Digital solutions could revolutionize energy trading if they were adopted more widely across the market.

One of the first unbiased, major comprehensive reviews of blockchain has concluded that the technology is “actually delivering on its promises in a number of areas directly related to energy”.

This week independent power producer Marubeni and LO3 Energy said they have started a pilot project in Japan where LO3 will administer an energy marketplace using blockchain to connect a number of Marubeni’s power production facilities, including renewables, with offices and factories around Japan in a virtual marketplace. The project will simulate energy transactions to test the viability of the concept with the ultimate goal of creating a full-scale commercially operational network in the future.

Last week, the Energy Web Foundation (EWF) announced it had officially signed more than 100 affiliates in an effort to become the world’s largest blockchain ecosystem.

Grid technology firm Kaluza is investing in British blockchain company Electron.

Last week, the Energy Web Foundation (EWF) announced it had officially signed more than 100 affiliates in an effort to become the world’s largest blockchain ecosystem.

ABB is working with Italian utility Evolvere on how to use blockchain technology to deliver transparent and secure peer-to-peer energy transactions.

The Energy Web Foundation (EWF) this week announced that it has launched the world’s first public, open-source, enterprise-grade blockchain tailored to the energy sector: the Energy Web Chain (EW Chain). As a refresher, blockchain allows for peer-to-peer energy market transactions.

Clearway Energy Group, one of the U.S.’s largest clean power developers, is launching a pilot electronic marketplace for renewable energy credits as more states push for solar and wind projects.

Power infrastructure in the East African countries of Uganda, Kenya, Tanzania and Rwanda is inherently connected to their economic growth. As urbanisation and industrialisation fuel the need for electricity in cities, the demand for electricity in East Africa is expected to grow at approximately 5.3 percent per year until 2020. To meet these requirements, generation capacity would have to increase by 37.7 percent in Uganda, 96.4 percent in Kenya, 75.3 percent in Tanzania and 115 percent in Rwanda. The government, in conjunction with development partners, must build a more favourable business environment to facilitate growth.

Dream Global Partners (Dream Chain) announced on Sep 4th that it will launch a highly  reliable real estate blockchain platform for developers and final users. The blockchain  technology minimizes the possibility of malicious frauds or forged documents, because the ledger is store in a decentralized way and not concentrated in the availability of the parties involved. When this technology is applied to real estate transactions, sources of conflicts for pos...

On 31 March 2015, the German Federal Cartel Office (“Bundeskartellamt”, BKartA) announced that it has blocked the proposed takeover of approximately 450 Kaiser’s Tengelmann supermarket branches by EDEKA, the leading German food ret...

On 11 May 2016 the Commission blocked an acquisition of Teléfonica UK’s O2 by Hutchison 3G UK’s Three, casting doubt on the acceptability of ‘four to three’ mergers in the mobile sector. The Commission expressed concer...

The Covid-19 Block Exemption for the Retail Property Sector (the “Regulations”) were published on 24 March 2020 in response to the declaration of the National State of Disaster. The Regulations exempt certain agreements or practices with...

One of the most pondered questions following the U.S.’s withdrawal from the Joint Comprehensive Plan of Action (“JCPOA”) has been - how will the EU Blocking Regulation fair in protecting the interests of EU businesses trading with ...

In the first article of our blockchain series, we explained how the use of blockchain technology had the potential to offer s...

The petition demanded that the funds be directly transferred to Palestinian workers and needy families.

Press freedom in Bangladesh has been in decline long before the coronavirus came to our shores. Over the last decade, thanks to increasingly repressive media laws and highhanded measures adopted by the authorities, the health of journalism has been deteriorating in such a way that even the stalwarts of the fourth estate began to worry […]

The post Blocking media access during Covid-19 appeared first on Inter Press Service.

A group of irate youths got their lives handed to them when they attempted to block Deputy President William Ruto’s bloackade.

Hrithik Roshan had an extraordinary 2019, having made two hit movies in a row

Blockchain technology offers great promise and great risk. We need to better understand how it works and how to use it safely and effectively.

CHENNAI: The Kotturpuram branch of Indian Bank has invited tenders for auction of a property belonging to film producer and director Gautham Vasudev Menon in Adyar. As per details on Tenders India (a government tender information system), the auction process for the property located on First Main Road in Indira Nagar, has begun with the tender value being quoted at 12.26 crore. The winning bidder, expected to put up 50 lakh as a deposit. The property is 7,091 sqft, and the market price of each ground (2,400 sqft) in the area is 4.5 crore to 5 crore. “This particular account has been a non-performing asset (NPA) for some time and […]

Quarks are the subatomic particles thought to make up nearly everything we can see. Now it turns out they could be an illusion created by quantum trickery

Most molecules exist in mirror-image forms, and yet life prefers one over the other. How this bias began and why it persisted is one of the most baffling questions in biology – but now we have an answer

Most molecules exist in mirror-image forms, and yet life prefers one over the other. How this bias began and why it persisted is one of the most baffling questions in biology – but now we have an answer

Most molecules exist in mirror-image forms, and yet life prefers one over the other. How this bias began and why it persisted is one of the most baffling questions in biology – but now we have an answer

A 3D printed grate can be used to make a smart window that blocks heat from sunlight out in the summer while letting it through in the winter, conserving energy

Title: Secondhand Smoke Blocks Artery Repair
Category: Health News
Created: 4/30/2008 2:00:00 AM
Last Editorial Review: 4/30/2008 12:00:00 AM

Title: Smartphone App Blocks Teens From Texting, Phoning While Driving
Category: Health News
Created: 4/27/2015 12:00:00 AM
Last Editorial Review: 4/28/2015 12:00:00 AM

Title: How Is the Infraorbital Nerve Block Performed?
Category: Procedures and Tests
Created: 4/21/2020 12:00:00 AM
Last Editorial Review: 4/21/2020 12:00:00 AM

Title: How Do You Give a Mental Nerve Block?
Category: Procedures and Tests
Created: 4/21/2020 12:00:00 AM
Last Editorial Review: 4/21/2020 12:00:00 AM

Title: How Long Does a Retrobulbar Block Last?
Category: Procedures and Tests
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/24/2020 12:00:00 AM

There is a need to develop novel approaches to improve the balance between efficacy and toxicity for transcription factor–targeted therapies. In this study, we exploit context-dependent differences in RNA polymerase II processivity as an approach to improve the activity and limit the toxicity of the EWS-FLI1–targeted small molecule, mithramycin, for Ewing sarcoma. The clinical activity of mithramycin for Ewing sarcoma is limited by off-target liver toxicity that restricts the serum concentration to levels insufficient to inhibit EWS-FLI1. In this study, we perform an siRNA screen of the druggable genome followed by a matrix drug screen to identify mithramycin potentiators and a synergistic "class" effect with cyclin-dependent kinase 9 (CDK9) inhibitors. These CDK9 inhibitors enhanced the mithramycin-mediated suppression of the EWS-FLI1 transcriptional program leading to a shift in the IC₅₀ and striking regressions of Ewing sarcoma xenografts. To determine whether these compounds may also be liver protective, we performed a qPCR screen of all known liver toxicity genes in HepG2 cells to identify mithramycin-driven transcriptional changes that contribute to the liver toxicity. Mithramycin induces expression of the BTG2 gene in HepG2 but not Ewing sarcoma cells, which leads to a liver-specific accumulation of reactive oxygen species (ROS). siRNA silencing of BTG2 rescues the induction of ROS and the cytotoxicity of mithramycin in these cells. Furthermore, CDK9 inhibition blocked the induction of BTG2 to limit cytotoxicity in HepG2, but not Ewing sarcoma cells. These studies provide the basis for a synergistic and less toxic EWS-FLI1–targeted combination therapy for Ewing sarcoma.

ABSTRACT

In the absence of a vaccine, multidrug-resistant Neisseria gonorrhoeae has emerged as a major human health threat, and new approaches to treat gonorrhea are urgently needed. N. gonorrhoeae pili are posttranslationally modified by a glycan that terminates in a galactose. The terminal galactose is critical for initial contact with the human cervical mucosa via an interaction with the I-domain of complement receptor 3 (CR3). We have now identified the I-domain galactose-binding epitope and characterized its galactose-specific lectin activity. Using surface plasmon resonance and cellular infection assays, we found that a peptide mimic of this galactose-binding region competitively inhibited the N. gonorrhoeae-CR3 interaction. A compound library was screened for potential drugs that could similarly prohibit the N. gonorrhoeae-CR3 interaction and be repurposed as novel host-targeted therapeutics for multidrug-resistant gonococcal infections in women. Two drugs, methyldopa and carbamazepine, prevented and cured cervical cell infection by multidrug-resistant gonococci by blocking the gonococcal-CR3 I-domain interaction.

IMPORTANCE Novel therapies that avert the problem of Neisseria gonorrhoeae with acquired antibiotic resistance are urgently needed. Gonococcal infection of the human cervix is initiated by an interaction between a galactose modification made to its surface appendages, pili, and the I-domain region of (host) complement receptor 3 (CR3). By targeting this crucial gonococcal–I-domain interaction, it may be possible to prevent cervical infection in females. To this end, we identified the I-domain galactose-binding epitope of CR3 and characterized its galactose lectin activity. Moreover, we identified two drugs, carbamazepine and methyldopa, as effective host-targeted therapies for gonorrhea treatment. At doses below those currently used for their respective existing indications, both carbamazepine and methyldopa were more effective than ceftriaxone in curing cervical infection ex vivo. This host-targeted approach would not be subject to N. gonorrhoeae drug resistance mechanisms. Thus, our data suggest a long-term solution to the growing problem of multidrug-resistant N. gonorrhoeae infections.

ABSTRACT

The obligatory intracellular pathogen Ehrlichia chaffeensis lacks most factors that could respond to oxidative stress (a host cell defense mechanism). We previously found that the C terminus of Ehrlichia surface invasin, entry-triggering protein of Ehrlichia (EtpE; EtpE-C) directly binds mammalian DNase X, a glycosylphosphatidylinositol-anchored cell surface receptor and that binding is required to induce bacterial entry and simultaneously to block the generation of reactive oxygen species (ROS) by host monocytes and macrophages. However, how the EtpE-C–DNase X complex mediates the ROS blockade was unknown. A mammalian transmembrane glycoprotein CD147 (basigin) binds to the EtpE-DNase X complex and is required for Ehrlichia entry and infection of host cells. Here, we found that bone marrow-derived macrophages (BMDM) from myeloid cell lineage-selective CD147-null mice had significantly reduced Ehrlichia-induced or EtpE-C-induced blockade of ROS generation in response to phorbol myristate acetate. In BMDM from CD147-null mice, nucleofection with CD147 partially restored the Ehrlichia-mediated inhibition of ROS generation. Indeed, CD147-null mice as well as their BMDM were resistant to Ehrlichia infection. Moreover, in human monocytes, anti-CD147 partially abrogated EtpE-C-induced blockade of ROS generation. Both Ehrlichia and EtpE-C could block activation of the small GTPase Rac1 (which in turn activates phagocyte NADPH oxidase) and suppress activation of Vav1, a hematopoietic-specific Rho/Rac guanine nucleotide exchange factor by phorbol myristate acetate. Vav1 suppression by Ehrlichia was CD147 dependent. E. chaffeensis is the first example of pathogens that block Rac1 activation to colonize macrophages. Furthermore, Ehrlichia uses EtpE to hijack the unique host DNase X-CD147-Vav1 signaling to block Rac1 activation.

IMPORTANCE Ehrlichia chaffeensis is an obligatory intracellular bacterium with the capability of causing an emerging infectious disease called human monocytic ehrlichiosis. E. chaffeensis preferentially infects monocytes and macrophages, professional phagocytes, equipped with an arsenal of antimicrobial mechanisms, including rapid reactive oxygen species (ROS) generation upon encountering bacteria. As Ehrlichia isolated from host cells are readily killed upon exposure to ROS, Ehrlichia must have evolved a unique mechanism to safely enter phagocytes. We discovered that binding of the Ehrlichia surface invasin to the host cell surface receptor not only triggers Ehrlichia entry but also blocks ROS generation by the host cells by mobilizing a novel intracellular signaling pathway. Knowledge of the mechanisms by which ROS production is inhibited may lead to the development of therapeutics for ehrlichiosis as well as other ROS-related pathologies.

Site-specific arrest of RNA polymerases (RNAPs) is fundamental to several technologies that assess RNA structure and function. Current in vitro transcription “roadblocking” approaches inhibit transcription elongation by blocking RNAP with a protein bound to the DNA template. One limitation of protein-mediated transcription roadblocking is that it requires inclusion of a protein factor extrinsic to the minimal in vitro transcription reaction. In this work, we developed a chemical approach for halting transcription by Escherichia coli RNAP. We first established a sequence-independent method for site-specific incorporation of chemical lesions into dsDNA templates by sequential PCR and translesion synthesis. We then show that interrupting the transcribed DNA strand with an internal desthiobiotin-triethylene glycol modification or 1,N6-etheno-2'-deoxyadenosine base efficiently and stably halts Escherichia coli RNAP transcription. By encoding an intrinsic stall site within the template DNA, our chemical transcription roadblocking approach enables display of nascent RNA molecules from RNAP in a minimal in vitro transcription reaction.

B-cell receptor (BCR) signaling pathway components represent promising treatment targets in multiple B-cell malignancies including diffuse large B-cell lymphoma (DLBCL). In in vitro and in vivo model systems, a subset of DLBCLs depend upon BCR survival signals and respond to proximal BCR/phosphoinositide 3 kinase (PI3K) blockade. However, single-agent BCR pathway inhibitors have had more limited activity in patients with DLBCL, underscoring the need for indicators of sensitivity to BCR blockade and insights into potential resistance mechanisms. Here, we report highly significant transcriptional upregulation of C-X-C chemokine receptor 4 (CXCR4) in BCR-dependent DLBCL cell lines and primary tumors following chemical spleen tyrosine kinase (SYK) inhibition, molecular SYK depletion or chemical PI3K blockade. SYK or PI3K inhibition also selectively upregulated cell surface CXCR4 protein expression in BCR-dependent DLBCLs. CXCR4 expression was directly modulated by fork-head box O1 via the PI3K/protein kinase B/forkhead box O1 signaling axis. Following chemical SYK inhibition, all BCR-dependent DLBCLs exhibited significantly increased stromal cell-derived factor-1α (SDF-1α) induced chemotaxis, consistent with the role of CXCR4 signaling in B-cell migration. Select PI3K isoform inhibitors also augmented SDF-1α induced chemotaxis. These data define CXCR4 upregulation as an indicator of sensitivity to BCR/PI3K blockade and identify CXCR4 signaling as a potential resistance mechanism in BCR-dependent DLBCLs.

Oncolytic virotherapy can lead to systemic antitumor immunity, but the therapeutic potential of oncolytic viruses in humans is limited due to their insufficient ability to overcome the immunosuppressive tumor microenvironment (TME). Here, we showed that locoregional oncolytic virotherapy upregulated the expression of PD-L1 in the TME, which was mediated by virus-induced type I and type II IFNs. To explore PD-1/PD-L1 signaling as a direct target in tumor tissue, we developed a novel immunotherapeutic herpes simplex virus (HSV), OVH-aMPD-1, that expressed a single-chain variable fragment (scFv) against PD-1 (aMPD-1 scFv). The virus was designed to locally deliver aMPD-1 scFv in the TME to achieve enhanced antitumor effects. This virus effectively modified the TME by releasing damage-associated molecular patterns, promoting antigen cross-presentation by dendritic cells, and enhancing the infiltration of activated T cells; these alterations resulted in antitumor T-cell activity that led to reduced tumor burdens in a liver cancer model. Compared with OVH, OVH-aMPD-1 promoted the infiltration of myeloid-derived suppressor cells (MDSC), resulting in significantly higher percentages of CD155⁺ granulocytic-MDSCs (G-MDSC) and monocytic-MDSCs (M-MDSC) in tumors. In combination with TIGIT blockade, this virus enhanced tumor-specific immune responses in mice with implanted subcutaneous tumors or invasive tumors. These findings highlighted that intratumoral immunomodulation with an OV expressing aMPD-1 scFv could be an effective stand-alone strategy to treat cancers or drive maximal efficacy of a combination therapy with other immune checkpoint inhibitors.

In Lysobacter enzymogenes OH11, RpfB1 and RpfB2 were predicted to encode acyl coenzyme A (CoA) ligases. RpfB1 is located in the Rpf gene cluster. Interestingly, we found an RpfB1 homolog (RpfB2) outside this canonical gene cluster, and nothing is known about its functionality or mechanism. Here, we report that rpfB1 and rpfB2 can functionally replace EcFadD in the Escherichia coli fadD mutant JW1794. RpfB activates long-chain fatty acids (n-C_16:0 and n-C_18:0) for the corresponding fatty acyl-CoA ligase (FCL) activity in vitro, and Glu-361 plays critical roles in the catalytic mechanism of RpfB1 and RpfB2. Deletion of rpfB1 and rpfB2 resulted in significantly increased heat-stable antifungal factor (HSAF) production, and overexpression of rpfB1 or rpfB2 completely suppressed HSAF production. Deletion of rpfB1 and rpfB2 resulted in increased L. enzymogenes diffusible signaling factor 3 (LeDSF3) synthesis in L. enzymogenes. Overall, our results showed that changes in intracellular free fatty acid levels significantly altered HSAF production. Our report shows that intracellular free fatty acids are required for HSAF production and that RpfB affects HSAF production via FCL activity. The global transcriptional regulator Clp directly regulated the expression of rpfB1 and rpfB2. In conclusion, these findings reveal new roles of RpfB in antibiotic biosynthesis in L. enzymogenes.

IMPORTANCE Understanding the biosynthetic and regulatory mechanisms of heat-stable antifungal factor (HSAF) could improve the yield in Lysobacter enzymogenes. Here, we report that RpfB1 and RpfB2 encode acyl coenzyme A (CoA) ligases. Our research shows that RpfB1 and RpfB2 affect free fatty acid metabolism via fatty acyl-CoA ligase (FCL) activity to reduce the substrate for HSAF synthesis and, thereby, block HSAF production in L. enzymogenes. Furthermore, these findings reveal new roles for the fatty acyl-CoA ligases RpfB1 and RpfB2 in antibiotic biosynthesis in L. enzymogenes. Importantly, the novelty of this work is the finding that RpfB2 lies outside the Rpf gene cluster and plays a key role in HSAF production, which has not been reported in other diffusible signaling factor (DSF)/Rpf-producing bacteria.

The impact on survival of steroids and TNFα blockade to treat immune-related toxicity from checkpoint blockade with ipilimumab, nivolumab/pembrolizumab, or combined ipilimumab and nivolumab was assessed using data from a large national database. Using steroids was associated with better survival than the use of TNFα-blocking antibodies such as infliximab.

See related article by Verheijden et al., p. 2268

Symmetric division of stem cells positive for gastrin receptor CCK2R is linked to gastric cancer.

Cho tôi hỏi bảng giá xây tô gạch bê tông siêu nhẹ bao nhiêu 1m2? Tô trần tô dầm tô cột? Hàng rào cao 3m xây bằng gạch block 10x20x40 dk 500x1000 giá bao nhiêu?

A 3D printed grate can be used to make a smart window that blocks heat from sunlight out in the summer while letting it through in the winter, conserving energy

The Oscar-winning sword-and-sandals Russell Crowe vehicle refreshed old cliches, before ushering in a spate of copycats

“Joey, do you like movies about gladiators?” the creepy pilot asks the small boy in Airplane!. To younger audiences, the joke no longer makes any sense. In Airplane!’s day, sword-and-sandals movies had become an outdated, unwittingly homoerotic joke. But then came Gladiator, and the joke was on us. Released 20 years ago this month, Ridley Scott’s Roman epic gave the old cliches a new lease of life. It was all here: Colosseum action! Rippling man-flesh! Tigers! But Gladiator had its cheesecake and ate it. It served up crowd-pleasing spectacle and airline-ad visuals but also solemn, Oscar-worthy drama (and, in retrospect, a fair degree of camp).

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Conservation groups are fighting the creation of 3,500 gas wells in Wyoming that threaten a 170-mile path

The Path of the Pronghorn is a 170-mile migration route that the antelope-like creatures have traveled annually for 6,000 years. It is one of North America’s last remaining long-distance terrestrial migration corridors.

And it is at risk. This week conservation groups filed a legal petition challenging the Trump administration’s plan to allow 3,500 new gas wells in south-western Wyoming that would block the route.

Read our live coronavirus updates HERE Coronavirus: The symptoms

A man was tasered and held by police after he was found brandishing a knife on a south-east London housing block.

If the pandemic lasts another three months, news brands could suffer a £50 million loss