Darling Harbour is a harbour adjacent to the city centre of Sydney, New South Wales, Australia that is made up of a large recreational and pedestrian precinct that is situated on western outskirts of the Sydney central business district.
Finding medicines that can kill cancer cells while leaving normal tissue unscathed is a Holy Grail of oncology research. In two new papers, scientists at UC San Francisco and Princeton University present complementary strategies to crack this problem with “smart” cell therapies—living medicines that remain inert unless triggered by combinations of proteins that only ever appear together in cancer cells.
Biological aspects of this general approach have been explored for several years in the laboratory of Wendell Lim, PhD, and colleagues in the UCSF Cell Design Initiative and National Cancer Institute– sponsored Center for Synthetic Immunology. But the new work adds a powerful new dimension to this work by combining cutting-edge therapeutic cell engineering with advanced computational methods.
For one paper, published September 23, 2020 in Cell Systems, members of Lim’s lab joined forces with the research group of computer scientist Olga G. Troyanskaya, PhD, of Princeton’s Lewis-Sigler Institute for Integrative Genomics and the Simons Foundation’s Flatiron Institute.
Using a machine learning approach, the team analyzed massive databases of thousands of proteins found in both cancer and normal cells. They then combed through millions of possible protein combinations to assemble a catalog of combinations that could be used to precisely target only cancer cells while leaving normal ones alone. In another paper, published in Science on November 27, 2020, Lim and colleagues then showed how this computationally derived protein data could be put to use to drive the design of effective and highly selective cell therapies for cancer.
“Currently, most cancer treatments, including CAR T cells, are told ‘block this,’ or ‘kill this,’” said Lim, also professor and chair of cellular and molecular pharmacology and a member of the UCSF Helen Diller Family Comprehensive Cancer Center. “We want to increase the nuance and sophistication of the decisions that a therapeutic cell makes.”
Over the past decade, chimeric antigen receptor (CAR) T cells have been in the spotlight as a powerful way to treat cancer. In CAR T cell therapy, immune system cells are taken from a patient’s blood, and manipulated in the laboratory to express a specific receptor that will recognize a very particular marker, or antigen, on cancer cells. While scientists have shown that CAR T cells can be quite effective, and sometimes curative, in blood cancers such as leukemia and lymphoma, so far the method hasn’t worked well in solid tumors, such as cancers of the breast, lung, or liver.
Cells in these solid cancers often share antigens with normal cells found in other tissues, which poses the risk that CAR T cells could have off-target effects by targeting healthy organs. Also, solid tumors also often create suppressive microenvironments that limit the efficacy of CAR T cells. For Lim, cells are akin to molecular computers that can sense their environment and then integrate that information to make decisions. Since solid tumors are more complex than blood cancers, “you have to make a more complex product” to fight them, he said.
For those longing to know where their favorite scenes in “Poldark” were filmed, Pitkin’s latest addition to the Film Locations series goes behind the scenes of the hugely popular TV series and follows in the footsteps of Ross and Demelza along windswept cliffs, rugged coastline, and untouched, pristine beaches. From Padstow to the Lizard peninsula, Cornwall takes center stage, providing the breath-taking backdrop that brings the series to life.
The latest awarding-winning adaptation of Winston Graham’s Poldark, produced by the BBC, captured the hearts of millions of viewers worldwide. Over its five seasons, it brought the region’s rich heritage back to life, with tales of smugglers, shipwrecks, and the secrets of the mines gripping viewers’ imaginations. Filled with walks in beautiful places and useful information about the region and the series’ filming locations, this is a perfect introduction to Britain’s best-kept secret.
About The Author
Gill Knappett has worked on many Pitkin books over a 20-year period, specializing in royal titles and Britain’s best-loved places to visit. Her Pitkin titles include Catherine Duchess of Cambridge, The Queen, and Walk London.
The 140-km bike path will offer amazing views over Italy’s largest lake and the mountains that surround it. It is expected to attract many bike enthusiasts who already travel to the area to ride on the Dolomites paths.
It will circle beautiful Lake Garda in northern Italy from Capo Reamol on the lake’s western shore to Limone sul Garda at the border with Trentino. The path crosses three regions, Lombardy, Trentino and Veneto and uses both existing cycling tracks and newly built paths.
Lake Garda is already a paradise for those who love exploring on a bike; from 2021, even more so, as the so-called Garda by Bike project, is scheduled to be completed.
The project has been in the works for two years and the stretch that is yet to be completed promises to be one of the most spectacular as it’s built right above the lake, next to cliffs that almost jut out into the water.
The Patagonia Better Sweater Fleece Vest is by far one of the brand’s most popular products. It’s also one of its most divisive. Over the last five years, the vest became a must-have accessory for Wall Street workers in Manhattan’s financial district to tech bros in Silicon Valley.
The company says at its height, it was fielding 60 requests for co branded vests, a day. But Patagonia, a private company that values environmental and political activism, never sought out to become the go-to status symbol for some of the biggest and richest corporations in the world.
The combination of hefty price tags and a professional-class of super fans earned it the nickname “Patagucci” prompting it to reevaluate which companies it allowed to put a moniker on the vest as a way to ensure their partners align with their progressive culture.
Patagonia even discouraged consumers from partaking in Black Friday sales and snuck political messages into the tags of its clothing. Here’s how Patagonia’s anti consumption philosophy helped it build a billion dollar outdoor brand.
Auchendennan House is an impressive A-listed Baronial castle featuring two turrets, set centrally amidst its 55 acres of beautifully designed landscape of parkland and woods. Located close to the southwest bank of Loch Lomond, it enjoys remarkable views across the loch to the mountains of the national park beyond.
The four-storey sandstone castle is approached from the main road, along a private tarmac drive with speed bumps, lined with trees. Through secure gates fitted with a telephone entry system, the driveway incorporates a carriage turning circle, with an attractive water fountain carved with dolphins and shells.
On arrival, shelter is provided by a striking Porte Cochere with arched coach openings, turrets and a vast array of decorative details.
Entered on basement level, you are welcomed into a grand 20th century vestibule, with oak panelling and a large carved fireplace including cherub and female figurines and inscriptions. Hidden in the panelling one secret door leads to a WC, whilst another leads to an office, various storage rooms, and a two-bedroom staff apartment with bathroom, kitchen and living area. Also on this level is a large reception room with its own garden entrance, currently used as a gym.
Truffle hunters and their dogs are combing Croatia’s northwest as the winter hunting season for the delicacy gets under way.
A truffle is the fruiting body of a subterranean ascomycete fungus, predominantly one of the many species of the genus Tuber. In addition to Tuber, many other genera of fungi are classified as truffles including Geopora, Peziza, Choiromyces, Leucangium, and over a hundred others.
Truffles — the non-chocolate kind, sorry — are edible fungi, like mushrooms. … Though multiple species are found worldwide, prestige truffles come from specific areas, much like wine from celebrated regions of Europe and California. Black truffles from France and white truffles from Italy are the two most highly valued.
Travel video from beautiful Slovakian mountains – Mala Fatra and remains of the castle Strecno. The trail chosen is connected to a place of a Slovakian national hero – highway man – Juraj Janosik – who lived about 300 years ago and was hiding in this area – so called Slovakian Robin Hood:). The late august weather was hot and dry, but the top of the mountains was quite windy and chilly.
Malá Fatra is a mountain range in the Western Carpathians in the north-west of Central Slovakia. In the geomorphological system, it is a part of the Fatra-Tatra Area. It is situated approximately between the cities of Nitrianske Pravno, Strečno, Martin and Zázrivá.
Magic vision of Campo Imperatore plateau, in Italy. An amazing timelapse video, entirely shooted in night time, both with or without moon. Tha dance of the cloud and fog, the run of stars and milky way.
Campo Imperatore is a mountain grassland or alpine meadow formed by a high basin shaped plateau located above Gran Sasso massif, the largest plateau of Apennine ridge. Known as “Little Tibet”, it is located in Gran Sasso e Monti della Laga National Park, near L’Aquila, Abruzzo, Italy.