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Intraneuronal beta-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation

Holly Oakley
Oct 4, 2006; 26:10129-10140
Neurobiology of Disease




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Intraneuronal beta-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation

Holly Oakley
Oct 4, 2006; 26:10129-10140
Neurobiology of Disease




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FAO launches new South-South Cooperation Gateway: an information sharing platform

South-South Cooperation is the mutual sharing and exchange of development solutions - knowledge, experiences and good practices, policies, technology and resources - between and among countries in the global [...]




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Ask Smithsonian: Are Humans the Only Animals to Use the Stars to Navigate?

Yet another reason to fight light pollution




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Meet the Italian 'Fruit Detective' Who Investigates Centuries-Old Paintings for Clues About Produce That Has Disappeared From the Kitchen Table

Renaissance paintings, medieval archives, cloistered orchards—how one Italian scientist is uncovering secrets that could help combat a growing agricultural crisis




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Dextran Amine-Conjugated Neural Tracing in Mosquitoes

To understand the circuitry of the brain, it is often advantageous to visualize the processes of a single neuron or population of neurons. Identifying sites where a neuron, or neurons, originates and where it projects can allow a researcher to begin to map the circuitry underlying various processes, including sensory-guided behaviors. Furthermore, neural tracing allows one to map locations where processes terminate onto regions of the brain that may have known functions and sometimes to identify candidate upstream or downstream connections, based on proximity. Many methods of neural tracing are available; here, we focus on loading fluorescent dyes into a neuron (fluorescent dye filling). Different options for dyes exist to label neurites. Among the most versatile and easy to use are dextran amine–conjugated dyes. They fill neurons bidirectionally, not discriminating between anterograde or retrograde loading direction. Dye filling must be done in unfixed tissue, as the dye needs to move through the neurons; however, dextran amine conjugates are aldehyde-fixable and once cells have been fully loaded with dye the tissue can be fixed and subjected to immunostaining. Coupling neural tracing with immunofluorescence is a useful way to determine specific brain or ventral nerve cord (VNC) regions where a neuron projects. This protocol describes methods for loading dextran amine conjugated dyes into a sensory tissue in the mosquito to visualize sites of sensory neuron innervation in the central nervous system, as well as efferent projections to these structures. This protocol is described for Aedes aegypti, for which it was optimized, but it also works across a variety of insects.




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SolidWorks extends DWGgateway publishing capability to support Adobe PDF

DWGgateway plug-in lets AutoCAD users share designs with virtually anyone




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DWGgateway software provides free alternative to new AutoCAD upgrades

More than 100,000 AutoCAD software users download free compatibility solution from SolidWorks Corporation




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Penn State Tailgate Ambassadors help make game days less trashy

A group of students called Tailgate Ambassadors, supported by Penn State Sustainability, the Office of Physical Plant, and Pepsi, are working reduce the amount of waste generated on game days. This partnership is incentivizing fans to learn about game-day recycling — and offering prizes to those who do.




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Jesus on the front gate

The participants of the Intensive Training programme begin neighbourhood evangelism by gluing paintings about God's love to the sides of their front gate.





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DOJ secures Manafort and Gates-connected entity dissolutions 

The Delaware Department of Justice secured Friday a Court of Chancery ruling dissolving four LLCs and two corporations owned by Paul J. Manafort, Jr. and Richard W. Gates, III after the Court approved an Order granting a default judgment. “This is another victory for the integrity of Delaware’s corporate brand,” said Attorney General Jennings. “Paul Manafort […]



  • Department of Justice
  • Department of Justice Press Releases
  • News

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DOJ secures Manafort and Gates-connected entity dissolutions

The Delaware Department of Justice secured Friday a Court of Chancery ruling dissolving four LLCs and two corporations owned by Paul J. Manafort, Jr. and Richard W. Gates, III after the Court approved an Order granting a default judgment. “This is another victory for the integrity of Delaware’s corporate brand,” said Attorney General Jennings. “Paul Manafort and […]



  • Department of Justice
  • Department of Justice Press Releases
  • News

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Cartoon: Gated-Ade

Young entrepreneurs are crushing it on collecting personal data




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Want to use Transmission Gate in my design?

I want to use a transmission gate in my design, but it is not available as a standard cell for Genus RTL synthesis. How can I perform an analysis of area, power, and critical path delay that includes the transmission gate alongside standard cells?

Could you provide guidance or a methodology for integrating custom cells, like the transmission gate, into the synthesis flow for accurate analysis?




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Characterization of Full adder that use transmission gates using liberate

Hello,
I'm trying to characterize a full adder that use transmission gate.
Unfortunately, the power calculation are wrong for the cell are always negative.
Is there any method or commands that can can help in power calculation or add the power consumption by the input pins to the power calculation ?
Another question, Is liberate support the characterization or transmission gate cells as standard cells or I should use liberate AMS for these type of cells ?
Thanks in advance,
Tareq 




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Is Design Power Estimation Lowering Your Power? Delegate and Relax!

The traditional methods of power analysis lag by various shortcomings and challenges:

  • Getting an accurate measure of RTL power consumption during design exploration
  • Getting consistent power through the design progress from RTL to P&R.
  • System-level verification tools are disconnected from the implementation tools that translate RTL to gates and wires.

The Cadence Joules RTL Power Solution closes this gap by delivering time-based RTL power analysis with system-level runtimes, capacity, and high-quality estimates of gates and wires based on production implementation technology. The Cadence Joules RTL Power Solution is an RTL power analysis tool that provides a unified engine to compute gate netlist power and estimate RTL power. The Joules solution delivers 20X faster time-based RTL power analysis and can analyze multi-million instance designs overnight, with impressive accuracy within 15% of signoff power.

Moreover, it integrates seamlessly with numerous Cadence platforms, eliminating compatibility and correlation issues! In addition, the Joules RTL Power Solution GUI (Graphical User Interface) helps you analyze/debug the power estimation/results using several GUI capabilities.

Want to take a tour of this power estimation world? Gear up to attend the training class created just for you to dive deep into the entire flow and explore this exciting power estimation method/flow with hands-on labs in two days!

Training

In the Joules Power Calculator Training course, you will identify solutions and features for RTL power using Cadence Joules RTL Power Solution. You will set up and run the RTL power flow with Joules RTL Power Solution and identify Joules's Graphical User Interface (GUI) capabilities. The training also explores how you can estimate power using vectorless power, stimulus flow, RTL Stim to Gate flow, and replay flow, and also interfaces Joules with Cadence's Palladium Emulation Platform. You will estimate power at the chip level and understand how to navigate the design and data mining using Joules.

The training also covers power exploration features and how to analyze ideal power and ODC-driven sequential clock gating. You will identify low-activity registers at the clock gate. You will also identify techniques to analyze power, generate various reports, and analyze results through Joules GUI. The training covers multiple strategies to debug low stimulus annotation and how you can better correlate RTL power with signoff. You also identify Genus-Joules Integration. In addition, we ensure that your learning journey is smooth with hands-on labs covering various design scenarios.

Lab Videos

To start you on your exciting journey as an RTL power analysis expert, we have created a series of short channel lab videos on our Customer Support site: Lab Demo: Setting Up and Running Basic RTL Power Flow in Joules RTL Power Solution (Video). You can refer to each lab module's instructions in demo format. This will help accelerate your tool ramp-up and help you perform the lab steps more quickly if you are stuck. You might be a beginner in the RTL power analysis world, but we can help you sail through it smoothly.

What's Next?

Grab your badge after finishing the training and flaunt your expertise!

Related Training

Related Blogs




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Free State Department of Education halts food sales inside and outside schools gates amid cases of food poisoning




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Palau’s president secures 2nd term amid attempt to navigate US-China competition

Taipei, Taiwan — Palau’s President Surangel Whipps Jr. has secured another term in office after defeating former President Tommy Remengesau Jr. in its Nov. 5 election that was closely monitored. Palau sits on the front line of competition for geopolitical influence between the United States and China in the Pacific Ocean. Analysts say the outcome shows more Palauan voters support Whipps’ policy agenda, which includes tax reforms and deeper engagement with the United States. “It seems Palau’s closer relationship with the United States under Whipps Jr.’s leadership makes sense for the majority of Palauans,” said Henryk Szadziewski, an expert on Pacific affairs at the University of Hawaii at Manoa. While election authorities still haven’t finished counting absentee ballots, Whipps has won the vote with one of the biggest margins in Palau’s electoral history, 57.5%. Remengesau, who is Whipps’ brother-in-law, took 41.3%. Whipps thanked supporters for allowing him to continue “building on the progress” that his administration has achieved over the last four years. “Your decision to grant me a second term as president is a responsibility I hold with the utmost respect,” he said in a statement shared with VOA on Monday. The president can only have two consecutive four-year terms and must step down after that, but he can run again after a four-year gap in between. Remengesau has served a total of four terms already. Separately, the spokesperson for Palau’s election commission told Radio New Zealand the following day that it was “highly unlikely” that Whipps would lose the election. Meanwhile, in a concession speech broadcast by a local radio station, the Palau Wave Productions, on November 7, Remengesau said the election is finished and the Palauan people have “spoken through a peaceful and free election.” Palau has a population of around 20,000 people and is situated around 890 kilometers (550 miles) east of the Philippines. It is one of three Pacific Island countries that receive significant economic support from the U.S. under agreements known as the Compacts of Free Association, or COFA. Under the accords, the U.S. provides economic aid worth billions of dollars, while Palau, the Marshall Islands, and the Federated States of Micronesia give the U.S. exclusive military access to their land, water and airspace, as well as the right to deny China access to their ports and territorial waters. In September, U.S. lawmakers passed funding for key provisions in COFA for Palau. The U.S. military is also helping to repair a runway on a World War II-era Japanese airfield on the island of Peleliu and installing two radar systems on Palau. Experts say they expect Palau to keep deepening ties with the U.S. during Whipps’ second term and relevant efforts will likely include increasing the frequency of U.S. military visits and enhancing connectivity with Palau. “There’s going to be a much stronger U.S. presence in terms of military visits, joint actions to combat transnational crime and illegal fishing, and boost transport and digital connectivity,” Meg Keen, a senior fellow at the Lowy Institute in Australia, told VOA by phone. During his first term, Whipps repeatedly said “presence is deterrence,” referring to the increased U.S. military presence in Palau, and characterized the Pacific island country as “part of the U.S. homeland” when it comes to security. In an interview with VOA last month, Whipps said U.S. protection plays a key role in safeguarding Palau’s territorial integrity. “Since Palau is small, having the protection of the United States is important because we see what’s happening now in the South China Sea between the Philippines and China,” he said during an interview at his office in Koror, Palau. Since 2023, the Chinese and Philippine coast guards have repeatedly confronted each other at several disputed shoals that both sides claim to be their territories. While Beijing views almost the entire South China Sea as its territorial water, a 2016 ruling by an international arbitration court found that most Chinese claims in the South China Sea were invalid. Beijing refuses to abide by the ruling. While many Palauans support the Whipps administration’s efforts to deepen security ties with the U.S., some political observers say some Palauans are still concerned about the negative impacts associated with the increased U.S. military presence across the Pacific island country. “Some Palauan people hold this apprehensiveness about the implication of increased U.S. military presence in Palau because they rarely saw U.S. soldiers in military uniforms in the past,” Kambes Kesolei, editor of one of Palau’s main newspapers, Tia Belau, told VOA by phone. “Some Palauans wonder what they can do to prevent Palau from becoming over-militarized,” he added. In addition to deepening ties with the U.S., some analysts say Palau will maintain its diplomatic ties with Taiwan, which could lead to “increased coercive pressure” from China. Beijing considers Taiwan part of its territory and has repeatedly vowed to reunite with the island, by force if necessary. “I expect ties between Palau and Taiwan to remain robust but increasing coercive pressure from the People’s Republic of China, [PRC,] may increase risks for Palau, which will need strong support from the U.S. and like-minded partners to maintain resiliency against PRC coercion,” Parker Novak, a nonresident fellow at the Atlantic Council's Global China Hub, told VOA in a written response. Whipps has accused China of weaponizing tourism against Palau and posing a wide range of threats to the Pacific island country’s national security, including cyberattacks and illegal incursion of Palau’s territorial water by Chinese vessels. “In 2015 and 2016, tourism numbers from China went through the roof, which helped Palau’s economy grow 30%, but since Palau never switched diplomatic recognition [from Taiwan] to China, that number just basically collapsed in the following years,” Whipps told VOA. In response to questions about Whipps’ claim that China has pressured Palau to sever diplomatic ties with Taiwan, Chinese foreign ministry spokesperson Mao Ning said during a regular press conference on November 4 that only a small number of countries, including Palau, still maintain diplomatic relations with Taiwan. “China urges these countries to fulfill their obligations under international law, stand on the right side of history, and make right decisions that truly serve their fundamental and long-term interests at an early date,” she said. While Whipps is likely to remain critical of China’s attempt to coerce Palau, Keen in Australia said the Palauan president is not going to completely “shut the door for China.” “He is very much wary of how China has used land and tourism to build pressure, but if the investment is in the national interests of Palau, he is willing to consider,” she told VOA.




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Public Protector declines to investigate Ramaphosa over Simelane loan scandal




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SIU investigates corruption allegations against SASRIA following July 2021 unrest




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When Unbelief Investigates a Miracle




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Russian frigate with hypersonic missiles conducts drills in English Channel, enters Atlantic


Russia started mass supplying its military with Zicron missiles to attempt to boost its nuclear forces.




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Strategic Patience can Mitigate Conflict Between Israel & Iran

How will Israel respond to Iran’s recent ballistic missiles barrage? “Strategic patience” is the best course. Israel has its hands full with Hamas and Hezbollah. Now is not the time to escalate a new major war with Iran, which could have nuclear implications. Israeli intelligence is still chafing from its failure to preempt Hamas’ attack […]




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Cuba’s Coastal Dwellers Mitigate the Effects of Climate Change



When the weather is bad, the residents of the Litoral neighborhood in Manzanillo, Cuba, are forced to evacuate their houses. When it’s calm, the sea penetrates the foundations of houses, leaving them vulnerable. Now the community is getting together to restore the mangroves and improve the environment to return their homes to safety.




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Developing Green and Inclusive Regional Gateway

The proposed Facility will finance five small-scale activities to support preparation and implementation of transformative projects. The activities will include feasibility studies, detailed designs, preparation of safeguard documents, financial and economic analysis and operation and maintenance for ensuing projects, as well as pilot-testing of advanced technologies and management approaches, extending capacity building and implementation support, governance reform support and knowledge products.




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Is life better as a dog? A philosopher investigates

What is it like to be a dog? And what can we learn from them? Mark Rowlands's take, in his book The Happiness of Dogs, is full of insights, finds Abigail Beall




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AI helps robot dogs navigate the real world

Four-legged robot dogs learned to perform new tricks by practising in a virtual platform that mimics real-world obstacles – a possible shortcut for training robots faster and more accurately




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Nonclinical Pharmacokinetics Study of OLX702A-075-16, N-Acetylgalactosamine Conjugated Asymmetric Small Interfering RNA (GalNAc-asiRNA) [Articles]

In this study, the nonclinical pharmacokinetics of OLX702A-075-16, an RNA interference therapeutic currently in development, were investigated. OLX702A-075-16 is a novel N-acetylgalactosamine conjugated asymmetric small-interfering RNA (GalNAc-asiRNA) used for the treatment of an undisclosed liver disease. Its unique 16/21-mer asymmetric structure reduces nonspecific off-target effects without compromising efficacy. We investigated the plasma concentration, tissue distribution, metabolism, and renal excretion of OLX702A-075-16 following a subcutaneous administration in mice and rats. For bioanalysis, high-performance liquid chromatography with fluorescence detection was used. The results showed rapid clearance from plasma (0.5 to 1.5 hours of half-life) and predominant distribution to the liver and/or kidney. Less than 1% of the liver concentration of OLX702A-075-16 was detected in the other tissues. Metabolite profiling using liquid chromatography coupled with high-resolution mass spectrometry revealed that the intact duplex OLX702A-075-16 was the major compound in plasma. The GalNAc moiety was predominantly metabolized from the sense strand in the liver, with the unconjugated sense strand of OLX702A-075-16 accounting for more than 95% of the total exposure in the rat liver. Meanwhile, the antisense strand was metabolized by the sequential loss of nucleotides from the 3'-terminus by exonuclease, with the rat liver samples yielding the most diverse truncated forms of metabolites. Urinary excretion over 96 hours was less than 1% of the administered dose in rats. High plasma protein binding of OLX702A-075-16 likely inhibited its clearance through renal filtration.

SIGNIFICANCE STATEMENT

This study presents the first comprehensive characterization of the in vivo pharmacokinetics of GalNAc-asiRNA. The pharmacokinetic insights gained from this research will aid in understanding toxicology and efficacy, optimizing delivery platforms, and improving the predictive power of preclinical species data for human applications.




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Ghrelin Modulates Voltage-Gated Ca2+ Channels through Voltage-Dependent and Voltage-Independent Pathways in Rat Gastric Vagal Afferent Neurons [Article]

The orexigenic gut peptide ghrelin is an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHSR1a). Systemic ghrelin administration has previously been shown to increase gastric motility and emptying. While these effects are known to be mediated by the vagus nerve, the cellular mechanism underlying these effects remains unclear. Therefore, the purpose of the present study was to investigate the signaling mechanism by which GHSR1a inhibits voltage-gated Ca2+ channels in isolated rat gastric vagal afferent neurons using whole-cell patch-clamp electrophysiology. The ghrelin pharmacological profile indicated that Ca2+ currents were inhibited with a log (Ic50) = –2.10 ± 0.44 and a maximal inhibition of 42.8 ± 5.0%. Exposure to the GHSR1a receptor antagonist (D-Lys3)-GHRP-6 reduced ghrelin-mediated Ca2+ channel inhibition (29.4 ± 16.7% vs. 1.9 ± 2.5%, n = 6, P = 0.0064). Interestingly, we observed that activation of GHSR1a inhibited Ca2+ currents through both voltage-dependent and voltage-independent pathways. We also treated the gastric neurons with either pertussis toxin (PTX) or YM-254890 to examine whether the Ca2+ current inhibition was mediated by the Gαi/o or Gαq/11 family of subunits. Treatment with both PTX (Ca2+ current inhibition = 15.7 ± 10.6%, n = 8, P = 0.0327) and YM-254890 (15.2 ± 11.9%, n = 8, P = 0.0269) blocked ghrelin’s effects on Ca2+ currents, as compared with control neurons (34.3 ± 18.9%, n = 8). These results indicate GHSR1a can couple to both Gαi/o and Gαq/11 in gastric vagal afferent neurons. Overall, our findings suggest GHSR1a-mediated inhibition of Ca2+ currents occurs through two distinct pathways, offering necessary insights into the cellular mechanisms underlying ghrelin’s regulation of gastric vagal afferents.

SIGNIFICANCE STATEMENT

This study demonstrated that in gastric vagal afferent neurons, activation of GHSR1a by ghrelin inhibits voltage-gated Ca2+ channels through both voltage-dependent and voltage-independent signaling pathways. These results provide necessary insights into the cellular mechanism underlying ghrelin regulation of gastric vagal afferent activity, which may benefit future studies investigating ghrelin mimetics to treat gastric motility disorders.




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SNP ministers urged to 'mitigate' UK Government's ‘chilling’ anti-terror strategy

Human rights campaigners are calling on SNP ministers to do all they can to “mitigate” Prevent, the UK Government's controversial anti-terror strategy.




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Limogate: Neil Gray to address use of ministerial car for football trips

Health Secretary Neil Gray will address concerns around his use of a ministerial car to attend football games at Hampden.




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Anderson Cooper Literally Calls Bulls*** on Surrogate’s Trump Defense

CNN

CNN anchor Anderson Cooper was flabbergasted Wednesday by a surrogate’s defense of Donald Trump, calling his explanation for the former president’s bombastic statements literal “bulls---.”

On AC360, former California Lieutenant Gov. Abel Maldonado, a Republican, said that Trump’s recent comments calling for the military to “handle” Democrats were simply his way of expressing his inner New Yorker. “He’s a fighter,” Maldonado added.

The conversation began when Cooper brought up Trump’s former chairman of the Joint Chiefs of Staff, Mark Milley, who, alongside other military leaders, have begun to warn of the dangers of re-electing the former president. Milley has called Trump a “fascist to his core.”

Read more at The Daily Beast.




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Baldur’s Gate 3's reactivity didn’t ruin Veilguard's linearity for me - it let me enjoy it more

Minor spoilers for the first few hours of Veilguard and heavy spoilers for Baldur’s Gate 3

For all the things I ended up enjoying about Dragon Age: The Veilguard, it isn’t much of an RPG. What little roleplaying it does offer revolves around what flavour of supportive hero you prefer, and you can count the number of impactful dialogue decisions on a three-fingered hand. This might sound utterly damning in the wake of Baldur's Gate 3’s incredible reactivity, and if I approached games as some sort of tedious comparative intellectual exercise rather than just, y’know, seeing how I felt about them, then I suppose it would be. Weirdly, though, the recent memory of Baldur’s Gate 3 didn’t diminish my time with Veilguard at all. It was actually the opposite: it freed Dragon Age from having to carry the torch for a certain period in Bioware’s history, and let me enjoy Veilguard for what it was.

Read more




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ESA prepares Hera mission to investigate aftermath of NASA DART impact

The European Space Agency's Hera spacecraft must be thoroughly tested before being sent to investigate the aftermath of the collision of NASA's DART probe with Dimorphos




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Bill Gates's Netflix series offers some dubious ideas about the future

In What's Next? Bill Gates digs into AI, climate, inequality, malaria and more. But the man looms too large for alternative solutions to emerge, says Bethan Ackerley




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AI helps robot dogs navigate the real world

Four-legged robot dogs learned to perform new tricks by practising in a virtual platform that mimics real-world obstacles – a possible shortcut for training robots faster and more accurately




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N.L. institution says due diligence on OceanGate wasn't necessary prior to Titan implosion

The Marine Institute and OceanGate signed a partnership in early 2023, but it remains unclear if the Memorial University campus knew the ill-fated Titan submersible was unregulated, unclassed and uncertified.



  • News/Canada/Nfld. & Labrador

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Emma Raducanu crowned BBC Sports Personality of the Year 2021 as Gareth Southgate scoops best coach award

Emma Raducanu has been crowned BBC Sports Personality of the Year on another history-defining night for Britain’s teenage phenomenon.

]]>




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Sportswomen of the year: The candid superstars who opened the floodgates to make sport stronger




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Scientists Investigate Inner Workings of DNA Methylation in Plants

DNA methylation is one of several epigenetic mechanisms crucial for regulating gene expression in eukaryotic organisms.

The post Scientists Investigate Inner Workings of DNA Methylation in Plants appeared first on Sci.News: Breaking Science News.




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South Africa investigates local shops as death toll passes 20

More than 20 people are believed to have died in one South African province after consuming food from local shops. Gauteng Premier Panyaza Lesufi said the majority of deaths have been children aged between six and nine. “The first uniform approach across the province was to adopt a mechanism of... Continue Reading




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Frontgate Sale: Take 25% Off Any One Item

Shop outdoor furniture, decor, bedding and more for your home at Frontgate.

[[ This is a content summary only. Visit my website for full links, other content, and more! ]]




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NASA completes spacecraft for TRACERS mission to investigate hazardous solar storms

Solar storms have the ability to harm astronauts and force massive blackouts




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‘Sikandar Ka Muqaddar’ trailer: Jimmy Shergill untiringly investigates a diamond heist

Tamannaah Bhatia, Avinash Tiwary and Rajiv Mehta play three unlikely suspects in director Neeraj Pandey’s latest




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Moss Agate: Meaning, Metaphysical Properties, and Healing Uses

Moss Agate meaning revolves around growth, emotional healing, and nature's balance. Discover its grounding energy and how it fosters abundance and inner peace.




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Agate Stone: Meaning, Uses, and How to Benefit from Its Energy

Discover agate meaning: learn how this beautiful crystal supports emotional healing, balance, and grounding energy, making it a must-have for spiritual wellness.





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YouTube Beauty Stylist Andrea Brooks Reveals Holiday Party Beauty Tips in Latest Colgate� Optic White� Smile Show� Episode �� - Video Sneak-Peek

Exclusive sneak-peek of how Andrea gets her #BrilliantSmile holiday ready in Episode 7 of The Smile Show.




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AI helps robot dogs navigate the real world

Four-legged robot dogs learned to perform new tricks by practising in a virtual platform that mimics real-world obstacles – a possible shortcut for training robots faster and more accurately