(Dartmouth College) Expanded Dartmouth awards program gives prizes for 'spec fic' playwriting on what it means to be human in a computerized world.

The currently available therapeutic radiopharmaceutical for high-risk neuroblastoma, ¹³¹I-MIBG, is ineffective at targeting micrometastases due to the low linear energy transfer (LET) properties of high-energy beta particles. In contrast, Auger radiation has high-LET properties with nanometer ranges in tissue, efficiently causing DNA damage when emitted in close proximity to DNA. The aim of this study was to evaluate the cytotoxicity of targeted Auger therapy in pre-clinical models of high-risk neuroblastoma. Methods: Using a radiolabeled poly(ADP-ribose) polymerase (PARP) inhibitor, ¹²⁵I-KX1, we delivered an Auger emitter iodine-125 to PARP-1: a chromatin-binding enzyme overexpressed in neuroblastoma. In vitro cytotoxicity of ¹²⁵I-KX1 was assessed in nineteen neuroblastoma cell lines, followed by in-depth pharmacological analysis in a sensitive and resistant pair of cell lines. Immunofluorescence microscopy was used to characterize ¹²⁵I-KX1-induced DNA damage. Finally, in vitro/in vivo microdosimetry was modeled from experimentally derived pharmacological variables. Results: ¹²⁵I-KX1 was highly cytotoxic in vitro across a panel of neuroblastoma cell lines, directly causing double strand DNA breaks. Based on subcellular dosimetry, ¹²⁵I-KX1 was approximately twice as effective compared to ¹³¹I-KX1, whereas cytoplasmic ¹²⁵I-MIBG demonstrated low biological effectiveness. Despite the ability to deliver focused radiation dose to the cell nuclei, ¹²⁵I-KX1 remained less effective than its alpha-emitting analog ²¹¹At-MM4, and required significantly higher activity for equivalent in vivo efficacy based on tumor microdosimetry. Conclusion: Chromatin-targeted Auger therapy is lethal to high-risk neuroblastoma cells with potential use in micrometastatic disease. This study provides the first evidence for cellular lethality from a PARP-1 targeted Auger emitter, calling for further investigation into targeted Auger therapy.

Autoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. Immunoglobulins and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. We investigated associations of total circulating IgG and peripheral blood mononuclear cells glycosylation with AITD and the influence of genetic background in a case-control study with several independent cohorts and over 3,000 individuals in total. The study revealed an inverse association of IgG core fucosylation with TPOAb and AITD, as well as decreased peripheral blood mononuclear cells antennary α1,2 fucosylation in AITD, but no shared genetic variance between AITD and glycosylation. These data suggest that the decreased level of IgG core fucosylation is a risk factor for AITD that promotes antibody-dependent cell-mediated cytotoxicity previously associated with TPOAb levels.

Host Matt Egan is joined by Online Editor at Techworld.com Scott Carey to break down Microsoft's mega acquisition of LinkedIn. Staff Writer at PC Advisor Chris joins in to discuss all of the news coming out of E3 and how Xbox and Playstation are set to battle it out again this summer, or will Nintendo and Zelda steal the show? (13:00). Finally, David Price comes on to talk about all of the news coming out of Apple's WWDC developer conference this week, from Hair Force One to watchOS, tvOS, macOS and iOS (26:30) And please do share, rate and review the UK Tech Weekly Podcast.  

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In Matt Egan's absence first time host Henry Burrell heroically steps in to chat about Pokemon Go with producer Chris. Then fellow staff writer Chris Minasians discusses iOS 10 beta and all of the rumoured features for the latest Apple operating system, including dark mode (10:30). Finally, Lewis Painter, staff writer at PC Advisor, talks about Playstation VR being released for the PS4, pricing and games (23:30).  

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Henry Burrell is the master of ceremonies this week, dropping beats on the hottest tech topics. First up, producer Chris joins to chat about the latest Android OS: Nougat. Then staff writer at Techworld.com Scott Carey jumps in to chat about the Deliveroo strikes this week and what this means for sharing economy companies like Uber and Airbnb in general (15:30). Finally, staff writer at Tech Advisor Lewis Painter has some Playstation console rumours to discuss (27:00).  

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This week Ashleigh Allsopp is simultaneously fascinated and worried by the UK launch of Amazon's Dash buttons, and discusses the many wonderful and not-so-wonderful things they enable you to buy on a drunken whim. Then David Price takes his turn to shine a spotlight on Apple's mysterious tax affairs (12:20) and tries to explain why the Irish government doesn't want to be given 13 billion euros. Finally a surprisingly riled-up Neil Bennett explains why women wearing headphones are not fair game for dimwitted pick-up artists (25:00), and ponders the social conventions surrounding the place of technology in each of our lives.  

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Matt Egan is back on hosting duties this week to break down the demise of the Samsung Galaxy Note 7 with producer Chris. Then staff writer at PC Advisor Lewis Painter comes on to talk about the Playstation VR release, games and pricing and compares it to the flagging Oculus Rift and HTC Vive (13:00). Finally, Scott Carey, online editor at Computerworld UK reports back from the biggest tech conference in the world, Dreamforce, chats about Salesforce's rumoured bid for Twitter and tries to make CRM interesting (25:00).  

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We let one huge, scary story dominate proceedings before allowing two lighter-weight topics return the pod to its family friendly roots.

The Cambridge Analytica and Facebook scandal is decoded and discussed, with one podder especially susceptible to influence thanks to their insane third party app access numbers.

The gang then tackles Sea of Thieves, a return to form for Rare on Xbox, before Dom (with no spoilers) says just how bad Ready Player One is.

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Ankylosing Spondylitis (AS) is a common, inflammatory rheumatic disease, which primarily affects the axial skeleton and is associated with sacroiliitis, uveitis and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine if plasma from patients with AS contained autoantibodies and if so, characterize and quantify this response in comparison to patients with Rheumatoid Arthritis (RA) and healthy controls. Two high-density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis in order to determine patterns of signalling cascades or tissue origin. 44% of patients with Ankylosing Spondylitis demonstrated a broad autoantibody response, as compared to 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The AS patients autoantibody responses were targeted towards connective, skeletal and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic Acid Programmable Protein Arrays constitute a powerful tool to study autoimmune diseases.

While most of the attention will fall on the players who are expected to make the Opening Day roster, manager Kevin Cash and the rest of the organization will be keeping a close eye on some of the players that could find their way to the big leagues at some point within the next year.

Twenty-seven years after signing Barry Bonds to a then-record free-agent contract, the Giants are in the market for yet another superstar outfielder. San Francisco's interest in Bryce Harper remained a prominent topic of conversation during Saturday's FanFest at Oracle Park, with CEO Larry Baer weighing in on the potential franchise-altering benefits of landing a marquee player.

Local real estate players say it could take years for the sector to recover from the economic fallout brought on by the COVID-19 pandemic. While local estimates were unavailable, the international real estate market is projecting a decline from US$...

I wish we had played on all night, African cowboys with not much, Else to do, I wish we had challenged the fish in the sea and, Called out to the Bison, My father and his band, And his -strike while the iron is hot- Jive, Johnstone, his brother, On the drums, Kicking up a […]

Here's a look at 10 stars that you may have forgotten played for the Braves.

Pitch clocks are set to make their Spring Training debuts this week, and it will be in games featuring hordes of players for whom playing on a timer is nothing new.

By winning his arbitration case against the Astros, pitcher Gerrit Cole stands to make $2,075,000 more this season than if he'd lost. That's a significant victory for Cole, who will double his salary this year and make $13.5 million, and a significant victory for other players to come, the veteran pitcher said.

BRIDGETOWN, Barbados (CMC): Former Windies fast bowler Kenny Benjamin says that cricket in the Caribbean is suffering from players’ lack of loyalty and commitment and that intervention is required to save the sport. The Antiguan called for coaches...

Looking after a young child is hard enough, but when that child has learning difficulties and displays challenging behaviour - the burden on parents can be extreme. That behaviour may prompt a visit to the doctor, and in this podcast we’re talking about how parents can be supported in that - what services are available. We’ll also be discussing...

The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ~26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where placental DNA methylation was associated with Matsuda index (P < 6.94 x 10^–8). Among genes annotated to these 188 CpGs, we found enrichment in targets for miRNAs, in histone modifications, and in parent-of-origin DNA methylation including the H19/MIR675 locus (paternally imprinted). We identified 12 known placenta imprinted genes, including KCNQ1. Mendelian randomization analyses revealed five loci where placenta DNA methylation may causally influence maternal insulin sensitivity, including the maternally imprinted gene DLGAP2. Our results suggest that placental DNA methylation is fundamentally linked to the regulation of maternal insulin sensitivity in pregnancy.

Reds reliever Michael Lorenzen's top priority in Spring Training will be to get innings and prepare himself to pitch in what could be a multitude of roles. However, Lorenzen's offseason workouts also included outfield work and batting practice -- and that could continue in the spring.

We are looking at the players on each active roster who are making history for their franchises every time they step on the field. We're looking at the player who has compiled the highest WAR (per Baseball Reference) for his current team so far in his career.

In an effort to help develop their players on and off the field, the D-backs have added a mental skills department to their baseball operations staff.

When you think of the D-backs, what players spring to mind? Luis Gonzalez, Randy Johnson, Paul Goldschmidt and Matt Williams are probably some of the names that arise. But what names are familiar to baseball fans but might have even some D-backs fans saying, "He was a Diamondback?"

Monday morning, D-backs manager Torey Lovullo will stand in front of his entire team prior to the first full-squad workout of the spring.

The sale of two Jewel properties will inject US$60 million into loss-making Playa Resorts while reducing the hotel rooms it operates in Jamaica by more 40 per cent. Playa announced the sale of Jewel Runaway Bay Beach Resort...

Playing in Taiwan once was a last option Justin Nicolino had to continue a professional baseball career. Now the former Miami Marlins pitcher is one of many ex-MLB players who provide entertainment for U.S. sports fans.

A Michigan family said their 6-foot-tall emu was found playing in another resident's sprinkler about a mile from home one day after escaping.

When Dr. Gil Rivera became a dentist, he had no idea his career would take him to the bloodied and bruised front lines of the NHL, but nearly 18 years later, he continues to treat the ravaged mouths of professional hockey players as the team dentist of the Tampa Bay Lightning.

What band was he with before?

Amid a significant reshaping of immigration policy by the Trump administration, a range of immigration topics that have not been at the forefront of debate merit further information sharing with the public and policymakers. This report examines eight issues areas that are deserving of additional review and could form the basis for future action by Congress, including H-1B reform and treatment of unaccompanied minors.

A few days ago, Hamas fighters stormed Fatah strongholds in Gaza that were allied with Palestinian Authority President Mahmoud Abbas and effectively took control of one of the two pillars of the evolving Palestinian state. Fatah groups struck back in the West Bank, the other Palestinian pillar, and...

What do you think is more dangerous? Terrorists getting their hands on a biological weapon that can be smuggled into the country or another hurricane like Katrina? Which is the smarter way to keep Social Security solvent? Raise the retirement age or raise taxes? How can the current economic crisi...

It happens all the time: Two guys in a garage come up with a cool new technology -- and dream of making it big. A thousand people take time off work to campaign for a visionary politician because they feel they are doing something to change the world. A million kids hit baseballs -- and wonder what...

The U.S. government has made important progress in shoring up weaknesses at the nexus of immigration and national security since September 11, 2001. But as new threats emerge and evolve—including public-health emergencies such as the COVID-19 pandemic—the question is whether the post-9/11 system is up to the task of meeting these challenges, as this report explores.

From Argentina to New Zealand and points beyond, a growing number of countries have begun exploring refugee sponsorship as a way to expand protection capacity at a time of rising need, involving individuals and communities more directly in resettlement. This brief takes stock of what both new and well-established programs need to succeed, and outlines opportunities for private philanthropic actors to support them.

Every business begun before the Internet now faces the same challenge: How to transform to compete in a digital economy? This is the leadership challenge examined by BRITE founder and Columbia Business School faculty member David Rogers in his newest book, The Digital Transformation Playbook (April 5, 2016; Columbia Business School Publishing). In the book, […]

The Virginia Beach City schools, urged on by parents, decided to make a big change, doubling the amount of recess the district offered, from just 15 minutes a day to 30.

An unusual program in Cincinnati provides academic coaches to help high school players meet eligibility requirements to stay in the game.

Governors' races in Kentucky and Mississippi took center stage, testing the political muscle of teacher activists and yielding possible policy implications for everything from public employee pensions to teacher pay.

Less than four months before the scheduled kickoff of the college football season, not one of the 14 schools in the Big Ten Conference can say for sure it will have students back on campus this fall - a crucial step for sports. Uncertainty about how the coronavirus pandemic will unfold through the summer has kept universities from making a definitive decision about the fall semester, which typically begins in late August. The football season, for now, is due to begin Aug. 29, though Big Ten schools don't begin play until the following week.

Hubbard was the AP Big 12 Offensive Player of the Year and finished eighth in the Heisman Trophy voting, the third-best finish for a Canadian player. It was the second-best single-season total in school history, trailing only Barry Sanders' 1988 Heisman season. Hubbard was the runner-up for the Cornish Trophy in 2019 after his redshirt freshman season.

Reconnecting with mentors, friends, coaches and professors, these football greats reflected on the experiences that they carried with them well beyond their college years. While they all share different stories, their journeys to the NFL were each met with adversity, and whether on or off the field, these obstacles served as tests for each individual athlete to overcome. These challenges made them stronger, earning them valuable lessons and helping them create special connections with the university they will always call ‘home.’

Geoff Schwartz joins the latest Talkin' Ducks Podcast with host Jordan Kent

"One scenario we are not working on is not playing football."

The south is going to play, so should the west coast.

"A light-hearted take on the Australian toilet paper shortage. With a lot of worry and fear in the world today (2020), it is important to be informed and make good decisions based on the facts at hand. Panic buying caused supply shortages for some products. In Australia, one of the bizarre products to fall to panic buying was toilet roll. This little book, produced as a light-hearted response, offers a reminder that there is always an alternative. Contained in this book are sixteen "sheets". It may be single ply, but we are sure you will agree the 70lb paper has plenty of bulk" -- from the introduction.