Two lawsuits were filed Monday challenging a proposition that Arizona voters approved to impose an additional 3.5% tax on individuals earning above $250,000 to pay school teacher salaries and training.
No one was injured in the blast, and authorities are investigating why the ordnance detonated after so many years underground
I have a confession to make. After taking a handful of autonomous taxi rides, I have gone from a hater to a friend of robot cars in just a few weeks, says Annalee Newitz
Glioblastoma (GBM) is a disease of the whole brain, with infiltrative tumor cells protected by an intact blood-brain barrier (BBB). GBM has a poor prognosis despite aggressive treatment, in part due to the lack of adequate drug permeability at the BBB. Standard of care GBM therapies include radiation and cytotoxic chemotherapy that lead to DNA damage. Subsequent activation of DNA damage response (DDR) pathways can induce resistance. Various DDR inhibitors, targeting the key regulators of these pathways such as ataxia telangiectasia mutated and Rad3-related (ATR), are being explored as radio- and chemosensitizers. Elimusertib, a novel ATR kinase inhibitor, can prevent repair of damaged DNA, increasing efficacy of DNA-damaging cytotoxic therapies. Robust synergy was observed in vitro when elimusertib was combined with the DNA-damaging agent temozolomide; however, we did not observe improvement with this combination in in vivo efficacy studies in GBM orthotopic tumor-bearing mice. This in vitro–in vivo disconnect was explored to understand factors influencing central nervous system (CNS) distribution of elimusertib and reasons for lack of efficacy. We observed that elimusertib is rapidly cleared from systemic circulation in mice and would not maintain adequate exposure in the CNS for efficacious combination therapy with temozolomide. CNS distribution of elimusertib is partially limited by P-glycoprotein efflux at the BBB, and high binding to CNS tissues leads to low levels of pharmacologically active (unbound) drug in the brain. Acknowledging the potential for interspecies differences in pharmacokinetics, these data suggest that clinical translation of elimusertib in combination with temozolomide for treatment of GBM may be limited.
This study examined the disconnect between the in vitro synergy and in vivo efficacy of elimusertib/temozolomide combination therapy by exploring systemic and central nervous system (CNS) distributional pharmacokinetics. Results indicate that the lack of improvement in in vivo efficacy in glioblastoma (GBM) patient-derived xenograft (PDX) models could be attributed to inadequate exposure of pharmacologically active drug concentrations in the CNS. These observations can guide further exploration of elimusertib for the treatment of GBM or other CNS tumors.
Inositol 1,4,5-triphosphate receptor type 1 (ITPR1) is an endoplasmic reticulum–bound intracellular inositol triphosphate receptor involved in the regulation of intracellular calcium. Pathogenic variants in ITPR1 are associated with spinocerebellar ataxia (SCA) types 15/16 and 29 and have recently been implicated in a facial microsomia syndrome. In this report, we present a family with three affected individuals found to have a heterozygous missense c.800C > T (predicted p.Thr267Met) who present clinically with a SCA29-like syndrome. All three individuals presented with varying degrees of ataxia, developmental delay, and apparent intellectual disability, as well as craniofacial involvement—an uncommon finding in patients with SCA29. The variant was identified using clinical exome sequencing and validated with Sanger sequencing. It is presumed to be inherited via parental germline mosaicism. We present our findings to provide additional evidence for germline mosaic inheritance of SCA29, as well as to expand the clinical phenotype of the syndrome.
Sega are delisting several bundles of 'classic' games from digital stores, along with "select individual" games. On Steam specifically, this adds up to over 60 games in total, including several actual classics including the original Streets Of Rage trilogy, Crazy Taxi, and Jet Set Radio.
The games will be removed on December 6th but will remain playable to those who already own them.
Autonomous taxis are already operating on US streets, while Elon Musk has spent years promising a self-driving car and failing to deliver. The newly announced Tesla Cybercab is unlikely to change that
I have a confession to make. After taking a handful of autonomous taxi rides, I have gone from a hater to a friend of robot cars in just a few weeks, says Annalee Newitz
BBC Tech Correspondent Lily Jamali analyses the 'robocabs' and if their technology is up to par.
Alcon Entertainment says it denied a request to use material from the film at the Tesla cybercab event.
The OECD has released its Taxing Wages 2020 report, which highlights that taxes on labor across the OECD countries fell for the sixth consecutive year in 2019.
The OECD has released its Taxing Wages 2020 report, which highlights that taxes on labor across the OECD countries fell for the sixth consecutive year in 2019.
If eVTOL aircraft companies are to achieve their commercial ambition of becoming flying taxis, then first they’ll need to ensure their aircrafts are quiet enough to work in cities without disturbing residents. WSJ’s George Downs looks into just how quiet these crafts need to be to take off. Photo composite: George Downs
Waymo is operating fully driverless robotaxis in Chandler, Ariz., and recently took a step toward offering the same to riders in San Francisco. It is a test that could provide a roadmap for Waymo’s expansion and help the Google sister company build a revenue-generating business. Photo: Karl Mollohan
Dubai's first aerial taxi vertiport near the airport is set to launch in 2026, enhancing urban aerial transport with sustainable technology.
Lucie Mascord has a one-of-a-kind job, she fixes, repairs and conserves bad and decaying taxidermy for museums all round the world. It's a poorly understood trade, but she's convinced it has a long future. She shows us her collection of eyes, what she's working on and explains some of the misconceptions about her trade. Including, that she's a "conservator" not a "conservative".
The ‘online payment only’ rule for property tax should be implemented gradually, feels K. Sukumaran
Once the price war is over, we can all collaborate, says Blue Bird president director Noni Purnomo.
The post Taxis can coexist with ride-hailers, says Blue Bird president appeared first on DealStreetAsia.
An OMer learning Turkish was encouraged when she shared the message of the gospel with a taxi driver in a city in Western Turkey.
In order to get this service, the customers need to update their Rapido Android app. All details here.
Advanced economies are pushing up carbon emissions, traffic congestion and air pollution by under-taxing company cars and diesel fuel, according to new OECD research.
This country note explains how Hungary taxes energy use. The note shows the distribution of effective energy tax rates across all domestic energy use. It also details the country-specific assumptions made when calculating effective energy tax rates and matching tax rates to the corresponding energy base.
The tax wedge for the average single worker in Hungary decreased by 0.4 percentage points from 45.0 in 2018 to 44.6 in 2019. The OECD average tax wedge in 2019 was 36.0 (2018, 36.1). In 2019 Hungary had the 6th highest tax wedge among the 36 OECD member countries, occupying the same position in 2018.
This country note explains how France taxes energy use. The note shows the distribution of effective energy tax rates across all domestic energy use. It also details the country-specific assumptions made when calculating effective energy tax rates and matching tax rates to the corresponding energy base.
The tax wedge for the average single worker in France decreased by 0.3 percentage points from 47.0 in 2018 to 46.7 in 2019. The OECD average tax wedge in 2019 was 36.0 (2018, 36.1). In 2019 France had the 5th highest tax wedge among the 36 OECD member countries, occupying the same position in 2018.
This country note explains how Iceland taxes energy use. The note shows the distribution of effective energy tax rates across all domestic energy use. It also details the country-specific assumptions made when calculating effective energy tax rates and matching tax rates to the corresponding energy base.
The tax wedge for the average single worker in Iceland decreased by 0.3 percentage points from 33.4 in 2018 to 33.1 in 2019. The OECD average tax wedge in 2019 was 36.0 (2018, 36.1). In 2019 Iceland had the 25th lowest tax wedge among the 36 OECD member countries, compared with the 24th in 2018.
This country note explains how Greece taxes energy use. The note shows the distribution of effective energy tax rates across all domestic energy use. It also details the country-specific assumptions made when calculating effective energy tax rates and matching tax rates to the corresponding energy base.
The tax wedge for the average single worker in Greece decreased by 0.2 percentage points from 41.0 in 2018 to 40.8 in 2019. The OECD average tax wedge in 2019 was 36.0 (2018, 36.1). In 2019 Greece had the 14th highest tax wedge among the 36 OECD member countries, compared with the 13th in 2018.
This country note explains how Italy taxes energy use. The note shows the distribution of effective energy tax rates across all domestic energy use. It also details the country-specific assumptions made when calculating effective energy tax rates and matching tax rates to the corresponding energy base.
The tax wedge for the average single worker in Italy increased by 0.2 percentage points from 47.8 in 2018 to 48.0 in 2019. The OECD average tax wedge in 2019 was 36.0 (2018, 36.1). In 2019 Italy had the 3rd highest tax wedge among the 36 OECD member countries, occupying the same position in 2018.