Public-use airports, metropolitan planning organizations (MPOs), and local land-use/ transportation planning agencies all have independent yet interrelated planning processes bound by legal and policy requirements to ensure compatibility. This means that they should work cooperatively to solve joint transportation challenges in the most effective and efficient manner. The TRB Airport Cooperative Research Program's ACRP Research Report 216: Guidebook for Assessing Collaborative Planning Efforts Among Airp...

Incompatible land uses can threaten the safe utility of airports and expose people living and working nearby to potentially unacceptable levels of noise or safety risk. At the state level, all 50 states have enacted some form of airport zoning legislation since the 1950s. The majority of states (90 percent) have enacted laws mandating or enabling local governments to adopt, administer, and enforce airport zoning regulations. The TRB Airport Cooperative Research Program's ACRP Research Report 206: Guidebo...

Decarbonizing Argentina’s Transport System: Charting the Way Forward , released by the International Transport Forum

International Society for Structural Health Monitoring of Intelligent Infrastracture will host Tenth International Conference on Structural Health Monitoring of Intelligent Infrastructure on June 30 - July 2, 2021 in Porto, Portugal. TRB is pleased to cosponsor this event. The conference provides a forum for idea exchanges, knowledge sharing, and technology-need matchmaking in the global Structural Health Monitoring and Nondestructive Testing community. It serves as a unique venue to showcase U.S. and gl...

TRB's Airport Cooperative Research Program (ACRP) Report 150: NextGen for Airports, A Primer broadly address potential airport impacts and include background information so that airport personnel can discern which NextGen programs will impact them and how. View the suite of materials related to ACRP Report 150: NextGen for Airports: Volume 1 : Understanding the Airport’s Role in Performance-Based Navigation: Resource Guide Volume 2 : Engaging Airport Stakeholders: Guidebook Volume 3 : Resources for Airpo...

TRB's Airport Cooperative Research Program (ACRP) WebResource 5: Tools and Case Studies for NextGen for Airports is a companion to the five-volume ACRP Report 150: NextGen for Airports. It provides downloadable engagement materials from the NextGen Outreach Toolkit, discussed in Volume 2: Engaging Airport Stakeholders, and the Public Information Toolkit, discussed in Volume 3: Resources for Airports. A table that identifies the volume and page number of all case studies discussed in the five volumes is a...

Most general aviation (GA) airports are minimally staffed and rarely employ environmental specialists, and the National Environmental Policy Act (NEPA) can be overwhelming to work through for those not familiar with the requirements. The TRB Airport Cooperative Research Program's ACRP Research Report 211: Guidance for Using the Interactive Tool for Understanding NEPA at General Aviation Airports , and the accompanying interactive tool that was developed, will help airport staff from GA airports understan...

Although general aviation airports have historically been funded by federal, state, and local entities, the private sector is increasingly playing a larger role. This involvement has ranged on a continuum from service and management contracts to singular projects at airports that involve leasing mechanisms to long-term leases and the whole-scale private development of general aviation airports. In an era of declining resources and increasingly scrutinized public expenditures, private-sector involvement i...

Airports — especially in the past two decades—have generally sought to promote and increase collaboration among the members of the airport community, particularly between an airport and its airlines. One metric of this trend has been the increase in the number of U.S. airports with full-time emergency managers, from fewer than 10 in 2007 to more than 120 today. Collaboration and increased professionalism in airport emergency management have gone hand in hand. No matter whether the incident is aircraft-re...

Incompatible land uses can threaten the safe utility of airports and expose people living and working nearby to potentially unacceptable levels of noise or safety risk. At the state level, all 50 states have enacted some form of airport zoning legislation since the 1950s. The majority of states (90 percent) have enacted laws mandating or enabling local governments to adopt, administer, and enforce airport zoning regulations. The TRB Airport Cooperative Research Program's ACRP Research Report 206: Guidebo...

The needs of airports may vary depending on the types of operations typically conducted at the airport, as well as the type of weather common to the airport. The TRB Airport Cooperative Research Program's ACRP Syntheis 105: Airport Surface Weather Observation Options for General Aviation Airports aims to provide the operators of general aviation (GA) airports a comprehensive source of information about airport-based weather observation options so they may make informed decisions to support the specific o...

The eight episode, half-hour series will be written by showrunner Alexandra Rushfield and will be produced by Rogen's Point Grey Pictures as part of their multiplatform partnership with Lionsgate.

The Genetics Society of America (GSA) is pleased to announce the 2020 recipients of its annual awards for distinguished service in the field of genetics. The awardees were nominated and selected by their colleagues and will be recognized with presentations at The Allied Genetics Conference (TAGC), held April 22-26, 2020, in the metro Washington, DC area.

We got Storm when he was 13 weeks old as a companion for our Border Collie, Shadow. We decided on a Labrador because they were the opposite of BC's. Storm

-Album Details- Title: The Legend of Zelda: Link’s Awakening Original Soundtrack Publisher: Nippon Columbia Catalog Number: COCX-41117~20 Release Date: March 18th, 2020 Ripped by: Razakin -Info- Soundtracks to the new Switch and the way better Game Boy versions of Link’s Awakening. Enjoy. Purchase Link(s) CDJapan

In a nutshell: editing offspring DNA at the embryo stage will eventually offer so many advantages that lots of people will cave in on some advantage. Don't want to make your kid smarter? Make him or her better looking? Don't want that? How about a throwing arm competitive in major league baseball? Opposed to that? How about avoiding passing along your terrible allergies, need for braces, terrible eyesight, tendency to get depressed or perhaps anxiety attacks or eating disorders? Lots of ways to be persuaded to step over the line once the tech becomes safe. If asked whether one would genetically engineer one's offspring today many people would answer "No" to the hypothetical question. But today choosing genes for your...

Already we've hit the $1000 genome and faster and cheaper DNA sequencing is on the way. DNA sequencing is going through a speed-up and cost-cutting rate that is similar to that which computer processors have been going through for decades. While the doubling rate of computer power has slowed quite a bit the rate of decrease in DNA sequencing costs has kept up the pace and, in fact, the rate of decline in DNA sequencing costs suddenly accelerated at the end of 2007 has been going down pretty sharply ever since. The cost decline seemed to halt during 2014 only to plunge in 2015. So why should you care? Really cheap massive amounts of DNA sequencing of cancerous cells will...

Check out: The FDA Is Cracking Down On Rogue Genetic Engineers. Apparently the US Food and Drug Administration wants to classify genetically altered dogs as drugs. When this is done to humans will they become drugs too? I think Huey Lewis has foreseen this possibility. A substantial part of the population is going to continue to insist on owning highly inbred genetically messed up dog breeds with serious health issues (e.g. bulldogs and pugs). If you do not want to me like them then avoid the unhealthiest dog breeds. But given that these breeds will continue to exist it certainly makes sense to genetically fix the fixable ones (some are, by breed standard, probably not fixable). So genetic engineers who...

Whether mutations in cancer driver genes directly affect cancer immune phenotype and T cell immunity remains a standing question. ARID1A is a core member of the polymorphic BRG/BRM-associated factor chromatin remodeling complex. ARID1A mutations occur in human cancers and drive cancer development. Here, we studied the molecular, cellular, and clinical impact of ARID1A aberrations on cancer immunity. We demonstrated that ARID1A aberrations resulted in limited chromatin accessibility to IFN-responsive genes, impaired IFN gene expression, anemic T cell tumor infiltration, poor tumor immunity, and shortened host survival in many human cancer histologies and in murine cancer models. Impaired IFN signaling was associated with poor immunotherapy response. Mechanistically, ARID1A interacted with EZH2 via its carboxyl terminal and antagonized EZH2-mediated IFN responsiveness. Thus, the interaction between ARID1A and EZH2 defines cancer IFN responsiveness and immune evasion. Our work indicates that cancer epigenetic driver mutations can shape cancer immune phenotype and immunotherapy.

BACKGROUND The anti–programmed cell death 1 (anti–PD-1) antibody pembrolizumab is clinically active against non–small cell lung cancer (NSCLC). In addition to T cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of patients with advanced NSCLC, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC.METHODS In total, 109 enrolled patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1% or higher were randomly allocated to group A (n = 55 patients given pembrolizumab plus NK cells) or group B (n = 54 patients given pembrolizumab alone). The patients received i.v. pembrolizumab (10 mg/kg) once every 3 weeks and continued treatment until the occurrence of tumor progression or unacceptable toxicity. The patients in group A continuously received 2 cycles of NK cell therapy as 1 course of treatment.RESULTS In our study, patients in group A had longer survival than did patients in group B (median overall survival [OS]: 15.5 months vs. 13.3 months; median progression-free survival [PFS]: 6.5 months vs. 4.3 months; P < 0.05). In group A patients with a TPS of 50% or higher, the median OS and PFS was significantly longer. Moreover, the patients in group A treated with multiple courses of NK cell infusion had better OS (18.5 months) than did those who received a single course of NK cell infusion (13.5 months).CONCLUSIONS Pembrolizumab plus NK cell therapy yielded improved survival benefits in patients with previously treated PD-L1+ advanced NSCLC.TRIAL REGISTRATION ClinicalTrials.gov NCT02843204.FUNDING This work was supported by grants from the National Natural Science Foundation of China (NSFC) – Guangdong Joint Foundation of China (no. U1601225); the NSFC (no. 81671965); the Guangdong Provincial Key Laboratory Construction Project of China (no. 2017B030314034); and the Key Scientific and Technological Program of Guangzhou City (no. 201607020016).

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.

Facioscapulohumeral muscular dystrophy (FSHD) results from expression of the full-length double homeobox 4 (DUX4-FL) retrogene in skeletal muscle. However, even in cases of severe FSHD the presence of DUX4 is barely detectable. In this issue of the JCI, Bosnakovski et al. used an inducible, muscle-specific human DUX4 to reproduce the low-level, sporadic DUX4 expression of human FSHD muscle as well the myopathology seen in human FSHD disease. Notably, dysregulated fibroadipogenic progenitors accumulated in affected muscles, thus providing a mechanism for the replacement of muscle by fibrosis and fat.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Although gene-environment interactions have been implicated in the etiology of several disorders, the impact of paternal and/or maternal metabolic syndrome on the clinical phenotypes of offspring and the underlying genetic and epigenetic contributors of NAFLD have not been fully explored. To this end, we used the liver-specific insulin receptor knockout (LIRKO) mouse, a unique nondietary model manifesting 3 hallmarks that confer high risk for the development of NAFLD: hyperglycemia, insulin resistance, and dyslipidemia. We report that parental metabolic syndrome epigenetically reprograms members of the TGF-β family, including neuronal regeneration–related protein (NREP) and growth differentiation factor 15 (GDF15). NREP and GDF15 modulate the expression of several genes involved in the regulation of hepatic lipid metabolism. In particular, NREP downregulation increases the protein abundance of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and ATP-citrate lyase (ACLY) in a TGF-β receptor/PI3K/protein kinase B–dependent manner, to regulate hepatic acetyl-CoA and cholesterol synthesis. Reduced hepatic expression of NREP in patients with NAFLD and substantial correlations between low serum NREP levels and the presence of steatosis and nonalcoholic steatohepatitis highlight the clinical translational relevance of our findings in the context of recent preclinical trials implicating ACLY in NAFLD progression.

Fibroblasts are key effector cells in tissue remodeling. They remain persistently activated in fibrotic diseases, resulting in progressive deposition of extracellular matrix. Although fibroblast activation may be initiated by external factors, prolonged activation can induce an “autonomous,” self-maintaining profibrotic phenotype in fibroblasts. Accumulating evidence suggests that epigenetic alterations play a central role in establishing this persistently activated pathologic phenotype of fibroblasts. We demonstrated that in fibrotic skin of patients with systemic sclerosis (SSc), a prototypical idiopathic fibrotic disease, TGF-β induced the expression of DNA methyltransferase 3A (DNMT3A) and DNMT1 in fibroblasts in a SMAD-dependent manner to silence the expression of suppressor of cytokine signaling 3 (SOCS3) by promoter hypermethylation. Downregulation of SOCS3 facilitated activation of STAT3 to promote fibroblast-to-myofibroblast transition, collagen release, and fibrosis in vitro and in vivo. Reestablishment of the epigenetic control of STAT3 signaling by genetic or pharmacological inactivation of DNMT3A reversed the activated phenotype of SSc fibroblasts in tissue culture, inhibited TGF-β–dependent fibroblast activation, and ameliorated experimental fibrosis in murine models. These findings identify a pathway of epigenetic imprinting of fibroblasts in fibrotic disease with translational implications for the development of targeted therapies in fibrotic diseases.

Seizures often herald the clinical appearance of gliomas or appear at later stages. Dissecting their precise evolution and cellular pathogenesis in brain malignancies could inform the development of staged therapies for these highly pharmaco-resistant epilepsies. Studies in immunodeficient xenograft models have identified local interneuron loss and excess glial glutamate release as chief contributors to network disinhibition, but how hyperexcitability in the peritumoral microenvironment evolves in an immunocompetent brain is unclear. We generated gliomas in WT mice via in utero deletion of key tumor suppressor genes and serially monitored cortical epileptogenesis during tumor infiltration with in vivo electrophysiology and GCAMP7 calcium imaging, revealing a reproducible progression from hyperexcitability to convulsive seizures. Long before seizures, coincident with loss of inhibitory cells and their protective scaffolding, gain of glial glutamate antiporter xCT expression, and reactive astrocytosis, we detected local Iba1+ microglial inflammation that intensified and later extended far beyond tumor boundaries. Hitherto unrecognized episodes of cortical spreading depolarization that arose frequently from the peritumoral region may provide a mechanism for transient neurological deficits. Early blockade of glial xCT activity inhibited later seizures, and genomic reduction of host brain excitability by deleting MapT suppressed molecular markers of epileptogenesis and seizures. Our studies confirmed xenograft tumor–driven pathobiology and revealed early and late components of tumor-related epileptogenesis in a genetically tractable, immunocompetent mouse model of glioma, allowing the complex dissection of tumor versus host pathogenic seizure mechanisms.

BACKGROUND Glucose-6-phosphate dehydrogenase (G6PD) deficiency decreases the ability of red blood cells (RBCs) to withstand oxidative stress. Refrigerated storage of RBCs induces oxidative stress. We hypothesized that G6PD-deficient donor RBCs would have inferior storage quality for transfusion as compared with G6PD-normal RBCs.METHODS Male volunteers were screened for G6PD deficiency; 27 control and 10 G6PD-deficient volunteers each donated 1 RBC unit. After 42 days of refrigerated storage, autologous 51-chromium 24-hour posttransfusion RBC recovery (PTR) studies were performed. Metabolomics analyses of these RBC units were also performed.RESULTS The mean 24-hour PTR for G6PD-deficient subjects was 78.5% ± 8.4% (mean ± SD), which was significantly lower than that for G6PD-normal RBCs (85.3% ± 3.2%; P = 0.0009). None of the G6PD-normal volunteers (0/27) and 3 G6PD-deficient volunteers (3/10) had PTR results below 75%, a key FDA acceptability criterion for stored donor RBCs. As expected, fresh G6PD-deficient RBCs demonstrated defects in the oxidative phase of the pentose phosphate pathway. During refrigerated storage, G6PD-deficient RBCs demonstrated increased glycolysis, impaired glutathione homeostasis, and increased purine oxidation, as compared with G6PD-normal RBCs. In addition, there were significant correlations between PTR and specific metabolites in these pathways.CONCLUSION Based on current FDA criteria, RBCs from G6PD-deficient donors would not meet the requirements for storage quality. Metabolomics assessment identified markers of PTR and G6PD deficiency (e.g., pyruvate/lactate ratios), along with potential compensatory pathways that could be leveraged to ameliorate the metabolic needs of G6PD-deficient RBCs.TRIAL REGISTRATION ClinicalTrials.gov NCT04081272.FUNDING The Harold Amos Medical Faculty Development Program, Robert Wood Johnson Foundation grant 71590, the National Blood Foundation, NIH grant UL1 TR000040, the Webb-Waring Early Career Award 2017 by the Boettcher Foundation, and National Heart, Lung, and Blood Institute grants R01HL14644 and R01HL148151.

THE AMERICAN PEOPLE IN THIS PARTICULAR MOMENT IN OUR HISTORY MUST MAKE A VERY FUNDAMENTAL DECISION, AND THAT DECISION IS DO WE CONTINUE THE STATUS QUO WHICH INCLUDES A 40-YEAR DECLINE OF OUR MIDDLE CLASS AND A HUGE AND GROWING GAP BETWEEN THE VERY, VERY RICH AND EVERYONE ELSE, OR DO WE FIGHT FOR A BOLD AND MEANINGFUL ECONOMIC AGENDA THAT CREATES JOBS, RAISES WAGES, PROTECTS OUR ENVIRONMENT AND PROVIDES HEALTH CARE FOR EVERY AMERICAN Continue reading →

we know how politics works in the United States. Whoever—whatever political party gets into government is going to merge with the bureaucracy pretty damn fast. It will be in a position where it has some levers in its hand. And so, as a result, corporate lobbyists will move in to help control those levers. So it doesn’t make much difference in the end. What does make a difference is political accountability, a general deterrence set to stop political organizations behaving in a corrupt manner. Continue reading →

Jimmy Dore: The intelligence agencies have been releasing the reports to convince us that we should be upset at Russia because they hacked our election. First of all, who gives a shit if they did? The United States tapped Angela Merkel’s … Continue reading →

GENE SIMMONS пятого мая опубликовал в Твиттере ответ на следующее сообщение:

«Разве это не хорошие новости? Не связан ли рост случаев с увеличившимся количеством тестов, так что летальность начинает снижаться?» — ссылаясь на данные CNN, спросил у Gene'a один из подписчиков.

Gene ответил:

«Увы, но новости не лучшие. У нас порядка 3 000 новых зараженных КАЖДЫЙ ДЕНЬ. Умножьте на 365. В ближайшие пару месяцев количество умерших будет от 130 000 до 200 000 человек. Печально».

Согласно данным университета Джонса Хопкинса, в США от коронавируса умерли более 71 000 человек и более 1 200 000 человек заразились этой болезнью. #Gene_Simmons #GeneSimmons #HardRock #Hard_Rock

TED NUGENT в рамках разговора с "The Joe Pags Show" подверг критике губернатора Мичигана Гретхен Уитмер за жёсткие требования находиться дома из-за пандемии COVID-19.

Губернатор-демократ в прошлом месяце продлила одно из самых жёстких в стране предписаний по нахождению по домам в целях предотвращения распространения коронавируса. Согласно этому предписанию, запрещаются все виды работ, кроме жизненно важных. Уитмер сказала, что введение одних из самых жёстких ограничений в стране необходимо из-за того, что стремительно растёт число случаев и смертей, которые грозят перегрузкой больниц.

Nugent, который переехал в Техас из Мичигана в 2005 году, прокомментировл агрессивный приказ Уитмер «оставаться по домам»:

«Есть все доказательства — нельзя отрицать неопровержимые доказательства того, что у либералов аллергия на здравый смысл, логику, Конституцию, понимание того, что мы, люди, наняли их на основании их клятвы Конституции, которая ограничивает их власть; но это вовсе не ограничивает нашу власть.

Я каждый день благодарю Бога за Нэнси Пелосис и Гретхен Уитмерс, потому что они настолько оскорбительны, настолько прогнили до глубины души, настолько нечестны и не сколько злоупотребляют властью, сколько навязывают власть другим людям.

Гретхен Уитмер — это позор для хороших, порядочных, трудолюбивых американских семей, особенно в моём любимом штате Мичиган, откуда я родом.

Это не её вина. Это апатия консерваторов, которые не голосовали...

Если бы мы с тобой говорили 20 лет назад, то это было бы моим первым осуждением Американской Мечты — апатия привела к тиранам у власти и преступникам вроде [бывшего директора ФБР] Джеймса Коми и [бывшего директора ЦРУ] Джона Бреннана и Гретхен Уитмер».

Nugent также защищал сотни демонстрантов, протестовавших против чрезвычайных мер в Мичигане в связи с коронавирусом. Во вторник Уитмер утверждала, что некоторые из людей, устроивших демонстрацию в здании Капитолия штата, «несли петли, флаги Конфедерации и свастики».

Nugent продолжил:

«Гретхен Уитмер не только противная, но вдобавок и лгунья. Она утверждала, что там были парни с автоматическим оружием. Я точно знаю, что в этом протесте не было ни одного автомата. Они лжецы — они лгут, они лгут, они лгут. Они одержимы ненавистью к свободе и индивидуальному выбору по некоторым вопросам, но потом они заставляют сделать этот индивидуальный выбор всем остальным по другим вопросам — нужно ли что-то ещё объяснить?

Итак, да благословит Господь протестующих, но сейчас время гражданского неповиновения незаконным законам, несправедливым указам, и я горжусь тем, что это происходит. И семья Nugent стоит плечом к плечу со всеми этими великими независимыми, свободолюбивыми... Нельзя просто любить свободу — нужно её требовать. Так что благослови их Господь!» #Ted_Nugent #TedNugent #HardRock #Hard_Rock

As the 2015 Atlantic hurricane season gets underway, communities in severe weather-prone regions are anxiously tracking pending storms and working to create effective disaster response plans. IBM, through its strategic alliance with The Weather Company and its global B2B division WSI, today announced a new emergency management solution that features sophisticated analytics and the use of real-time weather data to help communities predict and plan for natural disasters far more accurately and deploy the right resources in advance.

IBM and Sesame Workshop today announced that Georgia’s Gwinnett County Public Schools, one of the nation’s top urban school districts, has completed an initial pilot of the industry’s first cognitive vocabulary learning app, built on the IBM and Sesame intelligent play and learning platform. The new platform, powered by IBM Cloud, enables an ecosystem of software developers, researchers, educational toy companies, and educators to tap IBM Watson cognitive capabilities and Sesame Workshop’s early childhood expertise to build engaging experiences to help advance children’s education and learning. The cognitive vocabulary app is one of the first of many cognitive apps, games, and educational toys that will be built over time on this new platform, as a result of the two companies’ collaboration announced last year.

IBM and the University of California San Diego have announced a multi-year project to enhance quality of life and independence for aging populations through the new Artificial Intelligence for Healthy Living Center (AIHL), located on the campus of UC San Diego. The groundbreaking center will bring together the technology, artificial intelligence and life sciences knowledge of IBM and UC San Diego to promote critical research and applications in two thematic areas: Healthy Aging and the Human Microbiome.

IBM today announced the opening of IBM Studio Groningen, where IBM design, digital and industry experts will work with clients to help them engage with their customers using big data, mobile, cloud and social innovations.

IBM and MIT today announced that IBM plans to make a 10-year, $240 million investment to create the MIT–IBM Watson AI Lab in partnership with MIT. The lab will carry out fundamental artificial intelligence (AI) research and seek to propel scientific breakthroughs that unlock the potential of AI. The collaboration aims to advance AI hardware, software and algorithms related to deep learning and other areas, increase AI’s impact on industries, such as health care and cybersecurity, and explore the economic and ethical implications of AI on society. IBM’s $240 million investment in the lab will support research by IBM and MIT scientists.

IBM today announced that Vancouver-based company Fusion Genomics selected IBM’s cloud capabilities to help advance Fusion’s ability to detect pandemics before they happen. Fusion Genomics has developed disruptive DNA and RNA technology that it believes can positively identify infectious diseases and enhance the surveillance of emerging pathogens like MERS, SARS, avian flu, and swine flu.

Mayo Clinic and IBM Watson Health today unveiled results from early use of the Watson for Clinical Trial Matching, an IBM cognitive computing system. Use of this system in the Mayo Clinic oncology practice has been associated with more patients enrolled in Mayo’s breast cancer clinical trials.

IBM today unveiled its next-generation Power Systems Servers incorporating its newly designed POWER9 processor. Built specifically for compute-intensive AI workloads, the new POWER9 systems are capable of improving the training times of deep learning frameworks by nearly 4x allowing enterprises to build more accurate AI applications, faster.