He's still giving the money back though.

He's still giving the money back though.

The former Palm Beach, Fla., home of John Lennon and Yoko Ono is for sale at $47.5 million.

Unilever is recalling Wall’s Mini Calippo (Orange and Lemon-Lime) multi-packs because they may contain small pieces of metal. The presence of metal makes this product unsafe to eat.

Valparaiso Vikings were set up for a tournament run before defection of star guard, who has offers from IU and Purdue.

The Boilermakers open the 2018 ESPN Charleston Classic against Appalachian State, with the winner facing Davidson or Wichita State.

Now you can read all of IndyStar's sports content in one place with our free INSports app.

Indianapolis police arrested a man on Saturday near the location of the fatal police shooting of Dreasjon "Sean" Reed days earlier.

Demonstrators describe an arrest and pepper ball use by IMPD during a protest over the death of Dreasjon Reed near 62nd Street and Michigan Road.

Indianapolis police arrested a man on Saturday near the location of the fatal police shooting of Dreasjon "Sean" Reed days earlier.

Emacs "predates Linux, and was once far more popular," writes LWN.net, while adding that the text editor "has fallen into relative obscurity over the years." Then it reports on a "mega-thread" on the emacs-devel mailing list about how to make Emacs more appealing and attractive to users: The discussion started with a post from "ndame" asking why Emacs is "so square"; the appearance of things like buttons could be improved with rounded corners, they said. Richard Stallman, one of the original authors of Emacs, seemed somewhat dismissive in his reply: "Perhaps we should implement a mode that puts cosmetics on Emacs so it will appeal to those who judge by the surface of things." But Stefan Kangas thought there was more to it than that: I think it's unfortunate if we assume that this is all bells and whistles. Graphical design elements can also improve usability. I also don't know that it's helpful to assume that the rest of the world will take the enlightened stance.... He wondered if there was "any reason not to improve the default look". Stallman said that there are some technical barriers in finding someone interested in and capable of doing the work needed, but there is an overarching problem that needs to be addressed first: The code to interface Emacs to X-based GUIs needs rewriting by an expert, and has needed it for decades. Until it gets that rewrite, changes in it are likely to break something. Stallman did agree that the graphical design could improve usability, "but I have a feeling that the changes that would help are deeper issues than the shape of corners". It was a long and interesting discussion, touching on the popularity of both Vim and Visual Studio Code, while another post questioned whether Emacs should even be prioritizing its menu bar and tool bar. One post suggested "starter kits" to make the text editor more friendly to newcomers, another suggested making Cntrl-C cut-and-paste the default key binding, and one asked whether it was Emacs' terminology and keyboard shortcuts that might be confusing to users coming from Microsoft Word. "You are basically making a commitment to being or becoming a power user..." argued another post. "If you just want to do 'casual' text editing emacs is a very weird choice in 2020."

Read more of this story at Slashdot.

Apple India Website Puts Siri in Silent Mode

Filed under: North America, United States, Airlines, Airports, News

The new application process allows U.S. citizens to directly enroll in TSA Pre✓[TM], an expedited screening program that allows travelers to leave on their shoes, light outerwear and belt, keep their laptop in its case and their 3-1-1 compliant liquids/gels bag in a carry-on, in select screening lanes. To date, passengers have only been eligible through existing programs such as U.S. Custom and Border Protection's Global Entry program and frequent flier programs with certain airlines, but this announcement will allow travelers to apply directly for the expedited screening program.

Continue reading TSA Lets Travelers Apply for PreCheck

TSA Lets Travelers Apply for PreCheck originally appeared on Gadling on Wed, 04 Dec 2013 16:58:00 EST. Please see our terms for use of feeds.

South Africans must insist on innovative solutions and new policies to ensure that when the country emerges from this governance and economic crisis, it does so not only aware of the country’s weaknesses but also primed to effect the necessary changes, writes Pieter du Toit.

Some kids took advantage of the opportunity to show their appreciation for their moms on Saturday afternoon at the Love You Mama event.

Soon after CTV News Edmonton aired a story about a local wood carver who had one of his carvings stolen, he got a knock on his door.

SuperSport United winger Aubrey Modiba says a conversation with club CEO Stanley Matthews convinced him to stay despite interest from Mamelodi Sundowns.

Former captain Paul O'Connell says it will be vital for the British & Irish Lions to pick a leader capable of beating the Springboks at their own game.

A Skipper Butterfly, photographed today in my backyard in Bendigo, Victoria.

The DML News App offers the best in news reporting.

The post REPORT: UFC bout dropped from card after fighter tests positive appeared first on Dennis Michael Lynch.

Canadians working aboard two cruise ships who weren't allowed to come to shore because of concerns about COVID-19 are finally able to return home.

Police and City of Vancouver park rangers escorted the last person living in Oppenheimer Park out of the tent city Saturday afternoon, moments before crews with excavators moved in to clean up the mountains of trash left behind.

School, friends and normal day to day interactions have taken a virtual shift. However, for those with limited access to the internet, devices and other technology, isolation can be challenging.

Research Event

Event participants

Jeremy Gordon, Director, China Business Services
Chair: Roderic Wye, Associate Fellow, Asia Programme, Chatham House

geoffiths posted a photo:

Challenge #17 the inspiration for today’s photo is to come from the VERY next thing you audibly hear. I heard someone say "Welcome" so my interpretation was a future of getting close again would be welcome.

gali_nette posted a photo:

Although a robust inflammatory response is needed to combat infection, this response must ultimately be terminated to prevent chronic inflammation. One mechanism that terminates inflammatory signaling is the production of alternative mRNA splice forms in the Toll-like receptor (TLR) signaling pathway. Whereas most genes in the TLR pathway encode positive mediators of inflammatory signaling, several, including that encoding the MyD88 signaling adaptor, also produce alternative spliced mRNA isoforms that encode dominant-negative inhibitors of the response. Production of these negatively acting alternatively spliced isoforms is induced by stimulation with the TLR4 agonist lipopolysaccharide (LPS); thus, this alternative pre-mRNA splicing represents a negative feedback loop that terminates TLR signaling and prevents chronic inflammation. In the current study, we investigated the mechanisms regulating the LPS-induced alternative pre-mRNA splicing of the MyD88 transcript in murine macrophages. We found that 1) the induction of the alternatively spliced MyD88 form is due to alternative pre-mRNA splicing and not caused by another RNA regulatory mechanism, 2) MyD88 splicing is regulated by both the MyD88- and TRIF-dependent arms of the TLR signaling pathway, 3) MyD88 splicing is regulated by the NF-κB transcription factor, and 4) NF-κB likely regulates MyD88 alternative pre-mRNA splicing per se rather than regulating splicing indirectly by altering MyD88 transcription. We conclude that alternative splicing of MyD88 may provide a sensitive mechanism that ensures robust termination of inflammation for tissue repair and restoration of normal tissue homeostasis once an infection is controlled.

Bacterial products such as lipopolysaccharides (or endotoxin) cause systemic inflammation, resulting in a substantial global health burden. The onset, progression, and resolution of the inflammatory response to endotoxin are usually tightly controlled to avoid chronic inflammation. Members of the NF-κB family of transcription factors are key drivers of inflammation that activate sets of genes in response to inflammatory signals. Such responses are typically short-lived and can be suppressed by proteins that act post-translationally, such as the SOCS (suppressor of cytokine signaling) family. Less is known about direct transcriptional regulation of these responses, however. Here, using a combination of in vitro approaches and in vivo animal models, we show that endotoxin treatment induced expression of the well-characterized transcriptional repressor Krüppel-like factor 3 (KLF3), which, in turn, directly repressed the expression of the NF-κB family member RELA/p65. We also observed that KLF3-deficient mice were hypersensitive to endotoxin and exhibited elevated levels of circulating Ly6C+ monocytes and macrophage-derived inflammatory cytokines. These findings reveal that KLF3 is a fundamental suppressor that operates as a feedback inhibitor of RELA/p65 and may be important in facilitating the resolution of inflammation.

Antibodies are widely used as cancer therapeutics, but their current use is limited by the low number of antigens restricted to cancer cells. A receptor tyrosine kinase, receptor tyrosine kinase-like orphan receptor 2 (ROR2), is normally expressed only during embryogenesis and is tightly down-regulated in postnatal healthy tissues. However, it is up-regulated in a diverse set of hematologic and solid malignancies, thus ROR2 represents a candidate antigen for antibody-based cancer therapy. Here we describe the affinity maturation and humanization of a rabbit mAb that binds human and mouse ROR2 but not human ROR1 or other human cell-surface antigens. Co-crystallization of the parental rabbit mAb in complex with the human ROR2 kringle domain (hROR2-Kr) guided affinity maturation by heavy-chain complementarity-determining region 3 (HCDR3)-focused mutagenesis and selection. The affinity-matured rabbit mAb was then humanized by complementarity-determining region (CDR) grafting and framework fine tuning and again co-crystallized with hROR2-Kr. We show that the affinity-matured and humanized mAb retains strong affinity and specificity to ROR2 and, following conversion to a T cell–engaging bispecific antibody, has potent cytotoxicity toward ROR2-expressing cells. We anticipate that this humanized affinity-matured mAb will find application for antibody-based cancer therapy of ROR2-expressing neoplasms.

Prevention of aberrant cutaneous wound repair and appropriate regeneration of an intact and functional integument require the coordinated timing of fibroblast and keratinocyte migration. Here, we identified a mechanism whereby opposing cell-specific motogenic functions of a multifunctional intracellular and extracellular protein, the receptor for hyaluronan-mediated motility (RHAMM), coordinates fibroblast and keratinocyte migration speed and ensures appropriate timing of excisional wound closure. We found that, unlike in WT mice, in Rhamm-null mice, keratinocyte migration initiates prematurely in the excisional wounds, resulting in wounds that have re-surfaced before the formation of normal granulation tissue, leading to a defective epidermal architecture. We also noted aberrant keratinocyte and fibroblast migration in the Rhamm-null mice, indicating that RHAMM suppresses keratinocyte motility but increases fibroblast motility. This cell context–dependent effect resulted from cell-specific regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation and expression of a RHAMM target gene encoding matrix metalloprotease 9 (MMP-9). In fibroblasts, RHAMM promoted ERK1/2 activation and MMP-9 expression, whereas in keratinocytes, RHAMM suppressed these activities. In keratinocytes, loss of RHAMM function or expression promoted epidermal growth factor receptor–regulated MMP-9 expression via ERK1/2, which resulted in cleavage of the ectodomain of the RHAMM partner protein CD44 and thereby increased keratinocyte motility. These results identify RHAMM as a key factor that integrates the timing of wound repair by controlling cell migration.

The EU-U.S. relationship is one of the most significant partnerships among wealthy nations. Interconnections between the two on migration issues make dialogue necessary and inevitable, as each relies on each other to attain a number of policy objectives, most clearly in the case of travel and border security.

This final report summarizes and reflects upon the key findings of the Improving EU and U.S. Immigration Systems: Learning from Experience comparative research project undertaken by MPI and the European University Institute through a grant from the European Commission.

Declaring it has been “pained” by the Jodian Fearon situation, the embattled Andrews Memorial Hospital (AMH) is speaking out, saying it has never been approached for or rejected efforts at registration or certification since it began operating 76...

At least 10 stores inside the Portmore Mall have fallen casualty to the economic chokehold brought on by the COVID-19 pandemic, with several others struggling to stay afloat as St Catherine businesses grapple with revenue losses. And with a 14-day...

Almost five years ago, lawmakers on a bipartisan committee of Parliament agreed unanimously to amend the law to give the Independent Commission of Investigations (INDECOM) the power to arrest and prosecute cops. That proposed amendment, which was...

Education officials across the Caribbean and Latin America have asserted that teachers will be in need of psycho-social support for their return to the classroom, following the COVID-19 pandemic. Approximately 91,710 teachers and seven million...

Ce manuel pratique et simple d’utilisation à l’usage des décideurs et des praticiens fait le point des mesures les plus récentes prises par les pouvoirs publics en direction des diasporas. La question qui se pose aux responsables politiques n’est pas tant de savoir si les diasporas peuvent être utiles à leur pays d’origine, mais comment elles le sont et quels types de politiques et de programmes publics sont à même de favoriser ces relations.

Sweden’s strong economic record continues to be marred by its struggles to integrate immigrants, especially those who come through humanitarian or family channels. This report describes how Sweden is trying to overcome these labor market integration challenges and analyzes how successful its workforce development and integration policies have been in helping immigrants progress from low-skilled work to middle-skilled jobs.