This exclusive clip from the movie "Stray" shows Zeytin hunting for stray bones on a public sidewalk, as admiring humans look on.
This exclusive clip from the movie "Stray" shows Zeytin hunting for stray bones on a public sidewalk, as admiring humans look on.
– CFT7455 Demonstrated High Cereblon Binding Affinity and Rapid, Deep IKZF1/3 Degradation Enabling Activity across a Panel of Multiple Myeloma Cell Lines Including IMiD-Resistant Models – – CFT7455 Promotes Sustained Degradation of IKZF1/3 and Durable Anti-tumor Response, Including Regressions in an IMiD-Insensitive Myeloma Tumor Xenograft Model – – CFT7455 Phase 1/2 Trial in Multiple Myeloma and Non-Hodgkin Lymphomas On Track for 1H 2021 Initiation – WATERTOWN, Mass., April 10, 2021 (GLOBE NEWSWIRE) -- C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a biopharmaceutical company pioneering a new class of small-molecule medicines that selectively destroy disease-causing proteins through degradation, today presented preclinical data for CFT7455, the Company’s lead program, a MonoDACTM degrader targeting IKZF1/3 for the treatment of hematologic malignancies. These results, which support clinical evaluation of CFT7455 in multiple myeloma, were delivered as a late-breaking oral presentation during the first session of the American Association for Cancer Research (AACR) Annual Meeting 2021. “IKZF1/3 proteins are critical dependencies of B cell malignancies including multiple myeloma and subsets of non-Hodgkin’s lymphoma,” said Stewart Fisher, Ph.D., chief scientific officer of C4 Therapeutics. “We are pleased to share preclinical data demonstrating that potent catalytic IKZF1/3 degradation activity of CFT7455, coupled with optimized pharmacological properties, can result in regression of multiple myeloma xenograft tumors not responsive to approved IMiD therapies. We are optimistic that the in vitro and in vivo data we saw preclinically will translate into improved, clinically meaningful outcomes for patients and we look forward to initiating our CFT7455 Phase 1/2 clinical trial in the first half of this year.” Summary of Results C4T conducted in vitro studies to confirm CFT7455’s intended mechanism. Notable observations include: CFT7455 binds with high affinity to the E3 ligase adapter protein, cereblon (Kd = 0.9 nM);In vitro, CFT7455 treatment results in deep, rapid degradation of IKZF1/3 proteins, resulting in apoptotic cell death; andCFT7455 demonstrated broad, potent anti-proliferative activity in a panel of multiple myeloma cell lines. In mouse xenograft models of IMiD-insensitive multiple myeloma, data further established CFT7455 as a highly potent, catalytic degrader of IKZF1/3, capable of generating anti-tumor activity as a single agent and in combination with dexamethasone. Notable observations include: In the H929 myeloma xenograft tumor model, daily oral administration of CFT7455 at 0.1 mg/kg for three weeks led to partial or complete tumor regression, with the latter being durable even after stopping treatment.CFT7455 produced deep and durable degradation of IKZF3 in the RPMI-8226 myeloma xenograft tumor model, which is relatively insensitive to pomalidomide. Tumor regression resulted from treatment with CFT7455 in both naïve RPMI-8226 tumors, as well as those previously exposed, but unresponsive, to pomalidomide.The combination of CFT7455 and dexamethasone in the RPMI-8226 tumor xenograft model yielded expected improvements in efficacy and survival outcomes in mice bearing RPMI-8226 xenograft tumors, compared to either agent used alone. Based in part on these results, C4T plans to explore the therapeutic applications of CFT7455 for the treatment of relapsed or refractory multiple myeloma and non-Hodgkin’s lymphomas and expects to initiate a Phase 1/2 clinical study of CFT7455 in the first half of 2021. C4T’s AACR Annual Meeting 2021 presentation will be archived on the “Scientific Publications” page in the Investors section of the Company’s website, located at www.c4therapeutics.com. About CFT7455CFT7455 is an orally bioavailable MonoDAC™ (Monofunctional Degradation Activating Compound) degrader designed to bind with high affinity to the E3 ligase adapter protein, cereblon, to target and degrade IKZF1/3 for the treatment of hematologic malignancies such as multiple myeloma and non-Hodgkin’s lymphoma, including peripheral T cell lymphoma and mantle cell lymphoma. In preclinical studies, CFT7455 has demonstrated potent and selective protein degradation with favorable pharmacological properties. About C4 TherapeuticsC4 Therapeutics (C4T) is a biopharmaceutical company focused on harnessing the body’s natural regulation of protein levels to develop novel therapeutic candidates to target and destroy disease-causing proteins for the treatment of cancer and other diseases. This targeted protein degradation approach offers advantages over traditional therapies, including the potential to treat a wider range of diseases, reduce drug resistance, achieve higher potency, and decrease side effects through greater selectivity. To learn more about C4 Therapeutics, visit www.C4Therapeutics.com. Forward-Looking StatementsThis press release contains “forward-looking statements” of C4 Therapeutics, Inc. within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements may include, but may not be limited to, express or implied statements regarding our ability to develop potential therapies for patients; the design and potential efficacy or safety profile of our therapeutic approaches; the potential timing, design and advancement of our preclinical studies and clinical trials, including the potential timing for regulatory authorization related to clinical trials; our ability and the potential to successfully manufacture and supply our product candidates for clinical trials; our ability to replicate results achieved in our preclinical studies or clinical trials in any future studies or trials; our current resources and cash runway; and regulatory developments in the United States and foreign countries. Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: uncertainties related to the initiation, timing and conduct of preclinical and clinical studies and other development requirements for our product candidates and the risk that the results of preclinical studies and/or clinical trials will or will not be predictive of future results in connection with future studies or trials. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in C4 Therapeutics’ most recent Annual Report on Form 10-K and/or Quarterly Report on Form 10-Q, as filed with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and C4 Therapeutics undertakes no duty to update this information unless required by law. CONTACT: Investor & Media Contact Kendra Adams SVP, Communications & Investor Relations Kendra.Adams@c4therapeutics.com
Vanderbilt guard Scotty Pippen Jr. has declared for the NBA draft without signing with an agent to keep his options open. Pippen announced his intentions Saturday morning with a social media post. “We all have dreams and I am ready to pursue mine," Pippen said.
LONDON — Britain's Prince Charles offered a heartfelt tribute to his “dear Papa,'' on Saturday as Buckingham Palace offered the broad outlines of a royal funeral that will be attended by the family and broadcast to the world. As Queen Elizabeth II and other relatives mourned, Charles offered a deeply personal video message saying the royal family was “deeply grateful’’ for the outpouring of support they’ve received following the death Friday of his 99-year-old father, Prince Philip. The heir to the throne said he was touched by the number of people around the world who have shared his family’s loss and sorrow. “My dear Papa was a very special person who I think, above all else, would have been amazed by the reaction and the touching things that have been said about him,? Charles said, speaking from his southwestern England home of Highgrove. “And from that point of view we are, my family, deeply grateful for all that. It will sustain us in this particular loss and at this particularly sad time.’’ Philip’s royal ceremonial funeral will take place April 17 at Windsor Castle — a slimmed-down service amid the COVID-19 pandemic that will be entirely closed to the public. The palace insisted the royals would strictly adhere to national virus guidelines, measures that in theory would entail mask wearing in an enclosed space and social distancing. The palace declined to comment on specifics. Philip, the queen's husband of 73 years who was also known as the Duke of Edinburgh, took part in planning his own funeral and its focus on family was in accordance with his wishes. The duke also took part in designing the modified Land Rover that will carry his coffin. “Although the ceremonial arrangements are reduced, the occasion will still celebrate and recognize the duke’s life and his more than 70 years of service to the Queen, the UK and the Commonwealth,” a palace spokesman said Saturday while speaking on condition of anonymity in line with policy. Prince Harry, Philip’s grandson who stepped away from royal duties last year and now lives in California, will attend the service at Windsor along with other members of the royal family. His wife Meghan, the Duchess of Sussex, is pregnant and has been advised by her doctor not to make the long journey to the U.K. Another no-show will be Prime Minister Boris Johnson, whose office said he would not attend because current coronavirus restrictions limit funerals to 30 people, so by staying away that would “allow for as many family members as possible.'' The palace appealed to the public not to gather in Windsor or at Buckingham Palace in London to pay their respects to Philip — advice that was roundly disregarded by many. Earlier Saturday, military teams across the U.K. and on ships at sea fired 41-gun salutes to mark Philip's death, honouring the former naval officer whom they considered one of their own. Batteries in London, Edinburgh, Cardiff and Belfast — the capitals of the four nations that make up the United Kingdom — as well as other cities around the U.K. and the Mediterranean outpost of Gibraltar fired the volleys at one-minute intervals beginning at midday. Ships including the HMS Montrose, a frigate patrolling the Persian Gulf, offered their own salutes. “The Duke of Edinburgh served among us during the Second World War, and he remained devoted to the Royal Navy and the Armed Forces as a whole,” Gen. Nick Carter, chief of the defence staff, said in a statement. “A life well-lived. His Royal Highness leaves us with a legacy of indomitable spirit, steadfastness and an unshakeable sense of duty.” Members of the Commonwealth, a group of 54 countries headed by the queen, were also invited to honour Philip. The Australian Defence Force began its salute at 5 p.m. outside Parliament House in Canberra, and New Zealand planned to offer its own tribute on Sunday. Philip joined the Royal Navy as a cadet in 1939 and once had a promising military career. In 1941, he was honoured for his service during the battle of Cape Matapan off the coast of Greece, when his control of searchlights aboard the HMS Valiant allowed the battleship to pinpoint enemy vessels in the dark. Philip rose to the rank of commander before he retired from active duty. Two years after the war ended, Philip married Elizabeth at Westminster Abbey when she was 21 and he was 26. Philip’s naval career came to an abrupt end when King George VI died in 1952 and his wife became queen. At the queen’s coronation in 1953, Philip swore to be his wife’s “liege man of life and limb” and settled into a life supporting the monarch. The couple had four children — Charles, the heir to the throne, Anne, Andrew and Edward. Before he retired from official duties in 2017, the prince carried out more than 22,000 solo public engagements and supported over 780 organizations, including the Duke of Edinburgh’s Award for young people. Members of the public continued to honour Philip’s life of service, leaving flowers Saturday outside Buckingham Palace and Windsor Castle. “I think everyone would like to pay their respects,” Maureen Field, 67, said outside Windsor Castle. “Because of the virus, a lot of people have to stay away. He didn’t want a big funeral. He wanted a very private time with his family to say their goodbyes. So, we’ve all got to respect that.” Mike Williams, 50, travelled from his home in Surrey, southwest of London, to Buckingham Palace to honour the prince. “He’s a massive loss to the country and to the world, I think, so we wanted to come and pay respects,” Williams said. “I don’t know what it achieves, but it just felt like the right thing to do.” ___ Associated Press Writer James Brooks and Tom Rayner contributed. ___ For AP’s full coverage of the death of Prince Philip go to https://apnews.com/hub/prince-philip Danica Kirka, The Associated Press
Here's why cannabis investors should keep their eye on Curaleaf Holdings (TSXV:CURA) right now. The post The Top Cannabis Stock Every Investor Should Consider Today appeared first on The Motley Fool Canada.
Linamar Corporation (TSX:LNR) has made investments that align with its innovation and diversification strategy by bringing value to several early-stage companies. The post TFSA Investors: 1 Value Stock Set to Benefit From Electric Vehicles appeared first on The Motley Fool Canada.
Reguilón on for Bergwijn: how José Mourinho blew Spurs’ title charge Fear has become the manager’s defining principle and at Anfield a typically defensive substitution was the unravelling Sergio Reguilón comes on as a substitute to replace Steven Bergwijn at Anfield nine days before Christmas. A win for Spurs would have put them top of the Premier League. Photograph: Jon Super/Reuters
NEW YORK, April 10, 2021 (GLOBE NEWSWIRE) -- WHY: Rosen Law Firm, a global investor rights law firm, reminds purchasers of the securities of Athenex, Inc. (NASDAQ: ATNX) between August 7, 2019 and February 26, 2021, inclusive (the “Class Period”), of the important May 3, 2021 lead plaintiff deadline. SO WHAT: If you purchased Athenex securities during the Class Period you may be entitled to compensation without payment of any out of pocket fees or costs through a contingency fee arrangement. WHAT TO DO NEXT: To join the Athenex class action, go to http://www.rosenlegal.com/cases-register-2051.html or call Phillip Kim, Esq. toll-free at 866-767-3653 or email email@example.com or firstname.lastname@example.org for information on the class action. A class action lawsuit has already been filed. If you wish to serve as lead plaintiff, you must move the Court no later than May 3, 2021. A lead plaintiff is a representative party acting on behalf of other class members in directing the litigation. WHY ROSEN LAW: We encourage investors to select qualified counsel with a track record of success in leadership roles. Often, firms issuing notices do not have comparable experience or resources. The Rosen Law Firm represents investors throughout the globe, concentrating its practice in securities class actions and shareholder derivative litigation. Rosen Law Firm has achieved the largest ever securities class action settlement against a Chinese Company. Rosen Law Firm was Ranked No. 1 by ISS Securities Class Action Services for number of securities class action settlements in 2017. The firm has been ranked in the top 4 each year since 2013 and has recovered hundreds of millions of dollars for investors. In 2019 alone the firm secured over $438 million for investors. In 2020 founding partner Laurence Rosen was named by law360 as a Titan of Plaintiffs’ Bar. Many of the firm’s attorneys have been recognized by Lawdragon and Super Lawyers. DETAILS OF THE CASE: According to the lawsuit, defendants throughout the Class Period made false and/or misleading statements and/or failed to disclose that: (1) the data included in the Oral Paclitaxel and Encequidar New Drug Application (“NDA”) presented a safety risk to patients in terms of an increase in neutropenia-related sequalae; (2) the uncertainty over the results of the primary endpoint of objective response rate (“ORR”) at week 19 conducted by blinded independent central review (“BICR”); (3) the BICR reconciliation and re-read process may have introduced unmeasured bias and influence on the BICR; (4) Athenex’s Phase 3 study that was used to file the NDA was inadequate and not well-conducted in a patient population with metastatic breast cancer representative of the U.S. population, such that the FDA would recommended a new such clinical trial; (5) as a result, it was foreseeable that the FDA would not approve Athenex’s NDA in its current form; and (6) as a result, defendants’ public statements were materially false and misleading at all relevant times. When the true details entered the market, the lawsuit claims that investors suffered damages. To join the Athenex class action, go to http://www.rosenlegal.com/cases-register-2051.html or call Phillip Kim, Esq. toll-free at 866-767-3653 or email email@example.com or firstname.lastname@example.org for information on the class action. No Class Has Been Certified. Until a class is certified, you are not represented by counsel unless you retain one. You may select counsel of your choice. You may also remain an absent class member and do nothing at this point. An investor’s ability to share in any potential future recovery is not dependent upon serving as lead plaintiff. Follow us for updates on LinkedIn: https://www.linkedin.com/company/the-rosen-law-firm, on Twitter: https://twitter.com/rosen_firm or on Facebook: https://www.facebook.com/rosenlawfirm/. Attorney Advertising. Prior results do not guarantee a similar outcome. Contact Information: Laurence Rosen, Esq. Phillip Kim, Esq. The Rosen Law Firm, P.A. 275 Madison Avenue, 40th Floor New York, NY 10016 Tel: (212) 686-1060 Toll Free: (866) 767-3653 Fax: (212) 202-3827 email@example.com firstname.lastname@example.org email@example.com www.rosenlegal.com
Kim Kardashian shares children North, Saint, Chicago and Psalm with estranged husband Kanye West
The reality TV star has died aged 38.
Argentine Economy Minister Martin Guzman will travel to Europe on Sunday to build support among G7 and G40 nations for a renegotiation of its multibillion-dollar debts to the International Monetary Fund (IMF) and the Paris Club group of creditor nations. Guzman will travel to Germany, France, Italy and Spain, where he will meet his counterparts and other officials to outline Argentina's restructuring plans during a five-day trip. "The objective is to get the necessary support from IMF shareholders (especially G7 and G20) to finalize a program that will serve Argentina," the Ministry of Economy said in a statement.
The Queen has decided the royal family will enter two weeks of royal mourning, and engagements will continue appropriate to the circumstances.
The Valkyries scored 10 unanswered on way to state semifinals victory.
The Rock backed President Biden in last year’s smackdown of an election, but Dwayne Johnson may have caught the White House bug himself to one day succeed Uncle Joe. Always savvy on social media, the Fast & Furious franchise star went online this morning to weigh in on a recent Newsweek poll that found almost […]
(This article contains some light spoilers for the new Amazon horror series “Them”) Amazon’s “Them,” from creator Little Marvin, tells the story of a Black family from North Carolina who moves to Los Angeles in 1953 after they suffer an unimaginable tragedy. The Emorys have family out there, and they’re hoping things will be better for them out there in Southern California. Unfortunately, troubles arises when they move into what was otherwise an all-white neighborhood — and the white folks who live there are extremely unhappy about having Black neighbors. And so they do a lot of bad stuff to the Emorys, who also have some other literal demons to deal with since this is a horror show. The Emorys that we see on “Them” are not real people, and this is not a true story. But it is firmly rooted in actual history. “Them” puts a horror lens on stuff like racist covenants, predatory lending, redlining — it is, in a lot of ways, a big picture examination of the shape of institutional racism in America in the 20th Century. It’s got a focus on housing in particular, but it’s certainly not limited to that topic. Also Read: 'For All Mankind': Margot Really Needs to Stop Talking to Aleida Like That As we see at the very beginning of the first episode, the Emorys’ move across the country was part of a major trend in the mid-20th Century, when millions of Black families moved out of the South and into other parts of the country. But while things may have been overall better in general in California, that doesn’t mean there wasn’t still plenty of racism to go around out there. The beginning of the fifth episode, dubbed “COVENANT I,” gives you a partial overview of the racist mid-20th Century housing situation. In this scene, a bunch of bankers discuss the way they use dramatically unfair policies to create neighborhoods full of Black people who are paying outrageous interest rates on their homes. Interest rates that are much, much higher than what the white people have to pay. The country was still a long way away from the Fair Housing Act of 1968 — though that hardly put an end to racist housing discrimination. This scene is just part of the story. The Federal Housing Administration in the first half of the 20th Century enacted overtly racist policies with the specific goal of segregating neighborhoods and keep people of color out of white neighborhoods. Though they tried to use what they presumably thought was well-meaning language — “incompatible racial groups should not be permitted to live in the same communities” — it’s not difficult at all to see what they were doing. Also Read: Incel Captain America Is So Perfect In the scene I mentioned above, we see maps of Los Angeles with the neighborhoods assigned a color based on “residential security.” Areas in red are “hazardous” — and red areas, not at all coincidentally, also represent Black neighborhoods. This is something called “redlining,” and it had a larger tangible effect than just what we see here. That’s because that map doesn’t belong to the banks represented in this scene. It was an official government map. And the FHA would not insure mortgages for homes in the areas shaded in red. Which, in essence and function, meant Black people had (and still have) a much harder time getting mortgages than white people, and when they were able to, they paid much higher interest rates to offset the increased risk of uninsured loans. Without insurance on the loan, the bank would issue a predatory mortgage with interest so high that the standard monthly payments won’t even cover the interest, locking them into a lifetime of debt because they’ll never be able to afford to actually pay down the loan at all unless they start making a whole lot more money. Which isn’t too likely given all the other ways American racism manifests. And then on top of all that, the banks themselves were racist and just generally favored white people, and were happy to exploit Black folks. The story of the Emorys on “Them” appears to actually be something a little bit different, and an example of another racist trick the banks used to pull. When Lucky (Deborah Ayorinde) goes to the bank to try to get the ball rolling on selling the house because the neighbors are so racist, the woman there tells her it isn’t possible. “It’s not a lease in the technical sense. There’s no bank mortgage, and the debt is amortized without any accrual of equity,” she tells Lucky. What the Emorys bought is a contract. The bank buys the house from another bank, keeps the deed, and then basically rents it out under awful, unforgiving terms with the promise that the family will only own it once the debt is paid in full. Which, as mentioned above, probably won’t ever happen because the terms are structured to prevent them from ever being able to. And also the Emorys don’t get any of the wealth accrual benefits of owning a home, because they don’t actually own it. This is basically a rent-to-own scheme, but much worse. Also Read: So Who Actually Won in 'Godzilla vs Kong'? On top of that, we have the covenant. In the Emorys’ agreement with the bank, there’s a pretty weird provision: “No lot in said tract shall be sold, rented or leased to any persons whose blood is not entirely that of the Caucasian race. No persons of Negro blood or heritage shall occupy the premises, notwithstanding domestic servants actually employed by a person of the Caucasian race.” These racist covenants were also a thing, and they were made illegal in 1948 in the court case Shelley v. Kraemer when the Supreme Court declared such nonsense as violations of the 14th Amendment, which claims to guarantee equal protection under the law. So the woman from the bank isn’t just messing with the Emorys when she says those covenants aren’t enforceable. And, yes, Compton had some of these covenants in place back in the day. In the present, Compton is quite ethnically diverse. But, as it is on “Them,” it wasn’t always the case. In the early days of the 20th Century the town was actually an enclave of Japanese-American folks — but the government put them all in concentration camps during World War II, leaving the neighborhood mostly white. The demographics began to change in the 1950s. To the north of Compton is Watts, already a predominantly Black neighborhood in the early 1950s. As the Black population of Los Angeles grew, some families moved into nearby West Compton. East Compton was much slower to change, and it stayed mostly white for a couple more decades. So while “Them” is not “based on a true story” in the traditional sense, it is definitely has its basis on many, many real things that many Black people have in the past experienced and still experience to this day. Creator Little Marvin and co. crafted an original horror tale, but it’s a tale rooted in real suffering. Read original story Is the Amazon Series ‘Them’ Based on a True Story? At TheWrap
USC exploded for 11 runs from the fifth inning on Saturday.
After searching an inmate, the deputies began experiencing symptoms because of the powerful opioid.
Jordan Larmour strikes twice as Leinster knock out holders ExeterExeter 22-34 LeinsterLarmour’s double tilts topsy-turvy clash Leinster’s way An elated Jordan Larmour touches down for Leinster. Photograph: James Crombie/INPHO/REX/Shutterstock
One stoppage-time goal slowed Manchester City's march to the Premier League title. Another ignited Liverpool's push for the Champions League qualification positions. A day of dramatic finishes in England's top flight began with City losing 2-1 to 10-man Leeds, whose winning goal — scored by Stuart Dallas for his second of the match — came from a breakaway in the first minute of added-on time at Etihad Stadium. City's fourth league defeat of the season should only delay the inevitable as it closes in on regaining the title. Pep Guardiola's team leads by 14 points with six matches remaining, though second-place Manchester United has two games in hand. At Anfield, Liverpool was heading for another disappointing result at home when Trent Alexander-Arnold curled a stunning effort into the corner also in the first minute of stoppage time to secure a 2-1 win against Aston Villa. Liverpool, which had lost its last six league games at Anfield, moved into fifth place and stayed two points behind Chelsea, which jumped to fourth after a 4-1 win at Crystal Palace in Saturday's other game. U.S. international Christian Pulisic scored twice for Chelsea at Selhurst Park. West Ham started the day in fourth place but dropped to sixth ahead of its match against third-place Leicester on Sunday. ___ More AP soccer: https://apnews.com/hub/soccer and https://twitter.com/AP_Sports ___ Steve Douglas is at https://twitter.com/sdouglas80 Steve Douglas, The Associated Press
Nikki Grahame, a reality TV star best known for her apperance in the seventh season of Big Brother UK, has died aged 38. “Nikki Grahame passed away in the early hours of Friday 9th April 2021,” said a statement from her representative. “Please respect the privacy of Nikki’s friends and family at this tragic and […]
The Colorado Avalanche acquired goaltender Devan Dubynk from the San Jose Sharks on Saturday in exchange for defenceman Greg Pateryn and a fifth-round pick in the 2021 draft. Dubnyk, 34, gives NHL-leading Colorado some insurance in net behind starter Philipp Grubauer. Dubnyk has 26 games of Stanley Cup playoff experience during his career. This season, he has a 3.18 goals-against average and .898 save percentage for struggling San Jose. “Devan brought the element of consummate professionalism and class to our dressing room in what has been an extremely unique and challenging season,” Sharks general manager Doug Wilson said. “He fit seamlessly within our group and helped mentor many of our younger players. We thank him for his contributions to our club on and off the ice this season and wish him the best in Colorado.” Dubnyk and Pateryn are set to become free agents after this season. Colorado acquired Pateryn earlier this season in a salary-shedding deal that sent defenceman Ian Cole to Minnesota. The Avalanche have made two trades in two days after acquiring defenceman Patrik Nemeth from Detroit for a fourth-round pick on Friday. Their 58 points through 40 games are the most in the league and have them four up on Vegas for first place in the West Division. Grubauer has been at the centre of that success. He leads the league with 24 victories and has a 1.87 GAA and .922 save percentage in 33 games but has never played in more than 37 games during a regular season in his NHL career. Colorado GM Joe Sakic may not be done dealing. With goalie Pavel Francouz and defenceman Erik Johnson on long-term injured reserve and even without San Jose retaining any of Dubnyk's salary, the Avalanche have $4.4 million more in space to use before the deadline Monday afternoon. ___ More AP NHL: https://apnews.com/NHL and https://twitter.com/AP_Sports Stephen Whyno, The Associated Press