Relationship between freight accessibility and logistics employment in US counties

This paper analyzes the relationship between freight accessibility and logistics employment in the US. It develops an accessibility measure relevant for logistics companies based on a gravity model. This allows for an analysis of the accessibility of US counties focusing on four different modes of transportation: road, rail, air, and maritime. Using a Partial Least Squares model, these four different freight accessibility measures are combined into two constructs, continental and intercontinental freight accessibility, and related to logistics employment. Results show that highly accessible counties attract more logistics employment than other counties. The analyses show that it is very important to control for the effect of the county population on both freight accessibility and logistics employment. While county population explains the most variation in the logistics employment per county, there is a significant relationship between freight accessibility and logistics employment, when controlling for this effect

Payers' views of the changes arising through the possible adoption of adaptive pathways

Payers are a major stakeholder in any considerations and initiatives concerning adaptive licensing of new medicinal products, also referred to as Medicines Adaptive Pathways to patients (MAPPs). Firstly, the scope and necessity of MAPPs need further scrutiny, especially with regard to the definition of unmet need. Conditional approval pathways already exist for new medicines for seriously debilitating or life-threatening diseases and only a limited number of new medicines are innovative. Secondly, MAPPs will result in new medicines on the market with limited evidence about their effectiveness and safety. Additional data are to be collected after approval. Consequently, adaptive pathways may increase the risk of exposing patients to ineffective or unsafe medicines. We have already seen medicines approved conventionally that subsequently proved ineffective or unsafe amongst a wider, more co-morbid population as well as medicines that could have been considered for approval under MAPPs but subsequently proved ineffective or unsafe in Phase III trials and were never licensed. Thirdly, MAPPs also put high demands on payers. Routine collection of patient level data is difficult with high transaction costs. It is not clear who will fund these. Other challenges for payers include shifts in the risk governance framework, implications for evaluation and HTA, increased complexity of setting prices, difficulty with ensuring equity in the allocation of resources, definition of responsibility and liability and implementation of stratified use. Exit strategies also need to be agreed in advance, including price reductions, rebates, or reimbursement withdrawals when price premiums are not justified. These issues and concerns will be discussed in detail including potential ways forward

Loss of Nuclear Activity of the FBXO7 Protein in Patients with Parkinsonian-Pyramidal Syndrome (PARK15)

Mutations in the F-box only protein 7 gene (FBXO7) cause PARK15, an autosomal recessive neurodegenerative disease presenting with severe levodopa-responsive parkinsonism and pyramidal disturbances. Understanding the PARK15 pathogenesis might thus provide clues on the mechanisms of maintenance of brain dopaminergic neurons, the same which are lost in Parkinson's disease. The protein(s) encoded by FBXO7 remain very poorly characterized. Here, we show that two protein isoforms are expressed from the FBXO7 gene in normal human cells. The isoform 1 is more abundant, particularly in primary skin fibroblasts. Both isoforms are undetectable in cell lines from the PARK15 patient of an Italian family; the isoform 1 is undetectable and the isoform 2 is severely decreased in the patients from a Dutch PARK15 family. In human cell lines and mouse primary neurons, the endogenous or over-expressed, wild type FBXO7 isoform 1 displays mostly a diffuse nuclear localization. An intact N-terminus is needed for the nuclear FBXO7 localization, as N-terminal modification by PARK15-linked missense mutation, or N-terminus tag leads to cytoplasmic mislocalization. Furthermore, the N-terminus of wild type FBXO7 (but not of mutant FBXO7) is able to confer nuclear localization to profilin (a cytoplasmic protein). Our data also suggest that overexpressed mutant FBXO7 proteins (T22M, R378G and R498X) have decreased stability compared to their wild type counterpart. In human brain, FBXO7 immunoreactivity was highest in the nuclei of neurons throughout the cerebral cortex, intermediate in the globus pallidum and the substantia nigra, and lowest in the hippocampus and cerebellum. In conclusion, the common cellular abnormality found in the PARK15 patients from the Dutch and Italian families is the depletion of the FBXO7 isoform 1, which normally localizes in the cell nucleus. The activity of FBXO7 in the nucleus appears therefore crucial for the maintenance of brain neurons and the pathogenesis of PARK15

Second Language Processing Shows Increased Native-Like Neural Responses after Months of No Exposure

Although learning a second language (L2) as an adult is notoriously difficult, research has shown that adults can indeed attain native language-like brain processing and high proficiency levels. However, it is important to then retain what has been attained, even in the absence of continued exposure to the L2—particularly since periods of minimal or no L2 exposure are common. This event-related potential (ERP) study of an artificial language tested performance and neural processing following a substantial period of no exposure. Adults learned to speak and comprehend the artificial language to high proficiency with either explicit, classroom-like, or implicit, immersion-like training, and then underwent several months of no exposure to the language. Surprisingly, proficiency did not decrease during this delay. Instead, it remained unchanged, and there was an increase in native-like neural processing of syntax, as evidenced by several ERP changes—including earlier, more reliable, and more left-lateralized anterior negativities, and more robust P600s, in response to word-order violations. Moreover, both the explicitly and implicitly trained groups showed increased native-like ERP patterns over the delay, indicating that such changes can hold independently of L2 training type. The results demonstrate that substantial periods with no L2 exposure are not necessarily detrimental. Rather, benefits may ensue from such periods of time even when there is no L2 exposure. Interestingly, both before and after the delay the implicitly trained group showed more native-like processing than the explicitly trained group, indicating that type of training also affects the attainment of native-like processing in the brain. Overall, the findings may be largely explained by a combination of forgetting and consolidation in declarative and procedural memory, on which L2 grammar learning appears to depend. The study has a range of implications, and suggests a research program with potentially important consequences for second language acquisition and related fields

UNCOVER: A NIRSpec Identification of a Broad-line AGN at z = 8.50

Deep observations with the James Webb Space Telescope (JWST) have revealed an emerging population of red pointlike sources that could provide a link between the postulated supermassive black hole seeds and observed quasars. In this work, we present a JWST/NIRSpec spectrum from the JWST Cycle 1 UNCOVER Treasury survey of a massive accreting black hole at z = 8.50 displaying a clear broad-line component as inferred from the Hβ line with FWHM = 3439 ± 413 km s−1, typical of the broad-line region of an active galactic nucleus (AGN). The AGN nature of this object is further supported by high ionization, as inferred from emission lines, and a point-source morphology. We compute a black hole mass of log 10 ( M BH / M ⊙ ) = 8.17 ± 0.42 and a bolometric luminosity of L bol ∼ 6.6 × 1045 erg s−1. These values imply that our object is accreting at ∼40% of the Eddington limit. Detailed modeling of the spectral energy distribution in the optical and near-infrared, together with constraints from ALMA, indicate an upper limit on the stellar mass of log 10 ( M * / M ⊙ ) < 8.7 , which would lead to an unprecedented ratio of black hole to host mass of at least ∼30%. This is orders of magnitude higher compared to the local QSOs but consistent with recent AGN studies at high redshift with JWST. This finding suggests that a nonnegligible fraction of supermassive black holes either started out from massive seeds and/or grew at a super-Eddington rate at high redshift. Given the predicted number densities of high-z faint AGN, future NIRSpec observations of larger samples will allow us to further investigate galaxy-black hole coevolution in the early Universe

Analysis of current situation and expected future bottlenecks and challenges in air cargo - First results of CargoMap project

The paper focuses on the first results of the EU Air Cargo Technology Roadmap project (CargoMap). The project investigates if novel aircraft is needed to satisfy the demand for air cargo and develops an air cargo technology roadmap. The goal of this study is to identify and examine the factors influencing medium to long-term air freight development in order to gain a better understanding of the air freight transport system and its interdependencies. The outcome of this analysis is intended to provide a basis for the development of a technology roadmap for future concepts (e.g. vehicles, operations, etc.) in air freight transport

CargoMap: An Air Cargo Technology Road Map

This paper focuses on the first results of the Air Cargo Technology Roadmap project (CargoMap) that is supported by the European Commission. The project investigates if novel aircraft are needed to satisfy the demand for air cargo in the long term future and develops an air cargo technology roadmap. The outcome of the market analysis is intended to provide a basis for the development of technology for future concepts (e.g. vehicles, operations, etc.) in air freight transport. The study is supporting the content of the Horizon 2020 technology program

Carvacrol Induces Heat Shock Protein 60 and Inhibits Synthesis of Flagellin in Escherichia coli O157:H7▿

The essential oils of oregano and thyme are active against a number of food-borne pathogens, such as Escherichia coli O157:H7. Carvacrol is one of the major antibacterial components of these oils, and p-cymene is thought to be its precursor in the plant. The effects of carvacrol and p-cymene on protein synthesis in E. coli O157:H7 ATCC 43895 cells were investigated. Bacteria were grown overnight in Mueller-Hinton broth with a sublethal concentration of carvacrol or p-cymene, and their protein compositions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and confirmed by Western blotting. The presence of 1 mM carvacrol during overnight incubation caused E. coli O157:H7 to produce significant amounts of heat shock protein 60 (HSP60) (GroEL) (P < 0.05) and inhibited the synthesis of flagellin highly significantly (P < 0.001), causing cells to be aflagellate and therefore nonmotile. The amounts of HSP70 (DnaK) were not significantly affected. p-Cymene at 1 mM or 10 mM did not induce HSP60 or HSP70 in significant amounts and did not have a significant effect on flagellar synthesis. Neither carvacrol (0.3, 0.5, 0.8, or 1 mM) nor p-cymene (0.3, 0.5, or 0.8 mM) treatment of cells in the mid-exponential growth phase induced significant amounts of HSP60 or HSP70 within 3 h, although numerical increases of HSP60 were observed. Motility decreased with increasing concentrations of both compounds, but existing flagella were not shed. This study is the first to demonstrate that essential oil components induce HSP60 in bacteria and that overnight incubation with carvacrol prevents the development of flagella in E. coli O157:H7