Innovation in a Legal Vacuum: The Uncertain Legal Landscape for Shared Micro-Mobility

The last few years have seen an explosion in the number and size shared micro-mobility systems (“SMMS”) across the United States. Some of these systems have seen extraordinary success and the potential benefit of these systems to communities is considerable. However, SMMS have repeatedly ran into legal barriers that either prevent their implementation entirely, confuse and dissuade potential users, or otherwise limit SMMS’s potential positive impact. This paper reflects a detailed study of state laws relating to SMMS and the platforms commonly used in these systems. The study uncovered many inconsistencies with micro-mobility laws across the country. Currently, many states lack clear definitions for these emerging forms of transportation, which do not otherwise fit neatly in the categories contemplated by existing law. Several states lack clear, state-level policies, which has led to discrepancies between state and local regulations. Further, there are several areas of micro-mobility law that are sharply inconsistent between states. All of these differences leave users confused as to what the law is and may discourage them from riding. A number of states are attempting to remedy inconsistencies and legislative silence by passing and proposing laws that regulate the use of electric bikes (“e-bikes”) and electric scooters (“e-scooters”), but even these efforts are unlikely to bring the consistency that is needed. Federal authorities should act to create uniform laws and work with states to adopt them, otherwise, the lack of a legal infrastructure may threaten to stifle the innovation and undermine SMMS’s promised returns

Mitsui-7, heat-treated, and nitrogen-doped multi-walled carbon nanotubes elicit genotoxicity in human lung epithelial cells.

Background: The unique physicochemical properties of multi-walled carbon nanotubes (MWCNT) have led to many industrial applications. Due to their low density and small size, MWCNT are easily aerosolized in the workplace making respiratory exposures likely in workers. The International Agency for Research on Cancer designated the pristine Mitsui-7 MWCNT (MWCNT-7) as a Group 2B carcinogen, but there was insufficient data to classify all other MWCNT. Previously, MWCNT exposed to high temperature (MWCNT-HT) or synthesized with nitrogen (MWCNT-ND) have been found to elicit attenuated toxicity; however, their genotoxic and carcinogenic potential are not known. Our aim was to measure the genotoxicity of MWCNT-7 compared to these two physicochemically-altered MWCNTs in human lung epithelial cells (BEAS-2B & SAEC). Results: Dose-dependent partitioning of individual nanotubes in the cell nuclei was observed for each MWCNT material and was greatest for MWCNT-7. Exposure to each MWCNT led to significantly increased mitotic aberrations with multi- and monopolar spindle morphologies and fragmented centrosomes. Quantitative analysis of the spindle pole demonstrated significantly increased centrosome fragmentation from 0.024-2.4 [mu]g/mL of each MWCNT. Significant aneuploidy was measured in a dose-response from each MWCNT-7, HT, and ND; the highest dose of 24 [mu]g/mL produced 67, 61, and 55%, respectively. Chromosome analysis demonstrated significantly increased centromere fragmentation and translocations from each MWCNT at each dose. Following 24 h of exposure to MWCNT-7, ND and/or HT in BEAS-2B a significant arrest in the G1/S phase in the cell cycle occurred, whereas the MWCNT-ND also induced a G2 arrest. Primary SAEC exposed for 24 h to each MWCNT elicited a significantly greater arrest in the G1 and G2 phases. However, SAEC arrested in the G1/S phase after 72 h of exposure. Lastly, a significant increase in clonal growth was observed one month after exposure to 0.024 [mu]g/mL MWCNT-HT & ND. Conclusions: Although MWCNT-HT & ND cause a lower incidence of genotoxicity, all three MWCNTs cause the same type of mitotic and chromosomal disruptions. Chromosomal fragmentation and translocations have not been observed with other nanomaterials. Because in vitro genotoxicity is correlated with in vivo genotoxic response, these studies in primary human lung cells may predict the genotoxic potency in exposed human populations

Overview and Guidance on Agile Development in Large Organizations

A continual debate surrounds the effectiveness of agile software development practices. Some organizations adopt agile practices to become more competitive, improve processes, and reduce costs. Other organizations are skeptical about whether agile development is beneficial. Large organizations face an additional challenge in integrating agile practices with existing standards and business processes. To examine the effects of agile development practices in large organizations, we review and integrate scientific literature and theory on agile software development. We further organize our theory and observations into a framework with guidelines for large organizations considering agile methodologies. Based on this framework, we present recommendations that suggest ways large organizations with established processes can successfully implement agile practices. Our analysis of the literature and theory provides new insight for researchers of agile software development and assists practitioners in determining how to adopt agile development in their organizations

Tryptophan metabolism in the central nervous system: medical implications

The metabolism of the amino acid L-tryptophan is a highly regulated physiological process leading to the generation of several neuroactive compounds within the central nervous system. These include the aminergic neurotransmitter serotonin (5-hydroxytryptamine, 5-HT), products of the kynurenine pathway of tryptophan metabolism (including 3-hydroxykynurenine, 3-hydroxyanthranilic acid, quinolinic acid and kynurenic acid), the neurohormone melatonin, several neuroactive kynuramine metabolites of melatonin, and the trace amine tryptamine. The integral role of central serotonergic systems in the modulation of physiology and behaviour has been well documented since the first description of serotonergic neurons in the brain some 40 years ago. However, while the significance of the peripheral kynurenine pathway of tryptophan metabolism has also been recognised for several decades, it has only recently been appreciated that the synthesis of kynurenines within the central nervous system has important consequences for physiology and behaviour. Altered kynurenine metabolism has been implicated in the pathophysiology of conditions such as acquired immunodeficiency syndrome (AIDS)-related dementia, Huntington's disease and Alzheimer's disease. In this review we discuss the molecular mechanisms involved in regulating the metabolism of tryptophan and consider the medical implications associated with dysregulation of both serotonergic and kynurenine pathways of tryptophan metabolism

Overview and Guidance on Agile Development in Large Organizations

A continual debate surrounds the effectiveness of agile software development practices. Some organizations adopt agile practices to become more competitive, improve processes, and reduce costs. Other organizations are skeptical about whether agile development is beneficial. Large organizations face an additional challenge in integrating agile practices with existing standards and business processes. To examine the effects of agile development practices in large organizations, we review and integrate scientific literature and theory on agile software development. We further organize our theory and observations into a framework with guidelines for large organizations considering agile methodologies. Based on this framework, we present recommendations that suggest ways large organizations with established processes can successfully implement agile practices. Our analysis of the literature and theory provides new insight for researchers of agile software development and assists practitioners in determining how to adopt agile development in their organizations

Fluxes and fate of dissolved methane released at the seafloor at the landward limit of the gas hydrate stability zone offshore western Svalbard

Widespread seepage of methane from seafloor sediments offshore Svalbard close to the landward limit of the gas hydrate stability zone (GHSZ) may, in part, be driven by hydrate destabilization due to bottom water warming. To assess whether this methane reaches the atmosphere where it may contribute to further warming, we have undertaken comprehensive surveys of methane in seawater and air on the upper slope and shelf region. Near the GHSZ limit at ?400 m water depth, methane concentrations are highest close to the seabed, reaching 825 nM. A simple box model of dissolved methane removal from bottom waters by horizontal and vertical mixing and microbially mediated oxidation indicates that ?60% of methane released at the seafloor is oxidized at depth before it mixes with overlying surface waters. Deep waters are therefore not a significant source of methane to intermediate and surface waters; rather, relatively high methane concentrations in these waters (up to 50 nM) are attributed to isopycnal turbulent mixing with shelf waters. On the shelf, extensive seafloor seepage at <100 m water depth produces methane concentrations of up to 615 nM. The diffusive flux of methane from sea to air in the vicinity of the landward limit of the GHSZ is ?4–20 ?mol m?2 d?1, which is small relative to other Arctic sources. In support of this, analyses of mole fractions and the carbon isotope signature of atmospheric methane above the seeps do not indicate a significant local contribution from the seafloor source

Predicting functional gains in a stroke trial.

A number of therapies in development for patients with central nervous system injury aim to reduce disability by improving function of surviving brain elements rather than by salvaging tissue. The current study tested the hypothesis that, after adjusting for a number of clinical assessments, a measure of brain function at baseline would improve prediction of behavioral gains after treatment.Twenty-four patients with chronic stroke underwent baseline clinical and functional MRI assessments, received 6 weeks of rehabilitation therapy with or without investigational motor cortex stimulation, and then had repeat assessments. Thirteen baseline clinical/radiological measures were evaluated for ability to predict subsequent trial-related gains.Across all patients, bivariate analyses found that greater trial-related functional gains were predicted by (1) smaller infarct volume, (2) greater baseline clinical status, and (3) lower degree of activation in stroke-affected motor cortex on baseline functional MRI. When these 3 variables were further assessed using multivariate linear regression modeling, only lower motor cortex activation and greater clinical status at baseline remained significant predictors. Note that lower baseline motor cortex activation was also associated with larger increases in motor cortex activation after treatment.Lower motor cortex activity at baseline predicted greater behavioral gains after therapy, even after controlling for a number of clinical assessments. The boosts in cortical activity that paralleled behavioral gains suggest that in some patients, low baseline cortical activity represents underuse of surviving cortical resources. A measure of brain function might be important for optimal clinical decision-making in the context of a restorative intervention

Circadian rhythm of hepatic cytosolic and nuclear estrogen receptors

The distribution of estrogen receptor between the cytosolic and nuclear compartments were evaluated in liver of male rats to determine whether a circadian rhythm exists. Cytosolic receptor reached a maximum level at 400 hours and a minimum at 2000 and 2400 hr. Nuclear receptor reached a maximum level at 800 hr and was lowest at 1600 and 2000 hr. Serum estradiol levels were also highest at 800 hr and lowest at 1600 hr. The variations in cytosolic and nuclear receptors are not reciprocal; in fact, the overall content of receptor in the liver is not constant and also displays a circadian rhythm. © 1986 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

NMR studies of the phosphotransfer domain of the histidine kinase CheA from Escherichia coli: assignments, secondary structure, general fold, and backbone dynamics

Multidimensional heteronuclear NMR techniques were applied to study the phosphotransfer domain, residues 1 - 134, of the histidine kinase CheA, from Escherichia coli, which contains the site of autophosphorylation, His48. Assignments of the backbone amide groups and side chain patons are nearly complete. Our studies show that this protein fragment consists of five a-helices (A-E)connected by turns. Analysis of NOE distance restraints provided by two-dimensional (2D) ^1H-^1H and three-dimensional (3D) ^(15)N-edited NOESY spectra using model building and structure calculations indicates that the five helices form an antiparallel helix bundle with near-neighbor connectivity. The amino-tenninal four helices are proposed to be arranged in a right-handed manner with helix E packing against helices C and D. From ideal hydrophobic helical packing and structure calculations, the site of autophosphorylation, His48, is nearly fully exposed to the solvent. We measured the NMR relaxation properties of the backbone ^(15)N nuclei using inverse detected two-dimensional NMR spectroscopy. The protein backbone dynamics studies show that CheA1-134 is formed into a tight and compact structure with very limited flexibilities both in helices and turns. Structural implications of titration and phosphorylation experiments are briefly discussed