Karndean Design flooring has expanded its premium Art Select Woods collection by adding eleven new skillfully-crafted designs that replicate the beauty of natural timber.

The Pentagon on Wednesday disclosed additional capabilities selected for its Replicator initiative to get after fielding innovative technology rapidly at scale, which includes small drones from an Army program, loitering […]

Пентагон представил новую серию воздушных и морских беспилотников в рамках программы Replicator - масштабного проекта, направленного на ускорение поставок беспилотных систем вооружений в вооруженные силы США.

To celebrate the 85th anniversary of the Batman franchise, Warner Bros. is making 10 drivable replicas of the Caped Crusader's iconic Tumbler armored vehicle available for a cool US$3 million apiece.

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Category: Automotive, Transport

Tags: batman, Batmobile, Memorabilia, Car

A man flying a replica of a plane used by the U.S. Army Air Corps and British Royal Air Force in World War II had to make an emergency landing on U.S. Route 17 in Polk County, Florida, earlier this week.

Concerns about how movie studios will use AI helped fuel last year’s film and television strikes by the union, which lasted four months.

The post Robert Downey Jr. says he ‘intends to sue’ all future executives who use his AI replica appeared first on Boston.com.

The post Exploratory Studies to Investigate Mechanisms of HIV infection, Replication, Latency, and/or Pathogenesis in the Context of Substance Use Disorders (R01 Clinical Trial Not Allowed) [Letter of Intent Due Date: July 14] was curated by information for practice.

On-Demand Webinar > Watch Now!SPONSORED BY: Juniper NetworksWatch this FREE on-demand webinar to hear the experts walk you through the 10 most famous outages and how to make sure you avoid anything...

While computational reproducibility in scientific research is generally expected when the original data and code are available, lack of ability to replicate a previous study -- or obtain consistent results looking at the same scientific question but with different data -- is more nuanced and occasionally can aid in the process of scientific discovery, says a new congressionally mandated report from the National Academies of Sciences, Engineering, and Medicine.

Imagine giving one recipe to 10 different chefs and getting 10 completely different results. This inconsistency could be due to any number of factors — variables that cannot be controlled, omission of details, or shortcomings in design and execution.

The Time Machine car is deemed one of the top three most iconic movie cars. The crowd-funding window will be open for 30 days only.

Recording Venue: MongoSF, San Francisco Guest: Dwight Merriman As application data size and throughput have outgrown the processing and storage needs of commodity servers, replication has become an increasingly important strategy. In this episode, Robert talks with Dwight Merriman about database replication. Topics covered include replication basics, master-slave versus master-master, failure and recovery, replication versus […]

Suffering from a severe case of midlife crisis? Just won the lottery and need some ideas on what to spend it on? If your answer is "yes" to one or the other (or both), you might be interested in purchasing one of the ten Batman Tumbler replicas being made by Warner Bros. Discovery Global Consumer Products (WBDGCP) and Relevance International.

Ángel Víctor Torres asegura que los recursos desplegados por el Ejecutivo han salvado la vida de 36.907 personas, aboga por un "pacto de Estado" y anuncia un "alto comisionado" para la reconstrucción Leer

La empresa castellonense EnerHi trabaja en una modificación del mayor parque solar de la provincia, adaptado a «la realidad del terreno» y en acortar de 42 a 5 km la red de evacuación Leer

Gov. Gavin Newsom on Tuesday signed bills that offer actors more AI protections and address AI-generated false content in political ads.

The physical strain this type of motion work entails, and the hours put into it, are part of the reason why he believes all video-game performers should be protected equally from the use of unregulated artificial intelligence.

Is this ode to the Dark Lord of the Sith most impressive or does it choke on its own aspirations?

$50 Numskull SEGA Shenmue Ryo Hazuki Figure 10" 28cm Collectible Replica Statue Amazon

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Science experiments are not considered completely valid unless they can be replicated. Replicating an experiment is pretty much impossible unless you've been steeped in the various factors of scientific theory. And even if you are thoroughly trained in those factors, it's easy to lose track when you're doing a casual experiment at home. That goes double when your aim is to debunk something that you find obviously wrong.

Sage the Bad Naturalist jumped into such a debunking experiment with both feet, and then got entangled in them. She spent an entire year trying to replicate a dubious TikTok, which turned into an embarrassing adventure in how not to do science. But negative results are still results, and the goal of science is always to learn something. She bravely admits all the things she did wrong, because scientists have to have humility to be accepted. What's funniest is how many things went wrong, and how they all piled up to the end. What she ended up with is an amusing and rather charming video on the dangers of throwing your heart (and time) into debunking something you saw on the internet. -via Metafilter

DNA polymerases are today used throughout scientific research, biotechnology, and medicine, in part for their ability to interact with unnatural forms of DNA created by synthetic biologists. Here especially, natural DNA polymerases often do not have the “performance specifications” needed for transformative technologies. This creates a need for science-guided rational (or semi-rational) engineering to identify variants that replicate unnatural base pairs (UBPs), unnatural backbones, tags, or other evolutionarily novel features of unnatural DNA. In this review, we provide a brief overview of the chemistry and properties of replicative DNA polymerases and their evolved variants, focusing on the Klenow fragment of Taq DNA polymerase (Klentaq). We describe comparative structural, enzymatic, and molecular dynamics studies of WT and Klentaq variants, complexed with natural or noncanonical substrates. Combining these methods provides insight into how specific amino acid substitutions distant from the active site in a Klentaq DNA polymerase variant (ZP Klentaq) contribute to its ability to replicate UBPs with improved efficiency compared with Klentaq. This approach can therefore serve to guide any future rational engineering of replicative DNA polymerases.

Replication protein A (RPA) is a eukaryotic ssDNA-binding protein and contains three subunits: RPA70, RPA32, and RPA14. Phosphorylation of the N-terminal region of the RPA32 subunit plays an essential role in DNA metabolism in processes such as replication and damage response. Phosphorylated RPA32 (pRPA32) binds to RPA70 and possibly regulates the transient RPA70-Bloom syndrome helicase (BLM) interaction to inhibit DNA resection. However, the structural details and determinants of the phosphorylated RPA32–RPA70 interaction are still unknown. In this study, we provide molecular details of the interaction between RPA70 and a mimic of phosphorylated RPA32 (pmRPA32) using fluorescence polarization and NMR analysis. We show that the N-terminal domain of RPA70 (RPA70N) specifically participates in pmRPA32 binding, whereas the unphosphorylated RPA32 does not bind to RPA70N. Our NMR data revealed that RPA70N binds pmRPA32 using a basic cleft region. We also show that at least 6 negatively charged residues of pmRPA32 are required for RPA70N binding. By introducing alanine mutations into hydrophobic positions of pmRPA32, we found potential points of contact between RPA70N and the N-terminal half of pmRPA32. We used this information to guide docking simulations that suggest the orientation of pmRPA32 in complex with RPA70N. Our study demonstrates detailed features of the domain-domain interaction between RPA70 and RPA32 upon phosphorylation. This result provides insight into how phosphorylation tunes transient bindings between RPA and its partners in DNA resection.

Programmed ribosomal frameshifting (PRF) is a mechanism used by arteriviruses like porcine reproductive and respiratory syndrome virus (PRRSV) to generate multiple proteins from overlapping reading frames within its RNA genome. PRRSV employs −1 PRF directed by RNA secondary and tertiary structures within its viral genome (canonical PRF), as well as a noncanonical −1 and −2 PRF that are stimulated by the interactions of PRRSV nonstructural protein 1β (nsp1β) and host protein poly(C)-binding protein (PCBP) 1 or 2 with the viral genome. Together, nsp1β and one of the PCBPs act as transactivators that bind a C-rich motif near the shift site to stimulate −1 and −2 PRF, thereby enabling the ribosome to generate two frameshift products that are implicated in viral immune evasion. How nsp1β and PCBP associate with the viral RNA genome remains unclear. Here, we describe the purification of the nsp1β:PCBP2:viral RNA complex on a scale sufficient for structural analysis using small-angle X-ray scattering and stochiometric analysis by analytical ultracentrifugation. The proteins associate with the RNA C-rich motif as a 1:1:1 complex. The monomeric form of nsp1β within the complex differs from previously reported homodimer identified by X-ray crystallography. Functional analysis of the complex via mutational analysis combined with RNA-binding assays and cell-based frameshifting reporter assays reveal a number of key residues within nsp1β and PCBP2 that are involved in complex formation and function. Our results suggest that nsp1β and PCBP2 both interact directly with viral RNA during formation of the complex to coordinate this unusual PRF mechanism.

Viral infection is one environmental factor that may contribute to the initiation of pancreatic β-cell destruction during the development of autoimmune diabetes. Picornaviruses, such as encephalomyocarditis virus (EMCV), induce a pro-inflammatory response in islets leading to local production of cytokines, such as IL-1, by resident islet leukocytes. Furthermore, IL-1 is known to stimulate β-cell expression of iNOS and production of the free radical nitric oxide. The purpose of this study was to determine whether nitric oxide contributes to the β-cell response to viral infection. We show that nitric oxide protects β-cells against virally mediated lysis by limiting EMCV replication. This protection requires low micromolar, or iNOS-derived, levels of nitric oxide. At these concentrations nitric oxide inhibits the Krebs enzyme aconitase and complex IV of the electron transport chain. Like nitric oxide, pharmacological inhibition of mitochondrial oxidative metabolism attenuates EMCV-mediated β-cell lysis by inhibiting viral replication. These findings provide novel evidence that cytokine signaling in β-cells functions to limit viral replication and subsequent β-cell lysis by attenuating mitochondrial oxidative metabolism in a nitric oxide–dependent manner.

Environmental factors, such as viral infection, are proposed to play a role in the initiation of autoimmune diabetes. In response to encephalomyocarditis virus (EMCV) infection, resident islet macrophages release the pro-inflammatory cytokine IL-1β, to levels that are sufficient to stimulate inducible nitric oxide synthase (iNOS) expression and production of micromolar levels of the free radical nitric oxide in neighboring β-cells. We have recently shown that nitric oxide inhibits EMCV replication and EMCV-mediated β-cell lysis and that this protection is associated with an inhibition of mitochondrial oxidative metabolism. Here we show that the protective actions of nitric oxide against EMCV infection are selective for β-cells and associated with the metabolic coupling of glycolysis and mitochondrial oxidation that is necessary for insulin secretion. Inhibitors of mitochondrial respiration attenuate EMCV replication in β-cells, and this inhibition is associated with a decrease in ATP levels. In mouse embryonic fibroblasts (MEFs), inhibition of mitochondrial metabolism does not modify EMCV replication or decrease ATP levels. Like most cell types, MEFs have the capacity to uncouple the glycolytic utilization of glucose from mitochondrial respiration, allowing for the maintenance of ATP levels under conditions of impaired mitochondrial respiration. It is only when MEFs are forced to use mitochondrial oxidative metabolism for ATP generation that mitochondrial inhibitors attenuate viral replication. In a β-cell selective manner, these findings indicate that nitric oxide targets the same metabolic pathways necessary for glucose stimulated insulin secretion for protection from viral lysis.

DNA polymerase from bacteriophage T7 undergoes large, substrate-induced conformational changes that are thought to account for high replication fidelity, but prior studies were adversely affected by mutations required to construct a Cys-lite variant needed for site-specific fluorescence labeling. Here we have optimized the direct incorporation of a fluorescent un-natural amino acid, (7-hydroxy-4-coumarin-yl)-ethylglycine, using orthogonal amber suppression machinery in Escherichia coli. MS methods verify that the unnatural amino acid is only incorporated at one position with minimal background. We show that the single fluorophore provides a signal to detect nucleotide-induced conformational changes through equilibrium and stopped-flow kinetic measurements of correct nucleotide binding and incorporation. Pre-steady-state chemical quench methods show that the kinetics and fidelity of DNA replication catalyzed by the labeled enzyme are largely unaffected by the unnatural amino acid. These advances enable rigorous analysis to establish the kinetic and mechanistic basis for high-fidelity DNA replication.

The origin recognition complex (ORC), composed of six subunits, ORC1–6, binds to origins of replication as a ring-shaped heterohexameric ATPase that is believed to be essential to recruit and load MCM2–7, the minichromosome maintenance protein complex, around DNA and initiate DNA replication. We previously reported the creation of viable cancer cell lines that lacked detectable ORC1 or ORC2 protein without a reduction in the number of origins firing. Here, using CRISPR-Cas9–mediated mutations, we report that human HCT116 colon cancer cells also survive when ORC5 protein expression is abolished via a mutation in the initiator ATG of the ORC5 gene. Even if an internal methionine is used to produce an undetectable, N terminally deleted ORC5, the protein would lack 80% of the AAA+ ATPase domain, including the Walker A motif. The ORC5-depleted cells show normal chromatin binding of MCM2–7 and initiate replication from a similar number of origins as WT cells. In addition, we introduced a second mutation in ORC2 in the ORC5 mutant cells, rendering both ORC5 and ORC2 proteins undetectable in the same cells and destabilizing the ORC1, ORC3, and ORC4 proteins. Yet the double mutant cells grow, recruit MCM2–7 normally to chromatin, and initiate DNA replication with normal number of origins. Thus, in these selected cancer cells, either a crippled ORC lacking ORC2 and ORC5 and present at minimal levels on the chromatin can recruit and load enough MCM2–7 to initiate DNA replication, or human cell lines can sometimes recruit MCM2–7 to origins independent of ORC.

Faithful replication of the mitochondrial genome is carried out by a set of key nuclear-encoded proteins. DNA polymerase γ is a core component of the mtDNA replisome and the only replicative DNA polymerase localized to mitochondria. The asynchronous mechanism of mtDNA replication predicts that the replication machinery encounters dsDNA and unique physical barriers such as structured genes, G-quadruplexes, and other obstacles. In vitro experiments here provide evidence that the polymerase γ heterotrimer is well-adapted to efficiently synthesize DNA, despite the presence of many naturally occurring roadblocks. However, we identified a specific G-quadruplex–forming sequence at the heavy-strand promoter (HSP1) that has the potential to cause significant stalling of mtDNA replication. Furthermore, this structured region of DNA corresponds to the break site for a large (3,895 bp) deletion observed in mitochondrial disease patients. The presence of this deletion in humans correlates with UV exposure, and we have found that efficiency of polymerase γ DNA synthesis is reduced after this quadruplex is exposed to UV in vitro.

A London blacksmith has perfected a technique known as pattern welding to create elaborately-designed replica Saxon swords and knives. He demonstrates his technique on camera.

Featuring more than 100 original artifacts, a new immersive exhibition in New York City will explore the young Jewish diarist's life and legacy

Here's all you need to know about the two vendors that deal with the finest quality Rolex replica watches

The default behaviour of Place replicate update is to select every new net item connected to the replicate module. This leads to an abundant number of clines, vias and shapes being selected, most of which I don't want to add to the replicate group. It is very tedious to unselect all these items and more often than not, I miss one or two items and then end up with a via or cline in a completely different place on the board or outside of the board.

Is there a way to change this rather annoying behaviour? I haven't found any way to disable it or to batch deselect everything the tool has decided to add to the replicate group.

The question has been asked before, but it didn't get any answers and the thread is now locked.

/F

This video introduces a new publication presenting five case studies of projects in the People's Republic of China that illustrate how effective solutions to environmental and social problems have been applied in different contexts.

Title: How Reliable Are Medical Studies? Half of Findings Couldn't Be Replicated
Category: Health News
Created: 8/27/2015 12:00:00 AM
Last Editorial Review: 8/28/2015 12:00:00 AM

Our Future Chronicles column explores an imagined history of inventions and developments yet to come. This time, Rowan Hooper takes us to the early 2030s, when a technological step change enabled us to produce all the food we needed without the use of animals

"Jack Reacher: Never Go Back"; Director: Edward Zwick; Cast: Tom Cruise, Cobie Smulders, Aldis Hodge, Danika Yarosh, Patrick Heusinger, Holt McCallany, Robert Knepper; Rating: **1/2

John Hatleberg creates replicas of famous diamonds. Watch as the conceptual gem artist takes us all the way through his process, from making molds of original famous diamonds to cutting his own versions.

In cells, inhibitor created by fragment-based drug design prevents rhinovirus from reproducing

Akash Kamble fell in love when he was a little boy. And once he set eyes on her languid, unending, lithe body, he was hooked.

His mother would take him along on the Mumbai local, from Bhayandar to Charni Road every day, so that her in-laws could babysit while she finished a day's work at her Fort office. Travelling in the train, watching it fly past through the window grill, had Kamble realise he loved trains deeply enough to work around them.

To acquire the weather beaten look of a diesel locomotive, Kamble uses candle light against the aluminium sheets

"I would observe them carefully during the commute and went on to make my first cardboard train model of a two-coach local when I was in Class VIII," says Kamble, 23, who is a mechanical engineer and holds the job of a Station Master with the Mumbai Monorail.

The rail model enthusiast thought the lockdown was the perfect opportunity to wrap up a few more models. He has, in the last five weeks, made 11 models of hi-class trains, from locomotives to local coaches.

"I first started with cardboard and foam-based train and engine models, but later moved to working with aluminium. My research involves reading about trains, their specifications and poring over their drawings. I make models of 1:35 scale, realistic and a perfect match [to the original]. The continuous involvement slowly leads to perfection," says Kamble, a resident of Ambernath, adding, "I have made a model of the most powerful green coloured WAG-9 electric locomotive and two coaches of the Garib Rath train. Besides this, one of my favourites is the diesel locomotive, a few coaches of the Mumbai local and a mail express."

He has also found the time to give finishing touches to earlier models, giving them a realistic feel. To acquire a weather beaten look of a diesel locomotive, he uses candle light against the aluminium sheets.

In 2019, Kamble joined what he calls his dream job. And, next on his agenda is to make a "replica of my employer". He has acquired drawings and technical specifications of the Mumbai Monorail and hopes to complete the project before the city chugs back to normal.

1:35
The ratio scale to which the mechanical engineer makes his models

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"Jack Reacher: Never Go Back"; Director: Edward Zwick; Cast: Tom Cruise, Cobie Smulders, Aldis Hodge, Danika Yarosh, Patrick Heusinger, Holt McCallany, Robert Knepper; Rating: **1/2

Pia Miller's nearest and dearest certainly know how to spoil her.  

The post Replicating whale fossils found in Chile appeared first on Smithsonian Insider.

While computational reproducibility in scientific research is generally expected when the original data and code are available, lack of ability to replicate a previous study -- or obtain consistent results looking at the same scientific question but with different data -- is more nuanced and occasionally can aid in the process of scientific discovery, says a new congressionally mandated report from the National Academies of Sciences, Engineering, and Medicine.

Imagine giving one recipe to 10 different chefs and getting 10 completely different results. This inconsistency could be due to any number of factors — variables that cannot be controlled, omission of details, or shortcomings in design and execution.

The era of ersatz Eames chairs and knockoff Noguchi coffee tables comes to an end.