Eric Franklin Wood, a world-renowned hydrologist who did groundbreaking work in drought prediction and served on the Princeton faculty for 43 years, died from cancer in Brooklyn, New York, on Nov. 3. He was 74.

Jacques R. Fresco, the emeritus Damon B. Pfeiffer Professor in the Life Sciences and an emeritus professor of molecular biology, died on Dec. 5. He served on Princeton's faculty for 53 years before retiring in July 2013.

Arden helped usher computers into widespread use and played a key role in establishing Princeton's Department of Computer Science.

Ronald Surtz, professor of Spanish and Portuguese languages and literatures, emeritus, died peacefully at home in Cranbury, New Jersey, on Nov. 14. He was 75.

Hale Freeman Trotter, an emeritus professor of mathematics, died at 91 at his home in Princeton, New Jersey.

Austin Newton, a founding member of the Department of Molecular Biology, established a new experimental system and mentored generations of undergraduates, graduate students and postdoctoral fellows. He died May 13 in Princeton at age 85.

Daniel Osherson, Princeton’s Henry R. Luce Professor in Information Technology, Consciousness, and Culture, Emeritus, known for his  creative scientific explorations with collaborators in many disciplines, died at home on Sept. 4. 

Simon Morrison, author of the new musical biography "Mirror in the Sky,” is a professor of music and Slavic languages and literatures, and a sought-after lecturer in the humanities.

Hisashi Kobayashi, whose steady leadership as dean guided Princeton's School of Engineering and Applied Science through a rapid expansion of programs and facilities in the late 1980s and early 1990s, died on March 9. He was 84.

Morgan's paper on plate tectonics revolutionized the field of geology in the late 1960s. He taught at Princeton from 1966 to 2004.

“His mathematical legacy is enormous,” said John D’Angelo *76. “Joe was among the most friendly, popular and influential mathematicians of his generation.”

Laurie joined the Princeton faculty in 1966 and transferred to emeritus status in 2000.

Lisk taught biology at Princeton for 30 years before transferring to emeritus status in 1990.

Nearly every Wednesday of the semester, The Mossavar-Rahmini Center for Iran and Persian Gulf Studies invites a scholar to speak on their area of study. Topics relate to Iran and the Persian Gulf area while employing an interdisciplinary lens. To view the details of upcoming seminar topics, please visit iran.princeton.edu/upcoming-events.

Pulitzer Prize-winning poet Paul Muldoon, Princeton’s Howard G.B. Clark ‘21 University Professor in the Humanities and Professor of Creative Writing, offers a brief survey of Irish history from earliest times to the present day through the prism of his own poems. No tickets required.

Nearly every Wednesday of the semester, The Mossavar-Rahmini Center for Iran and Persian Gulf Studies invites a scholar to speak on their area of study. Topics relate to Iran and the Persian Gulf area while employing an interdisciplinary lens. To view the details of upcoming seminar topics, please visit iran.princeton.edu/upcoming-events.

The versatile actor had hundreds of screen credits to his name, including Platoon, The Rock and Final Destination.

In addition to his philanthropy, Marcus was an outspoken advocate for free-market capitalism and small businesses.

The man was pronounced dead at the scene after CPR efforts from cabin crew

Jos Buttler hits a blistering 83 from 45 balls as England cruise to a seven-wicket win over West Indies in the second T20.

1. Manipur on boil: 2 more bodies found, 6 missing  The Times of India
2. Additional paramilitary forces rushed to Manipur amid spike in ethnic violence  Hindustan Times
3. Three women, three children missing after Jiribam gunfight; Meiteis and Kukis hold bandhs in Manipur  The New Indian Express
4. Letters to The Editor — November 13, 2024  The Hindu
5. Centre rushes 20 more CAPF companies to Manipur after fresh violence  Deccan Herald

Nvidia might have some serious competition in the AI chip space coming. Amazon is now seeking to bring its own… Continue reading Amazon readies new AI chip to compete with Nvidia

The post Amazon readies new AI chip to compete with Nvidia appeared first on ReadWrite.

Announcing the brand new Tom the Dancing Bug book: Volume 8 of The Complete Tom the Dancing Bug book program is "IT'S THE GREAT STORM, TOM THE DANCING BUG!" Now accepting orders right HERE! Get your personalized / signed / sketched / swagged copy today! — Read the rest

The post Tom the Dancing Bug: "Hey, Ladies! Trump will be your protector!" appeared first on Boing Boing.

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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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

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

This manuscript has been withdrawn by the Author.

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.

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.

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.

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.

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.

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.

Which types of exercise can help keep the brain healthy?

TED Fellow and equity bioengineer Erika Moore investigates how cells controlling inflammation behave differently depending on a patient's background. By focusing on the "who" behind the disease, Moore is uncovering why certain diseases disproportionately affect certain ethnicities, paving the way for more inclusive and effective health care.

Oregon is the latest state to consider adding an ethnic studies curriculum.

Lucille Bridges, the mother of civil rights activist Ruby Bridges, who walked with her then-6-year-old daughter past crowds screaming racist slurs as she became the first Black student at her all-white New Orleans elementary school, has died at the age of 86.

The mix of hybrid learning approaches is dizzying, but schools are learning valuable lessons about what is worth replicating.

Dez-Ann Romain, a Brooklyn principal, is believed to be the first full-time, front-line educator to die from COVID-19.

A former high school athletic standout and homecoming king, Pedro Garcia III “could connect with anybody,” no matter the language, said a teaching colleague in Cozad, Neb.

Data suggest low-income communities are hit much harder than affluent ones, writes researcher Heather C. Hill.