Learn how some of the great structures of the world—the Eiffel Tower, the Great Pyramids, and more—were built.

Stories of brilliant innovations and inventions by the world’s greatest minds.

Enjoy these NOVA staff favorites.

Repeat Signage software has a number of free tools including the Batch PDF splitter. This shows you how to add your PDF to a folder and create an empty output folder. Then click run and in seconds, individual PDF pages appear in your output folder, leaving the original PDF as it was.

Director Wendy Sachs attributes the steep rise in antisemitism to social media, from where so many young people get news that has no validation.

The end of the pay dispute sounded too good to be true. And now some are wondering if it might be.

Covid inquiry hears harrowing testimony from ex-adviser in emergency preparedness at NHS England.

Sir Stephen Powis says points-based tool was drawn up should need to prioritise patients have arisen.

The new president tells the BBC thousands of illegal Zimbabweans should be given temporary permits.

Nadezhda Buyanova denied making the remarks and called the case absurd.

We are doing what we do best when something threatens the consumer supply chain: rushing to buy mountains of toilet paper. Experts say the dockworkers' strike won't result in shortages, but the panic-buying might so long as the panic-buying lasts.

"They cleaned out the toilet paper at my local Walmart in Virginia.

— Read the rest

The post Toilet paper buying panic recommences as dockworkers strike appeared first on Boing Boing.

Late last year I wrote about my transition from being work-driven to being life-driven. It hit a chord – many of you are on similar journeys, particularly those of us who are looking toward, and past, middle age. Buried a couple of thousand words into that post, in the section about what I was up … Continue reading "Introducing DOC"

It’s been quiet here for a few months. Yesterday I posted a longish piece on LinkedIn explaining why, and for those of you wondering what I’ve been up to lately, I figured I’d repost it here…. — DOC – The First Chapter More than 200 eclectic, incisive, and peripatetically curious folks gathered last week, bound … Continue reading "What I’ve Been Up To This Past Year: DOC"

Visual Abstract

Mouse embryonic stem cells (mESCs) display unique mechanical properties, including low cellular stiffness in contrast to differentiated cells, which are stiffer. We have previously shown that mESCs lacking the clathrin heavy chain (Cltc), an essential component for clathrin-mediated endocytosis (CME), display a loss of pluripotency and an enhanced expression of differentiation markers. However, it is not known whether physical properties such as cellular stiffness also change upon loss of Cltc, similar to what is seen in differentiated cells, and if so, how these altered properties specifically impact pluripotency. Using atomic force microscopy (AFM), we demonstrate that mESCs lacking Cltc display higher Young's modulus, indicative of greater cellular stiffness, compared with WT mESCs. The increase in stiffness was accompanied by the presence of actin stress fibers and accumulation of the inactive, phosphorylated, actin-binding protein cofilin. Treatment of Cltc knockdown mESCs with actin polymerization inhibitors resulted in a decrease in the Young's modulus to values similar to those obtained with WT mESCs. However, a rescue in the expression profile of pluripotency factors was not obtained. Additionally, whereas WT mouse embryonic fibroblasts could be reprogrammed to a state of pluripotency, this was inhibited in the absence of Cltc. This indicates that the presence of active CME is essential for the pluripotency of embryonic stem cells. Additionally, whereas physical properties may serve as a simple readout of the cellular state, they may not always faithfully recapitulate the underlying molecular fate.

Bone morphogenetic protein-9 (BMP-9) is a circulating cytokine that is known to play an essential role in the endothelial homeostasis and the binding of BMP-9 to the receptor activin-like kinase 1 (ALK-1) promotes endothelial cell quiescence. Previously, using an unbiased screen, we identified ALK-1 as a high-capacity receptor for low-density lipoprotein (LDL) in endothelial cells that mediates its transcytosis in a nondegradative manner. Here we examine the crosstalk between BMP-9 and LDL and how it influences their interactions with ALK-1. Treatment of endothelial cells with BMP-9 triggers the extensive endocytosis of ALK-1, and it is mediated by caveolin-1 (CAV-1) and dynamin-2 (DNM2) but not clathrin heavy chain. Knockdown of CAV-1 reduces BMP-9–mediated internalization of ALK-1, BMP-9–dependent signaling and gene expression. Similarly, treatment of endothelial cells with LDL reduces BMP-9–induced SMAD1/5 phosphorylation and gene expression and silencing of CAV-1 and DNM2 diminishes LDL-mediated ALK-1 internalization. Interestingly, BMP-9–mediated ALK-1 internalization strongly re-duces LDL transcytosis to levels seen with ALK-1 deficiency. Thus, BMP-9 levels can control cell surface levels of ALK-1, via CAV-1, to regulate both BMP-9 signaling and LDL transcytosis.

The cornea is densely innervated, mainly by sensory nerves of the ophthalmic branch of the trigeminal ganglia (TG). These nerves  are important to maintain corneal homeostasis, and nerve damage can lead to a decrease in wound healing, an increase in corneal ulceration and dry eye disease (DED), and neuropathic pain. Pathologies, such as diabetes, aging, viral and bacterial infection, as well as  prolonged use of contact lenses and surgeries to correct vision can produce nerve damage. There are no effective therapies to alleviate DED (a multifunctional disease) and several clinical trials using -3 supplementation show unclear and sometimes negative results. Using animal models of corneal nerve damage, we show that treating corneas with pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) increases nerve regeneration, wound healing, and tear secretion. The mechanism involves the activation of a calcium-independent phospholipase A2 (iPLA2) that releases the incorporated DHA from phospholipids and enhances the synthesis of docosanoids neuroprotectin D1 (NPD1) and a new resolvin stereoisomer  RvD6i. NPD1 stimulates the synthesis of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and of semaphorin 7A (Sema7A).  RvD6i treatment of injured corneas modulates gene expression in the TG resulting in enhanced neurogenesis; decreased neuropathic pain and increased sensitivity. Taken together, these results represent a promising therapeutic option to re-establish the homeostasis of the cornea.

α-Synuclein (α-Syn) is a protein implicated in the pathogenesis of Parkinson's disease (PD). It is an intrinsically disordered protein that binds acidic phospholipids. Growing evidence supports a role for α-Syn in membrane trafficking, including, mechanisms of endocytosis and exocytosis, although the exact role of α-Syn in these mechanisms is currently unclear. Here we investigate the associations of α-Syn with the acidic phosphoinositides (PIPs), phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2). Our results show that α-Syn colocalizes with PIP2 and the phosphorylated active form of the clathrin adaptor protein 2 (AP2) at clathrin-coated pits. Using endocytosis of transferrin as an indicator for clathrin-mediated endocytosis (CME), we find that α-Syn involvement in endocytosis is specifically mediated through PI(4,5)P2 levels on the plasma membrane. In accord with their effects on PI(4,5)P2 levels, the PD associated A30P, E46K, and A53T mutations in α-Syn further enhance CME in neuronal and nonneuronal cells. However, lysine to glutamic acid substitutions at the KTKEGV repeat domain of α-Syn, which interfere with phospholipid binding, are ineffective in enhancing CME. We further show that the rate of synaptic vesicle (SV) endocytosis is differentially affected by the α-Syn mutations and associates with their effects on PI(4,5)P2 levels, however, with the exception of the A30P mutation. This study provides evidence for a critical involvement of PIPs in α-Syn–mediated membrane trafficking.

Our purpose was to prospectively assess the distribution of NETPET scores in well-differentiated (WD) grade 2 and 3 gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and to determine the impact of the NETPET score on clinical management. Methods: This single-arm, institutional ethics review board–approved prospective study included 40 patients with histologically proven WD GEP NETs. ⁶⁸Ga-DOTATATE PET and ¹⁸F-FDG PET were performed within 21 d of each other. NETPET scores were evaluated qualitatively by 2 reviewers, with up to 10 marker lesions selected for each patient. The quantitative parameters that were evaluated included marker lesion SUV_max for each tracer; ¹⁸F-FDG/⁶⁸Ga-DOTATATE SUV_max ratios; functional tumor volume (FTV) and metabolic tumor volume (MTV) on ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET, respectively; and FTV/MTV ratios. The treatment plan before and after ¹⁸F-FDG PET was recorded. Results: There were 22 men and 18 women (mean age, 60.8 y) with grade 2 (n = 24) or grade 3 (n = 16) tumors and a mean Ki-67 index of 16.1%. NETPET scores of P0, P1, P2A, P2B, P3B, P4B, and P5 were documented in 2 (5%), 5 (12.5%), 5 (12.5%) 20 (50%), 2 (5%), 4 (10%), and 2 (5%) patients, respectively. No association was found between the SUV_max of target lesions on ⁶⁸Ga-DOTATATE and the SUV_max of target lesions on ¹⁸F-FDG PET (P = 0.505). ¹⁸F-FDG/⁶⁸Ga-DOTATATE SUV_max ratios were significantly lower for patients with low (P1–P2) primary NETPET scores than for those with high (P3–P5) primary NETPET scores (mean ± SD, 0.20 ± 0.13 and 1.68 ± 1.44, respectively; P < 0.001). MTV on ¹⁸F-FDG PET was significantly lower for low primary NETPET scores than for high ones (mean ± SD, 464 ± 601 cm³ and 66 ± 114 cm³, respectively; P = 0.005). A change in the type of management was observed in 42.5% of patients after ¹⁸F-FDG PET, with the most common being a change from systemic therapy to peptide receptor radionuclide therapy and from debulking surgery to systemic therapy. Conclusion: There was a heterogeneous distribution of NETPET scores in patients with WD grade 2 and 3 GEP NETs, with more than 1 in 5 patients having a high NETPET score and a frequent change in management after ¹⁸F-FDG PET. Quantitative parameters including ¹⁸F-FDG/⁶⁸Ga-DOTATATE SUV_max ratios in target lesions and FTV/MTV ratios can discriminate between patients with high and low NETPET scores.

Our objective is to explore quantitative imaging markers for early prediction of treatment response in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) undergoing [¹⁷⁷Lu]Lu-DOTATATE therapy. By doing so, we aim to enable timely switching to more effective therapies in order to prevent time-resource waste and minimize toxicities. Methods: Patients diagnosed with unresectable or metastatic, progressive, well-differentiated, receptor-positive GEP-NETs who received 4 sessions of [¹⁷⁷Lu]Lu-DOTATATE were retrospectively selected. Using SPECT/CT images taken at the end of treatment sessions, we counted all visible tumors and measured their largest diameters to calculate the tumor burden score (TBS). Up to 4 target lesions were selected and semiautomatically segmented. Target lesion peak counts and spleen peak counts were measured, and normalized peak counts were calculated. Changes in TBS (TBS) and changes in normalized peak count (nPC) throughout treatment sessions in relation to the first treatment session were calculated. Treatment responses were evaluated using third-month CT and were binarized as progressive disease (PD) or non-PD. Results: Twenty-seven patients were included (7 PD, 20 non-PD). Significant differences were observed in TBS_second-first, TBS_third-first, and TBS_fourth-first (where second-first, third-first, and fourth-first denote scan number between the second and first, third and first, and fourth and first [¹⁷⁷Lu]Lu-DOTATATE treatment cycles), respectively) between the PD and non-PD groups (median, 0.043 vs. –0.049, 0.08 vs. –0.116, and 0.109 vs. –0.123 [P = 0.023, P = 0.002, and P < 0.001], respectively). nPC_second-first showed significant group differences (mean, –0.107 vs. –0.282; P = 0.033); nPC_third-first and nPC_fourth-first did not reach statistical significance (mean, –0.122 vs. –0.312 and –0.183 vs. –0.405 [P = 0.117 and 0.067], respectively). At the optimal threshold, TBS_fourth-first exhibited an area under the curve (AUC) of 0.957, achieving 100% sensitivity and 80% specificity. TBS_second-first and TBS_third-first reached AUCs of 0.793 and 0.893, sensitivities of 71.4%, and specificities of 85% and 95%, respectively. nPC_second-first, nPC_third-first, and nPC_fourth-first showed AUCs of 0.764, 0.693, and 0.679; sensitivities of 71.4%, 71.4%, and 100%; and specificities of 75%, 70%, and 35%, respectively. Conclusion: TBS and nPC can predict [¹⁷⁷Lu]Lu-DOTATATE response by the second treatment session.

Canada ordered striking dock workers back to the ports of Vancouver, Prince Rupert and Montreal on Tuesday to clear out more than a week of container congestion bound for the United States and Canada.

2025 Luis J. Alvarez and Admiral Grace M. Hopper Postdoc Fellowship in Computing Sciences - 102564 Division: AC-Computing Luis J. Alvarez Postdoctoral Fellowship and Admiral Grace M. Hopper Postdoctoral Fellowship in Computing Sciences The Computing Sciences Area (https://cs.lbl.gov/) at Lawrence Berkeley National Laboratory (https://www.lbl.gov) is now accepting applications for two distinguished postdoctoral fellowships in Computing Sciences: • Luis W. Alvarez Postdoctoral Fellowship, and • Admiral Grace M. Hopper Postdoctoral Fellowship. Researchers in computer science, mathematics, data science, or any computational science discipline who have received their Ph.D. no earlier than January 1, 2022 but no later than September 30, 2025 are encouraged to apply. Only one (1) application is needed and it will be considered for both postdoctoral fellowships. The successful candidates will participate in research activities in computer science, mathematics, data science, or any computational science discipline of interest to the Computing Sciences Area and Berkeley Lab. Alvarez Fellows apply advances in computer science, mathematics, computational science, data science, machine learning or AI to computational modeling, simulations, and advanced data analytics for scientific discovery in materials science, biology, astronomy, environmental science, energy, particle physics, genomics, and other scientific domains. Hopper Fellows concentrate on the development and optimization of scientific and engineering applications leveraging high-speed network capability provided by the Energy Sciences Network or run on next-generation high performance computing and data systems hosted by the National Energy Research Scientific Computing Center at Berkeley Lab. Since its founding in 2002, Berkeley Lab’s Luis W. Alvarez Postdoctoral Fellowship (go.lbl.gov/alvarez) has cultivated exceptional early career scientists who have gone on to make outstanding contributions to computer science, mathematics, data science, and computational sciences. The Admiral Grace Hopper Postdoctoral Fellowship (go.lbl.gov/hopper) was first awarded in 2015 with the goal of enabling early career scientists to make outstanding contributions in computer science and high performance computing (HPC) research. About Computing Sciences at Berkeley Lab: Whether running extreme-scale simulations on a supercomputer or applying machine-learning or data analysis to massive datasets, scientists today rely on advances in and integration across applied mathematics, computer science, and computational science, as well as large-scale computing and networking facilities, to increase our understanding of ourselves, our planet, and our universe. Berkeley Labs Computing Sciences Area researches, develops, and deploys new tools and technologies to meet these needs and to advance research in our core capabilities of applied mathematics, computer science, data science, and computational science. In addition to fundamental advances in our core capabilities, we impact such areas as astrophysics and cosmology, accelerator physics, chemical science and materials science, combustion, fusion energy, nuclear physics, biology, climate change, and HPC systems and network technology. Research areas in Computing Sciences include but are not limited to: • Developing scientific applications and software technologies for extreme-scale and energy-efficient • Developing mathematical modeling for complex scientific problems • Designing algorithms to improve the performance of scientific applications • Researching digital and post-digital computer architectures for science • Developing and advancing extreme-scale scientific data management, analysis, and visualization • Developing and advancing next-generation machine learning, AI, and data science approaches for science • Advancing quantum computing and networking technologies, software, algorithms and applications • Evaluating or developing new and promising HPC systems and networking technologies • Researching methods to control and manage next-generation networks • Managing scientific data and workflows in distributed environments Qualifications: • Requires a Ph.D. in computer science, mathematics, computational science, or related discipline. • Candidates must have no more than 3 years of Postdoctoral Researcher or similar experience. • Expertise with advanced algorithms, software techniques, HPC systems and/or networking in a related research field. • Demonstrated creativity and the ability to perform independent research. • Demonstrated excellence in a related research field. • Ability to develop new cross-disciplinary partnerships that use advanced computational and/or mathematical techniques to produce unique lab capabilities. • Excellent communication skills with the ability to facilitate communications and collaborations with internal and external stakeholders. Additional Desired Qualifications: • Knowledge of advanced computing and high-performance computing. Application Process: 1. As part of your application process, you must upload and submit the following materials with your online application. 1. Cover letter 2. CV, with publication list included 3. Research Statement (no more than five (5) pages in length when printed using standard letter-size (8.5 inch x 11 inch) paper with 1-inch margins (top, bottom, left, and right) and a font size not smaller than 11 point; figures and references cited, if included, must fit within the five-page limit) 4. Contact information (name, affiliation, and email address) of at least three (3) individuals who will be able to provide letters of reference. 2. Application deadline: October 31, 2024. * It is highly advisable that you have all the required application materials and information ready and available prior to completing and submitting your application. Your application will not be considered complete if any of the above information is missing. Tentative Application Timeline: The Computing Sciences Fellowship Selection Committee is made up of a diverse representation of scientists and engineers across Berkeley Lab’s Computing Sciences Area who will conduct a thorough review of all applications received. • Application deadline: October 31, 2024 • Review and Selection: October 2024 - December 2024 • Decisions made: January/February 2025 Want to learn more about working at Berkeley Lab? Please visit: careers.lbl.gov How To Apply Apply directly online at http://50.73.55.13/counter.php?id=290341 and follow the on-line instructions to complete the application process. Berkeley Lab is committed to inclusion, diversity, equity and accessibility and strives to continue building community with these shared values and commitments. Berkeley Lab is an Equal Opportunity and Affirmative Action Employer. We heartily welcome applications from women, minorities, veterans, and all who would contribute to the Labs mission of leading scientific discovery, inclusion, and professionalism. In support of our diverse global community, all qualified applicants will be considered for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, disability, age, or protected veteran status. Equal Opportunity and IDEA Information Links: Know your rights, click here (http://www.dol.gov/ofccp/regs/compliance/posters/ofccpost.htm) for the supplement: Equal Employment Opportunity is the Law and the Pay Transparency Nondiscrimination Provision (https://www.dol.gov/sites/dolgov/files/ofccp/pdf/pay-transp_%20English_formattedESQA508c.pdf) under 41 CFR 60-1.4.

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.

A federal judge on Tuesday sentenced former Massachusetts Air National Guardsman Jack Teixeira to 15 years in prison for stealing classified information and sharing it online.

Canada ordered striking dock workers back to the ports of Vancouver, Prince Rupert and Montreal on Tuesday to clear out more than a week of container congestion bound for the United States and Canada.

Scala Mercalli hosted by Italian environmentalist Luca Mercalli begins filming in the Sheikh Zayed Centre in FAO this week! 

Episodes will be shot in front of a live audience every Thursday [...]

FAO is making publically available for the first time, a series of internal documents relating to programme and project management, among others. These documents range from the guidelines on the [...]

Further to the Director-General’s speech delivered to the 159^th Session of the FAO Council this morning, Monday 4 June and specifically with reference to the letter from [...]

Kennedy Center president Deborah Rutter interviews the co-founder of MIT’s Little Devices Lab about democratizing health technology

Watch Dr. Suzan Murray perform her morning rounds (Kenneth R. Fletcher)

Selected by Martin Parr for our special issue, this up-and-coming photographer discusses his work

A new exhibition in New York City uses more than 200 texts and artifacts to contemplate Lincoln's rise to the nation's highest office

A woman who says she was repeatedly denied emergency care last spring is blasting the Newfoundland and Labrador health-care system, saying she’s been left psychologically scarred after being told several times that her gangrenous appendix was simply anxiety or constipation.

An exhibition at the Huntington Library, Art Museum and Botanical Gardens explores how Western intellectuals viewed the climate crisis between 1780 and 1930

CBC Winnipeg News host Brittany Greenslade speaks with Canadian gynecologist Dr. Jen Gunter, who is part of a Tuesday panel discussion about health misinformation and how to separate fact from fiction. It's part of Together Against Misinformation Week, a nationwide event that runs until Nov. 17.

The pay cut comes after city council had already taken a number of steps against the mayor, including stripping him of his duties as a city spokesperson, removing him from the Thompson Nicola Regional District board and Shuswap Watershed Council and relocating his office to the basement of city hall. 

A federal judge sentenced a Massachusetts Air National Guard member to 15 years in prison Tuesday for leaking classified military documents about the war in Ukraine, actions prosecutors said put the country's national security at risk, endangered other military members and damaged U.S. relationships with its allies.

Interactive 3D manuals increase customer appreciation and satisfaction

A Malagasy witch doctor comes to faith in Christ during an OM outreach and is baptised just one week before his death.

OM’s ships connect with local churches in every port of call. Existing fellowships have added new believers, and new churches have been planted in the wake of a ship visit.

On a recent outreach to several towns in the Amazon jungle, OM Peru worked with the Presbyterian Church of Moyabamba and its annexes.

A team from OM Costa Rica hikes three days in the jungle of Talamanca to meet a witch doctor.

The film follows three Indianapolis adults as they seek to overcome obstacles on the path to earning an educational credential that they missed earlier.