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After years under the radar, RNA vaccines are finally emerging as immunotherapies to combat pandemics and cancer. But as Laura DeFrancesco reports, clinical validation remains elusive.
'Vaccines on demand' is an alluring, yet misleadingly simple, concept. Find an antigen of choice against a scourge of choice. Sequence and synthesize it. Formulate a product and deliver it to a site in the body where it elicits a clinically meaningful immune response. Such a vaccine would enable rapid-response agents against pandemic threats. Alternatively, it could provide personalized cancer immunotherapy, with each new batch of vaccine tailored to reflect the antigenic content of a patient's evolving drug-resistant tumors.
RNA—long overlooked as a starting point for immunotherapy—potentially ticks many of the boxes for a vaccine on demand, offering advantages in manufacture, flexibility, scalability and cost of goods. At the same time, clinical validation faces formidable barriers, such as antigen discovery, product formulation and delivery. To emphasize the challenge, vaccine developer CureVac reported in January that its prostate cancer product—the first RNA vaccine to be put into humans—had failed to improve survival over standard of care. Even so, a recent flux of funding and research interest promises to reinvigorate the field.
For many years, RNA languished as the 'ugly stepchild' of nucleic acid vaccine development, with DNA reigning supreme. One reason for the slow development was that few in the research community considered RNA a good starting point (Box 1).
In recent years, a crucial impetus for advances in RNA vaccine technology—and their application to rapid response efforts—has been support from the US Defense Department's Defense Advanced Research Projects Agency (DARPA)—specifically its Biological Technology Office (BTO) in Washington, D.C. Since 2011, DARPA has provided substantial funding for several early-stage RNA vaccine programs (Table 1). “We like to think of ourselves as [funders of] early-breakthrough, high-risk, things that would not normally be funded. If you were going to do a safe biomedical research program, with incremental approaches to solving a problem, that would not be us,” says Matt Hepburn, a program manager at DARPA's BTO. Their overriding interest is in having platforms in place that can respond quickly in the case of a pandemic. “Our mindset, day, night, 24/7, is what do we need to do to be ready for the next pandemic,” he says.
The potential of RNA vaccines to perform in such a setting was demonstrated in 2013 during an outbreak of a deadly strain of (H7N9) influenza in China. The Chinese Center for Disease Control and Prevention deposited the sequence in GenBank, a web-based database, and folks at Novartis (with funding from DARPA and the Biomedical Advanced Research and Development Authority, BARDA) set out to see whether they could make an effective vaccine based on the electronic sequence. “We were lucky enough to be collaborating with Craig Venter's teams [Synthetic Genomics and Synthetic Genomics Vaccines, both based in La Jolla, California], so we made a vaccine in 8 days, put it in mice in 13 days and showed that, indeed, it works”, says Andrew Geall, who was running Novartis's mRNA vaccine program until it was moved to GlaxoSmithKline (GSK) Vaccines in Rockville, Maryland, as part of an asset swap1. (Geall currently serves as VP of formulations at the RNAi company Avidity BioSciences in La Jolla, California). By “it works,” Geall means that the vaccine raised neutralizing antibodies after one injection of 1 mg and all protect mice had HI titers considered protective after two doses.
DARPA could not be happier. “What you are seeing in the field now is that using a nucleic acid to get the body to do what you want it to do, whether it's a vaccine or other responses, is really exploding. We find that profoundly exciting,” says Hepburn. Recently a DARPA-funded Moderna program in Zika was handed off to BARDA—which serves the application and delivery side, as opposed to development side, of the US government's medical countermeasures program. DARPA is providing funding for preclinical development and a phase 1 trial of a chikungunya vaccine.
To infection and beyond
Although several commercial RNA vaccine programs are already moving forward in infectious disease, rapid response is not yet a theme (Table 2). Ingmar Hoerr, co-founder, chairman and CEO of CureVac in Boston–based CureVac, is focusing on rabies as a first proof of principle. According to Hoerr, infectious disease indications offer a wealth of traditional vaccines against which to benchmark RNA vaccine responses. “There is a vaccine and [World Health Organization] guidelines for titer level.” This contrasts with cancer, where the lack of conventional vaccines makes it difficult for developers to assess effectiveness of RNA as an immunogen. In infectious disease, “you can see where you are,” says Hoerr.
CureVac's rabies vaccine, which encodes the viral glycoprotein, stimulates both B-cell and T-cell responses in volunteers. “We have a safe product, you don't need eggs or cell culture. It's quite cheap and it could be a dollar a dose,” says Hoerr. The company also recently showed that it is possible to immunize against more than one pathogen at a time, having combined several (up to six) flu hemagglutinin (HA) antigens in one vial. According to Hoerr, it's unusual to receive immune responses against all HA antigens at the same level in one vial.
Another company with an RNA vaccine in the clinic is Argos Therapeutics, based in Durham, North Carolina (and known as Merix until 2004). According to CEO Charles Nicolette, the company has been investigating the use of RNA encoding a modified form of the CD40 ligand protein to pretreat antigen-presenting dendritic cells (DCs). Nicolette notes that this protocol imitates the presence of CD4+ helper T cells2. “The DC thinks it's in a healthy individual and is able to do its job and generate the immune response that we want”, he says. Having a functioning DC that is independent of the requirement for CD4+ T-cell help brought AIDS to mind. “The [human immunodeficiency] virus has elevated to an art form the destruction of CD4+ T cells; it's what kills you in the end. So we asked the question: can we use our RNA technology to target autologous virus and be able to immunize the patients effectively?” According to Nicolette, the answer may be yes. The company has been able to induce antiviral immunity in HIV patients and, on the basis of this work, has attracted funding from the US National Institutes of Health (NIH) Division of AIDS. “We were awarded a contract for $40 million. Our HIV program is alive and kicking, and we're pretty excited about it.”
Early signs that RNA might have some use in a therapeutic setting came in 1990, with the publication of pioneering work by John Wolff, Phil Felgner and colleagues at the University of Wisconsin–Madison demonstrating that native RNA can be injected directly into muscle in mice and expressed3. CureVac's Hoerr, at the time a PhD student at the University of Tübingen, was amazed that no one picked up on in vivo administration of RNA. Although still a student, he was able to directly administer RNA, but most other researchers steered clear of RNA, he says. “Nobody was trying our approach or taking account of what we were doing, although we published a lot of papers.” In recent years, that has been changing, particularly as ways of making, delivering and expressing mRNA have improved and flagship companies such as CureVac and Moderna have sprung up, attracting both researchers and investors to the space.
The technology improvements that contribute to an effective RNA vaccine come in several forms. Modifications to the RNA molecule itself improve its stability and increase its expression upon delivery. These include adding a cap (m7GpppG) to the 5′ end and tacking on a poly(A) tail to the 3′ end, optimizing codon usage and GC content, providing 5′ and 3′ untranslated elements that facilitate ribosome binding and boost expression4.
But to get efficient translation, the RNA has to stick around, and cells have various mechanisms to dispose of incoming, presumably pathogenic nucleic acids. Upon engagement, these pathways—involving Toll-like receptors, the RNA helicase RIG-I and protein kinase R—induce an innate immune response, which, among other things, shuts down the cell's translational machinery. In 2005, Kaitlin Kariko, then at the University of Pennsylvania in Philadelphia, showed that it is possible to 'de-immunize' RNAs by incorporating naturally occurring modified bases5, and that the translational efficiency of mRNA can be improved by replacing uridine with pseudouridine6. Following this work, Derrick Rossi, a co-founder of Moderna who is at Harvard Medical School in Boston, took it a step further and showed that substituting pseudouridine for uridine and 5-methylcytidine for cytidine works even better7.
Another refinement to the RNA molecule that enhances its efficacy as a vaccine is the addition of the coding region of viral replicases, which render the molecule self-amplifying. First described for RNA in the 1990s by Peter Lijestrom, using Semliki Forest virus8, self-amplifying replicons can reduce the amount of material required to raise an immune response. More recently, the Novartis vaccine group incorporated this feature into its RNA vaccine designs. Their influenza vaccine, for example, which uses the alphavirus replication machinery (Fig. 1), requires a single dose of less than 1 μg to get a response equivalent to two 80 μg doses with an unamplified RNA vaccine1.
Finally, Moderna's new CSO Melissa Moore, who joined the company in October 2016, is applying her expertise on riboncleoprotein structure to enhance ribosome engagement. Moore has shown that secondary structure positively impacts translational efficiency9.
Delivery, delivery, delivery
The development of delivery vehicles is another critical component to getting RNA to function in vivo (see 'Worth the risc?' doi:10.1038/nbt.3810). The vehicles primarily protect the RNA from degradation, but their composition can also influence uptake and localization in vivo, according to Philip Santangelo at The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University both in Atlanta. Santangelo is developing imaging systems for live-animal-based visualization of RNA using 64Cu-labeled molecules and positron emission tomography (PET) scanning10. With support from DARPA, Santangelo has been tracking RNA after delivery and, in unpublished work presented recently at a DARPA-sponsored conference, showed time series data of monkeys after intramuscular injection of in vitro–transcribed RNA. “The whole idea was to come up with a methodology that would allow you to come up with the whole picture,” says Santangelo.
There are almost as many delivery vehicles as there are groups working in the space. Some encapsulate the RNA molecules in particles, whereas others use positively charged polymers to grab onto the RNA through charge interactions. Geall, who had worked on delivery systems for small interfering RNA (siRNA) at Novartis before heading up the vaccine program, borrowed from that work and used a cationic lipid nanoparticle (LNP) originally developed by Peter Cullis at the University of British Columbia for systemic delivery of siRNAs and commercialized by several RNA therapeutic companies. For a proof of concept, Geall's group used 1,2-dilinoleyosxy-3-dimethylaminopropane, which had been demonstrated to be effective at delivering siRNA intravenously11. In parallel, the team at Novartis vaccine developed a cationic nanoemulsion (CNE), based on the company's proprietary adjuvant MF59, which has an established clinical safety profile12. This adsorbs mRNA on the surface of an emulsion droplet, whereas the LNP encapsulates the mRNA in a lipid envelope. Both approaches provide protection to the mRNA from enzymatic degradation from RNases.
Mainz, Germany–based BioNTech, which was spun out of Johannes Gutenberg University in 2008, recently reported on a delivery platform that localizes in lymphoid tissue after intravenous injection. By systematic varying of lipid nanoparticle parameters (charge, size and lipid composition), they found that particles with a slightly negative charge home to lymphoid tissues. According BioNTech CEO Ugur Sahin, most people use positively charged vehicles, because they stick to cell membranes (regardless of cell type), giving good transfection efficiencies. Because they were interested in maximizing transfection efficiencies, many groups have stayed with positively charged particles, he says. But researchers at BioNTech found that with their negative particles, comprising two common lipids (DOTMA and DOPE), they can restrict uptake to DCs, capitalizing on the biological process of macropinocytosis, by which DCs and macrophages sweep up solutes from their environment. In addition to protecting the payload and mediating its uptake and eventual expression, the particle triggers interferon-γ (IFN–γ) release, leading to maturation of DCs in situ and a strong T-cell response. “At the end of the day, what we accomplished is that we have particles that behave like viruses,” Sahin says13.
Researchers at the Massachusetts Institute of Technology's Koch Institute in Cambridge have developed a 'tunable' dendrimer-based particle, comprising molecules of high amine density with organized branching structures that condense around mRNA molecules, folding them into monodisperse spheres. Omar Khan, a chemical engineer at the Koch Institute, points out the repurposing the delivery technology developed for siRNAs is not the right approach for mRNA that can be an order of magnitude larger. “If people are using old technology that was designed for siRNA, which is ∼19 nucleotides long, and then we want these replicons that are at least 10,000 nucleotides long—so to us, making the molecular structure tailored for the replicon made sense,” says Khan. Using their vaccine, Khan and his collaborators at MIT have shown that after a single intramuscular injection, mice are protected from a lethal exposure of influenza (using hemagglutinin protein antigen), Ebola (using Ebola glycoprotein antigen) and Toxoplasma gondii (with six T. gondii–specific antigens)14. Khan and Jasdave Chahal, a virologist who designed the replicon RNA molecules used in the vaccines, have formed a company with their faculty mentors, Tiba Biotech (tiba is a Swahili word for 'cure'). They also have partnerships with Charles Shoemaker at Tufts Veterinary School in North Grafton, Massachusetts, and the US Army Medical Research Institute of Infectious Diseases in Frederick, Maryland, to develop vaccines against the parasitic worm Schistosoma mansoni and Ebola, respectively. Ultimately, the duo would like to see their technology—which is self-assembling, fast (taking only 7 days to go from pathogen sequence to vaccine), single dose and capable of carrying multiple antigens—be applied in the global health arena.
Cancer in the crosshairs
There are two ways to administer an RNA vaccine. One is injection of complexed or encapsulated RNA under the skin or into muscle; the other is pre-loading of DCs (or a cell population enriched for such antigen-presenting cells) ex vivo with RNAs and using those cells as both delivery vehicle and RNA translator.
One of the earliest RNA vaccines to enter clinical trials was the latter type of platform, developed by researchers at Duke University in Durham, North Carolina15. The technology was licensed to Argos in 1997 (formerly Merix), which currently has two cancer immunotherapies in the clinic (Table 2). The company's platform involves extracting and amplifying mRNA from a tumor and transfecting a patient's DCs ex vivo with the entirety of the products. Before transfection, the DCs are preconditioned with a mixture of agonists to IFN-γ receptor and/or tumor necrosis factor-α receptor followed by secondary transient conditioning with a CD40 agonist. According to Argos CSO Charles Nicolette, “We do not sort through what is normal and what is mutated.” He adds, “we amplify all the mRNA from the tumor sample, and we let nature figure out what it can attack and what it should leave alone.” As a result, Argos departs from many cancer vaccine companies that attempt to sort through identified neoantigens and predict what ends up presented. “That's how we parted company [with the RNA vaccine field]. A lot of people don't think of us as a RNA company.”
Argo's first product in human testing is for renal cell carcinoma (RCC) in combination with the tyrosine kinase inhibitor Sutent (sunitinib). The RCC patient population in the trial normally survive only 15 months from diagnosis. In a phase 2b trial of 21 patients, those immunized with tumor RNA had a median survival time of 30 months, and two patients remained in long-term remission for more than 7 years16.
The vaccine, rocapuldencel-T (also called AGS-003), is now in a pivotal randomized phase 3 ADAPT (autologous dendritic cell immunotherapy plus standard treatment) trial, with 462 RCC patients stratified by risk factors for progression. Argos plans to expand clinical development to other tumor types, such as bladder cancer and non-small-cell lung cancer.
The alternative and more common direct injection route of vaccination was pioneered by German researchers at the University of Tübingen, using protamine-complexed RNA17. This program, which became the foundation of CureVac, which, after receiving regulatory clearance on RNA made following good manufacturing practice (GMP) standards, put its first RNA cancer vaccine product (CV9103) into patients in 2008, targeting four antigens: prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), prostate stem cell antigen (PSCA) and six transmembrane epithelial antigen of the prostate 1 (STEAP1). “We did sequence modulation looking for natural elements that allow for high expression, ribosomes binding, RNA to be stable for a couple of days, not just a couple of hours,” says Hoerr. With their optimized sequence, they observed strong T-cell responses in preclinical work.
Bolstered by the positive regulatory result for the DNA prostate cancer vaccine Provenge (sipuleucel-T, made by Dendreon, based in Seattle) and other positive data from vaccines in oncology trials, Hoerr focused initially on cancers where strong T-cell responses are needed. “When we planned our first trial, everybody thought monotherapy would be enough. You would have to encode a number of antigens make them immunogenic, inject them and it would be a beautiful T-cell response,” he says. On the basis of promising phase 1/2 results—strong CD4+ and CD8+ responses, as well as responses to all four antigens18—the company initiated a phase 2b trial in castration-resistant prostate cancer with an updated vaccine (CV9104) carrying two additional antigens: prostatic acid phosphatase (PAP) and mucin 1 (Muc1).
Hoerr says that the CureVac team is still analyzing the data from the phase 2b trial—only the top-line results were reported in January. They are also looking toward combination trials with their lung cancer vaccine and checkpoint inhibitors. Since 2014, they have collaborated with Boehringer Ingelheim, based in Ingelheim am Rhein, Germany. They also have a recently completed trial in non-small-cell lung cancer, in which patients receive radiation, which has been shown to be synergistic, before RNA vaccination.
Elsewhere, BioNTech recently reported early results with a small cohort of melanoma patients treated with their RNA-lipoplexes delivery system, which contains RNA for four tumor-associated antigens: NY-ESO-1, MAGE-A3, tyrosinase and transmembrane phosphatase with tensin homology. The company detected α-interferon release as well as an immune response against the four antigens13. Sahin is encouraged by the response to these antigens, which go against the current craze for neoantigens. “If you go to the literature, you will hardly find convincing tyrosinase immunogenicity in patients. We continue to see strong T-cell response, with these non-neoantigens... I am excited that this [liposomal RNA vaccines] might open the door to explore also non-neoantigens with different types of cancer,” he says.
BioNTech is also working on two kinds of personalized cancer vaccines, which draw from a library of shared (off-the-shelf) antigens and from a library constructed from individually tailored approach constructed from the tumor neo-epitope of each patient19. Using a set of synthesized RNAs identified via algorithms that can identify neo-epitopes binding major histocompatibility (MHC) class II molecules, company researchers have shown that they can induce tumor regression in mice and have reported they can identify similar sequences in human tumors20. Both types of personalized vaccines are currently in phase 1 trials for melanoma and triple negative breast cancer.
It is still early days for RNA vaccines—probably too early to tell whether they will fulfill their promise in the clinic. “If you look at the history of all the new technologies, what happens initially is a huge amount of enthusiasm,” says Margaret Liu, a consultant in the field of vaccines, who pioneered DNA vaccines at Merck in the early 1990s and has worked on vaccines and immunotherapies since. Fueling the recent wave of enthusiasm, in no small part, has been the amount of money that Moderna raised in short order. “People are afraid of missing out and would rather invest and be wrong than miss out. I don't think it's predictive of whether it will be a success, it certainly enables success,” says Liu. By some measures, this has been borne out.
According to public disclosures, Moderna has advanced five programs into clinical trials and established four biopharma partnerships. It is building out a $110-million GMP clinical manufacturing facility.
But several key questions about this vaccine technology remain unanswered: how is RNA transcribed and then processed into epitopes on the cell surface? What is the best route of delivery, and how do responses differ depending on which tissues are targeted? What kind of immune response is protective, in the case of infectious diseases, or curative, in the case of cancer?
One issue that may be keeping pharma from entering the field is competition from existing vaccines. Geall says that at Novartis, he had to work against the notion that RNA vaccines would not measure up to commercial products. But, he says, his group was able to show that for both influenza and rabies, their product performed well in animal models, which he feels bodes well for human use. Not everyone agrees that the probability of success is high, based on animal results. Liu says, “Preclinical studies don't predict very well for vaccines. They can be negative, and that can be useful, but [positive results] don't mean that products are around the corner.”
Despite the disappointment surrounding the results from CureVac's first RNA vaccine trial in humans, people working on these programs remain optimistic. “The failure was in a very difficult indication in oncology with an asset that they developed a long time ago,” points out Geall. And encouraging preclinical successes continue to come. Just last month, a group of investigators reported results with a lipid nanoparticle mRNA vaccine for Zika; they were able to raise neutralizing antibodies as well as protect both mice and rhesus monkeys with a single dose21.
“Ultimately, it will boil down to picking the right target—the right antigen being coded—and the right disease, whole pathophysiology of the disease,” says Liu. But BioNTech's Sahin has no doubts. “I'm absolutely convinced, it's not hype. RNA is anti-hype. It remained under the radar for many years, and it's now mature enough to fulfill promises.”
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DeFrancesco, L. The 'anti-hype' vaccine. Nat Biotechnol 35, 193–197 (2017). https://doi.org/10.1038/nbt.3812
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This year’s U.S. Dramatic category sees a filmmaker moving up the Sundance ranks—Justin Chon, who directed the tight-fisted, black-and-white LA Riots drama “Gook” (which played the festival’s NEXT section in 2016), now has a film in the so-called main competition program. With this family study, co-written by Chris Dinh, Chon continues to be an exciting but flawed filmmaker, sometimes struggling to balance his desire for both revelatory intensity and tenderness.
Steered by an introspective and emotional performance from Tiffany Chu, “Ms. Purple” tells of a sister (Chu’s Kasie) and her estranged brother Carey (Teddy Lee) in Los Angeles who have to take care of their dying, bed-ridden father. Their mother has been long gone, as flashbacks indicate. Kasie refuses to put their father in hospice care, and helps pay for the health expenses by being a host in karaoke rooms for rich, often obnoxious men. This latter story detail is the way Chon initially brings us into Kasie’s world, showing us the ranges of masculinity with which she interacts, a long time removed from the days when she was called beautiful by her father as a little girl. Chon’s camera has a great affection for Chu, and it paints a holistic image of her, mourning the many instances in which the world has broken her heart.
Having more than a couple things in common with last Sundance’s family dramedy “What They Had,” the movie gets its greatest strength out of watching these siblings quietly bond after so many years, finding some type of peace within themselves and also their relationship with their dying father. It also has some unexpected comedy, like when Carey wheels his father out into the Los Angeles to the tune of “500 Miles.” In one of the story’s more delicate touches, it becomes apparent that these trips outside are more for the son than the father, the former trying to silently connect with someone that he left long ago.
But Chon remains an inconsistent dramatist, overbaking some of his most important moments for the sake of making his emotional beats unmistakable. Characters have explosive interactions that go from zero to ten instantly in terms of seriousness, the dialogue hitting right on the nose. It all risks cheapening the fictional beings that he continues to make fascinating as the story goes along, corroding their liveliness.
But while nuance can sometimes be absent, especially with a selection of instrumental pieces that demand your emotions, Chon has an eloquence with scenes of spare dialogue, as with the framing storytelling device and flashback, of Kasie and Carey as young kids observe their father affected by the abandonment by their mother. It’s often the moments in between Chon’s loudest notes that make the best impression in “Ms. Purple,” a striking character study on the responsibilities of family, and the importance of sticking around.
Shot in Chicago, “Hala” is a coming-of-age story with inconsistent storytelling but a strong lead performance from Geraldine Viswanathan. Written and directed by Minhal Baig, it tells of a skateboarding, crossword-solving Muslim high schooler dealing with life-changing concepts. First, her parents Eram (Purbi Joshi) and Zahid (Azad Khan) may not have the happy marriage that she thought they did. And then there’s Jesse (Jack Kilmer), a classmate who causes her to challenge her conservative Muslim upbringing.
Baig’s script is largely driven by dialogue, which is not a problem so much as it plays out like a storytelling crutch. One of its earnest storytelling devices is a “What is your point of view?” essay assignment that Hala receives in English class, and the movie can’t build beyond this cliche to make it interesting. The same flagging dramatic tactics pop up in scenes where Hala learns more about her parents’ history of romance (and arranged marriage) through expository dialogue.
While told with delicacy that can sometimes feel too loose, “Hala” is able to articulate much its inner conflict with an exceptional and largely contemplative performance from Geraldine Viswanathan. Watching her skateboard with ease, or wonder what she wants for herself, can prove to be the most engaging emotional spectacle of her story. She is a fully-formed character, like Antoine Doinel or Lady Bird before her, and this story feels like just the beginning.
Writer/director Pippa Bianco’s “Share” is a very straight-forward observation of a high school nightmare: Mandy (Rhianne Barreto) has been assaulted at a party, and though there’s footage of it that gets texted around by her classmates, no one knows who did it. She doesn’t remember what happened, and no one is coming forward. Bianco’s script, based on her 2015 short film, takes an almost too-procedural angle on the process, starting with Mandy being asleep on the lawn, and then plunging into shame and anxiety when the video comes out, and removing herself from her social life while taking therapy. The aftermath affects her social life, including with the boys who may or may not have had something to do with the incident, isolating her from the world. Given so much pain to carry in each scene and often with little dialogue, Barreto vividly captures the tragedy of someone who has been so affected.
Her parents, (played by Poorna Jagannathan and J.C. Mackenzie), are out for answers: They collectively offer a visceral idea to the anxiety experienced by a family changed by this incident, especially as the victim and their parents diverge on what they consider to be closure. While the scenes of watching Mandy wrap her head around what has happened are assuredly effective, it is almost just as hard to see the parents seek a type of justice. These characters also take the story in a more compelling direction, as Bianco’s script spends a lot of its time in the grayness of Mandy’s day-to-day life, its developments about the case feeling more matter-of-fact than wholly compelling drama.
There is a quiet ambition to this movie—to not be a character study so much as a study of headspace, locking viewers into the day-by-day moment of a young woman dealing with the aftermath of her assault. We are supposed to share her frustration in not remembering, to space out with her as she monotonously plays a racing game, to feel like we always see the green and blue that she stares at with a device in her light therapy sessions. This makes for many pained sequences, especially as it becomes apparent what resolve will and will not reach her, and the story echoes numerous true examples of these similar events in high schools.
The complete seriousness of this movie indirectly makes clear what “Share” won’t do, which is add any air to its concrete sadness. If it's true that there's no great drama without comedy and vice versa, "Share" is ineffectively defiant against such a balance. With its hazy cinematography and sparse yet mournful score, “Share” risks becoming a total dirge, but is enlivened in large part by the honesty within its lead performances. It proves to be as much of a tribute to those who have experienced this story in real life, as it is a documentation of what could happen if such a disturbing life-changing event came into a parent's or student’s home.


Inside this issue
End frame: Gneiss Boulders, Isle of Harris by Lizzie Shepherd
Gill Moon chooses one of her favourite images
Gill Moon is a professional photographer based on the Suffolk Coast. She specialises in landscapes, waterscapes and marine photography and is passionate about promoting a connection with the environment through her work.
Gill has been taking photographs for most of her life but decided to turn her hobby into a profession in 2010 when she moved to the Suffolk Coast. Her passion for the outdoors also extends to the sea and Gill is an experienced sailing photographer working with the national yachting press and sailing organisations along the East Coast.
Gill’s real passion is the landscape and the natural world and she is increasingly keen to help others foster a connection with both. “For me photography is not just about the technical side of taking a photograph, it is about observation, emotion and portraying a connection with the world around you. These are the things that I believe contribute the most towards creating a compelling image.”
When I was asked to write an End Frame article, I knew immediately which photographer I wanted to write about, but choosing one of her images was much harder. Picking my favourite from so many outstanding compositions was really difficult because so many of them resonate with me in many different ways. In the end, I chose Gneiss Boulders from the Isle of Harris (by Lizzie Shepherd) because there is so much in this image that fits with my own work, the things that I love and the way I see the world.
I was brought up in the countryside, surrounded by nature, with parents who encouraged and facilitated a connection to the wild. I learned to identify the local wildlife, went birdwatching, drew plants and butterflies and collected rocks and fossils. I was nature connected from a young age, and it is something I feel has really helped with my photography. I think this is part of the reason Lizzie's work, and in particular, this image really appeals to me.
I had the pleasure of meeting Lizzie for a 1-2-1 workshop in the Yorkshire Dales back in 2018, a few months after my Dad had died suddenly and at a time when I was struggling with my own photography.
I was really inspired by Lizzie’s work and admired the quiet beauty that she was able to achieve in her images with her use of light and tone. Her work intrigued me, and I was interested to spend some time in the landscape with her. Despite having the worst weather imaginable (flat, grey and drizzly), I came away from the workshop with a renewed sense of connection facilitated by Lizzie’s attention to detail, particularly around composition, which is definitely something that has stayed with me and influenced my work going forward.
The first thing that attracted me to this image was the geology. It takes me back to my childhood, and I am immediately transported to the beach, standing amongst the boulders listening to the sea. Despite the complexity of the scene and the haphazard nature of the foreground elements, the image has an overall simplicity to it, which I think helps the viewer appreciate all the different elements that make up this landscape.


Catering to the needs of the noisy. www.fstateaudio.com
4 months ago
A noisy generative soundscape with video from Cathodemer, and additional video elements and processing from…
Semi-generative rhythmic noise patch.
Noisy generative soundscape.The video is footage from Cathodemer, processed with Acid Cam. There are actually…
5 months ago
A remix of the FS track “Spaced Out” done in VCV Rack. Feel free to…
Playing around with generative patching.
Another expansion of the “3-module challenge” thing I posted a while ago. This one’s a…
6 months ago
This is an expansion of the “3-module challenge” thing I posted a while ago. More…
A bit of ambient soundscape created for the EP “Nebular.” fuguestate.bandcamp.com/album/nebular
A bit of droney stuff this time.
More noisy soundscape action.
7 months ago
Way back in the days of Windows 95, there was a little program called Sound…
Noisy ambientish soundscape.
This patch is an attempt to recreate my DIY hardware modular setup in VCV Rack….
A Lunetta-inspired patch, attempting to recreate the Slacker Melody Generator circuit. The original schematic can…
8 months ago
A “3 Module Challenge” patch based on feedback, using Bogaudio’s Mix 4, Vult’s Lateralus filter…


June 6, 2016 - 1:00 pm
CARSON CITY — The state Board of Transportation on Monday approved using a design-build process for a $60 million highway improvement project for the Faraday Future electric car factory now under construction at Apex.
The process is expected to get the road project finished a year earlier than using traditional bidding methods.
The agency will now solicit proposals for the project.
“This is one of those projects that is very important to infrastructure,” said Gov. Brian Sandoval, chairman of the board.
Construction of the five-mile-long widening of U.S. Highway 93 at Interstate 15 for the Faraday plant now under construction is projected to begin in June 2017.
The design-build process will allow the Department of Transportation to concurrently pursue the environmental clearance while proceeding with the preparation of the design-build documents, shaving off a year for the completion of the project.
Parsons Brinckerhoff is performing the preliminary design, engineering and environmental work.
The planned development in the Apex area in the near future is projected to be significant and is planned to commence within the next several months. The project is needed to facilitate this dramatic projected growth, the agency told the board in a memo.
The project will benefit other anticipated development at Apex in coming years.
The project at the Garnet Interchange will include a flyover exit from U.S. 93 into the $1 billion, 3-million-square-foot plant being built by Faraday.
The Legislature in December approved a package of incentives to bring the company to Southern Nevada. The Faraday tax breaks and other improvements, including the road project, totaled $320 million. The company broke ground on the factory in April.
The improvements to U.S. 93 will expand the road from two to four lanes and include a frontage road at Grand Valley Parkway inside the Apex Industrial Park.
Contact Sean Whaley at firstname.lastname@example.org or 775-461-3820. Find him on Twitter: @seanw801


text:
Oh no – your Halloween party is coming up soon and you have nothing to wear! Maybe your office co-workers just made a spur-of-the-moment decision to dress up when they come back to work on Monday. Have no fear! You can conjure up a great last-minute costume in no time. And because you're a music-lover (since you clicked on this article and all), your costume is going to be extra awesome.
Thanks to notable music videos, album covers, and generational trends, there are several last-minute costume ideas available to you if you're a music nerd. Below are 10 great ideas we've found online or have come up with ourselves! Since you're in a hurry, we'll spare you the long-winded article intro and get right to it!
1. Taylor Swift in the "You Belong With Me" Music Video
Taylor Swift is all the rage at the moment due to Midnights mania, so why not pay homage to one of her earliest eras? All you need for this costume is some pajama bottoms (preferably with a buffalo check pattern, but anything works), a white t-shirt, Sharpie markers, and some glasses. If you want to go the extra mile, you can carry a notepad around with you like Swift does in the music video. We recommend writing "You Okay?" or "I <3 You" like she does in the visual! And if you're stressed out by all the designs on Taylor's Junior Jewels shirt, you can always fill the blank space with your own signatures and references – just like a Swiftie does in the DIY tutorial below.
2. The Members of KISS
Sure, you could go all out and get a cool rocker outfit to go with your black and white KISS makeup...but do you really need to? People get the message that you're either Paul Stanley, Gene Simmons, Ace Frehley, or Peter Criss just from your face alone. Therefore, getting some black and white makeup from your local Halloween store and slapping it onto your face is a perfect last-minute idea. This also works as a last-minute group costume idea!
3. An 80s Rocker Look
Our Halloween motto is that when all else fails, just find some leather, bright makeup, funky jewelery, and a heavy metal band tee to use for an easy 80s rocker look. Make sure to tease your hair like crazy and wear a bandana or headband with a funky print. Bonus points if you're able to carry an electric guitar around with you.
4. Or an Emo Kid Look
Alternatively, you can dig up that old My Chemical Romance or New Found Glory shirt and use it to create an emo kid look. Get some black skinny jeans, maybe a black zip-up hoodie or leather jacket and some dark makeup, and voila – you're emo! You could also brush your hair forward to create those iconic emo bangs, spray your hear black, or get some wristbands if you want to go the extra mile. Or, you could always dress up as an iconic emo look from a music video – like the folks below did. They dressed up as Gerard Way and the actress from My Chemical Romance's "Helena" music video.
5. Freddie Mercury in Queen's "I Want to Break Free" Music Video
Popular YouTuber Nicole Rafiee broke out this look last year and we still haven't gotten over how clever it is. True music fans will appreciate this iconic queer look from Queen's "I Want to Break Free" music video. All you need is a short black skirt, tights, heels, a purple sleeveless turtleneck (you could always get a regular long-sleeve turtleneck and cut off the sleeves), and a fake mustache. Depending on your hair length, you may also need a wig. If you've got extra time, you could also paint your nails pink like Freddie's and find something that works for the pink chunky earrings he's wearing. If you're debuting this look at your own house party, you MUST roll a vacuum cleaner around with you. If you're heading to a friend's place, a feather duster is a good prop alternative.
6. David Bowie
Just like with the members of KISS, all you really need for this costume is some makeup. Seriously – all you need is some red, black, and blue-colored makeup to splotch across your face in a lightning bolt design. This look is from David Bowie's Aladdin Sane album cover, and it's considered his most recognizable look. Besides the makeup, we also recommend giving the front of your hair some volume and wearing 70s appropriate clothing, spacy/sparkly attire, or your favorite Bowie shirt.
7. Olivia Rodrigo's Sour Album Cover
Got some extra stickers you need to get rid of? How about covering them all over your face to recreate Olivia Rodrigo's Sour album cover? Butterflies, stars, flowers, and other cutesy designs work best for this look. (The tongue letters are totally optional.) After that, all you need is a light-colored tank top and plaid skirt and you're done! If you've got extra time and are worried about the pain of taking off the stickers later on, we recommend going to your local Halloween store and purchasing some spirit gum or liquid latex as a better sticker-to-skin adhesive.
Black leotard and big boots with a heel to them? Boom, you're Beyoncé. If you've got some cool gold bits/jewelery/baubles to go on your hand, you can be Beyoncé in her "Single Ladies" video. Got more leather, lace, and fishnets? You can be Beyoncé during the 2013 Super Bowl. Seriously: all you need is a black leotard and some high-heeled boots, and people know you're Beyoncé. Just make sure to get your hair to an extra voluminous state before you "get in formation" while trick or treating.
9. A Classical Composer (Beethoven, Mozart, etc.)
If you're lucky enough to have a spare white wig lying around (or can find one at a Halloween costume shop), you've already got the main ingredient to make a killer classical composer costume. After that, all you need is a suit jacket, a white button-down shirt, white or red frilly scarf, and black pants with boots. You could also carry a baton or sheet music around with you.
10. PSY from the "Gangnam Style" video
If you happen to have a blue suit jacket, black bowtie, and black shades lying around, this is an easy costume to put together. Complete the look with a white button-down and some black pants, and you've got that Gangnam Style! If you've got time, you could probably make those black jacket outlines with some black duct/fabric tape, but it's not totally necessary. Remember to do those iconic "Gangnam Syle" dance moves when posing for photos.
BONUS IDEA - "Karma Is a Cat"
Instead of a trick, we're giving you a treat with this extra idea! Okay, this is just an idea that we hope to see people tackle in 2022, so we're giving it to you! It's so easy to dress up as a black cat for Halloween – all you need is some all-black attire, some cat ears (that you can totally find at a dollar store) and a drawn-on nose with whiskers. But if you print out a piece of paper with the word "Karma" on it and tape it to yourself, guess what? You're a lyric in one of the most popular Taylor Swift songs right now! Since Midnights was just released this month, we know people will get this joke – especially if the people you're partying with this Halloween are hardcore Swifties.
We hope these ideas have filled you with inspiration. From all of us here at Live365, we hope you have a happy Halloween!
Check out our selection of free stations streaming Halloween music at Live365.com.
Rather listen on our app? Download the Live365 app on iOS or Android. Ready to start your own station? Contact one of our Product Consultants or visit our website today. Keep up with the latest news by following us on Facebook (Live365 (Official) and Live365 Broadcasting) and Twitter (@Live365 and @Broadcast365)!
Article Image: Nicole Rafiee dressed up as Freddie Mercury, @bayleemartinn in her Olivia Rodrigo Sour costume, a man donning David Bowie lightning bolt makeup. (@nicolerafiee, @bayleemartinn, and @toniguyscottsdale via Instagram.)

domain: artistic


text:
Ford Original Quality
The S197 Mustang is getting to a point now where some of them are now 10 years old. If your Mustang sits out in the sun a lot, then sooner or later you're going to experience a faded or cracked roof rail molding. This is a Ford original 2005-14 Mustang passenger side roof rail molding. This molding goes along the roof line and window opening on the passenger side. It comes in the factory black textured finish and is a direct replacement for your original roof rail molding.
Ford Motor Company Genuine Parts, Motorcraft® Parts and Ford and Motorcraft Remanufactured Parts are all excellent choices when it comes to performance, longevity and value for your Mustang or SVT Lightning. And they’re all backed by a Ford Motor Company limited parts warranty*, so you know their parts you use are going to perform like they should. Put the same parts on your Lighting & Mustang that came from the factory!

domain: hobby


text:
The Tiiliskivi (brick) pattern was designed by Marimekko’s founder Armi Ratia in 1952. The pattern reflects her belief in the simple beauty of everyday life.The lightweight towel has cream and brown fringes at the ends, making for a unique and stylish design. The brown and white coloring is reversible and creates a timeless pattern that compliments any home interior. Mix and match these towels to create a unique yet cohesive linen closet that will be the envy of your guests.
Care: Machine washable. Follow instructions on tag.
The bold prints of Marimekko are the first to come to mind for many when thinking about Finnish design. Marimekko’s impact reaches beyond Finland, however, as Marimekko is said to be one of the world’s first real lifestyle brands offering fashion and accessories alongside h... More Marimekko

domain: design


text:
[UPDATE BELOW] The battle for power at Occupy Wall Street continues! Yesterday firefighters seized a generator belonging to a licensed food vendor who operates a cart on the sidewalk outside Zuccotti Park. The vendor, who has only been identified as Ali, was reportedly running a power cord from his cart to the protesters' media tent. In seizing the generator, the FDNY cited "failure to provide a permit for the storage of gasoline and failure to have a permit to change out propane tanks." Regarding the first violation, Ali tells A Great Big City the gasoline canister was empty. Here's the first video:
Fire Marshals Cite Occupy Wall Street Electricity Supporting Food Vendor - NYC from JoeyBoots on Vimeo.
A Fire Marshal at the scene explained that in New York City, "The fire code states that an empty gasoline canister is equivalent to a full canister." See, the crackdown on Ali had nothing to do with helping Occupy Wall Street! Here's a second video, recorded after the generator was seized. It shows what appears to be few grouchy undercover cops being scolded by a handful of tenacious protesters, as the offending generator is taken to a nearby firehouse.
The photographer who took the photo above writes, "The number of firefighters who showed up to remove the empty gas container and generator was so silly; they, I think, felt kind of ridiculous, just sort of milling around to no purpose, and in full gear. Unsurprisingly, the NYPD presence was huge as well. And then the news crews were right there, recording the solemn 'handing of the violations' to poor Ali, who looked totally stricken.
"What was funny was, toward the end of drama, an Occupier starting strumming and singing an improvised 'Ballad of Ali's Generator.' Even the cops were cracking a smile at some of the lyrics." The FDNY and an Occupy Wall Street representative did not immediately respond to requests for comment; we'll update if we hear back.
Speaking of generators, don't think the protesters have forgotten about the other ones the FDNY seized last week. Lawyers for the demonstrators have now sent two letters to the FDNY demanding the return of their property. Here's fiery letter number two, in which the attorneys threaten to take the FDNY to court to get the generators back:
In the meantime, there's always pedal power. Surely the authorities can't have any problem with the protesters operating bikes on the sidewalk.
Update: Occupy Wall Street spokesman Patrick Bruner tells us, "From what I know the vendor was merely helping to charge cell phones and the like. This is obviously a continuation of the Mayor's extralegal policies aimed at silencing our First Amendment rights. A few days ago the mayor was lambasting our movement for hurting small businesses—in spite of the fact that the businesses are being hurt due to unnecessary barricades, and in spite of the fact that we saved Liberato's Pizza from bankruptcy—and now he's using the police to shut down street vendors for using their own permitted generators to help a cause that they believe in."

domain: news


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IHCeasy PSME2 Ready-To-Use IHC Kit
PSME2 Ready-to-use reagent kit for IHC.
Human, Mouse, Rat
Cat no : KHC0449
PA28B, PA28beta, PSME2, REG beta, REGbeta
KHC0449 is a ready-to-use IHC kit for staining of PSME2. The kit provides all reagents, from antigen retrieval to cover slip mounting, that require little to no diluting or handling prior to use. Simply apply the reagents to your sample slide according to the protocol and you're steps away from obtaining high-quality IHC data.
|Product name||IHCeasy PSME2 Ready-To-Use IHC Kit|
|Sample type||FFPE tissue|
|Primary antibody type||Rabbit Polyclonal|
|Secondary antibody type||Polymer-HRP-Goat anti-Rabbit|
|Reactivity||Human, Mouse, Rat|
|Antigen Retrieval Buffer||100 mL||50×|
|Washing Buffer||100 mL ×2||20×|
|Blocking Buffer||5 mL||RTU|
|Primary Antibody||5 mL||RTU|
|Secondary Antibody||5 mL||RTU|
|Chromogen Component A||0.2 mL||RTU|
|Chromogen Component B||4 mL||RTU|
|Signal Enhancer||5 mL||RTU|
|Counter Staining Reagent||5 mL||RTU|
|Mounting Media||5 mL||RTU|
The principal function of the proteasome is targeted degradation of intracellular proteins. Activity of the 20S proteasome is controlled by regulatory complexes that bind to the ends of the cylindrical proteasome. 11S regulator (REG or PA28), is a complex that is thought to activate proteasomes toward the production of antigenic peptides. Human PSME1 and PSME2 genes encode the two proteasome activators PA28 alpha and beta, respectively, which have been implicated in antigen processing for loading class I MHC molecules. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome.
|Storage Instructions||All the reagents are stored at 2-8°C. The kit is stable for 6 months from the date of receipt.|
|Synonyms||PA28B, PA28beta, PSME2, REG beta, REGbeta|

domain: biology


text:
I went to New York for the first time this week. I had been dreading the 7 hour flight but in the end it was fine. I got up to stretch my legs a few times, drank LOADS of water, they serve food as various intervals so that keeps you occupied, and I read a bit (though not as much as I’d planned – I foolishly thought I’d have time to study but no chance!). Travelling overnight on the way back was a poor decision, though – there was no way of sleeping properly, but at least I could nap when I got home. I’d been warned of a potential one-and-a-half hour wait at immigration on arrival in the US, but through a combination of a morning flight and it being a national holiday, the whole process took well under an hour. The immigration officer told me “you’re all set” as he let me through, kicking off an adoration for all the little American phrases I heard which took me by surprise.
The view from my hotel window (the distinctive tower is the Chrysler Building)
I soon checked into the hotel and WHAT A VIEW! And what a privilege. I was in a huge room on the 36th floor. Of course I made the most of this by barely sleeping (kept waking up, woke up at 5am both mornings, didn’t reset my body clock at all as it was such a quick visit!). They provided optional ‘fit kits’ for healthy types so I actually took them up on the offer and did some weights every morning. I’m unhinged…
Some excitable observations:
I found it very easy to get around New York without internet access on my phone, I used a little pop-up map (and the grid system makes it easy to just walk for a certain number of blocks certain you’re heading the right way). I felt very at home as a Londoner, I walked everywhere and didn’t mind the crowds. As soon as I arrived at Penn Station in Manhattan, I was hit by the 30 degree heat and raced for the comfort of air-con in the huge Macy’s opposite. I had a wander around the Macy’s themed souvenirs and wasn’t best impressed, overall the World’s Largest Store aspires to be Selfridges but ends up feeling like a Debenhams.
Grand Central Station – it’s really interesting that such a stunning building is still being used for its intended purpose. People were queuing at the lovely ticket office windows, although there were also lots of tourists like me taking photos. The most fascinating thing for me was the combined use of this public space with corporate consumerism – a whole two balconies were being used as an Apple Store complete with Genius Bar, though you were welcome to just wander around it all being nosey. It was well integrated and not too dominant, I only realised it was an Apple Store when I actually got up there, from afar it could’ve been a very laptop-y cafe!
I went straight to see the Rockefeller Center on the same afternoon I arrived – I felt on a high the whole time I was there pottering around as I had the 30 Rock theme in my head (I love 30 Rock. Sadly they didn’t have much merchandise for it in the NBC Shop as it’s old hat by now!). On the off-chance there wasn’t a queue, I went to see if I’d be able to go to the Top of the Rock that afternoon (I’d heard you had to book a timeslot, very busy, etc) and – to my delight – I could buy a ticket and go straight up! It was admittedly 5pm on a sunny Memorial Day, I have since been reliably informed that all Americans would have been at a barbeque(!). The view was amazing – I could see sunbathers in Central Park, a spectacular view of the Empire State Building, the Statue of Liberty in the distance – it really did look like I was gazing down at a map, especially with the grid system to the streets so the buildings all looked like they had been neatly lined up.
People had told me not to bother with Times Square but I found myself wandering around in that area so popped to take a look, it was just crowded and chaotic and not particularly impressive, as predicted.
The main Public Library building was well worth a visit – it’s a beautiful building inside, and outside it’s based in a lovely little park which hosts events like outdoor theatre. I enjoyed a fascinating and beautifully laid out free exhibition – the ABC of it, why children’s books matter. New Yorkers roll their eyes and say, that’s still on is it? but for a first time visitor I was extremely glad to have caught it, it was lovely!
NY Public Library
Lots of classic kids books, even a bit about Hans Christian Andersen’s fairytales for us Scandi enthusiasts. The shop was excellent, too – I bought some souvenirs here including a lovely book for the baby, rather than in Macy’s where the only souvenirs were tacky!
the High Line
I walked all along the High Line – a park converted from a former railway line – and ended up in the meatpacking district and Chelsea Market. The High Line was beautiful, even on a breezy grey day. I loved the juxtaposition of the cultivated greenery with the industrial buildings and in places the remaining train tracks, it was cleverly done. The meatpacking district, especially when viewed from above (standing on the High Line) reminded me of the Spitalfields Market area in East London, all industrial units which have been regenerated into trendy and expensive clothes shops and the like.
High Line sign & assorted Americana
Signpost in Chelsea Market
Chelsea Market was fun – lots of foodie shops and stalls, I had a delicious rice paper wrap from a vegan sushi place (one of the top ten vegan sushi restaurants in the US, it said – are there more than ten?!). It was very ‘New York’ – as well as vegan sushi you could find mini donuts with your choice of a selection of flavoured sugars, a ‘dairy bar’ with yogurt, ice cream, milkshakes, cupcakes of many varieties, a loose spices and tea stall, and Vietnamese sandwiches.
Later I walked around some of Central Park even though by now it was a bit grey and chilly, just to say I’d been there. It is really lovely, loads of different parts within it such as a huge lake and undulating hills and pretty arches/bridges.
London is ridiculous for the number of chains on the same street, you can stand in some spots and be within sight of three Prets for example, and wherever you walk you’ll find a Costa, Starbucks, Caffe Nero, or an indie coffee shop or three. On the way to my meeting I walked a good twenty minutes between my hotel and the Consulate and didn’t see one Starbucks, in fact I kept walking in order to find somewhere for a decent caffeine fix. There are however lots of delis and shops where you can pick up a watery black ‘drip’ filter coffee. The reason for free coffee refills in diners is that this coffee is weak and insubstantial. The UK’s penchant for espresso-based coffee has clearly not caught on in New York, and it got me wondering whether if someone opened a competing chain to Starbucks and had one on every corner, whether they’d make millions. Maybe not – even Pret in Manhattan has a selection of drip coffees for people to pour themselves, they’ve customised their offering for the market I suppose. I missed a good flat white – although it was far too hot on the first two days for hot coffee, iced coffee is the way to go!
One of the best foods New York has to offer! I had a couple, an everything bagel (‘everything’ being everything savoury like poppy and sesame seeds, onion, wholewheat) with a schmear of scallion cream cheese but I should have branched out and tried more, one for every meal would be about right I think. Next time (please let there be a next time!) I will have honey and pecan cream cheese on a cinnamon bagel. I really should stop planning my meals so far in advance…
…is dirty, smelly, and difficult to navigate – I know, I’m already a confessed London Transport fanatic, but you realise just how amazing the tube in London is after using the New York subway.
I foolishly found myself too exhausted and far away to walk back to my hotel on the last afternoon, so needed to top up my Metro card using the remainder of my cash in order to make one journey. There are far too few ticket machines, and they all use an old technology form of touchscreen which is maddening (hit the screen a few times, it registers the wrong number, start again…), and they often reject your perfectly adequate dollar bills! Thankfully despite the queue forming behind me for the only machine of the three accepting cash(!), no one was huffy or rude (an impossibility if the same scenario had occurred in London!), in fact the man behind me exchanged my faulty dollar bill for quarters and blamed the machine. All the lines and many of the stations are numbered, so that must be annoying if you have dyscalculia or any problem remembering numbers (‘was it line 4 to 33rd Street or line 3 to 44th Street?’). This is why people take taxis, I guess!
I kept in touch with my partner online from the hotel, we just chatted briefly via messenger. The time difference meant we couldn’t catch up at the end of my day (the UK is five hours ahead) but it was nice to still have that connection during the day. He was spending four days at home covering childcare for the duration of my trip. He insisted I shouldn’t micro-manage by planning him things to do while we swapped roles (I’m usually at home doing most of the childcare, around my studies) – “on principle you shouldn’t have to help me, I should be doing this without us reverting to stereotype of the useless dad who needs to be told what to do” – but in the end I did make some successful suggestions, including toddler soft play at the leisure centre, a couple of hours at our combined childcare/workspace for a well-earned break, a few easy meal ideas, the regular childcare swap at home with another mum friend.
The purpose of my trip
I spoke at an informal meeting of translators (of Danish to English) at the Consulate General of Denmark, invited by my funders (the Danish Arts Foundation), on the work I’d been doing on establishing the network for Da-En translators in the UK/Europe. The meeting went well, I think, although perhaps everyone was left with more questions than answers (should there be two networks or shall we combine networks?) and was followed by a fantastic dinner at the official residence of the Danish Ambassador of the Consul General, a penthouse on the 76th floor of NY by Gehry overlooking Brooklyn Bridge and the World Trade Center – absolutely stunning views, as you might imagine!
It was a lovely group of people to spend the afternoon and evening with, speaking Danish and talking about translation, books, and New York.
An amazing privilege, quite unreal the whole thing. Now my legs ache from walking so much!

domain: geography


text:
On July 1, 1903, the first Tour de France commenced in a Parisian suburb with five dozen competitors originating from France, Germany, Switzerland, Italy, and Belgium. The brainchild of a struggling bi-monthly sports-based publication called L'Auto, the Tour de France was created with the intention of raising viewership and funding for upcoming issues. Bikers raced across over 1,500 miles of sometimes uncharted terrain in hopes of securing the championship title and a healthy 20,000 franc prize.
Today, the Tour de France encompasses over 2,000 miles and has three times the amount of riders, broadcasting each year in nearly 200 countries with billions of global spectators watching both at home and on the sidelines each year. This year, the competition, which has been delayed until August 29, will look a bit different, with smaller viewing crowds and a ban on “faire la bise,” the traditional shared kiss between riders and prize-presenters. The race will follow the same intended route from Nice to Paris, concluding the competition on September 20. As we await the 107th edition of the race and celebrate the anniversary of its inception, CR revisits archival images of the landscapes, competitions, and spectators over the course of the event’s history.
Cyclist Maurice Gavin wins the first Tour de France in 1903. He beat other competitors by only one minute.
Cyclists pass a French mountain range in the 1937 competition.
Gino Bartali, an Italian cyclist, races along the track in 1945. He won the race in both 1938 and 1948.
Bikers riding down a main street in the Nord section of France in 1947.
French cyclist and champion of the 1947 Tour de France, Jean Robic, greets fans after the race.
A view from Livry-Gargan, the starting point of the 1949 Tour de France.
The caravan rides through the Alps mountain range in 1950.
An image taken on July 4, 1952, during the 10th stage of the race, across the Lausanne-Alpe d'Huez mountain.
Italian cyclist Fausto Coppi proudly displays a bouquet of flowers after winning the 1952 competition.
Louison Bobet riding up-hill in the Rhône Valley, 1955.
André Darrigade, a French biker, crashes into a Tour de France officiator during the 1958 race.
A sweeper car clears the rider's pathways in July 1960.
English cyclist Tom Simpson competing in 1960.
An unknown rider embraces a woman at the completion of the 1960 Tour de France.
French cyclists Jacques Anquetil and Raymond Poulidor speed down a secluded pathway circa 1960.
Anquetil, the esteemed French cyclist, wins the competition in 1961. He was the first rider in the history of the Tour de France to take home first place five different times.
Spectators of the 1962 competition await riders in the French Alps.
Poulidor (#19) and Anquetil (#1) are watched by fans during the 1964 race.
Biker Julio Jimenez is cheered on by fans along the competition's route circa 1966.
Rider Eddy Merckx from Belgium tears down the French countryside in the 1968 competition. He is one of the most famous Tour de France competitors in history, having won the competition four times.
Merckx's wife congratulates him at the 1969 finish line, where he was awarded first place.
Merckx enters the final stage of the 1970 competition. It would become his third win.


text:
Armenian police have used force to thwart a small opposition protest in a central Yerevan square that re-opened only a few days ago after remaining closed to the public for nearly two years.
About a dozen activists gathered near one of the statues in Liberty Square on Friday evening protesting “human rights violations” in Armenia and calling for “an end to torture in the army and prisons”, including against several opposition members remaining in jail. They also held banners demanding that the government allow an independent television company controversially taken off the air eight years ago to resume broadcasts.
Acting on orders of Colonel Robert Melkonian, chief of the Armenian Police’s Patrol Service, police workers roughed up some of the protesters, trying to remove them from the square. They managed to force several activists to move across the streets telling them that their protest was disturbing public order. However, the oppositionists returned to Liberty Square some time later and attempted to continue their protest.
This was the first time opposition members attempted to hold a political gathering in the square after public access to it was allowed on Tuesday.
The square remained closed from September 2008 due to construction of a large underground car park that began several months after the violent dispersal of an opposition tent camp protesting the outcome of a disputed presidential election. The opposition has insisted that the launch of a construction project in the area was designed to prevent its members from staging more rallies in the square, which, since the anti-Soviet demonstrations in the late 1980s, had turned into a traditional place for political assemblies in Yerevan. The government has brushed aside the accusations.
While the square stayed closed, activists and supporters of the opposition Armenian National Congress (HAK) would gather in an adjacent boulevard where they also regularly encountered police restrictions resulting in scuffles. Dozens of opposition members staging protests in Northern Avenue and elsewhere in the city have been detained by police in the past two years. Criminal cases have been brought against some of them for resisting police officers.
The police action against the presumed violation of public order also appeared to have affected some unsuspecting citizens who claimed they had been mistaken for demonstrators while they were taking an evening stroll in the capital’s favored public place.
“I am an ordinary citizen of the Republic of Armenia. Today is a public holiday, and I have come here to take a walk,” asserted one such person. “I asked the policeman to show me a map so I could see in which part of the city I was allowed to walk and where I was not.”
While police remained in control of the square, a number of protesters would not give up. One of them, Vardges Gaspari, told RFE/RL: “We won freedom in 1988. We will never again allow this freedom to be trampled upon.”
A senior HAK member told RFE/RL earlier this week that the Armenian opposition would seek to stage its next rally in the re-opened square, which he described as "the cradle of Armenian democracy". Levon Zurabian did not specify, however, when such a rally would be held.

domain: sociology


text:
The best-selling book "Megatrends" predicted in 1982 that minority demographics would change the U.S. work force, economy, and political structure. Three years earlier, Hispanic Business began documenting this change by tracking data on Hispanic empowerment. The magazine's 25th anniversary provides a historic moment to look back at the Hispanic market's transformation over the past quarter century, as well as to look forward to the changes yet to come.
VIDEO: A New Millennium
Twenty-five years ago, futurists had an easy task in pointing to a future Hispanic population wave. But with surprising speed, Hispanics have advanced beyond "new immigrant" status to enter the U.S. middle class. The implications of this transition will continue to define the progress for the U.S. Hispanic market during the next 25 years.
"Certainly, the U.S. Hispanic market can be characterized as being in a state of dynamic flux, especially during the last 25 years," states the introduction to "Hispanic Consumers in Transition," a book from HispanTelligence, the research service unit of Hispanic Business. "This market's growth has been dramatic – fueled by demographic expansion, as well as by rising demand and opportunity in the U.S. labor and entrepreneurial markets."
|POPULATION GROWTH (in millions)|


text:
Freedom of Speech is our fundamental right, a right meant for the greater good of society. Everyone should be able to voice out their opinions and discerns, regardless of what group or caste they belong to.
But then some politician, actor, YouTuber, or any random social media user says something insanely outrageous, and boom – there goes my belief that everyone should be allowed to speak their minds out.
It has been happening way too often lately. This time it is all the more shocking because it is coming from a professor at a law college in Goa named Shilpa Singh.
The Professor’s Absurd Comparison Lands Her In Trouble
The political science professor at Panaji’s VM Salgaocar College of Law compared women wearing mangalsutras to chained dogs in a Facebook post dated April 21 this year.
This post was perceived as anti-Hindu, hurting religious sentiments. Naturally, it garnered lots of attention, and as we know, too much of something is never good in the long run.
Her post caught the eye of Rajiv Jha, a member of Rashtriya Hindu Yuva Vahini’s Goa unit, who filed an FIR against her for derogatory comments against a religious value.
Rajiv is not directly friends with Shilpa on Facebook. He has 20-25 mutual friends with her on the platform.
He first noticed her post when the ABVP sought her termination from the position of professor on the grounds of promoting “socially hateful thoughts about a particular religion.” ABVP’s demand, however, was dismissed by the college authorities, who found no solid reason to suspend Singh.
Hours before the FIR was lodged, Singh posted a formal apology on Facebook, “(I) express my regrets to my fellow women if any of my Facebook posts have caused them hurt and offended them”.
Events That Followed After The FIR Was Lodged
“If she has thoughts, she should keep it to herself, and not publicise on social media. She is a professor; if this is what she writes here, wonder what she must be teaching her students,” posted Jha. He also called Singh “Hindu-phobic”.
After Jha’s post, Singh filed an FIR against him and he has been booked for criminal intimidation and insulting the modesty of a woman.
Jha, however, said, “Since she is a woman I went to the police station. She has filed a counter-compliant of abuse and threat to life. I could have gone directly to the college and sought action. (But) I have not.”
Singh, explaining the intention behind her “ill-perceived” post, wrote, “Since my childhood, I have been curious on questions why we have exclusive marital status symbols for women and not for the men in various cultures practices.” She denies the allegations of being “atheist” or “anti-Hindu” against her.
Her thought process behind the post is understandable, but the language used by her is not. Wearing a mangalsutra is a woman’s personal choice. While it might be suffocating for a few, it is a symbol of sanctity for many others.
Clearly, she is not in favour of such practices. However, it was not her place to compare all the mangalsutra-wearing women to chained dogs.
Image Sources: Google Images
Find The Blogger: @TinaGarg18
This post is tagged under: Mangalsutras, Indian wedding rituals, Hindu bride, Hindu wedding, married women, anti-Hindu, Anti-national, chained dogs, derogatory remarks, breach of peace, abuse of freedom of speech, political science professor, Rashtriya Hindu Yuva Vahini, professor compares women wearing mangalsutras to chained dogs, hurting religious sentiments, propagating hate on Social media


text:
Batu Caves is one of Malaysia's most famous tourist destinations. Every year hundreds of thousands of Hindu devotees congregate here for the colourful Thaipusam festival.
Batu Caves is one of Malaysia's most famous tourist destinations especially for the colourful Thaipusam festival. This attracts up to 800,000 devotees and spectators; the highlight is seeing devotees in a trance carry kavadi , a metal frame attached to the body.
Rising almost 100m above the ground, Batu Caves actually consists of three main caves and a few smaller ones. The biggest, referred to as the Temple Cave, has a 100m-high ceiling, and features ornate Hindu shrines. To reach it, visitors have to climb a steep flight of 272 steps.
Below the Temple Cave is the Dark Cave, with its amazing rock formations and a number of animals found nowhere else. Stalactites jutting from the cave's ceiling and stalagmites rising from the floor form intricate formations such as cave curtains, flow stones, cave pearls and scallops which took thousands of years to form. The Malaysian Nature Society organises regular educational and adventure trips to the Dark Caves .
The other main cave is the Art Gallery Cave located at the foot of the steps. Statues and wall paintings depicting Hindu deities and mythology are displayed here. The walk to the entrance is itself quite a pleasant experience through a lake and ponds filled with hundreds of colourful fish.
Lord Murugan statue is the tallest statue of a Hindu deity in Malaysia, another master craft by sculptors from India. Lord Murugan statue is about 42.7-meter (141 feet) tall, It is located at the Sri Subramaniar Temple at the foot of Batu Caves, It declared open on Jan 29, 2006 (Sunday)
The Batu Caves were discovered in 1892. When Hindu devotees set up a shrine to Lord Murugan, it began to attract many pilgrims.
Most come for the Thaipusam festival that celebrates two events: the birthday of Lord Murugan, the son of Lord Siva and his wife Parvati, and Lord Murugan's defeat of the evil demon Soorapadman with the aid of a powerful lance given to him by his mother.
Others come to see the 42.7m tall statue of Lord Murugan, and the cave decorated with images of Hindu deities.


What is affordable housing?
Housing is affordable for essential workers if housing costs are less than 30% of gross household income. Households spending more than 30% of income on housing costs are described as being in housing stress. Housing stress impacts on quality of life and the ability to afford other living costs.
Affordable housing is designed for the needs of low to moderate income households and is priced so families are able to meet other basic living costs such as food, clothing, transport, medical care and education. affordable housing differs from social housing. Social housing is a form of affordable housing that caters to households experiencing high levels of housing stress and social disadvantage.
As Council cannot directly influence affordability in the local housing market, or reasonably provide the required volume of affordable rental housing within the LGA, Council adopted a policy position to prioritise affordable housing for moderate income households that are vital to the prosperity of the local economy. Council defines these families as key and essential worker households.
Who are essential workers?
In Australia and internationally, workers whose wages are typically set at a national or state level, including teachers, nurses, police and fire and emergency personnel, are considered essential workers. This also includes support/ancillary workers in healthcare, education and emergency services; workers who support the labour force (e.g., childcare and aged care workers and ICT support professionals and technicians); and low paid workers who are important for local economies, such as hospitality and retail workers.
Benefits of affordable housing
The primary benefit of affordable housing programs is a social one, providing low to moderate income renters with an affordable, secure housing option, leading to improved health and employment outcomes, a greater sense of safety, independence and social connectedness.
An increased supply of affordable housing also provides opportunities for local young people to continue to live and work in their community.
Affordable housing also delivers significant benefits to the local economy through diversification of the labour market, increased job retention and increased productivity.
How can we provide affordable housing?
Willoughby City Council was one of the first metropolitan Councils to recognise the need for more affordable housing.
Council recognises affordable housing as a vital element of social and economic infrastructure and has committed to increase the supply of affordable rental housing through affordable housing targets and policy.
We do this by requiring the dedication to Council of complete dwellings or their cash equivalent equalling 4% of the accountable total floor space of new mullti-unit dwellings in identified zones within the Willoughby local government area.
These essential worker assets are then strategically managed to optimise social outcomes and financial sustainability.
Affordable housing partnership
Willoughby City Council currently has 37 essential worker housing units (2022) that are managed by Evolve Housing to provide affordable housing to essential workers in our community. Evolve Housing is an award-winning, Tier-1 nationally registered community housing provider. Evolve Housing provide housing solutions to eligible people on very low to moderate incomes who are unable to access appropriate housing in the private market. Current vacancies and information on the application process can be found on the Evolve Housing website.
New projects and initiatives
Willoughby City Council is currently undertaking planning for the following essential worker housing project:
1. Abbott Road essential worker housing project
More information to come soon.
Stuart Gibb, Community Development Team Leader
02 9777 7505


text:
Driven by continued strong growth in the lithium-ion battery market for electric vehicles, Arkema will increase the capacity of its high-performance polymer PVDF dedicated to this market at its Changshu plant by approximately 50 percent. The investment further supports the Group’s ambition to accelerate growth in Advanced Materials
The increase in capacity is scheduled to come on stream in the final quarter of 2020.
With this project, Arkema further consolidates its world-leading position in PVDF.
This is consistent with Arkema’s strategy to supply its customers from plants located in the same region.
The battery business continues to demonstrate strong sustainable growth, driven primarily by electric passenger vehicles. As a pioneer in high-performance PVDF binders and separator coatings, Arkema continues to invest in research and development and to actively support the growth of its global battery customers here in Asia and across the globe

domain: chemistry


Anthropologists have excavated sphero-conical vessels throughout the Middle East and Central Asia for decades. Yet the purposes of these containers, which often feature cone-shaped bases and tiny openings to prevent spills, are still unclear; hypotheses range from beer canteens to smoking pipes.
A recent analysis of four such vessels – found in Jerusalem’s Old City in the 1960s and dating back to the 11th or 12th century – points to a different theory. According to a team of researchers led by molecular anthropologist Carney Matheson, three of these ceramic pots likely contained oils, perfumes and medicines, consistent with earlier expectations of these vessels. But the fourth, they say, may have been used as a medieval hand grenade during the Crusades.
Inside its ultra-thick and completely undecorated walls, anthropologists have found residues of sulfur as well as mercury and magnesium (compatible with explosives). Their findings were Posted in PLOS ONE earlier this year.
Matheson, now an associate professor at Griffith University in Australia, says the hand grenade theory is supported by Arabic and Crusader texts. Specifically, he and his colleagues note historical accounts of the siege of Jerusalem in 1187 AD, which mention flashes of light and big bangs that could be consistent with flash grenades.
“Further research into these vessels and their explosive contents will allow us to understand ancient explosive technology from the medieval period and the history of explosive weapons in the Eastern Mediterranean,” Matheson said in a statement. Press release.
Scientists and historians have long sought to understand how warfare was fought thousands of years ago. The first known incendiary weapons date back to the 7th century. From this time the Byzantine Greeks used a fluid known as “greek fireto engage in combat on the high seas.
The exact components behind the Greek Fire were a closely guarded military secret and remain a mystery to this day, but oil was probably the main ingredient. Other potential elements include sulfur or pitch, saltpeter (namely potassium nitrate, a salt that forms on the surface of rocks) and turpentine, which is an oily extract obtained from conifers.
How the flammable mixture was ignited is another mystery, although it’s possible that Byzantine fighters used a compound called quicklime or calcium oxide. They threw the flammable mixture into pots or ejected it from tubes mounted on the bow of a boat and reminiscent of medieval flamethrowers. Supposedly, Greek fire could not be extinguished by water – only with sand or vinegar, which made it particularly devastating in naval warfare.
It has been cited as one of the main reasons for the long reign of the Byzantine Empire, which lasted a few thousand years after the collapse of the western half of the Roman Empire. Certainly, technology helped the Byzantines defend Constantinople against Arab sieges in AD 673 and 717, and again against Russian forces in the 10th century.
In the East, the Chinese monks discover “black powder», the precursor to modern gunpowder, in the 9th century during their quest for the elixir of immortality. Its key ingredient, saltpeter, had been used there for centuries in medicine; but somewhat surprisingly, it turned into an incendiary weapon when mixed with sulfur and charcoal.
At the time of its creation, the monks believed that the most effective chemical formula was one part sulphur, three parts charcoal and nine parts saltpeter. In the 18th century, however, scholars concocted an even more effective ratio (10:15:75), which many gunpowder makers continue to use to this day.
During the Song dynasty, the Chinese used gunpowder extremely effectively in siege warfare, especially against the Mongols. This led to the development of rudiments rockets, bombs, guns and mines. Most scholars agree that another result of these international conflicts was the introduction of gunpowder to the Middle East in the 13th century – although others argue that the technology arrived in the region still earlier and was simply kept a military secret.
Adding their two cents to the ongoing debate, Matheson and his team say their latest study of sphero-conical vessels from medieval Jerusalem – one of which contained sulfur but not saltpeter – definitively proves that the pot did not contain black powder. Instead, the alleged explosive was likely developed by locals in the immediate area. It remains to be seen if other ships of this type will tell the same story.


text:
np000068s_si_001.pdf (626.74 kB)
Molecular Structure and Activity Toward DNA of Baicalein, a Flavone Constituent of the Asian Herbal Medicine “Sho-saiko-to”
journal contributionposted on 2000-11-18, 00:00 authored by Miriam Rossi, Ryan Meyer, Pamela Constantinou, Francesco Caruso, Deborah Castelbuono, Megan O'Brien, Vasantha Narasimhan
Baicalein (5,6,7-trihydroxyflavone, 1) is of interest because of its broad spectrum of biological activity. It is a constituent of the east Asian herbal remedy, “Sho-saiko-to”. The 3D structure of 1 was determined using X-ray diffraction. The compound exists in an almost planar conformation with a C-2C-1‘ bond distance of 1.476(5) Å. Hydrogen-bonding interactions predominate in the crystal structure. The position of the three hydroxyl groups maximizes intramolecular hydrogen bonding, and each of the hydroxyl hydrogen atoms is a donor in a three-center hydrogen bond. The carbonyl oxygen, O-4, is an acceptor in an intramolecular hydrogen bond (with OH-5). Two molecules of 1 exist as hydrogen-bonded dimers related by inversion center (−x + 1, −y, −z + 1). O-4 is also an acceptor in an intermolecular hydrogen bond with OH-6. The planarity of the flavone framework is dependent on structural and/or electronic forces that stabilize the negative charge on the exocyclic oxygen atom, O-4. Compound 1, therefore, is planar in any situation where forces can stabilize the negative charge on O-4. Consistent with this, UV absorbance studies performed on 1−DNA complexes with varying concentrations of 1 strongly suggest intercalation of 1 within the double helix, followed by possible interstrand cross-links.


text:
Children suffering from trauma or adversity in their early life are more prone to complain of gastrointestinal issues later, reveals a latest study. These gastrointestinal complaints may also affect their brain and behaviour, said the study published in the journal Development and Psychopathology.
"One common reason children show up at doctors' offices is intestinal complaints. Our findings indicate that gastrointestinal symptoms in young children could be a red flag to primary care physicians for future emotional health problems," said Nim Tottenham, senior author of the study.
This is not the first time someone has pointed at links between trauma and tummy problems. Previous studies have also shown that past trauma has affected many adults with irritable bowel syndrome (IBS). IBS is a disorder that affects your colon and results in difficulty in passing stool. Poor diet is said to be the major cause behind IBS.
"The role of trauma in increasing vulnerability to both gastrointestinal and mental health symptoms is well established in adults but rarely studied in childhood," said study lead author Bridget Callaghan."Our study is among the first to link disruption of a child's gastrointestinal microbiome triggered by early-life adversity with brain activity in regions associated with emotional health."
For the study the researchers focussed on children who suffered extreme psychological pain or deprivation.
115 children who were adopted from orphanages or foster care on or before they were two years old and 229 children raised by a biological caregiver,were analysed as part of the study.
Scientists studied the data which had their behavioral information, stool sample and brain images from all the children. The findings revealed that the children exhibited distinct gut microbiomes who had early care giving disruptions from those raised by their biological parents.
"It is too early to say anything conclusive, but our study indicates that adversity-associated changes in the gut microbiomeare related to brain function, including differences in the regions of the brain associated with emotional processing," says Tottenham.
(With Inputs ANI)

domain: health


text:
Whether it is covered in a blanket of moody clouds or showing off against a crisp cloudless blue sky, Table Mountain is always a spectacular sight. It dominates the Cape Town skyline from almost every angle and with good reason, was voted one of the New Seven Wonders of the World in 2011.
The City takes its mood from the Mountain and no visitor should ever return home without taking the trip to the top, usually via the cableway. After a considerable refit in 1997, the cars now carry up to 65 passengers per trip. The trip takes about five minutes and the cars rotate through 360 degrees as you go, providing spectacular views of the City and the Bay. Cars depart from the lower cable station on Tafelberg Road every 10 to 15 minutes, but you can expect a long wait during the peak season.
The Mountain is often shrouded in cloud, the famous “tablecloth”, and since one of the objectives is to enjoy the view from the top, you should take the first opportunity you get. Otherwise you run the risk that you never get a perfectly clear day. The cableway doesn’t operate if the wind is too strong or the visibility too poor, but you probably wouldn’t want to go there then anyway.
Whilst the cableway is the gentle route to the top, some people actually climb the mountain face itself! Platteklip Gorge is probably the most popular route, it is quite steep but relatively straightforward, taking between one and three hours depending on fitness level. There are other routes but none that I am qualified like to comment on! If you do decide to hike up, please go in pairs and leave enough time to get down before dark.
Once you get to the top, there is a small curio shop for a cool drink and a snack, and there are at least three easy walks you can make. You will also come across a number of large rodent like animals, usually basking in the sun on large rocks. This is the famous Dassie, otherwise known as the rock badger, an animal which is commonly believed to be the closest related relatives to the Elephant. Can you believe that?

domain: travel


text:
Things to see or do
- Directions: Rinuccini Restaurant, restaurant, is located opposite Kilkenny Castle on the parade.
- Affiliations:: Taste of Kilkenny Food Trail. Ristorante Rinuccini a multi award-winning Italian restaurant see website for details.
- Lunch: Monday to Friday: 12pm to 3pm Saturday/Sunday: 12pm to 3.30pm
- Early Bird: Sunday to Friday: 5pm to 9pm Saturday: 5pm to 6.30pm
- Dinner: Monday to Saturday: 5pm to 10pm Sunday: 5pm to 9.30pm
- Opening Times: Days open: 7 days - lunch & dinner days closed: 25th & 26th December. Lunch: Mon - Sat: 12.pm - 3pm: Sunday: 12pm. - 3.30pm: Early Bird: 6 Days: 5pm - 9pm: Saturday: 5pm - 6.30pm. Dinner: Mon - Sat: 5pm - 10pm: Sunday: 5pm - 9.30pm.
- Method of Payment: All major credit cards accepted
Rinuccini RestaurantKilkenny City Kilkenny - Ireland South
Ristorante Rinuccini is a family run, restaurant committed to delivering fresh local and Irish produce. The sourcing and quality of their produce is of utmost importance and has been a key factor in their 22 Year success. Being from Lazio, Italy, and owning and running an Italian restaurant, Chef Antonio Cavaliere strives to produce classic Italian cuisine using the very best Irish and local ingredients. All wines and Italian products are imported directly from selected vineyards and quality Artisan producers in Italy. Rinuccini's boasts one of Ireland's most extensive Italian wine lists and invite guests to visit our custom-built wine cellar at the restaurant.
ContactTelephone+353 (0)56 776 1575
Address: Rinuccini Restaurant, Opposite Kilkenny Castle, 1 The Parade, Co Kilkenny, Republic of Ireland

domain: food


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