Hundreds of football fans are expected to descend on Ashfield on Friday morning, when Portugal take on Poland in the quarter-final of UEFA Euro 2016.

(United States Fifth Circuit) - Held that an excess insurer could not sue an insured's lawyers for negligent misrepresentation. The insurer claimed that the lawyers led it to believe that a product liability suit posed no threat of exposure to its policy. Concluding that the law firm was immune from suit under these circumstances, the Fifth Circuit reversed the denial of a motion to dismiss and rendered a judgment of dismissal.

"Whiskey And Cigarettes" Country Radio Show, In Association With The European Academy Of Country Music (EACM) Has Announced Their Top 30 Of 2018 Year-end Chart. The Show Is Syndicated On More Than 25

They're trying to reschedule.

The post RAMMSTEIN Officially Cancels European Stadium Tour 2020 appeared first on Metal Injection.

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Hepatocellular carcinoma (HCC) is clearly age-related and represents one of the deadliest cancer types worldwide. As a result of globally increasing risk factors including metabolic disorders, the incidence rates of HCC are still rising. However, the molecular hallmarks of HCC remain poorly understood. Neuropeptide Y (NPY) and NPY receptors represent a highly conserved, stress-activated system involved in diverse cancer-related hallmarks including aging and metabolic alterations, but its impact on liver cancer had been unclear. Here, we observed increased expression of NPY5 receptor (Y5R) in HCC, which correlated with tumor growth and survival. Furthermore, we found that its ligand NPY was secreted by peritumorous hepatocytes. Hepatocyte-derived NPY promoted HCC progression by Y5R activation. TGF-β1 was identified as a regulator of NPY in hepatocytes and induced Y5R in invasive cancer cells. Moreover, NPY conversion by dipeptidylpeptidase 4 (DPP4) augmented Y5R activation and function in liver cancer. The TGF-β/NPY/Y5R axis and DPP4 represent attractive therapeutic targets for controlling liver cancer progression.

BACKGROUND Neurofibroma/schwannoma hybrid nerve sheath tumors (N/S HNSTs) are neoplasms associated with larger nerves that occur sporadically and in the context of schwannomatosis or neurofibromatosis type 2 or 1. Clinical management of N/S HNSTs is challenging, especially for large tumors, and established systemic treatments are lacking.METHODS We used next-generation sequencing and array-based DNA methylation profiling to determine the clinically actionable genomic and epigenomic landscapes of N/S HNSTs.RESULTS Whole-exome sequencing within a precision oncology program identified an activating mutation (p.Asp769Tyr) in the catalytic domain of the ERBB2 receptor tyrosine kinase in a patient with schwannomatosis-associated N/S HNST, and targeted treatment with the small-molecule ERBB inhibitor lapatinib led to prolonged clinical benefit and a lasting radiographic and metabolic response. Analysis of a multicenter validation cohort revealed recurrent ERBB2 mutations (p.Leu755Ser, p.Asp769Tyr, p.Val777Leu) in N/S HNSTs occurring in patients who met diagnostic criteria for sporadic schwannomatosis (3 of 7 patients), but not in N/S HNSTs arising in the context of neurofibromatosis (6 patients) or outside a tumor syndrome (1 patient), and showed that ERBB2-mutant N/S HNSTs cluster in a distinct subgroup of peripheral nerve sheath tumors based on genome-wide DNA methylation patterns.CONCLUSION These findings uncover a key biological feature of N/S HNSTs that may have important diagnostic and therapeutic implications.FUNDING This work was supported by grant H021 from DKFZ-HIPO, the University Cancer Center Frankfurt, and the Frankfurt Research Funding Clinician Scientist Program.

Treating neuropathic pain is challenging and novel non–opioid-based medicines are needed. Using unbiased receptomics, transcriptomic analyses, immunofluorescence, and in situ hybridization, we found that the expression of the orphan GPCR Gpr160 and GPR160 increased in the rodent dorsal horn of the spinal cord following traumatic nerve injury. Genetic and immunopharmacological approaches demonstrated that GPR160 inhibition in the spinal cord prevented and reversed neuropathic pain in male and female rodents without altering normal pain response. GPR160 inhibition in the spinal cord attenuated sensory processing in the thalamus, a key relay in the sensory discriminative pathways of pain. We also identified cocaine- and amphetamine-regulated transcript peptide (CARTp) as a GPR160 ligand. Inhibiting endogenous CARTp signaling in spinal cord attenuated neuropathic pain, whereas exogenous intrathecal CARTp evoked painful hypersensitivity through GPR160-dependent ERK and cAMP response element–binding protein (CREB). Our findings de-orphanize GPR160, identify it as a determinant of neuropathic pain and potential therapeutic target, and provide insights into its signaling pathways. CARTp is involved in many diseases including depression and reward and addiction; de-orphanization of GPR160 is a major step forward understanding the role of CARTp signaling in health and disease.

Regenerative pain medicine, which seeks to harness the body’s own reparative capacity, is rapidly emerging as a field within pain medicine and orthopedics. It is increasingly appreciated that common analgesic mechanisms for these treatments depend on neuroimmune modulation. In this Review, we discuss recent progress in mechanistic understanding of nociceptive sensitization in chronic pain with a focus on neuroimmune modulation. We also examine the spectrum of regenerative outcomes, including preclinical and clinical outcomes. We further distinguish the analgesic mechanisms of regenerative therapies from those of cellular replacement, creating a conceptual and mechanistic framework to evaluate future research on regenerative medicine.

Today IBM and Eurobank announced the first cloud-based digital platform for online international commercial trading. Using IBM's industry-leading Digital Experience software, with advanced cloud capabilities and social offerings, Eurobank is uniting exporters and importers from around the globe to enhance international trade operations and increase transactions.

Dans l’objectif d’une recherche permanente d’innovation et d’anticipation, cette alliance stratégique couvre le co-développement de nouvelles offres commerciales pour l’installation et la maintenance de systèmes informatiques, monétiques et d’objets connectés. Ce domaine représente un potentiel de marché dont la croissance est estimée à 12% par an.

Valerie Hansen has a new book just out: THE YEAR 1000: When Explorers Connected the World — and Globalization Began.  New York:  Scribner, 2020. A NYT review of Hansen's landmark volume is copied below, but let's first look at some interesting language notes concerning the background of the word for "slave" (Chapter 4 is on […]

Our latest viewpoint in a series on neurological conditions comes from Gerard Gahagan, Head of Service - Epilesy, Quarriers.

Scientists have gotten their best look to date at three chaotic patches on the icy surface of Jupiter's moon Europa thanks to decade-old images from a long-defunct spacecraft.

As global climate change leads to more hot and dry weather, the resulting droughts are stressing plants, making them less able to remove ozone — which at ground level is a dangerous pollutant — from the air.

If only you knew how to make your employees care as much as you do. If only you knew how to motivate them. Then, they'd be more productive, more enthusiastic. Here's the simple and direct great leaders motivate a team member.

New rules come in this week

Demand comes as TUI China resumes some tours

It asks for patience while it processes refunds and credit notes

I love walking on my own. It is never a lonely experience. There is too much to see and too much to take in . Even on Day 24 of the lockdown I am still finding nooks and a cranny or two in our village that I have never investigated before . Yes I am coveri

We should have taken it as a sign of what was to come a gruff taxi driver who reeked of cigarette smoke greeted us with little more than a grunt and yelled out arschloch half a dozen times during our short journey to the train station. One scary frau

The German cabinet on Monday agreed to an unprecedented aid package to prop up the country's economy as the coronavirus pandemic takes hold. Parliament is set to approve the package later this week.

Many countries in Eastern Europe are taking drastic measures to slow the spread of COVID-19 -- in part because their health-care systems may not be up to the task.

The European Commission is limited in what it can do to combat the spread of the SARS-CoV-2 virus, but this only makes it more imperative for Brussels to set the correct priorities.

The German government's rejection of eurobonds is selfish, small-minded and cowardly. Existing mechanisms will not be enough to contain the crisis we are facing. We need to act now.

Faced with a growing economic crisis, many European Union member states are clamoring for the introduction of so-called corona bonds. Just like it was in the euro crisis, though, Germany is opposed. In the end, Berlin may not have a choice. By DER SPIEGEL Staff

L'Europa è più di una mera alleanza di egocentrici. Non esistono alternative agli Eurobond in una crisi come questa.

Europa es más que una coalición de ególatras. En una crisis como esta no existe alternativa para los eurobonos.

On Thursday, European leaders will discuss how to navigate the block through the economic crisis triggered by the novel coronavirus. In a DER SPIEGEL interview, European Commissioner Paolo Gentiloni talks about what is at stake and the need to find at least 1 trillion euros.

The Austrian winter-sports mecca of Ischgl is well known for its parties. But after helping spread the virus across Europe, the town's reputation is changing to one of incompetence and greed.

Just as Volkswagen was undergoing a radical restructuring to focus on e-mobility and driverless cars, the company has announced it is shutting down factories across Europe due to the coronavirus. There is hope in China, however.

Freelancers and small companies are getting hit especially hard by the corona crisis. DER SPIEGEL has learned that the federal government is planning a massive financial aid package. It would mark the end of Germany’s balanced budget policy.

Eurozone ministers have formally approved €240 billion in credit lines to help European countries meet the crippling costs of fighting the coronavirus outbreak.

The Flat racing calendar in the northern hemisphere remains mired in uncertainty, but in one jurisdiction the first Classics of the season have been staged as the coronavirus pandemic rages.

A new study suggests a half-ton bird roamed Europe nearly 2 million years ago, around when our Homo predecessors were first entering the region.

A new analysis of a skull found in Greece decades ago suggests that early humans may have been in Eurasia as early as 210,000 years ago.

The deadline for Real ID has been postponed for a year and the need for paperwork to visit 26 European countries is also delayed.