Is your organization aiming to increase the participation of minority-and women-owned businesses in state and local transportation projects? TRB will conduct a webinar on Wednesday, May 27, 2020, from 2:00 PM to 3:30 PM Eastern to discuss how to meet the goals set by the U.S. Department of Transportation Disadvantaged Business Enterprise (USDOT DBE). State and local transportation projects that receive federal funding are mandated to go through the triennial DBE goal-setting process. Make your next goals...

A report from the Office of the Inspector General at the U.S. Department of Transportation

Airports and the communities they serve view robust air service as an important element for economic well-being and overall quality of life. Incentive programs are often used to encourage airlines to maintain or augment service to a community. Recent airline industry trends, including airline consolidation, use of larger aircraft, the rise of ultra-low-cost airlines, and challenges with pilot supply as well as regulatory and policy developments, have affected the significance of these programs. The TRB A...

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.

Chicago high school junior Jessica Tansey was concerned about her classmates whose families would struggle with food insecurity during the school closure for COVID-19. At the same time, she was concerned about the restaurants in her neighborhood and the negative effect the COVID-19 shutdowns were having on them. She came up with and launched a campaign called “A Meal Today, A Meal Tomorrow” to help with both community issues.

It works by a customer buying one gift card at a nearby restaurant, and the restaurant agreeing to donate a second gift card to Tansey’s high school, which is then given to a school family in need. While some of the larger restaurant chains are able to commit to matching gift cards dollar-for-dollar, many smaller restaurants are donating gift cards worth a percentage of the one purchased to help out. Tansey said, “If we can connect restaurants and students with one solution, maybe it can make a difference for everybody. I want to get all of us thinking about how to bring communities together to support each other during rough times.”

UC San Diego Health launches pilot project using drones to move medical samples, supplies and documents between Jacobs Medical Center, Moores Cancer Center and the Center for Advanced Laboratory Medicine, speeding delivery of services and patient care currently managed through ground transport.

Familial dysautonomia (FD) is the most prevalent form of hereditary sensory and autonomic neuropathy (HSAN). In FD, a germline mutation in the Elp1 gene leads to Elp1 protein decrease that causes sympathetic neuron death and sympathetic nervous system dysfunction (dysautonomia). Elp1 is best known as a scaffolding protein within the nuclear hetero-hexameric transcriptional Elongator protein complex, but how it functions in sympathetic neuron survival is very poorly understood. Here, we identified a cytoplasmic function for Elp1 in sympathetic neurons that was essential for retrograde nerve growth factor (NGF) signaling and neuron target tissue innervation and survival. Elp1 was found to bind to internalized TrkA receptors in an NGF-dependent manner, where it was essential for maintaining TrkA receptor phosphorylation (activation) by regulating PTPN6 (Shp1) phosphatase activity within the signaling complex. In the absence of Elp1, Shp1 was hyperactivated, leading to premature TrkA receptor dephosphorylation, which resulted in retrograde signaling failure and neuron death. Inhibiting Shp1 phosphatase activity in the absence of Elp1 rescued NGF-dependent retrograde signaling, and in an animal model of FD it rescued abnormal sympathetic target tissue innervation. These results suggest that regulation of retrograde NGF signaling in sympathetic neurons by Elp1 may explain sympathetic neuron loss and physiologic dysautonomia in patients with FD.

Nerve growth factor (NGF) regulates many aspects of neuronal biology by retrogradely propagating signals along axons to the targets of those axons. How this occurs when axons contain a plethora of proteins that can silence those signals has long perplexed the neurotrophin field. In this issue of the JCI, Li et al. suggest an answer to this vexing problem, while exploring why the Elp1 gene that is mutated in familial dysautonomia (FD) causes peripheral neuropathy. They describe a distinctive function of Elp1 as a protein that is required to sustain NGF signaling by blocking the activity of its phosphatase that shuts off those signals. This finding helps explain the innervation deficits prominent in FD and reveals a unique role for Elp1 in the regulation of NGF-dependent TrkA activity.

IL-17–producing RORγt+ γδ T cells (γδT17 cells) are innate lymphocytes that participate in type 3 immune responses during infection and inflammation. Herein, we show that γδT17 cells rapidly proliferate within neonatal lymph nodes and gut, where, upon entry, they upregulate T-bet and coexpress IL-17, IL-22, and IFN-γ in a STAT3- and retinoic acid–dependent manner. Neonatal expansion was halted in mice conditionally deficient in STAT5, and its loss resulted in γδT17 cell depletion from all adult organs. Hyperactive STAT5 mutant mice showed that the STAT5A homolog had a dominant role over STAT5B in promoting γδT17 cell expansion and downregulating gut-associated T-bet. In contrast, STAT5B preferentially expanded IFN-γ–producing γδ populations, implying a previously unknown differential role of STAT5 gene products in lymphocyte lineage regulation. Importantly, mice lacking γδT17 cells as a result of STAT5 deficiency displayed a profound resistance to experimental autoimmune encephalomyelitis. Our data identify that the neonatal microenvironment in combination with STAT5 is critical for post-thymic γδT17 development and tissue-specific imprinting, which is essential for infection and autoimmunity.

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.

The mechanisms by which prostate cancer shifts from an indolent castration-sensitive phenotype to lethal castration-resistant prostate cancer (CRPC) are poorly understood. Identification of clinically relevant genetic alterations leading to CRPC may reveal potential vulnerabilities for cancer therapy. Here we find that CUB domain-containing protein 1 (CDCP1), a transmembrane protein that acts as a substrate for SRC family kinases (SFKs), is overexpressed in a subset of CRPC. Notably, CDCP1 cooperates with the loss of the tumor suppressor gene PTEN to promote the emergence of metastatic prostate cancer. Mechanistically, we find that androgens suppress CDCP1 expression and that androgen deprivation in combination with loss of PTEN promotes the upregulation of CDCP1 and the subsequent activation of the SRC/MAPK pathway. Moreover, we demonstrate that anti-CDCP1 immunoliposomes (anti–CDCP1 ILs) loaded with chemotherapy suppress prostate cancer growth when administered in combination with enzalutamide. Thus, our study identifies CDCP1 as a powerful driver of prostate cancer progression and uncovers different potential therapeutic strategies for the treatment of metastatic prostate tumors.

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.

Cornel West and Tavis Smiley criticize President Barack Obama for being to the right of even President Richard Nixon. Continue reading →

Bernie Sanders would have already won this nominating contest if we had received an accurate accounting of the vote. It is deeply troubling the Senator would be sending out surrogates to talk about his allegiance to the Democratic party and Clinton in general in the face of the Party instituting theft against its own constituents. It is no mystery HOW to win. Count the votes and contest fraud. A tough Sane Progressive call out. Continue reading →

Bernie Sanders and Jane Sanders are mere actors serving as pressure valves which release from time to time all excess heat emanating from failed policies, scandals, and the worsening economic conditions, so that a catastrophic systems’ collapse can be prevented. They are sheepdogs for Hillary Clinton, preventing progressives from supporting a third party progressive candidate and to herd them back into the corral of the Democratic Party. Continue reading →

Grow a spine. Bernie Sanders, when are you going to risk losing your friendship with the Democrats to help your country? When are you going to risk doing that? You had a stupid secret agreement not to attack Hillary Clinton, and you stayed by it, and then when the country needed you to do something with your movement, you told them to go work for the Machine. And now you're telling them to back Chuck Schumer. Continue reading →

Bernie Sanders' voting record is not progressive. It has been reported on Facebook that Bernie has voted 98% of the time in agreement with Senate Democrats and 93% of the time in agreement with Hillary Clinton. And here is Bernie Sanders' illustrious "progressive" voting record...LOL. Show this to all his crazed cult followers who claim he is a progressive and has done so much for us...LOL. Continue reading →

Tucker Carlson: Elizabeth Warren's enemies on Wall Street and Big Tech are not really her enemies. Elizabeth Warren is really just this season's Hillary Clinton -- faithful party robot, stalwart defender of the prerogatives of the establishment. Continue reading →

IBM Watson Health and Tiatros Inc, a digital health company, today announced that the Tiatros-enabled post-traumatic stress disorder programs achieved up to 73% completion rate for veterans who begin the PTSD sessions. The Tiatros Post Traumatic Growth for Veterans is a Tiatros psychotherapy program designed as a secure social network to support veterans suffering from post-traumatic stress disorder. The program connects veterans with their peers online, in a platform that is designed to reduce barriers to access and deliver evidence-based cognitive behavioral therapy that is personalized to each individual, with help from Watson APIs.

The Weather Company, an IBM Business and Rogers Media announced today an agreement to provide weather information and content customized specifically for the Canadian market. With this agreement, The Weather Company will provide in-depth weather data and forecasts, as well as curated content, across Rogers Media properties. In turn, Rogers Media will provide locally relevant articles, photos and video content across the Canadian versions of The Weather Channel app and website (weather.com) to provide residents with the most pertinent information possible. The Weather Company and Rogers Media will also align to enhance advertising across both companies’ properties, with Rogers leveraging its ad sales capabilities to monetize The Weather Channel properties in Canada.

La enfermedad de Parkinson es un trastorno neurológico degenerativo crónico que afecta a una de cada 100 personas mayores de 60 años. Se estima que más de 5 millones de personas en el mundo tienen Parkinson y el número está aumentando con la población actual que envejece.

Después de un mes de haber iniciado la consultoría pro-bono de IBM, denominada Corporate Service Corps (CSC), el día de hoy se hizo entrega de los resúmenes ejecutivos a cada uno de los Directores de las organizaciones receptoras de este apoyo: DIF-Dirección de Innovación Guadalajara, Cuerpos de Paz-AIPROMADES, Asociación Nacional de Bancos de Alimentos (BAMX).

Vodafone New Zealand, a leading telecommunications services provider, and IBM (NYSE: IBM) today announced a partnership to deliver the Digital Vodafone 2021 program in New Zealand. The vision for Digital Vodafone 2021 is to create the most engaging digital customer experience by adopting agile as a way of working, embracing new technologies and simplifying business models. The program is supported by IBM iX, one of the world’s largest digital agencies and global business design partners.

Zoo and Aquarium Association Uses IBM Technology to Support Endangered Species Programme

Hello! Everyone who is waiting for the print release of Chapter 2, here is a progress report! The Deimos mini-smut-comic is finished, which is great, and I'm now in the middle of working on the Cain and Abel mini-smut-comic… which I have been waiting FOREVER to do! I'm so glad to get my black claws into this. So hold tight, my sweethearts, these goodies are on their way to you! I'll make more announcements as things develop!

Thank you so much for your patience! -Hamlet

The last data has been sent out, but our work on Nebula - the final phase of data analysis - is picking up steam. However, not all ideas are good ideas. Read about Multiplet scoring: back to the drawing board.