An improved coupler-knuckle assembly is comprised of a coupler body, a knuckle, and at least two knuckle retainer plugs. The knuckle has an internal coring geometry that increases the cross-sectional area of the throat portion of the knuckle compared to previous designs. The present invention's knuckle design includes a top and a bottom tapered holes in the knuckle with a locking groove at the bottom of each tapered hole for the knuckle retainer plugs to snap into. The knuckle retainer plugs are inserted through the coupler body and into the tapered holes in the knuckle. The improved coupler-knuckle assembly of the present invention reduces fatigue on the coupler, knuckle, and knuckle pin, prevents misalignment of the coupler-knuckle assembly, and prevents knuckle pin breakage.

A system for filling a jar with powdery material, for example for the manufacture of nuclear fuel, including a device for connection between the jar and a material feed system, where the device includes: a stationary connection portion connected to the feed system,a connection portion which moves relative to the stationary connection portion intended to be connected to the container's filling orifice, where the moving connection portion includes in the area of a downstream end a lip seal to achieve a tight connection by contact with the contours of the jar's filling orifice and where the said downstream end is connected to the stationary connection portion by a bellows so as to provide mechanical disengagement between the downstream end of the moving connection portion and the stationary connection portion.

A method for filtration of harmful gas effluents from a nuclear power plant including the steps of providing a gas effluent from a nuclear power plant, the effluent including a mixture of gases; filtering the harmful, notably radioactive elements from the gas effluent by membrane separation through at least one membrane, the membrane separation being achieved by sifting, sorption and/or diffusion; storing the filtered harmful elements in storage reservoirs, and discharging the processed gas effluent to the atmosphere.

The invention relates to a device for dressing a grinding wheel, comprising a sleeve to hold a corundum rod laterally and to guide it along its longitudinal axis, a ram to apply constant thrust force onto the corundum rod held in place and guided in the sleeve, to bring it into contact with the grinding wheel, means of rigidly connecting the ram shaft to the end of the corundum rod, and linear guide means for the sleeve for translating the corundum rod parallel to the axis of the grinding wheel while keeping the rod pressed against the grinding wheel with a constant force. Application to a centerless grinder in which the grinding wheel is used to grind nuclear fuel pellets.

An improved apparatus strips HPNA's from hydroprocessed streams in a fractionation column having a split shell configuration. Only one vapor stripping feed is required to the split shell of the fractionation column. The resulting reduction in steam requirement provides a superior fractionation in the column.

The invention relates to polynucleotide agents targeting the complement component C5 gene, and methods of using such polynucleotide agents to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.

In one aspect, the invention relates to a method of loading exosomes with oligonucleotide cargo, by incubating an oligonucleotide comprising one or more hydrophobic modifications with a population of exosomes for a period of time sufficient to allow loading of the exosomes with the oligonucleotide. Exosomes loaded with hydrophobic ally modified oligonucleotide cargo, and uses thereof, are also provided.

Provided herein are compositions and methods for modifying a predetermined nucleic acid sequence. A programmable nucleoprotein molecular complex containing a polypeptide moiety and a specificity conferring nucleic acid (SCNA) which assembles in-vivo, in a target cell, and is capable of interacting with the predetermined target nucleic acid sequence is provided. The programmable nucleoprotein molecular complex is capable of specifically modifying and/or editing a target site within the target nucleic acid sequence and/or modifying the function of the target nucleic acid sequence.

Methods for controlled microstructure creation utilize seeding of amorphous layers prior to annealing. Seed crystals are formed on an amorphous layer or layers. The material, size, and spacing of the seed crystals may be varied, and multiple seed layers and/or amorphous layers may be utilized. Thereafter, the resulting assembly is annealed to generate a crystalline microstructure. Via use of these methods, devices having desirable microstructural properties are enabled.

A heat transfer system includes a substrate having a heat exchange region including a surface having an enhancement region including alternating regions of selectively placed plurality of nucleation sites and regions lacking selectively placed nucleation sites, such that bubble formation and departure during boiling of a liquid in contact with the enhancement region induces liquid motion over the surface of the regions lacking selectively placed nucleation sites sufficient to enhance both critical heat flux and heat transfer coefficient at the critical heat flux in the enhancement region of the system.

The Guns N' Roses rocker is embroiled in an online spat with the U.S. Secretary of the Treasury after putting the latter on blast in a foul-mouthed post on social media.

With the threat of nuclear war once again a part of the national conversation, Reveal looks at nuclear threats both foreign and domestic. This episode takes listeners to Iran and finds out what life is actually like inside North Korea.

As the Trump administration pushes for the biggest increase in spending on nuclear weapons since the Cold War, Reveal explores how they’ve changed. Instead of annihilation, think “flexible” nuclear weapons that can threaten “limited” nuclear war. That’s the idea anyway.

Head over to revealnews.org for more of our reporting.

Follow us on Facebook at fb.com/ThisIsReveal and on Twitter @reveal.

And to see some of what you’re hearing, we’re also on Instagram @revealnews.

By all accounts, 2020 has been, to put it mildly, a weird year. This week alone has already seen a 5-year-old boy from Utah attempt a solo drive to California on a mission to buy a Lamborghini, a llama named Winter emerge as a potential key player in the race for a treatment targeting the […]

By all accounts, 2020 has been, to put it mildly, a weird year. This week alone has already seen a 5-year-old boy from Utah attempt a solo drive to California on a mission to buy a Lamborghini, a llama named Winter emerge as a potential key player in the race for a treatment targeting the […]

ALBUQUERQUE, N.M. (AP) — A top nuclear security official says the U.S. must move ahead with plans to ramp up production of key components for the nation’s nuclear arsenal despite the challenges presented by the coronavirus. Federal officials have set a deadline of 2030 for increased production of the plutonium cores used in nuclear weapons. […]

ALBUQUERQUE, N.M. (AP) — A top nuclear security official says the U.S. must move ahead with plans to ramp up production of key components for the nation’s nuclear arsenal despite the challenges presented by the coronavirus. Federal officials have set a deadline of 2030 for increased production of the plutonium cores used in nuclear weapons. […]

By all accounts, 2020 has been, to put it mildly, a weird year. This week alone has already seen a 5-year-old boy from Utah attempt a solo drive to California on a mission to buy a Lamborghini, a llama named Winter emerge as a potential key player in the race for a treatment targeting the […]

The hope of nuclear fusion is the dream of a fossil-fuel free future - of limitless baseload power. Enthusiasts say fusion offers all the benefits of nuclear energy without the dangers. In theory and in practice fusion energy is already a reality, but getting the economics right is proving much more difficult than imagined.

Jervis Bay one of Australia's world-renowned coastal tourist hotspots, celebrated for its idyllic white beaches, nearly became home to Australia's first nuclear power plant.

FOI documents also reveal the Federal Government knows the process is creating division in small towns and causing some businesses to be boycotted.

Leonora, a small town in the West Australian Goldfields, is being touted as a suitable location for an underground, low and intermediate-level nuclear waste storage facility.

Legal action is threatening the latest proposed sites for storing nuclear waste in South Australia, and the debate is dividing communities and traditional owners.

A South Australian Aboriginal group loses a bid to stop a council ballot on whether a nuclear storage facility should be built on the Eyre Peninsula.

Thousands of scientists and soldiers once lived at the Maralinga nuclear site, but now it's home to just three people who are in love with the country.

In 44 seasons as Eaton's head coach from 1972 to 2015, Danley was 807-163-2, a Colorado-best for wins and tied for the nation's top prep winning percentage (83.1%).

Most nuclear data measurements are performed at accelerators large enough to occupy a geologic formation a kilometer wide. But a portable device that can reveal the composition of materials quickly on-site would greatly benefit cases such as in archaeology and nuclear arms treaty verification. Research published this week in AIP Advances used computational simulations to show that with the right geometric adjustments, it is possible to perform accurate neutron resonance transmission analysis in a device just 5 meters long.

Neutron star innards are not your mom’s lasagna.

Tyler Toffoli, who scored a hat trick in his last game with the Kings on Saturday, was traded to the Vancouver Canucks on Monday.

Among the elite private schools that have received federal loans amid COVID-19 is the Brentwood School in West L.A., which Mnuchin's children attend.

President Trump and Treasury Secretary Mnuchin say elite private schools with significant endowments shouldn't get Paycheck Protection Program loans.

The exclusive Brentwood School has returned money it received under the Paycheck Protection Program after President Trump and Treasury Secretary Mnuchin leveled criticism at private schools that took funds from the federal coronavirus aid program.

KIM JONG-UN is building a massive facility outside the capital Pyongyang, satellite images have shown, suggesting he is planning to beef up his stockpile of nuclear weapons.

A recent IAEA report on Iran’s nuclear program was portrayed by most Western mainstream media and politicians as new proof Iran is close to building nuclear weapons. The US Senate passed sanctions on Iran targeting its central bank in response.

However, the report does not say what the mainstream media and politicians claim. It has been much more guarded and much of it is about the state of Iran’s program up to 2003. After that period, the report is much more uncertain. Furthermore, many experts contend that the speculations (not definitive proof) that are in the report are misguided, too, leaning on unreliable sources, for example.

This update to the page on Iran has more information about this. Although the page is long, look for the new section about half way down under the heading of Regurgitating old stories as new information to justify sanctions?

Read full article: Iran

Bộ phim Cái chết của Stalin của đạo diễn Armando Iannucci đặt ra một câu hỏi có thể ứng với nhiều quốc gia khác trong lịch sử.

Assembled α-synuclein in nerve cells and glial cells is the defining pathological feature of neurodegenerative diseases called synucleinopathies. Seeds of α-synuclein can induce the assembly of monomeric protein. Here, we used sucrose gradient centrifugation and transiently transfected HEK 293T cells to identify the species of α-synuclein from the brains of homozygous, symptomatic mice transgenic for human mutant A53T α-synuclein (line M83) that seed aggregation. The most potent fractions contained Sarkosyl-insoluble assemblies enriched in filaments. We also analyzed six cases of idiopathic Parkinson's disease (PD), one case of familial PD, and six cases of multiple system atrophy (MSA) for their ability to induce α-synuclein aggregation. The MSA samples were more potent than those of idiopathic PD in seeding aggregation. We found that following sucrose gradient centrifugation, the most seed-competent fractions from PD and MSA brains are those that contain Sarkosyl-insoluble α-synuclein. The fractions differed between PD and MSA, consistent with the presence of distinct conformers of assembled α-synuclein in these different samples. We conclude that α-synuclein filaments are the main driving force for amplification and propagation of pathology in synucleinopathies.

Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2.

The ribosome biogenesis factor Las1 is an essential endoribonuclease that is well-conserved across eukaryotes and a newly established member of the higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain-containing nuclease family. HEPN nucleases participate in diverse RNA cleavage pathways and share a short HEPN nuclease motif (RφXXXH) important for RNA cleavage. Most HEPN nucleases participate in stress-activated RNA cleavage pathways; Las1 plays a fundamental role in processing pre-rRNA. Underscoring the significance of Las1 function in the cell, mutations in the human LAS1L (LAS1-like) gene have been associated with neurological dysfunction. Two juxtaposed HEPN nuclease motifs create Las1's composite nuclease active site, but the roles of the individual HEPN motif residues are poorly defined. Here using a combination of in vivo experiments in Saccharomyces cerevisiae and in vitro assays, we show that both HEPN nuclease motifs are required for Las1 nuclease activity and fidelity. Through in-depth sequence analysis and systematic mutagenesis, we determined the consensus HEPN motif in the Las1 subfamily and uncovered its canonical and specialized elements. Using reconstituted Las1 HEPN-HEPN' chimeras, we defined the molecular requirements for RNA cleavage. Intriguingly, both copies of the Las1 HEPN motif were important for nuclease function, revealing that both HEPN motifs participate in coordinating the RNA within the Las1 active site. We also established that conformational flexibility of the two HEPN domains is important for proper nuclease function. The results of our work reveal critical information about how dual HEPN domains come together to drive Las1-mediated RNA cleavage.

The CRISPR/Cas9 nucleases have been widely applied for genome editing in various organisms. Cas9 nucleases complexed with a guide RNA (Cas9–gRNA) find their targets by scanning and interrogating the genomic DNA for sequences complementary to the gRNA. Recognition of the DNA target sequence requires a short protospacer adjacent motif (PAM) located outside this sequence. Given that the efficiency of target location may depend on the strength of interactions that promote target recognition, here we sought to compare affinities of different Cas9 nucleases for their cognate PAM sequences. To this end, we measured affinities of Cas9 nucleases from Streptococcus pyogenes, Staphylococcus aureus, and Francisella novicida complexed with guide RNAs (gRNAs) (SpCas9–gRNA, SaCas9–gRNA, and FnCas9–gRNA, respectively) and of three engineered SpCas9–gRNA variants with altered PAM specificities for short, PAM-containing DNA probes. We used a “beacon” assay that measures the relative affinities of DNA probes by determining their ability to competitively affect the rate of Cas9–gRNA binding to fluorescently labeled target DNA derivatives called “Cas9 beacons.” We observed significant differences in the affinities for cognate PAM sequences among the studied Cas9 enzymes. The relative affinities of SpCas9–gRNA and its engineered variants for canonical and suboptimal PAMs correlated with previous findings on the efficiency of these PAM sequences in genome editing. These findings suggest that high affinity of a Cas9 nuclease for its cognate PAM promotes higher genome-editing efficiency.

20 April 2020

Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in the 21st century. Researchers at Chatham House have worked with eight experts to produce this collection of essays examining four contested themes in contemporary policymaking on deterrence.

1 May 2020

1 May 2020

Assembled α-synuclein in nerve cells and glial cells is the defining pathological feature of neurodegenerative diseases called synucleinopathies. Seeds of α-synuclein can induce the assembly of monomeric protein. Here, we used sucrose gradient centrifugation and transiently transfected HEK 293T cells to identify the species of α-synuclein from the brains of homozygous, symptomatic mice transgenic for human mutant A53T α-synuclein (line M83) that seed aggregation. The most potent fractions contained Sarkosyl-insoluble assemblies enriched in filaments. We also analyzed six cases of idiopathic Parkinson's disease (PD), one case of familial PD, and six cases of multiple system atrophy (MSA) for their ability to induce α-synuclein aggregation. The MSA samples were more potent than those of idiopathic PD in seeding aggregation. We found that following sucrose gradient centrifugation, the most seed-competent fractions from PD and MSA brains are those that contain Sarkosyl-insoluble α-synuclein. The fractions differed between PD and MSA, consistent with the presence of distinct conformers of assembled α-synuclein in these different samples. We conclude that α-synuclein filaments are the main driving force for amplification and propagation of pathology in synucleinopathies.

1 May 2020

HNF4α is a nuclear receptor produced as 12 isoforms from two promoters by alternative splicing. To characterize the transcriptional capacities of all 12 HNF4α isoforms, stable lines expressing each isoform were generated. The entire transcriptome associated with each isoform was analyzed as well as their respective interacting proteome. Major differences were noted in the transcriptional function of these isoforms. The α1 and α2 isoforms were the strongest regulators of gene expression whereas the α3 isoform exhibited significantly reduced activity. The α4, α5, and α6 isoforms, which use an alternative first exon, were characterized for the first time, and showed a greatly reduced transcriptional potential with an inability to recognize the consensus response element of HNF4α. Several transcription factors and coregulators were identified as potential specific partners for certain HNF4α isoforms. An analysis integrating the vast amount of omics data enabled the identification of transcriptional regulatory mechanisms specific to certain HNF4α isoforms, hence demonstrating the importance of considering all isoforms given their seemingly diverse functions.

The CRISPR/Cas9 nucleases have been widely applied for genome editing in various organisms. Cas9 nucleases complexed with a guide RNA (Cas9–gRNA) find their targets by scanning and interrogating the genomic DNA for sequences complementary to the gRNA. Recognition of the DNA target sequence requires a short protospacer adjacent motif (PAM) located outside this sequence. Given that the efficiency of target location may depend on the strength of interactions that promote target recognition, here we sought to compare affinities of different Cas9 nucleases for their cognate PAM sequences. To this end, we measured affinities of Cas9 nucleases from Streptococcus pyogenes, Staphylococcus aureus, and Francisella novicida complexed with guide RNAs (gRNAs) (SpCas9–gRNA, SaCas9–gRNA, and FnCas9–gRNA, respectively) and of three engineered SpCas9–gRNA variants with altered PAM specificities for short, PAM-containing DNA probes. We used a “beacon” assay that measures the relative affinities of DNA probes by determining their ability to competitively affect the rate of Cas9–gRNA binding to fluorescently labeled target DNA derivatives called “Cas9 beacons.” We observed significant differences in the affinities for cognate PAM sequences among the studied Cas9 enzymes. The relative affinities of SpCas9–gRNA and its engineered variants for canonical and suboptimal PAMs correlated with previous findings on the efficiency of these PAM sequences in genome editing. These findings suggest that high affinity of a Cas9 nuclease for its cognate PAM promotes higher genome-editing efficiency.