Abstract. A number of the compounds proposed as replacements for substances controlled under the Montreal Protocol have extremely short atmospheric lifetimes, on the order of days to a few months. An important example is n-propyl bromide (also referred to as 1-bromopropane, CH2BrCH2CH 3 or simplified as 1-C3H7Br or nPB). This compound, useful as a solvent, has an atmospheric lifetime of less than 20 days due to its reaction with hydroxyl. Because nPB contains bromine, any amount reaching the stratosphere has the potential to affect concentrations of stratospheric ozone. The definition of Ozone Depletion Potentials (ODP) needs to be modified for such short-lived compounds to account for the location and timing of emissions. It is not adequate to treat these chemicals as if they were uniformly emitted at all latitudes and longitudes as normally done for longer-lived gases. Thus, for short-lived compounds, policymakers will need a table of ODP values instead of the single value generally provided in past studies. This study uses the MOZART2 three-dimensional chemical-transport model in combination with studies with our less computationally expensive two-dimensional model to examine potential effects of nPB on stratospheric ozone. Multiple facets of this study examine key questions regarding the amount of bromine reaching the stratosphere following emission of nPB. Our most significant findings from this study for the purposes of short-lived replacement compound ozone effects are summarized as follows. The degradation of nPB produces a significant quantity of bromoacetone which increases the amount of bromine transported to the stratosphere due to nPB. However, much of that effect is not due to bromoacetone itself, but instead to inorganic bromine which is produced from tropospheric oxidation of nPB, bromoacetone, and other degradation products and is transported above the dry and wet deposition processes of the model. The

Human retinol dehydrogenase 10 (RDH10) was implicated in the oxidation of all-trans-retinol for biosynthesis of all-transretinoic acid, however, initial assays suggested that RDH10 prefers NADP ؉ as a cofactor, undermining its role as an oxidative enzyme. Here, we present evidence that RDH10 is, in fact, a strictly NAD ؉ -dependent enzyme with multisubstrate specificity that recognizes cis-retinols as well as all-trans-retinol as substrates. RDH10 has a relatively high apparent K m value for NAD ؉ (ϳ100 M) but the lowest apparent K m value for alltrans-retinol (ϳ0.035 M) among all NAD ؉ -dependent retinoid oxidoreductases. Due to its high affinity for all-trans-retinol, RDH10 exhibits a greater rate of retinol oxidation in the presence of cellular retinol-binding protein type I (CRBPI) than human microsomal RoDH4, but like RoDH4, RDH10 does not recognize retinol bound to CRBPI as a substrate. Consistent with its preference for NAD ؉ , RDH10 functions exclusively in the oxidative direction in the cells, increasing the levels of retinaldehyde and retinoic acid. Targeted small interfering RNAmediated silencing of endogenous RDH10 or RoDH4 expression in human cells results in a significant decrease in retinoic acid production from retinol, identifying both human enzymes as physiologically relevant retinol dehydrogenases. The dual cis/ trans substrate specificity suggests a dual physiological role for RDH10: in the biosynthesis of 11-cis-retinaldehyde for vision as well as the biosynthesis of all-trans-retinoic acid for differentiation and development.Retinoic acid is a small lipophilic molecule derived from vitamin A that regulates gene expression through binding to nuclear transcription factors, retinoic acid receptors (1). The oxidation of retinol to retinaldehyde is the rate-limiting step in retinoic acid biosynthesis (2); however, the identity of the physiologically relevant retinol dehydrogenase(s) has long been controversial. Two types of enzymes have been implicated in the oxidation of retinol: cytosolic alcohol dehydrogenases (ADH) 2 of the medium-chain alcohol dehydrogenase superfamily and microsomal dehydrogenases (RoDH) of the short-chain dehydrogenase/reductase (SDR) superfamily (reviewed in Ref.3). Several criteria have been suggested for evaluation of the candidate retinoid oxidoreductases. First of all, it was proposed that to function in the oxidative direction in vivo, the enzyme has to prefer NAD ϩ as a cofactor (reviewed in Ref. 4), because unlike NADP ϩ , NAD ϩ exists mostly in the oxidized form in the majority of cells (5). Second, it was argued that the physiologically relevant retinol dehydrogenase must recognize retinol bound to cellular retinol-binding protein type I (holoCRBPI) as a substrate, because holoCRBPI is the predominant form of retinol in the cells (2). Finally, the enzyme essential for the oxidation of retinol to retinaldehyde was expected to be expressed in the "hot spots" of retinoic acid biosynthesis during various stages of development and be relatively well conserved to supp...

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Optically-coupled semiconductor laser arrays are described by coupled rate equations. The coupled mode equations and carrier densities are included in the analysis, which inherently incorporate the carrier-induced nonlinearities including spatial hole burning and amplitude-phase coupling. We solve the steady-state coupled rate equations and consider the cavity frequency detuning and the individual laser pump rates as the experimentally controlled variables. We show that the carrier-induced nonlinearities play a critical role in the mode control, and we identify gain contrast induced by cavity frequency detuning as a unique mechanism for mode control. Photon-mediated energy transfer between cavities is also discussed. Parity-time symmetry and exceptional points in this system are studied. Unbroken parity-time symmetry can be achieved by judiciously combining cavity detuning and unequal pump rates, while broken symmetry lies on the boundary of the optical locking region. Exceptional points are identified at the intersection between broken and unbroken parity-time symmetry.

In the United States there are not currently enough critical care-trained practitioners to provide care to all critically ill patients. With calls for "high-intensity" staffing and 24-hour coverage of our intensive care units, the board-certified intensivists we do have are being stretched ever more thin. Nonphysician providers (physician assistants and nurse practitioners) are being used with increasing frequency in critical care settings to provide care to critically ill patients. In this review, we explore the impact of introducing nonphysician providers into the adult intensive care unit.

The antiviral activity of a new series of thymidine analogs was determined against vaccinia virus (VV), cowpox virus (CV), herpes simplex virus, and varicella-zoster virus. Several compounds were identified that had good activity against each of the viruses, including a set of novel 5-substituted deoxyuridine analogs. To investigate the possibility that these drugs might be phosphorylated preferentially by the viral thymidine kinase (TK) homologs, the antiviral activities of these compounds were also assessed using TK-deficient strains of some of these viruses. Some of these compounds were shown to be much less effective in the absence of a functional TK gene in CV, which was unexpected given the high degree of amino acid identity between this enzyme and its cellular homolog. This unanticipated result suggested that the CV TK was important in the mechanism of action of these compounds and also that it might phosphorylate a wider variety of substrates than other type II enzymes. To confirm these data, we expressed the VV TK and human TK1 in bacteria and isolated the purified enzymes. Enzymatic assays demonstrated that the viral TK could efficiently phosphorylate many of these compounds, whereas most of the compounds were very poor substrates for the cellular kinase, TK1. Thus, the specific phosphorylation of these compounds by the viral kinase may be sufficient to explain the TK dependence. This unexpected result suggests that selective phosphorylation by the viral kinase may be a promising new approach in the discovery of highly selective inhibitors of orthopoxvirus replication.

Coherently coupled vertical-cavity surface-emitting laser arrays offer unique advantages for nonmechanical beam steering applications. We have applied dynamic coupled mode theory to show that the observed temporal phase shift between vertical-cavity surface-emitting array elements is caused by the detuning of their resonant wavelengths. Hence, a complete theoretical connection between the differential current injection into array elements and the beam steering direction has been established. It is found to be a fundamentally unique beam-steering mechanism with distinct advantages in efficiency, compactness, speed, and phase-sensitivity to current.

Children with medical complexity (CMC) account for a disproportionate share of pediatric health-care utilization and cost that is largely attributable to long hospitalizations, frequent hospital readmissions, and high use of emergency departments. In response, the Centers for Medicare and Medicaid Services Health Care Innovation Center supports the development and testing of innovative health-care payment and service delivery models. The purpose of this article is to describe the CMS-funded coordinated health care for complex kids (CHECK) program, an innovative system of health-care delivery that provides improved, comprehensive, and well-coordinated services to CMC. The CHECK program uses a combination of high-tech and low-tech interventions to connect patients, stakeholders, and providers. It is anticipated that the investment in additional support services to CMC will result in improved quality of care that leads to a reduction in unnecessary inpatient hospitalizations, readmissions, and emergency department visits and a total cost savings. The CHECK program has the potential to inform future cost-effective health-care models aimed at improving the quality of life and care for CMC and their families.