TRB released a straight-to-recording series in April that presents highlights and findings of the NCHRP Domestic Scan 16-02 on Landscape Design Practices for Roadside Water Management . This scan investigated how transportation agencies are applying principles and practices of green infrastructure (GI) for roadside water management to mitigate adverse impacts of flooding, drought, and temperature extremes affecting their infrastructure. The videos are available on-demand at no charge. Presenters: Garrett...

How do transportation agencies apply principles of green infrastructure (GI) to roadside water management? TRB is hosting a webinar on Monday, May 18, 2020 from 2:00 to 3:30 PM Eastern that aims to answer this question. Presenters will identify how GI may be used to mitigate impacts of flooding, drought, and temperature extremes that affect infrastructure. This webinar draws on research from the National Cooperative Highway Research Program (NCHRP) Domestic Scan Program 16-02: Leading Landscape Design Pr...

As a reliever airport for the Phoenix Sky Harbor International Airport, Phoenix–Mesa Gateway Airport must keep track of information for nearly 300,000 aircraft operations and 1.4 million passengers a year. To meet this challenge, the airport developed an innovative, digitally connected solution with the help of ACRP Research Report 182: Guidancefor Planning, Design, and Operationsof Airport Communications Centers . The TRB Airport Cooperartive Research Program's ACRP Impacts on Practice 182: Redesigning ...

The September 2015 issue of TRB’s Airport Cooperative Research Program (ACRP) Impacts on Practice explores how Philadelphia International Airport, Fort Lauderdale-Hollywood International Airport, and Changi Airport in Singapore applied guidance from ACRP Report 52 : Wayfinding and Signing Guidelines for Airport Terminals and Landside to help passengers find their way in and around an airport.

TRB’s Airport Cooperative Research Program (ACRP) Research Report 163: Guidebook for Preparing and Using Airport Design Day Flight Schedules explores the preparation and use of airport design day flight schedules (DDFS) for operations, planning, and development. The guidebook is geared towards airport leaders to help provide an understanding of DDFS and their uses, and provides detailed information for airport staff and consultants on how to prepare one.

In short… I overdid it last year. I wrote two new books for publication in the first six months. Also during that time I expanded a previously written book by at least 25%, a lot of reference material for which didn’t really exist yet. Over the rest of the year, I wrote the second half […]

A compelling addition to repo house – but is the Redmond flavour too strong?

GitHub had a lot to say about its plans at its virtual Satellite event yesterday, but the most far-reaching was the advent of Codespaces, the ability to edit code online, integrated into the GitHub user interface.…

High-frequency audio could be used to stealthily track netizens

Technical folks looking to improve web privacy haven't been able to decide whether sound beyond the range of human hearing poses enough of a privacy risk to merit restriction.…

iGiant not only screwed up the wiring, it knew it was shipping dodgy gear, it is claimed

Apple is potentially facing a class-action lawsuit over the failure of displays on its MacBook Pro line.…

With Internet marketing and Search engine optimization, crucial components to owning a company site, most web designers are adding SEO to their arsenal of capabilities. The concern is that most of these designers neglect to understand the whole picture of… Continue Reading →

Interior decoration is a tremendously crucial element of any kind of dining establishment. If you are in the planning stages of opening up a dining establishment, if you already own one and also are thinking about making adjustments, you will… Continue Reading →

Mobile phones have become a must for this generation. They are the devices that are the most helpful for all. You can talk to your loved ones, play music, play videos, play games and do many more other things. In… Continue Reading →

Organ shortage continues to limit the lives of patients who require liver transplantation. While extending criteria for liver organs provides a needed resource, tissue damage from prolonged ischemic injury can result in early allograft dysfunction and consequent rejection. In this issue of the JCI, Nakamura et al. used a mouse transplantation model with prolonged ex vivo cold storage to explore liver graft protection. The authors found that liver grafts with absent carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) exhibited increased ischemia-reperfusion injury inflammation and decreased function in wild-type recipients. The authors went on to correlate CEACAM1 levels with postreperfusion damage in human liver transplant recipients. Notably, this study identified a potential biomarker for liver transplant donor graft quality.

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.

An in-depth understanding of immune escape mechanisms in cancer is likely to lead to innovative advances in immunotherapeutic strategies. However, much remains unknown regarding these mechanisms and how they impact immunotherapy resistance. Using several preclinical tumor models as well as clinical specimens, we identified a mechanism whereby CD8+ T cell activation in response to programmed cell death 1 (PD-1) blockade induced a programmed death ligand 1/NOD-, LRR-, and pyrin domain–containing protein 3 (PD-L1/NLRP3) inflammasome signaling cascade that ultimately led to the recruitment of granulocytic myeloid-derived suppressor cells (PMN-MDSCs) into tumor tissues, thereby dampening the resulting antitumor immune response. The genetic and pharmacologic inhibition of NLRP3 suppressed PMN-MDSC tumor infiltration and significantly augmented the efficacy of anti–PD-1 antibody immunotherapy. This pathway therefore represents a tumor-intrinsic mechanism of adaptive resistance to anti–PD-1 checkpoint inhibitor immunotherapy and is a promising target for future translational research.

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.

The editors of JCI and JCI Insight are revisiting our editorial processes in light of the strain that the COVID-19 pandemic places on the worldwide scientific community. Here, we discuss adjustments to our decision framework in light of restrictions placed on laboratory working conditions for many of our authors.

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 →

Leaders of political revolutions never quit before the official battle begins, and say that they will vote for and support their enemies. When the moment arrived of walking all that endless talk of Bernie Sanders about fighting his political revolution, he caved out of self interest Continue reading →

I remember reading somewhere that if the earth was shrunk to the size of a pool ball, or a pool ball expanded to the size of the earth, the earth would be the smoother of the two.

European Union leaders have offered Britain a Brexit extension until May 22.

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.

Now it is set up so that any click off of the main menu leads you to a whole spectrum of bodies at a particular height. Check it out! Also, in the middle of the big and tall men, there are two guys standing next to each other who happen to both be wearing kilts.

When the No Parking signs aren't doing the job, I add some of my own.

I posted a second round of pirate signs and heard from the city parking manager.

Photos of Menu Signs from 2011-2019

A few people sent in STL files for their 3D models. Here's what they look like in plastic!

A new style of wooden fencing has begun to pop up around Sacramento homes

IBM today announced it is building an industry-first insurance platform on the IBM Cloud that aims to improve the processes and economics for new product development, underwriting, and benefits delivery.