Matrix Metalloproteinases and Glaucoma Treatment.

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade extracellular matrix (ECM) components such as collagen and have important roles in multiple biological processes, including development and tissue remodeling, both in health and disease. The activity of MMPs is influenced by the expression of MMPs and tissue inhibitors of metalloproteinase (TIMPs). In the eye, MMP-mediated ECM turnover in the juxtacanalicular region of the trabecular meshwork (TM) reduces outflow resistance in the conventional outflow pathway and helps maintain intraocular pressure (IOP) homeostasis. An imbalance in the MMP/TIMP ratio may be involved in the elevated IOP often associated with glaucoma. The prostaglandin analog/prostamide (PGA) class of topical ocular hypotensive medications used in glaucoma treatment reduces IOP by increasing outflow through both conventional and unconventional (uveoscleral) outflow pathways. Evidence from in vivo and in vitro studies using animal models and anterior segment explant and cell cultures indicates that the mechanism of IOP lowering by PGAs involves increased MMP expression in the TM and ciliary body, leading to tissue remodeling that enhances conventional and unconventional outflow. PGA effects on MMP expression are dependent on the identity and concentration of the PGA. An intracameral sustained-release PGA implant (Bimatoprost SR) in development for glaucoma treatment can reduce IOP for many months after expected intraocular drug bioavailability. We hypothesize that the higher concentrations of bimatoprost achieved in ocular outflow tissues with the implant produce greater MMP upregulation and more extensive, sustained MMP-mediated target tissue remodeling, providing an extended duration of effect

Selection of Source and Use of Traffic Information in Emergency Situations

The access and the use of advanced traveler information systems (ATISs) by drivers during normal commuting have been extensively assessed and analyzed. Emergency managers and transportation officials have extended the results of studies of ATIS use under routine conditions to emergency scenarios under the assumption that drivers\u27 responses to information under emergency conditions mimic those seen under normal driving conditions. A recent survey of potential hurricane evacuees suggests the need to revisit this assumption. Results indicate that although commercial radio reports and variable message signs continue to be the sources of traffic information cited the most frequently, other information sources (mobile phones, in-car systems such as Global Positioning System devices, and the Internet) have significantly increased in importance. Rapid growth in user rates and the relatively low cost of implementation suggest that a revision of plans for emergency transportation information communications may be warranted. Better, more effective use of ATISs during emergency situations, especially when traffic incidents occur, may lead to improved and more reliable travel times and improved safety and emergency response. With the use of factor analysis, four driver personalities are identified, with each one characterized by the proclivity for and response to traffic information. This information will be of interest to developers and users of ATISs and to those responsible for emergency management and transportation planning

Integrating Truck Emissions Cost in Traffic Assignment

The adverse impacts of greenhouse gasses (GHG) and the imperative for reducing the existing rate of GHG production are well established. In the United States, the largest source of GHG emissions from human activities is from burning fossil fuels, primarily for the generation of electricity and transportation. The transportation sector accounts for 28% of all U.S. GHG production. Heavy-duty vehicles, such as large freight trucks, account for nearly one-fifth of the U.S. total, and this fraction is expected to grow rapidly. Consequently, many efforts are being used to reduce the total emissions of freight trucks. Most efforts emphasize one of four areas: engineering improvements to improve fuel economy or reduce emissions, shifts to other transport modes, improved logistics to reduce the movement of partially full or empty containers, and reduced travel costs for individual trucks. A few studies have assessed modifications to route choice considerations as a means of improving the fuel economy of individual vehicles and show potential gains. In this study, the potential gains of emissions-based route choice were assessed by integrating the U.S. Environmental Protection Agency motor vehicle emission simulator with a macroscopic regional traffic demand model. For this integration, route choices included a simplified emissions calculation within the repeated model iteration runs of an algorithm of the Frank–Wolfe type. The analyses suggested that reductions of freight truck emissions were possible and showed an example in which the total system’s truck emissions were reduced by up to 0.61% (88.8 tons)

Route Change Decision Making by Hurricane Evacuees Facing Congestion

Successful evacuations of metropolitan areas require overcoming unexpected congestion that reduces traffic flows. Congestion may result from accidents, incidents, or other events that reduce road capacity. Traffic professionals and emergency managers may promote deviations from planned routes to bypass an area of congestion and speed mass exit. However, some route changes may actually reduce traffic flow rates, and in these cases decision makers may want to discourage use of alternate routes. By using results of a behavioral survey of potential hurricane evacuees, this study identifies variables associated with the decision to alter routes and also identifies frequently used information sources. A dynamic traffic simulation with a decision-making model using this information is proposed as a means for evacuation decision makers to assess impacts of driver decisions. Results from more than 800 responses showed the potentially strong influence of effective advanced traveler information systems to support decisions made by hurricane evacuees on whether to use an alternate route when faced with congestion. Results of this study are a timely contribution to those seeking a better understanding of driver behavior during evacuations and improvement of emergency management efficiency and efficacy

Prenatal Human Immunodeficiency Virus Testing and Patient Management by Obstetricians in a High Seroprevalence Community

Objective: In order to determine the practice habits of obstetricians concerning frequency of prenatal human immunodeficiency virus (HIV) testing and management strategies for HIV-seropositive obstetric patients, we conducted a telephone survey of practicing obstetricians over a 3-month period

Evacuee Route Choice Decisions in a Dynamic Hurricane Evacuation Context

Very high traffic volumes may lead to extensive congestion during hurricane evacuations. Evacuation planners reduce this congestion by careful planning for multiple hurricane scenarios and assignment of evacuation routes and timing. This planning may be for naught if obstructions block key roadways. An advanced traveler information system (ATIS) may be used to guide evacuees to alternate routes, but how effective will that guidance be? Should the use of alternate routes be encouraged? How are drivers likely to respond to delays and information? Will information shorten or improve the reliability of travel times in emergency conditions? Integration of a dynamic evacuation simulation and a decision-making model (representative of the decisions made by potential hurricane evacuees when provided with information on downstream traffic congestion and alternate routes) can help emergency planners prepare for the unexpected. Advance modeling of likely accident locations and the severity can forecast the effects of alternate route use, help determine the best locations and timing of alternate route information, and support decision making. This study integrated an evacuee route choice decision model and a mesoscopic evacuation transportation simulation for southeastern Virginia. Study results show how the effects of ATIS can be tested in advance, thus allowing more comprehensive planning by emergency management and transportation professionals. Simulations of ATIS\u27 effectiveness in evacuation scenarios have been largely unexplored. Methods presented can be applied in a variety of evacuation scenarios and may be of particular value to emergency planners

The impact of infrastructure investment on economic growth in the United Kingdom

ABSTRACT Infrastructure investment has long been held as an accelerator or a driver of the economy. Internationally, the UK ranks poorly with the performance of infrastructure and ranks in the lower percentile for both infrastructure investment and GDP growth rate amongst comparative nations. Faced with the uncertainty of Brexit and the likely negative economic impact this will bring, infrastructure investment may be used to strengthen the UK economy. This study aims to examine how infrastructure funding impacts economic growth and how best the UK can maximize this potential by building on existing work. The research method is based on interviews carried out with respondents involved in infrastructure operating across various sectors. The findings show that investment in infrastructure is vital in the UK as it stimulates economic growth through employment creation due to factor productivity. However, it is critical for investment to be directed to regional opportunity areas with the potential to unlock economic growth and maximize returns whilst stimulating further growth to benefit other regions. There is also a need for policy consistency and to review UK infrastructure policy to streamline the process and to reduce cost and time overrun, with Brexit likely to impact negatively on infrastructure investment. Keywords: infrastructure; economic growth; investment; constructio

Phosphorylation of Sli15 by Ipl1 is important for proper CPC localization and chromosome stability in <em>Saccharomyces cerevisiae</em>

The chromosomal passenger complex (CPC) is a key regulator of eukaryotic cell division, consisting of the protein kinase Aurora B/Ipl1 in association with its activator (INCENP/Sli15) and two additional proteins (Survivin/Bir1 and Borealin/Nbl1). Here we have identified multiple sites of CPC autophosphorylation on yeast Sli15 that are located within its central microtubule-binding domain and examined the functional significance of their phosphorylation by Ipl1 through mutation of these sites, either to non-phosphorylatable alanine (sli15-20A) or to acidic residues to mimic constitutive phosphorylation (sli15-20D). Both mutant sli15 alleles confer chromosome instability, but this is mediated neither by changes in the capacity of Sli15 to activate Ipl1 kinase nor by decreased efficiency of chromosome biorientation, a key process in cell division that requires CPC function. Instead, we find that mimicking constitutive phosphorylation of Sli15 on the Ipl1 phosphorylation sites causes delocalization of the CPC in metaphase, whereas blocking phosphorylation of Sli15 on the Ipl1 sites drives excessive localization of Sli15 to the mitotic spindle in pre-anaphase cells. Consistent with these results, direct interaction of Sli15 with microtubules in vitro is greatly reduced either following phosphorylation by Ipl1 or when constitutive phosphorylation at the Ipl1-dependent phosphorylation sites is mimicked by aspartate or glutamate substitutions. Furthermore, we find that mimicking Ipl1 phosphorylation of Sli15 interferes with the 'tension checkpoint'--the CPC-dependent mechanism through which cells activate the spindle assembly checkpoint to delay anaphase in the absence of tension on kinetochore-microtubule attachments. Ipl1-dependent phosphorylation of Sli15 therefore inhibits its association with microtubules both in vivo and in vitro and may negatively regulate the tension checkpoint mechanism