicronemia.

Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined by LC coupled to MS/MS and MALDI coupled to MS imaging. The omega-3 content in the lipids of plasma and erythrocytes suggests that PLs as well as TGs are good omega-3 carriers for retina. However, a significant increase in DHA content in retina was observed, especially molecular species as di-DHA-containing PC and PE, as well as an increase in very long chain PUFAs (more than 28 carbons) following PL-EPA and TG-DHA diets only. All supplemented diets triggered spatial organization changes of DHA in the photoreceptor layer around the optic nerve. Taken together, these findings suggest that dietary omega-3 supplementation can modify the content of FAs in the rat retina.

Ankylosing Spondylitis (AS) is a common, inflammatory rheumatic disease, which primarily affects the axial skeleton and is associated with sacroiliitis, uveitis and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine if plasma from patients with AS contained autoantibodies and if so, characterize and quantify this response in comparison to patients with Rheumatoid Arthritis (RA) and healthy controls. Two high-density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis in order to determine patterns of signalling cascades or tissue origin. 44% of patients with Ankylosing Spondylitis demonstrated a broad autoantibody response, as compared to 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The AS patients autoantibody responses were targeted towards connective, skeletal and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic Acid Programmable Protein Arrays constitute a powerful tool to study autoimmune diseases.

Antibodies play essential roles in both diagnostics and therapeutics. Epitope mapping is essential to understand how an antibody works and to protect intellectual property. Given the millions of antibodies for which epitope information is lacking, there is a need for high-throughput epitope mapping. To address this, we developed a strategy, Antibody binding epitope Mapping (AbMap), by combining a phage displayed peptide library with next generation sequencing. Using AbMap, profiles of the peptides bound by 202 antibodies were determined in a single test, and linear epitopes were identified for >50% of the antibodies. Using spike protein (S1 and S2)-enriched antibodies from the convalescent serum of one COVID-19 patient as the input, both linear and conformational epitopes of spike protein specific antibodies were identified. We defined peptide-binding profile of an antibody as the Binding Capacity (BiC). Conceptually, the BiC could serve as a systematic and functional descriptor of any antibody. Requiring at least one order of magnitude less time and money to map linear epitopes than traditional technologies, AbMap allows for high-throughput epitope mapping and creates many possibilities.

The increasing consumption of high-fat foods combined with a lack of exercise is a major contributor to the burden of obesity in humans. Aerobic exercise such as running is known to provide metabolic benefits, but how the over-consumption of a high fat diet (HFD) and exercise interact is not well characterized at the molecular level. Here, we examined the plasma proteome in mice for the effects of aerobic exercise as both a treatment and as a preventative regime for animals on either HFD or a healthy control diet. This analysis detected large changes in the plasma proteome induced by the HFD, such as increased abundance of SERPINA7, ALDOB, and down-regulation of SERPINA1E, CFD (adipsin). Some of these changes were significantly reverted using exercise as a preventative measure, but not as a treatment regime. To determine if either the intensity, or duration, of exercise influenced the outcome, we compared high-intensity interval training (HIIT) and endurance running. Endurance running slightly out-performed HIIT exercise, but overall, both provided similar reversion in abundance of plasma proteins modulated by the high-fat diet including SERPINA7, APOE, SERPINA1E, and CFD. Finally, we compared the changes induced by over-consumption of HFD to previous data from mice fed an isocaloric high saturated fat (SFA) or polyunsaturated fat (PUFA) diet. This identified several common changes including increased APOC2 and APOE, but also highlighted changes specific for either over-consumption of HFD (ALDOB, SERPINA7, CFD), SFA-based diets (SERPINA1E), or PUFA-based diets (Haptoglobin - Hp). Together, these data highlight the importance of early intervention with exercise to revert HFD-induced phenotypes and suggest some of the molecular mechanisms leading to the changes in the plasma proteome generated by high fat diet consumption. Web-based interactive visualizations are provided for this dataset (larancelab.com/hfd-exercise), which give insight into diet and exercise phenotypic interactions on the plasma proteome.

To identify novel autoantibodies of Takayasu arteritis (TAK) using HuProt array-based approach. A two-phase approach was adopted. In Phase I, serum samples collected from 40 TAK patients, 15 autoimmune disease patients, and 20 healthy subjects were screened to identify TAK-specific autoantibodies using human protein (HuProt) arrays. In Phase II, the identified candidate autoantibodies were validated with TAK-focused arrays using an additional cohort comprised of 109 TAK patients, 110 autoimmune disease patients, and 96 healthy subjects. Subsequently, the TAK-specific autoantibodies validated in Phase II were further confirmed using Western blot analysis. We identified and validated eight autoantibodies as potential TAK-specific diagnostic biomarkers, including anti-SPATA7, -QDPR, -SLC25A2, -PRH2, -DIXDC1, -IL17RB, -ZFAND4, and -NOLC1 antibodies, with AUC of 0.803, 0.801, 0.780, 0.696, 0.695, 0.678, 0.635 and 0.613, respectively. SPATA7 could distinguish TAK from healthy and disease controls with 73.4% sensitivity at 85.4% specificity, while QDPR showed 71.6% sensitivity at 86.4% specificity. SLC25A22 showed the highest sensitivity of 80.7%, but at lower specificity of 67.0%. In addition, PRH2, IL17RB and NOLC1 showed good specificities of 88.3%, 85.9% and 86.9%, respectively, but at lower sensitivities (<50%). Finally, DIXDC1 and ZFAND4 showed moderate performance as compared with the other autoantibodies. Using a decision tree model, we could reach a specificity of 94.2% with AUC of 0.843, a significantly improved performance as compared to that by each individual biomarker. The performance of three autoantibodies, namely anti-SPATA7, -QDPR and -PRH2, were successfully confirmed with Western blot analysis. Using this two-phase strategy, we identified and validated eight novel autoantibodies as TAK–specific biomarker candidates, three of which could be readily adopted in a clinical setting.

Deep proteome coverage in bottom-up proteomics requires peptide-level fractionation to simplify the complex peptide mixture before analysis by tandem mass spectrometry. By decreasing the number of co-eluting precursor peptide ions, fractionation effectively reduces the complexity of the sample leading to higher sample coverage and reduced bias towards high abundance precursors that are preferentially identified in data-dependent acquisition strategies. To achieve this goal, we report a bead-based off-line peptide fractionation method termed CIF or Carboxylate modified magnetic bead-based isopropanol gradient peptide fractionation. CIF is an extension of the SP3 (single-pot solid-phase-enhanced sample preparation) strategy and provides an effective but complementary approach to other commonly used fractionation methods including strong cation exchange (SCX) and reversed phase (RP)-based chromatography. We demonstrate that CIF is an effective offline separation strategy capable of increasing the depth of peptide analyte coverage both when used alone or as a second dimension of peptide fractionation in conjunction with high pH RP. These features make it ideally suited for a wide range of proteomic applications including the affinity purification of low abundance bait proteins.

Healthy Diets from Sustainable Production: Indonesia Research paper sysadmin 24 January 2019

Indonesia has an uncommon chance to bypass the negative trajectory of diets in other emerging economies and build a healthy and sustainable food system.

Summary

• Indonesia is approaching a key point on its development pathway. Rapidly declining poverty, a growing and urbanizing middle class with increased purchasing power and consumption patterns, and a diminishing contribution of agriculture to overall GDP are all set to fundamentally reorient much in society.
• Dietary change is at the heart of the public health and environmental challenges now facing Indonesia. Rates of obesity and diet-related non-communicable diseases such as type 2 diabetes are on the increase, while high levels of childhood undernutrition persist. This double burden of malnutrition presents a critical challenge for the future of Indonesian public health.
• At the same time, shifts in diet are placing increased pressure on the environment, threatening biodiversity and species loss and rapidly increasing risks for land-use change, climate change and freshwater use. In Indonesia, these environmental impacts of agriculture are driven both by domestic consumption of food and biofuels, and by a focus on export-led agricultural growth – particularly palm oil, rubber, coffee and cocoa.
• A core political focus on achieving national self-sufficiency in five strategic commodities – soy, rice, maize, sugar and beef – which has led to some price distortion, and the growing influence of modernized retail are potentially at odds with a transition to healthy diets from sustainable production.
• The components to support an ambitious national food strategy already exist, but are either underutilized or misdirected. Indonesia’s national dietary guidelines and examples of successful food-based social services, together with the country’s potential to lead the sustainable production and consumption agenda, both regionally and internationally, and its commitments under both the UN Sustainable Development Goals and the Paris Agreement on climate change, can all be harnessed to foster improved diets.
• There is a need to align high-level policy strategies across environment, public health and food issues. Mainstreaming the principles of a healthy diet within existing food policy and partnering with food providers and local pioneers to champion these efforts can help to ensure that healthy diets, produced sustainably, become the norm.
• Between now and 2020, when Indonesia embarks on the final five-year tranche of its National Long-Term Development Plan, there is an important window of opportunity to take decisive action that will influence the future trajectory of the population’s health and that of its environment, as well as contribute substantively to the global fight against climate change and biodiversity loss.
• 2019 will, meanwhile, be a critical election year in Indonesia, with both presidential and legislative elections due. Signals from Indonesian media and civil society organizations indicate that poverty reduction and social equity – including affordability of good food and healthcare – will be among the flagship issues for voters.
• The moment is thus ripe for a bold new vision for a sustainable food system that supports healthy diets for all. In choosing to act now, Indonesia could lay the foundations for a more resilient and equitable development pathway that prioritizes improved public health while at the same time safeguarding some of the world’s most important ecosystems for future generations.

Subsidies and Sustainable Agriculture: Mapping the Policy Landscape Research paper sysadmin 10 December 2019

Agricultural subsidies shape production and consumption patterns, with potentially significant effects on poverty, nutrition and other sustainability concerns. This paper maps the different types of support provided by governments to the agricultural sector, and highlights some of the complex political economy dynamics that underpin the relevant policies.

Summary

• Agricultural subsidies, a mainstay of government policy, have a large part in shaping production and consumption patterns, with potentially significant effects as regards poverty, food security, nutrition, and other sustainability concerns such as climate change, land use practices and biodiversity.
• There are multiple types of direct and indirect support provided by governments to various actors in the agricultural sector; and in terms of political economy, there are complex dynamics underpinning the policies that sustain these subsidies.
• Overall, subsidies targeting producers have the most significant effect on production, and the greater trade-distorting effect. These subsidies promote domestic production and discourage imports, leading to overproduction that is largely disposed of on the international market, with the help of export subsidies. This can tend to intensify negative environmental agricultural practices, such as cultivating marginal land, unsustainable types of intensification, or incentivizing excessive pesticide and fertilizer use.
• On the other hand, producer subsidies that are not tied to output of a specific commodity (i.e. delinked) have far fewer distorting impacts and could help to deliver sustainable outcomes. For example, this type of subsidies can require crop diversification or be linked to conservation of permanent grassland.
• Subsidies that enable transfers to consumers, for example through food stamp programmes, also serve to delink production from consumption, can foster healthier diets, can play an important role in delivering food accessibility and security among low-income groups, and can represent one of the less trade-distorting subsidies.
• If subsidies are to be reformed to help promote healthier diets and encourage more sustainable production, it is essential to understand not only the type and amount of support that key countries provide, but also the domestic dynamics that can shape such policies.
• While price support, input subsidies or investment aids remain the central pillars of programmes in large developing countries such as Brazil, China or India, other economies – notably including the EU and Japan – focus on direct payments, support for general services and set-aside schemes, as well as significant border protection. The US, for its part, has tended to focus on subsidized insurance schemes and food programmes for poorer consumers.
• If subsidies are to deliver policy objectives, their design and implementation should delink production from consumption. For example, consumer subsidies designed to deliver nutrition and food security, or payments for environmental services to enable more environmentally friendly production systems, could prove to be the most effective, least trade-distorting means of achieving more sustainable and equitable agricultural production.
• The political economy of food means that the removal of subsidies is often highly sensitive, and tends to be met with significant resistance. However, reform that delinks support from production through a gradual transition process could ultimately prove successful in delivering effective subsidy schemes.
• Effective subsidy schemes must by design be truly result- and performance-based, supported by robust and objective indicators. At the same time, engaging multiple actors along key commodity value chains – including leading importing and exporting countries, traders and transporters – could lead to the development of international, commodity-specific arrangements that are able to deliver effective nutrition and sustainability goals.

Bispecific antibodies (bsAbs) are engineered to target 2 different epitopes simultaneously. About 75% of the 16 clinically approved bsAbs have entered the clinic internationally since 2022. Hence, research on biomedical imaging of various radiolabeled bsAb scaffolds may serve to improve patient selection for bsAb therapy. Here, we provide a comprehensive overview of recent advances in radiolabeled bsAbs for imaging via PET or SPECT. We compare direct targeting and pretargeting approaches in preclinical and clinical studies in oncologic research. Furthermore, we show preclinical applications of imaging bsAbs in neurodegenerative diseases. Finally, we offer perspectives on the future directions of imaging bsAbs based on their challenges and opportunities.

Ukraine's military intelligence has intercepted what it claims are radio communications between North Korean soldiers in Russia, amid media reports of a massive troop buildup ahead of an attack in the Kursk region.

Oct. 17, 2024 — UC San Diego Alumnus Roman Gerasimov, who recently earned his doctorate from the university, has received the International Astronomical Union (IAU) Stars and Stellar Physics Division Award […]

The post UC San Diego Doctoral Graduate Recognized for Achievement in Astronomy appeared first on HPCwire.

Gerry Faust, who won five Ohio high school football state titles before taking over as coach at Notre Dame in the early 1980s, has died, his family announced. He was 89.

FC Cincinnati midfielder Marco Angulo has died from injuries he sustained from a car crash, the MLS franchise and Ecuadorian Football Association announced Tuesday. He was 22.

LONDON and TORONTO, Sept. 30, 2024 — Alphawave Semi, a global leader in high-speed connectivity and compute silicon for the world’s technology infrastructure, has unveiled the availability of the industry’s […]

The post Alphawave Semi and TSMC Collaborate on 3nm UCIe Die-to-Die Subsystem for AI and HPC appeared first on HPCwire.

After a decade of forward deployment in Japan, the USS Germantown departed U.S. Fleet Activities Sasebo on Wednesday.

The U.S. Army is investigating the suspected suicides of three soldiers based at New York's Fort Drum.

A low-carbohydrate diet may help adults with type 2 diabetes gain better blood sugar control and make it possible to decrease diabetes medication, a new study suggests.

Quantum computing pioneer D-Wave today announced it had completed calibration and benchmarking the latest latest version of its Advantage2 quantum processor, a 4,400-plus-qubit device. D-Wave said that compared with the […]

The post D-Wave Readies 4,400-plus-qubit Advantage2 System for Use appeared first on HPCwire.